[Germ-line mutation of BRCA1 in patients with breast and/or ovarian cancer in high risk families in Northern France].
The BRCA1 gene modification is responsible for an autosomal dominant syndrome of inherited early onset breast and/or ovarian cancer. This gene is estimated to account for almost half of inherited breast cancers and three quarters of inherited breast/ovarian cancers. This suggests that about 1 out of 500 women may carry BRCA1 mutation. The BRCA1 gene was isolated by positional cloning in 1994. More than 100 different mutations have been found in the germline of affected individuals. We looked by systematic sequencing at BRCA1 germline mutations in 36 patients treated at the Centre Oscar-Lambret for breast and/or ovarian cancer and that belonged to high risk families. We have found 24 mutations: 9 true mutations inducing modifications of the BRCA1 protein (BRCA1+), 5 mutations with unknown consequences on the BRCA1 protein and 10 mutations corresponding to polymorphisms that had been previously described. All the BRCA1+ cases had a HPG3 tumor. The median age of discovery and the receptor positivity percentage are lower in hereditary breast cancer than in the standard population of the breast cancers treated in our center. Consequently, BRCA1 mutations are associated to parameters thought to be of bad prognosis.


Weighted integration method for local cerebral blood flow measurements with positron emission tomography.
A new technique called the weighted integration method for the measurement of local CBF (LCBF) in humans with positron emission tomography (PET) is presented. LCBF is calculated from weighted time integrals of the blood and tissue radioactivity curves. This method is computationally efficient and achieves nearly optimal statistical estimation of LCBF. The predicted root mean squared error of the weighted integration method is verified by simulation studies and is only 1-2% larger than the minimum possible error that can be achieved by an ideal estimation algorithm. For LCBF of greater than 30 ml/min/100 g, the weighted integration method provides reduced noise compared with the integrated projection technique, the PET autoradiographic method, and the steady-state technique. In addition, an error analysis is performed to study the sensitivity of the weighted integration method to tissue mixtures, blood sample timing errors, and changes in LCBF during the data collection period.


Serological relationships and epitope profiles of isolates of okra leaf curl geminivirus from Africa and the Middle East.
A panel of seven murine monoclonal antibodies (mAbs) was raised against particles of okra leaf curl virus (OLCV), a whitefly-transmitted geminivirus which is prevalent in West Africa. The mAbs detected at least six distinguishable epitopes, two continuous and four discontinuous. In tests with these mAbs, relatively little antigenic variation was found among 24 OLCV isolates from Burkina Faso, Chad, Ghana, Ivory Coast, Nigeria, Oman and Saudi Arabia, each virus isolate reacting with at least five of them. However, on the basis of their reactions with 17 mAbs raised against particles of a group A isolate of African cassava mosaic virus (ACMV), the OLCV isolates could be assigned to two groups, which have geographical distributions that overlap in West Africa. A network of antigenic relationships was revealed by reactions between the OLCV mAbs and other whitefly-transmitted geminiviruses from six plant species in 12 countries. OLCV shared the most epitopes with tobacco leaf curl (African isolates) virus, ACMV, Indian cassava mosaic virus and bean golden mosaic virus. Selected OLCV mAbs are suitable for routine detection of OLCV, and a panel of three mAbs can be used to identify it.


How does posture influence the haemodynamic assessment of a cardiovascular drug? Experience with nicardipine.
The extent to which posture altered the haemodynamic response to slow calcium channel blocker nicardipine was evaluated in 22 male patients with angiographically confirmed coronary artery disease. Patients were randomly allocated to supine or upright posture and an otherwise identical protocol performed in each group. At rest, following a control saline period, four doses of the drug (log cumulative dosage: 1.25, 2.5, 5.0, and 10.0 mg) were administered by i.v. infusion over a total period of 40 min; haemodynamic indices were recorded during the 3-5 min following each 5 min infusion. The exercise effects of the drug, in each posture, were determined by comparison of a control predrug exercise with observations at the same workload following the maximal cumulative dose. Nicardipine reduced resting mean blood pressure (MBP) and systemic vascular resistance index (SVRI) in both postures, the decrease being more pronounced when upright (MBP, -12%, -18%; p less than 0.01: SVRI, -30%, -46%; p less than 0.01). The increases in cardiac index (CI) and stroke volume index (SVI) were higher when upright (29 and 54% vs. 10 and 27%; p less than 0.01). Pulmonary artery occluded pressure (PAOP) increased by 29% when upright, without change when supine. On exercise, the effects for HR, MBP, CI, SI, and SVRI responses were independent of posture; however, a qualitative difference was apparent for PAOP (-17% vs. +14%; p less than 0.05). Thus, although the actions of nicardipine were qualitatively similar, quantitative differences related to posture were confirmed. These differences appeared to relate to posture-related baseline haemodynamic differences between the groups but with similar postnicardipine absolute values.


Psychometric properties of the suffering assessment questionnaire in adults with chronic diseases or life-threatening illness.
Suffering has been considered by many authors to be a difficult concept to assess and measure, as it is subjective and unique. However, to guide the diagnosis and decision-making of healthcare professionals, it is important to develop an instrument that differentiates the different suffering dimensions, namely, intra- and interpersonal suffering, awareness of suffering and spiritual suffering. The aim of this study was thus to design and validate an instrument for the assessment of the dimensions of suffering in adult patients with chronic diseases or life-threatening illnesses. A methodological study was developed. The data were collected from two self-help organisations and a palliative care unit. The theoretical model was tested using confirmatory factor analysis. The study sample consisted of 251 patients with chronic diseases or life-threatening illnesses. The Sense of Coherence Scale, the Spiritual Assessment Scale and the Suffering Assessment Questionnaire in Adults with Chronic Diseases or Life-Threatening Illness (SAQ) were applied to each participant and were later returned for analysis. An SAQ version with 12 items showed adequate psychometric characteristics of validity and internal consistency after being adapted to a four-dimensional structure that assesses the four dimensions of suffering. The results of confirmatory analysis indicated a good model fit that suggested that the advocated theoretical model is plausible.


Platelet serotonin concentration at term pregnancy and after birth: physiologic values for Croatian population.
The aim of this study was to determine physiological value of platelet serotonin (5-HT) and its variations in the group of women in term pregnancy and after birth. Obtained results were compared to the platelet 5-HT level in nonpregnant women group. Determination of normal level of 5-HT in pregnancy and after could help in its further measurement and evaluation of different psychologic and psychiatric disorders related to pregnant and postpartal period, including better understanding of mood changes after the birth. A total of 137 healthy Croatian women were enrolled in the study--82 of them were pregnant and 55 were not. Their blood was sampled and the platelet serotonin concentration was determined. In pregnant women the blood was sampled twice: at term pregnancy, and soon after birth. The mean value of 5-HT in pregnant women was 1.209 nmol/mg protein, after the delivery 1.045 nmol/mg protein, and in non pregnant 1.088 nmol/ mg protein. The concentrations were significantly different in those three groups. We did not find differences in 5-HT levels in groups divided by age.


Pulmonary nontuberculous mycobacterial infection: radiologic manifestations.
The nontuberculous mycobacteria (NTMB) are a group of bacteria that can infect the cervical lymph nodes, skin, soft tissues, and lung. Pulmonary NTMB disease is increasing in prevalence and is most commonly caused by Mycobacterium avium-intracellulare or M kansasii. Occasionally, M xenopi, M fortuitum, or M chelonae also causes pulmonary disease. Diagnosis of pulmonary NTMB infection is often difficult because isolation of the organism from sputum or bronchoalveolar lavage fluid can represent airway colonization. The radiologic manifestations of pulmonary NTMB infection are protean and include consolidation, cavitation, fibrosis, nodules, bronchiectasis, and adenopathy. Pulmonary NTMB infection has five distinct clinicoradiologic manifestations: (a) classic infection, (b) nonclassic infection, (c) nodules in asymptomatic patients, (d) infection in patients with achalasia, and (e) infection in immunocompromised patients. Although classic NTMB infection may be indistinguishable from active tuberculosis, it is usually more indolent. The radiologic features of nonclassic NTMB infection are characteristic: bronchiectasis and centrilobular nodules isolated to or most severe in the lingula and middle lobe. In patients with acquired immunodeficiency syndrome, mediastinal or hilar adenopathy is the most common radiographic finding. Knowledge of the full spectrum of clinical and radiologic features of pulmonary NTMB infection is important to facilitate diagnosis and treatment.


Air blast circuit breaker noise and hearing loss: a multifactorial model for risk assessment.
The assessment of the risk to hearing from impulse noise exposure may be a problem for the occupational physician because existing legislative and international noise exposure standards deal primarily with continuous noise, and are not valid in excess of the peak exposure limit of 200 pa (140 dB). Noise exposure in excess of this level, for example that due to firearms, is frequently perceived as harmful, but this is not necessarily the case, as impulse noise standards do, in fact, allow exposure with a maximum in the order of 6.3 kPa (170 dB). To illustrate this, a cross-sectional group of electrical transmission workers have been studied who were exposed to significant levels of impulse noise from air blast circuit breakers and firearms. Important hearing loss factors have been identified by means of a specially designed questionnaire. Using the Health & Safety Executive definition, the risk of hearing loss was determined by calculating prevalence odds ratios (ORs) for exposure to these factors. The OR for those with fewer than eight unprotected air blast circuit breaker exposures was 2.27 (95% confidence interval (CI), 1.01-5.08), whilst for those with more than eight exposures the OR was 2.10 (95% CI, 0.97-4.54). For firearm exposure, ORs of 1.61 (95% CI, 0.95-2.74) were noted in the medium exposure group and 2.05 (95% CI, 1.08-3.86) in the high exposure group. When all the factors were included in the model, the most significant factor was age. The study gives support to the impulse noise exposure criteria, confirming the borderline risk from air blast circuit breaker noise exposure and the relative safety of moderate gunfire exposure.


NCI series of cell lines: an historical perspective.
The NCI series of cell lines represent a unique collection of permanent human tumor cell lines established by one laboratory over a period of approximately 16 years. More than 300 cell lines were established, mainly from human lung cancers (both small cell and non-small cell types). In addition, smaller numbers of lines were established from rare and unusual tumors such as cutaneous T cell lymphomas, myelomas and adrenal cortical carcinoma. The T cell lines played a pivotal role in the isolation of human retroviruses including HTLV-1 and HIV. The establishment of such a large panel of lines was aided by the development of defined media for culturing specific cell types. The lines are well characterized, and full clinical data are available for most of them. Many of the lines have been deposited with the American Type Culture Collection, Rockville, MD, where they are readily available for a modest handling fee. The lines have been widely distributed to investigators, and have had a major impact on biomedical research.


Synergistically enhanced osteoconductivity and anti-inflammation of PLGA/β-TCP/Mg(OH)2 composite for orthopedic applications.
Synthetic biodegradable polymers including poly(lactide-co-glycolide) (PLGA) have been widely used as alternatives to metallic implantable materials in the orthopedic field due to their superior biocompatibility and biodegradability. However, weak mechanical properties of the biodegradable polymers and inflammatory reaction caused by the acidic degradation products have limited their biomedical applications. In this study, we have developed a PLGA composite containing beta-tricalcium phosphate (β-TCP) and magnesium hydroxide (Mg(OH)2) as additives to improve mechanical, osteoconductivity, and anti-inflammation property of the biopolymer composite simultaneously. The β-TCP has an osteoconductive effect and the Mg(OH)2 has a pH neutralizing effect. The PLGA/inorganic composites were uniformly blended via a twin extrusion process. The mechanical property of the PLGA/β-TCP/Mg(OH)2 composite was improved compared to the pure PLGA. In particular, the addition of Mg(OH)2 suppressed the inflammatory reaction of normal human osteoblast (NHOst) cells and also inhibited the differentiation of pre-osteoclastic cells into osteoclasts. Moreover, synergistically upregulated late osteogenic differentiation of NHOst cells was observed on the PLGA/β-TCP/Mg(OH)2 composite. Taken all together, we believe that the use of β-TCP and Mg(OH)2 as additives with synthetic biodegradable polymers has great potential by the synergistic effect in orthopedic applications.


Career goals of trainee physicians in internal medicine.
To survey Internal Medicine trainees' future career choices and factors influencing their decision-making. Cross-sectional study. The Aga Khan University Hospital, Karachi, from November 2006 to January 2007. A standard questionnaire was administered to the residents and Interns working in the Department of Internal Medicine of The Aga Khan University Hospital. The questionnaire covered demographic details, specialty choice, work-time distribution and factors influencing career choice. Descriptive statistics were applied. A total of 49 doctors participated with 57% females; and 43% males, having 33% interns and 67% residents. A minority (22%) opted for internal medicine, while 78% selected sub-specialties with cardiology (20%) being the most sought- after sub-specialty. Majority (69%) wanted to spend more time in clinical activities compared to administration (18%) or research (13%). Majority (92%) wanted to work in an academic setting. Availability of a structured training program (61%), ability to practice broad area of medicine (41%) and prestige of the specialty (41%) highly influenced their career choices. Forty one (82%) wanted to proceed abroad for further training and 80% wanted to eventually practice in Pakistan. Most of the interviewed under-training physicians wanted to pursue sub-specialty. Clinical work was more attractive compared to research. A structured training program was detrimental in affecting their choices. Majority wanted further training abroad but eventual settlement in Pakistan. The study results can help us create the basis for reforming the current training programs.


Segmentation of British Sign Language (BSL): mind the gap!
This study asks how users of British Sign Language (BSL) recognize individual signs in connected sign sequences. We examined whether this is achieved through modality-specific or modality-general segmentation procedures. A modality-specific feature of signed languages is that, during continuous signing, there are salient transitions between sign locations. We used the sign-spotting task to ask if and how BSL signers use these transitions in segmentation. A total of 96 real BSL signs were preceded by nonsense signs which were produced in either the target location or another location (with a small or large transition). Half of the transitions were within the same major body area (e.g., head) and half were across body areas (e.g., chest to hand). Deaf adult BSL users (a group of natives and early learners, and a group of late learners) spotted target signs best when there was a minimal transition and worst when there was a large transition. When location changes were present, both groups performed better when transitions were to a different body area than when they were within the same area. These findings suggest that transitions do not provide explicit sign-boundary cues in a modality-specific fashion. Instead, we argue that smaller transitions help recognition in a modality-general way by limiting lexical search to signs within location neighbourhoods, and that transitions across body areas also aid segmentation in a modality-general way, by providing a phonotactic cue to a sign boundary. We propose that sign segmentation is based on modality-general procedures which are core language-processing mechanisms.


Priming of microglia in a DNA-repair deficient model of accelerated aging.
Aging is associated with reduced function, degenerative changes, and increased neuroinflammation of the central nervous system (CNS). Increasing evidence suggests that changes in microglia cells contribute to the age-related deterioration of the CNS. The most prominent age-related change of microglia is enhanced sensitivity to inflammatory stimuli, referred to as priming. It is unclear if priming is due to intrinsic microglia ageing or induced by the ageing neural environment. We have studied this in Ercc1 mutant mice, a DNA repair-deficient mouse model that displays features of accelerated aging in multiple tissues including the CNS. In Ercc1 mutant mice, microglia showed hallmark features of priming such as an exaggerated response to peripheral lipopolysaccharide exposure in terms of cytokine expression and phagocytosis. Specific targeting of the Ercc1 deletion to forebrain neurons resulted in a progressive priming response in microglia exemplified by phenotypic alterations. Summarizing, these data show that neuronal genotoxic stress is sufficient to switch microglia from a resting to a primed state.


Identification of Zinc Finger, MYM-type 2 (ZMYM2) as a regulator of sorafenib resistance in hepatocellular carcinoma cell lines.
Hepatocellular carcinoma (HCC) is an aggressive malignancy with a very complex molecular process. There is no successful therapy for advanced HCC at present. Recently, sorafenib has been used as a systemic therapy to improve survival in patients with advanced HCC, but increasing reports of recurrence or non-responsiveness indicate the limitations of sorafenib as a therapeutic agent. Therefore, identification of genes involved in sorafenib resistance is important to effectively treat advanced HCC. We performed a genomic screening with a short-hairpin RNA library cassette on HCC cell lines to find genes relating resistance to sorafenib. Zinc finger, MYM type 2 (ZMYM2) was sequenced after three successive screens in vitro as a challengeable target. The inhibition of ZMYM2 resulted in sorafenib-resistance in formerly sensitive HCC cell lines. Immunohistochemical comparison of tumor and non-tumor regions showed stronger ZMYM2 staining intensities in non-tumor regions than in tumor regions. ZMYM2 may play an important role in sorafenib resistance.


A case of external ophthalmomyiasis in a deployed U.K. soldier.
Infestation of the eye by larval fly forms (ophthalmomyiasis) is rarely seen in the Western world. We present the case of a 21 year old British soldier who developed external ophthalmomyiasis during an operational tour of southern Afghanistan. This case report and discussion illustrates the potential for ophthalmomyiasis in personnel deployed to this theatre; the possibility of infestation without an identifiable episode of exposure; the importance of proper assessment and follow-up in order to identify sight-threatening complications; and the balance between optimal patient care and the risks inherent to casualty evacuation demanded by modern day stability operations.


Stimulatory effect of hnRNA on template activity of isolated rat liver chromatin.
Transcription of chromatin isolated from rat liver with E. coli RNA polymerase was stimulated up to five-fold with heterogeneous nuclear RNA (hnRNA) from rat liver. The transcription product had features of DNA-primed RNA. Neither cytoplasmic poly(A)-containing RNA nor high or low molecular weight cytoplasmic poly(A)-lacking RNA from rat liver exhibited stimulation of transcription. The stimulatory effect seems to be confined to middle repetitive sequences of hnRNA. With purified DNA templates, addition of hnRNA resulted in complete inhibition of transcription. The stimulatory effect of hnRNA on chromatin transcription was also observed with endogenous RNA polymerase. This effect was dependent ionic strength and was most pronounced under conditions optimal for RNA-polymerase B activity.


[Left-sided pectobrachialgia].
Left pectorobrachialgia, described here in 41 patients, is a frequent rheumatoid affection seen in general practice. It causes anterior chest pain with irradiation into the left arm, and patients often interpret it as being of coronary origin. The latter, however, is characterized by its different clinical presentation. Two forms can be distinguished: the typical form, which is an isolated entity, and the second, associated with and modified by fibromyalgia. It may coexist with angina pectoris and occur after myocardial infarction.


Mutation models for DVI analysis.
In recent years, the use of DNA data for personal identification has become a crucial feature for forensic applications such as disaster victim identification (DVI). Computational methods to cope with these kinds of problems must be designed to handle large scale events with a high number of victims, obtaining likelihood ratios and posterior odds with respect to different identification hypotheses. Trying to minimize identification error rates (i.e., false negatives and false positives), a number of computational methods, based either on the choice between alternative mutation models or on the adoption of a different strategy, are proposed and evaluated. Using simulation of DNA profiles, our goal is to suggest which is the most appropriate way to address likelihood ratio computation in DVI cases, especially to be able to efficiently deal with complicating issues such as mutations or null alleles, considering that data about these latter are limited and fragmentary.


Cortisol Awakening Response in Elite Military Men: Summary Parameters, Stability Measurement, and Effect of Compliance.
The cortisol awakening response (CAR) holds promise as a clinically important marker of health status. However, CAR research is routinely challenged by its innate complexity, sensitivity to confounds, and methodological inconsistencies. In this unprecedented characterization of CAR in elite military men (N = 58), we established summary parameters, evaluated sampling stability across two consecutive days, and explored the effect of subject compliance. Average salivary cortisol concentrations increased nearly 60% within 30 minutes of waking, followed by a swift recovery to waking values at 60 minutes. Approximately one in six were classified as negative responders (i.e., <0% change from waking to 30-minute postawakening). Three summary parameters of magnitude, as well as three summary parameters of pattern, were computed. Consistent with our hypothesis, summary parameters of magnitude displayed superior stability compared with summary parameters of pattern in the total sample. As expected, compliance with target sampling times was relatively good; average deviations of self-reported morning sampling times in relation to actigraph-derived wake times across both days were within ±5 minutes, and nearly two-thirds of the sample was classified as CAR compliant across both days. Although compliance had equivocal effects on some measures of magnitude, it substantially improved the stability of summary parameters of pattern. The first of its kind, this study established the foundation for a program of CAR research in a profoundly resilient yet chronically stressed population. Building from this, our forthcoming research will evaluate demographic, biobehavioral, and clinical determinants of CAR in this unique population.


D1 dopamine receptors in the nucleus accumbens modulate cocaine self-administration in the rat.
Previous work using systemic injections of dopamine receptor antagonists has established that dopamine D1 receptors may have a role in cocaine self-administration. The purpose of the present study was to test the hypothesis that these effects were mediated by dopamine D1 receptors in the region of the nucleus accumbens. Animals were trained to perform operant responses to self-administer cocaine via an IV catheter on a fixed-ratio 5 (FR 5) schedule of reinforcement. SCH23390, a selective D1 dopamine antagonist, significantly increased the self-administration of cocaine when injected into the nucleus accumbens. This increase in self-administration is thought to reflect decreases in the magnitude of the reinforcer, similar to the increase observed when the dose of cocaine is reduced. Similar doses of SCH23390 injected into the posterior caudate nucleus failed to alter cocaine self-administration. These data suggest that D1 receptors in the nucleus accumbens are important for the reinforcing properties of cocaine.


The catabolism of amino acids to long chain and complex alcohols in Saccharomyces cerevisiae.
The catabolism of phenylalanine to 2-phenylethanol and of tryptophan to tryptophol were studied by (13)C NMR spectroscopy and gas chromatography-mass spectrometry. Phenylalanine and tryptophan are first deaminated (to 3-phenylpyruvate and 3-indolepyruvate, respectively) and then decarboxylated. This decarboxylation can be effected by any of Pdc1p, Pdc5p, Pdc6p, or Ydr380wp; Ydl080cp has no role in the catabolism of either amino acid. We also report that in leucine catabolism Ydr380wp is the minor decarboxylase. Hence, all amino acid catabolic pathways studied to date use a subtly different spectrum of decarboxylases from the five-membered family that comprises Pdc1p, Pdc5p, Pdc6p, Ydl080cp, and Ydr380wp. Using strains containing all possible combinations of mutations affecting the seven AAD genes (putative aryl alcohol dehydrogenases), five ADH genes, and SFA1, showed that the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.)


Influence of hypertonic saline on bacterial translocation in controlled hemorrhagic shock.
Translocation of enteric bacteria has been described in rats following hemorrhagic shock (HS). The aim of the present study was to evaluate the effect of hypertonic saline (HTS) on bacterial translocation (BT) in the setting of controlled HS in rats. The study included 2 arms. Arm I was a qualitative assessment of translocation. Sixty-eight anesthetized animals were studied. The rats were divided into 5 groups. Group I (n = 10) was sham shock controls. In groups II-V, HS was induced by arterial bleeding to mean arterial pressure (MAP) of 35-45 mmHg, which was maintained for 30 min. The animals were then allocated into 4 groups: group II (n = 19) untreated HS; group III (n = 13) normal saline (NS) treated; group IV (n = 13) HTS-treated; and group V (n = 13) HTS and blood treated. Mesenteric lymph nodes, liver, spleen, portal, and systemic blood were sent for culture after 24 h. Translocation occurred if enteric bacteria were cultured from at least one site. Arm II was a quantitative assessment of translocation. Two groups were studied: untreated HS (n = 7) and HTS treated (n = 6). In the qualitative arm, the 24-h mortality in untreated rats (group II) was 31.5% compared to 5.1% in treated animals (groups II-V) (P = 0.01). No BT was detected in control animals (group I). BT after HS was not different between groups II, III, and IV (92.3%, 91.6%, and 100%, respectively). Group V showed fewer translocations than groups II-IV, a difference that was especially significant compared with group IV (P = 0.039). However, BT to distant sites (systemic blood and spleen) was significantly lower in group V than in groups II-IV (P < 0.05). In the quantitative arm, the mortality rate was 16.7% in the untreated group. Although no qualitative significant difference in the translocation rate was found between the two groups (67% in untreated animals vs. 50% in HTS treated), there was significant quantitative difference: in HTS-treated group a significantly lesser bacteria translocated than in untreated animals (0.4 x 10(5) cfu/g vs. 4.2 x 10(5) cfu/g, respectively [P = 0.001]). We concluded that whereas assessed qualitatively, in this model of severe HS in rats, the hemorrhagic insult itself resulted in BT in most animals and treatment with NS, HTS, and blood resulted in reduced early mortality but did not alter significantly the translocation rate. Only the combination of HTS and blood resulted in reduced BT to distant sites. However, quantitative assessment showed that HTS significantly reduced the number of translocating bacteria.


Differential quantitative analysis of MHC ligands by mass spectrometry using stable isotope labeling.
Currently, no method allows direct and quantitative comparison of MHC-presented peptides in pairs of samples, such as transfected and untransfected, tumorous and normal or infected and uninfected tissues or cell lines. Here we introduce two approaches that use isotopically labeled reagents to quantify by mass spectrometry the ratio of peptides from each source. The first method involves acetylation and is both fast and simple. However, higher peptide recoveries and a finer sensitivity are achieved by the second method, which combines guanidination and nicotinylation, because the charge state of peptides can be maintained. Using differential acetylation, we identified a beta catenin-derived peptide in solid colon carcinoma overpresented on human leucocyte antigen-A (HLA-A)(*)6801. Guanidination/nicotinylation was applied to keratin 18-transfected cells and resulted in the characterization of the peptide RLASYLDRV (HLA-A(*)0201), exclusively presented on the transfectant. Thus, we demonstrate methods that enable a pairwise quantitative comparison leading to the identification of overpresented MHC ligands.


A highly sensitive fluorescent probe based on simple pyrazoline for Zn2+ in living neuron cells.
We develop a pyrazoline-based fluorescent sensor for biological Zn(2+) detection. The sensor shows good binding selectivity for Zn(2+) over competing metal with 40-fold fluorescence enhancement in response to Zn(2+). The new probe is cell-permeable and can be used to detect intracellular zinc ions in living neuron cells.


[The experimental evaluation of antiradiation effectiveness of genistein by survival rates and bone marrow hemopoiesis of mice irradiated by X-rays].
The study was aimed at evaluating the radioprotective effectiveness of genistein administered at different times before or after acute irradiation. Evaluation ofradioprotective efficiency was performed by studying the 30-day survival rate, life expectancy, bone marrow hemapoiesis using the method of endogenous and exogenous colony formation. We have established that genistein at a dose of 200 mg/kg when administered 1 hour prior to irradiation has the highest radioprotective efficiency. In this case, genistein protects mice against death due to X-ray radiation at doses LD(50-90/30), increasing their survival rate by 30-44%, and reduces expression of post radiation disorders of bone marrow hematopoiesis.


Early catheter removal and reduced length of hospital stay following transurethral prostatectomy: a retrospective analysis of 100 consecutive patients.
We reviewed the charts of 100 consecutive patients who underwent transurethral prostatectomy between January 1986 and April 1987. Average length of hospital stay was 2.9 days, which was considerably shorter than that reported previously in the literature. We usually hospitalize patients on the day of the operation and remove the catheters the following morning. A total of 15 patients required reinsertion of the catheter for hemorrhage or retention. Of these patients 13 had 1 or more of 3 predisposing risk factors (preoperative total urinary retention, preoperative gross hematuria or resected prostatic specimen weight greater than 30 gm). We conclude that early removal of the catheter and reduced lengths of hospitalization will be safe for the majority of patients.


[Quality Evaluation of the Performance Study of Diagnostic Tests Using STARD Checklist and Meta-Analysis for the Pooled Sensitivity and Specificity of Third Generation Anti-HCV EIA Tests.].
The third generation anti-hepatitis C virus (HCV) enzyme immunoassay (EIA) is now in use for screening HCV infection. The aim of this study was to pool the data on the sensitivity and specificity of third generation anti-HCV EIA tests after evaluating the quality of the studies using Standards for Reporting of Diagnostic Accuracy studies (STARD) checklist. We searched MEDLINE and PubMed databases using keywords about the accuracy of diagnostic tests for HCV infections. Methodological quality was assessed by two persons with a modified STARD checklist. A heterogeneity test was performed, and in case heterogeneity was present, a sub-group analysis was done. Fixed-effects model was used to obtain pool sensitivity and specificity with 95% confidence intervals (CI). A total of 41 studies from 16 papers were selected. The quality score ranged from 6 to 13 (median 10.5); Inter-observer agreement was 93.62% (k=0.69); and 41 studies revealed heterogeneity. We performed a sub-group analysis with only 28 studies from 13 papers that were evaluated to be of high quality. A subgroup using polymerase chain reaction as the reference test revealed homogeneity and was calculated the pooled sensitivity and specificity of 99.92% (CI 99.77-100.07%) and 99.66% (CI 99.45-99.86%) respectively. Studies on test kits with an increased reactivity to the core region also showed homogeneity in sensitivity and the pooled sensitivity was 99.78% (CI 99.53-100.03%). For the first time in Korea, the diagnostic accuracy of test kits was evaluated by meta-analysis using STARD checklist. The methodology shown in this study should help extending laboratory medicine to an evidence-based medicine.


Expression profile of PTPIP51 in mouse brain.
This study demonstrates the expression of the novel protein protein tyrosine phophatase-interacting protein 51 (PTPIP51) in mammalian brain tissue. Serial sections of the whole adult mouse brain were analyzed for PTPIP51 protein and mRNA by immunohistochemistry, immunoblotting, RT-PCR, and in situ hybridization. Recent investigations by Yu et al. (2008) describe PTPIP51 as being capable of activating Raf-1, thereby modulating the MAPK pathway. The role of Raf-1, as well as of 14-3-3, in neurological disorders is well established. PTPIP51 expression was confined to neurons in the following structures: the piriform cortex and their connections to the anterior commissure, nucleus accumbens, paraventricular and supraoptical nuclei, neurohypophysis, superior colliculus, genu of facialis nerve, spinal trigeminal tract, inferior cerebellar peduncle, and cerebellum. In the cerebellum, a subpopulation of Purkinje cells and their dendrites was strongly PTPIP51 positive. Moreover, PTPIP51 was found to be colocalized with vasopressin and its transport protein neurophysin II in the neuroendocrine nuclei and their connections to the neurohypophysis. The data presented here suggest a role of PTPIP51 in neuronal homeostasis, axonal growth, and transport.


Learning and memory deficits in rats induced by chronic thinner exposure are reversed by melatonin.
Thinner is a neurotoxic mixture which is widely used as an aromatic industrial solvent. This product has been shown to cause functional and structural changes in the central nervous system. We investigated the effect of exposure to high concentrations (3000 p.p.m.) of thinner for 45 days (1 hr/day) on cognitive functions and the levels of neural cell adhesion molecules (NCAM) and lipid peroxidation products (LPO) in the hippocampus, cortex and cerebellum of rats. The actions of melatonin on the effects produced by thinner exposure were also tested. Thinner exposure caused a significant increase in LPO (malondialdehyde and 4-hydroxyalkenals) in all brain regions. Melatonin administration significantly reduced LPO and elevated glutathione levels in the brain regions. NCAM (180 kDa) was significantly decreased in hippocampus and cortex of thinner-exposed rats. Furthermore, thinner-exposed rats showed cognitive deficits in passive avoidance and Morris water maze tasks, whereas in the rats chronically treated with melatonin these effects were reversed. This study indicates that treatment with melatonin prevents learning and memory deficits caused by thinner exposure possibly by reducing oxidative stress and regulating neural plasticity.


Pharmacokinetic properties of the synthetic cannabinoid JWH-018 and of its metabolites in serum after inhalation.
Each year, synthetic cannabinoids are occurring in high numbers in the illicit drug market, but data on their pharmacology and toxicology are scarcely available. Therefore, a pilot study was performed to assess adverse effects of JWH-018, which is one of the oldest and best known synthetic cannabinoids. Six subjects inhaled smoke from 2 and 3mg JWH-018. The drug and nine of its metabolites were analyzed in their blood samples taken during the following 12h by liquid chromatography-mass spectrometry (LC-MSMS). The maximum concentration of JWH-018 reached 2.9-9.9ng/ml after inhalation and markedly decreased during the next 1.5h, followed by a multiexponential decline (t1/2 in median 1.3h and 5.7h). The concentration of the pentanoic acid metabolite was slightly higher than that of the 3-, 4- and 5-hydroxypentyl metabolites and of the 6-hydroxyindol metabolite. The data also suggest a multiexponential decline and slow terminal elimination of JWH-018 and all metabolites. The detection of JWH-018 and of its metabolites in serum requires high analytical sensitivity. The pharmacokinetic properties of inhaled JWH-018 are similar to that of THC. A slow terminal elimination of drug and metabolites may lead to accumulation in chronic users.


Discrepancy, dissonance, and the "dissonant" smoker.
This paper reexamines, in the light of social psychological research, the theoretical assumptions made by McKennell and Thomas in their study of smoking habits and attitudes in Britain. One assumption made by them is that antismoking messages which are very discrepant from the opinions held by smokers should be avoided since they may produce attitude change in the opposite direction to that intended. It is argued that there is little empirical basis for this assumption, and that the discrepancy of a communication from the initial attitudes of a target audience is not necessarily the most important determinant of its effectiveness. McKennell and Thomas also distinguish "consonant" from "dissonant" smokers--the latter being those who say that they would like to give up smoking if they could do so easily. It is argued that the term "dissonant" is a misnomer when applied to smokers who see themselves as unable to choose not to smoke. Practical and theoretical implications are discuseed.


[Use of mirtilene forte and adrusen zinco for correction of oxidative lesions in mitochondria in rats OXYS with inherited hyperproduction of free radicals].
A long-term uptake of a diet supplemented with Mirtilene Forte (Vaccinum myrtillus extract) or Adrusen Zinco (a vitamin E complex with zinc, copper, selenium and omega-3 polyunsturated fatty acid) improved the functional state of liver mitochondria in OXYS rat strain. Adrusen Zinco sharply decreases the level of protein and lipid oxidation products. Possible mechanisms of the drug action are considered in relationship with their antioxidant properties.


Rhinitis and asthma in children: comorbitity or united airway disease?
The association of rhinitis with asthma symptoms in children is thought to be part of the united airway disease's theory which proposed three possible explanatory pathophysiological mechanisms: postnasal dripping, naso-bronchial reflex and systemic immune response. However, it is not clear if the relation is a co-morbid, precipitating or triggering condition or an epiphenomenon as an integrated part of the disease. In an attempt to evaluate the association, a review of all articles that were published in the last 10 years which referred to the relation of childhood rhinitis with asthma were analysed, whereas the recent knowledge on physiology and phenotype was reported as background. Even though both diseases share common etiology, epidemiology and immunology, there are important differences between the upper and lower airway system related both to inner organ cytology, immunity and heredity. Allergy seems to be the major causable factor for rhinitis and asthma association; however, ageenvironment interactions enhance the inspection that in preschoolers the diseases coexist, whereas in older children, they represent the manifestation of one united syndrome.


Disproportionate trends in ulnar collateral ligament reconstruction: projections through 2025 and a literature review.
Medial ulnar collateral ligament (UCL) injuries of the elbow that require surgical management are uncommon. There is growing evidence, however, suggesting that the incidence of UCL reconstruction (UCLR) procedures is rapidly increasing. We sought to quantify the incidence of age-related trends for UCLR from 2003 to 2014 and subsequently to project future trends through 2025. We hypothesized that as the total number of UCLRs performed increased, a disproportionate incidence among younger patients would be observed. New York State's Statewide Planning and Research Cooperative System database was queried from 2003 to 2014 to identify individuals between 10 and 40 years old undergoing UCLR. Poisson regression was used to develop future projections for UCLR and New York State population through 2025, and incidence estimates per 100,000 people were calculated. In New York State between 2003 and 2014, there were 890 patients who underwent UCLR, with average annual incidence per 100,000 people equaling 6.3 ± 2.8 for ages 15 to 19 years, significantly greater than for all other age groups (P < .001). Projections from 2015 through 2025 suggest that incidence in 15- to 19-year-olds and 20- to 24-year-olds will continue to rapidly increase while rates for other age groups will remain relatively stable. The number of UCLRs performed between 2003 and 2014 increased by 343%, and a disproportionate trend in average annual incidence for patients between 15 and 19 years old was observed. As our review of the literature questioned outcomes in adolescent athletes after UCLR, continued attempts at preventing these injuries in the young throwing athlete remain paramount.


[Effects of the health sector reform upon tuberculosis control interventions in Valle del Cauca, Colombia].
Implementation of the General System of Social Security in Health (GSSSH) was initiated for the control of tuberculosis (TBC) in the state of Valle del Cauca, Colombia, between 1991-2000. A study of its effects was centered in 7 municipalities of Valle del Cauca with a complementary set of qualitative and quantitative techniques for data collection and analysis. A reduction in planning, control and regulation of TBC activities by state agencies was observed. New administrative structures and new funding sources did not produce the expected positive effects on tuberculosis control. Instead, the quantity and quality of tuberculosis control activity were reduced as a consequence of the health sector reform. In conclusion, GSSSH implementation affected negatively tuberculosis control activity.


Development and application of test methods for the detection of dietary constituents which protect against heterocyclic aromatic amines.
This article describes the development and use of assay models in vitro (genotoxicity assay with genetically engineered cells and human hepatoma (HepG2) cells) and in vivo (genotoxicity and short-term carcinogenicity assays with rodents) for the identification of dietary constituents which protect against the genotoxic and carcinogenic effects of heterocyclic aromatic amines (HAs). The use of genetically engineered cells expressing enzymes responsible for the bioactivation of HAs enables the detection of dietary factors that inhibit the metabolic activation of HAs. Human derived hepatoma (HepG2) cells are sensitive towards HAs and express several enzymes [glutathione S-transferase (GST), N-acetyltransferase (NAT), sulfotransferase (SULT), UDP-glucuronosyltransferase (UDPGT), and cytochrome P450 isozymes] involved in the biotransformation of HAs. Hence these cells may reflect protective effects, which are due to inhibition of activating enzymes and/or induction of detoxifying enzymes. The SCGE assay with rodent cells has the advantage that HA-induced DNA damage can be monitored in a variety of organs which are targets for tumor induction by HAs. ACF and GST-P(+) foci constitute preneoplastic lesions that may develop into tumors. Therefore, agents that prevent the formation of these lesions may be anticarcinogens. The foci yield and the sensitivity of the system could be substantially increased by using a modified diet. The predictive value of the different in vitro and in vivo assays described here for the identification of HA-protective dietary substances relevant for humans is probably better than that of conventional in vitro test methods with enzyme homogenates. Nevertheless, the new test methods are not without shortcomings and these issues are critically discussed in the present article.


[Regeneration of the heart muscle after myocardial infarct].
Myocardial infarction is characterized by the loss of contractile cardiomyocytes. This results in an increased load on the spared myocardium. The aim of this article is to describe the response of the non-affected myocardium after infarction. Human hearts were investigated by microscopical, biochemical and cytophotometrical methods. The number of nuclei was calculated from the numerical ratio of connective tissue nuclei/myocyte nuclei, the values of the total DNA amount and the percentage proportion of the various ploidy classes in the myocyte nuclei. After myocardial infarction the DNA concentration as well as the DNA content was increased. Different DNA distribution pattern could be found in infarcted hearts. Percentage proportion of higher ploid nuclei and aneuploid nuclei was increased. Number of connective tissue nuclei was increased in infarcted hearts. And, in spite fibrosis of the necrotic area, number of myocyte nuclei did not change significantly. Beside scarring of the necrotic tissue, hypertrophy and hyperplasia of cardiomyocytes occur after myocardial infarction and may compensate the loss of contractile fibres to guarantee myocardial function.


The use of the lactone motif in chemical communication.
A wide variety of organisms communicate via the chemical channel using small molecules. A structural feature quite often found is the lactone motif. In the present paper, the current knowledge on such lactones will be described, concentrating on the structure, chemistry, function, biosynthesis and synthesis of these compounds. Lactone semiochemicals from insects, vertebrates and bacteria, which this article will focus on, are particularly well investigated. In addition, some ideas on the advantageous use of lactones as volatile signals, which promoted their evolutionary development, will be discussed.


Trends in Collection of Microbiological Cultures Across Veterans Affairs Community Living Centers in the United States Over 8 Years.
To describe and evaluate changes in the collection of microbiological cultures across Veterans Affairs (VA) Community Living Centers (CLCs) nationally. Descriptive study. 146 VA CLCs. We identified both positive and negative microbiological cultures collected during VA CLC admissions from January 2010 through December 2017. We measured the average annual percentage change (AAPC) in the rate of cultures collected per 1000 bed days and per admission, overall and stratified by culture type (ie, urine, blood, skin and soft tissue, and respiratory tract). AAPCs were also calculated for the proportion and rate of positive cultures collected, overall and stratified by culture type and organism (ie, Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Enterococcus spp, Pseudomonas aeruginosa, Klebsiella spp, Enterobacter spp, Morganella morganii, Citrobacter spp, Serratia marcescens, and Streptococcus pneumoniae). Joinpoint regression software was used to assess trends and estimate AAPCs and 95% confidence intervals (CIs). Over 8 years, 355,329 cultures were collected. The rate of cultures collected per 1000 bed days of care decreased significantly by 6.0% per year (95% CI -8.7%, -3.2%). The proportion of positive cultures decreased by 0.9% (95% CI -1.4%, -0.4%). The most common culture types were urine (48.4%), followed by blood (27.7%). The rate of cultures collected per 1000 bed days of care decreased per year by 6.3% for urine, 5.0% for blood, 4.4% for skin and soft tissue, and 4.9% for respiratory tract. In 2010, S aureus was the most common organism identified, and in all subsequent years E coli was the most common. We identified a significant reduction in the number of cultures collected over time among VA CLCs. Our findings may be explained by decreases in the collection of unnecessary cultures in VA CLCs nationally due to increased antibiotic stewardship efforts targeting unnecessary culturing and antibiotic treatment.


Evaluation of very rapid emit Qst methods for measuring serum procainamide and N-acetylprocainamide concentrations.
This study assessed the Emit Qst procainamide (PA) and N-acetylprocainamide (NAPA) assays. Accuracy and intraday precision were evaluated by repeatedly measuring PA and NAPA concentrations in spiked serum samples using Qst and high-performance liquid chromatography methods. Interday precision was evaluated by measuring concentrations in spiked samples over 4 weeks. Correlation between methods was assessed in patient samples, and proportional, constant, and random errors were estimated. Intraday coefficients of variation (CVs) were below 6.4% for PA and NAPA for both methods; interday CVs were below 7.8%. The proportional, constant, and random errors of the PA Qst assay in patient samples were 5.7%, -0.224 mg/L, and +/- 0.574 mg/L, respectively. The same errors in the NAPA Qst assay were 17.2%, 0.229 mg/L, and +/- 1.79 mg/L, respectively. The Qst assays are rapid, accurate, and precise methods for routine clinical measurement of PA and NAPA, although the proportional error in the NAPA assay should be recognized.


Phase 2 study evaluating intermittent and continuous linsitinib and weekly paclitaxel in patients with recurrent platinum resistant ovarian epithelial cancer.
Linsitinib, an oral, dual inhibitor of insulin-like growth factor-1 receptor and insulin receptor, in combination with weekly paclitaxel, may improve clinical outcomes compared with paclitaxel alone in patients with refractory or platinum-resistant ovarian cancer. This open-label phase 1/2 clinical trial (NCT00889382) randomized patients with refractory or platinum-resistant ovarian cancer (1:1:1) to receive either oral intermittent linsitinib (600mg once daily on Days 1-3 per week) combined with paclitaxel (80mg/m2 on Days 1, 8, and 15; Arm A) or continuous linsitinib (150mg twice daily) in combination with paclitaxel (Arm B), or paclitaxel alone (Arm C). Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety/tolerability. A total of 152 women were randomized to treatment (n=51 Arm A; n=51 Arm B, n=50 Arm C). In combination with paclitaxel, neither intermittent linsitinib (median PFS 2.8months; 95% confidence interval [CI]:2.5-4.4) nor continuous linsitinib (median PFS 4.2months; 95% CI:2.8-5.1) improved PFS over weekly paclitaxel alone (median PFS 5.6months; 95% CI:3.2-6.9). No improvement in ORR, DCR, or OS in either linsitinib dosing schedule was observed compared with paclitaxel alone. Adverse event (AE) rates, including all-grade and grade 3/4 treatment-related AEs, and treatment-related AEs leading to discontinuation, were higher among patients receiving intermittent linsitinib compared with the other treatment arms. Addition of intermittent or continuous linsitinib with paclitaxel did not improve outcomes in patients with platinum-resistant/refractory ovarian cancer compared with paclitaxel alone.


The use of human repetitive DNA to target selectable markers into only the human chromosome of a human-hamster hybrid cell line (AL)
We used the plasmid BLUR-8 that contains an 800-base pair (bp) sequence of human repetitive Alu DNA in a cotransfection protocol to target the plasmids pSV2neo or EBO-pcD-leu-2 (hygro) into a single site of the sole human chromosome, number 11, of a Chinese hamster-human hybrid cell line (AL). The neo and hygro plasmids confer resistance to the antibiotics G418 and hygromycin, respectively. Of the 33 cotransfected clones with single-site insertions, 1/13 without BLUR-8 and 6/20 with BLUR-8 were only in human chromosome 11. A frequency of insertion of 1/13 is not different than expected by chance (rho = 0.3512). On the other hand, the probability that 6/20 insertions, as seen with BLUR-8, occurred by chance is low (rho = 0.0003). We suggest that the human DNA sequences contained in BLUR-8 targeted insertions into only the human chromosome.


Rotavirus antibody assays on monkey sera: a comparison of enzyme immunoassay with neutralization and complement-fixation tests.
An enzyme immunoassay (EIA) for the detection of rotaviral antibodies was developed, using a purified, cell culture-grown SA 11 viral antigen and alkaline phosphatase as an enzyme label. This technique was evaluated by comparative testing with tube neutralization and complement-fixation assays on a collection of simian sera. There was close correlation between positive and negative results obtained by EIA and by neutralization. The EIA was as easy to perform as complement fixation testing, but showed greater sensitivity and fewer nonspecific reactions. Thus, EIA was shown to be a very suitable test for routine detection of rotaviral antibodies in serum. Results of neutralization tests suggested that the monkeys (mostly rhesus macaques) in the present study were infected with viruses varying in their antigenic relatedness to SA 11 virus and to a British isolate of calf rotavirus.


A Drosophila melanogaster homologue of the T-cell oncogene HOX11 localises to a cluster of homeobox genes.
The human homeobox gene HOX11 has been identified at the site of a chromosomal translocation in a subset of T-cell acute leukaemias. In the mouse genome, the hox11 family consists of at least three related genes, each of which possesses a highly conserved homeobox. To assist in elucidating the roles of this gene, a homologue was studied from Drosophila melanogaster. This gene, 311, shares similar identity to all three murine family members and contains the threonine residue in helix 3 of the homeodomain characteristic of the Hox11 family. It maps to a cluster of NK-homeobox genes which function in muscle development. Gene 311 exhibits a similar temporal pattern of expression to the NK genes in this cluster. Therefore, 311 may constitute part of a homeobox cluster in which the genes are both co-ordinately regulated and functionally related.


Is fluoride-induced hyperthyroidism a cause of psychosis among East African immigrants to Scandinavia?
East African immigrants to Scandinavia are admitted to mental hospitals far more frequently than native Scandinavians. Most of these patients are admitted for psychosis, commonly ascribed to problems adapting to the new culture. However, psychosis is also known to be associated with hyperthyroidism, and the high frequency of psychosis among East Africans in Scandinavia may at least in part be due to hyperthyroidism rather than cultural problems. Large areas in East Africa are notorious for high natural concentrations of fluoride in water and plants. Fluoride inhibits the production of thyroid hormones. To maintain normal thyroxin levels the body increases the capacity for thyroxin production. Goitre is caused by such a compensatory mechanism, and endemic goitre is widespread in many high-fluoride areas, even where dietary access to iodine is adequate. When people from such areas arrive in a low-fluoride area, their elevated capacity to produce thyroid hormones may lead to hyperthyroidism and subsequently to psychosis.


The integration of primary care and behavioral healthcare in northern California Kaiser-Permanente.
Integration of behavioral healthcare and primary care has a number of presumed benefits, including better communication between providers and systems, leading to improved patient care. There are studies showing medical cost offsets, although they tend to be in circumscribed research settings. Northern California Kaiser-Permanente has designed a new primary care system providing mental health clinicians on a primary care team. Those clinicians evaluate patients, create treatment plans, provide brief interventions, coordinate care with specialty behavioral healthcare, and consult with primary care physicians. Those physicians also have an increased role in the detection and treatment of behavioral health problems via guidelines developed with behavioral health. Structural changes within the overall system, including regional call centers and computerized clinical information systems, support the integration. Quality programs also support the ongoing improvement of the integration process. There are investment expenses in this type of re-design, but also expected cost savings. An infrastructure is now in place to measure both clinical outcomes, and cost effects of the new model.


Thrombin enhances release of tissue plasminogen activator from bovine corneal endothelial cells.
The effect of thrombin on release of plasminogen activators (PAs) was studied using cultivated endothelial cells of the bovine cornea. Species of PAs released into the conditioned medium were determined by fibrin autography and immunological analyses. Chromogenic peptide (S-2251) microassay was used for a quantitative estimation of the PA activity in conditioned medium and enzyme-linked immunosorbent assay (ELISA) for tissue plasminogen activator concentration. Fibrin autography revealed that cultured bovine corneal endothelial cells released into the conditioned medium tissue plasminogen activator (t-PA) and urokinase type plasminogen activator (u-PA). Addition of increasing concentrations (0.1 to 10.0 U/ml) of thrombin to the confluent cultures led to a dose-dependent increase in the rate of release of t-PA, while there was no significant increase in the release of u-PA. About a 2-fold increase in the t-PA concentration occurred when 10.0 U/ml thrombin was to the confluent cultures for 24 hr. Thrombin induced an increase in the release of t-PA, in a time-dependent manner. The addition of cycloheximide or actinomycin D to the thrombin-treated cultures resulted in a reduction of t-PA levels in the media. These findings indicate that the enhancing effect of thrombin is due to an increase in t-PA production, via protein synthesis. Thrombin inactivated with diisopropylfluorophosphate (DFP) did not induce an increase in t-PA levels. A 100-fold excess of DFP-treated thrombin did not inhibit the thrombin-induced increase. These findings indicate that binding ability and the effect of t-PA release depend on the enzymatically active site of thrombin.


Oral health status and related behaviours of U.S. nursing home residents, 1995.
The 1995 U.S. National Nursing Home Survey. A descriptive overview of reported oral health status and related behaviours for residents. Cross-sectional survey. 8,056 residents. Interviews by knowledgeable staff, examination of charts and/or personal knowledge. Information on the overall condition of oral health, edentulous status, presence/absence of dentures, difficulty chewing or biting, dental care received in past month, and method of payment for dental services in addition to personal characteristics and medical information. Fifteen percent of the residents were described as having excellent or very good oral health. Forty-one percent of the residents had difficulty chewing and biting. Almost one half of nursing home residents (47%) were totally edentulous. Twenty-six percent of residents had dental services paid for during the past month. Nursing home residents have multiple known barriers to oral health: ability to pay, extended periods of time without direct access to the dental care delivery system, and serious chronic medical conditions. There are serious deficiencies in achieving one of the US national health objectives: ensuring adequate oral health care for institutionalized individuals.


A Canadian survey of issues in cancer pain management.
We report the analysis of a cancer management survey mailed to a representative group of health professionals in 1994. The goals of the study were to gather information on cancer pain treatment practices, and to obtain health professional views on obstacles to ideal pain management. The survey, designed by a working party of pharmacists, nurses and physicians, was distributed to 14,628 physicians. A total of 2,686 physicians responded to the survey, including 39% of medical or radiation oncologists, and 18.19% of physicians who listed their primary interest as Family Medicine. Reflecting the modest emphasis placed on palliative care and cancer pain management in the current Canadian milieu, 67% of physicians rated their past teaching experience as only "fair" or "poor." Lack of exposure to pain education was reflected in the response to a series of hypothetical case scenarios exploring physician choices in managing severe cancer pain. For example, in the initial management of a cancer patient with severe pain, 50% of physicians would not use a strong opioid in the absence of other contraindications to opioid use. A wide variety of analgesics and non-pharmacologic techniques is available to Canadian physicians to assist patients with pain. Few physicians identified the unavailability of analgesics or analgesic techniques as limiting factors in pain management. We conclude that greater emphasis should be placed on pain education in our training programmes. We suggest that further surveys of this type, sponsored by our provincial colleges and medical organizations, can provide feedback which will enhance the adherence by Canadian physicians to published guidelines for pain management.


Toxicity and uptake of heavy metals by human spermatozoa.
The effects of metallic copper on human spermatozoa are described. Incubation with the metal caused a fall on the percentage of motile sperm, which was directly related to the surface area of copper employed and to the copper content of whole semen. These changes were accompanied by a decrease in semen zinc levels and an uptake of copper by individual sperm cells, as determined by X-ray microanalysis. Low concentrations of ionic copper caused a less marked fall in sperm motility, although the metal was generally more toxic than zinc or cadmium ions. All three metals were accumulated by spermatozoa on incubation, with cadmium causing a decrease in sperm nuclear zinc concentrations.


Shaggy (zeste-white 3) and the formation of supernumerary bristle precursors in the developing wing blade of Drosophila.
The development of supernumerary bristle precursors induced by the mutation shaggy (sgg; also known as zeste-white 3) was examined in the developing wing blade of imaginal and pupal Drosophila. sgg clones were induced by mitotic recombination; clones were marked using enhancer-trap flies which express beta-galactosidase ubiquitously in imaginal tissues, while bristle precursors were identified using sensillum and bristle-specific enhancer-trap lines. It was shown that the precursors of supernumerary sgg bristles in the wing blade mimicked the development of morphologically similar margin bristles, developing in a manner similar to that of anterior sensory bristles in anterior clones and posterior noninnervated bristles in posterior clones. Interestingly, supernumerary anterior sensory bristles appeared outside the normal regions of "proneural" gene activity as identified using anti-achaete. Moreover, sgg could induce the ectopic expression of achaete in anterior clones. Thus, in the anterior wing blade the sgg mutation leads to the formation of ectopic proneural regions.


On the importance of retaining stresses and strains in repositioning computational biomechanical models of the cervical spine.
Human body models are created in a specific posture and often repositioned and analyzed without retaining stresses that result from repositioning. For example, repositioning a human neck model within the physiological range of motion to a head-turned posture prior to an impact results in initial stresses within the tissues distracted from their neutral position. The aim of this study was to investigate the effect of repositioning on the subsequent kinetics, kinematics, and failure modes, of a lower cervical spine motion segment, to support future research at the full neck level. Repositioning was investigated for 3 modes (tension, flexion, and extension) and 3 load cases. The model was repositioned and loaded to failure in one continuous load history (case 1), or repositioned then restarted with retained stresses and loaded to failure (case 2). In case 3, the model was repositioned and then restarted in a stress-free state, representing current repositioning methods. Not retaining the repositioning stresses and strains resulted in different kinetics, kinematics, or failure modes, depending on the mode of loading. For the motion segment model, the differences were associated with the intervertebral disc fiber reorientation and load distribution, because the disc underwent the largest deformation during repositioning. This study demonstrated that repositioning led to altered response and tissue failure, which is critical for computational models intended to predict injury at the tissue level. It is recommended that stresses and strains be included and retained for subsequent analysis when repositioning a human computational neck model.


2-Hydroxy-5-nitrobenzyl bromide as a specific reagent for tryptophan residues in membrane proteins: bacteriorhodopsin as an example.
The use of 2-hydroxy-5-nitrobenzyl bromide for the modification of tryptophan residues in integral membrane proteins is exemplified by its application to bacteriorhodopsin from Halobacterium halobium. Complete elimination of the unreacted reagent requires delipidation of the sample with detergents and posterior chromatography. This method also allows separation of the modified from the unmodified bacteriorhodopsin molecules. Modified molecules have lost the retinal, and are thus bleached, whereas the unmodified molecules appear to retain all the characteristics of solubilized native bacteriorhodopsin.


Associations between airway hyperresponsiveness, obesity and lipoproteins in a longitudinal cohort.
Epidemiological data have linked obesity with an increased risk of asthma, but the mechanisms responsible for this relationship remain unknown. One possible mechanism, which has received little attention, could be the effect of cholesterol metabolism on airway smooth muscle function. The present study investigated the association between airway hyperresponsiveness (AHR) to methacholine and body mass index (BMI) and plasma lipoproteins [low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol]. Associations between AHR, BMI and plasma lipoproteins were assessed in a population-based cohort at ages 14 and 20 years. In unadjusted analyses, higher LDL cholesterol levels at age 14 were associated with AHR at age 20 in both sexes (P < 0.05). HDL, LDL/HDL ratio and total cholesterol were not associated with AHR. In multiple regression analyses adjusted for sex, lung function, smoking and asthma, only higher levels of BMI at age 14 or 20 years were significantly associated with increased AHR at age 20 years, while neither LDL, HDL and LDL/HDL ratio nor total cholesterol were significantly associated with AHR. We confirmed that in teenagers there is a strong association between BMI and AHR to methacholine. This association seems to be independent of the plasma lipoprotein levels at that age.


Isolation of BVDV from bovine serum by EMEA/CVMP and 9 CFR: a comparison.
Data derived from both experience and validation exercises on the behaviour and properties of BVDV is presented as applied to recovery of the virus from bovine serum used in the industrial production of animal biologicals. Licensed products both in the EU and the U.S. must use ingredients shown to be free of this agent and both regulatory agencies have published regulations governing this topic (EU: EMEA/CVMP and US: 9 CFR). The two systems differ in some specifics covering cell cultures used, timing of testing within the assays and the use of multiple approaches to the isolation of this virus. It was found that selected cell lines instead of primary cells could be used for BVDV isolation. FA tests, however, needed to be performed weekly for maximum sensitivity instead of once at the end of the test. BVDV interference assay (comparative titration) was found to be an unreliable test for the detection of non-CPE BVDV in cell culture. BVDV neutralization assays, while desirable from an informational standpoint, were determined to be unnecessary in serum that was to be adequately irradiated. Ultracentrifuge concentration of BVDV from serum was found to be a satisfactory method of increasing the sensitivity of assays for this agent, although quantification of the virus was found unnecessary in serum to be irradiated. Recommendations for the harmonization of 9 CFR and EMEA/CVMP into one assay are given.


Epithelial Nuclear Factor-x03BA;B Activation in Inflammatory Bowel Diseases and Colitis-Associated Carcinogenesis.
Prolonged inflammatory bowel diseases (IBD) may lead to colitis-associated carcinogenesis (CAC). Previous studies had shown that nuclear factor-x03BA;B (NF-x03BA;B) activation in both macrophages and epithelia in inflamed colonic tissue is associated with CAC development. However, the mechanism by which epithelial NF-x03BA;B activation leading to CAC development had not previously been rigorously studied. We and others had observed the increased expression of the type 2 receptor for tumor necrosis factor (TNFR2/TNFRSF1b/p75) in IBD models. Myosin light chain kinase (MLCK) is suggested to be associated with epithelial permeability via TNF signaling. Therefore, the relationship between epithelial MLCK expression and NF-x03BA;B activation via TNFR2 signaling on CAC development was investigated. Pro-tumorigenic cytokines such as interleukin (IL)-1β, IL-6 and macrophage inflammatory protein-2 at the lamina propria were increased in the setting of colitis and further increased in tumor tissues with upregulated epithelial TNFR2 and MLCK expressions in an animal model of CAC. The upregulated MLCK expression was also observed in TNF-stimulated colonic epithelial cells in vitro in association with the upregulation of TNFR2 but not TNFR1/TNFRSF1a/p55. Gene silencing of tnfrsf1b, but not tnfrsf1a, resulted in restoration of epithelial tight junction (TJ) associated with decreased MLCK expression. The presence of anti-TNF antibody also resulted in restoration of TJ in association with suppressed MLCK expression, and interestingly, similar results including the suppressed TNFR2 and MLCK expressions were observed by inhibiting MLCK in the epithelial cells. MLCK silencing also led to suppressed TNFR2 expression, suggesting that the restored TJ leads to reduced TNFR2 signaling. Such suppression of MLCK as well as blockade of TNFR2 signaling resulted in reduced CAC development, restored TJ, and decreased pro-tumorigenic cytokines. These imply that TNF-induced NF-x03BA;B activation and MLCK expression may be a potential target for the prevention of IBD-associated carcinogenesis.


Physiological and cognitive responses to cold exposure in 11-12-year-old boys.
This study investigated the effects of cold and exercise in the cold on the physiological and cognitive responses of 11-12-year-old boys. Children were dressed in sweat suits and exposed to cold (CD, 7°C), cool (CL, 13°C), and neutral (N, 22°C) environments for 110 minutes, with 10 minutes of light exercise (1 watt · kg body wt-1 ) midway through the exposure. A 30-minute "recovery" in neutral conditions followed each session. Session order was randomized. Rectal temperature (Tre) decreased significantly more in CD compared to CL and N, and continued to decrease during the recovery period. Chest skin temperature (Tch) was significantly different between conditions and remained stable even in CD, despite the decrease in Tre. Tch returned to prechamber values during the recovery period. Hand temperature (Th) decreased during CL and CL, and remained significantly lower than prechamber values following the recovery. Exercise heart rate was lower in the CD and CL(115 ± 13 and 119 ± 20 beats · min-1 ) compared to N (130 ± 17 beats · min-1 ). No differences were observed in oxygen consumption between sessions. No differences were also observed between sessions in cognitive performance on language and math tests. It was concluded that while the study conditions did not appear to affect cognitive capacity in boys, they proved sufficient to disturb core temperature. This disturbance was not corrected 30 minutes following cold exposure. Am. J. Hum. Biol. 9:39-49 © 1997 Wiley-Liss, Inc.


Water-gas shift on gold catalysts: catalyst systems and fundamental studies.
Since the pioneering finding by Haruta et al. that small gold nanoparticles on reducible supports can be highly active for low-temperature CO oxidation, the synthesis, characterization, and application of supported gold catalysts have attracted much attention. The water-gas shift reaction (WGSR: CO + H2O = CO2 + H2) is important for removing CO and upgrading the purity of H2 for fuel cell applications, ammonia synthesis, and selective hydrogenation processes. In recent years, much attention has been paid to exploration the possibility of using supported gold nanocatalysts for WGSR and understanding the fundamental aspects related to catalyst deactivation mechanisms, nature of active sites, and reaction mechanisms. Here we summarize recent advances in the development of supported gold catalysts for this reaction and fundamental insights that can be gained, and furnish our assessment on the status of research progress.


The (interconnected) reasons elder Americans file consumer bankruptcy.
Since the early 1990s, the age distribution of the bankruptcy population has shifted. Specifically, the age distribution curve has flattened, due in large part to an increase in the number of elder Americans (65 and older) who are filing bankruptcy. To date, the reasons for elder bankruptcies have not been studied. Quantitative and qualitative data from 381 elder bankruptcy respondents who participated in the 2007 Consumer Bankruptcy Project suggest that overwhelming interest and fees on credit cards, illnesses and injuries, income problems, aggressive debt collectors, and housing problems are the leading reasons that elder debtors file bankruptcy. Further, the vast majority of elder bankruptcies result not from a single cause, but rather from multiple interconnected causes.


Ehrlichia ruminantium grows in cell lines from four ixodid tick genera.
Continuous cell lines from the ticks Amblyomma variegatum, Boophilus decoloratus, Boophilus microplus, Hyalomma anatolicum anatolicum, Ixodes scapularis, Ixodes ricinus and Rhipicephalus appendiculatus were tested for ability to support growth of the rickettsial pathogen Ehrlichia (previously Cowdria) ruminantium. Five E.ruminantium isolates, from West Africa, South Africa and the French West Indies, were used. Twelve tick cell lines were inoculated with E.ruminantium derived either from cultures of a bovine endothelial cell strain designated BPC or from other tick cell lines. Successful infection resulted in either continuous growth (in which the pathogen/cell line system could be perpetuated through regular subculture on fresh, uninfected cells for many months or years) or finite growth (in which the pathogen disappeared after one or a few subcultures). Infection with E.ruminantium from BPC was established in I.scapularis, I.ricinus and A.variegatum cell lines; E.ruminantium was transferred from these infected cell lines to B.decoloratus, B.microplus and R. appendiculatus cell lines. H.a.anatolicum cells could not be infected with E.ruminantium by any procedure. All five E.ruminantium isolates grew continuously in at least one tick cell line at temperatures between 28 degrees C and 37 degrees C; three of the isolates were successfully re-established in BPC following prolonged maintenance in tick cells. This study demonstrates that E.ruminantium is not intrinsically restricted to growth in cells from ticks of the natural vector genus Amblyomma.


[Semi-synthesis and proposed structure of platelet-activating factor (P.A.F.): PAF-acether an alkyl ether analog of lysophosphatidylcholine].
We have studied the molecular structure of platelet-activating factor" (P.A.F.), a mediator of inflammation obtained from blood leukocytes, macrophages, and platelets themselves. We have semi-synthetized a substance that possesses all the known physicochemical and biological characteristics of P.A.F. from hog leukocytes. This was performed by successive methylation, hydrogenation, and acetylation of lysophosphatidylethanolamine plasmalogen. We therefore propose the following structure for P.A.F.: 1-0-alkyl-2-acetyl-glyceryl-3-phosphorylcholine. This molecular structure is not yet described among the numerous substances capable of inducing platelet aggregation and release.


The combination of 5-fluorouracil, leukovorin, etoposide, and cisplatin (FLEP) in patients with metastatic esophageal cancer. A single-institution experience.
A retrospective analysis was carried out on the efficacy and toxicity of the combination of 5-fluorouracil, leucovorin, etoposide and cisplatin (FLEP) in patients with metastatic esophageal cancer treated at our institution. Patients received intravenous 5-fluorouracil 500 mg/m2, leucovorin 300 mg/m2, etoposide 100 mg/m2 and cisplatin 30 mg/m2, on days 1 to 3. Courses were repeated every 4 weeks until progression or up to a maximum of 6 courses. Patients were evaluated for response after every three courses using computed tomography. Eighteen patients received a total of 76 courses (median 4, range 1-6). The median time to progression was 9.2 months and the overall response rate was 22% (one complete response i.e. 5%, and three partial responses i.e. 17%). Seven patients (39%) had stable disease, while another 7 progressed during therapy. The median survival for all patients was 10.2 months. The most common hematological toxicities were leukocytopenia and neutropenia grade 3, which occurred in two patients (11%) each, while grade 3 and 4 infection was seen in one patient each (5%). Anemia grade 3 occurred in 2 patients (11%). Nonhematological toxicities consisted of nausea/vomiting grade 3 in 3 (17%), diarrhea grade 3 in one (5%) and mucositis grade 3 in 3 patients (17%). We conclude that the FLEP combination is a safe and active regimen for patients with metastatic esophageal cancer.


Analysis and prevention of cerebral infarction in patients with traumatic brain injury.
We reviewed the clinical data of 32 cases of cerebral infarction after traumatic brain injury, aiming to explore the pathogenesis and assess the prognosis of the condition so as to find effective prevention and treatment measures. According to Glasgow Outcome Scale (GOS) scores, 12 patients were classified as having good recovery, 5 moderate neurological deficit, 4 severe neurological deficit, and 3 in vegetative state. Death occurred in 8 cases. These results indicate the mortality and morbidity of this condition are relatively high, and early diagnosis and treatment may improve prognosis, which should await further investigation.


Heat/burning sensation induced by topical application of capsaicin on perineal cutaneous area: new approach in diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome?
To investigate the feasibility, safety, and efficacy of perineal cutaneous application of capsaicin as a test for the diagnosis, as well as a potential therapeutic tool, in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We recruited 22 patients (mean age 34.5 years, range 19 to 56), who had been diagnosed with CP/CPPS according to the National Institutes of Health criteria, and 6 healthy control subjects. Both groups received a topical application of 5 mL capsaicin at a concentration of 10(-5) M to the perineal body skin. The patients were asked to mark on a visual analogue scale the intensity of any heat or burning sensation. All the patients had completed a National Institutes of Health Chronic Prostatitis Symptom Index before and 1 week after the test. The scores of the two groups were compared using the Mann-Whitney U test. The patients with CP/CPPS reported a heat/burning sensation intensity that was statistically greater than that of the healthy controls (7.5 versus 4.3, P <0.001) and a shorter time to heat sensation onset and maximal intensity (1.5 versus 3.4 minutes, P <0.001, and 2.5 versus 7 minutes, P <0.001, respectively). Of the 22 patients, 16 reported an improvement of symptoms after 7 days and the mean National Institutes of Health Chronic Prostatitis Symptom Index score decreased from 27 to 16 (P <0.01). We found a statistically significant difference in the pain visual analogue scale and interval between topical application and the onset of the heat/burning sensation between patients with CP/CPPS and healthy controls. The small sample size strongly suggests the need for additional larger and more controlled studies.


Determination of the bactericidal activity of different calcium hydroxide presentations on a dentin model.
Calcium hydroxide placed as a temporary dressing in the root canal helps sterilize infected canals. Hycal and Roeko calcium hydroxide points are two delayed-action medications containing Ca(OH)2 recommended for root canal treatment. The purpose of this study was to test their bactericidal activity in comparison with that of C-PMCP on Streptococcus sanguins strain NCTC 7823. Artificially infected 4-mm high blocks of dentin obtained from bovine incisors were used as an experimental model (n = 192). After three days of treatment with the two antiseptics, intracanal dentin powder was collected by serial drillings and used to inoculate a culture broth. The turbidity of this broth after 24 hours showed if the bacteria were eliminated or not and was used as criterion of antiseptic efficacy. No bacterial growth was observed in the samples treated with C-PMCP. Hycal had a considerable bactericidal activity with 94% of negative cultures whereas first-generation Roeko points had no activity on the strain of S. sanguis tested.


Novel methods for the quantification of changes in actin organization in chondrocytes using fluorescent imaging and linear profiling.
We present three novel reproducible methodologies for the quantification of changes in actin organization from microscope images. Striation and integrative analysis were devised for the investigation of trans-cellular filaments and F-actin localization, respectively, in response to physiological or mechanical actin-modulatory conditions. Additionally, the Parker-Qusous (PQ) formula was developed as a measure of total quantity of F-actin, independent of cell volume changes, whereby fluorescence intensity was divided by the cube root of cell volume, squared. Values obtained were quantified in Mauricean Units (Mu; pixel/μm(3)). Upon isolation, there was a 49% decrease in total F-actin fluorescence from 1.91 ± 0.16 pixel/μm(3) (Mu) to 0.95 ± 0.55 Mu, whereas upon culture, an apparent increase in total fluorescence was deemed insignificant due to an increase in average cell volume, with a rise, however, in striation units (StU) from 1 ± 1 to 5 ± 1 StU/cell, and a decrease in percentage cortical fluorescence to 30.45% ± 1.52% (P = 7.8 × 10(-5)). Freshly isolated chondrocytes exhibited a decrease in total F-actin fluorescence to 0.61 ± 0.05 Mu and 0.32 ± 0.02 Mu, 10 min posthypertonic and hypotonic challenges, respectively. Regulatory volume decrease was inhibited in the presence of REV5901 with maintenance of actin levels at 1.15 Mu. Following mechanical impact in situ, there was a reduction in total F-actin fluorescence to 0.95 ± 0.08 Mu and 0.74 ± 0.06 Mu under isotonic and hypotonic conditions, respectively, but not under hypertonic conditions. We report simple methodologies for quantification of changes in actin organization, which will further our understanding of the role of actin in various cellular stress responses. These techniques can be applied to better quantify changes in localization of various proteins using fluorescent labeling.


Relationships between the onset of pustulosis palmaris et plantaris, periodontitis and bacterial heat shock proteins.
Relationships between the onset of pustulosis palmaris et plantaris, periodontitis and heat shock proteins were studied by using enzyme-linked immunosorbent assay to examine levels of immunoglobulin G (IgG) against Escherichia coli GroEL, a recombinant DnaJ of Actinobacillus actinomycetemcomitans heat shock protein, a synthetic peptide made from the 180th to the 188th amino acids of Mycobacterium bovis BCG Hsp65, and a recombinant human Hsp60, in sera obtained from 43 pustulosis palmaris et plantaris patients judged to have chronic infectious diseases of the oral cavity. We found that the titers of IgG against E. coli GroEL and A. actinomycetemcomitans DnaJ in the sera from pustulosis palmaris et plantaris patients were significantly higher than those in the control group, whereas the titers of IgG against the synthetic M. bovis Hsp65 and the recombinant Hsp60 did not differ significantly. Periodontal therapy and extraction of teeth with periapical infectious resulted in remission of pustulosis palmaris et plantaris and a statistically significant reduction in the levels of IgG against E. coli GroEL in 9 of the 22 patients (41%) examined. We also found that the IgG levels against A. actinomycetemcomitans DnaJ in 6 serum samples of 16 (37%) were reduced, but not significantly, after the treatment. These results suggest that the IgG responses to heat shock proteins partially induced by oral bacteria may be related to the onset of pustulosis palmaris et plantaris in some patients.


Isolation of Blastomyces dermatitidis from soil.
Through the intravenous inoculation of soil suspensions in the tail vein of mice, Blastomyces dermatitidis was recovered from a Lexington, Kentucky, soil sample. The positive specimen was collected in a tobacco-stripping barn. The shed had sheltered a dog that died of blastomycosis 2 years before the sample was collected.


[Craniopharyngiomas in children and adolescents].
In sixtheen children and adolescents primary operation of craniopharyngioma over the period from January 1987 to February 1992 was carried out. The age of these patients ranged from nine months to eighteen years. There were nine females and seven males. Microsurgical operation was performed in fifteen cases, and stereotaxic biopsy with intracystic instillation of Y90 in one patient. Within the first month after the operation three patients died (18.8%). The total mortality was 31.2%. In nine out of thirteen patients tumour recurrence occured (69%). No tumour recurrence was noted in four patients: one after radical surgery, two after subtotal resection of craniopharyngioma, and a boy with stereotaxic biopsy and instillation of Y90. Second operation for tumour recurrence was carried out in three patients. Two children were lost from evidence, and four were subjected to radiotherapy. The authors analyse operation proceedings and results of treatment. They work out criteria for the optimal treatment, pointing out the neuroradiological, anatomosurgical and histopathological characteristics of these tumours.


[Correlation of the stress reaction and temperament in children with bronchial asthma].
To study the correlation between the temperament dimension and the stress reaction in children with bronchial asthma. Between February 2008 and May 2010, two hundred and twenty children with bronchial asthma and aged from 3-7 years were enrolled (asthma group). Eighty children without asthma, respiratory tract infections, serious body diseases and mental disorders who were age- and gender-matched to the asthma group served as the control group. The Carry temperament rating scales were filled by the children's parents from the asthma and control groups. The serum levels of cortisol at 8am and 4pm and nerve growth factor (NGF) were measured by immunochemiluminescent assays. The scores of the rhythmicity and persistence in temperament dimensions in the asthma group were significantly lower than those in the control group; in contrast, the scores of phobotaxis, response intensity, emotion entity, adaptability and attention dispersion in the asthma group were significantly higher than those in the control group (P<0.05). The levels of serum cortisol at 8am and 4pm were lower, while the serum level of NGF was higher in the asthma group than those in the control group (P<0.05). The scores of response intensity, emotion entity and adaptability in temperament dimensions were positively correlated with serum NGF level (r=0.348,0.468,0.195, respectively; P<0.05), and inversely correlated with serum cortisol level at 8 am (r=-0.297, -0.462, -0.152, respectively; P<0.05) in the asthma group. The temperament dimension is associated with the stress reaction in children with bronchial asthma. This provides a basis for the treatment of bronchial asthma by neuropsychological adjustment.


Accuracy of tRNA charging and codon: anticodon recognition; relative importance for cellular stability.
Cellular homeostasis and the mechanisms which control homeostasis are important for understanding such fundamental processes as ageing and the origin of life. Several models have studied the importance of accurate protein synthesis for cellular stability, but these models have not considered the complexities of the translation process in any detail. Here we develop a new model which describes the interplay between aminoacyl-tRNA (aatRNA) synthetases, the cellular pool of charged tRNAs and the process of codon: anticodon recognition. We also take the processive character of the ribosomes into account. In common with previous work, our model predicts that the cellular translation apparatus can either be stable or deteriorate progressively with time. However, because our model explicitly describes different subreactions of the overall translation process, we are also able to assess the relative importance of accurate tRNA charging and codon: anticodon recognition for cellular stability. It appears that the tRNA charging by the aatRNA synthetases plays the key role in controlling the long-term stability of the cell. Ribosomal errors are less important because error-prone ribosomes, being processive, produce mainly inactive proteins which do not contribute to error propagation within the translation machinery.


Quantitation of early myocardial ischemia using acridine orange fluorescence--an experimental study.
It has been observed in the present investigation that ischemic myocardium consistently produces bright green fluorescence after Acridine Orange (AO) staining. The area of ischemia in the left ventricular myocardium at different time intervals after onset of experimental ischemia has been calculated by use of this AO fluorescence technique. Zonal distribution of ischemia in the epicardial, middle, and endocardial zones has also been evaluated quantitatively from ten minutes to six hours after ligation of the anterior descending branch of the left coronary artery in the Wistar strain of albino rats. No similar study was available for comparison from the literature reviewed. The total area of left ventricular ischemia showed an increase with the prolongation of duration of coronary ligation from 13.39 +/- 2.69 mm2 at ten to twenty-five minutes to 32.99 +/- 5.69 mm2 at six hours after ligation. Statistical analysis of the zonal area of ischemia has shown that ischemia in the middle and endocardial zones was greater than that in the epicardial zone at all time intervals recorded. Middle zone ischemia extended over a larger area than that over the endocardial zone at all intervals except at intervals II (30-45 min), IV (2-2 1/2 hrs) and V (3-4 hrs). The results of this experimental investigation are significant for these point to the value of Acridine Orange fluorescence in detecting early myocardial ischemia and in demarcating zonal differences in ischemia. The authors have successfully utilized the method in a few human cases of clinically suspected myocardial infarction and recommend the technique for routine use to detect early human myocardial ischemia.


Changes of serum complement and eosinophil count in antigen induced bronchospasm.
By using house dust antigens, in addition to the relation between specific IgE antibody, precipitin antibody and bronchial provocation test (BPT), the changes of serum complement activities and eosinophil counts after BPT were studied. Decreased serum concentrations of C4 and Factor B were found in three of 15 skin-test positive asthmatic children, thus confirming the involvement of complement in the pathogenesis of immediate type BPT reaction. Eosinophil counts tended to increase after BPT but the increase did not correlate with the occurence of the immediate type BPT reaction.


In vitro antimicrobial activities of 1-methoxyficifolinol, licorisoflavan A, and 6,8-diprenylgenistein against Streptococcus mutans.
The objective of the study was to investigate the antimicrobial effects of purified single compounds from ethanol-extracted licorice root on Streptococcus mutans. The crude licorice root extract (CLE) was obtained from Glycyrrhiza uralensis, which was subjected to column chromatography to separate compounds. Purified compounds were identified by mass spectrometry and nuclear magnetic resonance. Antimicrobial activities of purified compounds from CLE were evaluated by determining the minimum inhibitory concentration and by performing time-kill kinetics. The inhibitory effects of the compounds on biofilm development were evaluated using crystal violet assay and confocal microscopy. Cell toxicity of substances to normal human gingival fibroblast (NHGF) cells was tested using a methyl thiazolyl tetrazolium assay. Chlorhexidine digluconate (CHX) was used in the control group. Three antimicrobial flavonoids, 1-methoxyficifolinol, licorisoflavan A, and 6,8-diprenylgenistein, were isolated from the CLE. We found that the three flavonoids and CHX had bactericidal effects on S. mutans UA159 at the concentration of ≥4 and ≥1 µg/ml, respectively. The purified compounds completely inhibited biofilm development of S. mutans UA159 at concentrations over 4 μg/ml, which was equivalent to 2 μg/ml of CHX. Confocal analysis showed that biofilms were sparsely scattered in the presence of over 4 μg/ml of the purified compounds. However, the three compounds purified from CLE showed less cytotoxic effects on NHGF cells than CHX at these biofilm-inhibitory concentrations. Our results suggest that purified flavonoids from CLE can be useful in developing oral hygiene products, such as gargling solutions and dentifrices for preventing dental caries.


Treatment of electrostatic interactions in simulations of the interface between transition metal surfaces and organic matter: the discrete classical model and the reaction-field dielectric method.
A more efficient molecular dynamics model is devised to study the interface between platinum(111) and liquid isopropanol. The faster reaction-field dielectric method (RFD) is investigated as the alternative to the very accurate discrete classical model (DCM) (M. W. Finnis, Surf. Sci., 1991, 241, 61) to account for the electrostatic interactions at the interface. Differences in static and dynamic properties of the interface are examined. The mass-density and number-density distributions showed only a little sensitivity towards the choice of the method. The orientational structure revealed notable but still small quantitative changes for highly-polarized parts of the isopropanol molecules if the RFD is used instead of the DCM. The general qualitative picture is still preserved. The simulations of the platinum(111)/isopropanol interface with the DCM or the Ewald summation were carried out for longer times than in our previous contribution (K. B. Tarmyshov and F. Müller-Plathe, J. Chem. Phys., 2007, 126, 74702). The analysis disclosed that the influence of chemical or electrostatic interactions at the interface on the relative orientation of the neighbouring hydroxyl groups, which are adsorbed on the surface, is notably smaller than reported before. Overall, the reaction-field dielectric method can be used to study the properties of the interface between transition metals and organic matter, if there appears a chemical bond of 10 kT or higher between the surface and adsorbate molecules or their parts.