Cellient™ automated cell block versus traditional cell block preparation: a comparison of morphologic features and immunohistochemical staining.
Traditional cell block (TCB) sections serve as an important diagnostic adjunct to cytologic smears but are also used today as a reliable preparation for immunohistochemical (IHC) studies. There are many ways to prepare a cell block and the methods continue to be revised. In this study, we compare the TCB with the Cellient™ automated cell block system. Thirty-five cell blocks were obtained from 16 benign and 19 malignant nongynecologic cytology specimens at a large university teaching hospital and prepared according to TCB and Cellient protocols. Cell block sections from both methods were compared for possible differences in various morphologic features and immunohistochemical staining patterns. In the 16 benign cases, no significant morphologic differences were found between the TCB and Cellient cell block sections. For the 19 malignant cases, some noticeable differences in the nuclear chromatin and cellularity were identified, although statistical significance was not attained. Immunohistochemical or special stains were performed on 89% of the malignant cases (17/19). Inadequate cellularity precluded full evaluation in 23% of Cellient cell block IHC preparations (4/17). Of the malignant cases with adequate cellularity (13/17), the immunohistochemical staining patterns from the different methods were identical in 53% of cases. The traditional and Cellient cell block sections showed similar morphologic and immunohistochemical staining patterns. The only significant difference between the two methods concerned the lower overall cell block cellularity identified during immunohistochemical staining in the Cellient cell block sections.


Osteoporosis in transplant recipients: recommendations for avoidance and therapy.
Osteoporosis is a frequent and severe complication of transplantation that substantially reduces the recipient's quality of life. However, strategies to prevent or to treat osteoporosis have as yet not been established. Determination of bone mass and density is the basis for interventions following transplantation. Therefore, bone mineral density should be measured in all patients awaiting transplantation to assess their individual risk of fracture. Prophylaxis should be considered in patients at high risk in view of the rapid initial bone loss after transplantation. Treatment of acute rejection with corticosteroids induces more bone loss than maintenance therapy with corticosteroids. Once manifest osteoporosis has occurred, treatment with a triple therapy consisting of calcium, vitamin D and either calcitonin or bisphosphonates is possible without negative effects on graft function. Therapy should be initiated according to the general guidelines for osteoporosis therapy, but several aspects specific for this patient group have to be considered. The present recommendations for the management of osteoporosis after transplantation need to be proven by further intervention studies.


Effects of grassland restoration programs on ecosystems in arid and semiarid China.
We explored the ecological effects of grassland restoration programs using satellite imagery and field plots sampling data and analyzing the patterns and mechanisms of land cover change and vegetation activities in arid and semiarid China during the period from 1982 to 2008. The grassland cover in the 1980s, 2000 and 2005 was compared before and after the restoration programs. The variability of net primary production (NPP) and rain use efficiency (RUE) were analyzed as indicators of vegetation productivity. Our study showed that changes in grassland cover were closely related to the relative area of farmland, with increases in grassland being caused by returning farmland to grassland and decreases being caused by reclamation for agriculture. The results of NPP and RUE measurements over the past 30 years showed systematic increases in the area of grassland in most regions, especially from 2000 to 2008. This fact was reflected by intensified vegetation activity and cannot be completely explained by the warmer and wetter climate, which suggested a contribution from restored, ungrazed grasslands. Our analysis indicates that both vegetation activity and grassland cover increased in regions in which grassland and rangeland restoration programs were implemented.


Improvement of preservation with cardioplegia induced by heat stress is mediated by calcitonin gene-related peptide.
Previous studies have shown improvement of preservation with cardioplegia by calcitonin gene-related peptide (CGRP)-induced preconditioning. Therefore we examined the hypothesis that endogenous CGRP may be involved in the protection of heat stress against myocardial damages after prolonged cardioplegic arrest in isolated rat heart. Reperfusion after 4 h of hypothermic ischemia caused a decline of cardiac function and an increase of creatine kinase (CK) release. Heat stress induced by pretreatment with whole body hyperthermia (rectal 42 degrees C) for 15 min produced a significant increase in the plasma content of CGRP, an improvement of cardiac function and a decrease in the release of CK. However, after pretreatment with capsaicin (50 mg/kg, s.c.) to deplete CGRP in cardiac sensory nerves, the plasma concentration of CGRP was no longer increased and the cardioprotection afforded by heat stress was abolished. These findings suggest that improvement of preservation with cardioplegia by heat stress may be mediated by endogenous CGRP in the rat.


[Losartan versus enalapril in the reduction of left ventricular hypertrophy secondary to systemic arterial hypertension].
To compare losartan and enalapril on reduction of left ventricular hypertrophy. Longitudinal, prospective, comparative, controlled study, of patients with moderate systemic arterial hypertension and echocardiographically proven left ventricular hypertrophy, randomized for treatment during six months with losartan 100 mg daily or enalapril 20 mg daily. The reduction of left ventricular mass index, was evaluated by echocardiogram basal and to six months. Student's t, Spearman and Pearson correlation coefficients. 85 patients finished the study (43 in the losartan group and 42 in the enalapril group). After six months of treatment, the blood pressure values and the left ventricular mass index decreased in losartan and enalapril (p = .0000001 y .00001 respectively), without significative difference in the intergrupal comparative. We found correlation between diastolic and media blood pressure reduction (but not for systolic) and the decrease in left ventricular mass index in both groups. Both drugs were equally effective for control systemic arterial hypertension and produced a significant reduction of left ventricular hypertrophy, with modification of geometrical pattern to short time.


A novel antioxidant peptide derived from wheat germ prevents high glucose-induced oxidative stress in vascular smooth muscle cells in vitro.
The ingestion of whole wheat products is responsible for the prevention of a number of chronic diseases. The aim of this study is to characterize the molecular properties of a novel wheat germ-derived antioxidant peptide (AOP) in protection against high glucose-induced oxidative stress in vascular smooth muscle cells (VSMCs). AOP (amino acid sequence AREGETVVPG) was isolated from wheat germ albumin using dual-enzymatic hydrolysis/separation, followed by MS/MS. The in vitro IC50 value for Fe2+ chelation was 0.77 mM. The stability of purified AOP was confirmed by hydrolyzation in a simulated gastrointestinal (GI) digestion system in vitro. Furthermore, AOP significantly prevented high glucose-induced cell growth by 37.4 ± 2.7%, decreased the generation of intracellular reactive oxygen species (ROS) by 22.3 ± 4.6%, suppressed the phosphorylation of PKCζ, AKT and Erk1/2, and inhibited Nox4 protein expression. Our findings suggested that AOP exerted a protective role against high glucose-induced oxidative stress through the inhibition of the PKCζ/Nox4 signaling pathway in VSMCs.


Cyclopropylmethylation of benzylic and allylic chlorides with cyclopropylmethylstannane catalyzed by gallium or indium halide.
Benzylic and allylic chlorides easily coupled with cyclopropylmethylstannane in the presence of GaCl(3) or InBr(3) catalyst, in which an intermediate of an active butenylgallium or -indium species was confirmed by NMR spectroscopy and X-ray analysis. An ionic reaction process is plausible for this coupling.


Purification and characterization of an alpha-1,2-mannosidase involved in processing asparagine-linked oligosaccharides.
A calcium-dependent alpha-1,2-mannosidase involved in the processing of asparagine-linked oligosaccharides was purified to homogeneity from rabbit liver microsomes. N-terminal amino acid analysis was consistent with the presence of a homogeneous protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, under both reducing and nonreducing conditions, revealed a single protein band with an apparent molecular weight of 52,000. Gel filtration and sedimentation analysis under nondenaturing conditions suggested that the purified enzyme is a monomeric protein. The mannosidase is a glycoprotein based on the presence of protein-linked sugar and specific binding of the enzyme to concanavalin A-Sepharose. Purified mannosidase was optimally active between pH 5.0 and 6.0. The enzyme was inactive with p-nitrophenyl-alpha-D-mannopyranoside and was inhibited by deoxymannojirimycin but not by swainsonine. The enzyme was specifically activated by Ca2+, with half-maximal activation occurring at concentrations of 10 microM or less and was inhibited by Mn2+, Co2+, Ba2+, and Zn2+. Calcium ions protected the enzyme against inactivation by p-chloromercuribenzoate. Rabbit liver mannosidase hydrolyzed alpha-1,2-mannosyl-mannose linkages in a variety of substrates including methyl-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (Schutzbach, J. S. (1987) Anal. Biochem. 167, 279-283), ovalbumin glycopeptide IV, and the high mannose chains of thyroglobulin and phytohemagglutinin-P. Approximately 70% of the alpha-1,2-linked mannosyl units in the oligosaccharides of thyroglobulin were accessible to rabbit liver alpha-mannosidase, whereas most of the alpha-1,2-mannosyl units in phytohemagglutinin were resistant to digestion prior to heat denaturation of the plant lectin.


Delineation and characterization of the actin nucleation and effector translocation activities of Salmonella SipC.
Salmonella type III secreted SipC possesses dual functions: translocation of effectors and actin modulation. The biological significance of SipC's actin nucleation activity in Salmonella-induced actin cytoskeleton rearrangements has not been studied. We report here the delineation of the actin nucleation activity from the effector translocation activity of SipC. Our data show that the central amino acid region (residues: 201-220) is essential for its actin nucleation activity and the C-terminal amino acid region (321-409) is required for translocation of effectors. A SipC nucleation-deficient mutant, which maintained its effector translocation activity, was obtained. This nucleation-deficient mutant had significantly reduced ability to induce actin cytoskeleton rearrangements, resulting in lower bacterial invasion into HeLa cells. Contrary to a previous report, we found that the purified recombinant wild-type SipC(199-409) protein is monomeric in solution by size exclusion chromatography coupled with multiangle laser light scattering assays (SEC-LS). Our data established that the actin nucleation activity of SipC plays a vital role in Salmonella-induced membrane ruffles and subsequent bacteria invasion.


X-ray microanalysis of crystalline material in the liver of a narcotics user.
A 22-year-old athlete, who had had intravenous injections of narcotics in the past, developed a viral hepatitis with markedly altered liver enzyme values. Studies revealed evidence of a virtual cure of hepatitis B virus and a current infection with delta agent. Liver biopsy showed a mixed-cell portal inflammation and doubly refractile crystalline particles. These particles were shown by energy-dispersive x-ray microanalysis to contain calcite, silica, talc, and a variety of elements including Al, P, S, Cl, K, Ti, Cr, Fe, Ni, Br, Yb, Os, Ir, and a trace U. The predominance of Ca-containing compounds suggested that the foreign material was present as a result of the chemical preparation of the narcotic or as a narcotic diluent. The potential for pathologic alteration by the various substances is discussed. These observations support the idea of particulate-induced hepatic disease advanced previously by others.


Short-Term Outcomes of Totally Laparoscopic Central Hepatectomy and Right Anterior Sectionectomy for Centrally Located Tumors: A Case-Matched Study with Propensity Score Matching.
Recent advances in technology and accumulation of surgical experience have expanded the indications for laparoscopic liver resection (LLR). However, compared to open liver resection (OLR), the feasibility of laparoscopic anatomical liver resection for centrally located tumor (CLT) has not been clearly established. The aim of our study was to assess the feasibility and safety of laparoscopic anatomical major liver resection for CLT. From April 2011 to March 2016, 20 cases of anatomical LLR and 86 cases of OLR for CLTs such as central hepatectomy (CH) and right anterior sectionectomy (RAS) were performed at a single institution. We performed one-to-one propensity score matching and analyzed short-term outcomes between the LLR (n = 20) and OLR (n = 20) groups. Among 20 cases in the LLR group, two cases underwent open conversion due to common bile duct injury and anatomical distortion, respectively. There were no statistically significant difference between the LLR and OLR groups regarding clamping time of the Pringle maneuver (p = 0.502), blood loss (p = 0.746), surgical margin (p = 0.198), or length of hospital stay (p = 0.110). However, surgical time was significantly longer in the LLR group than in the OLR group (388 vs 268 min; p < 0.001). There were no significant differences between the two groups with regard to morbidity rate or mean comprehensive complication index (p = 0.716 and p = 0.819, respectively). Total anatomical LLR can be performed safely in selected CLT patients by experienced surgeons. Laparoscopic CH or RAS appears feasible with non-inferior perioperative outcomes compared to OLR.


Treatment and clinical research in myasthenia gravis: how far have we come?
Although once an often fatal illness, myasthenia gravis can now be well managed with relatively safe and effective therapies. Prior to 1960 mortality for myasthenia gravis was approximately 30%. In the current era, mortality should be less than 5%. Major therapeutic advances by decade were: physostigmine and thymectomy (1930s); mechanical ventilation (1950s); corticosteroids and plasmapheresis (1960s); azathioprine (1960s-1970s); cyclosporine (1980s); intravenous gamma globulins (1980s-1990s); and most recently mycophenolate mofetil (1990s-2000s). Modern management involves a graded approach, beginning with cholinesterase inhibitors for mild symptoms and advancing to immunomodulating medications for more severe weakness. We now have several immunomodulating agents from which to choose: selection is based largely on time to clinical effect and adverse effects. The various available treatment modalities all have their limitations. In addition, some controversies remain regarding the effectiveness of some of the commonly used myasthenia gravis treatments. Recently completed and ongoing clinical trials suggest that there is still equipoise regarding the benefit of mycophenolate mofetil and thymectomy. Hopefully, the future will be promising, with clinical trials involving novel immunotherapeutic strategies.


[Preoperative autologous blood donation in cardiac surgery. Reduction of allogeneic blood requirements].
Preoperative autologous blood donation is an effective method to reduce allogeneic transfusion requirement. However, this method is only rarely utilized in cardiac surgery. Besides economic concerns one essential argument against predonation is the lack of sufficient time due to the short waiting lists. The aim of the present study was to investigate the efficacy of autologous predonation to reduce allogeneic blood transfusion in routine cardiac surgery on a center without longer preoperative waiting lists. A total of 2,626 cardiac surgery patients were included. Primary endpoint of the study was the perioperative incidence of allogeneic packed cell transfusion. If time between diagnosis and admission to the hospital was >10 days, predonation was offered to the patients. Data were stratified for preoperative risk score. Logistic and linear regression analysis tested the influence of different variables on the incidence of allogeneic blood transfusion and the total amount of allogeneic blood. Of all patients 267 (11.2%) underwent predonation. The incidence of allogeneic packed cell transfusion was reduced from 53% to 19% by autologous predonation (p<0.001). The total amount of allogeneic blood transfused was significantly different between the groups (2.2+/-4.2 vs. 0.84+/-6.3 units; p<0.001). Autologous predonation in cardiac surgery was effective in reducing blood transfusions even in the absence of longer preoperative waiting times. It is a safe and effective method to minimize blood transfusion in cardiac surgery.


Competing pathways in metabolism-mediated cytotoxicity in vitro.
The metabolism of most xenobiotics to reactive metabolites is accompanied by competition with inactivation pathways, and the balance of these activation/inactivation pathways is critical in determining the precise circumstances in which metabolism-mediated cytotoxicity may be detected in vitro. Discussion of the importance of this balance must also take into account the nature of the question posed at the start of an in vitro study, and the choice of metabolizing system used. In quantitative terms, liver microsomal cytochrome P-450-mediated monooxygenase activity and conjugation with glutathione (GSH) are the major routes of activation and inactivation, respectively. Results of recent studies on the cytotoxicity of cyclophosphamide, bromobenzene and paracetamol measured in a liver homogenate fraction-cultured cell co-incubation have confirmed the importance of activation/inactivation balance and stability of the reactive metabolite as determinants of metabolism-mediated cytotoxicity in vitro. Competition between metabolism by P-450-mediated enzyme activity and conjugation with GSH may be used as the basis of a screen for detection of reactive metabolites by measurement of GSH depletion or conjugation with GSH. The use of cells in culture for studies of metabolism-mediated cytotoxicity is confounded by the time-dependent alterations in various enzyme activities that occur and so distort the balance of activation/inactivation. This, in turn, reduces the reliability of such systems as predictors of the events likely to occur in vivo; the lack of a distribution component in the in vitro system further distorts this in vivo/in vitro comparison. Rational development of in vitro systems for detection of reactive metabolites can only occur with an understanding of the role of competing pathways in metabolism.


Humerus length measurement in Down syndrome screening.
To compare the predictive values of different humeral shortness assessment methods in Down syndrome screening. 674 high-risk singleton pregnancies with a valid last menstrual period (LMP) date were studied. Nomogram and formulas were derived from a subset of the studied group. Sensitivities of fifth percentile and cut-off values of 0.9 for observed-to-expected (obs/exp) humerus length (HL) ratio according to biparietal diameter (BPD) and gestational age (GA) were compared. Sensitivities were 20%, 46.7% and 60% for the 5th percentile, a cut-off value of 0.9 for obs/exp HL by BPD and a cut-off value of 0.9 for obs/exp HL by GA, respectively. Using gestational age instead of BPD when calculating expected humeral length may increase the predictive role of humeral shortness in Down syndrome screening of pregnant women with valid and correct LMP.


Detection of fentanyl and its analogs by enzyme-linked immunosorbent assay.
A prototype enzyme-linked immunosorbent assay (ELISA) for fentanyl, a potent synthetic narcotic analgesic, was used to detect the presence of fentanyl and its analogs in human urine. Human drug-free urine was spiked with 0.02 to 100 ng/mL of fentanyl or with 0.1 to 500 ng/mL of each analog and used as a sample in the ELISA. Sensitivity and precision of the assay were analyzed specifically for detection of fentanyl. Cross-reactivities of fentanyl and nine analogs, acetylfentanyl, p-methylfentanyl, p-fluorofentanyl, butyrylfentanyl, (+/-)trans-3-methylfentanyl, (+/-)cis-3-methylfentanyl, alpha-methylfentanyl, benzylfentanyl, and alfentanil for this assay were also determined. The results indicate that the ELISA was capable of detecting urinary fentanyl with a limit of detection of 0.25 ng/mL and a reasonable "working cutoff" of 0.5 ng/mL. The assay was moderately precise with within-run precision, determined at fentanyl concentrations of 10.0 and 2.5 ng/mL, showing coefficients of variation from 7.7 to 10.4% and between-run precision, determined at concentrations of 10.0 and 2.5 ng/mL, showing coefficients of variation from 14.2 to 23.7%. Acetylfentanyl, p-fluorofentanyl, p-methylfentanyl, and butyrylfentanyl show good cross-reactivity in the assay relative to fentanyl. The cross-reactivities equivalent to 2 ng/mL of fentanyl for acetylfentanyl, p-fluorofentanyl, p-methylfentanyl, and butyrylfentanyl were 111, 93, 87, and 77%, respectively. The (+/-)trans-3-methylfentanyl, alpha-methylfentanyl, and (+/-)cis-3-methylfentanyl show less cross-reactivity; their percent cross-reactivities equivalent to 2 ng/mL of fentanyl were 50, 19, and 3%, respectively. Benzylfentanyl and alfentanil, however, do not show any cross-reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)


Unusual CNS presentation of neuroblastoma.
Neuroblastoma is a common tumor of childhood, usually occurring in children under 4 years of age [1]. We report a case of a 10-year old child who initially presented with a large calvarial mass representing a solitary site of metastasis from an occult adrenal neuroblastoma. The sunburst pattern of the calvarial metastasis noted in this case is rarely seen with neuroblastoma. The age of our patient, solitary focus of metastasis at presentation, and imaging appearance of the tumor are very uncommon findings of neuroblastoma.


HER2 as a prognostic factor in breast cancer.
HER2 amplification/overexpression is a marker of poor prognosis in breast cancer. The prognostic impact of HER2 positivity is lower in node-negative compared with node-positive women. The only significant, independent prognostic factors in breast cancer are node status, HER2 status and menopausal status. HER2-positive tumors also contain p53 abnormalities, tend to be hormone receptor and bcl-2 negative, have lymphoid infiltration (LI) and a high mitotic index. Patients with LI who are HER2 positive have a better prognosis than those who are HER2 negative, whereas HER2-positive patients without LI have a significantly worse prognosis than HER2-negative patients. Morphological and biological alterations appear to identify two categories of breast tumor. Two hypotheses may explain the progression to two tumor types: (1) atypical ductal hyperplasia (ADH) is a precursor of ductal carcinoma in situ (DCIS), which is a precursor of invasive ductal carcinoma (IDC); or (2) ADH is a precursor of HER2-negative IDC whereas DCIS is a precursor of HER2-positive IDC. The second theory fits well with two breast cancer subsets and the characteristics of ADH and DCIS. The first type of IDC occurs in older patients, progresses slowly due to estrogen dependency but is aggressive long term. The other type progresses rapidly, is HER2 positive and is more likely to occur in young patients.


Occupational bladder cancer in textile dyeing and printing workers: six cases and their significance for screening programs.
Occupational bladder cancer due to aniline dye intermediates such as beta-naphthylamine and benzidine has long been known; benzidine congeners (o-tolidine and o-dianisidine) are highly suspect. Among 400 men from the Amalgamated Clothing and Textile Workers Union (ACTWU) Dyers locals in New York and New Jersey screened over a 4-year period, two cases of bladder cancer were detected. (Microscopic hematuria, not cytological evaluation, prompted further investigation.) Before a 1984 ACTWU screening program in North Carolina, three workers from the same plant self-reported bladder cancers. Another member, with inconclusive screening results, was diagnosed 2 years later. For these six cases, the mean age at detection was 56.5 years (age range, 38 to 79 years), a decade earlier than age at diagnosis of nonoccupational bladder cancer in men. The average latency from onset of exposure to diagnosis was 23.3 years. These cancers provide evidence to support the initiation of screening programs for high-risk workers. To overcome the emotional and economic disincentives faced by potential victims of occupational bladder cancer, training programs are needed. Worker involvement is required, through trade union representation where possible, to assure reliable training and the equitable distribution of screening and treatment costs.


Carbonic anhydrase inhibitors. Inhibition of the Rv1284 and Rv3273 beta-carbonic anhydrases from Mycobacterium tuberculosis with diazenylbenzenesulfonamides.
A series of diazenylbenzenesulfonamides obtained from sulfanilamide or metanilamide by diazotization followed by coupling with phenols or amines, was tested for the inhibition of the beta-carbonic anhydrases (CAs, EC 4.2.1.1) encoded by the genes Rv1284 and Rv3273 of Mycobacterium tuberculosis. Several low micromolar inhibitors of the two enzymes were detected, with prontosil being the best inhibitor (K(I)s of 126-148nM). Inhibition of pathogenic beta-CAs may lead to the development of antiinfectives with a new mechanism of action, devoid of resistance problems encountered with classical antibiotics.


Electron flow between photosystem II and oxygen in chloroplasts of photosystem I-deficient algae is mediated by a quinol oxidase involved in chlororespiration.
In Chlamydomonas reinhardtii mutants deficient in photosystem I because of inactivation of the chloroplast genes psaA or psaB, oxygen evolution from photosystem II occurs at significant rates and is coupled to a stimulation of oxygen uptake. Both activities can be simultaneously monitored by continuous mass spectrometry in the presence of (18)O(2). The light-driven O(2) exchange was shown to involve the plastoquinone pool as an electron carrier, but not cytochrome b(6)f. Photosystem II-dependent O(2) production and O(2) uptake were observed in isolated chloroplast fractions. Photosystem II-dependent oxygen exchange was insensitive to a variety of inhibitors (azide, carbon monoxide, cyanide, antimycin A, and salicylhydroxamic acid) and radical scavengers. It was, however, sensitive to propyl gallate. From inhibitors effects and electronic requirements of the O(2) uptake process, we conclude that an oxidase catalyzing oxidation of plastoquinol and reduction of oxygen to water is present in thylakoid membranes. From the sensitivity of flash-induced O(2) exchange to propyl gallate, we conclude that this oxidase is involved in chlororespiration. Clues to the identity of the protein implied in this process are given by pharmacological and immunological similarities with a protein (IMMUTANS) identified in Arabidopsis chloroplasts.


Alveolar macrophage kinetics and multinucleated giant cell formation after lung injury.
Multinucleated giant cells (MGC) are a prominent feature of some chronic inflammatory states in the lung. These cells are formed by macrophage fusion, but how this process relates to the kinetics of alveolar macrophage (AM) production and proliferation is not clear. In this serial study, we compare AM kinetics and MGC formation after instilling carbon, silica, asbestos, bleomycin, and saline into the lungs of mice. Animals were killed up to 16 weeks later with [3H]thymidine injected 1 h before death. Counts of AM and MGC were carried out after bronchoalveolar lavage, and cell labeling was assessed by autoradiography. All test substances induced an inflammatory response with equal AM numbers recovered up to 2 weeks. Subsequently, the number returned to normal after carbon but remained elevated in the other groups. After carbon the lung structure was normal, there was no increase in AM label, and no MGC formed. Bleomycin-injected lungs progressed to fibrosis with only a brief, small increase in AM labeling and no MGC formation. After silica, and particularly asbestos, the lungs showed fibrosis, and many granulomas with large MGC were seen. Lavaged AM from these lungs showed a significant increase in DNA synthesis after 2 weeks, followed by higher numbers of MGC, none of which were labeled. Labeled AM tended to be free of particles, whereas MGC after 4 weeks contained many particles. The results indicate a relationship between AM proliferation and fusion, whereby AM growth appears to be prerequisite for cell infusion and MGC formation as a feature of granulomatous disease.


In vitro potency assays for nonreplicating veterinary vaccines: comparison to in vivo assays and considerations in assay development.
Each finished batch or serial of veterinary vaccine must be potency tested to assure the quality of marketed product. The potency assay must be correlated to efficacy in the target species. Potency assays of nonreplicating vaccines have traditionally measured the immune response to the vaccine in host or laboratory animals by serology or protection from challenge. Such tests are expensive, time-consuming, and raise animal welfare concerns. As disease agent protective antigens are described, in vitro techniques for quantitating them can be applied to vaccine potency measurement. However, in many cases the immunological adjuvants critical to the efficacy of the biological interfere with in vitro antigen quantitation techniques. The development of techniques that remove or compensate for the effect of adjuvants on the assays, sham vaccines containing no antigen, reference preparations containing a proven protective immunogen dose, characterization of the immunological reactants, and appropriate design and data analysis have contributed to the development of rapid, reproducible, humane, and relatively inexpensive in vitro potency assays to be used in the evaluation of veterinary biologicals.


Valuation of childhood risk reduction: the importance of age, risk preferences, and perspective.
This article explores two problems analysts face in determining how to estimate values for children's health and safety risk reductions. The first addresses the question: Do willingness-to-pay estimates for health risk changes differ across children and adults and, if so, how? To answer this question, the article first examines the potential effects of age and risk preferences on willingness to pay. A summary of the literature reporting empirical evidence of differences between willingness to pay for adult health and safety risk reductions and willingness to pay for health and safety risk reductions in children is also provided. The second dimension of the problem is a more fundamental issue: Whose perspective is relevant when valuing children's health effects-society's, children's, adults-as-children, or parents'? Each perspective is considered, followed ultimately by the conclusion that adopting a parental perspective through an intrahousehold allocation model seems closest to meeting the needs of the estimation problem at hand. A policy example in which the choice of perspective affects the outcome of a regulatory benefit-cost analysis rounds out the article and emphasizes the importance of perspective.


The effects of Moufarrege total posterior pedicle reduction mammaplasty on breastfeeding: a review of 931 cases.
Since its original description in 1979, the Moufarrege total posterior pedicle reduction mammaplasty technique has proven to be a safe and reliable procedure providing aesthetic and functional enhancement. To determine if the Moufarrege total posterior pedicle reduction mammaplasty affects successful breastfeeding. Retrospective chart review was performed for patients operated on between 1981 and 1997, and a written questionnaire was given. Patients were asked about their ability to lactate and successfully breastfeed preoperatively and postoperatively. The t test and χ(2) test were used to compare means and categorical variables, respectively. Values were also compared with a sample of women (n = 2223) from the Quebec general population as collected by the Longitudinal Study of Child Development in Quebec (ELDEQ, 1998-2002). A total of 931 patients (all women) underwent reduction mammaplasty during the study period at Jewish General Hospital, Montreal, Quebec, Canada (H.S.) or Hopital Hotel-Dieu, Montreal, Quebec, Canada (E.B. and R.M). There was a 62% response rate to the questionnaire. There were no statistically significant differences in the percentage of women able to lactate postoperatively vs preoperatively (98% vs 100%, respectively; P = .2). The percentage of women able to successfully breastfeed for 4 and 6 months was also not statistically different when comparing postoperative vs preoperative ability (4 months: 33% vs 44 %, P = .13; 6 months: 29% vs 28%, P = .77). The sample of women from the Quebec population did not differ statistically from those undergoing the Moufarrege breast reduction in terms of successful breastfeeding for 1, 2, 3, and 4 months (59% vs 67%, 52% vs 47%, 42% vs 41%, and 40% vs 33%, respectively). The Moufarrege breast reduction technique is a reliable and safe procedure that does not seem to negatively affect the success of breastfeeding based on the results of our retrospective chart review and patient questionnaire. 4.


[Effect of solcoseryl on oxygen metabolism and growth of experimental tumors].
Antihypoxant and antitumour properties of solcoseryl were studied on intact and tumour-bearing rats and mice. By the polarographic method it is found that solcoseryl increases the oxygen metabolism only in animal hypoxic tissues and improves, probably, energy production of their mitochondria. On many tumour strains it is shown that the injections of solcoseryl decelerate the growth of some tumours, inhibit the metastatic process and produce no toxic effect on the animals.


DNA vaccines suppress tumor growth and metastases by the induction of anti-angiogenesis.
Four novel oral DNA vaccines provide long-lived protection against melanoma, colon, breast, and non-small cell lung carcinoma in mouse model systems. The vaccines are delivered by attenuated Salmonella typhimurium to secondary lymphoid organs and are directed against targets such as carcinoembryonic antigen, tyrosine-related protein, vascular endothelial growth factor receptor-2 [also called fetal liver kinase-1 (FLK-1)], and transcription factor Fos-related antigen-1 (Fra-1). The FLK-1 and Fra-1 vaccines are effective in suppressing angiogenesis in the tumor vasculature. All four vaccines are capable of inducing potent cell-mediated protective immunity, breaking peripheral T-cell tolerance against these self-antigens resulting in effective suppression of tumor growth and metastasis. It is anticipated that such research efforts will contribute toward the rational design of future DNA vaccines that will be effective for prevention and treatment of human cancer.


[Effectivity of Inpatient Psychosomatic Treatment - Results of a Naturalistic Two-Year Survey in a Psychosomatic Service at a General Hospital].
Hospital psychosomatic treatment matches care expectations of a modern society. Evidence of its effectiveness through investigation in different settings is of importance because of prominent role of psychotherapy in German Healthcare System. First, to explore whether clinical as well as personal resources could improve significantly due to a hospital psychosomatic treatment. Second, to assess possible associations between outcome variables and other variables from the multidimensional profile of the sample. The sample consists of all 2014 - 2015 admitted patients who agree with investigation (N=283). Pre-post comparisons of results from validated questionnaires were performed by means of t-tests, including effect sizes. Associations between outcome variables (pre-post differences of clinical and resources related variables) and variables from the multidimensional profile were performed by means of bivariate and multivariate regression tests. Outcome differences were assessed by means of logistic regression models. Drop-out-rate due to refusal of participation amounts 11.8%; from remaining participants uncompleted datasets additional 6.9%; due to declining further participation during hospitalisation additional 4.1% (total drop-out rate amounted 22.8%). Functionality, self-efficacy, disease severity, psychological as well as physical symptom burden, depressiveness, interpersonal concerns, and embitterment improved significantly (p<0.001) displaying effect sizes between 0.39 and 1.42 (average level for clinical variables 0.98). Considerable associations between clinical and resources related variables in both directions were found. 10% of patients reported worsening. Psychosomatic hospital treatment is effective according to clinical improvement as well as to perceived quality of treatment. Clinical and resources related variables are positively bidirectional associated notwithstanding the kind of working causality. Robust prognostic factors are hard to identify. Inpatient psychosomatic treatment is effective when the admission is indicated and the unit accomplishes mandatory quality criteria. The outcome occurs individually and is hard to be predicted. Depressiveness and embitterment could be considered as epiphenomena of all psychosomatic illnesses.


Linkage analysis and physical mapping near the gene for X-linked agammaglobulinemia at Xq22.
The gene for X-linked agammaglobulinemia (XLA) has been mapped to Xq22. No recombinations have been reported between the gene and the probe p212 at DXS178; however, this probe is informative in only 30-40% of women and the reported flanking markers, DXS3 and DXS94, are 10-15 cM apart. To identify additional probes that might be useful in genetic counseling, we examined 11 polymorphisms that have been mapped to the Xq21.3-q22 region in 13 families with XLA. In addition, pulsed-field gel electrophoresis and yeast artificial chromosomes (YACs) were used to further characterize the segment of DNA within which the gene for XLA must lie. The results demonstrated that DXS366 and DXS442, which share a 430-kb pulsed-field fragment, could replace DXS3 as proximal flanking markers. Probes at DXS178 and DXS265 identified the same 145-kb pulsed-field fragment, and both loci were contained within a 200-kb YAC identified with the probe p212. A highly polymorphic CA repeat (DXS178CA) was isolated from one end of this YAC and used in linkage analysis. Probes at DXS101 and DXS328 shared several pulsed-field fragments, the smallest of which was 250 kb. No recombinations were seen between XLA and the DXS178-DXS265-DXS178CA complex, DXS101, DXS328, DXS87, or the gene for proteolipid protein (PLP). Key crossovers, when combined with the linkage data from families with Alport syndrome, suggested the following order of loci: cen-DXS3-DXS366-DXS442-(PLP, DXS101, DXS328, DXS178-DXS265-DXS178CA complex, XLA)-(DXS87, DXS94)-DXS327-(DXS350, DXS362)-tel.(ABSTRACT TRUNCATED AT 250 WORDS)


Etoposide combined with cyclophosphamide plus vincristine compared with doxorubicin plus cyclophosphamide plus vincristine and with high-dose cyclophosphamide plus vincristine in the treatment of small-cell carcinoma of the lung: a randomized trial of the Bristol Lung Cancer Study Group.
A total of 353 patients with previously untreated small-cell lung cancer (SCLC) were accrued in this multicenter trial. Patients were randomly assigned to receive one of the following three regimens: cyclophosphamide 1,000 mg/m2 intravenously (IV) day 1, vincristine 1.4 mg/m2 IV day 1, and etoposide 50 mg/m2 IV day 1, followed by etoposide 100 mg/m2/day orally days 2 through 5 (CEV); cyclophosphamide 1,000 mg/m2 IV day 1, vincristine 1.4 mg/m2 IV day 1, and doxorubicin 50 mg/m2 IV day 1 (CAV); cyclophosphamide 2,000 mg/m2 day 1 and vincristine 1.4 mg/m2 IV day 1 (CV). Cycles were repeated every 3 weeks. Treatment groups were comparable with respect to extent of disease, age, sex, performance status, and metastatic sites. No significant differences in response rates, response duration, or survival could be detected in limited disease, although there appeared to be a trend favoring CEV. Among extensive-disease patients, response duration on the CEV regimen was longer than on the CV regimen or the CAV program (P less than .001). The superiority of the CEV regimen was also demonstrated in the survival analysis in which differences attained statistical significance (P = .01). In this group the median survival was increased from 29 weeks on CV to 31 weeks on CAV and 39 weeks on CEV. Myelosuppression was the most frequent toxicity. It was more severe with CV than CEV or CAV. Most nonhematologic side effects were comparable among the three treatment groups. However, the high doses of cyclophosphamide in the CV regimen produced a higher incidence of hemorrhagic cystitis than in the CEV or CAV programs (P less than .001). Cardiotoxicity only occurred in the CAV group (P = .05). The addition of etoposide to the CV regimen resulted in significantly longer response duration and survival without increased toxicity. Similarly, the substitution of etoposide for the doxorubicin in the CAV regimen was associated with prolonged survival and reduced cardiotoxicity.


Morphological changes of neural and vascular peptides in human skin suction blister injury.
Suction blister injury is an experimental model for the investigation of the possible derangement of dermal/epidermal interaction in injury. An extensive fibre network can be stained in skin using antisera to the pan-neuronal marker protein gene product 9.5 (PGP) and the sensory neuropeptide calcitonin gene-related peptide (CGRP), while microvessels are identifiable with antisera to the endothelial marker von Willebrand's factor (vWf) and the peptide endothelin (ET). To investigate the possible involvement of superficial cutaneous innervation and microcirculation during the repair process in injury, human skin biopsies taken at different times after suction blister injury were investigated by quantitative immunohistochemistry. Neural and endothelial changes were seen in both edge and blister areas. PGP- and CGRP-immunoreactive nerves showed an increase in both areas compared with control skin up to 6 h after injury, followed by a decrease which lasted until 72 h. This was followed by a gradual increase of both nerve types starting from the blister edge and lasting up to 8 days after injury when the values were similar to controls. Similarly, in the blister area of the skin, vWF-immunoreactive capillaries showed statistically significant increases between 0 and 6 h after injury, followed by a decrease at 12 and 18 h which was maintained up to 72 h. ET-1 immunoreactivity showed a similar, although more variable, pattern of changes. At the blister edge from 23 h onwards, both vWf and ET-1 immunoreactivities showed a second increase from the edge of the blister spreading towards the centre of the blister ahead of the nerve increase. This lasted up to 8 days, when vWf immunoreactivity showed a statistically significant increase compared with control skin. Generally the numerical increase observed at early time points was accompanied by a strong staining intensity, which reverted to a normal staining intensity at later time points. These results suggest that there is a reactive process for all immunoreactive elements in the early stages of injury, followed by changes indicative of neuronal and endothelial damage (depletion phase) and the subsequent repair process. The repair started with re-epidermalization from the blister edge, followed by revascularization and, lastly, by reinnervation of the tissue. These results indicate a close relationship between epidermis, blood vessels, and nerve fibres during the healing process which follows suction blister injury.


[Loss of life expectancy analysis for cancer risk in Tianjin area].
Loss of Life Expectancy was proposed as the single metric for health risk assessment. Based on the statistical data of population in Tianjin, it was calculated that the unit cancer risk (10(-5)) equivalents to 58.47 and 66.82 minutes of life expectancy loss for male and female, respectively. The results depend strongly on the background rate of cancer, with little response for associated parameters.


Cryptogenic oculomotor nerve palsy. The need for repeated neuroimaging studies.
Five children between ages 3 and 17 years developed slowly progressive oculomotor nerve palsies. No cause was found on initial clinical or neuroradiologic investigations. Subsequent computed tomography or 1.5-T magnetic resonance imaging revealed a mass along the course of the involved oculomotor nerve in three of the five cases. The clinical and radiologic characteristics of these tumors are consistent with the diagnosis of schwannoma or, less likely, meningioma. Children with acquired oculomotor nerve palsies of initially unknown etiology should undergo imaging every two years with the expectation of eventually detecting a small tumor somewhere along the course of the oculomotor nerve.


Changes in Renal Peritubular Capillaries in Canine and Feline Chronic Kidney Disease.
Renal capillary rarefaction is a crucial event that leads to tubulointerstitial damage during the progression of chronic kidney disease (CKD). In the present study, changes in CD34-positive renal capillaries were investigated in dogs and cats with CKD. A significant decrease in CD34-positive capillaries was observed in canine diseased kidneys, even at the early stage of disease. In cats, CD34-positive capillaries were well preserved in the diseased kidneys, with no link to the severity of CKD. Renal capillary rarefaction might be a trigger event that leads to the progression of CKD in dogs, rather than in cats.


Adhesion of rheumatoid lymphocytes to mucosal endothelium: the gut revisited.
By a study of the adhesion of rheumatoid mononuclear cells, we have sought to clarify the homing properties and origins of cells likely to be involved in the pathogenesis of this disease. The adhesion of mononuclear cells from patients with rheumatoid arthritis (RA) was enumerated by an in vitro adherence assay using frozen sections of endothelium-containing gut lamina propria (EGLP) from porcine small intestine. Preliminary studies verified the involvement of known adhesion molecules by inhibition assays using monoclonal antibodies Meca-367, Mel-14 and Hermes-3. Twenty-five paired samples of peripheral blood (PB) and synovial fluid (SF) were studied, plus six from synovial membrane (SM) and eight from patients with other diseases. There was a significantly greater degree of adherence to EGLP by SF cells than PB (mean adherence 266 +/- 22 cells/mm(2), compared to 136 +/- 13 cells/mm(2), respectively, the majority of which were CD8+ cells; P=0.02, Mann-Whitney U-test for 25 paired samples). The results of the monoclonal antibody inhibition assays were in keeping with the involvement of homing receptors to gut endothelium in our assay system. Synovial fluid lymphocytes from RA patients exhibited adhesion properties more in keeping with lymphocytes of mucosal than of lymph node origin. Synovial membrance lymphocytes, by contrast, showed poor adherence to endothelium-containing lamina propria. The gut, as an immune lymphoid organ, may thus play a contributory role in this disease, possibly through the pathological seeding of cells into the synovial space.


Feasibility and outcomes of insulin therapy in elderly patients with diabetes mellitus.
The use of insulin in elderly patients raises special considerations. Most people who develop diabetes mellitus late in life have type 2 diabetes mellitus, in which there is some residual endogenous insulin secretion. This pancreatic insulin secretion, when present, stabilises their metabolic status. However, some elderly people lose virtually all their endogenous insulin secretory capacity over time, or may even have type 1 (autoimmune) diabetes mellitus with no endogenous insulin. Generally, older patients with diabetes mellitus can be managed for years, often decades, with nutritional therapy and oral agents. More options exist now than did previously. In addition to a variety of sulfonylureas, there is metformin, troglitazone, and/or alpha-glucosidase inhibitors, that are viable options to be used before turning to insulin. The goals of insulin therapy in the elderly must be considered. When hyperglycaemia causes symptoms (polyuria, polydypsia and bodyweight loss) blood glucose levels are generally >200 mg/dl, and insulin is needed if maximal doses of oral agents have been used. Insulin is also indicated when hyperglycaemia puts patients at risk of hyperosmolar states, for example, when blood glucose is >300 mg/dl during a normal day. Clinical judgement dictates whether to use insulin to control glycaemia in the attempt to avoid long term complications such as neuropathy, retinopathy or nephropathy. In people with relatively short life expectancy, major comorbities and no sign of diabetic complications, the risk may be small. On the other hand, in patients for whom neuropathy, in particular, is a major risk, controlling glycaemia (with insulin if necessary) does reduce that risk. Most patients with type 2 diabetes mellitus can be managed with relatively simple insulin regimens thanks to their endogenous insulin secretion. A single bedtime dose of neutral protamine Hagedorn (NPH) insulin, with or without continuation of daytime oral agents, may control fasting blood glucose. A pre-mix combination of NPH and Regular insulin such as 70/30 or 50/50 may be used pre-meal. More customised, 'intensive' insulin regimens are needed when the glycaemia is unstable. Hypoglycaemia is clearly the most significant risk of insulin therapy. If mild and easily treated, it is of no real concern. On the other hand, nocturnal hypoglycaemia, and, in particular, hypoglycaemia unawareness, are clear signs that the insulin regimen should be modified. In summary, insulin therapy may be necessary, and can be used effectively, in elderly patients. However, risk:benefit considerations must be taken into account when deciding which patients to treat with insulin and what insulin regimen to use.


[Long-term treatment of central diabetes insipidus with oral DDAVP].
Clinical use of the DDAVP (1-Deamino-8-D-Arginine Vasopressin) is now the first choice in treatment of Central Diabetes Insipidus. It is an analogue of Vasopressin with a higher antidiuretic potency, less vasopressor activity, and a longer duration of action. This drug still presents some problems of administration route. A lot of studies were published about different administration routes of DDAVP: sublingual tablets, parenteral solution, nose spray and suction de-epithelialized skin. Some authors have utilized the oral route (solution or tablets) with good results in short-term treatment. We think the formulation in tablets of DDAVP is an efficacious support of the therapy in this disease also for long-treatment. In our study 3 patients with Central Diabetes Insipidus (aged 22-56; 2 idiopathic and 1 post-surgery) previously treated with DDAVP nasal solution (10 micrograms/day; 36-156 months), have been submitted to a chronic treatment with DDAVP tablets for a period of 24-36 months. The DDAVP tables were administered at the dosage of 400-600 micrograms/day in 2-3 administrations. The patients were studied at intervals of 3-6 months, and on each occasion full blood count, glucose, azotaemia, creatinine, liver function tests, electrolytes, urine volume, density and osmolality were estimated. The long-treatment with oral DDAVP was able to keep a good control of the disease in all patients. In case 1 we had a significant reduction of urine volume (p < 0.01) and a significant increase (p < 0.01) of urine osmolality in comparison with previous treatment with nasal solution; in case 2 and 3 no significant changes were observed. No side effects were noted during this study. The drug has been well tolerated and the compliance of patients was better during oral DDAVP than nasal solution. In our opinion the oral DDAVP is an effective and safe solution for the treatment of Central Diabetes Insipidus, and give to the patients a better quality of life in comparison to the nasal solution.


Polyphenol-Rich Foods Alleviate Pain and Ameliorate Quality of Life in Fibromyalgic Women.
Objectives: The present study aimed to describe the antioxidant dietary intake of patients with fibromyalgia and explore the association of the results with glutathione status, pain, quality of life, and socioeconomic status. 38 fibromyalgic female patients and 35 female controls (mean age = 48.6 ± 8.1 and 47.6 ± 10.0 years, respectively) were evaluated. The number of tender points, pain threshold, quality of life, physical activity, socioeconomic status, nutritional status, intake of antioxidant micronutrients and foods with high total antioxidant capacity, and total salivary glutathione were evaluated. The number of tender points, pain threshold, and quality of life were worse in the fibromyalgia group. The consumption of vegetable juices was more common among women with fibromyalgia and consumption of red wine and beer were more common among healthy women. The adjusted mean intakes of antioxidant vitamins as well as selenium were higher for the control group (p ≤ 0.01). There was no difference for salivary levels of glutathione between the groups and no correlation for intake of antioxidant micronutrients and pain or quality of life among fibromyalgic women. However, intake of foods rich in polyphenols was associated with lower numbers of tender points (coffee, r = - 0.346; pear, r = - 0.331) and better quality of life (red fruits, r = - 0.342; dark chocolate, r = - 0.404) in the fibromyalgic group. In these women, associations between glutathione levels and food intake, pain or quality of life were not found. This study indicated that antioxidant protection from bioactive compounds present in fruit and vegetables could have an adjuvant role in fibromyalgia treatment.


[On the plasmatic filaments in assimilate conducting cells, their development and fine structure].
Taking into account the literature on the so-called sieve-tube slime ("mictoplasm", "slime strands") and regarding its fine structure more in detail the term plasmatic filament ("Plasmafilament") is proposed and will be used in this paper to characterize the individual exceedingly fine subunit of the plasmatic network (or slime) in sieve elements. Up to now plasmatic filaments have mostly been erroneously called "fibrils". The dimension of a fibrill has now been defined anew and differentiated from its subunit "plasmatic filament".In the first part of these investigations some aspects of the development of plasmatic filaments and their spreading over the total lumen of Dioscorea sieve elements will be reported.Previous to the first appearance of filaments the later sieve element abounds in plasmatic components, the groundplasm being extremely rich in ribosomes (Fig. 1). The difference between young sieve elements and the neighbouring parenchyma cells is nearly imperceptible apart from a slight variation in ribosome density. Plastids are very useful in distinguishing these two cell types from each other. The development of osmiophilic inclusions that characterize sieve-element plastids in Dioscorea has already been initiated in these very young cells.The earliest stages in the formation of plasmatic filaments that up to now have been revealed in Dioscorea show masses of filaments, some short and granular in appearance (Fig. 2: *), some already elngated and filamentous (Fig. 2: F). After expanding over the entire cell those filaments still look like having their origin directly in groundplasm (Fig. 5). Elements of the ER-system and many ribosomes cross the plasmatic filaments during all developmental stages of their network, which is at no time surrounded by any membrane.In sieve elements of Dioscorea, Primula, Cuscuta and Cucumis our investigations furthermore yielded some detail on the filament substructure. A cross-sectioned plasmatic filament is composed of an osmiophilic outer ring with a light centre (Fig. 11) corresponding in a longitudinal view to two deeply contrasted outer layers and an inner one without any contrast (Fig. 8). An individual filament has an overall diameter of 120-150 Å and an up to now indeterminable length that exceeds at least several microns.The real nature of these fine structures will be discussed in relation to similar structures and their meaning in plant and animal cells.


Altered norepinephrine turnover in the brown fat of rats with chronic renal failure.
Disturbances of the sympathetic nervous system (SNS) have been described in chronic renal failure, but their role in the metabolic derangements of uremia has not been well established. In these studies, SNS activity has been measured in the ventromedial hypothalamic (VMH) nuclei and in the intercostal brown adipose tissue (IBAT) of Sprague Dawley 5/6 nephrectomized or sham-operated rats. SNS activity was determined by calculating the norepinephrine (NE) turnover rate (in picograms per milligram per hour) 3, 6, and 12 h after the inhibition of NE synthesis with L-methyltyrosine. The endogenous NE concentration was significantly (P < 0.01) higher in the VMH (14,567 +/- 1,130 pg/mg wet wt) and IBAT (17,902 +/- 2,308 pg/mg wet wt) of uremic than control rats (9,600 +/- 1,110 and 5,752 +/- 320 pg/mg wet wt, respectively). The turnover rates of NE in the VMH (582 +/- 146 pg/mg per hour) and in the IBAT (1,432 +/- 179 pg/mg/hr) of uremic rats were significantly faster (P < 0.01) than in control rats (192 +/- 96 and 173 +/- 58 pg/mg per hour, respectively). These studies demonstrate a significant increase in NE turnover in the VMH nuclei and IBAT of uremic rats. It is suggested that increased efferent sympathetic nerve discharge from the VMH to the IBAT may play a role in the pathogenesis of malnutrition in uremia.


Effects of exercise training on quality of life, symptoms of depression, symptoms of anxiety and emotional well-being in type 2 diabetes mellitus: a systematic review.
Psychological problems are relatively common in people with type 2 diabetes. It is unclear whether exercise training exerts an effect on quality of life, symptoms of depression, symptoms of anxiety and emotional well-being in people with type 2 diabetes. The aim of this study was to conduct a systematic review to assess the effects of exercise training on these outcomes in people with type 2 diabetes. MEDLINE, PsycINFO, Embase and ClinicalTrials.gov databases were searched. The review included randomised controlled trials (RCTs) of at least 4 weeks' duration in people with type 2 diabetes that evaluated the effect of exercise training on quality of life, symptoms of depression, symptoms of anxiety and/or emotional well-being compared with usual care. Of 1,261 retrieved articles, 20 RCTs were included with a total of 1,719 participants. Quality of life was assessed in 16 studies. Between-group comparisons showed no significant results for aerobic training with the exception of one study, and mixed results for resistance and combined training. Symptoms of depression were assessed in four studies. In only one study did the intervention decrease symptoms of depression. Emotional well-being was evaluated in four studies, which also showed conflicting results. Symptoms of anxiety were evaluated in one study, which showed a significant improvement. The effects of exercise training on psychological outcomes in people with type 2 diabetes are conflicting. Therefore, there is a need for further high-quality RCTs in order to gain greater insight into the role of exercise training in people with type 2 diabetes.


Myelodysplastic and myeloproliferative neoplasms: updates on the overlap syndromes.
Myelodysplastic and myeloproliferative neoplasms (MDS/MPN) is a rare and distinct group of myeloid neoplasms with overlapping MDS and MPN features. Next generation sequencing studies have led to an improved understanding of MDS/MPN disease biology by identifying recurrent somatic mutations. Combining the molecular findings to patho-morphologic features has improved the precision of diagnosis and prognostic models in MDS/MPN. We discuss and highlight these updates in MDS/MPN nomenclature and diagnostic criteria per revised 2016 WHO classification of myeloid neoplasms in this article. There is an ongoing effort for data integration allowing for comprehensive genomic characterization, development of improved prognostic tools, and investigation for novel therapies using an international front specific for MDS/MPN. In this article, we discuss updates in prognostic models and current state of treatment for MDS/MPN.


The role of the transferrin receptor for the activation of human lymphocytes.
The proliferative response of peripheral blood mononuclear cells (PBMC) in synthetic serum-free media depends on the presence of sufficient amounts of transferrin (Tf). In the present communication we show that the reduction of Tf concentration in culture media results in a decreased proliferation, whereas lymphokine production and the expression of activation markers (IL-2 receptor; transferrin receptor, (TfR); HLA class II) remain unchanged. To examine whether this effect is due to iron depletion we added iron chelates (ferric citrate, FeCi; ferric nitrilotriacetic acid, FeNTA) which can be internalized by cells without the requirement for Tf. The iron chelates could fully restore the proliferative response even in complete absence of Tf, suggesting that the observed inhibitory effect was indeed caused by iron depletion. Addition of a monoclonal TfR antibody, J 64, also caused a marked inhibition of proliferation of PBMC in regular serum-containing medium as well as in Tf-free synthetic medium; this effect could not be overcome by any of the tested iron chelates. Therefore, growth inhibition caused by J 64 cannot simply be attributed to iron starvation. These data suggest that J 64 may interfere with processes others than iron uptake and that the TfR might confer a necessary promoting signal for lymphocyte proliferation.


Identification of bacterial DNA in noninfectious pleural fluid with a highly sensitive PCR method.
Bacterial DNA due to bacterial translocation has been identified in noninfectious ascitic fluid samples. This study investigated the possible presence of bacterial DNA in the pleural fluid of patients with pleural effusions of noninfectious origin, using a highly sensitive PCR-based method. Pleural fluid samples from 175 patients (average age ± SD: 69 ± 14 years) with noninfectious pleural effusion (62 transudates, 113 exudates) were analyzed. Bacterial DNA was detected using nested PCR with amplification of a fragment of the gene r16S, with 2 amplification protocols, i.e. low sensitivity (10 and 40 cycles) and high sensitivity (40 and 40 cycles). With the less sensitive amplification process, only 1 sample was positive (Haemophilus parainfluenzae in a patient with hepatic hydrothorax). With the highly sensitive nested PCR method, bacterial DNA was identified in the pleural fluid, of both transudative and exudative origin, of 75 of the 175 patients (43%). In cases of isolation of a single bacterium, the more frequent were Escherichia coli, Salmonella enterica and Streptococcus pneumoniae. Regardless of its origin, bacterial DNA can be identified in almost half of noninfectious pleural effusions by using a highly sensitive PCR-based method. The possible clinical significance or prognostic value of these findings deserves to be evaluated.


[Pain sensitivity in healthy teeth].
Considerable differences in tenderness are observed during the diagnostic testing of dental sensitivity (so-called vitality tests). Tenderness of the teeth varies during the course of the day; differences in the amount of tenderness correlated with the thickness of the layer of dental enamel.


Determinations of trace boron in superalloys and steels using laser-induced breakdown spectroscopy assisted with laser-induced fluorescence.
Boron (B) is widely applied in microalloying of metals. As a typical light element, however, determination of boron in alloys with complex matrix spectra is still a challenge for laser-induced breakdown spectroscopy (LIBS) due to its weak line intensities in the UV-visible-NIR range and strong spectral interference from the matrix spectra. In this study, a wavelength-tunable laser was used to enhance the intensities of boron lines selectively. The intensities of B I 208.96 nm from boron plasmas were enhanced approximately 3 and 5.8 times while the wavelength-tunable laser was tuned to 249.68 and 249.77 nm, respectively. Utilizing the selective enhancement effect, accurate determinations of trace boron in nickel-based superalloys and steels were achieved by laser-induced breakdown spectroscopy assisted by laser-induced fluorescence (LIBS-LIF), with limits of detection (LoDs) of 0.9 and 0.5 ppm, respectively. The results demonstrated that LIBS-LIF can hopefully be used in boron determinations and has great potential for improving the ability of LIBS to determine light elements in alloys with a complex matrix.


Diabetes and hypertension.
Diabetes mellitus is associated with increased risk of cardiovascular morbidity and mortality which often can be attributed to the frequent coexistence of arterial hypertension. There is an additive effect of high blood pressure and elevated blood sugar on the severity, extent and rate of progression of atherosclerotic macrovascular disease. Current evidence has also linked hypertension to acceleration of the chronic microvascular complications of diabetes mellitus including diabetic nephropathy and retinopathy. These facts emerge to place diabetic hypertension as a most important public health issue. Questions of frequency, aetiology and the implications of intervention therapy for hypertension in diabetes mellitus are reviewed in this article and can be found in several recent reviews.


Calcium-selective electrode with liquid ion exchanger.
A simple calcium-selective electrode has been developed which is capable of measuring calcium ion activity in the presence of many common interfering ions. The electrode utilizes a liquid ion exchanger membrane containing the calcium salt of a disubstituted phosphoric acid.


The Cys(X)5Arg catalytic motif in phosphoester hydrolysis.
The Yersinia protein tyrosine phosphatase (PTPase) was identified in the genus of bacteria responsible for the plague or the Black Death and was shown to be essential for pathogenesis. The three-dimensional structure of the catalytic domain of the Yersinia PTPase has been solved, and this information along with a detailed kinetic analysis has led to a better understanding of the catalytic mechanism of the PTPase. Mutational and chemical modification experiments have established that an invariant Cys residue (Cys403) is directly involved in formation of a covalent phosphoenzyme intermediate. We have shown that Arg409 plays a critical role in PTPase action and that the Cys(X)5Arg active site motif forms a phosphate-binding loop which appears to represent the essential features necessary for catalysis by the PTPases, the dual specific phosphatases, and the low molecular weight acid phosphatases.


[Ultrasonography in the diagnostics of reasons for the urinary incontinence at the postmenopausal woman. Part II--Three-dimensional ultrasonography].
In this article a new abilities of lower urinary tract diagnosis in three-dimensional sonography were shown. The examination's components, which allow us to estimate anatomical changes in patients with urinary incontinence were described.


[A case report: retroperitoneoscopic nephrectomy for a giant hydronephrosis of a horseshoe kidney].
A 30-year-old female was referred to our hospital complaining of left flank pain. She was diagnosed with a giant hydronephrosis in a horseshoe kidney. We performed a retroperitoneoscopic nephrectomy on the non-functioning moiety of the horseshoe kidney. After the placement of a ureteral catheter, she underwent a retroperitoneal nephrectomy. The feeding vessels consisted of four arteries and four veins. The thin isthmus of the horseshoe kidney was divided using scissors, without the need for electrocautery, and hemostasis was achieved using monopolar shears. Laparoscopic nephrectomy on a horseshoe kidney is a difficult surgery given the aberrant vessels and isthmus, so it tends to be avoided for reasons of safety. However, if appropriate preoperative imaging is carried out and the procedure is conducted in a careful manner, it can be made a safe and minimally invasive operation.


Sleep problems and physical pain as moderators of the relationship between PTSD symptoms and aggression in returning veterans.
This study investigated sleep problems and physical pain as moderators of the relationship between PTSD symptoms and aggression among returning veterans. Prior research has demonstrated associations between PTSD symptoms and aggression, but little work has sought to identify moderators of this relationship. Sleep problems and physical pain are both common clinical problems among veterans and have theoretical links to aggression. Participants were 103 returning service members and veterans recruited from the greater Boston area and enrolled in the VA Translational Research Center for Traumatic Brain Injury (TBI) and Stress Disorders (TRACTS). Aggression outcomes included physical and psychological intimate partner aggression (IPA), as well as physical and psychological general aggression (GA). Variables were measured via self-report questionnaires, with the exception of PTSD symptoms, which were assessed via clinician interview. Bivariate correlations revealed significant associations between PTSD symptoms, sleep problems, physical pain, and aggression outcomes. Both sleep problems and physical pain significantly moderated the relationship between PTSD symptoms and physical GA, such that this relationship became stronger at higher levels of these moderator variables. However, moderation was not found for the other aggression outcomes. Findings suggest that sleep problems and physical pain strengthen the relationship between veterans' PTSD symptoms and physical aggression toward others. Although further replication and elucidation is needed, these factors may disinhibit aggression among those at higher risk due to their PTSD symptoms. (PsycINFO Database Record


Field studies on animal trypanosomiasis in Mozambique. I. Effectiveness of the prophylactic drugs isometamidium chloride and pyrithidium bromide.
The efficacy of the trypanocides Samorin and Prothidium to protect beef cattle in areas of different trypanosome challenge was studied in Muabsa, Mozambique during an 18 month period. The performance of two groups of 1.5- to 3-year old bulls was observed, the first group in an area of high tsetse density, the second in an area of low to medium tsetse density. Glossina morsitans and G. pallidipes were present and their respective densities were determined using standard fly rounds, a mobile electric screen and biconical traps. The trypanosome challenge was determined using parameters of tsetse density and infection rates; the trypanosome risk was determined by Berenil Indices in both groups of animals. The Berenil Indices in the two study areas were not significantly different despite a great difference in apparent densities of the tsetse flies. The period of protection afforded by Samorin and Prothidium was similar in both areas which would appear to indicate that the tsetse density had no apparent effect on the degree of challenge. Samorin gave a slightly better protection than Prothidium as shown by a lower frequency of infections as well as higher packed cell volumes. There was no difference in growth rates between the treatment groups and study areas during the entire study period. It was concluded that in the study area Samorin usage is preferable to that of Prothidium. Tsetse densities obtained from standard fly rounds were found unsatisfactory in assessing the challenge, possibly because this method does not sample all components of the population. The Berenil Index, however, was found to be a useful indicator of trypanosome risk and thus frequency of treatment required.


Osseointegration of metallic devices: current trends based on implant hardware design.
Osseointegration of metallic devices has been one of the most successful treatments in rehabilitative dentistry and medicine over the past five decades. While highly successful, the quest for designing surgical instrumentation and associated implantable devices that hastens osseointegration has been perpetual and has often been approached as single variable preclinical investigations. The present manuscript presents how the interplay between surgical instrumentation and device macrogeometry not only plays a key role on both early and delayed stages of osseointegration, but may also be key in how efficient smaller length scale designing (at the micrometer and nanometer scale levels) may be in hastening early stages of osseointegration.


[Effect of low serum culture on the synchrony of cell cycle of mesenchymal stem cells].
To investigate a suitable method of inducing cell cycle synchronization at G0/G1 stage of mesenchymal stem cells (MSCs). MSCs were cultured and identified with CD44, CD90, CD71 and CD11b by flow cytometer. Cell cycle and apotosis under normal and low serum culture were detected by flow cytometer. MSCs were positive for CD44, CD90 and CD71 and negative for CD11b. The cells at G0/G1 cell stage decreased, while the cells at S and G2 cell stage increased in 1 day of 50 mL/L fetal bovine serum (FBS) and 1 to 3 days of 5 mL/L FBS. However, prolonged culture in serum-starvation medium induced cell cycle arrest at G0/G1 stage. The ratio of apoptotic cells did not increase in 50 mL/L FBS. In 5 mL/L FBS, the ratio of apoptotic cells increased in 3 days and then decreased in 4 to 5 days. The proportion of cells at G0/G1 phase was significantly increased from 75.9% to 89.4% while the ratio of apoptotic cells was only 0.162% in 5 days of 5 mL/L FBS. It is a good method to induce the synchrony of cell cycle of MSCs at G0/G1 stage in five days of 5 mL/L FBS.


Hydrolysis, hydrosulfidolysis, and aminolysis of imido(methyl)rhenium complexes.
The tris(imido)methylrhenium complex CH3Re(NAd)3 (1a, Ad = 1-adamantyl) reacts with H2O to give CH3Re(NAd)2O (2a) and AdNH2. The resulting di(imido)oxo species can further react with another molecule of H2O to generate CH3Re(NAd)O2 (3a). The kinetics of these reactions have been studied by means of 1H NMR and UV-vis spectroscopies. The second-order rate constant for the reaction of 1a with H2O at 298 K in C6H6 is 3.3 L mol-1 s-1, which is much larger than the value 1 x 10(-4) L mol-1 s-1 obtained for the reaction between CH3Re(NAr)3 (1b, Ar = 2,6-diisopropylphenyl) and H2O in CH3CN at 313 K. Both 1a and 1b react with H2S to produce the rhenium(VII) sulfide, (CH3Re(NR)2)2(mu-S)2 (4a, R = Ad; 4b, R = Ar), with second-order rate constants of 17 and 1.6 x 10(-4) L mol-1 s-1 in C6H6 and CH3CN, respectively. Complex 4b has been structurally characterized. The crystal data are as follows: space group C2/c, a = 30.4831 (19) A, b = 10.9766 (7) A, c = 18.1645 (11) A, beta = 108.268(1) degrees, V = 5771.5 (6) A3, Z = 4. The reaction between CH3Re(NAr)2O (2b) and H2S also yields the dinuclear compound 4b. Unlike 1b, 1a reacts with aniline derivatives to give mixed imido rhenium complexes.


The homeotic protein dlk is expressed during peripheral nerve development.
To investigate the molecular events controlling myelination of the peripheral nervous system, we compared gene expression of normal mouse sciatic nerves to that of the trembler mouse, whose Schwann cells are blocked in a pre-myelinating phenotype. Using cDNA array, we assessed expression levels of 1176 genes, and we found that delta-like protein (dlk), an epidermal growth factor-like homeotic protein, was expressed in the normal developing nerves, but at a low level in the dysmyelinating mutant trembler. Moreover, dlk expression was down-regulated when myelin protein expression was up-regulated, and no expression was observed in the developing brain. These results suggest that dlk expression is required for Schwann cell acquisition of the myelinating phenotype.


Editorial.


[Sonographic problems in the assessment of abdominal aortic aneurysms].
Ultrasound has taken a solid position in the diagnostic management of aneurysms of the abdominal aorta as it is a non-invasive, simple and quickly practicable method with a low expenditure. After clinical examination ultrasound holds the second place in the sequence of various diagnostic procedures in the case of an aneurysm of abdominal aorta. Diagnostic problems are demonstrated in the sonographic judgement of aortic aneurysms. 42 patients with an abdominal aortic aneurysm have been evaluated in relation to the sonographic features of the aneurysm.


[Effect of testosterone preparations on the function of the hypothalamic pituitary axis in Klinefelter's syndrome].
This article prospectively observed the suppressive effects of the testosterone preparations on the elevated gonadotropin levels in Klinefelter's syndrome (KS). After sublingual administration of methyl testosterone 5 mg Bid, the serum T levels increased 97 and 126 ng/ml respectively in 6 normal men and 9 patients of KS and the serum FSH and LH levels did not changed significantly. After intramuscular injection of testosterone propionate 25 mg 3/week testovirone 100 mg 1/10 days and testosterone enanthate 200 mg/20 days, the serum T levels increased significantly both in 6 normal mon and 17 patients with KS. It took about 1 month for the LH levels to decrease to normal range and 3-6 months for the FSH levels to become normal. Our result indicates that it is necessary to treat the KS patients for long period to normalize the increased hypothalamic pituitary function.


Modification of in vitro degradation behavior of pure iron with ultrasonication treatment: Comparison of two different pseudo-physiological solutions.
An ultrasonication treatment is developed as an external method to control the degradation behavior of pure iron. Immersion tests (weight loss measurements) and electrochemical measurements were conducted in two different pseudo-physiological solutions, simulated body fluid (SBF) and Dulbecco's modified Eagle medium (DMEM) solution. By the comparison study in these two different solutions, more information and the mechanism of the degradation process can be revealed. Degradation morphologies (with and without ultrasonication treatment) were observed by scanning electron microscope (SEM), and degradation products on the surface were characterized by Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). Moreover, the biocompatibility of iron surfaces after being ultrasonicated was evaluated. Ultrasonication was found to accelerate the degradation rate in DMEM, while it makes no difference in SBF solution; the origin of this different behavior is investigated and discussed. The parameters of the ultrasonication treatment, intensity and frequency, show an influence on the degradation rate. No adverse effects on the proliferation and adhesion of human osteoblast-like cells (MG-63) are observed on surfaces after ultrasonication treatment, as compared to bare iron. Based on these results, ultrasonication treatment is considered to have high potential to control the biodegradation behavior of iron-based materials in an external and flexible manner.


Preparation of chitosan/amine modified diatomite composites and adsorption properties of Hg(II) ions.
A green functional adsorbent (CAD) was prepared by Schiff base reaction of chitosan and amino-modified diatomite. The morphology, structure and adsorption properties of the CAD were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy and Brunauer Emmett Teller measurements. The effect of pH value, contact time and temperature on the adsorption of Hg(II) ions for the CAD is discussed in detail. The experimental results showed that the CAD had a large specific surface area and multifunctional groups such as amino, hydroxyl and Schiff base. The optimum adsorption effect was obtained when the pH value, temperature and contact time were 4, 25 °C and 120 min, respectively, and the corresponding maximum adsorption capacity of Hg(II) ions reached 102 mg/g. Moreover, the adsorption behavior of Hg(II) ions for the CAD followed the pseudo-second-order kinetic model and Langmuir model. The negative ΔG0 and ΔH0 suggested that the adsorption was a spontaneous exothermic process.


Molecular characterization of a novel tobacco pathogenesis-related (PR) protein: a new plant chitinase/lysozyme.
A new PR (pathogenesis-related) protein was isolated from tobacco leaves (Nicotiana tabacum cv. Samsun NN), reacting hypersensitively to tobacco mosaic virus (TMV), by zinc chelate chromatography and was therefore named Pz. Its reactivity toward several lectins indicated the presence of bound sugar residues. From the amino acid sequence of tryptic peptides, Oligonucleotide primers were derived which allowed the synthesis of Pz cDNA by PCR. Using this cDNA as probe, near full-length clones were isolated from a library made from poly(A)+ RNA purified from TMV-infected leaves. Sequence analysis revealed similarities with chitinases/lysozymes of various origins and the purified protein was, indeed, shown to hydrolyse different N-acetylglucosamine-containing substrates. Comparison of peptide and cDNA sequences indicated that Pz protein is synthesized as a pre-pro-protein, a seven-amino acid C-terminal peptide probably being involved in the vacuolar targeting of the protein. Pz mRNA and protein were demonstrated to accumulate strongly in TMV-infected tobacco leaves. Pz transcripts were also found in various tissues of healthy plants, indicating that Pz gene expression is developmentally regulated.


The common T60N polymorphism of the lymphotoxin-alpha gene is associated with type 2 diabetes and other phenotypes of the metabolic syndrome.
Associations between variations in the lymphotoxin-alpha gene (LTA) and myocardial infarction, cerebral infarction and type 1 diabetes have previously been reported. We hypothesised that, in its homozygous form, the functional T60N variant of LTA is associated with type 2 diabetes and other features of the metabolic syndrome among Danish Caucasian individuals. The T60N polymorphism of LTA was genotyped in the population-based Inter99 study cohort (6,514 Caucasian subjects) and in a group of type 2 diabetic patients by analysis of PCR-generated primer extension products using high-throughput chip-based matrix-assisted laser desorption/ionisation time-of-flight mass spectronomy. Comparison of 1,401 diabetic patients with 1,470 matched glucose-tolerant control subjects from the Inter99 cohort revealed that the frequency of the mutant at codon 60 in its homozygous form (N/N genotype) was higher among the diabetic patients than among the control subjects (14.6% [95% CI 12.8-16.5] vs 12.0% [95% CI 10.3-13.7], p=0.048; odds ratio=1.24). This association was even stronger among the 131 patients with early-onset (diagnosis at 40 years or younger) diabetes (21.4% [95% CI 14.4-28.4] vs 12.0% [95% CI 10.3-13.7], p=0.004; odds ratio=1.99). Additionally, studies of the metabolic syndrome (as defined by the 1999 World Health Organization criteria) in the Inter99 study cohort revealed that the frequency of the N/N LTA genotype was higher among subjects presenting one or more features of the metabolic syndrome (n=4,425) than among subjects with no characteristics of this syndrome (n=1,752) (p=0.026). The T60N LTA polymorphism is associated with type 2 diabetes and other features of the metabolic syndrome among Caucasian individuals.


[Clinical study of long graft survival in renal transplantation recipients].
A total of 110 patients, in whom kidneys from 95 living related and 15 cadaver donor, had experienced renal transplantation between February 1985 and October 1996 in our clinic. This study was conducted to evaluate the influence of the various pre-operative factors to the graft survivals and clinical course of patients in living related renal transplantation. In 95 recipients, 17 adult patients had long term graft survivals over 5 years including 6 recurrent or denovo nephritis without chronic allografts nephropathy. Eight failed to graft loss attributed to chronic allografts nephropathy diagnosed within 5 years. Retrospective analysis were performed to elucidate the differences of these recipients. Donors of long graft survival recipients were younger (49.1 +/- 12.1 v.s. 58.9 +/- 10. 2) and had a better renal function evaluated by preoperative creatinine clearance in living related donors (115.5 +/- 37.0 v.s. 79.7 +/- 22.0 1/day). Graft long survival recipients had experienced less frequencies of acute rejection within 6 months (0.53 +/- 0.62: 8 patients, 9 times) compared with chronic allografts nephropathy recipients (1.00 +/- 0.53: 7 patients, 8 times). Long graft survival recipients had better responses to the antirejection therapy. Additionally acute rejection over 6 months were experienced only in chronic allografts nephropathy recipients. Higher serum creatinine level was revealed in recipients with chronic allografts nephropathy at 1 year after transplantation (1.27 +/- 0.27 v.s. 1.88 +/- 0.42 mg/dl). We concluded that donor age and renal function are related to the graft long survival as background factors. Long graft survival recipients had less frequency of acute rejection and good response to the antirejection therapy. In recipients with of acute rejection and good response to the antirejection therapy. In recipients with chronic allografts nephropathy, serum cretine level had already increased gradually within 1 year.


[Development of a new allogeneic hematopoietic stem cell transplantation method with co-thymus transplantation from the same donor--mechanism and application for intractable diseases].
Allogeneic Hematopoietic stem cell transplantation (allo-HSCT) is effective for several diseases, including leukemia, solid tumors, and immunodeficiency. However, there are still some intractable diseases that cannot be treated with HSCT alone. We have developed a new HSCT method, allo-HSCT + thymus transplantation (TT) from the same donor, which induces elevated T cell function with mild graft-versus-host disease (GVHD) in comparison to conventional HSCT alone and HSCT + donor lymphocyte infusion (HSCT + DLI). This method leads to improvement of immune function and the ability of engraftment, and is effective for treatment of autoimmune chronic pancreatitis and sialoadenitis in aging, lupus nephritis in hosts with radioresistance, and supralethal irradiation, in which conventional HSCT alone is ineffective. This method may become a valuable form of clinical therapy for intractable diseases.


Reactions of N-heterocyclic carbenes (NHCs) with one-electron oxidants: possible formation of a carbene cation radical.
One-electron oxidation of N-heterocyclic carbenes (NHCs) has been carried out using oxidising agents such as tetracyanoethylene (TCNE) and ferrocenium [Cp(2)Fe](+); the formation of carbene radical cations is postulated.


Low-Rate Dynamic Contact Angles on Poly(methyl methacrylate) and the Determination of Solid Surface Tensions.
Low-rate dynamic contact angles of nine liquids on a poly(methyl methacrylate) (PMMA) polymer are measured by an automated axisymmetric drop shape analysis-profile (ADSA-P). It is found that two liquids dissolved the polymer on contact. From the experimental contact angles of the other seven polar and nonpolar liquids, it is found that the liquid-vapor surface tension times cosine of the contact angle changes smoothly with the liquid-vapor surface tension (i.e., gammalnucos theta depends only on gammalnu for a given solid surface). The dependence of gammalnucos theta on gammasnu is explicitly illustrated by replacing the solid surface from the PMMA to other methacrylate polymers: such a procedure shifts the curves in a very regular manner. Thus, because of Young's equation, gammasl depends only on gammalnu and gammasnu. This contact angle pattern is in harmony with those from other inert and noninert (polar and nonpolar) surfaces. The solid-vapor surface tension of PMMA calculated from the equation of state approach for solid-liquid interfacial tensions is found to be 38.5 mJ/m2, with a 95% confidence limit of +/-0.5 mJ/m2 from the experimental contact angles of the seven liquids. Copyright 1998 Academic Press.


In vitro and clinical evaluation of optical coherence tomography for the detection of subgingival calculus and root cementum.
This study evaluated the effectiveness of swept-source optical coherence tomography (ss-OCT) for detecting calculus and root cementum during periodontal therapy. Optical coherence tomography (OCT) images were taken before and after removal of subgingival calculus from extracted teeth and compared with non-decalcified histological sections. Porcine gingival sheets of various thicknesses were applied to the root surfaces of extracted teeth with calculus and OCT images were taken. OCT images were also taken before and after scaling and root planing (SRP) in human patients. In vitro, calculus was clearly detected as a white-gray amorphous structure on the root surface, which disappeared after removal. Cementum was identified as a thin, dark-gray layer. The calculus could not be clearly observed when soft tissues were present on the root surface. Clinically, supragingival calculus and cementum could be detected clearly with OCT, and subgingival calculus in the buccal cervical area of the anterior and premolar teeth was identified, which disappeared after SRP. Digital processing of the original OCT images was useful for clarifying the calculus. In conclusion, ss-OCT showed potential as a periodontal diagnostic tool for detecting cementum and subgingival calculus, although the practical applications of subgingival imaging remain limited.


Circulatory effects of acute normovolaemic haemodilution in rats with healed myocardial infarction.
This study evaluated the haemodynamic response to different degrees of acute normovolaemic haemodilution with hetastarch at rest and during preload and afterload stress in 123 anaesthetised Sprague-Dawley rats divided according to cardiac status (sham operated, n = 46; no myocardial infarction, n = 47; large myocardial infarction, n = 30). Histological infarct size was 41 (SEM 2)%. Cardiac output was recorded using an electromagnetic flow probe. The preload test was achieved by rapid infusion of blood adjusted for packed cell volume, while the afterload test was achieved by an aortic clamp technique. Prior to haemodilution, rats with large myocardial infarction had lower (p less than 0.05) cardiac index, stroke volume index, left ventricular dp/dt, and oxygen delivery, and higher left ventricular end diastolic pressure compared with sham operated rats and rats with no myocardial infarction. Haemodilution to a haematocrit of 30% in all three groups resulted in a similar significant (p less than 0.05) rise in cardiac index and stroke volume index such that blood pressure was maintained despite the decrease (p less than 0.05) in peripheral resistance. Compared with sham operated rats, rats with large myocardial infarcts haemodiluted to packed cell volume of 20% had a more limited rise in cardiac index of 14 (SEM 6) v 45(12)%, p less than 0.05, and a greater fall in oxygen delivery of 50(5) v 28(9)%, p less than 0.05 which was associated with a higher left ventricular end diastolic pressure of 6.6(1.0) v 3.7(0.4) mm Hg, p less than 0.05. Following preload and afterload stress, rats with large myocardial infarcts had lower (p less than 0.05) left ventricular developed pressure, peak cardiac index and peak stroke volume index compared with sham operated rats and rats with no myocardial infarction, independent of packed cell volume. The data suggest that large myocardial infarctions impaired the ability of the left ventricle to pump blood and generate pressure. This diminished left ventricular performance was most apparent in response to preload and afterload stress and at the lowest level of haemodilution employed (packed cell volume 20%).


Paclitaxel-induced apoptosis in BJAB cells proceeds via a death receptor-independent, caspases-3/-8-driven mitochondrial amplification loop.
Caspase-8 is a key effector of death-receptor-triggered apoptosis. In a previous study, we demonstrated, however, that caspase-8 can also be activated in a death receptor-independent manner via the mitochondrial apoptosis pathway, downstream of caspase-3. Here, we show that caspases-3 and -8 mediate a mitochondrial amplification loop that is required for the optimal release of cytochrome c, mitochondrial permeability shift transition, and cell death during apoptosis induced by treatment with the microtubule-damaging agent paclitaxel (Taxol). In contrast, Smac release from mitochondria followed a different pattern, and therefore seems to be regulated independently from cytochrome c release. Taxol-induced cell death was inhibited by the use of synthetic, cell-permeable caspase-3- (zDEVD-fmk) or caspase-8-specific (zIETD-fmk) inhibitors. Apoptosis signaling was not affected by a dominant-negative FADD mutant (FADD-DN), thereby excluding a role of death receptor signaling in the amplification loop and drug-induced apoptosis. The inhibitor experiments were corroborated by the use of BJAB cells overexpressing the natural serpin protease inhibitor, cytokine response modifier A. These data demonstrate that the complete activation of mitochondria, release of cytochrome c, and execution of drug-induced apoptosis require a mitochondrial amplification loop that depends on caspases-3 and -8 activation. In addition, this is the first report to demonstrate death receptor-independent caspase-8 autoprocessing in vivo.


[The hand project: more hugs, no shakings].
The purpose of the study was to determine if an educational program for parents of newborns can be useful to prevent Shaken Baby Syndrome in Puerto Rican families. Staff training was performed, parents observed an educational video & infant crying management strategies were discussed. Pre-post tests, follow up phone calls and medical chart reviews (53%) were conducted. A total of 65 newborns participated (62 mothers, 11 fathers). Parents reported that 50% had college studies, 78.7% lived together and 83.1% had government insurance. Pre-post tests demonstrated increase in knowledge (p < 0.05). Over 75% were contacted; 94% recalled learned strategies & 98% reported the infants had been well. Two infants were removed from home; no incidents of head trauma were reported. Almost half (44.5%) indicated taking care of the baby was difficult; managing the baby's crying was most difficult. All reported the program helped them. The program should be offered in other hospitals.


Rabovirus: a proposed new picornavirus genus that is phylogenetically basal to enteroviruses and sapeloviruses.
We have sequenced the genome of a novel picornavirus, rabovirus A (rat-borne virus, RaBoV-A, NC_026314), which was present in the feces of a Norway rat (Rattus norvegicus) from Berlin, Germany. This virus is related to members of the genera Enterovirus and Sapelovirus. RaboV-A contains a type II IRES that is unlike the type I IRES elements of enteroviruses and the type IV elements of sapeloviruses. Its genome is marked by an L protein and a chymotrypsin-like 2A protease. Our analysis of genome organization, pairwise identities, motif, phylogenic and UTR (GIMPU) indicates that RaBoV-A potentially represents a new picornavirus genus, for which we propose the name "Rabovirus". Spread by their rodent hosts and detected in New York and Berlin rats, these viruses may have a wide geographic distribution.


Polymorphisms of human aryl hydrocarbon receptor (AhR) gene in a French population: relationship with CYP1A1 inducibility and lung cancer.
The Ah receptor (AhR) is a ligand-dependent transcription factor that positively regulates the expression of the CYP1A1 gene. We investigated the genetic polymorphisms of the AhR gene including the promoter, and examined the link between these polymorphisms, CYP1A1 inducibility and the lung cancer incidence. The AhR promoter region and the 11 exons of 30 subjects were screened. Among the three polymorphisms found, two [(2417)(A/G) ((157)G/A)] have never been described previously. The (1721)(G/A) and (2417)(A/G) are localized in exon 10 and lead to Arg(554)Lys and Met(786)Val substitutions, respectively. The other polymorphism was found in the 5'-untranslated region, resulting in the substitution of a G by an A at position 157 (157)(G/A). To evaluate the frequency of this allelic variant found, a DNA library of a case-control study of lung cancer (162 controls and 177 patients) was studied. There is no significant association between (1721)(G/A), (157)(G/A) and lung cancer: (1721)(G/A) and (157)(G/A) were detected at the same allele frequency of 0.086 and 0.25, respectively in both controls and patients. (2417)(A/G) was found in only one control of 100 (allele frequency 0.005). Statistical analysis did not show any relationship between both (1721)(G/A) and (157)(G/A) polymorphisms found and CYP1A1 inducibility. Considering the rareness of the (2417)(A/G) allelic variant we were not able to evaluate its association with inducibility. In conclusion, none of the polymorphisms were found to play a key role in the CYP1A1 inducibility or in the susceptibility to develop lung cancer.