Analysis of correlations between the occurrence of anti-MAP antibodies in blood serum and the presence of DNA-MAP in milk.
Paratuberculosis (Johne's disease) is a chronic, infectious enteritis of both domestic and wild ruminants. Unfortunately, the problem of MAP infections is not linked only with the health status of animals and potential direct and indirect economic losses in bovine herds (of dairy cattle in particular). MAP bacilli present in food of animal origin (milk in particular) are likely to lead to the development of the disease in humans. Fast and effective diagnosis of the disease in animals, especially of its subclinical form, may prevent the transmission of the germ to humans. The study was aimed at analyzing the correlations between the occurance of seropositive and serodoubtful reaction in the ELISA test and the presence of DNA-MAP in udder milk. The results suggest that half of the population of animals with positive and doubtful serological responces against John's disease are likely to be a potential source of germ transmission into humans. The fact of detecting DNA-MAP in 1/3 of all milk samples points to the likelihood of occurrence of MAP bacilli in milk of animals not displaying seropositive or serodoubtful responses.


Preliminary array analysis reveals novel genes regulated by ovarian steroids in the monkey raphe region.
We hypothesize that ovarian hormones may improve serotonin neuron survival. We sought the effect of estradiol (E) and progesterone (P) on novel gene expression in the macaque dorsal raphe region with Affymetrix array analysis. Nine spayed rhesus macaques were treated with either placebo, E or E+P via Silastic implant for 1 month prior to euthanasia (n=3 per treatment). RNA was extracted from a small block of midbrain containing the dorsal raphe and examined on an Agilent Bioanalyzer. The RNA from each monkey was labeled and hybridized to an Affymetrix HG_U95AV Human GeneChip Array. After filtering and sorting, 25 named genes remained that were regulated by E, and 24 named genes remained that were regulated by supplemental P. These genes further sorted into functional categories that would promote neuronal plasticity, transmitter synthesis, and trafficking, as well as reduce apoptosis. The relative abundance of four pivotal genes was examined in all nine animals with quantitative RT-PCR and normalized by glyceraldehyde 3-phosphate dehydrogenase (GAPDH). E+/-P caused a significant threefold reduction in JNK-1 (a pro-apoptosis gene, p<0.007); and a significant sixfold decrease in kynurenine mono-oxygenase (produces neurotoxic quinolones, p<0.05). GABA-A receptor (alpha3 subunit; benzodiazepine site) and E2F1 (interferes with cytokine signaling) were unaffected by E, but increased sevenfold (p<0.02) and fourfold (p<0.009), respectively, upon treatment with P. In summary, subsets of genes related to tissue remodeling or apoptosis were up- or down-regulated by E and P in a tissue block containing the dorsal raphe. These changes could promote cellular resilience in the region where serotonin neurons originate.


Kardar-Parisi-Zhang universality class and the anchored Toom interface.
We revisit the anchored Toom interface and use Kardar-Parisi-Zhang scaling theory to argue that the interface fluctuations are governed by the Airy1 process with the role of space and time interchanged. The predictions, which contain no free parameter, are numerically well confirmed for space-time statistics in the stationary state. In particular, the spatial fluctuations of the interface computed numerically agree well with those given by the GOE edge distribution of Tracy and Widom [Commun. Math. Phys. 177, 727 (1996)].


Characterizing dose response relationships: Chronic gamma radiation in Lemna minor induces oxidative stress and altered polyploidy level.
The biological effects and interactions of different radiation types in plants are still far from understood. Among different radiation types, external gamma radiation treatments have been mostly studied to assess the biological impact of radiation toxicity in organisms. Upon exposure of plants to gamma radiation, ionisation events can cause, either directly or indirectly, severe biological damage to DNA and other biomolecules. However, the biological responses and oxidative stress related mechanisms under chronic radiation conditions are poorly understood in plant systems. In the following study, it was questioned if the Lemna minor growth inhibition test is a suitable approach to also assess the radiotoxicity of this freshwater plant. Therefore, L. minor plants were continuously exposed for seven days to 12 different dose rate levels covering almost six orders of magnitude starting from 80 μGy h(-1) up to 1.5 Gy h(-1). Subsequently, growth, antioxidative defence system and genomic responses of L. minor plants were evaluated. Although L. minor plants could survive the exposure treatment at environmental relevant exposure conditions, higher dose rate levels induced dose dependent growth inhibitions starting from approximately 27 mGy h(-1). A ten-percentage growth inhibition of frond area Effective Dose Rate (EDR10) was estimated at 95 ± 7 mGy h(-1), followed by 153 ± 13 mGy h(-1) and 169 ± 12 mGy h(-1) on fresh weight and frond number, respectively. Up to a dose rate of approximately 5 mGy h(-1), antioxidative enzymes and metabolites remained unaffected in plants. A significant change in catalase enzyme activity was found at 27 mGy h(-1) which was accompanied with significant increases of other antioxidative enzyme activities and shifts in ascorbate and glutathione content at higher dose rate levels, indicating an increase in oxidative stress in plants. Recent plant research hypothesized that environmental genotoxic stress conditions can induce endoreduplication events. Here an increase in ploidy level was observed at the highest tested dose rate. In conclusion, the results revealed that in plants several mechanisms and pathways interplay to cope with radiation induced stress.


Evidence for succinate production by reduction of fumarate during hypoxia in isolated adult rat heart cells.
It has been demonstrated that perfusion of myocardium with glutamic acid or tricarboxylic acid cycle intermediates during hypoxia or ischemia, improves cardiac function, increases ATP levels, and stimulates succinate production. In this study isolated adult rat heart cells were used to investigate the mechanism of anaerobic succinate formation and examine beneficial effects attributed to ATP generated by this pathway. Myocytes incubated for 60 min under hypoxic conditions showed a slight loss of ATP from an initial value of 21 +/- 1 nmol/mg protein, a decline of CP from 42 to 17 nmol/mg protein and a fourfold increase in lactic acid production to 1.8 +/- 0.2 mumol/mg protein/h. These metabolite contents were not altered by the addition of malate and 2-oxoglutarate to the incubation medium nor were differences in cell viability observed; however, succinate release was substantially accelerated to 241 +/- 53 nmol/mg protein. Incubation of cells with [U-14C]malate or [2-U-14C]oxoglutarate indicates that succinate is formed directly from malate but not from 2-oxoglutarate. Moreover, anaerobic succinate formation was rotenone sensitive. We conclude that malate reduction to succinate occurs via the reverse action of succinate dehydrogenase in a coupled reaction where NADH is oxidized (and FAD reduced) and ADP is phosphorylated. Furthermore, by transaminating with aspartate to produce oxaloacetate, 2-oxoglutarate stimulates cytosolic malic dehydrogenase activity, whereby malate is formed and NADH is oxidized. In the form of malate, reducing equivalents and substrate are transported into the mitochondria where they are utilized for succinate synthesis.


The effect of cognitive impairment on self-generation in Hispanics with TBI.
The objective of this study was to determine the moderating effect of cognitive impairment (CI) on the usefulness of the generation effect to improve learning and memory in Hispanics with traumatic brain injury (TBI). Sixty-one Hispanic individuals with TBI (29 without CI, 22 with mild to moderate CI, and 10 with severe CI) and 44 healthy controls (HC) were required to remember the last word in each of 32 sentences. Target words were presented in a self-generated and provided condition. Recall and recognition were examined immediately, after 30 minutes, and at one week. Individuals remembered and recalled significantly more words in the generated condition than the provided condition, regardless of group or time. The self-generation technique equally benefitted all participants regardless of TBI status or degree of CI. Future cognitive rehabilitation programs designed to improve short-term recall and recognition in Hispanic individuals with TBI should include the self-generation technique. Further research into the longer-term effects of the generation effects is warranted.


Four new cases of double heterozygosity for BRCA1 and BRCA2 gene mutations: clinical, pathological, and family characteristics.
Double heterozygosity (DH) for BRCA1 and BRCA2 mutations is a very rare finding, particularly in non-Ashkenazi individuals, and only a few cases have been reported to date. In addition, little is known on the pathological features of the tumors that occur in DH cases and on their family history of cancer. Four carriers of pathogenic mutations in both BRCA1 and BRCA2 were identified among women who underwent genetic counseling for hereditary susceptibility to breast and ovarian carcinoma at three different Italian institutions. Clinical, pathological, and family history data were collected from medical records and during genetic counseling sessions. All identified DH cases developed breast carcinoma and three of them were also diagnosed with ovarian carcinoma. Mean ages of breast and ovarian cancer diagnosis were 42.7 and 48.6 years, respectively. The majority of breast cancers showed a BRCA1-related phenotype, being negative for hormone receptors and HER2. Two cases reported different gastrointestinal tumors among relatives. Although the individuals described in this study show more severe clinical features in comparison to previously reported BRCA1 and BRCA2 DH cases, our observations support the hypothesis of a non specific phenotype of DH cases in terms of age of disease onset. In addition, our observations indicate that in DH patients breast carcinogenesis appears to be driven mainly by the mutations in BRCA1. The possible association of DH for BRCA gene mutations with gastrointestinal tumors is in keeping with previous reports, but needs to be confirmed by further analyses.


Partial characterization of the DNA repair protein complex, containing the ERCC1, ERCC4, ERCC11 and XPF correcting activities.
The nucleotide excision repair (NER) protein ERCC1 is part of a functional complex, which harbors in addition the repair correcting activities of ERCC4, ERCC11 and human XPF. ERCC1 is not associated with a defect in any of the known human NER disorders: xeroderma pigmentosum, Cockayne's syndrome or trichothiodystrophy. Here we report the partial purification and characterization of the ERCC1 complex. Immunoprecipitation studies tentatively identified a subunit in the complex with an apparent MW of approximately 120 kDa. The complex has affinity for DNA, but no clear preference for ss, ds or UV-damaged DNA substrates. The size of the entire complex determined by non-denaturing gradient gels (approximately 280 kDa) is considerably larger than previously found using size separation on glycerol gradients (approximately 120 kDa). Stable associations of the ERCC1 complex with other known repair factors (XPA, XPC, XPG and TFIIH complex) could not be detected.


Around-the-clock, rapid diagnosis of influenza by means of membrane chromatography antigen testing confirmed by polymerase chain reaction.
One rapid membrane chromatography test and 2 immunofluorescence tests were compared with polymerase chain reaction as tools for the diagnosis of influenza in 277 patients treated in an emergency department. The sensitivity on days 1-3 of symptoms was 71% for the rapid membrane chromatography test, 70% for the first immunofluorescence test, and 79% for the second immunofluorescence test. Rapid tests are useful for round-the-clock identification of influenza, with follow-up polymerase chain reaction used for confirmation.


Effects of Motivational Self-Talk on Endurance and Cognitive Performance in the Heat.
We tested the effectiveness of a 2-wk motivational self-talk (MST) intervention-specific to heat tolerance-on endurance capacity and cognitive function in the heat. Eighteen trained male (n = 14) and female (n = 4) cyclists randomly received 2 wk of MST training (n = 9) or a control regimen (CON, n = 9). The experimental protocol was a PRE/POST design consisting of 30 min of cycling at 60% peak power output (PPO) in the heat (35°C, 50% relative humidity, ~3.0 m·s airflow), a 30-min rest period, followed by a time to exhaustion (TTE) test at 80% PPO, and an identical rest period. Executive function, reaction time, and working memory were tested at baseline and each rest period. Key measures included TTE, speed and accuracy on the cognitive tests, rectal temperature, HR, oxygen consumption, and RPE. Group (MST vs CON) × test (PRE vs POST) × time repeated-measures ANOVA revealed that MST significantly increased TTE from PRE (487 ± 173 s) to POST (679 ± 251 s, P = 0.021) concurrent with a higher terminating rectal temperature (PRE, 38.5°C ± 0.2°C; POST, 38.8°C ± 0.4°C; P = 0.023); no TTE (PRE, 531 ± 178 s; POST, 510 ± 216 s; P = 0.28) or rectal temperature (PRE, 38.4°C ± 0.3°C; POST, 38.4°C ± 0.2°C; P = 1.000) changes were found in CON. MST significantly improved both speed and accuracy for executive function from PRE/POST, with no PRE/POST differences for CON on any cognitive measure. There were no interactions (all P > 0.05) for other key measures. Motivational self-talk is effective in altering the internal psychophysiological control of exercise and plays a role in improving endurance capacity and executive function in the heat.


Pathological basis of surgery in the management of postradiotherapy cervical metastasis in nasopharyngeal carcinoma.
Radical neck dissection was performed on 43 patients with nasopharyngeal carcinoma in whom persistent or recurrent cervical metastasis developed after radiotherapy. The pathologic nature of the tumor in the cervical lymph nodes was studied with step serial sectioning of the entire radical neck dissection specimen at 3-mm intervals. In 70% of patients, more tumor-harboring lymph nodes were detected in the specimen when compared with clinical examination. The extensive behavior of the tumor in the cervical metastases was reflected by the presence of extracapsular spread in 70% of the lymph nodes and the existence of isolated clusters of tumor cells in 35% of the specimens studied. Tumor tissue lying in close proximity to the spinal accessory nerve was demonstrated in 27.5% of the specimens, and 72% of the tumor-bearing lymph nodes were located in the posterior triangle. Radical neck dissection is recommended as the salvage procedure for these patients.


Black currant reversion disease--the probable causal agent, eriophyid mite vectors, epidemiology and prospects for control.
Black currant reversion disease and the vector of its causal agent, the black currant gall mite Cecidophyopsis ribis, have been recognised for at least 100 years and are the two most damaging organisms of black currant crops world-wide. However, the molecular characterisation of these two organisms has begun to be determined in only the last few years. The probable causal agent of reversion disease, Black currant reversion associated virus (BRAV), belongs to the genus Nepovirus, has isometric particles c. 28 nm in diameter that contain a single major polypeptide of c. 55 KDa and two polyadenylated ssRNA species of 7700 nt and 6400 nt. Some particle preparations also contain a satellite ssRNA species of 1432 nt. Using immuno-capture RT-PCR and primers based on the genomic RNA of BRAV, this virus was shown to be closely associated with reversion disease. Analysis of Cecidophyopsis mite rDNA, identified rapidly and unambiguously the three known species on Ribes and distinguished four new ones. Resistance to the reversion agent and to the gall mite vector has been introduced into black currant and has given effective control of these respective organisms in the field. These findings and their significance for the ecology, epidemiology and control of variants of these two organisms are reviewed and discussed.


Impact of laparoscopic radical prostatectomy on clinical T3 prostate cancer: experience of a single centre with long-term follow-up.
To investigate the oncological safety and effectiveness of laparoscopic radical prostatectomy (LRP) for patients with clinical T3 (cT3) prostate cancer compared with patients with cT1 and cT2 prostate cancer. In all, 2375 consecutive LRPs were evaluated between 1999 and 2013. Of the 1751 patients enrolled with complete follow-up data (>24 months), patients were divided into three groups according to clinical stage of prostate cancer using Tumour-Node-Metastasis (TNM) classification. Group 1 consisted of patients with cT1 stage prostate cancer, group 2 those with cT2, and group 3 those with cT3. Demographic, postoperative, and long-term data of patients were recorded and statistical analyses were performed. The mean (SD) age was 63.6 (6.2) years. The mean (SD) follow-up was 104 (28.4) months. There were 417 patients in group 1, 842 patients in group 2, and 492 patients in group 3. The mean prostate-specific antigen level, biopsy Gleason score, tumour volume, body mass index, and age, were all higher in group 3 (P < 0.001). Nerve-sparing techniques were used more in group 1 than in the other groups (P < 0.001). Extracapsular extension, seminal vesicle invasion, Gleason score, positive surgical margin (PSM), and rate of adjuvant hormone and radiotherapies were highest in group 3. However, urinary continence was similar in all groups. Group 1 contained the most patients with an erection sufficient for intercourse. Group 1 had the best cancer-specific survival rate, whereas overall survival (OS) rates and complications were similar in all groups. LRP seems effective and safe for patients with cT3 prostate cancer with similar OS rates as for those with cT1 and cT2; however, additional therapies may have contributed to these rates. LRP can be considered for the treatment of patients with cT3 prostate cancer.


[Differential diagnosis of metaphyseal dysplasias and osteodysplasty (osteodysplasty of Melnick and Needles) (author's transl)].
The article reports on 4 patients with rare modeling defects of the long bones. These defects are metaphyseal dysplasia, craniometaphyseal dysplasia, frontometaphyseal dysplasia, and osteodysplasty (osteodysplasty of Melnick and Needles). The differential diagnostic criteria are shown in a table to allow diagnosis already in children. This appears important in respect of the therapy to be employed (corrective surgery) and for prognosis, as well as for giving patients proper genetic and vocational advice.


Genetic synthesis and characterization of pH- and temperature-sensitive silk-elastinlike protein block copolymers.
The purpose of this work was to synthesize and characterize a pH- and temperature-sensitive block copolymer containing repeating sequences from silk (Gly-Ala-Gly-Ala-Gly-Ser) and elastin (Gly-Val-Gly-Val-Pro) protein. The monomer contained one repeat of silk and eight repeat units of elastin, with the first valine in one of the elastin repeats being replaced by glutamic acid. The copolymer was synthesized using genetic engineering techniques. The sensitivity of the copolymer to pH and temperature was examined at various polymer concentrations and ionic strengths. Turbidity measurements were carried out over a temperature range of 20 to 100 degrees C at various pH, concentration, and ionic strength values. The introduction of an ionizable residue (glutamic acid) rendered the copolymer sensitive to changes in pH. The transition termperature (T(t)), the temperature at which the polymer became insoluble upon increase in temperature, was modulated by changing the pH. In general, the T(t) value, was found: (1) to increase with an increase in pH, (2) to decrease with increasing ionic strength, and (3) to decrease with increasing concentration. Results of these studies suggest that by strategic placement of charged amino acids in genetically engineered silk-elastinlike protein block copolymers it is possible to precisely control sensitivity to stimuli such as pH and temperature.


Estimation of the lactate threshold from heart rate response to submaximal exercise: the pulse deficit.
In this study, we evaluated the validity of a sharp increase in pulse deficit (PD) as a noninvasive index for estimation of the first lactate threshold (LT (1)) in healthy individuals with various levels of aerobic fitness. Three groups of healthy male subjects participated in the study: 15 sedentary individuals, 14 students of physical education, and 13 competitive athletes. Each subject performed a maximal incremental exercise test on the cycle ergometer for the determination of the LT (1), the second lactate threshold, and peak power output. On different days, subjects performed several 8-min bouts of constant-load exercise on the cycle ergometer, corresponding to each of the power outputs of the maximal test, to evaluate PD, which was calculated as the total number of heart beats of the last 4 min minus the total number of heart beats in the first 4 min of exercise. The three groups presented similar blood lactate, heart rate and pulse deficit responses to exercise. For the first power output up to the LT (1), PD showed no significant changes. For the three groups, a sharp increase in PD was seen at the intensity immediately above LT (1). There was a significant correlation between PD and blood lactate changes from the rest to 4th min of submaximal exercise (r = 0.83, p < 0.05). The power output before a sharp increase in PD detected during constant-load exercise (112 +/- 38 W) and the power output corresponding to the LT (1) detected during the incremental test (111 +/- 37 W, p = 0.323) were similar and strongly correlated (r = 0.99, p = 0.0001). The absolute cut-point value of 25 beats for PD had a sensitivity of 100 %, a specificity of 95 %, and a positive predictive value of 90 % for the detection of LT (1). The determination of PD provides an accurate noninvasive estimate of the LT (1) in healthy young men with different levels of fitness. One 8-min submaximal exercise bout can establish if an individual is exercising above or below the LT (1).


A new Tay-Sachs disease B1 allele in exon 7 in two compound heterozygotes each with a second novel mutation.
Three novel Tay--Sachs Disease (TSD) mutations have been identified in two unrelated, non-Jewish compound heterozygous patients. A G772C transversion mutation causing an Asp258His substitution is shared by both patients. The mutant enzyme had been characterized, on the basis of previous kinetic studies (1) as a B1, or alpha-subunit active site mutation. This is the first B1 mutation not found in codon 178 (exon 5). A C508T transition causing an Arg170Trp substitution also occurred in one of the patients. The third mutation is a two base deletion occurring in exon 8 involving the loss of either nts 927-928 or 929-930 in codon 310. The deletion creates an inframe termination codon 35 bases downstream. The Arg170Trp mutation was also detected in a third unrelated TSD patient. In both families this allele was traced to French Canadian ancestors originating in the Estrie region of the province of Quebec. This mutation is the third TSD allele unique to the French Canadian population and the ancestral origins of the carrier parents are distant from the center of diffusion of the more common 7.6 kb deletion mutation which is in the eastern part of the province.


Traditional usages, botany, phytochemistry, pharmacology and toxicology of Polygonum multiflorum Thunb.: a review.
Polygonum multiflorum Thunb., which is known as Heshouwu ( in Chinese) in China. It is traditionally valued and reported for hair-blacking, liver and kidney-tonifying and anti-aging effects as well as low toxicity. The aim of this review is to provide comprehensive information on the botany, traditional uses, phytochemistry, pharmacological research and toxicology of Polygonum multiflorum, based on the scientific literature. Moreover, trends and perspectives for future investigation of this plant are discussed. It will build up a new foundation for further study on Polygonum multiflorum. A systematic review of the literature on Polygonum multiflorum was performed using several resources, including classic books on Chinese herbal medicine and various scientific databases, such as PubMed, SciFinder, the Web of Science, Science Direct, China Knowledge Resource Integrated (CNKI). Polygonum multiflorum is widely distributed throughout the world and has been used as a traditional medicine for centuries in China. The ethnomedical uses of Polygonum multiflorum have been recorded in many provinces of China and Japan for nine species of adulterants in six families. More than 100 chemical compounds have been isolated from this plant, and the major components have been determined to be stilbenes, quinones, flavonoids and others. Crude extracts and pure compounds of this plant are used as effective agents in pre-clinical and clinical practice due to their anti-aging, anti-hyperlipidaemia, anti-cancer and anti-inflammatory effects and to promote immunomodulation, neuroprotection, and the curing of other diseases. However, these extracts can also lead to hepatotoxicity, nephrotoxicity and embryonic toxicity. Pharmacokinetic studies have demonstrated that the main components of Polygonum multiflorum, such as 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucopyranoside and emodin are distributed among many organs and tissues. Therapeutic potential of Polygonum multiflorum has been demonstrated in the conditions like Alzheimer׳s disease, Parkinson׳s disease, hyperlipidaemia, inflammation and cancer, which is attributed to the presence of various stilbenes, quinones, flavonoids, phospholipids and other compounds in the drug. On the other hand, the adverse effects (hepatotoxicity, nephrotoxicity, and embryonic toxicity) of this plant were caused by the quinones, such as emodin and rhein. Thus more pharmacological and toxicological mechanisms on main active compounds are necessary to be explored, especially the combined anthraquinones (Emodin-8-O-β-d-glucopyranoside, Physcion-8-O-β-d-glucopyranoside, etc.) and the variety of stilbenes.


Simultaneous intraocular and bilateral extraocular muscle involvement in a case of disseminated cysticercosis.
We report an unusual case of disseminated cysticercosis having simultaneous intraocular and extraocular involvement. This 21-year-old male presented with recent loss of vision in one eye and history of a single seizure. Examination revealed intravitreal cysticercosis with exudative retinal detachment. Computed tomographic scan showed disseminated neurocysticercosis and cysticercosis of the medial and inferior recti of both the eyes. The patient was started on albendazole and prednisolone under neurologist's supervision. Subsequent computed tomographic scan showed resolution of the extraocular muscle cysts and decrease in the number of neurocysticerci. The patient has had no further seizures. This is the first report of simultaneous intraocular and extraocular cysticercosis.


[Combined surgical and pharmacological treatment of diabetic maculopathy].
There are at least three avenues of investigation that support the theoretical value of vitrectomy for the treatment of DME, based on (1) vitrectomy with ILM peeling for the relief of traction on the macula, (2) vitrectomy to improve oxygenation of the macula leading to decreased vascular permeability with subsequent resolution or decrease in DME, and (3) ILM peeling to remove a part of the Müller cell endfeet and the horizontal gliosis. Visual improvement could be due to the induction of a higher overexpression of GFAP at the Müller cells level. It is likely that the proliferation of GFAP-stained gliofibrils, observed in these cells, preserves the blood-retinal barrier, reinforces architectural cohesion, and opposes the installation of the edema. In addition, the search for a specific pharmacological treatment is ongoing on the basis of new findings regarding the involvement of cytokines and growth factors in the formation of macular edema. Vascular endothelial growth factor (VEGF), inhibitors are currently being investigated in clinical studies. However, endogenous VEGF is required for visual function. Growing body evidence indicates that VEGF acts also on nonvascular cells, it plays survival role on Müller cells and photoreceptors. Therefore anti-VEGF therapies should be administered with caution.


Late-onset bleb leaks after glaucoma filtering surgery.
To determine the incidence of focal, late-onset, conjunctival bleb leaks after glaucoma filtering surgery. Prospective, cross-sectional analysis. Tertiary care outpatient referral center. Consecutive patients who underwent glaucoma filtering surgery prior to June 1996 presenting for evaluation from September 2,1996, through November 15,1996. Five hundred twenty-five eyes of 525 consecutive patients were enrolled in the study. Bleb height (elevated or flat), area (diffuse or localized), and wall thickness (thin, thick, or encapsulated) were classified. Each bleb was tested for focal leakage using a moistened fluorescein strip, cobalt blue illumination, and slit-lamp biomicroscopy. Diffuse transconjunctival aqueous flow did not qualify as a focal leak. Seidel-positive aqueous leakage. Bleb leakage occurred in 14 eyes following trabeculectomy (mitomycin C treatment, 10 eyes; 5-fluorouracil treatment, 3 eyes; no antifibrosis agent, 1 eye) and in 1 eye following combined cataract and glaucoma surgery with adjunctive mitomycin C therapy. Bleb leakage occurred more frequently in eyes that received mitomycin C (10 [3.7%] of 273 eyes) than 5-fluorouracil (3 [1.4%] of 213 eyes) or no antifibrosis agent (1 [2.6%] of 39 eyes), using Kaplan-Meier estimates (P=.008, log-rank test). Conjunctival blebs were significantly thinner after trabeculectomy with mitomycin C than with 5-fluorouracil (P=.001). Bleb wall thickness was greater following combined cataract and glaucoma surgery than following trabeculectomy alone (P=.008). Age (P=.84), sex (P=.68), race (P=.77), duration of mitomycin C exposure (P=.62), number of antiglaucoma medications (P=.16), and total 5-fluorouracil dose (P=.85) were not associated with late-onset leaks. The risk of late-onset focal bleb leakage increases following trabeculectomy with mitomycin C therapy. Late leakage after combined cataract and glaucoma surgery is infrequent.


Meat Juice Serology and Improved Food Chain Information as Control Tools for Pork-Related Public Health Hazards.
The seroprevalence of Salmonella spp., pathogenic Yersinia spp., Toxoplasma gondii and Trichinella spp. was studied in 1353 finishing pigs from 259 farms that were allocated according to farm types: large fattening farms (≥ 1000 pig places), small fattening farms (< 1000 pig places) and farrow-to-finish farms. The antibodies were analysed with commercial ELISA kits in meat juice samples that were collected at Finnish slaughterhouses. Salmonella antibodies were rare (3% of pigs, 14% of farms) when the cut-off optical density (OD) value 0.2 was used. Antibodies to pathogenic Yersinia spp. and T. gondii were detected in 57% of pigs and 85% of farms (OD ≥ 0.3) and in 3% of pigs and 9% of farms (OD ≥ 0.15), respectively. No antibodies to Trichinella spp. were detected (OD ≥ 0.3). The European Food Safety Authority (EFSA) considers Salmonella spp., Yersinia enterocolitica, T. gondii and Trichinella spp. as the most relevant biological hazards in the context of meat inspection of pigs. The seroprevalence of these important zoonotic pathogens was low in Finland, except that of Yersinia. The seroprevalence of Toxoplasma was significantly higher in pigs originating from small-scale fattening farms (P < 0.05). Strong positive correlation was observed at the animal level between Salmonella and Yersinia seropositivity and between Salmonella and Toxoplasma seropositivity (P < 0.05). We suggest that these results reflect the level and importance of biosecurity measures applied on the farms. Meat juice serology at slaughter is a useful tool for targeting measures to control these pathogens. The information obtained from analyses should be used as part of the food chain information (FCI).


Early endoscopic retrograde cholangiopancreatography versus conservative management in acute biliary pancreatitis without cholangitis: a meta-analysis of randomized trials.
Early endoscopic retrograde cholangiopancreatography (ERCP) should be performed in all patients with acute biliary pancreatitis (ABP) and coexisting acute cholangitis. In patients without cholangitis and predicted mild ABP it is generally accepted that early ERCP should not be performed. Nevertheless, there is a controversy regarding the role of early ERCP in the treatment of patients with predicted severe ABP without cholangitis. We reviewed randomized trials on early ERCP versus conservative management in patients with ABP without acute cholangitis. Relevant publications in 3 electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials) were systematically reviewed and meta-analyzed. Seven randomized trials on ERCP in acute pancreatitis were found, of which 3 including a total of 450 patients (230 in the invasive arm and 220 in the control arm) qualified for a meta-analysis according to predefined criteria. In all patients with ABP (predicted mild and severe), early ERCP was associated with a nonsignificant reduction in overall complications [risk ratio (RR) 0.76; 95% confidence interval (CI) 0.41-1.04; P = 0.38] and a nonsignificant increase in mortality (RR 1.13; 95% CI 0.23-5.63; P = 0.88). Subgroup analysis based on predicted severity did not affect these outcomes (overall complications: predicted mild: RR 0.86; 95% CI 0.62-1.19; P = 0.36; predicted severe: RR 0.82; 95% CI 0.32-2.10; P = 0.68; mortality: predicted mild: RR 1.90; 95% CI 0.25-14.55; P = 0.53; predicted severe: RR 1.28; 95% CI 0.20-8.06; P = 0.80). In this meta-analysis, early ERCP in patients with predicted mild and predicted severe ABP without acute cholangitis did not lead to a significant reduction in the risk of overall complications and mortality.


What happens between an external stimulus and an overt response? A study of covert behavior.
Peripheral components of feedthrough loops were psychophysiologically measured from the brain, both forelimbs, the tongue and the eyes during simple and choice reaction time tasks using linguistic and non-linguistic stimuli. Closing a microswitch with the little finger was the overt response. Covert electromyographic (EMG) responses were computer identified in the following average temporal order: generally, the earliest covert reactions were in the tongue, brain, eyes, and passive arm-hand region. Next were complex EMG events in the active limb. These covert reactions may function in feedthrough loops to generate and transmit codes during internal information processing. The passive arm-hand responses occurred significantly earlier than the onset of the covert EMG burst for closing the microswitch; perhaps there is an inhibitory response "commanding" the passive arm not to respond, before the other (active) limb can overtly respond. Mean response patterns to linguistic and non-linguistic stimuli were almost identical. Reaction time to the onset of the EMG burst for switch closing was from 40 to 95 milliseconds earlier than the usual overt reaction time measure (that to switch closing), suggesting that reaction time studies might be improved by using the onset of EMG increase as the more sensitive and precise measure.


Modified Selective Neurectomy for the Treatment of Post-Facial Paralysis Synkinesis.
To address functional and smile dysfunction associated with post-facial paralysis synkinesis, the senior author (B.A.) has offered "modified selective neurectomy" of the lower division of the facial nerve as a long-term solution. This article examines technical considerations and outcomes of this procedure. A retrospective review was conducted of patients who underwent modified selective neurectomy of buccal and cervical branches of the facial nerve performed by a single surgeon over a 4½-year period. House-Brackmann facial grading scores, electronic clinician-graded facial function scale, and onabotulinumtoxinA (botulinum toxin type A) dosages were examined before and after the procedure. Sixty-three patients underwent modified selective neurectomy between June 20, 2013, and August 12, 2017. There were no serious complications. The revision rate was 17 percent. Temporary oral incompetence was reported in seven patients (11 percent) postoperatively. A statistically significant improvement was achieved in electronic clinician-graded facial function scale analysis of nasolabial fold depth at rest, oral commissure movement with smile, nasolabial fold orientation with smile, nasolabial depth with smile, depressor labii inferioris lower lip movement, midfacial synkinesis, mentalis synkinesis, platysmal synkinesis, static score, dynamic score, synkinesis score, periocular score, lower face and neck score, and midface and smile score. There was a significant decrease in botulinum toxin type A dosage and House-Brackmann score after surgery. Modified selective neurectomy of the buccal and cervical divisions of the facial nerve is an effective long-term treatment for smile dysfunction in patients with post-facial paralysis synkinesis. Therapeutic, IV.


Application of spinal ablative techniques for the treatment of benign chronic painful conditions: history, methods, and outcomes.
The literature on current neuroablative techniques for treating benign chronic painful conditions is comprehensively reviewed. To provide the reader with an understanding of the indications, techniques, and outcomes for the various ablative procedures used to treat chronic pain syndromes. Neuromodulatory techniques are rapidly supplanting the traditional neuroablative procedures used to treat many types of pain. A MEDLINE search was conducted for each of the following procedures: radiofrequency facet denervation, cordotomy, myelotomy, sympathectomy, DREZotomy, rhizotomy, and ganglionectomy. In the review of each article, special attention given to the outcome, length of follow-up, complications, and number of patients. Summaries of this data were compiled to provided historical perspective, current techniques, indications, and outcomes for each of the aforementioned procedures. The outcomes cited for each procedure generally represent the data from the three or four largest series with adequate follow-up length. The aforementioned procedures have 30% to 90% success rates, with success defined as at least a 50% reduction in perceived pain. These results tend to diminish with time. However, most are associated with a significant degree of morbidity and relatively high complication rates. In addition, many of the techniques lead to deafferentation pain syndromes. Ablative spinal techniques offer pain relief for many patients, but the use of these methods should be considered carefully in the light of available nondestructive procedures that may achieve similar goals with potentially lower morbidities.


Concentration of extracellular vesicles isolated from blood relative to the clinical pathological status of dogs with mast cell tumours.
Extracellular vesicles (EVs) are membrane-enclosed fragments shed from all cell types, including tumour cells. EVs contain a wide range of proteins, biolipids and genetic material derived from mother cells and therefore may be potential biomarkers for tumour diagnosis, disease progression and treatment success. We studied the effect of canine mast cell tumours (MCTs) on EV concentrations in blood isolates in association with MCT's histological grade, Ki-67 proliferative index, KIT-staining pattern and number of PLT. The average EV concentration in blood isolates from nine dogs with MCTs was considerably higher than that in blood from eight healthy dogs. But there were no statistically significant differences in EVs concentration in the population of dogs with MCT according to a different histological grade of malignancy (Patnaik, Kiupel), KIT-staining pattern and Ki-67 proliferation index. The results show that these variables statistically do not significantly predicted EV concentrations in blood isolates (P > .05), except the KIT-staining pattern I which added statistically significantly to the prediction (P < .05). The results confirmed the impact of neoplasms on the morphological changes to cell membranes, which result in greater vesiculability and higher EV concentrations.


Intravenous ribavirin for hantavirus pulmonary syndrome: safety and tolerance during 1 year of open-label experience. Ribavirin Study Group.
Intravenous ribavirin was provided non-selectively for investigational open-label use among persons with suspected hantavirus pulmonary syndrome (HPS) in the United States between 4 June 1993 and 1 September 1994. Therapy was initiated prior to laboratory confirmation of hantavirus infection because most deaths from HPS occur within 48 h of hospitalization. Thirty patients with confirmed HPS, 105 patients without HPS and 5 patients without adequate diagnostic testing for HPS were enrolled. This observational study arguably provides the most complete information available on ribavirin-associated adverse effects. Although ribavirin was generally well tolerated, 71% of recipients became anaemic and 19% underwent transfusion. An apparent excess of hyperamylasaemia/pancreatitis was either therapy-associated or due to enrollment bias. The 30 enrolled HPS patients had a case-fatality rate of 47% (14/30). It is not possible to assess efficacy with this study design. However, comparison of survival curves for the 30 enrolled HPS patients and 34 patients who developed HPS during the same time period but were not enrolled did not suggest an appreciable drug effect. A randomized, placebo-controlled trial that enrolls patients during the prodrome phase would be necessary to assess the efficacy and further define the safety of intravenous ribavirin for HPS.


Bothrops asper metalloproteinase BaP1 is inhibited by alpha(2)-macroglobulin and mouse serum and does not induce systemic hemorrhage or coagulopathy.
The ability of the P-I metalloproteinase BaP1, isolated from the venom of the snake Bothrops asper, to induce systemic bleeding, thrombocytopenia and defibrinogenation was assessed in an experimental mouse model. Intravenous administration of BaP1 caused neither systemic bleeding nor any evidence of pathology in lungs, kidneys, liver, heart and brain. Moreover, there were no alterations in the whole blood clotting time or in platelet numbers. In addition, BaP1 did not inhibit collagen-induced platelet aggregation in vitro. Proteolytic and hemorrhagic activities of BaP1 were readily inhibited by the plasma proteinase inhibitor, alpha(2)-macroglobulin, and normal mouse serum also inhibited hemorrhage. Such inhibition may explain why BaP1 induces multiple local tissue-damaging effects, but is largely devoid of systemic toxicity.


Clinical presentation of Paget's disease of the bone in older patients.
To determine the clinical presentation and manifestations of Paget's disease of the bone in patients older than 60 years, we reviewed the cases of 56 patients attending a bone clinic. Pain was the presenting symptom in 34 cases. It was attributed to the disease process in 21 cases, to osteoarthritis in 11, to trigeminal neuralgia in 1, and to osteosarcoma in 1. Other clinical manifestations included deformities (15 cases), diminished mobility and unsteady gait (9), hearing impairment (7), lethargy (4), diminished vision (3), cognitive deficit (3), sense of warmth in limbs (2), ill-fitting dentures (1), and fracture (1). We concluded that in patients older than 60 years, Paget's disease of the bone may present itself in a variety of ways, some of which may be mistakenly attributed to the "aging process" or some other disease. Furthermore, in this age group, osteoarthritis is responsible for the pain experienced by about one third of symptomatic patients.


The relationship between plasma membrane lipid composition and physical-chemical properties. III. Detailed physical and biochemical analysis of fatty acid-substituted EL4 plasma membranes.
Murine leukemia EL4 cells were modified by supplementation of culture media with fatty acids for 24 h. A plasma membrane-enriched fraction was prepared from substituted and normal cells. Analyses were performed to determine fatty acyl composition, phospholipid headgroup composition and cholesterol content. The two major membrane phospholipids, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were isolated by thin-layer chromatography and ESR measurements were done on liposomes prepared from these lipids as well as on the intact plasma membrane preparations. Slight perturbations in overall plasma membrane lipid composition were observed when EL4 cells were supplemented with a single exogenous fatty acid. This may be consistent with the idea that the incorporation of exogenous fatty acid induces compensatory changes in membrane lipid composition. On the other hand, we observed no significant difference in two ESR motional parameters between the unsubstituted control and various fatty acid-substituted plasma membranes. ESR measurements carried out on PE and PC liposomes derived from 17:0- and 18:2c-substituted membranes also failed to detect major differences between these liposomes and those made from normal EL4 phospholipids. In the case of liposomes prepared from 18:2t,-substituted membranes, the order parameter was significantly changed from the normal. However, the change was in opposite directions in PE and PC, perhaps accounting for the fact that no change parameter is seen in intact 18:2t-substituted plasma membrane. Measurements of order parameter (S) in mixed lipid vesicles showed that at up to 50 mol% mixture of a synthetic PC with plasma membrane PC, the value of S was only marginally different from that of the plasma membrane PC vesicles. We interpret these data as an indication that the two ESR parameters used are not sufficiently sensitive to detect changes due to modifications of the acyl chain composition of a complex biological membrane.


Does long-lasting hand dermatosis have an influence on everyday living among teenagers?
The purpose of this longitudinal study was to examine a cohort of secondary school pupils, aged 16-19 years (47 females and 18 males) with a 1-year prevalence of hand dermatosis. The study deals with the pupils' history of atopy, self-reported symptoms, exacerbating factors, protection habits, choice of education programme, self-rated health and impact on everyday life. The results showed that 61.5% of the pupils had a history of atopic dermatitis; 78% did not use protective gloves. Females reported use of corticosteroids more often than males. In all, 60% had not been given information at school about future occupational risks, when choosing education. The cohort changed education programme significantly more often than pupils reporting not having hand dermatosis. However, the cohort estimated their health as being as good as that of adolescents in the general population. The neglect of risks in choosing a future profession may cause not only suffering for the individual, but also costs for society.


Genetic characterization of Staphylococcus aureus isolates causing bloodstream infections in Austria.
A total of 112 Staphylococcus aureus bloodstream isolates were genetically characterized. Spa typing and DNA microanalysis exhibited high diversity, resulting in 64 different spa types and 9 different SplitsTree clusters. Methicillin-resistant S. aureus (MRSA) were found in 6 cases only, including the first case of life-stock-associated MRSA (MRSA ST398) in bloodstream infection in Austria.


[8-Quinolinol-5-sulfonic acid-loaded resin as a preconcentrating agent in the neutron activation analysis of the chalcophile elements (author's transl)].
A chelating agent-loaded resin consisting of 8-quinolinol-5-sulfonic acid and an anion-exchange resin (HOx-resin) was prepared in order to concentrate trace chalcophile elements in natural water samples selectively before neutron activation analysis. The exchange capacity of the Diaion SA No. 100 for the reagent (1.8 meq . g-1 resin) corresponds approximately to that for chloride ion (1.83 meq . g-1 resin), indicating that 8-quinolinol-5-sulfonic acid is adsorbed quantitatively on the exchange site of the resin through the sulfonate anion in the reagent. The basic conditions for the adsorption of the metal ions on the resin were investigated by employing the column method. The nitrate concentration and the pH of the sample solution affect the adsorption behavior of metal ions. Several solutions containing metal ions with varying pH or varying nitrate concentration were applied to the resin column (35 mm x 7 mm phi) with a flow rate of 2.0 cm3 . min-1. As a result, the optimum conditions for the quantitative adsorption of copper(II), zinc(II), cadmium(II), cobalt(II), nickel(II) and manganese(II) were as follows: NO3- less than 0.01 mol . dm-3 pH greater than 4.6. Furthermore, the feasibility of the above conditions as well as quantitative adsorption of the chalcophile elements was confirmed through the neutron activation analysis of the synthesized metal solutions.


In what clinical settings should Cushing's syndrome be suspected?
Despite its low frequency, endogenous Cushing's syndrome is not an exceptional clinical entity. A growing number of cases are currently derived to specialized centers suggesting an increasing knowledge of the clinical features of hypercortisolism by specialists of diverse branches of clinical medicine. Clinical signs derive from an exaggeration of the physiological actions of cortisol inducing protein breakdown, hyperglycemia, fat mobilization, dyslipidemia, hydrosaline retention, immunosuppression and increased susceptibility to infection. Despite its low specificity, symptoms such as unexplained development of central obesity, mood changes, fatigue, weakness, myopathy, easy bruisability, red striae, arterial hypertension, diabetes and hyperlipidemia, are suggestive of the diagnosis. From an epidemiological point of view, Cushing's syndrome is to be suspected and consequently searched for among patients with uncontrolled high blood pressure or diabetes mellitus, metabolic syndrome, polycystic ovarian syndrome, osteoporosis, depression or adrenal incidentaloma. True Cushing's syndrome has to be differentiated from pseudo syndromes. Most sensitive physical signs for discriminating Cushing's syndrome from pseudo-Cushing states are the presence of supraclavicular fat pads, myopathy, thin skin and easy bruising. The recognition of the clinical manifestations of Cushing's syndrome and of the sub-populations at risk of contracting the disease should be improved through medical education at the medical school and at postgraduate levels. Clinical detection of Cushing's syndrome must be performed mainly by non-endocrinologists, yet its etiological diagnosis and therapeutic management is to be carried out in highly experienced and specialized centers, to ensure the best results in the treatment of this really challenging endocrine disturbance.


Cyclodextrin dimers as receptor molecules for steroid sensors.
The dansyl-modified dimer 9 complexes strongly with the steroidal bile salts. Relative to native beta-cyclodextrin, the binding of cholate (1a) and deoxycholate (1b) salts is especially enhanced. These steroids bind exclusively in a 1:1 fashion. For other bile salts (1c-1e) both 1:1 and 1:2 complexes were observed with stabilities similar to those of native beta-cyclodextrin. This indicates that only one cavity is used, with a small contribution from the second. The difference is attributed to the absence of a 12-hydroxy group in the second group of steroids. Comparison with a dimer that lacks the dansyl moiety (6) shows that this group especially hinders the cooperative binding of la and 1b. The smaller interference in the binding of the other steroids indicates that self-inclusion of the dansyl moiety hardly occurs. This weak self-inclusion is supported by fluorescence studies. The dansyl fluorescence of dimer 9 is less blue-shifted than that of other known dansyl-appended cyclodextrin derivatives; this is indicative of a more polar micro-environment. Addition of guests causes a change in fluorescence intensity.


Nutrition and nonalcoholic fatty liver disease in children.
Nonalcoholic fatty liver disease (NAFLD) is an obesity-associated liver disease found in 3% to 9% of children in the United States. NAFLD represents a spectrum of liver disease and is frequently associated with features of the metabolic syndrome. Nutrition's role in NAFLD is complex. It does not appear that overweight children with NAFLD have an unusual diet compared with their overweight counterparts without NAFLD. It is more likely that they have increased genetic susceptibility to the general poor diet and state of positive calorie balance currently found in many children. The available treatment studies using nutrition counseling and increased physical activity are promising. We recommend initiating sustainable family-oriented lifestyle changes in all children with NAFLD.


Acanthamoeba keratitis.
The incidence of Acanthamoeba keratitis has decreased significantly, and it is no longer a reportable condition in the United States. Corneal abrasion and contact lenses play an important role in the development of Acanthamoeba keratitis. One of the most important features of the disease is severe pain, which is atypical for herpes simplex. The pathognomonic sign for Acanthamoeba is radial neuritis or inflammation around the corneal nerve caused by the parasites. The most important step in prevention of Acanthamoeba keratitis is effective education of patients about the care of contact lenses. A combination of Brolene and Neomycin is the best approach in treating Acanthamoeba keratitis. However, if treatment with these drugs fails, clotrimazole is recommended.


Hepatitis C transmission and infection by orthotopic heart transplantation.
The transmission and clinical consequences of hepatitis C viral (HCV) infection acquired by orthotopic heart transplantation (OHT) from an HCV-infected donor to an HCV-naive recipient have not been well described. We report our experience in 5 HCV-naive patients who were transplanted with hearts from HCV-positive donors. All transplants occurred within a 1-year period. After cardiac transplantation we retrospectively examined the recipients' clinical course, liver-associated enzymes, HCV-antibody serology, quantitative HCV RNA level, and HCV genotype. Five subjects with rapidly deteriorating heart failure and negative serum antibodies to HCV received an emergent OHT from a donor known to be infected with HCV. Liver-associated enzymes peaked at 2 to 6 weeks post-transplant: mean peak alanine aminotransferase was 180 U/L (normal, 9 to 52) and aspartate aminotransferase was 111 U/L (normal, 14 to 36). Liver enzymes had returned to normal limits by 6 and 12 months post-OHT. At a mean 15 months after transplantation, only 1 of 5 patients has developed antibodies to HCV, but 4 of 5 have evidence of infection, as shown by serum HCV RNA. No patient has developed evidence of liver failure. (1) Transmission of HCV from an HCV-positive donor to an HCV-naive recipient at the time of OHT is likely. (2) Antibodies to HCV post-OHT may remain negative for more than 1 year in these patients. (3) Hepatitis C viral RNA using polymerase chain reaction should be the test of choice for diagnosis of HCV infection post-OHT. (4) Hepatitis C viral donor hearts should be limited to critically ill patients in extremis until the long-term consequences of acquisition of HCV by an OHT recipient are known.


Age-related alterations in gonadotropin, adrenocorticotropin and growth hormone secretion.
This review addresses some relevant aspects of the aging of the neuroendocrine system, particularly the reproductive and the adrenocortical axis. Deterioration of the reproductive function, one of the most striking endocrine alterations occurring in aging, is related to a complex interplay of factors. They comprise alterations occurring at the level of all the three components of the reproductive axis, the gonads, the pituitary and the brain, acting synergistically to disrupt the normal pulsatile release of gonadotropins. Particular relevance is given to the neurotoxic action of estrogens during the constant estrous phase occurring in aged female rodents, at the level of hypothalamic nuclei regulating gonadotropin secretion. This effect, to be found also in women during the anovulatory period of the perimenopause, would worsen the dysregulation of the central mechanisms controlling the reproductive function. The activity of the adrenocortical (HPA) axis increases with advancing age in rodents but also, although less strikingly, in humans. The main alteration which can be evidenced in both species is a delayed post-stimulus decline in plasma corticosteroid levels, indicating a diminished sensitivity to glucocorticoids of HPA axis feedback regulation in the elderly. Increased exposure to the highly catabolic adrenal glucocorticoids appears to be associated to a loss of cerebral neurons, particularly in the hippocampus, and the emergence of cognitive deficits in the aged rats. The relevance of experimental data performed in rodents to healthy and pathological human aging is extensively discussed. Finally, this chapter considers the age-related impairment in growth hormone secretion, a common finding of all the animal species investigated so far. The etiology of the hyposomatotropism of aging is namely linked to a progressive defect in growth hormone releasing hormone-producing hypothalamic neurons, although alterations of somatostatin-producing neurons have also been described. This background knowledge makes the use of neuroactive compounds aimed at restoring the physiologic function of hypothalamic hypophysiotropic hormones a rational approach to rectify the alterations of the neuroendocrine system occurring in elderly individuals.


[Standardization of forced spirometry. Analysis of the basal pulmonary function (PEF, FEF2575, FEF50) in a selected group of children].
This is a study of the ventilatory function (FEF2575, FEF50, PEF) by dry spirometer Vitalograph in 1,566 children of both sexes with ages ranging from 7 to 14 years; 1,156 children (73.6%) were selected as reference population. Height was the biometric parameter with the greatest correlation to the functional variables studied in both sexes, except to PEF in females. Significant differences were observed in functional variables between male and female subjects. Multiple and simple linear regression equations and percentiles tables for each sex are presented.


Cerebrovascular risk factors in Alzheimer's disease: brain hemodynamics and pharmacogenomic implications.
Recent evidence indicates that different vascular risk factors are present in Alzheimer's disease (AD) and other prevalent dementia types probably contributing to deterioration of cerebrovascular function, thus enhancing neurodegeneration and premature neuronal death due to a reduction in brain perfusion. Brain blood flow shows a reduced velocity and increased pulsatility (PI) and resistance indices (RI) in different types of dementia and in diabetes and hypertension, as well. High levels of diastolic blood pressure correlate with diminished brain blood flow and elevated PI and RI, accompanied by cognitive deterioration. Nitric oxide (NO) levels are found increased in the sera and brain tissue of AD patients. Vascular risk factors (hyperglycemia, LDL-cholesterol, triglycerides, hypertension) and altered brain hemodynamic parameters correlate with APOE genotypes of which APOE-4/4 carriers represent the AD population with the highest cerebrovascular risk. In addition, the genomic profiles of patients with dementia integrating AD-related genes (APOE, PS1, PS2, cFOS) in a mini-tetragenic haplotype significantly differ from controls with an absolute genetic variation of about 50%-60%. Cerebrovascular dysfunction is a factor common to most types of dementia; however, genetic variation among different dementia types might be determinant for the activation of early vascular events inducing or accelerating neurodegeneration. In this regard, cerebrovascular dysfunction should be considered a potential therapeutic target in dementia.


Nickel-catalyzed direct thiolation of C(sp(3))-H bonds in aliphatic amides.
Nickel-catalyzed thiolation of the inactivated methyl C(sp(3))-H bonds of aliphatic amides with disulfide is described. It is a novel strategy for the synthesis of thioethers with the ultimate goal of generating thioether carboxylic acids with various functional groups.


Synthesis of analogs of forodesine HCl, a human purine nucleoside phosphorylase inhibitor-Part II.
Forodesine HCl is being investigated as a potential therapeutic target for the control of T-cell proliferation. During the filing process for a New Drug Application (NDA) it became evident that there was a need to synthesize some stereo-isomers of forodesine HCl. Herein we present the synthesis of these three novel compounds (2-4).


Work and vocational psychology: theory, research, and applications.
Work is integral to human functioning, and all psychologists need to understand the role of work in people's lives. Understanding factors influencing work choices and helping individuals effectively make career decisions is the focus of vocational psychologists. However, external changes, such as shifts in the economy and labor force, as well as initiatives within the field are challenging the assumptions within vocational psychology. This chapter reviews the empirical work since 1995 in four areas: (a) what factors influence career choices, (b) how people make career decisions, (c) how context influences career choices, and (d) effective interventions for help with the first three questions. The review focuses first on vocational psychology's rich tradition of theoretically driven research, and then discusses research in career development that crosses a number of theoretical approaches, and finally identifies the assumptions in the field and questions for future examination.


Conceptual and perceptual memory: retrieval orientations reflected in event-related potentials.
In memory retrieval, search can be guided by mental sets towards different subsets of the available evidence. Such retrieval orientations have been suggested to leave an imprint on event-related potentials (ERPs). The present study aimed at characterizing orientations towards perceptual and conceptual evidence in a recognition task, where pictures and words were studied. In the recognition test, items were presented in either the same format as at study or in the opposite format. A between-subjects manipulation modified the task, instructing an Exclusion group to endorse only items that preserved their format from study, and an Inclusion group to endorse both formats of a studied item. It was hypothesized that exclusion instructions would instill a perceptual and inclusion instructions a conceptual orientation. As a corollary, instructions were expected to dissociate the high end from the low end of the picture-word mirror effect. This expectation was confirmed in a behavioural experiment. In an ERP experiment, retrieval orientations were examined in their effects on correct rejections of new pictures and words. Confirming earlier findings [Hornberger, M., Morcom, A. M., & Rugg, M. D. (2004). Neural correlates of retrieval orientation: effects of study-test similarity. Journal of Cognitive Neuroscience, 16(7), 1196-1210], a perceptual orientation was accompanied by more positive-going amplitudes over widespread areas. The difference was larger for pictures than for words, supporting behavioural evidence that new pictures are more easily rejected on perceptual grounds than are new words. The Exclusion group showed no ERP evidence of cross-format old-new effects, despite reaction times indicative of involuntary conceptual recognition. The results indicate that perceptual and conceptual retrieval orientations imprint distinct signatures on ERPs. They further suggest that the examined old-new effects in ERPs are mainly linked to voluntary aspects of memory, even in a task where involuntary memory exerts effects on reaction times.


Outer membrane proteins profiles of Pseudomonas aeruginosa after the post-antibiotic effect of imipenem.
A suppression of bacterial growth of three Pseudomonas aeruginosa strains after 30 min treatment with imipenem at supra-inhibitory concentrations (post-antibiotic effect; PAE) was observed. Imipenem (4x MIC) showed PAEs in the range of 0.5-0.9 h for stains studied. The PAEs manifested by imipenem at 8x MIC concentration varied between 2.4 and 4.0 h. Supra-inhibitory concentrations of imipenem did not affect the profiles of the outer membrane proteins of the stains. The treated strains revealed the same protein bands (45, 38, 35 and 23 kD) compared with controls.


How to improve exposure of tumor cells to drugs: promoter drugs increase tumor uptake and penetration of effector drugs.
Solid tumors are characterized by an abnormal architecture and composition that limit the uptake and distribution of antitumor drugs. Over the last two decades, drugs have been identified that improve the tumor uptake and distribution of drugs that have direct antitumor effects. We propose to refer to these drugs as promoter drugs, and as effector drugs to drugs that have direct antitumor effects. Some promoter drugs have received regulatory approval, while others are in active clinical development. This review gives an overview of promoter drugs, by classifying them according to their mechanism of action: promoter drugs that modulate tumor blood flow, modify the barrier function of tumor vessels, induce tumor cell killing, and overcome stromal barriers. Eventually, we discuss those that we feel are the main conclusions to be drawn from promoter drug research that has been performed so far, and suggest areas of future investigation to improve the efficacy of promoter drugs in cancer therapy.


[Cerebellar hypoplasia in the newborn: association with respiratory control disorders and mental retardation].
Cerebellum malformations are frequently diagnosed since the advent of the neuroradiological studies (computed tomography, magnetic resonance imaging and ultrasonography). Cerebellar hypoplasia is found in association with a wide variety of neurologic and systemic disorders. Clinical picture in newborn may be different than in other periods of life. Two characteristics are interesting in neonatal period: their relation with abnormal respiratory control and mental retardation. The pathophysiology of cerebellar hypoplasia is uncertain, however experimental studies suggest than an abnormality of the Bergman glia may lead to the observed granulle cell layer deficiency in this malformation. It is tempting to speculate that a similar migrational abnormality in the cerebrum accounts for the intellectual impairment seen in some affected patients. Respiration is a complex neural function requiring precise coordination of numerous neural circuits. Cerebellar hypoplasia may be important in the pathogenetic mechanism of abnormal respiratory control due to cerebellar respiratory control disturbance. Also diaphragmatic dysfunction may occur in association with cerebellar atrophy. We report two newborns with cerebellar hypoplasia (vermis and hemispheres) associated with central respiratory and neurological dysfunction, and mental retardation.


Focal Hypoperfusion in Acute Ischemic Stroke Perfusion CT: Clinical and Radiologic Predictors and Accuracy for Infarct Prediction.
Perfusion CT may improve the diagnostic performance of noncontrast CT in acute ischemic stroke. We assessed predictors of focal hypoperfusion in acute ischemic stroke and perfusion CT performance in predicting infarction on follow-up imaging. Patients from the Acute STroke Registry and Analysis of Lausanne data base with acute ischemic stroke and perfusion CT were included. Clinical and radiologic data were collected. We identified predictors of focal hypoperfusion using multivariate analyses. From the 2216 patients with perfusion CT, 38.2% had an acute ischemic lesion on NCCT and 73.3% had focal hypoperfusion on perfusion CT. After we analyzed 104 covariates, high-admission NIHSS, visual field defect, aphasia, hemineglect, sensory deficits, and impaired consciousness were positively associated with focal hypoperfusion. Negative associations were pure posterior circulation, lacunar strokes, and anticoagulation. After integrating radiologic variables into the multivariate analyses, we found that visual field defect, sensory deficits, hemineglect, early ischemic changes on NCCT, anterior circulation, cardioembolic etiology, and arterial occlusion were positively associated with focal hypoperfusion, whereas increasing onset-to-CT delay, chronic vascular lesions, and lacunar etiology showed negative association. Sensitivity, specificity, and positive and negative predictive values of focal hypoperfusion on perfusion CT for infarct detection on follow-up MR imaging were 66.5%, 79.4%, 96.2%, and 22.8%, respectively, with an overall accuracy of 76.8%. Compared with NCCT, perfusion CT doubles the sensitivity in detecting acute ischemic stroke. Focal hypoperfusion is independently predicted by stroke severity, cortical clinical deficits, nonlacunar supratentorial strokes, and shorter onset-to-imaging delays. A high proportion of patients with focal hypoperfusion developed infarction on subsequent imaging, as did some patients without focal hypoperfusion, indicating the complementarity of perfusion CT and MR imaging in acute ischemic stroke.


[A man with a palpable node on the prostate].
A 64-year-old man was referred to our urology outpatient clinic with lower urinary tract symptoms (LUTS). During rectal examination a smooth nodule was identified. MRI-images showed a prostatic cyst, originating from the utriculus. An utriculus cyst is a relatively rare finding and originates from a persistent remnant of the Müllerian duct.


Mapping, genetic effects, and epistatic interaction of two bacterial canker resistance QTLs from Lycopersicon hirsutum.
Two quantitative trait loci (QTL) from Lycopersicon hirsutum, Rcm 2.0 and Rcm 5.1, control resistance to Clavibacter michiganensis subsp. michiganensis ( Cmm). To precisely map both loci, we applied interval mapping techniques to 1,056 individuals in three populations exhibiting F(2) segregation. Based on a 1-LOD confidence interval, Rcm 2.0 mapped to a 14.9-cM interval on chromosome 2 and accounted for 25.7-34.0% of the phenotypic variation in disease severity. Rcm 5.1 mapped to a 4.3-cM interval on chromosome 5 and accounted for 25.8-27.9% of the phenotypic variation. Progeny testing of recombinant plants narrowed the QTL location for Rcm 2.0 to a 4.4-cM interval between TG537-TG091 and to a 2.2-cM interval between CT202-TG358 for Rcm 5.1. A population of 750 individuals exhibiting F(2) segregation was used to detect epistasis between both loci using ANOVA and orthogonal contrasts ( P=0.027), suggesting that resistance was determined by additive gene action and an additive-by-additive epistatic interaction. A partial diallel mating design was used to confirm epistasis, advance superior genotypes, randomize genetic backgrounds, and create recombination opportunities. This crossing scheme created a more balanced population ( n=112) containing the nine F(2) genotypic classes. Parents in the diallel were selected from the previous population based on resistance, genotype at the Rcm 2.0 and Rcm 5.1 loci, and horticultural traits. A replicated trial using the diallel population confirmed additive-by-additive epistasis ( P<0.0001). These results validate the gene action, intra -locus interaction, and map position of two loci controlling resistance to Cmm.


Technical note: a landmark-based approach to the study of the ear ossicles using ultra-high-resolution X-ray computed tomography data.
Previous study of the ear ossicles in Primates has demonstrated that they vary on both functional and phylogenetic bases. Such studies have generally employed two-dimensional linear measurements rather than three-dimensional data. The availability of Ultra- high-resolution X-ray computed tomography (UhrCT) has made it possible to accurately image the ossicles so that broadly accepted methodologies for acquiring and studying morphometric data can be applied. Using UhrCT data also allows for the ossicular chain to be studied in anatomical position, so that it is possible to consider the spatial and size relationships of all three bones. One issue impeding the morphometric study of the ear ossicles is a lack of broadly recognized landmarks. Distinguishing landmarks on the ossicles is difficult in part because there are only two areas of articulation in the ossicular chain, one of which (the malleus/incus articulation) has a complex three-dimensional form. A measurement error study is presented demonstrating that a suite of 16 landmarks can be precisely located on reconstructions of the ossicles from UhrCT data. Estimates of measurement error showed that most landmarks were highly replicable, with an average CV for associated interlandmark distances of less than 3%. The positions of these landmarks are chosen to reflect not only the overall shape of the bones in the chain and their relative positions, but also functional parameters. This study should provide a basis for further examination of the smallest bones in the body in three dimensions.


Apoptogenic interactions of plasmalemmal type-1 VDAC and Aβ peptides via GxxxG motifs induce Alzheimer's disease - a basic model of apoptosis?
Human type-1 porin/VDAC (voltage-dependent anion channel) carries a GxxxG motif in its N-terminal part, traversing the β-barrel, while the Alzheimer's disease (AD) relevant amyloid peptides Aβ1-42 and Aβ1-40 show a series of corresponding motifs close to their C-terminus. GxxxG motifs are established as aggregation/membrane perturbation motifs. These peptide primary structure data support a proposal I recently made on the basis of a synopsis of recent literature. Accordingly, amyloid Aβ, cut from APP by beta-secretase BACE1 and gamma-secretase, has been insinuated to induce Alzheimer's disease via apoptosis by opening type-1 porin/VDAC in cell membranes of hypometabolic neuronal cells. Considering the ubiquitous expression modus of APP, beta- and gamma-secretases and type-1 VDAC/eukaryotic porin a basic model of apoptosis might be given.


Studies on the GPI-anchored enzyme, hepatic 5'-nucleotidase. Microheterogeneity of the anchor, processing and localization.
Hepatic 5'-nucleotidases of vertebrates were investigated for localization in the lysosomes and the plasma membrane, microheterogeneity of the glycosylphosphatidylinositol (GPI)-anchor moiety and minimal requirement of the C-terminal signal peptide for GPI attachment. Using PIPLC of Bacillus thuringiensis and subcellular fractionation by Percoll gradient centrifugation, we found that chicken liver 5'-nucleotidase can be transferred from plasma membrane to lysosomes in the GPI-anchored or soluble form. Bovine liver ecto 5'-nucleotidase was solubilized by PIPLC, purified to a homogeneous state, and analyzed for the structures of GPI-anchor isoforms by HPLC and ESI-MS in combination with glycosidase treatments, after peptide-bond cleavage by CNBr or trypsin. Several isomers of the GPI anchor were thus characterized; major components contained two phosphorylethanolamine residues, whereas the component containing three phosphorylethanolamine residues was present only as a small percentage of the total. The cleavage/attachment site of the GPI anchor in the C-terminal of 5'-nucleotidase was shown to be Ser523. The peptide region cleaved off at the posttranslational processing has a length of 25 amino acid residues which contains a hydrophobic stretch of 17 amino acids. By site-directed mutagenesis, we determined the minimal length of the hydrophobic peptide to be 13 amino acids for expression of 5'-nucleotidase as a GPI-anchored form on the COS cell surface. When peptide length was shortened to less than 13 amino acids, the expressed enzyme was not sorted to the cell surface but present within, or secreted out of the cells.


Changing the behaviour of children living in Dutch disadvantaged neighbourhoods to improve breakfast quality: Comparing the efficacy of three school-based strategies.
Children's breakfast habits are suboptimal. A novel school-based education programme was developed and tested with the aim of improving children's attitude, knowledge and breakfast quality. A pre- and post-test design was used with four conditions: group-based education, role modelling, tailored feedback with goal setting, and a combination of these three delivery modes. Two hundred eighty children from disadvantaged communities (9.3 ± 0.8 years) participated in three lessons at school over a two-month period. Children's attitude, knowledge and breakfast behaviour were evaluated by a pre- and post-questionnaire completed by the children. A follow-up measure was executed at 24 weeks. The data were analysed by repeated measures ANOVA. At baseline, 90% of the children ate breakfast on the measurement day; 60-76% of the children ate breakfast daily. Between pre- and post-test, a significant time effect was found for children's attitude, self-efficacy, knowledge and behaviour (all p < 0.05). Children in the feedback condition improved most favourably: correct classification of breakfast products increased by 10 products (out of 44) and breakfast quality score improved by 25 points (on a 100-point scale). The feedback condition also resulted in positive changes in the home setting. The follow-up test showed a decline in children's knowledge and their breakfast quality across conditions. To conclude, this study showed that a three-lesson school programme based on individual feedback and goal setting is most effective for changing knowledge on breakfasting and self-reported breakfast quality among children aged 8-10 years living in disadvantaged neighbourhoods. To maintain effectiveness, longer-term programmes embedded in the school curriculum are needed to enhance breakfast quality. Future research should explore the optimal duration and intensity of such programmes and should incorporate the topic of suitable portion sizes.


Hand assisted laparoscopic radical nephrectomy for renal carcinoma using a new abdominal wall sealing device.
We report our initial experience with a hand assisted laparoscopic radical nephrectomy for patients with renal carcinoma, and compare our results to those of conventional open radical nephrectomy. The clinical data on 6 consecutive patients who underwent hand assisted laparoscopic radical nephrectomy for stage T1N0M0 renal cell carcinoma were reviewed. We performed hand assisted laparoscopic surgery using the new LAP DISC* abdominal wall sealing device. We compared the results of this procedure with those of conventional open radical nephrectomy in 12 patients with stage T1N0M0 renal cell carcinoma. The hand assisted laparoscopic radical nephrectomy for renal carcinoma was successfully performed without any major or minor complications in all 6 patients. Mean operation time for the laparoscopic group was significantly longer than that for the open surgery group (303 minutes versus 224 minutes, p = 0.0042). However, no significant difference was observed in mean estimated blood loss for the 2 groups (264 ml. in the laparoscopic group versus 341 ml. in the open surgery group). The frequency of parenteral analgesia postoperatively in the laparoscopic group was significantly lower than that in the open surgery group (16.7% versus 75.0%, p = 0.043). In addition, the laparoscopic group seemed to recover more rapidly than the open surgery group. The abdominal wall sealing device was easy to attach to the abdominal wall, and allowed rapid hand removal and reinsertion. Our preliminary results indicate that a hand assisted laparoscopic radical nephrectomy with the abdominal wall sealing device is an effective and safe surgical procedure, and is less invasive than open radical nephrectomy.


[Transfusion medicine: debate, field of application, the stakes].
Transfusion medicine has aroused much controversy as to the definition of its field of application, as the Etablissement Français du Sang (EFS) is being set up. One argument put forward by supporters of transfusion medicine in hospital--including nominal attribution and clinical immunohematology--is the possible influence of blood component producers on the decisions of prescribers. The EFS considers transfusion medicine as the rationale underlying a therapeutic chain applied to blood products and possibly to cell therapy products, within a coherent structure. Any disruption in the chain would result in reduced visibility at each stage of the chain, diluted responsibilities, and less efficient communication between blood collection and actual needs. It is, however, extremely important to clearly distinguish between the activities related to the production of biological products for therapeutic use from the activities of evaluation, in the setting of clinical protocols, which are the clinicians' responsibility. The EFS views the production of blood components as one of the various aspects of its missions as a transfusion medicine operator. The involvement of blood transfusion centers in the development of biotechnologies is a historical reality which justifies EFS's ambition to integrate cell therapy activities within its field of competence. The EFS, with its 18 blood transfusion centers, will have to play a part in health care, research and teaching networks, at the regional or inter-regional level. Irrespective of the progress achieved in substitution products and the evolution to be expected in transfusion-related jobs, transfusion as a discipline must maintain its coherence to be able to better assume its responsibilities.


The influence of model order reduction on the computed fractional flow reserve using parameterized coronary geometries.
Computational fluid dynamics (CFD) models combined with patient-specific imaging data are used to non-invasively predict functional significance of coronary lesions. This approach to predict the fractional flow reserve (FFR) is shown to have a high diagnostic accuracy when comparing against invasively measured FFR. However, one of the main drawbacks is the high computational effort needed for preprocessing and computations. Hence, uncertainty quantification may become unfeasible. Reduction of complexity is desirable, computationally inexpensive models with high diagnostic accuracy are preferred. We present a parametric comparison study for three types of CFD models (2D axisymmetric, Semi-3D and 3D) in which we study the impact of model reduction on three models on the predicted FFR. In total 200 coronary geometries were generated for seven geometrical characteristics e.g. stenosis severity, stenosis length and vessel curvature. The effect of time-averaged flow was investigated using unsteady, mean steady and a root mean square (RMS) steady flow. The 3D unsteady model was regarded as reference model. Results show that when using an unsteady or RMS flow, predicted FFR hardly varies between models contrary to using average flows. The 2D model with RMS flow has a high diagnostic accuracy (0.99), reduces computational time by a factor 162,000 and the introduced model error is well below the clinical relevant differences. Stenosis severity, length, curvature and tapering cause most discrepancies when using a lower order model. An uncertainty analysis showed that this can be explained by the low variability that is caused by variations in stenosis asymmetry.


Amyloidosis in leprosy.
Histopathologic studies were performed on systemic amyloidosis of leprosy patients in two Japanese leprosaria. Amyloid deposits were observed in 23 of 50 cases (46%) autopsied from 1955 to 1959 (Group A), and in 17 of 110 cases (15.4%) from 1962 to 1971 (Group B). These incidences are higher than those of the pre-chemotherapeutic period in Japan. The average age of amyloidal cases was significantly lower than that of nonamyloidal cases in both groups. There was no predilection for either type of leprosy in Group B. Pyelonephritis was frequently observed in both groups; the incidence of amyloidosis in Group B correlated with pyelonephritis. Amyloid deposits may be related to renal disorders associated with lepra reactions or inflammatory lesions. Amyloidosis has been classified into primary and secondary type, but the criteria seem uncertain. We referred to a classification based on immunologic finginds. In the severely affected lesion of the kidney of one case, we observed foci of foreign body type giant cells, suggesting a possibility of resorptive process in human renal amyloidosis.


Urinary enzyme measurements as early indicators of renal insult in type 2 diabetes.
The association between urine microalbumin, alpha1-microglobulin concentration (alpha1MG) and the urinary enzyme activities of alanine aminopeptidase (AAP), N-acetyl-beta-D-glucosaminidase (NAG), alpha-glutathione-S-transferase (alphaGST) and pi-glutathione-S-transferase (piGST) is investigated in 36 type 2 diabetic and 15 age- and sex-matched non-diabetic subjects. Diabetic subjects were grouped into those with microalbuminuria <3 mg/L (group A: 7M/5F), 3-30 mg/L (group B: 5M/7F) and 30-300 mg/L (group C: 6M/6F). While serum creatinine concentration remained within the laboratory reference range (<115 mmol/L) in all experimental groups, alpha1MG excretion increased with the severity of microalbuminuria (control group and groups A, B and C mean [SD] values were 1.3 [0.21], 1.6 [0.11], 2.18 [0.42] and 2.8 [0.51] mg/mmol urinary creatinine, respectively). Activities of NAG (U/mmol creatinine) were significantly elevated in groups A, B and C at 98.7 (8.6), 112.8 (12.9) and 147.4(16.2), respectively, compared with the reference range <35 U/mmol creatinine (group C vs. groups A and B: P < 0.01). Activity of AAP (U/mmol creatinine) was significantly elevated in groups B and C at 7.6 (0.5) and 7.9 (0.6), respectively (both P < 0.001), compared to the control and group A values (2.5 [0.2]). Activity of piGST (U/mmol creatinine) was elevated in groups B and C at 2.6 (0.4) and 2.8 (0.5), respectively (both P < 0.001), compared to the control and group A values (1.1 [0.1]). Similarly, urine piGST activity was also elevated in groups B and C at 2.9 (0.6) and 3.1 (0.5), respectively (both P < 0.001), compared to control and group A values (1.3 [0.1] and 1.4 [0.2]). These results suggests that site-specific urinary biochemical markers provide valuable information about early renal proximal and distal tubular insult that ultimately may precede enhanced glomerular permeability in subjects with type 2 diabetes.


Kinetic parameters and thermodynamic values of beta-xylosidase production by Kluyveromyces marxianus.
Kinetic parameters for production of beta-xylosidase by Kluyveromyces marxianus were determined in growth media containing glucose, xylose, cellobiose, sucrose and lactose as carbon sources. K. marxianus achieved maximum beta-xylosidase specific product yield (Y(P/X)) when grown on xylose. Basal level of activity was achieved in cultures grown on glucose. Kinetic parameters of enzyme production and cell mass formation were correlated. Enzyme synthesis was regulated by an induction mechanism and growth-dependent repression mechanism. Thermodynamic analysis revealed that the cell system exerted protection against thermal inactivation. A partially purified enzyme showed good stability when incubated at 60 degrees C and was quite stable at a pH of 5.0-7.0 and may be exploited for commercial applications.


[Effect of eggplant on plasma lipid levels, lipidic peroxidation and reversion of endothelial dysfunction in experimental hypercholesterolemia].
To study the effect of egg plant on endothelium-dependent relaxation, and plasma lipids in hypercholesterolemic rabbits, and to assess influence of this plant on the malondialdehyde (MDA) content of LDL particles and the arterial wall. Thirteen male rabbits were randomly assigned to control (C), hypercholesterolemic (H) and egg plant (E) treated groups (n = 10 each). The H and E rabbits were fed a diet supplemented with cholesterol (0.5%) and coconut oil (10%) for 4 weeks. In addition, group E received 10 mL of the fruit juice/day during the last 2 weeks. The animals were killed and the aorta removed to measure MDA content and the endothelium dependent relaxation responses. Total plasma cholesterol, VLDL, LDL, HDL and triglyceride levels were determined using commercial kits. MDA was quantified in native and oxidized LDL and in the arterial wall. After 4 weeks, the E group rabbits had a significantly lower weight, plasma cholesterol, LDL, triglyceride and aortic cholesterol content than group H(p < 0.05). The MDA content that was significantly increased in the LDL particles and in the arterial wall of H rabbits was reduced in the E group (p < 0.05). Endothelium-dependent relaxation were significantly higher in the E group compared H group rabbits (p < 0.05). In hypercholesterolemic rabbits egg plant juice significantly reduced weight, plasma cholesterol levels, aortic cholesterol content and the MDA concentrations in native-oxidized LDL and in the arterial wall and increased the endothelium-dependent relaxations.


A new species of Fibularia from Japanese waters with a redescription of F. japonica and F. ovulum (Echinodermata: Echinoidea: Clypeasteroida).
A new species, Fibularia coffea sp. nov., occurs from shallow waters in Japan. This new species is distinguished from the other species of Fibularia by the following characters: test height is low, oral surface is slightly depressed toward the peristome, number of pores of petal III continues to increase with the test growth, reaching over 30 at TL > 7.5 mm, and black pigments form symmetric pentaradial on aboral surface in living animals. Two further Japanese species, Fibularia japonica and F. ovulum, are redescribed based on the type specimens (F. japonica) and additional specimens (F. ovulum), respectively. A tabular key to the extant species of Fibularia is also provided. A partial fragment of the mitochondrial gene cytochrome oxidase subunit I (COI) of the type specimens of F. coffea sp. nov. and the additional specimen of F. japonica was sequenced for barcoding in future works.


Synthesis and cyclooxygenase inhibitory properties of novel (+) 2-(6-methoxy-2-naphthyl)propanoic acid (naproxene) derivatives.
Halomethylation of naproxene (1) occurs regioselectively in position 5 and subsequently--in situ or on treatment with silver nitrate--leads to naproxene-"dimers" with two naproxene units, 5,5'-connected through a ethenylene (3) and a methylene (4) bridge, respectively. Two of the new naproxene derivatives were screened for their cyclooxygenase inhibitory properties relative to naproxene. Both 5-chloromethyl naproxene (2) and 2-(5-((carboxyethyl)-2-methyloxynaphthyl)-6-methoxy-2-naphthyl)propanoic acid (4) were inactive in the concentration range of 0.1-10 mumole against both COX-1 and COX-2, indicating that bulky substituents in position 5 in naproxene are unfavourable for both COX-1 and COX-2 inhibition.


Measurement of activation of the endoplasmic reticulum stress response in autoimmune myositis.
Evidence suggests that both immune (cell-mediated and humoral) and nonadaptive immune (endoplasmic reticulum (ER) stress and autophagy) mechanisms play a role in muscle fiber damage and dysfunction in idiopathic inflammatory myopathies (IIM). More recently, the ER stress response pathway, the activation of unfolded protein response, and the ER overload response are being studied to understand their contribution in the progression of IIM. A variety of qualitative and quantitative techniques are used to measure the activation of the endoplasmic reticulum stress response in myopathy. Accurately assessing the activation of ER stress response pathway would not only help in the understanding of disease pathogenesis but would also help to assess the response to therapy. Here, we describe common techniques such as western blotting, immunohistochemistry, immunofluorescence, and determination of mRNA levels for the gene of interest to monitor the ER stress in skeletal muscle tissues.


A comparison of the methods applied to detect apoptosis in genotoxically-damaged lymphocytes cultured in the presence of four antimutagens.
The sensitivity of the available methods of apoptosis detection in lymphocyte cultures was tested. Cells were preincubated with genotoxic agents: hydrogen peroxide (0.2 mM; 20 min.) and benzo[a]pyrene (40 microM; 90min.), and then cultured for 36h in the presence of a lectin (PHA-M; 1% v/v) and one of the following potentially antimutagenic agents: alkylresorcinols, anthocyanins, todralazine and fluphenazine. It was established that staining with a mixture of fluorochromes (ethidium bromide and acridine orange) provided the highest amount of detected apoptotic cells, and the best repeatability of the results in subsequent experiments. Calculation of the Spearman's rank correlation coefficients proved that there was a high correlation between the results obtained by the ethidium bromide/acridine orange method and those obtained by identifying genomic DNA fragmentation by means of FIGE-electrophoresis. Therefore, these two methods were chosen for further studies of the tested antimutagens' impact on apoptosis in genotoxically-damaged lymphocytes.


Vascular changes in morphea.
Vascular changes in morphea were studied in skin biopsies from 14 patients. Small vessels with pericytes present the changes in three different patterns. The first was the endothelial cells in a stimulated condition and thickened vascular wall with infiltrating macrophages and mast cells. The second was characterized by thick basal lamina of pericytes and the third by activated pericytes with infiltrating lymphocytes and plasma cells. Otherwise, all patterns showed altered endothelial cells and infiltrating macrophages and mast cells similar to the first pattern. The first pattern was mostly found in uninvolved skin. The second and the third were found in the inflammatory and sclerotic areas. It seems, therefore, that activated pericytes are the most essential changes in vessels of morphea. Probably, muscular vessels are simply involved in the fibrotic process.


Four-day Follow-up Study on the Self-reported Voice Condition and Noise Condition of Teachers: Relationship Between Vocal Parameters and Classroom Acoustics.
This study aimed to determine the changes in self-reported voice and noise condition over a follow-up of 4 days (equivalent to one working week), to define the relationship between the objective voice parameters and the self-reported voice condition, as well as to characterize the relationship between classroom acoustics and the self-reported noise condition. This is a cohort study. We performed voice monitoring of 27 teachers for four working days using the Voice-Care device, which provides information on the fundamental frequency, vocal sound pressure level, and phonation time percentage. The participants performed a pre-monitoring, which consisted of a brief conversation, before each monitoring session, and filled in a questionnaire after each monitored lesson, in which they indicated their opinions about their voice condition and the classroom noise conditions. The teachers who, during the pre-monitoring, showed a higher standard deviation of the vocal sound pressure level and a greater phonation time percentage difference between the entire monitoring and the pre-monitoring sessions, reported fewer voice complaints. Decay time (DT40ME), a reverberation measure from the speakers' perspective, resulted to be associated with the self-reporting of the noise condition. Voice disorders at work prevention programs should include strategies to exercise the respiratory and laryngeal components of voice production, because these elements may influence the variation in the vocal sound pressure level, which was found to be significantly associated with the self-reported voice condition. This study also highlights the importance of including reverberation measures, from the speakers' perspective, in the design of schools.


Techniques for cryosectioning and x-ray microanalysis in the study of normal and injured myocardium.
An improved system has been developed for analytical electron microscopic studies of diffusible electrolytes in normal and diseased myocardium. The rabbit interventricular septum preparation was used for an in vitro perfusion model system. Thin (0.5mm diameter) right ventricular papillary muscles were left attached to the septa during perfusions. The muscles were subsequently positioned in a special clamp device, removed from the septa, and quick frozen in liquid nitrogen-cooled propane. The muscles were used for cryoultramicrotomy and freeze substitution. Modifications of the ultratome cryochamber and methods of improved cryosectioning also were made. The methods reported here resulted in reproducible cryosections with good ultrastructure and relatively mild ice crystal damage. Good preservation of intracellular electrolytes also was demonstrated by analytical electron microscopy.