Discordant repeat size and phenotype in Kennedy syndrome

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease.     

Effects of Helicobacter pylori on histamine and carbachol stimulated acid secretion by human parietal cells.

Helicobacter pylori (H pylori) infection is associated with hypo, normal, and hypersecretory disorders of the gastric mucosa. Pathophysiological pathways by which H pylori interacts with acid secretion are still unclear. The effects of H pylori on (14C) aminopyrine uptake by human parietal cells were examined as an indirect assay for acid secretion. Isolated oxyntic glands were stimulated with submaximal concentrations of histamine or carbachol and incubated with sonicates of different H pylori strains. Omeprazole and sonicates of Campylobacter jejuni served as positive and negative controls, respectively. Two of four H pylori strains reduced hydrochloric acid sequestration within the parietal cells significantly and in a dose dependent manner in up to 80%. Interaction with acid secretion may therefore constitute a factor contributing to a distinct pathogenicity of H pylori strains.     

Physiologic responses to heavy-resistance exercise with very short rest periods

Heavy-resistance exercise utilizing very short rest periods is commonly used by body builders to prepare for competition. The purpose of this study was to compare the acute responses of this type of heavy-resistance exercise protocol in competitive body builders (BB) and power lifters (PL). Nine male BB and eight PL were matched for age, size and experience. A ten-station heavy-resistance exercise protocol was used. Each subject performed three sets of 10 repetition maximum (RM) with 10-s rest between sets and alternated 30-s and 60-s rest periods between exercises. No differences were observed in total work between the groups, but BB used a significantly (P less than 0.05) higher percentage of their 1 RM in the bench press and leg press exercises. Heart rate, ratings of perceived exertion (RPE), and lactate levels were obtained during the exercise protocol; significant (P less than 0.05) increases were observed above rest for these variables. RPE was significantly correlated with lactate levels (r = 0.84). Plasma epinephrine, norepinephrine, dopamine, cortisol, and lactate levels significantly increased from pre- to 5 min post-exercise. Mean plasma volumes were reduced -16.6 (+/- 3.64)% and -20.6 (+/- 8.32)% following the exercise protocol for BB and PL, respectively. Significant (P less than 0.05) decreases in eosinophil counts were observed following exercise. No significant differences were observed between BB and PL for any of the physiologic responses measured. PL exhibited a higher incidence (100%) of clinical symptoms of dizziness and nausea compared to BB (11.1%).(ABSTRACT TRUNCATED AT 250 WORDS)     

A longitudinal study of the effect of different social rearing conditions on cerebrospinal fluid norepinephrine and biogenic amine metabolites in rhesus monkeys

The purpose of this study was to determine whether disruption of early social attachment alters the activity of brain biogenic amine systems in rhesus monkeys (Macaca mulatta). Male rhesus monkey infants were deprived of maternal interaction, peer interaction, or both, during the first 22 months of life. Cerebrospinal fluid (CSF) was collected under rigorously controlled conditions approximately every month and assayed for levels of norepinephrine (NE), its major metabolite, and the metabolites of dopamine and serotonin. Mother-Deprived infants had lower levels of CSF NE than Mother-Reared infants. Mother-Deprived infants also failed to develop the same pattern of intercorrelations between compounds and month-to-month stability in levels of neurotransmitter and metabolites in CSF as the Mother-Reared infants. Finally, there were changes in CSF NE levels associated with social separation and social group formation. The brain NE system appears to be sensitive to changes in the social environment. Its level of activity, as reflected in levels of NE in CSF, appears to depend on both the prevailing social environment and the prior rearing environment.     

The MTT assay for chemosensitivity testing of human tumors of the central nervous system

In this study we assessed the influence of patient- and drug-specific parameters in the short-term MTT-chemosensitivity assay in 150 primary cell cultures derived from human brain tumors. In 45 patients the MTT assay was directly compared with the CFA (Colony Forming Assay). Resistance was 10-20% higher in the MTT assay than in the CFA, but there was a good agreement in both assays, that more malignant gliomas had a higher in vitro chemosensitivity against ACNU and BCNU. Overall the results demonstrate, that there is no uniform correlation between the in vitro chemosensitivity and the histopathological classification of the tumors, which corresponds well to the clinical situation. On the basis of this study we suggest prospective clinical trials with the MTT assay in human brain tumors.     

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Activation of guinea pig eosinophil respiratory burst by leukotriene B4: role of protein kinase C

Leukotriene B4 (LTB4) and the protein kinase C activator, 4-beta-phorbol dibutyrate (PDBu), both induced a pronounced and concentration-dependent stimulation of hydrogen peroxide (H2O2) generation by purified guinea pig peritoneal eosinophils in the concentration range 1 nM-1 microM. The LTB4 response was inhibited competitively by the specific LTB4 receptor antagonist, U-75302, with a KB of 25 nM, while the concentration-response curves for both stimuli were shifted rightwards (3.8-fold and 2.8-fold for LTB4 and PDBu, respectively) by the competitive protein kinase C inhibitor, 1-O-hexadecyl-2-O-methylglycerol at a concentration of 300 microM. LTB4 appears, therefore, to induce respiratory burst in eosinophils via a receptor-mediated mechanism involving protein kinase C.