Mortality and cancer incidence in males with Y polysomy in Britain: a cohort study

The mortality and cancer incidence risks among males with Y polysomy are unknown because there have been no large long-term cohort studies carried out of such men. We conducted a cohort study of 667 men diagnosed with the abnormality in Britain since 1959 to compare their mortality and cancer incidence rates with those of the general population. Sixty deaths occurred during follow-up to December 2005, twice the number expected from general population rates (standardised mortality ratio (SMR) = 2.0 (95% confidence interval (CI) 1.5–2.6)). Significantly raised mortality was observed for diseases of the nervous system (SMR = 7.0, 95% CI: 2.3–16.4), circulatory system (SMR = 2.1, 95% CI: 1.3–3.2), respiratory system (SMR = 4.0, 95% CI: 1.8–7.5), genitourinary system (SMR = 10.2, 95% CI: 1.2–36.9), and congenital anomalies (SMR = 11.9, 95% CI: 3.2–30.5). Four of the five nervous system deaths were from epilepsy, the risk of death from this condition being more than 20-fold raised. The rates of cancer incidence and mortality among these men was not significantly different from those in the general population. This study provides evidence that mortality rates from several specific causes are raised among men with Y polysomy. The use of these data in genetic counselling should be cautious particularly for cases of Y polysomy that are detected prenatally. Further investigations are required to confirm these findings and to elucidate the possible role of genes on the Y chromosome in the aetiology of these causes of death.     

Nitrile hydrolysis activity of Rhodococcus erythropolis NCIMB 11540 whole cells

The nitrile hydrolyzing properties of the bacterium strain Rhodococcus erythropolis NCIMB 11540 have been investigated. Using whole cells of the microorganism, a wide variety of aromatic and aliphatic cyanide-containing substrates was successfully hydrolyzed to the corresponding amide or acid. In the case of dicyanides, selective monohydrolysis took place, which was further explored in the desymmetrization of malononitriles resulting in the corresponding cyano amides in enantiomeric excesses of up to 98%.     

Vasospasm is a significant factor in cyclosporine-induced neurotoxicity: Case report

Background

The aetiology of central nervous system lesions observed in cerebral cyclosporine neurotoxicity remains controversial.

Case presentation

We report a 48-year-old woman with a non-severe aplastic anaemia who presented with stroke-like episodes while on cyclosporine treatment.Transcranial Doppler ultrasound revealed severely elevated flow velocities in several cerebral vessels, consistent with vasospasm. Immediately after reducing the cyclosporine dose, the stroke-like episodes disappeared. Only after cyclosporine withdrawal the transcranial Doppler ultrasound abnormalities fully resolved.

Conclusions

This case demonstrates a significant role of vasospasm in the pathway of cyclosporine-induced neurotoxicity. Transcranial Doppler ultrasound is an effective tool for the diagnosis and follow-up of cyclosporine-induced vasospasm.

     

Escherichia coli polypeptide controlled by the lon (capR) ATP hydrolysis-dependent protease and possibly involved in cell division

Mutation in the gene lon (capR) of Escherichia coli K-12 causes conditional inhibition of cell division. Two-dimensional gel electrophoresis was used to compare polypeptides from isogenic capR+ and capR strains. One polypeptide was present in the capR strain but absent in the wild-type strain, and it was proteolyzed when the pure capR+ protease was added to the capR extract. This polypeptide could only be detected in the capR strain when cell division was inhibited, and its synthesis was independent of the SOS response.     

Optimization of stereoselective ketone reduction by the white-rot fungus Merulius tremellosus ono991

A recently isolated white-rot fungal strain, Merulius tremellosus ono991, displays high stereoselectivity during the reduction of arylketones. In order to increase the productivity and specific yield of the optically active alcohols, the culture conditions for the reduction of the model ketone compound 1'-acetonaphtone to alpha-methyl-1-naphtalenemethanol were optimized with respect to oxygen supply, choice of primary substrate and arylketone concentration. Alternative electron acceptors were also used to elucidate the role of reduction equivalents in the reduction process. The optimal yields of alpha-methyl-1-naphtalenemethanol were obtained in N2-flushed incubations with glycerol as primary substrate. The specific yield was increased from 57% to 98% compared to incubations under air with glucose. Most of the yield increase was due to N2-flushing and could be attributed to two factors. First, an increased stability of the product, alpha-methyl-1-naphtalenemethanol, in anaerobic compared to aerobic atmosphere was demonstrated. Second, fermentative metabolism increased reduced enzyme cofactors available for the reduction. Diverting reducing equivalents away from fermentation with alternative electron acceptors correlated with a decreased yield of alpha-methyl-1-naphtalenemethanol. Furthermore, the dependency of ketone reductase for common occurring metabolic reducing equivalents, NAD(P)H, was demonstrated by the reduction of 1'-acetonaphtone in cell extracts of M. tremellosus ono991.     

C-2 Epimer Formation of Tetrose, Pentose and Hexose Sugars by Xylose Isomerase

We describe novel tetrose isomerizations and C-2 epimerizations by the industrially important d -xylose ketol-isomerase (E.C.5.3.1.5) with both the d - and l -forms of the sugars. We further show that in addition to isomerization to d -fructose, d -glucose is slowly C-2 epimerized to d -mannose. The formation rate of the C-2 epimer was 0.03 mg mg -1 min -1 from d -glucose, 0.56 mg mg -1 min -1 from d -arabinose and 3.0 mg mg -1 min -1 from d -erythrose. The equilibria of the reaction products as a function of temperature were measured for threose/erythrulose/erythrose, arabinose/ribulose/ ribose and glucose/fructose/mannose.     

Characterization of in vitro proteolytic processing of β-endorphin by reversed-phase HPLC

In vitro, central and peripheral proteolytic processing of β-endorphin by membrane-bound enzymes results in the formation of specific active fragments that have been recently shown to function in behavior, intestinal motility and in the central control of urinary bladder activity. A high resolution, reversed phase high performance liquid chromatography system capable of separating 28 β-endorphin related fragments simultaneously was used to study the time-course processing of β-endorphin by membrane associated peptidases in the brain and regions of the small intestine. The hypothesis we tested was that a homeostatic balance between α- and γ-type endorphins exists in these tissues. The results of the study show that the rate and quantity of fragments produced between the mucosa and nerve-muscle regions of the small intestine are significantly different. Metabolic rates, pattern, and the ratio of α/γ-type endorphins in the brain were very similar to the nerve-muscle region of the small intestine. This suggests that β-endorphin processing to active fragments is occurring at the nerves of the small intestine and that a specific and similar balance of α/γ-type endorphin exists in the brain and gastrointestinal system at neutral pH.     

Characterization of in vitro proteolytic processing of beta-endorphin by reversed-phase HPLC

In vitro, central and peripheral proteolytic processing of beta-endorphin by membrane-bound enzymes results in the formation of specific active fragments that have been recently shown to function in behavior, intestinal motility and in the central control of urinary bladder activity. A high resolution, reversed phase high performance liquid chromatography system capable of separating 28 beta-endorphin related fragments simultaneously was used to study the time-course processing of beta-endorphin by membrane associated peptidases in the brain and regions of the small intestine. The hypothesis we tested was that a homeostatic balance between alpha- and gamma-type endorphins exists in these tissues. The results of the study show that the rate and quantity of fragments produced between the mucosa and nerve-muscle regions of the small intestine are significantly different. Metabolic rates, pattern, and the ratio of alpha/gamma-type endorphins in the brain were very similar to the nerve-muscle region of the small intestine. This suggests that beta-endorphin processing to active fragments is occurring at the nerves of the small intestine and that a specific and similar balance of alpha/gamma-type endorphin exists in the brain and gastrointestinal system at neutral pH.     

Estrogenic effects of the new opioid antagonist naltrexone-estrone azine on pituitary luteinizing hormone secretion in ovariectomized rats.

The effect of the new opioid antagonist naltrexone-estrone azine (EH-NX) on pituitary luteinizing hormone (LH) secretion in the ovariectomized rat was studied. EH-NX is a hybrid between the steroid component estrone and the opioid antagonist naltrexone (NX). It is a potent and long-acting opioid antagonist in vitro and in vivo, but its effect upon in vivo LH secretion has not been tested before. The aims of the study were to investigate whether, unlike naltrexone, EH-NX can stimulate LH secretion without the need of additional estrogen pretreatment and whether EH-NX has peripheral estrogenic effects upon the uterine weight, when administered chronically to long-term ovariectomized rats. Female rats were injected subcutaneously with EH-NX 21 days after ovariectomy. The effects of EH-NX injections on LH secretion were compared to the effects of NX and estrone hydrazone (EH) alone, or in combination, with or without estradiol-benzoate (EB) pretreatment. Inhibition of LH secretion and uterine proliferation were observed in rats treated chronically with EH-NX in dosages of 0.250 mg/kg bw and higher. These effects were similar to those caused by EH and EB. In short-term OVX rats EH-NX appeared to act faster than EH. In contrast to NX, no stimulatory effect on LH secretion was seen with EH-NX in EB primed OVX rats. These results surprisingly demonstrate that EH-NX behaves like an estrogen and not like an opioid antagonist. The unexpected pharmacological profile of this new drug may open up doors for several medical applications.