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V James

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Journal Article↗

Association between MHC class II alleles and clearance of circulating hepatitis C virus. Members of the Trent Hepatitis C Virus Study Group.

The frequencies of HLA class I antigens and class II haplotypes were compared in subjects with previous (polymerase chain reaction [PCR]-negative) or with persistent (PCR-positive) hepatitis C virus (HCV) infection and in HCV patients with mild versus severe histologic activity scores on liver biopsy. The DRB1*11 allele group was found in 11 (31.4%) of 35 subjects with previous infection and in 11 (8.2%) of 135 subjects with persistent infection (P < .001). The DQB1*0301 allele was found in 18 (51.4%) of 35 subjects with previous infection and in 33 (24.4%) of 135 patients with persistent infection (P < .002). Both observations remained significant after correction for multiple testing. No significant association was shown between severity of disease and any HLA class I or II type. Thus, the HLA class II alleles DRB1*11 and DQB1*0301 are associated with clearance of circulating HCV.

Adult↗

Ankylosing spondylitis and secretor status: a re-evaluation.

Non-secretion of ABO blood group substances in body fluids is associated with susceptibility to some bacterial infections. Non-secretors were previously found to be over-represented in patients with ankylosing spondylitis (AS) (49%) compared to controls (27%). Re-evaluation of secretor status in a population of 92 AS patients and 103 controls revealed identical proportions of non-secretors (28%). Of 43 patients studied in both surveys, 6/22 typed initially as non-secretors proved to be secretors using both haemagglutination inhibition assay (HAI) and enzyme-linked immunosorbent assay (ELISA) techniques. Loss of secreted blood group antigens in the saliva is the cause of this mis-typing. Careful attention to the method of collection, handling and preservation of saliva specimens is essential for accurate assessment of secretor status. Therefore, there is no link between secretor status and AS.

ABO Blood-Group System↗

Changes of extracellular matrix in a baboon (Papio hamadryas) model of insulin dependent diabetes: studies using electron microscopy and X-ray diffraction techniques.

Extracellular matrix plays an important role in many physiological functions and its abnormalities are thought to play a key role in the pathogenesis of diabetic complications. In this paper we used the techniques of electron microscopy, immunostaining and X-ray diffraction to document some of the early events in the changes of extracellular matrix in a model of insulin dependent diabetes in baboons. Our results show that thickening of basement membrane and enlargement of mesangium are demonstrable in the glomeruli of prepubertal diabetic baboons within 2 years from the onset of diabetes. Concomitant with this was the accumulation of type IV collagen and laminin in the mesangium. By contrast, even the very sensitive technique of X-ray diffraction failed to demonstrate changes in the equatorial direction of collagen molecules of the skin and tendon. We conclude that changes of glomerular extracellular matrix are demonstrable early in insulin dependent diabetes even in prepubertal baboons. These can be used as endpoints in evaluating the efficacy of pharmacological agents such as aminoguanidine in preventing diabetic complications.

Animals↗

Regulatory systems modulating the transcription of the pectinase genes of Erwinia chrysanthemi are conserved in Escherichia coli.

To depolymerize plant pectin, the phytopathogenic enterobacterium Erwinia chrysanthemi produces five isoenzymes of pectate lyases encoded by the five genes pelA, pelB, pelC, pelD and pelE. In Er. chrysanthemi, all genes involved in pectin degradation are specifically controlled by the KdgR repressor and are induced in the presence of a pectin catabolic product, 2-keto-3-deoxygluconate (KDG). transcription of the pectinase genes is dependent on many environmental conditions. Transcriptional fusions present on low-copy-number plasmids were used to study the regulation of the pel genes in a heterologous host, Escherichia coli. Some physiological regulations that take place in Er. chrysanthemi are conserved in E. coli. The five pel fusions in E. coli are affected by growth phase, catabolite repression and anaerobic growth conditions and are induced in the presence of galacturonate, a sugar whose catabolism leads to the formation of KDG, the inducer of pel transcription in Er. chrysanthemi. Expression of pelE increased with the osmolarity of the culture medium. In contrast, the regulation of pel expression by temperature or nitrogen starvation, observed in Er. chrysanthemi, was not conserved in E. coli, suggesting that the mechanisms responsible for these regulations are specific to Er. chrysanthemi. Analysis of different E. coli mutants allowed some regulators affecting the transcription of the pel genes to be identified. In E. coli, the growth-phase regulation of the pel genes is not dependent on the RpoS sigma factor and the fnr gene is not involved in the increase of pel expression in oxygen-limited conditions. The gene hns, involved in the regulation of numerous genes, appears to affect pel expression but the effects of E. coli hns mutations are not related to osmoregulation. In contrast, this analysis clearly demonstrates the interchangeability of two regulatory systems of E. coli and Er. chrysanthemi: the global control exerted by the catabolite activator protein CAP and the specific regulation mediated by the KdgR repressor.

Anaerobiosis↗

Who has the power? Some problems and issues affecting the nursing care of dying patients.

Nurses play a central role in the care of dying people, yet they may find themselves marginalized, devalued or in conflict with other health professionals. This paper examines a number of problems and issues related to nursing power and control in the workplace. The factors we consider are: the relative effects of personal and structural influences; the 'medicalization' of dying; the demands and challenges of interdisciplinary work; ethical issues raised by euthanasia and AIDS; patients' rights to make informed decisions about their care; philosophies and policies of health care.

Ethics, Nursing↗

Risk factors for hepatitis C virus infection. A case-control study of blood donors in the Trent Region (UK).

The introduction of screening for hepatitis C virus (HCV) by the National Blood Transfusion Service identified donors who had acquired HCV infection. We undertook a case-control study amongst blood donors in the Trent Region to determine risks for HCV infection. A total of 74 blood donors confirmed positive for hepatitis C infection and 150 age, sex and donor venue matched controls were included in the study. Fifty-three percent of hepatitis C infected blood donors reported previous use of injected drugs compared to no controls; relative risk (RR) not estimatable (lower limit 95% CI = 20). Other risk factors were a history of: receipt of a blood transfusion or blood products RR = 3.6 (95% CI 1.5-8.3), having been a 'health care worker' RR = 2.8 (95% CI 1.1-7.6), tattooing RR = 3.3 (95% CI 1.2-8.7), and an association with having been born abroad RR = 3.2 (95% CI 1.1-9.5). No risk was shown for a history of multiple sexual partners, ear piercing or acupuncture. Injecting drug use explains more than 50% of hepatitis C infections in blood donors, a group who are less likely to have injected drugs than the general population.

Adult↗

Failure of the revised pre-donation guidelines to prevent people with a history of high-risk behaviour from donating blood.

We have evaluated the effectiveness of the alteration in the literature aimed at the self-exclusion of blood donors with a history of high-risk behaviour. Since the introduction of anti-HCV screening on 1 September 1991 all HCV-positive donors in the Trent Region have been invited for interview by Blood Transfusion medical staff to ascertain risk factors for HCV infection. We have compared the 5-month periods before (1 September, 1992 to 31 January, 1993) and after (1 February, 1993 to 30 June, 1993) the introduction of the amended literature on 1 February, 1993. No differences between the two time periods were noted for the prevalence rate of HCV infection amongst new or repeat donors, or history of risk factors or specific exclusion criteria. The new literature is failing to exclude people with a history of high-risk behaviour from donating blood and further study of this problem is urgently required.

Adult↗

Autoradiographic comparison of cholinergic and other transmitter receptors in the normal human hippocampus.

The vulnerability of the human hippocampal complex to disease, trauma, and aging indicates the necessity to target this area therapeutically. The distribution and density of transmitter receptors provide a rational basis for this approach, and in this study the topography of 11 different pharmacological sites is compared with the cholinergic innervation, which is particularly vulnerable in dementia. The regional distribution of cholinergic innervation to the normal adult human hippocampus and adjacent cortex, marked by acetylcholinesterase (AChE) fiber and terminal reactivity, is notable for its concentration in CA2/3 of Ammon's horn and the dentate fascia. Neither nicotinic (high-affinity nicotine binding) nor muscarinic ("M1" or "M2") cholinergic receptor binding paralleled this distribution. In Ammon's horn, 5-HT2 and kainate receptor binding more closely resembled the pattern of AChE, being concentrated in CA2-4 compared with CA1. By contrast, muscarinic M1 and M2, 5-HT1A, benzodiazepine (including zolpidem-insensitive binding), NMDA (MK801), and AMPA/QUIS receptors were higher in CA1 and/or subiculum. Kainate binding, like AChE, was high in CA4. 5-HT2 and nicotinic binding partially mimicked the pattern of AChE around the granule layer. In the subicular complex and parahippocampal gyrus, where cholinergic activity is relatively lower, muscarinic, 5-HT1A, and benzodiazepine binding were relatively high and the nicotinic receptor was remarkable for its highest density compared to other areas examined. In stratum lacunosum-moleculare of CA1, which was relatively low in AChE activity, there was a dense band of nicotinic, M2, and benzodiazepine receptor binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗

Use of anti-GOR testing in the screening of blood donors for hepatitis C virus infection.

Sera from 12/1,155 (1%) anti-HCV-negative (Elisa) UK blood donors were found to be anti-GOR positive. None out of 12 of those sera were positive for HCV RNA by the reverse transcriptase/polymerase chain reaction (RT/PCR). In a cohort of 316 anti-HCV Elisa-positive sera, 27/57 RIBA-positive, and 1/188 RIBA-negative sera were anti-GOR positive, resulting in a sensitivity of 47% and a specificity of 99.5% for anti-GOR as a marker for RIBA-confirmed HCV infection. Four out of 71 (6%) of RIBA-indeterminate sera were anti-GOR positive. Donors with anti-GOR reactivity were more likely to have antibodies against each of the individual HCV antigens represented in the RIBA, and those antibodies were of greater intensity, when compared to the anti-GOR negative cohort. Twenty out of 36 (55.6%) of RT/PCR-positive sera were anti-GOR positive, compared to 1/7 (14.3%) of RT/PCR-negative sera (p = 0.09). The usefulness of anti-GOR testing of UK blood donors is discussed in the light of these results.

Autoantibodies↗