HIV infection and AIDS in England and Wales: general practitioners' workload and contact with patients.

In mid-1988 a postal survey was conducted of one in five general practitioners in England and Wales, to examine their contact with people with human immunodeficiency virus (HIV) infection, with the acquired immune deficiency syndrome (AIDS) or with worries about HIV infection or AIDS. The response rate was 63.9%. Of the 3339 respondents 22.7% knew of an asymptomatic HIV positive patient within their practice, 5.4% knew of a symptomatic HIV positive patient and 6.4% knew of a patient with AIDS. The estimated annual rate for HIV-related consultations in general practice (including consultations with the 'worried well') was 6.5 per 1000 population. HIV-related consultations occurred more frequently in the four Thames health regions than elsewhere. A sample of 715 practitioners who reported consultations with HIV infected people or those with worries about infection in the previous month, were invited to keep a diary of HIV-related consultations for one week. The response rate to the diary was 64%. Nineteen per cent of the 273 consultations recorded in the diaries were initiated by homosexual men, 16.5% by injecting drug users, 10.3% by the sexual partners of people at risk of infection; 42.9% of consultations were not associated with recognized risk factors. The results indicate that general practitioners have substantial contact with patients with HIV infection, with AIDS and with worries about HIV infection or AIDS. This contact is likely to increase, alongside the anticipated spread of HIV infection, with consequent implications for general practice resources.     

Cdc7 is required throughout the yeast S phase to activate replication origins

The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7^ts allele were first arrested in G₁ at the cdc7 block by incubation at 37°C, and then were allowed to enter S phase by brief incubation at 23°C. During the S phase, after return to 37°C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.     

Squamous cell carcinoma antigen as an adjunct tumour marker in primary carcinoma of the lung.

AIMS--To determine (1) the detection rate of primary carcinoma of the lung by serological assay of CEA (carcinoembryonic antigen); and (2) whether addition of seroassay of squamous cell carcinoma related antigen before treatment improves detection sensitivity. METHODS--A prospective study spanning 27 months was conducted at the University Hospital, Kuala Lumpur. Serum CEA (Abbott IMx) and serum squamous cell carcinoma antigen (Abbott IMx) from patients clinically suspected of having primary carcinoma of the lung, were assayed using the microparticle enzyme immunoassay method. RESULTS--Thirty seven cases of histologically confirmed primary lung carcinoma were studied. Of these, 17 were squamous cell carcinomas, 10 adenocarcinomas, nine small cell carcinomas, and one large cell carcinoma. The patients' ages ranged from 34-82 years. The male:female ratio was 3.6:1. Squamous cell carcinoma antigen was raised above the cutoff value of 1.5 ng/ml in 94.1% of squamous cell carcinomas, 20.0% of adenocarcinomas, and 11.1% of small cell carcinomas. By comparison, CEA was raised above the cutoff value of 3.0 ng/ml in 70.6% of squamous cell carcinomas, 77.8% of small cell carcinomas, and 100% of adenocarcinomas. CEA and squamous cell carcinoma antigen were not raised in the patient with large cell carcinoma and in 14 healthy volunteers. None of 15 patients with a variety of benign lung diseases showed a rise of CEA, while two patients--a 25 year old Indian woman with pneumonia and a 64 year old Malay man with bronchial asthma--had raised squamous cell carcinoma antigen values above the cutoff. Serum CEA and squamous cell carcinoma antigen values did not seem to correlate with stage or degree of differentiation of the tumours. CONCLUSIONS--The findings suggest that CEA is a good general marker for carcinoma, particularly adenocarcinoma. In contrast, squamous cell carcinoma antigen is more specific for squamous carcinoma.     

Cigarette smoke prevents apoptosis through inhibition of caspase activation and induces necrosis

Emphysema is characterized by enlargement of the distal airspaces in the lungs due to destruction of alveolar walls. Alveolar endothelial and epithelial cell apoptosis induced by cigarette smoke is thought to be a possible mechanism for this cell loss. In contrast, our studies show that cigarette smoke condensate (CSC) induces necrosis in alveolar epithelial cells and human umbilical vein endothelial cells. Furthermore, study of the cell death pathway in a model system using Jurkat cells revealed that in addition to inducing necrosis, CSC inhibited apoptosis induced by staurosporine or Fas ligation, with both effects prevented by the antioxidants glutathione and dithiothreitol. Time course experiments revealed that CSC inhibited an early step in the caspase cascade, whereby caspase-3 was not activated. Moreover, cell-free reconstitution of the apoptosome in cytoplasmic extracts from CSC-treated cells, by addition of cytochrome-c and dATP, did not result in activation of caspases-3 or -9. Thus, smoke treatment may alter the levels of pro- and antiapoptogenic factors downstream of the mitochondria to inhibit active apoptosome formation. Therefore, unlike previous studies, cell death in response to cigarette smoke by necrosis and not apoptosis may be responsible for the loss of alveolar walls and inflammation observed in emphysema.     

Evaluation of a Standard Protocol for Retentive Encopresis: A Replication

Replicated the efficacy of a short-term, combined medical andbehavioral intervention protocol for retentive encopresis. Fifty-ninechildren who had failed standard medical management for retentiveencopresis and their parents participated in six 1-hour grouptreatment sessions. Treatment protocol combined the medicalmanagement strategies of enema clean out, increasing dietaryfiber, and daily toilet sitting with the child behavior managementstrategies of differential attention, contingency management,and contracting. For the overall sample, the number of soilingincidents decreased 85%, the weekly frequency of independentbowel movements increased 15%, the weekly frequency of parent-promptedbowel movements increased 9%, and daily dietary fiber intakeincreased 121% pre-to posttreatment. The majority of the sample(86%) stopped soiling by the end of treatment and did not requirefurther treatment. Results are discussed in terms of the comparabilitywith previous findings and the utility of combined medical andpsychological treatments for children with encopresis who havefailed standard medical approaches     

Excitation of units in the lateral geniculate and contiguous nuclei of the cat by stretch of extrinsic ocular muscles

Summary In cats, anaesthetized with chloralose and paralysed, the responses of units in the right lateral thalamus were recorded while the extrinsic ocular muscles (EOM) of the right eye were stretched in the dark. Phasic responses were found in all layers of the dorsal lateral geniculate nucleus (LGNd) and in the perigeniculate nucleus (PGN). A given unit usually responded to stretch of more than one EOM and thus to more than one direction of rotation of the eye in the orbit. LGNd. Of a sample of 76 units in LGNd, 55 (72%) gave visual but no muscle responses and 21 (28%) responded to EOM stretch. In all, 40 units with EOM responses were examined and 25 of the 27 tested (93%) also had visual responses. Of the 40 units, 32 could be allocated to layers, thus: layer A, 8 (25%); layer A1, 20 (63%); layer B, 3 (9%); central interlaminar nucleus, 1 (3%). It is interesting that most of the EOM responses were found in layer A1 which receives the excitatory visual input from the eye whose EOM were stretched. Muscle responsive units occurred with ON- and OFF-centre visual responses of sustained and transient types. PGN. In PGN, 21 units gave EOM responses and most of them were also excited by visual input.The conclusion is that the LGNd and PGN recieve an extraretinal proprioceptive signal which should be present during at least large saccadic eye movements. The anatomical pathways which may be involved and the significance of the signal are discussed briefly.     

Sequential movement representations based on correlated neuronal activity

We tested the hypothesis that sequential movements are represented in the correlated activity of motor cortical neurons. We simultaneously recorded multiple single neurons in the motor cortex while monkeys performed a two-segment movement sequence. Before any movement began the correlated spike firing between pairs of neurons differed when these sequences were planned as whole (planned) as compared to when they were planned one segment at a time (unplanned) even when the firing rates of these neurons did not distinguish between the two conditions. Moreover, the correlation strength was significantly larger when the directional preferences of the neurons matched the direction of the final segment of the sequence. Our results suggest that spatially distributed groups of MI neurons form dynamic correlation structures that distinguish different forms of sequential action. Electronic Publication     

The pathogenicity of long versus short fibre samples of amosite asbestos administered to rats by inhalation and intraperitoneal injection.

For many years it has been accepted that fibre dimensions are the most important factor in the development of asbestos related disease with long fibres being more dangerous than short for all types of asbestos. This information has been derived from in vitro experiments and injection or implantation experiments since the kilogramme quantities of specially prepared dusts that are necessary for long term inhalation have not been available. The present study has taken advantage of the availability of a sample of amosite produced so that almost all fibres were less than 5 micron in length. The effects of this dust were compared to dust prepared from raw amosite that contained a very high proportion of long fibres. Previous data from studies with UICC amosite, which was intermediate in length, were also available for comparison. At the end of 12 months of dust inhalation, significantly more short fibre amosite was present in the lung tissue compared to the long but while the long fibre dust caused the development of widespread pulmonary fibrosis, no fibrosis at all was found in animals treated with short fibre. One third of animals treated with long fibre dust developed pulmonary tumours or mesotheliomas but no pulmonary neoplasms were found in animals treated with short fibre dust. Following intraperitoneal injection, the long fibre amosite produced mesotheliomas in 95% of animals with a mean induction period of approximately 500 days. With short fibre dust, only a single mesothelioma developed after 837 days. In previous inhalation studies with UICC amosite, relatively little pulmonary fibrosis had developed and only two benign pulmonary tumours. This would suggest that to produce a significant carcinogenic response in rat lung tissue amosite fibres must be longer than those in the UICC preparation. Following the injection of UICC amosite, however, mesotheliomas developed in the same proportion of animals and with the same mean induction period as with long fibre dust. From this it would appear that while very short fibres exhibit little carcinogenicity to either lung or mesothelial tissues, mesotheliomas can be produced by dust preparations consisting of shorter fibres than are needed to produce tumours.     

Compartmentalized immune responses: antigen-specificity of cerebrospinal fluid T-cell lines maintained in the absence of antigen

The generation of long-term interleukin 2-dependent T-cell lines from anatomically compartmentalized sites of pathology offers a unique approach to the investigation of certain autoimmune diseases. However, it is generally believed that antigen-specific T-cell lines and clones lose antigen reactivity and specificity when propagated in the absence of antigen. Therefore, the optimal application of this approach to such diseases in which the pathogenetic antigens are unknown may be difficult. In approaching this problem, we have recently demonstrated that a proportion of antigen-specific T-cell lines derived from the peripheral circulation can maintain antigen specificity if propagated with antigen-presenting cells alone or with antigen-presenting cells together with OKT3 antibody, but in either case in the absence of antigen. In this report we describe the use of this approach to maintain the antigen specificity of T cells obtained from an anatomically compartmentalized site of pathology--the cerebrospinal fluid from a patient with tuberculous meningitis. We report here that a proportion of the T-cell lines generated from such cerebrospinal fluid lymphocytes can be maintained as antigen specific in the absence of antigen if propagated with either antigen-presenting cells alone or with antigen-presenting cells and OKT3 antibody. The approach illustrated in this report should now find broad applicability in the investigation of a number of autoimmune disease.