Stimulatory and suppressive effects of infection of dendritic cells with HIV-1.

Two effects of HIV infection on human dendritic cells (DC) in vitro have been examined. The first was the stimulation of primary responses to HIV antigens in autologous lymphocytes from normal donors. When DC were exposed to HIV (10(4) TCID/10(5) cells) for up to 24 h before addition to autologous lymphocytes, a marked primary proliferative response to the virus was observed. No proliferative response was seen when the period of pre-exposure of DC to virus was extended. Cytotoxic T cells specific for HIV-infected target cells developed in stimulated cultures. The second effect of HIV infection of DC was to block responses to other antigens, such as alloantigens and the recall antigens tetanus toxoid and influenza virus. This inhibitory effect was only evident when the DC were exposed to HIV for longer than 24 h before being added to cultures. These in vitro studies suggest that infection of DC can produce both stimulatory and inhibitory responses in lymphocytes. Such effects operating through DC might underlie in vivo activity of HIV both in stimulating the proliferation of lymphocytes (e.g., in persistent generalised lymphadenopathy) and in the development of immunosuppression.     

Direct and indirect memory performance in patients with senile dementia

The performance of patients with a presumptive clinical diagnosis of Senile Dementia of the Alzheimer's Type was compared to that of a group of normal elderly on several memory and neuropsychological tasks. The patients were impaired on tasks of free and cued recall, but exhibited normal performance on a word-completion procedure similar to that used by Graf et al. (1984). Reasons for the discrepancy between these findings and those from related research which reports impairment of word completion in patients with Alzheimer's Disease are discussed. Of particular interest is the role the orientating task plays in word-completion performance.     

A trial of intranasal Atrovent versus placebo in the treatment of vasomotor rhinitis

Twenty-six patients with perennial rhinorrhea were treated by Atrovent, the anticholinergic agent, or placebo in a randomized double-blind crossover trial. The severity and duration of rhinorrhea were significantly reduced by Atrovent. Local side effects were more frequent with the active drug. These were reduced in a later open trial by a reduction in dosage.     

Inappropriate peripheral blood lymphocyte responses to herpes viruses in patients with behçet's syndrome

Specific antibody production and the proliferative response of peripheral blood lymphocytes (PBLs) to a variety of viruses, including herpes simplex virus-type-1 (HSV-1) and varicella zoster (VZ), were studied in 7 patients with Behçet's syndrome. None of the patients produced an antibody response against HSV-1 or VZ. Furthermore, none of the patients showed a proliferative response to VZ, and three of them also failed to mount a response to HSV-I. These results suggest that the PBLs of patients with Behçet's syndrome make an inappropriately poor antibody and proliferative response when stimulated by HSV-1 and VZ.     

General practitioners and clinical guidelines: a survey of knowledge, use and beliefs.

BACKGROUND: Clinical practice guidelines are being developed for a variety of reasons. To date, there has been little investigation of the perspectives of those who are recommended to use them. AIM: The survey reported here set out to investigate how familiar general practitioners are with a range of published guidelines, to assess whether they have used them, and to describe their attitudes to the guidelines and the methods of implementing them. METHOD: A postal questionnaire was sent to a random sample of 559 general practitioners in the North and Yorkshire region in March 1995. Questions were organized around the topics of: knowledge; use; practice change; beliefs; pressure felt to use the guidelines; and methods of implementation. Basic classificatory data on gender; year of qualification; partnership and fundholding status were also collected. RESULTS: Replies were received from 300 doctors (54%). Knowledge and use of the three selected guidelines varied, but was generally towards the 'high' end of the scale. Doctors showed a high degree of homogeneity in their attitudes to guidelines, which were generally positive. Only single-handed practitioners varied from this pattern of responses. Most of the pressure to use the guidelines was felt to come from the Department of Health, and the least pressure from patients. Doctors felt that the methods of implementation that involved them in educational events and discussion with colleagues were most likely to have an impact on them. CONCLUSION: General practitioners are receptive to guideline initiatives, and their views are in line with existing or proposed implementation strategies. More investigation of the concept of 'use' is needed.     

Entry of genital Chlamydia trachomatis into polarized human epithelial cells.

To study the initial invasion process(es) of genital chlamydiae, a model system consisting of hormonally maintained primary cultures of human endometrial gland epithelial cells (HEGEC), grown in a polarized orientation on collagen-coated filters, was utilized. After Chlamydia trachomatis inoculation of the apical surface of polarized HEGEC, chlamydiae were readily visualized, by transmission electron microscopy, in coated pits and coated vesicles. This was true for HEGEC maintained in physiologic concentrations of estrogen (proliferative phase) and of estrogen plus progesterone (secretory phase), despite the finding that association of chlamydiae with secretory-phase HEGEC is significantly reduced (P = 0.025; A.S. Maslow, C.H. Davis, J. Choong, and P.B. Wyrick, Am. J. Obstet. Gynecol. 159:1006-1014, 1988). In contrast, chlamydiae were rarely observed in the clathrin-associated structures if the HEGEC were cultured on plastic surfaces. The same pattern of coated pit versus noncoated pit entry was reproducible in HeLa cells. The quantity of coated pits associated with isolated membrane sheets derived from HeLa cells, grown on poly-L-lysine-coated cover slips in medium containing the female hormones, was not significantly different as monitored by radiolabeling studies and by laser scanning microscopy. These data suggest that culture conditions which mimic in vivo cellular organization may enhance entry into coated pits for some obligate intracellular pathogens.     

Differentiation of Normal and Malignant Human Squamous Epithelium in Vivo and in Vitro: A Morphologic Study

We would like to thank John Ellis for expert photographic assistance, Mervin Jones and Linda Lovell for expert animal husbandry, and Dr. Dorothy Easty for establishing the cell line LICR-LON-HN-5, without which this study would not have been possible.

We report a light microscopic and ultrastructural analysis of the comparative degrees of differentiation seen in keratinocytes derived from the tongue and epidermis with those of a well-differentiated human squamous carcinoma cell line (LICR-LON-HN5). When growing on plastic substrates, all cultures had a similar morphology, with multilayering and the production of cornified envelopes. When cultured on collagen gels the structure was more organized, with keratohyalin granules and keratin whorl formation in both the normal and the malignant cultures. Normal keratinocytes injected into athymic mice produced epidermal cysts, while cells from the cell line produced well-differentiated squamous cell carcinomas, which were partially solid and partially cystic. The tumor was well organized, with identifiable basal cells, spin-ous cells, keratohyalin granules, and a prominent basal lamina at the stromal/epithelial interface. This model is to be developed for comparative studies between normal and malignant cells, with particular reference to basement membrane production and to investigations of the relative importance of extrinsic and intrinsic factors in the control of squamous differentiation.     

Susceptibility of Anopheles quadrimaculatus (Diptera: Culicidae) to subperiodic Brugia malayi and Brugia pahangi (Nematoda: Filarioidea) adapted to nude mice and jirds

Anopheles quadrimaculatus and Aedes aegypti (Black-eyed Liverpool strain) were fed on jirds and nude mice (jird-jird infection, jird-mouse infection, and mouse-jird infection) infected with subperiodic Brugia malayi and B. pahangi. Microfilariae of B. malayi from jird-mouse and mouse-jird infections developed normally in An. quadrimaculatus, whereas those from jird-jird infections did not develop. Microfilariae of both species from jirds and nude mice developed normally in Ae. aegypti and those of B. pahangi developed normally in An. quadrimaculatus. It is suggested that microfilariae from nude mice are modified physiologically, immunologically, or both so that they can develop in refractory An. quadrimaculatus, thus indicating that susceptibility and refractoriness of An. quadrimaculatus to B. malayi also is influenced by factors relating to the vertebrate host in addition to mosquito genetic factors.