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Biomedical subjects

E Hall

Publications and source records attributed to E Hall.

At least 73 records · Page 4Linked to original sources

Effect of zimeldine and its metabolites on [3H]thymidine incorporation in lymphocyte cultures from psychiatric patients with or without a hypersensitivity reaction during zimeldine therapy.

Lymphocyte transformation test (LTT) was applied to 28 patients who had developed a hypersensitivity syndrome (HSS) during treatment with the antidepressant drug zimeldine. Twenty-seven patients treated with zimeldine without any symptom of an HSS were matched controls. Zimeldine and its metabolites norzimeldine and CPP 200 all induced statistically significant increased [3H]thymidine incorporation in cultured lymphocytes from the HSS patients compared with the controls, norzimeldine being the most potent inducer. The results indicate an immunoreactive process in the development of the HSS induced by zimeldine.

Adult↗

Cough production, leucocytosis and serology of rats infected intrabronchially with Bordetella pertussis.

Adult Sprague-Dawley rats infected intrabronchially with Bordetella pertussis strain 18-323 encased in agarose beads (BP-beads), developed a paroxysmal cough and leucocytosis, both of which peaked at around day 10. When animals were exposed to ether for 2 min after delivery of the beads, there was an enhancement of the number of subsequent coughing episodes. Inclusion of carrageenan in the beads also enhanced coughing. Control rats, given sterile beads or left untreated, showed only a low level of coughing or no coughing, depending upon their source. Rats challenged by the same route with heat-killed B. pertussis in beads, or with live organisms in suspension (without beads) showed no cough induction or leucocytosis. However, intranasal delivery of B. pertussis suspension gave rise to a moderate amount of coughing and leucocytosis. Serum IgG responses to B. pertussis antigens were greatest in rats infected with BP-beads and antibodies against both pertussis toxin and filamentous haemagglutinin were detected. Since the rat is the only conveniently accessible laboratory animal species in which B. pertussis induces an intermittent paroxysmal cough, as in man, it merits further study for determining the mechanisms of pathogenesis and immunity in pertussis.

Animals↗

Responses to Bordetella pertussis mutant strains and to vaccination in the coughing rat model of pertussis.

Phase I strains 18-323, Tohama and L-84 of Bordetella pertussis produced paroxysmal coughing when encased in agarose beads and administered intrabronchially to adult Sprague-Dawley rats. In contrast, the Phase IV variant of strain L-84 was inactive in cough induction, as was strain BP 357, a transposon-insertion mutant which is deficient only in pertussis toxin (PT). Strain BPM 1809, which lacks only the heat-labile toxin, was similar to the unmodified Phase I strains for cough induction, indicating that this toxin is not needed to induce coughing. B. parapertussis also was inactive as a cough inducer. These results indicate that PT, present in Phase I strains of B. pertussis, and absent from Phase IV strains, strain BP 357 and B. parapertussis, is essential for the induction of paroxysmal coughing in this rat model of whooping cough. Prior injection of DTP (whole-cell) vaccine greatly reduced the incidence of coughing in rats challenged subsequently with Phase I B. pertussis. Serological responses were monitored after intrabronchial infection with the various bacterial strains and after vaccination and challenge. The PT-positive or -negative status of the strains in vivo was confirmed by the appropriate presence or absence of anti-PT IgG in the convalescent sera.

Animals↗

Combined effect of infection and heavy wrapping on the risk of sudden unexpected infant death.

Three methods were used to investigate the role of infection in sudden unexpected infant death (SUD): (i) microbiological comparison of SUD victims and matched, live, community controls; (ii) postmortem classification of the contribution of infection to death; and (iii) case-control analysis of the relative risk associated with both infection and heavy wrapping. Limited sampling from the upper respiratory tract and gut in SUD victims and controls showed no significant excess of viral infection in the SUD victims (odds ratio = 1.98, 95% confidence interval (CI) 0.9 to 4.5). At postmortem examination, infection explained death in 3/95 babies and may have contributed to death in 37/95. Over 70 days of age, the combined presence of viral infection and wrapping in excess of 10 togs produced an odds ratio of SUD of 51.5 (95% CI 5.64 to 471.48) compared with wrapping of less than 6 togs. Viral infection was not a major risk factor as long as babies were lightly wrapped. In heavily wrapped babies the presence of a viral infection greatly increased the risk of SUD.

Bacterial Infections↗

Differences in residency performances and specialty choices between graduates of three- and four-year curricula.

This study identified differences in the specialty choices and residency program directors' performance ratings of residents graduated from two different curricula of the same medical school. One curriculum was three years long, and compressed two years of the basic sciences into one year of study. The other was a four-year program devoting two years each to the basic and clinical science, but with elements unifying the two areas. Using an 18-item form, the program directors rated the performance of 42-96% of the residents who had graduated in the classes of 1982, 1984, 1985, and 1986. (1982 was the only class of the three-year curriculum that was studied.) Graduates of the three-year program showed less strength in background medical knowledge and in their experience of using research data; their greatest strengths seemed to be in the sorts of skills that normally would be acquired during the course of residency experiences. Graduates of the four-year curriculum seemed more able to integrate background medical knowledge and effective care of patients. Their weaknesses appeared to be in those skills that would be developed during the course of the residency experience. The only marked differences between the two groups in terms of residency specialty choice were in surgery and medicine.

Career Choice↗

Job strain and ambulatory blood pressure profiles.

Occupational characteristics were used to study the role of job stress in the pathogenesis of hypertension. Ambulatory 24-h recordings of blood pressure were made for 161 men with borderline hypertension. From the occupational classification system scores for psychological demands, control, support, physical demands, and occupational hazards were obtained. The results indicated that the ratio between psychological demands and control (strain) was significantly associated with diastolic (but not systolic) blood pressure at night and during work. The association between job strain and diastolic blood pressure at night and during work was greatly strengthened when the subjects with occupations classified as physically demanding were excluded from the analysis. The conclusion was reached that a measure of job strain derived from the occupational classification is useful in predicting variations in diastolic blood pressure levels during sleep and work for men with borderline hypertension.

Adult↗

The cytoplasmic tail of CD4 targets chimeric molecules to a degradative pathway.

Many different cell surface receptors undergo endocytosis via coated pits. Once having entered the cell, the receptors are sorted into diverse pathways. Which path a given receptor will follow is determined by signals inherent in the receptor's structure. The nature of these structural features is not yet known. In this study, we have taken the approach of constructing chimeric molecules to localize the domain of the T-cell surface molecule CD4 which is responsible for targeting it for degradation. Chimeric molecules bearing the cytoplasmic domain of CD4 and the extracellular domain of either the low-density lipoprotein receptor or a major histocompatibility complex (MHC) class I molecule were both internalized in response to phorbol 12-myristate 13-acetate and were subsequently degraded, indicating that the cytoplasmic tail of CD4 contains all the information required for both processes. The ability to modulate the level of MHC class I molecules on the cell surface offers an approach to investigating quantitative aspects of antigen presentation, the initial possibilities of which are explored herein.

CD4 Antigens↗

Hairpatches, a single gene mutation characterized by progressive renal disease and alopecia in the mouse. A potential model for a newly described heritable human disorder.

A new murine mutation, hairpatches (Hpt), is on chromosome 4, 18.1 recombination units distal to brown near the interferon alpha and beta chain structural gene complex. On the inbred HPT/Le strain background, Hpt is semi-dominant, and Hpt/Hpt mice die in utero by 6 to 8 days of gestation. Such death in utero is associated with abnormalities of embryonic ectodermal derivatives. However on the (C57BL/6J x C3HeB/FeJ-a/a) segregating hybrid background, Hpt is a fully dominant mutation. HPT/Le Hpt/+ mice can be recognized by 3 to 4 days of age by patches of lightly pigmented skin. These mice show reduced numbers of hair follicles, abnormalities in hair follicle structure, and patchy absence of hair throughout life. By 2 weeks of age, abnormal hair follicle development is accompanied by thickening of the epidermis, reduction in levels of subcutaneous fat, and dermal inflammation. Progressive glomerulosclerosis, resulting in chronic kidney failure, is accompanied by increases in glomerular mesangial matrix, deposition of immune complexes, and glomerular enlargement. Scanning electron microscopic studies revealed abnormalities of podocytes including disorganization, swelling, and fusion of the foot processes. Increase in serum blood urea nitrogen levels accompanies conspicuous renal histopathologic changes. Cardiovascular changes in Hpt/+ mice are evidenced by hypertrophy of the left heart ventricle. Increased systolic blood pressure in these animals was found by 3 months of age. Anemia occurs in Hpt/+ mice by 40 weeks. The Hpt/+ mutation provides a valuable new animal model for chronic kidney disease accompanied by skin abnormalities and ventricular hypertrophy. The pathologic changes caused by this mutation are similar to those reported in affected family members with a newly described autosomal dominant human disease.

Alopecia↗

Interaction between bedding and sleeping position in the sudden infant death syndrome: a population based case-control study.

OBJECTIVE: To determine the relation between sleeping position and quantity of bedding and the risk of sudden unexpected infant death. DESIGN: A study of all infants dying suddenly and unexpectedly and of two controls matched for age and date with each index case. The parents of control infants were interviewed within 72 hours of the index infant's death. Information was collected on bedding, sleeping position, heating, and recent signs of illness for index and control infants. SETTING: A defined geographical area comprising most of the county of Avon and part of Somerset. SUBJECTS: 72 Infants who had died suddenly and unexpectedly (of whom 67 had died from the sudden infant death syndrome) and 144 control infants. RESULTS: Compared with the control infants the infants who had died from the sudden infant death syndrome were more likely to have been sleeping prone (relative risk 8.8; 95% confidence interval 7.0 to 11.0; p less than 0.001), to have been more heavily wrapped (relative risk 1.14 per tog above 8 tog; 1.03 to 1.28; p less than 0.05), and to have had the heating on all night (relative risk 2.7; 1.4 to 5.2; p less than 0.01). These differences were less pronounced in the younger infants (less than 70 days) than the older ones. The risk of sudden unexpected death among infants older than 70 days, nursed prone, and with clothing and bedding of total thermal resistance greater than 10 tog was increased by factors of 15.1 (2.6 to 89.6) and 25.2 (3.7 to 169.0) respectively compared with the risk in infants of the same age nursed supine or on their side and under less than 6 tog of bedding. CONCLUSIONS: Overheating and the prone position are independently associated with an increased risk of sudden unexpected infant death, particularly in infants aged more than 70 days. Educating parents about appropriate thermal care and sleeping position of infants may help to reduce the incidence of the sudden infant death syndrome.

Age Factors↗

Effect of genetically determined immunodeficiency on epidermal dendritic cell populations in C57BL/6J mice.

Mice homozygous for three different recessive mutations known to cause pleiotropic defects in the immune system and in the skin were used to evaluate the relationship between the classical immune system and dendritic epidermal cell populations. Numbers of Langerhans cells (LCs) and Thy-1+ dendritic cells (Thy-1+DEC) were determined using indirect immunofluorescence microscopy of epidermal whole mounts taken from viable motheaten (mev), nude (nu), and rhino (rhhr) mice. All mutants were maintained on the C57BL/6J strain background and were compared with their respective littermate normal controls. Viable motheaten mice had normal numbers of LCs at 1 month of age. However, by 8 weeks of age, LC density had decreased threefold. Nude and rhino mice had normal numbers of LCs at all ages tested. There was no significant effect of the viable motheaten mutation on numbers of Thy-1+DEC. Although nude mice showed normal numbers of Thy-1+ DEC at 1 month of age, these athymic mice had a threefold decrease in numbers of such cells by 6 months. In contrast to the reduced numbers of Thy-1+DEC seen in nude mice, rhino mice showed a four- to fivefold increase in the numbers of these epidermal cells at all ages tested. These findings suggest new mouse models for investigating the development, regulation, and biological properties of epidermal dendritic cell populations.

Animals↗