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Biomedical subjects

D Black

Publications and source records attributed to D Black.

At least 217 records · Page 12Linked to original sources

Simian alphaherpesviruses and their relation to the human herpes simplex viruses.

Biochemical and immunological properties of structural and non-structural polypeptides of the human simplex viruses (HSV1 and HSV2) and four related herpesviruses of non-human primates [Herpesvirus simiae (B virus), H. cercopithicus (SA8), H. saimiri 1 (HVS 1), and H. ateles 1 (HVA 1)] were compared. Using a radioimmunoassay (RIA), the presence of antigenic determinants shared among all six viruses was demonstrated. The relative degree of antigenic cross-reactivity among these viruses was further assessed by competition RIA. Antigenically, HSV 1 and HSV 2 were most closely related to each other although both SA 8 and B virus were also very closely related to HSV 1. Considerably less cross-reactivity existed between either HVS 1 or HVA 1 and the other four primate herpesviruses. Cross-hybridization between simian and human herpesvirus genomes demonstrated that extensive homology exists between each of the simian viruses and both HSV1 and HSV 2. Viral polypeptides bearing common antigenic determinants were identified by immune precipitation of infected cell polypeptides and by immunoblotting. Among the polypeptides of HSV which were recognized by antisera to simian viruses were the VP 5 and p40 proteins, both of which are structural components of the virion nucleocapsid. Using recombinant plasmids containing sequences of the HSV 1 VP5, p40, DNA polymerase, major DNA binding protein, and TK enzyme genes, homologous sequences were detected in all four simian viruses. Together, these results demonstrate that HSV 1, HSV 2, SA 8, and B virus form a closely related sub-group of the primate herpesviruses; HVS 1 and HVA 1 are also related to the other four primate herpesviruses, albeit more distantly.

Antigens, Viral↗

Relatedness of glycoproteins expressed on the surface of simian herpes-virus virions and infected cells to specific HSV glycoproteins.

The antigenic relatedness of the surface glycoprotein antigens of six herpesviruses indigenous to human and nonhuman primates was examined. Binding of anti-viral sera to viral antigens expressed on the surface of infected cells demonstrated that the surface antigens of herpes simplex virus type 1 (HSV 1), HSV 2, simian agent 8 (SA8), and Herpesvirus simiae (B virus) exhibit extensive cross-reactivity. Surface antigens of two viruses isolated from South American primates, H. saimiri 1 (HVS 1) and H. ateles 1 (HVA 1), were comparatively more virus-specific in their antigenic reactivity. Endpoint neutralization tests performed in the presence and absence of complement confirmed these results. Immunoprecipitation of viral proteins was used to identify those representing cross-reactive surface antigens. A glycoprotein of approximately 110,000-125,000 Daltons (110-125 k) was immunoprecipitated from cells infected with each of the six primate herpesvirus by antisera to each of the viruses. Using monospecific antisera, these glycoproteins were shown to be antigenically related to the gB glycoproteins of HSV. Although these glycoproteins were antigenically conserved among all six viruses, antibodies to the gB glycoproteins did not cross-neutralize heterologous viruses. A glycoprotein of approximately 60-70 k was precipitated from HSV 1, HSV 2, SA8, and B virus infected cells by antisera to each of these four viruses. These SA8 and B virus glycoproteins were shown to be antigenically related to the gD glycoproteins of HSV 1 and HSV 2 and to be involved in cross-neutralization among these viruses. Antisera to HVS 1 and HVA 1 did not recognize these gD glycoproteins nor was a glycoprotein of similar molecular weight precipitable from HVS 1 or HVA 1 infected cells by antisera to the other four viruses. Southern blot hybridizations using probes for HSV glycoprotein genes confirmed the conservation of the gB glycoproteins among all the simian viruses and of the gD gene in SA8 and B virus. A glycoprotein of approximately 75-80 k was, however, precipitated from HVS 1 and HVA 1 infected cells by antisera to either of these two viruses. In addition, at least one glycoprotein which appeared to be predominantly virus-specific in its reactivity was identified for five of the viruses.

Animals↗

Excretion of pyridinium cross-links of collagen in ovariectomized rats as urinary markers for increased bone resorption.

Groups of 19-day-old rats were ovariectomized or were given sham operations. Measurements in urine of the pyridinium cross-links of collagen, pyridinoline and deoxypyridinoline, 7 weeks after surgery showed significantly higher amounts of cross-links relative to creatinine in the ovariectomized groups compared with the controls. Analyses before and after acid hydrolysis of the urine revealed that the increased excretion was only as free cross-link with no change in the concentrations of the bound forms. The loss of trabecular bone in the ovariectomized group was confirmed by immunocytochemical staining with antibodies to type I collagen. There were no differences between the ovariectomized and control groups in the concentrations of cross-links in the tibial bone or the articular cartilage. Measurements of free pyridinoline and deoxypyridinoline in urine therefore appear to provide a good index of the increased bone resorption induced by estrogen deficiency.

Amino Acids↗

Expensive medical and surgical technology.

In summary, new developments in technology, as applied to medical and surgical practice, are to be encouraged, which is just as well, since they are probably inevitable. But they also call for critical assessment and, perhaps, a measure of formal control. It is, however, important that the criteria for their acceptance (or rejection) should not be limited to economic considerations but should also include their clinical applicability and their likely effect on outcomes.

England↗

Changes in lymphocyte number and phenotype in seven lymphoid compartments after thermal injury.

Thermal injury is associated with dysfunction of host defense systems. The present study used flow cytometric immunofluorescence analyses to investigate changes in number and phenotype of lymphocytes in seven different lymphoid compartments at 2, 6, 12, 24, 48, and 60 days after 50% total body-surface area thermal injury in the rat. Relative to sham-injured control rats, at postburn day 2, significant lymphopenia was observed in the peripheral blood along with depletion of lymphocytes from the spleen and thymus. By day 6 after injury, lymphocytes in the bone marrow and cervical lymph nodes decreased significantly while numbers in the spleen and thymus remained depressed. Splenic and cervical node lymphocyte numbers normalized by day 12, the bone marrow and thymus numbers still were significantly lower than control, and a 6.5-fold increase in number of lymphocytes was observed in the nodes draining the burn wound, pooled axillary, brachial, inguinal, and lumbar lymph nodes. At day 24 after injury, the thymus and bone marrow virtually were depleted of lymphocytes, the mesenteric lymph nodes manifested a significant decrease, and lymphocytes in the nodes draining the burn wound continued to increase in number. This same pattern was maintained on day 48, but numbers of lymphocytes in the mesenteric nodes normalized. At day 60 after injury, lymphocyte numbers in all tissues were normalized, but the spleen and nodes draining the burn wound where increased numbers compared to control persisted. Cell-surface phenotyping was performed on all lymphoid tissues at all time intervals to determine the percentages of lymphocytes comprising the following subsets: Ia+ cells (B cells and activated T cells), T cells, T-Helper/Inducer cells (T-H/I), and T-Suppressor/Cytotoxic (T-S/C) cells. Although changes in lymphocyte subset percentages were complex, they could be divided grossly into two phases. First, all compartments showed significant phenotypic changes in the first six days after burn. With the exception of the nodes draining the burn wound and the blood, this was followed by a return towards normal on day 12. The second phase then ensued with significant phenotypic changes again occurring in most tissues from days 24 to 60 after injury. These studies demonstrate that burn injury results in dramatic alterations in lymphocyte numbers and subset percentages in different lymphoid compartments. Immune alterations observed following thermal injury may be due, in part, to a redistribution of the cellular elements responsible for generation of the immune response.

Animals↗

Urinary excretion of the hydroxypyridinium cross links of collagen in patients with rheumatoid arthritis.

Values for urinary hydroxypyridinium cross links of collagen measured by high performance liquid chromatography in a group of 19 seropositive patients with rheumatoid arthritis (RA) were compared with 19 controls matched for age and sex. The amounts of pyridinoline, expressed relative to creatinine, were significantly higher in the RA group, but there was no significant increase in a bone specific analogue, deoxypyridinoline. There were significant positive correlations between pyridinoline excretion and both C reactive protein and erythrocyte sedimentation rate, whereas there was an inverse relation with grip strength. The data indicated that pyridinoline concentrations in urine are strongly associated with disease activity in patients with RA.

Adult↗

The BMA and science.

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History, 19th Century↗

Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) pilot study.

The pilot study of the Systolic Hypertension in the Elderly Program was a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension. It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months. Mean age of the participants was 72 years; 63% were women, and 82% were white. Pretreatment blood pressures averaged 172/75 mm Hg. Participants were randomly assigned to treatment with chlorthalidone or placebo as Step I medication. Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups, respectively, with 60% and 33% of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit. All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk, and rates for definite "first stroke" were 8.3 and 12.8 per 1,000 years of risk. Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates. A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates.

Antihypertensive Agents↗

Day-hospital and community treatment for acute psychiatric illness. A critical appraisal.

Findings on the efficacy of day-hospital and community treatment for acutely ill psychiatric patients have been contradictory. This review confirms the methodological problems previously noted, but highlights the variation in feasibility of day care: staffing levels and the attitudes of staff appear to have been responsible, along with the severity and chronicity of illness. The comparison of day and in-patient care to see which is 'superior' has been unrewarding, and further research is needed. Day-hospital treatment is unlikely to be more widely used for acutely ill patients until: (a) there is clear evidence that certain patients are best treated in this way; (b) the social and clinical characteristics of such patients are defined; (c) adequate staffing is achieved (i.e. day care is not regarded as a cheap option); and (d) day centres are available for chronic patients.

Community Mental Health Services↗

Influence of age, renal function and heart failure on procainamide clearance and n-acetylprocainamide serum concentrations.

Twenty Caucasian adult patients with ventricular tachycardia were treated with intravenous procainamide. Seven patients also had moderate congestive heart failure. Steady-state procainamide (PA) and n-acetylprocainamide (NAPA) concentrations were used to compute procainamide clearance and NAPA/PA concentration ratio. Using stepwise multiple linear regression age, creatinine clearance and congestive heart failure were found to influence procainamide clearance significantly (p less than 0.05). Age and creatinine clearance effected the NAPA/PA concentration ratio (p less than 0.05). Based on this data, age appears to have an independent effect on both procainamide clearance and the NAPA/PA ratio that is separate from the decline in renal function that occurs in elderly patients.

Acecainide↗

Comparison of cefoperazone and mezlocillin with imipenem as empiric therapy in febrile neutropenic cancer patients.

Seventy-eight patients with cancer experienced 88 episodes of fever while neutropenic and were randomly assigned to receive empiric antibiotic therapy with cefoperazone 2 g intravenously every 12 hours and mezlocillin 4 g intravenously every six hours or imipenem/cilastatin 500 mg intravenously over 30 to 60 minutes every six hours. Within 96 hours of starting antibiotic treatment, 24 patients (57 percent) treated with cefoperazone and mezlocillin and 34 patients (74 percent) receiving imipenem/cilastatin became afebrile. One half of the patients in each arm required changes in the antibiotic regimen because of side effects, persistent fever with a site suspicious for infection, resistant organisms, or breakthrough bacteremias. Forty patients (95 percent) receiving cefoperazone and mezlocillin and 43 patients (93 percent) receiving imipenem/cilastatin recovered from the neutropenic episode. Two patients in each regimen group died of their underlying disease. One patient in the imipenem/cilastatin arm died of Pseudomonas aeruginosa sepsis. Although the two regimens are comparable in efficacy, the incidence of side effects favored the cefoperazone and mezlocillin group. No seizures or bleeding were seen in either arm; however, 19 patients (41 percent) receiving imipenem/cilastatin required pretreatment antiemetic drugs for nausea.

Adult↗

Extraction of an infected tusk in an adult African elephant.

An 18-year-old African elephant was determined to have a nonrepairable crack in its left tusk. Treatment included extraction of the tusk, using rotational and extractional forces, and administration of antibiotics, followed by 1 year of flushing the opened tusk cavity with warm tap water. Two years after surgery, the elephant was healthy, and the tusk cavity was 80% filled with normal tissue.

Animals↗