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Biomedical subjects

P Conrad

Publications and source records attributed to P Conrad.

At least 37 records · Page 2Linked to original sources

Specific cleavage of the alpha 4 integrin associated with activation of peripheral T lymphocytes.

The heterodimeric VLA-4 integrin has been implicated in lymphocyte migration to inflamed peripheral tissues, lympho-haemopoiesis and autoimmune disease. To determine the structure and function of VLA-4 in physiological processes, molecular forms of the VLA-4 alpha-chain were analysed during T-cell activation. The results showed that prolonged activation of human peripheral T cells was associated with increased cleavage of the 150,000 MW alpha 4 chain into 80,000 and 66,000 MW fragments. Similar-sized alpha 4 fragments could also be generated from 150,000 MW alpha 4 on intact resting T cells by brief trypsinization, whereas trypsin treatment of isolated 150,000 MW alpha 4 resulted in nearly complete protein degradation. Native 80,000 and 66,000 MW alpha 4 chains on activated T cells could not be digested further by trypsin. These results indicated that specific cleavage of 150,000 MW alpha 4 was largely dependent on the tertiary structure of native alpha 4 chains. To determine the specific cleavage site in alpha 4 on peripheral T cells, VLA-4 was isolated and purified from in vitro-activated T cells and the N-terminus of the 66,000 MW fragment was partially sequenced. The sequence SKR/STE was identified as the specific alpha 4 cleavage site on T cells. These results indicate that T cells, upon activation, acquire an enhanced dipeptidase processing activity, which cleaves alpha 4 at a specific site.

Amino Acid Sequence↗

Mechanism of peripheral T cell activation by coengagement of CD44 and CD2.

A number of CD44 antibodies are known to augment peripheral T cell proliferation stimulated with suboptimal concentrations of activating pairs of CD2 mAb. These findings have implicated the CD44 adhesion receptor in the activation of peripheral T cells via CD2. We have investigated early events after CD44 and CD2 coengagement on peripheral T cells. CD44 and CD2 coengagement resulted in enhanced [Ca2+]i mobilization. However, the increase in [Ca2+]i mobilization did not occur until at least 3 min after CD2 and CD44 coengagement, suggesting that other events precede the elevation in [Ca2+]i. Using a T cell/fibroblast adhesion assay, we could demonstrate a dramatic increase in T cell adhesiveness after about 1 min after CD44 and CD2 coengagement. The increase in T cell adhesiveness was comparable to that induced by PMA. In the absence of antibodies or treatment with mAb directed to other T cell surface Ag, there was little if any adhesion between unstimulated peripheral T cells and fibroblasts. Enhancement of T cell adhesiveness through CD44 engagement was not mediated by a direct effect on lymphocyte-function associated Ag-3, the known ligand of CD2. However, cross-linking of CD44 resulted in epitopic modulation of CD2 as demonstrated by the increased expression of the T11(3) activation epitope. Furthermore, anti-CD44 could substitute for anti-T11(2) in the activation of peripheral T cells via CD2. These results suggest that CD44 ligation has profound effects on CD2-mediated events by inducing epitopic modulation of CD2.

Antigens, CD↗

The new corporate health ethic: lifestyle and the social control of work.

A corporate health ethic, forged in U.S. industry in the 20th century, clearly demarcated boundaries between private and workplace health concerns. This article advances evidence that the boundary is blurring, and argues that trends in workplace initiatives, including employee assistance, wellness programs, and drug screening, are giving shape to a new corporate health ethic. The new ethic emphasizes workers' lifestyles on and off the job, engendering a shift in corporate jurisdiction over employee health and behavior. Economic arguments such as "health care cost containment" are commonly offered as explanations for these new health initiatives. But the authors see the new ethic as a deeper response to a changing corporate environment and, more fundamentally, as emblematic of changes in the social control of work and productivity. They argue that the new health ethic may be a harbinger of new forms of social control in the workplace.

Health Behavior↗

Hemolytic anemia caused by Babesia gibsoni infection in dogs.

Babesia gibsoni caused severe hemolytic anemia in 11 dogs from southern California. The most common clinical signs of B gibsoni infection were lethargy, anorexia, anemia, and thrombocytopenia. Acute infection with B gibsoni may be misdiagnosed as autoimmune hemolytic anemia. Diagnosis was most reliably determined by identification of the intraerythrocytic parasites on Giemsa-stained blood smears. The pathogenicity of B gibsoni, difficulties in diagnosis, the parasite's resistance to treatment with available drugs, and frequent interstate movement of dogs indicate that this disease may be a serious threat to dogs throughout the United States.

Anemia, Hemolytic↗

Human interleukin-7 induces proliferation of neoplastic cells from chronic lymphocytic leukemia and acute leukemias.

The biologic effects of interleukin-7 (IL-7) and the expression of specific IL-7 membrane receptors on isolated neoplastic cells from previously untreated patients with chronic lymphocytic leukemia as well as acute leukemias were investigated in vitro. Leukemic cells were incubated for up to 6 days with various concentrations of IL-7 (0.01 to 2,000 U/mL). Neoplastic cells of the T- or B-phenotype from chronic as well as from acute leukemias proliferated in a dose-dependent manner. Cells from acute myeloid leukemias also proliferated in response to IL-7. An optimal proliferative effect was achieved between 96 and 120 hours with 200 U/mL IL-7. Combinations of IL-7 with IL-2 and tumor necrosis factor-alpha showed an additive effect on [3H]TdR incorporation. IL-7 binding assays gave a value of approximately 33 to 180 high-affinity (kd approximately 20 pmol/L) binding sites/cell and approximately 241 to 3,280 low-affinity (kd approximately 600 pmol/L) binding sites/cell. Receptor expression correlated with the proliferation in response to IL-7. These data indicate that IL-7 can induce proliferation of relatively mature tumor cells, and that this effect is not restricted to the lymphoid lineage.

Adult↗

Enhancement of CD2-mediated T cell activation by the interaction of VLA-4 with fibronectin.

Human fibroblasts were shown to enhance the proliferation of peripheral T cells in the presence of suboptimal concentrations of anti-CD2 antibodies (anti-T112 and anti-T113) and agonistic anti-VLA-4 antibody. Evidence is provided that the interaction of VLA-4 with immobilized fibronectin can enhance the proliferation of T cells subjected to suboptimal stimulation via CD2. Our results suggest that the fibroblast-stimulated T cell proliferative response to low doses of anti-T112 and T113 antibodies is due to the interaction of VLA-4 with fibroblast fibronectin. These findings also suggest a role for the fibronectin/VLA-4 interaction in the inflammatory process.

Antibodies, Monoclonal↗

Neutral-sugar transport by rat liver lysosomes.

Transport of D-glucose was studied in Percoll-gradient-purified rat liver lysosomes. D-Glucose uptake had a Km of 22 mM and a t1/2 of approx. 30 s. D-Fucose, 2-deoxyglucose and methyl alpha-glucoside were the most effective competitors for uptake of D-glucose, although D-galactose, D-mannose, D-xylose and L-fucose also appeared to compete for uptake. L-Glucose was a poor competitor for uptake. No competition was observed with N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-glucuronic acid, N-acetylneuraminic acid, D-glucosamine or the amino acids L-glycine, L-lysine and L-proline. Uptake was unaffected by N-ethylmaleimide, dithiothreitol, KCl, NaCl, ATP/Mg or alteration of buffer pH. D-Glucose efflux from lysosomes was temperature-dependent, with a Q10 of 2.3, and was inhibited by cytochalasin B. Counter-transport could not be demonstrated. In contrast, L-fucose uptake had a Km of 65 mM and was largely unaffected by 5 M excess of neutral D-sugars. Both uptake and efflux of L-fucose were inhibited by cytochalasin B. It appears that lysosomes possess a facilitated transport system for D-glucose and perhaps other neutral D-sugars that is discrete from transport systems for acetylated and acidic sugars.

Animals↗

Health and fitness at work: a participants' perspective.

In the 1980s worksite health promotion or wellness programs have become more common in American corporations. Corporations see them as a way to control rising health care costs and to improve employee health. This paper examines participants' perspectives on participation in a health and fitness program, based on participant-observation and 35 in-depth interviews with members of one corporate program. Participants have a decided fitness-orientation (as opposed to a health-orientation), focusing on staying in shape and controlling weight. The consequences of this orientation for the promotion of health, the future of wellness programs, and the corporation are discussed.

Adult↗

Olfaction and hemodialysis: baseline and acute treatment decrements.

The effect of hemodialysis (HD) on olfactory recognition and memory function was investigated in people receiving chronic HD treatment. Fifteen subjects were given an olfactory recognition task 0.5 h before and 0.5 h after a dialysis session in counterbalanced order. Ten dialysis patients received a verbal recall task twice. Ten age-matched normal subjects received the olfactory task twice. Results were: (1) olfactory scores in the HD group were significantly lower than control subjects scores; (2) within the dialysis sample, olfactory identification scores were significantly lower after treatment than before, and (3) there were no parallel decreases in memory performance of the dialysis group after a HD treatment. We therefore conclude that those subjects receiving HD treatment demonstrate acute and chronic deficits in olfactory recognition which are unlikely to be due to fatigue, cognitive disequilibrium, anticoagulant treatment or high levels of uremic toxins.

Adolescent↗

Who comes to work-site wellness programs? A preliminary review.

Work-site wellness programs have emerged in the past decade with the goals of modifying employee health risks and potentially reducing health care costs. The question of who comes to wellness programs is a key one for achieving these goals. This reviews the available studies on participation in wellness programs and briefly reports the results from a comparative study at one site. Although the current studies are limited, the data suggest that participants appear to be somewhat healthier and more concerned with fitness and health matters than nonparticipants. Factors like employees' age, sex, and position in a company may affect participation, although more specific research is needed.

Health Promotion↗

Wellness in the work place: potentials and pitfalls of work-site health promotion.

In the past decade work-site health promotion programs have been developed by many American corporations. Although the potential for these programs to improve worker health and productivity is appealing, there is yet only limited data on their effectiveness or their pitfalls. Evaluation of the benefits of work-site health promotion must consider the sociopolitical context as well as cost-containment outcomes.

Cost Control↗

German pelviscopic statistics for the years 1978-1982.

The second set of statistics on pelviscopy in Germany included information on 269,603 pelviscopies done in 322 general hospitals, and 22,859 pelviscopies done in private clinics between 1978 and 1982. In general hospitals the rate of serious complications was 1.9% and in private clinics 2.0%. Injuries to large blood vessels headed the list of complications. The main technique for tubal sterilization was the bipolar high-frequency current method with 75% in general hospitals and 73.1% in private clinics, followed by the endocoagulation technique according to Semm (36.8%). Sterilization failures were reported in 2.6%. Most failures were reported after sterilization with the bipolar electrocoagulation technique, followed by the clip technique. The rate of post-sterilization ectopic pregnancies was 1.06%. The highest rate of ectopic pregnancies was reported after using the bipolar tubal sterilization method (1.4%).

Blood Vessels↗