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Biomedical subjects

W R Clark

Publications and source records attributed to W R Clark.

At least 127 records · Page 7Linked to original sources
PubMed1978

In vivo and in vitro induction of cytotoxic lymphocytes by alloantigen-reactive lymphocytes fractionated on spleen cell monolayers.

The generation of cytotoxic T cells by normal and primed lymphocytes fractionated on spleen cell monolayers was examined by two methods. In the first method, sublethally irradiated recipients were inoculated with the fractionated cells, and 5 to 6 days later the spleens were tested for cytotoxicity against 51Cr tumor target cells syngeneic to the host. Significant reduction of cytotoxic activity was observed in one-half of the experiments. In the second method, the fractionated cells were cultured with mitomycin C-treated stimulated cells and tested 6 days later for cytotoxicity. A slight reduction of cytotoxic activity was observed. In both methods, the cytotoxic response generated by the fractionated alloantigen-primed lymphocytes was similar to the response obtained with unprimed cells.

Animals↗
PubMed1978

Reversal of diabetes in rats using fetal pancreases stored at -196 C.

Fetal rat pancreases frozen to and stored at -196 C were used for transplantation into streptozotocin-induced diabetic syngeneic adult recipients. Transplantation was carried out either directly after thawing from -196 C, or after a 21-day growth period in a syngeneic, normoglycemic adult carrier. All transplants were placed under the kidney capsule. A single, frozen fetal rudiment was sufficient to restore blood glucose, urine volume, and urine glucose to normal, provided it had first been grown for 21 days in a normal carrier. It vitro perfusion studies showed that fetal pancreases stored at -196 C were equivalent to fresh rudiments in their responses to a glucose stimulus.

Animals↗
PubMed1978

Interpretation of 51Cr-release data: a kinetic analysis.

An analysis of 51Cr-release data from cell-mediated cytotoxicity assays, plotted in the form of effector cell dilution curves, is analyzed in detail in terms of a saturation kinetics model for effector-target interaction. The effect of nonimmune (bystander) cells in the effector population is particularly examined. The theoretical development of the saturation model predicts that, at low concentrations of target cells, increasing proportions of bystander cells should broaden the range of effector cell concentration required to achieve a given increment of target cell lysis, but that at high target cell concentration this effect should disappear. Experimental validation of this prediction is presented.

Animals↗
PubMed1978

Progressive changes in cytotoxic potential during mixed lymphocyte culture.

In a previous study it was shown that at least one round of DNA synthesis is required for initial expression of cytotoxic function in mouse lymphocytes responding to alloantigen in vitro. In the experiments reported here we ask whether subsequent rounds of cell division are required simply for clonal expansion of this initial level of cytotoxic function within the population, or whether the amount of cytotoxicity per cytotoxic cell is altered during subsequent rounds of cell division. The amount of cytotoxicity per unit number of cells at various stages of culture was compared with the frequency of cytotoxic cells as estimated principally by effector-target cell conjugates. Our results strongly suggest that the amount of cytotoxicity per cell (cytotoxic potential) is not a static property of cytotoxic cells, but can be modulated up or down during the course of a reaction.

Animals↗
PubMed1978

Regional burn survey: two years of hospitalized burned patients in central New York.

A 2-year survey of burn victims in a 15-county region was conducted to help define the need for a burn unit. There were 1,165 patients hospitalized for burn care; 58 patients were transferred; 32 to more sophisticated facilities, 15 out of state. The mean hospitalization rate was 33/100,000; 95/100,000 for persons under 2 year old. The 42 hospitals, in the region treated an average of 14 burn patients each year. Scalds accounted for 39% of all burns and 85% of burns in children under 2. Burn-related deaths numbered 143: 4/100,000. House fires were responsible for 90 deaths. Despite incomplete records and the lack of firm criteria for burn severity, regional burn data describe the health care system, as it relates to burns, and identify high risk groups. The range inseverity of thermal injuries is great; the quality of care provided is difficult to assess.

Adolescent↗
PubMed1978

Prehospital burn care for emergency medical technicians.

The development, objectives, content, and evaluation of a unique, 60-minute synchronized slide/tape program on prehospital burn care for Emergency Medical Technicians is described. A design for valid content-referenced formative evaluation is presented.

Achievement↗
PubMed1977

Lectin-driven maturation of cytotoxic effector cells: the nature of effector memory.

In an attempt to define further the activation of effector T-cell function with concanavalin A (Con A), we examined the ability of Con A to generate effector memory in mouse lymph node cells in vitro. In the course of these studies, it became necessary to define parameters by which memory could be defined. These parameters include length of time of exposure to signal required to generate full cytotoxic function; time of onset and kinetics of blast cell formation; requirement for DNA synthesis; sensitivity to the drug 5'-bromodeoxyuridine; and kinetics of the cytotoxic response to alloantigen. By these criteria, mouse lymph node cells exposed 12 days previously to Con A behave qualitatively differently from unprimed mouse lymphocytes. We found that the time of onset and kinetics of DNA synthesis could not be used to distinguish primary and secondary cytotoxic responses. We propose that the parameters defined in these stidues can be applied generally in determining whether a given cytotoxic response involves primed (memory) or unprimed cells.

Animals↗
PubMed1977

Complete reversal of experimental diabetes mellitus in rats by a single fetal pancreas.

Complete reversal of streptozotocin-induced diabetes mellitus in adult rats will follow transplantation of a single fetal pancreas if the organ is first grown in a normal syngeneic carrier before transfer to the diabetic recipient. Careful control of the blood sugar of diabetic recipients may enhance the function of a single donor organ and thus improve histocompatibility matching.

Animals↗
PubMed1977

Psychiatric complications of burned adults: a classification.

The psychiatric complications occurring in a group of adult burn patients were correlated with pertinent data in the literature and a classification constructed, based on the three stages of the acute grief response to injury: psychiatric complications occur when the process of mourning is arrested in a regressive episode. Thirty-five adult patients with burns of greater than 7% body surface area were studied. It was found that Body Surface Area burned, the presence of a Premorbid Psychiatric Diagnosis, and Age are all significantly correlated with the occurrence of psychiatric complications following burn injuries and account for 61% of the variance in the sample. The implications of these findings and possibilities for further research are discussed.

Adult↗
PubMed1976

Fetal pancreas transplantation for reversal of streptozotocin-induced diabetes in rats.

Streptozotocin-induced diabetes in rats was completely reversed by transplantation of syngeneic fetal pancreases placed beneath the kidney capsule. To accomplish complete reversal of diabetes, four or more pancreases were necessary; three resulted in partial reversal, and two produced a slight but significant effect in some recipients. Removal of the transplants resulted in the prompt return of diabetes. The islets of Langerhans in the transplants functioned homeostatically; this was indicated by regular normal blood glucose values, in addition to normal findings in blood IRI response and glucose disappearance rate after glucose injection. Disappearance of exocrine elements, with only ducts and fibrous tissue remaining, resulted in a pure endocrine organ. The advantages of this technie, such as ease of accessibility for placement, observation, and removal, are of great importance for possible application to humans.

Animals↗
PubMed1976

Activation of cytotoxic function in T lymphocytes.

The requirements for activation of cytotoxic function in mouse T lymphocytes were investigated. Initial generation of cytotoxicity in normal lymphocytes was equal in magnitude with either Con A or specific alloantigen, and in either case required DNA synthesis. Cytotoxic function in MLC-primed cells could also be regenerated by Con A, the magnitude and target specificity of the cytotoxicity thus generated being indistinguishable from that recalled by specific alloantigen. Cytotoxicity could also be regenerated by third party-stimulating cells; however, the cytotoxicity evoked by third party cells was always specific only for target cells of the original stimulating cell H-2 genotype. The data presented suggest that there are a number of ways to activate cytotoxicity in effector T cells, and are most consistent with a model for T cell triggering that minimizes a strict informational function of antigen-receptor interactions.

Animals↗
PubMed1975

The requirement for DNA synthesis and gene expression in the generation of cytotoxicity in vitro.

The requirement for cell division and expression of new genes was examined in the primary and secondary mouse mixed leukocyte culture (MLC). Hydroxyurea (HU) was used to block DNA synthesis and cell division, and 5-bromo-2'-deoxyuridine (BUdR) was used to probe for the expression of new cell-specific genes. In the primary MLC, inhibition of DNA synthesis and cell division by HU almost totally suppressed the generation of initial, target-specific cytotoxicity. When HU was washed out of the cultures, cytotoxicity was generated after a lag time approximately equal to the period of treatment with HU. The rate of development and maximal value of cytotoxicity in HU-reversed cultures was identical to untreated controls, suggesting that the inhibition was not due to a nonspecific lethal effect of the drug. Development of initial cytotoxicity in primary MLC was similarly suppressed by levels of BUdR 25 to 75-fold below the levels of this drug having nonspecific mutagenic effects in lymphocytes, indicating that development of cytotoxicity was also dependent on the expression of a new genetic program. In the secondary MLC, regeneration of both DNA synthesis and cytotoxicity was apparent 12-15 h after re-exposure to initial stimulating antigen. In this reaction, however, generation of cytotoxicity was insensitive to both HU and BUdR. Thus, the cytotoxic program developed in the primary MLC appears to be genetically stable through the production of effector memory cells, and into regeneration of fully cytotoxic memory cells in secondary MLC.

Animals↗
PubMed1973

Radiobacteriolysis: a new technique using chromium-51 for assaying anti-Vibrio cholerae antibodies.

A new method for detecting and quantitating antibodies against Vibrio cholerae is described. The reaction involves the release of radiochromium from prelabeled vibrios in the presence of specific antibody and complement. The entire assay can be completed within 5 hr. The method is highly reproducible, immunologically specific, temperature- and complement-dependent, and significantly more sensitive than other methods currently used for titration of anti-Vibrio cholerae antibodies. The technique is also potentially applicable to titration of antibodies against other gram-negative bacteria.

Aeromonas↗