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Biomedical subjects

C Kaufman

Publications and source records attributed to C Kaufman.

At least 37 records · Page 2Linked to original sources
PubMed1986

Allospecificity of activated T cells grown from endomyocardial biopsies from heart transplant patients.

Studies were conducted to determine the functional characteristics of lymphocytes infiltrating human heart allografts. We have developed methodologies to generate lymphocyte cultures from endomyocardial biopsies. Thirteen biopsies from four heart transplant recipients, obtained at different days during a posttransplant period of less than two months, were cultured in interleukin-2 (IL-2)-containing medium supplemented with irradiated autologous peripheral blood lymphocytes as feeder cells. Lymphocyte cultures were obtained from all 13 biopsies and they exhibited a proliferative response to IL-2, suggesting the presence of activated T cells that express IL-2 receptors. Several cultures consisted of Leu 3 (helper/inducer) T cells, whereas others were primarily Leu 2 (cytotoxic/suppressor) T cells or a mixture of both types of cells. Cultured lymphocytes were also shown to be able to undergo secondary proliferation to donor-specific leukocytes as measured by primed lymphocyte testing (PLT). The PLT specificity of these cells was frequently toward class II HLA antigens of the donor, but certain cultures had PLT specificity associated with class I HLA antigens. These results demonstrate the feasibility of growing functionally active T cells from heart transplant biopsies. An analysis of the phenotypes and allospecificity, as well as a functional characterization of these cells, should generate useful information about the types of T cells involved in cardiac transplant rejection.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Interaction of soluble pig heart glutamate-aspartate transaminase with various beta,gamma-unsaturated amino acids.

beta-Ethylidene-DL-aspartate (beta EA) and beta-methylene-DL-glutamate (beta MG) were synthesized and tested as potential suicide inhibitors of soluble pig heart glutamate-aspartate transaminase (sGAT). beta MG was found to be a) a substrate with a very low turnover number relative to glutamate and b) a competitive inhibitor with respect to aspartate (albeit with a large binding constant). At high concentrations beta MG inactivated the enzyme but only very slowly. beta EA was also found to be a substrate with a very low turnover number; it did not inactivate the enzyme (1 hr, 25 degrees C) even at a high concentration. However, beta EA was found to bind to the enzyme with an affinity comparable to that of aspartate and glutamate. beta-Methylene-DL-aspartate (beta MA) has been shown to rapidly inactivate glutamate-aspartate transaminase. Therefore, it appears that glutamate-aspartate transaminase can bind analogues of aspartate with alkene groups in the beta position. The conjugated carbonyl groups of beta MA and beta EA will enhance Michael addition in comparison with that expected for vinylglycine. On the other hand, the presence of the methyl groups should reduce the electrophilicity of the double bond of beta EA compared to beta MA. This deactivation and/or steric hindrance to Michael attack may account for the inability of beta EA to inactivate sGAT. Therefore, it may be possible to design selective suicide inhibitors of glutamate-aspartate++ transaminase with the following structure: HO2CC(= CHX)CH(CO2H)NH2, where X is an electron-withdrawing group. Ideally, X would increase the reactivity of the double bond while affording a minimum of steric hindrance to susceptible enzyme-bound bases.

Amino Acids↗
PubMed1985

Interactions between bronchoalveolar lymphocytes and macrophages in heart-lung transplant recipients.

Bronchoalveolar lavages (BAL) were obtained from heart-lung transplant patients. Following transplantation, the number of lymphocytes and macrophages are considerably increased. BAL lymphocytes frequently exhibit donor specific secondary allogeneic proliferation measured in primed lymphocyte testing (PLT) assays. We report our findings regarding a persistence of donor derived macrophages and lymphocytes in BAL during the posttransplant period. The presence of donor specific macrophages causes a proliferative response of alloreactive BAL lymphocytes from the recipient. This "Bronchoalveolar Macrophage Lymphocyte Reaction," or "BMLR," may represent a unique aspect of in vivo interactions associated with lung allograft responses. Comparative studies showed considerably lower PLT responsiveness of peripheral blood lymphocytes than that of BAL lymphocytes. These studies suggest that functional assays on BAL cells may be useful in monitoring lung transplant rejection and other immunological phenomena that affect pulmonary function of heart-lung transplant patients.

Bronchi↗
PubMed1983

Inhibition of glutamate-aspartate transaminase by beta-methylene-DL-aspartate.

beta-Methylene-DL-aspartate, a new beta, gamma-unsaturated amino acid, is an irreversible inhibitor of soluble pig heart glutamate-aspartate transaminase (Ki approximately 3 mM with respect to the L-form; limiting rate constant for inactivation approximately 0.4 min-1). The new amino acid is the most specific inhibitor of glutamate-aspartate transaminase thus far studied. It does not inactivate pig heart glutamate-alanine transaminase, soluble rat kidney glutamine transaminase K, gamma-aminobutyrate transaminase (from Pseudomonas fluorescens), glutamate decarboxylase (Escherichia coli), snake venom L-amino acid oxidase, or hog kidney D-amino acid oxidase. In addition, the following enzymes were not inhibited by beta-methylene-DL-aspartate in rat tissue homogenates: gamma-aminobutyrate transaminase (brain), tyrosine transaminase (liver), glutamine transaminase L (liver), asparagine, transaminase (liver), ornithine transaminase (liver) or branch-chain transaminase(s) (kidney). Intraperitoneal injection of beta-methylene-DL-aspartate into mice decreased kidney and liver glutamate-aspartate transaminase activities but had no effect on liver glutamate-alanine transaminase activity.

Amino Acid Oxidoreductases↗
PubMed1983

Pregnancy-induced leukocytosis in Yemenite Jews.

Benign neutropenia is often found among healthy Yemenite Jews. An assessment was made of the magnitude of labor-induced leukocytosis in 44 Yemenite Jewish women, by comparing their hematological values during labor with those of 27 non-Yemenite women. A statistically significant difference was found in the absolute counts of the white blood cells (WBC) during delivery between the two groups, the values being lower among Yemenite Jews [10,291 +/- 422] vs. [11,759 +/- 630] X 10(9)/1) and similar findings were detected among their infants. The low WBC counts in the Yemenite group at parturition were also associated with significantly lower plasma cortisol levels (Yemenite group: 33.7 +/- 3.5 micrograms/dl; controls: 49.3 X 2.9 micrograms/dl). A correlation was found between serum cortisol levels and the magnitude of leukocytosis in both groups of women and their infants. These results suggest that a low basal corticosteroid output may contribute to the low white blood cell counts detected in some ethnic groups like the Yemenite Jews.

Adult↗
PubMed1982

Use of crystalline hemoglobin as replacement of RBC mass.

Replacement of a circulatory RBC mass was performed isovolemically in experimental dogs using either 7% crystalline hemoglobin solution with a low P50 (the oxygen tension necessary to produce 50% saturation of hemoglobin at pH 7.4 and 37 degrees C) or with an albumin solution. Progressive RBC depletion caused increased cardiac output in both groups. Oxygen delivery was better preserved after using the crystalline hemoglobin solution, and, under conditions of extreme anemia, oxygen transport using this solution enabled dogs to survive the otherwise lethal insult. Although administration of crystalline hemoglobin preserved oxygen transport, oxygen off-loading was at a lower tension because of the lower P50. Decreased mixed venous oxygen tension, which presumably reflects lower tissue oxygen tension, was associated with systemic vasoconstriction. The administration of oxygen-carrying solutions with low P50 values results in a relatively vasoconstricted state. This vascular response is mediated by changes in tissue oxygen tension, rather than by impaired tissue oxygen consumption.

Animals↗
PubMed1982

Stretch reflexes of triceps surae in normal man.

In order to learn more about stretch reflex behaviour of triceps surae, normal human subjects sat in a chair with one foot on a platform attached to a torque motor that produced phasic dorsiflexion displacements on the ankle. EMG activity was recorded from triceps surae and responses were obtained for various conditions. When the subjects's foot was relaxed, stretch of triceps surae produced a single EMG component at short-latency which increased in magnitude with increasing velocity of stretch. The response was not altered if the subject was asked to plantarflex or dorsiflex the ankle voluntarily when he felt the perturbation. It was reduced by vibration of the Achilles tendon. If the triceps surae was stretched while the subject plantarflexed his ankle, the short-latency response was followed by one and sometimes two long-latency responses. Like the short-latency reflex when the foot was relaxed, none of these responses was altered by the subject's planned movement after feeling the perturbation. All of the responses were suppressed to a similar degree by vibration. The long-latency reflexes depended on long-duration of stretching and relatively slow acceleration of stretch. The reflexes persisted after anaesthesia to the foot suggesting that muscle afferents were responsible. Interactions between H-reflexes and stretch-reflexes revealed that the afferent volley producing a stretch reflex acted like the afferent volley producing a small H-reflex. Responses at an interval of 30 ms to both an electrical stimulus for an H-reflex and a stretch stimulus were possible if the electrical stimulus produced only a small H-reflex and if the subject had been plantarflexing the ankle. The short-latency reflex when the foot was relaxed or exerting a background force appears to be the monosynaptic, Ia mediated stretch reflex. The physiological properties of the long latency reflexes are similar to those of the short-latency reflex, and they may represent, at least to a certain extent, response of the motor neuron pool to successive Ia bursts.

Adult↗
PubMed1981

Physiological observations in Sydenham's chorea.

Involuntary movements in a patient with Sydenham's chorea were usually characterised by bursts of EMG activity lasting more than 100 ms, occurring asynchronously in antagonist muscles. The "hung-up" knee jerk was a choreic movement induced by the tendon tap. Exaggerated voluntary movements were produced with EMG burst longer than normal.

Child↗
PubMed1979

Familial absorptive hypercalciuria and renal tubular acidosis.

Hypercalciuria was considered as a secondary condition when associated with familial renal tubular acidosis. Later studies suggested that hypercalciuria could lead to renal tubular acidosis and nephrocalcinosis. Selected members of a family spanning five generations were studied. Renal tubular acidosis was present in eight subjects in three consecutive generations. Increased 24-hour urinary calcium excretion was present in nine subjects in three consecutive generations, alone in the younger generation, and in combination with renal tubular acidosis and nephrocalcinosis in the older generation. Calcium loading tests showed the absorptive nature of hypercalciuria in nine of 18 subjects studied. This report suggests that in this family the absorptive hypercalciuria is an autosomal dominant genetic defect with complete penetrance and variable expressivity which leads to renal tubular acidosis and nephrocalcinosis.

Acidosis, Renal Tubular↗