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Biomedical subjects

C Kaufman

Publications and source records attributed to C Kaufman.

At least 19 recordsLinked to original sources

A longitudinal psychopathological schedule.

A schedule is described for rating the symptoms of mental illness over a period of time which includes several episodes. The reliability was measured in a study involving six raters. The sources of information required were studied, in 20 patients, by comparing an interview with the patient, a similar interview with an informant and an analysis of the case records. A synopsis of interview and record data are necessary to obtain adequate information about longitudinal psychopathology and 'lifetime' diagnosis.

Adolescent

Schizophrenia, bipolar disorder and depression. A discriminant analysis, using 'lifetime' psychopathology ratings.

Discriminant and canonical variate analyses were performed using 302 patients, on whom ratings of lifetime psychopathology and course of illness has been made. DSM-III diagnoses were used to form the criterion groups. Bipolar disorder emerged as a distinct grouping, but there are reasons for dissatisfaction with its definition. The remaining patients formed a 'schizodepressive continuum', but this also had a tendency to bimodality. It is possible that the distinction between schizophrenia and depression was obscured by inadequacies in the data and the inclusion of excessive numbers of patients with schizoaffective depression in this study.

Adolescent

Propagation of alloreactive lymphocytes from histologically negative endomyocardial biopsies from heart transplant patients. Association with subsequent histological evidence of allograft rejection.

Endomyocardial biopsies from heart transplant patients were cultured in vitro in the presence of Interleukin-2 and irradiated feeder cells to propagate graft-infiltrating lymphocytes. A correlation was seen between the frequency of lymphocyte growth and the degree of cellular infiltration of the biopsies. In this study, 43 of 113 (38%) histologically negative biopsies obtained from 55 patients during the first month post-transplant yielded lymphocyte cultures. The cumulative incidence of subsequent histological rejection was considerably higher in patients with such "grower" biopsies than in patients with "nongrower" biopsies. In the grower group, we were able to obtain data on alloreactivity of 32 lymphocyte cultures assayed by primed lymphocyte testing (PLT). The presence of donor-specific PLT reactivity in the cultured lymphocytes was associated with an additional risk for subsequent histological rejection. These findings suggest that the in vitro culturing of histologically negative endomyocardial biopsies will identify patients at increased risk for developing heart transplant rejection.

Biopsy

In vitro studies of endomyocardial biopsies from heart transplant recipients on RATG and OKT3 immunoprophylaxis protocols.

Endomyocardial biopsy histology and the in vitro propagation of biopsy-infiltrating alloreactive T lymphocytes were analyzed in cardiac transplant patients on RATG (n = 24) and OKT3 (n = 9) immunoprophylaxis protocols. During the first three months posttransplant, 27% of the 167 biopsies in the RATG group showed histological grades of 2 or higher, significantly less than the 44% frequency of positive histology for biopsies in the OKT3 group (P = 0.035). For the histologically positive biopsies the frequency of lymphocyte growth, and the primed lymphocyte testing (PLT)* and CML activity of biopsy grown cells were similar in the RATG and OKT3 groups. However, for histologically negative biopsies, there was significantly more lymphocyte growth in the OKT3 than in the RATG groups (68% vs. 30%; P = 0.005). There was also significantly greater donor-specific CML activity of the biopsy-grown cultures in the OKT3 group. These data that suggest less cellular rejection is associated with RATG than with OKT3 immunoprophylaxis. They extend our previously reported clinical experience of a higher rejection-free survival in patients on the RATG protocol.

Adult

Assessment of c-myc expression in individual leukemic cells.

The expression of the proto-oncogene c-myc was studied at the protein level in cells obtained from patients with AML and CML. In florid AML and during the blastic phase of CML the majority of cells contain c-myc protein with the amount of protein differing widely among the cells of individual patients. In contrast, during complete remission in AML and during the chronic phase of CML cells containing c-myc protein are rare. Several studies demonstrated a discordance in the amount of c-myc transcript and the amount of c-myc protein present in cell populations thereby suggesting the presence of translational or post-translational regulation of c-myc expression. Further, the data suggest that high levels of c-myc protein in the leukemic cells of AML patients are associated with a poor response to therapy and that high levels in AML patients in CR or in the peripheral blood of chronic phase CML patients may be indicative of impending acute leukemia.

Gene Expression Regulation

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

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

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

Combining final impressions with maxillomandibular relation records in stabilized record bases.

The postinsertion problems of complete denture prostheses are closely related to accurate recording of maxillomandibular relationships. It is essential that these recordings be made with stable record bases; making the final impressions within the record bases prevents movement and tilting. Face-bow and centric relation records properly orient the casts in the articulator. A method to obtain all of these records in one dental appointments has been described.

Dental Articulators

The immediate overdenture. A case history.

A case is described of application of the immediate overdenture technique to restore function, speech and aesthetics in a patient with extreme resorption of the maxillary anterior residual ridge. In the opinion of the authors, retention of the roots of the remaining teeth most definitely contributed to the retention, stability and overall success of the denture (Figs. 9, 10).

Denture, Complete, Immediate

The overdenture: a concept.

Teeth that are unsuitable as abutments for a fixed bridge or removable partial denture may be retained as roots under an overdenture. While these roots remain, the vertical height of the bony ridge is preserved. In addition, the roots give support to the denture and reduce stress on the alveolar ridge.

Alveolar Process

Intranuclear rodlets in an intrathyroid tumor associated with hyperparathyroidism.

A tumor excised from the thyroid gland has been shown by electron microscopy to contain distinctive, intranuclear rodlets. This is the first report of such rodlets in a non-neuronal human tumor. While the parathyroid-like hormonal activity, histopathology, and clinical course are consistent with a parathyroid adenoma, the finding of the rodlets raises the question of origin from a special, neuron-related cell of the parathyroid or thyroid. The unusual cellular granularity and the abundant interstitial fibrillae also suggest an unusual cell of origin. Alternatively, a special metabolic activity may account for the rodlets, or they may have been overlooked in prior studies of adenomas.

Adenoma

A ten-laboratory study of lomefloxacin (NY-198 or SC 47111) antimicrobial activity in Argentina.

The antimicrobial activity of a new fluoro-quinolone, lomefloxacin (NY-198, SC47111), was evaluated by standardized susceptibility testing methods at ten laboratories in Argentina. Lomefloxacin was found to be the most active drug against 1,316 recent clinical isolates compared directly to norfloxacin, co-trimoxazole, and gentamicin. Only 1.4% of Enterobacteriaceae were lomefloxacin-resistant (MIC greater than 4 micrograms/ml), and the lomefloxacin MIC90 for all staphylococci was 2 micrograms/ml, including methicillin-resistant isolates. Streptococci, enterococci, and some Pseudomonads (9% resistance) were less susceptible to lomefloxacin. Lomefloxacin was the most active against Neisseria gonorrhoeae strains compared to penicillin, cefuroxime, and spectinomycin. Among the tested Mycobacteria, only the nontuberculosis, slow growers had lomefloxacin MICs of greater than 4 micrograms/ml.

4-Quinolones