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Biomedical subjects

P Pfeffer

Publications and source records attributed to P Pfeffer.

48 records · Page 3Linked to original sources

Identification of D-sorbitol 3-phosphate in the normal and diabetic mammalian lens.

The 31P NMR spectra of mammalian lenses show, in addition to previously identified compounds such as ATP, Pi, glycerophosphorylcholine, and alpha-glycerophosphate, an unusual phosphorylated metabolite resonating at 6.5 ppm. The concentration of this compound increases manyfold in the lenses of diabetic rats concomitant with activation of the aldose reductase pathway. We have purified this material and have identified it as D-sorbitol 3-phosphate. It appears likely that this unusual metabolite of sorbitol may reflect or be part of the metabolic aberration of diabetes in the lens.

Animals↗

Human heart transplantation. Rejection risk factors.

The present analysis of risk factors in human cardiac transplantation is based on a review of 682 endomyocardial biopsies from 52 grafts in 51 recipients. Acute rejection was diagnosed in 149 biopsies (21.8%). The cumulative 1-year graft survival was 91.5 4%. Four out of seven patients died of irreversible rejection. An univariate analysis using the linearized rate of total rejection showed significantly higher frequency of acute rejection when donor and recipient differed for two HLA-DR antigens compared to zero or one HLA antigen disparity (p less than 0.01), as well as in patients treated with low dose steroids, Cyclosporine (CyA) and Azathioprine (p less than 0.01), compared to treatment with CyA high dose steroids. Other risk factors were graft ischemia extending 60 minutes (p less than 0.05) and patient age exceeding 40 years (p less than 0.05). A multivariate analysis using the competing risk hazard model for irreversible (= lethal) rejection was performed. The presence of two HLA-DR mismatches between donor and recipient was found to be an independent risk factor (relative risk = 8.9), and immunosuppression with CyA and high dose steroids without Azathioprine another (relative risk = 15.3). Potential risk factors such as donor and recipient sex, donor age, prior surgery and time on extracorporeal circulation were not of significant prognostic value neither in regard to rejection nor irreversible rejection.

Azathioprine↗

Effects of methylprednisolone on the in vitro generation of human secondary cytotoxic lymphocytes.

The effects of methylprednisolone on the induction of secondary proliferative and cytotoxic lymphocytes in human mixed lymphocyte cultures (MLCs) have been studied. Concentrations of methylprednisolone (MP) as low as 0.01 microgram/ml proved highly effective in inhibiting the generation of cytotoxic memory cells if the steroid was present during the first 5 days of the priming mixed lymphocyte culture. The generation of cytotoxic lymphocytes was also inhibited if the steroid was added along with the restimulating cells on day 10, although the degree of inhibition was not as great as that seen when steroids were added to the cultures at their initiation. Cultures containing 1 microgram of MP per ml during the priming phase required 10 times as many effector cells to achieve a comparable level of cytotoxicity compared to control cultures without steroids. Our results indicate that an important aspect of the immunosuppressive role of steroids is the prevention of the generation of specific memory cells following exposure to alloantigens.

Cytotoxicity, Immunologic↗

Opposing effects of methylprednisolone on in vitro alloantigen-induced cytotoxic and suppressor lymphocytes in man.

The effects of the steroid methylprednisolone (MP) on the induction of cytotoxic or suppressive lymphocytes in human mixed lymphocyte cultures (MLC) have been examined. Concentrations of MP sufficient to inhibit both the cellular proliferation and the generation of cytotoxic lymphocytes in MLC appeared to have very little effect on the induction of suppressor cells in these cultures. In fact, over a certain dosage range of MP an increased number of suppressor cells appeared to be generated. Moreover, low concentrations of MP greatly potentiated the effects of alloantigen induced suppressor cells but had little or no effect on the action of cytotoxic lymphocytes as measured in the cell mediated lympholysis assay. It seems therefore that MP has an opposing effect both on the generation and function of suppressor or cytotoxic lymphocytes induced by allogeneic cells.

Cell Division↗

Bone marrow cell culturing in double diffusion chambers.

A double diffusion chamber technique (DDC) has been established. The bone marrow cells (BMC) were cultured in the peritoneal cavity of mice in DDC consisting of 2 compartments separated from one another by a Millipore membrane. One chamber half contained the mouse bone marrow target cells, and the other half (regulator compartment) either medium (control), spleen cells or BMC. In the controls the BMC proliferated rapidly from day 2, and the cell yield on day 7 was reduced by only 20% when compared with single diffusion chambers. Diffusible factors from spleen cells stimulated the growth of CFU-S and CFU-C in the bone marrow, and increased the number of granulocytes and macrophages harvested in 7 day cultures. Conversely, BMC in the regulator compartment depressed granulopoiesis in the other chamber half.

Animals↗