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Biomedical subjects

T M Schneider

Publications and source records attributed to T M Schneider.

10 recordsLinked to original sources
PubMed1986

Development of suppressor lymphocytes during acute rejection of rat cardiac allografts and preservation of suppression by anti-IL-2-receptor monoclonal antibody.

Suppressor activity was investigated in rats undergoing acute rejection of heterotopic cardiac allografts. Spleen cells were harvested at 7 days from LEW rats rejecting (LEW x BN)F1 heart grafts and fractionated into their T, T suppressor/cytotoxic, and T helper subpopulations. Transfer of alloimmune unseparated spleen cells to syngeneic recipients of (Lew x BN)F1 test grafts accelerated rejection from 8 to 6.5 days (P less than 0.01). Graft survival was prolonged to about 15 days (P less than 0.005) after transfer of the splenic T suppressor/cytotoxic fraction. Treatment of test graft recipients with ART-18, a mouse antirat monoclonal antibody directed against the rat interleukin 2 receptor on the surface of activated lymphocytes, increased graft survival to about 3 weeks (P less than 0.005), and to about 23 days (P less than 0.005) when test graft recipients were treated with ART 18 following transfer of alloimmune unseparated spleen cells. In contrast, ART-18 treatment of test graft recipients already injected with T suppressor/cytotoxic cells had no additive effect. Increased production of endogenous interleukin 2 occurred concomitantly with the onset of rejection in these animals; interleukin 2 release declined during the late stages of rejection when suppressor activity had increased. Similarly, in T-cell-depleted (B) rats, allograft rejection could be produced by immune reconstitution with sensitized lymphocytes, but could be significantly delayed by prior transfer of suppressor cells. These data document the presence of potent suppressor activity in the acutely rejecting host and suggest that the suppressor mechanisms are inhibited less than effector mechanisms by interleukin-2-receptor-targeted therapy.

Animals↗
PubMed1986

Cyclosporine and experimental skin allografts: long-term survival in rats treated with low maintenance doses.

Although cyclosporine (CsA) is a powerful immunosuppressive agent in organ transplantation, its efficacy in skin transplantation has not been examined completely. We have tested it as primary immunosuppression in a rat skin allograft model. Histoincompatible Brown-Norway skin grafts are rejected in untreated Lewis hosts within 9 +/- 1 days but survive for 22 +/- 3, 34 +/- 2, or 41 +/- 8 days after 7, 14, or 21 days of CsA treatment (15 mg/kg per day subcutaneously), respectively (p less than 0.001). Animals treated daily for 4 weeks died from drug toxicity; however, an initial 2-week course followed by a low maintenance dose (15 mg/kg every fourth day) produced indefinite (greater than 150 days) graft acceptance without side effects. The long-surviving grafts were supple, grew long hair, and showed normal histology. When the drug was stopped at any time during this maintenance period, early signs of rejection (hair loss, epidermal breakdown, and localized ulceration) occurred, which could be reversed completely by a short CsA "pulse" (15 mg/kg per day for 7 days). These experimental data support the potential application of CsA immunosuppression in human skin allotransplantation.

Animals↗
PubMed1985

T suppressor lymphocytes reverse ongoing acute allograft rejection.

(LEW X BN)F1 cardiac allografts are rejected within 8 days in untreated LEW recipients. At the critical time point of 5 days after transplantation, the obviously rejecting grafts are enlarged and maximally infiltrated by host cells as shown by 111In-labeled lymphocyte tracer studies. However, when such hearts were retransplanted back to naive (LEW X BN)F1 secondary hosts, they survive indefinitely, showing that even late rejection is reversible in the absence of sustained host immunological drive. Attempts were then made to abrogate this advanced immune responsiveness using Cyclosporine (CsA). CsA therapy (15 mg/kg/day for 7 days) starting from day 5 produced indefinite graft survival, similar as if initiated at the time of operation. Addition of exogenous IL-2, which drives the proliferation of Tc, could not reverse this effect. Serial changes in phenotype of lymphocyte subpopulations infiltrating both acutely rejecting and indefinitely functioning cardiac allografts in unmodified and CsA treated hosts, respectively, were then studied. Ratio of Th:Tc/s cells in acutely rejecting grafts was 1.6 by day 3; it inverted abruptly to 0.7 by day 5-6, suggesting predominance of Tc/s during the later stages of allograft rejection. Similarly, treatment with CsA produced a transient depression of Th, with recovery of original Th:Tc/s ratio during the next 2-3 weeks. Adoptive transfer experiments were then performed to investigate the functional significance of these findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Cyclosporine and experimental skin allografts. II. Indefinite survival and development of specific immunologic unresponsiveness.

Immunological unresponsiveness toward skin allografts was studied in cyclosporine (CsA)-treated rats. BN skin grafts survive about 22 days and about 34 days in LEW hosts following 7 or 14 days of daily CsA treatment (15 mg/kg/day), respectively; in unmodified hosts grafts are rejected by 9 days. Indefinite (greater than 100 days) survival can, however, be produced by administering maintenance 15 mg/kg CsA every fourth day, following an initial course of the agent for 14 days. Early signs of graft rejection (hair loss, localized epidermal breakdown, and ulcerations) occurring in some animals were reversed by a CsA "pulse" (15 mg/kg/day) for 7 days, reduced gradually to the maintenance dose. CsA was equally effective when started as late as 4 days after grafting, but ineffectual when started after day 4. Once BN grafts were rejected, the agent could not prevent second-set rejection of donor-specific grafts, but significantly prolonged the survival of third-party (WF) skins. Survival of original BN grafts was unchanged by the placement of second BN grafts during both the inductive and maintenance phases; these second grafts survived as long as the original grafts. In contrast, secondary third-party (WF) grafts were promptly rejected; their destruction did not influence survival of the original grafts. Thus, indefinite survival of rat skin allografts is feasible with low maintenance doses of CsA. Graft rejection at later stages can be reversed by resuming daily therapy. Host unresponsiveness is stable and specific both during the early inductive and later maintenance phases.

Animals↗
PubMed1983

The effect of intrauterine infusions of prostaglandin E2 on luteal function in nonpregnant gilts.

Two trials were conducted to study the effects of intrauterine infusions of prostaglandin E2 (PGE2) on luteal function in nonpregnant gilts. Cannulae were surgically implanted on day 9 postestrus into the lumen of each horn with a cephalic vein cannula inserted for collection of peripheral blood. Intrauterine infusions of 0, 25, 75 or 200 microg of PGE2 were initiated at 0900 h on day 12 and administered thereafter every 12 hr until estrus or day 22 in the first trial. The second trial protocol included an increase in the dose of PGE2 administered as well as the frequency of infusion. Infusion of 0, 200, 300 or 400 microg PGE2 was begun at 0300 h on day 12 and continued every 6 hr until estrus or day 22. Cephalic plasma samples for progesterone analysis were collected every six hours from 0300 h on day 11 to 2100 h on day 26 in both trials. In Trial 1 mean plasma progesterone concentrations for all treatments were not different (P>0.05) from the controls on any given day of the estrous cycle. Interestrous interval was unaffected by intrauterine infusion of PGE2. The mean plasma progesterone concentrations for all treatments were not different (P>0.05) from the controls on days 11-18 of the estrous cycle in Trial 2. However, plasma progesterone concentrations for the 200-microg and 300-microg PGE2 groups appeared to be greater than the controls on days 14 and 15, indicating a possible delay in the decline of progesterone for these groups. The mean plasma progesterone concentrations for the treatment groups were lower (P<0.05) than the controls on days 20-26 of the cycle. treatment cycle length did not differ (P>0.05) from previous cycle length; thus treatment with PGE2 had no effect on interestrous interval. PGE2 may have retarded the decline of progesterone secretion by the corpus luteum in some cases, but at these dosages and frequencies of administration PGE2 was ineffective in prolonging luteal maintenance.

Journal Article↗
PubMed1978

Pressure, temperature, and repetitive impulse generation in crustacean axons.

Increases in nerve axon excitability, including repetitive activity, have from time to time been reported in nerves subjected to high hydrostatic pressure. With the description of the high-pressure nervous syndrome (HPNS) in human divers and experimental animals, this phenomenon is of interest as a possible basis for the hyperexcitability associated with HPNS. The present study was designed to define the relationships between temperature, pressure, and repetitive activity in isolated crayfish axons. Crayfish claw nerves were exposed to helium pressures between 1 and 200 atmospheres absolute (ATA) in a temperature-controlled recording chamber. Repetitive and spontaneous impulses were reliably evoked on compression. The probability of repetitive response was increased by low temperature and high pressure; the frequency of the repetitive activity was increased by high temperature and pressure. Repetitive activity appeared spontaneously in the unstimulated preparation but could be entrained by the stimulus. The results are consistent with a mechanism involving changes in nerve membrane lipid fluidity and in the time course of membrane ionic channel state changes, including those involved in repolarization and accommodation.

Action Potentials↗
PubMed1978

Anesthetics inhibit pressure-induced repetitive impulse generation.

Repetitive and spontaneous impulse generation appears in nerve axons exposed to high pressure. This phenomenon is a possible basis for high-pressure nervous syndrome (HPNS) or pressure reversal of anesthesia, two examples of an antagonistic interaction between anesthetic drugs and high pressure. In the present study, the interactions between three classes of anesthetic drug (ethyl alcohol, the volatile inhalation agent halothane, and phenobarbital) and repetitive activity were explored. Ethyl alcohol (5% in solution) and halothane (1.3 and 3.4% in oxygen) inhibited pressure-induced repetitive activity. Phenobarbital at 0.25 mM in solution, the maximum concentration obtainable at low temperature, was partially effective. The three drugs produce an unconscious state that is "reversed" at hyperbaric pressure. Halothane and phenobarbital inhibit HPNS, but ethyl alcohol has not been tested for this property. The results thus support a relevance of repetitive activity to HPNS, to pressure reversal of anesthesia, or to both.

Action Potentials↗