摘要:

Abstract3'-azido-3'-deoxythymidine (AZT) was administered orally to 8 AIDS patients at a dose of 100 mg every 6 hours for 14 days. On days 8–14 the patients were also given lginosine-pranobex (INPX) every 6 hours. On day 7, while the subjects were taking AZT alone and on day 14 while they were receiving AZT + INPX, blood samples were obtained over a 6-hour dosing interval for measurement of AZT by a specific AZT radioimmunoassay. AZT levels on day 14 were significantly higher than the corresponding levels on day 7, resulting in a 2-fold increase of the area under the serum concentration-time curve (AUC) and a prolongation of the mean half-life of AZT (44 to 70 min) during the INPX treatment. INPX is an immunomodulatory drug with an inhibitory effect on HIV. The potential advantages of a combined treatment AZT+INPX are: 1) need for lower dose of AZT for maintaining a therapeutic anti-retroviral level; 2) a longer interval period between AZT treatments; 3) a potential to enhance immunological response resulting from INPX treatment; 4) reduced costs of care for patients.

ISSN:0892-3973    

DOI:10.3109/08923978809006447

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractProthymosinα(Prota), an immunologically active polypeptide derived initially from rat thymus, and now pig thymus, was tested for its effect on autoantigen-induced human T cell proliferation in vitro. Pig ProTa was found to enhance the autologous mixed lymphocyte response (auto-NLR). Optimum enhancement was achieved at doses which varied among different donors. Treatment of the stimulatory monocytes with ProTa resulted in considerably higher auto-MLR responses as compared to those with non treated monocytes. ProTa was without effect on T lymphocytes. In contrast, T lymphocytes exhibited enhanced proliferative activity when treated with ProTa in the environment of autologous monocytes. Horeover, supernatants from cultures of monocytes incubated with ProTa(ProTa-sup) were also shown to enhance the human auto-NLR either after addition in cultures or after preincubation with responder T lymphocytes. In addition, ProTa-sup did not demonstrate any detectable inter-leukin I (IL 1) or interleukin 2 (1L 2)-like activity Furthermore, ProTa-sup induced an increase in IL 2 production in auto-NLR cultures. The enhancement of T-cell proliferation and IL 2 production by ProTa-sup was maximal when this material was added at the beginning of the auto-MLR, and no effect of ProTa-sup was seen if the latter was added 3 days after initiation of the culture. Finally, Prota-sup was also shown to increase the expression of IL 2 receptors on T lymphocytes activated in the auto-MLR. These studies suggest that ProTa enhances the human auto-HLR through ProTa -sup which is released after interaction of monocytes with ProTa ProTa-sup then increases directly T lymphocyte proliferation by elevating IL 2 production and expression of IL 2 specific receptors on autoactivated T lymphocytes.

ISSN:0892-3973    

DOI:10.3109/08923978809006448

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractWhen lymphocytes are stimulated with mitogens or antigens they are enhanced via a cascade of lymphokines to produce interferon-y (IFN-y). IFN-y augments the H2O2secretion of human monocytes which indirectly can be measured by chemiluminescence. We tested prednisone, 16-methylen. prednisolone and ACTH for their effect to inhibit the Con-A induced stimulation of the chemiluminescence-activity. All three hormones inhibited significantly the stimulation: prednisone up to 52.5%(concentration = 150 m;g/ml, p=0.000005), 16-methylen-prednisolone up to 22.5%(concentration = 2.5&m g/ml, p=0.006) and ACTH up to 33%(concentration = 10 m g/ml, p=0.0036).

ISSN:0892-3973    

DOI:10.3109/08923978809006449

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractInvestigation on the effect of TNF on RNA and protein synthesis by tumorigenic and normal cell lines showed their synthesis in tumor cells to be increased at 12 h and to peak at 24 h of incubation with TNF, while that in normal diploid fibroblast (HEL) cells was apparently unaffected by the presence of TNF. The increase correlated with cell susceptibility to cytotoxic effect by TNF. Artificial inhibition of either RNA or protein synthesis by L-M cells. by addition of artinomycin D or cycloheximide, increased the cytotoxic effect of TNF and thus suggested that the elevated RNA and protrin synthesis is related not, to the cytotoxic reaction itself but rather to a defense mechanism. Similar incubaticin of HEL cells with TVF in the presence of either inhibtor resulted in the occurrence of cytotoxicity not observed with TNF alone, thus suggesting the existence of a defense mechanism in normal, TNF-resistant rolls which is absent, or greatly wealtend in tumor cells.

ISSN:0892-3973    

DOI:10.3109/08923978809006450

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractThe effects of some dopaminergic antagonists were investigated on mouse lymphocyte proliferative responsesin vitro. The mixed D1/D2dopaminergic antagonists chlorpromazine, haloperidol and fIupentixol inhibited3H-Thymidine incorporation into adult BALB/c mouse spleen cells stimulated by concanavalin A, lipopolysaccharide fromEscherichia coli, and allogenic cells in a mixed lymphocyte reaction. The inhibition was achieved at concentrations greater than 10−6M. It was not accounted for by decreased cell viability and it was no longer demonstrable when the compound was added 24h or 48h after the mitogenic stimulus. Conversely selective D2dopaminergic antagonists sulpiride, metoclopramide and domperidone had no inhibitory effect at concentrations ranging from 10−9to 10−5or 10−4M. The three mixed Dl/D2antagonists inhibited the mitogenic effect of interleukin-1 on concanavalin A-stimulated thymocytes, but not the activity of interleukin-2 on the proliferaiton of the CTLL-2 cell line. The mixed Dl/D2antagonists interfered with the production of interleukin-2 but not with that of interleukin-1. These results indicate that dopaminergic antagonists may differerentially affect lymphocyte proliferative responses to T or B cell mitogens or alloantigens. The mechanisms involved in terms of receptor specific or non specific phenomenons are discussed.

ISSN:0892-3973    

DOI:10.3109/08923978809006451

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractThe rate of collagen deposition in implanted polytetrafluoroethylene (PTFE) tubing in non-diabetic and streptozotocin-induced (STZ) diabetic mice was measured during 14 days post-wounding. At the time of implantation, test groups received injections of either Quadrol [N,N,N',N'-tetrakis(2-hydroxypropyl)ethylenediamine], glucan, or buffer in an area adjacent to the wound site. The accumulation of collagen in the implants of Quadrol-treated non-diabetic animals was more than 200% above control on days 8 to 11 and was 50% above control on day 14. In Quadrol-treated STZ-diabetic mice, the collagen accumulation gradually increased from 50% above control on day 8 to 200% above control on day 14. Treatment with glucan increased the collagen accumulation in normal mice 200 to 300% above control from days 8 to 11 respectively and then 30% above control on day 14. Collagen accumulation in the implants of the glucan-treated STZ-diabetic mice was similar to the control group. These results indicate that Quadrol promotes in vivo collagen synthesis and that Quadrol may be effective as a stimulator of wound healing in diabetic and non-diabetic animals.

ISSN:0892-3973    

DOI:10.3109/08923978809006452

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractGranulocyte-macrophage colony forming units (CFU-GM) were studied in cultures of bone marrow from 16 apparently healthy normal controls, 9 patients with the myelodysplastic syndrome, 5 patients with myeloproliferative disease and 2 with myeloma. Supernatants from non-stimulated 72 hr cultures of nonadherent mononuclear blood cells (“lymphocytes”) stimulated the forming of an average of 38.4 colonies per 100000 cells from normal marrow. The addition of GIBCO's commercial conditioned medium or of a medium produced by lymphocytes stimulated with different concentrations (5,10 and 20 mcg/ml) of an acid lysate of thymus (thymomoduline), increased growth to 65.2–55.4 colonies (p<0.001 to 0.05). Similarly, a significant increase (p<0.05) was found in the number of clusters and colonies formed in cultures of marrow from patients with the myelodys-plastic syndrome. In contrast, no growth was found when the thymus acid lysate was added directly to the bone marrow cultures, suggesting that the lysate induces the production of colony stimulating activity by lymphocytes, but does not contain it. Similarly no significant increase was found as regards the initially high number of colonies from the five patients with myeloproiferative disease, or as regards the initially low number in the two myeloma patients.

ISSN:0892-3973    

DOI:10.3109/08923978809006453

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractAnalysis of cellular effector function(s) of ten requires their isolation from other cellular types. Cel1 separatory techniques could mask, or select Out, clinically important functional lesions. We examined differences in canine peripheral blood neutrophil functions, i.e. migration and H2152 production, following two commonly used cell separation techniques: isotonic lysis. or density gradient (Percoll) centrifugation. Separation methodology was observed to have a significant impact on both metatlolic and mobility functions. In comparison to isotonic lysis, Percoll separation caused near 100% increases in random migration, near 40% decreases in chemotaxis and 70% Increases in H202 production.

ISSN:0892-3973    

DOI:10.3109/08923978809006454

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractThe pathologic features of the acute graft-vs-host disease occurring in unirradiated (C57B1/6 X A/J)F1mice injected intravenously with lymphocytes from the C57B1/6 parent are similar to those reported for other parental→F1hybrid combinations.When stimulated in culture with concanavalin A, lipopolysaccharide or alloantigen, spleen cells from B6AF1mice that had been injected 11 days previously with B6 lymphocytes exhibited proliferative responses that were drastically reduced in comparison to the responses of spleen cells from F1hosts injected with syngeneic lymphocytes. IL2 production in h7H spleen cell cultures was also diminished. Proliferative responses and IL2 production were partially restored in mice given immunosuppressive therapy with azathioprine, cyclosporin A or Sch 24937 a drug whose inhibitory effects on cellular and humoral immune responses in mice have recently been described.Phenotypic analyses by flow cytometry of the GVH splenocyte population indicated that the most consistent chanqe in the GVH spleen was the appearance of an Lyt2+L3T4+T cell subset which in the majority of experiments was accompanied by an increase in cells expressing only the Lyt2 antigen. Both subpopulations were reduced in mice that had recovered immunological responsiveness following immunosuppressive therapy. The results suggest that in this GVH model the development of an immunodeficient state is directly related to the induction of an active T suppressor cell population and that such cells are effectively eliminated from the splenocyte population following treatment with some immunosuppressive drugs.

ISSN:0892-3973    

DOI:10.3109/08923978809006455

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractRats bearing (or not bearing) the Dunning R3327 MAT-LyLu prostatic adenocarcinoma were treated with Bacillus Calmette-Guerin (BCG) and evaluated for immune competence using functional and phenotypic markers. Tumor presence significantly depressed total T and helper T cell representation along with the helper/ suppressor T cell ratio. Functional immunity, measured by phytohemmagglutinin (PHA) induced blastogenesis, was also significantly depressed. When BCG was administered to non-tumor bearing animals, it had no effect upon T cell subset distributions but significantly reduced PHA induced blastogenesis. BCG similarly administered to tumor bearing animals did not alter the depressed helper/ suppressor T cell ratio found in tumor bearing rats, but did significantly elevate PHA induced blastogenesis. However, these elevated levels of functional immunity in BCG treated tumor-bearing rats remained significantly below normal. These data demonstrate a poor correlation between functional and phenotypic assessments of immune capabilty.

ISSN:0892-3973    

DOI:10.3109/08923978809006456

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor