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Biomedical subjects

S Slavin

Publications and source records attributed to S Slavin.

At least 127 records · Page 7Linked to original sources
PubMed1982

Hemopoietic activity in bone marrow chimeras prepared with total lymphoid irradiation (TLI).

The hemopoietic status was examined in the blood, bone marrow and spleen of (BALB/c X C57BL/6)F1 hybrid mice treated with fractionated total lymphoid irradiation (TLI), with or without reconstitution with 30 X 10(6) syngeneic or parental C57BL/6 marrow cells. Colony forming units of pluripotent (CFUS) and granuloid committed stem cells (CFUC) were assayed in non-irradiated (femur) and irradiated bone marrow (humerus), and in spleen 9, 18, 73 and 109 days following TLI. Recovery of CFUS and CFUC was nearly complete as early as day 18, and fully recovered on day 73 in endogenously as well as exogenously (syngeneic and semiallogeneic) reconstituted mice. Mice transplanted with C57BL/6 bone marrow exhibited a 10-fold increase of CFUC in the spleen on day 9 and maintained a 4-fold increase of CFUC on day 109, with normal CFUC in shielded, and near normal CFUC in irradiated bones. In contrast, the number of CFUS in the irradiated humerus was below 10% of all controls on days 18-73 and below 30% on day 109. Also, the number of CFUS in the spleen was very much reduced at days 73-109. Unirradiated femora contained normal CFUC and only mildly depressed CFUS. The data suggest that repopulation of bone marrow is adequate although somewhat less efficient in irradiated as compared to shielded bones, whether or not exogenous marrow is transplanted. Semiallogeneic chimeras (C57BL/6 leads to F1) show low CFUS relative to high CFUC levels, particularly in irradiated organs (spleen and humerus). This may suggest an advantage, from a hemapoietic standpoint, to selective irradiation of lymphoid tissues, rather than the less selective wide fields that overlap marrow containing bones.

Animals↗
PubMed1982

Long-term enzyme replacement therapy in beta-glucuronidase--deficient mice by allogeneic bone marrow transplantation.

Enzyme replacement therapy was successfully accomplished in beta-Glu-deficient C3H/HeJ mice after transplantation of BM cells obtained from normal BALB/c donors. Marrow recipients were prepared for transplantation by fractionated TLI. Enzyme activity increased from 20.5 +/- 7.0 nmol/mg of protein per hour to 180 +/- 30.2 in the liver (p less than 0.001) and from 8.2 +/- 2.0 to 17.5 +/- 5.0 nmol/ml/hr in the plasma (p less than 0.05) at 50 days after marrow infusion. Normal enzyme activity was maintained in treated mice for at least 100 days after marrow transplantation, as documented by repeated liver biopsies and examination of plasma samples. The marrow donors and the recipients were fully histoincompatible. Both immunologic rejection of the marrow allograft and GVHD were prevented by the prior conditioning of the recipients with TLI, resulting in bilateral transplantation tolerance of host vs. graft and graft vs. host. The data suggest that allogeneic BM transplantation may provide a possible therapeutic approach for certain enzyme deficiency syndromes.

Animals↗
PubMed1981

Kidney allograft survival in dogs treated with total lymphoid irradiation.

Total lymphoid irradiation (TLI) is immunosuppressive and, in rodent, can induce a state where transplantation of allogeneic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. We attempted to apply this treatment to a large animal model. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950-3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned (serum creatinine level less than 2.0 mg/dl) for a mean +/- (SE) of 4.7 +/- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15-76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemagglutinin and in mixed lymphocyte culture was suppressed for at least on month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients.

Animals↗
PubMed1981

In-vitro T cell mediated function in patients with active rheumatoid arthritis.

In-vitro synthesis of peripheral blood lymphocytes from patients with rheumatoid arthritis was measured after stimulation with phytohaemagglutinin (PHA) in a short-term, serum-free culture system. Diminished responses were found in 16 out of 17 consecutive patients with active disease. Normal PHA responsiveness was recovered by assaying Ficoll-Hypaque isolated E rosette forming cells in serum-free medium, indicating basically normal T cell function in RA. Preincubation of normal peripheral blood lymphocytes (or isolated E rosette forming cells) with sera obtained from patients with active RA for 30 minutes at 4 degrees C or 37 degrees C blocked PHA responsiveness in 34 out of 43 tests. This suggests that serum blocking factors may be responsible for reduced T cell reactivity in RA.

Arthritis, Rheumatoid↗
PubMed1981

Ultrastructural, cell membrane, and cytogenetic characteristics of B-cell leukemia, a murine model of chronic lymphocytic leukemia.

A murine model of a spontaneous, transplantable BALB/c B-cell leukemia (BCL1) is described. Extreme leukemia and splenomegaly develop in H-2d-compatible recipients of tumor cells. Tumor cells are medium to large lymphocytes that can be transformed into plasmacytoid cells following in vitro stimulation with lipopolysaccharide. Karyotypic analysis of transformed tumor cells reveals 36 chromosomes with several monosomies and 7 markers chromosomes. The ultrastructure of the tumor cells was studied using transmission and scanning electron microscopy. Although the appearance of tumor cells seems normal by morphological criteria, an impaired capping ability was documented using the fluorescein-conjugated concanavalin A-binding test. Impaired capping ability was documented before leukemia was overt as early as 1 to 3 days following inoculation of tumor cells. The B-cell leukemia (BCL1) provides a useful murine model for the study of various aspects of human bone marrow-derived malignant disorders.

Animals↗
PubMed1980

Correction of enzyme deficiency in mice by allogeneic bone marrow transplantation with total lymphoid irradiation.

Enzyme deficiency was corrected in mice after allogeneic bone marrow transplantation with occurrence of graft versus host disease. beta-Glucuronidase-deficient C3H/HeJ mice were treated with total lymphoid irradiation. Normal bone marrow cells (30 X 10(6)) from BALB/c to C3H/HeJ chimeras (>90 percent circulating donor-type cells) without graft versus host disease. beta-Glucuronidase activity increases to normal levels in all chimeras as measured in the liver and in the plasma. Activity was maintained throughout an observation period of 7 months.

Animals↗
PubMed1980

Immunosuppression and organ transplantation tolerance using total lymphoid irradiation.

Total lymphoid irradiation (TLI) is a method which delivers irradiation daily in fractionated doses (200 rads) to lymphoid organs while shielding bones, lungs, and the majority of the gastrointestinal tract. TLI is lymphocytopenic in mice, rats, dogs, and humans, and both T cells and B cells are eliminated from the circulation. During the recovery phase in mice, B cells appear before Thy 1.2-bearing T cells, and TL-positive T cells are abundant in the spleen and lymph nodes. These T cells exhibit nonspecific suppressive activity on antibody production and cell-mediated immune responses. TLI permits establishment of specific and long-lasting tolerance to alloantigens. Permanent acceptance of allogeneic bone marrow cells without graft-versus-host disease was achieved in rats and dogs across major histocompatibility barriers. Recipients were tolerant to allografts of skin, hearts, and kidney from animals syngeneic to marrow donors or to organs from the marrow donor. This approach may be suitable for pancreas transplantation in diabetes.

Animals↗
PubMed1980

The role of the spleen in tumor growth kinetics of the murine B cell leukemia (BCL1).

BCL1 is a transplantable B cell leukemia resembling human chronic lymphocytic leukemia-lymphoma maintained by cell passage in BALB/c mice. After BCL1 inoculation (10(7) cells), all mice developed extreme B lymphocytosis in the blood (less than or equal to 440,000 lymphocytes/mm3) and marked splenomegaly (50 times normal nucleated cell numbers). BCL1 infiltrated the spleen before peripheral leukemia was overt (3 days vs 28 days, respectively). BCL1 development in splenectomized mice was characterized by a delayed onset of leukemia (greater than 20,000 cells/ mm3 at 59 vs 28 days in intact mice), doubled median survival (102 vs 53 days, respectively), and reduced peak level of leukemic counts in the blood (125,000 vs 440,000 cells/mm3). Early splenectomy at different time intervals, ranging between 1 hr to 3 days after BCL1 inoculation, significantly delayed onset of the disease and prolonged survival, indicating that homing to the spleen occurred as early as 1 hr after inoculation. Splenectomy at 7 days still delayed onset of leukemia but did not affect survival. No significant effect on BCL1 kinetics was noticed when splenectomy was done on day 21. All splenectomized mice showed significantly lower peripheral blood counts as compared to intact mice (98,000/mm3 vs 440,000/mm3, respectively). The data show that the spleen plays a major role in the pathogenesis and prognosis of BCL1.

Animals↗
PubMed1979

Is there postdefecation bacteremia?

An investigation was done to determine the incidence of postdefecation bacteremia. A study of 82 healthy volunteers was done. Among 164 predefecation cultures, only one (0.6%) from an anaerobic flask was positive for microorganism, which was identified as Staphylococcus epidermidis. In only two of 328 (0.6%) postdefecation cultures did microorganisms grow, which were shown to be Propionibacterium acnes. The results of this study suggest that either bacteremia after defecation does not occur or is a rare event in healthy individuals.

Adolescent↗