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Biomedical subjects

S Slavin

Publications and source records attributed to S Slavin.

At least 379 records · Page 21Linked to original sources

Transplantation of allogeneic bone marrow without graft-versus-host disease using total lymphoid irradiation.

Bone marrow (BM) and skin allografts from C57BL/Ka (H-2b/b) mice were transplanted to BALB/c (H-2d/d) recipients treated with total lymphoid irradiation (TLI), whole-body irradiation (WBI), or fractionated thymic irradiation TLI prolonged skin allograft survival about five times as long as that in untreated controls, and allowed for permanent engraftment of BM cells in approximately equal to 90% of recipients. None of the BM recipients showed clinical signs of graft-versus-host disease (GVHD) (diarrhea, weight loss, hunched back, etc.). On the other hand, recipients given WBI and allogeneic BM cells developed severe clinical GVHD. The majority of the latter recipients died within 12 days after BM transplantation, and 95% died within 61 days. Although TLI protected BALB/c mice against GVHD induced by BM cells, all recipients given TLI and allogeneic spleen cells developed lethal GVHD. Thymic irradiation alone marginally prolonged skin allograft survival, and did not allow for allogeneic BM engraftment. These results suggest that TLI may be a useful regimen in clinical BM transplantation, since this form of radiotherapy is used extensively in humans and has few severe side effects.

Animals↗

Transplantation tolerance in adult rats using total lymphoid irradiation: permanent survival of skin, heart, and marrow allografts.

Lewis rats given total lymphoid irradiation (TLI) accepted bone marrow allografts from AgB-incompatible donors. The chimeras showed no clinical signs of graft-versus-host disease. Skin allografts from the marrow donor strain survived for more than 150 days on the chimeras. However, third-party skin grafts were rejected promptly. Although heart allografts survived more than 300 days in Lewis recipients given TLI and bone marrow allografts, detectable levels of chimerism were not required for permanent survival.

Animals↗

Escherichia coli infection in mice and impaired fetal development.

Investigations were undertaken, using the mouse as an animal model, to study the effect of Escherichia coli on fetal development. The i.v. injection of 7.5 X 10(6) bacteria, originally obtained from a suspected case of human pyelonephritis, caused only a mild and transient disturbance of maternal health but caused severe fetal wastage. Groups of mice were examined 4, 7 and 11 days after infection and the numbers of organisms were determined in the spleen, liver, kidneys, placentas and resorptions. From the findings obtained, it was concluded that the Esch. coli grew preferentially in the placentas. By the 7th day the placentas showed marked degenerative and necrotic changes and the bacteria could be recovered from the majority of fetuses at this time. Histologically, no significant changes were seen in the spleen, liver and kidneys. As a result of these findings in an animal model, and taking into consideration the observations of other workers, it is suggested that coliform bacteraemia in human pregnancies may also cause infections of the placenta and bring about abortion or premature delivery.

Animals↗

Induction and mechanism of tolerance to bovine serum albumin in mice given total lymphoid irradiation (TLI).

BALB/c mice given total lymphoid irradiations (TLI) were injected i.p. with bovine serum albumin (BSA) in saline, and challenged with DNP-BSA in complete Freund's adjuvant 6 weeks later. The latter animals made no anti-DNP antibody response as measured by a modified Farr assay, but made a normal anti-DNP response after challenge with DNP-BGG in adjuvant. Normal mice or mice given whole body irradiation were not tolerized by the i.p. injection of BSA in saline. Spleen cells from unresponsive mice (TLI + BSA in saline) suppressed the adoptive secondary anti-DNP response of sublethally irradiated syngeneic hosts given BSA-primed T cells, DNP-BSA-primed B cells, and DNP-BSA in saline. The suppressor cells were antigen specific, and were inactivated by in vitro treatment with anti-Thy 1.2 antiserum and complement. The findings suggest that soluble antigens administered to mice after TLI evoke a state of tolerance that is maintained by antigen-specific suppressor T cells. A similar mechanism may be involved in the maintenance of tolerance to allografts. These findings may have important clinical implications for patients treated with TLI for lymphoid malignancies.

Animals↗

Induction of specific tissue transplantation tolerance using fractionated total lymphoid irradiation in adult mice: long-term survival of allogeneic bone marrow and skin grafts.

BALB/c mice were treated with fractionated high dose (3,400 rads) total lymphoid irradiation (TLI), and given semiallogeneic (BALB/c x C57BL/Ka) or allogeneic (C57BL/Ka) bone marrow and/or skin allografts. TLI alone prolonged the mean survival time (m.s.t.) of C57BL/Ka skin grafts to 49.1 days (control, 10.7 days). Shielding of the thymus during TLI produced only a slight increase in graft survival (m.s.t., 19 days). TLI combined with splenectomy was no more effective than TLI alone. Infusion of 10(7) semiallogeneic or allogeneic bone marrow cells after TLI produced stable chimeras in 7/8 and 8/15 recipients, respectively. Chimeras were specifically tolerant to donor tissues, since C57BL/Ka skin grafts were accepted for more than 250 days, but third-party (C3H/He) skin grafts were rejected rapidly. In addition, chimeric lymphocytes responded to C3H/He and C3H. Q but not to C57BL/Ka cells in the one-way mixed leukocyte reactions. BALB/c C57BL/Ka chimeras showed no clinical evidence of graft vs. host disease. These findings may have application of clinical organ transplantation, since (a) the recipient treatment (TLI) has already been shown to be safe in humans, (b) donors and recipients can be completely allogeneic, and (c) bone marrow and skin graft survival was permanent (greater than 250 days).

Animals↗

A case of adrenogenital syndrome with aberrant 11beta-hydroxylation.

A 17 year old female patient with hypertension, amenorrhoea and hirsutism was found to have subnormal levels of plasma and urinary cortisol, significant plasma levels of Reichstein's compound S and 21-deoxycortisol, high urinary levels of THS and pregnanetriolone as well as elevated levels of plasma and urinary testosterone. Treatment with 0.5 mg/day of dexamethasone or 25 mg/day cortisone reduced her hypertension and restored her menstrual cycles, but also resulted in the development of moon face, body striae and a gain in weight. Lower doses of cortisone were without effect. The deficient cortisol production coupled with the presence of unusual intermediates such as Reichstein's compound S and 21-deoxycortisol can be explained by a shift in the substrate specificity of 11beta-hydroxylase from C-21-hydroxylated substrates (i.e. compound S) to C-21-deoxy substrates (i.e. 17-hydroxyprogesterone).

17-Ketosteroids↗

Long-term survival of skin allografts in mice treated with fractionated total lymphoid irradiation.

Treatment of recipient Balb/c mice with fractionated, high-dose total lymphoid irradiation, a procedure commonly used in the therapy of human malignant lymphomas, resulted in fivefold prolongation of the survival of C57BL/Ka skin allografts despite major histocompatibility differences between the strains (H-2d and H-2b, respectively). Infusion of 10(7) (C57BL/Ka x Balb/c)F1 bone marrow cells after total lymphoid irradiation further prolonged C57BL/Ka skin graft survival to more than 120 days. Total lymphoid irradiation may eventually prove useful in clinical organ transplantation.

Animals↗

Excretion of liver antigens in the urine of patients with hepatic diseases.

Liver antigens were detected in the urine of 4 of 42 patients with various liver diseases. The urine of 25 healthy subjects and patients with diseases not affecting the liver was devoid of antigens in detectable amounts. The presence of hepatic antigens in the urine did not correlate with severity of jaundice and SGOT levels but correlated with parenchymal necrosis and was associtated with a high mortaltiy.

Adult↗

Osmotic behavior of normal and leukemic lymphocytes.

The response of normal human peripheral blood lymphocytes to a hypotonic environment may be divided into two phases: the cells first exhibit rapid osmotic swelling, followed by a slower shrinking phase, during which they regain their initial physiologic volume. This osmotic behavior is characteristic of most mammalian and avian nucleated cells so far examined. The normal human blood lymphocyte, however, shows the most rapid recovery phase (5 min). Lymphocytes from chronic lymphatic leukemia patients, in comparison, show a strikingly slower rate of return to their initial isotonic volumes. The mechanism underlying osmotic cell volume regulation and its significance are discussed.

Adolescent↗

Obstructive jaundice associated with carcinoma of the prostate.

An unusual case of prostatic carcinoma presenting as severe obstructive jaundice is reported. After treatment with stilbestrol and bilateral orchidectomy, liver function tests became normal and lung metastases disappeared. During a second episode of jaundice due to serum hepatitis, liver function deteriorated following stilbestrol administration, and the drug was temporarily discontinued. The patient has been followed up for three years and liver function tests remain normal.

Adenocarcinoma↗

Cell-mediated immunity in idiopathic autoimmune haemolytic disease.

Membrane antigens from autologous and from allogeneic red blood cells (RBC) induced migration inhibition of splenic leucocytes and transformation of peripheral blood lymphocytes from a patient with idiopathic autoimmune haemolytic disease (AHD). No migration inhibition occurred following stimulation of splenic leucocytes obtained during splenectomy from a patient with beta-thalassaemia major. Lymphocyte transformation did not occur when normal lymphocytes were stimulated by similar RBC membrane preparations. These findings indicate that autosensitization in AHD may be a function of both humoral and cellular immune mechanisms.

Adult↗

Nephrotoxic effect of parenteral and intraarticular gold. Ultrastructure and electron microprobe examination of clinical and experimental material.

The presence of gold in the kidney of a 58-year-old woman was confirmed by use of ultrastructural and microprobe examinations. A series of animal experiments were performed in which small single doses of gold were administered systemically and intraarticularly in rabbits. Both the colloidal suspension and the soluable salt gold sodium thiomalate (Myochrysine) were used. Selective lesions occurred in the proximal convoluted tubules and the mitochondria appeared to be the target organelle. They contained gold after gold sodium thiomalate but not after colloidal gold.

Animals↗