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Biomedical subjects

R Hoffman

Publications and source records attributed to R Hoffman.

At least 379 records · Page 21Linked to original sources

Migration and cell recruiting activity of specifically sensitized lymphocytes in sponge matrix allografts.

The migration of indium-III-labeled specifically sensitized lymphocytes (SSLs) and unsensitized spleen lymphocytes (ULs) into sponge matrix allografts was studied in irradiated mice. Intravenously injected SSLs were preferentially recruited to the graft bearing the sensitizing alloantigen. High numbers of these SSLs, however, were attracted regardless of their immunological specificity to a third-party graft, when cells sensitized against the third-party antigen were given simultaneously. When SSLs were injected locally into a specific and third-party graft, i.v. injected ULs also homed preferentially to the specific graft. Prior treatment of SSLs with anti-theta serum and complement abrogated their cell recruiting capacity. The percentage of injected lymphocytes recruited to the specific allograft during the first 36 hr increased with the number of SSLs injected. The duration of augmented lymphocyte recruitment, however, was inversely related to the number of SSLs injected into the graft. Furthermore, there is some evidence that SSLs which have been recruited to an allograft migrate to a second site of antigen challenge and initiate there a high lymphocyte recruitment. These results suggest that increased lymphocyte recruitment to an allograft is initiated by an immunologically specific interaction between SSLs and alloantigen. The cells, however, which are preferentially recruited to an allograft, comprise small unsensitized lymphocytes and SSLs regardless of their immunological specificity. Lymphocytes with cell recruiting activity are T cells and appear to be very mobile in vivo. The mechanism described might have an important amplifying effect on allograft rejection.

Animals↗

Skin test reactivity to dog-derived antigens.

Skin test reactivity to canine antigens was studied by testing atopic patients and veterinarians using a commercially prepared mixed-dog epithelial antigen and breed-specific antigens including dander extracts, serum and urine, obtained from thirty-one different pure-bred dogs. Increased skin test reactivity was noted using breed-specific antigens as compared to the mixed-dog commercial screening extract. Variation in skin test responsivity related to specific breed antigens was also noted. The results suggest that skin tests using canine urine and serum antigens, in addition to the conventional dander antigens, may be useful in the diagnosis of hypersensitivity to dogs.

Animals↗

A study of the immunosuppressive effect of allopurinol.

Allopurinol demonstrated to have an immunosuppressive action when given at the dose of 200 microgram daily to the mice receiving skin grafts. This effect was not as apparent in adult mongrel dogs receiving kidney allografts and immediate bilateral nephrectomy. If allopurinol was combined with azathioprine, however, a significant synergistic immunosuppressive effect was seen.

Allopurinol↗

Acute fluoride poisoning in a New Mexico elementary school.

Thirty-four persons became ill with acute fluoride poisoning shortly after drinking water in an elementary school in Los Lunas, NM. The water supply of the school was supplemented with a concentrated sodium fluoride solution designed to raise fluoride levels in drinking water to 1 to 5 ppm. Two water samples taken after the incident was reported showed elevated fluoride levels of 375 and 93.5 ppm. Malfunction of a relay switch controlling dilution of the fluoride solution produced toxic fluoride levels in the water. The symptoms of all patients were mild and generally of short duration, with two thirds of patients reporting complete resolution within 24 hours. The bitter, salty taste of the water deterred consumption of large amounts and prevented serious intoxication.

Acute Disease↗

A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction.

In the past decade, we have studied four unrelated children with what we believe is a previously unreported disorder affecting the bone marrow and exocrine pancreas. During infancy these patients had the onset of severe, transfusion-dependent, macrocytic anemia plus a variable degree of neutropenia and thrombocytopenia. Their bone marrows had normal cellularity but were characterized by remarkable vacuolization of erythroid and myeloid precursors, hemosiderosis, and ringed sideroblasts. The vacuoles probably represented manifestations of cellular degeneration and death. In two patients, in vitro bone marrow cultures showed abnormal erythroid and myeloid progenitor cell growth and, in one child, abnormal vacuolated erythroid colonies. Family histories were unrevealing, parents were hematologically normal, and both sexes were involved. There was no evidence of specific nutritional deficiencies or exposure to agents associated with marrow vacuolization. A number of therapeutic interventions produced no effect. One child had clinical malabsorption. This child and one other had extensive pancreatic fibrosis at autopsy. The other two patients had findings indicating exocrine pancreatic dysfunction. Two children had splenic atrophy. This new syndrome, with associated bone marrow and exocrine pancreatic dysfunctions, differs in several respects from the syndrome of pancreatic liposis and neutropenia described by Shwachman et all and Bodian et al, and from other conditions with vacuolization of the marrow or sideroblastosis.

Anemia, Sideroblastic↗

Partial characterization of cytotoxic cells infiltrating sponge matrix allografts.

Adapting the Roberts and Hayry sponge allograft model, we have demonstrated the presence of an enriched, specifically cytotoxic population of cells which infiltrate rejecting sponge allografts. The number of cells infiltrating a rejecting sponge allograft peaks on day 14 after transplantation. Utilizing a short-term 51chromium cytotoxicity assay, peak antiallogeneic killing was demonstrable on day 14 also. Only T cell killing was apparent for the first 15 days after transplantation. After day 20, specific cytolysis was present which was not sensitive to anti-theta serum and complement. The infiltrating cytotoxic cells are large, specifically cytotoxic, do not proliferate in culture, do not respond to mitogen, and do not respond in mixed lymphocyte culture even to the same alloantigen to which the animal had been sensitized. In contrast, spleens from sponge-bearing animals kill poorly, respond to mitogen, and respond vigorously in mixed lymphocyte culture to specific and nonspecific alloantigens. The following hypotheses are set forth with regard to the cytotoxic lymphocytes (1) Such cells may be end stage and cannot proliferate. (2) The cytotoxic cells may kill the stimulator cells more rapidly than they can be stimulated to proliferate. (3) The sponge cell population may be enriched for nonspecific supressor cells. (4) The sponge cells may be devoid of helper T cells.

Animals↗

The impact of political process on hospital psychiatry.

Political forces motivated the New York State Department of Health to withhold payment for Medicaid-financed inpatients on therapeutic passes. The elimination of therapeutic passes had many negative effects on patient care. The authors believe this experience demonstrates that political factors can overwhelm standard clinical practice and reasoned health planning to force irrational change on health care delivery.

Deinstitutionalization↗

Induction of erythropoietic colonies in a human chronic myelogenous leukemia cell line.

The ability of cells derived from the K562 cell line to generate erythropoietic colonies was studied. The K562 cell line was derived from a patient with chronic myelogenous leukemia 8 yr ago by Lozzio and Lozzio. Rare benzidine-positive colonies formed when these cells were cloned in plasma clots (3 +/- 1/10(4) cells), and their number was not substantially increased by the addition of erythropoietin (9.5 +/- 1/10(4) cells). Sodium butyrate was capable of markedly enhancing the number of benzidine-positive colonies (19.5 +/- 1/10(4) cells) formed, while the combination of sodium butyrate plus erythropoietin exerted a synergistic effect on erythropoietic colony formation (57 +/- 4/10(4) cells). The K562 cell line is a long-term culture system that contains human erythropoietic stem cells. This cell line should be useful in future studies on the cellular and molecular events associated with human erythroid cell differentiation.

Benzidines↗

Fetal hemoglobin in polycythemia vera: cellular distribution in 50 unselected patients.

Fetal hemoglobin was studied in 50 unselected patients with polycythemia vera with chemical determinations of Hb F and measurements of F-cell levels using fluorescent anti-Hb F antibodies. Although in the majority of the patients Hb F production did not differ from that in normal controls, in 20% of the patients F-cell values were above the normal range. There was no correlation between F-cell values and duration of disease, treatment modality, presence of myelofibrosis, or hematologic parameters at the time of study. In 5 of 50 patients 30%--45% of the erythrocytes contained Hb F; such striking elevations of F cells may reflect a distorted differentiation of erythroid precursor cells in certain patients with this disorder.

Erythrocytes↗

Erythropoietin-dependent primary pure erythrocytosis.

We investigated the pathogenesis of isolated erythrocytosis of 14 yr duration in a 28-yr-old man. The increase in red cell mass was attributed to increased erythropoietin production. An extensive search for recognized causes of secondary erythrocytosis was unrevealing. Family members were found to be hematologically normal. After reduction of the circulating red cell mass by 20%, erythropoietin activity nearly quadrupled, thus suggesting a normal erythropoietin response to phlebotomy. When bone marrow cells of the patient were cultured in plasma clots in the absence of added erythropoietin, endogenous erythroid colony formation was observed, a pattern previously believed to be specific for polycythemia vera bone marrow cells. Our observations suggest that the erythrocytosis in this individual is best explained by an abnormal "servoregulatory" mechanism of erythropoietin production. In addition, this is the first instance in which the rule that endogenous erythroid colony formation is correlated with the diagnosis of polycythemia vera has not held.

Adult↗

Antibody-mediated acquired sideroblastic anemia: response to cytotoxic therapy.

A 5 1/2-yr-old child developed severe anemia with erythroid hypoplasia and 50% ringed sideroblasts in his bone marrow. A serum inhibitor of erythropoiesis was demonstrated, utilizing syngeneic and autologous bone marrow in a plasma-clot culture system. The IgG fraction of the patient's serum effected similar suppression of erythroid colony formation. Prednisone therapy was ineffective, but following treatment with cyclophosphamide, normal erythropoiesis was established, ringed sideroblasts disappeared, and his serum no longer inhibited erythropoiesis in vitro. Cyclophosphamide was discontinued, and the patient has remained hematologically normal. This patient is an example of antibody-mediated sideroblastic anemia successfully treated with a cytotoxic drug.

Anemia, Sideroblastic↗