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Biomedical subjects

A A Hoffman

Publications and source records attributed to A A Hoffman.

At least 19 recordsLinked to original sources
PubMed1987

Genetic divergence under uniform selection. III. Selection for knockdown resistance to ethanol in Drosophila pseudoobscura populations and their replicate lines.

Replicate D. pseudoobscura lines from populations collected at different geographic locations were selected for increased knockdown resistance to ethanol. Population background affected the initial rate of response but not the extent that lines responded. Lines were tested for physiological traits contributing to increased knockdown resistance. Populations showed different correlated responses for two traits (tolerance of ethanol, and of acetone), suggesting that they had responded to selection by different mechanisms. Replicate lines had diverged for most traits. The results indicate that drift and/or differences in genetic background can lead to divergence under uniform selection, even when fairly large population sizes are maintained.

Animals↗
PubMed1984

Fibronectin deposition in delayed-type hypersensitivity. Reactions of normals and a patient with afibrinogenemia.

During development of delayed hypersensitivity (DH) skin reactions, fibronectin accumulates in two distinct sites: (a) the dermal interstitium in a pattern similar to fibrin and with a time course similar to that of fibrin deposition and mononuclear cell infiltration, and (b) blood vessel walls in a pattern suggestive of basement membrane staining and with a time course similar to that of endothelial cell proliferation. In vitro fibronectin can bind to monocytes or endothelial cells and simultaneously bind to fibrin or collagen matrices; by such interaction in vivo it may affect cell migration or proliferation. Thus, fibronectin deposition in DH reactions may facilitate cell-matrix interactions; however, the possibility exists that extravascular fibronectin accumulation may be only secondary to interstitial fibrin clot formation, and that blood vessel-associated fibronectin may be only a function of adsorption onto basement membrane (type IV) collagen. To address these possibilities, we investigated the association of fibronectin with fibrin, type IV collagen, and mononuclear cell infiltrates in DH reactions. Skin sites of DH reactions in normal volunteers were biopsied at 24, 48, and 72 h after intradermal challenge and examined by immunofluorescence technique. At all time points most of the interstitial fibronectin coincided with fibrin; however, some interstitial fibronectin was coincident with mononuclear cells positive for HLA-DR or monocyte-specific antigen. The coincidence of fibronectin with mononuclear cells was more apparent in a 48-h DH reaction from a patient with congenital afibrinogenemia. Vessel wall fibronectin was increased by 48 h after challenge and appeared as a fine linear band on the luminal side of a much thicker band of type IV collagen. Thus, the coincidence of extravascular fibronectin with mononuclear cells, its appearance without fibrin in the site from a patient with afibrinogenemia, and incomplete correspondence of vessel wall fibronectin with type IV collagen suggest that fibronectin localization in DH reactions involves endothelial cell and mononuclear cell binding as well as adsorption to fibrin and/or type IV collagen.

Afibrinogenemia↗
PubMed1979

Immunoregulation in New Zealand mice. I. Failure of the transfer of syngeneic spleen or thymus cells to influence the natural disease in New Zealand mice.

Young, syngeneic thymocytes and spleen cells were administered to F1 hybrids of New Zealand Black by New Zealand White (NZB/W) mice beginning at 3 weeks of age and were continuted at 2-week intervals for 8 to 9 months. The development of autoimmunity as assessed by measuring the incidence and level of anti-DNA antibody, the degree of renal involvement, and the survival of recipient mice was evaluated and compared to a control group of animals. No significant differences were noted in these parameters in mice receiving cell transfers as compared to the control group. Therefore, in contrast to other reports, these results suggest that the transfer of young thymus or spleen cells into aging NZB/W mice fails to influence immunoregulation and the subsequent development of autoimmunity.

Animals↗
PubMed1978

A naturally occurring antibody in New Zealand mice cytotoxic to dissociated cerebellar cells.

A spontaneously occurring antibody cytotoxic to dissociated cells of the neonate mouse cerebellum was found in the sera of some New Zealand (NZ) mice. No significant activity was found in the sera of six non-autoimmune mouse strains. The degree of cytotoxicity was similar towards both allogeneic and syngeneic cells. Absorption of the cytotoxic sera with brain and kidney homogenates removed the reactivity, while liver removed less reactivity. Absorptions with thymocytes and several other tissue homogenates and cells had no effect on the cytotoxicity levels, nor was there a correlation between the levels of thymocytotoxicity and cerebellar cell cytotoxicity. The antibody cytotoxic for cerebellar cells could not be demonstrated in the cerebrospinal fluid (CSF) of any mice examined, including a mouse with high serum cytotoxic levels. Gel filtration of reactive sera indicated that the antibody is of the IgM class.

Animals↗
PubMed1975

The prognostic and therapeutic implications of DNA:anti-DNA immune complexes in systemic lupus erythematosus (SLE).

Serum samples serially obtained from 50 patients with systemic lupus erythematosus (SLE) were studied for antibody to deoxyribonucleic acid (DNA) and circulating DNA:anti-DNA complexes during the active and inactive phases of their disease. The patients were divided into four categories: Group I: six patients without clinical evidence of central nervous system (CNS) or renal involvement. Group II: three patients with CNS lupus. Group III: nine patients with normal urinalyses and glomerular filtration rates, but morphologic evidence of glomerular disease. Group IV: 32 patients with overt lupus nephritis. Elevated anti-DNA levels were observed in 16 of 18 patients (88 per cent) in groups I, II and III during active disease. This persisted in 14 (77 per cent) during remission. DNA:anti-DNA complexes were demonstrated in four of 18 (22 per cent) during active disease and disappeared in all but one patient with progressive disease. In 30 of the 32 patients (94 per cent) in group IV, DNA binding was increased during active disease; this persisted in 21 (70 per cent) despite remission. Complexes were observed in 25 of the patients in group IV (78 per cent) with active disease. In six of these patients, complexes have persisted; two have died, one has progressed to renal failure and the remaining three patients continue to manifest active disease. This study suggests that measurement of DNA:anti-DNA complexes provides a valuable additional index of disease activity and prognosis in SLE.

Adolescent↗
PubMed1975

Use of arterial infusion of 5-fluorouracil either alone or in combination with supervoltage radiation as a treatment for carcinoma of the prostate and bladder.

Arterial infusion of 5-fluorouracil either alone or in combination with supervoltage radiation achieves a definite objective improvement in patients with estrogen-resistant adenocarcinoma of the prostate. This improvement has been documented by a decrease in tumor size, improvement in intravenous pyelograms, and a change in cancer grade from undifferentiated to well differentiated. The quality of life in each case has been good, with 45 per cent of the patients treated in this category currently alive and well. The use of protracted arterial infusion of 5-fluorouracil in patients with stage C and D adenocarcinoma and transitional cell carcinoma of the bladder has had an even more satisfying outcome. Of those patients treated, 90 per cent are still alive and free of disease from six to sixty-six months. Eight of the patients have survived over two years with an excellent quality of life. A long-term outpatient infusion program is necessary to achieve these good results. It is also difficult and time-consuming. In addition to having well trained paramedical personnel constantly available, the patients must live within a reasonable radius of the treatment center so they can be treated almost immediately if problems develop. A fairly large number of patients must be treated in order to develop familiarity with the technics and to maintain a level of proficiency.

Adenocarcinoma↗
PubMed1975

Clinical studies on the significance of DNA:anti-DNA complexes in the systemic circulation and cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus.

Evidence has gradually accumulated that DNA antibodies play a pathogenic role in SLE in combination with DNA, as DNA: anti-DNA complexes, but until recently there was no direct assay for such complexes. By measuring DNA binding before and after DN'ase digestion, an indication of the amount of DNA complexes in biological fluids was obtained. This assay was used to examine sera from patients with SLE or non-SLE nephritis. DNA:anti-DNA complexes were detectable only in the circulation of patients with SLE, almost invariably with active nephritis. When a large series (50) of SLE patients were serially examined, similar results were found. Significant amounts of DNA:anti-DNA complexes were found in the circulation only during active CNS and/or renal lupus. Persistence of the complexes was associated with treatment resistance and increased morbidity and mortality. In addition, DNA:anti-DNA complexes were found in the CSF of a patient with CNS lupus.

Adult↗
PubMed1971

Commentary.

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Coronary Disease↗