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Biomedical subjects

H Krakauer

Publications and source records attributed to H Krakauer.

At least 91 records · Page 5Linked to original sources
PubMed1986

Double-blind comparison of weekend and daily regimens of oral acyclovir for suppression of recurrent genital herpes.

The potential utility of intermittent regimens of oral acyclovir for suppression of recurrent genital herpes depends on how long the suppressive effect of the drug persists during pauses in treatment. To study this question, we admitted 38 patients in a double-blind controlled trial comparing the results of daily acyclovir treatment (200 mg t.i.d.) with treatment on weekend days only (400 mg t.i.d. on Saturday and Sunday) for suppression of recurrent genital herpes. Of the 35 patients completing the study, significantly more failures occurred in the weekend group (13/17) than in the daily group (3/18, P less than 0.001). Failures on the weekend regimen were more frequent as the week progressed (P = 0.005). The findings suggest a short-term persistence of suppression by acyclovir and hence that intermittent regimens with more closely spaced periods of treatment may be more effective than the regimen we studied. Most virus isolates studied, including all of those isolated from the patients during treatment, were sensitive to acyclovir.

Acyclovir↗
PubMed1986

Antibody to hepatitis B core antigen as a paradoxical marker for non-A, non-B hepatitis agents in donated blood.

The relationship between the presence of antibody to hepatitis B core antigen (anti-HBc) in donor blood and the development of hepatitis in recipients of that blood was studied in 6293 blood donors and 481 recipients who were followed for 6 to 9 months after transfusion. Of 193 recipients of at least 1 unit of blood positive for anti-HBc, 23 (11.9%) developed non-A, non-B hepatitis compared with 12 (4.2%) of 288 recipients of only anti-HBc-negative blood (p less than 0.001). Donor anti-HBc status was not significantly associated with the development of hepatitis B in the recipient and was negatively associated with the development of cytomegalovirus hepatitis. The relationship of donor anti-HBc status and the development of non-A, non-B hepatitis in the recipient was independent of transfusion volume and elevated donor transaminase level. Although 88% of anti-HBc-positive blood units were not associated with recipient non-A, non-B hepatitis, calculation of maximal corrected efficacy predicted that exclusion of anti-HBc-positive donors might have prevented 43% of the cases of non-A, non-B hepatitis with a donor loss of 4%. Because of the serious chronic consequences of non-A, non-B hepatitis, surrogate tests for non-A, non-B virus carriers must be seriously considered.

Alanine Transaminase↗
PubMed1985

Clinical applications of monoclonal antibodies.

This review highlights the properties, problems, and potentials of monoclonal antibodies as diagnostic and therapeutic agents. The most extensive experience has been obtained with antibodies specific for functionally distinct subsets of lymphocytes. They have been used to monitor the immunosuppression of organ-graft recipients and to attempt to elucidate the disturbance of immunologic function in a variety of conditions. Current therapeutic applications under trial include immunosuppression to treat organ-graft rejection and to eliminate cells responsible for graft-vs-host disease from the bone marrow. Applications to cancer diagnosis and treatment have been hampered by the difficulty of identifying truly tumor-specific antigens. Successes have, however, been obtained in the location of metastases and in the extracorporeal treatment of autologous marrow to purge it of malignant cells, and, more rarely, with the direct administration of monoclonal antibodies in vivo. The conjugation of cell-type specific monoclonal antibodies with cytotoxic agents should overcome a number of limitations.

Animals↗
PubMed1985

Isolation and characterization of a monoclonal antibody specific for epithelial cells.

Monoclonal antibodies were generated to antigens on human foreskin keratinocytes to identify epithelial-specific molecules. Spleen cells from BALB/c mice, immunized with membrane preparations from primary explants of foreskin epithelial cells, were fused with the NS-1 mouse myeloma line. Hybridoma supernatants were screened for the desired immunological reactivity using enzyme-linked immunosorbant binding assays. Hybridomas secreting antibodies reacting with epithelial cells, but not fibroblasts or lymphocytes, were cloned by limiting dilution, and two stable clones producing immunoglobulin M K antibodies were selected for study. Evaluation of fixed paraffin-embedded human tissue by an indirect immunoperoxidase technique revealed that the antibodies bound most strongly to normal stratified squamous and transitional epithelium, and squamous and transitional cell carcinomas. Antibodies from the cloned hybridomas also reacted with primary cell cultures of foreskin keratinocytes, pulmonary epithelium, fetal liver, and amnion cells, but not with primary cultures of nonepithelial cells. Further testing by enzyme-linked immunosorbent assays revealed that the antibodies reacted with some long-term cell lines derived from epithelial tumors. Nonepithelial cell lines were not stained by the antibodies. Indirect immunofluorescent studies indicated that staining was confined to the cell surface. These antibodies may prove useful in studies of differentiation markers of human epithelial cells.

Animals↗
PubMed1984

Calorimetric study of carbohydrate binding to concanavalin A.

Flow microcalorimetry has been used to examine the delta H of binding of two types of saccharides, a series of simple monosaccharides and a series of alpha-(1----4)-linked glucosides, to the lectin Concanavalin A. It has been found that the delta H decreases with any change in the stereochemistry of a hydroxyl group relative to methyl alpha-D-mannopyranoside. The data have allowed the calculation of the relative contribution of two of the hydroxyl groups. The delta H's of binding for the alpha-(1----4)-linked glucosides are approximately 31 kJ/mol, and the apparent association constants vary insignificantly with increasing length. This result indicates that only one glucose residue binds to concanavalin A by hydrogen bonds, and that the additional glucose residues have no interaction either by hydrogen bonds or by nonspecific hydrophobic interactions. This result confirms the absence of an extended binding site for alpha-(1----4)-linked glucopyranosides, in contrast to that proposed for alpha-(1----2)-linked mannopyranosides which show an increase in apparent association constants with increasing length.

Binding Sites↗
PubMed1983

Thymus-independent immunogenicity in vitro of the divalent antigen DNP-polyethylene oxide.

Chemically simple and physically well-defined dinitrophenyl derivatives of polyethylene oxide (DNP-PEO) can be prepared in a wide range of forms and sizes. These materials were used to investigate the molecular basis of immunogenicity and the binding of the antigens to membrane-bound receptors. Both di- and multivalent DNP-PEO activate normal murine B lymphocytes to yield primary anti-DNP antibody response in vitro. The immunogenicity is dependent on the carrier chain length but independent of T cells. Responses comparable to those induced by DNP-conjugated polymerized flagellin are induced by divalent linear materials of medium molecular weights of about 60,000. A highly multivalent material is moderately immunogenic, but at much lower antigen doses than divalent materials. The carrier PEO does not affect B-cell responses to DNP-PEO or T-cell response to succinyl concanavalin A. Moreover, it shows no polyclonal mitogenicity at concentrations as high as 1 mg/ml. Studies of antigen binding to cell surface DNP receptors show that the strongly immunogenic materials of medium molecular weights have an appreciable tendency to bind bivalently and thus potentially to crosslink receptors. The binding of smaller, less immunogenic antigen appears predominantly monovalent.

Animals↗
PubMed1983

The recent U.S. experience in the treatment of end-stage renal disease by dialysis and transplantation.

We determined survival rates and rates of graft retention for patients who had begun to receive dialysis or had received transplants between January 1, 1977, and December 31, 1980, using the data collected by the Medical Information System of the Health Care Financing Administration, which covers nearly all persons with end-stage renal disease in the United States. We found that among patients receiving transplants in successive years in the period from 1977 to 1980 the rates of graft retention showed progressive and substantial increases, whereas survival rates for both dialysis and transplant recipients remained stable. In addition, we found that transplant recipients were subject initially to high risks of graft loss and death, but that these risks decreased rapidly in the few months after transplantation. The population receiving dialysis was subject to a nearly constant death rate, which was generally higher than the stable late-mortality rate among transplant recipients. Blacks had higher survival rates than whites on dialysis, black and white patients had similar survival rates after transplantation, and black patients had lower rates of retention of functioning grafts. Finally, our analysis indicates that the best results were obtained in recipients of kidneys from related donors.

Adolescent↗