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Biomedical subjects

K H Stenzel

Publications and source records attributed to K H Stenzel.

At least 127 records · Page 7Linked to original sources

Adverse presensitization to renal transplants. Detection by utilization of a D locus antigen-defined lymphoblastoid cell panel as targets in antibody-dependent cell-mediated cytotoxicity assays.

Sera obtained before transplantation from 52 consecutive renal allograft recipients were tested for antibody-dependent cell-mediated cytotoxicity (ADCC) and for complement-dependent cytotoxic antibodies (CDC). A D locus antigen-defined lymphoblastoid cell panel (B lymphoblastoid cell panel) was used as targets for the ADCC, and a peripheral blood lymphocyte (PBL) panel from 40 donors was used as targets for the CDC. Of the 343 ADCC assays, 118 of 168 performed with pretransplant sera from 24 recipients with early graft loss were positive, whereas only 81 of 175 performed with pretransplant sera from 25 recipients with a successful graft outcome were positive (P less than 0.001). A significantly greater degree of presensitization to the B lymphoblastoid cell panel was found in the group that lost their grafts as compared to the group with successful grafts (69% versus 49%, P less than 0.001). Sera from all six recipients with hyperacute rejection were positive in the ADCC before and after absorption with pooled platelets. In contrast, pretransplant CDC results were not predictive of ultimate graft outcome. Utilizing any level of cytotoxicity against the PBL panel as an index of adverse presensitization, no significant correlation between pretransplant CDC results and graft outcome was observed. These results suggest a prognostic role for ADCC using a B lymphoblastoid cell panel as targets to screen and identify high-risk potential graft recipients.

Antibody-Dependent Cell Cytotoxicity↗

Human gamma globulin enhances the survival of renal allografts.

Ninety seven transplant recipients participated in a controlled, clinical trial measuring the graft-enhancing property of a human gamma globulin preparation. The latter was prepared from the blood of pregnant women (RPGG) and contained antibodies with specificities for HLA locus products. Data analysis indicated that RPGG treated recipients had enhanced survival rates of their grafts if they had received one or more blood transfusions prior to transplantation.

Antilymphocyte Serum↗

Collagen-induced platelet aggregation and release. I Effects of side-chain modifications and role of arginyl residues.

To investigate the mechanisms governing collagen interaction with blood platelets, the effects of side-chain modifications on collagen-induced platelet aggregation and release of serotonin were studied. Since many chemical modifications alter the ability of collagen to form fibers that, according to current theory, may complicate interpretation of data, we eliminated this possibility by using collagen stabilized in a native-type fibrillar structure by treatment with either glutaraldehyde or ultraviolet irradiation. Acetylation, methylation, succinylation, treatment with 2,4-dinitrofluorobenzene, 2,4,6-trinitrobenzene sulfonic acid or 1,2-cyclohexanedione, and deguanidination with hypobromite were used to modify collagen side-chain reactive groups: amino, carboxyl, hydroxyl and guanidino. Both unmodified monomeric dispersed and fibrillar collagen preparations initiated platelet aggregation and release, although the kinetics and magnitude of the response were different. Monomeric collagen which had been modified by deguanidination, methylation or succinylation, failed to polymerize in physiological conditions and did not induce platelet aggregation and release. However, none of the chemical modifications of stabilized native-type collagen fibers, except treatment with hypobromite or cyclohexanedione, had an effect on collagen-induced platelet aggregation and release. Both hypobromite and cyclohexanedione modified guanidino groups of arginyl residues. Results showed that the ability of a collagen sample to induce platelet aggregation and release of serotonin is dependent on the arginine content of fibrillar collagen. These data demonstrate that manipulation of amino, carboxyl and hydroxyl groups is unimportant as long as the native-type fibrillar structure is maintained, and that arginyl residues are directly involved in collagen-platelet interaction. Moreover, the data suggest that only the arginyl residues in the Y position of the tripeptide unit Gly-X-Y of collagen are responsible.

Amino Acid Sequence↗

Association between Streptococcus faecalis urinary infections and graft rejection in kidney transplantation.

In the first month after transplantation 50% of 193 consecutive renal transplant recipients had bacteriuria. The most common organisms isolated were Streptococcus faecalis (34), Escherichia coli (28), Pseudomonas spp. (11), and staphylococcus (9). There was a significant correlation between infection with Str. faecalis and graft failure at one, three, and twelve months. This observation suggests that urinary infection with Str. faecalis may be associated with graft failure which is probably the result of immunological factors.

Adult↗

Improved survival-rates in presensitised recipients of kidney transplants by immunosuppression with maternal-source gamma-globulin.

The effect on cadaver-kidney transplant survival-rates of a gamma-globulin concentrate, prepared from clotted blood centrifugally expressed from placental tissue recovered from postpartum women, was evaluated in a prospective controlled trial in 195 patients who were also given a standard immunosuppressive regimen. Allograft-survival rates were analysed according to whether or not the recipient had lymphocytotoxic antibodies before transplantation (responders) and whether the graft was a first or second transplant. The graft-survival rate was improved in responder-type recipients of first transplants who had received the gamma-globulin concentrate as adjunctive therapy (control group 28.8+/-10.1% vs. gamma-globulin 55.5 + 9.7% at 2 years, p less than 0.05). The survival-rate of grafts in non-responders was not affected by administration of gamma-globulin and data on its use in recipients of a second graft were insufficient for analysis. These results suggest that the gamma-globulin concentrate was suppressing immunological responses associated with humoral-type rejection.

Adult↗

Soluble gentamicin ophthalmic inserts as a drug delivery system.

A comparison was made of soluble 14C-gentamicin ophthalmic inserts with drop, ointment, and the subconjunctival routes of administration. The insert is a solid, solubilizable collagen polymer containing 14C-gentamicin. We compared the levels of 14C-gentamicin in the rabbit tear film and in multiple corneal and scleral biopsies to determine which route of administration gave the best results. The wafer route of administration gave the highest tear film and tissue concentration of drug. The tear film concentration by subconjunctival injection was surprisingly low. Soluble collagen inserts offer a new method of delivering high doses of gentamicin in infected corneal tissue in a convenient and atraumatic fashion.

Administration, Topical↗

Transglutaminase activity in human lymphocytes: early activation by phytomitogens.

Transglutaminase activity is present in human peripheral lymphocytes and is enhanced up to 15-fold within 10-30 min after treatment of the cells with concanavalin A. Phytohemagglutinin has a similar effect. The enzyme is not detected when intact cells are assayed; it is detected only in cell lysates. Concanavalin A enhances transglutaminase activity only when it is incubated with intact cells; concanavalin A treatment of cell lysates has no effect, alpha-Methyl-D-mannoside specifically inhibits the enhancement of transglutaminase activity in cells treated with concanavalin A results from the specific interaction of the lectin with its saccharide binding site on the cell surface, rather than by direct interaction with the enzyme itself. The increased activity of transglutaminase in cells treated with concanavalin A, as compared to unstimulated cells, is maintained under assay conditions in which saturating levels of Ca2+ are present. Transglutaminase may be involved in early cellular events leading to lymphocyte blastogenesis.

Animals↗

Pharmacokinetics of essential amino acids in chronic dialysis-patients.

Possible disorders of essential amino acid (EAA) metabolism in maintenance dialysis patients (D) were studied by measuring plasma amino acids before and sequentially after administering a mixture of 8 EAA po and iv. The EAA were in a ratio similar to that required for optimal utilization, and the total dose given was within physiological range. Ten D and six normals (N) received 150 mg/kg po as a 10.5 g/dl solution and 117 mg/kg iv as a 5.1 g/dl solution infused at a constant rate of mg/kg per min. Blood glucose and immunoreactive insulin were also measured. Both D and N were postabsorptive and at least 18 hr postdialysis. The fraction of the oral dose appearing in the systemic circulation was variable for each EAA in both N and D. Total body clearance was significantly lower in D (P less than 0.05) for theronine, phenylalanine, valine, leucine, and isoleucine, and this difference could not be explained by changes in renal excretion. The apparent volume of distribution did not differ between N and D for all EAA except for valine and phenylalanine. Blood glucose insulin varied only slightly in both N and D for all EAA except for valine and phenylalanine. Blood glucose and insulin varied only slightly in both N and D. These studies indicate that there are a variety of significant abnormalities in the metabolism of specific EAA in D. Decreased total body clearance of the branched-chain amino acids, since they are primarily metabolized total body clearance of the brnached-chain amino acids, since they are primarily metabolized by muscle, may result from a defect in muscle metabolism in D.

Administration, Oral↗

Hepatitis B immune globulin: final report of a controlled, multicenter trial of efficacy in prevention of dialysis-associated hepatitis.

In a randomized, double-blind multicenter trial, 284 patients and 282 staff members of renal dialysis units who lacked detectable hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) were randomly assigned to receive two 3-ml injections of immune serum globulin with high, intermediate, or low titers of anti-HBs four months apart. The incidence of infection with hepatitis B and of development of HBsAg was significantly lower in both patients and staff who received the high-titer material than in subjects who received the low-titer preparation eight but not 12 months after randomization (P less than 0.01 for patients and P less than 0.04 for staff, low-titer vs. high-titer at eight months). The high-titer hepatitis B immune globulin preparation did not appear to affect the severity of the cases of hepatitis that did occur, the proportion of subjects who developed persistent antigenemia, or the magnitude or timing of primary anti-HBs responses.

Antibodies, Viral↗

Potentiation of lymphocyte activation by colchicine.

Proliferation of human lymphocytes induced by IO4- is potentiated by 30 min exposure to colchicine (10(-6)M), whereas the response to Con A is inhibited. Treatment with colchicine before or after IO4- modification has similar enhancing effects. Lumicolchicine does not alter proliferative responses. In addition to the proliferation of IO4--oxidized cells, irradiated IO4- modified lymphocytes induce proliferation when mixed with untreated lymphocytes. Enhancement occurs in both these conditions only when IO4--modified cells are treated with colchicine. Preliminary data indicate that proliferation in mixed lymphocyte cultures is also potentiated when either stimulating or responding cells are pretreated with colchicine. These findings suggest a selective stimulatory effect of colchicine on lymphocyte responses induced by cell-cell contact. Agents that modify microtubular assemblies might regulate the induction of immune responses that involve cellular interactions.

Adult↗