PubMed Health⌕ Search

Biomedical subjects

K H Stenzel

Publications and source records attributed to K H Stenzel.

At least 91 records · Page 5Linked to original sources

Natural history of cadaveric kidney transplants in the absence of early acute rejection.

The foremost goal in organ transplantation is to achieve normal graft function without rejection. 31 (8.7%) of 357 cadaveric kidney transplant had no evidence of rejection for the first 3 months. Among these, 2 patients died with a functioning graft and four grafts failed during the 1- to 7-year follow-up period. Actuarial graft survival rates of these patients were 96.8 and 79.0% at 2 and 5 years, respectively, as compared with 64.6 and 51.2%, respectively, for the controls (p less than 0.01). Multiple preoperative blood transfusions and the adjunctive immunosuppressive therapy with retroplacental gamma globulin appeared to be playing a role for the induction of the 'no-rejection' state. However, continuous immunosuppressive therapy is necessary to maintain graft function.

Adolescent↗

Prognostic patterns in acute renal failure: the New York Hospital, 1981-1982.

Sixty four patients who developed acute renal failure at The New York Hospital between July 1981 and June 1982 were studied. The average age was found to be 59.5 years. The overall mortality rate was 62.5%. Patients with non-oliguric renal failure had a lower mortality rate (25%) than those with oliguric renal failure (79%). Those patients with non-oliguric renal failure were more likely to have a discrete cause of renal failure (drugs) and to be in a more stable cardiovascular status. Tachycardia, hypotension, respiratory failure, and documented (or presumed) sepsis all adversely affected prognosis.

Acute Kidney Injury↗

Maternal-fetal immunity: presence of specific cellular hyporesponsiveness and humoral suppressor activity in normal pregnancy and their absence in preeclampsia.

The hypothesis that aberrant maternal-fetal immunity might lead to the development of preeclampsia was examined using mixed lymphocyte culture reactions (MLC) as an in vitro analogue of maternal-fetal immunity. Maternal lymphocytes and serum from five normal pregnant women differed significantly from lymphocytes and serum from five preeclamptics. Maternal cells from normal pregnancy responded appropriately to unrelated control cells, but demonstrated selective hyporesponsiveness to fetal cells in the MLC. Serum from normal pregnancy suppressed MLCs when maternal cells were responder cells (RC) and maternal cells or fetal cells were stimulator cells (SC), and did not inhibit MLCs where maternal cells were RC and control cells were SC. Maternal lymphocytes and serum from preeclamptics did not demonstrate cellular hyporesponsiveness or humoral suppressor activity. Our findings support the notion that specific cellular hyporesponsiveness and humoral suppressor activity is responsible for normal pregnancy; absence of such adaptive immunity might lead to the development of preeclampsia.

Adult↗

Protein A-independent tumoricidal responses in dogs after extracorporeal perfusion of plasma over Staphylococcus aureus.

Protein A-positive or -negative Staphylococcus aureus preparations were used in an extracorporeal system to treat dogs with spontaneously occurring cancers. Tumor regression was seen in 4 of 7 dogs treated by reinfusion of plasma that had been incubated with protein A-positive S. aureus Cowan I strain (SAC). Therapy was associated with fever, liver enzyme abnormalities, and hypocomplementemia. Tumor response and toxicity could be diminished by more extensive washing of the SAC preparation. Tumor regression was also seen in 2 of 2 animals treated with protein A-negative S. aureus Wood strain 46. In addition, tumors regressed in 3 of 4 dogs treated with infusions of protein A-free saline extracts from S. aureus. These results suggest that the release of a non-protein A bacterial product contributes to tumor regression following incubation of plasma with S. aureus.

Alanine Transaminase↗

Cellular and growth factor requirements for activation of human T lymphocytes by neuraminidase and galactose oxidase-treated lymphoid cells.

Proliferation of peripheral blood mononuclear leukocytes (PBL) can be stimulated by irradiated autologous PBL that have been treated with neuraminidase and galactose oxidase (NAGO). We determined the types of cells that stimulate and respond by isolating populations of cells enriched for macrophages, B lymphocytes, and T lymphocytes. With PBL as responding cells, proliferation was stimulated by irradiated, NAGO-treated cells with the following hierarchy: macrophage greater than PBL greater than B cells greater than T cells. Irradiated NAGO-treated macrophages and PBL induced proliferation of isolated T cells greater than or equal to the proliferation they stimulated in PBL, indicating that T cells are the predominant responding cell type. Irradiated, NAGO-treated B cells or T cells were weak stimulators of isolated T cell proliferation when compared to their ability to stimulate PBL. The ability of irradiated NAGO-treated B cells or T cells to stimulate isolated T cell proliferation was greatly enhanced by the addition of untreated macrophages or by the addition of conditioned media from mitogen-activated PBL. Biologic, biochemical, and biophysical characterization of the conditioned media revealed it contained both lymphocyte polypeptide growth factors, interleukin 1 and interleukin 2. Semipurified preparations of either of these growth factors were capable of enhancing T cell proliferation stimulated by irradiated NAGO-treated B or T cells. These data indicate T cell proliferation induced by irradiated, NAGO-treated cells requires the aldehyde-bearing cells for the induction of soluble growth factor production and for the induction of putative membrane receptors for these growth factors.

Adult↗

Inhibition of phorbol ester-mediated interleukin-2 production by cellular differentiating agents.

Lymphocyte proliferation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is inhibited by agents known to induce differentiation in murine erythroleukemia cells and other cell lines. In the present study, we determined the cellular targets for the action of TPA among murine thymocyte subpopulations, the phase of blastogenesis that is activated by the tumor promoter, and the phase that is inhibited by the differentiating agents. Mouse thymocytes were fractionated into populations bearing receptors for peanut agglutinin (PNA; PNA-positive cells) and populations lacking such receptors (PNA-negative cells). TPA is comitogenic for lectin-treated, unfractionated thymocytes and PNA-negative thymocytes but not for PNA-positive thymocytes. PNA-negative cells, a minor population in unfractionated thymocytes, are therefore the cellular targets for the comitogenic activity of TPA. TPA induces the production of interleukin-2 (IL-2) in lectin-treated PNA-negative populations but not in PNA-positive cells. The differentiating agents inhibit TPA-mediated proliferation of unfractionated and PNA-negative, lectin-treated thymocytes. In contrast, IL-2-mediated proliferation of lectin-treated thymocyte subpopulations is resistant to inhibition by these agents. Inhibition appears to be related to decreased production of IL-2, since the differentiating agents inhibit IL-2 production by both PNA-negative thymocytes and by a human leukemic cell line.

Animals↗

The advantage of measurement of intact PTH in the prediction of clinical response and calcium metabolism after subtotal parathyroidectomy for renal osteodystrophy.

As previously reported, the circulating half-life of carboxyterminal PTH is greatly prolonged in renal failure (mean t1/2 33.20 +/- 10.18 hrs), while intact PTH is much less affected (t1/2 less than one hour). Preoperative intact PTH levels were strongly predictive of clinical response to subtotal parathyroidectomy, and may help to differentiate the nature of metabolic bone disease in symptomatic dialysis patients. Intact PTH levels showed strong correlation with postoperative calcium metabolism, allowing prediction of extent of postoperative hypocalcemia. Carboxyterminal PTH levels, influenced by renal function as well as by functional parathyroid state, were poorly predictive of response to parathyroidectomy and not correlated with postoperative calcium metabolism.

Adult↗

Hydroxyl radical scavengers inhibit lymphocyte mitogenesis.

Agents that are known to be scavengers of hydroxyl radicals inhibit lymphocyte mitogenesis induced by phorbol myristate acetate (PMA) to a greater extent than they inhibit mitogenesis induced by concanavalin A or phytohemagglutinin. These agents include dimethyl sulfoxide, benzoate, thiourea, dimethylurea, tetramethylurea, L-tryptophan, mannitol, and several other alcohols. Their inhibitory effect is not associated with cytotoxicity. The hydroxyl radical scavengers do not inhibit PMA-dependent amino acid transport in T cells or PMA-induced superoxide production by monocytes. Thus, they do not inhibit the primary interaction of PMA with responding cells. Treatment of peripheral blood mononuclear cells with PMA increased cellular guanylate cyclase in most experiments, and dimethyl sulfoxide tended to inhibit this increase. In addition to inhibition of PMA-induced mitogenesis, hydroxyl radical scavengers markedly inhibited the activity of lymphocyte activating factor (interleukin 1). The differential inhibition of lymphocyte mitogenesis induced by different mitogens appears to be related to the differential macrophage requirements of the mitogens. The data suggest that hydroxyl radicals may be involved in mediating the triggering signal for lymphocyte activation. Some of the hydroxyl radical scavengers are inducers of cellular differentiation,. nd it is possible that their differentiating activity is related to their ability to scavenge free radicals.

Benzoates↗

Immunosuppressive properties of polar organic compounds that induce cellular differentiation in Friend erythroleukemia cells.

We studied the effect of several polar organic compounds, known to induce erythroid differentiation in Friend leukemia (FL) cells, on in vitro human lymphocyte responses and on skin graft survival in mice. The short chain fatty acids, butyric acid (BA), propionic acid (PA), valeric acid, and the polar organic solvents, dimethyl sulfoxide, dimethylformamide, and dimethylacetamide, all mediated significant inhibition of alloantigen-induced proliferation and generation of cytotoxic T lymphocytes (CTLs) in human primary and secondary mixed lymphocyte culture (MLC) reactions. Hexamethylenebisacetemide, another potent inducer of differentiation in FL cells, also mediated significant suppression. Inhibition of MLC with polar organic compounds was accomplished at concentrations known to induce differentiation in FL cells and that are not cytotoxic to peripheral blood mononuclear cells. In distinct contrast, agents that are structurally related to BA, but that do not induce differentiation in FL cells, such as caproic acid, beta-OHBA, gamma-amino BA, and isobutyric acid, did not exhibit immunosuppressive properties. Pokeweed mitogen-driven polyclonal B cell activation was also suppressed by agents that induce erythroid differentiation in FL cells. In addition to potent in vitro immunosuppressive properties, supplementation of drinking water with BA or PA resulted in prolongation of full-thickness skin grafts in DBA/2 (H-2d) to C57BL/6 (H-2b) donor-recipient combinations. Our findings indicate that polar organic compounds that induce differentiation in FL cells are potent immunosuppressive agents.

3-Hydroxybutyric Acid↗

Enhanced kidney graft survival with retroplacental source gamma-globulin. Results of a 5-year prospective study at a single center.

We examined the possibility that retroplacental source gamma-globulin (RPGG), with its content of anti-HLA antibodies, would improve cadaver kidney graft survival rates. In a 5-year controlled prospective study of 208 transplants, we found that the addition of RPGG to a standard immunosuppressive drug regimen (azathioprine and prednisone) resulted in significant improvement of the cumulative survival rate (CSR) of first and second grafts. At 2 years, the overall CSR of first grafts increased from a control value of 37% +/- 6 to 52% +/- 6 (P = 0.037). Among second graft recipients, the CSR increased from a value of 19% +/- 8 to 50% +/- 10 (P = 0.014). This improvement in graft survival was seen as early as 3 months after surgery and was sustained through 3 years without added recipient morbidity or mortality. When recipient populations were stratified for various factors, those groupings remonstrative of an intact or active humoral immune response capacity were found to have the highest survival rates in the study; 2-year graft CSRs of 70% +/- 6 and 65% +/- 10 were found in recipients with preformed antibody resulting from blood transfusions (P - 0.003) and cytomegalovirus infectivity (P = 0.0006), respectively. These findings indicate that the improved graft survival seen in this study may have resulted from a recipient's immunological response to challenge with RPGG.

ABO Blood-Group System↗

Abrogation of proliferation and generation of cytotoxic T cells in human mixed lymphocyte culture reactions by modification of the cell surface with mitogenic oxidizing agents.

Multiple lectins with specificity for cell surface glyco-proteins inhibit cellular and humoral immune responses and induce transplantation tolerance. Because cell surface glycoproteins play a significant role in various immune events involving cell to cell interactions and because the mixed lymphocyte culture (MLC) reaction is a prototype of immune phenomenon involving cell to cell interactions as well as an in vitro analogue of graft-destructive immune events, the effect of modification of the cell surface with oxidizing mitogens was investigated. Treatment of responder or stimulator cells with neuraminidase and galactose oxidase (NAGO) or with sodium periodate (IO-4) resulted in marked suppression of alloantigen-induced proliferation and in vitro generation of primary cytotoxic T cells (CTLs) in human MLCs. A prominent coupling of mitogen-induced proliferation to abrogation of MLC was consistently observed with modification of stimulator or responder cell surface with either NAGO or IO-4. The possibility that destruction of receptor sites and/or stimulatory units was responsible for the suppression of MLCs was excluded by restoring both proliferation and generation of primary CTLs by reduction of mitogen-oxidized cell surfaces with sodium borohydride. The ability of polyclonal activators to inhibit antigen-specific responses might be useful in abrogating unfavorable alloimmune responses.

Adult↗