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Biomedical subjects

R H Haschemeyer

Publications and source records attributed to R H Haschemeyer.

At least 19 recordsLinked to original sources
PubMed1993

Excellent outcome with a calcium channel blocker-supplemented immunosuppressive regimen in cadaveric renal transplantation. A potential strategy to avoid antibody induction protocols.

Many transplant centers routinely utilize monoclonal antibody or polyclonal antibody based induction protocols in recipients of cadaver renal allografts. Given the potential complications associated with antibody-based immunosuppression regimens (e.g., CMV disease), we tested the hypothesis that a combination of a calcium antagonist and a triple drug protocol (cyclosporine + prednisone + azathioprine) would be an effective substitute for antibody-based induction protocols in ensuring excellent patient and graft survival rates. Our postulate was tested in a prospective study of 52 consecutive recipients of cadaver renal allografts (44 first, 5 second, and 3 third grafts) utilizing nifedipine as the first line calcium antagonist. Nifedipine was selected over verapamil or diltiazem due to its lack of interference with the metabolism of CsA. Some of the significant outcomes of our prospective trial were (A) a cumulative patient survival rate of 98.1% for the 52 recipients at 18 months posttransplantation; (B) a cumulative allograft survival rate of 92.1% for the 52 consecutive cadaver renal allografts at 18 months; (C) a cumulative allograft survival rate of 100% at 18 months for the 24 of 52 renal allografts without delayed graft function following transplantation; and (D) a cumulative allograft survival rate of 86% at 18 months for the 28 of 52 renal allografts with delayed graft function. Of the 4 of 52 who lost their grafts, 2 grafts were removed following discontinuation of immunosuppressive therapy while the remaining 2 had primary nonfunction; and (E) the lack of a requirement for monoclonal or polyclonal antibodies for the treatment of acute rejection episodes in this patient population. These gratifying results compare very favorably with (A) recent reports of the effects of long-term diltiazem therapy and of verapamil used in conjunction with an induction protocol that included Minnesota antilymphocyte globulin in recipients of cadaver renal allografts, and (B) the clinical outcome in many institutions with OKT3/ATG/ALG induction protocols. Whereas the mechanisms involved in the excellent clinical outcome found with the calcium antagonist remain undefined, our results strongly argue for a prospective, randomized and controlled study in which a calcium antagonist-supplemented immunosuppressive regimen is compared with antibody-based induction protocols.

Adult↗
PubMed1989

Hypertension in kidney transplant recipients. Effect on long-term renal allograft survival.

To examine the effects of hypertension on renal graft function, we studied the clinical course of 144 kidney transplant recipients who had functioning grafts for three to 13 years. The patients were divided into three groups: normotensive (n = 32), controlled hypertensive (n = 49) and uncontrolled hypertensive group (n = 63). In addition to the difference in their blood pressure status, the three groups had significantly different levels of serum creatinine at entry to the study (mean +/- SE in mg/dL: 1.41 +/- 0.02, 8.89 +/- 0.02 and 2.30 +/- 0.03, respectively, P = .0002). Cumulative graft survival (CGS) at ten years for normotensive patients was 81%, whereas it was 58% for controlled hypertensive patients and 50% for uncontrolled hypertensive patients. The difference of CGS between normotensive and hypertensive patients was significant (P = .01), whereas the difference between the two hypertensive groups, controlled v. uncontrolled, was not. If serum creatinine levels at entry to the study were adjusted and the CGS of hypertensive patients was compared to normotensive patients with comparable levels of serum creatinine, the differences in CGS between the two groups were no longer significant. Regression analyses for potential prognostic factors revealed that serum creatinine levels were of more primary importance as a prognostic variable than blood pressure status. We conclude that hypertension is an important risk factor for renal graft survival, but control of hypertension alone does not appear to improve it. Graft survival appears to be influenced more by the severity of graft dysfunction at entry to the study irrespective of blood pressure control.

Adolescent↗
PubMed1988

In vivo studies of cysteine metabolism. Use of D-cysteinesulfinate, a novel cysteinesulfinate decarboxylase inhibitor, to probe taurine and pyruvate synthesis.

Although several pathways contribute to the catabolism of L-cysteine, the products formed are few--taurine + CO2 and pyruvate + ammonia + sulfate. L-Cysteinesulfinate is a key intermediate that is either decarboxylated to ultimately yield taurine or transaminated to yield pyruvate. There is strong evidence that pyruvate is also formed by several cysteinesulfinate-independent pathways collectively referred to as "cysteine desulfhydrase." The quantitative importance of cysteinesulfinate-independent pathways of taurine synthesis is less clear, but it has been suggested that taurine synthesis from the cysteamine released during phosphopantetheine and CoASH turnover accounts for the high taurine content of tissues with very low levels of cysteinesulfinate decarboxylase activity (e.g. skeletal muscle and heart). In the present studies, the metabolic flux through each of these pathways was quantitated in vivo by monitoring the formation of respiratory 14CO2 in mice administered L-[1-14C]- or L-[3-14C]cyst(e)ine. Mice given 0.05 mmol/kg of L-cystine or 0.5 or 2.5 mmol/kg of L-cysteine catabolize 35, 51, and 72% of the dose, respectively, in 6 h; the relative contribution of taurine synthesis to total catabolism decreases from 63 to 51 to 42% as the L-cyst(e)ine dose is increased. To evaluate the role of L-cysteinesulfinate in taurine synthesis, D-cysteinesulfinate was characterized and used as a metabolism-resistant, potent, and specific inhibitor of cysteinesulfinate decarboxylase. Studies with L-[1-14C]- and L-[3-14C]cysteine in the presence of inhibitor indicate that 85-93% of taurine synthesis occurs from L-cysteinesulfinate: the calculated contribution of the phosphopantetheine pathway is small and may approximate zero. L-Cysteinesulfinate transmamination accounts for 25% of pyruvate synthesis from L-[14C]cystine (0.05 mmol/kg) but only 11% of pyruvate synthesis from L-[14C]cysteine (2.5 mmol/kg). Cysteine desulfhydrase reactions account for most of the pyruvate synthesis.

Animals↗
PubMed1982

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↗
PubMed1981

General solution to the inverse problem of the differential equation of the ultracentrifuge.

Whenever experimental data can be simulated according to a model of the physical process, values of physical parameters in the model can be determined from experimental data by use of a nonlinear least-squares algorithm. We have used this principle to obtain a general procedure for evaluating molecular parameters of solutes redistributing in the ultracentrifuge that uses time-dependent concentration, concentration-difference, or concentration-gradient data. The method gives the parameter values that minimize the sum of the squared differences between experimental data and simulated data calculated from numerical solutions to the differential equation of the ultracentrifuge.

Kinetics↗
PubMed1981

Isolation and characterization of lamellar body material from rat lung homogenates by continuous linear sucrose gradients.

A technique is described for isolating lamellar body material from rat lung. Membranes with relative densities ranging between 1.050 and 1.074 g/ml were isolated by centrifugation of crude lung homogenates upward through continuous linear sucrose gradients at 40,000 rpm (199,000 g) for 3 hr. Their protein and lipid content was characteristic of that of lamellar bodies. They were free of contaminating microsomal and mitochondrial marker enzymes but contained enzyme activities associated with lysosomes and Golgi complex. Longer or repeated centrifugation resulted in a reduced yield and an apparent transformation of some of the material to lower densities. Electron microscopy revealed that most of the images represent disrupted rather than intact lamellar bodies. Other methods for preparation of lamellar bodies entail either sedimentation or pelleting at interfaces between sucrose solutions. Such preparations are often contaminated with endoplasmic reticulum membranes and have apparently lost the more fragile bodies. The present technique reveals the heterogeneous nature of lamellar body material and should be useful in a search for lamellar body precursors and in the investigation of the mechanisms by which surfactant is synthesized or assembled.

Animals↗
PubMed1980

Electron microscopy of negatively stained and unstained fibrinogen.

Electron microscope images of negatively stained fibrinogen are predominantly asymmetric rods 450 A in length and about 60 A in width. The molecules appear to have considerable flexibility, and mass distribution along the major axis is not uniquely distinguished despite apparent beading in some particles. Scanning transmission electron microscopy of unstained fibrinogen again demonstrates that a majority of molecules are rodlike. The results differ from those obtained by negative staining in that a substantial fraction of images are trinodular with striking resemblance to those obtained by C. E. Hall and H. S. Slayter [J. Biophys. Biochem. Cytol. (1959) 5, 11--16] using the mica replica technique. The above results were obtained on glow-discharged carbon substrate films by a simple low-concentration, long-attachment-time modification of standard deposition methods that is diffusion controlled and depends on concentration and time but is independent of pH, buffer, and other staining conditions. Evidence is presented that standard attachment procedures result in artifactual images. Any models of fibrinogen in solution consequently must encompass properties that permit its visualization as an asymmetetric rod by electron microscopy as first suggested by Hall and Slayter 20 years ago.

Animals↗
PubMed1978

Oxygen-mediated heterogeneity of apo-low-density lipoprotein.

Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower molecular weight polypeptide components, as characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. This protein alteration, which correlates temporally with increases in the formation of lipid oxidation products and in the fluorescence of the apoprotein, is markedly reduced when oxygen is excluded or when EDTA or the free-radical-scavenging antioxidants, butylated hydroxytoluene or propyl gallate, are added. The conversion thus appears to be due to a reaction between the protein moiety and auto-oxidizing lipid. The presence of the antibacterial agent sodium azide markedly accelerates the oxidation, suggesting that it should only be used with caution in lipid-containing solutions.

Apolipoproteins↗