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Biomedical subjects

R M Lewis

Publications and source records attributed to R M Lewis.

At least 19 recordsLinked to original sources
PubMed1992

Regional distribution of DARPP-32 (dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein of Mr = 32,000) mRNA in mouse brain.

DARPP-32 (dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein of Mr = 32,000) mRNA distribution was examined in adult mouse central nervous system by in situ hybridization. In general, DARPP-32 mRNA was found in regions of brain where cells express the dopamine D1 subtype receptor. Cells of the olfactory tubercle, caudate-putamen, and nucleus accumbens had the highest levels of DARPP-32 mRNA, as did choroid plexus and Purkinje cells. Relatively high levels were found in medial habenula and lateral piriform cortex. Moderate levels were seen in cerebral cortex layer VI, medial piriform cortex, lateral entorhinal cortex, tenia tecta, anterior olfactory nucleus, and lateral bed nucleus of the stria terminalis. Low levels were observed in hippocampus, cerebral cortex layers II and III, olfactory bulb, and the nucleus of the lateral olfactory tract. DARPP-32 mRNA levels in the amygdaloid nuclei varied greatly.

Animals↗
PubMed1992

Equine glomerulonephritis and renal failure associated with complexes of group-C streptococcal antigen and IgG antibody.

A 12-year-old thoroughbred gelding died from diffuse global glomerulonephritis, 3 months after a lower respiratory infection from which Streptococcus zooepidemicus was isolated. Immunopathological studies (immunofluorescence, immunodiffusion, immunoperoxidase testing and immunoblotting) indicated the presence of an immune reactant renal disease associated with IgG antibody and streptococcal antigens.

Animals↗
PubMed1992

Influence of race on crossmatch outcome and recipient eligibility for transplantation.

Data from the Office of the Inspector General and the United Network for Organ Sharing suggested that black end-stage renal disease patients had unequal access to organ transplantation, in that they waited twice as long as white ESRD patients for a renal transplant. We hypothesized that preTx histocompatibility factors were more influential in determining how quickly an ESRD patient was transplanted than had been realized by either the Office of the Inspector General or UNOS. To test this hypothesis we compared the crossmatch reactivity of 378 white and 227 black ESRD patients awaiting a primary renal Tx against 100 consecutive cadaveric donors (80 white, 10 black, and 10 Mexican-American). A positive XM frequency of 16% (179 positive XM/1121 total XM) was observed when white ESRD patients were crossmatched against white donors. A comparable frequency of 21% (39/186) (+) XM was observed when white ESRD patients were crossmatched against black donors. Similarly, black ESRD patients crossmatched against black donors showed a 17% (20/115) (+) XM frequency. In contrast, a significantly higher (+) XM frequency of 43% (283/655) was observed when black ESRD patients were crossmatched against white donors (P less than 0.001). When black ESRD patients with a (+) preTx blood transfusion history were crossmatched against white donors, a 55% (241/438) (+) XM frequency was observed. This (+) XM frequency was 3.2 times greater than when black ESRD patients were matched against black donors (P less than 0.001). However, when untransfused black ESRD patients were matched against white donors only a 19% (42/217) (+) XM frequency was observed. Finally, preoperatively transfused black ESRD patients displayed a higher PRA of 47 +/- 12% vs. 27 +/- 10%, P less than 0.01, and a longer median waiting time to transplant of 329 vs. 181 days, P less than 0.01, than comparable white patients. The data suggest that presentization of blacks, following preTx blood transfusions from nonblack donors, predisposes black ESRD patients to present as immunologically inappropriate recipients for predominantly white donor allografts and results in their spending a longer time on renal transplant waiting lists.

Black People↗
PubMed1992

Immunopathology of glomerulonephritis associated with chronic woodchuck hepatitis virus infection in woodchucks (Marmota monax).

Retrospective analysis of necropsy findings of 705 woodchucks was performed to determine the prevalence and morphology of immune-mediated glomerulonephritis, its relationship to woodchuck hepatitis virus (WHV) infection, and the presence of major WHV antigens. Twenty-six woodchucks had glomerular lesions. Renal tissue of the 26 animals was evaluated histologically and immunohistochemically for immune-mediated glomerulonephritis. Of these 26 animals, immune-mediated glomerulonephritis was diagnosed in six, all of which were chronic WHV carriers. Membranous glomerulonephritis was identified in three animals, two of which also had mesangial proliferation. Host immunoglobulin was present within the mesangium and along capillary loops in all three. Woodchuck hepatitis virus core antigen (WHcAg) was present along capillary loops of two of these animals, one membranous and one mixed, and in the mesangium of all three. Woodchuck hepatitis virus surface antigen (WHsAg) deposition was similar to WHcAg deposition but was only present along capillaries in those animals with mixed nephritis. The remaining three animals had mesangial proliferation. WHsAg and host immunoglobulin deposition were predominately mesangial; WHcAg was not detected. Transmission electron microscopy showed thickening of the capillary loop basement membranes and subepithelial electron-dense deposits in animal one, and deposits in the mesangium in animal six.

Animals↗
PubMed1991

AHG and DTE/AHG procedure identification of crossmatch-appropriate donor-recipient pairings that result in improved graft survival.

We compared our standard NIH (extended incubation) crossmatch (XM) with antihuman globulin (AHG) and flow cytometry crossmatches (FCXM) and correlated the results with primary cadaveric and retransplant graft survivals. In addition, we treated the XM sera with the reducing reagent dithioerythritol (DTE) to discriminate IgM from IgG immunoglobulin reactivity. For the 166 CsA-Pred-treated primary cadaveric renal allograft recipients the 1-year graft survival rate following an NIH-NEG XM was 81%. NIH-XM-NEG recipients who were also AHG-XM-NEG displayed an 82% 1-year graft survival as well. In contrast, NIH-NEG, but AHG-POS XM primary CAD recipients displayed a significantly reduced graft survival rate of 67%. Treatment of AHG-POS XM sera with DTE-delineated DTE/AHG-NEG and POS crossmatches associated with significantly different graft survivals of 83% and 0%, respectively, for these primary recipients. Flow cytometry XM results did not improve on the AHG-NEG or DTE/AHG-NEG XM primary graft survivals. These results were seen whether testing pre-Tx or historical (Hx) sera. For Re-Tx recipients an AHG-NEG XM resulted in significantly improved graft survival compared with the NIH-XM-NEG results. The overall 1-year graft survival rate for the 70 Re-Tx recipients studied was 64% (following a NEG pre-Tx NIH-XM). Re-Tx recipients with an AHG-NEG XM displayed an improved graft survival compared with NIH-XM-NEG recipients (77% vs. 64%, P less than 0.05) and with AHG-POS recipients (77% vs. 36%, P less than 0.01). However, treatment of Re-Tx, AHG-POS sera with DTE resulted in comparably poor graft survival rates of 31% and 50% for DTE/AHG-NEG and POS crossmatches, respectively. A FCXM did not improve on the results of Re-Tx graft survival following an AHG-NEG XM. These results were obtained whether testing pre-Tx or Hx sera. HLA matching, PRA, and the time the first Tx was lost did not influence the Re-Tx graft survival outcome following an AHG-NEG XM. Therefore, successful primary cadaveric renal allograft survival can be accomplished following either an AHG-NEG XM or an AHG-DTE-NEG XM. Re-Tx graft survival is significantly improved following an AHG-NEG XM. Re-Tx recipients with an AHG-POS XM who are either DTE/AHG-POS or -NEG display reduced graft survivals compared with AHG-NEG Re-Tx recipients.

Cyclosporins↗
PubMed1991

Possible contribution of pretransplant immune responder status to renal allograft survival differences of black versus white recipients.

Black end-stage renal disease patients may present as an immunologically higher-risk group for renal allograft transplantation than white ESRD patients. To test this hypothesis, we correlated graft survivals in 124 black and 241 white cyclosporine-prednisone-treated primary cadaveric renal allograft recipients with pre-Tx nonspecific immune responder status (strong vs. weak immune responders), donor-recipient-specific MLC responsiveness, HLA match, and blood transfusion (BT) history. One-, 2- and 3-year patient survival rates of 95%, 94%, and 94% were identical for both groups. However, the 1-, 2-, 3-year graft survival rates for white recipients of 82%, 79%, and 75% were significantly higher than the 70%, 62%, and 55% rates for black recipients (P less than 0.01 for each, respectively). Pre-Tx nonspecific immune response values for blacks were significantly (P less than 0.01) higher than for whites (38% vs. 28% for active T cell; 1.8 vs. 1.3 for TH:TS ratio; 28,581 c.p.m. vs. 14,870 c.p.m. for spontaneous blastogenesis; and a stimulation index (SI) of 34 vs. 20 for panel mixed lymphocyte culture). Additionally, the specific recipient-donor MLC (SI) for black recipients was significantly greater than the specific recipient-donor MLC for white recipients (MLC SI of 40 vs. 18, P less than 0.01). Blacks present as pre-Tx strong immune responders with a greater frequency than whites (90% vs. 66%, P less than 0.01). Moreover, black strong responders experience a poorer 1-year graft survival than white strong responders (67% vs. 80%, P less than 0.01). Even though the pre-Tx BT histories of white and black ESRD patients studied herein were comparable, the immunoregulatory effect of pre-Tx BT was different in white vs. black patients. A significant reduction in TH:TS ratio was observed when comparing 0 vs. 1-4 pre-Tx white patient BT groups, whereas significant changes in TH:TS ratios were not observed until after comparing 0 vs. greater than or equal to 5 pre-Tx black patient BT groups. HLA matching and pre-Tx BT had no impact on improving the graft survivals of these CsA-Pred-treated white or black recipients. These data, therefore, support the hypothesis that black recipients present as an immunologically higher-risk group than white recipients.

Black People↗
PubMed1991

Chronic rejection in primary renal allograft recipients under cyclosporine-prednisone immunosuppressive therapy.

Although the introduction of cyclosporine-prednisone immunosuppression has improved early renal graft survival, chronic rejection remains a major cause of longterm graft dysfunction. This study retrospectively examined 69 cases of chronic rejection among 643 primary renal allograft recipients treated with cyclosporine-prednisone immunosuppression from July 1981 to October 1989. Chronic rejection was defined as a rejection episode diagnosed greater than 90 days posttransplantation with characteristics of progressive nonacute renal function deterioration, confirmed, in most cases, by renal biopsy. This group was compared with an equal-sized matched cohort. Among cadaveric recipients, 61 of 456 patients (13.4%) displayed chronic rejection, whereas among living-related recipients, 8 of 187 patients (4.3%) developed chronic rejection. The average time from the date of transplantation to diagnosis of chronic rejection was 15 +/- 14 months. One- and three-year graft survivals following diagnosis of chronic rejection were 51% (30/59) and 25% (13/51), respectively, compared with the cohort one- and three-year graft survivals of 98% (58/59) and 86% (32/37) at similar periods posttransplantation. HLA mismatch, PRA status, blood transfusion history, lipid levels, cyclosporine trough levels, incidence of prior acute rejection, and initial graft dysfunction were not significantly different between the chronic rejection group and the matched cohort. Hypertension and proteinuria were significantly associated with chronic rejection (P less than 0.001). Of 58 biopsies performed, findings solely consistent with chronic rejection were observed in 9 cases (15%) and "acute upon chronic" rejection in 49 cases (83%). Treatment of acute concomitants improved the renal function in 43% (27/63) by the time of hospital discharge. Nonetheless, at 12 months the incidence of improved renal function eroded to 22% (13/59), suggesting that the benefit was relatively short-lived. Although the overall incidence of chronic rejection in this group of cyclosporine-prednisone-treated patients was lower than previous azathioprine-prednisone cohorts, the clinical presentation and progression of chronic rejection was similar. Additionally, the incidence of chronic rejection within this series was lower among living-related recipients versus cadaveric recipients of donor organs.

Blood Transfusion↗
PubMed1991

Mechanisms of disease in hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome (HFRS) is a dramatic illness characterized by fever, and variable degrees of circulatory failure, hemorrhage, and renal insufficiency. Hantaviruses are the cause of this syndrome. In its severe form, it is associated with significant mortality. Vascular dysfunction is the key physiologic derangement in this disorder. There is a growing body of evidence that suggests that immune mechanisms account for this derangement.

Animals↗
PubMed1991

Preemptive transplantation--an analysis of benefits and hazards in 85 cases.

The benefit of transplantation without prior dialysis might be contravened by the failure to develop possible immunologic disabilities associated with chronic uremia and dialysis. This study compares graft and patient outcome, cyclosporine toxicity, pharmacokinetics, rejection episodes, nutritional status, and social and vocational rehabilitation between a preemptive group of 85 patients transplanted without prior dialysis and a cohort of 84 demographically, temporally, and disease-matched recipients of renal transplants after a minimum of 6 months' chronic dialysis therapy. The groups were matched for donor type, gender, and age, as well as immunologic risk factors of HLA-mismatch and percent panel-reactive antibody. All patients received CsA and prednisone immunosuppression. There were only two differences between the cohorts. The preemptive group included more diabetic patients: 32 versus 15 (P less than 0.01). The control cohort included more recipients who had received any pretransplant transfusion: 55 versus 28 (P less than 0.001). Both of these factors (if having any impact) would be expected to reduce graft survival in the preemptive group. All patients in the study had a minimum follow-up of 1 year and over half of the recipients are beyond 40 months. The preemptive patients showed survival rates of 94, 93, and 91 percent at 1, 2, and 5 years. These rates were not significantly different from those of the control group, namely 96, 96, and 93 percent, respectively. The actuarial graft survival rates in the preemptive group of 83, 81, 76, 73, and 73 percent at 1, 2, 3, 4, and 5 years were not statistically different from the control group rates, namely 90, 81, 80, 77, and 76 percent. Preoperative blood transfusion or percent positive panel-reactive antibodies had no effect on postoperative outcome in either group. The incidence of CsA nephrotoxicity was 9.4 percent in the preemptive group, which was not statistically different from the 17.9 percent in the control group. The incidence of rejection episodes in the absence of patient noncompliance was comparable between the groups. Seven of the irreversible rejection episodes in the preemptive group were due to noncompliance, compared with none in the control group (P less than 0.001). Preemptive recipients were also more likely than control group patients to be employed fulltime both before transplantation (36 vs. 22, P less than 0.05) as well as after transplantation (38 vs. 20, P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Biological Availability↗
PubMed1991

Antigen expression in cultured oral keratinocytes from dogs.

Oral keratinocytes from dogs were cultured on either collagen gels or artificial matrices at the air-liquid interface, and the expression of keratinocyte antigens and basement membrane components was determined, using various monoclonal and polyclonal antibodies. Keratinocytes grown on collagen gels expressed pemphigus vulgaris, pemphigus foliaceous, and bullous pemphigoid antigens. Diffuse, suprabasal, and superficial keratinocyte membrane differentiation antigens identified by various monoclonal antibodies also were expressed in a pattern identical to that observed in the native tissue. Laminin and type-IV collagen were deposited at the keratinocyte-collagen interface in a patchy distribution. When synthetic matrices were used, the oral keratinocytes differentiated, but to a lesser extent than cells grown on collagen gels. Antigen expression for cells grown on synthetic matrices was similar to that for cells on collagen, except for failure of the keratinocytes on synthetic membranes to express superficial cell antigens and pemphigus foliaceous antigens.

Animals↗
PubMed1990

A computer program to aid in the preparation of reagent solutions.

A computer program for calculating required amounts of reagents for making up chemical solutions is presented. The program also maintains a custom list of available reagents. Use of the interactive mode guides the novice in entering the required information. The program is written in the BASIC programming language for IBM compatible microcomputers. It is available without cost from the author.

Indicators and Reagents↗
PubMed1990

The impact of steady-state cyclosporine concentrations on renal allograft outcome.

It has been reported that initial cyclosporine levels over 400 ng/ml posttransplantation result in an increased incidence of delayed graft function (DGF). Several studies have shown early graft function to be a major determinant for long-term graft survival. Continuous intravenous infusion (CIVI) has been employed to induce immunosuppression establishing therapeutic drug levels while minimizing toxicity in renal allograft recipients. This study examines the impact of the achieved serum CsA steady-state concentration (Css) levels upon transplant outcome in 228 patients given CsA by CIVI. In spite of administration of a specific drug dose, interindividual variation in elimination rates yields a broad range of Css levels. Six groups were stratified by CsA Css levels: group A 0-75 ng/ml, group B 76-100 ng/ml, group C 101-150 ng/ml, group D 151-200 ng/ml, group E 201-250 ng/ml, and group F greater than 250 ng/ml. Group A showed a significantly lower age and greater incidence of rejection at 0-10 days. Group F had significantly higher incidences of nephrotoxicity, hepatotoxicity, and delayed graft function. The findings suggest that the antirejection Css threshold for CsA may be at least 75 ng/ml, and the toxicity threshold above 250 ng/ml. Controversy exists about whether CsA influences the incidence of DGF, therefore risk factors for DGF were examined among the groups stratified by CsA Css levels. While cold ischemia time for all 228 patients as a group was highly correlated with DGF (P less than 0.001), neither cold ischemia time nor donor age was significantly different among the groups. There does appear to be a synergistic effect between CsA Css and CIT, since the incidence of DGF was significantly higher when the cold ischemia time was 21-24 hr and CsA Css greater than 200 ng/ml. Long-term graft function did not appear to be affected by early CsA Css levels. The Css of 100-250 ng/ml appears to achieve a satisfactory outcome with a 19.5% incidence of rejection within 10 days, 29.7% DGF, and 5.1% nephrotoxicity. Only 118/228 patients (52%) in this study achieved that range despite a fixed low CIVI of CsA. Thus potential renal allograft recipients may benefit from a pretransplant pharmacokinetic study to predict the proper CIVI dose.

Adult↗
PubMed1990

Proteinuria in cyclosporine-treated renal transplant recipients.

Of 704 renal transplant recipients receiving long-term cyclosporine immunosuppression, 71 patients experienced proteinuria greater than 1 g/24 hr beyond the first month posttransplant. Eight patients displayed transient proteinuria, defined as lasting less than 3 months. In most cases this condition was attributed to biopsy-proved acute rejection. The transient proteinuria cohort experienced good graft outcome--namely, 87.5% one-year and 52.5% five-year actuarial graft survivals, which was similar to that observed in patients without proteinuria. In contrast, 52.4% of the 63 patients with nontransient proteinuria experienced graft loss within a median time of 6.1 months. The one- and five-year actuarial graft survivals in patients with nontransient proteinuria were 75.3% and 37.5%, respectively. Among the 63 patients with nontransient proteinuria, histopathologic diagnosis included chronic rejection in 19, transplant glomerulopathy in 14, acute rejection in 9, glomerulonephritis (GN) in 7 including 2 cases of membranous GN, and nonspecific interstitial fibrosis in 10 cases. Despite the overall poor prognosis for graft survival among the entire cohort of patients with nontransient proteinuria, the seven with allograft GN maintained prolonged graft function. They showed an 83.3% five-year actuarial graft survival versus 31.2% in patients with other causes of proteinuria (P = 0.043). These results suggest that posttransplant proteinuria in CsA-treated renal transplant recipients arises primarily as a consequence of allograft rejection and portends a poor graft outcome.

Cyclosporins↗
PubMed1990

Improved graft survival for flow cytometry and antihuman globulin crossmatch-negative retransplant recipients.

We compared our standard NIH (extended incubation) crossmatch (XM) with antihuman globulin (AHG) and flow cytometry XMs and correlated the results with rejection episodes and graft survivals. For 89 CsA-Pred, primary renal allograft recipients, AHG and/or FCXM results did not improve on the NIH-XM-negative (NEG) graft survival results, whether testing pretransplant or historical (Hx) sera. Similarly, there was no association of a positive (POS) AHG or FCXM with increased rejection episodes in these primary recipients. However, for retransplant (Re-Tx) recipients a neg AHG or FCXM did discriminate fewer rejections and an improved graft survival compared with the NIH-XM-neg. results. The overall one-year graft survival for the 47 Re-Tx recipients studied herein was 66% (based on a neg pre-Tx NIH-XM). Pre-Tx AHG-NEG, Re-Tx recipients displayed an improved graft survival compared with NIH-XM NEG recipients (77% vs. 66%, P less than 0.05) and with AHG-POS recipients (77% vs. 47%, P less than 0.05). Similarly, pre-Tx, FCXM-NEG, Re-Tx recipients displayed improved graft survivals compared with NIH-XM-NEG recipients (83% vs. 66%, P less than 0.05) and FCXM-POS recipients (83% vs. 48%, P less than 0.05). Re-Tx recipients displaying a POS AHG and/or FCXM experienced a significantly greater number of rejections than NEG-XM recipients (P less than 0.05, respectively). The AHG and FCXM results correlated with rejections and graft survivals whether testing pre-Tx or Hx high-PRA sera. Re-Tx recipients who were AHG-XM-NEG but FCXM-POS, experienced more rejection episodes than recipients who displayed a negative XM reactivity for both AHG and FCXM (P less than 0.02), but with no resulting differences in graft survival. HLA matching, pre-Tx blood transfusions and PRA did not impact on these crossmatch and graft survival results. Use of AHG and/or FCXMs for Re-Tx, but not primary, recipients should help to improve graft survival for these high-risk recipients.

Antibodies, Anti-Idiotypic↗