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Biomedical subjects

R D Guttmann

Publications and source records attributed to R D Guttmann.

At least 91 records · Page 5Linked to original sources
PubMed1987

Low-output left ventricular failure in end-stage renal disease.

To determine the factors associated with low-output left ventricular failure (LVF) in endstage renal disease (ESRD), we performed echocardiography and gated cardiac scan on 217 nondiabetic dialysis and transplant patients. The prevalence of low-output LVF (ejection fraction less than 55% and left ventricular end diastolic diameter greater than or equal to 5.5 cm) in dialysis patients was 18% and in transplant patients 2%. The 26 patients with LVF were compared to 52 controls without LVF, matched by age, sex and year of starting treatment for ESRD, but not for current ESRD therapy. Mean age was 55 +/- (SEM) 14 years; 73% of the patients in both groups were males. Duration of treatment for ESRD was 5.6 +/- 4.3 years in patients, compared to 5.1 +/- 4.1 years in controls. Significant differences between LVF patients and controls included current treatment (73% of cases were on hemodialysis and 8% were transplanted, compared to 48 and 42%; chi 2 = 9.9, p less than 0.01), high serum creatinine, smoking and high serum alkaline phosphatase. There were no differences for current blood pressure, proportion on treatment for hypertension, left ventricular wall thickness, symptomatic ischemic heart disease, proportion with functioning vascular access, degree of weight gain between dialyses, hemoglobin level or high transfusion requirement. Multiple logistic regression demonstrated the most significant and independent variables associated with LVF were high alkaline phosphatase (suggestive of hyperparathyroidism), smoking and high serum creatinine levels (reflecting degree of uremia). Dialysis patients with LVF (n = 23) were compared to dialysis patients who had normal echocardiograms (n = 29).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output, Low↗
PubMed1987

Major histocompatibility complex restriction of T-lymphocyte responses to islet cell antigens in IDDM rats.

BBUF rats, derived from BB rats, spontaneously develop a form of insulin-dependent diabetes mellitus (IDDM) associated with infiltration of the islets of Langerhans by lymphocytes (insulitis). BBUF rats bear the RT1u major histocompatibility complex (MHC) haplotype that we have shown to be necessary for the expression of this form of IDDM. A T-lymphocyte line obtained from the pancreas of a diabetic rat (UPCC.5) and three T-lymphocyte hybridomas derived by fusing T-lymphocytes of BBUF rats (MUS1.2, MUS1.13, and MUP3.21) respond to islet cell antigens in an MHC-restricted way. UPCC.5 responds to a combination of islet cell antigens (ICAg) and antigen-presenting cells by proliferation, whereas the T-hybridoma responses are detected on the basis of IL-2 production in a similar assay. This study reveals that an antiserum against mu-haplotype MHC antigens or a monoclonal antibody against the product of the D class II subregion of the rat MHC could inhibit ICAg recognition. A monoclonal antibody against the product of the B class II MHC subregion of the rat was not inhibitory. These results suggest that RT1.D antigens (analogous to human DR and mouse I-E) restrict islet cell recognition in this rat model of spontaneous IDDM.

Animals↗
PubMed1986

Dendritic cell-lymphoid cell aggregation and major histocompatibility antigen expression during rat cardiac allograft rejection.

To determine the pattern of cellular expression of donor MHC class I and class II antigens during the course of rat cardiac allograft rejection, ACI cardiac allografts transplanted to BN recipients were examined from day 2 to day 6 using immunohistologic and immunoelectron microscopic methods. We used both monomorphic and donor-specific mouse anti-rat MHC class I and class II mAbs in this study. In normal ACI hearts, MHC class I reactivity was confined to the vascular endothelium and to interstitial cells. Ongoing rejection was characterized by an increased donor MHC class I staining intensity of microvascular endothelium and induction of donor class I surface reactivity on cardiac myofibers. Donor MHC class II reactivity was exclusively confined to interstitial dendritic cells (IDC) in both normal ACI hearts and in rejecting allografts, although rejection was associated with marked fluctuations in class II IDC frequency. An early numerical depression in class II IDC present in both allografts and syngeneic heart grafts was attributed to a direct effect of the transplantation procedure. By days 3-4, allografts showed an absolute overall increase in donor class II IDC frequency, which was associated with the presence of multiple localized high-density IDC-lymphocyte aggregates. The lymphocytes present in the focal areas were predominantly of the class II-reactive Th cell subpopulation. These aggregates may thus represent the in vivo homologue of dendritic cell-lymphocyte clustering, which has been shown to be required for primary class II allosensitization in the rat and mouse in vitro. During the late phase of rejection, there was a marked numerical fall in donor class II IDC, which correlated with extensive overall graft destruction. This study has shown that acute rat cardiac allograft rejection can occur in the absence of donor MHC class II expression by allograft vascular endothelium and cardiac myofibers. The IDC, which are believed to represent the principal class II alloantigen presenting cells in the rat heart, remain the sole class II-expressing cellular constituents of the graft throughout the course of rejection.

Animals↗
PubMed1986

Reduction of azathioprine in renal transplant patients with chronic hepatitis.

To determine whether prolonged reduction of azathioprine in renal transplant recipients with chronic hepatitis affected the progression of liver disease without an adverse effect on graft survival we studied all transplant patients with a raised serum glutamic oxaloacetic transaminase level greater than normal for more than 1 year who had azathioprine reduced below 100 mg/day for longer than 1 year. Six HBsAg-positive patients had chronic hepatitis for 67 +/- 7 (SE) months before reduction of azathioprine and were followed for a further 49 +/- 14 months. None of the six patients remitted, 3 patients died from liver disease, and none returned to dialysis. In the group of 12 patients who did not have azathioprine reduced, none remitted, 4 died from liver disease, and none returned to dialysis during a follow-up of 115 +/- 9 months. Seven HBsAG-negative patients had chronic hepatitis for 32 +/- 11 months before reduction of azathioprine and were followed for a further 46 +/- 8 months. One of the seven remitted, none died from liver disease and one returned to dialysis. In the group of 15 patients who did not have azathioprine reduced 5 patients remitted, none died from liver disease, and none returned to dialysis. We conclude that prolonged reduction of azathioprine does not slow the progression of liver disease in renal transplant recipients with HBsAg-positive or HBsAg-negative chronic hepatitis, nor does it predispose to graft failure. However reduction of immunosuppression early in the course of hepatitis B disease may be necessary to prevent adverse long-term sequelae.

Adult↗
PubMed1986

Natural killer cell subsets in long-term renal allograft recipients. A phenotypic and functional study.

Natural Killer cell subsets were studied in 39 long-term renal allotransplant recipients receiving conventional immunosuppression and 26 normal controls. Two-color flow cytometry analysis was used to determine coexpression of 2 surface antigens known to allow a phenotypic and functional discrimination of NK cells--Leu-7 a marker of large granular lymphocytes, and Leu-11c directed against the FcgammaR. In 11 patients and controls, these NK cell subsets were compared with actual NK activity assessed by killing of K562 target cells. Our data clearly show that, in long-term kidney recipients, the absolute number of NK cells (Leu-11c+) is significantly decreased compared with that of the control group. Furthermore, the most cytotoxic NK cell subset (Leu-7-/Leu-11c+ phenotype) is markedly diminished in the transplant population, whereas the less cytotoxic subset (Leu-7+/Leu-11c+) is unchanged. Finally, actual NK cell activity closely correlates with both relative and absolute numbers of these 2 NK cell subsets. These data provide convincing evidence that NK activity is impaired in long-term kidney recipients because of a diminished number of NK effector cells.

Adult↗
PubMed1986

Immunological and genetic studies in primary generalized corticoreticular epilepsy.

Serum immunoglobulin and HLA investigations were carried out in 21 probands with primary generalized corticoreticular epilepsy (PGCE) and in 26 of their first degree relatives. The mean serum levels of IgG, IgA and IgM in the epileptic probands were not significantly different from controls. In the relatives, however, the mean serum levels of IgA and IgM were significantly decreased as compared to controls. With respect to HLA investigations, the frequencies of 63 HLA specificities determined and of 5 most commonly occurring haplotypes were not significantly different in the experimental groups as compared to controls. These findings are in agreement with a previous HLA investigation of PGCE but are in contrast with a similar study of partial epilepsy. It is suggested that the contrasting HLA findings between PGCE and partial epilepsy may reflect underlying differences in the etiology of these disorders.

Adolescent↗
PubMed1986

Methacholine-induced airway reactivity of inbred rats.

Dose-response curves to inhaled aerosolized methacholine chloride (MCh) were obtained in anesthetized spontaneously breathing rats. Thirty rats (10/strain), randomly selected from highly inbred ACI, Lewis (L), and Brown Norway (BN) strains and 40 rats (20/strain) from similarly inbred Wistar-Furth (WF) and Buffalo (Buf) strains were studied. Airway responses were quantitated from changes in pulmonary resistance (RL) and airway reactivity was calculated as the dose of MCh required to increase RL to 150% (ED150RL) and 200% (ED200RL) of base line. There were no statistically significant differences in ED150RL and ED200RL among the five rat strains. Large interindividual variability was present as evidenced by 128-fold differences in ED150RL and ED200RL between the least and most sensitive animal of the same strain. In contrast, seven animals studied repeatedly on different days had values of ED150RL that differed by an average of only 2.9-fold (range 1.6-5.3). Thirteen rats that were studied on two occasions separated by an interval of 3 mo showed no systematic changes in airway reactivity. We conclude that airway reactivity to inhaled methacholine in anesthetized nose-breathing rats is not strain related, and despite animals of a given strain being genetically identical, the variability in airway reactivity within strains suggests that environmental rather than genetic factors are the major determinants of that reactivity.

Airway Resistance↗