Ulrich Rudofsky - Academia.edu (original) (raw)

Papers by Ulrich Rudofsky

: These studies were designed to assess the in vivo effects of acute and chronic exposure to Pb o... more : These studies were designed to assess the in vivo effects of acute and chronic exposure to Pb on in vivo and in vitro humoral immune (HI) responses and cell-mediated immune (CMI) responses. In vivo and in vitro T-cell activities were evaluated by resistance to Listeria monocytogenes and mixed lymphocyte culture (MLC) reactivity, respectively; B-cell activities were quantitated by determination of plaque-forming cells (PFC); and macrophage activity was assessed by quantitating the degree of antigen (51 Cr-SRBC), binding, engulfment, and digestion. After acute and chronic in vivo Pb exposure, in vivo HI was consistently unaltered or in one case (0.5 mg Pb, Day 0), enhanced, and in vitro assessed HI usually was enhanced with the one exception of chronic exposure to 10 mM Pb which was suppressive. In vitro CMI (a direct correlate of T-cell reactivity) was inhibited by Pb to variable, but slight degrees (24-39% inhibition). Preliminary data also suggest that Pb does not inhibit macroph...

Striated muscle myosins are encoded by a large gene family in all mammals, including human. These... more Striated muscle myosins are encoded by a large gene family in all mammals, including human. These isoforms define several of the key characteristics of the different striated muscle fiber types including maximum shortening velocity. We have previously used recombinant isoforms of the motor domains of eight different human myosin isoforms to define the actin.myosin cross-bridge cycle in solution. Here, we use a recently developed modeling approach MUSICO to explore how well the experimentally defined cross-bridge cycles for each isoform in solution can predict the characteristics of muscle fiber contraction including duty ratio, shortening velocity, ATP economy and the load dependence of these parameters. The work shows that the parameters of the cross-bridge cycle predict many of the major characteristics of each muscle fiber type and raises the question of what sequence changes are responsible for these characteristics.

Journal of immunology (Baltimore, Md. : 1950), 2015

Clinical Immunology and Immunopathology, 1980

Clinical Immunology and Immunopathology, 1990

Clinical Immunology and Immunopathology, 1987

HLA A and B antigens were determined in a study of 125 patients with lung cancer. Differences bet... more HLA A and B antigens were determined in a study of 125 patients with lung cancer. Differences between antigen frequencies in cancer and control populations were determined by chi 2 analysis or Fisher&amp;#39;s exact test. Survival data were analyzed using the Cox model for censored data. Cancer patients had an increased frequency of the antigen Aw33 (relative risk = 10.5, P less than 0.016). The Cox model (D. R. Cox, J. R. Stat. Soc. B, 34, 187, 1972) indicated that four covariates had a significant effect on mean survival time independently: the presence of A3 (P less than 0.005) and of Aw33 (P less than 0.05) increased mean survival time of the cancer population; patients with anaplastic carcinoma and stage three of any histological type of cancer had a decreased mean survival time. The determination of HLA phenotypes, cancer type, and the stage of the disease can provide the expected mean survival time of any particular patient. This could be of importance for evaluating prognosis. The effect of Aw33 and A3 on survival time may be related to HLA closely linked genes, possibly coding for resistance to the disease.

Journal of immunology (Baltimore, Md. : 1950), 1974

Abstract C4d guinea pigs develop experimental autoimmune renal tubulointerstitial disease indisti... more Abstract C4d guinea pigs develop experimental autoimmune renal tubulointerstitial disease indistinguishable from the disease observed in guinea pigs with circulating C4. These data demonstrate that an antibody-mediated autoimmune renal disease can occur in the ...

Laboratory animal science, 1982

By 2 to 3 months of age, many fawn-hooded rats, particularly males, had indirect systolic blood p... more By 2 to 3 months of age, many fawn-hooded rats, particularly males, had indirect systolic blood pressures of greater than 145 mm Hg; by 4 months of age, most males had persistent elevations in blood pressure (greater than 160 mm Hg). Female fawn-hooded rats developed hypertension at 4-5 months of age. Concurrently, fawn-hooded rats develop a severe form of focal glomerular sclerosis. The causes of the hypertension and focal glomerular sclerosis are yet not known, nor has a relation been found between these abnormalities.

Clinical and experimental immunology, 1981

We have tested the effect of deposition of non-pathogenic amounts of induced anti-glomerular base... more We have tested the effect of deposition of non-pathogenic amounts of induced anti-glomerular basement membrane (GBM) autoantibodies on the development of the spontaneous lupus nephritis of female (NZB x NZW) F1 (B x W) mice. Female and male B x W mice were immunized with rabbit renal tubular basement membrane in adjuvant at 2 months of age and their kidneys were examined 35 to 66 days later; control B x W mice were injected with adjuvant only or remained untreated. By immunofluorescent and histopathological criteria, only the 4-month-old female B x W mice with anti-GBM autoantibody deposits had an accelerated onset of lupus nephritis resembling the findings not seen until 6 to 8 months of age in unmanipulated mice. Thus potentially pathogenic amounts of immune complexes are present in young female B x W mice, but these do not deposit in glomeruli until much later in life. Evidently, the anti-GBM autoantibodies modified the glomerular milieu sufficiently to facilitate accelerated imm...

Journal of immunology (Baltimore, Md. : 1950), 1971

Guinea pigs injected with heterologous renal basement membranes (RBM) and complete Freund9s adjuv... more Guinea pigs injected with heterologous renal basement membranes (RBM) and complete Freund9s adjuvant (FA) develop a new renal cortical tubular disease and form antibodies that react with renal tubular basement membrane (TBM) (1–3). We now document the characteristics and immunopathology of this renal tubular disease and the presence of anti-TBM antibodies in the serum and along the cortical TBM. Finally, we demonstrate a positive correlation between the incidence of severe tubular disease and large amounts of anti-cortical TBM autoantibodies. Materials and Methods. RBM, rich in TBM, were prepared from frozen New Zealand White rabbit kidneys 3 by a modification of Krakower and Greenspon9s method (4). Briefly, rabbit cortex was buttered through a 100-mesh metal screen. The screenings were washed by centrifugation in saline to remove free cells. By repeated shaking and washing of the residue, glomeruli settled faster than tubules. Supernatants rich in tubules were examined microscopically (4, 5).

Clinical and experimental immunology, 1977

Antisera to human C4 can discriminate circulating Ss protein (C4) levels in mice. Since there has... more Antisera to human C4 can discriminate circulating Ss protein (C4) levels in mice. Since there has been no information on early complement components (C1, C4, C2) in the renal lesions of B/W mice, we applied the indirect immunofluorescence technique to post-mortem sections of kidney from B/W female mice with advanced renal disease. C4 was present in fifteen of the sixteen specimens, usually in a distribution similar to that of IgG or C3. Specificity was demonstrated by differential absorptions with high-Ss serum from C57BL/6 male mice and low-Ss serum from C3H/HeJ female mice. High-Ss-absorbed antiserum did not stain, while low-Ss-absorbed antibody retained much of its activity. This finding parallels the demonstration of early complement components in lesions of clinical lupus nephritis, and is consistent with classic complement pathway activation in B/W disease.

Journal of immunology (Baltimore, Md. : 1950), 1976

Bone marrow transplants from normal Albany strain guinea pigs established a functional classical ... more Bone marrow transplants from normal Albany strain guinea pigs established a functional classical pathway of complement (C) in C4-deficient (C4D) guinea pigs. Seventeen days after transplant the Albany leads to C4D chimeras had detectable C4 and total hemolytic C activities. Maximum C4 levels (2 to 8% of normal were reachered by day 73 and restored total C to 40% of normal. Classical pathway function persisted for about 150 days and, thereafter, declined to undetectable levels by day 385. In contrast, Albany guinea pigs transplanted with C4D marrow maintained normal C4 levels throughout the experiment, suggesting that the C4-producing cells are radioresistant and long-lived. Unlike unmanipulated C4D animals, Albany leads to C4D chimeras were unable to produce antibodies to guinea pig C4 when immunized with normal guinea pig serum. These experiments suggest that bone marrow cell progeny produce C4 in vivo.

The American journal of pathology, 1978

Renal tubulointerstitial lesions (RTL) were observed with high frequency in CBA/J mice more than ... more Renal tubulointerstitial lesions (RTL) were observed with high frequency in CBA/J mice more than 2 months old. RTL were characterized by interstitial infiltrates of lymphocytes and macrophages in the corticomedullary zone. Multinucleated structures sometimes resembling giant cells were present, and there was destruction of tubules and tubular basement membranes in areas of infiltration. Glomeruli appeared normal. RTL were first seen in 12 to 22 CBA/J mice 2.5 to 3 months old. By the age of 7 to 9 months, 35 to 45 mice were affected, and all 24 mice 12 months old or older had RTL. CBA/J mice had these unique renal lesions whether they were purchased and examined immediately, were obtained as weanlings andreared in our quarters or those of another institution, or were fourth generation descendants of purchased breeders. The propensity to develop RTL has been present in this strain for at least 2 years. RTL were not observed in C57BL/6J mice housed for 14 months with affected animals o...

Clinical Immunology and Immunopathology, 1975

Central and Peripheral Mechanisms of Cardiovascular Regulation, 1986

Essential hypertension in its established phase is characterized by a raised total peripheral res... more Essential hypertension in its established phase is characterized by a raised total peripheral resistance which, in most cases, is accompanied by a normal cardiac output (Frohlich, Tarazi and Dustan, 1969). The disease in man has the property of multiplicity (Paul, 1976) in which hereditary factors play an important role (Page, 1961; Pickering, 1974), Probably over 95% of patients with hypertension have essential hypertension. By definition essential hypertension is a primary form of elevated blood pressure of undetermined causes. There seems to be a genetic predisposition and a slow and unrelenting progressiveness in the severity of the elevated blood pressure and increased vascular resistance. Therefore, in order to develop an experimental model that mimics aspects of the clinical conditions, it is necessary to have a naturally occurring form of hypertension that is predisposed genetically, that is progressive and that involves an adaptation of the circulatory system that is not rapid. The genetic component of essential hypertension is generally believed to be polygenic in nature, but by no means is this opinion unanimous (McKusich, 1960).

Immune Mechanisms in Renal Disease, 1983

It is well established that many types of glomerular diseases are caused by immune complexes or b... more It is well established that many types of glomerular diseases are caused by immune complexes or by autoantibodies to glomerular basement membrane (GBM) (Wilson, this volume). In experimental models and in cases of human glomerulonephritis, there also has been immunopathologic evidence for deposition of immune reactants along the tubular basement membrane (TBM) (Andres et al., 1978) although their role in the pathogenesis of tubular lesions remained largely unrecognized until about 7 years ago. As in glomerular diseases, compelling evidence for immune mechanisms in renal tubular diseases in man was obtained only after convincing animal models had been established (Andres and McCluskey, 1975) (Table 1).

Toxicology and Applied Pharmacology, 1986

The effect of administration of lead acetate (10 mM in the drinking water) for 8 weeks on the in ... more The effect of administration of lead acetate (10 mM in the drinking water) for 8 weeks on the in vivo sheep red blood cell (SRBC) specific plaque-forming cell (PFC) responses of inbred A, BALB/c, C57Bl/6, DBA/1, SJL, and NZW/NZB F1 mice and outbred CFW mice was examined to determine if lead was immunomodulatory in a genetically related manner. Lead did not suppress the SRBC-specific PFC/10(6) splenocytes or PFC/spleen response in any mouse strain when compared to the responses of strain-matched control mice. In addition, 10 mM lead-treated BALB/c mice manifested augmented PFC/10(6) splenocytes (17%; p less than .05) but unchanged PFC/spleen responses. Correspondingly, serum concentrations of SRBC-specific antibody (measured by radioimmunoassay) and serum immunoglobulin G, M, or A isotypes were also unchanged by lead acetate treatment in all tested mouse strains. There were no observable lead-related histopathological changes or deposition of immune complexes or antibasement membrane antibody in the kidneys of treated mice. Further, splenocytes from lead-treated, SRBC-immunized mice cultured with T-independent antigens (TNP-LPS, TNP-Ficoll) or with a T-dependent antigen (SRBC) exhibited direct and indirect specific PFC responses that were unchanged from those of control mice. The H-2K/D haplotypes of the outbred CFW mice were determined by microcytotoxicity to include r, q, u, and s. These results suggest that lead acetate (10 mM) administered po for 8 weeks does not suppress the primary direct humoral immune response to SRBC in inbred and outbred mice of several H-2 haplotypes (k/d; d; b; q; d,z; s; r; and u).