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Biomedical subjects

U H Rudofsky

Publications and source records attributed to U H Rudofsky.

At least 37 records · Page 2Linked to original sources
PubMed1984

Differences in the occurrence of hypertension among (NZB X NZW)F1, MRL-lpr, and BXSB mice with lupus nephritis.

Lupus-prone (NZB X NZW)F1 (B X W) mice and MRL-lpr and BXSB mice were examined for the prevalence of hypertension and levels of plasma renin activity (PRA). Hypertension (greater than 145 mmHg) was observed only in female and male B X W mice with severe nephritis; in female MRL-lpr and male BXSB mice severe nephritis developed without blood pressure elevation (80-135 mmHg). The B X W parental strains, NZB and NZW, and the MRL-lpr congenic partners, MRL- +, did not become hypertensive as they aged. Other strains of mice, aged 3-32 months (A/HeN, BALB/cJ, BALB/cByJ, B10.S/Sg, B10.D2/ oSn , CBA/J, C3H/HeJ, SJL/J and [SJL X NZW]F1), also had normal blood pressure (98-122 mmHg). All mice with lupus nephritis had low PRA, even those with hypertension; furthermore, the MRL-lpr strain had low or undetectable PRA (2 +/- 1 ng/ml/hr), even when kidneys were normal. NZB, NZW, and MRL- + mice had normal PRA (10-16 ng/ml/hr). Thus, B X W mice frequently developed low renin hypertension during the last phase of their renal disease; whereas MRL-lpr and BXSB mice died from renal disease without observable increases in blood pressure.

Animals↗
PubMed1983

Experimental autoimmune antiglomerular basement membrane antibody-induced glomerulonephritis. I. The effects of injecting sheep with human, homologous or autologous lung basement membranes and complete Freund's adjuvant.

We compared the effects of injecting human, homologous or autologous lung basement membrane (LBM) and complete Freund's adjuvant into 6-month-old sheep and injecting the same antigens into guinea pigs. All sheep receiving human LBM died of antiglomerular basement membrane (GBM) nephritis by Day 126. They had autoantibodies to antigenic determinants shared by fetal or adult sheep and human LBM and GBM and certain nonvascular basement membranes, but these autoantibodies did not localize in the lung in vivo or cause lung hemorrhages. No sheep injected with homologous or autologous LBM had any evidence of anti-GBM autoantibodies or nephritis or specific lung lesions. Their kidneys are indistinguishable by histologic, immunohistologic, and functional studies from kidneys of age-matched controls. Thus, sheep are very tolerant to their own LBM. Although all guinea pigs developed anti-GBM autoantibodies, they did not get anti-GBM nephritis or specific lung lesions. A hypothesis for the pathogenesis of Goodpasture's syndrome is presented.

Animals↗
PubMed1983

Effect of sulfhydryl-reactive ATPase inhibitors upon mast cell and basophil activation.

Ethacrynic acid is an inhibitor of Ca2+-Mg2+-activated ATPases which also inhibits histamine release. By testing analogs of ethacrynic acid, the molecular structural requirements for ATPase inhibition and for inhibition of histamine release were compared. The results indicated that effective inhibition involves several structural features of the molecule. Analogs void of chlorine atoms were ineffective as inhibitors of histamine release and ATPase activity. Inhibition of both ATPase and histamine release requires a sulfhydryl-reactive olefinic bond, but sulfhydryl reactivity alone is not sufficient, as certain analogs which have a high capacity to react with sulfhydryl moieties were not active. Replacement of carboxy by highly ionized moieties like sulfo, rendered the molecules ineffective as an inhibitor of histamine release. Compounds which did not inhibit ATPase activity did not inhibit histamine release. The data indicate that mast cells and basophils require an intact ATPase system for histamine release, and raises the question of whether both ecto and endo ATPases are essential.

Adenosine Triphosphatases↗
PubMed1983

Experimental autoimmune glomerulonephritis induced by anti-glomerular basement membrane antibody. II. Effects of injecting heterologous, homologous, or autologous glomerular basement membranes and complete Freund's adjuvant into sheep.

The effects of injecting human, rabbit, rat, or single-kidney homologous glomerular basement membrane (GBM) or autologous GBM, each in complete Freund's adjuvant (CFA), into 15- to 18-month-old sheep are compared. All sheep receiving heterologous GBM and 3 of 6 sheep receiving homologous GBM had anti-GBM nephritis, but such sheep did not bind autoantibodies or have Goodpasturelike lesions in their lungs. Sheep given injections of human GBM had autoantibodies to antigenic determinants shared by fetal or adult sheep and human GBM, by lung basement membranes, and by certain nonvascular basement membranes. Sheep given homologous GBM had two populations of autoantibodies: one was neither species- nor organ-specific; the other was sheep-specific. No sheep given autologous GBM had any evidence of anti-GBM autoantibodies or nephritis. Their kidneys were indistinguishable by histologic, immunohistologic, and functional studies from CFA-treated controls. Thus, sheep seem very tolerant to autologous GBM. These findings suggest that human anti-GBM nephritis may occur if the GBM is altered so that it becomes cross-reacting and induces autoantibodies, as does homologous GBM.

Animals↗
PubMed1982

Plasma renin activity decrease precedes spontaneous focal glomerular sclerosis in aging rats.

An association between the activity of the renin-angiotensin system and the development of spontaneous focal glomerular sclerosis (FGS) in rats has been observed: the onset is preceded by a decrease in plasma renin activity (PRA). This observation was facilitated by the use of Fawn-hooded rats, which develop spontaneous FGS at an early age. Male Fawn-hooded rats develop severe FGS as early as 3 months of age. Male Wistar rats do not develop similar lesions until after 1 year of age. Correspondingly the PRA drops much sooner in Fawn-hooded than in Wistar rats. The low PRA appears to be due to low plasma renin rather than a limitation of the renin substrate, angiotensinogen, which appears to be present in the Fawn-hooded plasma in nonlimiting quantities. In the FH male rats renin content of the kidney drops only after severe glomerular pathology is evident, implying that the low PRA may be due to a decrease in renin secretion by the chromaffin cells of the juxtaglomerular apparatus.

Aging↗
PubMed1982

Spontaneous hypertension in fawn-hooded rats.

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.

Animals↗
PubMed1981

Murine lupus nephritis is accelerated by anti-glomerular basement membrane autoantibodies.

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 immune complex deposition.

Animals↗
PubMed1979

Studies on the pathogenesis of experimental autoimmune renal tubulointerstitial disease in guinea pigs. VI. Induction of renal lesions by active or passive immunization of strain 2 guinea pigs.

It has been reported that strain 2 guinea pigs do not develop experimental autoimmune renal tubulointerstitial disease (RTD) by active or passive immunization. Under our experimental conditions strain 2 guinea pigs are susceptible to the induction of RTD. Typical moderate to severe renal lesions were seen 22 days after immunization with rabbit tubular basement membrane in complete Freund's adjuvant. Most Albany strain guinea pigs had severe RTD. Susceptibility to induction of RTD by passive transfer of antitubular basement membrane autoantibodies was studied in Albany (A) and strain 2 (2) guinea pigs, as well as in A leads to A, A leads to 2, and 2 leads to A radiation chimeras. Only some strain 2 guinea pigs had mild to severe renal lesions by day 9, but by day 19 all had typical histologic renal abnormalities. Albany guinea pigs already had moderate to severe RTD by days 9-10. Strain 2 differed from Albany recipients by a noticeable delay in the onset of lesions. Bone marrow transplants between Albany and strain 2 did not affect these susceptibility differences. A leads to 2 recipients responded like strain 2, and 2 leads to A like Albany. This indicates that the delay of onset of RTD in strain 2 is not a defect in the bone marrow-derived inflammatory cells.

Animals↗
PubMed1978

Dactinomycin treatment of murine lupus erythematosus. I. Renal disease and longevity.

Three groups of female (NZB X NZW)F1 hybrid mice were treated with an intermittent regimen of dactinomycin (actinomycin D), 3.5 microgram. daily. Median survival was doubled in two of the groups and increased by more than 75 per cent in the third. Most of the treated animals never had significant proteinuria. When kidneys from 14 treated mice, which died between the ages of 11 and 20 months, were examined by light and fluorescence microscopy, most showed the lesions of normal aged CBA and C57BL/6 mice, some expansion of the mesangial matrix and increased cellularity, consistent with deposition of immunoglobulins and complement components in the mesangium, generally sparing the capillary loops. Four of the 14 animals, three of them long-lived, had advanced renal glomerular disease. These data indicate that dactinomycin, by whatever therapeutic mechanism, permits very extended survival of B/W female mice, the large majority of them without significant renal disease.

Animals↗
PubMed1978

Renal tubulointerstitial lesions in CBA/J mice.

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 or in a survey of CBA/HUmc, C57BL/6J, A/J, BALB/cJ, or C3H/HeJ mice. Immunofluorescent examination of CBA/J kidneys appears to rule out antitubular basement membrane autoantibodies or immune complexes in the pathogenesis of RTL.

Age Factors↗
PubMed1977

C4 in glomerular lesions of NZB/NZW mice.

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.

Animals↗
PubMed1977

Studies on the pathogenesis of experimental autoimmune renal tubulointerstitial disease in guinea-pigs. IV. failure to inhibit mononuclear cell accumulation with niridazole.

Niridazole is a potent inhibitor of certain expressions of delayed-type hypersensitivity; however, its effect and specificity on other immunologically induced mononuclear cell infiltrates has not been determined. We therefore tested this drug in a model of auto-antibody-induced renal tubulointerstitial disease (RTD), which is characterized by the accumulation of lymphocytes and macrophages in the cortical interstitium. Niridazole-treated (100 mg/kg) and untreated guineapigs were injected with potent anti-tubular basement membrane serum from donors with RTD. Drug treatment was repeated 2-3 times during the course of 10 days. The characteristic renal lesions were found in both groups. However, a single dose of niridazole inhibited skin reactivity in tuberculin sensitive guinea-pigs for at least 8 days. These findings further support the contention that immunologic tissue injury in RTD does not involve mechanisms of delayed-type hypersensitivity.

Animals↗