Search PubMed⌕ Search

Biomedical subjects

J D Conger

Publications and source records attributed to J D Conger.

At least 55 records · Page 3Linked to original sources
PubMed1988

Smooth muscle calcium and endothelium-derived relaxing factor in the abnormal vascular responses of acute renal failure.

Abnormal renovascular reactivity, characterized by paradoxical vasoconstriction to a reduction in renal perfusion pressure (RPP) in the autoregulatory range, increased sensitivity to renal nerve stimulation (RNS), and loss of vasodilatation to acetylcholine have all been demonstrated in ischemic acute renal failure (ARF). To determine if ischemic injury alters vascular contractility by increasing smooth muscle cell calcium or calcium influx, the renal blood flow (RBF) response to reductions in RPP within the autoregulatory range and to RNS were tested before and after a 90-min intrarenal infusion of verapamil or diltiazem in 7-d ischemic ARF rats. Both calcium entry blockers, verapamil and diltiazem, blocked the aberrant vasoconstrictor response to a reduction in RPP and RNS (both P less than 0.001). In a second series of experiments the potential role of an ischemia-induced endothelial injury and of the absence of endothelium-derived relaxing factor (EDRF) production were examined to explain the lack of vasodilatation to acetylcholine. Acetylcholine, bradykinin (a second EDRF-dependent vasodilator), or prostacyclin, an EDRF-independent vasodilator, was infused intrarenally for 90 min, and RBF responses to a reduction in RPP and RNS were tested in 7-d ischemic ARF rats. Neither acetylcholine nor bradykinin caused vasodilatation or altered the slope of the relationship between RBF and RPP. By contrast, prostacyclin increased RBF (P less than 0.001), but did not change the vascular response to changes in RPP. It was concluded that the abnormal pressor sensitivity to a reduction in RPP and RNS was due to changes in renovascular smooth muscle cell calcium activity that could be blocked by calcium entry blockers. A lack of response to EDRF-dependent vasodilators, as a result of ischemic endothelial injury, may contribute to the increased pressor sensitivity of the renal vessels.

Acute Kidney Injury↗
PubMed1987

Effect of hemorrhagic reduction in blood pressure on recovery from acute renal failure.

The effect of hemorrhagic reduction in systemic blood pressure (SBP) to 90 mm Hg for four hours on autoregulation of renal blood flow (RBF), renal function, and renal histology was examined in control rats, one week norepinephrine-induced acute renal failure (NE-ARF) rats with intact renal nerves, and one week NE-ARF rats with prior renal denervation. The results showed that in control rats, hemorrhagic SBP reduction to 90 mm Hg had no effect on autoregulation of RBF (autoregulatory index = 0.09 +/- 0.02), creatinine clearance, or renal histology. However, in one week NE-ARF rats with intact renal nerves, hemorrhagic reduction in SBP to 90 mm Hg was associated with marked impairment of autoregulation of RBF (autoregulatory index = 3.49 +/- 0.25), further reduction in creatinine clearance from 0.59 +/- 0.08 ml/min to 0.36 +/- 0.14 ml/min, and histologic evidence of recurrent ischemic injury. Renal denervation prior to SBP reduction improved autoregulation of RBF (autoregulatory index = 0.30 +/- 0.09), prevented the further reduction in creatinine clearance, and significantly ameliorated the deleterious effect on renal histology seen in innervated NE-ARF rats. These results suggest the potential importance of the loss of autoregulation of RBF on the course of NE-ARF, and further support the pathogenetic role of renal nerves in the loss of autoregulation.

Acute Kidney Injury↗
PubMed1987

Clonal analysis of the anti-DNA repertoire of murine B lymphocytes.

The present studies characterize at the clonal level the repertoire of lipopolysaccharide-responsive murine B lymphocytes committed to the production of antibodies reactive with denatured DNA. This repertoire is vast in normal mice as 1-5% of total mitogen-induced antibody-forming cell clones secreted denatured DNA-reactive antibodies when the splenocyte donors were CBA (Ighj), BALB/c (Igha), C57BL/6 (Ighb), CBA nu/nu, and C57BL/6 nu/nu athymic mice. The autoimmune NZB (Ighe) strain did not display elevated proportions of anti-denatured DNA antibody-forming cell precursors. Cross-reactions shown by CBA anti-denatured DNA antibodies suggest that many antibodies might derive significant binding energy from interaction with the bases or similar hydrophobic moieties. Cross-reactions with other tested polynucleotides were frequent, but cross-reactions with phospholipids and phosphocholine were undetectable. Most anti-DNA antibodies bound preferentially or exclusively to single-stranded denatured DNA as compared to double-stranded native DNA. The frequency of anti-denatured DNA antibody-forming cell precursors among CBA peritoneal cells was not elevated. Fluorescence-activated cell sorter-selected Ly-1-positive NZB splenic B cells were not enriched, and Ly-1 negative B cells were not depleted of anti-DNA antibody-forming cell precursors. These results show that antibody-forming cell precursors specific for denatured DNA are not restricted to the Ly-1 positive B-cell subset.

Animals↗
PubMed1987

Glomerular dynamics in the hypothyroid rat and the role of the renin-angiotensin system.

Munich-Wistar rats underwent thyroidectomy (TX) with reimplantation of the parathyroid glands. Systemic hemodynamic and micropuncture studies were performed at 1 and 3 wk post-TX, and the results were compared with levothyroxine replaced controls (TXT4). Cardiac output (CO) in TX rats fell progressively and was 40% of that in TXT4 at 3 wk. Renal blood flow declined in parallel with CO. Systemic blood pressure did not fall in TX rats because of a 50% increase in systemic vascular resistance by 3 wk post-TX. Glomerular dynamics were not significantly different between TX and TXT4 rats at 1 wk; however, by 3 wk single-nephron glomerular filtration rate (SNGFR) had fallen to 16.5 +/- 1.1 vs. 34.1 +/- 3.4 nl/min in TXT4 controls (P less than 0.001). In 3-wk TX rats, glomerular plasma flow (QA) was 50.9 +/- 3.7 vs. 108.0 +/- 8.7 nl/min in TXT4 rats (P less than 0.001), net hydraulic ultrafiltration pressure (delta P) was 33 +/- 2 vs. 37 +/- 1 mmHg in TXT4 rats (P less than 0.01), and the ultrafiltration coefficient (Kf) was 0.025 +/- 0.003 vs. 0.084 +/- 0.008 nl X s-1 X mmHg-1 in TXT4 controls (P less than 0.001). Although the changes in systemic and glomerular hemodynamics were progressive over 3 wk, proximal tubular reabsorption fell maximally within 1 wk. Similar patterns of alterations in glomerular dynamics are known physiological consequences of angiotensin II (ANG II).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1987

Influence of xid on anti-azophenylarsonate (Ar) antibody responses of (CBA/N x A/J)F1 mice: differential idiotype expression induced by only one of two Ar antigens.

The influence of an X chromosome-linked immune deficiency gene (xid) on several properties of the anti-azophenylarsonate (Ar) antibody responses of (CBA/N x A/J)F1 (NAF1) mice was examined. With respect to response magnitude, it was found that male, xid-expressing NAF1 mice showed about 1/3 the concentration of serum anti-Ar antibody as normal female NAF1 mice in hyperimmune responses to Brucella abortus (BA)-Ar. In responses induced by keyhole limpet hemocyanin (KLH)-Ar, males showed responses of about 1/8 to 1/2 the female levels, depending on the assay time point. The kinetics of the latter response were identical in mice of the two sexes. No significant difference could be detected in the time-dependent avidity maturation of the anti-Ar antibody elicited by KLH-Ar in xid vs. normal mice. The isotype profile of the day 38 anti-Ar primary response elicited by KLH-Ar in male NAF1 mice differed from that of the female mice in two ways: IgG2a levels were depressed, and a significantly lower number of the male mice demonstrated detectable IgG3 anti-Ar antibody production. The primary focus of htis work was to determine the effect of xid on the expression of the major cross-reactive idiotype--CRIA--of A strain mice. It was found that while a significant higher proportion of the female mice could be classified as high CRIA producers in responses to BA-Ar, no difference could be demonstrated if the inducing antigen was KLH-Ar. It is proposed that the difference observed with the two antigens may be due to the more selective activation by KLH-Ar of a small subset of high affinity Ar-specific clones--which may be enriched for CRIA + precursors--in both normal and immune defective mice. In contrast, BA-Ar may 'sample' more of the total anti-Ar repertoire and thus reveal within it an xid-determined depression in the proportion of CRIA + clones. Finally, it is noted that the influence of xid appears to be largely of a stochastic, and not an absolute character.

Animals↗
PubMed1987

T-independent form of azophenylarsonate fails to reveal "silent" idiotype-positive B cells in idiotype-suppressed mice.

In three distinct chronic Ig-specific suppression systems in which suppression was initiated by injection of mice with anti-idiotype (Id) or anti-allotype sera, evidence has been presented by others that the differentiation of B cells bearing surface Ig with a target marker (Id or allotype) need not be totally disrupted. Normally "silent" Id+ B cells from Id-suppressed mice could be revealed by certain procedures, one of these being to make use of the powerful stimulatory properties of bacterial lipopolysaccharide. We have employed a similar strategy to determine whether cryptic CRIA+ B cells exist in significant numbers in hyperimmune, CRI-suppressed (HIS) A/J mice. Thus, following T cell removal, the Ar-specific B cell repertoire from HIS mice was probed using Ar- Brucella abortus as a T-independent Ag. No evidence for "silent" CRIA+ B cells was found. The results, taken in conjunction with those of others, suggests that there may exist multiple forms of long-term Ig-specific suppression.

Animals↗
PubMed1986

Influence of helper T cells on the expression of a murine intrastrain crossreactive idiotype.

The requirement for idiotype-specific helper T (Th) cells in the generation of a major intrastrain crossreactive idiotype was investigated. This idiotype, designated CRIA, is associated with a large proportion of anti-p-azobenzenearsonate (anti-Ar) antibodies in A/J mice. Secondary in vitro responses were studied. Using carrier-primed heterogeneous Th-cell populations, it was found that CRIA expression is determined by the mouse strain that provides the responding B cells and is independent of the strain of the Th cells functioning in vitro. Thus, A/J or A.BY (Ighe) B-plus-accessory-cell populations, primed in vivo to keyhole limpet hemocyanin-Ar (KLH-Ar), generated CRIA-dominant responses in vitro in the presence of KLH-Ar regardless of whether the KLH-primed Th cells were derived from CRIA+ strains (A/J or A.BY, Ighe) or CRIA- strains (B10.A or C57BL/10, Ighb). Further, when major histocompatibility complex-restricted, KLH-specific Th-cell clones were used, the CRIA dominance of the Ar-specific responses was again determined by the strain providing B plus accessory cells. Similar levels of expression of CRIA in Ar-specific antibodies were generated in the presence of heterogeneous or cloned Th cells. The results suggest that there is no absolute requirement for idiotype-specific Th cells in generating an Ar-specific secondary antibody response in vitro.

Animals↗
PubMed1986

Glomerular and tubular dynamics in mercuric chloride-induced acute renal failure.

Mercuric chloride (HgCl2)-induced acute renal failure has received considerable investigative attention but little agreement as to its pathogenesis. A source of some disagreement has been the lack of direct glomerular dynamics measurements in this disorder. We examined glomerular dynamics, tubular integrity, and whole kidney function at 24 hours in Munich-Wistar rats given either HgCl2, 3.5 mg/kg, or a similar volume of 0.9% saline solution intramuscularly. Arterial blood pressure was elevated in HgCl2-injected rats, but renal blood flow and its distribution were similar to those of controls. Inulin clearance, however, was reduced by 89% in HgCl2-injected animals. Glomerular dynamics experiments demonstrated similar glomerular plasma flow (QA) and glomerular capillary and tubular pressures in control and HgCl2-injected animals but a higher net afferent ultrafiltration pressure and lower ultrafiltration coefficient (Kf) in the HgCl2-injected group. Single-nephron glomerular filtration rate (SNGFR), when measured from Bowman's space and HgCl2-injected rats, was similar to that measured from late proximal tubules in controls. However, SNGFR determined from the later proximal tubule in HgCl2-injected rats was only one third of that measured from Bowman's space. QA estimated from glomerular counting was similar to that calculated from Bowman's space SNGFR in HgCl2-injected rats. 3H-inulin microinjection experiments confirmed the presence of tubular fluid backleak suggested by the discrepancy in Bowman's space and late proximal tubular SNGFR measurements. It is concluded that at 24 hours in low-dose HgCl2-induced acute renal failure, tubular fluid backleak is the major pathogenetic factor, with a decline in Kf having a potential secondary role.

Acute Disease↗
PubMed1985

Idiotypic properties of the murine anti-arsonate antibody response: B- and T-cell influences.

In a previous report characterizing the arsonate (ABA)-specific plaque-forming cell (PFC) responses of A/J mice induced by ABA-KLH, two interesting characteristics of the idiotypic (Id) profile were noted: (1) an apparent Id selectivity in the isotype switch since the earliest appearing IgG PFC in the primary response were significantly more "cross-reactive Id" (CRI)-dominant than the IgM PFC population, and, (2) a temporal waning of CRI dominance with time among IgG PFC, from 75-100% CRI+ PFC to about 25-45% CRI+ PFC in secondary responses. Experiments were performed to determine whether these effects are largely attributable to T or to B cells. Mice were immunized with a T-independent (TI) form of ABA (ABA-Brucella abortus) and apparent Id selectivity was observed; the earliest IgG PFC averaged 75% CRI+ while IgM PFC were only 39% CRI+. Due to the TI nature of the Ag, this provides suggestive, but not conclusive, evidence that the Id asymmetry in the isotype switch may be attributable to the direct interaction of Ag with B cells. Other studies addressed the temporal shift in CRI dominance. First, it was found that preexposure of mice to either KLH or to ABA (on an irrelevant carrier) resulted in diminished CRI dominance in subsequent "primary" responses to ABA-KLH. Secondly, adoptive transfer experiments with B and T cells from virgin mice (Bv, Tv) or ABA-KLH-primed mice (Bp, Tp) showed that recipients of Bv + Tp or Bp + Tv generated anti-ABA PFC responses with intermediate CRI levels. The Tv cells had some preferential tendency to activate CRI+ clones in the Bp population. The results demonstrate that CRI levels are jointly determined by the immune status of both B and T cells. A simple model is offered which accounts for early Id dominance and its gradual decline and has as its central postulate the assumption that CRI+ B cells in the virgin ABA-specific repertoire have an affinity advantage over CRI- clones.

Animals↗
PubMed1984

Nephron heterogeneity in ischemic acute renal failure.

To uncover the reasons for reported internephron heterogeneity in acute renal failure (ARF) serial micropuncture experiments in norepinephrine-induced ARF and sham-infused control rats were carried out to investigate this phenomenon. Proximal tubular pressures (PT) were scattered at 24, 48, and 72 hr in ARF rats ranging from 4 to 42 mm Hg, but the majority were greater than the mean control values (10 +/- 1 mm Hg). One week ARF PT were less variable than on previous days (5 to 17 mm Hg). The decreased variability was the result of a reduced number of PT values that were greater than controls. When single nephron filtration rates (SNGFR) were measured with spontaneous flow collections without maintaining the existent tubular pressures, results were widely scattered on each day. When SNGFR were measured at the existent PT, individual determinations were tightly clustered on each experimental day, clearly different from controls (all P less than 0.001), and correlated closely with predicted values from whole kidney inulin clearance (all P less than 0.001). Thus, existent internephron SNGFR was uniform in ARF rats and apparent heterogeneity, in large part, was attributable to an artifact of the tubular fluid collection technique. Despite the uniformity of SNGFR, values of PT ranging below as well as above controls, suggested that a mechanism in addition to tubular obstruction was operative in reducing SNGFR. Recoveries of microperfused 14C-inulin were similar to controls excluding significant backleak of tubular fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1984

Sympathetic nervous system in the loss of autoregulation in acute renal failure.

The responsiveness of the renal vascular system was investigated in uninephrectomized Sprague-Dawley rats in which acute renal failure had been induced by norepinephrine. The animals were studied at 1' and 3 wk after norepinephrine infusion. Uninephrectomized littermates served as controls. Compared with controls, there was an absence of renal blood flow autoregulation in 1-wk acute renal failure that returned in part by 3 wk. In 1-wk rats there was a marked increase, rather than decrease, in renovascular resistance as renal perfusion pressure was decreased. The renal vasculature was significantly less responsive in 1-wk rats than in control or 3-wk animals when acetylcholine, angiotensin II, or norepinephrine was infused into the renal artery at minimal vasoactive doses (all P less than 0.01). Paradoxically, renal vasoconstriction in response to renal nerve stimulation was greater in 1-wk than in 3-wk and control rats (P less than 0.01) and was not inhibited by renal artery infusion of phenoxybenzamine. Renal denervation significantly improved renal blood flow autoregulation in 1-wk animals (P less than 0.001) and completely abolished the increase in renovascular resistance as renal perfusion pressure was lowered. No effects of renal denervation on renal blood flow autoregulation were seen in control and 3-wk rats. It is concluded that renovascular responses to neurohumoral stimuli are aberrant in acute renal failure. The loss of renal blood flow autoregulation is related to an increased renovascular resistance that is due to increased activity of non-alpha-adrenergic mechanisms of the autonomic nervous system.

Acetylcholine↗
PubMed1983

Idiotype profile of an immune response. II. Reversal of the relative dominance of major and minor cross-reactive idiotypes in arsonate-specific T-independent responses.

Two different cross-reactive idiotype (CRI) groups are distinguishable in the Ab response of A/J mice to the p-azobenzenearsonate (ABA) hapten: CRIA and CRIm. These two groups showed distinct patterns of relative dominance in the ensuing response depending on whether the inducing Ag was a T cell-dependent (TD) form of ABA, such as ABA-KLH or ABA-CGG, or a T-independent type 1 (TI-1) form, such as ABA-Brucella abortus or ABA-lipopolysaccharide (LPS), and on whether the response was elicited in vivo or in vitro. The CRI+ component of primary in vivo plaque-forming cell (PFC) responses to TD ABA Ags was largely (greater than 90%) CRIA+ as was, to a slightly lesser extent (greater than 75%) the CRI+ portion of secondary or hyperimmune serum Ab or PFC responses to the same Ags. In contrast, in vivo primary and hyperimmune PFC responses to ABA-Bru or ABA-LPS showed a significantly lower CRIA/CRI ratio, averaging 0.5-0.6, with some individual mice giving figures as low as 0.2, indicating predominance of CRIm over CRIA. Serological analysis of hyperimmune anti-ABA Abs from a group of 5 A/J mice immunized with ABA-Bru gave a figure of less than 0.5 for the CRIA/CRI ratio. The most striking disparity from the TD pattern was seen in primary in vitro PFC responses to the TI ABA Ags; here ratios of less than 0.2 were generally seen. Since T cell removal did not alter the Id pattern in the TI responses, CRIA-specific Ts cells do not account for the weak expression of CRIA in such responses. We propose a model that explains these results on the basis of differential expression of IdX dominance by two distinct B cell subpopulations--equatable to the Lyb-5+ and Lyb-5- B cell subsets--along with differential relative activation of these subsets in different types of responses. Examination of anti-ABA PFC responses of F1 progeny of CBA/N and A/J mice to ABA-Bru lends support to this hypothesis since CRIA expression was significantly lower in mice with the xid defect.

Animals↗
PubMed1983

Vascular abnormalities in the maintenance of acute renal failure.

Male Sprague-Dawley rats were used to investigate renal vascular abnormalities in the maintenance phase of norepinephrine-induced ischemic acute renal failure. In this model uremia peaks in the first 5 days with progressive recovery of renal function which approaches control at 25 days. Renal blood flow returns to normal in the first week. Micropuncture experiments revealed that there was a dual nephron population during the first 3 days of acute renal failure. The majority of proximal tubules had elevated pressures from tubular obstruction. The nephron filtration rate responses in these nephrons were similar to normal if tubular obstruction was relieved, indicating that glomerular filtration dynamics were not impaired. In other nephrons tubular pressures were low, and venting the tubules did not increase nephron filtration. In these nephrons glomerular blood flowed and capillary pressures were reduced. There was no evidence of tubular fluid backleak from 14C-inulin microperfusion. A second vascular abnormality was an absence of renal blood flow autoregulation at 1 week in acute renal failure. The autoregulatory defect could be corrected by renal denervation.

Acute Kidney Injury↗
PubMed1981

Idiotype profile of an immune response. I. Contrasts in idiotypic dominance between primary and secondary responses and between IgM and IgG plaque-forming cells.

The primary response of A/J mice to p-azobenzenearsonate-keyhole limpet hemocyanin (ABA-KLH) was investigated. A day-by-day analysis at the plaque- forming cell (PFC) level was performed, with inhibition by anti-cross- reactive idiotype (CRI) serum to determine percentage of CRI(+) PFC. A regular pattern in the dynamics of Id (idiotype) dominance was observed. Just as in the NP-b and NP-a systems (9, 12), the major Id (CRI) is more dominant in primary than in secondary or hyperimmune responses. This trend is more apparent in IgG PFC which are generally 80-95 percent CRI(+) at day 10 in the primary response but only 30-40 percent CRI(+) at day 10 in secondary or hyperimmune responses. A somewhat different pattern is seen with IgM PFC. These may reach a peak of 85 percent CRI(+) in the primary response, but secondary or hyperimmune IgM PFC, which are lower in numbers than IgG PFC, remain high in CRI content at approximately 70 percent. The PFC data on extent of id dominance in secondary or hyperimmune responses is fully compatible with previously reported serological data by others. Analysis of IgG PFC by hapten inhibition indicated that heterogeneity was in the order secondary PFC {greater than} primary PFC {greater than} hybridoma AK-2.2 PFC with H(75)/H(25) values of 22.9, 6.2, and 2.7, respectively; where H(75) and H(25) are the hapten concentrations required to give 75 percent and 25 percent of inhibition of PFC, respectively. Hapten inhibition data also suggested that secondary IgG PFC were 10 times higher in median binding avidity for ABA-L-tyrosine than primary IgG PFC. The kinetic analysis strongly indicated that CRI(+) IgM PFC were preferentially switched to IgG PFC in the primary response. In both studies, the CRI content of the earliest-appearing IgG PFC was significantly higher than that of IgM PFC on that day. For example, in one case IgM PFC were 60 percent CRI + on day 6 whereas IgG PFC were 100 percent CRI(+). The high Id dominance and selective isotype switching may have either a B or a T cell basis.

Animals↗
PubMed1981

Glomerular dynamics and morphologic changes in the generalized Shwartzman reaction in postpartum rats.

The roles of glomerular functional and morphologic changes were examined in the acute renal failure associated with generalized Shwartzman reaction in postpartum Munich Wistar rats. The susceptibility of postpartum rats to acute deterioration in renal function after a 2-h endotoxin infusion was found to be greater than in virgin litter mates: glomerular filtration rate fell by 93% in the former vs. 24% in the latter group (P less than 0.001). In postpartum rats there were marked changes in platelet count and fibrinogen level (P less than 0.025) compatible with consumption coagulopathy. Renal blood flow and glomerular filtration rate fell from 5.5 +/- 0.9 and 0.74 +/- 0.12 to 2.0 +/- 0.7 and 0.12 +/- 0.01 ml/min, respectively (both P less than 0.001). Blood pressure did not change. Results of glomerular dynamics studies showed decreases in single nephron filtration rate from 28 +/- 7 to 6 +/- 4 nl/min and in glomerular plasma flow rate from 77 +/- 26 to 23 +/- 12 nl/min (both P less than 0.001). Afferent net ultrafiltration pressure fell from 20 +/- 3 to 5 +/- 4 mm Hg due to a fall in glomerular capillary hydraulic pressure from 47 +/- 1 to 29 +/- 5 mm Hg (P less than 0.001). There were four- and twofold increases in afferent and efferent arteriolar resistances, respectively. Less than 20% of glomeruli had evidence of fibrin deposition after 2 h of endotoxin infusion, a time when glomerular filtration rate was reduced by greater than 90%. [1-Sar, 5-Ile, 8-Gly] angiotensin II infusion before endotoxin significantly protected glomerular filtration rate, 62 vs. 7% of control in rats with no preinfusion (P less than 0.01) despite consumption coagulopathy and glomerular fibrin deposition similar to rats without pretreatment. These data suggest that the early deterioration in renal function in the generalized Shwartzman reaction in the postpartum rat is due to major changes in glomerular dynamics induced by neurohumoral agents and that glomerular fibrin deposition plays a lesser pathogenetic role at this time in this disorder. The study does not address the pathogenesis of renal failure in pregnancy nor peripartum renal failure in another species.

Animals↗