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S H Sacks

Publications and source records attributed to S H Sacks.

At least 73 records · Page 4Linked to original sources
PubMed1993

Endogenous complement C3 synthesis in immune complex nephritis.

Human renal epithelial and mesangial cells have been shown to synthesise complement C3 in culture, but the relevance of this finding to the development of complement-mediated nephritis is uncertain. We investigated C3 gene expression in tissue biopsies that showed three main categories of renal injury. By semiquantitative polymerase chain reaction, biopsies from patients with immune-complex glomerulonephritis and those with cell-mediated interstitial nephritis showed increased C3 expression (p < 0.05), but biopsies from patients with non-immune glomerular injury did not. These findings suggest that local C3 production is enhanced in immune-mediated nephritis and are consistent with the hypothesis that locally synthesised complement components are involved in the pathogenesis of tissue injury.

Complement C3c↗
PubMed1993

Interferon-gamma regulation of C4 gene expression in cultured human glomerular epithelial cells.

The fourth component of human complement is mainly produced in liver, but extrahepatic gene expression has been reported in human renal tissue and other tissues, and is thought to contribute to the inflammatory reaction in local tissue. To identify the cellular origin of C4 synthesis in human kidney, we studied C4 gene expression and regulation by interferon-gamma (IFN-gamma) and C4 protein biosynthesis in isolated glomerular epithelial cells. cDNA/polymerase chain reaction analysis showed that C4 transcripts are present in glomerular epithelial cells (GEC), and that gene expression is up-regulated by IFN-gamma. Metabolic labeling studies showed that GEC synthesize and secrete C4 as three polypeptide chains of approximately 90, 70, and 30 kDa, which correspond to the bands produced by hepatoma cells. These results suggest that the fourth component of complement is produced by GEC. The GEC has an important role in the maintenance of glomerular barrier function, which is lost in a number of complement-dependent conditions; glomerular epithelial synthesis of C4 could have a bearing on the possible physiological or pathological roles of complement under different circumstances.

Base Sequence↗
PubMed1993

Analysis of activated T cell infiltrates in rat renal allografts by gamma camera imaging after injection of 123iodine-interleukin 2.

Activated T cells bearing receptors for interleukin 2 (IL-2) play an important role in immunity and in immunopathological processes such as allograft rejection. In order to investigate the presence of activated T cells in lymphocytic infiltrates in transplanted kidneys, we investigated the uptake and retention of radioactivity after an intravenous injection of radioiodinated IL-2 in experimentally transplanted rats. IL-2 was enzyme radiolabelled with 123iodine using a glucose oxidase/lactoperoxidase method and shown to retain specific binding on an IL-2 receptor positive cell line, C58E6. To examine the kinetics of 123iodine-interleukin 2 (123I-IL-2) uptake in vivo, animals that had been transplanted five days previously with allogeneic or syngeneic grafts were injected with 123I-IL-2 and then imaged using an external gamma camera. Radioactivity was measured at time points up to 240 min after intravenous injection of 123I-IL-2. Four groups of animals were examined: allogeneic grafts (n = 7); syngeneic grafts (n = 6); ischaemic native kidneys (n = 5) all following injection with 123I-IL-2; and allogeneic transplants (n = 5) after injection of 123I-lactalbumin, an irrelevant molecule of similar molecular weight to IL-2. The peak radioactivity after injection was measured and the amount of radioactivity retained in the graft at increasing time intervals after injection was expressed as a function of initial peak radioactivity. At four hours after injection of 123I-IL-2, mean retention of activity by rejecting grafts was 77(+/- 2.68)% of peak activity, compared to 45(+/- 6.38)% in syngeneic controls (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Prevalence and outcome of renal impairment at prostatectomy.

Of 382 patients undergoing prostatectomy in Oxford in 1985 the prevalence of renal impairment (defined as plasma urea > 14 mmol/l or plasma creatinine > 200 mumol/l) was 8%; prostatectomy patients had significantly higher plasma ureas than age-matched patients undergoing herniorrhaphy and cholecystectomy in the same hospitals in the same year. A review of the case records of men with renal impairment showed that case history could not predict renal impairment. Although few case notes gave follow-up information, it was evident from the information available that recovery of renal function after prostatectomy did not occur invariably. Renal impairment in men undergoing prostatectomy represents substantial and unrecognised morbidity.

Aged↗
PubMed1993

Molecular mapping of the HLA class II region in HLA-DR3 associated idiopathic membranous nephropathy.

Susceptibility to IMN is associated, in European Caucasoids, with the extended HLA haplotype in A1, B8, and DR3. It is unclear from previous investigations of HLA class II genes whether the association with A1, B8, DR3 is due to an HLA-DR or -DQ locus, or both, or to another locus linked to HLA class II. To examine genetic polymorphism over a more extensive area of DNA than previously, we carried out long range mapping of the HLA class II region of A1, B8, DR3 patients and healthy controls to discover if new markers of disease could be identified at this level of organization. Large fragments of genomic DNA were cut using enzymes with infrequent restriction sites, and were separated by pulsed field gel electrophoresis (PFGE) and analyzed using a series of probes which cover the HLA class II region. In several different DR3 haplotypes examined, the overall content of DNA and organization of the class II region were similar. However, both patient and control B8, DR3 haplotypes contained an extra Pvul site in the DRB region, compared to the disease-neutral B18, DR3 haplotype. Further, the DP region of the patient B8, DR3 haplotypes contained an additional partial BssHII cutting site which was not identified in the control B8, DR3 haplotypes. This structural heterogeneity in the vicinity of DP could have implications for genetic susceptibility to IMN and for linkage disequilibrium.

Chromosomes, Human, Pair 6↗
PubMed1993

Complement C3 gene expression and regulation in human glomerular epithelial cells.

Extra-hepatic synthesis of complement is thought to mediate local tissue inflammatory injury. To investigate this phenomenon in the glomerular epithelial cell (GEC), we examined the biosynthesis and regulation of gene expression of the third component of complement in isolated human GEC derived from normal tissue. Metabolic labelling and immunoprecipitation studies demonstrated that C3 protein was synthesized, processed and secreted by GEC under basal conditions. The secreted C3 alpha and beta polypeptide chains had identical electrophoretic mobilities with those of hepatic C3. Examination of cellular RNA using semi-quantitative polymerase chain reaction (PCR) showed that C3 gene expression was present in unstimulated GEC and was increased by stimulation with interferon-gamma (IFN-gamma) in a time- and dose-dependent manner. Tumour necrosis factor-alpha (TNF-alpha), while mediating an increase in monocyte U937 C3 expression, revealed no evidence of regulation of GEC C3 gene expression. These results indicate that human GEC spontaneously express the C3 gene and that increased gene expression is regulated by IFN-gamma. These observations may reflect part of a wider mechanism of protection against or mediation of local, immune-mediated tissue injury.

Cells, Cultured↗
PubMed1992

Analysis of complement C4 loci in Caucasoids and Japanese with idiopathic membranous nephropathy.

Deletion of the HLA class III complement gene, C4A, has been linked with susceptibility to a number of autoimmune diseases. In this study, we show a strong positive association between C4A gene deletion and development of idiopathic membranous nephropathy (IMN) in European Caucasoids [patients, 17/27 (63%); healthy controls, 13/65 (20%); RR 6.8; P = 0.003]. To clarify whether C4A deletion is an independent risk factor for IMN or is increased secondarily to the Caucasoid HLA A1, B8, DR3 extended haplotype, we examined the frequency of C4A deletion in Japanese patients, in whom the disease is associated with another HLA haplotype (DR2-DQw1). Analysis of 31 Japanese patients and 46 healthy controls showed that C4A deletion was present in only one patient (3%) and one control (2%). In addition, examination of the C4B locus in Japanese patients showed that there was no significant increase in the estimated frequency of C4B deletion in patients against controls (31 vs. 27%) and no difference in the frequency of the C4B long gene (73 vs. 87%) or C4B short gene (77 vs. 78%). We conclude that although C4A deletion confers significant risk of IMN in Caucasoids, there is no significant association between C4 polymorphism, as detected here, and risk of IMN in Japanese. This suggests that either C4A deletion is irrelevant to the pathogenesis of IMN or that more than one genetic mechanism is involved.

Asian People↗
PubMed1992

Outcome of pregnancy in an Oxford-Cardiff cohort of women with previous bacteriuria.

To investigate the influence of asymptomatic bacteriuria in childhood on subsequent pregnancy, we reviewed the outcome of 139 pregnancies in 88 women who were first identified during a programme of screening schoolgirls for asymptomatic bacteriuria carried out between 1970-1972. Data were analysed for the following groups: 50 pregnancies in 28 women with known renal scars (group 1); 16 pregnancies in 14 women with normal kidneys and reflux (group 2); 73 pregnancies in 46 women with normal urinary tracts (group 3); 139 healthy controls. Women in group 1 had a 3.3-fold increased relative risk of hypertension (p < 0.01) and a 7.6-fold increased risk of pre-eclampsia (p < 0.05) compared to controls, and a higher rate of obstetric interventions, including emergency caesarean section. Women in groups 2 and 3 appeared to carry a slightly increased risk of hypertension during the last trimester (RR = 1.8) but there were no significant differences in this or the incidence of pre-eclampsia or mode of delivery. Bacteriuria was more prevalent in all index groups compared to controls (37 per cent vs. 8 per cent, p < 0.01) and included four cases of acute pyelonephritis in in the study group. Fetal outcome was satisfactory in all cases. These results suggest that women with renal scars are at risk of hypertension and pre-eclampsia during pregnancy but that modern obstetric care minimizes these risks.

Adult↗
PubMed1989

Late renal failure due to prostatic outflow obstruction: a preventable disease.

Nineteen patients presenting with late renal failure due to prostatic outflow obstruction (mean age 68.7 years; mean serum creatinine concentration 1158 mumol/l) were identified from the admission records of two renal units. As late renal failure secondary to prostatic enlargement is preventable case records were analysed retrospectively in an attempt to identify aspects of management in which preventive efforts might be of value. Delays in referral were common, with a mean of 2.8 years between the onset of prostatic symptoms and time of referral, six patients being referred who had had symptoms for more than three years. Four of five patients who had had a prostatectomy were known to be in renal failure at the time of operation but were not referred until 2-13 years later, when prostatic symptoms had recurred and there was evidence of progressive nephropathy with dilatation of the upper urinary tract. Two patients died on admission and eight (47% of survivors) required long term dialysis, most patients (80%) requiring some dialysis support during the initial period. These findings suggest that progressive nephropathy caused by prostatic outflow obstruction might, in part, be averted by more adequate screening of renal function in men with untreated prostatism and closer follow up of patients with uraemia at the time of prostatectomy.

Aged↗
PubMed1988

Surgical treatment of blindness secondary to intraorbital hemorrhage.

Rapid progression to blindness due to intraorbital hemorrhage following various forms of trauma requires immediate, aggressive intervention, with the potential to restore vision. Orbital decompression via either an external ethmoidectomy or transantral approach is described. The diagnosis, anatomy, and pathogenetic mechanisms relevant to these cases are reviewed.

Aged↗
PubMed1988

Evidence linking familial thrombosis with a defective antithrombin III gene in two British kindreds.

Using DNA probes in a structural study of the antithrombin III gene locus we found no evidence of gene deletion in two British kindreds with inherited antithrombin III deficiency. However, linkage analysis between a common DNA polymorphism and the antithrombin III deficiency trait showed that the defect lies at or close to the antithrombin III structural gene. The lod score for linkage within the larger Scottish kindred was 3.1 (theta = 0). These results are consistent with previously published data suggesting that mutation of the antithrombin III structural gene is the cause of inherited antithrombin III deficiency in some families.

Antithrombin III↗
PubMed1987

Effect of symptomless bacteriuria in childhood on subsequent pregnancy.

The outcome of 52 pregnancies in 34 women who had had bacteriuria in childhood was compared with that of normal control pregnancies. The prevalence of bacteriuria at the first antenatal visit was significantly higher (p less than 0.001) in previously bacteriuric women (35%) than in controls (5%), and acute pyelonephritis developed in 10% compared with 4% of controls. Pre-eclampsia (arterial pressure above 140/90 mm Hg with proteinuria above ++) developed in 4 of 12 previously bacteriuric women known to have renal scarring (5 of 16 pregnancies), in only 1 of 22 previously bacteriuric women without scars (1 of 36 pregnancies), and in 1 of 52 controls (p less than 0.001). Women with renal scars were also more likely to undergo induction of labour (44% of pregnancies) and operative delivery (57% of pregnancies) than previously bacteriuric mothers without scars (17%, 22%) or control mothers (16%, 20%). The infants of previously bacteriuric mothers were not significantly smaller than those of healthy control mothers, but Apgar scores were lower among offspring of previously bacteriuric mothers with scarred or normal kidneys (p less than 0.001). Fetal outcome was, however, satisfactory in all cases.

Adult↗
PubMed1987

Functional and biochemical subtypes of the haplotype HLA-DR3 in patients with celiac disease or idiopathic membranous nephropathy.

HLA class II beta-chain polymorphism was investigated in the haplotype HLA-DR3 to determine if patients with HLA-DR3-associated diseases express normal or variant class II polymorphisms. Analysis was carried out by two-dimensional gel electrophoresis of immunoprecipitated HLA class II molecules, DNA hybridization with DR beta and DQ beta gene probes on Taq 1, Bam H1, or Rsa 1 digests, and mixed lymphocyte culture. Two subtypes of HLA-DR3 were identified in normal homozygous DR3 individuals on the basis of polymorphism in one of two DR beta chains detected, corresponding to differences in DR beta restriction fragment patterns. These polymorphisms exhibited significant linkage disequilibrium with the A1,B8,DR3 and B18,DR3 haplotypes, respectively. In proliferative experiments, cells with the B18,DR3-associated polymorphism strongly stimulated cells from donors with the B8,DR3-related polymorphism, suggesting that a T-cell epitope recognized by B8,DR3 cells lies on the B18,DR3-associated DR beta chain. In seven HLA-DR3 homozygous patients with celiac disease and three HLA-DR3-homozygous patients with idiopathic membranous nephropathy, only the normal patterns of HLA class II molecules were displayed, the B8,DR3 type occurring in all patients and the B18,DR3 type in one patient. These data suggest that celiac disease and idiopathic membranous nephropathy are not related to disease-specific HLA-DR beta or -DQ beta gene variants within the DR3 population that are revealed by these methods.

Adult↗
PubMed1986

Chronic dermal sinuses as a manifestation of histiocytosis X.

Two young patients presented with generalised lymphadenopathy, otorrhoea, otitis, and rash. Over the next few years chronically discharging sinuses began to form over enlarged nodes and histological appearances were typical of histiocytosis X. In neither case were micro-organisms isolated from the lesions, and in both patients healing occurred with immunosuppressive agents. Chronic dermal sinus formation secondary to lymph node disease has never before been recorded as a manifestation of histiocytosis X. Histiocytosis X should therefore be considered in the differential diagnosis of "suppurative" lymphadenopathy so that appropriate treatment may be given without delay.

Adult↗
PubMed1986

Metallurgical analysis of failed Björk-Shiley cardiac valve prostheses.

An investigation into the mechanisms of failure of current Björk-Shiley cardiac valve prostheses is reported. Two failed valves, one apparently unfailed but defective valve, and one unused valve, were examined by scanning electron microscopy and metallographic section. In the first two valves (removed 12 and 23 months after implantation) fracture was associated with the welds joining the short strut to the valve ring. The fracture surfaces in all cases were heavily faceted and showed branching cracks. Extensive wear had occurred on one fracture surface in the first case, suggesting that one leg of the short strut had failed before the other, though this had been clinically undetectable. The third valve was removed owing to failure of the suturing (24 months after implantation) but one leg of the short strut was found to be completely fractured. The other leg showed extensive cracking and porosity in the weld region. A metallographic section taken through the weld region of the fourth (unused) valve illustrated several sizable defects directly attributable to the welding process. It is suggested that the valves failed by fatigue and that these problems could be overcome if the complete valve cage were machined as a single piece.

Aged↗