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Biomedical subjects

R E Kirsch

Publications and source records attributed to R E Kirsch.

At least 109 records · Page 6Linked to original sources
PubMed1986

Fibrinogen synthesis in the rat; role of the C terminal end of the gamma chain of fragment D1.

The terminal fibrinogen degradation product fragment D1 is known to regulate fibrinogen synthesis but the determinants in the D1 molecule responsible for this property are not known. The effect of fragment D1 on fibrinogen synthesis by the isolated perfused rat liver was studied using the (14C) carbonate method. Addition of 25 mg of fragment D1 to 100 ml of whole blood perfusate resulted in a significant increase in fibrinogen synthesis. When the C-terminal end of the gamma-chain of D1 was further plasmin-degraded to form fragment D3 this fibrinogen-enhancing effect was lost. Our studies suggest that the C-terminal of the gamma-chain of fragment D1 plays a role in regulating fibrinogen synthesis by the isolated rat liver.

Animals↗
PubMed1986

Limitations of multiple injection sclerotherapy sessions for acute variceal bleeding.

Sixty-six patients with active bleeding (127 episodes) from oesophageal varices treated by balloon-tube tamponade followed by injection sclerotherapy with a rigid endoscope were followed up for at least 1 year and analysed to determine whether the number of acute injection sessions during each hospital admission (87) or any other known parameter of liver function, e.g. Child's grading, affected the outcome. Definitive control of bleeding was achieved with one or two injections during 75 of these admissions (86%) with a mortality rate of 21%. However, the mortality rate in those patients who received three or four injections was 66% and reached 89% when Child's category A patients were excluded. It is concluded that the mortality rate in poor risk patients becomes unacceptably high when more than two injection sessions are required during a single hospital admission. Other methods of treatment, such as emergency portacaval shunting or devascularization procedures, should be instituted in the small subgroup of patients whose variceal bleeding is not controlled by two injection sessions.

Esophageal and Gastric Varices↗
PubMed1986

Porphobilinogen deaminase and the synthesis of porphyrin isomers in the Dubin-Johnson syndrome.

Porphyrin synthesis was studied in a family of 9.3 of whom had the Dubin-Johnson syndrome (DJS). Subjects with DJS had modest increases in urinary porphyrin concentration with a marked increase in the series I isomer of coproporphyrin (tetracarboxylic) as well as in the octa-, hepta-, hexa- and penta-carboxyl porphyrins. Activity of erythrocyte porphobilinogen deaminase (PBG-D) was also increased. Non-expressing carriers in the family had normal levels of urinary porphyrins but modest increases in both series I isomer accumulation and PBG-D activity. These results may provide a rationale for the altered synthesis of porphyrin in DJS.

Adolescent↗
PubMed1986

The identification of a glutathione S-transferase isozyme in fetal rat livers which is absent from adult livers.

The subunit composition of adult and fetal rat liver glutathione S-transferase was investigated by affinity chromatography followed by polyacrylamide gel electrophoresis in sodium dodecylsulphate. Adult livers contained four major GSH S-T subunits. A previously unidentified subunit was detected in fetal livers. This subunit(s), which differed from that found in rat placenta, had a molecular weight of about 25,500 daltons, gave two bands of pI 8.0 and 8.5 on isoelectric focussing, and reacted on "Western blots" with antibodies raised against the major GSH S-T subunits of adult liver. Densitometric measurements suggest that the newly detected transferase subunit accounted for as much as 26% of GSH S-T in fetal livers.

Animals↗
PubMed1984

Ligandin concentrations in the steroidogenic tissues of the rat during development.

Ligandin, a ubiquitous multifunctional cytoplasmic protein which exhibits glutathione S-transferase, glutathione peroxidase and delta 5-3-ketosteroid isomerase activities and binds to cortisol metabolites, is present in relatively high concentrations in gonadal and adrenal tissue. In contrast to hepatic ligandin, little is known about the ontogeny of ligandin in steroid-synthesising tissues. We report here the intracellular concentrations of ligandin as well as the serum concentrations of testosterone and progesterone measured by radioimmunoassay at different stages of development in the rat. Ligandin levels in testis, ovary and adrenal tissue were relatively high soon after birth, decreased by day 9 and increased rapidly during puberty to reach adult levels. These changes appeared to be paralleled by changes in the circulating levels of testosterone and progesterone. In contrast, ligandin levels in non-steroidogenically active tissues, such as liver and kidney, were low at birth and rose progressively to reach adult levels. Whereas hepatic ligandin concentration could be increased at all stages of development by phenobarbital induction, no induction occurred in the endocrine tissues.

Adrenal Glands↗
PubMed1984

Sclerotherapy for bleeding esophageal varices.

Patients with endoscopically proven variceal bleeding that continues despite conservative management require invasive emergency measures to stop hemorrhage and improve survival. Injection sclerotherapy is the simplest and most effective means currently available. The relative merits of the various techniques and sclerosants remain controversial.

Combined Modality Therapy↗
PubMed1984

Inhibition of rat GSH S-transferases by ethylene dibromide.

Incubation of ethylene dibromide (EDB) (37 mM) with a mixture of rat hepatic cytosol GSH S-transferases at 25 degrees resulted in diminished activity towards 1-chloro-2,4-dinitrobenzene (CDNB) and 3,4-dichloronitrobenzene (DCNB). The loss of both activities followed pseudo first order kinetics with a rate constant of 0.13 +/- 0.03 min-1. The concentration of EDB required for half maximal loss of enzymic activity towards CDNB was 3.2 mM. Removal of EDB from the enzyme by lyophilization or gel filtration did not result in the return of activity towards CDNB. GSH partially prevented the loss of activity, but could not reverse the loss. EDB decreased the activity of forms A(YbYb) and C(YbYb) of rat liver GSH S-transferases but not of forms AA(YcYc), B(YaYc) or B(YaYa). It is concluded that EDB inhibits forms A and C of the GSH S-transferases via a mechanism not involving suicide inhibition.

Animals↗
PubMed1983

Hepatic complications of antituberculosis therapy revisited.

Since 1973, when the incidence and pattern of adverse reactions to antituberculosis therapy were described by Rossouw and Saunders, para-amino-salicylic acid, the major cause of drug-induced hepatitis, has been withdrawn from the regimen used in Cape Town and replaced with pyrazinamide (PZA). Our study in the same hospital indicates that although the substitution has resulted in a significant reduction in the incidence of all side-effects (4,1% v. 9%; P less than 0,001), the incidence of hepatitis is unchanged (0,3%). PZA is currently the major cause of hepatitis associated with antituberculosis therapy.

Adolescent↗
PubMed1983

Glutathione S-transferase in human organs.

Glutathione S-transferase (GSH-T) distribution has been investigated in human tissues. The relative contribution of each species to total enzyme activity of the various tissues has been compared. "Cationic" (pI greater than 7.5) "neutral" (pI 6-6.5) and "anionic" (pI less than 5.4) species of GSH-T were separated by isoelectric focusing. "Cationic" GSH-Ts (ligandin) quantitated by radioimmunoassay were present in all tissues studied. Highest concentrations were in liver, kidney, duodenum, testis and adrenal. "Neutral" and "anionic" GSH-Ts were not present in every tissue or in every specimen of some tissues studied. Marked inter-organ and inter-individual variation in the relative concentration of the 3 GSH-T species may explain individual and organ susceptibility to drugs and toxins and underlines the need for future studies to examine individual enzymes rather than total activity.

Cytosol↗
PubMed1982

Identity of ligandin in rat testis and liver.

1. One of the main problems in the field of multifunctional proteins such as ligandin is the possibility that multiple forms and isoproteins may exist. Because liver ligandin [GSH (reduced glutathione) S-transferase B] consists of equal amounts of Ya (22 000 Da) and Yc (25 000 Da) subunits, and testis ligandin, prepared by the standard technique of anion-exchange and molecular-exclusion chromatography, contains more Yc subunit than Ya, it has been claimed that testis and liver ligandin are different entities. 2. We purified testis ligandin by immunoaffinity chromatography and have obtained a product identical with liver ligandin (Yc = Ya). This suggests that the differences previously described may be due to contamination of testis ligandin by a closely related species. In fact sodium dodecyl sulphate/polyacrylamide-gel-electrophoretic analysis of testis GSH S-transferases separated by CM-cellulose chromatography showed that GSH S-transferase AA, present in large amounts, migrated in the same region as Yc subunit. 3. Testis ligandin prepared by the standard technique was similar to that reported [Bhargava, Ohmi, Listowsky & Arias (1980) J. Biol. Chem. 255, 724-727] and contained more Yc subunit than Ya. CM-cellulose chromatography of this 'pure' preparation revealed significant amounts of GSH S-transferase AA migrating as Yc subunit, in addition to ligandin consisting of equal amounts of Ya and Yc subunits. 4. Our studies show that testis ligandin is identical with liver ligandin. Previously described differences are due to a contaminant identified as GSH S-transferase AA.

Animals↗
PubMed1981

The clinical spectrum of hepatic granuloma.

Hepatic granulomas diagnosed ante mortem by liver biopsy over a 9-year period at Groote Schuur Hospital, Cape Town, were reviewed. A diagnosis was made in 94% of the 116 cases studied. Tuberculosis was found to be the cause in 50% of all cases. In Black patients tuberculosis accounted for 83%. Lymphoma was a major cause in White patients, in whom it accounted for 28%. The clinical, haematological, biochemical and radiological features favouring each diagnostic category are described. The importance of follow-up and in some cases repeat biopsy is stressed.

Female↗
PubMed1981

Obstructive jaundice in pancreatitis.

Twelve patients with obstructive jaundice as a direct result of pancreatitis or its complications are described. The value of ultrasonography in the diagnosis of this condition is stressed. The criteria for surgical intervention and the operation of choice are discussed.

Adult↗
PubMed1981

Hepatic sequelae of congestive cardiac failure. Evidence for a liver lesion in patients in whom cardiac function has been restored to normal.

In order to test the hypothesis that clinical and biochemical features of liver disease due to cardiac failure regress upon relief of cardiac decompensation, 38 patients with constrictive pericarditis were studied before and after pericardiectomy for periods ranging from 1 week to 25 years. All patients were judged to be free of clinical evidence of heart failure. Hepatomegaly was present in 10 of the 38 patients studied. Of the patients studied 1-25 years after operation, 96% had elevated serum levels of total and conjugated bilirubin. The percentage Bromsulphalein (BSP) retention at 45 minutes was abnormal in all 29 patients studied 1 year or more after surgery. There was no significant correlation between the level of bilirubin or the percentage BSP retained when these were compared with the pre-operative height of jugular venous pressure, degree of pulsus paradoxus, duration of symptoms or degree of hepatic congestion. Our study reveals that the liver lesion of cardiac failure persists for up to 25 years after restoration of normal cardiac function.

Adolescent↗
PubMed1981

Leptospirosis experience at Groote Schuur Hospital, 1969-1979.

The diagnosis of leptospirosis requires a high index of suspicion and a knowledge of the wide variety of syndromes with which these patients present. The clinical and laboratory features of 14 patients with leptospirosis seen at Groote Schuur Hospital, Cape Town, between 1969 and 1979 are described.

Adult↗