Browsing by Author "Kirsch, Ralph"
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- ItemOpen AccessEpidemiology, molecular characterisation and tropism of the Hepatitis G Virus / GBV-C(1999) Tucker, Timothy Johan Paul; Kirsch, Ralph; Robson, SimonThe hepatitis G virus and GBV-C are recently discovered variants of the same virus belonging to the family Flavivirus (HGV/GBV-C). Although initially thought to be a hepatitis virus, it has been shown to have no association with liver disease. No work has been performed on the prevalence or molecular characteristics of HGV/GBV-C in southern Africa. In addition, although it is clear that the liver is not the primary site of replication, there is no data on the sites of HGV/GBV-C replication in normal subjects. Thus, this study aimed to assess the prevalence of HGV/GBV-C carriage in the urban and rural adult Black communities of the Western and Eastern Cape Provinces of South Africa, and compare it to the prevalence of serological markers of the hepatitis viruses A-E. In addition, this study aimed to assess the molecular features of South African HGV/GBV-C isolates and demonstrate the organs where viral replication was present. The mean prevalences of antibodies to hepatitis A lgG, hepatitis B surface antigen and antibodies to hepatitis B surface antigen were 98%, 4.3% and 61.1 % respectively. The mean prevalence of antibodies to hepatitis C was 1.8%. No significant differences in prevalence were shown between the urban and rural regions for these viruses. The mean anti-hepatitis E prevalence varied from 5.8% to 19.1 % in the different regions. Those living in mud houses without access to chlorinated tap water had a significantly higher prevalence of antihepatitis E. No anti-hepatitis D positive samples were isolated. The overall prevalence of HGV/GBV-C was 26.9%, with rural communities having a significantly lower prevalence than urban communities. A significant relationship was observed between HGV/GBV-C infection with the use of illicit drugs, female gender, younger age and past blood transfusions. Phylogenetic analysis demonstrated a novel fourth South African HGV/GBV-C genotype, distinct from the previously described genotypes 1-3. In addition, certain isolates showed a major deletion in the highly conserved 5' non-coding region of HGV/GBV-C. Analysis of 23 tissue biopsies from infected cadavers suggested that the spleen and bone marrow were the primary sites of HGV/GBVC replication.
- ItemOpen AccessA four-year study of cirrhosis at Groote Schuur hospital(1999) Solombela, Archie Cornelius Siyolo; Hift, Richard; Kirsch, RalphINTRODUCTION: Groote Schuur Hospital (GSH) is a large academic hospital Cape Town. It serves a population of about 2 million, comprising three population groups, black people of African origin, coloured, who are people of Asian or mixed origin, and white - of European descent. The hospital serves as a secondary referral centre for the surrounding regions, as a tertiary referral centre for the Western Cape province and much of the Eastern Cape province, and as a quaternary super-specialist centre for certain services, including liver and cardiac transplantation, for much of South Africa. A significant number of patients with cirrhosis present for the first time at Groote Schuur Hospital with decompensation and a diagnosis of cirrhosis is made on the basis of association of signs of liver failure, portal hypertension, radiological features consistent with cirrhosis with or without a proven cause of cirrhosis (personal observation). A study in Italy and another study done in Birmingham showed that a proportion of 63% and 65% respectively of patients have decompensated cirrhosis when first seen and in the English study the figure was unchanged in 18 years (Saunders et al 1981, D'Amico et al 1986). Most patients with cirrhosis remain compensated for many years and have a relatively long-life expectancy. Clinical decompensation, which is evidenced by the development of one or more complications, has a poor prognosis. The high rate of repeated consultations in patients with cirrhosis confirmed the high morbidity associated with this condition (Dufour et al 1993). In the United States between 1973 and 1983, cirrhosis mortality declined by one third to 10.2/100 000 deaths and the decline continued through to 1987 when the death rate reduced to 9.2/100 000 deaths. Furthermore, an increase in morbidity was observed with this decreasing mortality rate (Noble et al 1993). AIM OF THE STUDY: Accordingly, this study was intended to delineate the demographic and clinical profile of patients with cirrhosis admitted to our hospital, to assess the relative importance of the various underlying causes of cirrhosis, to assess the frequency of complications of cirrhosis and describe their presentation and management, to assess the outcome of treatment and to estimate its cost.
- ItemOpen AccessPurinergic angiogenesis : an investigation of the role of extracellular nucleotide mediated signaling in angiogenesis(2006) Jackson, Shaun William; Robson, Simon; Kirsch, RalphAngiogenesis refers to the growth and maturation of new vessels from pre-existing differentiated blood vessels. Co-ordination of angiogenic responses is crucial for a wide range of physiological and pathological processes. In particular, angiogenesis is hypothesized to facilitate tumour growth and promote metastasis, prompting research into anti-angiogenesis based cancer therapies. CD39/NTPDasel is an ectoenzyme expressed by vascular endothelium that hydrolyses extracellular nucleoside di- and triphosphates to the monophosphate derivatives. As such, this enzyme has a role in modulating endothelial responses to mucleotides that bind specific receptors termed Purinergic-type 2(P2) receptors. Since a number proliferation and migration in vitro, we propose that nucleotide signalling influences the process of angiogenesis in vivo.
- ItemOpen AccessRadioimmunoassay and characterization of ligandin in the rat(1978) Bass, Nathan Micahel; Kirsch, RalphLigandin, a major soluble hepatic protein with the distinctive property of binding a wide range of organic anions, is a relative newcomer to the field of hepatic physiology and biochemistry, and its importance in relation to various aspects of hepatic and renal function has been given considerable stress (1-13).
- ItemOpen AccessA study of aminolaevulinic acid synthase(2001) Nahman, Carolyn Joy; Kirsch, Ralph; Meissner, PeterDelta-aminolaevulinic acid synthase (ALAS) is the first enzyme in the haem biosynthetic pathway, and in mammals is present in two isoforms - differing in regulation and encoded for on different chromosomes. The hepatic form is up-regulated in states of haem deficiency and thus implicated in the acute attack of porphyria. Given the large number of patients who suffer from an acute form porphyria in South Africa the regulation of the human hepatic form of the enzyme is of considerable interest.
- ItemOpen AccessVariegate porphyria : molecular aspects of variegate porphyria in South Africa and their biochemical and clinical consequences(2000) Hift, R J; Kirsch, RalphVariegate porphyria (VP) is the clinical disorder associated with a deficiency of the haemsynthesising enzyme protoporphyrinogen oxidase (PPO). VP is one of the commonest monogenic inherited disorders in South Africa. The clinical effects include photocutaneous sensitivity and the development of potentially life-threatening acute porphyric crises. Section 1 of this dissertation examines the molecular basis for VP in South Africa.