Biomedical subjects
Publications and source records attributed to C Theodore.
Sixteen patients with adult metastatic renal cell carcinoma were treated with elliptinium acetate, 80 mg/m2.day, for 3 consecutive days every 3 weeks. Among the 14 patients evaluable, no objective effects were observed. The toxicity was mild and no patients experienced intravascular hemolysis.
One hundred fifty-three adult patients with metastatic renal carcinoma were treated over a 12-year period. Five successive chemotherapeutic protocols were used: vincristine or teniposide plus CCNU, elliptinium weekly or monthly, ifosfamide, and lastly, a multidrug regimen with adriamycin, vindesine, cyclophosphamide, cisplatinum, and dacarbazine. Results obtained with these different consecutive protocols were very disappointing with only ten (7%) objective responses encountered.
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The aim of this study was to assess the incidence of oesophageal abnormalities and to determine their nature in patients with retrosternal chest pain and normal coronary angiography with a negative coronary spasm provocation test. Oesophageal manometry was carried out in all cases with or without a spasm provocation (usually alkalosis) test. Forty consecutive patients were studied: 19 men (47.7 +/- 10.0 years) and 21 women (54.7 +/- 7.5 years). A history of gastro-intestinal disorder was obtained in 57 p. 100 of cases (hiatal hernia and/or gastro-oesophageal reflux, biliary lithiasis and/or cholecystectomy, gastritis). Seventeen patients had broad based powerful oesophageal contractions which are an established cause of pain; they were recorded under basal conditions in 5 cases and after a provocation test in 12 cases. Two patients had a megaoesophagus without giant waves. Thirteen patients had manometric signs of reflux (malposition and hypotonia of the lower oesophageal sphincter) of whom 7 had giant waves on provocation. In addition, three patients experienced pain during gastro-oesophageal reflux (1 case) or hypotonia of the lower oesophageal sphincter (2 cases). In all, a very probable oesophageal origin of the chest pain was demonstrated in 22 patients (55 p. 100 of cases).
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Four immunologically distinct subunits were characterized in glutathione (GSH) S-transferases of human liver. Five cationic enzymes (pI 8.9, 8.5, 8.3, 8.2 and 8.0) have an apparently similar subunit composition, and are dimers of 26 500-Mr (A) and 24 500-Mr (B) subunits. A neutral enzyme, pI 6.8, is a dimer of B-type subunits. One of the anionic enzymes, pI 5.5, is also a dimer of 26 500-Mr subunits. However, the 26 500-Mr subunits of this anionic enzyme form are immunologically distinct from the A subunits of the cationic enzymes, and have been designated as A'. Immunoabsorption studies with the neutral enzyme, BB, and the antibodies raised against the cationic enzymes (AB) indicate that A and B subunits are immunologically distinct. Hybridization in vitro of the A and B subunits of the cationic enzymes (AB) results in the expected binary combinations of AA, AB and BB. Studies with the hybridized enzyme forms indicate that only the A subunits express GSH peroxidase activity. A' subunits have maximum affinity for p-nitrobenzyl chloride and p-nitrophenyl acetate, and the B subunits have highest activity towards 1-chloro-2,4-dinitrobenzene. The other anionic form, pI 4.5, present in liver is a heterodimer of 22 500-Mr (C) and B subunits. The C subunits of this enzyme are probably the same as the 22 500-Mr subunits present in human lung and placental GSH transferases. The distinct immunological nature of B and C subunits was also demonstrated by immunoaffinity and subunit-hybridization studies. The results of two-dimensional polyacrylamide-gel-electrophoretic analyses indicate that in human liver GSH transferases, three charge isomers of Mr 26 500 (A type), two charge isomers of Mr 24 500 (B type) and two charge isomers of Mr 22 500 (C type) subunits are present.
Human brain contains one cationic (pI8.3) and two anionic (pI5.5 and 4.6) forms of glutathione S-transferase. The cationic form (pI8.3) and the less-anionic form (pI5.5) do not correspond to any of the glutathione S-transferases previously characterized in human tissues. Both of these forms are dimers of 26500-Mr subunits; however, immunological and catalytic properties indicate that these two enzyme forms are different from each other. The cationic form (pI8.3) cross-reacts with antibodies raised against cationic glutathione S-transferases of human liver, whereas the anionic form (pI5.5) does not. Additionally, only the cationic form expresses glutathione peroxidase activity. The other anionic form (pI4.6) is a dimer of 24500-Mr and 22500-Mr subunits. Two-dimensional gel electrophoresis demonstrates that there are three types of 26500-Mr subunits, two types of 24500-Mr subunits and two types of 22500-Mr subunits present in the glutathione S-transferases of human brain.
Six forms of glutathione S-transferases designated as GSH S-transferase I (pI 8.8), II (pI 7.2), III (pI 6.8), IV (pI 6.0), V (pI 5.3) and VI (pI 4.8) have been purified from rat lung. GSH S-transferase I (pI 8.8) is a homodimer of Mr 25,000 subunits; GSH S-transferases II (pI 7.2) and VI (pI 4.8) are homodimers of Mr 22,000 subunits; and GSH S-transferases III (pI 6.8), IV (pI 6.0) and V (pI 5.3) are dimers composed of Mr 23,500 and 22,000 subunits. Immunological properties, peptide fragmentation analysis, and substrate specificity data indicate that Mr 22,000, 23,500 and 25,000, are distinct from each other and correspond to Ya, Yb, and Yc subunits, respectively, of rat liver.
When butylated hydroxytoluene (BHT) was administered to rats, the smallest subunit Ya (Mr 22,000) of rat liver GSH S-transferases was found to undergo maximum induction. It is suggested that the differential induction of GSH S-transferase activities by BHT towards different substrates may be due to the differences in the induction of the constituent subunits of GSH S-transferases.
In rats, erythromycin has been shown to induce microsomal enzymes and to promote its own transformation into a metabolite which forms an inactive complex with reduced cytochrome P-450. To determine whether similar effects also occur in humans, we studied hepatic microsomal enzymes from six untreated patients and six patients treated with erythromycin propionate, 2 g per os daily for 7 days. In the treated patients, NADPH-cytochrome c reductase activity was increased; the total cytochrome P-450 concn was also increased but part of the total cytochrome P-450 was complexed by an erythromycin metabolite. The concn of uncomplexed (active) cytochrome P-450 was not significantly modified and the activity of hexobarbital hydroxylase remained unchanged. We also measured the clearance of antipyrine in six other patients; this clearance was not significantly decreased when measured again on the seventh day of the erythromycin propionate treatment. We conclude that the administration of erythromycin propionate induces microsomal enzymes and results in the formation of an inactive cytochrome P-450-metabolite complex in humans. However, the concn of uncomplexed (active) cytochrome P-450 and tests for in vitro and in vivo drug metabolism were not significantly modified.
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Two men aged 28 and 33 were found to have subcapsular haematoma of the spleen secondary to chronic alcoholic pancreatitis. One of the patients presented with a pancreatic pseudo-cyst, left amylase pleural effusion and thrombosis of the splenic vein. Selective coeliac and mesenteric angiography and, chiefly, echotomography pointed to the diagnosis, which was confirmed on abdominal incision and histopathological study of the lesions. From these two cases and a review of 63 cases previously published the authors describe the clinical symptoms (acute anaemia with abdominal tumour), pathogeny (vascular or enzymatic) and diagnosis of the condition. Echotomography of the pancreas seems to be the best non invasive method to detect splenic complications of chronic pancreatitis.
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