Stereostructure of amphotericin A.
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Biomedical subjects
Publications and source records attributed to J Pawlak.
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The gross structure of perimycin A was revised: the position of the keto group was changed from C-13 to C-5. The stereostructure of perimycin A was established based upon NMR studies.
NMR studies of rimocidin, consisting of DQF-COSY, ROESY, HSQC, HMBC and 1D-TOCSY experiments, resulted in the assignment of the absolute configuration of the rimocidin chiral centers as 2S, 3R, 9S, 11R, 13S, 14R, 15S, 17R, and 27R. The geometry of tetraene chromophore was found to be all-trans.
The aim of this work is to present the correlation between the initial microscopic pattern of the liver graft and clinical and laboratory findings. In the Department of General Surgery and Liver Diseases 6 specimens were taken from 4 livers destined for planned liver transplantations. They were taken from the organ rinsed in UW solution, processed and stained extemporaneously. Quick HE staining was performed in some cases. Two livers were qualified for transplantation although they showed negligible histopathological changes. In one of these cases there was a clinical and pathological disagreement. The results of histological examination were crucial in qualification of the liver for grafting. One organ was disqualified because of negative clinical and pathological findings, while two other livers were disqualified after clinical examination. We resigned from the transplantation of liver of the last donor, who exhibited unsatisfactory clinical tests in spite of good pathological results.
In December 1994 an orthotopic liver transplantation was performed in a 46-year old female patient with liver failure due to primary biliary cirrhosis. The patient was discharged on the 31-st postoperative day. The graft was obtained at the multi-organ harvesting. The results of the donor's biochemical tests and the histological estimation of the graft tissue allowed to prognose a successful postoperative course.
The authors present 225 patients with various forms of portal system venous thrombosis (PSVT), of various origin and etiology. The largest group (120 patients) were the young people suffering from portal hypertension due to pre-hepatic venous obstruction of uncertain etiology, lasting since childhood. The next group consisted of 75 patients with liver cirrhosis coexisting with PSVT. In other cases PSVT was diagnosed as coincident with: Budd-Chiari Syndrome (8 cases), liver tumors (9 cases), chronic pancreatitis (3 cases) and polycythaemia (2 cases). In 3 cases PSCT developed postoperatively and in 5 cases after oral contraceptives. Diagnosis of coexisting PSVT deteriorates the prognosis in liver cirrhosis. The overall mortality was 16%. The course of the disease depends on extensiveness and dynamism of thrombosis, but consequently leads to the development of portal hypertension. The most effective diagnostic procedures are: CT and USG with Doppler flowmetry. Bleeding esophageal varices require either sclerotherapy or surgical treatment--decompressive shunts or "non-shunt" procedures. In the cases of recent thrombosis, without bleeding varices, thrombolytic therapy appears to be effective.
The stereostructure of the heptaene macrolide antibiotic candidin was established on the basis of NMR studies: 13C, DQF-COSY, ROESY and C,H-COSY experiments. The absolute configuration of the candidin chiral centers were assigned as 3R, 5S, 10R, 11R, 13R, 15S, 16R, 17S, 19S, 34S, 35R, 36R and 37S.
Own material of 7 patients is presented pathology: venous thrombosis involving both hepatic veins and portal system, resulting in severe impairment of liver function and portal circulation, leading up to a fatal end (if not treated). Neither surgical decompression nor liver transplantation is feasible from the technical point of view. Patients were treated with activators of fibrinolysis. In four cases the treatment was effective and resulted in recanalisation of the previously occluded veins. Early re-thrombosis was the reason of death in one case. One patient died 4 years later because of cerebral vascular thrombosis. Two others live over 5 years, symptom-free. The authors consider thrombolytic treatment as a life saving procedure in cases of hepatic and portal venous thrombosis.
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A DNA cross-link adduct of the antitumor agent mitomycin C (MC) to DNA has been isolated and characterized; the results provide direct proof for bifunctional alkylation of DNA by MC. Exposure of MC to Micrococcus luteus DNA under reductive conditions and subsequent nuclease digestion yielded adducts formed between MC and deoxyguanosine residues. In addition to the two known monoadducts, a bisadduct was obtained. Reductive MC activation with Na2S2O4 (sodium dithionite) leads to exclusive bifunctional alkylation. The structure of the bisadduct was determined by spectroscopic methods that included proton magnetic resonance, differential Fourier transform infrared spectroscopy, and circular dichroism. Formation of the same bisadduct in vivo was demonstrated upon injection of rats with MC. Computer-generated models of the bisadduct that was incorporated into the center of the duplex B-DNA decamer d(CGTACGTACG)2 indicated that the bisadduct fit snugly into the minor groove with minimal distortion of DNA structure. A mechanistic analysis of the factors that govern monofunctional and bifunctional adduct formation is presented.
Thioesterase II, the key enzyme which regulates the production of medium-chain fatty acids by the mammary fatty acid synthetase, is expressed specifically in epithelial cells of the rat mammary gland, regardless of their state of differentiation, and we consider the enzyme to be a reliable marker for this cell type. The objective of this study was to determine whether this enzyme is expressed universally in tumors originating from rat mammary epithelial cells and whether it might be shed into the serum of host animals. Immunoreactive thioesterase II was detected in all of the epithelial derived mammary tumors tested, being highest in tumors that exhibited obvious epithelial morphology. Two of the tumors, R3230AC and DMBA 1, were transplanted into Fischer 344 rats and the levels of thioesterase II in the tumor and serum were monitored by enzyme immunoassay. Thioesterase II content of the transplanted tumors fell to, and remained at, a low level during the first week following transplantation. During this period the transplanted tumor established a new network of blood vessels; no thioesterase II was detectable in the serum. Subsequently, thioesterase II levels in the tumors returned to the values observed before transplantation and thioesterase II was detectable in the serum. Of 51 rats transplanted with the R3230AC tumor, 37 showed elevated serum thioesterase II levels; of 40 transplanted with the DMBA 1 tumor, 35 showed elevated serum thioesterase II. Furthermore, there was a statistically significant correlation between serum thioesterase II and tumor burden in both tumor model systems. The identity of the serum antigen reacting with anti-thioesterase II antibodies was confirmed, by Western immunoblotting, to be full-length thioesterase II polypeptide. Parallel studies with fatty acid synthetase, an enzyme with an ubiquitous tissue distribution, indicated as expected that serum levels of this enzyme were unlikely to provide a reliable index of mammary tumor status. These results indicate that thioesterase II may be a useful serum marker for mammary cancer.
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Metabolic, enzymologic, and immunohistochemical techniques have been used to show that a human cell line of breast epithelial origin synthesized medium chain fatty acids via the ubiquitous fatty acid synthetase and a mammary-specific chain-terminating enzyme, thioesterase II. Previous studies in our laboratory with rodents indicated that thioesterase II is expressed exclusively in mammary epithelial cells, an observation consistent with the physiologic role of the enzyme in milk fat synthesis. Results of the present study suggest that the enzyme exhibits a similar cell specificity in its expression in humans and that the specificity is maintained in normal and neoplastic tissues. Thus thioesterase II was detected immunohistochemically in normal human breast epithelia derived from both lactating and nonlactating breast tissue, in cultured cells derived from both primary breast epithelial tumors and from a metastatic tumor of breast origin, and in several human breast epithelial cell lines; the enzyme could not be detected in HeLa cells, in a colon carcinoma, or in a mammary myoepithelial cell line. These findings raise the possibility that thioesterase II may be of use as a diagnostic tool to identify human tumors of breast epithelial origin.
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