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Biomedical subjects

G E Austin

Publications and source records attributed to G E Austin.

At least 73 records · Page 4Linked to original sources

Sequence complexity of nuclear RNA from 2-acetylaminofluorene-induced rat hepatomas and host cirrhotic liver.

The sequence complexities of nuclear of RNAs from 2-acetylaminofluorene-induced rat hepatomas and host cirrhotic livers were compared in RNA-driven and host cirrhotic livers were compared in RNA-driven hybridization experiments using iodinated single-copy DNa as a probe. Normal liver nuclei RNA hybridized to 10.0 +/- 0.3+ (mean +/- S.D.) of the DNA, indicating an RNA sequence complexity of 3.8 x 10(8) nucleotides. Although nuclear RNAs from cirrhotic livers displayed a greater variation between animals, the mean values for percent DNA hybridized (9.5 +/- 2.0%) and RNA sequence complexity (3.6 x 10(8) nucleotides) for 5 cirrhotic livers examined did not differ significantly from normal. Analysis of nuclear RNAs from 10 tumors, 8 of which were classified as moderately to well differentiated histologically, revealed a level of hybridization (9.5 +/- 1.8%) and a mean value of RNA sequence complexity (3.6 x 10(8) nucleotides) that were almost identical with those for normal liver. Variation in the complexity amont tumors was slightly less than that among cirrhotic liver RNAs. These results suggest that while growth characteristics, biochemical properties, and physiology are known to vary between hepatomas and normal or cirrhotic liver tissue, there is no substantial or consistent difference in the RNA sequence complexity of chemically-induced hepatoma cells compared with normal or chemically-induced cirrhotic liver.

2-Acetylaminofluorene↗

A novel method for the small scale synthesis of N-acetoxy-2-acetylaminofluorene and its adducts.

The carcinogen N-acetoxy-2-acetylaminofluorene (N-acetoxy-AAF) can be synthesized effectively in milligram amounts by reacting N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF) with acetic anhydride in a continuously mixed, closed 2-phase system consisting of ethyl ether/petroleum ether (2 : 1 v/v) and dilute sodium bicarbonate. The organic phase containing N-acetoxy-AAF can be added directly to 10 mm sodium citrate/20% ethanol to synthesize nucleoside or nucleotide adducts without the need to crystallize or resuspend N-acetoxy-AAF in a polar solvent. The advantage of the method is that it makes possible the synthesis of nucleic acid derivatives of N-acetoxy-AAF with high specific activity in small quantities.

2-Acetylaminofluorene↗

Fatal veno-occlusive disease of the liver following high-dose 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and autologous bone marrow transplantation.

Veno-occlusive disease of the liver has recently been reported to occur in patients receiving multiagent chemotherapy together with total-body irradiation and bone marrow transplantation for malignancies. Reported is a case of a 22-year-old woman with disseminated diffuse histiocytic lymphoma in whom fatal hepatic veno-occlusive disease developed two and one-half weeks following high-dose 1,3-bis(2-chloroethyl)-1-nitrosourea) (BCNU) therapy and autologous bone marrow transplantation. This appears to be the first report of this entity in association with high-dose BCNU employed as a single chemotherapeutic agent.

Adult↗

Cholangiocarcinoma arising in Caroli's disease.

We studied the clinical, roentgenographic, and pathologic features of what is, to our knowledge, the seventh reported case of cholangiocarcinoma associated with Caroli's disease. Review of the literature reveals that the incidence of carcinoma in patients with this condition is higher than that previously reported for other forms of biliary-tract ectasia. Bile stasis, cholangitis, and the presence of carcinogens and promoters in bile may combine to produce the high incidence of carcinoma in these patients.

Adenoma, Bile Duct↗

Long-limbed campomelic dwarfism. A radiologic and pathologic study.

Comparison of the roentgenographic and pathologic features of a case of classic, long-limbed campomelic dwarfism with those of previously reported cases leads to the conclusion that the bony abnormalities in this disorder are not due to an intrinsic abnormality of cartilage formation or of osteoblast or osteoclast function. Likewise, no defect in bone collagen, ground substance, or mineralization is evident. The bowing of the long bones may be the result of poorly understood muscular stresses operative in utero. Widespread defects in other organ systems are present, with considerable variation from patient to patient. Phenotypic females with disorder commonly suffer from gonadal dysgenesis. Autosomal recessive inheritance is suggested for a subgroup of these patients, but environmental factors may be causative in some instances.

Abnormalities, Multiple↗

Abnormal cerebral cortical convolutions in an XYY fetus.

Because of maternal disease a pregnancy was electively terminated at 21 weeks of fetal gestation. At autopsy the fetus showed an abnormal pattern of cerebral cortical convolutions involving the frontal lobes. Karyotpic analysis revealed an XYY sec chromosome constitution. This observation, if confirmed in other XYY cases, raises the possibility that a developmental abnormality of the cerebral cortex may be involved in the higher-than-normal risk for behavioral disability exhibited by men with this genotype.

Cerebral Cortex↗

Pre-atherosclerotic lesions in Down syndrome.

Autopsy examination of seven non-institutionalised Down syndrome patients (age ten to twenty-five years) revealed normal prevalence of pre-atherosclerotic lesions. Atherosclerotic plaques were observed in one of these subjects (age fourteen years), refuting reported implications that this population is atheroma-free. However, atheromatous aortic lesions were not seen in an eighth subject (age fifty years), raising the possibility that an atheroma-free subgroup of patients with Down syndrome may exist.

Adolescent↗

Focal fatty change of the liver, a hitherto poorly recognized entity.

Fatty change of the liver is a well-recognized entity associated with many clinical situations. It is a diffuse lesion although it may show centrolobular or periportal accentuation. Focal fatty change, on the other hand, is a rarely recognized and poorly characterized entity. We are presenting 10 cases of this condition. The lesions were discovered incidentally at post mortem examination in patients ranging in ages from 26 mo to 79 yr. The nodules measured up to 4.0 cm in diameter, were predominantly subcapsular in location, and the majority occurred in livers with minimal diffuse steatosis. At autopsy some had been confused with abscesses and metastases. The underlying disease processes and therapy were examined to determine etiology. Focal ischemia superimposed upon conditions producing fatty change is postulated as a pathogenic mechanism for this entity. Focal fatty change may have importance in the differential diagnosis of space-occupying lesions of the liver.

Adult↗

Preatherosclerotic aortic lesions in cystic fibrosis.

Patients with cystic fibrosis have fat malabsorption, providing an experimental model for evaluation of the hypothesis that a low-fat intake may prevent atherosclerosis. We studied the frequency and extent of aortic precursor lesions (fatty streaks, early fibromusculoelastic lesions, late fibromusculoelastic lesions) found at autopsy in this disease as well as in other patients with debilitating disorders but with no apparent impairment of fat absorption. Fatty streaks were less common in the cystic fibrosis group, as were the late fibromusculoelastic lesions. There was no significant difference in the frequency, length, or thickness of the early fibromusculoelastic lesions. The findings suggest that fat may be responsible for progression but not initiation of the fibromusculoelastic precursor lesions, and support the concept that early restriction of dietary fat may prevent, delay, or otherwise modify atherosclerosis in the adult.

Adolescent↗

Differences in the circular dichroism spectra of of eu- and heterochromatin fractions from rat liver.

Significant differences are observed between the CD spectra of eu- and heterochromatin prepared by fractionating mechanically sheared rat liver chromatin on linear sucrose density gradients. Heterochromatin has a broad positive CD at 270--280 nm, a cross-over point at 256 nmn, and a negative shoulder at 248 nm. Euchromatin displays a shift in the positive peak to 267 nm and the cross-over point to 254 nm, as well as an intensification of the 267 nm peak. The negative shoulder at 248 nm is absent in euchromatin. These spectral differences between eu- and heterochromatin are present in both low and high ionic strength media. Mechanical shearing does not induce CD alteration and anomalous light scattering is absent in our system. The greater RNA content of euchromatin compared to heterochromatin cannot account for the spectral differences. These results suggest that the DNA conformation of euchromatin is distinct from that of heterochromatin and they may provide clues to the reasons for the greater transcription of euchromatin.

Animals↗

A search for antibodies to luteinizing hormone receptors in premature ovarian failure.

We recently published evidence of the presence of circulating antibodies in the sera of patients who had the diagnosis of premature menopause syndrome. This led to the question: Is there a circulating antibody in the sera of patients with premature menopause syndrome which interferes with gonadotropin-luteinizing hormone (LH) receptor interaction on the luteal cell surface? Serum samples from 14 women with the diagnosis of Premature menopause syndrome were examined to see whether they would block the binding of 125I-labeled human chorionic gonadotropin (hCG) to human corpora lutea. All patients had spontaneous cessation of menses before the age of 35 years and documentation of increased gonadotropin secretion and failure of estrogen secretion. When the sera of the study group were incubated with 125I-labeled hCG and LH receptor from human corpora lutea, no difference in binding was observed when compared with controls. This suggests that there is no circulating antibody that interferes with hCG-LH receptor interaction and that would thereby lead to loss of ovarian function in premature menopause syndrome.

Adult↗

Hepatic RNA synthesis in rats treated with ethylene thiourea.

The ability of ethylene thiourea (ETU) to inhibit RNA synthesis in rat liver was investigated. This compound, a possibly carcinogenic metabolite to the ethylene-bis-dithiocarbamate fungicides, was administered to rats by intraperitoneal injection, by nasogastric tube and in the diet, and rates of RNA synthesis were determined. By contrast with the carcinogens thioacetamide and acetylaminofluorene, high doses of ETU administered by any of these routes failed to inhibit the synthesis of nuclear or cytoplasmic RNA. In this respect ETU appears to differ from most hepatocarcinogens in its effect on cellular metabolism.

Animals↗