Comparative effects of cadmium, zinc, and lead in vitro on pulmonary, adrenal, and hepatic microsomal metabolism in the guinea pig

The in vitro effects of Cd, Zn, and Pb on pulmonary, adrenal, and hepatic microsomal enzyme activities in guinea pigs were compared. Cd and Zn produced concentration-dependent (20-200 microM) decreases in benzphetamine demethylase and biphenyl hydroxylase activities in adrenal, liver, and lung. Pb had no significant effect on either enzyme in any of the tissues studied. Adrenal and pulmonary enzymes were more sensitive to the effects of Cd and Zn than were hepatic enzymes. Benzo[a]pyrene hydroxylase and ethoxycoumarin deethylase activities were decreased by Zn, Cd, and Pb in adrenal, liver, and lung microsomes. The inhibitory effect on benzo[a]pyrene and ethoxycoumarin metabolism were far greater than those on benzphetamine or biphenyl metabolism. The relative potencies of the metals as inhibitors of xenobiotic metabolism were Zn greater than Cd greater than Pb. Cd and Zn also inhibited steroid 21-hydroxylase activity in adrenal microsomes, but Pb had no effect on steroid metabolism. In addition, microsomal epoxide hydratase activity in adrenal, liver, and lung was inhibited by Cd but not by Zn or Pb. The results demonstrate that adrenal and pulmonary microsomal enzymes, like those in liver, are inhibited by various metals. Inhibition of mixed-function oxidases by metals in vitro is apparently not related to changes in cytochrome P-450 levels or substrate binding to cytochrome P-450. In addition, the actions of Cd, Zn, and Pb in each tissue are highly dependent on the substrates employed.     

Sensitive radioimmunoassay for digoxin in plasma and urine

A reproducible and sensitive radioimmunoassay for digoxin in either serum, plasma or urine is described. Using 0.5 ml of serum or plasma, the assay sensitivity is 0.05 ng of digoxin/ml. The antiserum and tracer solutions employed are available in a kit sold in the United States. All other reagents were prepared in the laboratory. The assay allows measurement of digoxin in plasma or serum for 96 hours after single 0.5 mg doses of digoxin; this is necessary in human bioavailability studies to accurately estimate the total area under the digoxin concentration, time curve from zero to infinite time. In contrast, with the kit assay, employing 0.2 ml of plasma or serum, it has been reported that the 12 hr serum digoxin levels, after single 0.5 mg doses, are, in most subjects, below the sensitivity limit (about 0.5 ng/ml) of the assay.     

Pathogenesis of trimethyltin neuronal toxicity. Ultrastructural and cytochemical observations

The ultrastructural cytopathologic and cytochemical effects of trimethyltin (TMT) neurotoxicity were delineated in hippocampal and pyriform neurons of acutely intoxicated adult rats. TMT produced neuronal necrosis that preferentially involved hippocampal formation pyriform cortex. The first subcellular alterations were multifocal collection of dense-cored vesicles and tubules and membrane-delimited vacuoles in the cytoplasm of the perikaryon and proximal dendrite. Ultrastructural cytochemical examination revealed that the vesicles and tubules had acid phosphatase activity analagous to Golgi-associated endoplasmic reticulum (GERL). Shortly after the appearance of the GERL-like vesicles and tubules, autophagic vacuoles and polymorphic dense bodies accumulated in the neuronal cytoplasm. Some dense bodies appeared to arise from the dense-cored tubules. Neuronal necrosis was characterized by increased electron density of the cytoplasm and large, electron-dense intranuclear masses. Alterations of mitochondria and other organelles were not observed in the early stages of cell injury. No light- or electron-microscopic alterations were found in liver or kidney. Comparable subcellular alterations were observed in adult and neonatal rats chronically intoxicated with TMT. A series of other trialkyl and tricyclic tins and dimethyltin did not produce similar pathologic findings. The GERL-like accumulations are unique in neuronal cytopathology. These findings suggests that GERL and autophagy play an important role in the pathogenesis of TMT-induced neuronal injury.     

Effect of sulfate on carbon and electron flow during microbial methanogenesis in freshwater sediments

Rickettsiae of the spotted fever group were detected by haemocyte test in 8 (12%) of 51 partially engorged Dermacentor marginatus females collected in March/April 1975 in South Germany. Four strains of rickettsiae were isolated from ticks positive in haemocyte test. It was concluded with isolated strain BRD-1 and homologous immune guinea pig, hamster and mouse sera in CF cross reactions with antigens and immune sera against other members of the SF group, that the newly isolated strains are similar, almost undistinguishable from Rickettsia slovaca.     

Polyuridylic sequences and negative strands of Sindbis virus-specific RNAs: study by affinity chromatography on poly (A)-sepharose columns (author''s transl)

The experimental conditions of affinity chromatography on poly (A)-Sepharose columns have been determined. This method makes obvious the existence of polyuridylic acid sequences on the negative strands of Sinbis virus-spedific RNAs. The isolated RNAs are negative and positive strands hybrids. By polyacrylamide gel electrophoresis, it has been shown that the negative strands have the same length as the 26 S interjacent RNA at the 6th hour, and as the 42 S virion RNA at the 9th hour postinfection. The polyadenylic acid sequences of the virion RNA and of the replicative intermediate are therefore probably genetically coded.     

Histologic structures preserved for 21,300 years

Histologic examination of rehydrated tissue samples from late Pleistocene (Alaskan) mammal mummies demonstrates that the preservative effect of freezing and drying extends to remains 15,000 to 25,000 years old. Some muscle and liver tissue retained identifiable histologic structures. Most tissues were completely disintegrated and partly replaced by masses of bacteria, an indication of considerable postmortem decay before the remains were entombed beneath the permafrost zone.     

Ultrastructure and elemental composition of dormant and germinating Diplodia maydis spores

The ultrastructure of Diplodia maydis spores was studied in thin sections with a transmission electron microscope. Storage vacuoles were evenly distributed in the two cells. Some of the vacuoles that contained a dense osmiophilic sphere(s) were surrounded by a membrane, and had membranous aggregates around their periphery. The sport wall was composed of an electron-dense layer and an electron-translucent layer. An inner cytoplasmic membrane was present. Dormant and germinating spores were studied with scanning electron microscopy and also with a Si (Li) energy-dispersive X-ray analyzer. The dormant spore was ovate and usually two-celled with a central septum. Germination proceeded via a germ tube from the side of one end of the cell. Of several methods for preparation of specimens for X-ray analysis studied, freeze-dried spores mounted on carbon stubs and then further carbon coated gave the best results. X-ray analyses revealed that spore populations contained large amounts of Si, P, Cl, and K, smaller amounts of S and Ca, and trace amounts of Mg and Al. Analyses of single spores revealed high K and Cl and low P and Mg at one end of the cell with concomitant low K and Cl and high P and Mg in the central portion and other end of the cell. In two-celled germinating spores, high K and Cl occurred in the end of the nongerminating spore cell, whereas the germinating cell contained high P and Mg and low K and Cl. X-ray image maps revealed that K and Cl were located together at one end of the spore.