Early unconjugated hyperbilirubinaemia after paracetamol overdosage

A rapid increase of predominantly unconjugated bilirubin in the blood -- which was not due to haemolysis -- was observed in 38 of 60 patients who had taken an overdose of paracetamol. Studies in the rat given an overdose of the drug showed that within 24 hours there was a striking reduction in the activity of bilirubin glucuronyl-transferase and the content of cytochrome P.450 in the liver. It is suggested that such early damage of the hepatic endoplasmic reticulum contributes to the hyperbilirubinaemia of paracetamol poisoning.     

Intersubject variation of warfarin binding to protein in serum of normal subjects

The protein binding of warfarin was determined in the serum of 18 normal adult subjects (8 males and 10 females). A statistically significant negative correlation between free fraction of warfarin and albumin concentration was found. The free fraction of warfarin in the serum of women was significantly larger than that in the serum of men, apparently due to the lower albumin concentration in the serum of women.     

Endogenous oncornaviral DNA sequences: evidence for two classes of viral DNA sequences in guinea pig cells

The nature of the endogenous viral DNA sequences in guinea pig cells was studied by hybridization. A segment of the viral RNA (r-VRNA) hybridizing to abundant (or reiterated) DNA sequences (R-VDNA) was isolated by recycling to a Cot of 300. The hybridization of the recycled VRNA, as well as the total VRNA, was followed by determining their kinetics and by Wetmur-Davidson analysis. The kinetics of hybridization of total VRNA were complex, did not follow a second-order kinetics, and revealed two slopes by Wetmur-Davidson analysis. The recycled RNA, on the other hand, had a second-order reaction rate expected of the hybridization between a single species of RNA and DNA sequences and yielded a single straight line in a Wetmur-Davidson plot. The Cot1/2 and slope of the recycled r-VRNA was almost identical to that of the abundant VDNA sequences obtained from the hybridization data of the total VRNA. Guinea pig 28S rRNA with or without recycling was used in monitoring hybridization rate. The kinetics of hybridization of 28S RNA followed a second-order reaction and produced a single straight line by Wetmur-Davidson plot, with a second-order reassociation rate constant of 9.6 x 10(-3) liters/mol-s, a Cot1/2 of 104 mol-s/liter, and reiteration frequency of 146. There was no difference in the kinetics of hybridization of 28S RNA before and after recycling. These experiments showed that guinea pig cells contain two classes of VDNA sequences. (i) R-VDNA sequences with a second-order reassociation rate constant of 8.2 x 10(-4) liters/mol-s, a Cot1/2 of 1,219 mol-s/liter, and a reiteration frequency of 12 represent 37.5% of the viral genome. (ii) Unique VDNA sequences with a second-order reassociation rate constant of 1.2 x 10(-4) liters/mol-s, a Cot1/2 of 7,692 mol-s/liter, and a reiteration frequency of 2 represent 62.5% of the viral genome.     

The effect of vasectomy on pituitary-gonadal function in men

The testosterone concentration in allantoic fluid between 90 and 150 days of gestation in cattle can be used to determine the fetal sex; values were 442 +/- 20-3 (S.E.M.) pg testosterone/ml for males fetuses and 215 +/- 8-2 pg/ml for female fetuses.     

Haemoglobins of the shark, Heterodontus portusjacksoni II. Amino acid sequence of the alpha-chain

The amino acid sequence of the alpha-chain of the principal haemoglobin from the shark, H. portusjacksoni has been determined. The chain has 148 residues and is acetylated at the amino terminal. The soluble peptides obtained by tryptic and chymotryptic digestion of the protein or its cyanogen bromide fragments were isolated by gel filtration, paper ionophoresis and paper chromatography. The amino acid sequences were determined by the dansyl-Edman procedure. The insoluble "core" peptide from the tryptic digestion contained 34 residues and required cleavage by several prosteases before the sequence was established. Compared with human alpha-chain there are 88 amino acid differences including the additional seven residues which appear on the amino terminal of the shark chain. There is also one deletion and one insertion. The chain contains no tryptophan but has four cysteinyl residues which is the highest number of such residues recorded for a vertebrate globin. In the alpha1beta1 contact sites there are four changes in the oxyhaemoglobin form and six deoxy form. Nine of the 16, alpha1beta1 contact sites show variation while three of the haem contact sites have changed in comparison to the residues known to be involved in these interactions in horse haemoglobin alpha-chain. Use of the sequence data to estimate a time of divergence of the shark from the main vertebrate line yielded the value of 410 +/- 46 million years. The data, in general, support the palaeontological view that bony fishes arose before the elasmobranchs.     

Cell proliferation in the prostate complex of the castrate mouse

Cell proliferation during 100 h of continuous androgen challenge was studied in the seminal vesicle and coagulating gland of Balb/c mice castrated 3 days or 14 days prior to the first daily injection of 250 mug testosterone propionate. Continuous labelling with [3H] thymidine indicated that the seminal vesicle was almost totally responsive to androgen, as early as 3 days after castration, whereas the androgen sensitivity of the coagulating gland increased from 30% at 3 days after castration to 85% at 14 days after castration. In both tissues the magnitude of the proliferative reaction could be related to the extent of cell loss prior to stimulation. The duration of the pre-replicative phase in the response of the seminal vesicle to androgen was 20-25 h both at 3 and 14 days after castration. In the coagulating gland the pre-replicative phase was 40 h at 3 days after castration and 20 h at 14 days after castration. The maximum uptake of [7alpha-3H] testosterone administered to mice 3 days after castration was significantly greater (P less than 0-01) in the seminal vesicle compared to the coagulating gland. At 14 days the seminal vesicle and coagulating gland exhibited a similar capacity for uptake. The in vivo metabolism of [7alpha-3H] testosterone was studied by thin layer chromatography 30 min and 120 min after administration. A high proportion of the radioactivity extracted from all the tissues was associated with highly polar steroids. At 3 days after castration, the seminal vesicle, 2 h after administration of radioactive testosterone, retained a much higher proportion of radioactivity associated with dihydrotestosterone than did the coagulating gland. The localization of steroid in mice 3 days after castration was studied by dry-mount autoradiography at intervals up to 2 h after the injection of [1,2,6,7(n)-3H]-testosterone. A heavier deposition of silver grains was observed over autoradiographs of the seminal vesicle. In the seminal vesicle the grains were primarily located over nuclear areas whereas in the coagulating gland the grains were diffusely distributed over both nuclear areas and over cytoplasmic areas.     

A galactosidase immunosorbent test for human immunoglobulin E

We report here the development of a galactosidase-immunosorbent test (GIST) for immunoglobulin E (IgE) antibodies in which the amount of galactosidase adsorbed to a cellulose disc is a single valued function of IgE concentration in human serum. Rabbit anti-IgE immunoglobulin insolubilized on cellulose discs is incubated sequentially with human serum, sheep anti-IgE serum, and a covalent conjugate of rabbit antisheep immunoglobulin with the enzyme beta-D-galactoside galactohydrolase (E.C.) 3.2.1.23). Colorimetric assay of enzyme conjugate adsorbed to discs permits quantitation of 1.0 to 25 ng of IgE per test. Concentrations of IgE in 48 sera as measured by the GIST gave a linear correlation coefficient of 0.97 with IgE concentrations as determined by radioimmunoassay. Preliminary studies indicate that the GIST makes possible nonisotopic measurement of ragweed-specific IgE antibiotics in human serum. The GIST for IgE is simple to perform and requires neither short-lived radioisotopes, expensive scintillation detection equipment, nor scarce, purified IgE.     

Striated muscle in the pineal gland of swine

Striated muscle fibers (or cells) were observed in three of the six swine pineal glands. The muscle fibers occurred in clusters of several fibers about the parenchymal blood vessels. They were in general poorly developed, lacked regular cross striations and were not readily recognized histologically. The muscle fibers were, however, easily identified on electron microscopy because of the myofilaments they contain. In most of the muscle fibers, the myofilaments were arranged in ill-defined, disorderly bundles and rarely formed well-defined myofibrils and sarcomeres. The sarcotubular system was also poorly developed and triads were sparse and randomly scattered. Leptomeres were observed in several muscle fibers. The source of the muscle fibers in the pineal glands is not well understood and, whatever the source may be, the muscle fibers seem to remain poorly developed in the pineal glands.     

Trace element concentrations in higher fungi

The concentrations of ten trace elements, As. Br, Cd, Cu, Hg I, Mn, Se, Zn and V, have been determined in up to 27 species of higher fungi from several sites in Slovenia, Yugoslavia. Analyses were based on destructive neutron activation techniques. Data are presented and compared with the concentrations found in soils. Previously values were non-existent or scanty for these elements, so that the data represent typical levels for basidiomycetes. In addition to confirming high levels of mercury in many species, the survey also found that cadmium is accumulated to a surprising extent by most fungi, the average value being 5 ppm. Among other accumulations found was bromine by the genus Amanita, and selenium by the edible Boletus. Correlation analysis between all pairs of trace elements gave values for r of from 0.75 to 0.43 for 7 pairs (Cu and Hg, 0.75; Se and As, 0.69). As well as these features of biochemical interest, the values found and the pattern of accumulation suggest potential uses of fungi in environmental studies.