Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line.

A significant aspect of primary hepatic carcinoma in man is the high positive correlation of hepatocellular carcinoma with infection with hepatitis B virus (HBV)1. Analysis of the relationship between HBV infection and oncogenesis is difficult because natural infection with HBV is limited to man and experimental infection has been achieved only in chimpanzees and gibbons. Furthermore, because HBV has not been successfully propagated in cell culture, basic study of virus-cell interaction of the aetiological agent of one of the most widespread infections of man has been impossible. Recently, however, a cell line (PLC/PRF/5) derived from a human hepatoma biopsy was described which produces the HRV surface antigen (HBsAg) and so provides a tool for the experimental investigation of HBV in viro. We now report the derivation and characterisation of two additional cell lines primary liver carcinomas. In contrast to the PLC/PRF/5 cell line, these cell lines retain the capacity to synthesise many human plasma proteins, including both albumin and alpha-fetoprotein (AFP). One of these lines also produces BHsAg. We also present evidence that HBsAg synthesis and secretion in this cell line are correlated with the growth state of the culture. This finding is in contrast to the continuous HBsAg production found in the PLC/PRF/5 cell line.     

A structurally abnormal insulin causing human diabetes.

Insulin isolated from the pancreas of a diabetic patient with fasting hyperinsulinaemia showed decreased activity in binding to cell membrane insulin receptors and in stimulating cellular 2-deoxyglucose transport and glucose oxidation. Chemical studies suggest that the isolated hormone is a mixture of normal insulin and an abnormal variant which contains a leucine for phenylalanine substitution at position 24 or 25 of the insulin B-chain.     

Direct expression in Escherichia coli of a DNA sequence coding for human growth hormone.

DNA coding for human growth hormone was constructed by using chemically synthesised DNA in conjunction with enzymatically prepared cDNA. This 'hybrid' gene was expressed in Escherichia coli under the control of the lac promoter. A polypeptide was produced having the size and immunological properties characteristic of mature human growth hormone.     

Competence for genetic transformation in pneumococcus depends on synthesis of a small set of proteins.

In bacterial genetic transformation the uptake of DNA and its integration into the resident chromosome is dependent on a special cellular state, termed competence. In those species where appearance of competence has been studied, specific (but often poorly defined) growth conditions lead to a simultaneous development of competence in a substantial fraction of the cells in a culture. In Bacillus subtilis, and in Haemophilus species, competence appears in the stationary phase of growth or in certain other growth-limiting conditions. Streptococcus pneumoniae (pneumococcus) is perhaps unusual in that virtually all cells of a culture become competent, for a short period at a specific cell density during logarithmic growth, without perturbing the growth rate. The synchronous appearance of competence in pneumococcal cultures results from an autocatalytic effect of a small protein released by the cells that induces competence. The response to competence factor has been shown to require protein synthesis. We report here additional information on the nature of competence in pneumococcus: pulse-labelling studies show that for the brief period of competence protein synthesis is restricted to a few specific polypeptides.     

Evidence for the bilobal nature of diferric rabbit plasma transferrin.

Plasma transferrin is involved in iron transport within the circulatory system of vertebrates, and provides an iron source for haemoglobin synthesis and other metabolic requirements. However, despite extensive studies by spectroscopic, biochemical and physiological techniques, the nature of iron binding and the mechanisms of uptake and release of iron are not fully understood. Plasma transferrins are monomeric glycoproteins with a molecular weight of approximately 80,000 (ref. 2); they have two similar and very strong binding sites for Fe(III), together with two associated anion binding sites. Fragmentation studies on various transferrins have shown that the polypeptide chain is composed of two domains formed from the N-terminal and C-terminal halves of the polypeptide chain. Each domain contains one metal binding site. The marked sequence similarities which exist between the two halves may reflect a doubling of an ancestral structural gene during the phylogenetic development of the protein. Preliminary crystallographic investigations of diferric rabbit plasma transferrin have been reported from this laboratory. We now report initial studies of the X-ray structure determination of dife-ric rabbit plasma transferrin which have led to a 6-A resolution electron density map.     

Bombesin suppresses feeding in rats.

Bombesin (BBS) is a tetradecapeptide originally isolated from amphibian skin1. BBS-like immunoactivity is widely distributed in mammalian gut2-5, and plasma levels have been shown to rise sharply following feeding (ref. 6 and V. Erspamer, personal communication). The physiological actions of BBS are unknown. We have previously shown that the classic gut hormone cholecystokinin (CCK) is a powerful and specific suppressor of food intake7-9. Although CCK and BBS lack common amino acid sequences, they have certain common actions on gut viscera10,11. We have now shown that BBS also suppresses food intake, and we compare its action with that of CCK.     

0957 + 561 A, B: twin quasistellar objects or gravitational lens?

0957 + 561 A, B are two QSOs of mag 17 with 5.7 arc s separation at redshift 1.405. Their spectra leave little doubt that they are associated. Difficulties arise in describing them as two distinct objects and the possibility that they are two images of the same object formed by a gravitational lens is discussed.     

An independent microbial flora of the epithelium and its role in the ecomicrobiology of the rumen

IT has been suggested that the bacterial flora of the rumen should be considered as three distinct, interacting populations-the bacteria of rumen fluid (the population which has been studied most extensively), the bacteria associated with food particles, and the bacteria adhering to the epithelial wall of the organ(1). Until now, studies of the 'epithelial' population have been restricted to examination of postmortem samples of wall tissue and its attached bacterial flora(2-5). A recently developed technique(6) for feeding young sheep for long periods solely by infusion of protein and other essential nutrients into the abomasum, and of volatile fatty acids and bicarbonate buffer into the rumen, has provided us with an opportunity to study in isolation the role of the bacterial population of the wall in the ecomicrobiology of the rumen in the living animal. Our studies show that this population can exist independently of the other two populations, that it is primarily responsible for urea digestion in the rumen and that it initiates breakdown of dead epithelial tissue. Furthermore, our results point to an inverse relationship between ammonia concentration and ureolytic activity in rumen fluid, which may account for the control which ammonia exerts over flux of urea across the rumen wall(7-9).