Isolation of cDNA clones encoding T cell-specific membrane-associated proteins

Of 10 distinct cloned DNA copies of mRNAs expressed in T lymphocytes but not in B lymphocytes and associated with membrane-bound polysomes, one hybridizes to a region of the genome that has rearranged in a T-cell lymphoma and several T-cell hybridomas. These characteristics suggest that it encodes one chain of the elusive antigen receptor on the surface of T lymphocytes.     

Origin of a gene regulatory mechanism in the evolution of echinoderms

A rich diversity of ancient sea urchin lineages survives to the present. These include several advanced orders as well as the cidaroids, which represent the group ancestral to all other sea urchins. Here we show that all advanced groups of sea urchins examined possess in their eggs a class of maternal messenger RNA (mRNA) encoded by the evolutionarily highly conserved alpha-subtype histone genes. The maternal histone mRNAs are unique in their time of accumulation in oogenesis, their localization in the egg nucleus and their delayed timing of translation after fertilization. Cidaroid sea urchins as well as other echinoderm classes, such as starfish and sea cucumbers, possess the genes but do not have maternal alpha-subtype histone mRNAs in their eggs. Thus, although all the echinoderms examined transcribe alpha-subtype histone genes during embryogenesis, the expression of these genes as maternal mRNAs is confined to advanced sea urchins. The fossil record allows us to pinpoint the evolution of this mode of expression of alpha-histone genes to the time of the splitting of advanced sea urchin lineages from the ancestral cidaroids in a radiation which occurred in a relatively brief interval of time approximately 190-200 Myr ago. The origin of a unique gene regulatory mechanism can thus be correlated with a set of macroevolutionary events.     

Monoclonal antibodies define differential ras gene expression in malignant and benign colonic diseases

DNAS of some human tumours can transform NIH 3T3 fibroblast cells, thus demonstrating the transforming potential of human ras genes (Hu-rasHa, Hu-rasKi, and Hu-rasN, respectively Harvey, Kirsten and neuroblastoma ras genes). Only a small percentage of a given type of human carcinoma, however, scores positive in this assay system. Activation of ras and subsequent transformation of NIH 3T3 cells are either by a point mutation in the ras gene or enhanced expression of the normal, or proto-onc, ras gene. If the transformation of a given human tumour involves the enhanced expression of the normal or cellular ras gene and the resulting gene product, the tumour DNA would probably score negative in the NIH 3T3 transfection assay. In human colon carcinoma, for example, lesions at position 12 of Hu-rasKi have been found. None of nine colon carcinomas obtained at biopsy, however, contain the ras lesion at this position, using a Hu-rasHa probe; one other colon carcinoma does appear to contain amplified proto-onc ras, and other colon carcinomas do have increased levels of ras RNA. There are at least three explanations for these observations. Either very few colon carcinomas contain point-mutated ras, the lesion in the majority of colon carcinomas is at a position other than 12 or ras activation in many colon carcinomas involves the enhanced expression of either the point-mutated or proto-onc form of a ras gene. We have now used monoclonal antibodies directed against a synthetic peptide reflecting sequences of the human T24 ras gene product to define ras p21 protein expression in a spectrum of colonic disease states. Immunohistochemical analyses of individual cells within tissue sections reveal differences in ras p21 expression in colon carcinomas compared with normal colonic epithelium, benign colon tumours and inflammatory or dysplastic colon lesions. Our data suggest that ras p21 expression is correlated with depth of carcinoma within the bowel wall, and is probably a relatively late event in colon carcinogenesis.     

Brain potentials during reading reflect word expectancy and semantic association

The neuroelectric activity of the human brain that accompanies linguistic processing can be studied through recordings of event-related potentials (e.r.p. components) from the scalp. The e.r.ps triggered by verbal stimuli have been related to several different aspects of language processing. For example, the N400 component, peaking around 400 ms post-stimulus, appears to be a sensitive indicator of the semantic relationship between a word and the context in which it occurs. Words that complete sentences in a nonsensical fashion elicit much larger N400 waves than do semantically appropriate words or non-semantic irregularities in a text. In the present study, e.r.ps were recorded in response to words that completed meaningful sentences. The amplitude of the N400 component of the e.r.p. was found to be an inverse function of the subject's expectancy for the terminal word as measured by its 'Cloze probability'. In addition, unexpected words that were semantically related to highly expected words elicited lower N400 amplitudes. These findings suggest N400 may reflect processes of semantic priming or activation.     

Period multupling-evidence for nonlinear behaviour of the canine heart

Although there has recently been considerable interest in applying the theory of nonlinear dynamics to the analysis of complex systems, as yet applications of the theory to biological systems in vivo have been very limited. We report here evidence of nonlinear behaviour in the electrocardiogram and arterial blood pressure traces of the noradrenaline-treated dog. Noradrenaline produces variations in these traces that repeat themselves with regular periods of integral numbers of heart-beats (period multupling), an effect that resembles the 'period-doubling' and other 'bifurcative' behaviour observed when the driving frequency of a nonlinear oscillator is increased above a critical value. The simplest type of periodic variation that we report is the so-called 'electrical alternans', which has long been known as one response of cardiac electrical activity to certain stresses and disease states.     

Iscom, a novel structure for antigenic presentation of membrane proteins from enveloped viruses

We describe here a novel type of immunostimulating complex, called 'iscom', in which virus membrane proteins are presented in a multimeric form. The matrix of the iscom is the glycoside Quil A (Spikoside; Iscotec AB), extracted from the bark of Quillaja saponaria Molina, which forms micelles at the critical micellar concentration of 0.03%. In micelle form, Quil A probably has regions accessible for hydrophobic interaction with the membrane proteins so that it can form complexes with them. Iscoms have been prepared with membrane proteins of para-influenza-3 (PI-3), measles and rabies viruses, and their immunizing potency tested in animals. In these experiments, iscoms prove to be at least 10 times more potent than micelles formed by aggregation of the membrane proteins alone. Iscoms of PI-3 and measles viruses also stimulate the formation of antibody to the fusion (F) protein, which is considered to be poorly immunogenic. No side effects of iscoms or of protein micelles have been observed.     

现代技术中的微量级热现象

近年来，在制造具有新颖结构的微型器件和材料（例如微电子器件、微机电系统和各种先进材料）方面取得了巨大的进展。这种发展使得热科学领域中的热现象。从发生在大量级结构中转移到发生在级结构中。对于更好地理解和控制能量传递而言，这种转移既提出了挑战又提供了机遇。本文从微尺寸、微结构和微时间三方面说明了上述微量级热现象。     

Direct addition of insulin inhibits a high affinity Ca2+-ATPase in isolated adipocyte plasma membranes.

The mechanism by which insulin regulates cellular metabolism remains unknown although indirect evidence suggests that alterations in intracellular calcium are important. More specifically, it has been proposed that insulin triggers an increase in intracellular calcium which is responsible for the subsequent modification of metabolic activities. The cell maintains a large electrochemical gradient for ionised calcium between the cytoplasm (less than 10(-6) M, as determined for muscle and nerve) and the extracellular environment (less than 10(-3) M). The plasma membrane may, therefore, be important in the regulation of calcium homeostasis, as a slight alteration in the processes maintaining this gradient could result in marked changes in cytoplasmic calcium. One such process is the active extrusion of calcium from the cell by a high affinity calcium-stimulated ATPase (Ca2+-ATPase). Such a mechanism has been well established in red cells and is postulated in nerve, liver and muscle. We have identified a high affinity Ca2+-ATPase in a plasma membrane-enriched subcellular fraction isolated from rat adipocytes which may provide the enzymatic basis for a calcium extrusion pump. We demonstrate here that the Ca2+-ATPase is specifically inhibited by the direct addition of physiological concentrations of insulin to the direct addition of physiological concentrations of insulin to the isolated plasma membranes. This effect suggests that direct regulation of calcium homeostasis may represent an important event in the mechanism of action of insulin.     

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.