Multiple liquid crystal phases of DNA at high concentrations

DNA packaging in vivo is very tight, with volume concentrations approaching 70% w/v in sperm heads, virus capsids and bacterial nucleoids. The packaging mechanisms adopted may be related to the natural tendency of semi-rigid polymers to form liquid crystalline phases in concentrated solutions. We find that DNA forms at least three distinct liquid crystalline phases at concentrations comparable to those in vivo, with phase transitions occurring over relatively narrow ranges of DNA concentration. A weakly birefringent, dynamic, 'precholesteric' mesophase with microscopic textures intermediate between those of a nematic and a true cholesteric phase forms at the lowest concentrations required for phase separation. At slightly higher DNA concentrations, a second mesophase forms which is a strongly birefringent, well-ordered cholesteric phase with a concentration-dependent pitch varying from 2 to 10 micron. At the highest DNA concentrations, a phase forms which is two-dimensionally ordered and resembles smectic phases of thermotropic liquid crystals observed with small molecules.     

Incubation periods for paediatric AIDS patients

A recent seroprevalence study of newborns indicates that one in 62 children born in New York City has antibodies to the human immunodeficiency virus (HIV). The distribution of incubation periods for paediatric patients is needed to estimate future AIDS case loads from these seroprevalence data. Current estimates of incubation periods for paediatric patients are based on limited data. We use parametric and non-parametric methods to analyse incubation periods for 215 paediatric patients with AIDS whose only known route of infection is maternal. We conclude that incubation periods are longer than previously reported; that there is a distinct knee in the incubation period distribution at seven months which suggests two risk populations; and that there is an increase in incidence which is consistent with exponential growth.     

Positive selection of CD4+ thymocytes controlled by MHC class II gene products

The mature T-cell antigen receptor repertoire is characterized by lack of reactivity to self-components as well as by preferential reactivity to foreign antigens in the context of polymorphic self-proteins encoded within the major histocompatibility complex. Whereas the former characteristic (referred to as negative selection or tolerance) is associated with intrathymic deletion of T cells expressing T-cell antigen receptor beta-chain variable (V beta) domains, which confer a preferential reactivity to self antigens, the existence of the latter (referred to as positive selection or MHC restriction) has so far only been inferred indirectly from functional studies. We show here that intrathymic deletion of V+beta 6 T cells (reactive with a self-antigen encoded by the Mlsa locus) is controlled by polymorphic MHC class II determinants. Furthermore, in mice lacking expression of Mlsa, the same class II MHC loci control the frequency of occurrence of V+beta 6 cells among mature CD4+ T lymphocytes. These data are direct evidence for positive selection by MHC determinants in the thymus in unmanipulated animals.     

Identification of a new class of steroid hormone receptors

The gonads and adrenal glands produce steroids classified into five major groups which include the oestrogens, progestins, androgens, glucocorticoids and mineralocorticoids. Gonadal steroids control the differentiation and growth of the reproductive system, induce and maintain sexual characteristics and modulate reproductive behaviour. Adrenal steroids also influence differentiation as well as being metabolic regulators. The effects of each steroid depend primarily on its specific receptors, the nature of which could therefore provide a basis for classification of steroid hormone action. The successful cloning, sequencing and expression of the human glucocorticoid (hGR) (ref. 1), oestrogen (hER), progesterone (hPR), and mineralocorticoid (hMR) receptors, complementary DNA, plus homologues from various species, provides the first opportunity to study receptor structure and its influence on gene expression. Sequence comparison and mutational analysis show structural features common to all groups of steroid hormone receptors. The receptors share a highly conserved cysteine-rich region which functions as the DNA-binding domain. This common segment allows the genome to be scanned for related gene products: hMR cDNA for example, was isolated using an hGR hybridization probe. In this study, using the DNA-binding domain of the human oestrogen receptor cDNA as a hybridization probe, we have isolated two cDNA clones encoding polypeptides with structural features suggestive of cryptic steroid hormone receptors which could participate in a new hormone response system.     

Endocrine and exocrine pancreatic function after camostate-induced growth of the organ

It is well known that oral administration of camostate induces hyperplasia and hypertrophy of the rat pancreas. It is not clear, however, whether pancreatic hormone and enzyme secretion are affected by camostate treatment.In rats, daily administration of 200 mg camostate/kg b. wt for 14 days significantly increased pancreatic weight and pancreatic content of DNA, protein, amylase, lipase, trypsin and chymotrypsin, as well as the amount of insulin, glucagon and somatostatin. In the intact animal, blood glucose levels and serum concentrations of insulin and glucagon in response to an oral glucose load were not impaired after camostate treatment. In the isolated perfused pancreas, however, insulin and glucagon secretions were reduced, whereas somatostatin release was not affected. The volume of pancreatic juice produced by the unstimulated isolated perfused organ, as well as protein and enzyme secretion, were increased after camostate treatment. Likewise, the isolated perfused pancreas from camostate-treated rats secreted a larger volume of pancreatic juice and more protein in response to cholecystokinin (CCK), while enzyme secretion was affected in a non-parallel manner: amylase release was markedly reduced, lipase release was unchanged, and release of trypsin and chymotrypsin was increased.     

The influence of prostacyclin (PGI2) on contractile properties of isolated right ventricle of rat heart

The mechanism of the positive inotropic effect of prostacyclin (PGI₂) (2.6×10^?6 mol/l) on the isolated right ventricle of rat heart was studied. Our results show that the positive inotropic effect of prostacyclin is produced indirectly through beta adrenoceptors and slow Ca²⁺ channels, because blockade of slow Ca²⁺ channels with verapamil (10^?6 mol/l) and beta adrenoceptors with propranolol (10^?6 mol/l) abolishes this effect. Alpha adrenoceptors do not mediate the action of PGI₂.     

Suppression of in vitro haematopoiesis following human immunodeficiency virus infection

Viral infections are frequently associated with haematological disorders. Abnormalities including leukopenia, anaemia and thrombocytopenia are commonly observed in patients with the acquired immune deficiency syndrome (AIDS) or the AIDS-related complex (ARC). The underlying cause of these haematological abnormalities is poorly understood. We report here that bone marrow progenitors isolated from AIDS or ARC patients are responsive to recombinant human granulocyte-macrophage colony stimulating factor (rGM-CSF) and recombinant erythropoietin. Antibodies present in the serum of patients infected with the human immunodeficiency virus (HIV), however, could suppress the growth of these progenitors, but not the growth of progenitors from HIV seronegative controls. A component of this immune-mediated suppression appears to be antibodies directed towards the envelope glycoprotein (gp120) of HIV.