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.     

Pattern of covariation between life-history traits of European birds

A large amount of variation is found in most reproductive traits of birds. Clutch size for instance, can vary from 1 to 15 between species of similar body weight. The adaptive significance of this variation is only poorly understood. According to life-history theory, large clutch size and early onset of reproduction are expected when the chances of survival are low. There is some support for the existence of such a relationship from studies of single species. Here I present evidence that, in European birds, clutch size is increased, and onset of reproduction occurs earlier in life, when the probability of survival is low.     

Noradrenaline contracts arteries by activating voltage-dependent calcium channels

Noradrenaline (NA) regulates arterial smooth muscle tone and hence blood vessel diameter and blood flow. NA apparently increases tone by causing a calcium influx through the cell membrane. Two calcium influx pathways have been proposed: voltage-activated calcium channels and NA-activated calcium-permeable channels that are voltage-insensitive. Although voltage-activated calcium channels have been identified in arterial smooth muscle, voltage-insensitive calcium channels activated by NA have not. We show here that NA contractions of rabbit mesenteric arteries increase with depolarization. The increase parallels the elevation of open-state probability (P0) of single, voltage-dependent calcium channels. The action of noradrenaline can be explained by NA-activating voltage-dependent calcium channels, rather than by opening a second type of channel. We show directly that NA increases the open-state probability of single calcium channels. Thus, in the presence of NA, calcium entry through voltage-dependent calcium channels can regulate smooth muscle tone at physiological membrane potentials. These results may have relevance to pathophysiological conditions such as hypertension.     

Effect of intralipid infusion on serum high- and low-density lipoprotein cholesterol,lecithin: Cholesterol acyltransferase,and lipoprotein lipase in tumor-bearing rats

We compared the effects of 0.45% normal saline (NS), 5% Intralipid^® (IL), and 16.7% glucose (Glu) infusions on total serum triglycerides and cholesterol, serum high-(HDL-c) and low-density lipoprotein cholesterol (LDL-c), and activity of serum lecithin: cholesterol acyltransferase (LCAT), and serum lipoprotein lipase (LPL) in rats implanted with a fibrosarcoma. In tumor-bearing rats given NS, a two-fold increase in total serum cholesterol, a four-fold increase in LDL-c, and a five-fold decrease in the HDL-c/LDL-c ratio were observed compared to tumor-free rats. In tumor-bearing rats administered IL, a two-fold increase in total serum triglyceride and cholesterol, a three-fold increase in HDL-c and HDL-c/LDL-c ratio, and a two-fold increase in LPL activity were observed compared to tumor-bearing rats administered NS. In tumor-bearing rats administered Glu, a two-fold decrease in total serum cholesterol, a two-fold decrease in HDL-c, and a three-fold decrease in LDL-c were observed compared to tumor-bearing rats administered NS. Tumor weights and LCAT activity did not differ significantly between treatment groups. Previous results have demonstrated that lipophilic compounds that interact with plasma lipoproteins have altered pharmacological effects when administered with IL. Therefore, this study suggests that IL infusions alter the HDL-c/LDL-c ratio and could affect the pharmacological behavior of anticancer compounds that predominantly distribute into the LDL fraction upon entrance into the bloodstream.     

铬酸钒为基的PTC陶瓷的研究

本文使用ＳＥＭ、ＥＤＳ、ＥＡＳ、ＸＲＤ和电阻率测量技术，研究了工艺参数和加入（Ｃｏ，Ｆｅ２Ｏ３）对ＰＴＣ（Ｖ１－ｘ，Ｃｒｘ）２Ｏ３陶瓷的显微结构和电性能的影响。实验结果表明，为了制造优良性能、高可靠的热敏电阻器，必须精确控制陶瓷组份和工艺。引人象Ｃ。这样的添加物是重要的，它主要以金属形式分布在基体中，同时发现添加物对试样致密度和电性能的影响也是有益的。     

Monoclonal antibody and ligand binding sites of the T cell erythrocyte receptor (CD2)

The human T cell erythrocyte receptor (CD2 antigen) allows thymocytes and mature T cells to adhere to thymic epithelium and target cells through a cell surface protein, LFA-3 (refs 1-6). Monoclonal antibodies recognizing CD2 can either block adhesion or, in certain combinations, induce an antigen-independent T cell activation. We have identified the binding sites for 16 monoclonal antibodies against CD2 by a rapid and generally applicable mutational analysis. The binding sites fall in three discrete regions: antibodies that participate in activation and block erythrocyte adhesion bind to the first region; antibodies that block adhesion bind to the second region; and antibodies that participate in activation but do not block adhesion bind to the third region. A large number of mutations selected for loss of antibody reactivity in the first two regions also weaken the CD2-LFA-3 interaction. Good agreement was observed between mutational lesions blocking LFA-3 binding and lesions blocking binding by activating antibodies, which supports the view that such antibodies induce T cell activation by mimicking the effect of LFA-3 binding. CD2 sequences that participate in LFA-3 binding correspond to immunoglobulin variable region hypervariable sequences when the homologous domains are aligned.     

An AIDS-related cytotoxic autoantibody reacts with a specific antigen on stimulated CD4+ T cells

Patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related conditions are known to have abnormalities of T cell subpopulations, including a decreased helper/inducer (bearing the CD4 antigen) to suppressor/cytotoxic (bearing the CD8 antigen) T cell ratio and decreased absolute numbers of T cells with the CD4+ phenotype. Infection of T cells with a retrovirus, termed human immunodeficiency virus (HIV), is thought to be important in these abnormalities. HIV infection alone does not adequately explain the CD4+ T-cell abnormalities seen in AIDS, however, and the nature of T-cell destruction in this disease remains poorly characterized. Here we describe an AIDS-related serum autoantibody that reacts with an antigen of relative molecular mass 18,000 (Mr 18K) restricted to lectin-stimulated or HIV-infected CD4+ T cells. The antibody also suppresses proliferation of CD4+ T cells in vitro and induces cytotoxicity of these cells in the presence of complement. Its role in the development of AIDS merits attention.     

Identification of receptor contact site involved in receptor-G protein coupling

The mammalian G proteins transduce information from extracellular signals, including neurotransmitters, hormones and sensory stimuli, into regulation of effector enzymes or ion channels within cells. Triggered by appropriate extracellular signals, receptor proteins specifically activate members of the G protein family by catalysing replacement of GDP by GTP at the guanine nucleotide binding site. Like the receptor proteins, the heterotrimeric G proteins exhibit impressive structural similarities, suggesting that all receptor-G protein interactions use homologous structural elements and a single molecular mechanism. Topologically equivalent portions of each G protein may therefore interact with the appropriate receptor. We recently predicted the secondary structure of a composite G protein alpha-chain and proposed that a predicted amphipathic alpha-helix at the extreme carboxy-terminus of the polypeptide directly contacts receptors. This proposal has now been confirmed by sequencing complementary DNAs of the gene that encodes the alpha-chain (alpha s) of the stimulatory regulator (Gs) of adenylyl cyclase in wild-type cells and in a mutant mouse S49 lymphoma cell line, unc, in which Gs cannot be activated by hormone receptors. The sequences reveal a point mutation in the unc gene that substitutes a proline residue for an arginine near the carboxy-terminus of the alpha s-polypeptide. Expression of recombinant alpha s-unc in genetically alpha s-deficient S49 cells reproduces the unc phenotype.     

A new immunomodulating compound (AS-101) with potential therapeutic application

There has been interest in the potential of synthetic compounds to modify immune responses by imitation of cytokine action. Direct administration of interleukin 2 (IL-2) in conjunction with adoptive transfer of lymphokine activated killer cells has been used in the treatment of cancer, but there are toxic effects resulting from the high doses of IL-2 required. We have developed a new synthetic compound, ammonium tri-chloro(dioxoethylene-O,O'-)tellurate (AS-101), which has immunomodulating properties and minimal toxicity. The effects of AS-101 on the activation and function of immunocompetent cells have been assessed. We have found that AS-101 induces proliferation and IL-2 production by human lymphocytes in vitro, and enhances the production of IL-2 and colony-stimulating factor by mouse spleen cells. Splenocytes of BALB/c mice injected with AS-101 increased production of IL-2 and CSF in vitro in the presence of mitogen. Mononuclear cells of normal donors acquired responsiveness to recombinant IL-2 and bound monoclonal antibody to IL-2 receptor after incubation with AS-101. Splenocytes of mice treated in vivo with AS-101 expressed high levels of IL-2 receptor. The stimulation of lymphocytes by AS-101 apparently involves an increase in intracellular free calcium. AS-101 administered systemically to mice mediated antitumour effects which could be attributable to its immunomodulatory properties. In addition, AS-101 could directly enhance the ratio of OKT4 to OKT8-positive cells in cultured mononuclear cells from AIDS (acquired immune deficiency syndrome) patients. These results indicate that AS-101 is potentially useful in the treatment of clinical conditions involving immunosuppression.     

HIV F/3' orf encodes a phosphorylated GTP-binding protein resembling an oncogene product

Apart from the retroviral gag, pol and env the HIV genome contains the F (3' orf) gene which encodes a polypeptide of 206 amino acids which is myristylated at the N-terminal and whose function is unknown. We have expressed the F gene in Escherichia coli and from a recombinant vaccinia virus, VVTGfHIV. The F-protein produced in VVTGfHIV-infected mammalian cells is myristilated, and is phosphorylated by protein kinase C at a residue close to the N-terminus like pp60-src (ref. 5). Purified bacterial F-protein also shows the GTPase, autophosphorylation and GTP-binding activities reported for the ras gene product. Furthermore, we show that expression of F in a CD4+ cell line down-regulates the CD4(T4) antigen. These results suggest that F is important in the pathophysiology of AIDS (acquired immune deficiency syndrome).