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Biomedical subjects

J Armstrong

Publications and source records attributed to J Armstrong.

At least 163 records · Page 9Linked to original sources

HIV-1-specific production of IFN-gamma and modulation by recombinant IL-2 during early HIV-1 infection.

Specific cellular immune responses to human immunodeficiency virus type 1 (HIV-1) were assessed in mononuclear leukocyte cultures from homosexual men with documented, early phase HIV-1 infection. Cell cultures from men with a mean duration of 1.3 yr (range, 0.3 to 2.2 yr) of HIV-1 infection were treated with UV-inactivated, whole, purified HIV-1 Ag together with various concentrations of rIL-2. Cell supernatants were harvested after 5-day incubation and assayed for IFN activity against encephalomyocarditis virus in human WISH cells. IFN subtypes were characterized by neutralization of antiviral activity with antiserum specific for human IFN-gamma and IFN-alpha. Results showed that cultures from 68% (17 of 25) of the HIV-1-seropositive subjects produced "immune" IFN-gamma in response to whole HIV-1 Ag plus rIL-2. IFN-gamma was induced in only 20% (5 of 25) of cultures treated with HIV-1 Ag alone. Enhancement of HIV-1-specific IFN-gamma production by rIL-2 was synergistic rather than additive in that titers induced by the mixture were consistently higher than the sum of IFN titers induced by HIV-1 or rIL-2 alone. This effect was not demonstrable in cultures from 18 HIV-1-seronegative men. Similarly, HIV-1-immune specific augmentation of IFN-gamma production by rIL-2 was noted for PENV9, a recombinant HIV-1 envelope glycoprotein gp41 and gp120 fragment. Production of IFN-gamma may be an important, HIV-1-immune specific parameter in the host response to this retrovirus.

Acquired Immunodeficiency Syndrome↗

Concerted contractions of tumour fragments derived from a pure mucoid carcinoma of the breast in vitro.

Organized tissue fragments obtained by dissociation of a pure mucoid carcinoma of the breast were cultured in vitro. The cellular organization of the fragments appears similar to that observed in vivo, and consist of mucous-filled spherules surrounded by a single layer of tumour cells. Time-lapse video recordings revealed that the cells surrounding these fragments undergo a concerted contraction and relaxation over the time span of several hours. The presence of cytokeratin and oestrogen receptors in the cells suggests an epithelial derivation. Movement of tumour fragments of the type described here could potentially influence the metastatic process of some breast cancers.

Adenocarcinoma, Mucinous↗

Haematological and tissue abnormalities in chicks caused by acute and subclinical folate deficiency.

1. Haematological, histological and ultrastructural findings in young chicks fed on a purified diet severely deficient in folate are reported. 2. Growth of the birds was greatly depressed and they had a macrocytic anaemia. Other haematological changes included abnormal nuclear formations in erythrocytes, numerous mitoses and hypersegmented granulocytes. 3. Megaloblasts were observed in bone marrow and their fine structure is described for the first time in an avian species. 4. Morphological changes occurred also in the liver. The parenchyma had damaged sinusoidal endothelium, inflammatory cells and no glycogen. Mitochondria were damaged and many were associated with unusual crystalline structures. 5. Chickens fed on a semi-purified diet of low folate content showed no growth depression or clinical signs of deficiency but had abnormal haematological values and morphological changes that resembled those seen in birds fed on the purified diet. 6. These abnormalities responded to dietary supplements of pteroylmonoglutamic acid in a dose-related manner and may be useful in diagnosing subclinical folate deficiency.

Animals↗

Neuropharmacological characterization of serotoninergic stimulation of vasopressin secretion in conscious rats.

In this study we have evaluated a possible role for brain serotoninergic neurons in the regulation of vasopressin secretion using pharmacological methods. In order to accomplish this, we have developed a specific and sensitive vasopressin radioimmunoassay along with a highly reproducible plasma extraction protocol. These tools were used to evaluate the plasma vasopressin response to several pharmacological challenges in conscious rats. Treatment with the serotonin (5-HT) releaser p-chloroamphetamine caused a significant increase in plasma vasopressin concentration. This effect was blocked by posterior hypothalamic deafferentation which separates serotonin cell bodies in the midbrain from their nerve terminals in the hypothalamus. Administration of graded doses of several 5-HT agonists had no effect. However, treatment with MK212, a serotonin agonist with 5-HT1 + 5-HT2 activity, induced a significant increase in plasma vasopressin concentration. The effect of MK212 on plasma vasopressin was completely abolished by the selective 5-HT2 receptor blocker LY53857. These studies confirm and extend studies by others that provide pharmacological evidence for serotoninergic regulation of vasopressin secretion via a selective 5-HT2 receptor mechanism. The specific neuroanatomical site(s) where serotonin exerts this effect are unknown, and the physiological consequences of these studies remain to be established.

Amphetamines↗

Expression of coronavirus E1 and rotavirus VP10 membrane proteins from synthetic RNA.

Some viruses acquire their envelopes by budding through internal membranes of their host cell. We have expressed the cloned cDNA for glycoproteins from two such viruses, the E1 protein of coronavirus, which buds in the Golgi region, and VP10 protein of rotavirus, which assembles in the endoplasmic reticulum. Messenger RNA was prepared from both cDNAs by using SP6 polymerase and either translated in vitro or injected into cultured CV1 cells or Xenopus oocytes. In CV1 cells, the E1 protein was localised to the Golgi region and VP10 protein to the endoplasmic reticulum. In Xenopus oocytes, the E1 protein acquired post-translational modifications indistinguishable from the sialylated, O-linked sugars found on viral protein, while the VP10 protein acquired endoglycosidase-H-sensitive N-linked sugars, consistent with their localisation to the Golgi complex and endoplasmic reticulum, respectively. Thus the two proteins provide models with which to study targeting to each of these intracellular compartments. When the RNAs were expressed in matured, meiotic oocytes, the VP10 protein was modified as before, but the E1 protein was processed to a much lesser extent than in interphase oocytes, consistent with a cessation of vesicular transport during cell division.

Animals↗

The effect of lithium on the membrane molecular dynamics of normal human erythrocytes.

Erythrocytes from normal adults with no personal or family history of bipolar affective disorder were analyzed by fluorescence spectroscopy to determine what effect, if any, acute in vitro incubation with lithium had on erythrocyte membrane dynamics. The effects on erythrocyte membrane molecular dynamics of varying concentrations of Li2CO3 (0.25-2.0 meq/liter), varying incubation temperatures (25-40 degrees C), and varying incubation times (5-185 min) were investigated. Following incubation with Li2CO3, the erythrocytes were labeled with either 4-phenylspiro-[furan-2(3H),--1'phthalan]--3,3'-dione (fluorescamine), which binds to membrane surface primary amines, or 12(9)anthroyl stearate [12(9)AS], which inserts deep in the membrane hydrocarbon core. The membrane molecular dynamics were then determined by fluorescence anisotropy measurements. These studies demonstrate that clinically relevant concentrations of Li+ incubated with intact normal human erythrocytes significantly alters molecular dynamics on the erythrocyte membrane surface, with less striking changes in the hydrocarbon core. A possible interpretation of these findings is that hydrated Li+ alters the electrostatic interaction of membrane surface molecules, as well as the surrounding solvent (water) structure, with a resultant increase in the molecular motion of these molecules. Alterations in membrane receptor motion could potentially alter receptor functional activity. If similar motional alterations were to occur in the interior of a membrane channel, such as an ionophore, the functional activity of the channel could also be potentially altered. These findings provide additional insight into possible biological actions of Li+, as well as potential molecular alterations in bipolar affective disorder erythrocytes.

Adult↗

Transmission of infection with herpes simplex virus by renal transplantation.

Disseminated infection with herpes simplex virus type 2 was identified in two patients 20 days after they had received kidney transplants from the same organ donor. Neither patient had neutralizing antibody to herpes simplex virus before transplantation, and both had herpes simplex virus isolated from surveillance cultures of urine before the onset of clinical symptoms. A clear focus of primary infection was not found in either patient. Analysis of the patients' isolates by DNA restriction endonuclease analysis strongly suggested that the strains were identical. These data implicate the allografts as the source of the viral infection.

Adult↗

Static ataxia as a psychobiological marker for alcoholism.

Sons and daughters of male alcoholics were compared with the sons and daughters of controls on two measures of static ataxia. Increased sway was seen in the children of the alcoholic fathers who had an average of 3.7 first- and second-degree relatives meeting criteria for alcoholism. The possibility that static ataxia may be a psychobiological marker for the more genetically mediated variant of alcoholism is discussed.

Alcoholism↗

Relationship of biotin deposition in turkey eggs to dietary biotin and biotin-binding proteins.

The biotin and biotin-binding protein contents of egg yolk, egg albumen, and hen plasma were determined on eight groups of four turkey hens each that had been fed diets ranging from less than 10 to 3,475 micrograms available biotin per kilogram. Biotin deposition in the yolk was strongly dependent upon available dietary biotin below 100 micrograms/kg. Between 100 and 1,000 micrograms/kg the amount of biotin deposited in the yolk increased slightly and was directly related to and limited by a biotin-binding protein that transferred biotin from the plasma to the yolk. Over the entire dietary range, biotin deposition in yolk was proportional to the total biotin concentration in the plasma. In contrast, biotin deposition in the albumen, which was proportional to dietary biotin, increased several-fold over a very narrow range of plasma biotin concentration (56 to 62 micrograms/L). When dietary available biotin exceeded 160 micrograms/kg, there was more biotin deposited in the albumen than in the yolk. Although the concentration of unbound biotin in plasma is low, it appears to be the component of plasma biotin that is rapidly scavenged by avidin in the oviduct. It seems likely that avidin-bound biotin is available to the turkey embryo.

Animals↗

Prevention of diabetes in BB rats by intermittent administration of cyclosporine.

The successful prevention of spontaneous autoimmune diabetes in biobreeding (BB) rats--the closest animal model to human type I diabetes mellitus--by daily administrations of cyclosporine (CsA) has prompted clinical trials of CsA immunosuppression in human diabetes. Although remissions from hyperglycemia have been achieved in human subjects, nephrotoxicity and recurrence of diabetes after discontinuation of CsA have been observed. Therefore we studied the biologic efficacy of intermittent administration of CsA, a theoretically less dangerous immunosuppressive protocol, in the prevention of spontaneous diabetes in the BB rat. Beginning at 30 to 49 or 50 to 55 days of age, treated animals (n = 86) received daily injections of CsA (15 mg/Kg) for 2 weeks (induction phase) and then twice weekly (maintenance phase) until 160 days of age. A third group of animals (n = 31) received daily CsA for 14 days only. Control littermates (n = 121) were not injected. All animals were followed to 275 days of age. Intermittent administration of CsA was determined to be a biologically effective regimen in the prevention of spontaneous diabetes in the BB rat. Blood levels of CsA and the major CsA metabolites were undetectable intermittently during the course of therapy. Major complications associated with CsA immunosuppression (nephrotoxicity, malignancy, and infection) were not associated with the intermittent CsA protocol. We conclude that spontaneous diabetes can be delayed and often permanently prevented by intermittent administration of CsA. This immunosuppressive regimen deserves further consideration as a biologically effective, but theoretically less toxic, therapeutic regimen.

Animals↗

Riboflavin-binding protein. Concentration and fractional saturation in chicken eggs as a function of dietary riboflavin.

The concentration of riboflavin and riboflavin-binding protein were determined in the plasma, egg yolk and albumen from hens fed a riboflavin-deficient diet (1.2 mg/kg) supplemented with 0, 1, 2, 3, 10 and 40 mg of riboflavin/kg. We observed that the deposition of riboflavin in egg yolk and albumen is dependent on dietary riboflavin and reaches half-maximal values at about 2 mg of supplemental riboflavin/kg. The maximal amount of riboflavin deposited in the yolk is limited stoichiometrically by the amount of riboflavin-binding protein, whereas the maximum amount of riboflavin deposited in albumen is limited by other factors before saturation occurs. The amount of riboflavin-binding protein in yolk and albumen is independent of dietary riboflavin. If there is a specific oocyte receptor for riboflavin-binding protein, it cannot distinguish between the apo and holo forms of the protein. Riboflavin-binding protein is about six times more concentrated in yolk than in plasma.

Animals↗

Patterns of thought disorder on psychological testing. Implications for adolescent psychopathology.

One-hundred thirty-eight hospitalized adolescents exhibiting a broad range of psychopathology were divided into four groups based on the presence or absence of significant thought disorder on the Wechsler IQ (using Johnston and Holzman's Thought Disorder Index) and the Rorschach (using Exner's Schizophrenia Index). All subjects in the four IQ/Rorschach cross-classified groups (group A, low disordered IQ/low disordered Rorschach; group B, low disordered IQ/high disordered Rorschach; group C, high disordered IQ/high disordered Rorschach; group D, high disordered IQ/low disordered Rorschach) were rated as well on clinical symptomatology (using the Psychiatric Evaluation Form, a scale developed by Spitzer and Endicott). A multivariate analysis of variance comparing the means of the Psychiatric Evaluation Form variables for the four groups yielded significant interactions and significant main effects. The results portrayed a symptomatic picture of depression and acting out in group A, borderline-like traits in group B, psychosis in group C, and interpersonal difficulty in group D. These results are interpreted as support for the value of comparative measures of thought disorder in clinical evaluation. Further research to investigate the heretofore undescribed group D is recommended.

Acting Out↗

The effects of alpha adrenergic blockade on arachidonic acid metabolism and shock sequelae in endotoxemia.

Previous studies have suggested that increased alpha adrenergic activity stimulated prostaglandin synthesis and may be involved in the modulation of eicosanoid metabolism. These observations prompted investigation of the effect of the alpha adrenergic receptor antagonist phenoxybenzamine and the cyclo-oxygenase inhibitor indomethacin on endotoxin-induced shock severity, and on plasma immunoreactive iTxB2 and i6-keto-PGF1 alpha, the stable metabolites of TxA2 and PGI2, respectively. Pretreatment with indomethacin alone blunted the endotoxin- (8 mg/kg) induced hypoglycemia. Phenoxybenzamine pretreatment also blunted endotoxin-induced mortality (LD80), hypoglycemia, hemoconcentration, and decreased plasma beta-glucuronidase (BG). The combination of phenoxybenzamine and indomethacin resulted in the improvement of all indices of shock severity. Rats pretreated with phenoxybenzamine and indomethacin alone or conjointly also exhibited significantly (P less than 0.05) enhanced survival compared to that of shocked control rats. Percent survival at 48 hr was 24, 64, 80, and 92 in untreated, indomethacin, phenoxybenzamine, and indomethacin + phenoxybenzamine treated, respectively. Mean plasma iTxB2 values at 30 min postendotoxin (15 mg/kg i.v.) were 1,532 +/- 319 pg/ml (N = 10). Phenoxybenzamine pretreatment decreased iTxB2 to 719 +/- 114 pg/ml (N = 10). Phenoxybenzamine pretreatment decreased iTxB2 to 719 +/- 114 pg/ml (N = 10) (P less than 0.05). Plasma i6-keto-PGF1 alpha was increased 4 hr after endotoxin in shocked controls to 4,161 +/- 885 pg/ml (N = 5) and attenuated by phenoxybenzamine to a value of 1,184 +/- 363 pg/ml (N = 4) (P less than 0.05). The results suggest that increased alpha adrenergic activity may be an important stimulus for arachidonic acid metabolism during endotoxemia.

6-Ketoprostaglandin F1 alpha↗