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Biomedical subjects

A Hellman

Publications and source records attributed to A Hellman.

At least 55 records · Page 3Linked to original sources

Type C retrovirus activation and possible functions in the normal and tumor-bearing host.

The pathological consequences of tumor virus infection, transformation, and tumor development in certain experimental animals is a well-established and accepted fact. More recently, it has been suggested that these viruses may also have a physiological function participating in such processes as cellular differentiation, immune recognition, and embryogenesis. This paper delineates the current information giving some credence to physiological function for type C viruses.

Alcoholism↗

Protection against 7, 12-dimethylbenz[a]anthracene-induced rat mammary carcinoma by infection with mouse xenotropic type C virus.

A single ip inoculation of female, outbred Sprague-Dawley rats with a viable mouse xenotropic type C virus significantly reduced the incidence and/or retarded the development of mammary carcinoma induced by 7, 12-dimethylbenz[a]anthracene administered orally 7 days after virus. Although infectious virus could not be isolated from organs of infected rats, high titers of circulating and tumor-associated antibodies were detected against the viral internal core protein p30, and a low-grade antibody response to intact virus or envelope glycoprotein was found. Moreover, a cell-mediated immune response, measured by lymphocyte transformation, was detected with the use of intact virus but not with p30 antigen. No immunity developed after a single inoculation of UV-inactivated virus. These data indicated that inoculation of adult individuals of heterologous species with viable xenotropic mouse type C virus resulted in the rapid disappearance of infectious virus from the recipient, followed by the development of both humoral and cellular immunity to virion constituents. These events led, by unknown mechanisms, to the effective retardation of chemical carcinogenesis when infection preceded carcinogen administration.

9,10-Dimethyl-1,2-benzanthracene↗

Haemodynamic effects of different corticosteroids in controlled haemorrhagic shock in the dog.

The haemodynamic effects of massive doses of hydrocortisone (80-320 mg.kg-1), methylprednisolone (4-32 mg.kg-1), betamethasone (1.6-12.8 mg.kg-1) and aldosterone (0.1-0.8 mg.kg-1) and the interaction with phenoxybenzamine and propranolol have been studied during controlled haemorrhagic shock in the anaesthetized dog. Hydrocortisone was the only steroid which showed any significant vasodilating ability when given alone. The alpha-receptor blocking agent phenoxybenzamine distinctly decreased the total peripheral resistance. The effect of the phenoxybenzamine was increased in combination with hydrocortisone or methylprednisolone, especially if the steroid was given as the first drug. The vasodilation found was efficiently abolished by the beta-receptor blocking agent propranolol. The ability of hydrocortisone or methylprednisolone to potentiate phenoxybenzamine was not shared by betamethasone or aldosterone. Thus, the haemodynamic effect of the steroid does not seem to be correlated to either a glucocorticoid nor a mineralocorticoid effect. It is suggested that the steroid effect studied is related to the ability of hydrocortisone or methylprednisolone to block the extra neuronal amine uptake which decreases the rate of elimination of the sympathetic transmitter from the vicinity of the adrenergic receptor of the vascular smooth muscle.

Adrenal Cortex Hormones↗

Endogenous New World primate retrovirus: interspecies antigenic determinants shared with the major structural protein of type-D RNA viruses of Old World monkeys.

A reverse transcriptase-containing virus has recently been isolated from a squirrel monkey (Saimiri sciureus). Molecular hybridization studies demonstrate that the squirrel monkey retrovirus (SMRV) is endogenous to this New World primate, yet lacks detectable nucleotide sequence homology with cellular DNAs of representative Old World primates or with the genomes of previously isolated Old World primate retroviruses. The 35,000-dalton major structural protein (p35) of SMRV was purified and shown to possess antigenic determinants distinct from those of known retroviruses. While SMRV was found to lack antigenic determinants broadly shared among mammalian type-C viruses, immunologic crossreactivity was demonstrated between SMRV p35 and the major structural protein (p26) of Mason-Pfizer monkey virus, a prototype type-D retrovirus of Old World monkeys. These findings support the concept that SMRV and Mason-Pfizer monkey virus are evolutionarily related, and raise the possibility that a progenitor of type-D retroviruses became genetically associated with primates at a very early time in their evolution.

Animals↗

Binding characteristics of Rauscher leukemia virus envelope glycoprotein gp71 to murine lymphoid cells.

The major envelope glycoprotein (gp71) purified from Rauscher leukemia virus (R-MuLV) binds efficiently to murine lymphoid cells but not to either murine nonlymphoid cells or lymphoid cells from other species. Binding of 125I-labeled R-MuLV gp71 was competitively inhibited by unlabeled glycoprotein, as well as by whole R-MuLV, but not by murine xenotropic viruses, R-MuLV p30, and several unrelated proteins. Polyacrylamide gel electrophoresis profiles of iodinated gp71 after binding to lymphoid cells were similar to prebound profiles. Antibody to R-MuLV gp71 prevented binding, whereas normal serum had no effect. Adsorption of the glycoprotein to murine lymphoid cells occurs rapidly and is time and temperature dependent. The procedure described is sensitive for detecting the binding activity of approximately 10(4) cells. Binding was proportional up to 2.5 X 10(5) cells per ml and plateaued above 10(7) cells per ml. In the presence of excess R-MuLV gp71, BALB/c thymocytes bound approximately 2.4 X 10(4) molecules per cell.

Animals↗

Inhibition of lymphocyte transformation by disrupted murine oncornavirus.

Freeze-thaw preparations of banded Rauscher murine leukemia virus markedly suppressed the in vitro cellular-mediated blastogenic response of murine splenic lymphocytes to phytohemagglutinin-P and to allogeneic cells in two-way mixed-leukocyte reaction. Suppression was shown not to be due to cytotoxicity or to virus-mitogen binding. It is suggested that a virion envelope component interferes with cellular-mediated immunity by altering cell recognition sites.

Animals↗

Autogenous humoral immunity to baboon xenotropic endogenous type C virus.

A radioimmune precipitation assay was used to evaluate the humoral immune response of baboons (Papio cynocephalus) to their endogenous, xenotropic, type C (M7) virus. Using 125I or [3H]leucine-labeled intact virus preparation, we demonstrated that baboons possess naturally occurring virus-binding antibodies to this virus. Antibody appeared directed against envelope and not internal viral proteins. Immunoglobulins responsible for virus-binding were predominant in the IgG and IgA serum fractions, whereas IgM participated to a minor degree. The biologic activities of these immunoglobulins were investigated by means of a focus reduction assay for virus neutralization with a murine sarcoma virus (M7) pseudotype. We determined that, despite the presence of considerable virus binding, none of the normal baboon sera tested possessed neutralizing activity for M7 virus.

Animals↗

Suprresion of in vitro lymphocyte stimulation in mice by uterine and placental extracts.

The effects of uterine extracts from virgin mice and uterine and placental extracts from mice at various stages of gestation on lymphocyte stimulation in vitro were compared. Placental and uterine extracts from mice in gestation, at 1% final concentration by volume, caused marked depression of lymphocyte reactivity to phytohemagglutinin-P (PHA) and to allogeneic cells in two-way mixed leukocyte cultures (MLC). An equivalent concentration of uterine extract from virgin mice caused slight depression of uterine extract from virgin mice caused slight depression of lymphocyte reactivity. Suppression was most of lymphocyte reactivity. Suppression was most marked with uterine extracts of mice at 15 days of gestation. At least two factors of different m.w. in uterine and placental extracts were responsible for suppression of lymphocyte reactivity. The higher m.w. fraction, present in small amounts in the uteri of virgin mice, was markedly increased in uteri of pregnant mice. This fraction contained immunoglobulin G (IgG). These factors may be involved in a protective role for the fetus from rejection by the mother as an allograft, thus assuring successful pregnancy.

Animals↗

A comparative study on the presence of C-type viral particles in placentas from primates and other animals.

C-type particles are found in human, baboon, marmoset, rhesus, patas, and cynomolgus monkeys. A cebus monkey and two chimpanzee placentas have failed thus far to show the presence of these particles. Of the nonprimate tissues examined one mouse and one guinea pig placenta were positive whereas a rabbit placenta was negative. Variations in number of particles present in tissues as well as number of animals of a given species containing particles are noted. The isolation of foamyviruses from placenta cultures makes critical evaluation and interpretation of findings imperative. Several considerations suggest that the presence of foamyviruses is coincidental.

Animals↗

Oncornaviral protein modulation in mouse uterine tissue by estrogen (38467).

Treatment of ovariectomized NIH Swiss mice with estrogens elevated the level of the murine leukemia virus group specific protein and the activity of an RNA-directed DNA polymerase in the uterus. The extent that these markers were raised was dependent on the relative biological potency of the estrogen and on the time interval following treatment. Increases in the levels of both viral marker proteins were evident within 24 hr of treatment and were highest at 48 hr. Subsequently, viral protein levels declined to pretreatment levels.

Animals↗