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Biomedical subjects

R L Hirsch

Publications and source records attributed to R L Hirsch.

At least 55 records · Page 3Linked to original sources

Cellular immune responses during complicated and uncomplicated measles virus infections of man.

Lymphocytes from patients with measles showed profound and prolonged suppression of proliferative responses to mitogens. The degree of suppression was similar in patients with uncomplicated measles virus infection and in those with pneumonia or postinfectious encephalitis. Despite this suppression, lymphocyte responses to measles antigen and PPD were demonstrated in patients with encephalitis and uncomplicated disease, even early in infection. Most patients with pneumonia did not have demonstrable antigen-specific responses. The proportions of T helper (OKT 4) and T suppressor (OKT 8) cells and functional tests of Con A suppressor cell activity showed no significant difference between control and measles patients but, in contrast to controls, cells from measles patients cultured in the absence of any stimulant significantly suppressed the proliferation of allogeneic responder cells. Nine of 20 supernatant fluids from these cultures possessed a soluble suppressor factor. These studies indicate varied disruptions of immune reactivity during measles.

Adolescent↗

Development of antibody to measles virus polypeptides during complicated and uncomplicated measles virus infections.

Immune precipitation of 181 sera from 152 patients with natural measles was studied to determine the temporal course and frequency of antibody responses to nucleocapsid, fusion, hemagglutinin, and matrix proteins of measles virus. Large amounts of antibody to nucleocapsid protein developed in all patients by day one of the rash. Antibody to hemagglutinin and fusion proteins developed in all patients over the next 3 weeks, the former to high levels and the latter to low levels. Antibody to matrix protein developed to very low levels and was detectable in only 41% of the patients; this poor response to matrix protein was not correlated with the age of the patient or the acute neurological complications of measles.

Adolescent↗

Natural immunity to Sindbis virus is influenced by host tissue sialic acid content.

Recent studies have shown that the sialic acid content of Sindbis virus influences both its ability to active the alternative pathway in vitro and its susceptibility to complement dependent clearance from the bloodstream in vivo. Other studies have shown that the sialic acid content of Sindbis virus is determined by the host in which it is propagated. Because individuals vary in their cell surface sialic acid content, it is possible they also vary in their ability to defend themselves against Sindbis virus infection by virtue of their ability to modify the virus sialic acid content and thereby the capacity of the virus to activate the alternative pathway. To test this hypothesis, outbred Swiss mice were injected subcutaneously with Sindbis virus. There was a significant positive correlation between the level of viremia 18 hr after infection and the sialic acid content of the host's erythrocytes. In addition, animals with erythrocyte sialic acid levels equal to or greater than the mean had a higher level of viremia than animals with erythrocyte sialic acid levels less than the mean. Finally, animals that had muscle sialic acid levels equal to or greater than the mean had a higher incidence of viremia than animals with muscle sialic acid levels less than the mean. These studies suggest that the amount of tissue sialic acid in an individual host influences its ability to resist Sindbis virus infection.

Animals↗

Immunosuppression in goats inoculated with parainfluenza type 3 virus.

The humoral and cellular immune responses of goats experimentally infected with an ovine isolate of parainfluenza type 3 virus (PI-3) were examined. Virus neutralization and enzyme-linked immunosorbent assays were used to determine antibody in the serum and CSF. Lymphocyte stimulation, measured by [3H]thymidine incorporation into peripheral blood leukocytes, was used to determine cellular responses to phytomitogens and virus. There were significant suppression of peripheral blood leukocyte responses to T-cell mitogens early in the course of infection and delayed onset of virus-specific cell-mediated immunity. Delay in antibody formation did not occur. The suppression of mitogen response has been reported with other paramyxovirus infections. The importance of the suppressed cellular immune response for potentiating other infective agents is discussed.

Animals↗

Production of mononuclear cell chemotactic factors during Sindbis virus infection of mice.

Draining lymph node cells of mice infected subcutaneously with Sindbis virus (SV) produced two mononuclear chemotactic factors in vitro. One factor did not require the addition of SV in vitro and was only detectable during the first week after infection. A second factor, resembling lymphocyte-derived chemotactic factor, required the addition of SV in vitro, was first detectable at 3 days, reached a peak at 15 to 18 days, and was gone by 29 days after infection. The production of this factor was virus specific. Diluent-inoculated mice produced no detectable mononuclear chemotactic factors in response to SV. In vitro production of the virus-specific chemotactic factor was dependent on both adherent cells and sensitized Lyt1+ T cells. In vitro production of the spontaneous factor was associated only with adherent cells but also appeared to be T cell dependent, since the lymph node cells from SV-infected athymic nude mice failed to produce either factor. Infectious center assays showed that adherent cells contained infectious SV without replicating it, suggesting the engulfment of virus by macrophages in the lymph node draining the area of virus replication. These cells probably process virus as antigen for presentation to T cells, resulting in local production of chemotactic factors as well as production in more distant sites of viral replication after leaving the lymph node. These virus-stimulated, mononuclear cell-produced chemotactic factors are likely to be of importance in generating the mononuclear inflammatory response.

Animals↗

Development of age-dependent resistance to sindbis virus encephalitis: correlation with inactivation of virus within the blood stream.

The clearance of Sindbis virus from the blood stream and its localization in the reticuloendothelial system (RES) was studied in mice susceptible (2 weeks old) and resistant (6 weeks old) to fatal Sindbis virus encephalitis. No significant differences in the relative capacity of 2-week-old and 6-week-old mice to remove 125I-labelled virus from the blood stream and to localize virus within the liver were observed. However, the decline of infectious virus was more rapid in the blood of adult mice. These studies suggest that, in addition to physical removal of virus by the RES, inactivation of virus in the blood serum stream plays an important role in limiting viremia during infections with Sindbis virus.

Aging↗

Recommendations of the task force on record-keeping and blood distribution systems.

The objectives of an automated donor record system are reviewed and recommendations as to file content and structure of a computer-based system are outlined. Four sections are suggested, data related to donor identification, demography, date of last donation and special services requirements. Alternative means of data entry and donor-donation links are discussed as well as desirable capabilities of unit record and patient record systems. Two types of blood distribution systems are outlined, namely the reactive type where hospital blood bank inventories are replenished on demand and the predictive type where inventory requirements are predicted in advance and inventories are replenished on a fixed, previously agreed on schedule.

Blood Banks↗

Blood distribution systems and the exchange of information between hospital blood banks and regional blood centers.

The advantages and disadvantages of centralized or decentralized reactive or predictive blood distribution systems are presented. A decentralized, predictive distribution system, being used by the Long Island Blood Service Division of the Greater New York Blood Program is described and its applicability to most regional blood supply organizations is emphasized.

Blood Banks↗

Host modification of Sindbis virus sialic acid content influences alternative complement pathway activation and virus clearance.

Previous studies have shown that Sindbis virus, an enveloped alphavirus of the togavirus group, activates the alternative complement pathway in the absence of detectable antiviral immunoglobulin. The present studies examined the role of the host-determined sialic acid content of Sindbis virus on activation of the alternative complement pathway. Purified Sindbis virus grown in baby hamster kidney (BHK-SV) and in mosquito (MOSQ-SV) cells yielded virus with 10.2 and less than 2.0 nmol sialic acid/mg viral protein, respectively. Sindbis virus deficient in sialic acid (2.0 nmol sialic/mg) was also produced by treating the BHK-SV with neuraminidase (NANase-SV). When MOSQ-SV or NANase-SV was incubated in either C4DGPS or C2DHS, each consumed significantly more C3 than did BHK-SV, indicating that the ability of Sindbis virus to activate the alternative pathway is inversely related to its sialic acid content. Studies in vivo showed that virus deficient in sialic acid (MOSQ-SV) was cleared from the blood of mice much more efficiently than was virus rich in sialic acid (BHK-SV), after i.v. inoculation. Furthermore, when animals were depleted of C3 through C9 by cobra venom factor (CoVF) treatment, no differences in the clearance of high and low sialic acid-containing viruses were observed. Thus both the activation in vitro and complement-dependent clearance in vivo are significantly affected by the host-determined sialic acid content of Sindbis virus.

Animals↗

Natural killer cells appear to play no role in the recovery of mice from Sindbis virus infection.

Previous studies have suggested that non-specific defence mechanisms may be important in the development of age-dependent resistance to fatal Sindbis-virus infection and in the recovery of adult mice from non-fatal infection. In these studies, natural killer (NK) cell induction was studied in 7-day-old susceptible mice and 28-35-day-old resistant mice. It was found that Sindbis virus infection induced NK cells in both the young and older mice, suggesting that NK cells were not important in the acquisition of resistance to fatal Sindbis-virus infection. Transfer of 10(8) lymph node cells from adult, mice, at the peak of NK cell activity, did not protect young mice from fatal infections, supporting the in vitro findings. The pathogenesis of Sindbis virus infection in C57BL/6J bg/bg (NK-cell deficient) and bg/+ (NK-cell normal) mice was also studied. Despite a defect in the induction of NK cells by Sindbis virus infection in the bg/bg mice, there were no significant differences in the pathogenesis of either peripheral or intracerebral infection in these strains of mice. These studies suggest that although NK cells are induced, they may not be important in the recovery of mice from Sindbis virus infection.

Age Factors↗

Cerebrospinal-fluid lymphocyte populations and immune complexes in active multiple sclerosis.

A specific subpopulation of mononuclear cells bearing a surface receptor for the Fc portion of IgG was considerably reduced in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients during exacerbation, but returned toward normal levels as the patient entered remission. Low concentrations of immune complexes were found in the CSF in nearly 50% of MS patients during exacerbations but immune complexes were not found in patients with stable MS.

Acute Disease↗