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Biomedical subjects

L Z Cooper

Publications and source records attributed to L Z Cooper.

15 recordsLinked to original sources

Modulation of alpha interferon levels by AZT treatment in HIV-seropositive patients.

The effect of AZT on serum HIV p24 antigen and endogenous serum alpha interferon levels was studied in AIDS and ARC patients. Following administration of AZT there was a rapid decline in the serum levels of both HIV p24 antigen and alpha interferon. When AZT treatment was interrupted, the levels of both HIV p24 antigen and of interferon rapidly increased. These findings suggest that HIV or some other AZT sensitive microorganism is the inducer of interferon which is characteristically found in the serum of AIDS and symptomatic HIV infected patients. They also suggest that the rapid decline in interferon levels may underlie some of the symptomatic benefit that follows administration of AZT.

HIV Antigens

Rubella and mumps vaccines.

As a fetal infection occurring during early pregnancy, rubella's potential for teratogenicity is unparalleled. In the postnatal period it is a relatively benign disease. Mumps, on the other hand, causes moderate morbidity and occasional mortality. Both infections cause considerable morbidity and disruption in the lives of young people gathered for group activities. Widespread use of safe and effective live attenuated vaccines has dramatically reduced the incidence of rubella, congenital rubella, and mumps in the United States. Nevertheless, significant numbers of young children, especially in areas of urban and rural immigration and poverty, fail to be immunized in a timely fashion; and some adolescents and young adults remain susceptible either because they escaped immunization in childhood or are primary vaccine failures. These individuals remain the source of individual cases and small outbreaks of rubella and mumps. For total eradication of these infections, we need to intensify vaccine efforts and to maintain surveillance efforts for mumps, rubella, and congenital rubella syndrome.

Antibody Formation

Immunosuppression and isolation of rubella virus from human lymphocytes after vaccination with two rubella vaccines.

Two groups of young rubella-susceptible women were vaccinated with two rubella vaccines. Heparinized blood samples were taken from all individuals the day of vaccination and 5, 7, 15, 21, 30, 35, and 42 days later. Purified lymphocytes from these samples were cocultivated with AGMK cells for rubella virus isolation. Parallel samples of lymphocytes were stimulated with phytohemagglutinin, and the rate of [14C]thymidine incorporation was determined. Rubella virus was isolated from lymphocytes collected on days 7, 15, and 21 after RA27/3 vaccination in contrast to days 7 to 35 after HPV77 vaccination. The lymphocyte response to phytohemagglutinin was markedly suppressed from day 5 to 15. Normal lymphocyte responses were restored within 1 month after vaccination with RA27/3, but even later (1 week) after HPV77 vaccine. Lymphocytes from rubella-susceptible persons infected invitro with rubella virus vaccines and stimulated with phytohemagglutin displayed a decrease in their responsiveness to the mitogen similar to that observed with lymphocytes from vaccinees. The transient immunosuppression observed in vaccinees is probably due to virus-induced functional damage of the lymphocytes since no direct cytocidal effect of rubella vaccine has been demonstrated on human lymphocytes.

Adult

Impaired cell-mediated immune response in patients with congenital rubella: correlation with gestational age at time of infection.

Lymphocyte transformation, interferon, and leukocyte migration inhibition factor synthesis were studied in purified lymphocyte cultures for 20 children with congenital rubella and 18 healthy children (seven susceptible and 11 immune to rubella). Lymphocyte transformation after phytophemagglutinin stimulation was significantly lower in children with congenital rubella as compared to healthy controls. Responses to purified rubella virus were absent in the susceptible controls and absent or at least two times lower in congenital rubella children than in immune controls. After purified rubella virus stimulation, leukocyte migration inhibition factor production was detected in all immune controls, but in none of the susceptible controls, or the congenital rubella-infected children. The results varied with gestational age of intrauterine infection: the impairment of cellular immune response, both after phytohemagglutinin or rubella virus stimulation, was more severe in the children infected in the first two months than in the latter stages of gestation.

Age Factors

Progressive rubella panencephalitis: immunovirological studies and results of isoprinosine therapy.

Two patients with progressive rubella panencephalitis, one with and one without stigmata of congenital rubella, were treated for 9 months with isoprinosine and showed continued clinical deterioration. Immunoviorological studies performed before, during and after treatment were unaffected by drug therapy. The virus was recovered on one occasion from the lymphocytes of one of these cases. Neither patient showed any major defects in cellular or humoral immunity. However, the lymphocytes of the patient with stigmata of congenital rubella failed to respond to rubella virus in vitro and had a heat stable, non-dialysable serum inhibitor of in vitro protein A stimulated proliferative responses. Both patients' serum interfered with the production of interferon by normal donor lymphocytes following stimulation with rubella and varicella virus antigen. Increasing serum titres of interferon which did not appear to be lymphoid or immune-specific in origin were found in these two cases.

Adolescent

Interferon production in lymphocyte cultures after rubella infection in humans.

When stimulated with rubella virus irradiated with ultraviolet light, cultures of lymphocytes from individuals immune to rubella responded with production of 12-14 times more interferon than did cultures of lymphocytes from individuals susceptible to rubella. This property may be retained throughout life, since it was seen in individuals who had had rubella in their recent and remote pasts. Peak levels of interferon were detected six days after stimulation of lymphocytes with rubella virus antigen. In contrast, phytohemagglutinin induced production of interferon equally well in cultures of lymphocytes from persons immune and persons susceptible to rubella, with levels peaking three days after stimulation. Since there was a positive correlation among titers of hemagglutination-inhibiting antibody to rubella virus, incorporation of [14C]thymidine, and production of interferon after stimulation of lymphocyte cultures by rubella virus, interferon synthesis may be considered to be another measurable parameter of cell-mediated immunity in rubella.

Adolescent

Neonatal meningitis and mastoiditis caused by Hemophilus influenzae.

A newborn infant developed Hemophilus influenzae meningitis associated with acute coalescent mastoiditis and a cutaneous abscess in the mastoid region. Mastoidectomy was followed by prompt recovery from the meningitis, which had failed to clear previously despite antibiotic therapy. Mastoiditis may exist as an infective focus in neonatal meningitis more frequently than has been appreciated. Mastoid roentgenograms are usually the only clue to diagnosis of this infection and should be obtained in patients with neonatal meningitis responding poorly to antibiotic therapy.

Acute Disease

Study of the lymphocyte in vitro response to rubella antigen and phytohemagglutinin by a whole blood method.

A whole blood culture method was used to study lymphocyte in vitro responses to rubella antigen and to phytohemagglutinin (PHA) in rubella infection. The acute phase of infection in four cases was characterized by high spontaneous incorporation of 14C-thymidine in the cultures, unresponsiveness of lymphocytes to rubella antigen, and absence of response, or relatively low response, to PHA. Cells showing vigorous in vitro response to rubella antigen appeared at about two weeks after the onset of rash. Lymphocyte PHA response returned to normal by day 31. Three rubella vaccinees exhibited a similar response. The use of whole blood lymphocyte cultures stimulated with multiple doses of mitogen and with antigen appears to be a promising technique for studies of "general" and "specific" cell-mediated immunity in viral infections.

Adult

Immunization. A continuing need.

Many vaccines are available to prevent potentially fatal disease. It is especially important for all of us who provide care to review periodically the current recommendations, since they are not static. Changes are based not only on the availability of improved vaccines, but also on knowledge of the diseases and altering societal and epidemiologic circumstances. We owe it to all our patients to be meticulous in maintaining up-to-date immunization records as well as to be knowledgeable about the indications and contraindications for each vaccine. Finally, it is important to remember that the immunization status of adults has been overlooked too often. This is no longer justifiable in light of current knowledge.

Child

Cell-mediated immunity in rubella assayed by cytotoxicity of supernatants from rubella virus-stimulated human lymphocyte cultures.

Rubella virus-stimulated lymphocytes from rubella-seropositive donors produced in the culture medium cytotoxic activity with preferential action against rubella-infected over uninfected target cells. The ability of lymphocytes to produce the cytotoxic activity upon stimulation by rubella virus correlated with the humoral rubella-immunity status, i.e. no such cytotoxic activity developed in the supernatants of lymphocyte cultures of rubella-seronegative donors. Stimulation of lymphocytes from seropositive donors by rubella virus was also detected by thymidine incorporation, but the correlation of lymphocyte responsiveness to the humoral rubella antibody status was not so clear as in the cytotoxicity assay. Conversion of lymphocytes from unresponsive to responsive to rubella virus following natural rubella infection and after rubella vaccination was demonstrated using both methods. Following vaccination rubella-specific cell-mediated immunity first became demonstrable at 14 days. The responsiveness of lymphocytes to phytohaemagglutinin (PHA) after rubella vaccination was followed by studying thymidine uptake and the ability of lymphocytes to produce lymphootoxin. By both tests marked suppression of PHA response occurred at days 3 and 7 after vaccination.

Adult

Inhibition of HIV replication in lymphocyte cultures of virus-positive subjects in the presence of sho-saiko-to, an oriental plant extract.

An oriental remedy, Sho-saiko-to (SST) consisting of a mixture of aqueous extracts from seven different plants and whose most active component is the chemically defined compound baicalein was tested for its ability to inhibit the production of the human immunodeficiency virus (HIV). The testing was done with cultures of human lymphocytes obtained from HIV-positive asymptomatic subjects and patients with ARC or AIDS. The replication of the virus was monitored by quantitative assay of the reverse transcriptase (RT) activity and of the synthesis of antigen p24. The lymphocyte cultures (LC) were maintained in the absence and in the presence of 25, 50 or 100 micrograms/ml of SST, and monitored for up to 5 weeks. The results showed that in LC from asymptomatic subjects RT activity and synthesis of p24 was completely inhibited by low concentrations of SST. High concentrations of SST inhibited virus replication in 80% of LC from ARC patients, but were completely ineffective in LC from AIDS patients. It was observed that the RT activity was more sensitive to inhibition by SST than the synthesis of p24, and that the antiviral effect was dependent on the virus load of the LC.

AIDS-Related Complex