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Biomedical subjects

L Z Cooper

Publications and source records attributed to L Z Cooper.

At least 19 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

Growth in congenital rubella syndrome and correlation with clinical manifestations.

Growth patterns, final stature, and clinical manifestations were studied in a review of the records of 105 patients with congenital rubella syndrome followed longitudinally. Of the patients (35 male, 51 female), 86 had achieved final heights. Three patterns of growth were observed: normal growth, growth consistently below the 5th percentile, and growth within the normal range or slightly below the 5th percentile followed by early cessation of growth and final height usually below the 5th percentile. Significant cognitive deficits were not observed in patients with normal growth patterns, except for one patient with profound mental retardation. The magnitude of the cognitive deficits was closely correlated with the degree of growth failure (p less than 0.001). We postulate that the rubella virus exerts its effect on somatic growth both in utero and postnatally, at a central and peripheral level, through multiple mechanisms.

Adolescent

Virus isolation and immune studies in a cohort of homosexual men.

Virus shedding was detected in 77% of homosexual subjects and in only 6% of heterosexual controls. The overall virus isolation rate in homosexual subjects was not significantly different among HIV-seropositive (79%) and HIV-seronegative (74%) individuals. In about 20% of homosexual subjects, virus shedding from multiple sites was observed. The most frequently isolated virus was cytomegalovirus (CMV) (41%), followed by enteroviruses (23%), herpes simplex virus (HSV) (7%), and adenoviruses (6%). In the control group, about 50% of subjects were seronegative for HSV-1 and 2, and about 70% were negative for CMV and Epstein-Barr virus (EBV). Only 2% of homosexuals were seronegative for CMV, about 5% for HSV-1 and 2, and about 20% for EBV. No differences were found in antibody levels against varicella-zoster virus (VZV) among the control and homosexual groups. The proportion of seronegatives for Coxsackie and hepatitis viruses was significantly higher in control than in homosexual subjects. However, no differences in the proportion of seronegatives for measles, mumps, and rubella were observed. No HIV-antibody-negative individual was detected with an OKT4/OKT8 ratio of less than 0.75. On the other hand, only HIV-positive subjects, with a ratio of less than 0.75, had high serum IFN alpha titers. The results suggest that the high rate of virus shedding among HIV-negative homosexual subjects might be a factor in the development of AIDS in this high-risk population.

Adenoviruses, Human

Reverse transcriptase activity (RTA) in lymphocyte cultures of AIDS patients treated with HPA-23.

HPA-23 was used in a parallel, multiple dose study in patients with Centers for Disease Control (CDC)-defined AIDS. Sixteen patients were divided into four dosage groups, receiving 0.25, 0.5, 1.0, or 2.0 mg/kg HPA-23 respectively, by rapid IV infusion five days/week for eight weeks. Blood was collected before, at weeks 1, 3, and 7 of treatment, and two weeks post-therapy. Patient peripheral blood lymphocytes (PBL) were cultivated in the presence of fresh PBL from a healthy donor for 30 days. Media were changed and reverse transcriptase activity (RTA) was tested every four to five days. The results showed a significant decrease in RTA in patients treated with a dose of 0.5 or 1 mg/kg, but only a slight decrease in patients who received the lowest dose. In the group treated with the 2 mg/kg dose, two patients had toxic reactions and were discontinued; the other two showed a slight decrease in RTA. In 40% of treated patients, RTA did not increase again two weeks after the end of treatment. No significant immunologic and clinical changes were noticed during the observation period. In vitro experiments of Con A stimulated PBL in presence and absence of HPA-23 showed an increase in proliferation in the presence of the drug.

Acquired Immunodeficiency Syndrome

Long-term follow-up of serum-interferon and its acid-stability in a group of homosexual men.

For a period of over two years 99 volunteer healthy homosexual men were examined periodically for the presence of interferon (IFN) in their serum. Thirty-nine subjects had either undetectable IFN levels in serum or IFN was detected only once in three to five samples tested. In another 45 subjects low IFN levels were detected throughout the study period. None of these subjects had or developed any disease symptoms. In the remaining 15 subjects high serum IFN levels were detected at their enrollment or during the study period. All these subjects started to manifest clinical symptoms compatible with AIDS. In six subjects the mean time elapsed between the first detection of serum IFN and disease symptoms was 6.5 months. In all subjects but one, the IFN was of type alpha. The acid-stability of serum IFN alpha decreased with time, and when its decrease was abrupt it was associated with a more rapid evolution of AIDS. Sera containing acid-labile IFN alpha can induce IFN alpha synthesis in normal lymphocyte cultures (LC), but do not influence IFN gamma synthesis in LC stimulated with phytohemagglutinin. LC stimulated with viral antigens in the presence of serum with acid-labile IFN alpha synthesized IFN with an increased sensitivity for acid treatment. The results confirm the prognostic value of serum IFN alpha in the development of AIDS, and suggest that the transition to acid-lability may be a gradual process.

Acquired Immunodeficiency Syndrome

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