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Biomedical subjects

A Hayward

Publications and source records attributed to A Hayward.

At least 55 records · Page 3Linked to original sources
PubMed1991

Severe combined immunodeficiency among the Navajo. I. Characterization of phenotypes, epidemiology, and population genetics.

Previous studies have identified a high incidence of severe combined immunodeficiency (SCID) among the Navajo Native American population. To determine the incidence and population genetics of this condition, we reviewed the death certificates of all children who died between 1969 and 1982, established the cases that met criteria identified in previously investigated cases, and interviewed the selected children's families. SCID cases were distributed spatially and temporally. Segregation parameter estimates of 0.27-0.38 were obtained from data from 24 interviewed families, suggesting an estimated gene frequency of 2.1% (arguing against a multifactorial inheritance). SCID cases referred to specialty centers lacked T and B cells in their blood, and their serum immunoglobulins ranged from absent to near normal.

Arizona↗
PubMed1990

Cyclosporine A for the treatment of new-onset insulin-dependent diabetes mellitus.

It is not known whether early immunosuppressive treatment can preserve long-term endogenous insulin secretion in subjects with insulin-dependent diabetes mellitus. In the present study, clinical remissions during the first year and C-peptide production for 3 years were followed after 43 subjects with newly diagnosed insulin-dependent diabetes mellitus were randomly assigned to a cyclosporine A treatment group for 4 months or to a control group. Of the six cyclosporine A-treated subjects who had remissions, five were 19 years of age or younger, compared with two of the four in the control group. C-peptide production was present in 98% of all subjects after 4 months, in 88% after 1 year, and in 43% after 3 years. There were no significant differences in numbers of subjects with C-peptide production or in mean hemoglobin A1 levels, between cyclosporine A-treated and control subjects after 3 years. Cyclosporine A treatment of subjects with newly diagnosed insulin-dependent diabetes mellitus for a period of 4 months does not have the ability to preserve residual beta-cell function.

Adolescent↗
PubMed1989

Human newborn natural killer cell responses to activation by monoclonal antibodies. Effect of culture with herpes simplex virus.

Deficient responses by NK cells may contribute to the susceptibility of human newborns to severe HSV infections. Furthermore, HSV disseminates widely during neonatal infection and may also infect and interfere with the function of blood mononuclear cells (MNC). To determine whether the function of newborn NK cells would be affected by contact with HSV, and whether newborn NK cells might be permissive for HSV replication, newborn MNC were cultured with HSV in vitro for 3 days. Before culture, the intracellular calcium mobilization in newborn NK cells induced by mAb to CD2 and CD16 did not differ from that of adult NK cells. This result argues against immaturity of an early NK cell activation event in human newborns. After culture with HSV the Ca2+ flux response was unaffected by lysis of K562 targets by newborn NK cells and NK-dependent suppression of HSV replication in fibroblasts were preserved or increased. Incorporation of thymidine by NKH-1 cells following stimulation with PHA and IL-2 was not suppressed. NK cells recovered from these cultures did not contain infectious HSV and synthesis of HSV-specific proteins was not detected by immunoprecipitation although HSV genome was detected by DNA hybridization. Our results extend the in vitro model stimulation systems in which newborn NK cells respond positively to include triggering through the CD2 Ag, cross-linking of cell surface CD 16 Ag and response to a pathogen, HSV.

Antibodies, Monoclonal↗
PubMed1989

Persistence of varicella-zoster virus DNA in blood mononuclear cells of patients with varicella or zoster.

Varicella-zoster virus (VZV) DNA was detectable by in-situ hybridization in blood mononuclear cells (MNCs) of patients with varicella or zoster for 2-56 days after the onset of a rash. VZV DNA was present in many MNCs from one acute varicella patient 2 days after the onset of the rash and was rarely found in MNCs during acute zoster, convalescent zoster, and convalescent varicella. The morphology of MNCs containing VZV was heterogenous, although most viral-DNA-containing MNCs were large monocytoid cells. Serial examination of blood MNCs from one adult with varicella revealed VZV DNA up until 8 weeks, but not 16 weeks, after the appearance of the rash; parallel studies in four zoster patients showed VZV DNA up until 3 weeks, but not later than 7 weeks after the appearance of the rash. These results indicate that MNCs become infected with VZV during the primary encounter with VZV (varicella) and during reactivation (zoster) and that infection continues for weeks after the onset of the skin rash. Furthermore, the detection of VZV DNA in blood MNCs of uncomplicated zoster patients coincides with the period during which these patients experience pain.

Adult↗
PubMed1989

Phenotype, cytotoxic, and helper functions of T cells from varicella zoster virus stimulated cultures of human lymphocytes.

Blood mononuclear cells (MNC) were stimulated with VZV in the form of live cell-associated virus, glutaraldehyde-fixed VZV-infected fibroblasts or an extracted VZV antigen. After 7 days of culture with live virus, IL2 receptors (IL2R) were found on CD4 and CD8 cells while cultures stimulated with fixed or extracted antigen had IL2R only on CD4 cells. Clones derived by limiting dilution from these cultures were tested for specificity by cytotoxicity to autologous VZV-superinfected B lymphoblasts, and by proliferation in the presence of antigen and antigen presenting cells. The CD8+ clones were not VZV specific in tests of cytotoxicity or proliferation. 50% of the CD4+ clones with specificity for VZV also proliferated in cultures stimulated with individual VZV glycoproteins gp I, II or III. Included amongst these were clones cytotoxic for lymphoblast targets prepared with live VZV. Most of the VZV-specific T cell clones which failed to lyse targets prepared with live VZV lysed targets prepared with heat killed VZV. Target cells were susceptible to lysis after VZV antigens were no longer demonstrable on the cell surface by immunofluorescence and monoclonal antibodies to VZV glycoproteins failed to block cytotoxicity. 5 of 8 VZV-specific CD4+ clones provided antigen-specific help to B cells for IgG antibody production. The data are consistent with the view that CD4+ T cells respond to processed VZV antigen fragments, and that these fragments include epitopes present on gp I, gp II and gp III. Additionally, some the cloned progeny of VZV specific T cells were bifunctional (expressing cytotoxicity and help for B cells) in tissue culture.

Antigens, Viral↗
PubMed1988

Cocaine absorption from the nasal mucosa.

The absorption of cocaine from the nasal mucosa was measured by serial plasma analysis in patients who received nasal cocaine for routine nasal surgery using the modified Moffett's method. Two groups were compared: one received cocaine alone and one with adrenaline 1:1000 added. Changes in pulse rate and blood pressure were recorded in each group. The group that received intranasal cocaine and adrenaline solution had significantly lower plasma cocaine levels. There was no significant difference in cardiovascular parameters between the two groups.

Absorption↗
PubMed1988

Lysis of CD3 hybridoma targets by cloned human CD4 lymphocytes.

UCHT1, a CD3-producing hybridoma, is lysed by cloned human T cells of both CD4 and CD8 phenotypes. The lysis is specific for the CD3 receptor and is mediated by 90% or more of all T cells from blood, without evidence for a subset of CD4 T cells incapable of cytotoxicity. CD4 clones characterized as 'helper' cells by in vitro help for specific antibody production by B cells also lysed CD3 targets. Varicella zoster virus (VZV) super-infected B lymphoblasts were lysed by three of six VZV-specific T-cell clones and 1 Cl-specific T-cell clones lysed 1 Cl hybridoma targets. Resting B cells (from tonsil) coated with CD3 antibody were lysed by CD4 clones. The data suggest that the majority of clonable CD4+ T cells lyse target cells recognized via CD3 or through the antigen receptor.

Antigens, Viral↗
PubMed1988

Non-productive infection of human newborn blood mononuclear cells with herpes simplex virus: effect on T cell activation, IL-2 production and proliferation.

Proliferative responses by T cells from newborn cord blood stimulated with PHA or CD3 were reduced following infection with live (but not killed) herpes simplex virus in vitro although activation (measured by calcium flux) and IL-2 production were unaffected. The impairment of proliferation was not reversed by exogenous IL-2, phosphonoacetic acid, indomethacin or anti-alpha or anti-gamma interferon antibodies. HSV DNA was detected by hybridization in DNA extracted from unseparated MNC and from subsets sorted for CD3+ and for HLA DR+ expression. HSV DNA replication was not detected by thymidine uptake and only small amounts of virus were recovered in an infectious centre assay, suggesting that infection was non-permissive. Nevertheless, in-vitro synthesis of a limited range of HSV proteins including ICP4 was detected by metabolic labelling.

DNA, Viral↗
PubMed1986

IgG subclass of anti-HSV antibodies following neonatal HSV infections.

Ten survivors of neonatal HSV encephalitis had IgG1 and IgG3 antibodies to HSV 6 or more months after their infection. Six had IgG4 antibodies but only one had IgG2 antibodies. Titers of anti-HSV antibodies were similar following neonatal and later HSV infections. Antibody deficiency is thus not part of the selective deficiency of HSV-specific immunity following neonatal infection.

Adult↗
PubMed1981

An acute lymphoblastic leukemia which produces human T cell growth factor.

We report the production of T cell growth factor activity by a PHA stimulated acute lymphoblastic leukemia cell line designated HSB-2. Factor production was enhanced by the addition of phorbol myristate acetate to the cultures. The growth factor will enhance the proliferation of PHA stimulated thymocytes and sustain the proliferation of growth-factor dependent human T cell blasts. The characteristics of the cell line are described.

B-Lymphocytes↗
PubMed1979

"Ia-like" antigens on human T cells.

Human T lymphocytes have been tested for cell surface p. 28,33 "Ia-like" heteroantigen and DRw alloantigens. Small numbers (1--5%) of sheep (E) rosette or T antigen-positive, surface immunoglobulin-negative (E+, T+, smIg-) T cells were Ia+; these cells appeared to be restricted to the TG subset. Following activation by allogeneic lymphocytes or sperm, or by purified protein derivative of tuberculin (PPD), the proportion of positive T cells increased substantially. DRw typing indicated that Ia specificities on activated T cells were not acquired passively from the stimulator cells, suggesting therefore that either "selection" of a small DRw+ cell subset or derepression and/or exposure of DR locus gene products occurs during T cell activation.

Antigens, Surface↗