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Biomedical subjects

A L Cunningham

Publications and source records attributed to A L Cunningham.

At least 145 records · Page 8Linked to original sources
PubMed1986

Herpes simplex encephalitis in infants.

Two cases are reported of severe encephalitis in infants that were caused by a primary infection with herpes simplex virus type 1. Both patients presented with focal seizures; the clinical diagnosis was confirmed by the rapid appearance of IgM antibody to herpes simplex virus type 1 in cerebrospinal fluid and serum. In spite of the early use of acyclovir, which was administered by the intravenous route, the clinical response was poor and both infants were left with severe neurological impairment.

Acyclovir↗
PubMed1985

Transmission of human T-cell lymphotropic virus type III (HTLV-III) by artificial insemination by donor.

Four of eight recipients of artificial insemination (AI) with cryopreserved semen from a symptomless carrier of human T-cell lymphotropic virus type III (HTLV-III) were found to have antibody to the virus. One has generalised, persistent lymphadenopathy while the other three remain symptom free 3 years after insemination. Three subsequently became pregnant more than a year after contact with the infected semen; the children, who are now over 1 year of age, are in good health and do not have HTLV-III antibodies. These observations emphasise the need for a rigorous screening programme for potential AI donors; they also suggest that fresh semen should not be used in AI. The findings confirm the role of semen in heterosexual transmission of the virus and suggest that in women with HTLV-III antibodies pregnancy and subsequent breast-feeding does not necessarily lead to infection of the infant.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Antibody to G-actin in different categories of alcoholic liver disease: quantification by an ELISA and significance for alcoholic cirrhosis.

Autoantibodies to smooth muscle (ASMA), and to actin which is a major determinant of such reactivity, were measured in the serum of 94 patients with three defined categories of alcoholic liver disease, fatty liver, alcoholic hepatitis, and alcoholic cirrhosis, and in controls matched individually by age and sex with the patients. Autoantibody to monomeric G-actin was detected by an ELISA and autoantibody to polymeric F-actin by immunofluorescence staining of fibroblast stress fibers in cultured cells. Values for the ELISA were expressed as a percentage of the value for a strongly reactive standard serum. The mean value for antibody to G-actin in 40 patients with alcoholic cirrhosis (70 +/- 33%) was significantly greater than that for the matched controls (28 +/- 18%), but the mean value for the 30 patients with alcoholic hepatitis (46 +/- 16%) and the 24 with fatty liver (42 +/- 24%) did not differ significantly from the controls. High levels of reactivity with G-actin correlated significantly with HLA B7. ASMA was demonstrable to low titer in 11 of the 94 sera, and positive ASMA reactions by immunofluorescence correlated with high binding values to G-actin in the ELISA. Antibody to F-actin was found in only one serum and no controls. Thus in different liver diseases the reactivity of antibodies to monomeric G-actin and polymeric F-actin may differ, presumably because of specificity for different determinants of the actin molecule. Reactivity to G-actin may distinguish a group of alcoholic subjects in whom a predisposition to autoimmune reactivity is one of the determinants of progression of liver damage to cirrhosis.

Actins↗
PubMed1985

Role of macrophage D-region antigens and T-lymphocyte differentiation antigens in induction of gamma interferon.

Macrophage-T-lymphocyte cultures from patients with recent recurrent herpes labialis were stimulated to produce gamma interferon by either herpes simplex antigen or mitogens (PHA and Con A). The ability of monoclonal antibodies to HLA-DR and DC/DS, HSV glycoprotein antigens and T-lymphocyte surface antigens to inhibit interferon production and lymphocyte proliferation were studied. Anti-D region antibodies inhibited HSV antigen-induced but not mitogen-induced interferon and proliferation. The extent of inhibition varied mainly according to the determinants recognized by the antibodies and, to a lesser degree, between patients. Inhibition probably resulted from inhibition of antigen presentation, through antibody binding to macrophage D-region antigens. Interferon production was a more sensitive index of inhibition than lymphocyte proliferation. With one antibody (L227) a marked difference in inhibition in the two assays was noted, suggesting that lymphocytes producing gamma interferon may differ from the majority of the proliferating cells in their recognition of D-region determinants. Antibodies to the HSV glycoprotein antigens (gA/B, gC, gD, gE) did not produce consistent significant inhibition of interferon production and had no effect on proliferation. Anti-Leu 4 and -Leu 5 inhibited HSV antigen and mitogen induction of gamma interferon (and proliferation). Anti-Leu 2 and anti-Leu 3, mildly inhibitory alone, produced synergistic inhibition together. Hence, in human systems, the interaction between macrophages and T lymphocytes in producing gamma interferon appears to differ according to mode of induction. Macrophage D-region antigens are required for antigen induction probably via presentation whereas other factor(s), probably monokine secretion, are necessary for mitogen induction. Antibodies acting on the T-lymphocyte surface appear to affect a final common pathway of interferon induction, similar to their effects on proliferation and secretion of other lymphokines.

Antibodies, Monoclonal↗
PubMed1985

Persistent rubella virus infection of human synovial cells cultured in vitro.

Primary and passaged human synovial cell cultures inoculated with wild-type and vaccine strains of rubella virus were incubated at 32 C and 37 C. At 32 C, the temperature close to that in human peripheral joints, infection persisted with extracellular virus titers of approximately 10(4) fluorescent focus-forming units/ml. Extracellular titers at 37 C first stabilized at one-tenth the level of the titers at 32 C and then declined after 20 days to undetectable levels. Cellular expression of viral antigen rose at 32 C and fell at 37 C. Infection was noncytocidal at all stages. Virus yields reflected the temperature in the subsequent incubation rather than during virus adsorption. Interferon was found only in cultures held at 37 C and was mainly alpha with a minor beta fraction, a result suggesting retention of functional characteristics of the type A macrophage-like synovial cell. We conclude that persistent infection of synovial tissue in vivo is a feasible explanation for the presence of rubella virus in peripheral joints of patients with chronic arthritis.

Animals↗
PubMed1985

Interferon gamma production by herpes simplex virus antigen-specific T cell clones from patients with recurrent herpes labialis.

Nineteen herpes simplex virus (HSV) antigen-specific human T lymphocyte clones were established from three volunteers with recent recurrent herpes labialis. All produced interferon gamma (IFN-gamma) at titres of 200 to 700 units/ml when cultured in vitro with HSV antigen and irradiated peripheral blood mononuclear cells (PBMC) as filler cells. All 10 of those clones whose phenotype was determined were Leu 4+, Leu 2-, Leu 3+. Interleukin 2 alone failed to induce IFN-gamma in titres greater than 10 units/ml from these clones cultured at 10(4)/0.2 ml/well. However, the effect of different accessory or filler cells on IFN-gamma production by clones was quite marked. For example, high titres were produced when irradiated PBMC or plastic-adherent cells (predominantly monocytes) were added and low titres when macrophages and irradiated Epstein-Barr virus-transformed B (EBV-B) cells were added. When tested for HSV antigen-stimulated IFN production alone, the irradiated PBMC and adherent cells produced low titres, but no detectable interferon was produced by the others. However, with higher concentrations of EBV-B cells, low concentrations of IFN-alpha were occasionally produced. Irradiation strikingly reduced IFN-alpha-production by PBMC. The IFN-alpha and -gamma produced by accessory cells may contribute to total IFN production by priming the production by cloned cells, and acting in synergy with IFN-gamma produced by the cloned cells. Alternatively, the effect may be due to the presence of permissive concentrations of other lymphokines such as the interleukins. Interferon production by cloned T lymphocytes in the presence of non-producing macrophages was maximal within 24 h, much faster than with a similar polyclonal system, although attaining lower titres. EBV-B cells from only one of three patients supported antigen-specific lymphocyte activation. Almost all cells of the three cell lines expressed DR antigens, while DS/DC antigens were also expressed on nearly all cells of the antigen-presenting line and, at lower densities, on two-thirds of the cells of the other two lines.

Antigen-Presenting Cells↗
PubMed1985

Evolution of recurrent herpes simplex lesions. An immunohistologic study.

We performed immunoperoxidase stains on skin biopsies taken from nine patients with recurrent peripheral herpes simplex lesions at 12 h to 6 d after onset of signs of symptoms to phenotype the inflammatory infiltrate, to detect cells producing interferons alpha and gamma, and to locate herpes simplex virus antigen-containing cells. Viral glycoprotein antigen was located in the nuclei and cytoplasm of necrotic epidermal cells, often within vesicles, in biopsies taken between the first and third day. Histologically, biopsies of all stages showed intradermal focal perivascular and diffuse mononuclear inflammatory infiltrates. The cells constituting the infiltrates were predominantly T lymphocytes with lesser numbers of histiocytes; Leu 7+ (most natural killer/killer) cells and B cells were rare in the biopsy specimens. Leu 3a+ ("helper") T lymphocytes predominated in both subepidermal and perivascular regions of early lesions (12-24 h). Tissue helper/suppressor ratios ranged from 6.3 to 3.4 compared with 1.9-1.0 in blood. In later lesions (after 2 d), monocytes/macrophages were more prominent in tissue sections and the helper/suppressor ratios (2.3-2.5) more nearly approximated those of blood (1.6-2.7). The negative correlation of tissue ratios with time was significant (P less than or equal to 0.02). A large proportion of the infiltrated T lymphocytes expressed DR antigens. There was also diffuse strong DR expression on epidermal cells in five cases (all of two or more days). In six biopsies, scattered macrophages and small cells, presumably lymphocytes, demonstrated cytoplasmic or membrane staining for a substance which copurifies with interferon gamma. We identified such stained cells within vessels, suggesting that these cells circulate. Gamma interferon might have an important role within the herpetic lesions, possibly inducing macrophage activation and cytotoxic T lymphocytes and increasing DR expression on monocyte and epidermal cells.

Adult↗
PubMed1985

Ross River virus infection of human synovial cells in vitro.

Ross River virus (RRV) strains T48 and SC18006 produced a self-limited cytopathic infection of primary and passaged human synovial cell culture. Extracellular (EC) virus titres reached peak levels at 2 days in cell lines and at 4 days in primary cultures, ranging between 10(4.5) and 10(6.6) fluorescent focus-forming units (ffu)/ml. Thereafter titres declined rapidly to undetectable levels at 10-12 days. The proportion of adherent cells showing virus antigen exceeded 60% at 3 days and decreased in all cultures to less than 1/500 after 12 days. Cytopathic effects (CPE) were greatest at 4-8 days and destroyed between 25 and 75% of the cell layer, with subsequent partial regeneration by division of surviving cells. In contrast to rubella virus infection of synovial cells, cultures at 32 degrees and 37 degrees revealed only minor differences and persistent infection was not established. CPE were more extensive at 37 degrees in nearly all synovial cell cultures and in Vero cultures. At 37 degrees synovial cells infected with T48 strain produced higher maximum titres and were more extensively infected than at 32 degrees.

Cells, Cultured↗
PubMed1984

Leu-3+ T cells produce gamma-interferon in patients with recurrent herpes labialis.

Interferon-gamma (IFN-gamma) was spontaneously secreted by peripheral blood mononuclear cells cultured from patients soon after recurrent herpes labialis (RHL) or was induced from macrophage-T lymphocyte cultures in vitro with HSV antigen. Circulating Leu-3+/Leu-2- cells produced the spontaneous IFN almost exclusively. In the HSV antigen-stimulated culture system the same subset was the predominant producer of IFN-gamma. The IFN-gamma producing leu-3+ lymphocytes were plastic nonaderent but nylon wool adherent, and may be analagous to the murine Th 2 helper cell. In contrast to one lymphocyte subset being the major IFN-gamma producer in this viral disease, mitogen stimulation induced IFN-gamma from all (Leu-2+/2- and Leu-3+/3-) subsets, with panning as the separation technique. As mitogens circumvent the normal processing and presentation of antigen, the RHL system described above may provide a more accurate picture of the relative contributions of helper (Leu-3+) and cytotoxic/suppressor (Leu-2+) T cells to IFN-gamma production in herpes viral disease.

Antibodies, Monoclonal↗
PubMed1983

gamma Interferon production appears to predict time of recurrence of herpes labialis.

Peripheral blood mononuclear cells separated from the blood of 29 volunteers within 3 wk of the onset of recurrent oral herpes labialis spontaneously secreted IFN-gamma (and small amounts of IFN-beta) into the culture medium in varying amounts (mean = 77 U/ml, SE = 17). However, interferon could not be detected in the serum of 10 of these patients tested. In the group as a whole, peak levels of interferon were secreted in vitro at 6 to 20 days after the onset of herpes labialis. Serial studies in eight patients showed peak production in the second or third week, with subsequent decrease to undetectable levels at 6 wk. A strong correlation between peak supernatant interferon level and the time to the next recurrence of herpes labialis in each patient was noted (r = 0.82, p less than 0.0001). Herpes simplex antigen-stimulated mononuclear cell cultures from each patient produced a mixture of IFN-alpha and IFN-gamma. A less marked but still significant correlation was noted between the peak mixed interferon level and the inter-recurrence interval (r = 0.52, p less than 0.005). These results suggest that a recurrent herpes labialis acts as an in vivo stimulus to the induction of IFN-gamma-producing cells that circulate in peripheral blood. The IFN-gamma produced is either a direct determinant of frequency of recurrence of herpes or a quantitative marker for other cellular immune events determining frequency.

Female↗
PubMed1981

Cytology of synovial effusions in epidemic polyarthritis.

Examination of synovial fluid in eight patients with epidemic polyarthritis following Ross River virus infection showed cell counts ranging from 1,500 to 13,800 per mm3. Stained smears were notable for a paucity of neutrophils and high proportions of monocytes and vacuolated macrophages, which were further characterised by light and electron microscopy. Ross River virus antigen was detected by specific immunofluorescence in monocytes and macrophages of four cases early in the course of the illness, but intact virus was not identified by electron microscopy or cell culture. No cell-associated C3 component of complement or immunoglobulin of IgM or IgG class was detected in any cell-type. These findings indicate that cell counts and simple smears may be useful in the early diagnosis of suspected epidemic polyarthritis, and provide further information pertinent to the pathogenesis of this disease.

Adolescent↗
PubMed1980

Incubation time of epidemic polyarthritis.

The incubation time of epidemic polyarthritis was estimated in 20 patients with evidence of Ross River virus infection after spending less than three weeks in areas of risk. The smallest estimate consistent with all cases was a range of seven to nine days.

Arbovirus Infections↗
PubMed1980

Epidemic polyarthritis acquired in Fiji.

Four cases of epidemic polyarthritis which was acquired in Fiji between April and July of 1979 are described. The manifestations of the illness were similar to those of the disease in Australia. Knowledge of the geographic distribution of this disease can be valuable in diagnosis, but it is likely that its range is not yet fully known.

Adult↗
PubMed1980

Possible genetic determinants in epidemic polyarthritis caused by Ross River virus infection.

HLA D locus-related (DR) antigens and Gm phenotypes were determined in 30 patients with epidemic polyarthritis following Ross River virus (RRV) infection and contrasted with those in comparison series of 119 (DR) and 1220 (Gm) normal subjects. HLA DR7 (46.7% cf. 21.0%) and the heterozygous Gm phenotype a+x+b+ (33.3% cf. 15.3%) were significantly increased in the patients, with relative risks of 3.3 and 2.8 respectively. The occurrence of Gm a+x+b+ was independent of DR7, and conferred a relative risk of 4.3 in DR7-negative patients. Differences found in clinical features, specific lymphocyte proliferative responses and antibody titres did not reach significant levels. The association with DR7 was inversely related to age in residents of an area of moderate endemic risk, and to levels of natural cell-mediated immunity (natural killer cell activity). These correlations point to possible mechanisms by which genetic traits might influence the occurrence or consequence of RRV infection.

Adolescent↗
PubMed1979

A study of synovial fluid and cytology in arthritis associated with herpes zoster.

A case of herpes zoster complicated by acute arthritis with effusions is described. The white cell count in the synovial fluid was low, with a predominance of neutrophils. The synovium showed superficial deposits of fibrin, slight intimal hyperplasia, and subintimal polymorph infiltration. Varicella virus was not detected by culture or electron microscopy, but varicella antigen was demonstrated in the cytoplasm of macrophages in the effusion. Other findings did not determine whether the antigen had appeared in the joint from circulating immune complexes, or following synovial phagocytosis or proliferation of virus.

Aged↗