Ian Jack

Cytomegalovirus in Human Milk

KNOWLEDGE of the usual modes of transmission of cytomegalovirus (CMV) infection is incomplete.1 The possibility of viral transmission from infected cervical secretions to infants at the time of del...

A prospective study of the role of cytomegalovirus in post-transfusion mononucleosis.

Abstract After open-heart surgery post-transfusion mononucleosis developed in six patients who had had cytomegalovirus complement-fixing (CMV-CF) antibody before operation. Three of them showed an appreciable antibody rise during the episode of mononucleosis, and cytomegalovirus was isolated from the leukocytes of another two. One donor to a patient with mononucleosis and cytomegalovirus in the blood had a rising CMV-CF antibody titer. This donor, it is suggested, may have been viremic at the time of donating blood and that he constituted an exogenous source of virus. The cytomegalovirus in the blood of patients experiencing post-transfusion mononucleosis may be of endogenous as well as of exogenous derivation. It is questionable whether cytomegalovirus was responsible for the hematologic changes observed.

Reovirus Infection Enhances Expression of Class I MHC Proteins on Human β-Cell and Rat RINm5F cell

Viruses are implicated in the pathogenesis of β-cell destruction in type I (insulin-dependent) diabetes. The aim of our study was to investigate whether reovirus 1 or reovirus 3, which are known to infect β-cells and induce autoimmunity in susceptible mice, could alter the expression of the major histocompatibility complex (MHC) proteins by human β-cells and rat insulinoma RINm5F cells. Forty-eight hours after infection of either human β-cells or RINm5F cells with reovirus 1 or reovirus 3, cytopathic effects were noted. By flow-cytofluorometric analysis, infected RINm5F cells exhibited a seven- to eightfold increase in the surface expression of class I MHC proteins. Upregulation of class I MHC proteins on reovirus 3-infected RINm5F cells was inhibited by 80% after preexposure of the virus to reovirus 3 antiserum. When analyzed by double-indirect immunofluorescence microscopy, human β-cells infected with reoviruses 1 or 3 also exhibited markedly increased levels of class I MHC proteins. Reovirus infection of human β-cells or RINm5F cells was not accompanied by the induction of class II MHC proteins. These findings suggest that 1) in addition to direct cytopathic effects, reovirus infection may contribute to β-cell destruction by increasing expression of class I MHC proteins and therefore reactivity with cytotoxic T-lymphocytes; and 2) some viruses may increase MHC protein expression independent of and before the action of cytokines (e.g., interferon-γ and tumor necrosis factor) released by immunoinflammatory cells.

Unusual X chromosome inactivation in a mentally retarded girl with an interstitial deletion Xq27: implications for the fragile X syndrome

SummaryA de novo interstitial deletion (X)(q27.1q27.3), between the loci DXS 105 and F8, has been found in a mentally retarded female. The deleted X chromosome is preferentially early replicating in fibroblasts, B cells and T cells, suggesting that the missing region plays a role in inactivation of the X chromosome. None of the available DNA probes except DXS 98 maps to the deleted region of about 10000kb. The locus FRAXA is either included in the deletion, or located close to the distal break point.

Pneumonia associated with infection with pneumocystis, respiratory syncytial virus, chlamydia, mycoplasma, and cytomegalovirus in children in Papua New Guinea.

Paired serum samples were collected from 94 children with pneumonia admitted to Goroka Hospital, Papua New Guinea. All but three of the children were aged 1-24 months. Only nine children were malnourished, with weight for age less than 70% of the Harvard median (three had weight for age less than 60% of the Harvard median). Pneumocystis carinii antigen was detected in the serum of 23 children. Twenty two children had serological evidence of recent infection with respiratory syncytial virus. Five children were probably infected with Chlamydia trachomatis at the time of the study, and there was less convincing serological evidence of current infection in a further 11 children. Five children showed a fourfold rise in antibody to Mycoplasma pneumoniae. Although only one child showed a fourfold rise in antibody to cytomegalovirus, 86 children had this antibody. No child showed a fourfold rise in antibody to Ureaplasma urealyticum or Legionella pneumophila. P carinii, respiratory syncytial virus, C trachomatis, M pneumoniae, and cytomegalovirus may be important causes of pneumonia in children in developing countries.

LYMPHOCYTE VIRÆMIA IN CONGENITAL RUBELLA

Abstract Venous blood was taken from three babies with the congenital-rubella syndrome. Lymphocytes were separated out, cultured, and examined for the presence of rubella virus. It is concluded that the circulating small lymphocytes of some such patients do contain rubella virus.

Cellular Viraemia in Babies Infected with Rubella Virus before Birth

Chronic viraemia has been detected in 10 out of 12 rubella syndrome babies at periods ranging from 1 to 196 days. The virus was found to be associated with leucocytes, and it is assumed that removal of neutralizing antibody is the most likely explanation for the high success rate in detecting viraemia. The findings are discussed in relation to diagnosis by virus isolation, to pathogenesis, and to the possible significance in explaining the failure of the foetus to develop a tolerance to rubella virus. Several published reports of viraemia in the acute exanthematous disease are contrasted with the less frequent reports of viraemia in the chronic disease of early postnatal life.

Cytokine production in response to Epstein-Barr virus infection of peripheral blood mononuclear cells in vitro

To obtain a better understanding of the immune response to Epstein‐Barr virus (EBV), we measured the cytokines tumour necrosis factor (TNF)‐α/β, interleukin‐2 (IL‐2), interferon‐gamma (IFN‐γ), IL‐6 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in the conditioned medium of peripheral blood mononuclear cells from 10 healthy adults before and at 48 h and at 1, 2, 3 and 4 weeks following infection in vitro with EBV. Cultures were examined for regression of outgrowths of nascent virus‐transformed B cells, and populations of cells in the cultures were analysed by flow cytometry.

Identification of Two Possible Types of Virus Particle in Rubella-infected Cells

Summary Cultures of RK 13 and BHK 21 cells infected with rubella virus were examined by electron microscopy when the cultures showed maximal cytopathic effects. Infected RK 13 cells contained crystalline inclusions (spacing 190 A) as well as typical virus particles of total diameter 600 A, with a dense 300 A core. Identical particles also occurred in infected BHK 21 cells, but in these no crystals were observed. Neither crystals nor particles were found in control cells. The particles did not resemble myxoviruses.

Inhibition of whole blood antibody dependent cellular cytotoxicity by heat aggregated human IgG.

Inhibition of the whole blood antibody dependent cellular cytotoxicity (ADCC) of a lymphoblastoid cell line by heat aggregated human IgG (HAI) is described. Optimal sensitising antibody and effector cell concentrations were established to permit the detection of 0.1 microgram/ml HAI. Conditions which avoid the ADCC inhibitory effects of normal human sera were defined. Twelve paired normal human sera were stored at -70 degrees C for prolonged (greater than 3 years) and shorter (less than 6 months) periods of time. Sensitised sheep red cells were used to determine complement depletion in serum dilutions heated at 40 degrees C, 45 degrees C, 50 degrees C. Concentrations of human IgG (1 000-0.1 microgram/ml) were prepared in foetal calf serum before heating at 63 degrees C for 30 min to aggregate the IgG. ADCC inhibitory activity, frequently characteristic of normal human serum was minimised (less than 10%) when sera were stored at -70 degrees C and heated to 50 degrees C for 30 min to inactivate serum complement. This assay provides an economical, reproducible and sensitive test for the detection of circulating IgG complexes.