PubMed HealthSearch

Biomedical subjects

I Jack

Publications and source records attributed to I Jack.

At least 19 recordsLinked to original sources

Enhanced insulin-receptor tyrosine kinase activity associated with chromosomal translocation (1;19) in a pre-B-cell leukemia line.

The gene for the insulin receptor has been assigned to chromosome 19 near the breakpoint of the translocation t(1;19) which occurs in 25% of pre-B-cell leukemias. Insulin receptors in a pre-B-cell leukemia cell line (ACV) with t(1;19) were found to have 2-fold higher affinity for insulin, 5-fold higher basal and insulin-stimulated beta sub-unit autophosphorylation, and 2-fold higher basal and 4-fold higher insulin-stimulated beta sub-unit kinase activity on the synthetic peptide poly(Glu,Tyr), compared to receptors in a B-cell line (ADD) with normal karyotype from the same patient. ACV cells had a novel 13-kb receptor mRNA species and expressed a DNA polymorphism localized to the tyrosine kinase domain of the receptor gene. These findings suggest that t(1;19) in the ACV cell may result in rearrangement of the insulin receptor gene and translation of a receptor with enhanced tyrosine kinase activity.

Blotting, Northern

Reported measles immunisation and serological immunity in children attending general practitioners.

To determine the feasibility of serological testing for measles immunity in children attending general practitioners and to assess the validity of establishing immune status by reported immunisation history compared with serology, a cross-sectional descriptive study was conducted in general practices in the Illawarra area south of Sydney, New South Wales. Participants were 234 children under 15 years attending general practitioners. 87 per cent of children were reported to have been immunised against measles, but 46 per cent of these children were seronegative for measles antibody using an ELISA test on finger-prick blood. This could not be explained by inaccurate reporting of immunisation. No causes other than failure to seroconvert or inadequate specificity of the test on the blood samples were evident. Failure to seroconvert as a result of inadequate adherence to cold chain requirements is a possibility that needs further investigation. The results further question whether a single vaccination is adequate to achieve the public health aims of measles immunisation programs.

Adolescent

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

A 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 10,000 kb. The locus FRAXA is either included in the deletion, or located close to the distal break point.

Blotting, Southern

Failure of intraventricular gammaglobulin and alpha interferon for persistent encephalitis in congenital hypogammaglobulinaemia.

A boy with congenital hypogammaglobulinaemia died at the age of 12 years after a viral meningoencephalitis of two and a half years duration due to an untypable picornavirus. He had received intravenous immunoglobulin every four weeks from the time of the start of immunoglobulin replacement treatment at the age of 3 years. The encephalitis did not respond to high dose intravenous gammaglobulin (2500 g during 22 months). The virus could not be isolated during the administration of intraventricular immunoglobulin (38.15 g) and intraventricular recombinant alpha interferon (121 X 10(6) units), but recurred rapidly each time intraventricular treatment was stopped. Further modes of treatment are still required for prevention and treatment of this disorder.

Agammaglobulinemia

Reovirus infection enhances expression of class I MHC proteins on human beta-cell and rat RINm5F cell.

Viruses are implicated in the pathogenesis of beta-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 beta-cells and induce autoimmunity in susceptible mice, could alter the expression of the major histocompatibility complex (MHC) proteins by human beta-cells and rat insulinoma RINm5F cells. Forty-eight hours after infection of either human beta-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 beta-cells infected with reoviruses 1 or 3 also exhibited markedly increased levels of class I MHC proteins. Reovirus infection of human beta-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 beta-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-gamma and tumor necrosis factor) released by immunoinflammatory cells.

Adenoma, Islet Cell

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.

Child, Preschool

RCH-ACV: a lymphoblastic leukemia cell line with chromosome translocation 1;19 and trisomy 8.

A cell line (RCH-ACV) was established from a bone marrow sample of a child with acute lymphoblastic leukemia (ALL). The cell line lacked Epstein-Barr virus nuclear antigen and exhibited a recently described nonrandom chromosome translocation, 1;19, thought to be associated with pre-B-ALL and poor prognosis. Banding studies confirm that the breakpoint of chromosome #19 occurs at p13.3. Cell surface marker analysis using a panel of monoclonal antibodies revealed markers consistent with common ALL phenotype. Although the cells did not show cytoplasmic immunoglobulin, studies of the immunoglobulin gene rearrangement confirmed the pre-B phenotype. This cell line could be of great value to studies of the role of the specific translocation 1;19 in the etiology of pre-B-ALL.

Cell Line

Comparison between children treated at home and those requiring hospital admission for rotavirus and other enteric pathogens associated with acute diarrhea in Melbourne, Australia.

The etiology of acute diarrhea in children less than 42 months of age attending one pediatric hospital in Melbourne, Australia, was studied during a 7-month period encompassing the winter of 1984. Pathogens identified in 157 children treated as outpatients with mild disease were compared with those in 232 children hospitalized with severe disease. The pathogens (and frequencies among outpatients and inpatients, respectively) detected were rotaviruses (32.5 and 50.9%), enteric adenoviruses (8.9 and 7.4%), Campylobacter jejuni (7.2 and 1.3%), and Salmonella sp. (4.0 and 1.7%). Electropherotypes of rotavirus strains from outpatients and inpatients were compared. Two strains predominated during the 7 months of this study and were observed with equal frequency from outpatients and inpatients. Rotaviruses of the same electropherotype caused a wide spectrum of disease, with symptoms ranging from mild to severe, life-threatening diarrhea. The similarity of etiological agents identified from children with mild and severe forms of acute diarrhea suggests that the etiology of community enteric illness can be reasonably inferred from the etiology of inpatient disease in children in the same geographic area. During the winter epidemic period, the severity of symptoms associated with rotavirus infection in young children is likely to be determined by the inherent susceptibility of the host rather than by genetic differences in the strains of infecting rotaviruses.

Acute Disease

Molecular analysis of the RNA and protein components recognized by anti-La(SS-B) autoantibodies.

The aim of this study was to determine whether sera with autoantibodies to the La(SS-B) nuclear antigen react with the same or different sets of cellular or viral ribonucleoproteins (RNPs) and whether patients with anti-La(SS-B) comprised a homogeneous group with respect to phenotypic and serological markers. The 34 anti-La(SS-B) sera studied were detected in the course of screening 2,000 sera referred from patients with suspected or defined multisystem autoimmune disease. Analysis of the molecular components of the small nuclear (sn) RNPs isolated from immune complexes developed in vitro between the IgG fractions of the anti-La(SS-B) sera and cell lines selected for their content of viral and cellular (non-viral) RNA showed that all 34 anti-La(SS-B) sera reacted with the same group of cellular RNAs and with two viral RNAs encoded by Epstein-Barr virus. The La(SS-B) RNPs contained one major 50,000 dalton antigenic polypeptide that resolved into 5-6 heterogeneously charged isospecies on two-dimensional immunoblots. In addition to anti-La(SS-B) reactivity, all 34 sera were shown to contain anti-Ro(SS-A) activity by counterimmunoelectrophoresis (CIEP); however, with three exceptions, the antigenic Ro(SS-A) polypeptide was not detectable by immunoblotting. The homogeneity of this group with anti-La(SS-B) was indicated by the findings that of the 34 cases 31 (88%) had hypergammaglobulinaemia, 33 (97%) had rheumatoid factor and 27 (of 30 tested, 90%) were HLA-B8. Thus all anti-La(SS-B) sera react with the same set of RNAs associated with an antigenic 50,000 dalton nucleoprotein, and the presence of anti-La(SS-B) autoantibodies identified a homogeneous group of patients with the serological and phenotypic features of primary Sjögren's syndrome.

Antibodies, Antinuclear

S-adenosylhomocysteine hydrolase inactivation and purine toxicity in cultured human T- and B-lymphoblasts.

Accumulation of intracellular deoxyadenosine triphosphate and inactivation of the enzyme S-adenosylhomocysteine hydrolase by deoxyadenosine have been suggested as molecular mechanisms for lymphoid toxicity of inherited or acquired deficiency of adenosine deaminase. The relative roles of these two deoxyadenosine-mediated effects for lymphotoxicity have been explored by employing mutant human T- and B-lymphoblasts deficient in either adenosine kinase, deoxycytidine kinase, or both. At low concentrations (less than 25 mumol/L) of deoxyadenosine or ara-adenine, deoxycytidine kinase deficiency decreases growth sensitivity of human T-lymphoblasts to deoxyadenosine approximately fourfold, and to ara-adenine approximately twofold. Loss of both activities completely eliminates deoxyadenosine phosphorylation and cellular dATP accumulation, and decreases deoxyadenosine growth sensitivity approximately 200-fold and ara-adenine sensitivity approximately 80-fold. The inactivation by deoxyadenosine of intracellular S-adenosylhomocysteine hydrolase activity of human adenosine deaminase-deficient B-lymphoblasts and wild-type or deoxycytidine kinase-deficient T-lymphoblasts is comparable, despite the differing toxicity of this compound for these cell lines. Adenosine kinase deficiency in T-lymphoblasts results in resistance to 2'-deoxyadenosine--but not ara-adenine--associated inactivation of S-adenosylhomocysteine hydrolase, and this compound produces comparable degrees of inactivation of S-adenosylhomocysteine hydrolase in both the wild-type and double mutant cells, despite markedly different growth sensitivity. For B-lymphoblasts, 2'-deoxyadenosine together with adenosine produces comparable growth inhibition of wild-type and adenosine kinase-deficient cells, and this inhibition is more marked than with adenosine alone, but is independent of S-adenosylhomocysteine hydrolase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Kinase

A multiple-purpose automatic pressure regulator.

The Gairdner Hospital Automatic Pressure Regulator was developed to deliver a constant pre-set gas pressure for the continuous inflation of infusion pump cuffs or pneumatic tourniquets. It has been found to be economical, safe, reliable and easy to use. The device facilitates both continuous flushing of catheters and rapid intravenous infusions especially during emergency situations. It may also be used in other clinical situations where a continuous gas supply at a pre-set constant pressure is required.

Air Pressure

HLA-DR typing of fetal human spleen and liver lymphoblastoid cells transformed by Epstein-Barr virus.

Because few HLA-DR-positive cells are present in the fetal spleen and liver, full HLA typing cannot be performed. However, B lymphocyte precursors can be transformed with Epstein-Barr virus to produce lymphoblastoid cells which express HLA-A, B, and DR antigens. Successful transformation was achieved, usually with spleen and liver, in nine fetuses aged from 15 to 18 weeks, mostly within 7 to 14 days of initiation of the cultures. Spleen-derived lymphoblasts were more suitable for typing because of their greater homogeneity and higher viability. Tissues from two 13-week fetuses from prostaglandin-induced abortions and from a spontaneously aborted 22-week fetus could not be transformed. This is probably attributable to prolonged ischemia before the tissues were obtained but, in the 13-week fetuses, absence of B lymphocyte precursors was not excluded. HLA-DR typing may be useful in obtaining well matched donor-recipient pairs in fetal pancreatic islet transplantation.

Cell Line

Continuous culture of human/mouse lymphoid hybridomas: pattern of immunoglobulin secretion.

Fusion of human and mouse cells leads to preferential loss of human chromosomes. In this study the loss of human immunoglobulin heavy and light chain production by human/mouse lymphoid hybridomas has been followed longitudinally. A sensitive quantitative ELISA method has been used for measuring human immunoglobulins. The pattern of loss of heavy and light chain production suggests that the genes for human heavy and light chains are on separate chromosomes.

Animals

Adenosine- and deoxyadenosine-mediated altered pyrimidine metabolism in human adeosine deaminase-deficient lymphoblasts.

To evaluate the importance of altered pyrimidine synthesis in the relationship between immune dysfunction and deficiency of ADA, this pathway has been evaluated in normal and ADA-deficient human lymphoblasts. Adenosine and deoxyadenosine effect comparable reductions of radiolabeled bicarbonate incorporation in uridine nucleosides of both normal and deficient cells, with this effect being more prolonged in deficient cells. In ADA-deficient lymphoblasts this altered pyrimidine metabolism is accompanied by reduced intracellular concentrations of PP-ribose-P with adenosine but not deoxyadenosine. The altered PP-ribose-P levels are accompanied by orotic acid accumulation, but this block does not fully account for the net reduction in uridine nucleotide synthesis. This suggests interference of the pyrimidine pathway at another locus, possibly by altered carbamyl phosphate synthetase activity. The mechanism for deoxyadenosine-mediated inhibition is obscure. Despite the demonstrable adenosine- and deoxyadenosine-mediated alterations of pyrimidine metabolism, these changes are not accompanied by marked interference of cell growth for both normal and ADA-deficient lymphoblasts. These data support the hypothesis that altered pyrimidine metabolism is not the basis for the immune disorder in patients with deficiency of ADA.

Adenosine

Herpes virus in an obstetric hospital. III: Prevalence of antibodies in patients and staff.

Seventy per cent of 890 patients and staff members of an obstetric hospital tested for complement-fixing serum antibodies to herpes simplex virus (HSV) were found to be seropositive. Employment, age, socioeconomic and ethnic factors of patients and different categories of staff members were examined in relation to the prevalence of HSV antibodies. Significant differences in the prevalence of antibodies were found between these groups.

Antibodies, Viral

Herpes virus in an obstetric hospital. II: Asymptomatic virus excretion in staff members.

Serial studies of specimens of saliva from 384 asymptomatic members of staff of an obstetric hospital resulted in the isolation of herpes simplex virus (HSV) from 9.6%. This exposure rate of patients to HSV infection was contrasted with the very low incidence of HSV infection in neonates in Australia. Factors associated with the incidence of overt HSV infection and intermittent asymptomatic excretion of HSV were noted and assessed in relation to possible sites of virus location.

Adult