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Biomedical subjects

I Jack

Publications and source records attributed to I Jack.

At least 37 records · Page 2Linked to original sources

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↗

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.

Antibody-Dependent Cell Cytotoxicity↗

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↗

Herpes virus in an obstetric hospital: I: Herpetic eruptions.

In a one-year prospective study, 199 of 347 (34%) staff members in direct contact with patients reported 165 non-genital herpes simplex virus (HSV) infections. The mean working time lost due to these infections was 4.7 days (aggregate, 778 days for the year). Serum antibody titre was not significantly associated with the recurrence rate or the duration of infection. A comparison was made of the ethnic, social and environmental histories of staff members prone to HSV infections and of seronegative staff members with no record of cold sores. The absence of effective treatment at present is noted.

Adult↗

Association of respiratory virus infections with sudden infant death syndrome.

From September, 1974, to September, 1979, 488 cases of sudden infant death syndrome (SIDS) in Melbourne were studied for evidence of viral infection. One hundred and eighty-eight infants (39%) yielded one or more viruses, with respiratory viruses being detected in 102 cases (21%). Further evidence of a respiratory virus association with SIDS was obtained by comparing the monthy respiratory virus isolation rates at the Royal Children's Hospital from 1973 to 1979 with the incidence of SIDS in the same period. A highly significant correlation was obtained between these isolation rates and the incidence of SIDS, which suggests that respiratory viruses play a role in SIDS in Melbourne.

Adenoviridae↗

Seasonal pattern in childhood viral lower respiratory tract infections in Melbourne.

Respiratory syncytial virus and parainfluenza viruses are the major pathogens in acute lower respiratory infection in infants and younger children. They show distinct seasonal patterns. An annual epidemic of respiratory syncytial virus infection is seen in Melbourne and this coincides with the coldest months of the year. Parainfluenza virus Type 1, the most frequent cause of laryngotracheobronchitis, occurs as an autumn epidemic every second year. Parainfluenza virus Types 2 and 3 are present most years and do not show a clear seasonal pattern.

Acute Disease↗

Adult non-endemic Burkitt's lymphoma. An Australian case report.

This report describes the occurence in Australia of non-endemic Burkitt's lymphoma in a 43-yr-old European migrant. The patient presented with cervical lymphadenopathy and massive bone marrow involvement, and died 6 mth later with intracranial spread of the tumour. The pathological features, course and treatment of the disease are described.

Adult↗

A scanning electron microscopic examination of retinoblastoma in tissue culture.

Tissue cultures were established from 6 retinoblastomas and the cultured cells examined by scanning electron microscopy. Cells from cultures of normal fetal retinal and glial tissue were also examined by SEM. Though a number of different cell types were found to coexist in the retinoblastoma cultures, most had the features of cells of either glial or neuronal origin. Evidence of further differentiation of cells in each series was seen. These findings indicate that the cell of origin in retinoblastoma is a multipotential stem cell which, though neoplastic, is still capable of differentiation into both glial and neuronal series.

Brain↗

Studies of the aetiology of neonatal hepatitis and biliary atresia.

Aetiological factors were sought prospectively in 55 babies with extrahepatic biliary atresia, in 105 with neonatal hepatitis, and in 11 with intrahepatic biliary atresia, seen as a result of nearly complete ascertainment of these conditions in the State of Victoria between 1963 and 1974. In neonatal hepatitis infective causes were shown in 22 babies, galactosaemia in 6 and alpha1-antitrypsin deficiency in 8; familial occurrence was noted in 10 further babies and unrelated second diseases were present in 24 of the remaining 59 babies. The only clues to aetiology in extrahepatic biliary atresia were a suspicion of time-space clusters, a deficiency of affected babies born to young primiparous women, and an unexpected number of spontaneous abortions in the histories given by the mothers. Genetic factors appeared to be important in intrahepatic biliary atresia, but are not reported in detail. Hypotheses for the aetiology of neonatal hepatitis and of extrahepatic biliary atresia are presented. Both are considered syndromes with multiple causes. Recurrence risks in sibs are discussed, and are 1 in 7 for neonatal hepatitis of unknown cause, negligible in extrahepatic biliary atresia, and usually 1 in 2 or 1 in 4 in intrahepatic biliary atresia, depending upon the family history.

Abortion, Spontaneous↗