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Biomedical subjects

J Barker

Publications and source records attributed to J Barker.

At least 109 records · Page 6Linked to original sources

Mouse platelet-derived growth factor receptor alpha gene is deleted in W19H and patch mutations on chromosome 5.

The mouse W19H mutation is an x-ray-induced deletion of more than 2 centimorgans on chromosome 5 encompassing the white spotting mutation W (encoded by the Kit protooncogene), patch (Ph), and recessive lethal (l) loci. The platelet-derived growth factor receptor alpha gene (PDGFRA) like Kit encodes a transmembrane receptor tyrosine kinase. By using mouse-Chinese hamster somatic cell hybrids and haplotype analysis in interspecific backcross mice, mouse Pdgfra was mapped to chromosome 5 in tight linkage with Kit. Hybridization of a PDGFRA probe to DNAs from W19H/ + heterozygous mice and patch heterozygous mice, and their wild-type littermates, demonstrated deletion of Pdgfra. Pulsed-field gel electrophoresis indicated that Kit and Pdgfra are linked on a 630-kilobase Mlu I DNA fragment. Thus the W19H deletion removes at least two receptor tyrosine kinases and the results suggest Pdgfra as a candidate for the Ph locus.

Animals↗

The systemic influence of recombinant interleukin 2 on the manifestations of lepromatous leprosy.

14 patients with lepromatous leprosy received twice daily injections of 10 micrograms recombinant interleukin 2 (rIL-2), by the intradermal route, in the skin of the back for 8 d (total dose, 160 micrograms). Lymphokine administration was accomplished without drug toxicity, or the development of acute nerve damage. The majority of patients developed nontender axillary lymphadenopathy during the course of treatment. Local injection sites showed progressively larger zones of induration, peaking at 24 h and persisting for many days. Early 12-h reactions were of a macular, erythematous nature and exhibited an increasingly striking diurnal variation. The morning injection sites were three- to fourfold larger in diameter than those placed in the evening (9 am to 9 pm). Systemic manifestations of intradermal rIL-2 administration were noted. Peripheral blood T cells, including CD4+ and CD8+ phenotypes, increased 2-2.5-fold and NK cells increased sixfold. Elevations in [3H]TdR incorporation into peripheral blood mononuclear cells occurred to a variety of mycobacterial antigens, but not to those of Mycobacterium leprae. Within 2 wk, biopsies at sites far removed from the back showed increased infiltration of mononuclear cells in 12 of 14 patients. Immunocytochemistry revealed the presence of newly emigrated CD4+ T cells, monocytes, and dermal CD1+ Langerhans cells. Endothelial cells of small dermal vessels expressed major histocompatibility complex class II determinants on their surface. Transmission electron microscopy of these specimens revealed markedly enlarged endothelial cells with many surface projections extending into the lumen as well as extravasating lymphoid cells. The numbers of acid-fast M. leprae in the peripheral sites were examined by slit smear and in biopsies of matched leprosy lesions taken before and after IL-2 administration. Within 2 mo, slit smears showed a 0.5 log or greater reduction in 12 of 14 patients, with a mean for all patients tested of 0.5 log units. Biopsy specimens showed a 1 log unit or greater reduction in the bacterial index (B.I.) in 6 of 14 patients. Historical controls in this Nepalese population showed a 0.5 log unit reduction after multidrug therapy over a period of 12 mo. Thus, after 8 d of IL-2 injections, a fivefold reduction in B.I. was observed during the first 2 mo of the study. Antibody levels against M. leprae phenolic glycolipid 1 (PGL-1) and lipoarabinomanan B were markedly elevated after IL-2 injections, while PGL-1 antigen levels were reduced. We conclude that the administration of rIL-2 has had a significant effect in decreasing the total body burden of M. leprae.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Evaluation of human exposure to the heptachlor epoxide contamination of milk in Hawaii.

The commercial milk supply on Oahu was contaminated by heptachlor epoxide for as long as 15 months during 1981-82 at levels possibly as high as 1.2 ug/g, fat basis. Following the contamination, several investigators attempted to evaluate potential adverse health outcomes, especially among infants and young children. However, results of the initial investigations are inconclusive due to lack of reliable measures of heptachlor exposure, use of non-random sampling techniques, and lack of definitive health outcomes attributable to heptachlor epoxide. The design of a current study to assess the body concentrations of heptachlor epoxide and related pesticides in Hawaii is presented. The study is designed (1) to relate these concentrations to prior exposure via the milk contamination, and (2) to assess the reliability of breast milk and serum pesticide concentrations as objective biological markers of body burden. No attempt is made to relate these data to health outcomes; instead, the findings may provide the foundation for future health studies or surveillance of environmental exposure to pesticides in Hawaii.

Animals↗

Viruses associated with acute lower respiratory tract infections in children from the eastern highlands of Papua New Guinea (1983-1985).

This study, conducted at Goroka Hospital from January 1983 to June 1985, examined the viruses identified in nasopharyngeal aspirates (NPA) and urines collected from 716 hospitalised children with moderate or severe pneumonia, in NPA from 170 children with mild pneumonia treated as outpatients and in NPA from a control group of 428 children attending the outpatient department of Goroka Hospital suffering from minor ailments other than upper or lower respiratory tract infections. One or more viruses were identified from 68%, 51% and 43% of children with moderate or severe pneumonia, mild pneumonia and the control group, respectively. One-third of viruses were identified in conjunction with another virus in both control and sick children. Viral identification rates were highest in children under 1 year of age. Cytomegalovirus, adenoviruses, respiratory syncytial virus (RSV), measles and rhinoviruses were the most frequently identified viruses. RSV was associated with mild as well as moderate and severe disease. No virus was associated with an increased risk of death. Annual epidemics of RSV occurred during the wet season. An epidemic of influenza A virus and also influenza B virus and 3 epidemics of parainfluenza 3 virus occurred during the study period. The high viral identification rates in this study suggest a high frequency of transmission associated with the social structure and environment of Papua New Guinean highland villages and high population mobility.

Acute Disease↗

Clinical signs and risk factors associated with pneumonia in children admitted to Goroka Hospital, Papua New Guinea.

This study examined the clinical signs and symptoms in 897 children aged under 5 years presenting with pneumonia to Goroka Hospital in the highlands of Papua New Guinea between June 1982 and July 1985. The usefulness of the signs in predicting severity of disease was determined and risk factors for severe disease were identified. While cyanosis and poor feeding were the strongest predictors of death, bronchial breathing, grunting, and nasal flaring also significantly increased the risk of dying. First-born children, children under 1 year of age, females, malnourished children, and children with symptoms for more than 7 days were at increased risk of severe disease and of dying. Fever alone did not increase the risk of dying unless it was present for more than 7 days. These clinical signs of severity and risk factors may be used to improve the efficiency of health education programmes, for both health workers and mothers, aimed at reducing childhood mortality from pneumonia.

Anti-Bacterial Agents↗

Clinical signs that predict death in children with severe pneumonia.

It is important to define clinical signs that can be used to identify children who have a high risk of dying from pneumonia so that these children can be given more intensive therapy. We prospectively studied 748 children in Papua New Guinea who had severe pneumonia, as defined by the World Health Organization. There was a very high mortality in children with a prolonged illness, severe roentgenogram changes, cyanosis, leukocytosis, hepatomegaly or inability to feed, and there was a trend toward a higher mortality in children with grunting or severe chest indrawing. Afebrile malnourished children had a particularly high mortality, but afebrile children had an increased mortality only if they were malnourished, and malnourished children had an increased mortality only if they were afebrile. Mortality was not increased in very young children or in children with tachypnea or tachycardia. The World Health Organization has suggested that most children with pneumonia in developing countries can be treated with penicillin but has recommended that children who are cyanotic or too sick to feed be treated with chloramphenicol because of their high risk of dying; our findings confirm that children who are cyanotic or too sick to feed have a very high risk of dying from pneumonia.

Age Factors↗

Tissue PO2 and functional capillary density in chronically ischemic skeletal muscle.

In order to study changes in functional capillary density and tissue PO2 in chronically ischemic skeletal muscle, a new model, using the Syrian golden hamster was developed. In the hamster dorsal skin fold, which receives its vascular supply from two cranial and two caudal feeding arteries, a double frame chamber was implanted and ischemia was induced in the cranial part by heat coagulation of the cranial arteries outside of the chamber. This technique allows for analysis of microvascular hemodynamics and local tissue PO2 prior to and during a prolonged period of ischemia in skin muscle. As result of ischemia the diameters of the arterioles increased (p less than 0.001) over the whole 11 day observation period. Functional capillary density decreased significantly (p less than 0.01) during the first 7 days, while capillary RBC-velocity was reduced throughout the 11 days of observation. RBC-velocity in collecting venules was diminished significantly throughout the postischemic observation period. The diameters of the collecting venules first increased upon ischemia (p less than 0.001) but were found decreased at 4, 7 and 11 days. Measurements of tissue PO2 demonstrated a marked decrease from a mean PO2 of 20.5 mmHg prior, to 9.5 mmHg following induction of ischemia. The model allows for induction of chronic ischemia and is suitable to study the effect of therapeutic measures on the microcirculation in chronically ischemic skeletal muscle in vivo.

Animals↗

An intervention study using thiabendazole suspension against Strongyloides fuelleborni-like infections in Papua New Guinea.

In an isolated rural community in Papua New Guinea, 88 children were found to be infected with Strongyloides cf. fuelleborni; 50 of these also had hookworm infections. Their ages ranged from one to 124 months and all were treated with thiabendazole suspension, 25 mg/kg twice daily for 3 days. 2 patients with Strongyloides and 5 with hookworm were still passing ova 2 weeks after treatment although their egg counts were lower or the same as the pre-treatment counts. 26 children experienced some side effects from the drug, vomiting being the most common; in none did side effects prevent completion of therapy. No association between Strongyloides egg load and nutritional status, hepatosplenomegaly, respiratory ailments, oedema or serum albumin levels was found.

Child↗

v-abl activates embryonic globin gene expression in mouse erythroleukemia cells.

The Philadelphia chromosome translocation, which is present in 90-95% of chronic myelogenous leukemia patients, involves translocation of the c-abl protooncogene to chromosome 22 and is accompanied by activation of embryonic globin gene expression in the K562 chronic myelogenous leukemia cell line. To test directly if the protein products of the translocated c-abl protooncogene can activate embryonic globin gene expression, we transfected the v-abl oncogene (which shares the property of autophosphorylation with the translocated c-abl protooncogene) into mouse erythroleukemia cells. v-abl-transfected mouse erythroleukemia cells, which contained multiple copies of the v-abl transgenome, exhibited activation of mouse embryonic globin gene expression. These results suggest that the translocated c-abl protooncogene of the Philadelphia chromosome translocation is central to the pathogenesis of chronic myelogenous leukemia and that it may result in the activation of embryonic globin genes in some chronic myelogenous leukemia cell lines.

Abelson murine leukemia virus↗

Factors affecting growth of Legionella pneumophila in liquid media.

The growth in liquid media of Legionella pneumophila serogroups 1-6 was monitored turbidimetrically and factors affecting growth rate were studied. The presence of inhibitors, use of detoxifying agents and the method of broth preparation each had significant effects on cultivation. Cysteine was essential for growth; the optimal concentration was 100 micrograms/ml, but supplemental iron had no demonstrable effect.

Culture Media↗

Self-rated health as a predictor of hospital admission and nursing home placement in elderly public housing tenants.

We assessed the validity of self-rated health in a one-year prospective study of 155 elderly public housing tenants. Compared to studies of elderly community residents, tenants had poorer self-rated health, and higher hospital admission and nursing home placement rates. Poor self-rated health was a risk factor for both outcomes. We conclude that self-rated health may be useful in identifying persons at increased risk for hospital admission and nursing home placement.

Aged↗