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Biomedical subjects

W Green

Publications and source records attributed to W Green.

At least 19 recordsLinked to original sources

T-lymphocyte proliferation: tyrosine kinases in interleukin 2 signal transduction.

Interleukin 2 (IL-2)-induced tyrosine phosphorylation appears to play a major role in IL-2-induced cellular proliferation. Several intracellular substrates including the beta chain of the IL-2 receptor complex (IL-2R beta), raf, MAP2 kinase, the regulatory 83 kDa subunit of phosphatidylinositol-3 kinase and S6 kinases are substrates for the IL-2 receptor activated kinase(s). However, none of the identified members of the IL-2 receptor complex exhibits intrinsic tyrosine kinase activity. Therefore, the IL-2R complex must activate intracellular tyrosine kinases. We have demonstrated that specific tyrosine and serine/threonine kinases are coprecipitated with IL-2 receptor constructs that mediate IL-2-induced cell proliferation but not with those that do not. The IL-2-activated tyrosine kinase appears to be associated with a serine and proline rich intracellular domain which is highly conserved between IL-2R beta and the erythropoietin receptor. Although the responsible kinase has not been identified, lck, fyn, fgr, ltk, hck and lyn can be ruled out as obligatory mediators. Using methods to clone tyrosine kinases from T cells, we have identified potential candidate kinases, including several which had not been known to be expressed by T lymphocytes as well as several unique kinases which had not been previously identified in any cell type.

Amino Acid Sequence

Autopsy findings in HIV-infected inner-city patients.

To assess the importance of the autopsy in HIV-1 infection, we retrospectively reviewed the autopsy reports of 70 HIV-1-seropositive patients at Howard University Hospital. Of the 58 patients with AIDS, the diagnosis of AIDS was made after autopsy in 24 (41%) cases. The lung was the most common site of AIDS-diagnostic diseases, and was affected in 90% of patients. Pneumocystis carinii infection was the most common AIDS-diagnostic disease, and was present in 50% of the AIDS patients. Thirty-eight percent of AIDS diagnostic diseases were diagnosed antemortem, including 15 of the 29 Pneumocystis carinii infections. Most of the AIDS-diagnostic diseases were disseminated at autopsy and two or more diseases were found in some organs. Overall, Pneumocystis carinii pneumonia was the most common cause of death, accounting for a mortality of 43% among AIDS patients. Bacterial infections were common and contributed to the mortality and morbidity of both AIDS and non-AIDS patients. Bacterial infection was the cause of death in 15 AIDS and 9 non-AIDS patients. The clinical cause of death concurred with the pathological cause in 53% of our cases.

Adult

Hemodialysis with cuprophane membrane modulates interleukin-2 receptor expression.

Chronic dialysis patients have several indices of immune deficiency. We examined the hypothesis that the biocompatibility of dialysis membranes may influence the ability of lymphocytes to express interleukin-2 (IL-2) receptors on their surface, a key event in cellular immune response. We investigated the potential role of the dialysis membrane in eight chronic hemodialysis patients. The study design was a cross-over study using cuprophane and polymethylmethacrylate (PMMA) membranes. Chronic dialysis with new cuprophane membrane leads to an increase in baseline expression of the two subunits of IL-2 receptors. IL2R alpha (p55, CD25) and IL-2R beta (p70), in peripheral blood mononuclear cell (PBMC). However, Phytohemagglutinin (PHA) stimulation of PBMC harvested after two weeks of dialysis with cuprophane membrane showed a markedly decreased expression of high affinity IL-2 receptors. These findings are reversed when patients were dialyzed with a PMMA membrane which is also associated with minimal complement activation. The increased expression of IL-2 receptor subunits are reproduced in vitro by direct contact of PBMC with cuprophane membrane and by the addition of the anaphylatoxin C5a. This study confirms the participation of lymphocytes in the complex blood-membrane interactions that occurs during dialysis; the results may be relevant to observations of immune deficiency in dialysis patients.

Aged

Oral intubation in the multiply injured patient: the risk of exacerbating spinal cord damage.

The use of oral intubation during the resuscitation of seriously injured patients has been discouraged because of the fear that this technique may lead to cervical cord damage. We report a retrospective study of the 18-month experience of an emergency department in which oral intubation was the usual method of airway control for victims of blunt trauma. There were 237 injured patients intubated in the ED; 21 patients (8.9%) had cervical cord or bone injury. There were no patients in whom a neurologic loss followed an airway maneuver. Oral intubation was the definitive airway maneuver in 213 patients. There was no statistically significant difference in the type of definitive airway maneuver used (eg, oral intubation, nasal intubation, or cricothyrotomy-tracheotomy) between patients with cervical injuries and patients without such injuries. The risk of spinal cord injury secondary to oral intubation in the seriously injured patient was low in our population. Selection of the method for definitive airway control should be based primarily on the operator's skills and experience rather than the fear of inflicting cervical cord damage.

Adult

Evidence for thyroid hormone deficiency in iron-deficient anemic rats.

Iron-deficient anemic rats have previously been shown to have low plasma levels of thyroid hormone and a poor plasma thyroid hormone response to acute cold exposure. As an initial exploration, we examined thyroid hormone metabolism during iron deficiency in age-matched rats from three aspects: 1) plasma TSH (thyrotropin, thyroid stimulating hormone), T4 (thyroxine) and T3 (triiodothyronine) responses to graded doses of exogenous TRH (thyrotropin releasing hormone), 2) plasma T3 kinetics, and 3) rates of hepatic T3 production. Iron-deficient anemic rats had lower basal TSH values and blunted TSH responses to intravenous TRH injection at three different doses (10, 25 and 50 ng TRH/100 g body wt). Iron-deficient anemic rats also had a significant decrease in plasma T3 turnover (42 vs. 88 ng/h in controls), and significantly lower hepatic T4-5'-deiodinase activities than controls [26 vs. 44.0 ng T3/(mg protein.20 min)]. Thus, decreased rates of T3 production in iron-deficient anemic rats, as documented by turnover studies, may be related to decreased deiodinase activity and reduced peripheral formation of T3. The dampened TSH responses to TRH further facilitate or perpetuate this T3 deficiency. We propose that this abnormal thyroid state is partially responsible for impaired thermogenesis in iron-deficiency anemia.

Anemia, Hypochromic

Asthma and chronic airflow limitation in the highlands of Papua New Guinea: low prevalence of asthma in the Asaro Valley.

The prevalence of asthma in the South Fore region of Papua New Guinea was found to be 7.3%, which is thought exceptionally high for highland areas in this country. To investigate the prevalence of asthma and of chronic airflow limitation in a different highland region with similar living conditions, adults and children from 7 villages in the Asaro Valley were interviewed. Questions were asked about smoking history and about past and present symptoms of cough, of shortness of breath, of chest tightness and of asthma. Of 743 adults interviewed, 206 underwent a clinical study with measurements of lung function, bronchial responsiveness and skin prick tests. Dust was collected from the floors and blankets of 36 houses for counts of house dust mites. We did not find any children with symptoms of asthma. Only 2 adults (0.3%) had symptoms consistent with asthma, and a further 6.2% had symptoms and/or lung function consistent with chronic airflow limitation. Most bronchial hyperresponsiveness was associated with asthma or with chronic airflow limitation. The prevalence of atopy was similar in the Asaro and South Fore populations, but the South Fore had higher house dust mite counts in blanket dust. The low prevalence of asthma in the Asaro Valley is unexplained in terms of factors normally associated with asthma. Because asthma in this area does not appear in childhood and only develops in a small proportion of adults, it may be of different aetiology to asthma in Caucasian populations.

Adult

Relationship between mite densities and the prevalence of asthma: comparative studies in two populations in the Eastern Highlands of Papua New Guinea.

The recent dramatic rise from 0.1 to 7.3% in the prevalence of adult asthma in the South Fore area of the Eastern Highlands of Papua New Guinea (PNG) has not been matched by a similar increase in asthma in the adjacent Asaro valley, where the prevalence remains extremely low at 0.3%. While the living conditions of these two populations appear comparable, the mean density of house dust mite (principally Dermatophagoides pteronyssinus) in blankets of residents in the Asaro valley was found to be significantly lower (283/g dust) than that of a corresponding random selection in the south Fore (1371/g dust). Since from 200 to 600 mites per g dust have been reported to constitute a risk factor for asthma, the data suggest that the relative risk for asthma in the Asaro valley population is low compared with that in the South Fore. In randomly selected sera, both IgE and IgG antibodies to D. pteronyssinus from the Asaro valley were comparable with those of a group of non-asthmatics from the South Fore (mean 4.39 vs 3.43 U/ml for IgE antibodies and 1832 vs 1815 U/ml for IgG antibodies for Asaro valley vs South Fore, respectively) but significantly lower (P less than 0.001) than corresponding data for subjects in the South Fore with asthma (108.6 U/ml and 3365 U/ml, respectively). This study emphasizes the interplay between genetic and environmental factors in determining the development of asthma, and highlights the importance of house dust mites in the pathogenesis of asthma in the Eastern Highlands of Papua New Guinea.

Adult

High-affinity interleukin 2 binding by an oncogenic hybrid interleukin 2-epidermal growth factor receptor molecule.

Both interleukin 2 (IL-2) and epidermal growth factor (EGF) receptors exist in two forms that differ with respect to affinity for their ligand. Only the high-affinity receptors appear to be responsible for the proliferation signal delivered upon binding of the growth factor. Fibroblasts transfected with IL-2 receptor cDNA generate only low-affinity receptors for IL-2, but fusion of membranes from these fibroblasts with T-cell membranes converts some receptors to high affinity, indicating the involvement of a T cell-specific factor in the generation of high-affinity receptors. We have constructed a chimeric cDNA molecule containing the extracellular IL-2-binding domain of the IL-2 receptor cDNA and the transmembrane and intracellular tyrosine kinase domains of the EGF receptor cDNA. When transfected into fibroblasts, this IL-2-EGF receptor cDNA generated high-affinity receptors for IL-2. Moreover, fibroblasts transfected with the chimeric molecule were morphologically transformed and produced rapidly growing tumors in nude mice.

Animals