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Biomedical subjects

W Green

Publications and source records attributed to W Green.

At least 55 records · Page 3Linked to original sources

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↗

Mediators of hypersensitivity and "fog"-induced asthma.

Seven asthmatic and five normal subjects inhaled increasing amounts of nebulized water ("fog"). Neutrophil chemotactic activity (NCA), histamine and FEV1 measurements were undertaken before and at time intervals after challenge. In asthmatics, the mean maximal reduction in FEV1 (+/- 1 SD) was 46.6% +/- 11.5; whereas, in normal subjects, the reductions were less than 20% of pre-challenge values after the inhalation of 33 ml of water. There were no significant differences in the pre-challenge values for NCA between the asthmatics and the normal controls. When the highest values for NCA during the 30 min after challenge in the asthmatics were compared with controls there was a significant increase (P less than 0.02). The percentage change in NCA was also significantly greater in the asthmatics compared with the controls at 10 min after challenge (P less than 0.05). Fog-induced NCA was shown to be associated with proteins with approximate molecular weight of 600,000 daltons (as assessed by gel filtration chromatography on Sephacryl-S400). There was an increase in plasma histamine in the asthmatics after challenge but this was not significantly greater than the controls. These findings support the view that mediators might be involved in fog-induced asthma, possibly as a result of mast cell degranulation by "osmotic shock".

Adult↗

Effect of iron-deficiency anemia on hormone levels and thermoregulation during cold exposure.

When exposed to an ambient temperature of 4 degrees C, iron-deficient anemic rats become hypothermic. This lesion is related more to anemia than to tissue iron deficiency, since exchange transfusion to hematocrits over 25 restored normal thermoregulatory performance. Likewise poor cold responses were induced in control rats by transfusion to low hematocrits. Cold sensitivity in all anemic animals was paralleled by poor thyroid responses: there was a significant positive correlation between hematocrit and percent rise in triiodothyronine (r = 0.63) and thyroxine (r = 0.53) during 6 h at 4 degrees C. Basal levels of thyroid-stimulating hormone (TSH) were similar in control and iron-deficient animals: after cold exposure, TSH rose to higher levels in those animals with hematocrits over 25 than in those with lower hematocrits. Diminished O2 delivery to tissues responsible for heat production is probably a major component of the cold sensitivity of anemic rats. The novel finding that thyroid hormone responses are compromised by anemia implies effects on hormonal regulation that may also contribute to this functional lesion.

Anemia, Hypochromic↗

Low incidence of deletion of the esterase D locus in retinoblastoma patients.

Esterase D was quantitatively measured in the red blood cells from three patients from three separate kindreds who had abnormalities of chromosome 13. The esterase D activity was proportional to the number of copies of the q14 region of chromosome 13 present. These findings confirm published data localizing the esterase D gene to chromosome band 13q14, a region which is important in the etiology of retinoblastoma. Fifty-one additional retinoblastoma patients not known to have any chromosomal defect also underwent esterase D determination. In none of these patients did the esterase D measurement detect a 13q14 deletion. The normal esterase D levels in this series of 51 retinoblastoma patients suggest that deletion of an esterase D locus is infrequent in retinoblastoma patients. It must be noted that patients who are mosaics, with a 13q14 deletion in only a fraction of all somatic cells, could possibly have normal red blood cell esterase D levels. Further study is necessary to determine if esterase D determination of all retinoblastoma patients is a worthwhile clinical tool.

Adolescent↗

Defective thyroid hormone action in fibroblasts cultured from subjects with the syndrome of resistance to thyroid hormones.

Two preadolescent girls and their mother with the syndrome of central and peripheral resistance to thyroid hormones are reported. The sisters had goiters, high radioiodine uptakes, high plasma levels of thyroid hormones, normal TSH levels, and brisk increases in TSH after TRH administration, but had no clinical evidence of thyrotoxicosis. The mother, who had undergone partial thyroidectomy and radioiodine therapy, presented with mild hypothyroid symptoms, normal thyroid hormone levels, and a high TSH level. On T4 treatment, her TSH fell toward normal, and thyroid levels became elevated without thyrotoxic symptoms. Special studies were performed with cultured skin fibroblasts. T3 stimulated low density lipoprotein receptor activity in cells from normal subjects, but failed to do so in fibroblasts form the three patients, indicating that their fibroblasts had a defective response to T3. However, after incubation of fibroblasts with labeled T3, no abnormalities in the binding capacity or affinity of nuclei were observed. These findings suggest that in this family, the thyroid hormone resistance demonstrable in vivo and in vitro results from a cellular defect at a site other than at the nuclear binding site.

Adult↗

House dust mites in blankets and houses in the highlands of Papua New Guinea.

House dust mites were sought in indigenous houses of parts of the western and eastern highlands of Papua New Guinea during four field visits over a period of five years. A detailed search was made of various materials from different parts of the houses, including blankets. Findings showed that Dermatophagoides species reach very high concentrations in blankets but are relatively scarce in other places in the houses. A possible role for mite contaminated blankets in the reported increased prevalence of asthma in the Eastern Highlands Province is discussed.

Animals↗

Asthma in a rural highland area of Papua New Guinea.

Asthma is uncommon in the rural areas of Papua, New Guinea. Since 1976 an increasing number of people in the Fore linguistic group of the Eastern Highlands have been reported to have acute dyspnea responding to bronchodilator tablets. A preliminary investigation was undertaken to determine if these people had asthma. Forty-six patients who had been given bronchodilator therapy during the previous two years were examined by history, physical examination, lung function, methacholine provocation, skin prick tests, and IgE measurement. Nineteen patients had asthma with increased bronchial reactivity--defined as a 20% fall in FEV, after less than 0.75 mg of methacholine, or a greater than 20% rise in FEV1 after orciprenaline aerosol--together with a history of intermittent breathlessness. Eighteen had irreversible chronic airflow obstruction, and in nine patients it was not possible to distinguish between asthma and irreversible airflow obstruction. All but two of the asthmatics were over the age of 20, their symptoms began between 2 and 8 years previously, all were atopic, and all had elevated serum IgE levels. Non had a prior history of rhinitis or eczema. No obvious change in the environment or life style was found to explain the recent onset of severe asthma in these people.

Acute Disease↗

Hypothermia in iron deficiency due to altered triiodothyronine metabolism.

Iron-deficient rats become hypothermic and have an excessive catecholamine response when exposed to an ambient temperature of 4 degrees C. This is not due to changes in body insulation, since thickness is unaltered, since differences persist after removal of hair, and since cutaneous vasoconstriction is intact. On the other hand, oxygen consumption of iron-deficient animals at 4 degrees C is reduced, 39 +/- 3 ml . kg-1 . min-1 compared to 63 +/- 2 in control animals. Thyroxine (T4) values at 4 degrees C were 4.34 +/- 0.20 microgram/dl sera as compared to control values of 3.6 +/- 0.32. Triiodothyronine (T3) values of iron-deficient animals in the cold were 48 +/- 6.8 ng/dl as compared to 72 +/- 5.6 in control animals. Treatment of iron-deficient animals with iron was shown to normalize the plasma T3 response at 4 degrees C within 6 days. Thyroidectomized iron-deficient animals injected with T3 did not show hypothermia at 4 degrees C, whereas thyroidectomized iron-deficient animals injected with T4 showed hypothermia, increased catecholamines, and decreased T3 levels as compared to non-iron-deficient animals similarly treated. It is proposed that iron deficiency impairs conversion of T4 to T3 and that this is primarily responsible for the hypothermia observed.

Animals↗