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Biomedical subjects

C Scoggin

Publications and source records attributed to C Scoggin.

17 recordsLinked to original sources

Application of molecular biology to pulmonary disease.

The techniques of molecular biology now make it possible to clone specific genes, determine the nature of their molecular message, produce their protein product, and study their function in health and disease. DNA probes, particularly those for ribosomal RNA, offer a new way for the diagnosis of infectious diseases affecting the lung, particularly TB. In addition, recombinant DNA libraries of mycobacteria can be used to isolate mycobacterial antigens recognized by patients with TB. This may allow development of better immunologic tests and vaccines. A specific chromosomal abnormality of human chromosome 3 has been found in small cell lung cancer. It is hypothesized that loss of genes from this region may play a role in the pathogenesis of lung cancer. Another important factor in development of the disease is the expression of cancer-associated oncogenes. In addition to insights into the biology of lung cancer, these oncogenes might provide a method to classify various types of lung cancer and predict response to therapy. Specialized DNA markers known as RFLPs have now been linked with CF. This has resulted in localization of the CF gene to human chromosome 7 and the detection of the gene in most of its carriers who have been studied. Knowing where the gene resides and use of techniques of genetic engineering will eventually allow isolation of the CF gene (or genes) on chromosome 11 and determination of the biochemical defect for which it codes. Similarly, the gene for human alpha 1-antitrypsin has also been cloned. A practical benefit is the production of normal and mutant enzyme for replacement therapy in patients.

Cloning, Molecular

Four new DNA markers are assigned to the WAGR region of 11p13: isolation and regional assignment of 112 chromosome 11 anonymous DNA segments.

One hundred eighty-three human single copy clones were isolated from the Livermore Laboratory chromosome 11 library (ID code LL11NSO1) and 112 of them were mapped to chromosome 11. Using a panel of somatic cell hybrids segregating chromosome 11 translocations and short arm deletions, 54 of the clones were assigned to one of nine segments on the short arm of chromosome 11; the remainder were assigned to the long arm. Nine of these clones map to 11p13, and four of the nine [57(D11S89), 530(D11S90), 706(D11S93), and 1104(D11S95)] are confined to the same segment within p13 that contains catalase (CAT), the beta subunit of follicle stimulating hormone (FSHB), and the Wilms' tumor-aniridia (WAGR) gene complex.

Catalase

Exercise-induced asthma.

Exercise-induced bronchospasm is a common condition of patients who have asthma. Its mechanism appears to be related to cooling of the airways. Clinically, it can be managed by pretreatment with beta-adrenergic medications or cromolyn. Measures to protect the airway from excessive loss of heat, such as the use of scarves or participating in indoor activity, are also effective strategies in its management.

Adrenergic beta-Agonists

Chromosome 3q (22-ter) encodes the human transferrin receptor.

The human transferrin receptor is an integral membrane glycoprotein of 180,000 molecular weight (mol. wt.) formed from two subunits of 90,000 mol. wt. A clone panel of Chinese hamster-human somatic cell hybrids was screened using a single cell plating cytotoxicity assay and rabbit antiserum raised to purified human transferrin receptor. Chromosome 3 displayed the highest rate of concordance with the presence of human transferrin receptor, as assayed by cytotoxicity. Antitransferrin receptor serum-resistant segregants of chromosome 3 positive, receptor-positive hybrids were selected, using antiserum and complement. The segregants consistently lost chromosome 3. 125I human transferrin binding studies confirmed synteny between the functional human transferrin receptor and chromosome 3. Examination of hybrids with either translocated or deleted chromosome 3's allows regional mapping to 3q(22-ter).

Animals

Phosphorylation changes induced by cAMP derivatives in the CHO cell and selected mutants.

Phosphorylation analysis of CHO mutants selected for unresponsiveness to the Reverse Transformation reaction of cAMP derivatives has been carried out by 2D gel electrophoresis in hopes of finding mutants differing from the wild-type cell in a minimal number of such phosphorylations. Seven differences in protein phosphorylations in the parental CHO cell have been identified as a result of treatment with db-cAMP. db-cAMP-unresponsive mutants of two kinds have been found: One type has lost all seven of the phosphorylation changes induced by db-cAMP in the wild-type cell. The other type which is equally resistant to the Reverse Transformation response differs from the parental cell in only one (or possibly two) phosphorylation(s) involving a 55 000 D protein. This protein may, therefore, be directly related to the events of Reverse Transformation.

Animals

Somatic cell genetic approaches to Down's syndrome.

Somatic cell genetic analysis of mutants of Chinese hamster ovary cells with deficient purine synthesis and of hybrids between these mutants and human cells is described. Data are presented substantiating that two genes for enzymes of purine synthesis, AdeC and AdeG, can be coordinately regulated in mammalian cells. Analysis of a human-hamster hybrid cell, Ade C/21, which contains a normal complement of hamster chromosomes and human chromosome 21 as its only human genetic component recognizable by electrophoretic and immunogenetic techniques demonstrates that genes associated with the presence of human chromosome 21 and required for the synthesis of specific polypeptides and specific human lethal cell surface antigens can be detected in these hybrids.

Animals

Impaired oxygenation during sleep in excessive polycythemia of high altitude: improvement with respiratory stimulation.

Although polycythemia of high altitude is usually due to excessive hypoxemia, in some patients the hematocrit is elevated out of proportion to the degree of hypoxemia measured awake. One possible explanation is that severe hypoxemia occurs during sleep in these subjects. We therefore monitored oxygen saturation (SaO2), breathing pattern, and electroencephalogram (EEG) during sleep in five normal high-altitude residents and in five patients with excessive polycythemia. The polycythemic patients were studied as part of a placebo--drug double-blind crossover trial of the respiratory stimulant drug medroxyprogesterone acetate (MPA). The polycythemic patients while taking placebo were much more hypoxemic during sleep than the normals (all-night mean SaO2: 79.4 +/- 1.7% versus 87.8 +/- 1.7%, p less than 0.01). Abnormalities in breathing patterns were observed in all the subjects, especially during REM stage sleep. In polycythemic subjects, this resulted in precipitous hypoxemia with SaO2 as low as 50%--70%. Severe hypoxemia was not observed in control subjects despite similar abnormalities in breathing. Significant improvement in nocturnal SaO2 occurred when the polycythemic patients were taking MPA, mean SaO2 rising from 79.4 +/- 1.7% to 83.7 +/- 0.7%, p less than 0.05. Of probably greater importance, MPA largely prevented the precipitous drops in SaO2, mean lowest SaO2 rising from 64.6 +/- 4.7% to 76.0 +/- 2.1% p less than 0.05. The severe decreases in SaO2 during sleep may explain elevations in hematocrit that are out of proportion to the awake SaO2 in man at high altitude. The therapeutic effect of MPA in this condition may be due to amelioration of sleep hypoxemia.

Adult

The pathogenicity of Mycobacterium fortuitum and Mycobacterium chelonei in man: a report of seven cases.

The clinical records of 7 patients referred to the National Jewish Hospital and Research Center over a 6-year period for evaluation of an abnormal chest x-ray and repeated sputum isolates of rapidly growing mycobacteria (Runyon's Group IV) were reviewed to determine the potential pathogenicity of these organisms. Mycobacterium fortuitum was isolated from 5 patients and Mycobacterium chelonei from 2. Haemoptysis, cough and weight loss were prominent in 6. Three had rheumatoid arthritis. Although two demonstrated cutaneous anergy, lymphocyte responsiveness to PHA was normal. PPD-F was not useful in skin testing or in the in vitro evaluation of lymphocyte function. Histologic examination of the lungs of 2 patients demonstrated caseating granulomata. One patient died of massive pulmonary haemorrhage soon after intiation of therapy. Multi-drug treatment regimens generally resulted in progressive sterilization of the sutum and improvement in the appearance of the chest x-ray. We conclude that some rapidly growing mycobacteria can cause potentially fatal cavitary lung disease and that intensive anti-tuberculosis therapy may successfully alter its course.

Adult

Fiberoptic bronchoscopy in bronchial asthma. A word of caution.

Three instances of intense laryngospasm and bronchospasm occurred as a result of fiberoptic bronchoscopic examination in three patients with quiescent bronchial asthma. The indications for the procedure were hemoptysis in one patient and lobar collapse in two. It is likely that vagally mediated reflex laryngospasm and bronchoconstriction occur when irritant receptors are mechanically stimulated by the bronchoscope. Therefore, in the asthmatic population with its increased airway reactivity, indications for fiberoptic bronchoscopy should be absolute, and the procedure should be performed under optimal conditions. A rationale for minimizing the risk of this procedure in patients with bronchial asthma is discussed.

Asthma

Clinical evaluation of a new ear oximeter.

Ear oximetry offers a noninvasive method of determining and monitoring oxygen saturation in arterialized capillary blood. A new apparatus has recently been developed which provides improved accuracy as well as increased ease of use. We have found it to be at least as accurate as the American Optical oximeter which measures oxygen saturation directly from arterial blood. It has proved to be of value in clinical situations such as monitoring critically ill patients (particularly those being mechanically ventilated) and patients undergoing treadmill exercise or fiberoptic bronchoscopy and in the diagnosis of disorders characterized by periodic hypoxia.

Ear