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S Cole

Publications and source records attributed to S Cole.

18 recordsLinked to original sources
PubMed1992

The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis.

Tuberculosis is responsible for one in four of all avoidable adult deaths in developing countries. Increased frequency and accelerated fatality of the disease among individuals infected with human immunodeficiency virus has raised worldwide concern that control programmes may be inadequate, and the emergence of multidrug-resistant strains of Mycobacterium tuberculosis has resulted in several recent fatal outbreaks in the United States. Isonicotinic acid hydrazide (isoniazid, INH) forms the core of antituberculosis regimens; however, clinical isolates that are resistant to INH show reduced catalase activity and a relative lack of virulence in guinea-pigs. Here we use mycobacterial genetics to study the molecular basis of INH resistance. A single M. tuberculosis gene, katG, encoding both catalase and peroxidase, restored sensitivity to INH in a resistant mutant of Mycobacterium smegmatis, and conferred INH susceptibility in some strains of Escherichia coli. Deletion of katG from the chromosome was associated with INH resistance in two patient isolates of M. tuberculosis.

Amino Acid Sequence↗
PubMed1992

Assessment of a range of novel nitro-aromatic radiosensitizers and bioreductive drugs.

In a directed search for the best compounds for clinical evaluation, some 150 selected nitroaromatic compounds, representing 6 distinct types, namely, furans, thiophenes, imidazoles, pyrazoles, pyrroles, and triazoles, have been synthesized and tested as hypoxic cell radiosensitisers and bioreductive drugs. These compounds have a wide range of one-electron redox potentials, ranging from -700 mV for 3-nitropyrroles to -250 mV for 5-nitrofurans. Within each series, those agents bearing alkylating moieties on the side chain are generally the more effective radiosensitisers in vitro. Studies in vivo demonstrated that the bifunctional nitroimidazoles were superior to the other nitroarenes tested. In terms of bioreductive cell killing, the best differential between oxic and hypoxic cell toxicity was shown for the bifunctional 2-nitroimidazoles, which had values greater than 20. In contrast, the other classes of nitroarines generally showed differential toxicities of less than 10.

Animals↗
PubMed1992

Bioreductive drugs as post-irradiation sensitizers: comparison of dual function agents with SR 4233 and the mitomycin C analogue EO9.

Various bioreductive drugs that are potent hypoxic cell cytotoxins can also function as effective potentiators of radiation action when administered in vivo post irradiation. There is evidence that a contributory mechanism to this potentiation is enhanced sensitivity to the bioreductive drugs exhibited by cells that are damaged sublethally by radiation.

Animals↗
PubMed1992

Dual function nitroimidazoles less toxic than RSU 1069: selection of candidate drugs for clinical trial (RB 6145 and/or PD 130908.

Following the toxicity and synthetic difficulties encountered with the hypoxic cell radiosensitizer RSU 1069, efforts have focused on development of a superior analogue. Two compounds, RB 6145 and PD 130908, have emerged from this program which overcome the instability and synthetic problems associated with RSU 1069 while retaining favorable biological activity. Both agents show comparable radiosensitizing activity to RSU 1069 following oral or i.p. administration to mice bearing the KHT or RIF-1 tumors. Sensitizing efficiency is about 10 X greater than that observed for misonidazole or etanidazole. Toxicity toward hypoxic tumor cells in vivo is demonstrated by clamping tumors (for 60 min) following administration of PD 130908 or RB 6145. Both are effective hypoxic cytotoxins, but less potent than RSU 1069. Systemic toxicity is substantially reduced following oral drug administration. Further, doses achievable following fractionated drug treatments are sufficiently high to produce significant levels of radiosensitization.

Animals↗
PubMed1992

Pulmonary abnormalities in Klippel-Trenaunay syndrome. A histologic, ultrastructural, and immunocytochemical study.

Klippel-Trenaunay (KT) syndrome is a rare, sporadic, congenital vascular disease of unknown etiology. We describe pulmonary findings in an 18-year-old male patient followed up since birth with the KT syndrome. The patient developed pleural and pericardial serous effusions that led to an open lung biopsy. Previous pulmonary findings have been limited to thromboembolic phenomena and pulmonary vein varicosities. On the other hand, reports of lymphatic hyperplasia, aplasia, and hypoplasia in KT have been limited to the extremities. For the first time, we describe lymphatic involvement of the lung in KT. The plexiform hyperplasia of the lymphatic channels with smooth muscle hyperplasia leading to lymphatic obstruction, pleural and pericardial effusions are new findings. The lymphatic nature of the plexiform channels was confirmed by immunohistochemistry. Von Willebrand factor and QD-END/10 monoclonal antibodies either did not react or reacted poorly with lymphatic endothelium, features used to distinguish lymphatic and venous endothelium. Ultrastructurally, the absence of basement membrane continuity further substantiated the lymphatic nature of the channels. From our findings, the lymphatic abnormality in the syndrome appears to be more generalized than previously thought. This entity should be distinguished from lymphangioleiomyomatosis to which it bears a superficial morphologic appearance.

Adolescent↗
PubMed1979

Ultrastructural abnormalities of the carotid body in sudden infant death syndrome.

The carotid bodies of four infants who died of sudden infant death syndrome (SIDS) were compared, using electron microscopic techniques, with the carotid bodies of various control subjects. In the SIDS patients, there was a marked reduction or absence of the dense cytoplasmic granules of the carotid chemorecptor cells, as well as a reduction in cell number and size. These ultrastructural abnormalities may be pathophysiologically related to SIDS. A defect in this respiratory control organ could block normal stimulation of respiration during the periods of hypoxia that occur during episodes of sleep apnea in infancy. Further studies by electron microscopy are required to confirm degranulation of the carotid body as a pathognomonic sign of SIDS. Screening of high-risk infants should be directed at studying the carotid body and its mediated responses to hypoxia.

Carotid Body↗
PubMed1978

Malformation of bronchopulmonary foregut with systemic and pulmonary arterial blood supply.

A case of congenital malformation of the bronchopulmonary foregut with communication between the esophagus and sequestered lobe is reported in a six-month-old boy. Only 29 similar cases have been reported previously, and this case was especially unusual in that the communication was from the middle portion of the esophagus to a right apical sequestration. Another unusual feature was that the sequestered segment was supplied by four systemic arteries from the thoracic aorta, as well as by branches from the right pulmonary artery. Within the sequestration, there was shunting of blood from the systemic to pulmonary arterties with reversal of flow in the pulmonary arterial branches.

Bronchopulmonary Sequestration↗
PubMed1976

Fatal case of influenza pneumonia with suprainfection by multiple bacteria and Herpes simplex virus.

A case of influenza pneumonia is described in which death occurred from persistence of the influenza infection and suprainfection with two bacteria, Staphylococcus aureus and Escherichia coli, and another virus, Herpes simplex. Of additional interest were the observations that this overwhelming illness developed in a previously healthy person, that typical influenza virus particles were present in antemortem lung tissue, and that the patient died despite 6 days of extracorporeal membrane oxygenation and corticosteroids.

Adult↗