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Biomedical subjects

C Hanning

Publications and source records attributed to C Hanning.

9 recordsLinked to original sources

Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response.

Human HtrA2 is a novel member of the HtrA serine protease family and shows extensive homology to the Escherichia coli HtrA genes that are essential for bacterial survival at high temperatures. HumHtrA2 is also homologous to human HtrA1, also known as L56/HtrA, which is differentially expressed in human osteoarthritic cartilage and after SV40 transformation of human fibroblasts. HumHtrA2 is upregulated in mammalian cells in response to stress induced by both heat shock and tunicamycin treatment. Biochemical characterization of humHtrA2 shows it to be predominantly a nuclear protease which undergoes autoproteolysis. This proteolysis is abolished when the predicted active site serine residue is altered to alanine by site-directed mutagenesis. In human cell lines, it is present as two polypeptides of 38 and 40 kDa. HumHtrA2 cleaves beta-casein with an inhibitor profile similar to that previously described for E. coli HtrA, in addition to an increase in beta-casein turnover when the assay temperature is raised from 37 to 45 degrees C. The biochemical and sequence similarities between humHtrA2 and its bacterial homologues, in conjunction with its nuclear location and upregulation in response to tunicamycin and heat shock suggest that it is involved in mammalian stress response pathways.

Alanine↗

Thoracoscopic oesophago-gastrectomy--a new technique for intra-thoracic stapling.

A new technique for performing a standard Ivor Lewis oesophagectomy avoiding the need for a conventional right thoracotomy is described. The intrathoracic dissection and the intrathoracic anastomosis, using a conventional EEA circular staple-gun, is done thoracoscopically. Eight patients with carcinoma of the gastric cardia or distal oesophagus were prepared for a palliative Ivor Lewis two-stage oesophago-gastrectomy. The details of the technique for placing the anvil of a circular staple gun in the upper oesophagus and performing the intrathoracic stapled anastomosis are described. Intrathoracic stapling under thoracoscopic video control was successful in five of the eight patients. The three other patients received 10 cm mini-thoracotomies. All patients were transferred from the intensive care unit within 24 hours and were discharged from hospital within 14 days. There were no complications and no deaths. We believe that this procedure offers many patients better palliation with reduced morbidity because the standard right thoracotomy is avoided.

Adenocarcinoma↗

A study of the effect of Picolax on body weight, cardiovascular variables and haemoglobin concentration.

This study compared the effect of Picolax when administered for large bowel preparation in combination with preoperative fasting on body weight, haemoglobin concentration, haematocrit, and cardiovascular variables with matched subjects who were fasted before surgery. Picolax resulted in significantly greater weight loss, increases in haemoglobin concentration combined with cardiovascular changes suggesting hypovolaemia in the Picolax group. Intravenous fluid replacement is recommended in patients receiving Picolax.

Adult↗

Completion of the last half of the structure of the human gene for the Pro alpha 1 (I) chain of type I procollagen (COL1A1).

The nucleotide sequences of the 3'-half of the human gene for the pro alpha(I) chain of type I procollagen (COL1A1) is presented. The results provide the nucleotide sequences for 26 introns not previously analyzed. The sequences that are presented, together with those previously published, make it possible to design primers for the polymerase chain reaction for amplifying and sequencing the gene. The availability of such primers will greatly facilitate the current search for mutations that can cause common and rare diseases of connective tissue.

Base Sequence↗

Substituted 6,7-dihydroimidazo[1,2-a]purin-9(4H)-ones.

The synthesis of a series of substituted 6,7-dihydroimidazo[1,2-a]purin-9(4H)-ones is described. Several members of the series exhibit enhanced antiallergic and bronchodilator activity and reduced side effects as compared to theophylline. Structure-activity relationships and metabolic considerations are discussed for the series. Analogues substituted with a 4-(4-chlorobenzyl) moiety, such as 33 and 40, shown an optimal balance of antiallergic and bronchodilator activity and are of particular interest. Compound 33 is significantly more potent than theophylline against both metacholine- and antigen-induced bronchospasms, does not affect spontaneous motor activity, and shows minimal cardiovascular effects in the rat.

Animals↗