The Human Genome Project: for better or for worse?
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Biomedical subjects
Publications and source records attributed to K Dawson.
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Staphylococci which were considered to be lysostaphin susceptible on P agar containing Bacto-Agar showed different degrees of resistance to lysostaphin when tested on P agar made with BiTek agar. As a result, lysostaphin-susceptible strains were misidentified as lysostaphin-resistant strains.
A preparation has been developed that permits patch clamping of the basolateral membrane of Necturus gallbladder epithelial cells with a high success rate. The epithelium is separated from the underlying tissues mechanically, without enzymatic treatment. Its apical surface is attached to a plastic cover slip, and the basolateral surface, facing up, is cleaned with a suction pipette under microscopic observation. With this cleaning procedure, the success rate in obtaining gigaohm seals increases from less than 1% to approximately 10% of the attempts. The cells appear to retain their structural and functional integrity, as evidenced by electron-microscopic appearance and magnitude of cell membrane voltages. Major advantages of the preparation are that the basolateral membrane domain is preserved and that enzymatic treatment, which could potentially alter membrane proteins, is not necessary.
The effect of Zn2+ on Cl- transport across the apical membrane of Necturus gallbladder epithelium was studied with intracellular conventional and Cl(-)-selective microelectrodes and measurements of apparent base secretion. Most studies were done on tissues incubated in HEPES-buffered solutions; intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels were elevated by adding to the serosal bathing medium either theophylline or dibutyryl cAMP. Under these conditions, Zn2+ (added to mucosal solution) had no effect on membrane voltages, apparent cell membrane resistance ratio, or rapid depolarization induced by reducing mucosal solution [Cl-]. However, Zn2+ reduced the rate of cell membrane repolarization during exposure to the low-Cl- solution and decreased significantly the rate of fall of intracellular Cl- activity (alpha Cli) elicited by lowering mucosal solution [Cl-]. Both effects were time dependent, became significant after 10 min, and were slowly reversible. In tissues not stimulated by cAMP and incubated in a HCO3-CO2-buffered solution, Zn2+ also reduced the rate of fall of alpha Cli on lowering mucosal solution [Cl-]. Base secretion from cells to mucosal solution was assessed from changes in mucosal pH on stopping superfusion with a poorly buffered (1 mM HEPES) medium in the presence of 1 mM amiloride or a Na(+)-free medium, without cAMP stimulation. Exposure to Zn2+ reduced the alkalinization observed with both protocols. We conclude that Zn2+ has no effect on apical membrane Cl- conductance stimulated by cAMP and inhibits Cl(-)-HCO3- exchange. The slow onset and reversal of the effects suggests slow binding of Zn2+, a covalent modification of the exchanger, or an effect requiring Zn2+ transport to the cell interior.
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A total of 61 patients with gastro-oesophageal reflux; resistant to medical therapy, were entered into a prospective randomized trial comparing the Angelchik antireflux prosthesis with Nissen's fundoplication. Both groups had a similar age and sex distribution and their reflux profiles were comparable. An Angelchik prosthesis was inserted in 30 patients and 31 underwent fundoplication. The mean duration of postoperative follow-up was 38 months. At clinical assessment 23 (77 per cent) of the Angelchik group were graded Visick grade I or II, compared with 29 (94 per cent) of the Nissen group. Assessment by 24 h pH monitoring and manometry between 3 and 6 months after operation showed that both procedures were equally effective in reducing reflux and increasing lower oesophageal sphincter pressure. However, long-term endoscopic follow-up revealed grade III oesophagitis in seven patients in the Angelchik group. No patient in the fundoplication group had grade III oesophagitis. Three of eight patients with strictures in the Angelchik group reported persistent dysphagia. All seven patients with strictures in the Nissen group were relieved of their dysphagia. Migration or erosion of the prosthesis did not occur. Three prostheses (10 per cent) were removed, two for dysphagia and one because of sepsis.
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