Biomedical subjects
W R Cook
Publications and source records attributed to W R Cook.
Nonosmotic diabetic cataracts.
It has been suggested that sugar cataracts associated with diabetes mellitus result from the accumulation of excess sorbitol within lens fibrils. Swelling of lens fibrils occurs when water moves in to maintain osmotic balance; the excess water causes disruption of fibrils and cataract formation. Other studies have indicated that more than sorbitol-induced osmotic stress is involved. Our study used lenses collected from rats after 21 or 44 d of streptozotocin diabetes. Cataracts formed in untreated 44-d streptozotocin diabetic rats, but were not apparent in the 21-d untreated diabetic animals. Lens sorbitol increased in the diabetic animals both before and after cataract formation. Lens taurine varied inversely with the sorbitol content in a fashion that resulted in no net change in total lens osmoles. Lens water did not increase in the diabetic animals with or without cataracts. The aldose reductase inhibitor Sorbinil prevented the increase in lens sorbitol in both the 21- and 44-d streptozotocin diabetic rats; cataract formation was prevented in the 44-d diabetic animals. The lens water in untreated diabetic animals with cataracts did not differ from lens water in the Sorbinil-treated diabetic animals that did not develop cataracts. Sorbinil treatment of diabetic animals was associated with normalization of both lens sorbitol and taurine levels. Taurine has been shown to serve both as an osmoregulator and as an antioxidant. The apparent increase in lens osmolality attributed to sorbitol was counterbalanced by an equimolar reduction in taurine concentration. The reciprocal relationship between taurine and sorbitol reduces the likelihood of an osmotic mechanism for sugar cataractogenesis; the reduced lens taurine, however, may increase the risk of lens protein oxidation and subsequent cataract formation. Thus in vivo sugar cataract formation may be an oxidative process rather than an osmotic phenomenon.
Differentiation of the bacterial cell division site.
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Compartmentalization of the periplasm at cell division sites in Escherichia coli as shown by fluorescence photobleaching experiments.
Morphological evidence has previously indicated that the periplasmic space of Escherichia coli is compartmentalized at sites corresponding to future sites of cell division. The borders of these morphological compartments are formed by localized zones of adhesion (periseptal annuli). In the present study, the technique of fluorescence recovery after photobleaching was used to determine whether these structures act as barriers to the free movement of proteins within the periplasm. The recovery of fluorescence in the ftsA filaments was found to be uniformly low over at potential sites of cell division and at the cell poles, indicating that these regions are biochemically sequestered from the remainder of the periplasmic space. Our results provide direct evidence for local compartments within the periplasm, primarily located at the sites of past or future cell divisions. The implications of this finding for cell division and other periplasmic processes are discussed.
Indices of severity of obstructive sleep apnea syndrome do not change during medroxyprogesterone acetate therapy.
Medroxyprogesterone acetate (MPA) could change the frequency and/or duration of disordered breathing events (DBEs) in patients with the obstructive sleep apnea (OSA) syndrome by altering pharyngeal muscle function relative to diaphragm and external intercostal function. Ten male patients with OSA syndrome underwent an initial polysomnogram with monitoring of EEG, EOG, myohyoid EMG, oral and nasal airflow, abdominal and thoracic movement, and SaO2. The patients were then entered into a randomized, double-blind crossover study using MPA, 150 mg/day, and MPA placebo. Each patient took tablets for one week and then had a second polysomnogram. After a three week washout, the patient again took tablets for a week prior to the third and final sleep study. There was no significant difference between drug and placebo for DBE time (expressed as a percentage of sleep time), DBE frequency, DBE mean duration or mean fall in O2 saturation during DBEs. We conclude that treatment with MPA does not alter indices of severity of the OSA syndrome.
Hypotheses on exercise-induced pulmonary hemorrhage in horses.
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Periseptal annuli: organelles involved in the bacterial cell division process.
Specialized structures (periseptal annuli) appear at future cell division sites long before the division septum is formed. Studies of their biogenesis and localization are providing unexpected insights into the earlier stages of localization and differentiation of the division site.
Proposed mechanism for generation and localization of new cell division sites during the division cycle of Escherichia coli.
The earliest detectable event at future sites of cell division in Escherichia coli is the appearance of paired periseptal annuli that flank the site of formation of the division septum. The development and localization of these structures were followed as the cell progressed through the division cycle. The data suggest that (i) new periseptal annuli are generated from annuli already in position at the midpoint of the newborn cell; (ii) the nascent annuli are then displaced laterally during cell elongation to positions at 1/4 and 3/4 cell length; and (iii) the annuli at 1/4 and 3/4 cell length are retained during division, becoming the midpoint annuli of the newborn cells at the sites of the forthcoming division septum. The results indicate that the sites of future divisions can be identified and committed to the division process prior to the division cycle in which these sites are utilized for septum formation, and they suggest a model in which preexisting sites of cell division generate future division sites by a replication/displacement mechanism.
Membrane-murein attachment at the leading edge of the division septum: a second membrane-murein structure associated with morphogenesis of the gram-negative bacterial division septum.
Electron microscopy of plasmolyzed cells of Salmonella typhimurium revealed a continuous zone of membrane-murein attachment at the leading edge of the division septum at all stages of septal invagination. The membrane-murein attachment site had a characteristic ultrastructural appearance and remained as a bacterial birth scar at the new pole of each of the two daughter cells after cell separation. The continuous zone of membrane-murein attachment at the leading septal edge represents the second organelle based on a topologically ordered domain of membrane-murein adhesion to be described at the site of cell division.
Isolation of rat liver microsomal short-chain beta-ketoacyl-coenzyme A reductase and trans-2-enoyl-coenzyme A hydratase: evidence for more than one hydratase.
An enzyme preparation (IIIB) isolated from liver microsomes of untreated male rats was found to contain two activities--short-chain trans-2-enoyl-CoA hydratase and beta-ketoacyl-CoA reductase. The hydratase was purified more than 1000-fold, while the reductase activity was purified over 600-fold. Employing sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, a single band with a molecular weight of 76,000 was observed. Although attempts to separate these two activities have failed, it remains to be established whether the final preparation contains a single enzyme with two activities or two separate enzymes. The hydratase was most active toward crotonyl-CoA, followed by trans-2-hexenoyl-CoA (6:1) and -octenoyl-CoA (8:1); the enzyme was essentially inactive toward substrates containing more than eight carbon atoms. The Vmax for crotonyl-CoA was 2117 mumol/min/mg protein, while the Km was 59 microM. Using acetoacetyl-CoA as substrate, the Vmax for the beta-ketoacyl-CoA reductase was over 60 mumol/min/mg protein and the Km was 37 microM; the Vmax for beta-ketopalmitoyl-CoA was only 15% of that observed with acetoacetyl-CoA, although the Km was 6 microM. During the course of purification, a second short-chain hydratase was discovered (fraction IVA); unlike IIIB, this fraction catalyzed the hydration of 4:1, 6:1, and 8:1 at similar rates. The partially purified preparation yielded maximal activity with 8:1 CoA (apparent Vmax 35 mumol/min/mg), followed by 6:1 CoA, 4:1 CoA, and 10:1 CoA; longer chain CoA's were relatively poor substrates, with trans-2-hexadecenoyl CoA about 0.1 as active as 8:1 CoA. On SDS-gels, fraction IVA contained four bands, all of which were below 60,000 Mr. Proteases, such as trypsin, chymotrypsin, and subtilisin, were found to completely inactivate both enzyme fractions.
Accumulation of a murein-membrane attachment site fraction when cell division is blocked in lkyD and cha mutants of Salmonella typhimurium and Escherichia coli.
Membrane fractionation studies were performed on Salmonella typhimurium lkyD(Ts) and E. coli cha(Ts) mutants that appeared to be blocked at a late stage of the cell division cycle. In both cases growth of the mutant strains at nonpermissive temperatures was associated with accumulation of a characteristic cell envelope fraction (fraction OML) that contained inner membrane, murein, and outer membrane components. The isolated fraction corresponded in composition and bouyant density to a fraction from wild-type strains that had previously been suggested (M. H. Bayer, G. P. Costello, and M. E. Bayer, J. Bacteriol. 149:758-767, 1982; K. Ishidate, E. S. Creeger, J. Zrike, S. Deb, B. Glauner, T. J. MacAlister, and L. I. Rothfield, J. Biol. Chem. 261:428-443, 1986) to contain adhesion sites between inner membrane, murein, and outer membrane. The accumulation of OML in LkyD- and Cha- cells was prevented by treatments that blocked DNA synthesis. The effects of interference with DNA synthesis did not appear to involve the SOS response.
Compartmentalization of the periplasmic space at division sites in gram-negative bacteria.
Phase-contrast and serial-section electron microscopy were used to study the patterns of localized plasmolysis that occur when cells of Salmonella typhimurium and Escherichia coli are exposed to hypertonic solutions of sucrose. In dividing cells the nascent septum was flanked by localized regions of periseptal plasmolysis. In randomly growing populations, plasmolysis bays that were not associated with septal ingrowth were clustered at the midpoint of the cell and at 1/4 and 3/4 cell lengths. The localized regions of plasmolysis were limited by continuous zones of adhesion that resembled the periseptal annular adhesion zones described previously in lkyD mutants of S. typhimurium (T. J. MacAlister, B. MacDonald, and L. I. Rothfield, Proc. Natl. Acad. Sci. USA 80:1372-1376, 1983). When cell division was blocked by growing divC(Ts) cells at elevated temperatures, the localized regions of plasmolysis were clustered along the aseptate filaments at positions that corresponded to sites where septum formation occurred when cell division was permitted to resume by a shift back to the permissive temperature. Taken together the results are consistent with a model in which extended zones of adhesion define localized compartments within the periplasmic space, predominantly located at future sites of cell division.
Breathlessness and exercise in patients with cardiorespiratory disease.
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Transendoscopic electrosurgery for epiglottal entrapment in the horse.
Monopolar electrosurgical cutting was used to correct epiglottal entrapment in 5 horses. The operations were carried out in the conscious animal, using topical anesthesia. The procedure required the use of a coagulation electrode designed specifically for electrosurgery, introduced through the instrument channel of a fiberoptic endoscope. The results were satisfactory and serious complications were not encountered. In 2 horses, excessive submucosal swelling developed at the site of the surgical wound, and the tumefaction took several weeks to subside in one of these horses. In both horses, the long-term outcome was a minor degree of reentrapment. The main advantages of this technique, compared with other corrective procedures, related to the avoidance of the need for general anesthesia and laryngotomy, allowing racehorses to be treated without any major interruption in their training schedules. The surgery was simple, rapid, and bloodless, and was not followed by any dorsal displacement of the soft palate. It was suggested that transendoscopic electrosurgery has potential for use in the treatment of a number of other diseases of the respiratory tract and other systems, both in the horse and in other species. In the equine respiratory tract, the technique might usefully be applied to the treatment of guttural pouch tympany, soft palate cysts, nasopharyngeal polyps, choanal atresia, subepiglottic cysts, and tracheal granulomata. A review of 21 cases of epiglottal entrapment in horses revealed no evidence to support the suggestion that dorsal displacement of the soft palate is a cause of epiglottal entrapment or vice-versa.(ABSTRACT TRUNCATED AT 250 WORDS)
Obstructive sleep apnea: diagnosis and treatment.
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Carotid and cerebral angiography in the horse.
Carotid and cerebral angiography has been found to be a relatively simple technique to carry out in the horse. At most it involves a cutdown approach to the carotid artery, followed by catheterisation of the artery and selective catheterisation, if necessary, of one of its three branches. The technique can be carried out with standard equipment normally available within equine hospital facilities. The authors have employed angiography as a routine aid to diagnosis over the past nine years, without encountering any serious complications or adverse reactions. Carotid angiography has been especially valuable in the investigation of horses with guttural pouch mycosis. The technique has permitted the presence of aneurysms to be detected in many cases and significant vascular abnormalities in four cases. This information is valuable for the surgical treatment of horses with guttural pouch mycosis by ligation of the appropriate artery. Other indications for the use of carotid angiography include the investigation of ethmoidal haematoma, idiopathic Horner's syndrome, neoplasia of the head, venous aneurysms and arterial aneurysms in sites not associated with the guttural pouch. There are fewer occasions for the use of cerebral angiography in the horse, but it is indicated as an aid to the differential diagnosis of some abnormalities of the central nervous system.
Accumulation of cyclic GMP in filaments of Escherichia coli BUG6.
Experiments with Escherichia coli BUG6, a temperature-sensitive cell division mutant, have shown that at the restrictive temperature (42 degrees C) the loss of cell division potential (filamentation) was accompanied by an unusual increase in intracellular cyclic GMP (cGMP). At the permissive temperature (30 degrees C), cell division proceeded normally, and cGMP did not accumulate. Increasing the osmotic strength of the medium with NaCl suppressed filamentation in BUG6 at 42 degrees C and also suppressed the temperature-sensitive accumulation of cGMP. The addition of nalidixic acid to BUG6 at 30 degrees C induced filamentation but failed to cause cGMP accumulation. A similar accumulation of cGMP has not been observed in other E. coli strains.
Disordered breathing and hypoxia during sleep in coronary artery disease.
The occurrence of breathing disorders and hypoxia during sleep was studied in 17 male patients with coronary artery disease, demonstrated by coronary angiography, who did not have symptomatic pulmonary disease. Thirteen patients (76 percent) experienced disordered breathing during sleep; of these, 11 had obstructive apnea and the other two had Cheyne-Stokes breathing. There was an average of 20 episodes of disordered breathing per hour during sleep among the 13 patients, with a mean duration of 24 seconds per episode; significant oxygen desaturation occurred in ten of these 13 patients. There was no episode of angina pectoris, myocardial infarction or sudden death. Although cardiac arrhythmias occurred in 12 patients, disordered breathing with hypoxia was not proven to be causative. Therefore, obstructive disordered breathing and nocturnal oxygen desaturation commonly occurred during sleep in patients with coronary artery disease. Although no immediate ill effects were noted, the longterm effects remain to be determined.