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Biomedical subjects

S Saul

Publications and source records attributed to S Saul.

At least 19 recordsLinked to original sources

Studies on the enzymes involved in puparial cuticle sclerotization in Drosophila melanogaster.

The properties of cuticular enzymes involved in sclerotization of Drosophila melanogaster puparium were examined. The cuticle-bound phenoloxidase from the white puparium exhibited a pH optimum of 6.5 in phosphate buffer and oxidized a variety of catecholic substrates such as 4-methylcatechol, N-beta-alanyldopamine, dopa, dopamine, N-acetyldopamine, catechol, norepinephrine, 3,4-dihydroxyphenylglycol, 3,4-dihydroxybenzoic acid, and 3,4-dihydroxyphenylacetic acid. Phenoloxidase inhibitors such as potassium cyanide and sodium fluoride inhibited the enzyme activity drastically, but phenylthiourea showed marginal inhibition only. This result, coupled with the fact that syringaldazine served as the substrate for the insoluble enzyme, confirmed that cuticular phenoloxidase is of the "laccase" type. In addition, we also examined the mode of synthesis of the sclerotizing precursor, 1,2-dehydro-N-acetyldopamine. Our results indicate that this catecholamine derivative is biosynthesized from N-acetyldopamine through the intermediate formation of N-acetyldopamine quinone and N-acetyldopamine quinone methide as established for Sarcophaga bullata [Saul, S. and Sugumaran, M., F.E.B.S. Letters 251, 69-73 (1989)]. Accordingly, successful solubilization and fractionation of cuticular enzymes involved in the introduction of a double bond in the side chain of N-acetyldopamine indicated that they included o-diphenoloxidase, 4-alkyl-o-quinone:p-quinone methide isomerase, and N-acetyldopamine quinone methide:dehydro N-acetyldopamine isomerase and not any side chain desaturase.

Animals↗

Serum CEA and CA 19-9: potential future diagnostic or screening tests for gallbladder cancer?

The poor prognosis of gallbladder cancer and the presence of high-risk populations make the identification of a screening test for this disease very desirable. As part of an ongoing case-control study of gallbladder cancer being conducted in Mexico City, Mexico, and in La Paz, Bolivia, blood specimens were sought from all patients with cancer of the gallbladder and on controls of similar age and sex undergoing upper abdominal surgery. Each sample was analyzed for carcino-embryonic antigen (CEA) and CA 19-9. Using the specimens from Bolivia, a serum CEA cutoff of 4.0 ng/ml yielded a sensitivity of 50.0% and a specificity of 92.7%, while a serum CA 19-9 cutoff of 20.0 units/ml yielded a sensitivity of 79.4% and a specificity of 79.2%. Using ROC curve analysis, the latter was a much better test than the former (p less than 0.05). Using the tests in series or in parallel did not substantively improve the results. The specimens from Mexico were used for validation purposes, and yielded very similar results. In conclusion, serum CA 19-9 and CEA are fairly good tests for discriminating patients with gallbladder cancer from patients with gallstones and no cancer, the former being a better test than the latter. These tests may be useful in identifying disease recurrences. In addition, if a sufficiently high-risk population could be identified, this could potentially become a useful screening test for this serious disease, allowing early intervention. However, additional data are needed prior to recommending this clinically.

Antigens, Tumor-Associated, Carbohydrate↗

The application of joy in group psychotherapy for the elderly.

A range of joyful emotions may be woven into the therapeutic group process for older persons. Experiencing joy is a powerful healing factor because it helps reduce the pain of losses inherent in the aging process, restores self-confidence and hope, and renews an investment in living. This paper identifies ten facets of joy which can help develop a therapeutic group climate. Examples from the authors' practice illustrate conceptual approaches.

Adaptation, Psychological↗

A microcomputer-assisted study of nabumetone and slow release diclofenac in osteoarthritis.

20 UK general-practice centres entered 243 patients into a 6-week double-blind, double-dummy, randomised, parallel-group trial designed to compare nabumetone 1 g at night with slow release diclofenac 100mg at night in the treatment of osteoarthritis. Seven efficacy parameters were measured, adverse events were recorded and laboratory monitoring was performed. The study monitor entered trial data into a portable laptop microcomputer at the participating centres. Both treatment groups showed highly significant clinical improvements at the end of the 6-week study period and there were no significant inter-group differences. Overall, the incidence of adverse events was similar in the 2 groups, but significantly fewer patients in the nabumetone group (n = 21) than in the diclofenac group (n = 35) complained of gastrointestinal adverse events (p = 0.03). On-site use of the microcomputer contributed to increased monitoring efficiency and trialist motivation, resulting in rapid recruitment of patients, collection of high quality data and speedy analysis at the end of the study.

Adult↗

Pathophysiology of tumor progression in human gallbladder: flow cytometry, CEA, and CA 19-9 levels in bile and serum in different stages of gallbladder disease.

Gallbladder epithelium is unique among the gastrointestinal cell types because proteins and protein levels in the fluid bathing the luminal side of the cells (bile) are different from and can be compared with those in the fluid bathing the basal side (serum). To help identify cellular changes that occur during the development of gallbladder cancer, we obtained gallbladder tissue, serum, and bile specimens from 20 patients with invasive adenocarcinoma of the gallbladder, three with high-grade dysplasia (carcinoma in situ), six with low-grade dysplasia, 12 with hyperplasia, and 10 with acute or chronic cholecystitis. We obtained serum samples from 40 patients with invasive adenocarcinoma and bile samples from 29 of these patients; serum samples from three with high-grade dysplasia and bile specimens from two of these; serum and bile samples from five with low-grade dysplasia; serum or bile samples from 126 with metaplasia, hyperplasia, or cholecystitis, including serum samples from 121 and bile samples from 110; and serum and bile samples from eight with normal biliary tracts. The study was conducted in Mexico City, Mexico, and La Paz, Bolivia. We performed flow cytometric DNA analysis on gallbladder tissue specimens and measured levels of carcinoembryonic antigen (CEA) and CA 19-9 antigen in the serum and bile specimens. Analysis of the cell cycle compartments by flow cytometry revealed marked variations of the proliferation index for the different disease states (P less than .0001). The proliferation index increased with progression from cholecystitis to invasive adenocarcinoma. Of the bile and serum measurements, only serum CA 19-9 values were correlated with flow cytometry measurements (r = -.49, P = .005). Overall, the serum and bile measurements were in agreement (P less than .01). However, with the exception of the correlations among serum measurements for the patients with invasive adenocarcinoma, most of the correlations could be explained by differences in the disease state. In particular, the progression from normal tissue to invasive adenocarcinoma involved no change in bile CA 19-9 level and only a slight change in bile CEA level but much larger changes in serum CEA and CA 19-9 levels. It appears that the progression from normal tissue to invasive adenocarcinoma results in increased production of these antigens and often in loss of cell polarity as well, i.e., inability to prevent leakage of the antigens into the serum.

Antigens, Tumor-Associated, Carbohydrate↗

Nonenzymatic transformations of enzymatically generated N-acetyldopamine quinone and isomeric dihydrocaffeiyl methyl amide quinone.

We have recently demonstrated that the side chain hydroxylation of N-acetyldopamine and related compounds observed in several insects is caused by a two-enzyme system catalyzing the initial oxidation of catecholamine derivatives and subsequent isomerization of the resultant quinones to isomeric quinone methides, which undergo rapid nonenzymatic hydration to yield the observed products [Saul, S.J. and Sugumaran, M. (1989) FEBS Lett. 249, 155-158]. During our studies on o-quinone/p-quinone methide tautomerase, we observed that quinone methides are also produced nonenzymatically slowly, under physiological conditions. The quinone methide derived from N-acetyldopamine was hydrated to yield N-acetylnorepinephrine as the stable product as originally shown by Senoh and Witkop [(1959) J. Am. Chem. Soc. 81, 6222-6231], while the isomeric quinone methide from dihydrocaffeiyl methylamide exhibited a new reaction to form caffeiyl amide as the stable product. The identity of this product was established by UV and IR spectral studies and by chemical synthesis. We could not find any evidence of intramolecular cyclization of N-acetyldopamine quinone to iminochrome-type compound(s). The importance of quinone methides in these reactions is discussed.

Animals↗

Trapping of transiently formed quinone methide during enzymatic conversion of N-acetyldopamine to N-acetylnorepinephrine.

We have demonstrated that quinone methide formation is an important aspect of insect physiology and proposed that enzymatically generated quinone methides react nonenzymatically with water or other nucleophiles to form Michael-1,6-addition products [(1988) Adv. Insect Physiol. 21, 179-231; (1989) J. Cell. Biochem. suppl. 13C, 58]. Using a purified o-quinone isomerase from the larval cuticle of Sacrophaga bullata and mushroom tyrosinase, we now demonstrate that transiently formed N-acetyldopamine quinone methide from N-acetyldopamine can be trapped by methanol to produce beta-methoxy N-acetyldopamine. The methanol adduct thus formed was found to be a racemic mixture and can be resolved into the optical isomers on cyclodextrin chiral column. These results confirm our contention that enzymatically generated quinone methides are nonenzymatically and nonstereoselectively transformed to Michael-1,6-adducts by reaction with water or other nucleophiles.

Animals↗

A novel quinone: quinone methide isomerase generates quinone methides in insect cuticle.

Insoluble cuticle-bound enzyme(s) of Manduca sexta pharate pupae, which is known to convert N-acetyldopamine to N-acetylnorepinephrine through the intermediate formation of quinone methide, also converted exogenously supplied N-acetyldopamine quinone to N-acetylnorepinephrine. The presence of a quinone trap such as N-acetylcysteine in the reaction mixture containing N-acetyldopamine and cuticle prevented the formation of N-acetylnorepinephrine but readily yielded N-acetylcysteine-N-acetyldopamine quinone adduct as a dead-end product. These results indicate the oxidation of N-acetyldopamine to its quinone and its enzyme-catalyzed isomerization to quinone methide before yielding N-acetylnorepinephrine as the stable product. The role of this newly discovered isomerase in sclerotization of insect cuticle is discussed.

Animals↗

Nonspecific involvement of bowel adjoining Crohn disease.

Nonspecific changes in bowel segments adjacent to areas of Crohn disease were identified radiographically in 12 patients. In eight patients such changes were related to fistulization; in four patients they were due to close proximity of an inflammatory mass, abscess, or phlegmon of Crohn disease origin. The radiographic feature of nonspecific involvement was focal fold thickening, either in relation to the site of entry of fistulas or, together with mass effect, in response to the extrinsic inflammatory process. Radiographic differentiation of nonspecific bowel changes from actual Crohn disease is possible and is relevant to management, since nonspecific changes revert to normal once the underlying Crohn disease has been resected. Preoperative identification of nonspecificity supports a more conservative approach to surgery in patients with Crohn disease.

Adult↗

[Clinical experiences with a single layer uterine suture in cesarean section].

In this analysis 536 caesarean sections with a single layer uterine suture were compared to 256 sections with two layer closure. Their relations with regard to indications of operative delivery, complications during the puerperium and their courses in subsequent vaginal deliveries were taken into consideration. - The significant lower rate of pyrexia and shorter hospital stay of the patients may be a result of quicker and better healing of the single layer suture. The increased rate of complications in the puerperium is partially due to changes in the registry of dates. Absent disturbances during the placental period and the occurrence of only one uterine rupture, in the course of vaginal delivery in a patient with a previous single layer caesarean section suture, demonstrates the functional sufficiency of this technic.

Cesarean Section↗

Blood culture positivity: suppression by outpatient antibiotic therapy in patients with bacterial endocarditis.

Recognition of the increasing prevalence of outpatient antibiotic use prompted this review of 32 patients with verified infectious endocarditis. The results of 161 quantitative blood cultures obtained before definitive therapy were correlated with clinical information to determine whether outpatient antibiotic administration influenced blood culture positivity. In 17 patients receiving outpatient antibiotics, 56 (64%) of 88 blood cultures obtained before definitive treatment were positive, whereas all cultures obtained from 15 patients without recent antibiotic exposure were positive. Notably, seven patients showed a phase of total suppression, and two patients showed a phase of partial suppression of blood culture positivity after discontinuation of outpatient antibiotic treatment. Consequently, patients with recent antibiotic exposure and suspected endocarditis should have blood cultures obtained initially and periodically throughout the phase of potential suppression of bacteremia to optimize the chance of obtaining a positive result.

Ambulatory Care↗