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Biomedical subjects

M Sales

Publications and source records attributed to M Sales.

15 recordsLinked to original sources

Karyotypic aberrations of chromosomes 16 and 17 are related to survival in patients with breast cancer.

BACKGROUND: Breast cancer has a high incidence and associated mortality rate, yet little is known of the sequence of genetic events that underlie the clinical course. METHODS: The study was a comparative genomic hybridization analysis of 40 primary breast cancers with survival data at a mean of 8.4 years. RESULTS: The mean number of aberrations was 9.0, with a mean of 5.5 gains and 3.5 deletions per tumour. The most common aberrations were: gain of 1q (27 of 40), 8q (19 of 40) and 17q (13 of 40), and deletion of 17p (12 of 40) and 8p (11 of 40). These results are consistent with a distinctive pattern of large-scale (karyotypic) genetic change in primary breast cancer. CONCLUSION: The novel findings of this study were that only women who were disease-free had loss of 16q (E-cadherin) in association with a gain of 16p, and 17p13 (p53) loss combined with 17q12 (HER2) amplification was found only in the cancers of women who developed recurrent disease. The karyotypic changes seen in primary breast cancer seem to be associated with outcome and point to the underlying genetic events.

Breast Neoplasms↗

Syn-anti isomerization of aldols by enolization.

[reaction--see text] A variety of aldol adducts (i.e., 3-hydroxy ketones) are shown to undergo syn-anti isomerization in the presence of imidazole by an enolization mechanism with negligible retroaldol or elimination products.

Journal Article↗

Chromosomal imbalances in gastric and esophageal adenocarcinoma: specific comparative genomic hybridization-detected abnormalities segregate with junctional adenocarcinomas.

The incidence of adenocarcinoma arising at the esophagogastric junction (EGJ) is increasing at a rate greater than that for any other form of solid malignancy. Commensurate with this, the incidence of histologically similar tumors arising in the gastric body and antral mucosa is declining. The increased incidence of the proximal group of tumors may reflect, in part, the higher prevalence of Barrett esophagus. These epidemiological features suggest that histologically similar tumors arising at the EGJ and from the distal stomach are different, which may be reflected in the genetic abnormalities that characterize the two groups of tumors. The purpose of this study was to screen genomic DNA from adenocarcinomas of the esophagus and stomach for regions of chromosomal imbalance, using comparative genomic hybridization to determine whether tumors at the EGJ (junctional tumors) have a different profile compared with tumors of the distal stomach. Tumor samples were derived from a series of 48 gastroesophageal adenocarcinomas (20 junctional and 28 distal) that were acquired prospectively from patients undergoing esophagogastrectomy. These tumors are characterized by several regions of chromosomal imbalance with no obvious correlation between most regions of abnormal copy number and tumor type. However, our study shows for the first time cytogenetic abnormalities (5p+ and 18q-) that identify statistically significant differences (P < 0.02 and < 0.05, respectively) between junctional and distal gastric tumors. These differences are gain of 5p (55% [11/20] of junctional tumors vs. 21% [6/28] of distal gastric tumors) and loss of 18q (25% [5/20] cases of junctional tumors vs. 4% [1/28] of distal tumors) segregating with tumors of the EGJ. These abnormalities may distinguish distinct tumor subtypes that are recognized in epidemiological and clinical studies but that are otherwise histologically identical.

Adenocarcinoma↗

Postoperative necrotizing fasciitis of the thorax in cardiac surgery.

Necrotizing fasciitis is a rare soft tissue infection and a life-threatening emergency, often fatal. Its incidence and management are described plentifully in the medical literature regarding the most common anatomical sites involved like the abdomen, lower and upper limbs, and perineum. However, available data and case reports of chest wall necrotizing fasciitis after thoracic procedures are scarce, mainly after major cardiac operations. We report and discuss a case of necrotizing fasciitis of the chest wall occurring in the immediate postoperative period of a cardiac procedure, and include a brief review of the concepts, pathophysiology, and treatment reported in the medical literature. We emphasize the need for early diagnosis and urgent and effective surgical debridement. Of importance is the fact that we have not found any references in the literature to cases similar or equal to the one we describe here, which occurred in the postoperative period of a cardiac procedure.

Adult↗

Thiopyran route to polypropionates: aldol diastereoselectivity of linear and two-directional iterative homologations

[formula: see text] Aldol reaction of tetrahydro-4H-thiopyran-4-one with racemic 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde is easily controlled to give the 2,3-anti-3,4-syn or the 2,3-syn-3,4-syn adduct. Aldol homologations of these beta-hydroxy ketones with the same aldehyde occur with considerable mutual kinetic enantioselection (MKE) and, in each case, selectively give one of the eight possible diastereomers. Similar reactions of related beta-methoxy ketones are also very diastereoselective but proceed without significant MKE, resulting in two diastereomers. The adducts can be used for polypropionate synthesis.

Journal Article↗

Cloning and characterization of a novel human dual flavin reductase.

Flavoprotein reductases play a key role in electron transfer in many physiological processes. We have isolated a cDNA with strong sequence similarities to cytochrome P-450 reductase and nitric-oxide synthase. The cDNA encodes a protein of 597 amino acid residues with a predicted molecular mass of 67 kDa. Northern blot analysis identified a predicted transcript of 3.0 kilobase pairs as well as a larger transcript at 6.0 kilobase pairs, and the gene was mapped to chromosome 9q34.3 by fluorescence in situ hybridization analysis. The amino acid sequence of the protein contained distinct FMN-, FAD-, and NADPH-binding domains, and in order to establish whether the protein contained these cofactors, the coding sequence was expressed in insect cells and purified. Recombinant protein bound FMN, FAD, and NADPH cofactors and exhibited a UV-visible spectrum with absorbance maxima at 380, 460, and 626 nm. The purified enzyme reduced cytochrome c, with apparent K(m) and k(cat) values of 21 microM and 1.3 s(-1), respectively, and metabolized the one-electron acceptors doxorubicin, menadione, and potassium ferricyanide. Immunoblot analysis of fractionated MCF7 cells with antibodies to recombinant NR1 showed that the enzyme is cytoplasmic and highly expressed in a panel of human cancer cell lines, thus indicating that this novel reductase may play a role in the metabolic activation of bioreductive anticancer drugs and other chemicals activated by one-electron reduction.

3T3 Cells↗

Effects of ammonia and amino acids on the growth and proteolytic activity of three species of rumen bacteria: Prevotella albensis, Butyrivibrio fibrisolvens, and Streptococcus bovis.

The addition of increasing physiological concentrations of ammonia or amino acids had distinct effects on the growth and proteolytic activity of Streptococcus bovis JB1, Prevotella albensis, and Butyrivibrio fibrisolvens DSM3071. The growth of S. bovis and B. fibrisolvens was enhanced by NH(3) and AA, and that of P. albensis was reduced compared with a control with protein as the sole source of nitrogen. The proteolytic activity of S. bovis and P. albensis was reduced, but that of B. fibrisolvens was improved. NH(3) seemed to act mainly on the cell-associated fraction of the proteolytic activity, while the action of AA was not specific. In the rumen the proteolytic activity of S. bovis and P. albensis would be optimal at low concentrations of NH(3) or AA (<0.05 and <0.27 g/L respectively). In contrast, B. fibrisolvens would need higher concentrations (0.5 g/L of NH(3) or 2.7 g/L of AA). It can be assumed that these bacteria will grow in different ecological niches.

Amino Acids↗

Diastereoselective formation of cyanohydrins from alpha-alkoxy aldehydes

[reaction: see text] The reaction of alpha-alkoxy aldehydes with Et4NAg(CN)2 or Me3SiCN in the presence of MgBr2 x OEt2 in CH2Cl2 at 0 degrees C gives the corresponding syn cyanohydrins in good yield with high diastereoselectivity. Excess MgBr2 x OEt2 (typically 5 equiv) is required for high diastereoselectivity. Et4NAg(CN)2 (but not Me3SiCN) is sufficiently reactive to give cyanohydrins at -78 degrees C, and higher diastereoselectivity is obtained at this temperature.

Journal Article↗

Cloning and characterization of a novel human olfactory UDP-glucuronosyltransferase.

Xenobiotic metabolizing enzymes in the olfactory epithelium have been suggested to catalyse inactivation and facilitate elimination of odorants. We report here the molecular cloning and functional characterization of a human olfactory UDP-glucuronosyltransferase (UGT). The cloned protein is composed of 527 amino acids with an identity of 87% with a rat olfactory UGT and of 43-62% with other human UGT isoforms. Based on the sequence homology, it has been designated hUGT2A1. The gene was mapped to chromosome 4q13 by fluorescence in situ hybridization. The expression appeared to be specific for the olfactory tissue. The substrate specificity of this isoform was assessed using Chinese hamster V79 cells stably transfected with the isolated cDNA. The expressed enzyme showed a broad substrate spectrum including a range of phenolic compounds as well as aliphatic and monoterpenoid alcohols, among them many odorants. Furthermore, some steroids, especially androgens, some drugs and carcinogens were conjugated. The results support a role of the enzyme in olfactory perception and in protection of the neural system against airborne hazardous chemicals.

Alcohols↗

Health status of older male prisoners: a comprehensive survey.

Although prison populations remain predominantly young, the number of older inmates in state and federal correctional facilities has been increasing. This report describes the results of a health survey of 119 male inmates 50 years of age and older residing in Iowa state correctional facilities. Subject's disease history included hypertension (40%), myocardial infarction (19%), and emphysema (18%). Most participants (97%) had missing teeth, 42% had gross physical functional impairments, and 70% smoked cigarettes. These findings have implications for health care provision and release planning.

Activities of Daily Living↗

Major histocompatibility complex modulation of beta-adrenoceptor function.

Reciprocal interaction between beta-adrenoceptor specific ligand occupancy and alloantibody binding to specific antigens of cardiac and smooth muscle tissues was observed. Interference of alloimmune antibody fixation to both cardiac and oviductal tract preparations by beta 1 or beta 2 selective blockers, respectively, was obtained by means of indirect immunofluorescence assays. Reciprocally, alloimmune IgG and monoclonal antibodies directed to class I H-2 antigens, behaving as beta-adrenoceptor agonists, modified the contractility of both tissues, increasing intracellular levels of cyclic AMP (cAMP). Additionally, alloantibodies were also capable of inhibiting specific beta-adrenoceptor radioligand binding to purified cardiac and smooth muscle membranes. These data suggested a modulation of beta-adrenoceptor function by antibodies directed against H-2 class I histocompatibility molecules, probably through molecular interactions between both structures.

Animals↗

Health promotion and prevention.

Techniques of promotive and preventive health care include: The use of proactive skills in the consultation; and the co-ordinated use of posters and pamphlets with media campaigns. An efficient medical record and patient recall system; and a doctor initiated health check programme with selected patients. A cost effective method of informing practitioners includes: Ensuring access to continuing medical education by supporting FMP and post-graduate medical institutes. The provision of educational material for both the patient and doctor combined with media publicity campaigns. Supporting RACGP CHECKUP and library services for isolated practitioners. Suggested changes to undergraduate medical education are: Promotive and preventive health care delivery needs to be an inbuilt part of the curriculum. Promotive and preventive health care needs to be taught by both academic and private general practitioners who have received tutor training. It should be presented in tutorial form and during student attachment at surgeries. It needs to be followed up by continuing education by postgraduate institutes, the RACGP and FMP. Government input required includes: The provision of increased academic resources and continued funding of FMP. Remuneration for general practitioners who are involved in undergraduate teaching. Alteration of the fee structure to reward quality of care. Allowing Medicare rebate for promotive and preventive health care delivery.

Health Promotion↗

The regulation of the ammonia assimilatory enzymes in Rel+ and Rel- strains of Salmonella typhimurium.

The influence of the relA1 mutation on the regulation of the ammonia assimilatory enzymes, glutamate dehydrogenase (EC 1.4.1.4), glutamine synthetase (EC 6.3.1.2), and glutamate synthase (EC 1.4.1.3), was examined. When cells grown in rich media (either Luria broth or glucose-ammonia plus casamino acids) were transferred to a glucose-ammonia medium, the relA mutant failed to resume growth and did not have the same increase in any of the assimilatory enzyme activities as the rel+ strain. This effect was particularly dramatic for glutamate dehydrogenase, which increased 6-fold in the rel+ strain. Measurements of the guanosine nucleotide concentrations showed that the rel+ strain had a ppGpp concentration about 9 times that of the relA mutant 5 min after the shift to minimal medium. These results are consistent with those for other biosynthetic enzymes and show that the ammonia assimilatory enzymes require a relA product for their synthesis during shift from rich to minimal media. In addition, we examined the response of these strains to a change in nitrogen source. The relA mutant again failed to resume growth after a shift from glucose-ammonia to glucose-arginine medium. Even though the ppGpp concentration did not increase, the rel+ strain grew and increased glutamine synthetase activities about 2-fold. These changes the absence of increased ppGpp levels suggest that some other relA-mediated function is important during this change in nitrogen source.

Ammonia↗

[A new synthetic antiparkinsonian drug, tropatepine hydrochloride in extrapyramidal syndromes induced by neuroleptics].

Tropatepine hydrochloride was given per oral route to 184 patients and per injections to 34 patients. Average prescribed doses were about 20 mg (2 tablets). This clinical study has shown that tropatepine hydrochloride has an antiparkinson activity against neuroleptic-induced extra-pyramidal syndrome. In comparison to the activity of the other synthetic antiparkinson drugs, the activity of tropatepine hydrochloride is: -- similar on akineto-hypertonia and on tremor; -- better on akathisia and, though less frequently, on anormal dyskinetic movements due to long term neuroleptic treatment. Tolerance is good ; furthermore clinical and biological performed examinations have shown that the drug seems free of toxic effects In more than 200 treated patients no severe mental aberration and no habituation have been reported.

Adult↗

Library fungi at the University of São Paulo and their relationship with respiratory allergy.

In this study, we investigated the fungi most frequently found in the air and the books of 28 libraries at the University of São Paulo, Brazil. In a second phase, 314 librarians were questioned about the presence of asthmatic or rhinitic symptoms, and the relationship with the site of work. Forty-nine percent of them reported this type of symptoms and 80% related them to the place of work. In the third stage, librarians underwent intracutaneous tests against the 20 fungi most frequently isolated in libraries. Eighteen librarians presented positive tests, 12 of whom reported rhinitis and 6 of whom were asymptomatic. In 19.5% of symptomatic patients wheals > 15 mm were observed after 6 h, while 9% of the asymptomatic patients presented similar wheals. Fourteen librarians with positive tests underwent tests with each of the 20 fungi constituting the pool. The airborne fungi isolated in libraries are likely to be found anywhere in the city of São Paulo, but they are likely to be present in higher concentrations in libraries, subsequently producing respiratory allergies.

Adolescent↗