Enzymic synthesis of steroid sulphates. VII. Association-dissociation equilibria in the steroid alcohol sulphotransferase of human adrenal gland extracts.
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Biomedical subjects
Publications and source records attributed to J B Adams.
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1. Glycosidic linkage of carbohydrate to the primary hydroxyl groups of threonine and serine has been established in human blood-group A and Le(a) substances, bovine submaxillary-gland mucin and human pseudomyxomatous mucin. 2. Treatment of these substances in 0.09n-lithium hydroxide at 100 degrees for 1hr. led to beta-elimination at these glycosidic linkages with the resultant formation of alpha-oxobutyric acid and glycine from threonine linkages, and pyruvic acid from serine linkages. Though most of the threonine was destroyed in every case, about one-third to one-half of the serine residues resisted alkaline cleavage. Such results, indicative of the presence of unbound serine residues, allow, in submaxillary mucin, for a close correlation between the remaining serine, threonine, glutamic acid and aspartic acid and the available sialyl-(2-->6)-N-acetylgalactosamine prosthetic groups. 3. The stoichiometry of the beta-eliminations has been demonstrated for pseudomyxomatous mucin. The alpha-oxo acids were separated and determined as their quinoxalinol derivatives by thin-layer chromatography on silica gel. Reaction at the threonine centres favoured alpha-oxobutyric acid formation (70%, via the intermediary dehydropeptide) over the alternative pathway to glycine (30%). 4. 100% of the hexosamine was destroyed in submaxillary-gland mucin, 85% in pseudomyxomatous mucin and about 60% in the blood-group substances. In the latter cases, the glucosamine/galactosamine ratio was increased from about 4:1 to 8-10:1, suggesting a preferential destruction of galactosamine. Evidence was obtained, however, for a further destruction of hexosamine, in addition to that which could be theoretically attached to peptide at possible known binding sites. 5. The major part of the alkali-resistant hexosamine in the blood-group substances was non-diffusible and was accompanied by the constituent carbohydrates in similar molar proportions to the native materials.
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Microsomal preparations derived from bovine placenta cotyledons, previously investigated as a convenient source of fatty acyl coenzyme A: estradiol-17 beta-acyl transferase, have been shown to acylate other steroids bearing 3 beta- or 17 beta-hydroxyl groups. In the presence of 0.1 mM oleoyl CoA, the apparent Km values for dehydroepiandrosterone, testosterone, and 5-androstene-3 beta,17 beta-diol (delta 5-DIOL) were 45, 67, and 20 microM, respectively. Acylation of delta 5-DIOL occurred at either the 3 beta- or 17 beta-positions to give monoesters. Testosterone, estradiol-17 beta, and delta 5-DIOL acted as competitive inhibitors for the acylation of the 3 beta-hydroxyl group of dehydroepiandrosterone (Ki values 71, 75, and 41 microM, respectively). Such data indicate that a single enzyme of wide substrate specificity may be involved in these acylation reactions. When estrogen receptor (ER) positive and negative human mammary cancer cell lines were incubated with 10 nM [3H]delta 5-DIOL, intracellular accumulation of delta 5-DIOL long-chain fatty acid esters occurred; rates being higher (p less than 0.001) in ER negative cells (MDA-MB-231 and MDA-MB-330) compared to MCF-7 cells (ER positive), and higher (P less than 0.005) in MDA-MB-231 cells compared to ZR-75-1 cells (ER positive). After exposure to 10 nM [3H]delta 5-DIOL for 16 h, the total labeled steroid fatty acid fraction was composed predominantly of delta 5-DIOL-3 beta- and 17 beta-monoesters (approximately 85%), the remainder containing approximately equal amounts of delta 5-DIOL-diesters and dehydroepiandrosterone-3 beta-esters. Subsequent transfer to medium lacking delta 5-DIOL was accompanied by a breakdown of the labeled esters, which was more rapid in the ER positive cell lines. During this period, intracellular free delta 5-DIOL levels rapidly declined in MDA-MB-330 cells but were maintained in MCF-7 cells, presumably by binding to ER. This behavior parallels that of estradiol-17 beta previously observed in these cell lines and further emphasizes the potential importance of the adrenal-derived estrogen delta 5-DIOL in consideration of a hormone-based etiology of human breast cancer.
This article introduces an innovative collaboration between an orthopaedic surgeon's office and the hospital to assure complete and accurate admission information without duplication. With the use of point-of-care software, the assessment process was re-tooled. This change involved the patient/family assuming responsibility for completing paper and pencil in-depth history and systems review that was then used as part of the evaluation process and inputted into the database allowing for more effective outcomes assessment. In this re-tooling process, the concept of "sharing" information with the partnering hospital was explored. In collaborative discussions, the nursing admission assessment was targeted as a process where there was significant duplication. In fact, much of the information required on the 4-page form was already assessed and documented in the office setting. Consequently it was agreed that the majority of the inpatient nursing history/admission assessment form would be replaced with the assessment completed by the professional office staff. Because of incompatible software, the systems could not be linked but a printed copy of the form was sent to the hospital. Results measuring satisfaction, timesaving, and compliance with JCAHO documentation standards were part of the evaluation. Patients and clinicians were satisfied with the process. There was a significant timesaving for the in-patient RN which facilitated more direct contact with the patient and family.
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We conducted a case-control study of cigarette smoking and dysplasia and carcinoma in situ of the uterine cervix. Cases were black women 17 to 55 years of age who were attending a dysplasia clinic and had biopsy-confirmed cervical pathologic conditions. Controls were women who were attending the family planning clinic at the same hospital and who had at least two normal Papanicolaou smears. Results were adjusted for age, number of sexual partners, age at first intercourse, socioeconomic status, and oral contraceptive use. Cigarette smoking was significantly associated with carcinoma in situ, severe dysplasia, and mild-moderate dysplasia (relative risks, 3.6, 3.3, and 2.4, respectively). Cumulative exposure to cigarette smoking (as measured by pack-years smoked) was strongly related to the risk of these conditions; women with 12 or more pack-years of exposure had relative risks of 12.7, 10.2, and 4.3, respectively, for the three conditions. There was some evidence that the risk was greatest in women who began smoking in their early teenage years. A reduction in the risk of cervical cancer appears to be another inducement for young women not to smoke.
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