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Biomedical subjects

D Black

Publications and source records attributed to D Black.

At least 19 recordsLinked to original sources
PubMed1992

Hormone therapy to prevent disease and prolong life in postmenopausal women.

PURPOSE: To critically review the risks and benefits of hormone therapy for asymptomatic postmenopausal women who are considering long-term hormone therapy to prevent disease or to prolong life. DATA SOURCES: Review of the English-language literature since 1970 on the effect of estrogen therapy and estrogen plus progestin therapy on endometrial cancer, breast cancer, coronary heart disease, osteoporosis, and stroke. We used standard meta-analytic statistical methods to pool estimates from studies to determine summary relative risks for these diseases in hormone users and modified lifetable methods to estimate changes in lifetime probability and life expectancy due to use of hormone regimens. RESULTS: There is evidence that estrogen therapy decreases risk for coronary heart disease and for hip fracture, but long-term estrogen therapy increases risk for endometrial cancer and may be associated with a small increase in risk for breast cancer. The increase in endometrial cancer risk can probably be avoided by adding a progestin to the estrogen regimen for women who have a uterus, but the effects of combination hormones on risk for other diseases has not been adequately studied. We present estimates for changes in lifetime probabilities of disease and life expectancy due to hormone therapy in women who have had a hysterectomy; with coronary heart disease; and at increased risk for coronary heart disease, hip fracture, and breast cancer. CONCLUSIONS: Hormone therapy should probably be recommended for women who have had a hysterectomy and for those with coronary heart disease or at high risk for coronary heart disease. For other women, the best course of action is unclear.

Breast Neoplasms↗
PubMed1992

Psychiatric disorder and cognitive impairment in systemic lupus erythematosus.

OBJECTIVES: To determine the point prevalence of psychiatric disorder in patients with systemic lupus erythematosus (SLE). To investigate associations between psychiatric disorder and social stress, cognitive impairment, systemic disease activity, and corticosteroid therapy. METHODS: A cross-sectional study of 73 consecutive patients with SLE assessed using standardized psychiatric and clinical research methods. RESULTS: Current psychiatric disorder was present in 15 patients (20.5%) and was significantly associated with social stress, lack of social support, and impairment on 2 tests of cognitive function (Verbal Fluency Test and Benton Visual Retention Test, Part A, number of errors). There was no association with systemic disease activity or corticosteroid therapy. Cognitive impairment on 2 or more tests was found in 26% and was associated with clinical evidence of central nervous system (CNS) disease, but not systemic disease activity or corticosteroid therapy. CONCLUSIONS: The point prevalence of psychiatric disorder in this cohort of patients with SLE was found to be similar to that observed in patients with rheumatoid arthritis. It was independently associated with social stress and 2 indicators of cognitive impairment, but not with systemic disease activity or corticosteroid therapy. Marked cognitive impairment was present in a significant percentage of patients even when there was no overt evidence of CNS involvement.

Adult↗
PubMed1992

Site-matched calcaneal measurements of broad-band ultrasound attenuation and single X-ray absorptiometry: do they measure different skeletal properties?

Because of the differences in the interactions of ultrasound and x-ray waves with bone, quantitative ultrasound (QUS) techniques may yield information about skeletal status not accessible by regular bone densitometry (BD) techniques. However, relatively strong correlations have been reported between broad-band ultrasound attenuation (BUA) and several x-ray-based BD methods. We assessed the precision and association of single x-ray absorptiometry (SXA) and BUA of the calcaneus. We examined both BUA and SXA at the calcaneus using special software for matching the regions of interest. An algorithm was derived and applied to correct the observed correlation coefficients for the attenuation effect caused by the precision errors for BUA and SXA. In a group of 33 volunteers covering a wide range of age and calcaneal bone mineral densities, the site-matched and precision-adjusted correlation coefficient between BUA and SXA was r = 0.58, with a standard error of the estimate (SEE) of 14.41 dB/MHz, or 17.08%. For the subgroup of 25 women the correlation was stronger, with r = 0.72 and SEE = 11.53 dB/MHz, or 14.33%. SXA precision was 0.79% for the regular region of interest (ROI) and 1.22% for the site-matched ROI. BUA precision was 2.76% for the entire subject group and 1.63% for women of age 40 or older. The observed correlation coefficient between ultrasound and x-ray based techniques of the order of 0.7 is significant, but it leaves about 50% of the variability unexplained.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1992

The carboxy-terminal extension of the collagen binding domain of fibronectin mediates interaction with a 165 kDa membrane protein involved in odontoblast differentiation.

Terminal differentiation of the odontoblast is characterized by an elongation and a polarization of the cell. The change in the cell shape and the reorganization of the cytoplasm involve the microfilament system. An immunological approach has previously implicated a transmembrane interaction between fibronectin and vinculin in the control of odontoblast differentiation. A 165 kDa protein localized on the cell-surface of odontoblasts mediated this interaction. In order to define the nature of the interaction of the 165 kDa protein with fibronectin, peptides were prepared by proteolytic cleavage of fibronectin with alpha-chymotrypsin. The results indicate that the 165 kDa protein interacted with a 62 kDa peptide located towards the amino-terminal extremity of fibronectin, but not with a 47 kDa related fragment. Both these 62 kDa and 47 kDa peptides included the collagen-binding domain and were retarded on a heparin-Ultrogel column. Microsequences demonstrated that the 62 kDa and 47 kDa fragments had the same amino-terminal extremity and that the larger fragment was extended in the carboxy-terminal direction. This carboxy-terminal extension of the collagen binding domain of fibronectin is implicated in the interaction of this molecule with the 165 kDa protein. On the other hand, odontoblasts differentiated normally when tooth germs were cultured in the presence of GRGDS synthetic peptide, suggesting that RGD-dependent integrins were not involved in odontoblast differentiation. Staining of dental mesenchymal cells in primary culture and of differentiated odontoblasts in situ with antibodies directed against the beta 1-subunit of integrins confirmed previous observations and showed that although beta 1 integrins are involved in the attachment of cultured dental cells, they are not implicated in the process of odontoblast differentiation.

Actin Cytoskeleton↗
PubMed1992

Father kills mother: post-traumatic stress disorder in the children.

Results of a study of over 100 children whose father killed their mother have been summarized and principles for practice have been formulated. All children orphaned by the death of one parent at the other's hands should be seen as soon as possible in a child psychiatry department and assessed. An immediate crisis intervention will probably be needed if they witnessed the killing to prevent PTSD. Bereavement counselling will be helpful in most cases. The caretakers will need support and help with their own mourning. Placement, access and custody, compensation, seeing the body, attending the funeral and dealing with family conflict will all need consideration. Long-term follow-up and further research are recommended.

Bereavement↗
PubMed1992

Change in the NHS.

This paper tries to set the current changes in the British National Health Service in historical perspective. The NHS was born in 1948 amid controversy, both political and professional; but in the 50s and 60s a consensus was reached which won it the support of patients and doctors. But in the 70s and 80s it has undergone the stress of successive reorganizations, in the attempt to meet the economic strains imposed by an ageing population and expensive medical advances. The present changes aim to bring about an "internal market," regulated by contract between "purchases" and "providers." Reasons are given for the view that this artificial arrangement will impair the coherence of the NHS, will add administrative expense and complexity, and will impair the important role of general practitioners as "gate-keepers."

Delivery of Health Care↗
PubMed1991

Evidence that thymocyte-activating molecule is mouse CD26 (dipeptidyl peptidase IV).

We previously described a developmentally regulated, Mr 115,000 (reduced) and 110,000/128,000 (nonreduced) mouse T cell-activating molecule (THAM) also expressed on a variety of epithelial cell surfaces, and associated with neutral exoaminopeptidase activity. In the present study, we show that THAM is the mouse counterpart of the human T cell-activating ectoenzyme CD26 (dipeptidyl peptidase IV, DPP IV) and that highly purified THAM lacks neutral exoaminopeptidase activity. This conclusion is based on the following: 1) the N-terminal segments of the THAM Mr 110,000 and 128,000 components shared the same amino acid sequence with the rat DPP IV. These N-termini comprised a short intracytoplasmic tail of six residues followed by a downstream hydrophobic transmembrane segment. 2) THAM-specific mAb H194-112-Affi-Gel immunoadsorbent was capable of removing DPP IV enzymatic activity from mouse thymoma cell detergent extracts. 3) H194-112 reactivity pattern on developing thymocytes was found to parallel that previously reported for membrane-bound DPP IV enzymatic activity. The extent of THAM N-glycosylation, as measured by N-glycanase treatment of H194-112 immunoprecipitates, was found to be similar to that of human and rat DPP IV (i.e., approximately 20 kDa). Cross-linking experiments indicated that THAM was expressed at the cell surface as a dimer of approximately 220 kDa. Its two subunits were found to be structurally related but not identical as shown by their different Mr under nonreducing conditions and by their slightly distinct peptide profiles after proteolytic cleavage. We conclude from these data that DPP IV, in addition to its extracellular matrix receptor and ectoenzymatic functions, is a T cell-activating structure in both human and mouse species.

Amino Acid Sequence↗
PubMed1991

Purification and characterization of a brain-specific protein kinase C substrate, neurogranin (p17). Identification of a consensus amino acid sequence between neurogranin and neuromodulin (GAP43) that corresponds to the protein kinase C phosphorylation site and the calmodulin-binding domain.

Neurogranin, formerly designated p17 (Baudier, J., Bronner, C., Kligman, D., and Cole, R. D.) (1989) J. Biol. Chem. 264, 1824-1828), a brain-specific in vitro substrate for protein kinase C (PKC), has been purified to homogeneity from bovine forebrain. The purified protein has a molecular mass of 7837.1 +/- 0.5 Da, determined by electrospray mass spectrometry. In the absence of reducing agent, dimers and higher oligomers accumulated. On sodium dodecyl sulfate-polyacrylamide gels the protein monomer migrated abnormally with an apparent molecular mass of 15,000-19,000 Da, depending on the percentage of polyacrylamide. The native protein is blocked at its amino terminus. The majority of the primary amino acid sequence was determined following proteolytic and chemical fragmentation. A comparison of the amino acid sequence of neurogranin with that of the brain-specific PKC substrate neuromodulin, revealed a strikingly conserved amino acid sequence AA(X)KIQA-SFRGH(X)(X)RKK(X)K. The two proteins are not related over the rest of their sequences. Neurogranin was shown to be phosphorylated in hippocampal slices incubated with 32Pi and phorbol esters stimulated neurogranin phosphorylation, suggesting that neurogranin is likely to be an in vivo substrate for PKC. In vitro phosphorylation of neurogranin by PKC produced a shift of the isoelectric point of the protein (pI 5.6) to a more acidic value (pI 5.4). Tryptic digestion of the phosphorylated protein yielded a single phosphopeptide having the sequence IQASFR, where the serine residue is the phosphorylated amino acid. This phosphopeptide is part of the conserved sequence shared with neuromodulin and also corresponds to the PKC phosphorylation site on neuromodulin (Apel, E. D., Byford, M. F., Au, D., Walsh, K. A., and Storm, D. R. (1990) Biochemistry 29, 2330-2335). Evidence was obtained suggesting that neurogranin binds to calmodulin in the absence of Ca2+, a feature that also characterizes neuromodulin. We propose that the amino acid sequence shared by neurogranin and neuromodulin reflects a functional relationship between these two proteins and that the consensus sequence represents a conserved PKC phosphorylation site and a calmodulin binding domain that characterizes a class of brain-specific PKC substrates.

Amino Acid Sequence↗