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Biomedical subjects

D Bailey

Publications and source records attributed to D Bailey.

At least 73 records · Page 4Linked to original sources

Health professionals and breastfeeding counseling: client and provider views.

Health care providers are the most influential and trusted source of information about breastfeeding, yet many are neither prepared nor able to provide good breastfeeding counseling to their clients. This paper reports findings on low-income mothers' and on providers' perceptions of professional breastfeeding counseling. Data collection included focus group discussions with mothers recruited from public health department clinics in the Southeast USA and who were stratified by age, parity, rural/urban residence and feeding method, and focus groups and individual interviews were conducted with health care providers from the same geographic area. The results of the study indicate a gap between the promotion and support processes for breastfeeding, and point to areas where breastfeeding counseling can be strengthened.

Attitude of Health Personnel↗

Effects of P2-purinoceptor antagonists on ecto-nucleotidase activity of guinea-pig vas deferens cultured smooth muscle cells.

Ecto-nucleotidase activity was studied on primary cultures of guinea-pig vas deferens smooth muscle cells by measuring the inorganic phosphate (Pi) production using ATP as a substrate. The ecto-nucleotidase was insensitive to ouabain, oligomycin, sodium azide, p-nitrophenyl phosphate and B-glycerophosphate. Enzyme activity was highly dependent on either Ca2+ or Mg2+. Antagonists of P2X-purinoceptors, pyridoxalphosphate-6-azophenyl-2',4'- disulphonic acid, 4'4'-diisothiocyanatostilbene-2'2'- disulphonate, suramin and pyridoxal-5-phosphate, significantly inhibited ecto-nucleotidase activity. In contrast, the P1-purinoceptor antagonists, 8-p-sulphophenyl theophylline and 1,3-dipropyl-8-cyclopentylxanthine, did not affect the enzyme activity. Thus, when P2-purinoceptors are studied by testing agonists and antagonists potencies, the inhibition of ecto-nucleotidase activity by currently available P2-purinoceptor antagonists should be taken into account.

Adenosine Triphosphatases↗

Dipyridamole directly inhibits vascular smooth muscle cell proliferation in vitro and in vivo: implications in the treatment of restenosis after angioplasty.

OBJECTIVES: The effect of dipyridamole on smooth muscle cell proliferation and prevention of intimal thickening after arterial injury was investigated. BACKGROUND: In addition to antiplatelet activity, dipyridamole also inhibits cell proliferation. We examined whether the antiproliferative action of dipyridamole on smooth muscle cells, as demonstrated here, has a direct effect on intimal thickening after vascular injury. METHODS: Cell proliferation was determined by measuring deoxyribonucleic acid (DNA) synthesis and by cell counting. The in vivo effect of locally delivered dipyridamole was determined in a rabbit model with carotid or femoral artery injury. RESULTS: Dipyridamole produced a dose-dependent inhibition of smooth muscle cell proliferation, producing 50% inhibition at 7 micrograms/ml. Structural analogues SH-869 and mopamidol were 10 to 100 times less effective than dipyridamole, suggesting that cell growth inhibition may be unrelated to the antiplatelet activity of dipyridamole. Inhibition of cell proliferation by dipyridamole was attenuated by increasing the serum concentration in the culture medium. Bypassing serum by local delivery of dipyridamole at the periadventitial site produced 63% inhibition (p < 0.05) of cell replication in balloon-injured arteries. Locally delivered dipyridamole also inhibited intimal thickening (20%, p < 0.05) after balloon injury. CONCLUSIONS: Dipyridamole inhibited smooth muscle cell proliferation in vitro. This activity was attenuated by serum proteins. Locally delivered dipyridamole inhibited cell replication in arteries and intimal thickening after balloon injury. These results suggest that although systemic treatment with dipyridamole may not be efficacious because of inadequate serum levels, its antiproliferative action on smooth muscle cells may reduce restenosis when the drug is delivered locally after coronary angioplasty.

Angioplasty, Balloon↗

A structural comparison of 21 inhibitor complexes of the aspartic proteinase from Endothia parasitica.

The aspartic proteinases are an important family of enzymes associated with several pathological conditions such as hypertension (renin), gastric ulcers (pepsin), neoplastic disease (cathepsins D and E), and AIDS (HIV proteinase). Studies of inhibitor binding are therefore of great importance for design of novel inhibitors for potential therapeutic applications. Numerous X-ray analyses have shown that transition-state isostere inhibitors of aspartic proteinases bind in similar extended conformations in the active-site cleft of the target enzyme. Upon comparison of 21 endothiapepsin inhibitor complexes, the hydrogen bond lengths were found to be shortest where the isostere (P1-P'1) interacts with the enzyme's catalytic aspartate pair. Hydrogen bonds with good geometry also occur at P'2, and more so at P3, where a conserved water molecule is involved in the interactions. Weaker interactions also occur at P2, where the side-chain conformations of the inhibitors appear to be more variable than at the more tightly held positions. At P2 and, to a lesser extent, P3, the side-chain conformations depend intriguingly on interactions with spatially adjacent side chains, namely P'1 and P1, respectively. The tight binding at P1-P'1, P3, and P'2 is also reflected in the larger number of van der Waals contacts and the large decreases in solvent-accessible area at these positions, as well as their low temperature factors. Our analysis substantiates earlier proposals for the locations of protons in the transition-state complex. Aspartate 32 is probably ionized in the complexes, its charge being stabilized by 1, or sometimes 2, hydrogen bonds from the transition-state analogues at P1. The detailed comparison also indicates that the P1 and P2 residues of substrate in the ES complex may be strained by the extensive binding interactions at P3, P'1, and P'2 in a manner that would facilitate hydrolysis of the scissile peptide bond.

Ascomycota↗

Regional deposition of saline aerosols of different tonicities in normal and asthmatic subjects.

Nonisotonic aerosols are frequently used in the diagnosis and therapy of lung disease. The purpose of this work was to study the difference in the pattern of deposition of aerosols containing aqueous solutions of different tonicities. 99mTechnetium-diethyltriaminepentaacetic acid (99mTc-DTPA)-labelled saline aerosols, with mass median aerodynamic diameter 3.7-3.8 microns and geometric standard deviation 1.4, were inhaled under reproducible breathing conditions on two occasions. Hypotonic and hypertonic solutions were used in 11 normals subjects, isotonic and hypertonic solutions in 9 asthmatics. The regional deposition was quantified by a penetration index measured with the help of a tomographic technique. There was a small but significant increase (6.7%) in the penetration index of the hypotonic as compared to the hypertonic aerosols in the normal subjects. The region that was markedly affected was the trachea. The differences in the penetration of the isotonic and hypertonic aerosols in the asthmatics appeared to be strongly dependent on the state of the airways at the time of the study. These findings can be interpreted in terms of effects of growth or shrinkage of nonisotonic aerosols, as well as of airway narrowing, on regional deposition of aerosols. Tonicity of aerosols appears to affect their deposition both through physical and physiological mechanisms. This should be taken into account when interpreting the effects of inhaled aqueous solutions of various tonicities in patients in vivo.

Administration, Inhalation↗

Inhibition of cholesteryl ester transfer protein in normocholesterolemic and hypercholesterolemic hamsters: effects on HDL subspecies, quantity, and apolipoprotein distribution.

The effects of cholesteryl ester transfer protein (CETP) inhibition on the serum lipoprotein profile in both normocholesterolemic and hypercholesterolemic hamsters has been determined following subcutaneous injection of 12.5 mg/kg of the CETP neutralizing monoclonal antibody, TP2. Inhibition of CETP activity was greater than 60% and resulted in a 30-40% increase in high density lipoprotein (HDL) in both normal and hypercholesterolemic animals. These HDL effects were observed 1 day post-injection, were maximal by 4 days, and returned to control values by 14 days. Inhibition of CETP activity resulted in a decrease in both low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol concomitant with HDL increase, and in hypercholesterolemic animals resulted in increased total serum cholesterol. In addition to the quantitative differences in LDL and HDL, there were significant increases in the size of the HDL, a shift to smaller LDL particles, and changes in apolipoprotein (apo) composition as evaluated by FPLC and Western blot analysis. Large apoA-I-poor and apoE-containing HDL became prevalent in hypercholesterolemic hamsters after CETP inhibition. In addition, the size of the CETP-containing HDL particles increased with inhibition of transfer activity. While these effects were apparent in normocholesterolemic animals, the changes in apolipoprotein distribution and HDL subspecies as detected on native gels were more significant in the hypercholesterolemic animals. The changes in the HDL profile and apolipoprotein distribution after CETP inhibition in hamsters were similar to those reported in CETP-deficient Japanese subjects, suggesting the utility of the hypercholesterolemic hamster as an in vivo model for the understanding of the lipoprotein changes associated with CETP inhibition.

Animals↗

Cell cycle dependent regulation of the protein kinase TTK.

TTK is a novel protein kinase detectable in all proliferating human cells and tissues. Expression of the TTK gene is markedly reduced or absent in resting cells and in tissues with a low proliferative index. In view of the apparent association between TTK gene expression and cell proliferation, we examined the regulation of this protein kinase during transit of the cell cycle. We found very low levels of TTK mRNA and protein in starved cells. When cells are induced to enter the cell cycle, levels of TTK mRNA, protein and kinase activity increase at the G1/S phase of the cell cycle and peak in G2/M. TTK mRNA levels, as well as kinase activity, drop sharply in early G1, whereas protein levels are largely maintained. TTK may play a role in cell cycle control.

Cell Cycle↗

Mutations of the p53 gene do not occur in testis cancer.

To characterize the role of p53 in the development of testis cancer, we looked for mutations in the coding sequences of the p53 gene. DNA was obtained both from familial and sporadic testis cancer specimens, as well as from peripheral blood from members of a testis cancer kindred. Mutations in the p53 gene were screened using a combination of constant denaturant gel electrophoresis and single-strand conformational polymorphism analysis, 2 screening methods that can detect single base changes. Abnormalities detected by these methods were confirmed by sequencing of the corresponding cloned polymerase chain reaction products. All conserved regions of the p53 coding sequences were examined, encompassing all previously reported sites of mutations. No mutations were found in any of 22 germ cell cancers of the testis or in the germline DNA of 17 members of the testis cancer family. This is in striking contrast to most other human cancers, in which mutations of p53 are the most commonly described molecular event associated with tumorigenesis. We conclude that dysfunction of tumor suppressor gene or genes other than p53 may prove to play an important role in the development of germ cell cancers of the testis.

Genes, p53↗

X-ray-crystallographic studies of complexes of pepstatin A and a statine-containing human renin inhibitor with endothiapepsin.

H-189, a synthetic human renin inhibitor, and pepstatin A, a naturally occurring inhibitor of aspartic proteinases, have been co-crystallized with the fungal aspartic proteinase endothiapepsin (EC 3.4.23.6). H-189 [Pro-His-Pro-Phe-His-Sta-(statyl)-Val-Ile-His-Lys] is an analogue of human angiotensinogen. Pepstatin A [Iva(isovaleryl)-Val-Val-Sta-Ala-Sta] is a blocked pentapeptide which inhibits many aspartic proteinases. The structures of the complexes have been determined by X-ray diffraction and refined to crystallographic R-factors of 0.15 and 0.16 at resolutions of 0.18 nm (1.8 A) and 0.2 nm (2.0 A) respectively. H-189 is in an extended conformation, in which the statine residue is a dipeptide analogue of P1 and P'1 as indicated by the conformation and network of contacts and hydrogen bonds. Pepstatin A has an extended conformation to the P'2 alanine residue, but the leucyl side chain of the terminal statine residue binds back into the S'1 subsite, and an inverse gamma-turn occurs between P'1 and P'3. The hydroxy moiety of the statine at P1 in both complexes displaces the solvent molecule that hydrogen-bonds with the catalytic aspartate residues (32 and 215) in the native enzyme. Solvent molecules originally present in the native structure at the active site are displaced on inhibitor binding (12 when pepstatin A binds; 16 when H-189 binds).

Amino Acid Sequence↗

Impact tolerances of the rigidly fixated maxillofacial skeleton.

A study was designed to determine how soon an athlete who undergoes rigid fixation of a facial fracture can return to full competition. The impact resistance of a rigidly fixated malar complex fracture was studied and compared with that of an intact malar complex. Twelve fresh human cadaver heads were used. A custom-designed impact device was used to deliver a blow of a specific energy to each intact malar complex. The subsequent fractures were rigidly fixated at three points using titanium miniplates and screws. A second impact of identical energy was delivered. The forces generated and the subsequent displacement of hard and soft tissues were recorded after each impact. It was concluded from this study that an impact to a rigidly fixated malar complex fracture produced less force and greater displacement of hard and soft tissues than an impact of identical energy to an intact malar complex. The potential for sustaining more severe maxillofacial injuries after an initial facial fracture should be seriously considered. The results suggest that sufficient time should be allowed for the bony healing of a facial fracture to occur, even after rigid fixation, before an athlete can resume full contact activities.

Age Factors↗

A neuropsychological approach to the Bannatyne recategorization of the Wechsler Intelligence Scales in adults with learning disabilities.

An investigation was conducted of the diagnostic ability of the Bannatyne recategorization of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) into spatial, verbal-conceptual, and sequential components for adults with learning disabilities. A comparison among neuropsychological, intelligence, and achievement test data was made to evaluate the applicability of this recategorization. The Luria-Nebraska Neuropsychological Battery (LNNB), the WAIS-R, and the Wide Range Achievement Test-Revised (WRAT-R) were administered to 103 adult subjects with learning disabilities. The LNNB scales were cluster analyzed, and cluster membership was cross-tabulated against WAIS-R, WRAT-R, and demographic data. The major findings were that (a) the mean scores fit the Bannatyne pattern in two of the four clusters; and (b) the Bannatyne pattern was found in only about 20% of the total sample. It was concluded that identification of the Bannatyne pattern is of diagnostic utility, but its absence is inconclusive.

Adult↗

Extensive cutaneous plasmacytomas.

An unusual case of extensive cutaneous and subcutaneous plasmacytomas is reported. Breast involvement was also a feature in this individual. The relevant literature relating to this unusual presentation of myeloma is reviewed.

Breast Neoplasms↗