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Biomedical subjects

D Ward

Publications and source records attributed to D Ward.

At least 73 records · Page 4Linked to original sources
PubMed1997

Requirement of topoisomerase IV parC and parE genes for cell cycle progression and developmental regulation in Caulobacter crescentus.

We have identified the parC and parE genes encoding DNA topoisomerase IV (Topo IV) in Caulobacter crescentus. We have also characterized the effect of conditional Topo IV mutations on cell division and morphology. Topo IV mutants of C. crescentus are unlike mutants of Escherichia coli and S. typhimurium, which form long filamentous cells that are defective in nucleoid segregation and divide frequently to produce anucleate cells. Topo IV mutants of C. crescentus are highly pinched at multiple sites (cell separation phenotype) and they do not divide to produce cells lacking DNA. These results suggest unique regulatory mechanisms coupling nucleoid partitioning and cell division in this aquatic bacterium. In addition, distinctive nucleoid-partitioning defects are not apparent in C. crescentus Topo IV mutants as they are in E. coli and S. typhimurium. However, abnormal nucleoid segregation in parE mutant cells could be demonstrated in a genetic background containing a conditional mutation in the C. crescentus ftsA gene, an early cell division gene that is epistatic to parE for cell division and growth. We discuss these results in connection with the possible roles of C. crescentus Topo IV in the regulation of cell division, chromosome partitioning, and late events in polar morphogenesis. Although the ParC and ParE subunits of Topo IV are very similar in sequence to the GyrA and GyrB subunits of DNA gyrase, we have used DNA sequence analysis to identify a highly conserved 'GyrA box' sequence that is unique to the GyrA proteins and may serve as a hallmark of the GyrA protein family.

Alleles↗
PubMed1997

Single case evaluation of the effects of aromatherapy and massage on disturbed behaviour in severe dementia.

Aromatherapy and massage could provide a useful addition to psychological therapeutic interventions with clients suffering from dementia. The effects of aromatherapy and massage on disturbed behaviour in four individuals with severe dementia were evaluated using a single-case research design. Each participant received 10 treatment sessions of aromatherapy, aromatherapy and massage combined, and massage alone. The effects on each individual's behaviour in the hour following treatment were assessed against 10 'no treatment' control sessions. Reliable individualized disturbed behaviour scales were designed. The effects of the treatments were mixed. The opinion of the staff providing treatment was that all participants benefited. On close scrutiny, only one of the participants benefited from the aromatherapy and massage to a degree that reached statistical significance. In two of the cases aromatherapy and massage led to an increase in agitated behaviour. The importance of the single case study approach with this client group is discussed.

Aged↗
PubMed1997

Condom availability in New York City public high schools: relationships to condom use and sexual behavior.

OBJECTIVES: This study examines the impact of the condom availability program in New York City public high schools by comparing rates of sexual activity and condom use for New York students and similar students in Chicago. METHODS: A total of 7119 students from 12 randomly selected New York schools and 5738 students from 10 Chicago schools participated in a cross-sectional survey. RESULTS: New York students, compared with Chicago students, reported equal rates of sexual activity but higher rates of condom use at last intercourse (odds ratio [OR] = 1.36). For higher-risk students (those with three or more sexual partners in the past 6 months), condom use was greater in New York (OR = 1.85) than in Chicago. CONCLUSIONS: Condom availability has a modest but significant effect on condom use and does not increase rates of sexual activity. These findings suggest that school-based condom availability can lower the risk of HIV and other sexually transmitted diseases for urban teenagers in the United States.

Adolescent↗
PubMed1997

A pilot clinical/pharmacological study of the protein kinase C-specific inhibitor safingol alone and in combination with doxorubicin.

We performed a pilot clinical trial with safingol (L-threo-dihydrosphingosine), a protein kinase C-specific inhibitor that potentiates the effect of doxorubicin (DOX) in tumor-bearing animals. Safingol was initially administered as a 1-h infusion at escalating doses. Fourteen days later, patients received the same dose of safingol in combination with a fixed dose of DOX. The combination was repeated at 3-week intervals. Safingol dose levels ranged from 15 to 120 mg/m2. The plasma levels achieved at the final dose level were comparable to those associated with potentiation of DOX in animals. The mean Cmax and area under the curve for safingol at the 120 mg/m2 dose level were 1040 +/- 196 ng/ml and 1251 +/- 317 mg x h/ml, respectively. The mean plasma half-life for safingol was 3.97 +/- 2.51 h, the mean estimated clearance was 3140 +/- 765 ml/min, and the mean volume of distribution was of 995 +/- 421 liters. Coadministration of a fixed dose of DOX did not significantly change the pharmacokinetics of safingol, nor did increasing doses of safingol significantly affect the pharmacokinetics of DOX. Minor responses were observed in three patients with pancreatic cancer and one patient with angiosarcoma of the scalp. This pilot Phase I study indicates that the protein kinase C inhibitor safingol can be given safely with 45 mg/m2 of DOX at a dose that is potentially pharmacologically active without dose-limiting toxicity.

Adult↗
PubMed1996

Interleukin-4 blocks the release of collagen fragments from bovine nasal cartilage treated with cytokines.

Interleukin-1 (IL-1) in combination with other cytokines can induce a reproducible release of collagen fragments from bovine nasal cartilage in culture. Over 70% of the total collagen is released by day 14 and this release is accompanied by the appearance of collagenolytic activity in the medium that cleaves collagen specifically at the one quarter/three quarter position. Interleukin-4 is able to prevent the release of collagen fragments from the tissue and this is accompanied by a reduced secretion and activation of collagenase (MMP-1) with an increase in tissue inhibitor of metalloproteinases-1 (TIMP-1). IL-4, especially in the presence of IL-1, increased TIMP secretion by bovine nasal cartilage in culture. These results suggest that IL-4 is able to specifically block cartilage collagen resorption by down-regulating the production of collagenase (MMP-1) and up-regulating TIMP-1 by chondrocytes within the cartilage.

Animals↗
PubMed1996

Physical mapping of the human neurotensin gene (NTS) between markers D12S1444 and D12S81 on chromosome 12q21.

Neurotensin (NTS) is an endogenous tridecapeptide of the central nervous system and the gastrointestinal tract of different mammalian species including human. The human gene encoding neurotensin has previously been assigned to chromosome 12 but no regional localization was available. We now confirm this assignment and place the NTS gene on the physical and cytogenetic maps. The NTS gene is located on a yeast artificial chromosome contig that contains several polymorphic markers and is close to a polymorphic marker located at 95.8 cM on the Généthon linkage map. NTS is immediately proximal to four polymorphic markers, including D12S81 (AFM102xg9) and D12S88 (AFM158yb4). Using fluorescence in situ hybridization, we map the gene cytogenetically to band 12q21.

Animals↗
PubMed1996

Characterization of the cDNA and gene encoding human PDE3B, the cGIP1 isoform of the human cyclic GMP-inhibited cyclic nucleotide phosphodiesterase family.

Two distinct PDE3 [cyclic GMP-inhibited cyclic nucleotide phosphodiesterase (cGI PDE)] isoforms, cGIP1 and cGIP2, have been identified. Here we report cloning of the cDNA and gene encoding human (H)cGIP1 (classified as PDE3B). The cDNA encodes a protein of 1112 amino acids (approximately 123 kDa). Northern blots indicate that its mRNA is expressed in several adipose tissue depots. The human PDE3B gene is composed of 16 exons spanning more than 114 kb and was localized to chromosome 11p15 by in situ hybridization. Exon/intron boundaries were determined, and genetic polymorphism, confirmed by single-strand conformational polymorphism of DNA from 25 healthy subjects, was demonstrated in exon 4 at nucleotide 1389 (A/G). Two polymorphic dinucleotide repeat sequences were identified in introns 5 and 12.

Amino Acid Sequence↗
PubMed1996

Costs of HIV+/AIDS at CD4+ counts disease stages based on treatment protocols.

We report treatment protocols for HIV+/AIDS patients by CD4+ counts (T-lymphocyte cells/mm3: > or = 500, 499-200, 199-50, and < 50) as a tool to provide better definition and to project annual costs (total charges for services) and lifetimes costs for HIV+/AIDS. The treatment protocols, derived from the literature and an HIV+/AIDS Physician Panel, defined the resource use associated with antiretroviral therapy and opportunistic disease prophylaxis and treatment. Resource use costs were derived from the published literature, insurance database, Medicare fee schedules, surveys, and the Physician Panel. At CD4+ counts, the rates of opportunistic diseases were derived from the Physician Panel experience; the mean occupancy times were derived from the literature. The sensitivity analysis indicated stability of the lifetime costs to variation in mean occupancy times, rates of opportunistic diseases, rates of adverse events (AE), and costs. The total annual costs (1995 dollars) of HIV+/AIDS patients ranged from $1,934 (> or = 500), $6,015 (200-499), and $9,031 (50-199), to $25,239 ( < 50). The annual costs of opportunistic diseases are esophageal candidiasis (EC) ($2,194), tuberculosis (TB) ($2,924), cryptococcal meningitis (CM) ($17,264), toxoplasmosis ($17,631), Mycobacterium avium complex (MAC) (+20,153), Non-Hodgkin's lymphoma (NHL) ($22,329), wasting syndrome ($26,676), central nervous system (CNS) lymphoma ($27,333), Pneumocystis carinii pneumonia (PCP) [mild ($3,545), moderate ($4,889), and severe ($32,609)], Kaposi' sarcoma (KS) [mild/moderate ($5,902), and severe ($10,744)], and cytomegalovirus (CMV) retinitis ($100,337). The projected lifetime costs of HIV+/AIDS are $94,726 (annual costs $7,645). Our lower lifetime costs as compared with recent estimates may be due to including resources only for HIV+/AIDS-related treatment and not for non-HIV+/AIDS conditions, as well as reduced resource use resulting from more efficient diagnostic and therapeutic techniques and earlier prophylaxis provided by experienced HIV+/AIDS physicians. Nonetheless, our estimates are consistent with decreasing costs of HIV+/AIDS due to a reduction in the average length of stay and frequency of hospitalizations as well as to replacement of inpatient care by outpatient services.

AIDS-Related Opportunistic Infections↗