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Biomedical subjects

D Moore

Publications and source records attributed to D Moore.

At least 127 records · Page 7Linked to original sources
PubMed1997

Evaluation of a project to enhance knowledge of hereditary diseases and management.

During 1992 and 1993, in a designated suburban area of Perth, Western Australia, information on hereditary disease was provided for health professionals and the general community. This information was in the form of posters, pamphlets, postal flyers and return letter cards, a static display, newspaper articles, advertisements and radio broadcasts, and professional seminars. The aim of this project was to evaluate the effectiveness of combined strategies to convey practical information about hereditary disease to the community and health professionals. Multiple measures of response evaluation were used, which included structured questionnaire surveys of health professionals and members of the community before and after the project. In the community surveys, respondents who were female, married, middle aged, and parents, and had a higher level of education or were born in Australia, New Zealand, or the United Kingdom were generally better informed about hereditary diseases. This intervention resulted in only meagre changes in community knowledge about hereditary disease, even though promotional materials were shown to be appropriate. General Practitioners (GPs) and Child Health Nurses (CHNs) were supportive of clinical genetic services and recognised a need for continuation of education in this field. There is a rapidly increasing need for community and health professional comprehension of the applications of the new genetic technology. This project indicates that routine educational and health promotion strategies will not be enough to achieve desired levels of knowledge and attitude change.

Adult↗
PubMed1997

Coordinated cell elongation alone drives tropic bending in stems of the mushroom fruit body of Coprinus cinereus.

During tropic bending in the stem of the mushroom fruit body of Coprinus cinereus the majority of extension occurred in the upper 20-30% of the stem. By attaching inert markers to the stem, it was shown that the outer flank of the bend initially has a faster rate of extension, although the inner flank matches this growth rate later in the response. Thus bending results from differential enhancement of growth rate rather than sustained differences. Large voids, up to 85 micrometers in diameter, observed in tropically bent stems showed no significant difference in number between inner and outer flanks but are implicated in bending because of their absence from unbent stems. Such voids may prevent the propagation of cracks through the stem tissue during bending. Creases at the external and lumen surfaces were also peculiar to bent stems and could represent constrictions caused by localized accumulation of stresses. Cell morphometric analysis of transverse sections of both flanks of the bend revealed no significant differences in hyphal diameter, distribution, or populations of cell types, but cells of the outer flank were four to five times longer than those of the inner. Thus, tropic bending requires only an increase in length of pre-existing inflated hyphae in the outer flank tissue.

Cell Size↗
PubMed1997

Preventive resin restorations vs. amalgam restorations: a three-year clinical study.

A three-year clinical study was completed at the College of Dentistry comparing the overall performance of Class I amalgam restorations with preventive resin restorations (PRRs). Seventy-four PRRs and fifty-two amalgam restorations were placed in the posterior teeth of thirty-eight patients. The PRR was composed of two materials: P-50 (3M Corp.), a heavily filled composite resin, and White Sealant (3M Corp.), a light-cured sealant. Fast-set Dispersalloy (Johnson and Johnson Corp.) was used for the amalgam restorations. The restorations were evaluated at six months, one year, two years and three years. The USPHS/Ryge system was used to evaluate anatomic form, marginal adaptation, marginal discoloration and recurrent caries of both type restorations. A restoration was considered a failure if any part of the restoration was replaced due to secondary caries. There were two failures of PRRs at six months, and four failures at one year. Failures were due to non retention of the sealant of the PRR and possibly related to operator error. The failures were easily repaired and removed from the study. No PRR failed at the two or three year evaluations. No amalgam restoration failed within the three year period.

Adolescent↗
PubMed1997

[A study of the association between the aortic pulse wave velocity and atherosclerotic risk factors among Japanese Americans in Seattle, U.S.A].

Cardiovascular disease prevention screening was conducted among 1389 Japanese Americans in Seattle, Washington, U.S.A. from 1989 to 1994. The association between atherosclerotic risk factors and the aortic pulse wave velocity (PWV), an indicator of atherosclerosis, was examined by using multiple logistic regression method. Based on a study in 1996 by Suzuki et al. on the association between PWV and atherosclerotic indicators, abnormally high PWV was defined as 8.0 m/sec. and over for those less than 60 years of age and 9.0 m/sec. and over for those 60 years of age and older Significant odds ratios to estimate the risk for the presence of abnormally high PWV were found in age >or= 60 years (4.31, p < 0.001), hypertension (2.00, p < 0.001), diabetes (5.65, p < 0.001), current drinker (0.44, p < 0.001), ex-drinker (0.49, p < 0.05), and ex-smoker (1.82, p < 0.01) among men. Women showed a similar association: age > or = 60 years (3.03, p < 0.001), hypertension (1.94, p < 0.01), diabetes (2.47, p < 0.05), TC/HDL-C >or= 4.5 (1.98, p < 0.001), current drinker (0.47, p < 0.001), and ex-drinker (0.45, p < 0.05). Our findings are almost identical to those from other studies showing the association between coronary heart disease and its risk factors. The question of whether PWV can be a predictor of atherosclerotic diseases, particularly coronary heart disease, remains to be answered by additional studies. However, PWV may serve as a simple and valuable indicator to estimate the extent and severity of asymptomatic atherosclerosis in the large artery.

Alcohol Drinking↗
PubMed1996

A phase II Gynecologic Oncology Group trial of ifosfamide and mesna in advanced or recurrent adenocarcinoma of the endometrium.

In other Gynecologic Oncology Group (GOG) studies, ifosfamide demonstrated antineoplastic activity against ovarian epithelial tumors, squamous carcinomas of the cervix, uterine sarcomas, and trophoblastic disease. Responses were also observed in 15% of patients with endometrial adenocarcinoma previously exposed to chemotherapy. This is a phase II trial of ifosfamide in patients with chemotherapy-naive advanced or recurrent endometrial adenocarcinoma. Thirty-seven patients with advanced adenocarcinoma of the endometrium recurrent after surgery and/or radiotherapy were treated with ifosfamide 1.2 g/m2 intravenously daily for 5 days every 4 weeks and mesna 300 mg/m2 intravenously every 4 hr for 3 doses daily for 5 days with each course. Three patients were ineligible--one due to a second primary, one did not have an endometrial primary, and the other because of wrong cell type. One patient was inevaluable for response; thus, 33 were evaluable for response. All patients had undergone hysterectomy and 24 had received radiotherapy before entering the trial. Eleven had GOG performance status of 0, 18 had a status of 1, and 4 had performance status of 2. Median age was 68 years (range, 41-86 years). Grade 3 or 4 neutropenia occurred in eight patients each and grade 3 thrombocytopenia was observed in one patient. One patient had a grade 4 neurotoxicity. Complete responses were observed in two patients (6.1%) and partial responses in six (18.2%) for an overall response rate of 24.3%. Ifosfamide in this dose and schedule is an active drug in the treatment of patients with advanced or recurrent adenocarcinoma of the endometrium.

Adenocarcinoma↗
PubMed1996

Amplifications of oncogene erbB-2 and chromosome 20q in breast cancer determined by differentially competitive polymerase chain reaction.

A new method of measuring gene copy number in small samples of DNA was used to measure amplification of the erbB-2 gene and of chromosome 20q in breast cancer. This method, termed 'differentially competitive polymerase chain reaction' (DC-PCR) combines the advantages of two other techniques for measuring amplification by PCR, namely differential PCR and competitive PCR. The DC-PCR methodology was evaluated for sensitivity and specificity by comparing amplification of erbB-2 measured by DC-PCR with that obtained by fluorescence in situ hybridization (FISH) for 42 cases or Southern blotting and/or slot blot analysis for 34 cases. There was over 90 percent concordance with both FISH and Southern blotting and/or slot blot analysis. DC-PCR was used to further characterize the newly described amplicon at chromosome 20q. By analyzing DNA from 10 breast cancer cell lines at 7 different loci, we identified a potential common region of amplification of approximately 5 centimorgans at chromosome 20q13 bordered by loci D20S52 and RMC20C100-S1. One hundred and seventeen cases of primary breast cancer were evaluated for amplification at these two loci. Amplification at one or more loci, defined as > 1.5 fold higher copy number than that of normal DNA, was found in 25 cases (21%). Sixteen cases were amplified at only one of the two probes (12 cases for RMC20C001-S1 and 4 cases for D20S52), suggesting that the target gene lies between the two markers or that there are two independent target genes within a small chromosome region.

Blotting, Southern↗
PubMed1996

Graviresponses in fungi.

Although the orientation of mycelial hyphal growth is usually independent of the gravity vector, individual specialised hyphae can show response to gravity. This is exemplified by the sporangiophore of Phycomyces, but the most striking gravitropic reactions occur in mushroom fruit bodies. During the course of development of a mushroom different tropisms predominate at different times; the young fruit body primordium is positively phototropic, but negative gravitropism later predominates. The switch between tropisms has been associated with meiosis. The spore-bearing tissue is positively gravitropic and responds independently of the stem. Bracket polypores do not show tropisms but exhibit gravimorphogenetic responses: disturbance leads to renewal of growth producing an entirely new fruiting structure. Indications from both clinostat and space flown experiments are that the basic form of the mushroom (overall tissue arrangement of stem, cap, gills, hymenium, veil) is established independently of the gravity vector although maturation, and especially commitment to the meiosis-sporulation pathway, requires the normal gravity vector. The gravity perception mechanism is difficult to identify. The latest results suggest that disturbance of cytoskeletal microfilaments is involved in perception (with nuclei possibly being used as statoliths), and Ca2(+)-mediated signal transduction may be involved in directing growth differentials.

Coprinus↗
PubMed1996

Morphometric analysis of cell size patterning involved in gravitropic curvature of the stipe of Coprinus cinereus.

During gravitropic bending of the stipe of Coprinus cinereus the majority of elongation occurred in the apical region of the lower surface of the stipe, although some elongation was seen throughout the stipe. The final rate of elongation was similar at both the upper and lower stipe surfaces but the lower surface achieved this rate first (close to the reaction time 25 min), whilst the upper surface of the stipe only attained its final elongation rate after a period of acceleration of 150 min. Detailed morphometric analysis of cell size patterning in transverse sections revealed no significant differences in cross sectional area, spatial or proportional distribution of different cell types between the upper and lower regions of the gravitropic bend. Measurements of longitudinal cell size revealed significant differences in compartment size between the lower and upper region. Hyphal compartments of lower regions of the bend were on average four to five times longer than those of the upper region.

Cell Size↗
PubMed1996

The role of calcium accumulation and the cytoskeleton in the perception and response of Coprinus cinereus to gravity.

The role of Ca2+ in the gravitropic perception and/or response mechanism of Coprinus cinereus was examined by treating stipes with inhibitors of Ca2+ transport and calmodulin. Inhibitors had no effect on gravity perception but significantly diminished gravitropism. It is concluded that, under the conditions tested, Ca2+ is not involved in gravity perception by Coprinus stipes, but does contribute to transduction of the gravitropic impulse. The results would be consistent with regulation of the gravitropic bending process requiring accumulation of Ca2+ within a membrane-bound compartment. Treatment of stipes with an actin inhibitor caused a significantly delayed response, a result not observed with the Ca2+ inhibitors. This suggests that cytoskeletal elements may be involved directly in perception of gravity by Coprinus stipes while Ca(2+)-mediated signal transduction may be involved in directing growth differentials.

Calcimycin↗
PubMed1996

Effect of clinostat rotation on differentiation of embryonic bone in vitro.

We have investigated the effect of changes in the gravity vector on osteoblast behaviour, using the clinostat set at 8 rpm. Two sources of osteoblasts were used: secondary cultures of fetal rat bone cells, and the rat osteosarcoma line 17/2.8 (ROS). Cell number was determined by incubation with 3-(4,dimethyl-2yl)-2,3 diphenyl) tetrazolium bromide (MTT) and measurement of optical density at 570 nm (OD). Alkaline phosphatase activity was detected by standard cytochemical methods. Dividing cells were localised by labelling dividing nuclei with Bromodeoxyuridine (BrdU), detected by immunofluorescence. Cell culture was initiated at densities between 1-4x10(4) cells ml-1. Growth rates in all cultures during the first 48 hours exposure to clinostat rotation were less than in stationary controls. After 3 days, ROS cell numbers were 35% lower, and calvarial cells 39% lower than their respective controls. Alkaline phosphatase activity in calvarial control cultures was uniformly present in characteristically polygonal cells, but after culture in the clinostat the enzyme was present sporadically, and the cells were cuboid. There was also no BrdU uptake in nuclei, but it was present in cell cytoplasms. We conclude that the clinostat decreases cell numbers and cell division. Both cell shape and the distribution of alkaline phosphatase activity in calvarial cell cultures were also affected. This implies that changes in the gravity vector can affect osteoblasts directly, without interaction with other cell types.

Alkaline Phosphatase↗
PubMed1996

Gravimorphogenesis in agarics.

The shape changes which occur in agaric fruit bodies in response to change in the direction of gravity, usually referred to as gravitropism are morphogenetic changes. Our interest in what we prefer to call gravimorphogenesis is to use it to examine morphogenesis experimentally. We are examining two agarics, Coprinus cinereus and Flammulina velutipes, and applying the best available technologies, including video analysis, all forms of electron microscopy, computer-aided image analysis and experiments in orbit in Spacelab. Responses to gravity of the two organisms differ in ways which can be related to their ecological and structural adaptations. C. cinereus reacts extremely rapidly; its fruit body can regain the vertical within 3 h of being placed horizontal, whereas F. velutipes requires 12 h to bend through 90 degrees. The fungi also differ in the bulk of tissue involved in the response. In Coprinus, a zone extending several cm down from the apex is normally involved in bending. In Flammulina, gravisensing is limited to a region just a few mm immediately below the cap, although curvature is performed in a zone of up to 2 cm below. Flammulina cultures were flown on the Spacelab D-2 mission in 1993, and fruit body disorientation in orbit provides the first definitive proof that 'gravitropism' really is a response to the unidirectional gravity vector. Experiments with different clinostat rotation rates in Flammulina indicate that the perception threshold is about 10(-4) x g. Analysis of different times of exposure to an altered gravity vector prior to clinorotation in Coprinus reveals that the perception time is 7 minutes and that continued response requires continued exposure. Cell size determinations in Coprinus demonstrate that cells of the stem increase in length, not diameter, to produce the growth differential. In Flammulina a unique population of highly electron-transparent microvacuoles changes in distribution; decreasing in upper cells and increasing in the lower cells in a horizontal fruit body within a few minutes of disorientation. These are thought to contribute to vacuolar expansion which accompanies/drives cell elongation. Application of a variety of metabolic inhibitors indicates that the secondary messenger calcium is also involved in regulating the growth differentials of gravimorphogenesis but that gravity perception is unaffected by inhibitors of calcium signalling. In both Flammulina and Coprinus, gravity perception seems to be dependent on the actin cytoskeleton since cytochalasin treatment suppresses gravitropic curvature in Flammulina and, in Coprinus, significantly delays curvature without affecting stem extension. This, together with altered nuclear motility observed in living hyphae during reorientation suggests that gravity perception involves statoliths (possibly nuclei) acting on the actin cytoskeleton and triggering specific vesicle/microvacuole release from the endomembrane system.

Basidiomycota↗
PubMed1996

High response rates with short infusional 2-chlorodeoxyadenosine in de novo and relapsed low-grade lymphoma. Australian and New Zealand Lymphoma Study Group.

Thirty-five patients (eight de novo, 27 relapsed disease) with low-grade non-Hodgkin's lymphoma (diffuse small lymphocytic, follicular small cleaved cell, follicular mixed cell, and lymphoplasmacytoid) were treated with 2-chlorodeoxyadenosine (2CdA) at a daily dose of 0.14 mg/kg for 5d (2 h infusion) for an average of three cycles. Minor treatment delays, generally due to haematological toxicities, occurred in nine of 105 cycles. Major toxicities were lymphopenia, neutropenia and thrombocytopenia. Opportunistic infections occurred in seven patients. Overall response rate was 69% (five complete, 19 partial) reaching 88% for de novo patients (two complete, five partial). Elevated beta 2-microglobulin level was negatively predictive of response (P = 0.0014). Eight of 24 responders relapsed, with a median follow-up of 13 months. 2CdA administered as an intermittent infusion shows considerable single-agent activity in low-grade lymphomas achieving high response rates of prolonged duration. Consideration of schedules where 2CdA is alternatively administered with combination chemotherapy appears warranted.

Adult↗
PubMed1996

N-acetylglucosamine kinase and N-acetylglucosamine 6-phosphate deacetylase in normal human erythrocytes and Plasmodium falciparum.

The major pathways of glucose metabolism in the malaria parasite, Plasmodium falciparum, have now been elucidated, and the structures and properties of parasite-specific enzymes are presently being investigated. Little is known, however, about the enzymes catalysing monosaccharide interconversions in the parasite. In the present investigation we have examined the pathway of N-acetylglucosamine catabolism which, in higher organisms, involves the following reaction sequence: N-acetylglucosamine -->N-acetylglucosamine 6-phosphate-->glucosamine 6-phosphate-->fructose 6-phosphate. Assay of the specific kinase (E.C. 2.7.1.59) catalysing the phosphorylation of the sugar showed that the enzyme is present in Plasmodium extracts as well as in normal human erythrocytes; specific activities of 7.2 and 5.3 nmol/h/mg protein were measured for the parasite and erythrocyte extracts, respectively, N-Acetylglucosamine 6-phosphate deacetylase (E.C. 3.5.1.25), catalysing the second reaction, was also detected in both normal and Plasmodium-infected erythrocytes. At 75% parasitaemia, the deacetylase activity was close to 3 times higher than that of normal control cells. The erythrocyte deacetylase was purified approximately 16,000-fold by chromatography on DE52 cellulose, chromatofocusing, and size exclusion chromatography. Attempts to purify the parasite enzyme by the same procedures were unsuccessful due to loss of activity. A partially purified erythrocyte deacetylase preparation (eluted from DE52 cellulose) had a pH optimum of 7.5, a pI of 6.0, as indicated by chromatofocusing, and a K(m) of 29 microM. In conjunction with previous investigations, the present study indicated that all three enzymes required for N-acetylglucosamine utilization are present in Plasmodium parasites as well as in normal erythrocytes.

Amidohydrolases↗
PubMed1996

Construction of derivatives of the F plasmid pOX-tra715: characterization of traY and traD mutants that can be complemented in trans.

A derivative of the F plasmid, pOX38-tra715, expresses the entire F tra operon from a foreign promoter (PT7) derived from phage T7. A series of plasmids related to pOX38-tra715 were constructed which carry either deletion mutations or point mutations in traY. When the PT7 promoter was induced, these plasmids expressed the F pilus but were transfer deficient unless TraY was supplied In trans from compatible plasmids. Insertion of a kanamycin-resistance cassette in the traY gene of the pOX38 plasmid, which contains the wild-type PY promoter, resulted in loss of F piliation and transfer ability. Introduction of TraY in trans partially restored piliation and transfer suggesting that TraY has a role in positively regulating the PY promoter, pOX38-tra719-traD411, which contains a chloramphenicol-resistance cassette in place of the kanamycin-resistance cassette in pOX38-tra715 and a mutation in traD, was constructed to demonstrate the utility of this series of plasmids in studying the long (30 kb) F tra operon.

Bacterial Proteins↗
PubMed1996

A phase II trail of aminothiadiazole in patients with mixed mesodermal tumors of the uterine corpus: a Gynecologic Oncology Group study.

Aminothiadiazole (NSC 4728) is an analog of the thiadiazoles, a group of drugs that stimulated interest because they do not cause significant myelosuppression and have a unique ability to increase uric acid production unrelated to tissue damage. Previous articles have reported results in ovarian cancer, squamous cell cervical cancer, nonsquamous cell cervical cancer, and endometrial cancer. The Gynecologic Oncology Group chose to study aminothiadiazole in patients with mixed mesodermal tumors of the uterus refractory to prior chemotherapy. Twenty-two patients were entered into this study. Eligibility required that patients had histologically confirmed measurable malignancy. All patients received a starting dose of aminothiadiazole of 125 mg/m2 intravenously (30-45 min infusion) repeated at weekly intervals. All patients also took allopurinol, 300 mg orally per day, to prevent hyperuricemia. Subsequent therapy was not given unless the white blood cell count was > 3,000/microliters and platelets were > 100,000/microliters prior to treatment. One patient (5%) in this study had a partial response, which lasted only 1.2 months. The site of this response was a mesenteric mass. Most patients in this study had no toxicity whatsoever, and no life-threatening toxicity was seen. There were no complete responses. Aminothiadiazole in this dose schedule appears to have no utility in previously treated patients with mixed mesodermal tumors of the uterus.

Adult↗
PubMed1996

Monokine products as predictors of AIDS dementia.

OBJECTIVE: To determine whether or not soluble factors produced by peripheral blood mononuclear cells (PBMC) can predict AIDS dementia. DESIGN AND METHODS: PBMC were isolated from individuals with and without AIDS dementia complex (ADC) to determine if the levels of cytokines tumour necrosis factor (TNF)-alpha and interleukin (IL)-6, or the production of a neurotoxic substance, were significantly different. PBMC were studied after determining that the numbers of monocyte-derived macrophages isolated by adherence were highly variable from patients with ADC compared with individuals without ADC. We prospectively studied 16 AIDS dementia patients, 13 healthy HIV-seropositive individuals, and eight sero-negative controls. Supernatants from PBMC were assayed for TNF-alpha, IL-6 and alone for neurotoxicity on human neural cells in vitro. RESULTS: We observed a trend towards worse cognitive and motor performance in patients suffering from ADC but who had no opportunistic infections ('pure dementia'; n = 8). Levels of PBMC IL-6 were significantly higher in 'pure dementia' patients. There was a trend towards lower levels of PBMC TNF-alpha in the group of patients who had both dementia and opportunistic infections compared with "pure dementia' patients. Supernatant from PBMC of ADC patients was significantly more neurotoxic than that from healthy HIV-seropositive individuals. CONCLUSIONS: Macrophage isolation from PBMC of patients with ADC was altered. Soluble factors produced from PBMC were significantly more neurotoxic than soluble factors from PBMC of healthy HIV-seropositive individuals. PBMC production of TNF-alpha and IL-6 was not a significant predictor of ADC.

AIDS Dementia Complex↗