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Biomedical subjects

D Moore

Publications and source records attributed to D Moore.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1996

Analysis of the traLEKBP sequence and the TraP protein from three F-like plasmids: F, R100-1 and ColB2.

The sequence of a region of the F plasmid containing the traLEKBP genes involved in plasmid transfer was compared to the equivalent regions of two IncFII plasmids, R100-1 and ColB2. The traLEK gene products of all three plasmids were virtually identical, with the most changes occurring in TraE. The TraB genes were also nearly identical except for an 11-codon extension at the 3' end of the R100-1 traB gene. The TraP protein of R100-l differed from those of F and ColB2 at its N terminus, while the ColB2 TraP protein contained a change of sequence in a predicted loop which was shown to be exposed in the periplasmic space by TnphoA mutagenesis. The effect of the altered TraP sequences was determined by complementing a traP mutant with clones expressing the traKBP genes of F, R100-1, and ColB2. The traP mutation in pOX38 (pOX38-traP474), a derivative of F, was found to have little effect on pilus production, pilus retraction, and filamentous phage growth and only a moderate effect on transfer. The transfer ability of pOX38-traP474 was shown to be affected by mutations in the rfa (lipopolysaccharide) locus and in ompA in the recipient cell in a manner similar to that for the wild-type pOX38-Km plasmid itself and could be complemented with the traP analogs from R100-1 and ColB2 to give an F-like phenotype. Thus, the TraP protein appears to play a minor role in conjugation and may interact with TraB, which varies in sequence along with TraP, in order to stabilize the proposed transmembrane complex formed by the tra operon products.

Amino Acid Sequence↗
PubMed1996

Role of the propilin leader peptide in the maturation of F pilin.

F-pilin maturation and translocation result in the cleavage of a 51-amino-acid leader sequence from propilin and require LepB and TraQ but not the SecA-SecY secretion pathway. The unusual propilin leader peptide and the dependence of its cleavage on TraQ suggested that TraQ recognition may be specific for the leader peptide. An in vitro propilin cleavage assay yielded propilin (13 kDa), the pilin polypeptide (7 kDa), and a 5.5-kDa protein as the traA products. The 5.5-kDa protein comigrates with the full-length 51-amino-acid leader peptide, and [14C]proline labeling confirmed its identity since the only proline residues of propilin are found within the leader peptide. The in vitro and in vivo propilin-processing reactions proceed similarly in a single polypeptide cleavage step. Furthermore, TraQ dependence is a property of F-pilin maturation specifically rather than a property of the leader peptide. A propilin derivative with an amino-terminal signal sequence generated by deleting codons 2 to 28 required TraQ for processing in vivo. On the other hand, a chimeric protein with the propilin wild-type leader peptide fused to the mature portion of beta-lactamase was processed in a TraQ-independent manner. Thus, despite its unusual length, the propilin leader peptide seems to perform a function similar to that of the typical amino-terminal signal sequence. This work suggests that TraQ is not necessary for the proteolysis of propilin and therefore is likely to act as a chaperone-like protein that promotes the translocation of propilin.

Bacterial Outer Membrane Proteins↗
PubMed1996

Cyclosporin A does not reverse clinical resistance to paclitaxel in patients with relapsed non-Hodgkin's lymphoma.

PURPOSE: Cyclosporin A has been shown to reverse paclitaxel resistance in vitro by inhibiting P-gp function. Therefore, we determined whether addition of cyclosporine to paclitaxel reversed clinical paclitaxel resistance in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients with relapsed NHL were eligible if they had no intervening treatment after failure to respond to paclitaxel (200 mg/m2 over 3 hours), and if they had adequate marrow, renal, and hepatic function, no serious cardiac disease, no CNS involvement, and no antibodies to human immunodeficiency virus-1. A cyclosporin A bolus dose (5 mg/kg over 3 hours) was followed by intravenous infusion (15 mg/kg) over 24 hours. Six hours after the beginning of cyclosporin A, the immediately preceding paclitaxel dose was administered over 3 hours. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Response was assessed after two cycles, and those patients who achieved at least a partial response received a maximum of six courses. RESULTS: All 26 patients entered were assessable for toxicity and 25 were assessable for response. One patient whose disease had progressed during paclitaxel treatment had a partial remission after the addition of cyclosporin A (response rate, 4%; 95% confidence interval, 1% to 20%). Disease progressed in 17 patients (71%) and did not respond in seven (25%). Serum cyclosporin A A levels measured at the time of initiation of paclitaxel infusion were greater than 2,000 ng/mL during 81% of cycles. Treatment toxicity included peripheral neuropathy in 57%, myalgia or arthralgia in 30%, neutropenia in 53%, neutropenic fever in 8%, and thrombocytopenia in 42% of patients. One patient with preexisting asthma had an acute bronchospasm during the first cycle and was removed from the study. There were no renal or hepatic toxicity and no infectious or hemorrhagic deaths. CONCLUSION: Cyclosporin A administered on this schedule did not reverse established clinical resistance to paclitaxel, which suggests that P-gp-mediated drug efflux is unlikely to be the only cause of paclitaxel resistance in this patient population.

Adult↗
PubMed1996

Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study.

PURPOSE: Taxol (paclitaxel; Bristol-Myers Squibb, Princeton, NJ) is a new antineoplastic drug with broad-spectrum activity in solid tumors, including epithelial ovarian cancer, head and neck cancer, esophageal cancer, breast cancer, bladder cancer, and lung cancer. Its unique mechanism of action, polymerization of tubulin monomers, has stimulated both clinical and preclinical research on this agent. As limited drug supplies became more plentiful, a phase II trial of Taxol was initiated in patients with advanced squamous cervix cancer who had received no prior chemotherapy. PATIENTS AND METHODS: In this trial, 30 assessable patients were initially entered onto the study and four partial responses were seen. Further accrual of 22 assessable patients was then accomplished to define better the response rate with smaller confidence intervals. The starting dose of Taxol was 170 mg/m2 (135 mg/m2 for patients with prior pelvic radiation) given as a 24-hour continuous intravenous infusion with courses repeated every 3 weeks. Dose escalations to 200 mg/m2 and deescalations to 110 mg/m2 were allowed based on adverse effects. RESULTS: The final response rate was 17% (two complete responses and seven partial responses). The primary and dose-limiting toxicity was neutropenia. CONCLUSION: The response rate makes Taxol a drug with sufficient activity to explore it in combination with other agents with similar activity.

Adult↗
PubMed1996

Placebo-controlled trial of gabapentin in patients with amyotrophic lateral sclerosis. WALS Study Group. Western Amyotrophic Lateral Sclerosis Study Group.

We designed a phase II trial to evaluate the efficacy of gabapentin in slowing the rate of decline in muscle strength of patients with amyotrophic lateral sclerosis (ALS) and to assess safety and tolerability. Gabapentin (800 mg) or placebo was administered t.i.d. in a randomized, double-blinded, placebo-controlled, trial for 6 months. We enrolled 152 patients at eight sites in the United States. The primary outcome measure was the slope of the arm megascore, the average maximum voluntary isometric strength from eight arm muscles standardized against a reference ALS population. A secondary outcome measure was forced vital capacity. Slopes of arm megascores for patients on gabapentin were compared with slopes of those taking placebo using a two-way ANOVA. We observed a nonstatistically significant trend (p = 0.057-0.08) toward slower decline of arm strength in patients taking gabapentin compared with those taking placebo (mean difference 24%, median 37%). We observed no treatment effect on forced vital capacity. Gabapentin was well tolerated by patients with ALS. These results suggest that further studies of gabapentin in ALS are warranted.

Acetates↗
PubMed1996

Jealousy induction as a predictor of power and the use of other control methods in heterosexual relationships.

26 male and 87 female college students filled out Stets' Psychological Aggression Scale, Stets' Interpersonal Control Scale, Straus' Physical Violence Scale, and Fisch and Brainerd's Use and Approval of Jealousy-inducing Behaviors Scale. Use and approval of jealousy-inducing behaviors were good predictors of high need for interpersonal control and the use of psychological aggression. The use of jealousy-inducing behaviors but not the approval of these behaviors was a strong predictor of physical aggression in romantic relationships.

Adult↗
PubMed1996

Cholesterol levels among Japanese Americans and other populations: Seattle Nikkei Health Study.

The purpose of this study was to compare average cholesterol levels between Seattle based Japanese Americans and three other populations: U.S. population, native Japanese population and native Japanese urban workers. A total of 1,466 Japanese Americans (724 men and 742 women) participated in cardiovascular disease screening in the Seattle area during 1989 94. Data sources for comparisons are from the Third National Health and Nutrition Examination Survey for 1988-91, the results of the National Cardiovascular Disease Examination Survey in Japan for 1990, and cardiovascular disease screening conducted by the Epidemiological Arteriosclerosis Research Institute in Japan for 1989. Total cholesterol and triglyceride levels of Seattle Japanese American men and women were highest among the four populations. Among men, high density lipoprotein cholesterol (HDL-C) levels for Seattle Japanese Americans and native Japanese were similar and fell between those of urban Japanese workers and the U.S. population. In women, the average HDL C levels were highest in the Japanese urban workers, second highest in Seattle Japanese Americans, and lowest in both the U.S. population and native Japanese population. These differences in lipid levels may be caused by both genetic and environmental factors, which are now under investigation.

Adult↗
PubMed1996

Rapid and simultaneous quantification of rhamnose, mannitol, and lactulose in urine by HPLC for estimating intestinal permeability in pediatric practice.

Determination of intestinal permeability by measuring nonmetabolized sugars has been used to assess the integrity of intestinal mucosa. We have developed and validated a modified HPLC method for determining the concentration of L-rhamnose, mannitol, and lactulose in urine, using an amine-modified silica column and refractive index detection. Probe sugars are simultaneously resolved within 18 min. The calibration curve for each sugar is linear to 20 mmol/L. The minimum detectable concentration of lactulose is 0.05 mmol/L. Recovery of probe sugars is between 99.3% and 105.1%. Overall precision (CV) of estimation of probe sugars ranges from 4.2% to 6.5%. In 14 urine samples from healthy children who ingested the test solution containing 1 g of L-rhamnose, 1 g of mannitol, and 5 g of lactulose, the 5-h urinary excretion ratios of lactulose/rhamnose and lactulose/mannitol were 0.047 +/- 0.018 and 0.021 +/- 0.010 (mean +/- SD), respectively. This method presents a rapid, convenient, and practical technique for determining intestinal permeability in clinical pediatric practice.

Adolescent↗