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Biomedical subjects

D Moore

Publications and source records attributed to D Moore.

At least 181 records · Page 10Linked to original sources
PubMed1995

Three-hour paclitaxel infusion in patients with refractory and relapsed non-Hodgkin's lymphoma.

PURPOSE: Paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) is a novel antimicrotubule agent with anti-tumor activity against ovarian and breast carcinomas. Its activity when administered as a 3-hour intravenous infusion in patients with relapsed non-Hodgkin's lymphoma (NHL) has not been studied. PATIENTS AND METHODS: Patients with relapsed NHL were treated with a 3-hour infusion of 200 mg/m2 of Taxol every 3 weeks in an outpatient setting. All patients received premedication (dexamethasone, diphenhydramine, and cimetidine) to prevent allergic reactions. Responses were assessed after two courses of therapy, and patients who achieved at least partial remission (PR) continued to receive Taxol for a maximum of eight courses. RESULTS: Of 60 eligible patients, 54 (90%) were assessable for treatment toxicity and 53 (88%) were for treatment response (22 with primary refractory and 31 with relapsed disease). Twelve patients (23%) achieved a PR (n = 6) or complete remission (CR; n = 6) (95% confidence interval, 12% to 36%). Responses were observed in intermediate-grade (31%), low-grade (14%), and mantle-cell (17%) lymphomas. In the intermediate-grade lymphomas, there was a trend for a higher response rate in relapsed versus primary refractory disease (54% v 13%; P = .08). Treatment-related toxicity included alopecia (100%), peripheral neuropathy (37%), myalgia or arthralgia (25%), and neutropenic fever (11%). None of the patients had allergic reactions or cardiac toxicity. CONCLUSION: At this dose and schedule, Taxol is an active agent in patients with relapsed NHL and can be safely administered in an outpatient setting. Combination programs with Taxol should be investigated for treatment of NHL.

Adult↗
PubMed1995

Modified transnasal endoscopic Lothrop procedure: further considerations.

The Lothrop procedure resects the medial frontal sinus floor, superior nasal septum, and intersinus septum to create a large frontonasal communication. However, the external approach often allowed medial collapse of soft tissue and stenosis of the nasofrontal communication. We describe a modified transnasal endoscopic Lothrop procedure in which drills are used for cases in which frontal recess exploration fails to relieve obstruction of the frontal sinus. The lateral bony walls are preserved, and medial collapse does not occur. The mucosa of the posterior table and posterior nasofrontal duct is preserved, and a single common frontal opening is created. We have found this approach to be safe and reliable. Fourteen patients have undergone this procedure without complication, achieving resolution or improvement of their symptoms and maintaining wide patency of the frontonasal opening. We recognize that long-term follow-up will be required but remain encouraged with our favorable results to date.

Adult↗
PubMed1995

Human cytomegalovirus induces IL-6 and TNF alpha from macrophages and microglial cells: possible role in neurotoxicity.

Human cytomegalovirus (HCMV) can frequently infect the central nervous system (CNS) in the setting of immunosuppression such as transplantation and infection with the human immunodeficiency virus (HIV). Our laboratory previously reported that HCMV infection of human brain aggregates preferentially infected a microglial/macrophage (M/M) and caused a neuropathology that differed between strains and could occur in the absence of antigen expression. We extended these studies by infecting a human brain cell aggregate model with four low passage clinical isolates of HCMV. Two patterns of cytopathology emerged after infection; a lacy eosinophilic appearance or a glial nodular formation concomitant with a decreased aggregate size. None of the infections were positive for HCMV antigen; however, all were positive for HCMV DNA. We also infected primary macrophages and microglial cells with the same HCMV isolates. Microglial cells were more susceptible to HCMV infection resulting in a lytic infection. Production of potentially neurotoxic cytokines, IL-1, IL-6 and TNF alpha, from HCMV-infected macrophages and microglial cells were evaluated to explain brain aggregate cytopathology. Supernatants from HCMV-infected macrophages and microglial cells produced similar levels of TNF alpha (< 30 pg ml-1) but showed strain and cell source variation in the production of IL-6; microglial cultures produced > 4 fold higher levels. None of the supernatants contained IL-1. Treatment of brain aggregates with either IL-6 or TNF alpha resulted in morphologic alterations and/or a decrease in size consistent with HCMV infection or supernatant treatment.

Brain↗
PubMed1995

Altered membrane microviscosity in essential hypertension: relationship with family history of hypertension and sodium-lithium countertransport activity.

OBJECTIVE: To investigate the alterations in erythrocyte ghost membrane microviscosity in essential hypertensive patients and to determine the relationship between these changes and the sodium-lithium countertransport activity as a sensitive marker of membrane function. SUBJECTS: Forty-three normolipidaemic essential hypertensive patients (23 treated, 20 untreated) and 27 normotensive controls were studied. Patients were attending the hospital hypertension clinic or a local general practitioner's surgery. METHODS: Erythrocyte sodium-lithium countertransport activity was measured. The Michaelis constant (Km) for extracellular sodium and maximal reaction velocity for sodium-lithium countertransport were measured in a subgroup consisting of 22 essential hypertensive patients and 11 normotensive controls. Erythrocyte membrane microviscosity was measured using fluorescence polarization anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-trimethylammoniumphenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). RESULTS: There was no significant difference in the fluorescence polarization anisotropy of DPH or TMA-DPH between normotensive and essential hypertensive patients. However, the fluorescence polarization anisotropy of TMA-DPH was increased significantly (reflecting increased membrane microviscosity) in hypertensive patients with a family history of hypertension compared with in patients without a family history of hypertension. The standard sodium-lithium countertransport activity was elevated in essential hypertensive patients compared with normotensive controls, and the Km for sodium was significantly lower in patients with a family history of hypertension than in patients without a family history of hypertension. Patients with a family history of hypertension were clustered, with significantly lower Km for sodium and higher TMA-DPH anisotropies than either hypertensive patients without a family history of hypertension or normotensive controls. CONCLUSIONS: These findings suggest that a high membrane microviscosity affecting the outer region of the lipid bilayer is associated with altered sodium-lithium countertransport kinetics in a subgroup of essential hypertensive patients consisting of those with a family history of hypertension.

Antiporters↗
PubMed1995

Elevated frequency of glycophorin A mutations in erythrocytes from Chernobyl accident victims.

In 1986, when an explosion accident occurred at the Chernobyl, Ukraine nuclear power plant, a large number of people were exposed to significant amounts of ionizing radiation. During the time between 1986 and 1992, peripheral blood samples were obtained from 102 people who either were on site during the emergency or were brought to Chernobyl shortly thereafter to assist in the cleanup of radioactive contaminants and isolate the damaged reactor from the environment. These blood samples plus samples from 13 unexposed Soviet individuals were analyzed by flow cytometry using the allele-loss somatic mutation assay for glycophorin A. Results of these assays show that the frequency of N/O variant red cells increased in proportion to the estimated radiation exposure of each individual. The radiation dose-response function derived from this population closely resembles that determined previously for atomic bomb survivors whose blood samples were obtained and analyzed 40 years after their exposure. This suggests comparable mutation induction per unit dose for these two populations and long-term persistence of the mutational damage. In addition, measurements on multiple blood samples from each of 10 donors taken over a 7-year period showed no significant changes in N/O variant cell frequencies, confirming the persistence of radiation-induced somatic mutations in long-lived bone marrow stem cells.

Dose-Response Relationship, Radiation↗
PubMed1994

Novel synthesis of cyclic amide-linked analogues of angiotensins II and III.

Cyclic amide-linked angiotension II (ANGII) analogues have been synthesized by novel strategies, in an attempt to test the ring clustering and the charge relay bioactive conformation recently suggested. These analogues were synthesized by connecting side chain amino and carboxyl groups at positions 1 and 8, 2 and 8, 3 and 8, and 3 and 5, N-terminal amino and C-terminal carboxyl groups at positions 1 and 8, 2 and 8, and 4 and 8, and side chain amino to C-terminal carboxyl group at positions 1 and 8. All these analogues were biologically inactive, except for cyclic [Sar1, Asp3, Lys5]ANGII (analogue 10) which had high contractile activity in the rat uterus assay (30% of ANGII) and [Lys1, Tyr(Me)4, Glu8]ANGII (analogue 7) which had weak antagonist activity (PA2 approximately 6). Precyclic linear peptides synthesized using 2-chlorotrityl chloride resin and N alpha-Fmoc-amino acids with suitable side chain protection were obtained in high yield and purity and were readily cyclized with benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate as coupling reagent. Molecular modeling suggests that the ring structure of the potent analogue can be accommodated in the charge relay conformation proposed for ANGII.

Amino Acid Sequence↗
PubMed1994

Epidermal-growth-factor-receptor expression is associated with rapid tumor proliferation in bladder cancer.

Epidermal-growth-factor-receptor (EGF-r) expression has been proposed as a prognostic marker in bladder cancer and is associated with rapid proliferation in cell lines. Ninety-three fresh and 74 formalin-fixed bladder tumors were examined by fluorescence in situ hybridization (FISH) and immunohistochemistry to assess the relationship between EGF-r expression and proliferation as well as the prevalence of epidermal-growth-factor-receptor (EGF-r) gene amplification. EGF-r expression was strongly associated with BUdr labeling index, grade and stage. EGF-r expression emerged as a stronger predictor of tumor proliferation than grade or stage in analysis of variance. Rapid tumor proliferation might be responsible for bad prognosis reported in EGF-r positive bladder tumors. Also chromosome 7 copy number was associated with grade and stage. EGF-r gene amplification was uncommon (5 of 107 tumors). However, FISH analysis allowed characterization of the pattern of amplification, with clustering of signals suggestive of intrachromosomal amplification more common than diffuse distribution consistent with extrachromosomal amplification.

Bromodeoxyuridine↗
PubMed1994

Preliminary crystallographic studies on human complement pro-factor D.

The recombinant zymogen of the human complement protein factor D has been crystallized. Crystals were grown by vapor diffusion using polyethylene glycol 6000 as precipitant. Two crystal forms obtained at pH 5.4 belong to space group P2(1). The crystals grow to dimensions of 0.6 mm x 0.3 mm x 0.3 mm in three days, are stable in the X-ray beam, and diffract to 2.4 A.

Amino Acid Sequence↗
PubMed1994

Structure of human factor D. A complement system protein at 2.0 A resolution.

Factor D, an essential enzyme for the activation of the alternative pathway of the complement system, belongs to the serine protease superfamily. The crystal structure of the enzyme was solved by a combination of multiple isomorphous replacement and molecular replacement methods. The present model was refined to an R-factor of 18.8% using 23,681 observed reflections between 7.5 and 2.0 A resolution, with a root-mean-square deviation from standard bond lengths of 0.016 A. The two non-crystallographically related molecules in the triclinic unit cell have distinctive active site conformations. The protein has the general structural fold of a serine protease, but there are several unique amino acid substitutions resulting in significant alterations in the critical loops responsible for catalysis and substrate specificity in serine proteases. Factor D is the first complement serine protease whose three-dimensional structure has been determined.

Amino Acid Sequence↗
PubMed1994

Nucleotide sequence of the P1 region of serotype Asia1 foot-and-mouth disease virus.

Differences in the amino acid sequence of foot-and-mouth disease virus (FMDV) virion proteins (VP) among the various FMDV serotypes, particularly in the VP1 polypeptide, are the basis for antigenic diversity of this virus group. This phenomenon provides the basis for type diagnosis of FMDV by the polymerase chain reaction (PCR). In order to specifically identify the Asia1 FMDV serotype by PCR, the nucleotide sequence of its P1-coding region was determined. The sequence exhibited over 70% homology with the P1 gene segment of type O1k. The deduced amino acid sequence shares 79% homology with that of the P1 region of serotype O1k.

Amino Acid Sequence↗
PubMed1994

Brain choline in depression: in vivo detection of potential pharmacodynamic effects of antidepressant therapy using hydrogen localized spectroscopy.

1. Seven subjects with depression and matched controls were studied using proton spectroscopy to test the hypothesis that choline will be elevated in depression. 2. The proton spectroscopy was repeated after recovery from depression. 3. The study confirmed a state dependent increase in choline in the brain. 4. This change may be used as an in vivo marker of change in depression.

Aged↗
PubMed1994

Contributions of working memory and evaluation and regulation of understanding to adults' recall of texts.

We examined evaluation and regulation in adults and the relative contributions of working memory, components of working memory (storage and processing efficiency), and evaluation and regulation to text recall. Younger and older adults' sentence reading times, sentence rereadings, and memory for texts containing inconsistent information were assessed in an on-line analysis. Older adults detected inconsistent information during reading but failed to selectively regulate understanding by rereading problematic information. Failure to regulate understanding was related to poorer memory for problematic information, overall text recall, and ability to report text inconsistencies. Age differences in selective rereading were substantially reduced when processing efficiency was controlled, and age-related variance in passage recall was substantially reduced when differences in processing efficiency and selective rereading were controlled. Results indicate that processing efficiency and selective rereading contribute to adult age differences in text recall, and highlight the importance of distinguishing between a global strategy of rereading and selective rereading in response to comprehension problems.

Adult↗
PubMed1994

Gravitational biology of mushrooms: a flow-chart approach to characterising processes and mechanisms.

Flow charts are presented which systematise recently published work on gravitropic responses of the mushroom stipe of Coprinus cinereus. The hypothetical model represented by the charts suggests that the meiotic division is a pivotal point in the gravitational biology of the mushroom fruit body. The unilateral gravity vector seems to be required for formation of the tissues in which meiosis normally occurs, and stipes become gravitropically competent only after onset of meiosis. The gravitropism flow-chart also indicates that two signals emanate from the upper regions of the stipe, one promotes the process of gravitropic bending, and is followed by a second signal which compensates for excess bending and adjusts the stipe apex to the vertical. Formalisation of the various observations into flow-charts, even though comparatively simple at the moment, facilitates comparison with other species and concentrates attention on aspects requiring further experimental analysis.

Calcium↗
PubMed1994

Kinetics of stipe gravitropism in the mushroom fungus Coprinus cinereus under the conditions of microgravity simulation provided by clinostat treatment.

The extent of the gravitropic response, measured as the angle of the stipe apex at maximum curvature, was dependent upon the gravitational exposure time. The reaction time did not depend on exposure time, and interruption of gravitational exposure by a period of clinostating allowed the gravitational stimulus to decay. It is concluded that the gravitropic impulse is an 'all-or-nothing' signal in Coprinus cinereus, that perception and response probably occur in the same tissue regions, and that sustained exposure to the unidirectional gravity vector is necessary for the normal gravitropic response. The presentation time was found to be 7 min. Immediately after reaching curvature, stipes placed on the clinostat after various gravity exposure times 'relaxed' by 5 degrees. This relaxation suggests that gravitropic bending is a two-stage process with an initial, reversible, phase of plastic bending followed by a 'fixation' phase providing the gravitropic stimulus has been maintained.

Coprinus↗
PubMed1994

High concentrations of mannitol in the shiitake mushroom Lentinula edodes.

A quantitative analysis of mannitol, using gas-liquid chromatography (GLC), was carried out in the various tissues of Lentinula edodes (Berk.) Pegler in comparison with Agaricus bisporus (Lge) Imb. and Coprinus cinereus (Schaeff.: Fr.) S. F. Gray. Mycelia of L. edodes had a low level of mannitol (ca 1% on a dry wt basis) compared with the fruit body stipe and pileus (20-30%). The highest level of mannitol was observed in the pileus of A. bisporus (close to 50%). These observations of similar levels of accumulation of mannitol suggest that glucose catabolism in L. edodes and A. bisporus are similar. No mannitol was detectable in the pileus of C. cinereus.

Agaricus↗