Search PubMed⌕ Search

Biomedical subjects

G Moore

Publications and source records attributed to G Moore.

At least 19 recordsLinked to original sources
PubMed1999

Suppression of experimental abdominal aortic aneurysms by systemic treatment with a hydroxamate-based matrix metalloproteinase inhibitor (RS 132908).

BACKGROUND: Abdominal aortic aneurysms (AAAs) are associated with chronic inflammation, disruption of medial elastin, and increased local production of elastolytic matrix metalloproteinases (MMPs). The purpose of this study was to investigate how treatment with a hydroxamate-based MMP antagonist (RS 132908) might affect the development of experimental AAAs. METHODS: Male Wistar rats underwent intraluminal perfusion of the abdominal aorta with 50 units of porcine pancreatic elastase followed by treatment for 14 days with RS 132908 (100 mg/kg/day subcutaneously; n = 8) or with vehicle alone (n = 6). The external aortic diameter (AD) was measured in millimeters before elastase perfusion and at death, with AAA defined as an increase in AD (DeltaAD) of at least 100%. Aortic wall elastin and collagen concentrations were measured with assays for desmosine and hydroxyproline, and fixed aortic tissues were examined by light microscopy. RESULTS: AAAs developed in all vehicle-treated rats, with a mean AD (+/- SE) that increased from 1.60 +/- 0.03 mm before perfusion to 5.98 +/- 1.02 mm on day 14 (DeltaAD = 276.4 +/- 67.7%). AAAs developed in only five of eight animals (62.5%) after MMP inhibition, with a mean AD that increased from 1.56 +/- 0.05 mm to 3.59 +/- 0.34 mm (DeltaAD = 128.1 +/- 18.7%; P <.05, vs vehicle). The overall inhibition of aortic dilatation attributable to RS 132908 was 53.6 +/- 6.8%. Aortic wall desmosine fell by 85.4% in the vehicle-treated rats (1210.6 +/- 87.8 pmol/sample to 176.7 +/- 33.4 pmol/sample; P <.05) but only by 65.6% in the animals treated with RS 312908 (416.2 +/- 120.5 pmol/sample). In contrast, hydroxyproline was not significantly affected by either elastase perfusion or drug treatment. Microscopic examination revealed the preservation of pericellular elastin and a greater degree of fibrocollagenous wall thickening after MMP inhibition, with no detectable difference in the extent of inflammation. CONCLUSIONS: Systemic MMP inhibition suppresses aneurysmal dilatation in the elastase-induced rodent model of AAA. Consistent with its direct inhibitory effect on various MMPs, RS 132908 promotes the preservation of aortic elastin and appears to enhance a profibrotic response within the aortic wall. Hydroxamate-based MMP antagonists may therefore be useful in the development of pharmacologic approaches to the suppression of AAAs.

Animals↗
PubMed1999

Homologous chromosome pairing in wheat.

Bread wheat is a hexaploid (AABBDD, 2n=6x=42) containing three related ancestral genomes, each having 7 chromosomes, giving 42 chromosomes in diploid cells. During meiosis true homologues are correctly associated in wild-type wheat, but a degree of association of related chromosomes (homoeologues) occurs in a mutant (ph1b). We show that the centromeres are associated in non-homologous pairs in all floral tissues studied, both in wild-type wheat and the ph1b mutant. The non-homologous centromere associations then become homologous premeiotically in wild-type wheat in both meiocytes and the tapetal cells, but not in the mutant. In wild-type wheat, the homologues are colocalised along their length at this stage, but the telomeres remain distinct. A single telomere cluster (bouquet) is formed in the meiocytes only by the onset of leptotene. The sub-telomeric regions of the homologues associate as the telomere cluster forms. The homologous associations at the telomeres and centromeres are maintained through meiotic prophase, although, during leptotene, the two homologues and also the sister chromatids within each homologue are separate along the rest of their length. As meiosis progresses, first the sister chromatids and then the homologues associate intimately. In wild-type wheat, first the centromere grouping, then the bouquet disperse by the end of zygotene.

Meiosis↗
PubMed1998

Myocardial nuclear factor-kappaB activity and nitric oxide production in rejecting cardiac allografts.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a rapid response transcription factor for genes whose products are critical for inflammation and immunity. In a rat model of heterotopic cardiac transplantation, we studied NF-kappaB DNA binding activity and nitric oxide (.NO) production in untreated allografts and whether inhibition of NF-kappaB suppresses .NO production and prolongs graft survival. METHODS: In allograft recipients and isograft controls, NF-kappaB was assayed by electrophoretic mobility shift assay, daily from transplant until rejection. Myocardial .NO was directly detected in explanted allografts by electron spin resonance spectroscopy on day 6 after transplant. The potent inhibitor of NF-kappaB, pyrrolidine dithiocarbamate (PDTC; 250 mg/kg s.c.) was administered daily from transplant until day of rejection. The extent of graft lymphocytic infiltrate was assessed by routine hematoxylin and eosin staining. Immunohistochemical staining of NF-kappaB was per formed to identify the cell type responsible for NF-kappaB activity. RESULTS: A time-dependent increase in myocardial NF-kappaB activity was seen in untreated allografts as compared with isografts as determined by PhosphorImage analysis. Peak NF-kappaB activity occurred in allografts on day 4 with a ninefold increase as compared with isografts (24.0+/-3.7% vs. 2.7+/-0.5; P<0.05). On posttransplant day 6, electron spin resonance spectroscopy analysis of allografts demonstrated .NO identified by a triplet nitrogen signal centered at g=2.012 with hyperfine splitting of 17.5 Gauss, which is consistent with nitrosoheme formation and low-field signals at g=2.08 and g=2.03 consistent with nitrosomyoglobin. These signals were not seen in native hearts of allograft recipients. With PDTC administration, a threefold decrease in NF-kappaB activity within the transplanted heart was observed on posttransplant day 5 as compared with untreated allografts (9.7+/-1.6% vs. 23.5+/-2.5%; P<0.01). PDTC prolonged graft survival as compared with untreated allografts (11.7+/-0.3 vs. 6.6+/-0.2 days; P<0.05) and reduced the intensity of the nitrosoheme and nitrosomyoglobin signals. Allograft mononuclear cell infiltrate correlated with peak NF-kappaB activity with peak infiltrate on posttransplant day 4. PDTC treatment had no effect on the extent of infiltrate. Immunohistochemical staining localized NF-kappaB to the infiltrating mononuclear cells on posttransplant day 5. CONCLUSION: These data support a role for NF-kappaB in allograft rejection.

Animals↗
PubMed1998

Attenuation of intestinal and cardiovascular anaphylaxis by the salivary gland tripeptide FEG and its D-isomeric analog feG.

The effects of the submandibular gland peptide-T (SGP-T; Thr-Asp-Ile-Phe-Gly-Gly; TDIFEGG), its carboxy-terminal fragment (the tripeptide FEG; Phe-Glu-Gly), and the D-isomeric analog (feG) on intestinal and cardiovascular anaphylactic reactions were studied. The tripeptides, FEG and feG, when administered intravenously or orally to egg albumin-sensitized Hooded Lister or Sprague-Dawley rats 30 min prior to challenge with the antigen, totally prevented the disruption of intestinal motility and the development of anaphylaxis provoked diarrhea and inhibited anaphylactic hypotension by 66%. Submandibular gland peptides participate in the regulation of systemic inflammatory reactions, and the D-amino acid tripeptide, feG, is a potent, orally active anti-anaphylactic agent.

Anaphylaxis↗
PubMed1998

To pair or not to pair: chromosome pairing and evolution.

Chromosome pairing in wild-type wheat closely resembles the process in both yeast and Drosophila. The recent characterisation of a mutant Ph1 wheat and the observation that chromosome pairing in the absence of Ph1 more closely resembles that of mammals and maize has shed light on the evolution of chromosome pairing in the cereals.

Centromere↗
PubMed1998

Meiosis: vive la difference!

The application of molecular and modern cell biological techniques is beginning to show that the classical picture of the meiotic process is an oversimplification. The comparison of different species and analysis of mutants have recently demonstrated that many of the features previously thought to be an integral part of meiosis can be altered in their timing or even entirely dispensed with. In plants, differences in the meiotic pathway have been observed, by using methods for 3-D optical imaging, between the polyploids maize and wheat. The fact that two such closely related species differ may be the result of different mechanisms for dealing with polyploidy or may be species differences, but shows that a detailed understanding of the process in the particular species of interest is necessary.

Animals↗
PubMed1998

Endoscopic intracorporal abdominoplasty: a review of 85 cases.

The specialty of plastic surgery has witnessed an explosion of novel procedures with the advent of endoscopy. Surgeons are making more aggressive attempts to reduce the length of scars and subsequent morbidity associated with traditional "open" procedures. Our purpose is to present a new technique of endoscopic abdominoplasty that has largely replaced traditional "full open" techniques at our institution. Since 1985, 85 patients have undergone a procedure that we call the endoscopic intracorporal abdominoplasty. This technique combines traditional abdominal wall liposuction with endoscopic intracorporal plication of the rectus fascia by using a series of horizontal mattress sutures. The procedure is performed using three 1-cm incisions and a series of midline and lateral skin nicks. These 85 patients were compared with 25 patients who underwent traditional open abdominoplasty with anterior plication of the rectus fascia. Average length of surgery was 127 minutes compared to 149 minutes with the open techniques. Length of hospitalization at our institution was 1 postoperative day compared to an average of 3 days with open techniques. No drains were used with the endoscopic techniques, and all of the open procedures had two drains placed. The perioperative rate of morbidity for the intracorporal abdominoplasty was 15 percent (13 of 85 patients) and with the open abdominoplasty cases it was 24 percent (6 of 25 patients). Our conclusion is that the endoscopic intracorporal abdominoplasty reduces operative scars and effectively plicates the rectus fascia, thereby reducing abdominal wall laxity. It has a rate of morbidity in a skilled laparoscopist's hands no greater than with traditional open abdominoplasty.

Abdominal Muscles↗
PubMed1998

Overview of diseases and drug needs for sheep and goats. Veterinarians' and producers' perspectives.

A survey among small ruminant veterinary practitioners and producers of the United States was conducted to determine the most important health problems of sheep and goats and the need for drugs to treat these diseases. Gastrointestinal nematodes and pneumonia were the most important health concerns. Ceftiofur, long acting tetracyclines, penicillins, tilmicosin and enrofloxacin were the antibiotics most needed. The approval of ivermectin and albendazole for goats, and fenbendazole for sheep were among the most common requests for anthelmintics. Veterinarians also stressed the need for drugs to manipulate the estrous cycle, anti-inflammatory drugs, analgesics and anesthetics. Among the viral diseases, lentivirus infections (ovine progressive pneumonia and caprine arthritis encephalitis) and soremouth were the greatest concerns among veterinarians and producers. Both groups indicated that the availability of a generic antiviral drug would be important. The lack of a rabies vaccine was of great concern particularly among goat producers. Extra-label use of drugs in food animals may result in drug residues in tissues that may be hazardous for consumers. Therefore; in order for producers to provide high quality, safe products while remaining competitive in a global market economy, research to determine safety levels and tissue depletion times of new drugs is an urgent need for the sheep and goat industry.

Animal Husbandry↗
PubMed1997

Characterization of a novel TNF-like ligand and recently described TNF ligand and TNF receptor superfamily genes and their constitutive and inducible expression in hematopoietic and non-hematopoietic cells.

A novel (TL1), a recently described (TL2) TNF-like, and three recently described TNF receptor-like (TR1, TR2, TR3) molecules were identified by searching a cDNA database. TL1 and TL2 are type-II membrane proteins. TR2 and TR3 are type-I membrane proteins whereas TR1 appears to be a secreted protein. TL1, TL2, TR2 and TR3 were expressed in hematopoietic cells, whereas TR1 was not. Northern blots hybridized with the cDNA probes revealed multiple forms of RNA as well as inducible expression of TL1, TL2, TR2 and TR3. TL2 and TR3, in particular, were highly induced in activated CD4+ T cells. Radiation hybrid mapping localized TR1 and TL2 to 8q24 and 3q26, respectively, which are not near any known superfamily members. TL1 was mapped to 9q32, near CD30L (9q33) and TR2 and TR3 mapped to the region of chromosome 1 that contains the TNFR-II, 4-1BB, OX40 and CD30 gene cluster at 1p36. Only TR3 in this cluster possesses a death domain. Southern blot analysis revealed the presence of TL and TR genes in different mammalian species. TL2, TR1, TR2 and TR3 were recently described by others as TRAIL/Apo-2L, OPG, HVEM and DR3/WSL-1/Apo-3/TRAMP/LARD, respectively.

Amino Acid Sequence↗
PubMed1997

Association of homologous chromosomes during floral development.

Reduction in chromosome number and genetic recombination during meiosis require the prior association of homologous chromosomes, and this has been assumed to be a central event in meiosis. Various studies have suggested, however, that while the reduction division of meiosis is a universally conserved process, the pre-meiotic association of homologues differs among organisms. In the fruit fly Drosophila melanogaster, some somatic tissues also show association of homologues [1,2]. In the budding yeast Saccharomyces cerevisiae, there is some evidence for homologue association during the interphase before meiotic division [3,4], and it has been argued that such associations lead directly to meiotic homologue pairing during prophase I [5]. The available evidence for mammals suggests that homologous chromosomes do not associate in germ cells prior to meiotic prophase [6]. To study the occurrence of homologue pairing in wheat, we have used vibratome tissue sections of wheat florets to determine the location of homologous chromosomes, centromeres and telomeres in different cell types of developing anthers. Fluorescence in situ hybridization followed by confocal microscopy demonstrated that homologous chromosomes associate pre-meiotically in meiocytes (germ-line cells). Surprisingly, association of homologues was observed simultaneously in all the surrounding somatic tapetum cells. Homologues failed to associate at equivalent stages in a homologue recognition mutant. These results demonstrate that the factors responsible for the recognition and association of homologues in wheat act before the onset of meiotic prophase. The observation of homologue association in somatic tapetum cells demonstrates that this process and meiotic division are separable.

Cell Nucleus↗
PubMed1997

Orally active trifluoromethyl ketone inhibitors of human leukocyte elastase.

This paper describes the development a series of peptidyl trifluoromethyl ketone inhibitors of human leukocyte elastase which are found to have excellent pharmacological profiles. Methods have been developed that allow for the synthesis of these inhibitors in stereochemically pure form. Two of these compounds, 1k and 1l, have high levels of oral bioavailability in several species. Compound 1l has entered development as ZD8321 and is presently undergoing clinical evaluation. These compounds demonstrate that peptidyl trifluoromethyl ketone inhibitors can achieve high levels of oral activity and bioavailability, and therefore they may prove useful as therapeutic agents in the treatment of diseases in which elastase is implicated.

Administration, Oral↗
PubMed1997

Centromeric sites and cereal chromosome evolution.

Comparative genome analysis enables the sites of centromeres, telomeres and nucleolar organiser regions to be aligned with borders that define the sets of linked genes conserved across the cereal genomes. This provides a basis for studying cereal genome evolution.

Biological Evolution↗
PubMed1997

Propyl gallate-induced DNA fragmentation in isolated rat hepatocytes.

Incubation of isolated rat hepatocytes with propyl gallate (PG) at concentrations of > or = 1 mM induced cell killing, whereas PG at < or = 0.5 mM did not cause cell death during a 3-h incubation. PG at > or = 0.5 mM elicited the ladder formation of soluble low-molecular weight DNA fragments with integer multiples of approximately 180 bp and specific nuclear DNA cleavages detected cytopathologically by labeling of a digoxigenin-nucleotide complex to new 3'-OH ends. Both of these PG-induced changes observed in hepatocytes are characteristic features of apoptosis. In contrast, the pretreatment of N-acetylcysteine (4 mM), a precursor of intracellular glutathione (GSH) and antioxidant, prevented PG (0.5 mM)-induced formation of soluble DNA fragments and loss of cellular GSH, ATP, and formation of blebbing. These results suggest that when the concentration of PG is decreased, the effects of PG on hepatocytes change from acute necrotic to apoptotic mode, and that the onset of DNA fragmentation is associated with GSH depletion.

Acetylcysteine↗
PubMed1997

Centromeric behaviour in wheat with high and low homoeologous chromosomal pairing.

Control of homoeologous chromosomal pairing in hexaploid wheat stems from a balance between a number of suppressor and promoter genes. This study used centromeric behaviour as a tool to investigate the mechanism. Fluorescent in situ hybridization employing centromeric and telomeric sequences as probes was applied to pollen mother cells of wheat and wheat/alien hybrids having different pairing gene combinations. It showed: association of centromeres during pre-meiotic interphase; decondensation of centromeric structure; sister chromatid disjunction of univalent chromosomes in homoeologous pairing situations at anaphase I; and centromeric stretching between univalent sister chromatids in wheat/rye hybrids deficient for pairing genes. The implications of these results are discussed.

Anaphase↗
PubMed1997

Prestorage leukocyte reduction with in-line filtration of whole blood: evaluation of red cells and plasma storage.

OBJECTIVES: Prestorage filtration of blood components appears to be an effective method to reduce leukocyte-induced adverse reactions and other complications. To determine whether it is better to filter whole blood before component separation, we compared the efficiency of in-line filtration of whole blood with that of postseparation filtration. METHODS: Blood was collected from normal, healthy donors into either regular triple-bag containers or into whole-blood integral-filter container systems. We then compared the in vitro storage values of leukocyte-depleted red blood cell concentrates (RBCC) kept at 4 degrees C, and plasma frozen for 1 year with nonfiltered blood components as control. RESULTS: All counts of white blood cells after filtration were < 1 x 10(6) per unit. For almost all storage parameters no significant differences were found between leukocyte-reduced RBCC and control units. The plasma fibrinopeptide A values below 30 ng/ml prior to freezing indicate that filtration does not activate the coagulation factors. Furthermore, the filtration did not influence either the biological values or the coagulation factors of plasma units. CONCLUSIONS: Whole blood filtration prior to component preparation seems to offer a useful alternative technique for obtaining leukocyte-reduced RBCC and plasma.

Blood Preservation↗
PubMed1997

Detailed comparative mapping of cereal chromosome regions corresponding to the Ph1 locus in wheat.

Detailed physical mapping of markers from rice chromosome 9, and from syntenous (at the genetic level) regions of other cereal genomes, has resulted in rice yeast artificial chromosome (YAC) contigs spanning parts of rice 9. This physical mapping, together with comparative genetic mapping, has demonstrated that synteny has been largely maintained between the genomes of several cereals at the level of contiged YACs. Markers located in one region of rice chromosome 9 encompassed by the YAC contigs have exhibited restriction fragment length polymorphism (RFLP) using deletion lines for the Ph1 locus. This has allowed demarcation of the region of rice chromosome 9 syntenous with the ph1b and ph1c deletions in wheat chromosome 5B. A group of probes located in wheat homoeologous group 5 and barley chromosome 5H, however, have synteny with rice chromosomes other than 9. This suggests that the usefulness of comparative trait analysis and of the rice genome as a tool to facilitate gene isolation will differ from one region to the next, and implies that the rice genome is more ancestral in structure than those of the Triticeae.

Chromosome Mapping↗