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D Dean

Publications and source records attributed to D Dean.

At least 55 records · Page 3Linked to original sources
PubMed2000

Exercise diminishes the activity of acetyl-CoA carboxylase in human muscle.

Studies in rats suggest that increases in fatty acid oxidation in skeletal muscle during exercise are related to the phosphorylation and inhibition of acetyl-CoA carboxylase (ACC), and secondary to this, a decrease in the concentration of malonyl-CoA. Studies in human muscle have not revealed a consistent decrease in the concentration of malonyl-CoA during exercise; however, measurements of ACC activity have not been reported. Thus, whether the same mechanism operates in human muscle in response to physical activity remains uncertain. To investigate this question, ACC was immunoprecipitated from muscle of human volunteers and its activity assayed in the same individual at rest and after one-legged knee-extensor exercise at 60, 85, and 100% of knee extensor VO2max. ACC activity was diminished by 50-75% during exercise with the magnitude of the decrease generally paralleling exercise intensity. Treatment of the immunoprecipitated enzyme with protein phosphatase 2A restored activity to resting values, suggesting the decrease in activity was due to phosphorylation. The measurement of malonyl-CoA in the muscles revealed that its concentration is 1/10 of that in rats, and that it is diminished (12-17%) during the higher-intensity exercises. The respiratory exchange ratio increased with increasing exercise intensity from 0.84 +/- 0.02 at 60% to 0.99 0.04 at 100% VO2max. Calculated rates of whole-body fatty acid oxidation were 121 mg/min at rest and 258 +/- 35, 264 +/- 63, and 174 +/- 76 mg/min at 60, 85, and 100% VO2max, respectively. The results show that ACC activity, and to a lesser extent malonyl-CoA concentration, in human skeletal muscle decrease during exercise. Although these changes may contribute to the increases in fat oxidation from rest to exercise, they do not appear to explain the shift from mixed fuel to predominantly carbohydrate utilization when exercise intensity is increased.

Acetyl-CoA Carboxylase↗
PubMed1999

1-[N, O-bis-(5-isoquinolinesulphonyl)-N-methyl-L-tyrosyl]-4- phenylpiperazine (KN-62), an inhibitor of calcium-dependent camodulin protein kinase II, inhibits both insulin- and hypoxia-stimulated glucose transport in skeletal muscle.

Previous studies have indicated a role for calmodulin in hypoxia-and insulin-stimulated glucose transport. However, since calmodulin interacts with multiple protein targets, it is unknown which of these targets is involved in the regulation of glucose transport. In the present study, we have used the calcium-dependent calmodulin protein kinase II (CAMKII) inhibitor 1-[N, O-bis-(5-isoquinolinesulphonyl) -N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) to investigate the possible role of this enzyme in the regulation of glucose transport in isolated rat soleus and epitrochlearis muscles. KN-62 did not affect basal 2-deoxyglucose transport, but it did inhibit both insulin- and hypoxia-stimulated glucose transport activity by 46 and 40% respectively. 1-[N,O-Bis-(1, 5-isoquinolinesulphonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine (KN-04), a structural analogue of KN-62 that does not inhibit CAMKII, had no effect on hypoxia-or insulin-stimulated glucose transport. Accordingly, KN-62 decreased the stimulated cell-surface GLUT4 labelling by a similar extent as the inhibition of glucose transport (insulin, 49% and hypoxia, 54%). Additional experiments showed that KN-62 also inhibited insulin- and hypoxia-stimulated transport by 37 and 40% respectively in isolated rat epitrochlearis (a fast-twitch muscle), indicating that the effect of KN-62 was not limited to the slow-twitch fibres of the soleus. The inhibitory effect of KN-62 on hypoxia-stimulated glucose transport appears to be specific to CAMKII, since KN-62 did not inhibit hypoxia-stimulated 45Ca efflux from muscles pre-loaded with 45Ca, or hypoxia-stimulated glycogen breakdown. Additionally, KN-62 affected neither insulin-stimulated phosphoinositide 3-kinase nor Akt activity, suggesting that the effects of KN-62 are not due to non-specific effects of this inhibitor on these regions of the insulin-signalling cascade. The results of the present study suggest that CAMKII might have a distinct role in insulin- and hypoxia-stimulated glucose transport, possibly in the vesicular trafficking of GLUT4.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Three-dimensional magnetic resonance-based morphometrics and ventricular dysmorphology in schizophrenia.

BACKGROUND: Recent methodological refinements in magnetic resonance (MR) imaging have led to brain averaging and morphometric approaches that are sensitive to subtle anatomical distinctions in schizophrenia. METHODS: Using a novel morphometric technique for surface analysis, 48 selected landmarks of the rendered ventricular system were extracted and compared between the ventricles of 20 patients with schizophrenia and 20 normal subjects. RESULTS: There was no significant difference in ventricular shape between groups, but significant (p = .015) and highly localized shape deformity was detected at the foramen of Monro and at the proximal temporal horn of the lateral ventricle of male (but not female) patients relative to controls. CONCLUSIONS: Three-dimensional MR-based morphometrics complements established volumetric approaches and can detect minute shape deformities that may be associated with schizophrenia.

Adolescent↗
PubMed1999

Identification of bacterial pathogens in patients with endophthalmitis by 16S ribosomal DNA typing.

PURPOSE: To determine whether sequence analysis of 16S ribosomal DNA (rDNA) can be used to detect bacterial pathogens in patients with postoperative endophthalmitis. METHODS: In 10 eyes of 10 patients, vitreous specimens were collected for culture and rDNA typing. Variable segments of each ribosomal DNA specimen were amplified by polymerase chain reaction (PCR), sequenced, and aligned by BLAST, a computer alignment program, against sequences in GenBank at the National Institutes of Health. RESULTS: Specimens were available from five eyes with bacterial endophthalmitis diagnosed by Gram stain or culture. Amplified 16s rDNA sequences from the eyes of three patients were identical to microbiologic results. Polymerase chain reaction results were negative in two cases in which unusual organisms were detected. All five control specimens from patients with nonbacterial endophthalmitis or uveitis were PCR negative. Approximately 48 to 72 hours are required under ideal conditions for final species identification with this ribosomal typing technique. CONCLUSIONS: 16S rDNA typing shows potential as a relatively rapid technique for identifying bacteria in vitreous samples.

Bacteria↗
PubMed1999

Assessment of polycyclic aromatic hydrocarbon content of smoked fish by means of a fast HPLC/HPLC method.

Polycyclic aromatic hydrocarbon (PAH) concentrations in smoked food can reach levels hazardous for the human health, especially when the smoking procedure is carried out under uncontrolled conditions. In this work a simple and rapid method for the determination of PAHs in smoked fish samples is described. PAHs were extracted from the insoluble samples (together with fat substances) by homogenization with acidified chloroform. The fat extract was then submitted to a first LC sample preparation step (performed on a large silica column) to isolate PAHs from triglycerides. After reconcentration, the PAH fraction was finally injected into the reverse-phase analytical column. The proposed method, which presents good characteristics of recoveries and repeatability, was also used to analyze PAH content of some smoked trout samples packed under vacuum.

Animals↗
PubMed1999

Optimization of folate-conjugated liposomal vectors for folate receptor-mediated gene therapy.

A folate-targeted transfection complex that is internalized by certain cancer cells and displays several properties reminiscent of enveloped viruses has been developed. These liposomal vectors are comprised of a polycation-condensed DNA plasmid associated with a mixture of neutral and anionic lipids supplemented with folate-poly(ethylene glycol)-dioleylphosphatidylethanolamine for tumor cell-specific targeting. N-Citraconyl-dioleylphosphatidylethanolamine is also included for pH-dependent release of endosome-entrapped DNA into the cytoplasm, and a novel plasmid containing a 366-bp segment from SV40 DNA has been employed to facilitate transport of the plasmid into the nucleus. Because formation of the DNA core is an important step in the assembly of liposomal vectors, considerable effort was devoted to comparing the transfection efficiencies of various DNA condensing agents. It was found that complexation of plasmid DNA with high molecular weight polymers such as acylated-polylysine and cationic dendrimers leads to higher folate-mediated transfection efficiency than DNA complexed with unmodified polylysine. In contrast, compaction of plasmid DNA with small cationic molecules such as spermine, spermidine, or gramicidin S yields only weakly active folate-targeted liposomal vectors. Compared to analogous liposomal vector preparations lacking an optimally compacted DNA core, a cell-specific targeting ligand, a caged fusogenic lipid, and a nucleotide sequence that facilitates nuclear uptake, these modified liposomal vectors display greatly improved transfection efficiencies and target cell specificity.

Anions↗
PubMed1999

Osseointegration of preformed polymethylmethacrylate craniofacial prostheses coated with bone marrow-impregnated poly (DL-lactic-co-glycolic acid) foam.

Osseointegration of bone marrow-PLGA-coated, preformed polymethylmethacrylate cranioplasties offers the possibility of reducing: operative time, periimplant seroma and infection, metallic fixation, and periprosthetic resorption following surgical skull remodeling. These alloplastic materials are FDA-approved but previously have not been used together to promote cranioplasty incorporation. The objective of this study was to determine whether the use of PLGA foam coating improves host osseointegration of preformed, textured, polymethylmethacrylate prosthetic cranioplasties. A critical-sized cranial defect was created in two groups of 10 and one group of three rabbits. The defect was filled with either a textured, preformed polymethylmethacrylate disc or a textured, preformed polymethylmethacrylate disc coated with poly (DL-lactic-co-glycolic acid). Both implants were immersed in autologous bone marrow for 20 minutes before implantation. Half of each group of 10 were killed at 3 weeks, and the remainder at 6 weeks. A third group of three rabbits with excised periosteum was evaluated at 6 weeks. Histologic analysis of the discs determined relative amounts of cancellous bone formation adjacent to the prostheses. Woven trabecular bone was present at each host bone to implant perimeter interface at 3 weeks, with fine fibrous capsular formation around the implants. Thicker, lamellar trabeculae were present at 6 weeks with an increased fibrous layer surrounding both types of implants. Bone formed on the superficial and deep implant surfaces in a noncontiguous fashion. Two of five measures showed that total bone formation was significantly greater in the PLGA-coated implants. Polymethylmethacrylate discs coated with bone marrow-impregnated PLGA foam demonstrate increased bone formation at 3 and 6 weeks as compared with non-coated preformed polymethylmethacrylate discs. Only implants with preserved periosteum showed bone formation away from the host-implant interface (centrally) on the superficial surface at 6 weeks.

Animals↗
PubMed1999

Cytosolic citrate and malonyl-CoA regulation in rat muscle in vivo.

In liver, insulin and glucose acutely increase the concentration of malonyl-CoA by dephosphorylating and activating acetyl-CoA carboxylase (ACC). In contrast, in incubated rat skeletal muscle, they appear to act by increasing the cytosolic concentration of citrate, an allosteric activator of ACC, as reflected by increases in the whole cell concentrations of citrate and malate [Saha, A. K., D. Vavvas, T. G. Kurowski, A. Apazidis, L. A. Witters, E. Shafrir, and N. B. Ruderman. Am. J. Physiol. 272 (Endocrinol. Metab. 35): E641-E648, 1997]. We report here that sustained increases in plasma insulin and glucose may also increase the concentration of malonyl-CoA in rat skeletal muscle in vivo by this mechanism. Thus 70 and 125% increases in malonyl-CoA induced in skeletal muscle by infusions of glucose for 1 and 4 days, respectively, and a twofold increase in its concentration during a 90-min euglycemic-hyperinsulinemic clamp were all associated with significant increases in the sum of whole cell concentrations of citrate and/or malate. Similar correlations were observed in muscle of the hyperinsulinemic fa/fa rat, in denervated muscle, and in muscle of rats infused with insulin for 5 h. In muscle of 48-h-starved rats 3 and 24 h after refeeding, increases in malonyl-CoA were not accompanied by consistent increases in the concentrations of malate or citrate. However, they were associated with a decrease in the whole cell concentration of long-chain fatty acyl-CoA (LCFA-CoA), an allosteric inhibitor of ACC. The results suggest that increases in the concentration of malonyl-CoA, caused in rat muscle in vivo by sustained increases in plasma insulin and glucose or denervation, may be due to increases in the cytosolic concentration of citrate. In contrast, during refeeding after starvation, the increase in malonyl-CoA in muscle is probably due to another mechanism.

Acetyl-CoA Carboxylase↗
PubMed1999

Factors that may discourage annual mammography among low-income women with access to free mammograms: a study using multi-ethnic, multiracial focus groups.

Age-eligible women enrolled in the National Breast and Cervical Cancer Early Detection Program can obtain free or low-cost mammograms annually, but many do not routinely complete rescreening. This study investigated the rescreening behavior of low-income women by conducting 8 focus groups in Texas with enrollees who had access to free mammograms. Concerns mentioned in the focus groups included fear of radiation, anxiety that the test might not find a cancer that was there, and worries that cancer might be detected. In all groups, some women mentioned the embarrassment, discomfort, or pain they experienced during a prior mammogram, although no one indicated they would refuse to have another mammogram because of these concerns. Findings highlight the useful insights that can be obtained from focus groups and underscore the need for more research on aspects of the experience of mammography that may affect rescreening.

Adult↗
PubMed1999

Lichen sclerosus: evidence that immunological changes occur at all levels of the skin.

An immunohistochemical approach was used to characterize the inflammatory infiltrate in vulval lichen sclerosus, using monoclonal antibodies to CD3, CD4, CD8, CD68 and HLA-DR. Significant numbers of CD4 + and CD8 + lymphocytes were observed in the dermal band of inflammatory cells in approximately equal proportions. Less numerous CD4 + and CD8 + lymphocytes also occurred adjacent to the dermoepidermal junction and occasionally in the lower epidermis. Increased numbers of cells staining with the monocyte/macrophage marker CD68 were also present in the band of inflammatory cells as well as being scattered diffusely throughout the sclerotic region. Expression of HLA-DR in the lichen sclerosus specimens was increased within the inflammatory infiltrate and around blood vessels in the dermis. All the vulval lichen sclerosus specimens also demonstrated some HLA-DR expression around the keratinocytes, suggesting that these keratinocytes might be involved in antigen presentation. We also studied the expression of CD44 and its isoforms 3G5 (marker of V3), 8G5 (marker of V6), 3D2 (marker of V4/5) and IE8 (marker of V8/9). CD44 has been proposed to play a part in lymphocyte homing, cell-matrix interaction (particularly with hyaluronic acid), lymphocyte activation and malignant progression of certain tumours. The epidermis of the lichen sclerosus specimens appeared to demonstrate a greater intensity of staining with the pan-CD44 marker F10-44, and reduced staining with 3G5, 3D2 and IE8 compared with normal skin. Like normal skin, the dermis of the lichen sclerosus specimens did not demonstrate staining with 3G5, 3D2, 8G5 or 1E8, but did show staining with F10-44. However, the pattern of the dermal staining with F10-44 reflected the position of the inflammatory infiltrate and was sparse in the five sections where there was a prominent sclerotic zone, but increased in the three sections where there was a prominent band of inflammation cells. Our results demonstrate evidence of immunological changes at all levels of skin involved by lichen sclerosus, including the epidermis.

Antigens, CD↗
PubMed1998

Mammalian fauna and biostratigraphy of the pre-Neandertal site of Reilingen, Germany.

In 1978 three well-preserved pieces of a fossil human cranium (i.e., fused parietals, occipital and temporal) were found in a gravel pit near the southwest German town of Reilingen. It was recovered, with an accompanying mammalian fauna, as a side-product of commercial gravel mining. The sample was sorted from the dredgings of a boat-mounted crane reaching to a depth of 28 m below the surface. Here we present the mammalian fauna and discuss its biostratigraphical relevance. The fauna represents a mixture of Holstein interglacial to Würm glacial species. The occurrence of Holsteinian faunal components is indicated by presence of the extinct beaver, Trogontherium. Given the good preservation of specimens found at the lowest levels we can rule out reworking. The accompanying fauna indicates a Holstein to Würm time span bracketing the fossil hominid population.

Animals↗
PubMed1998

On the phylogenetic position of the pre-Neandertal specimen from Reilingen, Germany.

This paper describes the morphology and phylogenetic significance of a well-preserved fossil human cranium found near Reilingen, Germany in 1978. The specimen consists of two complete parietals, most of the right temporal, and 70% of the occipital. The specimen displays several features characteristic of early "archaic" Homo sapiens: maximum breadth at the supramastoid crests, roughly pentagonal occipital view, an angular torus, superoinferiorly elongate/ anteroposterior shortened squamous temporal, strong mastoid, and separation of the tympanic and mastoid temporal portions. Other features align the Reilingen cranium with the "classic" Neandertals: developed suprainiac fossa, bilaterally protuberant occipital torus, strong juxtamastoid eminence, a highly convex occipital plane, and lambdoid flattening. This morphology and our cephalometric analysis support the assignment of this specimen to a Stage 2 "pre-Neandertal" group (e.g., Steinheim, Swanscombe, and Atapuerca [SH site]). Following an "Accretion Model" of European hominid evolution, Stage 2 succeeds Stage 1 European "early-pre-Neandertals" (e.g., Mauer and Petralona), and precedes both the Saale-Eem Stage 3 "early Neandertals" (e.g., Biache 1), which present greater platycephaly, a reduced mastoid process, an enlarged juxtamastoid eminence, and true "en-bombe" (parieto-occipital form), and Weichsel Stage 4 "Neandertals" (sensu stricto, i.e., "classic" Neandertals).

Animals↗
PubMed1998

Spruce budworm elastase precipitates Bacillus thuringiensis delta-endotoxin by specifically recognizing the C-terminal region.

A gut juice protein from Choristoneura fumiferana (spruce budworm) larvae that precipitates certain delta-endotoxins shows a unique specificity for the C-terminal amino acid sequence. Using homolog scanning mutants, we have identified a contiguous region of the Cry1Aa toxin which interacts with the 75-kDa toxin precipitating protein (TPP-75)' resulting in precipitation. The contiguous region from Cry1Aa can be transferred to Cry1Ac and results in an identical precipitation reaction. The precipitation reaction occurs rapidly and is unique in that the ratio of precipitating protein to toxin is low (estimated at 0.01), unlike antibody-antigen reactions which exhibit mole ratios close to 1. TPP-75 has been characterized as an elastase-like serine protease. We have taken advantage of this serine protease character and incorporated a radiolabel using an irreversible inhibitor. The radiolabel has allowed us to show the coincidence of the catalytically-inhibited TPP-75 with the toxin in a blotting assay and to follow the degradation of TPP-75 during storage. TPP-75 represents the first evidence that gut juice proteins may selectively attenuate the activity of delta-endotoxins, prior to binding to putative receptors on susceptible cells. TPP-75 should be evaluated as a possible resistance mechanism for those larvae that do not exhibit a receptor-based resistance.

Animals↗
PubMed1998

Investigation of the role of delayed-type-hypersensitivity responses to myelin in the pathogenesis of Theiler's virus-induced demyelinating disease.

The contribution of autoimmune responses to the pathogenesis of Theiler's virus-induced demyelinating disease was investigated. Delayed-type hypersensitivity responses to myelin were examined in both symptomatic and asymptomatic mice at different times post-infection, in order to determine whether autoreactivity correlates with the development of demyelination. The results indicate that although autoimmune responses probably do not play a major role in the initiation of demyelination at early times post-infection, autoreactivity to myelin antigens dose eventually develop in symptomatic animals, perhaps through the mechanism of epitope spreading. Autoimmunity to myelin components is therefore an additional factor that may contribute to lesion progression in chronically diseased animals.

Animals↗
PubMed1998

Transmission of Chlamydia trachomatis and Neisseria gonorrhoeae among men with urethritis and their female sex partners.

Transmission of Chlamydia trachomatis and Neisseria gonorrhoeae among infected men and their female sex partners was examined using a design enhancing the likelihood that spread was directed from men to women. Chlamydia culture-negative specimens were examined using DNA amplification tests. Infection rates in women exposed to male sex partners with Chlamydia only were 65% (20/31) and with gonorrhea only were 73% (33/45). Infection of women by either agent was not influenced by the number of sexual exposures to or coinfection in men. There was a 98% (40/41) concordance of N. gonorrhoeae isolates among partners by auxotype and serovar. Chlamydia isolates were serotyped using ELISA and immunofluorescence testing and confirmed by nested polymerase chain reaction: 50% (6/12) of men and 57% (8/14) of women yielded mixed serovars. Sixty-four percent of pairs (9/14) were infected with identical serovars and an additional 28% shared at least one serovar. Multiple serovars of C. trachomatis, but not of N. gonorrhoeae, were common in sex partners and exchanged frequently.

Boston↗