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Biomedical subjects

M D Brown

Publications and source records attributed to M D Brown.

At least 127 records · Page 7Linked to original sources
PubMed1996

Effects of an acute decrease in non-esterified fatty acid levels on muscle glucose utilization and forearm indirect calorimetry in lean NIDDM patients.

The aim of the study was to evaluate an acute decrease in NEFA levels during an oral glucose tolerance test and its effects on glucose tolerance, muscle glucose uptake and muscle indirect calorimetry in ten lean non-insulin-dependent diabetic subjects. Two 75-g oral glucose tolerance tests were performed in random order. Placebo or 250 mg acipimox (to inhibit lipolysis) were administered orally 2 h before the start of the oral glucose tolerance test. Two hours after acipimox administration (time 0), non-esterified fatty acid, glycerol and 3-hydroxybutyrate levels decreased by 84, 68 and 77% respectively, compared to basal levels. Concomitantly, muscle lipid oxidation and non-oxidative glycolysis also decreased significantly. After placebo administration, non-esterified fatty acids, glycerol and 3-hydroxybutyrate and lipid oxidation increased by 29, 28, 106 and 33%, respectively (NS vs basal levels; p < 0.001 vs acipimox). There was a negative rate of net glucose storage (interpreted as glycogenolysis) during post-absorptive conditions and at time 0 after administration of both drugs. After oral glucose tolerance test, the incremental areas of blood glucose and insulin were significantly decreased by 18 and 19% after acipimox compared to placebo. In addition, the ratio between the incremental area of forearm muscle glucose uptake and the insulin levels was significantly increased by 45% during acipimox compared to placebo administration. Glucose oxidation and non-oxidative glycolysis were significantly higher while lipid oxidation was significantly lower after acipimox than after placebo. In conclusion, our study found that in lean non-insulin-dependent diabetic subjects, an acute decrease in non-esterified fatty acid levels improves glucose tolerance, muscle glucose uptake, glucose oxidation and non-oxidative glycolysis, but is unable to normalize glucose storage.

3-Hydroxybutyric Acid↗
PubMed1996

Coding sequences of both genome segments of a European 'very virulent' infectious bursal disease virus.

The sequences of segment A (encoding the VP2-VP4-VP3 polyprotein and VP5) and segment B (encoding VP1) of a recent, 'very virulent' (VV) European isolate (UK661) of infectious bursal disease virus (IBDV), a birnavirus, have been determined. There are 26 to 36 amino acid substitutions compared to any other type I IBDV within the segment A polyprotein (of these, 15 are unique) and about 50 substitutions within VP1 (of which 16 are unique). There is more variation compared to classical and antigenic variant viruses, of both virulent and attenuated phenotype, in VP1, VP3 and VP4 than in VP2, even though the latter has previously been identified as the most variable protein between different strains of type I IBDV. In VP3 and VP4, UK661 is the most diverged type I IBDV. Thus the origin of the virus is unclear. It is possible that strong functional constraints have preferentially maintained the primary structure of VP2, though the possibility of recombination cannot be excluded. There are no clear candidate mutations to account for the enhanced virulence of the VV IBDV. Polymerase motifs are well conserved in VP1 but there is an amino acid substitution next to the predicted active-site serine of the viral protease (VP4). In addition, there is a conservative substitution close to the postulated VP2-VP4 cleavage site. It is also now apparent that sequences of IBDV segment B (the segment encoding the RNA polymerase) do not group according to serotype (specified by the capsid proteins encoded on segment A), indicating that segment reassortment has occurred.

Amino Acid Sequence↗
PubMed1996

The significance of positive margins (known and unknown) at the conclusion of Mohs surgery in the orbital region.

The Mohs fresh tissue technique has provided a high rate of cure in cases of malignant tumors in the orbital region. However, in some patients, tumor may persist after Mohs surgery if margins are falsely negative or if the Mohs surgeon elects to terminate the procedure with known positive margins. We report six patients who had residual tumor present in the periorbital region after Mohs surgery. These patients have a serious prognosis associated with subsequent morbidity. Accurate communication between the Mohs surgeon and subsequent treating surgeons, combined with aggressive tumor management, may help to minimize morbidity and improve mortality.

Aged↗
PubMed1996

Appearance of the capillary endothelial glycocalyx in chronically stimulated rat skeletal muscles in relation to angiogenesis.

The endothelial glycocalyx layer of capillaries was stained with Ruthenium Red and examined by transmission electron microscopy in rat extensor hallucis proprius muscles after 2 or 4 days of indirect electrical stimulation via implanted electrodes. The layer appeared continuous on the luminal surface of 63% capillaries in control muscles and absent 13%. This situation was reversed in muscles stimulated for 2 or 4 days, with a continuous layer in 12 and 10% of capillaries and no glycocalyx in 44 and 58%, respectively. The greater disruption of the endothelial luminal glycocalyx in capillaries from stimulated muscles suggests that flow-related shear forces on endothelial cells could be important signals for initiation of angiogenesis in actively contracting skeletal muscle.

Animals↗
PubMed1996

Use of transmitochondrial cybrids to assign a complex I defect to the mitochondrial DNA-encoded NADH dehydrogenase subunit 6 gene mutation at nucleotide pair 14459 that causes Leber hereditary optic neuropathy and dystonia.

A heteroplasmic G-to-A transition at nucleotide pair (np) 14459 within the mitochondrial DNA (mtDNA)-encoded NADH dehydrogenase subunit 6 (ND6) gene has been identified as the cause of Leber hereditary optic neuropathy (LHON) and/or pediatric-onset dystonia in three unrelated families. This ND6 np 14459 mutation changes a moderately conserved alanine to a valine at amino acid position 72 of the ND6 protein. Enzymologic analysis of mitochondrial NADH dehydrogenase (complex I) with submitochondrial particles isolated from Epstein-Barr virus-transformed lymphoblasts revealed a 60% reduction (P < 0.005) of complex I-specific activity in patient cell lines compared with controls, with no differences in enzymatic activity for complexes II plus III, III and IV. This biochemical defect was assigned to the ND6 np 14459 mutation by using transmitochondrial cybrids in which patient Epstein-Barr virus-transformed lymphoblast cell lines were enucleated and the cytoplasts were fused to a mtDNA-deficient (p 0) lymphoblastoid recipient cell line. Cybrids harboring the np 14459 mutation exhibited a 39% reduction (p < 0.02) in complex I-specific activity relative to wild-type cybrid lines but normal activity for the other complexes. Kinetic analysis of the np 14459 mutant complex I revealed that the Vmax of the enzyme was reduced while the Km remained the same as that of wild type. Furthermore, specific activity was inhibited by increasing concentrations of the reduced coenzyme Q analog decylubiquinol. These observations suggest that the np 14459 mutation may alter the coenzyme Q-binding site of complex I.

Cell Line, Transformed↗
PubMed1996

Evaluation of Mesocyclops aspericornis (Cyclopoida:Cyclopidae) and Toxorhynchites speciosus as integrated predators of mosquitoes in tire habitats in Queensland.

This study addressed biological control of peridomestic Aedes notoscriptus, known to be a highly effective colonizer of tire habitats and a possible vector of Ross River virus. A laboratory trial of the compatibility of the predators Mesocyclops aspericornis and Toxorhynchites speciosus in small container habitats showed that 4th-instar Tx. speciosus did not significantly affect M. aspericornis mortality. Introduced M. aspericornis and naturally occurring Tx. speciosus were found to form a compatible predator pair for reduction of larval Ae. notoscriptus and Culex quinquefasciatus populations in tire habitats. Over 22 months of field survey, 97% of tires without predators contained mosquito larvae, at a median density of 43 larvae/liter. By comparison, 51% of tires containing both predator species held mosquito larvae at a median density of 4 larvae/liter. Predation by Tx. speciosus persisted for the duration of the study. The inability of the Lake Kurwongbah strain of M. aspericornis to tolerate temperatures of < or = 10 degrees C, which are prevalent in Brisbane during winter, resulted in a failure to deliver persistent reduction of mosquitoes in tires. The temperature-dependent population characteristics of M. aspericornis emphasize the long-recognized importance of matching a biological control candidate's physiological requirements to the environment in which control is sought.

Aedes↗
PubMed1996

Acute toxicity of selected pesticides to the estuarine shrimp Leander tenuicornis (Decapoda:Palaemonidae).

The shrimp Leander tenuicornis is abundant in southeastern Queensland intertidal marsh pools and was chosen as an indicator species for toxicological studies with pesticides. Acute toxicity to this crustacean of temephos and 3 pesticide compounds under evaluation for registration in Australia (Bacillus thuringiensis var. israelensis, s-methoprene, and pyriproxyfen) was tested in 96-h laboratory trials. Temephos was the most toxic compound, with a median lethal concentration (LC50) of 0.01 ppm (0.33 times the estimated field concentration [EFC] for a 15-cm-deep pool). s-Methoprene was the least toxic compound, with an LC50 of 14.32 ppm (1,790 times the EFC). Bacillus thuringiensis var. israelensis and pyriproxyfen produced LC50 values of 60.9 x 10(6) ITU (176 times the EFC) and 0.098 ppm (12.25 times the EFC), respectively.

Animals↗
PubMed1995

Epidermal growth factor-binding protein activates soluble and receptor-bound single chain urokinase-type plasminogen activator.

Epidermal growth factor-binding protein (EGF-BP) is a serine proteinase that reversibly associates with epidermal growth factor (EGF). We analyzed the reaction of EGF-BP with urokinase type plasminogen activator (u-PA), a serine proteinase that promotes pericellular proteolysis and cellular migration. EGF-BP cleaved single chain u-PA (scu-PA) between Lys158 and Ile159, converting the zymogen into enzymatically active two-chain u-PA (tcu-PA), as shown by SDS-PAGE, N-terminal sequence analysis, and enzymatic assay. The kcat and Km of the activation reaction were (5.6 +/- 0.6) x 10(-2)s-1 and 2.0 +/- 0.3 microM, yielding a catalytic efficiency of 2.8 x 10(4) M-1.s-1. EGF-BP also activated scu-PA bound to receptors on U937 monocytes as demonstrated by the generation of amidase activity against a tcu-PA-specific fluorogenic substrate. By activating scu-PA, EGF-BP may initiate u-PA-dependent cell surface proteolysis and therefore enhance EGF activities that require cellular migration and/or tissue remodeling.

Amino Acid Chloromethyl Ketones↗
PubMed1995

Mitochondrial DNA mutations in human degenerative diseases and aging.

A wide variety of mitochondrial DNA (mtDNA) mutations have recently been identified in degenerative diseases of the brain, heart, skeletal muscle, kidney and endocrine system. Generally, individuals inheriting these mitochondrial diseases are relatively normal in early life, develop symptoms during childhood, mid-life, or old age depending on the severity of the maternally-inherited mtDNA mutation; and then undergo a progressive decline. These novel features of mtDNA disease are proposed to be the product of the high dependence of the target organs on mitochondrial bioenergetics, and the cumulative oxidative phosphorylation (OXPHOS) defect caused by the inherited mtDNA mutation together with the age-related accumulation mtDNA mutations in post-mitotic tissues.

Adult↗
PubMed1995

The Rieger flap for nasal reconstruction.

OBJECTIVE: To repair surgical defects of the middle and distal third of the nose. DESIGN: The anatomic and technical design of the Rieger (dorsonasal) flap is described. CONCLUSION: When performed on properly selected patients, the Rieger flap is an aesthetically predictable, one-stage procedure.

Humans↗
PubMed1995

Leber's hereditary optic neuropathy plus dystonia is caused by a mitochondrial DNA point mutation.

A novel point mutation in the ND6 subunit of complex I at position 14,459 of the mitochondrial DNA (MTND6*LDY T14459A) was identified as a candidate mutation for the highly tissue-specific disease. Leber's hereditary optic neuropathy plus dystonia. Since the MTND6*LDYT14459A mutation was identified in a single family, other pedigrees with the mutation are needed to confirm its association with the disease. Clinical, biochemical, and genetic characterization is reported in two additional pedigrees. Leber's hereditary optic neuropathy developed in two family members in one pedigree. The daughter had clinically silent basal ganglia lesions. In a second pedigree, a single individual presented with childhood-onset generalized dystonia and bilateral basal ganglia lesions. Patient groups that included individuals with Leigh's disease, dystonia plus complex neurodegeneration, and Leber's hereditary optic neuropathy did not harbor the MTND6*LDYT14459A mutation, suggesting that this mutation displays a high degree of tissue specificity, thus producing a narrow phenotypic range. These results confirm the association of the MTND6*LDYT14459A mutation with Leber's hereditary optic neuropathy and/or dystonia. As the first genetic abnormality that has been identified to cause generalized dystonia, this mutation suggests that nuclear DNA or mitochondrial DNA mutations in oxidative phosphorylation genes are important considerations in the pathogenesis of dystonia.

Adolescent↗
PubMed1995

African, Native American, and European mitochondrial DNAs in Cubans from Pinar del Rio Province and implications for the recent epidemic neuropathy in Cuba. Cuba Neuropathy Field Investigation Team.

Genetic predisposition, particularly specific mitochondrial DNA (mtDNA) backgrounds, has been proposed as a contributing factor in the expression of an epidemic of bilateral optic neuropathy that has affected residents of Cuba since 1991. To substantiate or refute the possibility that specific subsets of mtDNAs could participate in disease expression, we took advantage of the heterogeneous ethnic origin of the Cuban population and the recent identification of a number of mtDNA polymorphisms that appear to be specific for Africans, Native Americans, and Europeans. The screening of both carefully selected people with epidemic neuropathy and control subjects from the Pinar del Rio Province for these polymorphisms revealed that African, Native American, and European mtDNA haplotypes were equally represented among case and control subjects, and suggested that approximately 50% of Cuban mtDNAs originated from Europeans, 46% from Africans, and 4% from Native Americans. These findings demonstrate that mutations arising in specific mtDNAs are unlikely to play a role in the epidemic neuropathy and indicate that analysis of mtDNA haplotypes can be a valuable tool for assessing the relative maternal contribution of Africans, Native Americans, and Europeans in a mixed population.

Africa↗
PubMed1995

Phylogenetic analysis of Leber's hereditary optic neuropathy mitochondrial DNA's indicates multiple independent occurrences of the common mutations.

The mitochondrial DNAs (mtDNA) from 17 Caucasian 11778-positive and 30 Caucasian 11778-negative Leber's hereditary optic neuropathy (LHON) patients were PCR-amplified and subjected to high resolution restriction endonuclease analysis. Concurrently, all patient mtDNAs were screened for the common primary LHON mtDNA mutations at nucleotide pairs (nps) 3460, 11778, and 14484, the ambiguous intermediate-risk LHON mtDNA mutations at nps 5244 and 15257, and the secondary LHON mtDNA mutations at nps 3394, 4216, 4917, 7444, 13708, and 15812. Phylogenetic analysis was performed using mtDNA haplotype data from the 47 LHON patients and 175 non-LHON Caucasian controls. The superimposition of the LHON mutation screening results upon the Caucasian mtDNA phylogeny revealed (1) 35 different LHON haplotypes, (2) that all three common primary mutations have occurred multiple times in Caucasians, (3) that while recurrent mutation is common for the primary mutations, secondary mutations tend to be lineage-specific, (4) that the np 15257 mutation was confined to a single mtDNA lineage but may be etiologically important in some LHON cases since it was found in a LHON pedigree which lacked a common primary mutation; complete sequence analysis of the proband mtDNA revealed only a single other candidate missense mutation (at np 10663 of the ND4L gene) of uncertain pathological significance; and (5) that the np 14484 mutation may be less pathogenic than either the np 3460 or np 11778 mutations, as this mutation most commonly occurred on a single mtDNA lineage and almost always in association with secondary LHON mutations. A phylogenetic approach to this genetically heterogeneous disease has thus provided key genetic data bearing on the relative pathogenicity of the LHON-associated mtDNA mutations.

DNA, Mitochondrial↗
PubMed1995

Differential effects of swimming versus weight-bearing activity on bone mineral status of eumenorrheic athletes.

To examine the role of skeletal loading patterns on bone mineral density (BMD), we compared eumenorrheic athletes who chronically trained by opposite forms of skeletal loading, intensive weight-bearing activity (gymnastics, n = 13), and nonweightbearing activity (swimming, n = 26) and 19 nonathletic controls. BMD (g/cm2) of the lumbar spine, femoral neck, trochanter, and whole body was assessed by dual energy X-ray absorptiometry (DXA). Subregion analysis of the whole body scan permitted BMD evaluation of diverse regions. Swimmers were taller (p = 0.0001), heavier (p < 0.005), and had a greater bone-free lean mass (p < 0.001) than gymnasts and nonathletic controls. When adjusted for body surface area, there was no difference in lean mass between swimmers and gymnasts, and both were higher than controls (p < 0.01). Gymnasts had a lower (p < 0.005) fat mass than swimmers and controls. There were no group differences for spine or whole body BMD, but gymnasts had higher spine BMD corrected for body mass than either swimmers or controls. Gymnasts (1.117 +/- 0.110) had higher femoral neck BMD than controls (0.974 +/- 0.105), who were higher than swimmers (0.875 +/- 0.105) (p = 0.0001). This result still applied when BMD was normalized for body weight and bone size. Trochanter BMD of gymnasts (0.898 +/- 0.130) was also higher than controls (0.784 +/- 0.097) and swimmers (0.748 +/- 0.085) (p = 0.0002), and remained higher when corrected for body mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Does exercise training play a role in the treatment of essential hypertension?

Endurance exercise training reduces systolic and diastolic blood pressures in approximately 75% of people who have essential hypertension; these reductions are approximately 10 mmHg for both systolic and diastolic blood pressures. Exercise training at intensities of 40-70% VO2max appears to lower systolic blood pressure somewhat more and diastolic blood pressure to the same degree as higher-intensity training. Additional benefits of endurance exercise training on other risk factors for coronary heart disease make such training an efficacious intervention for people who have mild-to-moderate elevations in blood pressure.

Blood Pressure↗
PubMed1995

Mechanism of mutagenesis induced by cytosine analogs bearing N(4)-substitutions.

The mechanism of mutagenesis induced by dihydropyrimido [4,5-c][1,2]oxazin-7-one deoxyriboside, P-nucleoside, was studied. This analog is highly mutagenic toward Escherichia coli and Salmonella typhimurium. In E. coli, it induces GC-to-AT and AT-to-GC transitions specifically. No transversions are inducible. P-nucleoside was highly mutagenic to a wild-type E. coli, but little mutagenic in a strain lacking thymidine kinase. This indicates that P-nucleoside may be phosphorylated by thymidine kinase after its uptake into bacteria. The mutagenesis induced by P-nucleoside was efficiently inhibited by the addition of thymidine. This inhibition further confirmed the involvement of thymidine kinase in the first step of the metabolism of P-nucleoside in the bacterial cells. These findings indicate that P-nucleoside is a mutagen of a nucleoside-analog type, causing mutations by the erroneous incorporation and replication. The experiments to prove its ambiguous nature in DNA synthesis is now under way.

Adenine↗