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Biomedical subjects

M Howe

Publications and source records attributed to M Howe.

At least 19 recordsLinked to original sources

Direct evidence for neutrino flavor transformation from neutral-current interactions in the Sudbury Neutrino Observatory.

Observations of neutral-current nu interactions on deuterium in the Sudbury Neutrino Observatory are reported. Using the neutral current (NC), elastic scattering, and charged current reactions and assuming the standard 8B shape, the nu(e) component of the 8B solar flux is phis(e) = 1.76(+0.05)(-0.05)(stat)(+0.09)(-0.09)(syst) x 10(6) cm(-2) s(-1) for a kinetic energy threshold of 5 MeV. The non-nu(e) component is phi(mu)(tau) = 3.41(+0.45)(-0.45)(stat)(+0.48)(-0.45)(syst) x 10(6) cm(-2) s(-1), 5.3sigma greater than zero, providing strong evidence for solar nu(e) flavor transformation. The total flux measured with the NC reaction is phi(NC) = 5.09(+0.44)(-0.43)(stat)(+0.46)(-0.43)(syst) x 10(6) cm(-2) s(-1), consistent with solar models.

Journal Article↗

Measurement of day and night neutrino energy spectra at SNO and constraints on neutrino mixing parameters.

The Sudbury Neutrino Observatory (SNO) has measured day and night solar neutrino energy spectra and rates. For charged current events, assuming an undistorted 8B spectrum, the night minus day rate is 14.0%+/-6.3%(+1.5%)(-1.4%) of the average rate. If the total flux of active neutrinos is additionally constrained to have no asymmetry, the nu(e) asymmetry is found to be 7.0%+/-4.9%(+1.3%)(-1.2%). A global solar neutrino analysis in terms of matter-enhanced oscillations of two active flavors strongly favors the large mixing angle solution.

Journal Article↗

Measurement of the rate of nu(e) + d --> p + p + e(-) interactions produced by (8)B solar neutrinos at the Sudbury Neutrino Observatory.

Solar neutrinos from (8)B decay have been detected at the Sudbury Neutrino Observatory via the charged current (CC) reaction on deuterium and the elastic scattering (ES) of electrons. The flux of nu(e)'s is measured by the CC reaction rate to be straight phi(CC)(nu(e)) = 1.75 +/- 0.07(stat)(+0.12)(-0.11)(syst) +/- 0.05(theor) x 10(6) cm(-2) s(-1). Comparison of straight phi(CC)(nu(e)) to the Super-Kamiokande Collaboration's precision value of the flux inferred from the ES reaction yields a 3.3 sigma difference, assuming the systematic uncertainties are normally distributed, providing evidence of an active non- nu(e) component in the solar flux. The total flux of active 8B neutrinos is determined to be 5.44+/-0.99 x 10(6) cm(-2) s(-1).

Journal Article↗

HIM-10 is required for kinetochore structure and function on Caenorhabditis elegans holocentric chromosomes.

Macromolecular structures called kinetochores attach and move chromosomes within the spindle during chromosome segregation. Using electron microscopy, we identified a structure on the holocentric mitotic and meiotic chromosomes of Caenorhabditis elegans that resembles the mammalian kinetochore. This structure faces the poles on mitotic chromosomes but encircles meiotic chromosomes. Worm kinetochores require the evolutionarily conserved HIM-10 protein for their structure and function. HIM-10 localizes to the kinetochores and mediates attachment of chromosomes to the spindle. Depletion of HIM-10 disrupts kinetochore structure, causes a failure of bipolar spindle attachment, and results in chromosome nondisjunction. HIM-10 is related to the Nuf2 kinetochore proteins conserved from yeast to humans. Thus, the extended kinetochores characteristic of C. elegans holocentric chromosomes provide a guide to the structure, molecular architecture, and function of conventional kinetochores.

Animals↗

A randomized study to evaluate the effect of a perioperative infusion of dopexamine on colonic mucosal ischemia after aortic surgery.

PURPOSE: Colonic ischemia after aortic surgery is associated with increased mortality and morbidity rates. This study was conducted as a single-center side arm to a multicenter, randomized, placebo-controlled study to evaluate the effect of dopexamine hydrochloride on its incidence. METHODS: Thirty patients, mean age 65.1 years (range, 46-84), undergoing elective infrarenal aortic surgery were entered. Preoperative hemodynamic and respiratory parameters were optimized. Patients were then randomly assigned to receive a perioperative infusion of dopexamine at 2 microg/kg per minute (n = 12) or 0.9% saline placebo (n = 18). All patients underwent colonoscopy and biopsy preoperatively and 1 week postoperatively. Specimens were assessed for evidence of mucosal ischemia, presence of mast cell tryptase, myeloperoxidase activity, and both the inducible and endothelial isoforms of nitric oxide synthase. RESULTS: There was no significant difference in perioperative fluid and blood requirements or hemodynamic and respiratory parameters between the two groups. However, there was significantly less evidence of mucosal ischemic changes in dopexamine-treated patients (n = 1) compared with placebo (n = 8) (P =.049). Furthermore, when preoperative biopsies were compared with those performed 1 week postoperatively, nine (50%) patients in the placebo group and two (16.7%) in the dopexamine group scored worse. Although there was no significant difference in inflammatory markers between the two groups, both mast cell tryptase and myeloperoxidase expression were increased in patients with histologic evidence of ischemia (P <.05). Furthermore, inducible nitric oxide synthase staining within the vascular (P =.001) and lamina propria (P <.05) components of the mucosa was also significantly greater. CONCLUSION: A perioperative dopexamine infusion affords significant histologic protection to colonic mucosa after aortic surgery.

Adult↗

Vascular surgical society of great britain and ireland: randomized double-blind study of dopexamine versus placebo in aortic surgery

BACKGROUND: Mechanisms involved in the development of colon- ic ischaemia are not fully understood and there are conflicting reports regarding predisposing factors. The aim of this study was to evaluate the effect of dopexamine hydrochloride on the incidence of colonic ischaemia following aortic surgery and to correlate immunohistochemical markers of inflammatory activation in its pathogenesis. METHODS: Thirty patients, of mean age 65 (range 46-84) years, undergoing elective infrarenal aortic surgery were randomized to receive a perioperative infusion of either dopexamine 2 &mgr;g kg-1 min-1 (n = 12) or 0.9 per cent saline placebo (n = 18). All patients underwent colonoscopy and biopsy following induction of anaesthesia and at 1 week after operation. Sections were stained with haematoxylin and eosin, and for mast cell tryptase (MCT), myeloperoxidase (MPO) and both the inducible (iNOS) and endothelial (eNOS) isoforms of nitric oxide synthase. Sections were analysed blindly and independently by two histopathologists. Patient and operative data were collected and stored separately. RESULTS: Colonic ischaemia was noted in nine patients based on microscopic findings. Endoscopy alone had a sensitivity of 56 per cent. There was a significantly lower incidence of colonic ischaemia in patients receiving dopexamine compared with placebo (P < 0.05). One death resulted from colonic infarction in the placebo group 11 days after operation. There was increased MPO and MCT expression in patients with histological evidence of ischaemia (P < 0.05); iNOS staining within the vascular (P = 0.001) and lamina propria (P < 0.05) components of the mucosa was also significantly greater. No association was found with eNOS. CONCLUSION: Perioperative dopexamine infusion confers a degree of protection to colonic mucosa following aortic surgery, possibly through an anti-inflammatory effect.

Journal Article↗

Identification and partial characterization of an Actinomyces pyogenes hemolysin.

Twenty-two Actinomyces pyogenes isolates were recovered from hepatic abscesses in cattle and evaluated for hemolysin production. Hemolysin was collected from supernatant of cultures grown in 6% CO2 in brain heart infusion (BHI) broth. The effect of oxidizing and reducing agents, enzymes, temperatures and pH on hemolytic activity were studied using sheep erythrocytes as the target cells. Our study showed that A. pyogenes hemolysin is oxygen stable; sensitive to treatment by protease, trypsin, and amylase; and destroyed by treatment at extreme temperatures (56 and 100 degrees C) and pH (pH 3 and 11). Production of hemolysin was studied in BHI, RPMI-1640, and a defined serum-free A. pyogenes medium under aerobic and anaerobic conditions. Maximum hemolysin was produced in BHI incubated aerobically in 6% CO2 and to a lesser degree anaerobically in RPMI-1640. No hemolysin was produced in the defined A. pyogenes medium. Differential filtration, isoelectric focusing and sodium dodecyl sulfate polyacrylamide gel electrophoresis identified two hemolysin proteins with pI values of 3.40 and 9.45 and estimated molecular masses of 62 and 58 kDa, respectively. Cell-free supernatant samples positive for hemolysin activity also were screened for leukotoxin activity. Significant levels of leukotoxin were detected in all samples screened.

Actinomyces↗

Use of selenium concentration in whole blood, serum, toenails, or urine as a surrogate measure of selenium intake.

We examined the validity of using the selenium level in a single biological specimen as a surrogate measure of usual intake. We used data from 77 free-living adults from South Dakota and Wyoming. Subjects provided multiple 1-day duplicate-plate food composites, repeated specimens of blood and toenails, and 24-hour urine collections. We developed a statistical calibration method that incorporated measurement error correction to analyze the data. The Pearson correlation coefficients between selenium intake and a single selenium status measure, after deattenuation to adjust for the effect of within-person variation in intake, were: 0.78 for whole blood, 0.74 for serum, 0.67 for toenails, and 0.86 for urine. We present formulas to estimate the intake of individuals, based on selenium levels in a single specimen of blood, toenails, or urine. In these data, the concentration of selenium in a single specimen of whole blood, serum, or toenails served reasonably well as a measure for ranking subjects according to long-term selenium intake but provided only a rough estimate of intake for each subject.

Adult↗

A genetic analysis of the Suppressor 2 of zeste complex of Drosophila melanogaster.

The zeste1 (z1) mutation of Drosophila melanogaster produces a mutant yellow eye color instead of the wild-type red. Genetic and molecular data suggest that z1 achieves this change by altering expression of the wild-type white gene in a manner that exhibits transvection effects. There exist suppressor and enhancer mutations that modify the z1 eye color, and this paper summarizes our studies of those belonging to the Suppressor 2 of zeste complex [Su(z)2-C]. The Su(z)2-C consists of at least three subregions called Psc (Posterior sex combs), Su(z)2 and Su(z)2D (Distal). The products of these subregions are proposed to act at the level of chromatin. Complementation analyses predict that the products are functionally similar and interacting. The alleles of Psc define two overlapping phenotypic classes, the hopeful and hapless. The distinctions between these two classes and the intragenic complementation seen among some of the Psc alleles are consistent with a multidomain structure for the product of Psc. Psc is a member of the homeotic Polycomb group of genes. A general discussion of the Polycomb and trithorax group of genes, position-effect variegation, transvection, chromosome pairing and chromatin structure is presented.

ATP-Binding Cassette Transporters↗

Cis-effects of heterochromatin on heterochromatic and euchromatic gene activity in Drosophila melanogaster.

Chromosomal rearrangements that juxtapose heterochromatin and euchromatin can result in mosaic inactivation of heterochromatic and euchromatic genes. This phenomenon, position effect variegation (PEV), suggests that heterochromatic and euchromatic genes differ in their regulatory requirements. This report describes a novel method for mapping regions required for heterochromatic genes, and those that induce PEV of a euchromatic gene. P transposase mutagenesis was used to generate derivatives of a translocation that variegated for the light+ (lt+) gene and carried the euchromatic white+ (w+) gene on a transposon near the heterochromatin-euchromatin junction. Cytogenetic and genetic analyses of the derivatives showed that P mutagenesis resulted in deletions of several megabases of heterochromatin. Genetic and molecular studies showed that the derivatives shared a euchromatic breakpoint but differed in their heterochromatic breakpoint and their effects on seven heterochromatic genes and the w+ gene. Heterochromatic genes differed in their response to deletions. The lt+ gene was sensitive to the amount of heterochromatin at the breakpoint but the heterochromatic 40Fa gene was not. The severity of variegated w+ phenotype did not depend on the amount of heterochromatin in cis, but varied with local heterochromatic environment. These data are relevant for considering mechanisms of PEV of both heterochromatic and euchromatic genes.

Animals↗

Selenium in diet, blood, and toenails in relation to human health in a seleniferous area.

To determine whether high dietary selenium intake was associated with adverse effects, selenium in diet, blood, and toenails was studied in relation to human health in adults residing in western South Dakota and eastern Wyoming. Over a 2-y period 142 subjects were recruited from households selected at random and from ranches where unusually high selenium intakes were suspected. Subjects completed health questionnaires, underwent physical examinations, provided blood samples for clinical assessment, and provided blood, urine, toenails, and duplicate-plate food collections for selenium analysis. About half of the 142 free-living subjects had selenium intakes greater than 2.54 mumol/d (200 micrograms/d) (range 0.86-9.20 mumol/d, or 68-724 micrograms/d). Physical findings characteristic of selenium toxicity were not present nor were clinically significant changes in laboratory tests or frequency of symptoms related to selenium in the blood, toenails, or diet. We found no evidence of toxicity from selenium in subjects whose intake was as high as 9.20 mumol/d (724 micrograms/d).

Adult↗

Selenium intake, age, gender, and smoking in relation to indices of selenium status of adults residing in a seleniferous area.

Duplicate meals, serum, whole blood, and toenails were collected every 3 mo for 1 y from a group of 44 free-living adults residing in high-selenium areas of South Dakota and Wyoming to assess the relation of selenium intake to indices of selenium status. The average selenium values for the group were as follows: dietary intake, 174 +/- 91 micrograms/d (mean +/- SD), 2.33 +/- 1.08 micrograms/kg body wt; serum, 2.10 +/- 0.38 mumol/L; whole blood, 3.22 +/- 0.79 mumol/L; and toenails, 15.2 +/- 3.0 nmol/g. Selenium intake (micrograms/kg body wt) was strongly correlated (all values, P less than 0.01) with selenium concentration of serum (r = 0.63), whole blood (r = 0.62), and toenails (r = 0.59). Men and women had similar mean values of serum, whole blood, and toenail selenium despite higher selenium intakes in men. Smokers had lower tissue selenium concentrations than did nonsmokers due, at least in part, to lower selenium intake. Age was not associated with tissue selenium content. Of the variables examined selenium intake was clearly the strongest predictor of tissue selenium concentration.

Adult↗