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Biomedical subjects

M Somers

Publications and source records attributed to M Somers.

At least 19 recordsLinked to original sources
PubMed2001

Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin.

BACKGROUND: Altered endothelial cell nitric oxide (NO(*)) production in atherosclerosis may be due to a reduction of intracellular tetrahydrobiopterin, which is a critical cofactor for NO synthase (NOS). In addition, previous literature suggests that inactivation of NO(*) by increased vascular production superoxide (O(2)(*-)) also reduces NO(*) bioactivity in several disease states. We sought to determine whether these 2 seemingly disparate mechanisms were related. METHODS AND RESULTS: Endothelium-dependent vasodilation was abnormal in aortas of apoE-deficient (apoE(-/-)) mice, whereas vascular superoxide production (assessed by 5 micromol/L lucigenin) was markedly increased. Treatment with either liposome-entrapped superoxide dismutase or sepiapterin, a precursor to tetrahydrobiopterin, improved endothelium-dependent vasodilation in aortas from apoE(-/-) mice. Hydrogen peroxide had no effect on the decay of tetrahydrobiopterin, as monitored spectrophotometrically. In contrast, superoxide modestly and peroxynitrite strikingly increased the decay of tetrahydrobiopterin over 500 seconds. Luminol chemiluminescence, inhibitable by the peroxynitrite scavengers ebselen and uric acid, was markedly increased in apoE(-/-) aortic rings. In vessels from apoE(-/-) mice, uric acid improved endothelium-dependent relaxation while having no effect in vessels from control mice. Treatment of normal aortas with exogenous peroxynitrite dramatically increased vascular O(2)(*-) production, seemingly from eNOS, because this effect was absent in vessels lacking endothelium, was blocked by NOS inhibition, and did not occur in vessels from mice lacking eNOS. CONCLUSIONS: Reactive oxygen species may alter endothelium-dependent vascular relaxation not only by the interaction of O(2)(*-) with NO(*) but also through interactions between peroxynitrite and tetrahydrobiopterin. Peroxynitrite oxidation of tetrahydrobiopterin may represent a pathogenic cause of "uncoupling" of NO synthase.

Acetylcholine↗
PubMed2001

Amniotic fluid insulin at 14-20 weeks' gestation: association with later maternal glucose intolerance and birth macrosomia.

OBJECTIVE: To examine the hypothesis that early second trimester amniotic fluid (AF) insulin concentration is elevated and later fetal growth is augmented in gravidas demonstrating later oral glucose intolerance. RESEARCH DESIGN AND METHODS: In this prospective observational cohort study, AF was sampled at 14-20 weeks' gestation in 247 subjects, and 1-h 50-g oral glucose challenge tests (GCTs) were performed at > or = 24 weeks. AF insulin was assayed by an automated immuno-chemiluminometric assay (8). Macrosomia was defined as birth weight above the 90th centile. RESULTS: AF insulin concentration (range 1.4-44.5 pmol/l) correlated positively with gestational age and maternal weight. A logistic regression analysis, adjusted for maternal age and midpregnancy weight, showed increased AF insulin multiples of gestational age-specific medians to be associated with subsequently diagnosed gestational diabetes mellitus (GDM) (OR 1.9, CI 1.3-2.4, P = 0.029). Among 60 subjects with GCT values > 7.2 mmol/l, each unit increase in AF insulin multiple of median (MOM) was associated with a threefold increase in fetal macrosomia incidence (3.1, 1.3-4.9, P = 0.048). CONCLUSIONS: An elevated AF insulin concentration at 14-20 weeks' gestation is associated with subsequently documented maternal glucose intolerance. Among gravidas with GCT values > 7.2 mmol/l, elevated early AF insulin concentration is associated with fetal macrosomia. Maternal glucose intolerance may affect fetal insulin production before 20 weeks' gestation.

Amniocentesis↗
PubMed1999

Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity.

Hydrolysis of the neuropeptide N-acetyl-L-aspartyl-L-glutamate (NAAG) by N-acetylated alpha-linked acidic dipeptidase (NAALADase) to release glutamate may be important in a number of neurodegenerative disorders in which excitotoxic mechanisms are implicated. The gene coding for human prostate-specific membrane antigen, a marker of prostatic carcinomas, and its rat homologue glutamate carboxypeptidase II have recently been shown to possess such NAALADase activity. In contrast, a closely related member of this gene family, rat ileal 100-kDa protein, possesses a dipeptidyl peptidase IV activity. Here, we describe the cloning of human ileal 100-kDa protein, which we have called a NAALADase- "like" (NAALADase L) peptidase based on its sequence similarity to other members of this gene family, and its inability to hydrolyze NAAG in transient transfection experiments. Furthermore, we describe the cloning of a third novel member of this gene family, NAALADase II, which codes for a type II integral membrane protein and which we have localized to chromosome 11 by fluorescent in situ hybridization analysis. Transient transfection of NAALADase II cDNA confers both NAALADase and dipeptidyl peptidase IV activity to COS cells. Expression studies using reverse transcription-polymerase chain reaction and Northern blot hybridization show that NAALADase II is highly expressed in ovary and testis as well as within discrete brain areas.

Alternative Splicing↗
PubMed1999

A high-sensitivity assay for amniotic fluid insulin at 14-20 weeks' gestation.

OBJECTIVE: To examine sensitivity, precision, and sample stability of an immunochemiluminomimetric insulin assay in 14-20 week amniotic fluid (AF) and fetal age distribution of second-trimester AF insulin concentrations. METHODS: We assayed fresh specimens from 576 gravidas who had amniocentesis at 14-20 weeks' gestation because of maternal age. In a preliminary study, samples were divided into aliquots and stored at 4C and -20C for 24 hours to assess freezing effect. Some samples stored at 4C were assayed repeatedly during a 14-day period and others, stored at -20C, were assayed after a 70-day period. RESULTS: This assay reliably measured AF insulin to a detection limit of 0.03 microIU/mL. Insulin could be measured in all amniotic fluid samples and demonstrated a log10 Gaussian distribution, ranging from 0.24 to 7.41 microIU/mL. Interassay coefficients of variation ranged from 4.4 to 8.9% at concentrations of 0.4-2.0 microIU/mL. Linearity of dilution from 1.5 to 10 times was 99.2 +/- 8.6%. Spike recovery of 10 microIU/mL was from 92-109%. Recovery after freezing to -20C for 24 hours (101%) and 70 days (97%) and after storage at 4C for 14 days (97%) demonstrated no significant loss. CONCLUSION: A two-site, dual monoclonal, immunochemiluminomimetric insulin assay was sufficiently sensitive and precise within the lower range of measured AF insulin concentrations to investigate clinical associations of 14-20 week AF insulin with maternal and fetal conditions. The insulin stability in this matrix suggests that assays can be reliable on specimens stored up to 70 days.

Adult↗
PubMed1997

Interactions of ultrapure bovine hemoglobin with renal epithelial cells in vivo and in vitro.

Using an ultrapurified hemoglobin (Hb) solution, we investigated the physiological effects and cellular processing of Hb in rat kidneys and in cultured opossum kidney (OK) cells. Rats infused with < 5.0 g/kg Hb showed no change in baseline serum creatinine (SCr) values (0.58 +/- 0.05 mg/dl) over 48 h, whereas transient acute renal failure followed infusion of 7.5 g/kg Hb (SCr 3.4 +/- 1.02 mg/dl, P = 0.02). Histology of Hb-infused kidneys demonstrated tubular epithelial cell injury. Renal injury was not caused by volume or oncotic load, cardiovascular effect, or ATP depletion. After Hb infusion, heme oxygenase, the rate-limiting enzyme in Hb catabolism, was induced in an organ-specific fashion. Inhibiting heme oxygenase activity with cimetidine did not alter Hb renal injury. Using OK cells, we determined that renal epithelia process Hb by fluid-phase endocytosis. Proton permeability of fluorescein Hb endosomes was unaltered compared with fluorescein dextran controls, demonstrating that Hb does not alter endosomal membrane integrity. These data suggest that Hb renal injury in rats occurs following large doses of ultrapure Hb, does not alter early steps in Hb endosomal processing by renal epithelia, and involves a mechanism that is not heme oxygenase dependent.

Acute Kidney Injury↗
PubMed1996

Phosphorylation of aquaporin-2 does not alter the membrane water permeability of rat papillary water channel-containing vesicles.

Antidiuretic hormone modulates the water permeability (Pf) of epithelial cells in the rat kidney by vesicle-mediated insertion and removal of the aquaporin-2 (AQP-2) water channel. AQP-2 possesses a single consensus cAMP-dependent protein kinase A (PKA) phosphorylation site (Ser-256) hypothesized to regulate channel Pf(Kuwahara, M., Fushimi, K., Terada, Y., Bai, L., Sasaki, S., and Marumo, F. (1995) J. Biol. Chem. 270, 10384-10387). To test whether PKA phosphorylation of AQP-2 alters channel Pf, we compared the Pf values of purified AQP-2 endosomes after incubation with either PKA or alkaline phosphatase. Studies using [gamma-32P]ATP reveal that AQP-2 endosomes contain endogenous PKA and phosphatase activities that add and remove 32P label from AQP-2. However, the Pf (0.16 +/- 0.06 cm/s) of endosomes containing phosphorylated AQP-2 (0.7 +/- 0. 3 mol of PO4/mol of protein) is not significantly different from the same AQP-2 endosomes where 95 +/- 8% of the phosphate has been removed (Pf 0.14 +/- 0.06 cm/s). These data do not support a role for PKA phosphorylation in alteration of AQP-2's Pf. Instead, AQP-2 phosphorylation by PKA may modulate AQP-2's distribution between plasma membrane and intracellular vesicle compartments.

Adenosine Triphosphate↗
PubMed1996

Drinking and gambling: a comparison with implications for theories of addiction.

There is current concern about the level of excessive gambling in a number of countries, but problem gambling still occupies an uncertain place in the addictions field. The present paper presents results from a pilot study comparing 16 problem gamblers and 16 problem drinkers. Results from a new Attachment Questionnaire suggested that gamblers were just as strongly attached to gambling as drinkers to drinking, although they were significantly less likely to experience withdrawal symptoms. Interviews with the problem gamblers suggested that excessive attachment to gambling was maintained by cyclical processes involving strong, negative feelings associated with gambling losses, shortage of money and the need to keep the extent of gambling secret. It is proposed that these 'secondary' processes, along with primary incentive motivation and the tertiary effects of losses associated with excessive behaviour, are sufficient to explain addiction. It is further suggested that neuroadaptation, tolerance and withdrawal, often thought to be central to the process of addiction, may in fact be of comparatively little importance.

Journal Article↗
PubMed1995

Non-nephrotic children with membranoproliferative glomerulonephritis: are steroids indicated?

Alternate-day steroids are currently recommended to treat children with membranoproliferative glomerulonephritis (MPGN). This recommendation is based largely on uncontrolled studies demonstrating improved renal survival with steroid therapy. We reviewed the outcome of 39 children who presented with MPGN between 1968 and 1990; 27 children were treated with steroids and 12 children received no drug therapy. Life-table analysis comparing renal survival of treated versus untreated children demonstrated no difference by log rank analysis. Treated and untreated groups were compared on the basis of nine features at presentation: age, sex, type of MPGN, presence and type of hematuria, hypocomplementemia renal insufficiency, hypertension, and nephrosis. Treated children were likely to be female (P < 0.01) and nephrotic (P < 0.02). Actuarial survival analyses were performed comparing the nine features with renal survival through 10 years of follow-up. Normotensive (P < 0.025) and non-nephrotic (P < 0.05) children had improved renal survival. The 11 non-nephrotic children demonstrated 100% long-term renal survival, including 7 who received no steroid therapy. At last follow-up, all non-nephrotic children had normal renal function, serum albumin levels > 3 g/dl, and were normotensive. These data suggest that non-nephrotic children with MPGN may forego steroid treatment without compromising long-term renal function. The current common practice of treating all children with MPGN with steroids should be re-examined.

Actuarial Analysis↗
PubMed1994

Permeability properties of rat renal lysosomes.

Although lysosomes maintain large pH gradients and may be subjected to significant osmotic gradients in vivo, little is known about their passive permeability properties. In recent studies, vacuolar H(+)-adenosine-triphosphatases (ATPases), such as those found in lysosomes, have been suggested to act as water channels. In addition, the erythrocyte and proximal tubule water channel CHIP28 is present on the plasma membrane of proximal tubule cells and may undergo endocytosis so that it is incorporated in lysosomes. We therefore examined water, proton, and small nonelectrolyte permeabilities in freshly purified lysosomes from rat renal proximal tubule. Lysosomes were purified by differential and Percoll gradient centrifugation. The preparation contained only lysosomes when examined by electron microscopy. Moreover, analysis by flow cytometry showed virtually all particles to be positive for acid phosphatase and cathepsin B activities. Permeabilities were measured on a stopped-flow fluorimeter by monitoring the self-quenching or pH-sensitive quenching of entrapped fluorescein derivatives. Osmotic water permeability (Pf) averaged 0.011 +/- 0.003 cm/s (n = 6), a value similar to that of biological membranes containing water channels. However, Pf was insensitive to the organic mercurial reagent p-chloromercuribenzene-sulfonate and to HgCl2 and exhibited an activation energy of 10.8 +/- 0.8 kcal/mol. These results indicate that water flux in lysosomes occurred via the lipid bilayer, and not via water channels. Addition of ATP led to lysosomal acidification (proton flux = 4.6 +/- 0.8 x 10(-11) mmol H+.s-1.cm-2), which was completely inhibited by 0.1 microM bafilomycin. Pf was insensitive to this agent as was the passive proton permeability (0.36 +/- 0.18 cm/s, n = 4). Permeabilities to small nonelectrolytes varied in proportion to the oil-water partition coefficient, confirming the applicability of Overton's rule to lysosomes. We conclude that proximal tubular lysosomes exhibit high Pf, which occurs via the lipid bilayer and not via vacuolar H(+)-ATPase.

Acids↗
PubMed1994

Enhancing customer service in the admitting process.

As a result of participating with 28 other healthcare organizations in a study on benchmarking the hospital admitting process, St. Marys Hospital Medical Center, Madison, Wisconsin, was able to speed-up its admitting process and improve its telephone system to serve patients better. St. Marys switched from an admitting system to a preadmitting system, coordinated its admitting system information, and improved its ability to identify triage patients.

Admitting Department, Hospital↗
PubMed1993

Heterogeneous effects of nitroglycerin on the conductance and resistance coronary arterial vasculature.

This study assessed the effects of nitroglycerin (NTG) on epicardial conductance and blood flow regulatory vessels over a wide dose range (10(-10) to 10(-6) mol NTG) in chronically instrumented awake mongrel dogs. NTG bolus injection caused dose-dependent dilation of both conductance and blood flow regulatory vessels. The dose-response curves for blood flow were shifted markedly to the right of the response of conductance vessels so that the proximal vessels had reached 50% of their maximum vasodilation before significant increases in blood flow. The calculated doses for half-maximal vasodilation were 2.8 x 10(-8) and 7.8 x 10(-7) mol for conductance and blood flow, respectively, indicating an approximately 39 times greater sensitivity of the proximal vessels to NTG. NTG had a striking dose-dependent effect on the duration of vasodilation of conductance vessels but did not have a dose-dependent duration effect on coronary blood flow. Although acetylcholine demonstrated a dose-dependent response effect on the conductance vessels similar to NTG, the conductance and resistance vessels demonstrated the same sensitivity to acetylcholine, supporting the view that differences in the mechanics of vasodilation of the two vessel segments did not account for the differential sensitivities to NTG.

Acetylcholine↗
PubMed1992

Drinking amongst medical patients: levels of risk and models of change.

Results are reported of a study in which 547 general hospital medical in-patients were screened, using a computer-administered questionnaire, for alcohol consumption, problems and concerns. Of males, 22.5% were classified as 'risk drinkers', of women 6.5%. Rates of risk were particularly high amongst younger male patients. It was concluded that certain screening questionnaire items were more useful than others in the general hospital context, and that standard questionnaires developed for other populations should not automatically be used in general hospitals. Comparisons with items relating to other health behaviours suggested that the medical profession, the general public and the patients themselves might be relatively insensitive to the risks associated with heavy drinking in comparison to those associated with smoking, weight and lack of exercise. Data from initial screening and from 75% of patients who were asked to repeat the questionnaire six months later, were used to test certain assumptions of a model of change based in part upon that of Prochaska & DiClemente (1986). Results suggested that processes of change were more complex than the model supposed.

Adolescent↗
PubMed1990

Analysis of the binding of glyceraldehyde-3-phosphate dehydrogenase to microtubules, the mechanism of bundle formation and the linkage effect.

The binding of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to microtubules was analysed by the determination of the concentration of the free enzyme in equilibrium with the complex. At low ionic strength (0.03 M) the binding data are best described by a sum of high (Kd = 0.28 microM) and low affinity (Kd = 7.14 microM) sites, showing positive cooperativity. Addition of 1 mM adenosine 5'-[beta,gamma-imido]triphosphate (p[NH]ppA) or increasing the ionic strength to 0.1 M reduces the binding constant of the high-affinity sites considerably. Adding microtubule-associated proteins (at I = 0.1 M) does not appreciably influence the affinities. Total stoichiometries vary over 2.1-1.2 tubulin dimers involved in a binding site for GAPDH. Bundling is reduced concomitantly with the reduction of the affinities and the increase of the stoichiometry to close to 1 mol GAPDH/mol tubulin dimer. The critical concentration of tubulin is practically not influenced by the binding of the enzyme. This behaviour is discussed in terms of the concept of linked functions. p[NH]ppA dissociates the bundles very rapidly. Analytical sedimentation studies showed that the dissociation of the bundles by p[NH]ppA is not due to the dissociation of the tetrameric enzyme. Bundling slows down association and dissociation of microtubules. The rate of bundle formation, after addition of GAPDH to preformed microtubules, is not dependent on the GAPDH concentration.

Adenosine Triphosphate↗
PubMed1990

Kinetics of the spontaneous organization of microtubules in solution.

Optically anisotropic zones occur spontaneously in solutions of microtubules. These tactoids, in which microtubules are arranged in parallel arrays, can be visualized by their birefringence. With microtubules assembled in the presence of associated proteins (MAPs), birefringence appears immediately after nucleation of polymerization, even at relatively low protein concentrations. It is not dependent on whether the assembly is initiated by temperature jump or by isothermal addition of GTP. With pure tubulin, assembled in buffers containing 25% glycerol or 4% dimethylsulfoxide and/or taxol, birefringence appears within a few hours, but it can be speeded up by gentle agitation. With tubulin assembled in the presence of MAPs, spontaneous orientation occurs simultaneously with polymerization. This may be due to the existence of more pronounced repulsive forces between microtubules when they are covered with MAPs. A simple calculation of the covolume, suggests that tactoid formation is expected for microtubules of lengths of 5 to 10 microns at protein concentrations in the range 1 to 3 mg/ml (as observed), and that repulsive forces will promote tactoid formation at even lower protein concentrations.

Alkaloids↗
PubMed1989

Update on epikeratophakia in children.

Epikeratophakia continues to be an extremely attractive option for younger children with unilateral aphakia who are noncompliant users of contact lenses but who are young enough to benefit from amblyopia therapy. The epikeratophakia procedure is much safer than IOL implantation. The epikeratophakia tissue lens is especially useful for children with traumatic aphakia and corneal lacerations because the lens can strengthen and smooth the cornea as well as correct the aphakia. This allows much quicker rehabilitation than could be accomplished with contact lenses. The epikeratophakia procedure may be combined with a cataract extraction and should be in those children with acquired cataracts who demonstrate contact lens noncompliance in an office trial of contact lens insertion before operation. Epikeratophakia should be used with caution in neonates and young infants because of the rapid growth of the eye. Extended-wear contact lenses are a safer option for these children, and epikeratophakia can be performed as a secondary procedure if and when problems with contact lens compliance arise. Surface ocular problems such as uncontrolled dry eyes or severe blepharitis will continue to be incompatible with the survival of epikeratophakia tissue lenses. Children who are treated with high doses of radiation for orbital tumors such as rhabdomyosarcomas invariably develop radiation cataracts, which can occur before the onset of radiation keratitis. These children do not do well with epikeratophakia tissue lenses. Likewise, children with severe metabolic disturbances who are not healthy or gaining weight have a diminished chance of graft healing, as do children with poor vision in whom oculodigital autostimulation produces persistent epithelial defects, which prevent survival of the tissue lens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Orientation discrimination and cortical function in the human newborn.

There is some controversy concerning whether or not the visual abilities of the newborn are mediated entirely through subcortical pathways or whether the visual cortex is functioning at birth. A critical test of cortical functioning is discrimination of orientation: orientation-selective neurons are found in the visual cortex but not in subcortical parts of the visual system. An experiment is described in which newborn infants were habituated to a square-wave grating oriented 45 degrees from vertical. After habituation, significant preferences for the novel, mirror-image, grating were found, a result which argues for some degree of visual cortical functioning at birth.

Arousal↗
PubMed1979

The effect of sulphur on 75Se absorption and retention in sheep.

Four Border-Leicester X Merino wethers were used in a 4 X 4 Latin square experiment to study the effects of dietary sulphur on selenium absorption and retention. The basal diet contained 0.05% S and sodium sulphate was added to give additional treatment levels of 0.11, 0.17 and 0.24% total sulphur. Sodium selenate was added to all diets to bring the dietary selenium level to a constant 0.25 mg/kg. One hundred muCi 75Se as sodium selenate (specific activity 50 muCi/mg Se) was administered to the rumen per fistulam after a 10-day period of adjustment on each diet. Radioactivity in blood, urine, faeces and rumen digesta was measured at intervals over the succeeding 7 days. Twenty percent of the total activity in the rumen fluid was in the TCA supernatant fraction after 3 hours, and this proportion tended to increase slightly as sulphur intake increased. Fecal excretion of selenium accounted for between 44 and 51% of the dose after 7 days, the high levels being associated with increasing sulphur intake. However, these differences were not significant. Urinary excretion of selenium accounted for between 12% (0.05% S) and 22% (0.24% S) of the dose after 7 days, with treatment differences being significant. Levels of radioactivity in blood were significantly higher in sheep fed the 0.05% S diet compared with those fed the higher levels. The results show that sulphur affects apparent selenium excretion and suggest that the metabolism of these two elements is intimately related.

Absorption↗