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Biomedical subjects

S M Miller

Publications and source records attributed to S M Miller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Relative Lewis basicities of six AI(ORF)4- superweak anions and the structures of LiA.

The relative Lewis basicities of six Al(ORF)4- ions, Al[OC(CH3)(CF3)2]4-, Al(OC(CF3)3]4-, Al(OCPh(CF3)2]4-, Al[OC[4-C6H4(tBu)](CF3)2]4-, Al(OC(Cy)(CF3)2]4-, and Al(OCPh2(CF3)]4-, have been determined by measuring their relative coordinating abilities towards Li+ in dichloromethane. The relative Li- Lewis basicities of the Al(ORF)4- ions are linearly related to the aqueous pKa values of the corresponding parent HORF fluoroalcohols. The Lewis basicity of Al[OCH(CF3)2]4- could not be measured because two of these anions can coordinate to one Li+ cation. The structures of LiAl[OCH(CF3)2]4 and [1-Et-3-Me-1,3-C3H3N2][Li[Al[OCH(CF3)2)4]2] were determined.

Alkalies↗
PubMed2001

Results from the Lake Michigan Mass Balance study: concentrations and fluxes of atmospheric polychlorinated biphenyls and trans-nonachlor.

In this paper, we summarize the data and methods used to estimate atmospheric exchange of polychlorinated biphenyls (PCBs) and trans-nonachlor with Lake Michigan. This work was conducted as part of the Lake Michigan Mass Balance (LMMB) study. For the atmospheric component of the LMMB, more than 400 gas- and particulate-phase samples were collected at eight sites on the shore around the lake (shoreline) and at 14 sites on the lake (over-water). We review the quality of the data set; describe the concentrations in atmospheric gas and particulate phases; report local, instantaneous, net gas fluxes; and estimate annual deposition of the particle-associated compounds. The quality of the data set is high except for a subset of over-water samples where PCB contamination is suspected. Gas-phase trans-nonachlor concentrations (although not the resulting gas fluxes) are inversely correlated with latitude and positively correlated with temperature. Gas-phase sigmaPCBs (sum of 98 congener groups) are highest in concentration at the Chicago site and lowest at the Sleeping Bear Dunes site. The resulting sigmaPCB gas fluxes exhibit a seasonality that reflects elevated summertime gas-phase concentrations not compensated by temperature-corrected Henry's law coefficients. Particulate-phase deposition is much smaller in magnitude than gas fluxes, for either compound. Gas and particulate fluxes are comparable only at the Chicago site and only when large (> 10 microm) particulates are considered.

Hydrocarbons, Chlorinated↗
PubMed2001

Monitoring for suspected pulmonary embolism.

It is fortunate that serious embolic phenomena are uncommon because, with the exception of neurosurgery in the sitting position and cardiac surgery, thoracic echocardiography and the precordial Doppler device, the most sensitive indicators of embolism, are seldom used. Vigilance is required of the anesthesiologist to recognize the rapid fall in end-tidal PCO2, the usual first indicator of a clinically significant PE. Any sudden deterioration in the patient's vital signs should include embolism in the differential diagnosis, particularly during procedures that carry a high risk of the complication.

Embolism, Air↗
PubMed2001

Psychological and screening profiles of first-degree relatives of prostate cancer patients.

The purpose of the present study was to systematically compare the psychological and screening profiles of first-degree relatives (FDRs) of prostate cancer patients versus non-FDRs. FDRs (n = 56) and non-FDRs (n = 100), recruited through prostate cancer index cases and newspaper advertisements, completed questionnaires via mail. FDRs reported feeling at greater risk for prostate cancer, estimated that they were at higher average lifetime risk for the disease, agreed more strongly that prostate cancer is inherited, and that less can be done to prevent the development of the disease. Increased age, but not FDR status, was associated with more frequent screening behavior. Taken together, the results indicate that FDRs are characterized by greater perceived vulnerability to prostate cancer and lower expectations about disease prevention. Yet, they are no more likely to be screened than non-FDRs. These findings underscore the importance of developing, and evaluating, evidence-based health communication protocols to promote screening adherence among at-risk patients.

Adult↗
PubMed2001

Haem oxygenase in enteric nervous system of human stomach and jejunum and co-localization with nitric oxide synthase.

Recent evidence suggests that carbon monoxide (CO) may be a neurotransmitter, similar to nitric oxide (NO) in the enteric nervous system. The distribution of haem oxygenase (HO), the biosynthetic enzyme for CO, has been determined in the enteric nervous system of animals, but little is known about the distribution of HO in human gastrointestinal tract. The present study investigated the expression of HO and its colocalization with NO synthase (NOS), the biosynthetic enzyme for NO, in human antrum and jejunum. HO isoforms were identified using immunohistochemistry and NOS was identified by immunohistochemistry or NADPH-d histochemistry. HO-2 immunoreactive (IR) cell bodies in enteric ganglia and nerve fibres in longitudinal and circular muscle were found in both antrum and jejunum. Co-localization of HO-2 and NOS was about 40% in HO-2 containing cell bodies of myenteric ganglia and only 10% or less in cell bodies of submucous ganglia. HO-1 immunoreactivity was not detected in antrum or jejunum. The results suggest that CO is produced in human enteric ganglion neurones and indicate a possible role of CO as a neurotransmitter and possible interaction between HO and NOS pathways in inhibitory neurotransmission in the human gastrointestinal tract.

Adult↗
PubMed2001

Relaxation of canine gallbladder to nerve stimulation involves adrenergic and non-adrenergic non-cholinergic mechanisms.

Electrical field stimulation (EFS) of dog gallbladder strips induced a frequency-dependent contractile response followed by an off-relaxation that was turned into a pure inhibitory response after atropine pretreatment. Guanethidine reduced the atropine-induced relaxing responses, so an adrenergic mechanism can partially account for the nerve-mediated gallbladder relaxation. However, guanethidine pretreatment also revealed a nonadrenergic noncholinergic (NANC) relaxation induced by EFS, which was frequency independent. NANC relaxations were reduced by L-arginine methyl ester (L-NAME, 100 micromol L-1), a nitric oxide synthase inhibitor (D-p-Cl-Phe6, Leul7; 10 micromol L-1), a vasoactive intestinal peptide (VIP) receptor antagonist, and an inhibitor of haem oxygenase, (copper protoporphyrin IX; CuPP-IX; 10 micromol L-1), suggesting that nitric oxide (NO), VIP and carbon monoxide (CO), respectively, are released in response to EFS. Immunoreactivities for haem oxygenase-2 (HO-2) and VIP, and histochemical staining for NADPH diaphorase were observed in nerve cell bodies and fibres, demonstrating the presence of CO, VIP and NO as putative NANC neurotransmitters in dog gallbladder. These data support the hypothesis that NO, VIP and CO contribute to NANC relaxation of the canine gallbladder.

Adrenergic Fibers↗
PubMed2001

Anxiety/uncertainty reduction as a motivation for interest in prophylactic oophorectomy in women with a family history of ovarian cancer.

Most women at familial risk for ovarian cancer must decide about prophylactic oophorectomy without conclusive genotypic information about their risk level. Some women with relatively low-risk profiles seek prophylactic oophorectomy or are recommended the procedure by their physicians, if they appear "cancerphobic." This study investigated the desire to reduce anxiety in relation to other factors associated with interest in prophylactic oophorectomy in a group of women with varying degrees of familial risk for ovarian cancer. Ninety-four women enrolled in an ongoing program for women with a family history of ovarian cancer received personalized risk counseling and were classified as having a sporadic, familial, or putative hereditary pedigree by a genetics counselor. Eligible enrollees were interviewed by telephone about current and future interest in prophylactic oophorectomy, perceived risk of ovarian cancer, severity of cancer anxiety, stress-related ideation, and reasons for and against surgery. Reduction of anxiety/uncertainty was the factor most strongly associated with current interest in prophylactic oophorectomy, independent of objective risk classification, perceived risk, severity of cancer anxiety, intrusive ideation, or other variables. Future interest in prophylactic oophorectomy was predicted by other perceived benefits of surgery. Current, but not future, interest in prophylactic oophorectomy appears motivated in part by seeking immediate relief from anxiety. Interest in prophylactic oophorectomy may fluctuate based on varying exposure to cues that trigger anxiety. Women seeking prophylactic oophorectomy, particularly those with lower-risk family pedigrees, should be offered options for anxiety management as part of informed consent for prophylactic oophorectomy.

Adult↗
PubMed2001

Communicating genetic test results to the family: a six-step, skills-building strategy.

As the availability of tests to identify hereditary predisposition to chronic diseases continues to grow, a need has arisen to prepare individuals receiving genetic test results to share this highly sophisticated and value-laden information with other at-risk family members. Responding to this need, a communication skills-building intervention, based on Buckman's model of "Breaking Bad News," was developed for use in the setting of genetic testing for BRCA1 and BRCA2 mutations. Outcomes will include knowledge, attitudes, and health behavior on the part of both the proband and her first-degree relatives.

Adaptation, Psychological↗
PubMed2001

Electrophysiological effects of GABA on cat pancreatic neurons.

In mammalian peripheral sympathetic ganglia GABA acts presynaptically to facilitate cholinergic transmission and postsynaptically to depolarize membrane potential. The GABA effect on parasympathetic pancreatic ganglia is unknown. We aimed to determine the effect of locally applied GABA on cat pancreatic ganglion neurons. Ganglia with attached nerve trunks were isolated from cat pancreata. Conventional intracellular recording techniques were used to record electrical responses from ganglion neurons. GABA pressure microejection depolarized membrane potential with an amplitude of 17.4 +/- 0.7 mV. Electrically evoked fast excitatory postsynaptic potentials were significantly inhibited (5.4 +/- 0.3 to 2.9 +/- 0.2 mV) after GABA application. GABA-evoked depolarizations were mimicked by the GABA(A) receptor agonist muscimol and abolished by the GABA(A) receptor antagonist bicuculline and the Cl(-) channel blocker picrotoxin. GABA was taken up and stored in ganglia during preincubation with 1 mM GABA; beta-aminobutyric acid application after GABA loading significantly (P < 0.05) increased depolarizing response to GABA (15.6 +/- 1.0 vs. 7.8 +/- 0.8 mV without GABA preincubation). Immunolabeling with antibodies to GABA, glial cell fibrillary acidic protein, protein gene product 9.5, and glutamic acid decarboxylase (GAD) immunoreactivity showed that GABA was present in glial cells, but not in neurons, and that glial cells did not contain GAD, whereas islet cells did. The data suggest that endogenous GABA released from ganglionic glial cells acts on pancreatic ganglion neurons through GABA(A) receptors.

Aminobutyrates↗
PubMed2001

Suspected allopurinol-induced aseptic meningitis.

Drug-induced aseptic meningitis is a syndrome with symptoms similar to those of infectious meningitis. A 60-year-old man with a history of recurrent renal stones was admitted to the hospital with fever, chills, and mental status changes after taking levofloxacin, allopurinol, and acetazolamide. No infectious source was identified. Once home, he resumed allopurinol, and within 2 hours, he experienced the same symptoms, requiring rehospitalization. He was diagnosed with suspected meningitis from an adverse drug reaction that we believe was due to allopurinol. It is important to remember, when all other causes are ruled out, that a patient's symptoms may be a drug-induced adverse effect. Drug-induced aseptic meningitis should be considered when patients with symptoms similar to those of infectious meningitis appear without infectious etiologies or cerebrospinal fluid pleocytosis, a suspected agent was recently started, and resolution of adverse effects occurs when the agent is withdrawn.

Allopurinol↗
PubMed2001

Potassium outward currents in freshly dissociated rabbit corpus cavernosum myocytes.

PURPOSE: Cavernous smooth muscle cells have a key role in the control of penile erection and detumescence. In this study the types of smooth muscle cells and currents present in isolated rabbit corpus cavernosum myocytes were characterized. MATERIALS AND METHODS: Immunohistochemical methods were used to identify cavernous smooth muscle cells. Currents were recorded from freshly dissociated myocytes using the whole cell and amphotericin perforated patch clamp techniques. RESULTS: Cavernous myocytes were identified by alpha-smooth muscle actin and smooth muscle myosin immunoreactivity. Based on electrical properties at least 2 types of myocytes were present. Type I cells showed more depolarized membrane potentials, lower capacitance, higher input resistance and increased current densities at positive potentials than type II cells. In types I and II cells at voltages positive to 30 mV, maxi K+ channel (Ca2+ activated large conductance K+ channel or BK) blockade with iberiotoxin or charybdotoxin reduced outward currents by approximately 40% to 80% at 80 mV. Maxi K+ channel blocking did not affect cell membrane potential. Type II cells showed delayed rectifier K+ channel-type outward currents that were not detected in type I cells. Delayed rectifier K+ channel-type currents were resistant to iberiotoxin or charybdotoxin, activated at approximately -50 to -40 mV. and inactivated weakly. CONCLUSIONS: The data suggest that cavernous smooth muscle cells are heterogeneous with at least 2 subtypes identified based on membrane potential, capacitance, input resistance, current density and delayed rectifier K+ channel expression. The activation threshold suggests that delayed rectifier K+ channels are open at the resting membrane potential and, therefore, contribute to control and regulation of the cavernous myocyte excitability.

Animals↗
PubMed2000

The three-dimensional structure of neurons in the guinea pig inferior mesenteric and pelvic hypogastric ganglia.

The three-dimensional (3-D) morphology of sympathetic inferior mesenteric ganglion (IMG) neurons and sympathetic-parasympathetic pelvic hypogastric ganglion (PHG) neurons was studied using confocal laser scanning microscopy. Cell bodies of IMG neurons were disc-shaped and were arranged orderly in layers. The dendritic arbor of individual neurons was confined to a plane with a thickness that did not exceed the thickness of the parent cell body. The actual dendritic surface area (71,400 micron 2) and volume (81,500 micron 3) of the IMG neurons were up to 100-fold larger than previously reported for similar sympathetic neurons using data of 2-D measurements and estimations of the third dimension. PHG neurons had a much smaller dendritic surface area (4100 micron 2) and volume (2400 micron 3) compared to IMG neurons. The ratio dendritic/somal surface area for individual IMG and PHG neurons ranged from 5:1 to 14:1 and from 0.1:1 to 6:1, respectively. The total dendritic path-length was 8-42 times greater for IMG than for PHG neurons. Neurons in the IMG were either stellate with radiating dendrites or bipolar-shaped with dendrites emerging from the two poles of the cell body. Neurons in the PHG were of two morphological types. One type (nearly 2/3 of all the imaged PHG neurons) had two to seven relatively long dendrites and an axon; the other type had only one to three short unbranched dendrites and an axon. The spatial organization of neurons within the ganglia and the structural features of individual neurons are likely to have important implications regarding connectivity patterns between neurons within the ganglion as well as on how information is processed by the ganglion.

Animals↗
PubMed2000

Transient kinetics and intermediates formed during the electron transfer reaction catalyzed by Candida albicans estrogen binding protein.

The transient kinetics of the reaction of the estrogen binding protein (EBP1) from Candida albicans in which hydride is transferred from NADPH to trans-2-hexenal (HXL) in two half-reactions were analyzed using UV-visible spectrophotometric and fluorometric stopped-flow techniques. The simplest model of the first half-reaction involves four steps including very rapid, tight binding (K(d) </= 50 nM) characterized by loss of NADPH fluorescence, subsequent rapid formation of a charge-transfer complex between NADPH and oxidized enzyme-bound flavin mononucleotide (FMN) cofactor, followed by rate-limiting reduction of the FMN, and finally dissociation of the oxidized pyridine nucleotide. The UV-visible absorbance behavior of this half-reaction is described by two apparent phases, with k(f)(obs) = 355 +/- 6 and k(s)(obs) = 3.30 +/- 0.03 s(-)(1), for the fast and slow phases, respectively. The reaction has also been evaluated in terms of the full, multi-equilibrium reaction scheme, and microscopic rate constants that lead to the observed behavior have been determined through convergent experimental techniques and computer simulation. Significant intrinsic kinetic isotope effects were noted on both the bond cleavage step and the preceding formation of the charge-transfer complex. The enzyme is reoxidized by transfer of hydride from the FMN to HXL in the second half-reaction that appears to consist of substrate binding to form a Michaelis-type complex and the subsequent chemical step. Characterization of the reaction in this simple manner allows determination of an apparent K(d) = 100 +/- 9 microM for the reduced enzyme.HXL complex.

Aldehydes↗
PubMed2000

Stabilization of a novel enzyme.substrate intermediate in the Y206F mutant of Candida albicans EBP1: evidence for acid catalysis.

EBP1-catalyzed reduction of alpha,beta-unsaturated ketones and aldehydes is proposed to proceed via transfer of hydride from the flavin to the beta-position of the olefinic bond, concomitant with or followed by uptake of a proton at the alpha-position. Structural analysis suggests that this proton is donated from Tyr206, and, hence, a protein was constructed in which it was replaced by phenylalanine. The mutation results in a slightly less stable protein than the wild type that nevertheless retains the fundamental flavin and phenol binding properties of EBP1 characterized previously. The pH profile for binding of phenol was characterized over the pH range 6.5-9.5 and was found to be simpler than that for the wild-type enzyme. Most importantly, a pK(a) of 8.7 that is perturbed to 9.4 upon binding of phenol to the wild-type enzyme is missing in the mutant, allowing assignment of this pK(a) to the Y206 hydroxyl group. Additionally, the pK(a) of phenol is further lowered from its value of 10.0 in solution to approximately 6.4 in the active site of the mutant, as compared to 7.1 in the wild type. Together, these perturbations lead to an increase of approximately 35-fold in the binding affinity of the mutant for phenol at high pH relative to the affinity of the wild-type enzyme. As expected, the mutation has little effect on the reductive half-reaction, in which a hydride equivalent is transferred from NADPH to the flavin. In contrast, the reduction of trans-2-hexenal by the reduced enzyme is significantly affected. The results indicate formation of a previously unobserved charge-transfer (CT) complex following formation of the Michaelis complex between substrate and reduced enzyme and preceding reduction of the substrate, which occurs at a greatly reduced rate (>/=440-fold) relative to wild type. Thus, while the oxidative half-reaction with wild-type enzyme is limited by the rate of formation of the CT complex, it is the chemical step that is rate-limiting in the reaction with EBP1:Y206F, consistent with the role of this residue as a general acid.

Base Sequence↗
PubMed2000

Weakly coordinating anions HA2-generated from oxoanions A- and their conjugate acids. Coordination equilibria, ionic conductivities, and the structures of [Cu2(H(CH3SO3)2)4]n and [Cu(CO)(H(CF3CO2)2)]2.

The coordination or ion pairing of the hydrogen-bonded anions H(CF3CO2)2- and H(CH3SO3)2- to NEt4+, Li+, Cu+, and/or Cu2+ was investigated. The structure of [Cu2(H(CH3SO3)2)4]n consists of centrosymmetric dimeric moieties that contain two homoconjugated (CH3SO2O-H...OSO2CH3)- anions per Cu2+ ion, forming typical Jahn-Teller tetragonally elongated CuO6 coordination spheres. The oxygen atoms involved in the nearly linear O-H...O hydrogen bonds (O...O approximately 2.62 A) are not coordinated to the Cu2+ ions. The structure of Cu2(CO)2(H(CF3-CO2)2)2 consists of pseudo-C2-symmetric dimers that contain one homoconjugated (CF3COO-H...OCOCF3)- anion per Cu+ ion, forming highly distorted tetrahedral Cu(CO)O3 coordination spheres. Three of the four oxygen atoms in each hydrogen-bonded H(CF3CO2)2- anion are coordinated to the Cu+ ions, including one of the oxygen atoms in each O-H...O hydrogen bond (O...O approximately 2.62 A). Infrared spectra (v(CO) values) of Cu(CO)(CF3CO2) or Cu(CO)(CH3SO3) dissolved in acetonitrile or benzene, with and without added CF3COOH or CH3SO3H, respectively, demonstrate that HA2- anions involving carboxylates or sulfonates are more weakly coordinating than the parent anions RCO2- and RSO3-. Direct current conductivities of THF solutions of Li(CF3CO2) containing varying concentrations of added CF3COOH further demonstrate that Li+ and NEt4+ ion pair much more weakly with H(CF3CO2)2- than with CF3CO2-.

Acids↗
PubMed2000

Interhemispheric switching mediates perceptual rivalry.

BACKGROUND: Binocular rivalry refers to the alternating perceptual states that occur when the images seen by the two eyes are too different to be fused into a single percept. Logothetis and colleagues have challenged suggestions that this phenomenon occurs early in the visual pathway. They have shown that, in alert monkeys, neurons in the primary visual cortex continue to respond to their preferred stimulus despite the monkey reporting its absence. Moreover, they found that neural activity higher in the visual pathway is highly correlated with the monkey's reported percept. These and other findings suggest that the neural substrate of binocular rivalry must involve high levels, perhaps the same levels involved in reversible figure alternations. RESULTS: We present evidence that activation or disruption of a single hemisphere in human subjects affects the perceptual alternations of binocular rivalry. Unilateral caloric vestibular stimulation changed the ratio of time spent in each competing perceptual state. Transcranial magnetic stimulation applied to one hemisphere disrupted normal perceptual alternations when the stimulation was timed to occur at one phase of the perceptual switch, but not at the other. Furthermore, activation of a single hemisphere by caloric stimulation affected the perceptual alternations of a reversible figure, the Necker cube. CONCLUSIONS: Our findings suggest that interhemispheric switching mediates perceptual rivalry. Thus, competition for awareness in both binocular rivalry and reversible figures occurs between, rather than within, each hemisphere. This interhemispheric switch hypothesis has implications for understanding the neural mechanisms of conscious experience and also has clinical relevance as the rate of both types of perceptual rivalry is slow in bipolar disorder (manic depression).

Adolescent↗