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Biomedical subjects

R R Smith

Publications and source records attributed to R R Smith.

At least 19 recordsLinked to original sources

Comparative study of C-H stretch and bend vibrations in methane activation on Ni(100) and Ni(111).

State-resolved measurements on clean Ni(100) and Ni(111) surfaces quantify the reactivity of CH4 excited to v = 3 of the nu4 bend vibration. A comparison with prior data reveals that 3nu4 is significantly less effective than the nu3 C-H stretch at promoting dissociative chemisorption, even though 3nu4 contains 30% more energy. These results contradict statistical theories of gas-surface reactivity, provide clear evidence for vibrational mode specificity in a gas-surface reaction, and point to a central role for C-H stretching motion along the reaction path to dissociative chemisorption.

Carbon↗

Preference for vibrational over translational energy in a gas-surface reaction.

State-resolved gas-surface reactivity measurements revealed that vibrational excitation of nu3 (the antisymmetric C-H stretch) activates methane dissociation more efficiently than does translational energy. Methane molecules in the vibrational ground state require 45 kilojoules per mole (kJ/mol) of translational energy to attain the same reactivity enhancement provided by 36 kJ/mol of nu3 excitation. This result contradicts a key assumption underlying statistical theories of gas-surface reactivity and provides direct experimental evidence of the central role that vibrational energy can play in activating gas-surface reactions.

Journal Article↗

Saturable brain-to-blood transport of endomorphins.

Opiate-modulating tetrapeptides such as tyrosine-melanocyte-stimulating hormone-release inhibiting factor-1 (Tyr-MIF-1; Tyr-Pro-Leu-Gly-NH2) and Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) are saturably transported from brain to blood. We examined whether two recently described endogenous opiate tetrapeptides with similar structures, the mu-specific endomorphins, also are transported across the blood-brain barrier (BBB). We found that the efflux rates of endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) were each self-inhibited by an excess of the respective endomorphin, thereby defining saturable transport. Cross-inhibition of the transport of each endomorphin by the other indicated shared transport. By contrast, no inhibition of the efflux of either endomorphin resulted from coadministration of Tyr-MIF-1, indicating that peptide transport system-1 (PTS-1) was not involved. Tyr-W-MIF-1, which is partially transported by PTS-1, significantly (P<0.01) decreased the transport of endomorphin-1 and tended (P=0.051) to decrease the transport of endomorphin-2, consistent with its role as both an opiate and antiopiate. Although involved in modulation of pain, coinjection of calcitonin gene-related peptide or constriction of the sciatic nerve did not appear to inhibit endomorphin efflux. Thus, the results demonstrate the existence of a new efflux system across the BBB which saturably transports endomorphins from brain to blood.

Animals↗

Decreases in endomorphin-2-like immunoreactivity concomitant with chronic pain after nerve injury.

Nerve injury often leads to chronic, sometimes excruciating, pain. The mechanisms contributing to this syndrome include neurochemical plasticity in neurons involved in the earliest stages of pain transmission. Endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) is an endogenous morphine-like substance that binds to the mu-opioid receptor with high affinity and selectivity. Endomorphin-2-like immunoreactivity (LI) is present in the superficial layers of the dorsal horn in the spinal cord and in primary afferents, suggesting a role for this peptide in pain transmission. To determine whether spinal endomorphin-2-LI is altered in an animal model of chronic pain, the left sciatic nerve of Swiss Webster and ICR mice was ligated in a modified Seltzer model of nerve injury. Changes in endomorphin-2-LI were assessed by immunocytochemistry at 2, 4 and 14 days after nerve injury. The side of the spinal cord ipsilateral to the nerve injury exhibited a dramatic decrease in endomorphin-2-LI relative to the contralateral side and to control animals. The change was restricted to the medial dorsal horn in the lumbar segments innervated by the sciatic nerve. Substance P-LI showed a small decrease, while calcitonin gene-related peptide-LI was unchanged. Both thermal hyperalgesia, as evidenced by significantly decreased paw withdrawal latencies, and decreased endomorphin-2-LI were observed within 2 days of injury and were most pronounced at 2 weeks after injury. The decrease in endomorphin-2-LI during the development of chronic pain is consistent with the loss of an inhibitory influence on pain transmission. These results provide the first evidence that reduction of an endogenous opioid in primary afferents is associated with injury-induced chronic pain.

Animals↗

Expression of liver fatty acid binding protein alters growth and differentiation of embryonic stem cells.

Although expression of liver fatty acid binding protein (L-FABP) modulates cell growth, it is not known if L-FABP also alters cell morphology and differentiation. Therefore, pluripotent embryonic stem cells were transfected with cDNA encoding L-FABP and a series of clones expressing increasing levels of L-FABP were isolated. Untransfected ES cells, as well as ES cells transfected only with empty vector, spontaneously differentiated from rounded adipocyte-like to fibroblast-like morphology, concomitant with marked reduction in expression of stage-specific embryonic antigen (SSEA-1). These changes in morphology and expression of SSEA-1 were greatest in ES cell clones expressing L-FABP above a threshold level. Immunofluorescence confocal microscopy revealed that L-FABP was primarily localized in a diffuse-cytosolic pattern along with a lesser degree of punctate L-FABP expression in the nucleus. Nuclear localization of L-FABP was preferentially increased in clones expressing higher levels of L-FABP. In summary, L-FABP expression altered ES cell morphology and expression of SSEA-1. Taken together with the fact that L-FABP was detected in the nucleus, these data suggested that L-FABP may play a more direct, heretofore unknown, role in regulating ES cell differentiation by acting in the nucleus as well as cytoplasm.

Animals↗

Hearing and whistling in the deep sea: depth influences whistle spectra but does not attenuate hearing by white whales (Delphinapterus leucas) (Odontoceti, Cetacea).

Hearing is attenuated in the aerial ear of humans and other land mammals tested in pressure chambers as a result of middle ear impedance changes that result from increased air density. We tested the hypothesis, based on recent middle ear models, that increasing the density of middle ear air at depth might attenuate whale hearing. Two white whales Delphinapterus leucas made dives to a platform at a depth of 5, 100, 200 or 300 m in the Pacific Ocean. During dives to station on the platform for up to 12 min, the whales whistled in response to 500 ms tones projected at random intervals to assess their hearing threshold at each depth. Analysis of response whistle spectra, whistle latency in response to tones and hearing thresholds showed that the increased hydrostatic pressure at depth changed each whale's whistle response at depth, but did not attenuate hearing overall. The finding that whale hearing is not attenuated at depth suggests that sound is conducted through the head tissues of the whale to the ear without requiring the usual ear drum/ossicular chain amplification of the aerial middle ear. These first ever hearing tests in the open ocean demonstrate that zones of audibility for human-made sounds are just as great throughout the depths to which these whales dive, or at least down to 300 m.

Animals↗

The role of rotational excitation in the activated dissociative chemisorption of vibrationally excited methane on Ni(100).

We have measured the sticking probability of methane excited to v = 1 of the v3 antisymmetric C-H stretching vibration on a clean Ni(100) surface as a function of rotational state (J = 0, 1, 2 and 3) and have investigated the effect of Coriolis-mixing on reactivity. The data span a wide range of kinetic energies (9-49 kJ mol-1) and indicate that rotational excitation does not alter reactivity by more than a factor of two, even at low molecular speeds that allow for considerable rotation of the molecule during the interaction with the surface. In addition, rotation-induced Coriolis-splitting of the v3 mode into F+, F0 and F- states does not significantly affect the reactivity for J = 1 at 49 kJ mol-1 translational energy, even though the nuclear motions of these states differ. The lack of a pronounced rotational energy effect in methane dissociation on Ni(100) suggests that our previous results for (v = 1, v3, J = 2) are representative of all rovibrational sublevels of this vibrational mode. These experiments shed light on the relative importance of rotational hindering and dynamical steering mechanisms in the dissociative chemisorption on Ni(100) and guide future attempts to accurately model methane dissociation on nickel surfaces.

Journal Article↗

An EPR investigation of surfactant action on bacterial membranes.

The effects of the surfactants, alcohol ethoxylate, amine ethoxylate, amine oxide and SDS on cell membranes were investigated using the lipid soluble spin label 5-doxyl stearic acid (5-DS). Electron paramagnetic resonance (EPR) spectroscopy revealed that the action of the surfactants was to significantly increase membrane fluidity of Proteus mirabilis, Staphylococcus aureus and Saccharomyces cerevisiae. The action of these surfactants as biocides was investigated and found to be dependent on the type of organism tested. There was, however, no direct correlation between enhanced membrane fluidity observed due to the action of the surfactants and biocidal activity. Data presented suggest that perturbing the fluidity of the cytoplasmic membrane is not immediately responsible for cell death.

Cell Membrane↗

Glucocorticoid resistance in premature pubarche and adolescent hyperandrogenism.

To determine whether glucocorticoid resistance due to mutations in the glucocorticoid receptor (GRL) gene is associated with premature pubarche, hirsutism, or oligo/amenorrhea, we performed single-strand conformational polymorphism analysis of genomic DNA obtained from 25 children and 16 adolescent girls referred for the evaluation of premature pubarche, hirsutism, or oligo/amenorrhea. A missense mutation, N363S, and a presumed polymorphism in the 3'-UTR of exon 9alpha were identified. We conclude that glucocorticoid resistance due to GRL mutations is an infrequent cause of mild hyperandrogenism.

3' Untranslated Regions↗

The presence of the 21-hydroxylase deficiency carrier status in hirsute women: phenotype-genotype correlations.

OBJECTIVE: To determine the role of heterozygosity for mutations in the 21-hydroxylase gene (CYP21) in the pathogenesis of hyperandrogenism. DESIGN: Controlled clinical study. SETTING: Tertiary care institutional hospital. PATIENT(S): Forty hirsute women and 13 healthy control women. INTERVENTION(S): The source of androgen excess was determined by the changes in serum testosterone levels in response to a single 3.75-mg i.m. dose of triptorelin. MAIN OUTCOME MEASURE(S): CYP21 molecular genetic analysis and serum 17-hydroxyprogesterone levels. RESULT(S): Eight patients and one control were heterozygous carriers of CYP21 mutations. Two patients with adrenal hyperandrogenism and one patient with ovarian hyperandrogenism, who carried the V281L mutation had an increased ACTH-stimulated 17-hydroxyprogesterone level (>4.1 ng/mL) that persisted during gonadal suppression. Another patient with adrenal hyperandrogenism carried the V281L mutation, and her ACTH-stimulated 17-hydroxyprogesterone level was elevated only during gonadal suppression. Four patients (three with idiopathic hirsutism, one with ovarian hyperandrogenism) and one control were carriers of CYP21 mutations typically associated with classic congenital adrenal hyperplasia but had normal basal and ACTH-stimulated 17-hydroxyprogesterone levels. Nine patients without CYP21 mutations had increased ACTH-stimulated 17-hydroxyprogesterone levels; these decreased to normal in six of the patients during gonadal suppression. CONCLUSION(S): The response of serum 17-hydroxyprogesterone to ACTH does not predict CYP21 carrier status. No clear concordance was found between the CYP21 genotype and the functional origin of androgen excess.

17-alpha-Hydroxyprogesterone↗

Suboccipital resection of a medial acoustic neuroma with hearing preservation.

BACKGROUND: Many reports indicate that acoustic neuromas greater than 2.0 cm should be removed without hearing preservation attempted, even if hearing is present preoperatively. These studies advocate a translabyrinthine approach because the likelihood of hearing preservation is low. Medial acoustic neuromas, unlike the more common lateral tumors that involve the internal auditory canal, originate medial to that portion of the eighth nerve complex where the cochlear and vestibular nerves are fused. This anatomical feature suggests that these tumors may be amenable to resection with hearing preservation. METHODS: A patient with a 3.5 cm medial acoustic neuroma and useful preoperative hearing is presented. RESULTS: Gross total tumor removal with functional hearing was achieved after a two-stage procedure using a suboccipital approach. CONCLUSION: Based on the anatomico-pathologic features in this case, we believe that, if a patient has reasonable preoperative hearing (speech discrimination score > 70%) and a medial acoustic neuroma, an approach to preserve hearing should be considered regardless of tumor size.

Female↗

Identity in political context: lesbian/gay representation in the public sphere.

Discourses constructed to represent lesbians and gay men in the public sphere generate an essentialist identity which is both necessary and damaging. Legislative debate illustrates the production of a constrictive and homogeneous identity rejected by many gay/lesbian scholars and activists. Discussion of the rhetorical power of identity claims has produced alternative stances toward variant sexuality. This discussion can be advanced by challenging dominant constructions of civil rights and the public sphere.

Adolescent↗

Temporal bone: comparison of isotropic helical CT and conventional direct axial and coronal CT.

OBJECTIVE: The objective of the study was to compare helical CT (with reformation of coronal images from the axial data set) with conventional direct axial and coronal CT of the temporal bones. SUBJECTS AND METHODS: Nineteen patients underwent both conventional 1-mm direct axial and coronal CT and helical 0.5-mm axial CT. The helical data set was reconstructed at 0.2-mm increments, and axial and coronal images were reconstructed in a plane similar to that of the conventional study, with a slice width of 0.5 mm and 0.5-mm increments. Forty small structures were evaluated independently by three observers, who were unaware of the method of imaging. Observers graded the 40 structures using a modified Likert scale. The graded differences between the two techniques were evaluated using a paired t test. Correlation between observers' gradings was evaluated using analysis of variance. RESULTS: The helical CT technique scored significantly higher than the conventional technique for many individual structures and groups of structures (scutum [p = .041], stapes footplate [p = .006], stapes crura [p = .004], oval window [p = .026], crista falciformis [p = .006], whole temporal bone [P = .012], middle ear [p = .033], inner ear [p = .021], ossicles [p = .044], and stapes [p = .010]). The correlation coefficient among observers was .91 for the whole temporal bone. CONCLUSION: Helical CT using 0.5-mm technique and reconstruction produces diagnostic images comparable with or superior to conventional 1-mm technique because helical CT can obtain thinner slices.

Adolescent↗

Use patterns for antipsychotic medications in medicaid patients with schizophrenia.

OBJECTIVE: We investigated the use patterns for antipsychotic medications generated by Medicaid patients with schizophrenia. METHOD: Paid claims data from the California Medicaid program (Medi-Cal) were used to identify 2655 patients with schizophrenia. Data from 1987-1996 were used, during which time Medi-Cal maintained prior authorization restrictions on second generation antipsychotic drugs. Prescription records were used to identify 3 patterns of antipsychotic drug use: no drug therapy for over 1 year; delayed onset of antipsychotic drug therapy; and switches in antipsychotic drugs within 1 year. Multiple logistic regression models were used to identify factors affecting these antipsychotic drug use patterns. RESULTS: Conventional antipsychotic medications account for over 98% of all patient treatment episodes. Over 24% of patients with schizophrenia do not use any antipsychotic medication for periods lasting up to 1 year. Over 24% of treated patients delayed the use of antipsychotic medications at least 30 days. For those patients who did not delay their use of antipsychotic medications, over 47% switched or augmented their initial antipsychotic medication during the first treatment year. Only 11.6% of treated patients achieved 1 year of uninterrupted antipsychotic drug therapy. The mean duration of uninterrupted therapy was 142 days. DISCUSSION: Antipsychotic drug use patterns suggest that conventional antipsychotic medications do not meet the therapeutic needs of patients with schizophrenia.

Ambulatory Care↗

Consensus opinion on diagnosis of cerebral circulatory arrest using Doppler-sonography: Task Force Group on cerebral death of the Neurosonology Research Group of the World Federation of Neurology.

BACKGROUND AND PURPOSE: Oscillating flow or systolic spikes are typical Doppler-sonographic flow signals found in the presence of cerebral circulatory arrest, which if irreversible, results in brain death. The Neurosonology Research Group (NSRG) of the World Federation of Neurology (WFN) created a Task Force Group in order to evaluate the role of Doppler-sonography as a confirmatory test for determining brain death. METHODS: The available evidence from the literature has been reviewed and discussed by a group of experts, the members of the Task Force Group on cerebral death of the NSRG. RESULTS AND CONCLUSIONS: Extra- and intracranial Doppler-sonography is a useful confirmatory test to establish irreversibility of cerebral circulatory arrest as optional part of a brain death protocol. Doppler-sonography is of special value when the therapeutic use of sedative drugs renders electroencephalography unreliable. Doppler-sonographic criteria are defined and guidelines for the use of Doppler-sonography in this setting are presented.

Blood Flow Velocity↗

The hochschild cohomology problem for von neumann algebras.

In 1967, when Kadison and Ringrose began the development of continuous cohomology theory for operator algebras, they conjectured that the cohomology groups Hn(M, M), n >/= 1, for a von Neumann algebra M, should all be zero. This conjecture, which has important structural implications for von Neumann algebras, has been solved affirmatively in the type I, IIinfinity, and III cases, leaving open only the type II1 case. In this paper, we describe a positive solution when M is type II1 and has a Cartan subalgebra and a separable predual.

Journal Article↗