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Biomedical subjects

G Rice

Publications and source records attributed to G Rice.

At least 37 records · Page 2Linked to original sources
PubMed1999

Male homosexuality: absence of linkage to microsatellite markers at Xq28.

Several lines of evidence have implicated genetic factors in homosexuality. The most compelling observation has been the report of genetic linkage of male homosexuality to microsatellite markers on the X chromosome. This observation warranted further study and confirmation. Sharing of alleles at position Xq28 was studied in 52 gay male sibling pairs from Canadian families. Four markers at Xq28 were analyzed (DXS1113, BGN, Factor 8, and DXS1108). Allele and haplotype sharing for these markers was not increased over expectation. These results do not support an X-linked gene underlying male homosexuality.

Alleles↗
PubMed1999

The natural history of multiple sclerosis: a geographically based study. 7. Progressive-relapsing and relapsing-progressive multiple sclerosis: a re-evaluation.

Classifications of multiple sclerosis subtypes have been largely based on clinical phenomenology. Nevertheless, definitions of relapse, remission and progression have been imprecise. Recently an international consensus group, as part of a reclassification of disease subtypes, recommended dropping the term 'relapsing-progressive' (RP) and retaining the term 'progressive-relapsing' (PR) multiple sclerosis. The term 'RP' multiple sclerosis had been applied when the early course combined both relapses and progression and was believed to identify some patients with a worse than average outcome. The PR group consisted of patients with primary progressive disease who later in their course developed relapses. Since the terminology has been largely arbitrary, we have evaluated the validity of the terms 'RP' and 'PR' multiple sclerosis in the context of long-term outcome within a large population-based cohort of progressive multiple sclerosis patients seen at the London Multiple Sclerosis Clinic (Canada) between 1972 and 1984. Mean follow-up of the entire cohort was 25 years. Designation of RP multiple sclerosis did identify a more rapidly progressive subgroup. To realign these natural history data with consensus recommendations, these patients were reassigned to secondary progressive (SP) or to primary progressive (PP) multiple sclerosis, with progression defined as at least 1 year of progressive deterioration. PP multiple sclerosis patients with relapses after a year were designated as having PR multiple sclerosis. Relapses in primary progressive multiple sclerosis occurred in 27.8% of patients at some point even two to three decades after onset. In general these relapses were mild and remitting, but served to blur the distinction between progressive and relapsing-remitting disease. The long-term outcomes of time to Kurtzke disability scores (DSS) of 3, 6, 8 and 10 were compared among the progressive subtypes. Times to these disability end-points and to death were not different between PR and PP multiple sclerosis. Survival curves for progressive patients have been amended to incorporate the reassignment of PR multiple sclerosis patients into the PP group and the RP multiple sclerosis patients into the PP and SP subgroups. The time to reach DDS 3, 6, 8 and 10 for a population-based cohort of primary and secondary progressive patients resulting from the elimination of the categories of RP multiple sclerosis and PR multiple sclerosis has been established. These results provide justification for retaining only PP and SP multiple sclerosis as the subgroups of progressive disease.

Adult↗
PubMed1999

A randomized controlled trial of a smoking cessation intervention during pregnancy.

This study was a randomized controlled trial of a smoking cessation intervention for pregnant smokers. Women who reported smoking at their first antenatal visit and satisfied the inclusion criteria were asked to participate in the trial. Analysis was restricted to 393 evaluable women in the control group (received usual antenatal care) and 339 women to the study group (received usual antenatal care plus the intervention). The primary hypotheses were that the intervention would result in a higher proportion of quitters and that the mean birth-weight of babies born to women receiving the intervention would be greater than that of babies born to women in the control group. The outcome measures were smoking status based on self-report combined with a urinary cotinine level of <115 ng/mL, and birth-weight. There was no significant difference in quit rate between women receiving the intervention and women in the control group (11.9% versus 9.8% p=0.41). Babies born to women receiving the intervention were on average 84 g heavier than babies born to controls (p=0.04). The factors that contribute to the lack of a significant increase in smoking cessation in the intervention group and the possible explanation for the changes in birth-weight are discussed.

Adult↗
PubMed1999

Reduced visual evoked responses in multiple sclerosis patients with optic neuritis: comparison of functional magnetic resonance imaging and visual evoked potentials.

The limited application of functional magnetic resonance imaging (fMRI) for investigations of multiple sclerosis (MS) patients has already shown that deficits of the motor, cognitive and visual systems may be identified by differences in the patterns of activation in response to a suitable stimulus. In MS patients with unilateral optic neuritis, the area of activation in the primary visual cortex, measured by fMRI techniques, is dramatically reduced in response to stimulation of the affected eye. The latency of the major positive component of the visual evoked potential (VEP) recorded upon stimulation of the affected eye is significantly increased in these patients, as compared to the unaffected eye and normal volunteers. We have found a correlation between the neural response measured using fMRI and the latency of the VEP. fMRI signal responses have the potential to provide more detailed topographic information relating to functional deficits in MS.

Evoked Potentials, Visual↗
PubMed1999

Characterization of risks posed by combustor emissions.

Risk characterization is the final step of the risk assessment process as practiced in the U.S. EPA. In risk characterization, the major scientific evidence and "bottom-line" results from the other components of the risk assessment process, hazard identification, dose-response assessment, and exposure assessment, are evaluated and integrated into an overall conclusion about the risks posed by a given situation. Risk characterization is also an iterative process; the results of a specific step may require re-evaluation or additional information to finalize the risk assessment process. Risks posed by atmospheric emissions are an example of an involuntary human health risk which typically receives a great deal of public attention. Characterization of the risks posed by atmospheric emissions typically requires the use of mathematical models to evaluate: 1) the environmental fate of emitted pollutants, 2) exposures to these pollutants, and 3) human dose-response. Integration of these models results in quantitative risk estimates. The confidence in a quantitative risk estimate is examined by evaluating uncertainty and variability within individual risk assessment components. Variability arises from the true heterogeneity in characteristics within a population or an event; on the other hand, uncertainty represents lack of knowledge about the true value used in a risk estimate. U.S. EPA's 1997 Mercury Study will illustrate some aspects of the risk characterization process as well as the uncertainty and variability encountered in the risk assessment process.

Air Pollutants↗
PubMed1997

Calculation of soil-water and benthic sediment partition coefficients for mercury.

To accurately model mercury transport to water bodies, an assessment of this pollutant's behavior in the watershed is critical. Partition coefficients, defined as an estimate of the ratio of the pollutant concentration sorbed onto soil/sediment particles to the pollutant concentration dissolved in pore water at equilibrium, is an important term in multimedia models. In this paper, partition coefficients are calculated for two broad species of mercury: inorganic mercuric mercury (Hg-II) and methylmercury (MHg). Although there is considerable variability in the calculated values, the approximate mean values for the soil-water partition coefficients range from 3.3 x 10(3) to 6.0 x 10(4) L/kg for Hg-II and 2.0 x 10(1) to 6.7 x 10(3) L/kg for MHg. For the benthic sediment partition coefficients, the values range from 5.7 x 10(3) to 9.9 x 10(5) L/kg for Hg-II, and 6.5 x 10(2) to 1.1 x 10(5) L/kg for MHg.

Animals↗
PubMed1997

The effects of post-treatment with lisofylline, a phosphatidic acid generation inhibitor, on sepsis-induced acute lung injury in pigs.

The effects of lisofylline [(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine] (LSF), an inhibitor of de novo phosphatidic acid (PA) generation, on sepsis-induced acute lung injury was studied using Hanford minipigs weighing 18 to 25 kg. Sepsis was induced by an intravenous infusion of Pseudomonas aeruginosa (1 x 10(6)/colony-forming units/kg/min over 2 h). Saline was used as the control vehicle. Six groups were studied: saline control group (SALINE: n = 5); sepsis control group (SEPSIS: n = 5); LSF control group (LSF: n = 5), which received a 25-mg/kgbolus of LSF 30 min before time zero followed by continuous infusion of 10 mg/kg/h throughout the study; LSF-treated septic groups, which were treated with LSF 30 min prior to sepsis (Pre: n = 5), 1 h postonset (Post-1 h: n = 8) or h postonset (Post-2 h: n = 8) of the bacterial infusion. Hemodynamics PaO2, neutrophil counts, and plasma porcine tumor necrosis factor-alpha concentrations were monitored for 6 h. After the minipigs were killed, lung tissue was sampled to measured wet-to-dry weight ratio (W/D), tissue albumin index (TAI), thiobarbituric acid-reactive material content (TBARM), and myeloperoxidase (MPO) activity. Compared with the SALINE group, the SEPSIS group showed significant systemic hypotension, pulmonary hypertension, arterial hypoxemia, neutropenia, and increase in TNF-alpha, MPO activity, W/D, TBARM, and TAI. LSF treatment attenuated sepsis-induced pulmonary hypertension, neutropenia, and hypoxemia, and increased MPO activity and lung injury measurements in the Pre and Post-1 h groups, but its efficacy was blunted in the Post-2 h group. Plasma TNF-alpha was decreased only in the Pre group. Thus, inhibition of intracellular PA generation through de novo pathways attenuates sepsis-induced acute lung injury.

Adjuvants, Immunologic↗
PubMed1997

Assessment of health risks due to hazardous air pollutant emissions from electric utilities.

Hazardous air pollutant (HAP) emissions from electric utilities were evaluated. Cancer risks, as well as noncancer effects, due to inhalation exposure were assessed for 67 HAPs. Also, cancer risks due to multipathway exposure to radionuclide emissions were assessed. In addition, an assessment of the fate of mercury (Hg) through various environmental media was included. Results suggest arsenic, chromium, and nickel are the HAPs that present the highest cancer risk due to inhalation exposure. For noncancer effects due to inhalation exposure, hydrogen chloride appears to present the greatest potential concern. The risks due to multipathway exposure to radionuclides are estimated to be of similar magnitude to the risks posed by inhalation of arsenic and nickel. Mercury is of potential concern for multipathway exposures because it persists in the environmental and bioaccumulates in the aquatic food web. The study suggests there is a plausible link between Hg emissions from utilities and the Hg found in soil, water, and freshwater fish.

Air Pollutants↗
PubMed1996

A full genome search in multiple sclerosis.

The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.

Chromosome Mapping↗
PubMed1996

Lisofylline decreases white cell adhesiveness and improves survival after experimental hemorrhagic shock.

OBJECTIVE: Lisofylline is an enantiomer-specific, alkyl-substituted methylxanthine, which has specific and potent activity in down-regulating leukocyte activation. This study was designed to test the efficacy of lisofylline in the resuscitation of rats subjected to experimental hemorrhagic shock. DESIGN: Prospective, randomized, and blinded survival studies were performed with two lisofylline dosing regimens added to fluid resuscitation in a shock model. In addition, white cell adhesiveness was measured to assess the effects of lisofylline. SETTING: Animal laboratory. SUBJECTS: Sixty Sprague-Dawley rats. INTERVENTIONS: Lisofylline or placebo was added to the resuscitation regimen, either as a single dose or over 24 hrs. MEASUREMENTS AND MAIN RESULTS: The 72-hr survival rate, white blood cell count, and platelet adhesiveness were determined. When a single 1-hr infusion of lisofylline was added to the initial resuscitation regimen, the 72-hr survival rate increased from 20% in controls to 50% (p < .009). When repeated doses of lisofylline were given over 24 hrs, the 72-hr survival rate increased from 40% in controls to 70% (p < .02). Control animals significantly increased leukocyte adhesiveness after shock and resuscitation. This increased adhesiveness was completely eliminated by lisofylline infusion. Platelet adhesiveness was not affected by lisofylline. CONCLUSIONS: Lisofylline improves survival in this model of hemorrhagic shock. Its beneficial effect may be related to down-regulation of leukocyte adhesiveness.

Adjuvants, Immunologic↗
PubMed1995

Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice.

Because phosphatidic acid (PA) pathway signaling may mediate many basic reactions involving cytokine-dependent responses, we investigated the effects of CT1501R, a functional inhibitor of the enzyme lysophosphatidic acid acyltransferase (LPAAT) which converts lysophosphatidic acid (Lyso-PA) to PA. We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also prevented neutrophil chemotaxis and adherence in vitro, and lung injury and lung neutrophil accumulation in mice subjected to hemorrhage and resuscitation. In addition, CT1501R treatment prevented increases in mRNA levels and protein production of a variety of proinflammatory cytokines in multiple lung cell populations after blood loss and resuscitation. Our results indicate the fundamental role of PA metabolism in the development of acute inflammatory lung injury after blood loss.

Acyltransferases↗
PubMed1993

Purification, receptor binding analysis, and biological characterization of human melanoma growth stimulating activity (MGSA). Evidence for a novel MGSA receptor.

Human melanoma growth stimulating activity (MGSA) is a mitogenic factor first identified in the conditioned media of human melanoma cells. Structurally, MGSA belongs to a superfamily of proteins that includes interleukin-8 (IL-8) and platelet factor 4. These proteins are involved in inflammatory processes, and an understanding of their mechanism of action should provide insight into their pathophysiology. In this study, we report the high level expression of recombinant human MGSA in Escherichia coli. The structure was confirmed by mass spectrometry and NH2-terminal amino acid sequencing. Receptor binding studies were carried out in a human melanoma cell line, Hs294T, and in U937 cells. Direct binding experiments with 125I-MGSA in Hs294T cells have allowed us to identify a novel MGSA receptor in these cells, with a KD of 3.9-4.25 nM and approximately 52,960-67,758 binding sites/cell. These MGSA-binding sites were specific and could not be displaced by unlabeled IL-8. The MGSA receptor in these cells is biologically active, and the addition of ligand induces cellular proliferation in a dose-dependent manner. In U937 cells, unlabeled IL-8 and MGSA were able to completely displace radiolabeled IL-8. Scatchard analysis of the displacement binding data was consistent with binding to a single class of binding sites, and the calculated KD values were 2.4 +/- 0.6 nM for IL-8 and 3.2 +/- 0.80 nM for MGSA. Treatment of U937 cells with IL-8 or MGSA produced a rapid increase in Ca2+ flux; however, subsequent incubation with either ligand failed to produce any further Ca2+ flux. The IL-8 receptor in U937 cells was covalently labeled with 125I-IL-8 to reveal a protein with a molecular mass of 69 kDa.

Amino Acid Sequence↗