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Biomedical subjects

R C Wood

Publications and source records attributed to R C Wood.

At least 19 recordsLinked to original sources

Involvement of methionine in the synthesis of certain membrane-associated nucleotide sugars by human amnion (WISH) cells.

A plasma membrane preparation from human amnion (WISH) cells contained uridine diphosphate sugars and methyl-uridine diphosphate (mUDP) sugars. The synthesis of mUDP-glucose, mUDP-mannose, and mUDP-fucose by the membrane preparation occurred when supplemented with uridine-5'-diphosphate-glucose and S-adenosyl-L-methionine. It is suggested that this newly recognized route for fucose biosynthesis might be employed by certain transformed cells, and may partly account for the methionine dependence of certain human tumors. Additionally, it is suggested that, in colon cancer, a deficiency of folic acid and methionine might affect mUDP-sugar biosynthesis rather than the methylation of DNA.

3T3 Cells

Increased prevalence of the Taq I A1 allele of the dopamine receptor gene (DRD2) in obesity with comorbid substance use disorder: a preliminary report.

In order to investigate the prevalence of the Taq I A1 allele of the dopamine receptor gene (DRD2) in obesity with and without comorbid substance use disorder, a total of 40 patients, from an outpatient neuropsychiatric clinic in Princeton, New Jersey, were genotyped for presence or absence of the Taq I DRD2 A1 allele. The primary inclusion criterion for 40 obese subjects was a body mass index (BMI) equal to or over 25 (uncharacterized); 11 obese subjects had severe substance use disorder; 20 controls had a BMI below 25; and, 33 substance use disorder (less severe) patients had a BMI below 25. The data were statistically compared with three different sets of controls divided into three separate groups (Group I, n = 20; Group II, n = 286; Group III, n = 714). They differed according to screening criteria (drug, alcohol, nicotine abuse/dependence, BMI below 25 and other related behaviours including parental history of alcoholism or drug abuse and DSM IV, Axis I and Axis II diagnoses). Groups II and III were population controls derived from the literature. The prevalence of the Taq I A1D2 dopamine receptor (DRD2) alleles was determined in 40 Caucasian obese females and males. In this sample with a mean BMI of 32.35 +/- 1.02, the A1 allele of the DRD2 gene was present in 52.5% of these obese subjects. Furthermore, we found that in the 23 obese subjects possessing comorbid substance use disorder, the prevalence of the DRD2 A1 allele significantly increased compared to the 17 obese subjects without comorbid substance use disorder. The DRD2 A1 allele was present in 73.9% of the obese subjects with comorbid substance use disorder compared to 23.5% in obese subjects without comorbid substance use disorder. Moreover, when we assessed severity of substance usage (alcoholism, cocaine dependence, etc.) increasing severity of drug use increased the prevalence of the Taq I DRD2 A1 allele; where 66.67% (8/12) of less severe probands possessed the A1 allele compared to 82% (9/11) of the most severe cases. Linear trend analyses showed that increasing use of drugs was positively and significantly associated with A1 allelic classification (p < 0.00001). These preliminary data suggest that the presence of the DRD2 A1 allele confirms increased risk not only for obesity, but also for other related addictive behaviours (previously referred to as the Reward Deficiency Syndrome) and that a BMI over 25 by itself (without characterization of macroselection or comorbid substance use disorders) is not a sufficient criterion for association with the DRD2 A1 allele.

Adult

The D2 dopamine receptor gene as a determinant of reward deficiency syndrome.

The dopaminergic system, and in particular the dopamine D2 receptor, has been profoundly implicated in reward mechanisms in the brain. Dysfunction of the D2 dopamine receptors leads to aberrant substance seeking behaviour (alcohol, drug, tobacco, and food) and other related behaviours (pathological gambling, Tourette's syndrome, and attention deficit hyperactivity disorder). We propose that variants of the D2 dopamine receptor gene are important common genetic determinants of the 'reward deficiency syndrome'.

Compulsive Behavior

Involvement of folic acid in the synthesis of membrane-associated nucleotide sugars by normal and transformed mouse fibroblasts.

A plasma-membrane-containing fraction isolated from Swiss mouse (3T3) fibroblasts was found to contain uridine diphosphate sugars and methyl-uridine diphosphate (mUDP) sugars. The synthesis of the mUDP sugars by membrane preparations of normal and transformed 3T3 cells occurred from the intrinsic membrane uridine-diphosphate sugars + methylenetetrahydrofolic acid. Compared to the normal 3T3 cells, the synthesis of mUDP sugars by the transformed 3T3 cells was reduced by 49%. It is proposed that the plasma-membrane-associated mUDP sugars may be essential for normal cell growth.

3T3 Cells

Assessment of a model for measuring drug diffusion through implant-generated fibrous capsule membranes.

Fibrous tissue, which encapsulates subcutaneously implanted silastic, vinyl, polyurethane and Teflon discs in rats, has been isolated, characterized and tested for drug permeability in order to develop an in vitro model for determining the effect of this tissue on drug disposition from implant sites. With all materials, capsule tissue thickness and collagen content (approximately 59%) was consistent from 2 to 4 months after implantation. Silastic implants afforded the most consistent and usable tissue in terms of thickness and lack of vascularity, and these capsule membranes were used for determining the transport of three model compounds in an in vitro diffusion cell model. The rank ordering of permeability through these membranes was estrone (60.2 x 10(-6) cm s-1) > 3-O-methylglucose (18.7 x 10(-6) cm s-1) > dextran of molecular weight 70 000 (5.6 x 10(-6) cm s-1), which is consistent with expectations based on the molecular weights and partitioning behaviour of the model compounds. The results of these studies indicate that implant-generated encapsulating membranes can be successfully isolated and employed to study drug diffusion in an in vitro model, providing a direct assessment of the barrier properties of encapsulating membranes.

3-O-Methylglucose

Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour.

Drug and alcohol seeking behaviour has become a great global problem affecting millions of inhabitants with a cost to society in the billions. Dopaminergic reward pathways have frequently been implicated in the etiology of addictive behaviour. While other neurotransmitters have also been implicated, to date the only molecular genetic defect which has been found to associate with alcoholism, drug dependency, obesity, smoking, pathological gambling, attention-deficit-hyperactivity disorder (ADHD), Tourette syndrome, as well as other related compulsive behaviours, are the variants of the dopamine D2 receptor gene (DRD2). In this review of the available data on the subject, we report a number of independent meta-analyses that confirm an association of DRD2 polymorphisms and impulsive-additive-compulsive behaviour (IACB), which we have termed "Reward Deficiency Syndrome". While we agree that Meta-analyses of all exant studies support an association of variants of DRD2 and IACB, correct negative findings with alcoholism may be due to differences in assessing controls and inclusion/exclusion criteria for selection of diseased probands.

Behavior, Addictive

Occupational exposure to human immunodeficiency virus (HIV)-infected blood in Denver, Colorado, police officers.

The authors undertook a study of Denver, Colorado, police department officers to measure their risk of exposure to blood and human immunodeficiency virus (HIV) by type of work assignment and to document how exposures occurred. From December 1989 through March 1991, 137 officers reported an exposure to either blood or saliva, and 42 exposures to blood were independently documented. The overall rate of exposure to HIV-infected blood for medium and high risk assignments was 0.10 per 10,000 person-days. Thirty-two source persons underwent voluntary testing for HIV antibodies, and five (15.6%) were seropositive. Two thirds of the 42 blood exposures occurred in circumstances in which 1) there was little or no time for the officer to put on protective gloves and clothing because the officer was restraining or being assaulted by a suspect or 2) gloves would have not been protective because of penetration by needles. The authors conclude that Denver police officers rarely have percutaneous or mucosal exposures to blood, but when they do, the risk of exposure to HIV-infected blood is quite high. A health department can provide to police officers a number of services: evaluation of an incident involving contact with blood or body fluids to determine whether there was potential for disease transmission; information about modes of transmission and prevention of bloodborne diseases; serologic testing of source persons; HIV counseling for exposed officers and source persons; documentation for worker's compensation claims; and consultation regarding the use of zidovudine for postexposure prophylaxis.

Adolescent

Evaluation of clinical and laboratory aspects of antibody tests for detection of hepatitis C virus infection in blood donors and recipients from a low-risk population.

BACKGROUND: When the first-generation enzyme immunoassay (EIA) for detection of antibody to hepatitis C virus (anti-HCV) was approved in May 1990, blood banking agencies recommended testing of all components in inventory. In many cases, one or more components from these units had already been transfused. STUDY DESIGN AND METHODS: Donors that reacted in first-generation EIAs and recipients of their components were identified, and anti-HCV test methods (including first-generation EIA, second-generation EIA, and recombinant immunoblot assay [RIBA]) were evaluated. RESULTS: Of 66 donors identified as anti-HCV-positive by first-generation EIA, 17 were positive in second-generation EIA. Of these 17, 9 reacted in RIBA; 6 of these showed evidence of HCV infection in polymerase chain reaction (4) and/or probable transmission of HCV to a transfusion recipient (3). Of the 48 specimens that were positive in first-generation EIA and negative in second-generation EIA, only 1 was positive in RIBA; serum was not available for polymerase chain reaction testing, and there were no living transfusion recipients in whom to assess evidence of transmission of HCV. CONCLUSION: This study documents the low predictive value of EIAs for anti-HCV in a low-prevalence blood donor population and emphasizes the need for additional testing to confirm the specificity of samples that react in the screening tests.

Adolescent

Prolonged P300 latency in a neuropsychiatric population with the D2 dopamine receptor A1 allele.

The role of the dopaminergic system in P300 has been implicated and previous studies have suggested the presence of a heritable component in the genesis of P300 or P3, a late positive component of the event-related potential. In the present investigation, 155 Caucasian male and female diagnosed neuropsychiatrically-ill patients with and without comorbid drug and alcohol abuse/dependence were genotyped for the presence or absence of the A1 allele of the D2 dopamine receptor gene (DRD2). The relationship of the A1 and A2 alleles to P3 amplitude and latency was also determined. The results showed no significant difference in P3 amplitude between all groups studied with A1 and A2 allele carriers. However, we now report prolonged P3 latency in neuropsychiatrically-ill patients (with or without polysubstance abuse) with those carrying two copies of the A1 allele (homozygote) of the DRD2 gene (quadratic trend, p = 0.01). Moreover, the age-adjusted mean P3 latency in the D2A2/A2 allele group was 327.8 +/- 3.08 ms compared by ANOVA, to 360.04 +/- 4.86 ms in the D2A1/A1 group. Our work suggests an association of polymorphisms of the DRD2 gene and a biological marker previously indicated to have predictive value in vulnerability to substance abuse.

Adult

Involvement of folic acid and methionine in the synthesis of certain membrane-associated nucleotide sugars by Enterococcus hirae.

A membrane preparation from Enterococcus hirae contained UDP and methyl-UDP (mUDP) monosaccharides. This preparation, when incubated with combinations of folic acid, L-serine, and S-adenosyl-L-methionine in a reaction system containing UDP-glucose, promoted synthesis of certain mUDP sugars. Folic acid and serine produced mUDP-glucose and mUDP-rhamnose; S-adenosylmethionine produced mUDP-glucose, mUDP-mannose, and mUDP-fucose.

Cell Fractionation

Mechanism of irrigation effects on gingivitis.

Although gingivitis is initiated by plaque and plaque removal controls gingivitis, gingival irrigation with water has been shown to reduce gingivitis without reducing plaque. This study attempted to explore possible mechanisms involved in the treatment of gingivitis by water irrigation. Patients (n = 125) with more than 20 teeth, less than 4 sites with probing depth (PD) deeper than 6 mm, bleeding on probing (BOP) frequency of 30% or higher, and no systemic disease were randomized to one of four treatment groups: toothbrushing alone (brush), toothbrushing plus chlorhexidine 0.12% rinse 2x/day (CHX), toothbrushing plus water irrigation 1x/day (irr+H2O), or toothbrushing plus chlorhexidine 0.04% irrigation 1x/day (irr+CHX). Six sites/tooth were examined at baseline, and at 3 and 6 months for BOP and PD using an automated probe, and for gingival index (GI) and plaque index (PI) by standard means. A prophylaxis and oral hygiene instructions were provided after baseline and 6 month measurements. Subgingival microbial samples and crevicular fluid (GCF) were collected from 2 teeth/subject at each time point. Microbial samples were processed for anaerobic culture and the predominant cultivable flora was determined. CHX and irr+CHX had a 30 to 35% decrease in mean PI, while brush and irr+H2O had only a 12 to 16% decrease. BOP was reduced by 14% in the brush group and 23 to 24% in the other groups. GI was significantly correlated with PI in the brush, CHX, and irr+CHX groups, but not in the irr+H2O group. Prevotella intermedia was significantly reduced in both irrigation groups, but not CHX or brush groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Allelic association of the D2 dopamine receptor gene with cocaine dependence.

The objective of the present study was to examine allelic prevalence of the D2 dopamine receptor (DRD2) gene in male cocaine-dependent (CD) Caucasian (non-Hispanic) subjects and to determine the relationship of DRD2 alleles to family history and selected behavioral measures. The prevalence of the A1 allele in CD subjects (n = 53) was 50.9%. It was significantly higher than either the 16.0% prevalence (P < 10(-4)) in non-substance abusing controls (n = 100) or the 30.9% prevalence (P < 10(-2)) in population controls (n = 265) wherein substance abusers were not excluded. Similarly, a significantly higher prevalence (P < 10(-2)) of the B1 allele was found in CD subjects (n = 52) compared with non-substance abusing controls (n = 53); 38.5% vs. 13.2%. Logistic regression analysis of CD subjects identified potent routes of cocaine use and the interaction of early deviant behaviors and parental alcoholism as significant risk factors associated with the A1 allele. The cumulative number of these three risk factors in CD subjects was positively and significantly (P < 10(-3)) related to A1 allelic prevalence. The data showing a strong association of the minor alleles (A1 and B1) of the DRD2 with cocaine dependence suggest that a gene, located on the q22-q23 region of chromosome 11, confers susceptibility to this drug disorder.

Adult

The role of nonionic myelography in the diagnosis of lumbar disc herniation.

RATIONALE AND OBJECTIVES: The accuracy and safety of nonionic myelography, unenhanced computed tomography (CT), and magnetic resonance (MR) in the diagnosis of lumbar disc herniation are reviewed. The comparative costs of these tests are also considered. METHODS: The accuracy of imaging tests that diagnose disc herniations was established by conducting a Medline search between 1985 and 1992. The morbidity associated with these tests are less formally established from selected articles. Finally, the mediocre reimbursement rates of these tests are reviewed. RESULTS AND CONCLUSIONS: The evolution of nonionic contrast media from the first to the second generation has been accompanied by a notable decrease in adverse reactions. Although nonionic myelograms are now better tolerated by patients, noninvasive imaging with CT and MR imaging has become as accurate as or more accurate than lumbar myelography, and should replace it as a screening test. Computed tomography may have advantages over MR imaging when issues of availability and cost are considered. In contrast to lumbar myelography, CT myelography may continue to be a useful method for clarifying ambiguous results of noninvasive tests. The morbidity associated with CT myelography can be minimized by using low doses of a nonionic agent, keeping the patient well hydrated, and using a small lumbar puncture needle. The incidence of adverse reactions can be expected to decrease further as new nonionic dimers become clinically available.

Contrast Media

Relationship of "bleeding on probing" and "gingival index bleeding" as clinical parameters of gingival inflammation.

Bleeding on probing (BOP) and the gingival index have been used to clinically characterize the degree of gingival inflammation. It is, however, unclear to what extent these parameters correlate to each other and to probing pocket depth (PD). The purpose of this clinical study was to evaluate the association between BOP and GI bleeding (scores of 2 and 3), as well as the relationship of these variables to PD, in a group of patients presenting with naturally-occurring gingivitis. Based on screening examinations of 125 subjects with at least 20 teeth, no more than 4 sites with PD over 6 mm, a BOP frequency of 30% or greater, and no systemic condition that would influence the inflammatory response, were selected. 2 weeks after screening they were examined at 6 sites per tooth for plaque index, GI, PD and BOP. A standardized pressure sensitive probe (Florida Probe) with 20 g probing force was used for BOP and PD measurements. In this population, means of 40.9% (S.E. = 1.36) BOP sites and 35.3% (S.E. = 1.81) GI bleeding sites per patient were found. A total of 20,008 sites ranging in PD up to 5.9 mm were evaluated; however, the majority of sites (19,723, 98.6%) presented with < 4 mm PD. When sites were evaluated, BOP demonstrated a positive correlation with PD, whereas GI bleeding correlated with PD. For sites characterized by the absence of BOP as well as the absence of GI bleeding (scores 0 and 1), the highest % of agreement between the 2 indices (77.7%) was found in shallow sites (0.1-2 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Building-related asthma in Denver office workers.

OBJECTIVES: Reported cases of building-related asthma and hypersensitivity pneumonitis among workers in a Denver office building prompted an epidemiologic investigation. METHODS: A cross-sectional, self-administered survey of employees in the office building of the reported cases was compared with that of employees in a comparison building. RESULTS: A significant excess of respiratory disease existed among 512 Denver workers (case building) compared with 281 office workers in a suburban agency (control building). Denver employees had a higher prevalence of respiratory symptoms, and the prevalence of physician-diagnosed asthma with onset or exacerbation since building occupancy was 4.9 times greater for Denver employees than for suburban employees. Asthma was not associated with any particular ventilation system in the building. Water incursion from a below-grade wall may have contributed to the problem, but the etiology is unknown. CONCLUSIONS: This investigation provided evidence of office building-related asthma. Individual cases may be sentinel events for other cases of work-related asthma or hypersensitivity pneumonitis and may indicate a need for public health investigation of remediable causes.

Adult

Campylobacter enteritis outbreaks associated with drinking raw milk during youth activities. A 10-year review of outbreaks in the United States.

OBJECTIVE: To determine the incidence of recognized outbreaks of Campylobacter enteritis associated with drinking raw milk during youth activities. DESIGN: Retrospective survey of 51 state and territorial health departments. SETTING: The 50 United States and the Territory of Puerto Rico. POPULATIONS: Persons in preschool through college. MEASUREMENT: Information was obtained for all Campylobacter outbreaks associated with consumption of raw milk during youth activities from 1981 through 1990 that were investigated by state and territorial health departments. RESULTS: Twenty outbreaks were identified in 11 states. Four hundred fifty-eight outbreak-associated cases occurred among 1013 persons who drank raw milk, with an overall attack rate of 45%. At least one outbreak was reported for each year of the 10-year period. Fourteen outbreaks (70%) occurred among children in kindergarten through third grade, compared with one outbreak (5%) among fourth through sixth graders. The remaining five outbreaks (25%) occurred in mixed groups of children and teenagers. Only nine (60%) of 15 outbreaks identified from 1981 through 1988 were reported to the Campylobacter national surveillance system maintained by the Centers for Disease Control and Prevention. CONCLUSION: Drinking raw milk on school field trips or other youth activities continues despite the occurrence of multiple Campylobacter outbreaks documented from this practice. Such illnesses can be prevented by educating dairy farmers and officials of schools and youth organizations about the hazards of drinking raw milk. Public health organizations need to develop and implement such educational programs.

Adolescent

What is twin birthweight discordance?

The purpose of this study was to define the level of twin birthweight discordance across gestational age at which perinatal morbidity, neonatal death, or congenital anomalies were more likely to occur. One hundred ninety-four sets of twins (1982-1985) were retrospectively studied. Discordance was defined as (birthweight of larger-birthweight of smaller/birthweight of larger) x 100. The mean discordance was 10.3 +/- 8.5% (26 to 32 weeks = 7.6 +/- 5.9%; 33 to 36 weeks = 9.5 +/- 9.5%; 37 to 42 weeks = 11.4 +/- 8.5%) (p = 0.07). The occurrence of morbidity, neonatal death, and anomalies was increased with prematurity or the occurrence of small for gestational age in both twins. However, neither morbidity, neonatal death, nor anomalies were significantly related to level of discordance. These data demonstrate that prematurity and birthweight below the tenth percentile may present a greater threat to twins than does birthweight discordance. These findings should be given due consideration in planning antepartum management.

Birth Weight