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Biomedical subjects

D H Hamer

Publications and source records attributed to D H Hamer.

At least 19 recordsLinked to original sources
PubMed2003

Beyond hormones: a novel hypothesis for the biological basis of male sexual orientation.

For the past several decades, research on the development of human sexual orientation has focused on the role of pre- or peri-natal androgen levels on brain development. However, there is no evidence that physiologically occurring variations in androgen exposure influence differences in sexual orientation. In this review, we discuss an alternative hypothesis involving genomic imprinting in the regulation of sex specific expression of genes regulating sexually dimorphic traits, including sexual orientation. A possible experiment to test this hypothesis is discussed.

Androgens↗
PubMed2001

Covariance structure of neuroticism and agreeableness: a twin and molecular genetic analysis of the role of the serotonin transporter gene.

The Revised NEO Personality Inventory domains of Neuroticism and Agreeableness are considered factorially distinct despite several intercorrelations between these domains. The genetic correlation, an index of the degree to which these intercorrelations are caused by genetic influences, was estimated using data from 913 monozygotic and 562 dizygotic volunteer twin pairs from Canada, Germany, and Japan. The serotonin transporter gene, 5-HTTLPR, was assayed in a sample of 388 nontwin sibling pairs from the United States to determine the contribution of the serotonin transporter locus to the covariation between the Neuroticism and Agreeableness scales. In all four samples, genetic influences contributed to the covariance of Neuroticism and Agreeableness, with the serotonin transporter gene accounting for 10% of the relationship between these domains.

Adult↗
PubMed2001

Incidence and predictors of surgical-site infections in Vietnam.

OBJECTIVE: To determine the incidence of, and risk factors for, surgical-site infections (SSIs). DESIGN: Prospective observational study of all patients undergoing surgery during a 3-month period. SETTING: Two urban hospitals in Hanoi, Vietnam. PATIENTS: All 697 patients admitted for emergent and elective surgery. METHODS: Data were collected on all patients undergoing surgery during a 3-month period at each hospital. We stratified the data by type of surgery, wound class, and Study on the Efficacy of Nosocomial Infection Control (SENIC) risk index. The analysis was done with the data sets from each hospital separately and with the combined data. The risk factors for SSI were identified using a logistic-regression model. RESULTS: During the period of observation, 10.9% of 697 patients had SSI. The SSI rate was 8.3% for clean wounds, 8.6% for clean-contaminated, 12.2% for contaminated, and 43.9% for dirty wounds. The lowest rate of SSI (2.4%) was found in obstetric-gynecologic procedures and the highest rate (33.3%) in cardiothoracic operations. Using the SENIC risk index, the incidence of SSI in low-risk patients was 5.1%; for medium-risk patients, 13.5%, and high-risk patients, 24.2%. In a logistic-regression model, abdominal surgery (odds ratio [OR], 4.46; P<.01) and wound class IV (OR, 5.67; P<.01) were significant predictors of SSI. All patients were treated with prolonged courses of perioperative antibiotics. Overall infection control practices were poor as a result of deficient facilities, limited surgical instruments, and a lack of proper supplies for wound care and personal hygiene. CONCLUSIONS: There was a higher incidence of SSI in low-risk patients in Vietnam compared with developed countries. Excessive reliance on antimicrobial therapy as a means to limit SSI places patients at higher risk of adverse effects from treatment and also may contribute to worsening problems with antimicrobial resistance. Establishment of an infection control program with guidelines for antimicrobial use should improve the use of prophylactic antibiotics and attention to proper surgical and wound-care techniques. These interventions also should reduce the incidence of SSI and its associated morbidity and costs.

Adolescent↗
PubMed2001

Association of DRD4 with attention problems in normal childhood development.

Several previous studies found an association of clinically diagnosed attention deficit hyperactivity disorder with long alleles of a variation in the DRD4 dopamine receptor gene exon III coding sequence. We evaluated the DRD4 polymorphism in a non-clinically selected sample of children for whom maternal reports of attention problems were available at 4 and 7 years of age. There was a significant elevation in attention problem scores in children carrying DRD4 long alleles that accounted for 3-4% of total variation at each age and for 5-7% of the temporally stable component of the phenotype. Our results show that the DRD4 gene influences normal as well as pathological attention processes, and the results highlight the utility of longitudinal measurements in psychiatric genetics.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

High-throughput SNP genotyping by allele-specific PCR with universal energy-transfer-labeled primers.

We have developed a new method for high-throughput genotyping of single nucleotide polymorphisms (SNPs). The technique involves PCR amplification of genomic DNA with two tailed allele-specific primers that introduce priming sites for universal energy-transfer-labeled primers. The output of red and green light is conveniently scored using a fluorescence plate reader. The new method, which was validated on nine model SNPs, is well suited for high-throughput, automated genotyping because it requires only one reaction per SNP, it is performed in a single tube with no post-PCR handling, the same energy-transfer-labeled primers are used for all analyses, and the instrumentation is inexpensive. Possible applications include multiple-candidate gene analysis, genomewide scans, and medical diagnostics.

Alleles↗
PubMed2000

Hepatic schistosomiasis.

Schistosomiasis is a major, worldwide cause of morbidity and mortality. Disease from the organism Schistosoma mansoni results from egg deposition in the liver, intestines, and other organs and is associated with an intense, granulomatous response from the human host. Clinical manifestations range from mild to severe intestinal forms, and hepatosplenic schistosomiasis, which is associated with hepatic fibrosis, portal hypertension, esophageal varices, and splenomegaly. This article presents information about the epidemiology, immunopathogenesis and clinical aspects of the disease, the relationship between hepatic schistosomiasis and viral infections, diagnosis, therapy, and control strategies for schistosomiasis.

Animals↗
PubMed2000

Interaction between the serotonin transporter gene and neuroticism in cigarette smoking behavior.

Cigarette smoking behavior is influenced by both personality traits and inherited factors. Previous research showed that neuroticism-a broad personality domain that includes anxiety, depression, impulsiveness and vulnerability-increases the risk of being a smoker, primarily because of difficulty in quitting. Neuroticism has also been associated with the 5-HTTLPR, a functional polymorphism in the promoter for the serotonin transporter gene. We used population and family-based methods to analyze the joint effects of the 5-HTTLPR and neuroticism on smoking behavior in a population of 759 never, current, and former smokers, all members of sib-pairs. Our main finding is that smoking behavior is influenced by an interaction between neuroticism and 5-HTTLPR genotype. Specifically, neuroticism was positively correlated with current smoking and negatively associated with smoking cessation in individuals and siblings with poorly transcribed 5-HTTLPR-S genotypes, but not in those with the more highly expressed 5-HTTLPR-L genotype. Individuals with both a 5-HTTLPR-S genotype and a high level of neuroticism had the greatest difficulty in quitting smoking. These data, if replicated, suggest that smoking behavior is more strongly influenced by the combination of the serotonin transporter gene and neuroticism than by either factor alone, and that personality scores and 5-HTTLPR genotype may predict the clinical efficacy of certain smoking cessation drugs.

Adolescent↗
PubMed2000

Pleiotropy of the serotonin transporter gene for seasonality and neuroticism.

Pleiotropy refers to the ability of a single gene to influence multiple traits. A polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) has previously been found to be associated both with the personality trait of neuroticism and with seasonal changes in mood and behavior, or seasonality. Hypothesizing that the contribution of the serotonin transporter gene to seasonality is specific, i.e. independent of neuroticism, we measured 5-HTTLPR genotypes and both psychological traits in 236 healthy volunteers. The results indicated that the 5-HTTLPR contributions to variation in the two traits are largely independent; approximately three-quarters of the effect of the gene on seasonality are not related to its effects on neuroticism. Moreover, the gene has a larger effect on the covariation between neuroticism and seasonality than it does on either trait alone. Sibling-pair analysis confirmed that the effects of the 5-HTTLPR are due to genetic pleiotropy rather than population stratification.

Adult↗
PubMed2000

Mediation of Cryptosporidium parvum infection in vitro by mucin-like glycoproteins defined by a neutralizing monoclonal antibody.

The protozoan parasite Cryptosporidium parvum is a significant cause of diarrheal disease worldwide. Attachment to and invasion of host intestinal epithelial cells by C. parvum sporozoites are crucial steps in the pathogenesis of cryptosporidiosis. The molecular basis of these initial interactions is unknown. In order to identify putative C. parvum adhesion- and invasion-specific proteins, we raised monoclonal antibodies (MAbs) to sporozoites and evaluated them for inhibition of attachment and invasion in vitro. Using this approach, we identified two glycoproteins recognized by 4E9, a MAb which neutralized C. parvum infection and inhibited sporozoite attachment to intestinal epithelial cells in vitro. 4E9 recognized a 40-kDa glycoprotein named gp40 and a second, >220-kDa protein which was identified as GP900, a previously described mucin-like glycoprotein. Glycoproteins recognized by 4E9 are localized to the surface and apical region of invasive stages and are shed in trails from the parasite during gliding motility. The epitope recognized by 4E9 contains alpha-N-acetylgalactosamine residues, which are present in a mucin-type O-glycosidic linkage. Lectins specific for these glycans bind to the surface and apical region of sporozoites and block attachment to host cells. The surface and apical localization of these glycoproteins and the neutralizing effect of the MAb and alpha-N-acetylgalactosamine-specific lectins strongly implicate these proteins and their glycotopes as playing a role in C. parvum-host cell interactions.

Animals↗
PubMed2000

Treatment of nosocomial pneumonia and tracheobronchitis caused by multidrug-resistant Pseudomonas aeruginosa with aerosolized colistin.

Gram-negative bacilli including multidrug-resistant (MDR) Pseudomonas aeruginosa are responsible for a significant proportion of episodes of nosocomial pneumonia. Since the development of new antibiotics with activity against gram-negative organisms has not kept pace with the increase in prevalence of MDR pathogens, there has been renewed interest in antimicrobial agents that had previously been used but had been abandoned because of toxic side effects. This report describes three patients with nosocomial pneumonia or tracheobronchitis due to multiresistant strains of P. aeruginosa for whom aerosolized colistin proved beneficial as supplemental therapy. Aerosolized colistin merits further consideration as a therapeutic intervention for patients with pulmonary infections due to MDR P. aeruginosa.

Administration, Inhalation↗
PubMed1999

A genetic association for cigarette smoking behavior.

Dopaminergic genes are likely candidates for heritable influences on cigarette smoking. In an accompanying article, Lerman et al. (1999) report associations between allele 9 of a dopamine transporter gene polymorphism (SLC6A3-9) and lack of smoking, late initiation of smoking, and length of quitting attempts. The present investigation extended their study by examining both smoking behavior and personality traits in a diverse population of nonsmokers, current smokers, and former smokers (N = 1,107). A significant association between SLC6A3-9 and smoking status was confirmed and was due to an effect on cessation rather than initiation. The SLC6A3-9 polymorphism was also associated with low scores for novelty seeking, which was the most significant personality correlate of smoking cessation. It is hypothesized that individuals carrying the SLC6A3-9 polymorphism have altered dopamine transmission, which reduces their need for novelty and reward by external stimuli, including cigarettes.

Adult↗
PubMed1999

Role of the serotonin transporter gene in temperament and character.

The biosocial model postulates that personality is comprised of two broad domains: temperament, which is largely due to inherited variations in specific monoamine neurotransmitter systems; and character, which arises from socioculturally learned differences in values, goals, and self-concepts and is the strongest predictor of personality disorders. The model also proposes that serotonin modulates the temperament trait of harm avoidance. We analyzed the association of temperament and character traits with the 5-HTTLPR, an inherited variation that modulates serotonin transporter gene expression, in 634 volunteer subjects. Contrary to theory, the 5-HTTLPR was most strongly associated with the character traits of cooperativeness and self-directedness. Associations with the temperament traits of reward dependence and harm avoidance were weaker and could be attributable largely to cross-correlations with the character traits and demographic variables. Psychometric analysis indicated that the serotonin transporter influences two broad areas of personality, negative affect and social disaffiliation, that are consistent across inventories but are more concisely described by the 5-factor model of personality than by the biosocial model. These results suggest that there is no fundamental mechanistic distinction between character and temperament in regard to the serotonin transporter gene, and that a single neurotransmitter can influence multiple personality traits.

Adult↗
PubMed1996

Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.

Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.

Adolescent↗