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PubMed2000

Serotonin and amino acids: partners in delirium pathophysiology?

Delirium may be the result of dysfunction of multiple interacting neurotransmitter systems. Changes in the levels of various amino acids being precursors of cerebral neurotransmitters may affect their function and, thus, contribute to the development of delirium. Serotonin is one of the neurotransmitters that may play an important role in medical and surgical delirium. Normal serotonin synthesis and release in the human brain is, among others, dependent on the availability of its precursor tryptophan (Trp) from blood. The essential amino acid Trp competes with the other large neutral amino acids (LNAA) tyrosine, phenylalanine, valine, leucine, and isoleucine for transport across the blood-brain barrier. This competition determines its uptake into the brain, represented by the ratio of the plasma level of Trp to the sum of the other LNAA. The plasma ratio of Trp/LNAA, plasma level of Trp, and serotonin in plasma and platelets have been used as indirect peripheral measures for central serotonergic functioning. Both increased and decreased serotonergic activity have been associated with delirium. Serotonin agonists can induce psychosis, both elevated Trp availability and increased cerebral serotonin have been associated with hepatic encephalopathy, and excess serotonergic brain activity has been related to the development of the serotonin syndrome of which delirium is a main symptom. On the other hand, alcohol withdrawal delirium, delirium in levodopa-treated Parkinson patients, and postoperative delirium have been related to reduce cerebral Trp availability from plasma suggesting diminished serotonergic function. Rick factors for delirium such as severe illness, surgery, and trauma can induce immune activation and a physical stress response comprising increased activity of the limbic-hypothalamic-pituitary-adrenocortical axis, the occurrence of a low T3 syndrome, and, possibly, changes in the permeability of the blood-brain barrier. There are indications that these changes have their effect on plasma amino acid concentrations, e.g., Trp, and multiple cerebral neurotransmitters, including serotonin. This stress response may be different depending on the stage of illness being acute or chronic. It will require further study to determine the complex influence of the stress response and immune activation on plasma amino acids, neurotransmitter function and the development of delirium, especially in the more vulnerable older patients.

Aged↗
PubMedDate not supplied

"Keep a blank face. I need to tell you what has been happening to me.

PURPOSE: To explore adolescents' experiences of abuse in the year before and during pregnancy. METHODS: This prospective study used structured and focused interviews and content analysis. Forty teens' stories of abuse were extracted from focused interview questions during a larger study of pregnant adolescents aged 18 to 20. Elements of the stories were coded and categorized according to content and meaning. Seven themes were identified using a generalized qualitative approach that blended content and thematic analysis. RESULTS: Teens reported abuse from a variety of individuals, including intimate partners, former partners, and family members. Thirteen of the 40 teens reported being pregnant in the year before the index pregnancy, with 11 of the pregnancies ending in miscarriage, elective abortion, or fetal demise. Four of the pregnancy losses were directly attributed to abuse. Seven themes were identified that reflected the teens' stories of violence: seeking safety (self-protection with risks and benefits); losing faith (negative experiences with police and social justice institutions); experiencing loss (compromised reproductive health); living on the edge (substance abuse concerns); taking the next step (developmental concerns); crying out for help (suicide attempts); and changing and temporary relationships (loss of family bonds and serial monogamy). CLINICAL IMPLICATIONS: Routine screening for violence prior to and during pregnancy should include questions about past pregnancies, sexual abuse, and multiple perpetrators, as well as perpetrators other than intimate partners. Adolescent developmental concerns should be incorporated in safety planning and advocacy interventions.

Adolescent↗
PubMed1996

New X-linked mental retardation syndrome with the gene mapped tentatively in Xp22.3.

X-linked mental retardation (XLMR) is genetically heterogeneous and clinically variable. We describe a new XLMR syndrome of severe mental retardation and multiple congenital anomalies. Two sisters have (with 3 different partners) 3 severely handicapped sons. In 2 cases, oligohydramnios and intrauterine growth retardation were noted. Common anomalies included a square-shaped face, high and broad forehead, frontal bossing, downward slant of palpebral fissures, hypertelorism, epicanthic folds, long philtrum, thin upper lip, and apparently low-set ears. One boy has bilateral microphthalmos and sclerocornea, and his cousin has atrophy of the optic nerve. All 3 patients are blind and have profound statomotor and mental retardation, seizures, and a grossly abnormal electroencephalographic pattern. Additional findings are short stature, delayed bone maturation, hydronephrosis, vesicorenal reflux, cryptorchidism, clinodactyly of the 5th fingers, and transverse palmar creases. The karyotype is normal (46,XY). Segregation analysis showed perfect coinheritance between the clinical phenotype and alleles at several loci in Xp22.3, whereas recombinants were identified with marker loci from Xp22.2-qter. Analysis of multiple informative meioses suggests that the disease locus maps in Xp22.3 distal to DXS16.

Abnormalities, Multiple↗
PubMed1997

Sexual risk factors for cervical cancer among rural Indian women: a case-control study.

BACKGROUND: The association between sexual behaviour and cervical cancer is well established. Despite a high incidence of cervical cancer in India, its role has not been widely investigated in Indian women among whom the rate of sexual promiscuity is known to be very low. A hospital-based case-control study was carried out to investigate the role of sexual risk factors in cervical cancer among rural Indian women. METHODS: A case-control design was used in which a total of 268 subjects, comprising 134 women with invasive cervical cancer as cases and 134 control women were studied. A multiple logistic regression model was used to analyse the data. RESULTS: The risk factors found to be associated with cervical cancer were early age at first coitus, extramarital sex partners of women and the time interval since first exposure. In a multiple logistic regression model, independent effects were observed for early age at first coitus, showing maximum risk in women who reported their first intercourse at < 12 years of age, compared to that of women at > or = 18 years (odds ratio [OR] = 3.5. 95% confidence interval [CI]: 1.1-10.9). Increased risk was also seen for women who had extramarital sex relationships (OR = 5.5, 95% CI: 1.5-19.5). The significant effect of early age at first coitus persisted after adjustment for latency period which also showed its independent risk association with cervical cancer in the multivariate analysis. CONCLUSION: These findings confirm the association between early age at first coitus and cervical cancer in women with a low rate of sexual promiscuity and define the role of these risk factors in cervical carcinogenesis among rural Indian women.

Adult↗
PubMed2004

CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion.

DNA microarray profiling of CD4(+) and CD8(+) cells from non-treated relapsing and remitting multiple sclerosis (MS) patients determined that the cytoplasmic binding partner of fragile X protein (CYFIP2, also called PIR121) was increased significantly compared to healthy controls. Western analysis confirmed that CYFIP2 protein was increased approximately fourfold in CD4(+) cells from MS compared to inflammatory bowel disorder (IBD) patients or healthy controls. Because CYFIP2 acts as part of a tetrameric complex that regulates WAVE1 activation we hypothesized that high levels of CYFIP2 facilitate T cell adhesion, which is elevated in MS patients. Several findings indicated that increased levels of CYFIP2 facilitated adhesion. First, adenoviral-mediated overexpression of CYFIP2 in Jurkat cells increased fibronectin-mediated adhesion. Secondly, CYFIP2 knock-down experiments using antisense oligodeoxynucleotides reduced fibronectin-mediated binding in Jurkat and CD4(+) cells. Thirdly, inhibition of Rac-1, a physical partner with CYFIP2 and regulator of WAVE1 activity, reduced fibronectin-mediated adhesion in Jurkat and CD4(+) cells. Finally, inhibition of Rac-1 or reduction of CYFIP2 protein decreased fibronectin-mediated adhesion in CD4(+) cells from MS patients to levels similar to controls. These studies suggest that overabundance of CYFIP2 protein facilitates increased adhesion properties of T cells from MS patients.

Adult↗
PubMed1984

Sociological and psychological predictors of STD infection in homosexual men: a study of four countries.

I investigated over 600 homosexual men in four countries (Sweden, Finland, Ireland, and Australia) regarding the number of times they had contracted a sexually transmitted disease (STD) and several psychological variables including masculinity and feminity, sex role conservatism, relationships with parents, number of sexual partners, attitudes towards homosexuality, and involvement in the homosexual subculture. Using multiple linear regression in each country, it was found that 19-42% of the variance of number of times infected could be accounted for by psychosocial factors, seven of which were common to all countries. The number of sexual partners was not a significant variable in any country. These data strongly suggest that numbers of infections in homosexual men are best predicted by psychological factors, and this has considerable implications for preventative and treatment programmes for homosexuals.

Adult↗
PubMed2006

Gene polymorphisms in CCR5, CCR2, CX3CR1, SDF-1 and RANTES in exposed but uninfected partners of HIV-1 infected individuals in North India.

Repeated exposure to human immunodeficiency virus (HIV) does not always result in infection. Understanding the mechanisms that give protection against progressive infection with HIV may help in the development of a vaccine. In order to determine the influence of host genetic factors on HIV resistance, we studied 35 exposed but uninfected (EU) partners of HIV-1 infected individuals for polymorphisms in multiple chemokine and chemokine receptor genes and compared the results with those for 75 HIV-1 seronegative normal healthy controls (HC) and 50 HIV infected controls. There was no association between CCR5-Delta32, CCR2-64I, CX3CR1-280 M, CX3CR1-249I, SDF-3'A, RANTES-28G and RANTES-403A polymorphisms and susceptibility against HIV in our cohort of EU individuals. An increased frequency of SDF-1 3'A and RANTES-403A genotypes was present in EU individuals but the difference was not statistically significant when compared to healthy and HIV infected controls. These observations suggest that mechanisms other than genetic mutations of these genes might be responsible for resistance to HIV infection in these individuals.

CX3C Chemokine Receptor 1↗
PubMed1998

Alcohol use, perceptions of the effects of alcohol use, and condom use in urban minority youth.

This study examined the relations between alcohol use, perceived effects of alcohol use, and condom use in three different types of sexual partners in African American and Hispanic youth. Data were drawn from a household probability sample of minority youth (N = 1435) living in Detroit. Relationships were examined among three types of sexual partners: "married/lived with" partners, "knew well" partners, and "casual" partners. The effects of alcohol on condom use and perceived effects of alcohol on condom use were investigated using multiple regression with controls for demographic variables and sexual history. The quantity of alcohol consumed with partners was negatively related to condom use in all types of partners. The quantity of alcohol use was also negatively related to the perceived effect of alcohol use on condom use only with "knew well" partners.

Adolescent↗
PubMed2005

Does pregnancy provide immunity from intimate partner abuse among Hong Kong Chinese women?

The level of intimate partner abuse that occurs in Hong Kong Chinese families and the type, nature, and severity of abuse are primary concerns of those who are engaged in efforts to reduce and control abuse. A total of 1200 postnatal women were recruited at a university-affiliated regional public hospital to participate in a study with a retrospective explorative comparative design. The women were identified as abused or non-abused using the Abuse Assessment Screen Questionnaire (AAS). The type, nature, and profile of intimate partner abuse were investigated by using the Revised Conflict Tactics Scale (CTS-2). The vulnerable factors and predictors of abuse during pregnancy were explored in their demographic, psycho-socio-economic-cultural, and obstetric aspects. Analysis of the data indicated that 134 (11.2%) of the women had experienced abuse during pregnancy. The majority of this abuse took the form of psychological aggression (79.1%), and nearly half (49.3%) of the abused women had experienced sexual abuse. The husband was the perpetrator in the majority of cases (82.1%). Women who were younger, born in Hong Kong, single or cohabiting, had poor socio-economic status, a poor partner relationship, and an unplanned pregnancy were more likely to be abused based on multiple logistic regression models of various nature and type of abuse (p<0.05). The findings provide fundamental information for the prevention of intimate partner abuse among the Hong Kong population. The implications, limitations, and future research are discussed.

Adolescent↗
PubMed1998

The first births and ongoing pregnancies associated with sperm cryopreservation within evacuated egg zonae.

This new procedure principally aims to avoid a second or possibly multiple surgical procedures for sperm extraction from the male partner in cases of limited amounts of sperm cells, where normal freeze-thaw protocols would fail. Patients (n = 34) diagnosed as azoospermic, extreme oligozoospermic, or oligoasthenozoospermic underwent the process of sperm cryopreservation within evacuated egg zonae. Other samples were allocated to conventional sperm freezing. Sperm samples were acquired using testicular sperm extraction (TESE), microepididymal sperm aspiration (MESA), or fresh ejaculate. Subsequently, five of these 34 couples have undergone in-vitro fertilization (IVF) and achieved normal fertilization using post-thawed spermatozoa frozen under zonae pellucidae in conjunction with intracytoplasmic sperm injection (ICSI). The average fertilization rate for the post-thaw injected spermatozoa was 65%. This is comparable with the regular fertilization rate of 65% for combined MESA and TESE using fresh spermatozoa. All patients underwent embryo transfer. The average implantation rate per embryo was 31%; nearly the same for regular MESA/TESE ICSI cycles (32%). The first pregnancy associated with this procedure concluded with the full term delivery of healthy twin girls on July 18, 1997. The remaining four thaw procedures resulted in another twin delivery, an ongoing singleton gestation, a negative pregnancy test and a biochemical pregnancy respectively.

Adult↗
PubMed2005

A prospective follow-up of Epstein-Barr virus LMP1 genotypes in saliva and blood during infectious mononucleosis.

To monitor multiple Epstein-Barr virus (EBV) infections during the early and convalescent stages of infectious mononucleosis (IM), a cloning and sequencing study of the LMP1 gene was conducted in saliva and peripheral blood mononuclear cells (PBMCs) from 23 patients with IM at day 0 (D0) and day 180 (D180) after the onset of the disease. Multiple EBV strains were detected in 9 (39%) of the patients during follow-up, with 7 of 9 cases detected as early as D0. Six of the nine patients harbored the same dominant strain in saliva and PBMCs during follow-up, with a trend toward a restriction of the number of EBV strains in saliva but not in PBMCs at D180. Furthermore, transmission of a minor strain was observed between partners in a heterosexual couple. There was no correlation between multiple infections and EBV DNA load in either compartment.

Cloning, Molecular↗
PubMed2002

A single-chain antibody/epitope system for functional analysis of protein-protein interactions.

Protein-protein interactions play a critical role in cellular processes such as signal transduction. Although many methods for identifying the binding partners of a protein of interest are available, it is currently difficult or impossible to assess the functional consequences of a specific interaction in vivo. To address this issue, we propose to modify proteins by addition of an artificial protein binding interface, thereby forcing them to interact in the cell in a pairwise fashion and allowing the functional consequences to be determined. For this purpose, we have developed an artificial binding interface consisting of a anti-Myc single-chain antibody (ScFv) and its peptide epitope. We found that the binding of an ScFv derived from anti-Myc monoclonal antibody 9E10 was relatively weak in vivo, so we selected an improved clone, 3DX, by in vitro mutagenesis and phage display. 3DX bound well to its epitope in a yeast two-hybrid system, and GST-fused 3DX also bound to several Myc-tagged proteins in mammalian cells. In vivo binding was relatively insensitive to the position of the ScFv in a fusion protein, but was improved by including multiple tandem copies of the Myc epitope in the binding partner. To test the system, we successfully replaced the SH3 domain-mediated interaction between the Abl tyrosine kinase and adaptor proteins Crk and Nck with an engineered interaction between 3DX and multiple Myc tags. We expect that this approach, which we term a functional interaction trap, will be a powerful proteomic tool for investigating protein-protein interactions.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Survey of the geometric association of domain-domain interfaces.

Considering the limited success of the most sophisticated docking methods available and the amount of computation required for systematic docking, cataloging all the known interfaces may be an alternative basis for the prediction of protein tertiary and quaternary structures. We classify domain interfaces according to the geometry of domain-domain association. By applying a simple and efficient method called "interface tag clustering," more than 4,000 distinct types of domain interfaces are collected from Protein Quaternary Structure Server and Protein Data Bank. Given a pair of interacting domains, we define "face" as the set of interacting residues in each single domain and the pair of interacting faces as an "interface." We investigate how the geometry of interfaces relates to a network of interacting protein families, such as how many different binding orientations are possible between two families or whether a family uses distinct surfaces or the same surface when the family has diverse interaction partners from various families. We show there are, on average, 1.2-1.9 different types of interfaces between interacting domains and a significant number of family pairs associate in multiple orientations. In general, a family tends to use distinct faces for each partner when the family has diverse interaction partners. Each face is highly specific to its interaction partner and the binding orientation. The relative positions of interface residues are generally well conserved within the same type of interface even between remote homologs. The classification result is available at http://www.biotec.tu-dresden.de/~wkim/supplement.

Amino Acid Sequence↗
PubMed2006

The evaluation of the JEWEL project: an innovative economic enhancement and HIV prevention intervention study targeting drug using women involved in prostitution.

The JEWEL (Jewellery Education for Women Empowering Their Lives) pilot study examined the efficacy of an economic empowerment and HIV prevention intervention targeting illicit drug-using women (n=50) who were involved in prostitution in Baltimore, Maryland. The intervention was comprised of six 2-hour sessions that taught HIV prevention risk reduction and the making, marketing and selling of jewellery. Bivariate comparisons examined behaviour change pre- and 3-months post-intervention. The intervention's effect on the change in the number of sex trade partners from baseline to follow-up was explored with multiple linear regression. Participants were 62.0% African American, 5.0% were currently employed, and the median age was 39 years old (Inter Quartile Range [IQR]: 34-45). Women attended an average of six (IQR: 4.5-6.0) sessions. The women sold over $7,000 worth of jewellery in eleven sales. In comparing self-reported risk behaviours pre and 3-month post intervention participation, we found significant reductions in: receiving drugs or money for sex (100% versus 71.0%, p<0.0005); the median number of sex trade partners per month (9 versus 3, p=0.02); daily drug use (76.0% vs. 55.0%, p=0.003); the amount of money spent on drugs daily (US$52.57 versus US$46.71, p = 0.01); and daily crack use (27.3% versus 13.1.0%, p = 0.014). In the presence of other variables in a multivariate linear model, income from the jewelry sale was associated with a reduction in the number of sex trade partners at follow-up. The pilot indicated effectiveness of a novel, HIV prevention, economic enhancement intervention upon HIV sexual risk behaviours and drug utilization patterns.

Adolescent↗
PubMed2003

The role of sequential and concurrent sexual relationships in the risk of sexually transmitted diseases among adolescents.

PURPOSE: To explore whether patterns of sexual relationships, such as sequential (nonoverlapping in time) or concurrent (overlapping in time), are more important indicators of sexually transmitted disease (STD) risk among adolescents than number of sexual partners. METHODS: Data from 4,707 sexually active adolescents from the National Longitudinal Study of Adolescent Health were analyzed based on reported heterosexual relationships during the past 18 months. Adolescents were categorized as engaging in single, sequential, or concurrent sexual relationships. Demographic, behavioral, and social characteristics of each group were compared and multivariate logistic models were fit to determine STD risk associated with sexual relationship patterns and overall number of sexual partners during this same time period. RESULTS: Thirty-five percent of sexually active teens had more than one partner in the past 18 months, and 40% of these multiple partnerships were overlapping or concurrent in time. Teens in sequential and concurrent relationships reported lower condom use and a higher degree of regret of having sex owing to alcohol use than those in single relationships. Teens in concurrent relationships also reported the lowest self-efficacy to use contraceptives. Teens in sequential or concurrent relationships were more likely to report an STD than single-relationship teens (odds ratio 2.3 and 3.9, respectively); however, they were not statistically different from each other. Number of sexual partners during this same time period was not associated with STD risk once relationship pattern was considered. CONCLUSIONS: Adolescents who engage in sequential or concurrent sexual relationships differ in some important demographic, behavioral, and social characteristics and, when compared with those who engage in single relationships, have a significantly greater risk for STDs over and above the number of sexual partners.

Adolescent↗
PubMed1992

Socio-economic factors associated with HIV infection in pregnant women.

The HIV epidemic in women in Edinburgh has characteristics which enable a total population study. We studied retrospectively all women with a known history of injection drug use or with a seropositive drug-using partner in a five year period from 1985-1990. We sought to quantitate lifestyle and environmental factors associated with HIV infection in pregnant women and to test two hypotheses: that infected women would have more adverse socio-economic features, and that there would be a change in these factors with time. There were 244 pregnant women in the study. They were slightly younger than all Edinburgh City women and much less likely to be married. They were much more likely to live in areas of multiple housing deprivation. Only 16% of women, and 28% of partners, were in paid employment; 90% of women smoked and 76% had a history of injection drug use. Some 28% of previous children were in the care of another, often a relative, 8% of women had a recent prison admission, and 58% of those tested had antibodies to Hepatitis B. Univariate analysis showed that none of these factors was significantly different in HIV seropositive women except for prison admission, previous infection with Hepatitis B, which probably all related to type of drug use. Linear logistic regression suggested two other variables which distinguished between groups, but because these are composite, and dependent on incomplete data, this must be interpreted with caution. The same overall associations were found when only women with a history of injection drug use were considered. There was no statistically significant change in these factors with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1999

Teaching partner-focused questions to individuals who use augmentative and alternative communication to enhance their communicative competence.

A single-subject, multiple-probe experimental design was used to investigate the effect of instruction on the acquisition, generalization, and long-term maintenance of partner-focused questions (i.e., questions about communication partners and their experiences) by individuals who use augmentative and alternative communication (AAC). Six participants who had severe speech impairments and used AAC participated in the study; they ranged in age from 10 to 44 years, had a variety of disabilities, and used a range of AAC systems. Instruction used a least-to-most prompting hierarchy in real-world interactions and during simulations. All of the participants successfully learned to ask partner-focused questions spontaneously in social interactions; they required an average of approximately 6 hours of instruction (range: 3-11 hours). The participants generalized the use of partner-focused questions to new situations in the natural environment and maintained use of partner-focused questions at least 2 months postinstruction; one participant required some "booster" instructional sessions 4 weeks postinstruction to maintain her long-term use of partner-focused questions. The participants all reported high levels of satisfaction with the outcomes of the instructional program, as did their facilitators. Members of the general public, blind to the goals of the study, judged the majority of the participants to be more competent communicators after instruction.

Adolescent↗

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