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PubMed1992

Drug use contexts and HIV-consequences: the effect of drug policy on patterns of everyday drug use in Rotterdam and the Bronx.

Epidemiological data on HIV seroprevalence has been essential in assessing the (future) extent of the AIDS epidemic. By coupling these data with quantifiable variables related to injection drug use (frequency of injecting, number of needle sharing partners) specific 'risk behaviors' could be determined, accounting for the rapid spread of the virus in the injecting drug user (IDU) population. Yet, such data give little information on the social mechanisms and setting generating such risk behaviors. In order to understand the transmission of HIV among the IDU population one needs to study the micro settings and social context of drug use. This paper describes and explores certain patterns of drug use, sharing, and natural support systems found amongst IDUs in two very different cities, Rotterdam (The Netherlands) and the Bronx, New York City (USA). By specifying details of the micro-settings of everyday drug use in both locales, it is possible to identify certain common elements and consequences of personal and social behavior driven by drug use per se (e.g. drug preference), and to differentiate these from behaviors and consequences determined by drug policy and the social context in which drug use actually occurs. These policies and the social context they create can in turn be shown to relate to risks for HIV transmission, e.g. the increased likelihood of sharing injection equipment. A more careful ethnographic approach, taking advantage of natural experimental opportunities, comparisons and controls, may be utilized to examine drug-related behaviors in their social context and to better assess their relevance to public health--especially to AIDS.

Cross-Cultural Comparison↗

PubMedDate not supplied

Association between low plasma tryptophan and blackouts in male alcoholic patients.

Alcohol has been observed to alter various aspects of memory function. Some of the most extreme forms of memory impairment experienced by alcoholics are blackouts. There are at present very few data on the biological mechanisms underlying alcohol-related memory impairment. A variety of mechanisms including the cholinergic and catecholaminergic systems have been implicated in learning and memory. More recently, however, the importance of the serotonergic system in memory function has been demonstrated. We investigated whether patients with a history of blackouts had lower plasma levels of the serotonin precursor tryptophan than patients without such a history. Tryptophan values were significantly lower in patients who had experienced blackouts than in patients who had not. No significant differences between the two group of patients were observed for other amino acids sharing with tryptophan the same transport carrier into the brain. Drinking history variables did not differentiate among the two patient groups. Our data suggest that a decrease in plasma tryptophan (and concomitant lowered brain serotonin) could increase the vulnerability of certain individuals to manifestations of various aspects of memory impairment including one of its most extreme forms, the blackout.

Adult↗

PubMed2006

Joint models for multivariate longitudinal and multivariate survival data.

Joint modeling of longitudinal and survival data is becoming increasingly essential in most cancer and AIDS clinical trials. We propose a likelihood approach to extend both longitudinal and survival components to be multidimensional. A multivariate mixed effects model is presented to explicitly capture two different sources of dependence among longitudinal measures over time as well as dependence between different variables. For the survival component of the joint model, we introduce a shared frailty, which is assumed to have a positive stable distribution, to induce correlation between failure times. The proposed marginal univariate survival model, which accommodates both zero and nonzero cure fractions for the time to event, is then applied to each marginal survival function. The proposed multivariate survival model has a proportional hazards structure for the population hazard, conditionally as well as marginally, when the baseline covariates are specified through a specific mechanism. In addition, the model is capable of dealing with survival functions with different cure rate structures. The methodology is specifically applied to the International Breast Cancer Study Group (IBCSG) trial to investigate the relationship between quality of life, disease-free survival, and overall survival.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Agent-specific responses in the cingulate cortex during economic exchanges.

Interactions with other responsive agents lie at the core of all social exchange. During a social exchange with a partner, one fundamental variable that must be computed correctly is who gets credit for a shared outcome; this assignment is crucial for deciding on an optimal level of cooperation that avoids simple exploitation. We carried out an iterated, two-person economic exchange and made simultaneous hemodynamic measurements from each player's brain. These joint measurements revealed agent-specific responses in the social domain ("me" and "not me") arranged in a systematic spatial pattern along the cingulate cortex. This systematic response pattern did not depend on metrical aspects of the exchange, and it disappeared completely in the absence of a responding partner.

Brain Mapping↗

PubMed1993

Gene replacement, integration, and amplification at the gdhA locus of Corynebacterium glutamicum.

Gene replacement and integration in a Corynebacterium glutamicum ATCC 21086 derivative were achieved by transformation with a nonreplicative plasmid that contains the C. glutamicum ATCC 17965 gdhA gene modified by the insertion of an aphIII cartridge. We isolated rare derivatives of the integrative transformants that have higher levels of expression of the integrated plasmid genes than the parent. Different types of such amplified clones were distinguished according to their antibiotic resistance levels, enzyme specific activities, and physical structures. All amplified clones share a structural DNA motif confined to the chromosomal gdhA locus: a variable number (up to 10) of tandem copies of a unit that includes the selected gene and one flanking repeat. A given clone contains subpopulations that differ in the number of repeats of this unit.

Cloning, Molecular↗

PubMed1999

Invasive and noninvasive group A streptococcal isolates with different speA alleles in The Netherlands: genetic relatedness and production of pyrogenic exotoxins A and B.

Streptococcal pyrogenic exotoxin A (SPE-A) and SPE-B have been implicated in the pathogenesis of severe group A streptococcal (GAS) disease. We studied 31 invasive GAS strains including 18 isolates from patients with toxic shock syndrome and 22 noninvasive strains isolated in The Netherlands between 1994 and 1998. These strains were associated with the different allelic variants of the gene encoding SPE-A. We selected endemic strains with speA-positive M and T serotypes: speA2-associated M1T1 and M22-60T12 strains, speA3-associated M3T3 strains, and speA4-associated M6T6 strains. Since speA1-positive isolates were not frequently encountered, we included speA1 strains of different serotypes. The GAS strains were compared genotypically by pulsed-field gel electrophoresis and phenotypically by the in vitro production of SPE-A and SPE-B. All strains within one M and T type appeared to be of clonal origin. Most strains produced SPE-A and SPE-B, but only a minority of the speA4-positive isolates did so. Among our isolates, speA1- and speA3-positive strains produced significantly more SPE-A than speA2- and speA4-carrying strains, while SPE-B production was most pronounced among speA1- and speA2-containing strains. There was a marked degree of variability in the amounts of exotoxins produced in vitro by strains that shared the same genetic profile. We conclude that the differences in the in vitro production of SPE-A and SPE-B between our selected strains with identical M and T types were not related to either genetic heterogeneity or the clinical course of GAS disease in the patient from whom they were isolated.

Alleles↗

PubMed2000

Characterisation and genetic mapping of a new X linked deafness syndrome.

BACKGROUND: Hereditary forms of hearing loss are classified as syndromic, when deafness is associated with other clinical features, or non-syndromic, when deafness occurs without other clinical features. Many types of syndromic deafness have been described, some of which have been mapped to specific chromosomal regions. METHODS: Here we describe a family with progressive sensorineural hearing loss, cognitive impairment, facial dysmorphism, and variable other features, transmitted by apparent X linked recessive inheritance. Haplotype analysis of PCR products spanning the X chromosome and direct sequencing of candidate genes were used to begin characterising the molecular basis of features transmitted in this family. Comparison to known syndromes involving deafness, mental retardation, facial dysmorphism, and other clinical features was performed by review of published reports and personal discussions. RESULTS: Genetic mapping places the candidate locus for this syndrome within a 48 cM region on Xq1-21. Candidate genes including COL4A5, DIAPH, and POU3F4 were excluded by clinical and molecular analyses. CONCLUSIONS: The constellation of clinical findings in this family (deafness, cognitive impairment, facial dysmorphism, variable renal and genitourinary abnormalities, and late onset pancytopenia), along with a shared haplotype on Xq1-21, suggests that this represents a new form of syndromic deafness. We discuss our findings in comparison to several other syndromic and non-syndromic deafness loci that have been mapped to the X chromosome.

Adult↗

PubMed2005

Oligophrenin 1 mutations frequently cause X-linked mental retardation with cerebellar hypoplasia.

BACKGROUND: Mutations of oligophrenin 1, one of the first genes identified in nonspecific X-linked mental retardation (MRX), have been described in patients with moderate to severe cognitive impairment and predominant cerebellar hypoplasia, in the vermis. OBJECTIVE: To further delineate the phenotypic and mutational spectrum of the syndrome, by screening oligophrenin 1 in two cohorts of male patients with mental retardation (MR) with or without known posterior fossa anomalies. METHODS: Clinical examination, cognitive testing, MRI studies, and mutational analysis (denaturing gradient gel electrophoresis and direct sequencing) on blood lymphocytes were performed in 213 unrelated affected individuals: 196 patients classified as MRX and 17 patients with MR and previously detected cerebellar anomalies. RESULTS: Four novel oligophrenin 1 mutations were identified. In the MRX group, two nonsense mutations were detected. In the MR group, two mutations were found: a deletion of exons 16 to 17 and a splice site mutation. All patients shared characteristic clinical, radiologic, and distinctive features with a degree of intrafamilial variability in motor and cognitive deficits. CONCLUSIONS: Oligophrenin 1 mutations were found in 12% (2/17) of individuals with mental retardatin and known cerebellar anomalies and in 1% (2/196) of the X-linked mental retardation group.

Adolescent↗

PubMed1995

Distribution and action of SALMFamide neuropeptides in the starfish Asterias rubens.

The SALMFamides S1 and S2 are two structurally related neuropeptides that are present in starfish, and which share the C-terminal amino acid sequence SXLXFamide, where X is variable. To establish the distribution of S1 and S2 in starfish, we have raised antisera that recognise specifically the C-terminal pentapeptide sequence of either S1 or S2. Here we describe the production and characterisation of an S2-specific antiserum designated CLII. This antiserum, together with an S1-specific antiserum (BLII), has been used in a radioimmunoassay to measure S1 and S2 levels in extracts of body parts from the starfish Asterias rubens. High concentrations (250-400 pmol g-1) of both peptides were detected in the radial nerve cords of the nervous system and lower concentrations were detected in other body parts, including neuromuscular organs such as the tube feet, apical muscle and cardiac stomach. We have examined the pharmacological effects of S1 and S2 on the contractility of these three preparations. Neither S1 nor S2 influenced the tone of tube foot and apical muscle preparations but S2 caused relaxation of cardiac stomach preparations, antagonising the contracting action of acetylcholine.

Animals↗

PubMed2006

Early autoimmune destruction of islet grafts is associated with a restricted repertoire of IGRP-specific CD8+ T cells in diabetic nonobese diabetic mice.

beta cell replacement via islet or pancreas transplantation is currently the only approach to cure type 1 diabetic patients. Recurrent beta cell autoimmunity is a critical factor contributing to graft rejection along with alloreactivity. However, the specificity and dynamics of recurrent beta cell autoimmunity remain largely undefined. Accordingly, we compared the repertoire of CD8+ T cells infiltrating grafted and endogenous islets in diabetic nonobese diabetic mice. In endogenous islets, CD8+ T cells specific for an islet-specific glucose-6-phosphatase catalytic subunit-related protein derived peptide (IGRP206-214) were the most prevalent T cells. Similar CD8+ T cells dominated the early graft infiltrate but were expanded 6-fold relative to endogenous islets. Single-cell analysis of the TCR alpha and beta chains showed restricted variable gene usage by IGRP206-214-specific CD8+ T cells that was shared between the graft and endogenous islets of individual mice. However, as islet graft infiltration progressed, the number of IGRP206-214-specific CD8+ T cells decreased despite stable numbers of CD8+ T cells. These results demonstrate that recurrent beta cell autoimmunity is characterized by recruitment to the grafts and expansion of already prevalent autoimmune T cell clonotypes residing in the endogenous islets. Furthermore, depletion of IGRP206-214-specific CD8+ T cells by peptide administration delayed islet graft survival, suggesting IGRP206-214-specific CD8+ T cells play a role early in islet graft rejection but are displaced with time by other specificities, perhaps by epitope spread.

Animals↗

PubMed1992

Biochemical characterization and zymodeme classification of Leishmania isolates from patients, vectors, and reservoir hosts in Kenya.

A total of 407 Leishmania and other Leishmania-like isolates obtained from patients, other vertebrates, sand fly vectors, and other arthropods from Kenya and other countries were characterized and compared with several World Health Organization and other well-characterized reference strains of Leishmania, Trypanosoma, Crithidia, Herpetomonas, and Leptomonas by cellulose acetate electrophoresis (CAE), using 20 enzyme systems. Analysis of the isoenzyme banding patterns (IBP) of the isolates generated isoenzyme profiles that were resolved as zymodemes and tabulated. Isolates that produced similar isoenzyme profiles in all 20 enzyme systems were placed into a particular Leishmania isoenzyme taxon, with the zymodeme designated numerically as Zn. A total of 66 zymodemes were recorded for the 407 isolates studied. To obviate the need to draw all 66 representative IBP for each of the 20 enzyme systems, the 66 zymodemes (Z1-Z66) were again placed into similarity groups represented by pattern number or Pn. This resulted in 23-50 IBP (Pn) per enzyme system. The highest number of IBP scored was for malate dehydrogenase (MDH) (P1-50) and the lowest score was for glucose-6-phosphate isomerase (GPI) (P1-23). From these different isoenzyme profiles or zymodemes, IBP of 14 (MDH, GPI, nucleoside hydrolase, phosphoglucomutase, malic enzyme, isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase, mannose-6-phosphate isomerase, 6-phosphogluconate dehydrogenase, glutamate oxaloacetate transferase/aspartate aminotransferase, glutathione reductase, superoxide dismutase, fumarase, and glyceraldehyde-3-phosphate dehydrogenase) of the 20 enzyme systems were selected for computer-calculated numerical taxonomy. Consistent individual isoenzyme bands with similar relative mobilities of the 14 enzyme systems were scored into groups (allelomorphs, allozymes, or electromorphs) and used in cluster analysis. For each pattern in every profile, the presence of a consistent band was entered as 1 and its absence as 0. A total of 419 allozyme characters (variables) were scored for the 14 enzyme systems. Lastly, all different zymodemes sharing a particular IBP (Pn) within an enzyme system were counted and the total number was shown as a zymodeme frequency (Zf). Final analysis of the CAE isoenzyme profiles and cluster-dendrograms resulted in the identification of several potentially new species and subspecies of Leishmania and other Leishmania-like isolates from patients, sand flies, and animal reservoir hosts collected from Kenya and other locations in Africa. Zymodeme analysis of the Kenyan visceral and cutaneous leishmaniasis isolates resulted in the identification of 11 subpopulations of the L. donovani species complex and six subpopulations of the L. tropica species complex endemic to different geographic areas of Kenya.

Animals↗

PubMedDate not supplied

Nursing staff attitudes toward the work environment in a skilled nursing facility.

This study examines the attitudes of nursing staff toward their work environment in one long-term-care facility. It was conducted in response to differences noted in job performance between two staff subgroups assigned to different work stations, a phenomenon not uncommon in institutions that are divided into wings, floors, or other subgroups. Through analysis of questionnaire responses and patient-care data, the authors identified an intragroup conflict between two subgroups of nursing aides that appeared to be a cause of low morale among one group of aides. The authors suggest several management strategies that could effectively improve morale and job performance. Most human-service and health professions have been primarily client- or patient-centered, particularly the nursing profession in which the majority of literature and research focuses on improving patient care. Less attention has been given to the stresses experienced by care-givers in health settings, and their potential effects on job performance. Issues such as burnout, stress-related illnesses, morale building, and new management approaches in long-term care only recently have been addressed. In a series of studies about the burnout syndrome in child care and mental health workers, it was noted that several institutional and personal variables affected people's attitudes toward their work, the institution, and patients. For example, when work relationships were good, staff members reported more positive feelings about their jobs. Other institutional variables relevant to long-term care included work schedules, work-sharing, degree of power or influence in decision-making, and feedback about job performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1999

The impact of relational activities on HMO organizational outcomes.

OBJECTIVE: To report the findings of an empirical study of health maintenance organization (HMO) organizational outcomes and relational activities in HMO-pharmaceutical manufacturer relations. STUDY DESIGN: A mailed survey of a national random sample of 273 HMOs. SUBJECTS AND METHODS: Data were obtained from 111 HMOs regarding their inter-organizational relations with a pharmaceutical manufacturer. Respondents reported on 3 relational activities (initiating behavior, flexibility, bidirectional communication) and 4 HMO organizational outcomes (long-term orientation, equity in sharing costs and benefits, commitment between partners, financial performance). Also, 3 control variables were assessed: number of enrolled beneficiaries, HMO type, and estimated annual acquisition costs of pharmaceuticals. Four multiple regression analyses were performed, each with one organizational outcome variable as the dependent variable. Measures of relational activities and the control variables were the independent variables in the regressions. RESULTS: The response rate was 40.7%. All 3 relational activities showed significant associations with HMO organizational outcomes. Two relational activities (bidirectional communication, initiating behavior) showed significant and positive associations with a long-term orientation. Independent practice association (IPA)-model HMOs were less likely to report a long-term orientation toward a pharmaceutical manufacturer than other types of HMOs (adjusted R2 = 0.40). Bidirectional communication and flexibility were significantly and positively associated with the equity of costs and benefits (adjusted R2 = 0.29). Commitment had significant positive associations with all 3 relational activities (adjusted R2 = 0.50). All 3 relational activities had significant positive associations with financial performance. HMOs with an annual acquisition cost > $2 million were less likely to report favorable financial performance associated with a pharmaceutical manufacturer than were HMOs with lower costs (adjusted R2 = 0.42). CONCLUSION: Relational activities, such as initiating behavior, flexibility, and bidirectional communication, can facilitate positive outcomes for HMOs. It is important for all parties interested in healthcare to recognize that managing care creates a tension between achieving patient outcomes and organizational outcomes.

Communication↗

PubMed1999

Cloning and functional characterization of a Caenorhabditis elegans muscarinic acetylcholine receptor.

A cDNA clone encoding a muscarinic acetylcholine receptor (mAChR) has been isolated from the nematode Caenorhabditis elegans. The nematode mAChR, consisted of 585 amino acids, displays a high degree of amino acid sequence homology to other invertebrate and vertebrate mAChRs. Excluding a highly variable middle portion of the third intracellular loop, the C. elegans mAChR shares about 51% amino acid sequence identity with a Drosophila mAChR and 42-44% identity with human m1-m5 mAChR subtypes. Comparison of the cDNA sequence with the corresponding genomic sequence reveals that the C. elegans mAChR gene contains ten introns, eight of them in the coding region. Pharmacological profiles of the C. elegans mAChR expressed in Chinese hamster ovary (CHO) cells were shown to be similar to those of mammalian counterparts, indicating that ligand binding domains of the receptor have been conserved during evolution. When this cloned receptor was expressed in Xenopus oocytes, acetylcholine evoked a transient Cl- current. Furthermore, activation of the receptor with oxotremorine, acetylcholine or carbachol resulted in the stimulation of phosphatidylinositol metabolism in CHO cells, suggesting that the receptor is coupled to phospholipase C activation.

Acetylcholine↗

PubMed2000

Analysis of expressed immunoglobulin heavy chain genes in familial B-CLL.

In this study, we wished to determine whether familial chronic lymphocytic leukemia of B-cell phenotype (CLL) shares with sporadic B-CLL the same immunoglobulin (Ig) heavy chain variable region (VH) gene usage and occurrence of somatic mutation, to gain insight into the pathogenetic relatedness of these epidemiologically distinct forms of CLL. We therefore analyzed the expressed Ig heavy chain genes in 23 cases (11 families) of familial CLL, and compared these results with data previously reported for sporadic CLL. In addition, we assessed the relationship of the occurrence of somatic mutation to several clinical and phenotypic features. The distribution of V genes among these cases was similar to that observed in sporadic CLL: VH3 > VH1 > VH4. Thirteen of the 23 cases (57%) showed germ line VH gene sequences, whereas somatic mutations were detected in 10 cases (43%). The average mutation frequency of these latter 10 cases of was 6.7% (ranging from 1.7% to 8.8%), and evidence of antigen selection was noted in 6. Intraclonal variation, followed by clonal evolution and the appearance of a second clone over a 20-year period was observed in 1 case, suggesting that mutations can continue to accumulate after neoplastic transformation. The presence of somatic mutations correlated with age at presentation, low white blood cell (WBC) count, and low fluorescence intensity of surface CD5, and the potential significance of these relationships is discussed. Our data indicate that familial and sporadic B-CLL display a similar pattern of immunoglobulin gene usage and frequency of somatic mutation, and are consistent with a common ontogeny and immunogenetic origin for these 2 epidemiologically distinct forms of CLL. (Blood. 2000;95:1413-1419)

Adult↗

PubMed2004

How learning one category influences the learning of another: intercategory generalization based on analogy and specific stimulus information.

We investigated the effect of learning one category structure on the learning of a related category structure. Photograph-name combinations, called identifiers, were associated with values of four demographic attributes. Two problems were related by analogous demographic attributes, common identifiers, or both to examine the impact of common identifier, related general characteristics, and the interaction of the two variables in mediating learning transfer from one category structure to another. Problems sharing the same identifier information prompted greater positive transfer than those not sharing the same identifier information. In contrast, analogous defining characteristics in the two problems did not facilitate transfer. We computed correlations between responses to first-problem stimuli and responses to analogous second-problem stimuli for each participant. The analogous characteristics produced a tendency to respond in the same way to corresponding stimuli in the two problems. The results support an alignment between category structures related by analogous defining characteristics, which is facilitated by specific identifier information shared by two category structures.

Generalization, Psychological↗

PubMed2005

Molecular analysis of a 348 base-pair segment of open reading frame 2 of human astrovirus. A characterization of Colombian isolates.

We are reporting computational studies of several genotyped strains of astrovirus isolated in Colombia which we have genotyped using the 348-bp segment located between nucleotides 258 and 606 close to the amino terminal region of the complete ORF 2. By biocomputational techniques this 348-bp segment from the different strains was translated into an amino acid sequence. The sequences were aligned and compared in order to build a dendrogram. Our results show that the 348 bp and the 116 amino acid peptides cluster in a very conservative way, showing slight genetic variations between them. This slight sequence variability does not allow us to identify common amino acid substitution patterns shared by all members of each HAstV specific type, thus suggesting that antigenic epitopes are probably located outside the 116 peptide fragment of this capsid protein. These results show that there is little recombination among different regions of the ORF2, thus suggesting that this genotyping method should continue to be useful for serotyping HAstV isolates.

Astroviridae Infections↗

PubMed2006

[Atrail fibrillation and heart failure: a complex relationship].

Atrial fibrillation (AF) and heart failure (HF) often coexist in the same patient, not only because they can result from the same heart disease, but also because each of them can directly lead to the other. In the genesis of AF, structural, electrical and functional factors share a key role, but the importance of any of them is variable, according to the different clinical situations. AF causes atrial changes, electrical, anatomical or both, that can result in maintenance, recurrence and even irreversibility of the arrhythmia. In addition, AF affects the ventricular function by: a) loss of atrioventricular synchrony; b) irregular ventricular response; c) rapid ventricular response, possibly leading to tachycardia-induced cardiomyopathy. AF, thus, can "beget" HF, even in subjects with a previously normal heart. On the other hand, HF often "begets" AF. The prevalence of AF in patients with HF, indeed, increases from 5% (NYHA class I) to 50% (NYHA class IV). The mechanisms of HF-induced AF, include: a) increase of "critical atrial mass"; b) atrial stretch, with mechanoelectrical feedback; c) neuroendocrine changes; and d) extracellular matrix fibrosis. In brief, there is an important association between HF and development of AF and vice versa. AF-induced prognosis worsening of HF patients is not always true: in advanced HF, thus, no evidence has been obtained that the arrhythmia is associated with a decreased survival. This observation, as well as the lesson from "rhythm" versus "rate" control clinical trials, can help the management of AF in HF. The so-called "non channel target therapy" could be of value in this context.

Atrial Fibrillation↗