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At least 109 records · Page 6Linked to original sources

Antihyperglycemic N-sulfonyl-1a,2,6,6a-tetrahydro-1H,4H- [1,3]dioxepino[5,6-b]azirines: synthesis, X-ray structure analysis, conformational behavior, quantitative structure-property relationships, and quantitative structure-activity relationships.

A series of 1-sulfonyl-1a,2,6,6a-tetrahydro-1H,4H- [1,3]dioxepino[5,6-b]azirines, 4, has been synthesized and evaluated for its effects on blood glucose-decreasing activity. These derivatives were prepared from 4,7-dihydro-1,3-dioxepins 1 via vic(acylamino)halogenodioxepanes 2 and dioxepinoazirines 3. Quantitative structure--property relationship and quantitative structure--activity relationship models, based on X-ray and molecular mechanics analyses, to our knowledge the first in the field of antihyperglycemics, were developed. They allow the prediction of properties (RP-HPLC attention times) and activities (hypoglycemic activity ratio) by the Connolly's molecular surface areas. The lead compound in these models, sulfonyldioxepinoazirine 4i, expressed superior antihyperglycemic activity in comparison to metformin in alloxanized mice, irrespective of route of application. It significantly reduced blood glucose levels in glucose-primed mice, but it did not cause a dose dependent decrease of blood glucose level in healthy (nondiabetic, control) animals.

Animals↗

Identification of the structural requirements of the receptor-binding affinity of diphenolic azoles to estrogen receptors alpha and beta by three-dimensional quantitative structure-activity relationship and structure-activity relationship analysis.

Three-dimensional (3D) quantitative structure-activity relationship (QSAR) and structure-activity relationship (SAR) analyses were applied concurrently to a data set of highly selective estrogen receptor beta (ERbeta) agonists. The data set consisted of diphenolic azoles characterized by similar structural skeletons but with different binding modes to the estrogen receptor site. Models were developed separately with respect to the relative binding affinities (RBAs) to ERalpha and ERbeta. Steric and electrostatic fields were calculated for a training set of 72 compounds using comparative molecular field analysis (CoMFA). The model developed for ERalpha RBA yielded R2 of 0.91 and q(cv)2 of 0.60. The model developed for ERbeta RBA yielded R2 of 0.95 and q(cv)2 of 0.40. Both models were validated successfully using an external test set of 32 compounds. A new concept of test set evaluation based on the variability of the biological response due to the variability of the living organism has been introduced. The CoMFA analysis was supported by a SAR study. In addition to the most favorable steric and electrostatic regions identified by CoMFA, a number of structural descriptors were identified as being important for binding. These are the number of substituents attached to the main skeleton of each compound, the largest distance between the oxygen atoms of each molecule, and the angle defined by the planes that split the phenyl or the naphthyl and the benzisoxazole or the benzoxazole moiety in a morphometrically longitudinal way.

Azoles↗

Quantitative structure-pharmacokinetics relationships: II. A mechanistically based model to evaluate the relationship between tissue distribution parameters and compound lipophilicity.

The tissue-to-unbound plasma distribution coefficients (Kpus) of 14 rat tissues after i.v. administration of nine 5-n-alkyl-5-ethyl barbituric acids, determined in a previous study, were used to identify a model of the relationship between tissue distribution and lipophilicity of the homologs, expressed in terms of their octanol to water partition ratio, P. Based on mechanistic considerations and assumptions, the parameter model was expressed as Kpu tau = fw.tau [1 + a tau (nPt.tau)Pb tau], where fw.tau is the tissue water content. (nPt. tau) is the binding capacity of the tissue, n is the number of the binding sites, a tau and b tau are the parameters of the relationship Ka tau = a tau Pb tau; and Ka tau is the binding association constant of each tissue. The parameter model was linearized and fitted to the predetermined Kpu values, yielding correlation coefficients ranging between .940 and .997. The predictive performance of the parameter model was evaluated using a leave-one-out procedure with subsequent computation of the mean prediction error (ME = measurement of the prediction bias) and the square root of the mean squared prediction error (RMSE = measurement of the prediction accuracy). The ME varied between -22.48 and 61.14%, indicating a slight tendency for overpredicting. The RMSE was between 24.73 and 102% for the individual tissues across the different homologs; and between 28.33 and 85.2% for the individual homologs across the different tissues. The apparently high Kpu prediction errors, when translated through the low sensitivity of the barbiturate whole-body physiologically based pharmacokinetic model, established previously, leads to predicted tissue concentration-time profiles within 5 to 20% of the original ones. Therefore, it is concluded, that the identified mechanistically based model is a good predictor of the tissue-to-unbound Kpus in the rat tissues.

Animals↗

[Risk assessment of benign asbestosis (dose-effect relationship, time-effect relationship, co-factors)].

Despite the lack of precision of asbestos exposure assessments and the limitations of the main diagnostic epidemiological tool for asbestos-related diseases (i.e. standard X ray films), several issues concerning the risk of development of asbestos-related diseases are well established. For asbestosis, now a rare disease, the existence of a positive dose-response relationship, with a threshold or no-effect level, has been clearly demonstrated. The slope of the relationship curve is steeper for amphiboles than for chysotile, as it is for increased fiber length. Asbestosis is associated with an increased risk of bronchial carcinoma, however it is now known that exposure to asbestos of itself increases the risk of cancer even in the absence of any radiographic signs of pulmonary fibrosis. Pleural plaques occur even when the level of asbestos exposure is low. They are not only dose-dependent but are also latency-related. They have no prognostic significance in asbestos-exposed workers, but are associated with an increased risk for the subsequent development of mesothelioma and bronchial carcinoma when compared to the risk of the general population. Diffuse pleural thickening is associated with higher levels of asbestos exposure than those associated with pleural plaques. It usually follows a benign pleural effusion, which is a less frequent but earlier consequence of asbestos exposure than the other asbestos-related diseases documented above.

Asbestosis↗

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗

The quality of social relationships as a public health issue: Exploring the relationship between health and community in a disadvantaged neighbourhood.

This paper explores the relationship between the health of residents and the quality of social relationships within a disadvantaged urban neighbourhood. The author draws on her experience both as a nurse and an elected district councillor to illuminate connections between crime, antisocial behaviour, health and well-being. It is argued that these connections are neglected in health literatures, to the detriment of the development of a theoretical basis for health related community development work.

Journal Article↗

The relationship of the family social environment, peer influences, and peer relationships to altruistic orientation in Chinese children.

This study investigated the correlation between the family social environment, peer influences, and peer relationships to altruistic orientation in Chinese children. Results in the present study showed that (a) altruistic orientation measured by the Child Altruism Inventory (H. K. Ma & M. C. Leung, 1991) was directly associated with a positive family social environment, (b) altruistic orientation was directly associated with positive peer influences and was inversely associated with negative peer influences, and (c) altruistic orientation was directly associated with perceived prosocial behavior of one's best friend and inversely associated with perceived antisocial behavior of one's best friend. The findings suggested that a good family social environment, positive peer influences, and good peer relationships tended to increase altruistic orientation.

Altruism↗

Relationship schema formulation: role-relationship models and intrapsychic conflict.

Recurrent maladaptive interpersonal relationship patterns are a central characteristic of the personality disorders and the main focus in dynamic, cognitive, and family psychotherapies. In dynamic formulations the emphasis is on examining conflict in terms of opposing wishes, fears, and defenses. Such formulations can take place at various levels of information, involving ideas, emotions, self and objects. This paper presents a system for formulating intrapsychic conflicts at the level of person schemas (Horowitz 1988a). It uses units called Role-Relationship Models (RRM).

Adult↗

Shared relationship analysis: ranking set cohesion and commonalities within a literature-derived relationship network.

MOTIVATION: There is a general scientific need to be able to identify and evaluate what any given set of 'objects' (e.g. genes, phenotypes, chemicals, diseases) has in common. Whether it is to classify, expand upon or identify commonalities and functional groupings, informational needs can be diverse and the best source to identify relationships among a potentially heterogeneous set of objects is the scientific literature. RESULTS: We first establish a network of related objects by their co-occurrence within MEDLINE records. A set of objects within this network can then be queried to identify shared relationships, and a method is presented to score their statistical relevance by comparing observed frequencies with what would be expected in a random network model. Using Gene Ontology (GO) categories, we demonstrate that this method enables a quantitative ranking of the 'cohesiveness' of a set of objects and, importantly, allows other objects related to this set to be identified and evaluated for their 'cohesion' to it. Supplemental information: A list of ranked genes related to each GO category analyzed can be found at http://innovation.swmed.edu/IRIDESCENT/GO_relationships.htm

Abstracting and Indexing↗

Relationship classification using grade of membership analysis: a typology of sibling relationships in later life.

The results of a comparison of two typologies of sibling relationships in old age are reported. Both analyses rely on the same data collected in individual interviews with adults over the age of 65. The first typology was constructed using constant comparative analysis; the second relied on the grade of membership (GOM) technique. This is the first time GOM has been used to create a taxonomy of human relationships based on psychosocial variables. The two typologies are compared in terms of number of types generated, the characteristics of each type, factors influencing typological construction, and the utility of empirical results. Implications for additional use of the GOM technique to study late-life sibling relations are discussed.

Aged↗

Facing rejection: new relationships, broken relationships, shame, and stalking.

This study provides a preliminary examination of the relationship among shame-proneness, emotions, and persistent, unwanted courting or pursuit behaviour. A total of 222 undergraduates completed a questionnaire measuring responses to the termination of a relationship or the declining of a date. The Test of Self-Conscious Affect was used to measure shame. Although shame was unrelated to types of intrusive behaviour, individuals who engaged more repetitively in covert pursuit tended to ruminate more over their love interest than did those who rarely engaged in such behaviour. Rumination was positively correlated with shame. Self-harm behaviours and harm toward others were associated with feelings of sadness and depression, and those who engaged more often in harm toward others also reported feelings of anger and jealousy. Conclusions are made regarding the function of shame and other emotions in intrusive behaviour and their potential relevance to treatment of stalkers.

Adolescent↗

The mediational role of relationship efficacy and resource utilization in the link between physical and psychological abuse and relationship termination.

This study examines the roles of physical and emotional abuse and resource utilization, relationship efficacy, and childhood abuse on relationship status (together or separated) in a sample of 69 low-income, nonsheltered battered women. Separate path models were conducted for physical and psychological abuse. Increased physical abuse was related to separated status, increased resource utilization, and decreased efficacy. The effect of physical abuse on status was mediated by resource utilization and efficacy, whereas the effect of psychological abuse on status was partially mediated only by utilization. Increased childhood abuse was associated with together status. Baseline psychological but not physical abuse predicted a longer term separated status thereby suggesting that the effects of psychological abuse may be enduring.

Adult↗

Relationship between stress and relapse in multiple sclerosis: Part II. Direct and indirect relationships.

OBJECTIVE: The aim of this two-year prospective study was to determine which factors were: (i) directly related and/or (ii) indirectly related to multiple sclerosis (MS) relapse. These factors included life-event stressors, disease, demographic, psychosocial and lifestyle factors. BACKGROUND: Relatively little attention has been paid to the role of non-clinical relapse predictors (other than stressful life-events) in MS, or factors that indirectly impact on the stress-relapse relationship. METHODS: A total of 101 consecutive participants with MS were recruited from two MS clinics in Sydney, Australia. Stressful life-events, depression, anxiety and fatigue were assessed at study-entry and at three-monthly intervals for two years. Disease, demographic, psychosocial and lifestyle factors were assessed at baseline. Patient-reported relapses were recorded and corroborated by neurologists or evaluated against accepted relapse criteria. RESULTS: MS relapse was predicted by acute stressor frequency counts, coping responses that utilized social support, and being born in Australia, but not by chronic stressors, disease, demographic, psychosocial or lifestyle factors. No factors were found to indirectly impact on the stress relapse relationship. CONCLUSIONS: The number rather than severity of stressors was most important in relation to MS relapse risk, along with coping responses that utilized social support, suggesting that MS patients should avoid situations that are likely to generate multiple stressors or which provide few avenues for social support.

Adult↗

Medicare program; physician financial relationships with, and referrals to, health care entities that furnish clinical laboratory services and financial relationship reporting requirements--HCFA. Final rule with comment period.

This final rule with comment period provides that, if a physician or a member of a physician's immediate family has a financial relationship with an entity, the physician may not make referrals to the entity for the furnishing of clinical laboratory services under the Medicare program, except under specified circumstances. It contains revisions to our proposal of March 11, 1992, based on comments submitted by the public. Further, it incorporates the new expansions and exceptions created by the Omnibus Budget Reconciliation Act of 1993 and the amendments in the Social Security Act Amendments of 1994 (SSA '94), that are related to referrals for clinical laboratory services and have a retroactive effective date of January 1, 1992. In addition, we are responding to comments received on the interim final rule with comment period (published on December 3, 1991) that set forth Medicare reporting requirements for the submission by certain health care entities of information about their relationships with physicians. That document implemented the reporting requirements of section 1877(f) of the Social Security Act. This rule revises those requirements to incorporate the amendments to section 1877(f) made by SSA '94, to apply to any further reporting we may require.

Budgets↗

[Phylogenetic relationship of street rabies virus strains and their antigenic reactivity with antibodies induced by vaccine strains. I. Analysis of phylogenetic relationship of street rabies virus strains isolated in Poland].

The aims of these studies were: genetic characteristic of street rabies virus strains isolated from different animal species in Poland and determination of phylogenetic relationships to reference laboratory strains of the street rabies viruses belonging to genotype 1 and 5. The variability of rabies isolates and their phylogenetic relationship were studied by comparing the nucleotide sequence of the virus genome fragment. The Polish strains of genotype 1 belong to four phylogenetic groups (NE, CE, NEE, EE) corresponding to four variants: fox-racoon dog (F-RD); European fox 1 (F1); European fox 2 (F2) and European fox 3 (F3). On the Polish territories there are no rabies strains representing the variant dog-wolf and typical for arctic fox variant. The similarity of nucleotide and amino acid sequences of street rabies strains belonging to genotype 1 and laboratory strain CVS is very high. It is about 91% similarity at nucleotide level and 95% at amino acid level. Rabies strain CVS is similar to genotype 5 bat strains (EBL 1) only in about 69% and 74% at nucleotide and amino acid level, respectively. The genetic divergence of rabies strains circulating in Poland raised the need of permanent epidemiological and virological surveillance. The genotype and variant of isolated strains should be determined (using PCR and RLFP methods).

Animals↗

The anxiety-buffering function of close relationships: evidence that relationship commitment acts as a terror management mechanism.

Three studies examined the terror management function of romantic commitment. In Study 1 (N = 94), making mortality salient led to higher reports of romantic commitment on the Dimensions of Commitment Inventory (J. M. Adams & W. H. Jones, 1997) than control conditions. In Study 2 (N = 60), the contextual salience of thoughts about romantic commitment reduced the effects of mortality salience on judgments of social transgressions. In Study 3 (N = 100), the induction of thoughts about problems in romantic relationships led to higher accessibility of death-related thoughts than did the induction of thoughts about either academic problems or a neutral theme. The findings expand terror management theory, emphasizing the anxiety-buffering function of close relationships.

Adaptation, Psychological↗

Relationship between birth order of spouses with different degrees of consanguineous relationship.

The relationship between birth order of spouses with different degrees of consanguinity is examined in a sample of 1826 couples belonging to the endogamous Vadde Fisherfolk of Kolleru Lake, Andhra Pradesh, India. We attempt to explain the wide variation in the frequency of different kinds of consanguineous marriages through the age-sex structure of the population in general and especially of the related families. This structure may also be manifested in the association between the birth orders of spouses. A highly significant and large correlation between the birth orders of spouses in uncle-niece marriages and a gradual decrease in the correlation with increase in remoteness of the relationship between the spouses were observed. Given the distribution of age differences between the spouses and assuming a standard age-sex structure, it seems possible to estimate the optimum frequency with which at least close consanguineous marriages occur in any particular population.

Age Factors↗

Embryonic axis orientation in the mouse and its correlation with blastocyst relationships to the uterus. II. Relationships from 4 1/4 to 9 1/2 days.

Each of the three primary axes of the primitive streak (6 3/4 days p.c.) to C-shaped (9 1/2 days) stage mouse embryo has a specific relationship to the uterine horn axes. By a retrograde analysis of younger sectioned embryos it has been possible to construct an axis fate map for the implanting 4 1/4-day blastocyst and to show how its implantation in one or the other of two specific orientations to the ends and walls of the horn leads to these embryo-horn relationships. The implanting blastocyst axis fate map can be related to an axis fate map of the attached blastocyst (Smith, 1980) since these too are in one or the other of two orientations to the ends and walls of the horn. It is suggested that the asymmetries of the attached and implanting blastocysts that allowed the distinctive attachment and implantation orientations to be recognized, are the initial expressions of a three-dimensional system of positional information that is present in the attached blastocyst.

Animals↗