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PubMed1996

Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency.

Holocarboxylase synthetase (HCS) catalyses the biotinylation of the four biotin-dependent carboxylases found in humans. A deficiency in HCS results in biotin-responsive multiple carboxylase deficiency (MCD). We have identified six different point mutations in the HCS gene in nine patients with MCD. Two of the mutations are frequent among the MCD patients analyzed. Four of the mutations cluster in the putative biotin-binding domain as deduced from the corresponding Escherichia coli enzyme and consistent with an explanation for biotin-responsiveness based on altered affinity for biotin. The two others may define an additional domain involved in biotin-binding or biotin-mediated stabilization of the protein.

Amino Acid Sequence↗
PubMed2004

Relationship of social cognitive theory factors to exercise maintenance in adults.

Modifiable variables related to Bandura's social cognitive theory were tested for their relationship to self-reported retrospective exercise maintenance in 178 adults. Significant bivariate correlations were found between length of adherence to regular moderate-to-vigorous exercise and item clusters reflecting social support (r = .42), self-management ability (r =.39), and ability to tolerate exercise-induced discomfort (r = .60). Stepwise multiple regression analysis indicated that each item cluster significantly contributed to the overall explained variance in length of exercise maintenance over 52 weeks (R2 =.43). When responses from each of the item clusters were summed, participants defined as adherents had significantly higher scores than drop-outs. Discussion emphasized the need for replication and implications for exercise adherence intervention.

Adult↗
PubMed2002

Activation of mouse Pi-class glutathione S-transferase gene by Nrf2(NF-E2-related factor 2) and androgen.

The Pi-class glutathione S-transferases (GSTs) play pivotal roles in the detoxification of xenobiotics, carcinogenesis and drug resistance. The mechanisms of regulation of these genes during drug induction and carcinogenesis are yet to be elucidated. Recently, Nrf2 (NF-E2-related factor 2; a bZip-type transcription factor) knockout mice were shown to display impaired induction of Pi-class GST genes by drugs. It is known that the mouse Pi-class GST gene GST-P1 is expressed predominantly in the male liver, and is regulated by androgen. To determine whether Nrf2 and the androgen receptor regulate GST-P1 directly, we analysed the molecular mechanism of activation of this gene by these factors. The promoter of the GST-P1 gene was activated markedly by Nrf2 in transient transfection analyses. Gel mobility shift assay and footprinting analyses revealed three Nrf2 binding sites: one at the proximal and two at distal elements, located at positions -59, -915 and -937 from the cap site. The fifth intron of the GST-P1 gene contains the androgen-responsive region. Multiple androgen receptor binding sites are clustered within a 500 bp region of this intron. The whole fragment contains a minimum of seven androgen receptor binding sites, which collectively display strong androgen-dependent enhancer activity. However, on division into small fragments containing two or three elements each, individual enhancer activities were dramatically decreased. This suggests that multiple elements work synergistically as a strong androgen-responsive enhancer. Our findings indicate that Nrf2 and the androgen receptor directly bind to and activate the mouse GST-P1 gene.

Androgens↗
PubMed1998

Personality disorders and relationship to personality dimensions measured by the Temperament and Character Inventory in patients with obsessive-compulsive disorder.

The occurrence of personality disorders was investigated in 36 patients with obsessive-compulsive disorder by means of the SCID Screen questionnaire. In addition, the personality dimensions were explored by means of the Temperament and Character Inventory (TCI). In total, 75% of the patients fulfilled the criteria for a personality disorder according to the SCID Screen questionnaire, mostly (55%) within cluster C. Several significant correlations were found between the separate personality disorders (PD) and subscales of the TCI, the most pronounced being between avoidant and obsessive-compulsive PD and novelty-seeking and self-directedness. Strong correlations were also found between self-directedness and paranoid and borderline PD. In multiple regressions where the presence of PD in clusters A, B and C, respectively, were used as dependent variables and where the separate subscales of the TCI were used as independent variables, the multiple R reached 0.68, 0.76 and 0.80 in clusters A, B and C, respectively. Thus 46-64% of the variance in the personality disorder clusters could be explained by the TCI subscales.

Adult↗
PubMed2002

Genetic risk determines the emergence of diabetes-associated autoantibodies in young children.

Timing of onset of autoimmunity is a prerequisite for unmasking triggers and pathogenesis of type 1 diabetes. We followed 4,590 consecutive newborns with 8 or 3% HLA-DQB1 conferred risk for type 1 diabetes at 3-, 6-, or 12-month intervals up to 5.5 years of age. Islet cell autoantibodies (ICAs) and, in the 137 children with ICAs, insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and IA-2 protein autoantibodies (IA-2As) were measured. Children with high genetic risk developed ICAs more often than those with moderate risk (log-rank P = 0.0015); 85 and 91% remained ICA negative by 5 years of age, respectively. The time of appearance of biochemical autoantibodies was then compared with the appearance of ICAs. IAAs and GADAs emerged usually before ICAs (means -1.8 and -1.5 months, respectively) and IA-2As after ICAs (mean 2.0 months). Ninety-five percent of all IAAs, GADAs, and IA-2As seroconversions occurred in a cluster (-12 to 8 months) around the ICA seroconversion. We conclude that diabetes-associated autoantibodies emerged in children with predisposing HLA-DQB1 alleles after 3 months of age at a constant tempo, determined by the genetic risk level, usually in the order of IAA, GADA, ICA, and IA-2A. Seroconversion to multiple autoantibody positivity usually occurred tightly clustered in time.

Alleles↗
PubMed1985

Multiple myeloma in three siblings.

All three siblings of a family developed multiple myeloma. Two siblings had a history of monoclonal gammopathy; in one of these two siblings and in the third sibling, the disease progressed rapidly. A review of the literature shows that of 38 previously reported pairs of siblings with plasma cell disorders, eight families had a third affected sibling and four another affected relative. This clinical clustering suggests that some cases of multiple myeloma may have a hereditary basis and that other family members may be at risk for developing the disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Vibrational shifts of OCS in mixed clusters of parahydrogen and helium.

We present a detailed theoretical study of the solvation structure and solvent induced vibrational shifts for an OCS molecule embedded in pure parahydrogen clusters and in mixed parahydrogen/helium clusters. The use of two recent OCS-(parahydrogen) and OCS-helium ab initio potential energy surfaces having explicit dependence on the asymmetric stretch of the OCS molecule allows calculation of the frequency shift of the OCS nu(3) vibration as a function of the cluster size and composition. We present results for clusters containing up to a full first solvation shell of parahydrogen (N=17 molecules), and up to M=128-N helium atoms. Due to the greater interaction strength of parahydrogen than helium with OCS, in the mixed clusters the parahydrogen molecules always displace He atoms in the first solvation shell around OCS and form multiple axial rings as in the pure parahydrogen clusters. In the pure clusters, the chemical potential of parahydrogen shows several magic numbers (N=8,11,14) that reflect an enhanced stability of axial rings containing one less molecule than required for complete filling at N=17. Only the N=14 magic number survives in the mixed clusters, as a result of different filling orders of the rings and greater delocalization of both components. The OCS vibration shows a redshift in both pure and mixed clusters, with N-dependent values that are in good agreement with the available experimental data. The dependence of the frequency shift on the cluster size and its composition is analyzed in terms of the parahydrogen and helium density distributions around the OCS molecule as a function of N and M. The frequency shift is found to be strongly dependent on the detailed distribution of the parahydrogen molecules in the pure parahydrogen clusters, and to be larger but show a smoother dependence on N in the presence of additional helium, consistent with the more delocalized nature of the mixed clusters.

Journal Article↗
PubMed2001

Multiple-goal pursuit and its relation to cognitive, self-regulatory, and motivational strategies.

BACKGROUND: The topic of academic goals has provided very important information about students' motivation. Traditional research has described several mutually exclusive goals that elicit different motivational patterns. Nevertheless, goal-orientation research has reported the possibility that more than one goal may operate simultaneously. AIM: The purpose of this study was to characterise multiple-goal groups of students, who use various types of cognitive, self-regulatory, and motivational strategies. SAMPLE: Participants were 595 Spanish-speaking university students at the University of A Coruña. METHOD: In order to examine the relationships between goal orientations and strategies, a Pearson correlational analysis was performed. Then, a cluster analysis was performed to identify potential subgroups of students with more than one simultaneously operative goal. Finally, a one-way test was conducted to determine whether the multiple-goal clusters differed in any of the nine strategies. RESULTS: Only those students who reported high task orientation tended to exhibit more frequent use of cognitive and self-regulatory strategies. Nevertheless, this does not mean that learning processes are only optimised by task orientation. When multiple-goal adoption was considered, students who developed the most positive self-regulation were characterised by their focus on learning, but also by their desire to avoid being judged negatively by others. CONCLUSIONS: Students should not adopt only task goals, which are sometimes overvalued, but also other kinds of goals that allow them to manage their learning and make it more flexible in each situation. This aspect characterises self-regulated learning, which is defined not only by cognitive and behavioural regulation but also by motivational regulation.

Adult↗
PubMed1994

GABAergic and pallidal terminals in the thalamic reticular nucleus of squirrel monkeys.

The ultrastructure of synaptic terminals from the external segment of the globus pallidus and of other synaptic terminals positive for gamma-aminobutyric acid (GABA) was examined in the thalamic reticular nucleus (TRN) of squirrel monkeys. Two GABA-positive terminals types were commonly encountered within the TRN neuropil. The most common type of GABAergic terminals (F terminals) are filled with dispersed pleomorphic synaptic vesicles and clusters of mitochondria. These terminals establish multiple symmetric synapses upon the somata and dendrites of TRN neurons. The external pallidal terminals, labeled with WGA-HRP, arise from thinly myelinated axons and correspond to the medium to large F terminals. A less prevalent population of smaller GABAergic synaptic profiles was also identified. The synaptic profiles in this second group contain considerably fewer pleomorphic synaptic vesicles in small irregular clusters and fewer mitochondria, establish symmetric synapses, are postsynaptic to other axonal terminals, are presynaptic to dendrites and soma, and are unlabeled following pallidal injections of WGA-HRP.

Animals↗
PubMed2006

Cytological features of prostatic intraepithelial neoplasia.

Fine-needle aspiration cytology (FNAC) is an acknowledged method for diagnosing prostate cancer. False-positive results are uncommon, but concerns have been raised that prostatic intraepithelial neoplasia (PIN) could be misinterpreted as carcinoma. Therefore, we attempted to describe cytological features of PIN. Cells were scraped from macroscopically normal areas of 177 radical prostatectomy specimens, smeared and Giemsa-stained. Histological slides from these areas were reviewed, and 17 samples with high-grade PIN and with no invasive cancer were selected. Smears from 17 invasive cancers were used for comparison. Cancer showed high cellularity and dissociation, while PIN smears only contained a few clusters of atypical cells. Pronounced nuclear atypia, prominent or multiple nucleoli and mucin were more common in cancer, while cytoplasmic granules, crystalloids and cluster size did not distinguish between PIN and cancer. In conclusion, PIN should not be diagnosed by FNAC alone. However, a highly cellular smear with pronounced atypia seems to preclude PIN.

Adenocarcinoma↗
PubMed2001

Crystal structure of Escherichia coli Fdx, an adrenodoxin-type ferredoxin involved in the assembly of iron-sulfur clusters.

Escherichia coli ferredoxin (Fdx) is an adrenodoxin-type [2Fe-2S] ferredoxin. Recent genetic analyses show that it has an essential role in the maturation of various iron-sulfur (Fe-S) proteins. Fdx probably functions as a component of the complex machinery responsible for the biogenesis of Fe-S clusters. Its crystal structure was determined by the multiple-wavelength anomalous dispersion method using the iron atoms in the [2Fe-2S] cluster of the protein and then refined to R and R(free) values of 0.255 and 0.278, respectively, at 1.7 A resolution. The structure of Fdx is similar to the structures of bovine adrenodoxin (Adx) and Pseudomonas putida putidaredoxin (Pdx) whose respective root-mean-square deviations of the corresponding Calpha atoms are 1.8 and 2.2 A. This analysis also revealed the structure of the C-terminal residues protruding into the solvent, which is missing in Adx and Pdx. The [2Fe-2S] cluster is located at the edge of the molecule and bonds with the Sgamma atoms of Cys42, Cys48, Cys51, and Cys87. Electrostatic potential analysis showed that the surface of Fdx has two negatively charged areas separated by a hydrophobic lane. One is conserved on the surface of Adx which is an area of interaction with adrenodoxin reductase. Cys46 is located on the molecular surface in the vicinity of the [2Fe-2S] cluster, an indication that it may be involved in Fe-S cluster formation.

Adrenodoxin↗
PubMedDate not supplied

Computer-aided semen analysis variables as predictors of male fertility potential.

A computer-aided semen analysis (CASA) was used to allow digitizing the motion of the spermatozoon. This procedure allows an objective means of judging semen quality, especially the translational movements of spermatozoa. Forty-three couples were included in the study. The average age of the male was 35.5 +/- 4.7 years and that of the female was 32.7 +/- 4.7 years. The average duration of infertility was 3.8 +/- 2.3 years. Using multiple linear regression analysis of 26 prognostic variables, a cluster of 8 variables significantly predicted pregnancy maximally. The 8 variables and the resultant multiple correlation coefficients were used to generate a multiple regression equation which allowed the correct separation of the population into fertile and infertile couples. The mean pregnancy predictor values of the fertile and infertile populations were significantly different using the analysis of variance.

Adult↗
PubMed1978

Morphologic and functional substrate of thyrotoxicosis caused by nodular goiters.

The pathogenesis of nonimmunogenic thyrotoxicosis caused by nodular goiters--with the exception of true toxic adenoma--was investigated in 11 patients by means of scintigraphic, morphologic and autoradiographic technics. The basic event is the appearance, for unknown reasons, of autonomously functioning follicles which are morphologically indistinguishable from normal follicles. Four basic patterns of intrathyroidal distribution of autonomously functioning follicles are individualized: Type I = multiple individual autonomously functioning follicles scattered throughout the goiter. Type II = clustered autonomous follicles without demarcation from less active parenchyma. Type III = multiple microadenomas. Type IV = autonomous function of the majority of all follicles. In all four types, the autonomous follicles occur without recognizable relation to nodule boundaries. Scintiscans cannot predict the microstructure of these types of goiters. More than one pattern of distribution of autonomously functioning follicles may occur within a single goiter. The growth of thyroid nodules is independent of, and certainly not a prerequisite to, thyrotoxicosis. Rather, the appearance of thyrotoxicosis in this type of multinodular goiter depends on (1) the number of autonomous follicles throughout the gland and (2) their mean hormone-producing capacity per unit of time.

Autoradiography↗
PubMed2001

Large-scale evaluation of imprinting status in the Prader-Willi syndrome region: an imprinted direct repeat cluster resembling small nucleolar RNA genes.

Loss of paternal gene expression at the imprinted domain on proximal human chromosome 15 causes Prader-Willi syndrome (PWS), a complex multiple-anomaly disorder involving variable mental retardation, hyperphasia leading to obesity and infantile hypotonia with failure to thrive. Although numerous paternally expressed transcripts have been identified that reside in the candidate region, the individual contributions to the development of PWS have not been firmly established. Recent studies of mouse models carrying a cytogenetic deletion suggest that paternal deficiency of the SNRPN-IPW interval is critical for perinatal lethality of potential relevance to PWS. Here we determined the allelic expression profiles of a total of 118 cDNA clones using monochromosomal hybrids retaining either a paternal or maternal human chromosome 15. Our results demonstrated a preponderance of unusual transcripts lacking protein-coding potential that were expressed exclusively from the paternal copy of the critical interval. This interval was also found to encompass a large direct repeat (DR) cluster displaying a potentially active chromatin conformation of paternal origin, as suggested by enhanced sensitivity to nuclease digestion. Database searches revealed an unexpected organization of tandemly repeated consensus elements, all of which possessed well-defined box C and D sequences characteristic of small nucleolar RNAs (snoRNAs). Southern blot analysis further demonstrated a considerable degree of phylogenetic conservation of the DR locus in the genomes of all mammalian species tested, but not in chicken, Xenopus and Drosophila. These findings imply a potential direct contribution of the DR locus, representing a cluster of multiple snoRNA genes, to certain phenotypic features of PWS.

Base Sequence↗
PubMed1997

Low insulin sensitivity is associated with clustering of cardiovascular disease risk factors.

Hyperinsulinemia is associated with multiple metabolic disorders including high triglyceride level, low high density lipoprotein (HDL) cholesterol level, hypertension, and impaired glucose tolerance (IGT). This metabolic constellation is also called the insulin resistance syndrome. All previous data on clustering of these risk factors are, however, based on insulin levels. Therefore, the authors examined the association of insulin sensitivity estimated by means of a frequently sampled intravenous glucose tolerance test and the minimal model with the number of metabolic disorders (dyslipidemia [high triglyceride level or low HDL cholesterol level or both], hypertension, and IGT according to the World Health Organization criteria). Of 153 nondiabetic subjects aged 53-61 years who had participated in a previous population-based study, 79 had no disorders, 55 had one disorder, 16 had two disorders, and 3 had three disorders. Insulin sensitivity index (S1) decreased with the increasing number of disorders (4.1, 3.5, 1.8, and 1.4 x 10(-4) min-1 microU-1 mL-1, in subjects with 0, 1, 2, and 3 disorders, respectively; p < 0.001 for trend). Similarly, fasting (7.5, 7.8, 15.3, and 22.0 microU/mL; p < 0.001) and 2-hour insulin levels (39.9, 49.0, 98.7, and 149.6 microU/mL; p < 0.001) increased by the increasing number of disorders. The relations of S1 and fasting and 2-hour insulin levels with multiple metabolic disorders were independent of sex, obesity, and body fat distribution. Furthermore, these associations were similar in men and women and in lean and obese subjects. The authors conclude that a clustering of cardiovascular disease risk factors in nondiabetic subjects is not only associated with hyperinsulinemia but also with insulin resistance.

Cardiovascular Diseases↗
PubMed1985

Basal cell carcinoma and breast carcinoma following repeated fluoroscopic examinations of the chest.

A 69-year-old white Italian woman was first seen at Memorial Sloan-Kettering Cancer Center in 1981 concerning several skin growths on her back. The patient had had several basal cell carcinomas surgically removed from her back during the preceding 5 years. There was no history of arsenic ingestion or prolonged sun exposure and her family history was negative for skin cancer. The patient had developed pulmonary tuberculosis in 1938 and was treated with pneumothorax therapy. She had had more than 50 fluoroscopic examinations of the chest following this therapy, as well as multiple diagnostic x-ray films since that time. She recalled that she had faced the fluoroscopy beam during the procedure. In 1959, she had a transabdominal hysterectomy for fibroid tumors. In 1980 she underwent a right modified radical mastectomy for adenoid cystic carcinoma of the breast; biopsies of lymph nodes were negative. Physical examination revealed a thin, white woman with a right mastectomy scar. On the back, clustered in the interscapular region, were multiple scars and nine erythematous nodules with pearly borders, telangiectasia, and translucent surfaces. Within several nodules there were areas of light and dark brown pigmentation. There were no other suspicious lesions on the head, chest, or extremities, nor did the patient show any evidence of the basal cell nevus syndrome. Biopsy of all lesions revealed basal cell carcinoma, some of which were pigmented, without evidence of chronic radiodermatitis. All lesions were treated with curettage and electrodesiccation three times with good cosmetic results (Fig. 1).

Breast Neoplasms↗
PubMed2005

Cervical coinfection with human papillomavirus (HPV) types and possible implications for the prevention of cervical cancer by HPV vaccines.

Coinfection with multiple types of human papillomavirus (HPV) and its implications for the development of efficacious HPV vaccines is a subject of great interest. To describe the occurrence of concurrent infection with multiple HPV types and to determine whether genital HPV infection modifies the risk of acquiring a new HPV infection with another HPV type, 1610 subjects were monitored for an average of 4.1 years in Bogota, Colombia. Information on risk factors for HPV infection and cervical cells was collected for detection of HPV DNA of 36 types at study entry and at 6 consecutive 6-month follow-up visits. Clustering or the concurrent acquisition of multiple types occurred more often than would be expected by chance. Subjects with incident HPV-16 or -18 infection had 5-7 times higher odds of acquiring a subsequent HPV-58 infection than subjects not infected with HPV-16 or -18. This might affect the protection conferred by effective HPV vaccines.

Adolescent↗