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Biomedical subjects

I Kraus

Publications and source records attributed to I Kraus.

At least 19 recordsLinked to original sources
PubMed2000

The N-terminal domain of thyroid hormone receptor-alpha is required for its biological activities.

Thyroid hormone (T3) receptors (T3Rs) are ligand-modulated transcription factors that belong to the nuclear receptor superfamily. Whereas the well-conserved DNA-binding domain and the relatively well-conserved ligand-binding domain in T3Rs have been characterized in detail, limited information is available on the contribution of the variable N terminus to the transcriptional properties of T3Rs. To gain greater insight into the function of the N terminus, we generated a deletion mutant of T3Ralpha, T3Ralpha-deltaN1, that lacks amino acids 7-45 and assessed the effect of this deletion on all known transcriptional activities of T3Ralpha. Despite the fact that T3Ralpha-deltaN1 was expressed and bound T3 with an affinity similar to that of wildtype T3Ralpha, all of its common transcriptional activities were lost. That is, T3Ralpha-deltaN1 did not activate transcription from a positive or negative T3 response element, and it could not interfere with AP-1 transcriptional activity. Surprisingly, T3Ralpha-deltaN1 lost its ability to bind DNA, which can account for its deficiencies as a transcriptional activator. In contrast, the ability of T3Ralpha-deltaN1 to interact with putative coactivators or corepressors was not significantly altered from that of wildtype T3Ralpha. However, overall folding of T3Ralpha-deltaN1 was altered, as indicated by differential sensitivity to limited protease digestion. These data document that the N terminus of T3Ralpha, albeit relatively short and representing a variable and unconserved region when compared with other nuclear receptors, has a critical role in proper folding of the DNA-binding domain and is required for the biological activities of full-length T3Ralpha.

Animals↗
PubMed2000

Chiral hedgehog textures in two-dimensional XY-like ordered domains

The textures associated with a point defect centered in a circular domain of a thin film with XY-like ordering have been analyzed. The family of equilibrium textures, both stable and metastable, can be classified by a new radial topological number in addition to the winding number of the defect. Chiral textures are supported in an achiral system as a result of spontaneously broken chiral symmetry. Among these chiral textures, our theoretical analysis accurately describes two categories of recently discovered "reversing spiral" textures, ones that are energetically stable and metastable.

Journal Article↗
PubMed2000

Family study of girls with attention deficit hyperactivity disorder.

OBJECTIVE: Because attention deficit hyperactivity disorder (ADHD) is relatively infrequent among girls, little is known about the causes of ADHD in girls. To help fill this gap in the literature, the authors assessed the familial transmission of ADHD in families ascertained through girls. METHOD: Interviewers who were blind to diagnosis administered structured psychiatric interviews to 140 girls with ADHD and their 417 first-degree relatives and to 122 girls without ADHD and their 369 first-degree relatives. RESULTS: The relatives of the ADHD girls had a significantly higher prevalence of ADHD, according to either the DSM-III-R or DSM-IV definition, than the relatives of the comparison girls. However, this did not differ from the prevalence the authors reported previously for families of boys with ADHD. Like the boys' families, the relatives of the girl probands also had significantly higher prevalences of antisocial, mood, anxiety, and substance use disorders, although the prevalence of familial antisocial disorders was lower than had been observed in the boys' families. There was no association between the DSM-IV subtypes of the probands and relatives. CONCLUSIONS: The familial transmission of ADHD and comorbid disorders generalizes to families of girls with ADHD. Neither proband gender nor subtype influences the familial transmission of ADHD.

Adolescent↗
PubMed2000

Mutational analysis of the androgen receptor AF-2 (activation function 2) core domain reveals functional and mechanistic differences of conserved residues compared with other nuclear receptors.

A short C-terminal sequence that forms the core of the activation function-2 (AF-2) domain is conserved in members of the nuclear receptor superfamily and is required for their normal biological function. Despite a high degree of sequence similarity, there are differences in the context and structure of AF-2 in different nuclear receptors. To gain deeper insight into these differences, we carried out an extensive mutational analysis of the AF-2 core in the androgen receptor (AR) and compared the changes in transcriptional activity with similar mutations that have previously been generated in other nuclear receptors. Mutagenesis of Met894 to Asp resulted in substantial decreases in both DNA and ligand binding activities and, consequently, a significant drop in ligand-dependent transcriptional activation. In contrast, substitution of Met894 with Ala did not affect DNA or hormone binding, and the transactivation potential was comparable to that of wild-type AR. Mutagenesis of Glu897 either with Val or Ala significantly impaired ligand-dependent activation that was not due to changes in DNA or ligand binding. There are both similarities and distinct differences between these findings compared with previous mutagenesis studies of the corresponding residues in other nuclear receptors. All mutants efficiently interfered with AP-1 activity, indicating that ligand-dependent activation of transcription and interference with AP-1 activity are separable functions in AR. For the Glu897 substitutions, the decrease in ligand-dependent transactivation could partially be reversed by overexpression of GRIP1 (GR-interacting protein 1) or CBP, putative coactivators for AR. However, there was no correlation between ligand-dependent in vitro or in vivo association with coactivators and the ability of the mutants to support ligand-dependent transactivation. This is in contrast to similar mutations in other nuclear receptors that lose interactions with putative coactivators concomitant with their loss of transcriptional activity. However, the Glu897 mutations disrupted the intramolecular interaction between the N-terminal domain and the ligand-binding domain of AR that was recently suggested to be required for normal AR function. We conclude that residues in the AF-2 core domain of AR make distinctly different contributions to its transcriptional activities compared with those of other nuclear receptors studied to date.

Animals↗
PubMed2000

Mutational analysis of two PWW sequence motifs in human aminoacylase 1.

Human and porcine aminoacylase 1 (Acy1) contain two peculiar sequence motifs located near the interface between the two major domains of the Acy1 subunit. Each motif consists of the sequence PWW preceded by four strongly polar residues. In order to examine the significance of these sequences for Acy1 stability and/or catalysis, we used site-directed mutagenesis of human Acy1 to replace the tryptophan residues in either motif with alanines. Both mutants showed unchanged zinc binding and normal substrate affinity. Modification in PWW motif 1 (residues 192 -194) and motif 2 (residues 321 - 323) resulted in markedly reduced specific activity in the first case and diminished stability in either mutant. Fluorescence quenching measurements showed that all four tryptophans of the PWW motifs are solvent-accessible. We conclude that PWW motif 1 maintains the native conformation of the active site by creating the proper spatial relationship between dimerization domains and catalytic domains, while motif PWW2 is necessary for the stability of the catalytic domain.

Amidohydrolases↗
PubMed2000

Anosmia induced with alpha interferon in a patient with chronic hepatitis C.

This is a report of the alpha interferon-induced acute anosmia in a 37-year old patient with chronic hepatitis C. This exceptionally rare side-effect started in our patient as a smelling problem 2 weeks after the initiation of the therapy, and anosmia is still present 13 months after the discontinuation of the alpha interferon. We presume that neurotoxic mechanism could be responsible for this side-effect.

Adult↗
PubMed1999

Transnasal transesophageal echocardiography: a modified application mode for cardiac examination in ventilated patients.

UNLABELLED: In 42 endotracheally intubated patients, we examined the utility of a miniaturized monoplane probe for transnasal transesophageal echocardiography (TEE). Transnasal TEE was prospectively evaluated in 26 deeply and 16 mildly sedated patients receiving topical anesthesia with lidocaine jelly 2%. The patients with deep sedation were additionally examined with transoral monoplane and multiplane TEE. Transnasal esophageal insertion of the TEE probe was successfully performed in 90% of patients. Endotracheal malpositioning was corrected in two patients. Nasal bleeding required treatment in another patient. Topical anesthesia was adequate in 82% of mildly sedated patients. Left ventricular short- and four-chamber long-axis views of good quality were obtained with transnasal (transoral) monoplane TEE in 76% (81%) and 92% (96%) of patients (differences not significant). Compared with conventional multiplane TEE, transnasal monoplane TEE missed diagnoses in 19% of patients. The relative error (mean +/- SEM) of quantification with transnasal TEE was <9% +/- 2% for ventricular diameters and <7% +/- 2% for cross-sectional area measurements, with a bias of 0.5 +/- 3.8 cm2 and 0.1 +/- 2.4 cm2 (mean +/- 2 SD) for left ventricular end-diastolic and end-systolic short-axis areas. The relative error in measuring intracardiac flow velocities was >40%, but systolic to diastolic peak velocity ratios at the valvular site were determined with an error <4% +/- 3%. Transnasal monoplane TEE can be performed even in mildly sedated patients with an endotracheal tube without further need for analgesia or sedation. The technique is as useful as conventional transoral TEE to image standard tomographic planes for quantification, but it is less suited for comprehensive echocardiographic diagnosing. IMPLICATIONS: Transnasal insertion of a miniaturized monoplane transesophageal echocardiography (TEE) probe was studied in endotracheally intubated patients. Nasal passage was well tolerated even by patients with only mild sedation. Imaging quality was similar to conventional transoral monoplane TEE with larger transducers, but technical restraints cause a deficit in complete cardiac diagnosing obtained with multiplane TEE.

Anatomy, Cross-Sectional↗
PubMed1999

Clinical correlates of ADHD in females: findings from a large group of girls ascertained from pediatric and psychiatric referral sources.

OBJECTIVE: The scientific literature about attention-deficit hyperactivity disorder (ADHD) is based almost exclusively on male subjects, and girls with ADHD may be underidentified and undertreated. The aim of this study was to examine clinical correlates of ADHD in females using comprehensive assessments in multiple domains of functioning. METHOD: Subjects were 140 girls with ADHD and 122 comparison girls without ADHD ascertained from pediatric and psychiatric referral sources of the same age and social class. Subjects were assessed with structured diagnostic interviews, psychometric tests assessing intellectual functioning and academic achievement, as well as standardized assessments of interpersonal, school, and family functioning by raters who were blind to clinical diagnosis. RESULTS: Compared with female controls, girls with ADHD were more likely to have conduct, mood, and anxiety disorders; lower IQ and achievement scores; and more impairment on measures of social, school, and family functioning. CONCLUSIONS: These results extend to girls previous findings in boys indicating that ADHD is characterized by prototypical core symptoms of the disorder, high levels of comorbid psychopathology, and dysfunction in multiple domains. These results not only support findings documenting phenotypic similarities between the genders but also stress the severity of the disorder in females.

Adolescent↗
PubMed1996

A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders.

BACKGROUND: Previous cross-sectional data showed that children and adolescents with attention-deficit hyperactivity disorder (ADHD) are at increased risk of comorbid conduct, mood, and anxiety disorders as well as impairments in cognitive, social, family, and school functioning. However, longitudinal data were needed to confirm these initial impressions. METHODS: Using DSM-III-R structured diagnostic interviews and raters blinded as to diagnosis, we reexamined psychiatric diagnoses at 1- and 4-year follow-ups in children with ADHD and controls. In addition, subjects were evaluated for cognitive, achievement, social, school and family functioning. RESULTS: Analyses of follow-up findings revealed significant differences between children with ADHD and controls in rates of behavioral, mood, and anxiety disorders, with these disorders increasing markedly from baseline to follow-up assessments. In addition, children with ADHD had significantly more impaired cognitive, family, school, and psychosocial functioning than did controls. Baseline diagnosis of conduct disorder predicted major depression and bipolar disorder at follow-up, and anxiety disorders at baseline predicted anxiety disorders at follow-up. CONCLUSION: These results confirm and extend previous retrospective results indicating that children with ADHD are at high risk of developing a wide range of impairments affecting multiple domains of psychopathology such as cognition, interpersonal, school, and family functioning. These findings provide further support for the value of considering psychiatric comorbidity in both clinical assessment and research protocols involving children with ADHD.

Achievement↗
PubMed1995

Clinical correlates of enuresis in ADHD and non-ADHD children.

Enuresis and attention deficit hyperactivity disorder (ADHD) are common childhood disorders that often co-occur. Although each has been linked to neurodevelopmental immaturity and increased risk for psychopathology, the clinical correlates of enuresis remain unclear. Subjects were 140 6-17-year-old boys with DSM-III-R ADHD and 120 non-ADHD controls. Information on enuresis and psychiatric diagnoses was obtained in a standardized manner blind to the child's clinical status. Our results show that (1) enuresis did not increase the risk for psychopathology in children with or without ADHD; (2) enuresis was not associated with psychosocial adversity or developmental immaturity; (3) enuresis was associated with increased risk for learning disability, impaired intellectual functioning, and impaired school achievement in normal control children but not in children with ADHD; and (4) the same pattern of findings was obtained after stratifying children with enuresis by primary versus secondary and by nocturnal versus diurnal subtypes. These results suggest that the clinical implications of enuresis may differ for ADHD and non-ADHD children.

Adolescent↗
PubMed1995

CBCL clinical scales discriminate prepubertal children with structured interview-derived diagnosis of mania from those with ADHD.

OBJECTIVE: To evaluate the discriminative ability of the Child Behavior Checklist (CBCL) to identify children with structured interview-derived diagnosis of bipolar disorder. METHOD: We evaluated the convergence of CBCL scales with the diagnosis of mania in 31 children with mania, 120 children with attention-deficit hyperactivity disorder, and 77 prepubertal normal control children aged 12 years or younger. We evaluated the strength of association between each CBCL scale and structured interview-derived diagnoses with total predictive value and the odds ratio. RESULTS: Excellent convergence was found between the CBCL scales of Delinquent Behavior, Aggressive Behavior, Somatic Complaints, Anxious/Depressed, and Thought Problems and the diagnosis of mania. CONCLUSIONS: These findings indicate that the CBCL could serve as a rapid and useful screening instrument to identify manic children in clinical settings.

Attention Deficit Disorder with Hyperactivity↗
PubMed1993

Effect of ACE inhibitors on atrial natriuretic factor in the brains of rats with reduced renal mass.

We tested the effect of renal insufficiency, with and without angiotensin (Ang) converting enzyme (ACE) inhibition, on blood and brain atrial natriuretic factor (ANF) in rats. Two ACEs, one which penetrates into the CNS and one which does not, were used to distinguish between peripheral and central ACE effects. Rats underwent 5/6 nephrectomy (5/6-NPX) by ligation of renal arterial branches. After seven days, 28 5/6-NPX rats received lisinopril 20 mg/kg/day and 28 5/6-NPX rats received quinapril 30 mg/kg/day orally for five days, while 28 5/6-NPX control rats and 28 sham rats did not. Body weight, blood pressure, drinking and urine volume were monitored. At sacrifice, urine, plasma, and brain tissue was collected. ANF in 16 brain areas was measured by radioimmunoassay. 5/6-NPX resulted in increased blood pressure, increased urine volume, proteinuria, and increased drinking. Both ACEs lowered blood pressure to sham values and decreased proteinuria. Both ACEs increased plasma renin activity and decreased plasma ANF. However, only lisinopril decreased drinking and urine volume. 5/6-NPX increased ANF values in six brain areas, namely the periventricular preoptic nucleus, the arcuate nucleus, the perifornical nucleus, the periventricular hypothalamic nucleus, the paraventricular nucleus, and the dorsal raphe nucleus compared to sham rats. These same increases in brain ANF were also observed in 5/6-NPX rats given quinapril, compared to shams. However, lisinopril lowered ANF to sham levels in the periventricular preoptic nucleus, the arcuate nucleus, and the perifornical nucleus. In the three additional brain areas, namely the periventricular hypothalamic nucleus, the paraventricular nucleus, and the dorsal raphe nucleus, lisinopril did not effect the elevated ANF concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Convergence of the Child Behavior Checklist with structured interview-based psychiatric diagnoses of ADHD children with and without comorbidity.

We evaluated the convergence of CBCL scales with the diagnosis of ADHD and comorbid disorders in 133 ADHD and 118 normal control boys, aged 6-17 years old. We evaluated the strength of association between each CBCL scale and structured-interview derived diagnoses with Total Predictive Value (TPV) and the odds-ratio (OR). Excellent convergence was found between the CBCL Attention Problems scale with the diagnosis of ADHD, between the Delinquent Behavior scale and the diagnosis of CD, and between the Anxiety/Depression scale and the diagnoses of Anxiety Disorders. These findings indicate that the CBCL could serve as a rapid and useful screening instrument to identify comorbid and non-comorbid cases of ADHD.

Adolescent↗
PubMed1993

Evidence for the independent familial transmission of attention deficit hyperactivity disorder and learning disabilities: results from a family genetic study.

OBJECTIVE: The purpose of the study was to clarify the relationship between attention deficit hyperactivity disorder and learning disabilities. METHOD: The authors assessed learning disabilities in a sample of 140 children with attention deficit hyperactivity disorder and in 120 normal comparison children. They also assessed a sample of the probands' 822 first-degree relatives. RESULTS: The risk for learning disabilities was highest among relatives of probands with both attention deficit hyperactivity disorder and learning disabilities. The two disorders did not cosegregate in families. There was nonrandom mating between spouses with attention deficit hyperactivity disorder and learning disabilities. CONCLUSIONS: The two disorders are transmitted independently in families, and their co-occurrence may be due to nonrandom mating. Attention deficit hyperactivity disorder is likely to be etiologically independent from learning disabilities.

Adult↗
PubMed1992

Administrative ethics in the 1990s: CEOs confront payment, access dilemmas.

The 1990s are presenting new challenges to hospital CEOs. One theme currently emerging is the ethics of resource allocation. As they search for ways to fulfill their community responsibilities under pressures related to reimbursement, technology and community desires, hospitals are finding that they must make some very tough choices in how they allocate resources. Given the opportunity, how would you respond? Compare your response to an ethical scenario with those of three nationally recognized hospital CEOs.

Attitude of Health Personnel↗