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Biomedical subjects

A Reiss

Publications and source records attributed to A Reiss.

At least 19 recordsLinked to original sources

Cholesterol 7-hydroxylase knockout mouse: a model for monohydroxy bile acid-related neonatal cholestasis.

BACKGROUND & AIMS: Cyp 7-/- mice lack a functional cholesterol 7alpha-hydroxylase enzyme and develop cholestasis before up-regulation of 27-hydroxycholesterol 7alpha-hydroxylase activity. Because 7alpha-hydroxylation is not the initial step in this metabolic pathway, we tested the hypothesis that cholesterol 27-hydroxylase is expressed at an earlier step and leads to the production of monohydroxy bile acids. METHODS: Polymerase chain reaction with specific oligonucleotides was used to detect messenger RNA (mRNA) coding for cholesterol 27-hydroxylase in 5-day-old normal and Cyp 7-/- mice. Gas-liquid chromatography-mass spectrometry and reverse isotope dilution were used to identify intermediates in the cholesterol 27-hydroxylase metabolic pathway. Light and electron microscopy were used to evaluate the morphological appearance of the liver. RESULTS: mRNA for cholesterol 27-hydroxylase was identified in the liver and spleen. The monohydroxy bile acids 3beta-hydroxy-5-cholenoate and 3alpha-hydroxy-5beta-cholanoate together with their precursor, 27-hydroxycholesterol, were identified in liver homogenates. Cholestasis, present focally, was manifested as dilated bile canaliculi, partial loss of microvilli, and retention of electron-dense biliary material. CONCLUSIONS: The cholesterol 27-hydroxylase metabolic pathway of bile acid synthesis is expressed in neonatal life. The absence of 7alpha-hydroxylase activities unmasks the cholestatic potential of monohydroxy bile acids. The Cyp 7-/- knockout mouse mimics cholestatic events known to occur in humans and provides a unique opportunity for studying regulatory determinants.

Animals↗

Clinical significance of tumor angiogenesis in patients with localized renal cell carcinoma.

OBJECTIVES: To determine the relationship between angiogenesis and various histopathologic features as well as clinical outcome in patients with localized renal cell carcinoma (RCC). METHODS: Microvessel density was quantified by using immunocytochemical staining of endothelial cells for factor VIII-related antigen of 36 specimens taken from patients with pathologic Stage pT1 or pT2 RCC. All patients underwent radical nephrectomy and were followed for a mean time of 97.3 months. RESULTS: No association was noted between microvessel count (MVC) and either cell type, architecture, or tumor size. Inverse correlation was noted between MVC and nuclear area (P = 0.006), nuclear elipticity (P = 0.016), nuclear roughness (P = 0.039), and histologic grade (P = 0.047). Patients having tumors with low MVC had significantly better survival rate compared with those with high MVC neoplasms (P = 0.0014, by Cox proportional hazards method). CONCLUSIONS: Despite lack of correlation with known predictors of survival, MVC provides independent prognostic information for patients with localized RCC.

Adult↗

The function of image control in the psychophysiology of posttraumatic stress disorder.

The physiological response to trauma-related stimuli of up to one third of participants with posttraumatic stress disorder (PTSD) cannot be discriminated from that of controls. Psychophysiological measures (heart rate and blood pressure) of 22 PTSD and 23 control civilian participants, all exposed to missile attacks during the Gulf War, were recorded while listening to five scripts. The physiological response of PTSD subjects with high image control (IC) was lower than that of PTSD participants with low IC and similar to that of non-PTSD subjects. The physiological response poorly discriminated high IC PTSD participants from controls, but was successful in discriminating low IC PTSD subjects from controls with 91% specificity and 92% sensitivity. Image control is proposed as a function influencing physiological response in PTSD.

Adult↗

Early detection of social interaction problems: development of a social interaction instrument in young children.

Children with developmental or psychiatric disorders often have problems with social interaction. This study reports on the development of the Ghuman-Folstein Screen for Social Interaction (SSI), a parent/caregiver questionnaire designed to measure the capacity for basic social interaction skills across a variety of contexts in preschool children. The SSI was administered to 51 clinically referred children with a high probability of deficits in social interaction and 60 healthy control subjects to establish reliability and validity. The children were 24 to 61 months of age, with diverse ethnic and socioeconomic backgrounds. Strong internal consistency, significant correlation for test/retest reliability, moderate correlation for interrater reliability and support for external validity of the SSI was established. The SSI scores differentiated between the clinically referred subjects and healthy control subjects and between children with pervasive developmental disorder (PDD) of the autistic type and other non-PDD developmental disorders. The SSI is a relatively simple, efficient, reliable, and valid measure for the capacity for basic social interaction skills in children 24 months to 5 years of age. The SSI has a potential to be useful in primary health care settings to identify children at risk who may need tracking and/or further evaluation and treatment services.

Child Behavior↗

Lack of effect of methylphenidate on serum growth hormone (GH), GH-binding protein, and insulin-like growth factor I.

The aim of this study was to assess the growth hormone (GH) axis in methylphenidate (MPH)-treated and untreated boys with attention-deficit and hyperactivity disorder (ADHD), by evaluating serum GH, GH-binding protein (GHBP) activity, and insulin-like growth factor I (IGF-I) levels as compared to age-matched normal controls. Blood samples were taken from 42 boys (aged 6-16 years) diagnosed as having ADHD according to DSM-III-R criteria and confirmed by using the Schedule for Affective Disorder and Schizophrenia for school-age children (K[Kiddle]-SADS). A total of 21 patients were treated with MPH (5-20 mg/day; 0.15-0.77 mg/kg/day), on a drug holiday protocol, for 1-36 months, and 21 were drug naive. A total of 46 age-matched normal boys at height and weight within normal range served as controls. No significant differences were detected between the MPH-treated ADHD children, the untreated ADHD children, and the control children on fasting serum GH levels, GHBP activity, or IGF-I levels. Active treatment with MPH, in ADHD children on a drug holiday protocol, does not cause changes in GH axis as manifested by normal values of GH, GHBP, and IGF-I.

Adolescent↗

Trajectories and profiles of adaptive behavior in males with fragile X syndrome: multicenter studies.

We conducted two multicenter studies on adaptive trajectories and profiles in males with fragile X syndrome. Study 1 longitudinally assessed 29 males ages 1-20 years using age-equivalent scores from the Vineland Adaptive Behavior Scales. Fragile X boys ages 1-10 years showed significant gains in adaptive skills from first to second testing; males ages 11-20 years were stable in their adaptive development. Study 2 cross-sectionally examined 132 males ages 1-20 years. Significant age-related gains were found in boys ages 1-10, particularly in preschool children. Subjects ages 11-20 showed increased variability and nonsignificant relations between age and adaptive skills. Preliminary findings from 26 young adults with fragile X syndrome ages 21-40 years showed stable age-equivalent adaptive scores during these years. Relative strengths in daily living skills and weaknesses in communication were only evident among older subjects. Significant relations were found between adaptive behavior standard scores and IQ; these two scores also showed age-related declines that likely parallel one another. Findings are related to adaptive features in other genetic syndromes, and to directions for future adaptive behavior research.

Activities of Daily Living↗

Altered platelet peripheral-type benzodiazepine receptor in posttraumatic stress disorder.

Peripheral-type benzodiazephine receptors (PBR) are involved in steroidogenesis and are sensitive to stress. Reduced platelet PBR density has been demonstrated in generalized anxiety disorder (GAD), but not in obsessive-compulsive disorder (OCD). We extended this observation to another anxiety disorder, namely, posttraumatic stress disorder (PTSD). Eighteen post-Persian Gulf War PTSD patients and 17 age- and sex-matched controls were included in the study. All subjects were evaluated using the Structured Clinical Interview for DSM-III-R-Patient Version. The severity of symptoms was assessed using the DSM-III-R scale for PTSD, the Impact of Event Scale, the Beck Depression Inventory, and the State-Trait Anxiety Inventory. [3H]PK 11195 was used to label platelet PBR. All psychological parameters (except trait anxiety) were higher in PTSD patients compared to controls. Decreased platelet PBR density (-62%; p < .001) was observed in the PTSD patients compared to controls. The reduction in PBR observed in PTSD patients was in accordance with the findings in GAD patients, but differed from those obtained in OCD patients. It is possible that the receptoral downregulation is an adaptive response aimed at preventing chronic overproduction of glucocorticoids in hyperarousal states.

Adult↗

Bupropion hydrochloride in attention deficit disorder with hyperactivity.

OBJECTIVE: This is a multisite, double-blind, placebo-controlled trial to determine the safety and efficacy of bupropion in the treatment of children with attention deficit disorder with hyperactivity (ADDH). METHOD: In a four-center, double-blind comparison of bupropion (n = 72) and placebo (n = 37), children aged 6 to 12 years meeting DSM-III criteria for ADDH were randomized to receive bupropion 3 to 6 mg/kg per day or placebo, administered twice daily, at 7 A.M. and 7 P.M. Measures of efficacy included the Conners Parent and Teacher Questionnaires (93-item, 39-item, and 10 item), Clinical Global Impressions Scales of Severity and Improvement, the Sternberg Short-Term Memory Task, and the Continuous Performance Test. Screen and posttreatment physical examinations, electrocardiograms, electroencephalograms, and clinical laboratory evaluations were performed. Height, weight, and vital signs were measured and adverse experiences were assessed weekly. RESULTS: A significant treatment effect, apparent as early as day 3, was present for both conduct problems and hyperactivity on the Conners 10-item and 39-item teacher's checklist, and at day 28 for conduct problems and restless-impulsive behavior on the 93-item parent questionnaire. Findings were of smaller magnitude for parent ratings than teacher ratings. Significant treatment effects were present on both the Continuous Performance Test and memory retrieval test. Effect sizes of bupropion/placebo differences for teacher and parent ratings in this study were somewhat smaller than for standard stimulant drugs used to treat ADDH. Bupropion appeared to be well tolerated in most children. Dermatological reactions were twice as frequent in the drug group as the placebo group, with four reactions involving rash and urticaria that were serious enough to require discontinuation of medication. CONCLUSIONS: Bupropion may be a useful addition to available treatments for ADDH. Comparative trials with such standard drugs as methylphenidate are warranted to determine the relative clinical merits of bupropion.

Antidepressive Agents, Second-Generation↗

Abdominal stab wound protocol: prospective study documents applicability for widespread use.

Traditionally, stab wounds violating the abdominal wall fascia led to exploratory celiotomy that was often nontherapeutic. In an attempt to limit the number of nontherapeutic celiotomies (NTC), we devised a protocol to prospectively study stab wounds violating the anterior abdominal wall fascia. Through protocol, abdominal stab wounds were explored in stable adults. If the anterior fascia was violated, paracentesis and, if necessary, peritoneal lavage was undertaken in the absence of previous abdominal surgery. If evisceration was noted, it was reduced and the patient lavaged. Fascial penetration was noted in 72 patients. 46 patients underwent celiotomy: because of shock/peritonitis in 8 (2 NTC), fascial penetration with a history of previous celiotomy in 7 (5 NTC), positive paracentesis in 20 (5 NTC), or positive lavage in 10 (4 NTC). One patient underwent late celiotomy without ill-effect after a negative lavage because she subsequently developed fever and localized peritonitis (ice pick injury to cecum). Eleven patients had evisceration; nine underwent celiotomy. Patients with abdominal stab wounds can be selectively managed safely. More than one-third with fascial penetration, some with evisceration, avoided exploration. Only one patient underwent delayed celiotomy and did so without detriment. Nontherapeutic celiotomy rates were highest in patients with previous abdominal surgery who, thereby, could not undergo paracentesis/lavage; excluding these patients, the nontherapeutic celiotomy rate was 17% (11/65) for those with fascial penetration.

Abdomen↗

Platelet adenylate cyclase activity in Israeli victims of Iraqi Scud missile attacks with post-traumatic stress disorder.

Platelet adenylate cyclase activity was measured in 16 control subjects and 16 patients who developed post-traumatic stress disorder (PTSD) as a result of damage inflicted on their homes during the Iraqi Scud missile attacks on Israel which occurred during the 1991 Gulf War. There were no differences in basal, NaF-stimulated, PGE1-stimulated or forskolin-stimulated activity between controls and PTSD subjects. Epinephrine inhibition of forskolin-stimulated activity, an effect mediated by alpha 2 adrenergic receptors, was slightly but not significantly increased in the PTSD patients compared to the controls, while 5-HT induced inhibition, an effect mediated by putative 5-HT1a-like receptors, was unchanged. The relationship of these activities to measures of anxiety and depression in these patients is discussed.

Adenylyl Cyclases↗

Rat liver cytochrome P450 2B3: structure of the CYP2B3 gene and immunological identification of a constitutive P450 2B3-like protein in rat liver.

The cytochrome P450 2B subfamily in the rat contains an estimated eight to eleven members at the genomic level. Synthesis in the liver of the prototypic forms P450 2B1 and P450 2B2 is dramatically induced by phenobarbital. The 1.9-kb mRNA for P450 2B3, a third member of the P450 2B subfamily, is constitutively present in rat liver but is not inducible by phenobarbital. We have now cloned and sequenced exonic sequences corresponding to the entire 2B3 mRNA and determined their exon-intron structure, which is identical to that of CYP2B1/CYP2B2 and other CYP2B genes. A putative CYP2B3 transcription start site was identified and CYP2B3 5'- and 3'-flanking sequences were compared to those of CYP2B1 and CYP2B2. CYP2B3, like CYP2B1 and CYP2B2, has a modified TATA box preceding the transcription start site and lacks the canonical polyadenylation signal preceding the poly(A) site. A 2B3 expression vector, pMT2-2B3, directed the synthesis in COS-1 cells of an approximately 50-kD protein detectable on Western blots with a polyclonal antibody and with one of four monoclonal antibodies raised against 2B1 but not with a polyclonal antibody raised against P450 PB6. The 2B3 protein migrated with a slightly higher electrophoretic mobility than 2B1 and comigrated with a protein detected by anti-2B1 antibodies in liver microsomes from untreated rats. The results indicate that a 2B3-like protein is present in rat liver and that it is distinct from P450 PB6 and other known constitutive rat hepatic P450s.

Animals↗

Magnetic resonance imaging measurement of posterior fossa structures in schizophrenia.

OBJECTIVE: Previous research has yielded conflicting results regarding the hypothesis that structural abnormalities of the cerebellar vermis and other posterior fossa structures are associated with schizophrenia. The purpose of this study was to apply techniques of measuring posterior fossa structures from magnetic resonance imaging scans that have proven reliable in identifying structural abnormalities in other patient populations. METHOD: Midsagittal areas of cerebellar vermis and its subsections (anterior vermis, lobules VI-VII, and lobules VIII-X), brainstem (pons, medulla, and midbrain), and fourth ventricle, as well as intracranial area and cortical area, were measured. Subjects included 36 schizophrenic patients and 51 normal comparison subjects. Groups were matched on age, sex, race, and family socioeconomic status. RESULTS: No significant group differences were detected for any posterior fossa structure. When corrected for intracranial area, fourth ventricle area was significantly larger in patients than in the comparison group. Fourth ventricle area was not, however, correlated with any measures of symptom severity. CONCLUSIONS: The size of posterior fossa structures is not abnormal in schizophrenia.

Adolescent↗

Alteration of platelet benzodiazepine receptors by stress of war.

Mitochondrial benzodiazepine receptors play a major role in steroidogenesis. The authors determined plasma cortisol levels, platelet levels of mitochondrial benzodiazepine receptors, and anxiety and depression scores in 11 civilians exposed to the Persian Gulf war. The density of mitochondrial benzodiazepine receptors was 22% and 15% lower before and during the war, respectively, than 4 weeks after the end of the war. Relief of stress led to an increase in receptors, which correlated with the improvement in anxiety but not mood.

Anxiety Disorders↗

The human dioxin-inducible NAD(P)H: quinone oxidoreductase cDNA-encoded protein expressed in COS-1 cells is identical to diaphorase 4.

NAD(P)H: quinone oxidoreductase (NQO1) is believed to be protective against cancer and toxicity caused by exposure to quinones and their metabolic precursors. This enzyme catalyzes the two-electron reduction of compounds, compared with one-electron reduction mediated by NADPH: cytochrome-P450 oxidoreductase which produces toxic and mutagenic free radicals. Recently we cloned and sequenced the cDNA encoding human 2.3,7,8-tetrachlorodibenzo-p-dioxin (dioxin)-inducible cytosolic NQO1 [Jaiswal et al. (1988) J. Biol. Chem. 263, 13572-13578] and provided preliminary evidence that this enzyme may correspond to diaphorase 4, an enzymatic activity present in various tissues that catalyzes the reduction of a variety of quinones by both NADH and NADPH [Edwards et al. (1980) Biochem. J. 187, 429-436]. In the present report we characterize the catalytic properties of the protein encoded by the NQO1 cDNA. The enzyme was synthesized in monkey kidney COS-1 cells transfected with a pMT2-based expression plasmid containing the NQO1 cDNA. Western blot analysis of the transfected cells using an antibody against rat liver cytosolic NQO1 revealed a 31-kDa band that was not detected in nontransfected cells. This band corresponded to a polypeptide with the same electrophoretic mobility as the endogenous NQO1 protein detected in the human hepatoblastoma (Hep-G2) cells with the same antibody. The immunoreactive protein detected in human Hep-G2 cells was induced approximately fourfold by exposure of the cultures to dioxin, an increase commensurate with the increased in quinone oxidoreductase activity. These studies suggest that the protein encoded by NQO1 cDNA is indeed similar, if not identical, to the dioxin-inducible protein band detected in human Hep-G2 cells. Further characterization of the product of NQO1 cDNA, which was present at approximately 20-30-fold higher levels in transfected COS cells than the endogenous product in uninduced human Hep-G2 cells indicated that it had very high capacity (greater than 1000-fold over background) to catalyze the reduction of 2.6-dichloroindophenol and menadione. Besides these two commonly used substrates for quinone reductase, the expressed NQO1 protein also effectively metabolized 2,6-dimethylbenzoquinone, methylene blue, p-benzoquinone, 1,4-naphthoquinone, 2-methyl-1,4-benzoquinone, with the latter being the most potent electron acceptor at 50 microM concentration of the substrate.

Animals↗

Area and volume measurement of posterior fossa structures in MRI.

This study was undertaken to determine the extent to which area measures of posterior fossa structures can be used confidently to represent structure volumes. MRI scans were obtained from three groups: fragile X males, males with other developmental disabilities, and males with normal IQ. The areas of the midbrain, pons, medulla, cerebellar vermis, and fourth ventricle were measured in midsagittal sections. Volumes of midbrain, pons, medulla, cerebellum, fourth ventricle, and third ventricle were obtained by measuring these structures in contiguous axial slices. In addition, the largest axial area for each structure was identified. Analysis revealed that midsagittal area measures for pons, medulla, and fourth ventricle were significantly correlated with structure volumes, and that all of the largest axial area measures were significantly correlated with structure volumes. However, only the midsagittal area measure of fourth ventricle and the largest axial area measures of fourth ventricle and cerebellum were correlated with volume measures with an r of .80 of greater. Results of this study suggest that area measures may not accurately represent three-dimensional structure size.

Adolescent↗