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Biomedical subjects

E Spitz

Publications and source records attributed to E Spitz.

At least 19 recordsLinked to original sources

Role of the serotonin transporter gene in the behavioral expression of autism.

The promoter polymorphism of the serotonin transporter gene (HTT, locus SLC6A4) is of special interest in autism given the well-replicated platelet hyperserotonemia of autism, treatment effects of serotonin reuptake inhibitors, and the role of serotonin in limbic functioning and neurodevelopment. Parent-offspring transmission of the long (l) and short (s) alleles of the deletion/insertion polymorphism in the HTT promoter region was examined in families of 71 children with autism using the transmission test for linkage disequilibrium (TDT). Transmission of HTT promoter alleles did not differ between probands with autism and their unaffected siblings. However, allelic transmission in probands was dependent upon severity of impairments in the social and communication domains, with greater s allele transmission in severely impaired individuals and greater l transmission in mild/moderately impaired individuals. This relationship between HTT promoter alleles and severity of autistic impairment was also seen when ratings of social and communication behaviors were compared across genotypes. The data indicate that HTT promoter alleles by themselves do not convey risk for autism, but, rather, modify the severity of autistic behaviors in the social and communication domains. The results require replication and, given the size of the groups and subgroups examined, must be considered still preliminary. The results suggest that future research on the genetics of autism should carefully assess each of the major behavioral domains and seriously consider the possible role of modifying loci.

Adolescent↗

Long-term effect of placental type on anthropometrical and psychological traits among monozygotic twins: a follow up study.

The long-term effect of differences in placentation in MZ twins is a controversial subject. An effect has been clearly established for birth weight but data on psychological traits are still under debate. We studied 20 pairs of monochorionic MZ (MC MZ) and 24 pairs of dichorionic MZ (DC MZ) twins. A chorion effect was observed for Block Design (WISC-R) confirming a previous report: MC MZ co-twins were more similar that DC MZ co-twins. For anthropometrical measures, an expected effect in the opposite direction was found. No chorion effect was significant for the other variables. A follow up was undertaken 3 years later using cognitive, national academic evaluations, and personality variables. The sample included 16 pairs of MC MZ and 22 pairs of DC MZ twins. Again a chorion effect was observed on anthropometrical variables but results on the Block Design were not replicated. However, the MC MZ co-twins were more similar than the DC MZ co-twins for two other cognitive variables: Perceptual Organization Index from the WISC-R and Global Visualisation from a Belgian reasoning test. Among the personality variables only one was sensitive to a chorion effect. The discussion focuses on the need for larger samples to achieve adequate power in statistical comparisons.

Adolescent↗

Platelet mitochondrial respiratory chain function in Parkinson's disease.

Reports on mitochondrial respiratory chain (MRC) complex I (CI) dysfunction in the substantia nigra in Parkinson's disease (PD) support the oxidative stress hypothesis in the neuropathogenesis of PD. Studies in peripheral tissue have found variable decreased CI and occasionally other complex activity suggestive of systemic impairment of MRC function in PD; however, MRC activity may be influenced by numerous variables. We conducted spectrophotometric measurements of MRC function in platelet mitochondrial preparations in 13 individuals with PD and 9 age-matched controls (CON) and have identified additional variables that may affect MRC activity. Mean CI, CIII, CIV, and citrate synthase (CS) activities were similar between PD and CON. CIII and CIV, specific and CS-corrected, activities were significantly positively correlated with CI in combined and individual group data, with the exception of CIII CS-corrected and CIV specific activities in CON and PD, respectively. CIII and CS specific activities were negatively correlated with age in CON, but varied randomly in PD. In PD, CIII specific activity was 1.4-fold higher in those with a history of environmental risk factors for PD and CIV specific activity was lower in those with a positive family history of PD [8.34 +/- 0.74 (n = 4) vs. 12.4 +/- 1.1 (SEM) min-1 mg-1; p = 0.046]. Group heterogeneity, variables affecting enzyme activity, and intrinsic properties of cells may thus contribute to conflicting data in studies of MRC function in platelets and other tissues.

Adult↗

Allergenicity of the pollen of Pistacia.

Differences in IgE binding and skin responses to pollen extracts of four species of Pistacia, and some immunochemical characteristics of this pollen were investigated. The incidence of positive SPT among atopic patients varied between 31.5% to the pollen extracts of P. vera and 24.6% to P. palaestina. The antigens are located on the exine of the grains as well as in their cytoplasm. Some of the antigens are common to all four species, whereas others seem to be specific. Cross-reactivity was found among the four species of Pistacia and between them and Schinus terebintifolious. Five conspicuous IgE-binding bands were observed in the immunoblots of the four examined species, the bands of 49, 57, 64, 68, and 79 kDa. The 36-37-kDa band of P. lentiscus and the 60- and 84-kDa bands of P. atlantica and P. vera were also noticeable. As the flowering seasons of Pistacia and Schinus do not overlap, the patients are exposed to such pollen for more than 4 months a year. Apparently, Pistacia pollen is a major source of allergy.

Binding Sites, Antibody↗

Manual performance and laterality in twins of known chorion type.

Manual performance, direction, and degree of laterality were tested in monozygotic (MZ) twins (8-12 years old) of known chorion type and dizygotic (DZ) twins. Three manual tasks rarely employed in twin studies were used; dot-filling, tapping, and peg-moving tasks. No chorion effect was observed: the monochorionic and dichorionic MZs differed neither for frequency of discordant pairs nor for handedness, laterality measurements, and manual performance. The pooled MZs and DZs were then compared in a classic twin design. The within-pair resemblance was not higher in MZs than in DZs for variables measuring level of manual performance. For laterality scores intraclass correlations were close to zero in MZ and DZ twin groups.

Child↗

Comparative diagnoses of twin zygosity by SSLP variant analysis, questionnaire, and dermatoglyphic analysis.

Zygosity diagnosis has been performed in 79 pairs of twins using three methods. Simple sequence repeat length polymorphism (SSLP) analysis allows an efficient classification (MZ or DZ) with only a few markers following a simplified technique of extraction and amplification. A method based on a full questionnaire completed by parents about twin similarity correctly classifies 97.46% of the pairs; 92.41% are correctly classified using only four questions as suggested by logistic regression analysis. The third method, using dermatoglyphic analyses, correctly classifies 86.76% of pairs. To lower the cost of DNA diagnosis we stress the possibility of limiting its use to pairs with scores in the overlap area between MZ and DZ twins with a validated questionnaire.

Child↗

Identification of nuclear substrates of the cyclic AMP-dependent protein kinase in Dictyostelium discoideum.

A search for nuclear substrates of the cAMP-dependent protein kinase (cAMP-d PK) of Dictyostelium discoideum led to the identification of several such proteins. Identification was based initially on increased phosphorylation of the proteins in nuclear extracts catalyzed by added cAMP-d PK. One protein of Mr 38,000 was phosphorylated also in intact nuclei and in vivo; the amount of phosphoprotein or the level of phosphorylation increased during development. Both the Mr 38,000 protein and another substrate of Mr 195,000 were found in the nuclei of prespore and prestalk cells. Phosphorylation of other potential substrates of the cAMP-d PK was either prespore or prestalk cell-specific.

Cell Differentiation↗

A cytosolic cyclic AMP-dependent protein kinase in Dictyostelium discoideum. II. Developmental regulation.

The cAMP-dependent protein kinase of the cellular slime mold, Dictyostelium discoideum, is developmentally regulated; there is an approximately 4-fold increase in activity during development. The incorporation of [3H]leucine into the enzyme demonstrates that there is de novo synthesis of the cAMP-dependent protein kinase. The activities of the catalytic and regulatory subunits increase in parallel. The maximal rate of increase of cAMP-dependent protein kinase activity precedes "tip" formation, a stage of development characterized by a sharp increase in mRNA complexity. The high level of cAMP-dependent protein kinase activity, attained at this stage of development, persists when aggregates are dispersed and the amoebae are kept in suspension without added cAMP. The synthesis of the developmentally regulated mRNAs under these conditions is dependent on exogenous cAMP. The increase in cAMP-dependent protein kinase activity during development does not require sustained cell-cell contact insofar as it occurs in single cell suspensions of amoebae. Furthermore, the increase does not require exogenous cAMP, although added cAMP stimulates the synthesis of the enzyme to a level higher than that found, when cAMP is not added. These observations support the hypothesis that in D. discoideum cAMP-dependent protein kinase mediates the effects of cAMP on development.

Cyclic AMP↗

A cytosolic cyclic AMP-dependent protein kinase in Dictyostelium discoideum. I. Properties.

A cAMP-dependent protein kinase was isolated and partially purified from Dictyostelium discoideum. The cytosolic holoenzyme has an apparent Mr = 160,000-180,000; its activity was stimulated significantly by cAMP when Kemptide served as substrate. The enzyme was dissociated and the regulatory subunit purified by affinity chromatography on 8-aminoethylamino-cAMP. Only one type of regulatory subunit was found; it has an apparent Mr = 41,000 and is a substrate for the in vitro phosphorylation by the homologous catalytic subunit and by purified bovine catalytic subunit. Antibody against the regulatory subunit was prepared. The D. discoideum catalytic subunit was separated from cAMP-independent protein kinase by chromatofocusing. The apparent molecular weight of the catalytic subunit of the D. discoideum cAMP-dependent protein kinase is 33,000 and its pI is 6.4. The enzyme catalyzed the phosphorylation of bovine RII but not of RI regulatory subunit and was inhibited by high concentrations of the inhibitor of mammalian cAMP-dependent protein kinase. The evolution of the functional domains of cAMP-dependent protein kinases is discussed on the basis of a comparison of the analogous D. discoideum and vertebrate enzymes.

Animals↗

Differential cellular distribution of cAMP-dependent protein kinase during development of Dictyostelium discoideum.

It was shown previously by us that cAMP-dependent protein kinase activity in the cellular slime mold Dictyostelium discoideum increased during the early stages of development. Results from other laboratories showed that during the subsequent stage of cell differentiation and positioning, the accumulation of a number of prespore mRNAs and proteins (but not prestalk mRNAs and proteins) was dependent upon cAMP. The present communication describes the cellular distribution of the cAMP-dependent protein kinase at that stage of development. Pseudoplasmodia were disrupted, and prespore cells were separated from prestalk cells by sedimentation through a Percoll gradient. Prespore cells had approximately 4-5 times as much of both the catalytic and regulatory subunits of the cAMP-dependent protein kinase as did the prestalk cells. That the increase of cAMP-dependent protein kinase during development reflected de novo synthesis of the enzyme in both prespore and prestalk cells was demonstrated on the basis of [(3)H]leucine incorporation into the regulatory subunit. The findings are consistent with a role of the cAMP-dependent protein kinase in mediating the effects of cAMP on the synthesis of prespore-specific mRNAs and proteins at the stage at which cAMP appears to be required for the cell type-specific syntheses.

Journal Article↗

Treatment of hypertension in mild asthmatic patients with atenolol.

Fourteen patients with uncomplicated essential hypertension and mild asthma were treated with Atenolol 50-125 mg/day for up to 8 months. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), rate pressure index (RPI), stress testing time (STT) and peak expiratory flow rate (PEFR) were measured before, during and after stress testing (ST) before and during treatment. Atenolol significantly lowered HR, SBP, DBP and RPI. It prolonged STT and had no effect on PEFR. Furthermore, Atenolol did not worsen the patient's asthma except for one patient. The drug did not interfere with the bronchodilatation effect of salbutamol. Atenolol can be used cautiously to treat hypertension in asthmatic patients under certain conditions.

Adult↗

A double blind crossover trial of lithium carbonate in asthma.

Lithium carbonate was evaluated in a double-blind, crossover study for prophylactic therapy in five patients with severe perennial asthma. There were no significant differences in symptom scores, salbutamol inhalations, PEFR and pulmonary function tests when the baseline, placebo and lithium periods were compared in all patients.

Adult↗

Regulation of the synthesis of adenylate cyclase in Escherichia coli by the cAMP -- cAMP receptor protein complex.

The synthesis of the adenylate cyclase [ATP pyrophosphatelyase-(cyclizing), E.C. 4.6.1.1.] of Escherichia coli, appears to be regulated negatively by the cAMP receptor protein, CRP. This conclusion is based on a comparison of adenylate cyclase activities measured in vitro with the rates of cAMP synthesis by intact bacteria. The activity of adenylate cyclase, depending on conditions of growth, is also regulated by CRP; this effect, however, is indirect insofar as it is mediated by a protein or proteins under CRP control.

Adenylyl Cyclases↗