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Biomedical subjects

S Schmitz

Publications and source records attributed to S Schmitz.

At least 55 records · Page 3Linked to original sources
PubMed1998

Family variables in substance-misusing male adolescents: the importance of maternal disorder.

Selected family variables, especially maternal behaviors, were studied as predictors of alcohol and drug misuse in severely disturbed adolescent boys from largely father-absent homes. The families of 50 male youths (mean age 15.8 years) in a residential center for alcohol and substance misuse were compared with the families of a community control group (mean age 16.3 years). Within-subject group comparisons also were made. Family structure, interactive processes, maternal and paternal alcohol and substance use, and criminality were assessed through direct interview and/or self-report. The families of alcohol- and substance-misusing boys were markedly disadvantaged or impaired on numerous family structure, process, and substance-misusing behavioral variables in comparison with community controls. Within the alcohol- and substance-misusing group itself, family process variables, maternal alcohol symptoms, and maternal criminality differentiated boys with more vs. less severe drug-dependence symptoms. Maternal alcohol problems and criminality were more important than family process variables. Paternal alcohol or substance misuse or criminality did not differentiate proband symptom severity. We concluded that maternal alcohol symptoms and criminality differentiate severity of drug dependence in severely disturbed, substance-misusing adolescent males from largely father-absent homes. Maternal substance misuse should be evaluated carefully in adolescent substance abuse treatment settings.

Adolescent↗
PubMed1998

Genetic association between atopy and behavioral symptoms in middle childhood.

The relationship of atopic and behavioral symptoms in a community sample of 66 monozygotic and 141 dizygotic twin pairs, ages 4-11 years, was investigated via mother report questionnaires. Within-person correlation between atopic symptoms and Child Behavior Checklist internalizing symptoms (CBCL-INT) was .21 (p < .001) for the total sample. Cross-correlations between atopy and CBCL-INT were .26 for monozygotic and .04 for dizygotic twins. A common and specific factor model applied to the data revealed that the cross-correlation between atopy and CBCL-INT was mainly due to genetic influences (77% of the covariance). This study supports the hypothesis that there is a shared genetic risk for atopy and internalizing symptoms.

Analysis of Variance↗
PubMed1997

Pharmacokinetics of the liver-specific contrast agent Gd-EOB-DTPA in relation to contrast-enhanced liver imaging in humans.

This study was performed to evaluate the effect of dose on the pharmacokinetics and efficacy of the gadolinium-based contrast medium gadoxetic acid, disodium, [gadolinium (4S)-4-(4-ethoxybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6, 9-triazaundecandioic acid-disodium salt] (Gd-EOB-DTPA) as a liver-specific hepatobiliary contrast medium for computed tomography. Pharmacokinetics in serum and the pattern of elimination were investigated in 18 healthy volunteers up to 6 days after a 10-minute infusion of 0.2 mmol, 0.35 mmol, and 0.5 mmol of gadolinium per kilogram of body weight. Pharmacokinetic behavior was compared with the compute tomographic attenuation data in the liver parenchyma after the same doses in patients. Urinary and fecal excretion accounted for approximately equal portions of the administered dose. The degree of renal elimination increased with increasing doses, whereas renal clearance and half-life from urine data were not affected by dose. Dose-normalized area under the concentration-time curve was significantly increased with increasing doses indicating saturation in liver uptake for the highest dose. This finding was in agreement with the measured net increase in liver attenuation by computed tomography. Hepatic disposition revealed slight saturation phenomena for the highest dose (0.5 mmol gadolinium/kg). Nevertheless, this dose resulted in sufficient uptake by human liver, allowing for computed tomographic imaging.

Adult↗
PubMed1996

Glutamate 94 of [2Fe-2S]-ferredoxins is important for efficient electron transfer in the 1:1 complex formed with ferredoxin-glutamate synthase (GltS) from Synechocystis sp. PCC 6803.

We have analyzed the role of critical amino acid residues involved in the interaction between ferredoxin and ferredoxin-glutamate synthase (GOGAT) encoded by the gltS gene from the cyanobacterium Synechocystis sp. PCC 6803. Our results indicated that the glutamate 94 residue of Anabaena 7120 ferredoxin (= E92 of the Synechocystis 6803 ferredoxin) was necessary for an efficient electron transfer to GOGAT comparable to ferredoxin:NADP-reductase, nitrite reductase and nitrate reductase [Schmitz and Böhme (1995) Biochim. Biophys. Acta 1231, 335-341]. The K(m) value determined for wt-ferredoxins and mutant E94Q (and E92Q) was 1 muM, respectively, and activity loss of E94Q was due to a lowered Vmax. Exchange of residue F65 for aliphatic substitutions, which was crucial to electron transfer to ferredoxin:NADP-reductase and nitrite reductase, exhibited only small effects on glutamate synthase-dependent activity while heterocyst ferredoxin and flavodoxin were almost inactive as electron donors. In contrast to data reported for the spinach system, the stoichiometry of the cross-linked complex between ferredoxin and glutamate synthase was 1:1.

Amino Acid Oxidoreductases↗
PubMed1996

Expression of ferredoxin-NADP+ reductase in heterocysts from Anabaena sp.

The expression of ferredoxin-NADP+ reductase (FNR) from Anabaena sp. PCC 7119 in heterocysts and vegetative cells has been quantified. Specific reductase activity in heterocysts was approximately 10 times higher than in vegetative cells, corresponding to the increased FNR protein content. This was confirmed by immunoquantification of the FNR protein from whole filaments of Anabaena sp. PCC 7120 grown in media with and without combined nitrogen. Transcription of the petH gene was markedly enhanced in the absence of combined nitrogen. This suggests that the increased RNA level is mainly responsible for the up-regulation of FNR in heterocysts. As has been observed for nif genes, iron deficiency also increased transcription of petH. Characterization of the FNR purified from isolated heterocysts showed no detectable differences from the enzyme from vegetative cells. Although nitrogen stress was a key regulatory factor, localization of the petH gene in the genomic map of Anabaena PCC 7120 showed that this gene is not physically associated with the nif cluster.

Anabaena↗
PubMed1996

Comorbidity in hyperactive children: issues related to selection bias, gender, severity, and internalizing symptoms.

Parental behavior ratings of hyperactive boys and girls aged 6-11 years seen for evaluation in a general outpatient child psychiatry clinic and in a specialty "attention deficit disorder" (ADD) program were analyzed. The pattern of comorbidity in the two groups showed no significant differences. Most of the associated internalizing and externalizing behavioral scales in hyperactive boys and in hyperactive girls were elevated and in clinical ranges except for the "somatic complaints" scale. Comorbidity in both hyperactive boys and girls was related to the severity of the hyperactivity itself.

Attention Deficit Disorder with Hyperactivity↗
PubMed1996

Model analysis of the contrasting effects of GM-CSF and G-CSF treatment on peripheral blood neutrophils observed in three patients with childhood-onset cyclic neutropenia.

Human cyclic neutropenia (CN) is a rare haematological disorder characterized by regular fluctuation in the serial count of blood neutrophils. The oscillations occur at subnormal levels with a stable 3-week period. To reduce the risk of serious infections during the severe neutropenic nadir phases (< 0.25 x 10(9) neutrophils/l) patients are usually treated with recombinant growth factors. Compared with G-CSF, which has been shown to enhance the amplitudes substantially, the response to GM-CSF is poor: neutrophil numbers are not amplified, the cycles remain unchanged or are dampened. However, two cases with a modest neutrophil increase have been reported in the literature. In a recently published clinical study the different effects of GM-CSF and G-CSF application have been investigated in the same patients. Based on a mathematical model of CN we previously proposed, the detailed neutrophil data measured in this study are analysed by simulation. The contrasting clinical results can be quantitatively explained by the model concept of regulatory control together with possible individual feedback defects, i.e. abnormally reduced mitotic responsiveness of granulopoietic progenitor cells to GM-CSF and G-CSF.

Cell Division↗
PubMed1996

Genetic and environmental influences on temperament in middle childhood: analyses of teacher and tester ratings.

Parent ratings of temperament in infancy and childhood yield evidence for genetic influence in twin studies but not in adoption studies. The present study used the sibling adoption design to investigate teacher and tester ratings of temperament in middle childhood. When each child was 7 years old, ratings on the Colorado Childhood Temperament Inventory were obtained from a teacher and tester for more than 50 pairs each of adoptive and nonadoptive siblings in the Colorado Adoption Project. Significant genetic influence emerged for both teacher and tester ratings of Activity, for tester ratings of Sociability, and for teacher ratings of Emotionality. Results obtained from bivariate genetic analysis suggest that the modest covariance between teacher and tester ratings of Activity is entirely mediated genetically. Except for teacher ratings of Attention Span, evidence of shared family environment was nonsignificant, despite the power of the sibling adoption design to detect it.

Adoption↗
PubMed1995

[Prognostic relevance of oncologic after-care].

Follow-up programs in oncology after potentially curative therapy intent to detect recurrent cancer, to initiate a new curative therapy, to detect side-effects and secondary cancer. The prognostic relevance of follow-up in oncology can be defined as the rate of asymptomatic detected potentially curable recurrences. Follow-up programs of different tumors usually combine various diagnostic methods in a standardized schedule. The prognostic relevance of this follow-up programs is investigated in only very few studies. While efficacy of the follow-up in gastro-intestinal cancer must be questioned, follow-up in non-seminomatous germ cell cancer has proven to be effective. This shows that global statements about prognostic relevance of follow-up can not be made. It is therefore necessary to investigate the actual follow-up programs in clinical studies whether they are effective to improve the prognosis in cancer patients. Where the actual programs fail to be effective new risk-adapted follow-up concepts must be created. New approaches in diagnosis and treatment of cancer have to tested whether they can improve the effect of follow-up programs.

Aftercare↗
PubMed1995

Photodynamic action of ultraviolet A: induction of cellular hydroperoxides.

Long-wavelength ultraviolet radiation (UVA) can cause cancer. A carcinogenic mechanism involved may be the induction of harmful reactive oxygen species resulting from photodynamic effects. UVA is generally assumed to induce photodynamic effects, but evidence from experiments with viable biological materials has been indirect until present. Here we measured the induction of (lipid) hydroperoxides as direct indicators of photodynamic reactions. Cultured human fibroblasts were irradiated with 10J UVA/cm2. The induced hydroperoxides were measured by an enzymatic method using glutathione peroxidase and glutathione reductase (GR). Additionally, reduced glutathione (GSH) was determined as parameter for the constitutive antioxidant defense. UVA was found to increase lipid hydroperoxides in fibroblasts by 116% (p < 0.001), when compared to nonirradiated controls. Conversely GSH was decreased in the irradiated cells by 51% (p < 0.001). Because of the induced hydroperoxides, it is concluded that the UVA effects were mediated by a photodynamic mechanism. The photodynamic mechanism resulted in the formation of reactive oxygen species and the consumption of constitutive antioxidants. This suggests a role for antioxidants during the photodynamic mechanism. Photodynamic mechanisms may play a crucial role in carcinogenic events, especially after UVA.

Antioxidants↗
PubMed1995

The effect of continuous G-CSF application in human cyclic neutropenia: a model analysis.

Human cyclic neutropenia (CN) is a rare haematological disorder characterized by oscillations of blood neutrophils at subnormal levels with a stable period of approximately 21 d. During the phase of severe neutropenia (neutrophils < 250 cells/microliters), which last 4-10 d, the patients are endangered by serious infections. Several authors report that continuous G-CSF application can elevate the blood neutrophils to such a level that the risk of infections is significantly reduced. Although the characteristic cycles are not eliminated by G-CSF, the period of the oscillations is shortened to 12-14 d. Based on a previously proposed computer-simulation model of human CN, the effects of continuous G-CSF application on CN are studied. It is shown how the known different cell-kinetic effects of G-CSF on granulopoiesis explain the clinical data in CN. The reduced length of the cycles emerges as a result of the transit time reduction of the post-mitotic granulopoietic cells by G-CSF. The measured increase of the neutrophil maxima is reproduced by the additional mitoses of the immature granulopoietic bone marrow cells induced by G-CSF. The slight elevation of the neutrophil nadirs can be attributed to a weak effect of G-CSF on the assumed underlying defect in CN (an abnormally small variance of the granulopoietic bone-marrow transit time).

Cell Cycle↗
PubMed1995

Distinct and differently regulated Mo-dependent nitrogen-fixing systems evolved for heterocysts and vegetative cells of Anabaena variabilis ATCC 29413: characterization of the fdxH1/2 gene regions as part of the nif1/2 gene clusters.

Two different fdxH genes (fdxH1, fdxH2) have been isolated from the nitrogen-fixing, heterocyst-forming cyanobacterium Anabaena variabilis ATCC 29413. They are part of two different nif gene clusters, nif1 and nif2. fdxH1 encodes the [2Fe-2S] ferredoxin that is known as the direct electron donor to nitrogenase in heterocysts, and is very similar to FdxH from Anabaena sp. PCC 7120. FdxH2 has more residues in common and shares its oxygen sensitivity with the single FdxH from the non-heterocystous, filamentous cyanobacterium Plectonema boryanum PCC 73110. The latter expresses nitrogenase early (< or = 3-4h) after nitrogen depletion in vegetative cells and exclusively under anaerobic conditions. fdxH2 and the nif2 genes of Anabaena 29413 are also transcribed < or = 4 h after onset of nitrogen-stepdown, exclusively under anaerobic growth conditions and long before functional heterocysts appear. At this time, no fdxH1 and nif1 gene transcription was observed. It occurred later and was associated with nitrogen fixation under aerobic conditions, i.e. within heterocysts. fdxH2 and nifHDK2 were not transcribed during aerobic, nitrogen-fixing growth. In addition, neither was an fdxH2-type gene found nor an anaerobically and early inducible Nif2 system detectable in Anabaena 7120. These data reveal that in filamentous cyanobacteria two different Nif systems have evolved based on molybdenum nitrogenases. It is concluded that a Nif2-type system operates in vegetative cells of non-heterocystous and some, but not all, heterocyst-forming filamentous cyanobacteria. It is environmentally regulated by the levels of both oxygen and combined nitrogen in the habitat. To simultaneously allow for oxygen-evolving photosynthesis and oxygen-sensitive nitrogen fixation, the Nif1-type system probably branched from an ancestral Nif2-type system and has evolved for an exclusive operation within heterocysts. Accordingly, its expression has become an obligate late event in the developmental programme of heterocyst differentiation, irrespective of aerobic or anaerobic growth conditions.

Amino Acid Sequence↗
PubMed1995

Problem behavior in early and middle childhood: an initial behavior genetic analysis.

Twin samples were used to estimate the relative importance of genetic and environmental influences on problem behavior in children, assessed by the Child Behavior Checklist (CBCL). For the younger cohort, mothers completed the CBCL/2-3, while for the older cohort the CBCL/4-18 was used. Nearly half of the older sample had also been assessed with the questionnaire for younger children at a prior date, providing tentative answers regarding continuity and change in the etiology of problem behavior. Results suggested that shared environmental influences may be more important in early childhood than in middle childhood, while the reverse holds for genetic influences.

Child↗
PubMed1995

Dual role of melanins and melanin precursors as photoprotective and phototoxic agents: inhibition of ultraviolet radiation-induced lipid peroxidation.

Ultraviolet radiation (UVR) is one of the risk factors for skin cancer and the main inducer of melanin pigmentation, the major protective mechanism of mammalian skin against radiation damage. The melanin pigments, eumelanin and pheomelanin, are likely to be important in protection against UVR, but their precursors are generally considered as phototoxic. The available data suggest DNA damage as the mechanism of phototoxicity. However, the effect of melanin precursors on membrane damage through lipid peroxidation, another important and probably more relevant (from the point-of-view of the melanosomal confinement of these molecules) mechanism of phototoxicity, not known. As a model system for UVR-melanin-membrane interactions, we irradiated liposomes in the presence of eumelanin, pheomelanin and two of their major precursors, 5,6-dihydroxyindole (DHI) and 5-S-cysteinyldopa (SCD). The presence of the two melanin precursors substantially reduced the formation of lipid peroxidation products resulting from UVR exposure. The antioxidant activity of the melanin precursors was diminished under strong prooxidant conditions (presence of Fe3+). These results suggest that melanin precursors may have an important role in the protection of skin against the harmful effects of UVR including photocarcinogenesis.

Animals↗