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Biomedical subjects

A Schulte

Publications and source records attributed to A Schulte.

At least 19 recordsLinked to original sources
PubMed2002

Workshop report. Children as a special subpopulation: focus on immunotoxicity. Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV), 15-16 November 2001, Berlin, Germany.

An international symposium on the impact of environmental hazards, chemicals and drugs on the developing immune system of children was held in Berlin (Germany) organized by the BgVV. Epidemiological evidence indicates that an immature immune system challenged early in life by bacterial antigens may prevent, to some extent, allergic reactions including asthma bronchiale triggered by environmental pollutants. However, the prevalence for infectious disease is increased in childhood, especially when exposure to contaminants takes place in the period of pregnancy and breast-feeding. The effects of chlorinated biphenyls, dioxin, endotoxins, hexachlorobenzene, and direct and indirect in utero tobacco smoke exposure are examples. All participants recommend comparative and follow-up epidemiological studies and clinical examination of infants and children at risk during upbringing. There is ample evidence from experimental studies that indicates adverse effects on the developing immune system after in utero and postnatal exposure to chemicals and drugs. The adverse reactions of aciclovir, benzodiazepines, hexachlorobenzene, organotins (di-n-octyltin dichloride, tributyltin oxide), pesticides (methoxychlor, heptachlor) and polyhalogenated aromatic hydrocarbons (2,3,7,8-tetrachlorodibenzo-p-dioxin) are presented and reviewed. To determine the predictive value of test data in risk assessment for neonates and children, development, differentiation and maturation of the immune system in humans and laboratory rodents is compared in their pre- and postnatal stages. Considering some differences in immunocompetence at birth and after lactation, and differences in the time frame for maturation of the immune system, reaction types are thought to be common, comparable and similar in human childhood and early adolescence and the postnatal lifetime of laboratory rodents. The participants of the symposium felt strongly that regulatory steps urgently need to be initiated to incorporate some relevant aspects into existing test guidelines for testing developmental immunotoxicity. In this context, it is recommended that animals culled otherwise in one- and two-generation studies be examined for developmental immunotoxicity according to the valid methods and parameters discussed. The majority of participants agreed that a safety factor of 10 is too low in risk assessment and management to protect a sensitive subpopulation of children against man-made environmental pollutants.

Animals↗
PubMed2002

Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer's disease.

Cholesterol and 24S-hydroxycholesterol are involved in the pathogenesis of Alzheimer's disease (AD). Increased serum cholesterol concentrations have been detected in patients with AD. 24S-Hydroxycholesterol is the primary cholesterol elimination product of the brain and possesses neurotoxic properties in vitro. The enzyme catalyzing the conversion of cholesterol to 24S-hydroxycholesterol, cholesterol 24S-hydroxylase (CYP46), is mainly expressed in neurons. Concentrations of 24S-hydroxycholesterol in cerebrospinal fluid (CSF) and serum differ significantly between AD patients and non-demented subjects. To test the hypothesis if polymorphisms in the CYP46 gene might influence the function of the respective enzyme and thus cholesterol metabolism in the human brain, we screened for polymorphisms in 114 AD patients and 144 healthy controls. Two intronic single nucleotide polymorphisms were observed and their allelic distribution was investigated. In our study sample, carriers of the C allele of the IVS3+43C --> T polymorphism were more prevalent in the group of AD patients than in healthy controls, while another IVS2-150A --> G polymorphism did not show a significant association with AD. The CC genotype of the IVS3+43C --> T polymorphism was associated with an increased 24S-hydroxycholesterol/cholesterol ratio in the CSF of AD patients. Our results indicate that the CYP46 gene locus may predispose to AD by increasing the 24S-hydroxycholesterol/cholesterol ratio in the brain.

Aged↗
PubMed2001

Association of caries experience in 12-year-old children in Heidelberg, Germany, and Montpellier, France, with different caries preventive measures.

UNLABELLED: In Germany and France, different approaches to oral health promotion have been chosen. OBJECTIVES: It was the aim of the present study to assess whether different preventive measures were positively or negatively associated with caries experience in 12-year-old children in Heidelberg, Germany, and in Montpellier, France. METHODS: In the school year 1998/99, 12-year-old children were examined in Heidelberg (n=864) and in Montpellier (n =828). D3+4MFT, D3+4MFS (D3+4=dentinal caries), prevalence of fissure sealants and use of fluorides were recorded. RESULTS: The mean D3+4MFT scores of the pupils in Heidelberg and Montpellier were 1.56 and 1.42, the proportion of caries-free children being 43.5% and 46.9%, respectively. In 63.2% of the children in Heidelberg and in 6.8% of the children in Montpellier, at least one fissure sealed tooth was found. Fluoridated salt was used by 38.8% of families of the 12-year-olds from Heidelberg and the corresponding value was 73.3% in Montpellier. Topical fluorides were applied by 39.9% of the children in Heidelberg, but only by 5.4% of pupils in Montpellier. Multiple regression analysis revealed that, in Heidelberg, fissure sealants and the combination of topical fluorides and fluoridated salt were negatively associated with the D3+4MFT values, while in Montpellier the frequency of dental visits was positively associated with the D3+4MFT scores. CONCLUSION: A further decrease in the caries experience of 12-year-old children may well be obtainable by enlarging the share of marketed fluoridated salt in Heidelberg, by increasing the application of fissure sealants in Montpellier, and by extending the use of topical fluorides in both cities.

Chi-Square Distribution↗
PubMed2001

Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self.

Expression of peripheral antigens in the thymus has been implicated in T cell tolerance and autoimmunity. Here we identified medullary thymic epithelial cells as being a unique cell type that expresses a diverse range of tissue-specific antigens. We found that this promiscuous gene expression was a cell-autonomous property of medullary epithelial cells and was maintained during the entire period of thymic T cell output. It may facilitate tolerance induction to self-antigens that would otherwise be temporally or spatially secluded from the immune system. However, the array of promiscuously expressed self-antigens appeared random rather than selected and was not confined to secluded self-antigens.

Animals↗
PubMed2000

Protective effect of amifostine on dental health after radiotherapy of the head and neck.

PURPOSE: The cytoprotective agent amifostine has been shown to reduce the radiation-induced acute and chronic xerostomia in head and neck cancer patients. The purpose of this study was to evaluate whether or not amifostine also reduces the incidence of dental caries associated with the radiation-induced xerostomia. METHODS AND MATERIALS: The dental status before and 1 year after radiotherapy was retrospectively compared in 35 unselected patients treated as part of the prospective randomized and multicenter open-label Phase III study (WR-38) at the University Hospitals of Heidelberg, Freiburg, and Erlangen. The WR-38 study compared radiotherapy in head and neck cancer with and without concomitant administration of amifostine. RESULTS: Patient and treatment characteristics (particularly the radiation dose and percentage of parotids included in the treatment volume) were equally distributed between the patients who received (n = 17) or did not receive (n = 18) amifostine. Fifteen patients of the amifostine group showed no deterioration of the dental status 1 year after radiotherapy as compared to 7 patients who did not receive the cytoprotector (p = 0. 015, two-tailed Fisher exact test). CONCLUSION: Our data suggest a protective effect of amifostine on the dental health after radiotherapy of the head and neck. The dental status should be used as a primary endpoint in future studies on amifostine.

Adult↗
PubMed2000

Progressive reduction of CMV-specific CD4+ T cells in HIV-1 infected individuals during antiretroviral therapy.

Visualization of antigen-specific T cells has become an important tool in studying immune responses. The aim of this study was to analyze CMV-specific CD4+ T cells in healthy and HIV-infected individuals. Peripheral blood mononuclear cells (PBMC) were examined for antigen-induced intracellular cytokine responses. We found significant numbers of CMV-specific CD4+ T cells detectable in most CMV-IgG+ HIV-1 infected individuals, whereas CMV-specific CD4+ T cells could not be demonstrated in CMV-IgG- patients. Median frequency of CMV-specific CD4+ T cells were lower in HIV-infected subjects who had been treated with highly active antiretroviral therapy (HAART) for more than 1 year than in untreated HIV-infected individuals. In patients under therapy for less than 1 year median CMV-specific CD4+ T cell responder frequency was higher than in subjects treated for more than 1 year but lower than in untreated subjects. HIV suppression with HAART might lead to a progressive reduction of CMV-specific CD4+ T cells indicating an efficient elimination of an opportunistic pathogen.

Adult↗
PubMed1999

Outcome of occupational asthma due to platinum salts after transferral to low-exposure areas.

OBJECTIVE: To assess the health effects of transferral to low-exposure jobs on subjects with occupational asthma (OA). METHODS: We performed a cross-sectional survey of 83 workers in 2 platinum (Pt) refineries and 2 catalyst production plants, all with diagnosed OA due to Pt salts. In all, 9 workers (group A; 11%) continued to be exposed at the time of examination, 16 subjects (group B; 19%) had been transferred to other workplaces within the production building, 39 subjects (group C; 47%) had been transferred to areas outside the building but inside the plant, and 19 subjects (group D; 23%) had left the plant. The median period from transferral to examination was 54 months (lower quartile 23 months, upper quartile 84 months, n = 74). Symptoms, skin-prick tests (SPT) with environmental allergens and Pt salt, total serum IgE, lung function, and bronchial hyperresponsiveness were assessed by standard procedures. RESULTS: Asthma symptoms were reported by all subjects in the production area but by only 37 of 74 subjects (50%) after transferral, with no difference being found between groups B, C, and D. Both the proportion of subjects sensitized to Pt salts (100%, 88%, 67%, and 42% in groups A, B, C, and D, respectively) and the degree of sensitization were associated with exposure (P < 0.0002). Total IgE was higher in group A as compared with groups B, C, or D (P < 0.002). There was no association between bronchial hyperresponsiveness and exposure. Although no univariate difference in FEV1 was found between the groups, regression analysis showed an association between FEV1 and exposure (P < 0.002). In all, 13 subjects demonstrated a predicted FEV1 value of <80% (22%, 6%, 10%, and 32% in groups A, B, C, and D, respectively). They were older (median 49 versus 37 years; P < 0.002) and had worked over longer periods in high-exposure areas in spite of symptoms (median 43 versus 10 months; P < 0.003). Fifteen subjects of groups C or D had been removed from areas B previously, eight of them due to respiratory symptoms. CONCLUSIONS: For the majority of subjects with OA due to Pt salts transfer to low exposure areas as defined in this study may not be associated with a more unfavorable outcome as compared with complete removal from exposure sources.

Adult↗
PubMed1999

Longevity of cast gold inlays and partial crowns--a retrospective study at a dental school clinic.

From 1963 to 1993, 890 patients were treated with 3518 cast gold restorations by students and postgraduate dentists. The longevity of these restorations was studied retrospectively using the patient files. Longevity was calculated using the method described by Kaplan and Meier. After the observation period, 111 (3.2%) of the examined restorations were not in place anymore. The most frequent reasons for failure were caries (33.7%), lack of retention (32.7%), endodontic treatment (29.6%), insufficient marginal adaptation (3.1%) and extraction (1%). The cumulative survival rate and a 95% interval of confidence was calculated for all restorations and for each of the locations and surfaces included in the trial. The 10-year survival rate for occlusal inlays was, 76.1% (12.1) for MO inlays 88.3% (4.2), for DO inlays 83.4% (4.6), for MOD inlays 87.5% (2.4), for partial crowns 86.1% (3.3) and 85.7% (1.7) for all restorations. Based on the statistical method used, the cast gold restorations demonstrated satisfactory longevity results.

Adult↗
PubMed1999

[Ready-made crowns in the deciduous dentition].

The following review of the literature on "prefabricated crowns for deciduous teeth" attempts to highlight the benefits and limitations of this treatment modality. The use of prefabricated crowns is indicated in the following situations: severe destruction of the clinical crown, deep approximal cavities, bilateral approximal cavities, circumferential caries, history of root canal treatment, and need for fixed space retention. Compared to amalgam restorations involving two or more surfaces, prefabricated crowns on deciduous molar teeth gave very high survival rates. They consist of a chromium-nickel-steel alloy and are reported to have an acceptable gingival tolerance profile. In contrast to the Anglo-American countries this treatment modality is quite uncommon in Germany. A probable reason for this reservation could be that many clinicians often fail to see the need for a filling in the deciduous dentition. Besides, many dentists are reluctant to use local anesthesia in children, which is inevitable in preparing and fitting a prefabricated crown. In the United States and UK dentists are less frequently confronted with this problem, as complex treatments are often carried out under nitrous oxide sedation or insufflation anesthesia. Modern filling materials have been introduced which have the potential to narrow the indications for prefabricated stainless steel crowns. Against this background, future studies are necessary to compare the survival rates of prefabricated crowns and modern filling materials.

Child↗
PubMed1998

Extrasynaptic vesicular transmitter release from the somata of substantia nigra neurons in rat midbrain slices.

Substantia nigra neurons release dopamine from their somatodendritic regions. A long-unresolved question is whether this release occurs by exocytosis or by a nonvesicular mechanism. We used carbon fiber microelectrodes in a brainstem slice to assay secretion from single cell bodies that had been cleared of connective tissue. Amperometry at the carbon fiber microelectrodes revealed unitary events in approximately 90% of cells in resting conditions. These events had charge integrals ranging from a few femtocoulombs to several hundred femtocoulombs (fC). Local glutamate application enhanced the event frequency by 3.5-fold on average and up to 10-fold in highly responsive cells, although the mean charge integral was not modified. Local application of a high K+-containing saline had effects similar to those of glutamate. The frequency of resting and stimulated amperometric events was much lower at 21-22 degreesC than at 32-35 degreesC. The addition of Cd2+ (50 microM), a blocker of voltage-dependent Ca2+ channels, to the bath solution blocked the stimulatory effects of glutamate. These results suggest that dopamine is released from the somata of substantia nigra neurons by exocytosis and that this mechanism is regulated by neuronal electrical activity. More generally, this study demonstrates the applicability of carbon fiber microelectrodes to the measurement of quantal monoamine secretion in brain slices.

Animals↗
PubMed1998

Prevalence and quality of root canal fillings in a German adult population. A survey of orthopantomograms taken in 1983 and 1992.

The few studies in which prevalence, technical quality, and success rates of root canal fillings performed in daily practice have been assessed demonstrated a high proportion of inappropriate root fillings and a great variety of periapical radiolucencies (25-60%). The aim of the present retrospective radiographic study was to determine if changes in prevalence, technical quality, and success of root canal fillings had occurred within a decade. To achieve this goal, orthopantomograms taken in patients who attended a University Dental Clinic for the first time in 1983 (group A) and in 1992 (group B) were evaluated by a calibrated examiner. The following criteria were applied to assess the root-filled teeth: length and homogeneity of the root fillings and the periapical state. The prevalence of root-filled teeth increased significantly from an average 0.5 per person in 1983 to 0.8 per person in 1992. The increase was proportionally greater in older patients. In group A, 55.2% of the root fillings ended 0-2 mm before the radiographic apex and in group B this percentage was 56.8. Insufficient homogeneity was found in 25.0% (group A) and 21.9% (group B) of the root fillings. The prevalence of root-filled teeth without periapical destructions was 76.1% (group A) and 74.1% (group B). It is concluded that, in the future, endodontic treatment need will increase because of the steadily growing number of older people. Further efforts in research and dental education should focus on the treatment of curved root canals.

Adolescent↗
PubMed1998

The electrical resistance of enamel-dentine cylinders. Influence of NaCl content in storage solutions.

OBJECTIVES: To investigate the influence of different electrolyte concentrations on the electrical resistance of sound human enamel-dentine cylinders in vitro. METHODS: Forty cylinders of 3-mm diameter and 2-mm length were drilled from 40 extracted caries-free third molar teeth. For ease of handling the samples were fixed in Perspex discs by means of a cyanoacrylate-adhesive. An a.c. source (frequency 500 Hz, amplitude 1 microA) with a high internal resistance was applied. Only Ohm's resistance was measured. The resistance measurements on the samples were made after storage in distilled water, 0.16 mM NaCl, 1.6 mM NaCl and 16 mM NaCl and 160 mM NaCl for 24 h. RESULTS: The mean resistance values were 2026 +/- 152, 1835 +/- 178, 1605 +/- 364, 483 +/- 265 and 60 +/- 33 k omega, respectively. All values were statistically significantly different (Wilcoxon test; P < 0.0001). CONCLUSION: It is concluded that the choice of electrolyte solution influences the resistance values of the enamel-dentine samples. This effect should be taken into account when measuring electrical resistances in vivo and in vitro.

Cyanoacrylates↗
PubMed1998

Carcinogenicity and DNA adduct formation observed in ACI rats after long-term treatment with madder root, Rubia tinctorum L.

Madder root, Rubia tinctorum L., is a traditional herbal medicine used against kidney stones. Recently we reported that lucidin, a hydroxyanthraquinone derivative present in this plant, is mutagenic in bacteria and mammalian cells. We also demonstrated the formation of DNA adducts in tissue culture and mice after treatment with this compound. To elucidate the possible carcinogenicity of madder root, three groups of male and female ACI rats received either a normal diet or a diet supplemented with 1 or 10% drug for a total period of 780 days. Weight gain and morbidity were not different among the three groups. Non-neoplastic lesions related to the treatment were evident in the liver and kidneys of both sexes. Moreover, dose-dependent increases in benign and malignant tumour formation were observed in the liver and kidneys of treated animals. 32P-post-labelling analysis showed an increase in the overall level of DNA adducts observed in the liver, kidney and colon of rats treated with 10% madder root in the diet for 2 weeks. HPLC analysis of 32P-labelled DNA adducts revealed a peak co-migrating with an adduct obtained after in vitro treatment of deoxyguanosine-3'-phosphate with lucidin. These observations suggest that the use of madder root for medicinal purposes is associated with a carcinogenic risk.

Animals↗
PubMed1998

Cognitive-behavioral psychotherapy for children and adolescents with posttraumatic stress disorder after a single-incident stressor.

OBJECTIVE: To test the efficacy of a group-administered cognitive-behavioral psychotherapy (CBT) protocol for pediatric posttraumatic stress disorder (PTSD) after a single-incident stressor. METHOD: After a school-wide selection-to-treatment procedure conducted in two elementary and two junior high schools, children and adolescents with DSM-IV PTSD by structured interview were entered into an 18-week, group-administered CBT protocol using a single case across time and setting experimental design. Assessments of PTSD, anxiety, depression, trait anger, locus of control, and disruptive behavior were conducted at baseline, posttreatment, and at 6-month follow-up. RESULTS: Experimental control across time (staggered start date) and setting (school and age) was demonstrated. Fourteen of 17 subjects completed treatment. Of these, 8 (57%) no longer met DSM-IV criteria for PTSD immediately after treatment; 12 (86%) of 14 were free of PTSD at 6-month follow-up. On intent-to-treat analyses, treatment produced a robust beneficial effect posttreatment on the Clinician-Administered PTSD Scale-Child and Adolescent Version, with additional improvement accruing at follow-up (p < .001). Improvements of a similar magnitude were seen for depression (p < .001), anxiety (p < .001), and anger (p < .005). Locus of control remained external from pre- to posttreatment but became strongly internal at follow-up (p < .001). CONCLUSION: More clinical trials are required to confirm that CBT is a safe, acceptable, and effective treatment for PTSD in children and adolescents.

Adolescent↗
PubMed1997

Vibrational frequency shifts as a probe of hydrogen bonds: thermal expansion and glass transition of myoglobin in mixed solvents.

The contribution of hydrogen bonds to protein-solvent interactions and their impact on structural flexibility and dynamics of myoglobin are discussed. The shift of vibrational peak frequencies with the temperature of myoglobin in sucrose/water and glycerol/water solutions is used to probe the expansion of the hydrogen bond network. We observe a characteristic change in the temperature slope of the O-H stretching frequency at the glass transition which correlates with the discontinuity of the thermal expansion coefficient. The temperature-difference spectra of the amide bands show the same tendency, indicating that stronger hydrogen bonding in the bulk affects the mainchain solvent interactions in parallel. However, the hydrogen bond strength decreases relative to the bulk solvent with increasing cosolvent concentration near the protein surface, which suggests preferential hydration. Weaker and/or fewer hydrogen bonds are observed at low degrees of hydration. The central O-H stretching frequency of protein hydration water is red-shifted by 40 cm-1 relative to the bulk. The shift increases towards lower temperatures, consistent with contraction and increasing strength of the protein-water bonds. The temperature slope shows a discontinuity near 180 K. The contraction of the network has reached a critical limit which leads to frozen-in structures. This effect may represent the molecular mechanism underlying the dynamic transition observed for the mean square displacements of the protein atoms and the heme iron of myoglobin.

Animals↗
PubMed1997

Pressure effects on the proximal heme pocket in myoglobin probed by Raman and near-infrared absorption spectroscopy.

The influence of high pressure on the heme protein conformation of myoglobin in different ligation states is studied using Raman spectroscopy over the temperature range from 30 to 295 K. Photostationary experiments monitoring the oxidation state marker bands demonstrate the change of rebinding rate with pressure. While frequency changes of vibrational modes associated with rigid bonds of the porphyrin ring are <1 cm(-1), we investigate a significant shift of the iron-histidine mode to higher frequency with increasing pressure (approximately 3 cm(-1) for deltaP = 190 MPa in Mb). The observed frequency shift is interpreted structurally as a conformational change affecting the tilt angle between the heme plane and the proximal histidine and the out-of-plane iron position. Independent evidence for iron motion comes from measurements of the redshift of band III in the near-infrared with pressure. This suggests that at high pressure the proximal heme pocket and the protein are altered toward the bound state conformation, which contributes to the rate increase for CO binding. Raman spectra of Mb and photodissociated MbCO measured at low temperature and variable pressure further support changes in protein conformation and are consistent with glasslike properties of myoglobin below 160 K.

Animals↗
PubMed1995

High-pressure near-infrared Raman spectroscopy of bacteriorhodopsin light to dark adaptation.

Near-infrared (NIR) Raman spectroscopy is employed as an in situ probe of the chromophore conformation to study the light to dark-adaptation process in bacteriorhodopsin (bR) at variable pressure and temperature in the absence of undesired photoreactions. In dark-adapted bR deconvolution of the ethylenic mode into bands assigned to the all-trans (1526 cm-1) and 13-cis (1534 cm-1) isomers yields a 13-cis to all-trans ratio equal to 1 at ambient pressure (Schulte et al., 1995, Appl. Spectrosc. 49:80-83). Detailed spectroscopic evidence is presented that at high pressure the equilibrium is shifted toward the 13-cis isomers and that the light to dark adaptation kinetics is accelerated. The change in isomeric composition with temperature and pressure as well as the kinetics support a two-state model activation volumes of -16 ml/mol for the transition of 13-cis to all-trans and -22 ml/mol for the reverse process. These compare with a conformational volume difference of 6.6 ml/mol, which may be attributed to the ionization of one or two residues or the formation of three hydrogen bonds.

Bacteriorhodopsins↗