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Biomedical subjects

J Schmid

Publications and source records attributed to J Schmid.

At least 73 records · Page 4Linked to original sources

Enzymatic properties of chorismate synthase isozymes of tomato (Lycopersicon esculentum Mill.).

Three plastidic chorismate synthase isozymes (CS1, CS2 and CS2 delta) of tomato were identified by isolation of the corresponding cDNAs. These three cDNAs are derived from only two genes (LeCS1 and LeCS2). This additional complexity results from differential splicing of the primary transcript of one of the genes (LeCS2) giving rise to two different transcripts (CS2 and CS2 delta transcripts). All three isozymes were individually expressed in Escherichia coli both as precursor proteins with N-terminal transit peptides and as mature proteins. Only the mature but not the precursor isozymes CS1 and CS2 were enzymatically active. The enzyme CS2 delta was unstable in E. coli. Both CS1 and CS2 were purified to near homogeneity and their enzymatic properties were analyzed. They differ substantially in their Km values for the substrate 5-enol-pyruvylshikimate 3-phosphate (11 and 80 microM for the mature forms of CS1 and CS2, respectively). The two isozymes appear to be active only as oligomers, and the potential physiological implications of this result are discussed.

Amino Acid Sequence↗

Suicidal behavior in Swiss students: an 18-month follow-up survey.

Suicidal behavior and its relationship with other mental disturbances was assessed in an epidemiological study of 1937 Swiss adolescents aged 14 to 19 years. During the most recent 12 months, 27.5% of the females and 16.1% of the males reported suicidal ideation, while 3.3% of the girls and 1.0% of the boys reported suicidal ideation. Suicidality was significantly correlated with physical and mental impairment, alcohol and drug abuse. Of the total epidemiological sample, 475 students (24.5%) were reassessed 12 and 18 months later. Of this follow-up sample, 37 females (12.4%) and 10 males (5.6%) described suicidal ideation as a continuing problem. They revealed significantly more psychiatric symptoms than nonpersistent ideators. Three girls (1.0%) and one boy (0.6%) reported suicide attempts during the follow-up period of 18 months. Only one out of six of the ideators of both sexes received psychiatric treatment. The findings indicate that transient suicidal ideation is common in adolescents. Persistent suicidal behavior appears to be a sign of severe social and psychological disturbances and is associated with serious physical and mental impairment. There is a high risk of completed suicide for youths who demonstrate persistent suicidal ideation, and far more substantial prevention efforts should be designed and implemented to address the circumstances of these youths.

Adolescent↗

A novel model system for the study of experimental guided bone formation in humans.

The aim of the present experiment was to test a novel model system, designed to obtain human specimens of regenerated and also newly regenerated jaw bone, for the study of the biological events under a variety of conditions. Following information and disclosure of possible risks associated with a minor oral surgical procedure, 9 systemically healthy subjects (5 men, 4 women, mean age 31.7 years) signed consent forms and volunteered to participate in this study. Hollow test cylinders with an outer diameter of 3.5 mm, an inner diameter of 2.5 mm, and 4 mm in height were used. They were manufactured from commercially pure titanium and exhibited a highly polished inner surface and a titanium plasma sprayed outer rough surface. A mucoperiosteal flap was raised in the retromolar area of the mandible corresponding to standard retrained third molar surgery. Following flap reflection a standardized hole was drilled through the cortical bone into the bone marrow using round burs. The congruent test cylinders were firmly placed into the prepared bony bed yielding primary stability. One-and-a-half to 2 mm of the test device were submerged below the level of the surrounding bone, while the remainder surpassed the level of the bone surface. The bone-facing end of the cylinder was left open, while the coronal soft tissue facing end was closed by an ePTFE-membrane. The flap was sutured to obtain primary wound closure. In order to prevent infection, penicillin was prescribed systemically and oral rinses of chlorhexidine were administered. After 2, 7, and 12 weeks one test device including the regenerated tissue was surgically harvested, while after 16, 24 and 36 weeks respectively, 2 devices were harvested and processed for soft or hard tissue histology or histochemistry. The two surgical procedures and the presence of the test cylinders during the time of healing were well tolerated by the volunteers. In all 9 subjects generated tissue could successfully be harvested. The tissue generated after 2 and 7 weeks presented with a cylindrical shape, whereas the specimens harvested at 12 weeks and thereafter resembled the form of an hourglass. Specimens of 12 weeks and less regeneration time were almost entirely comprised of soft tissue, while specimens with regeneration time of 4 months and more were composed of both soft and increasing amounts of mineralized tissue. It is concluded that the presented model system is suitable to study temporal dynamics and tissue physiology of bone regeneration in humans with minimal risk for complications or adverse effects to the volunteers.

Adult↗

Saccharomyces cerevisiae chorismate synthase has a flavin reductase activity.

Chorismate synthase (CS) catalyses the conversion of 5-enolpyruvylshikimate 3-phosphate (EPSP) to form chorismate, which is the last common intermediate in the synthesis of the three aromatic amino acids phenylalanine, tyrosine and tryptophan. Despite the overall redox-neutral reaction, catalysis has an absolute requirement for reduced flavin. In the fungus Neurospora crassa, a flavin reductase (FR) activity able to generate reduced flavin mononucleotide in the presence of NADPH is an intrinsic feature of a bifunctional CS. In all bacterial and plant species investigated to date, purified CSs lack an FR activity and are correspondingly 8-10 kDa smaller than the N. crassa CS (on the basis of SDS-PAGE). The cloning of N. crassa CS and subsequent characterization of the purified heterologously expressed enzyme indicates that, surprisingly, the FR probably resides within a region conserved amongst both mono- and bifunctional CSs and is not related to non-homologous sequences which contribute to the larger molecular mass of the N. crassa CS. This information directed this work towards the smaller Saccharomyces cerevisiae CS, the sequence of which was known, although the protein has not been extensively characterized biochemically. Here the characterization of the S. cerevisiae CS is reported in more detail and it is shown that the protein is also bifunctional. With this knowledge, S. cerevisiae could be used as a genetic system for studying the physiological consequences of bifunctionality. The phylogenetic relationship amongst known CSs is discussed.

Amino Acid Sequence↗

Cytosolic and plastidic chorismate mutase isozymes from Arabidopsis thaliana: molecular characterization and enzymatic properties.

The three aromatic amino acids phenylalanine, tyrosine, and tryptophan are synthesized in the plastids of higher plants. There is, however, biochemical evidence that a cytosolic isoform exists of the enzyme catalysing the first step of that branch of the pathway which is specific for the synthesis of phenylalanine and tyrosine, i.e. chorismate mutase (CM). We now report on the isolation of a cDNA clone encoding a cytosolic CM isozyme from Arabidopsis thaliana that was identified by complementing a CM-deficient Escherichia coli strain. The deduced amino acid sequence of this isozyme was 50% identical to that of a previously isolated plastidic CM, and 41% identical to that of yeast CM. The organ-specific expression patterns of the two CM genes were rather similar, but only the gene encoding the plastidic isozyme was elicitor- and pathogen-inducible. The plastidic CM expressed in E. coli was activated by tryptophan and inhibited by phenylalanine and tyrosine, whereas the cytosolic isozyme was insensitive. The existence of a cytosolic CM isozyme implies that either a cytosolic pathway (partial or complete) for the biosynthesis of phenylalanine and tyrosine exists, or that prephenate, originating from chorismate in the cytosol, is utilized for the synthesis of metabolites other than these two aromatic amino acids.

Amino Acid Sequence↗

The sink-specific and stress-regulated Arabidopsis STP4 gene: enhanced expression of a gene encoding a monosaccharide transporter by wounding, elicitors, and pathogen challenge.

A cDNA for the Arabidopsis STP4 gene (for sugar transport protein 4) was isolated, and the properties of the encoded protein were studied in Schizosaccharomyces pombe. The STP4 monosaccharide H+ symporter is composed of 514 amino acids and has a calculated molecular mass of 57.1 kD. RNA gel blot analyses revealed that STP4 is expressed primarily in roots and flowers of Arabidopsis. This was shown in more detail with STP4 promoter-beta-glucuronidase (GUS) plants yielding strong STP4-driven GUS activity in root tips and anthers. Wounding of plants transformed with STP4-GUS constructs resulted in a rapid increase in GUS activity in cells directly adjacent to the lesion. This was confirmed by RNase protection analyses in Arabidopsis wild-type plants showing a strong, wound-induced increase in STP4 mRNA levels. STP4 expression was induced rapidly in suspension-cultured Arabidopsis cells that were treated with the Pseudomonas syringae elicitor or with chitin or in Arabidopsis plants that were exposed to fungal attacks. Our data suggest that the role of STP4 is to catalyze monosaccharide import into classic sinks, such as root tips and anthers, and, most importantly, to meet the increased carbohydrate demand of cells responding to environmental stress.

3-O-Methylglucose↗

Epidemiology of eating behaviour and weight distribution in 14- to 19-year-old Swiss students.

A sample consisting of 1944 Swiss students of both sexes was investigated with regard to distribution over weight categories based on BMI age percentiles and eating behaviour (EAT-26) in relation to age, sex and socio-economic status (SES). In addition, the relationship between BMI and Eating Attitudes Test scores was analysed. More subjects than expected were found to be in the obese weight categories. No clear effect of age and sex on the distribution of the sample across the five BMI classes was observed. There was an inverse relationship between BMI and socio-economic status. On the EAT scale girls scored twice as high as boys. Age had no effect on the EAT scores in females, although it did in males. Socio-economic status and EAT scores were inversely associated. Three risk categories based on the EAT scores were described: EAT 0-9 = no risk (77.5% girls, 93.0% boys), EAT 10-19 = low risk (14.1% girls, 5.5% boys), and EAT > or = 20 = high risk (8.3% girls, 1.5% boys). With regard to both aspects, weight and eating behaviour, female students showed more disturbed eating behaviour and fewer instances of deviation from normal weight. In male subjects there were more deviations from normal weight than instances of disturbed eating behaviour.

Adolescent↗

Relationship between disturbed eating behavior and other psychosomatic symptoms in adolescents.

BACKGROUND: There has been relatively little research on subthreshold eating disorders and factors which might promote their transition to eating disorders. METHODS: A sample consisting of 1,944 Swiss adolescents of both sexes, 14-19 years of age, was investigated for eating behavior (EAT-26), psychological (SCL-90-R) and physical symptoms (GSCL-C). In addition, the relationship between eating behavior and other psychosomatic symptoms was analyzed. RESULTS: The results revealed significantly higher scores for females than males on all except one scale of the questionnaires. Three categories of disturbed eating behavior based on the EAT scores were described: EAT 0-9 = not disturbed (77.5% girls, 93.1% boys), EAT 10-19 = moderately disturbed (14.1% girls, 5.5% boys), and EAT > or = 20 = severely disturbed (8.3% girls, 1.5% boys). With regard to the three aspects, eating habits, psychosomatic symptoms and suicidality a significant correlation between disturbed eating behavior and concurrent psychological and physical symptoms was found in female but not in male subjects. CONCLUSIONS: The results emphasized that disordered eating behavior has to be seen as part of a broader psychopathological syndrome, especially in young women.

Adolescent↗

Field test to evaluate telepathology in telemedicine.

Telepathology is currently performed only on prototype systems. The application of telepathology consultations differs from the conventional procedure because of the technical and cost restrictions. This paper outlines technical concepts and the principal hardware and software modules necessary for telemicroscopy equipment. A field test to gather information concerning the user needs and to evaluate parameters of telepathology consultation sessions is reported.

Computer Communication Networks↗

[Anomalous origin of the left coronary artery from the right sinus of Valsalva with acute symptoms].

The case of a 52-year-old man with an anomalous origin of the left coronary artery from the right sinus of valsalva coursing between the aorta and pulmonary trunk is reported with an acute myocardial ischemia. He had an additional high-grade main-stem stenosis in the course behind the pulmonary artery. The anatomical variants, clinical significance, and cause of ischemia are discussed. Also, technical considerations in both diagnosis and management are given.

Coronary Angiography↗

Studies on the chronic oral toxicity of an analgesic drug combination consisting of acetylsalicylic acid, paracetamol and caffeine in rats including an electron microscopical evaluation of kidneys.

The analgesic drug combination Thomapyrin consisting of acetylsalicylic acid (CAS 50-78-2, ASA), paracetamol (CAS 103-90-2, NAPAP) and caffeine (CAS 58-08-2) in the ratio 5:4:1 was investigated for its chronic toxicity in rats. For comparison the individual drugs ASA and NAPAP as well as the double combination ASA+NAPAP were tested in equipotent doses. 20 male and 20 female rats per group (Chbb:THOM/SPF) received doses of 50, 100 and 200 mg/kg of the combination ASA+NAPAP+caffeine, 45 and 180 mg/kg of the combination ASA+NAPAP, and 50 and 200 mg/kg of the individual drugs ASA or NAPAP over a period of 6 months. The daily dose was splitted into two parts and administered 3 h apart. The rats were single housed under standardized conditions with free access to food and drinking water. Plasma concentrations were measured in four additional animals of all high dose groups after the last dosing at seven time points. Besides the usual routine toxicological investigations the kidneys of five females per group were investigated by transmission electron microscopy. All investigations were performed according to GLP regulations. All animals behaved unobtrusively throughout the study with only minor impairment of general conditions in some animals of all ASA, ASA+NAPAP+caffeine and the high dose NAPAP groups. Dose related mortality was observed in the groups receiving ASA alone or in combination, partly with rales and tonic convulsions immediately prior to death. Body weight gain was decreased in males but not in females of the ASA+NAPAP+ caffeine and ASA groups. No consistent drug- and dose-dependent changes in hematological, clinico-chemical or urinanalytical parameters were observed, except for a slight increase in excretion of epithelial cells in both genders of the ASA groups. Plasma drug level monitoring demonstrated that the pharmacokinetics of ASA were not altered by co-administration of caffeine or NAPAP or vice versa. In males, maximum plasma concentrations (Cmax) and areas under the curve (AUC) for ASA and NAPAP tended to be slightly lower than in females. The plasma concentrations reached in the study represent a low multiple (2.2-7.9) of therapeutic plasma levels. Therefore, the results reported in the study can be considered representative for normal therapeutic use of the analgesic combination ASA+NAPAP+caffeine. Gastric erosions in the ASA and ASA+NAPAP+caffeine groups, increased kidney weights in females given 200 mg/kg ASA+NAPAP+caffeine, and dose-dependently increased liver weights in females given 200 mg/kg ASA and decreased liver weights in males at 100 and 200 mg/kg ASA-NAPAP+caffeine were the only consistent drug-induced changes observed at necropsy. Except for the above mentioned ulcer, all histopathological findings were iatrogenic or spontaneous lesions. The kidneys demonstrated initial stages of age-associated nephropathy at comparable incidence and severity in all groups including controls. Semi-thin section evaluation and transmission electron microscopy showed only minor changes. Taking all tubular and vascular changes together (total mean), the animals of the NAPAP group were slightly more affected than those of the other groups. Summing up it can be concluded that the nephrotoxic potential of the combination ASA+NAPAP+caffeine, if existing at all, was marginal even after prolonged administration, and that it does not exceed that of the monosubstances when given at pharmacologically equipotent doses and clinically relevant exposures.

Acetaminophen↗

Cloning and characterization of a heterologously expressed bifunctional chorismate synthase/flavin reductase from Neurospora crassa.

Activities of all chorismate synthases (CS) so far analyzed are absolutely dependent upon reduced flavin. For monofunctional CSs, which represent the only class of CSs that have yet been cloned, the flavin must be reduced either (photo-)chemically or by a separable flavin reductase (FR) for in vitro activity. Neurospora crassa CS, in contrast, possesses an intrinsic FR activity and represents the only firmly established member of a bifunctional class of CSs. To better understand this bifunctional protein, a cDNA from an N. crassa expression library encoding a 46.4-kDa protein was cloned by complementation of the CS-deficient Escherichia coli strain AB2849. The deduced amino acid sequence was highly similar (79%) to a previously isolated Saccharomyces cerevisiae CS. The N. crassa sequence was unequivocally shown to encode the bifunctional CS/FR by analysis of the purified protein expressed in E. coli. Based on sequence comparisons with known monofunctional CSs, two regions of 18 internal residues and 29 C-terminal residues unique to N. crassa CS were deleted, and the constructs were also expressed in E. coli. The presence of these regions was found not essential for complementation of the CS- phenotype of E. coli strain AB2849. Although a 3.5-fold decline in specific activity of the purified CS from cells expressing the C-terminal deletion construct was observed, bifunctional activity was not eliminated. These data strongly suggest that the domain(s) responsible for reduction of flavin lie(s) within regions in which homology is also shared among monofunctional CSs.

Amino Acid Sequence↗

Temporally distinct accumulation of transcripts encoding enzymes of the prechorismate pathway in elicitor-treated, cultured tomato cells.

The accumulation of phenylalanine-derived phenolic compounds is a well-known element of a plant's defense in response to pathogen attack. Phenylalanine, as well as the other two aromatic amino acids, tyrosine and tryptophan, is synthesized by way of the shikimate pathway. The first seven steps of the shikimate pathway (the prechorismate pathway) are common for the biosynthesis of all three aromatic amino acids. We have studied transcript levels of six genes--i.e., two 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase genes, one shikimate kinase gene, one 5-enolpyruvylshikimate 3-phosphate synthase gene, and two chorismate synthase genes--corresponding to four steps of the prechorismate pathway, in cultured tomato cells exposed to fungal elicitors. The abundance of transcripts specific for some of these genes increased 10- to 20-fold within 6 h after elicitor treatment, as did the abundance of phenylalanine ammonialyase-specific transcripts and the synthesis of ethylene. Interestingly, transcript accumulation occurred more rapidly for shikimate kinase than for the enzymes preceding or following it in the prechorismate pathway. Neither the inhibition of ethylene biosynthesis by aminoethoxyvinylglycine nor inhibition of phenylalanine ammonia-lyase (EC 4.3.1.5) activity by 2-aminoindan-2-phosphonic acid affected the time course or extent of transcript accumulation. Thus, the increased demand for phenylalanine in the phenylpropanoid pathway required after elicitor treatment appears to be met by increased de novo synthesis of its biosynthetic enzymes.

Journal Article↗

Transcranial magnetic stimulation of the trigeminal nerve: intraoperative study on stimulation characteristics in man.

We studied responses from the masseter and nasalis muscles following magnetic stimulation (magStim) and compared these responses with those obtained by direct electrical stimulation of the trigeminal (NV) and facial (NVII) nerve near the root exit zone during microvascular decompression operations of NVII. We found that (1) magStim threshold to excite the nerve is high for NV and low for NVII; (2) excitation of all motor fibers is impossible for NV, and easy for NVII; (3) optimal coil placement is critical for NV, but not critical for NVII; and (4) between and within subjects, the excitation site is variable on NV, but stable on NVII. We estimated that the anatomical location of magStim to be either within or outside the cerebrospinal fluid for NV, and to be in the labyrinthine segment of the facial canal for NVII. Physical models explain and clinical lesion models support these differences found between NV and NVII.

Adult↗

Temporal dynamics of healing in rabbit cranial defects using guided bone regeneration.

PURPOSE: The objective of this study was to histologically evaluate the early stages of bone regeneration using rabbit calvaria defects in conjunction with guided tissue regeneration. MATERIALS: A semilunar cutaneous-periosteal flap was raised on the forehead of four rabbits exposing the top of the skull. A standardized transosseous skull defect (> or = 15 mm in diameter) was made in the area of the right parietal bone with a rotating round bur. Care was taken not to damage the underlying dura. A flat expanded polytetrafluoroethylene (ePTFE) membrane was placed to cover the defect. The membrane was tightly adapted, extending at least 4 mm onto intact bone, and the flap was sutured. One, 2, 3, and 5 weeks later, the specimens were removed and processed using standard, undecalcified, hard-tissue histologic techniques. Contact radiographs were also taken. RESULTS: Bone growth increased with time, starting at the borders of the defect. At 1 week, trabeculae of woven bone grew into the highly vascularized loose connective tissue occupying the defect. Two weeks postsurgery, isolated islands of new bone were detected in this connective tissue. Subsequently, neighboring small islands merged to form large islands. In later stages, the primary trabeculae of woven bone were reinforced by layers of regularly deposited lamellar bone. CONCLUSION: Rabbit calvaria defects treated by guided tissue regeneration heal by ingrowth of woven bone from the defect margins and by formation of bony islands within the defect area. Bone healing showed the histophysiological characteristics of intramembranous bone.

Animals↗

Organ-specific differences in the ratio of alternatively spliced chorismate synthase (LeCS2) transcripts in tomato.

The primary transcript of one of the two chorismate synthase genes (LeCS2) of tomato is differentially processed due to an alternative splicing of the third intron. A novel observation was made when the abundances of the two LeCS2-specific transcripts in different organs were analysed. The ratio of these two transcripts differs in RNA populations from different organs. Possible explanations for this finding and its potential physiological impact for plant metabolism are discussed.

Alternative Splicing↗

Physiological traits associated with success of Candida albicans strains as commensal colonizers and pathogens.

DNA fingerprinting with the moderately repetitive sequence Ca3 has repeatedly identified groups of genetically similar strains of Candida albicans that are more frequently isolated than other groups of strains from human hosts in a geographical locale. Members of these groups are found in approximately 30% of healthy individuals and in up to 70% of patients suffering from candidiasis. The high prevalence of these strains implies that they are more successful in colonizing human hosts and in causing disease than other strains (J. Schmid, Clin. Adv. Treatment Fungal Infect. 4(6):12-16, 1993). In the present study, we have compared one such group of highly prevalent strains with other strains from the same locale to identify physiological traits a larger number of chemicals than other strains in a resistogram assay. When resistance to individual chemicals used in the resistogram assay was analyzed, strains from the group of highly prevalent strains were significantly more often resistant to boric acid, cetrimide, chlorhexidine, 5-fluorocytosine, and high sodium chloride concentrations than other strains. Strains from the group of highly prevalent strains also adhered significantly (1.5 times) better to saliva-coated surfaces than did other strains. Because members of highly prevalent groups of strains are the most common infectious agents in candidiasis, these physiological traits may be involved in determining not only the success of C. albicans in colonizing human hosts in general but also its ability to cause disease. Sodium chloride resistance and increased adherence were also associated with infectious isolates outside the group of highly prevalent strains, indicating that they may be of particular importance in pathogenesis.

Anti-Infective Agents↗