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Biomedical subjects

J Schmid

Publications and source records attributed to J Schmid.

At least 127 records · Page 7Linked to original sources

Plasminogen activator in human periodontal health and disease.

Plasminogen activators, proteases associated with the fibrinolytic system, also play a major part in extravascular processes such as tissue remodelling, cell migration and activation of prohormones, growth factors and other proteases. It is likely that plasminogen activators participate in the pathophysiology of periodontal disease. Plasminogen activator has been identified in human gingival crevicular fluid in a concentration 100-fold greater than in plasma. The local activity of plasminogen activator in gingival tissues was examined and changes detected in its distribution in relation to the extent of disease. Frozen sections from human gingival biopsies were overlaid on fibrin-coated slides; tissue-type plasminogen activator activity was found in all samples. Focal activity was observed in healthy tissue, originating from the most superficial cells of the junctional epithelium. Biopsies of clinically healthy sites obtained 6 weeks after treatment for periodontitis also showed epithelial plasminogen activator activity localized to this area. In contrast, in diseased tissue the entire epithelium lining the periodontal pocket showed activity. This differential pattern of activity in health and disease is consistent with the hypothesis that plasminogen activator is a modulator of periodontal homeostasis.

Gingiva↗

Purification and Characterization of Chorismate Synthase from Euglena gracilis: Comparison with Chorismate Synthases of Plant and Microbial Origin.

Chorismate synthase was purified 1200-fold from Euglena gracilis. The molecular mass of the native enzyme is in the range of 110 to 138 kilodaltons as judged by gel filtration. The molecular mass of the subunit was determined to be 41.7 kilodaltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Purified chorismate synthase is associated with an NADPH-dependent flavin mononucleotide reductase that provides in vivo the reduced flavin necessary for catalytic activity. In vitro, flavin reduction can be mediated by either dithionite or light. The enzyme obtained from E. gracilis was compared with chorismate synthases purified from a higher plant (Corydalis sempervirens), a bacterium (Escherichia coli), and a fungus (Neurospora crassa). These four chorismate synthases were found to be very similar in terms of cofactor specificity, kinetic properties, isoelectric points, and pH optima. All four enzymes react with polyclonal antisera directed against chorismate synthases from C. sempervirens and E. coli. The closely associated flavin mononucleotide reductase that is present in chorismate synthase preparations from E. gracilis and N. crassa is the main difference between those synthases and the monofunctional enzymes from C. sempervirens and E. coli.

Journal Article↗

Telomeric and dispersed repeat sequences in Candida yeasts and their use in strain identification.

Several different repetitive DNA sequences have been isolated from the pathogenic yeast Candida albicans. These include two families of large dispersed repeat sequences (Ca3, Ca24) and a short (23-bp) tandemly repeated element (Ca7) associated with C. albicans telomeres. In addition, a large subtelomeric repeat (WOL17) has been cloned. DNA fragments containing the telomeric repeats are highly variable among different C. albicans strains. We have shown that the Ca3 repeat is relatively more stable and is suitable for use as a species-specific and strain-specific probe for C. albicans.

Base Sequence↗

Genetic dissimilarity of commensal strains of Candida spp. carried in different anatomical locations of the same healthy women.

Candida spp. carriage and strain relatedness were assessed in 52 healthy women at 17 anatomical locations by using an isolation procedure which assesses carriage intensity and by using a computer-assisted DNA fingerprinting system which computes genetic similarity between strains on the basis of the patterns of Southern blots probed with the moderately repetitive sequence Ca3. Candida spp. were cultured from 73% of the test individuals, most frequently from the oral (56%), vulvovaginal (40%), and anorectal (24%) regions. Half of the test individuals with Candida spp. carried the organism simultaneously in more than one of the three general areas of carriage. Isolates from different body locations of the same individual were either completely unrelated, identical, or highly similar but nonidentical. In 11 cases in which Candida spp. were simultaneously isolated from the oral cavity and vaginal canal, seven pairs of isolates were genetically unrelated and four pairs were similar but nonidentical. In the latter cases, the isolate pairs each appear to have arisen by genetic divergence from a single progenitor. A comparison of the genetic relatedness of isolates from different individuals further uncovered a single strain which was vaginospecific in the Iowa City, Iowa area and reduced genetic diversity among vulvovaginal strains compared with those isolated from other body locations. These results suggest that strains adapt to different anatomical locations and, conversely, that in a healthy individual there is anatomical selection of vaginotropic, anotropic and orotropic strains of Candida spp.

Adult↗

Influence of peripheral nerve stimulation on the responses in small hand muscles to transcranial magnetic cortex stimulation.

The influence of afferent median nerve stimulation on the responses of small hand muscles (CMAPs) to cortical stimulation (CortStim) was investigated by applying short stimulus trains to the median nerve at the wrist and slightly suprathreshold magnetic stimuli to the scalp. Train stimulus frequency (TSF), train stimulus intensity (TSI), and train onset (TO) in relation to the CortStim were varied. Amplitudes and latencies of CMAPs were compared with those obtained by CortStim alone. When applying short trains of 10 msec duration, of 300/sec-400/sec TSF, and of threshold or supramaximal intensity for motor fibers, both facilitatory and inhibitory effects on the responses to CortStim were achieved depending on the timing of the train onset. With a TO of 8-10 msec before CortStim, mean amplitudes of CMAPs were enhanced 3-10 times; mean amplitudes reached up to 20 times the baseline values when the TO was greater than 45 msec before CortStim. With a TO of 15-35 msec before CortStim, amplitudes were diminished below control values. No systematic changes in latency were noted with TO of 8-10 msec, but when the TO was 45-60 msec before CortStim the latencies of CMAPs were 1.5-3 msec shorter than baseline latencies. With afferent stimuli that were subthreshold for motor fibers facilitation only occurred when the TO was about 45 msec before CortStim. The differences were statistically significant (Wilcoxon-Mann-Whitney Test). This biphasic pattern of facilitation and inhibition probably reflects spinal and supraspinal reflex phenomena mediated by spindle receptor and various cutaneous afferents.

Action Potentials↗

[Does breast self-examination affect the stage of breast carcinoma?].

The regular self-examination of the breast is one of the possibilities to detect breast cancer early. Our aim was to test the sensitivity of the method on rural, poorly informed patients. Almost one fourth of the 90 cancer patients belonged to the self-examination group. 52% of these women had a stage-I tumor. 58% of the women who didn't examine themselves entered hospital with stage-III or stage-IV tumor. In the self-examination group, in 71% of the lymph nodes were negative. This cohort showed also a better result concerning tumor extension. The average size was 1.9 cm compared to 3.8 cm in the 'non-analyser group'. We summarize that women controlling themselves have a better prognosis. Therefore, self-examination, combined with mammography and clinical control, is one of the best methods for early detection of mammary-cancer.

Adult↗

[Disseminated, highly malignant non-Hodgkin's lymphoma and pregnancy: polychemotherapy in the 2d and 3d trimester].

The coincidence of Non-Hodgkin-lymphoma (NHL) and pregnancy is rare. Even rarer is the use of chemotherapy in pregnancy complicated by NHL. We report on a case of malignant NHL IVa, where diagnosis was established in the 24th week of gestation. The patient was treated with polychemotherapy in the second and third trimester of pregnancy and delivered a normal infant. We review the literature and discuss possibilities and risks of chemotherapy in pregnancy.

Adult↗

Developmental and environmental regulation of a bean chalcone synthase promoter in transgenic tobacco.

Regulatory properties of a 1.4-kilobase promoter fragment of the bean chalcone synthase CHS8 gene were examined by analysis of glucuronidase (GUS) activity in transgenic tobacco containing a CHS8-GUS gene fusion. The promoter was highly active in the root apical meristem and in petals, exclusively in those cells of the inner epidermis that accumulate anthocyanins. The gene fusion was only weakly expressed in other floral organs, mature leaves, and stems. The early stages of seedling development were characterized by an apparent wound induction of the promoter in the endosperm and strong expression in the immature root, which became localized to the apical meristem and perivascular tissue at the root-hypocotyl junction. The promoter became active during lateral root formation in both the new root and damaged tissue of the main root. The gene fusion was also expressed in greening cotyledons and primary leaves but not in the shoot apical meristem. Light modulated expression in the cotyledons and root-shoot junction but had no effect on other aspects of the developmental program. Wounding or fungal elicitor treatment of mature leaves activated the promoter in a well-defined zone adjacent to the stress site. Stress induction occurred in mesophyll and vascular tissues as well as in the epidermis. We conclude that the CHS8 promoter contains cis-elements required to establish temporal and spatial control of flavonoid biosynthesis during development and in response to diverse environmental stimuli.

Acyltransferases↗

Autoradiographic evaluation of monoclonal antibodies' access to melanoma-associated antigens in melanoma xenografts.

Autoradiography of nude mice bearing human malignant melanoma xenografts was performed to characterize the distribution pattern of radioiodinated anti-melanoma monoclonal antibodies (MoAb) and fragments in macroscopic tumor nodules. Non-uniformity of radioactivity distribution was seen in all MoAb-xenograft combinations. The predominant patterns were marked deposition of radioactivity either in the periphery of nodules or in sharply delimited intra-tumoral foci. These patterns were generated by limitations in the accessibility of melanoma tissue rather than gross necrosis or heterogeneity of antigen expression. Computer-aided densitometry of autoradiograms was used to elaborate the difference of accumulation in intra-tumoral hot spots versus cold areas. It was found that increasing uniformity was achieved by increasing the dose of MoAb (i.e., intact IgG) injected, whereas a reduction in the size of MoAb (IgG greater than F(ab')2 greater than Fab) showed no such effect.

Animals↗

A clinical trial on efficacy and safety of teicoplanin in combination with beta-lactams and aminoglycosides in the treatment of severe sepsis of patients undergoing allogeneic/autologous bone marrow transplantation.

Early institution of empiric therapy with a broad-spectrum antibiotic has markedly reduced the morbidity and mortality from infections complicating severe or prolonged cytopenia in patients receiving either an allogeneic or autologous bone marrow transplant. Ceftazidime in combination with an aminoglycoside, i.e. netilmicin, has been established as a combination schedule offering low or even avoiding therapy-related toxicity. We evaluated teicoplanin for suspected Gram-positive infections after inadequate response to initial beta-lactam and aminoglycoside combination therapy. All 11 patients so far included in this study received either an allogeneic (five patients) or an autologous (six patients) bone marrow transplant for acute myeloid leukaemia (AML), non-Hodgkin lymphoma (NHL, high grade) or other malignant diseases. All patients developing a primary septicaemia of unknown origin (10 patients) or a catheter related septicaemia (one patient) were treated with 400 mg teicoplanin, administered i.v. once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g, i.v., t.i.d., netilmicin 400 mg once daily). All 11 patients responded to therapy, 10 patients were clinically cured, one patient improved under therapy. The therapeutic regimen was well tolerated and adverse drug reactions did not occur. We have not observed any delayed take of prolonged neutropenia or thrombocytopenia with this therapeutic regimen when compared to other bone marrow transplant patients who did not receive this antimicrobial therapy. Our preliminary results suggest that teicoplanin is a potentially effective and well-tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta-lactams and aminoglycosides.

Adolescent↗

Computer-assisted methods for assessing strain relatedness in Candida albicans by fingerprinting with the moderately repetitive sequence Ca3.

When used to probe EcoRI-digested Candida albicans DNA, the moderately repetitive sequence Ca3 generated a Southern blot hybridization pattern which included 15 to 25 bands, depending upon the strain. The pattern was stable through 400 generations in each of three independent strains but variable between most of 46 unrelated tester strains, making it a very effective probe for discrimination between strains. Computer-assisted methods (Dendron) were developed for storage of Ca3 patterns in data files, calculation of similarity (SAB) values between strains based upon band positions and intensities, and generation of histograms and dendrograms based on SAB values for all strains or any subset of strains in large epidemiological studies. In testing the effectiveness of the system, it was found that (i) multiple isolates from different body locations of the same healthy individual could represent either the same strain or different strains, (ii) isolates from oral lesions of a husband and wife represented the same strain, (iii) strains isolated from the mouths of 10 healthy individuals on the same day and in the same geographical location were as dissimilar on average as the 46 unrelated tester strains, and (iv) strains isolated from seven immunocompromised patients hospitalized over a 2.5-month period in the same hospital were highly similar, indicating nosocomial origin. The apparent effectiveness of these fingerprinting methods and the Dendron program suggests that interlaboratory procedures for fingerprinting should be standardized and all patterns should be analyzed and stored in a common and accessible data base for broad epidemiological analysis.

Blotting, Southern↗

Magnetic and electrical stimulation of cervical motor roots: technique, site and mechanisms of excitation.

Cervical motor roots and the brachial plexus were excited transcutaneously with magnetic (MagStim) and electrical stimulation (ElStim) applied dorsally over the spine and over the supraclavicular fossa (Erb's point). The compound muscle action potentials (CMAPs) from the abductor digiti minimi (ADM) and the biceps muscles (BICEPS) could be evoked with either stimulating technique in all 52 subjects tested. With MagStim over the spinous process C7, greater CMAPs were obtained from ADM (p less than or equal to 0.0001, paired t test) and BICEPS (p less than or equal to 0.005) when the inducing current in the coil as viewed from behind was clockwise for the right arm and vice versa. ElStim with the cathode over C7/T1 and the anode directed cranially provided greater CMAPs from the ADM (p less than or equal to 0.0001) and smaller CMAPs from the BICEPS (p less than or equal to 0.01) than with the inverse polarity. MagStim of the cervical roots provided CMAPs which were smaller from ADM (p less than or equal to 0.0001), and greater from BICEPS (p less than or equal to 0.0001), than ElStim (cathode C7/T1), whereas latencies did not differ significantly (p less than or equal to 0.3). When comparing ElStim and MagStim applied over Erb's point, the former yielded greater CMAPs and 0.5 ms longer latencies from both the ADM and BICEPS (p less than or equal to 0.001). From these data and additional studies in four patients, including direct intraoperative root stimulation in one of them, it is concluded that ElStim and MagStim over the spine excite the motor roots at a similar site, that is, within a few cm outside the intervertebral foramina. The site of stimulation is difficult to predict and depends on the placement of the stimulating devices and the intensities used. In contrast, MagStim of the brachial plexus over Erb's point occurs on average about 3.5 cm distal to the site of ElmStim.

Adult↗

[Smoking, the pill and pregnancy].

The intake of modern low-dose oral contraceptives (estrogen dose less than 50 micrograms, gestagen without androgen function) does not augment the danger for cardiovascular disease, especially if individual risk factors are missing. These include besides age, hypertension, obesity and disturbances of lipid and carbohydrate metabolism especially smoking. Women older than 35 years of age who smoke (more than 15 cigarettes per day) should strongly be advised to use other contraceptive means. There are numerous disturbances that may occur in utero and post partum in the child if the pregnant woman or mother smokes actively. Most obvious are intrauterine retardation of fetal growth, neurological and psychic disorders, pulmonary problems and an increased risk for cancer in small children. Since there is also danger for unborn and small children in passive smoking, we must become more aware of the problem and take measures accordingly.

Abortion, Spontaneous↗

Vascular expression of a bean cell wall glycine-rich protein-beta-glucuronidase gene fusion in transgenic tobacco.

In French bean (Phaseolus vulgarisL.), the glycine-rich wall protein GRP 1.8 is specifically synthesized in protoxylem tracheary elements of the vascular system. A 494 bp upstream promoter fragment of the gene encoding GRP 1.8 was isolated and translationally fused to the beta-glucuronidase reporter gene. Transgenic tobacco plants containing this construct expressed the gene in vascular tissue of roots, stems, leaves and flowers. The gene was developmentally expressed during differentiation of both primary and secondary vascular tissue and was also rapidly induced (in < 30 min) after excision-wounding of young stems. This wound response is more rapid than in bean hypocotyls, indicating possible differences between the activation mechanism for glycine-rich protein gene expression in wounded bean and tobacco. Only a subset of cells were found to participate in the wound response. In young stems, the GRP wound induction was localized in pith parenchyma cells adjacent to the wound surface, where vessel regeneration is known to occur. Thus, a promoter fragment of 494 bp, including 427 bp upstream from the transcription start site, contains information for tissue-specific and wound-induced gene regulation. The cell-type specificity of expression suggests that the GRP 1.8 promoter is regulated by very specific developmental and environmental signals.

Journal Article↗

Molecular characterization of plasminogen activator in human supragingival plaque.

Extravascular participation of the serine protease plasminogen activator (PA) in tissue remodelling and cell migration may be relevant in the regulation of periodontal homeostasis and the pathogenesis of periodontal disease. The molecular nature of authentic PA in crevicular fluid has been characterized, and this study has sought to determine whether human supragingival plaque also contains PA; if so, of which molecular species and from what source. Thirty samples of supragingival plaque plaque from 10 individuals, extensively washed to remove adherent saliva, were all found by substrate analysis to have tissue-type PA (tPA) activity. Unstimulated parotid or mixed saliva also showed tPA activity, but submandibular saliva had no measurable PA activity. Freshly isolated plaque microbes cultured under aerobic or anaerobic conditions contained no PA activity (preliminary investigation). PA activity was restricted to individual epithelial cells suggesting that the origin of PA activity in human supragingival plaque is in part from plaque-adherent epithelial cells.

Adult↗

Developmental and environmental regulation of a phenylalanine ammonia-lyase-beta-glucuronidase gene fusion in transgenic tobacco plants.

A 1.1-kilobase promoter fragment of the bean (Phaseolus vulgaris L.) phenylalanine ammonia-lyase (EC 4.3.1.5) gene PAL2 was translationally fused to the beta-glucuronidase reporter gene and transferred to tobacco by Agrobacterium tumefaciens-mediated leaf disk transformation. The distribution of beta-glucuronidase activity in these transgenic plants is very similar to that of endogenous PAL2 transcripts in bean, with very high levels in petals; marked accumulation in anthers, stigmas, roots, and shoots; and low levels in sepals, ovaries, and leaves. Histochemical analysis of the spatial pattern of beta-glucuronidase activity showed that the PAL2 promoter is highly active in the shoot apical meristem, the zone of cell proliferation immediately adjacent to the root apical meristem, and in the early stages of vascular development at the inception of xylem differentiation. Wounding and light evoke specific changes in the spatial pattern of beta-glucuronidase activity in stems, including induction in the epidermis. These data indicate that the PAL2 promoter transduces a complex set of developmental and environmental cues into an integrated spatial and temporal program of gene expression to regulate the synthesis of a diverse array of phenylpropanoid natural products.

Ammonia-Lyases↗

Switching of Candida albicans during successive episodes of recurrent vaginitis.

Strain relatedness and switching were monitored in Candida albicans strains isolated from different body locations through three episodes of recurrent vulvovaginal candidiasis separated by two treatment-latency periods in a single patient. Strain relatedness was assessed by comparing Southern blot hybridization patterns with the relatively immobile mid-repeat sequence Ca3. The following conclusions are demonstrated. (i) Three different strains of C. albicans colonized the mouth, the area under the breasts, and the vulvovaginal, anal, and rectal regions, respectively, at the time of the first infection. (ii) The same strain of C. albicans was responsible for the three vaginal infections. (iii) Switching of colony phenotype occurred with each new vaginal infection. (iv) Enrichment of drug-resistant switch phenotypes (assessed in vitro) was unlikely the basis for the changes in the switch phenotypes of the strain found in the vulvovaginal, anal, and rectal areas after treatment of the first infection with clotrimazole. (v) The same strain of C. albicans was responsible for the recurrent increases in mouth colonization and was distinct from the recurrent vaginal strain. The results of this case study demonstrate the need for further detailed analyses of full-body mycofloras, strain relatedness, switching repertoires, and changes in drug susceptibility during successive episodes of recurrent vulvovaginal candidiasis.

Antifungal Agents↗