Biomedical subjects

T Schmidt

Publications and source records attributed to T Schmidt.

At least 91 records · Page 5Linked to original sources

PubMed2001

Identification of pharmaceutical glasses by laser ablation ICP-MS.

The chemical composition of pharmaceutical glasses (ampoules, infusion bottles, plunger) has been determined by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). A Nd:YAG laser with 10 Hz repetition rate in the Q-switch mode at its fundamental wavelength (1064 nm) was used to identify common types of pharmaceutical glasses. The following isotopes were used for measurements: 7Li, 11B, 23Na, 24Mg, 27Al, 28Si, 29Si, 30Si, 39K, 42Ca, 47Ti, 57Fe, 90Zr, 121Sb, 137Ba. Each analysis included the measurement of 12 craters. Relative standard deviations between 1.8% and 8.0% of the quantitative results were obtained. 29Si was used as internal standard. Standard reference materials (soda-lime-, lead- and borosilicate glasses) were used for external calibration of laser sampling. Linear calibration functions for each isotope were found. All samples and standard materials were digested in a two-step-procedure by nitric/fluoric acid, then measured and externally calibrated by ICP-MS with multi-elemental standard solutions using 45Sc as internal standard. Digestion and laser ablation results agree within 8% (confidential interval 95%) with the certified values. Intensity ratios of most isotopes also agree sufficiently with the corresponding theoretical values (+/- 18%). The developed method allows to distinguish different types of pharmaceutical glasses.

Calibration↗

PubMed2000

Possibilities of sterility therapy in a patient with a premature menopause due to an X-chromosomal anomaly - a case report.

Our report concerns a patient with a climacterium praecox and an X-chromosomal anomaly (86% 46, XX; 7% 47, XXX; 7% 45, X0) desiring to give birth. She conceived once after down-regulation of the gonadotrophins by means of a cyclical hormone replacement therapy followed by gonadotrophin stimulation, as well as a second time under down-regulation with a GnRH-analogue and gonadotrophin stimulation. On the basis of the case report and of the literature, a possible interval therapy in such a patient, especially one even with increasing ovarian insufficiency, will be portrayed and discussed.

Adult↗

PubMed2000

Cell cycle regulation of the murine cdc25B promoter: essential role for nuclear factor-Y and a proximal repressor element.

Expression of the cdc25B gene is up-regulated late during cell cycle progression (S/G(2)). We have cloned the murine cdc25B promoter to identify elements involved in transcriptional regulation. A detailed structure-function analysis led to the identification of several elements that are located upstream of a canonical Inr motif at the site of transcription initiation and are involved in transcriptional activation and regulation. Activation of the promoter is largely mediated by NF-Y and Sp1/3 interacting with one and four proximal binding sites, respectively. In addition, NF-Y plays an essential role in cell cycle regulation in conjunction with a repressor element (cell cycle-regulated repressor) located approximately 30 nucleotides upstream of the putative Inr element and overlapping a consensus TATA motif. The cell cycle-regulated repressor is unrelated to the previously described cell cycle-regulated repressor elements. Taken together, our observations suggest that expression of the cdc25B gene is controlled through a novel mechanism of cell cycle-regulated transcription.

3T3 Cells↗

PubMed2000

The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3.

STAT factors act as signal transducers of cytokine receptors and transcriptionally activate specific target genes. The recently discovered protein PIAS3 binds directly to STAT3 and blocks transcriptional activation. Here, we present experimental evidence implementing the zinc finger protein Gfi-1 as a new regulatory factor in STAT3-mediated signal transduction. The interaction between the two proteins first became evident in a yeast two-hybrid screen but was also seen in coprecipitation experiments from eukaryotic cells. Moreover, we found that both Gfi-1 and PIAS3 colocalize in a characteristic nuclear dot structure. While PIAS3 exerts a profound inhibitory effect on STAT3-mediated transcription of target promoters, Gfi-1 can overcome the PIAS3 block and significantly enhances STAT3-mediated transcriptional activation. In primary T cells, Gfi-1 was able to amplify IL-6-dependent T-cell activation. As Gfi-1 is a known, dominant proto-oncogene, our findings bear particular importance for the recently described ability of STAT3 to transform cells malignantly and offer an explanation of the oncogenic potential of Gfi-1 in T lymphocytes.

Animals↗

PubMed2000

A novel protein (Fbf-1) that binds to CD95/APO-1/FAS and shows sequence similarity to trichohyalin and plectin.

The Fas/Apo-1/CD95 cell surface receptor belongs to the TNF receptor family of cell death inducing molecules. A number of cytosolic adapter proteins that mediate signal transduction of CD95 have been characterized, but some features of the molecular mechanisms of CD95-induced cell death remain elusive. We describe here a novel protein that can interact with the cytosolic domain of the murine CD95 receptor in a yeast two-hybrid assay. This novel protein was termed Fbf-1 for Fas binding factor and bears no sequence similarity to the known CD95 adapter proteins. Fbf-1 is 1173 aa long and has a theoretical molecular weight of around 130 kDa. The protein is expressed in a wide variety of tissues and is localized in the cytoplasm. Fbf-1 is a very hydrophilic protein, highly conserved between mouse and human and bears a carboxyterminal leucine heptad repeat reminiscent of leucine zipper protein interaction domains. In addition, it shows sequence similarity to trichohyalin and plectin pointing to a function as a structural protein.

Adaptor Proteins, Signal Transducing↗

PubMed2000

A sequence in the carboxy-terminus of the alpha(1C) subunit important for targeting, conductance and open probability of L-type Ca(2+) channels.

The role of the 80-amino acid motif 1572-1651 in the C-terminal tail of alpha(1C) Ca(2+) channel subunits was studied by comparing properties of the conventional alpha(1C,77) channel expressed in HEK-tsA201 cells to three isoforms carrying alterations in this motif. Replacement of amino acids 1572-1651 in alpha(1C,77) with 81 non-identical residues leading to alpha(1C,86) impaired membrane targeting and cluster formation of the channel. Similar to alpha(1C, 86), substitution of its 1572-1598 (alpha(1C,77L)) or 1595-1652 (alpha(1C,77K)) segments into the alpha(1C,77) channel yielded single-channel Ba(2+) currents with increased inactivation, reduced open probability and unitary conductance, when compared to the alpha(1C,77) channel. Thus, the C-terminal sequence 1572-1651 of the alpha(1C) subunit is important for membrane targeting, permeation and open probability of L-type Ca(2+) channels.

Amino Acid Sequence↗

PubMed2000

Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM.

Individuals with systemic lupus erythematosus and rheumatoid arthritis are characterized by the presence of high levels of circulating IgM and IgG autoantibodies. Although IgG autoantibodies often are pathogenic, the role of IgM autoantibodies in autoimmune disease is not clear. Using mice that are unable to secrete IgM but are able to express surface IgM and IgD and to secrete other classes of immunoglobulins, we examined the effect of the absence of secreted IgM in the development of IgG autoantibodies and autoimmune disease in lupus-prone lymphoproliferative (lpr) mice. Compared with regular lpr mice, lpr mice that lack secreted IgM developed elevated levels of IgG autoantibodies to double-stranded DNA and histones and had more abundant deposits of immune complexes in the glomeruli; they also suffered more severe glomerulonephritis and succumbed to the disease at an earlier age. Similarly, the absence of secreted IgM also resulted in an accelerated development of IgG autoantibodies in normal mice. These findings suggest that secreted IgM, including IgM autoantibodies produced naturally or as part of an autoimmune response, may lessen the severity of autoimmune pathology associated with IgG autoantibodies.

Animals↗

PubMed2000

[Patient-oriented anesthesia] .

Goals of this study were to quantify patients' preferences for anaesthesia care and to identify what they know about various tasks of an anaesthetist. On the day before surgery, 122 patients scheduled for elective procedures were interviewed using a structured questionnaire. A reliable pain relieve and unawareness as well as stable vital functions have priority in patients' preferences. Patients are also concerned with good postoperative pain relieve and the avoidance of nausea and vomiting. Not important are short preoperative soberness, rapid awakening and initial wide awakeness. Not informed about typical tasks of an anaesthetist are 28-51% of the patients. In order to obtain maximum patient satisfaction, a thorough education plus further continuous training are the essential items for a patient orientated health care management in anaesthesia, along with good medical and technical equipment. The wide spectrum of tasks of an anaesthetist must be better represented in order to strengthen the position of anaesthesia in the competition for rare resources. A postoperative visit, which is judged of 77% of the patients as important, offers a beginning.

Adult↗

PubMed2000

Determination of analytical limits in solid sampling ETAAS: a new approach towards the characterization of analytical quality in rapid methods.

In the present study the lower analytical limits of solid sampling electrothermal atomization atomic absorption spectrometry (SS-ETAAS) were characterized by means of blank measurements and--for the first time--by means of the calibration curve method, where a calibration near the range of these limits (limit of decision, detection and quantification) was performed. The limit of decision as derived from blank measurements was calculated according to the 3sigma-criterion to be 0.003 and 0.019 ng for Cd and Pb, respectively. For Pb and Cd a roughly three-fold increase of these limits was observed when the calibration method according to DIN 32 645 was applied. When solid reference material was used, only a slight increase could be observed. The analytical limits were 2 to 20 times lower than reported for sample decomposition methods. The blank measurement and conventional calibration curve method, however, do not account for factors relating to solid sampling such as sample mass and matrix. Therefore, the calibration curve model was applied to data derived from comparisons between direct solid sampling ETAAS and a compound reference method (ETAAS following sample homogenization and digestion). The observed analytical limits were not found to be substantially increased if enough samples with low element contents were available for calibration. Coupling of the calibration curve model with the comparison of methods included real test samples and thus the relevant maximum sample mass and analyte content in the range of the lower analytical limits. As validation procedures frequently include comparisons of methods, the present approach might prove to be of some general interest for the characterization of analytical quality in rapid methods.

Animals↗

PubMed2000

[Endoscopically controlled surgery with the micro-drill and intubation of the lacrimal ducts].

PURPOSE: Operative procedures to manage lacrimal outflow obstruction were made traditionally without endoscopic assistance. For dacryoendoscopy we previously used a 0.5-mm endoscope with a special wash cannula. We now use the microendoscope Vitroptic T for dacryoendoscopy and for endoscopically controlled surgery with a microdrill. METHODS: In an attempt to perform microinvasive lacrimal surgery we use a 1.1-mm endoscope (Vitroptik T) with a wash cannula, a channel for the microoptic and a channel for a microdrill. We report on our initial experiences and on the results of eight patients with stenosis of the lacrimal outflow system who were treated with an endoscopic microdrill and silicone tubing. One patient had lacrimal stenosis after external dacryocystorhinostomy (DCR), and seven patients showed punctual stenosis in the nasolacrimal duct. RESULTS: Using the dacryoendoscope (Vitroptic T) we were able to visualize pathologic changes of the lacrimal outflow system. Intraoperative situations during dacryoendoscopy are demonstrated. The Vitroptic T allows dacryoendoscopy and endoscopically controlled surgery of the lacrimal drainage system. Three months after surgery in six patients (75%) the lacrimal outflow system was patent with the silicone tube in place, and these patients had no epiphora. The patient with re-stenosis after external DCR showed patency. CONCLUSIONS: Dacryoendoscopy and endoscopic controlled surgery of the lacrimal drainage system enables atraumatic and minimally invasive surgery. The Vitroptik T with the microdrill allows endoscopically controlled microsurgery. Possible indications for the microdrill are punctual stenosis and re-stenosis after external DCR.

Dacryocystorhinostomy↗

PubMed2000

Long-term efficacy of medium-dose UVA1 phototherapy in atopic dermatitis.

BACKGROUND: UVA1 (340-400 nm) therapy proved to be highly effective in patients with severe atopic dermatitis. The optimal dose regarding therapeutic efficacy and possible side effects is still to be evaluated. In vitro cell culture as well as in vivo animal studies recently indicated that a correlation between UVA irradiation and photoaging, skin carcinogenesis, or melanoma induction may exist. Therefore it seems appropriate to focus research activities on reducing the UVA1 dose applied during phototherapeutic regimens minimizing nonbeneficial side effects. OBJECTIVE: The present study was performed to evaluate the therapeutic effectiveness and long-term efficacy of medium-dose UVA1 irradiation in patients treated for acute exacerbated atopic dermatitis. METHODS: Thirty-two patients underwent a medium-dose UVA1 therapy consisting of 15 treatments applied from Monday to Friday for a period of 3 weeks. The applied dose per treatment was 50 J/cm(2) resulting in a cumulative dose of 750 J/cm(2). Clinical severity was assessed according to the SCORAD index before and after irradiation as well as in monthly intervals up to 3 months after cessation of phototherapy. RESULTS: Medium-dose UVA1 phototherapy is effective for alleviating acute exacerbated atopic dermatitis as shown by a significant reduction of SCORAD ratings (P <.001) at the end of the active UV treatment period. A significant skin improvement was still present 1 month later (P <.001). However, at the end of the 3-month posttreatment observation period the skin condition had reached the pretreatment level. CONCLUSION: According to our data, medium-dose UVA1 phototherapy is a highly effective, nonsteroidal, therapeutic alternative for treatment of acute exacerbated atopic dermatitis. However, effectiveness is merely short term, limited, and is followed by recurrence of symptoms within a 3-month observation interval.

Adolescent↗

PubMed2000

Changes in collagen I and collagen III metabolism in patients with generalized atopic eczema undergoing medium-dose ultraviolet A1 phototherapy.

Fourteen patients suffering from acute, exacerbated atopic eczema were screened for changes in collagen I and collagen III metabolism in serum (n = 11), urine (n = 11) and skin biopsies (n = 9) before and after medium-dose ultraviolet (UV) A1 phototherapy (15 exposures of 50 J/cm2 over a 3-week period, total dose 750 J/cm2). Mature collagen I and, to a lesser extent, mature collagen III were found to be decreased after the therapy in skin samples from the irradiated patients. As markers of collagen I degradation, the cross-links pyridoline and deoxypyridoline were analysed in urine using high-performance liquid chromatography. Both cross-links were found to be mildly increased after UVA1 phototherapy, without reaching statistical significance. As markers of de novo collagen synthesis we screened for the procollagen I-carboxyterminal peptide (PICP) and procollagen III-aminoterminal peptide (PIIINP) levels in serum and skin. The ratio of PICP to PIIINP in serum dropped significantly after the UVA1 phototherapy, suggesting a different impact of UVA1 on the two collagens. These findings were paralleled by a diminished ratio of PICP to PIIINP in tissue samples. Staining for matrix metalloproteinase 1 (MMP-1) and its specific counterpart, tissue inhibitor of MMP-1 (TIMP-1), showed slight increases for both proteins by therapeutic UVA1; this was also seen in serum for TIMP-1 but not MMP-1. In our study, high-energy UVA1 doses induced changes of the skin collagens in patients with atopic eczema which are measurable by their metabolites in serum and urine.

Chromatography, High Pressure Liquid↗

PubMed2000

Persistent annular erythema of infancy associated with intestinal Candida colonization.

We report a case of persistent annular erythema of infancy in a 4-month-old boy. Physical and laboratory parameters showed no sign of internal disease or specific infection except a massive Candida albicans colonization (> 103 organisms/mm3) of the lower gastrointestinal tract. Oral treatment with amphotericin B for 2 weeks resulted in a complete remission of the skin lesions indicating Candida colonization as a trigger.

Amphotericin B↗

PubMed2000

Collagenolytic and gelatinolytic matrix metalloproteinases and their inhibitors in basal cell carcinoma of skin: comparison with normal skin.

Tissue from 54 histologically-identified basal cell carcinomas of the skin was obtained at surgery and assayed using a combination of functional and immunochemical procedures for matrix metalloproteinases (MMPs) with collagenolytic activity and for MMPs with gelatinolytic activity. Collagenolytic enzymes included MMP-1 (interstitial collagenase), MMP-8 (neutrophil collagenase) and MMP-13 (collagenase-3). Gelatinolytic enzymes included MMP-2 (72-kDa gelatinase A/type IV collagenase) and MMP-9 (92-kDa gelatinase B/type IV collagenase). Inhibitors of MMP activity including tissue inhibitor of metalloproteinases-1 and -2 (TIMP-1 and TIMP-2) were also assessed. All three collagenases and both gelatinases were detected immunochemically. MMP-1 appeared to be responsible for most of the functional collagenolytic activity while gelatinolytic activity reflected both MMP-2 and MMP-9. MMP inhibitor activity was also present, and appeared, based on immunochemical procedures, to reflect the presence of TIMP-1 but not TIMP-2. As a group, tumours identified as having aggressive-growth histologic patterns were not distinguishable from basal cell carcinomas with less aggressive-growth histologic patterns. In normal skin, the same MMPs were detected by immunochemical means. However, only low to undetectable levels of collagenolytic and gelatinolytic activities were present. In contrast, MMP inhibitor activity was comparable to that seen in tumour tissue. In previous studies we have shown that exposure of normal skin to epidermal growth factor in organ culture induces MMP up-regulation and activation. This treatment concomitantly induces stromal invasion by the epithelium (Varani et al (1995) Am J Pathol 146: 210-217; Zeigler et al (1996b) Invasion Metastasis 16: 11-18). Taken together with these previous data, the present findings allow us to conclude that the same profile of MMP/MMP inhibitors that is associated with stromal invasion in the organ culture model is expressed endogenously in basal cell carcinomas of skin.

Blotting, Western↗

PubMed2000

[Treatment of perioperative anxiety in suspected breast carcinoma with a phytogenic tranquilizer].

OBJECTIVE: The present study examined the anxiolytic effect of the herbal preparation Kavosporal forte in 20 patients with situationally induced anxiety. MATERIAL AND METHODS: The degree of anxiety was acute in that the patients were waiting for the results of a histopathological diagnosis, carried out on account of suspect mammary findings, and therefore feared they were suffering from a mammary carcinoma. RESULTS: A significant reduction of anxiety compared with the placebo control was seen after a week's treatment with Kavosporal forte, levels of anxiety being measured a priori from the combined scores of two self-rating scales and one observer-rated scale. In addition, a significant increase was noted in alertness and a lessening of fatigue, introverted behavior and excitability as well as a reduction in levels of depression under the real therapeutic agent over the observation period. In none of the cases examined did any undesirable side effects occur, and the overall tolerance was also consistently good. CONCLUSIONS: It could therefore be concluded that the preparation under investigation is well suited of amelioration of the anxiety that arises regularly in connection with a mammary biopsy.

Adult↗

PubMed2000

[The significance of leptin for reproduction].

Leptin is mainly synthesized by adipocytes and might represent the connecting link between fatty tissue and brain. In reference to reproduction, leptin resistance could play a role particularly in the pathogenesis of the PCO syndrome. However, there exists at present contradictory data on this, so that further clarification is necessary. Leptin interacts with the steroid synthesis to a degree not yet precisely clarified and possesses receptors in numerous tissues, which suggests extensive local and endocrine effects. Its exact significance for the initiation of puberty still remains unknown. The same is true for first data regarding leptin and endometriosis and the interpretation of hyperleptinemia during pregnancy. It is clear that this protein mediates between fatty tissue and the reproductive function. However, the detailed physiologic and pathophysiologic role of leptin in reproduction can only be clarified through further extensive studies. To date there is not yet a practical importance for the measurement of leptin in routine work in reproductive medicine.

Adipose Tissue↗

PubMed2000

[MRI-controlled preoperative wire marking of uncertain breast lesions].

PURPOSE: Small suspicious breast lesions that are only visible at MR imaging were preoperatively marked with a hook wire under MR-guidance to allow the removal of the lesion with tissue-sparing surgery. METHOD: In all patients the suspicious lesions were marked preoperatively under MR guidance with a hook wire using a commercially available stereotactic device. Interventions were performed with MR guidance on a 1.0 T and on a 1.5 T system. RESULTS: In 19 patients 22 lesions were localized. One lesion was missed and removed in a second procedure. The mean duration for localization was 66 +/- 20 min (range 38-119 min). In two patients two lesions were localized. The mean deviation of the wire tip to the lesion was 2.0 +/- 2.6 mm. In this series, 6 of 22 lesions were malignant. The mean diameter of the lesion was 7.6 +/- 2.6 mm (range 3-14 mm). CONCLUSION: Suspicious breast lesions detectable only in MR imaging can be accurately localized with a hook wire preoperatively under MR control to remove the lesion with a tissue-saving surgery.

Adult↗

PubMed2000

Does ischemic preconditioning require reperfusion before index ischemia?

BACKGROUND: Ischemic preconditioning (IP) is initiated through one or several short bouts of ischemia and reperfusion which precede a prolonged ischemia. To test whether a reperfusion must precede the prolonged index ischemia, a series without reperfusion (intraischemic preconditioning: IIP) and a series with gradual onset of ischemia, i.e. ramp ischemia (RI), which is possibly related to the development of hibernation, was compared to conventional IP (CIP). METHOD: Experiments were performed an 27 blood-perfused rabbit hearts (Langendorff apparatus) that were randomized into one of four series: (1) control (n = 7): 60 min normal flow - 60 min low flow (10%) ischemia - 60 min reperfusion. (2) CIP (n = 7): 4 times 5 min zero flow with 10 min reperfusion each - 60 min low flow (10%) - ischemia 60 min reperfusion. (3) IIP (n = 7): 50 min normal flow - 10 min no flow - 60min low flow (10%) ischemia -4 60min reperfusion. (4) RI (n=6): gradual reduction to 10% flow during 60min - 60min low flow (10%) ischemia - 60min reperfusion. At the end of each protocol, the infarcted area was assessed. RESULTS: The infarct area in control hearts was 6.7+/-1.4% (means+/-SEM) of LV total area, in CIP hearts 2.6+/-0.8%, in IIP hearts 3.1+/-0.5%, and in RI hearts 3.0+/-0.3% (all p<0.05 vs. control). The differences between the three protection protocols were statistically not significant, and no protective protocol reduced post-ischemic myocardial dysfunction. CONCLUSION: The preconditioning effect (infarct size reduction) appears not to depend on intermittent reperfusion. Thus, the protective mechanism of IP develops during the initial ischemia that precedes the index ischemia. Alternatively, low-flow ischemia is effectively a sort of reperfusion.

Animals↗