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Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 235 records · Page 13Linked to original sources
PubMed2000

Body dimensions and birth and organ weights of calves derived from in vitro produced embryos cultured with or without serum and oviduct epithelium cells.

Body dimensions, birth and organ weights of calves derived from embryos produced in 2 in vitro culture systems (modified SOFaa with 20% cattle serum and co-cultured with oviduct-epithelium cells [IVPserum, n=8], and modified SOFaa with 3 mg/mL PVA [IVPdefined, n=6]) were compared with calves originating from artificial insemination (AI, n=85). Three additional IVP calves were included which had been vitrified as mature oocytes by the open pulled straw (OPS) method, warmed, fertilized and cultured to the blastocyst stage in modified SOFaa with 5% cattle serum, then again OPS-vitrified and warmed prior to transfer (IVPops, n=3). At birth, gestation length and birth weights were registered for all calves. At 1 wk of age all 17 IVP and 7 of the AI calves were killed, and their body dimensions and organ weights recorded. Birth weight was higher for the IVPserum and IVPops calves than for AI control calves (kg +/- SEM: IVPserum 46.9+/-1.8, IVPops 50.6+/-2.4, AI 41.8+/-0.8; P < 0.002). There was no difference between IVP and AI calves regarding gestation length and no effect of culture conditions on body dimensions or organ weights, except for longer hind legs in IVPdefined calves compared with AI calves (cm +/- SEM: IVPdefined 93+/-2, AI 87+/-2; P < 0.04). The IVPops calves had an increased liver weight compared with AI and the other IVP calves (g +/- SEM: IVPops 1.457+/-59; AI 1,117+/-37; IVPserum 1,159+/-34, IVPdefined 1,073+/-39; P < 0.0003). It is concluded that in vitro culture of bovine embryos in the presence of serum and oviduct epithelium cells increased birth weight but not organ weight and body dimension in 1-wk-old calves. However, vitrification of the ova as oocyte and again as blastocysts increased birth weight and liver size. This possible effect of cryopreservation of oocytes on subsequent fetal development awaits further investigation.

Animals↗
PubMed2000

(A)symptomatic necrotizing arteritis of the female genital tract.

AIMS: The vasculitides represent a heterogenous set of disorders that differ in prognosis and response to therapy. Beside systemic vasculitides, the development of localized forms of arteritis is well known though uncommon and the etiopathogenesis is not yet definitely clear. METHODS: Patients with necrotizing arteritis of the female genital tract proven by histology are studied in a retrospective analysis. RESULTS: Three cases of necrotizing arteritis with histological features of panarteritis nodosa apparently confined to the female genital tract are presented. None of these patients had prior history of systemic vasculitis. The acute necrotizing vasculitis was confined only to the uterine cervix in two patients and involved all the internal genital organs in the third patient. The patients have been observed for up to 4 years without any therapy for these lesions and without any manifestation of systemic vasculitic progression. CONCLUSION: It is to speculate that focal arteritis of the female genital tract is a benign form of panarteritis nodosa or moreover a totally different entity with identical morphogenesis but possibly different pathogenesis. Furthermore it seems to be important to be aware of the specificity of focal arteritis in female genital tract as distinct from the generalized form to prevent unnecessary surgical or chemotherapeutical therapy for this lesion. The benign entity of local arteritis in the female genital tract is discussed in contrast to the severe prognosis of systemic panarteritis nodosa.

Aged↗
PubMed2000

Congenitally corrected transposition of the great arteries (L-TGA) with situs inversus totalis in adulthood: findings with magnetic resonance imaging.

Diagnosis of congenitally corrected transposition of the great arteries (L-TGA) with situs inversus totalis in two adult patients was made by magnetic resonance imaging (MRI). Visualization of the complete anatomy and quantification of ventricular function was possible. Relevant concomitant disease such as perimembraneous ventricular septal defect, atrial secundum septal defect, tricuspid regurgitation, valvular pulmonic stenosis, and pulmonary artery dilatation were clearly depicted by MRI using standard spin-echo and gradient-echo techniques. Findings were confirmed by cardiac catheterization in both patients. In this rare and complex congenital cardiac anomaly, MRI is an excellent imaging modality as echocardiography may be difficult to interpret due to restricted imaging windows. MRI may help in the decision about the necessity to undergo further invasive evaluation and may help to make cardiac catheterization a straightforward procedure.

Adult↗
PubMed2000

Fluoroscopically triggered contrast-enhanced 3D MR DSA and 3D time-of-flight turbo MRA of the carotid arteries: first clinical experiences in correlation with ultrasound, x-ray angiography, and endarterectomy findings.

The aim of this article was to obtain initial experiences with fluoroscopically triggered contrast-enhanced (CE) 3D MR DSA with elliptical centric k-space order and 3D time-of-flight (TOF) turbo MRA of the carotid arteries. In this prospective study we examined 16 consecutive patients with suspicion of atherosclerotic disease involving the carotid arteries. Ultrasound was available in all, x-ray angiography in 12, surgical correlation in 9, and intraoperative x-ray angiography in 4 patients. All examinations were done on a 1.5 T unit applying: transverse plain 3D TOF turbo MRA and coronal CE MRA with fluoroscopic triggering. Combining head and neck array coils allowed the visualization of supraaortic arteries from the aortic arch to the circle of Willis. MRA results (maximum intensity projections) were compared with x-ray angiography, ultrasound, and inspection of endarterectomy specimens. Volume rendering was performed in selected cases additionally. Agreement between CE MRA, 3D TOF turbo MRA and x-ray angiography regarding stenoses of the internal and external carotid artery was very good. CE MRA was able to detect correctly intracranial stenoses, but delineation of the aortic arch and proximal common carotid arteries was sometimes reduced. Volume rendering was suited for visualization of MRA images providing a realistic three-dimensional impression. In conclusion, high-resolution fluoroscopically triggered CE MRA as non-invasive technique is another important step on the way to replace invasive x-ray angiography for the evaluation of atherosclerotic carotid artery disease. High resolution 3D TOF turbo MRA might be a helpful adjunct to increase the diagnostic reliability for the carotid bifurcation.

Aged↗
PubMed2000

In vivo functional analysis of the daughter of sevenless protein in receptor tyrosine kinase signaling.

One mechanism used by receptor tyrosine kinases to relay a signal to different downstream effector molecules is to use adaptor proteins that provide docking sites for a variety of proteins. The daughter of sevenless (dos) gene was isolated in a genetic screen for components acting downstream of the Sevenless (Sev) receptor tyrosine kinase. Dos contains a N-terminally located PH domain and several tyrosine residues within consensus binding sites for a number of SH2 domain containing proteins. The structural features of Dos and experiments demonstrating tyrosine phosphorylation of Dos upon Sev activation suggested that Dos belongs to the family of multisite adaptor proteins that include the Insulin Receptor Substrate (IRS) proteins, Gab1, and Gab2. Here, we studied the structural requirements for Dos function in receptor tyrosine kinase mediated signaling processes by expressing mutated dos transgenes in the fly. We show that mutant Dos proteins lacking the putative binding sites for the SH2 domains of Shc, PhospholipaseC-gamma (PLC-gamma) and the regulatory subunit of Phosphoinositide 3-kinase (PI3-K) can substitute the loss of endogenous Dos function during development. In contrast, tyrosine 801, corresponding to a predicted Corkscrew (Csw) tyrosine phosphatase SH2 domain binding site, is essential for Dos function. Furthermore, we assayed whether the Pleckstrin homology (PH) domain is required for Dos function and localization. Evidence is provided that deletion or mutation of the PH domain interferes with the function but not with localization of the Dos protein. The Dos PH domain can be replaced by the Gab1 PH domain but not by a heterologous membrane anchor, suggesting a specific function of the PH domain in regulating signal transduction.

Amino Acid Sequence↗
PubMed2000

Radioiodination and astatination of octreotide by conjugation labeling.

Octreotide was coupled to 3-iodobenzoyl and 3-iodonicotinoyl moieties to obtain [N-(3-iodobenzoyl)-D-Phe(1)]octreotide (IBO) and [N-(3-iodonicotinoyl)-D-Phe(1)]octreotide (INO), respectively. The IC(50) values for the binding of IBO and INO to CA20948 rat pancreatic tumor membranes were 0.90 and 0.13 nM, respectively, compared with 0.35 nM for octreotide itself. Starting from N-succinimidyl 3-[(131)I]iodobenzoate and N-succinimidyl 5-[(131)I]iodopyridine-3- carboxylate, [(131)I]IBO and [(131)I]INO were prepared in overall radiochemical yields of 35%-50%. Likewise, ¿N-(3-[(211)At]astatobenzoyl)-D-Phe(1)¿octreotide ([(211)At]ABO) was prepared in similar yield from N-succinimidyl 3-[(211)At]astatobenzoate. In vitro assays with AR42J rat pancreatic tumor cells demonstrated a higher retention of cell-internalized radioiodine activity for [(131)I]INO compared with [(125)I]IBO. Tissue distribution studies with both conjugates revealed low levels of activity in the thyroid suggesting that dehalogenation of these peptides was minimal.

Animals↗
PubMed2000

Accuracy of deadspace free ventilatory measurements for lung function testing in ventilated newborns: a simulation study.

OBJECTIVE: A deadspace free method based on simultaneous ventilatory measurements in the inspiratory and expiratory limb of the ventilator circuit was compared to the conventional endotracheal method where the flow is measured between ETT and Y-Piece. The aim of our study was to find out how the arrangement of this setup affects the measuring accuracy of 1) the ventilatory and 2) the lung mechanical parameters by means of a computer simulation. METHOD: The system consisting of ventilator tubes and lung was described in state space and the flow signals of endotracheal method, of deadspace free method and the pressure at the Y-piece were simulated in the time domain. To investigate the influence of the position of the pneumotachographs (PNTs) in the ventilator circuit on measuring accuracy, the distance d0 of the PNT from the Y-piece was varied between 0 and 900 mm. The respiratory compliance C, resistance R and inertance I were calculated by least square method using the simulated flow and pressure signals of both methods. RESULTS: Compared to the endotracheal method, with increasing d0, the tidal volume measured with the deadspace free method rose linearly, depending on the ratio between the compliance of the ventilator tubes to the respiratory compliance. The differences of C and R for both methods were acceptable (< 10%) if the distance between each PNT and the y-piece didn't exceed 200 mm and the shorter do the higher the measuring accuracy. The inertance could not be measured by this method with satisfactory accuracy if d0 was higher than 100 mm. IN CONCLUSION: The dead space free method can be used for accurate ventilatory measurements during mechanical ventilation. However, for lung mechanic measurements in very low birth weight infants the position of the PNTs must be as short as possible.

Airway Resistance↗
PubMed2000

Pulmonary manifestation of systemic mast cell disease.

Systemic mast cell disease is a rare disease of unknown aetiology. Systemic infiltration and proliferation of mast cells in skin, bone marrow, gastrointestinum and lymph nodes is the central pathological feature. This study reports a patient with mastocytosis of the skin (urticaria pigmentosa) for 10 yrs. The patient was referred to hospital for dyspnoea. Chest radiograph showed moderate reticular infiltration of both lungs, computerized tomography revealed multiple lymph nodes of the mediastinum and faint nodular lesions of middle and upper areas of lungs. Transbronchial biopsy demonstrated mast cell infiltration of the lung with formation of mast cell granuloma. According to the current literature, systemic mast cell disease with pulmonary involvement is a very rare entity. After a treatment with interferon alpha-2a over 6 months, the patient's condition and particularly dyspnoea showed improvement in parallel with an amelioration of the lesions as demonstrated by thorax computed tomography.

Humans↗
PubMed2000

Q-sort assessment of attachment security during the preschool years: links from home to school.

This study investigated relations among preschoolers' secure-base behavior with mother at home, stressful family conditions, and qualities of developing relationships with peers and teachers in preschool. Preschool-age children (N = 94; 51 boys and 43 girls) and their mothers were observed during multiple home visits, and their security of attachment was assessed with the Attachment Q-Set. Children in families with lower levels of stress had more secure attachment relationships with mothers. Both boys and girls who were less securely attached to their mothers expressed significantly more anger-aggression in preschool. For boys, higher levels of family stress were also significantly related to anger-aggression and to social competence in preschool. In addition, boys who were more securely attached to their mothers were more securely attached to their preschool teachers and were more popular with peers in preschool.

Child, Preschool↗
PubMed2000

Activated protein C inhibits lipopolysaccharide-induced nuclear translocation of nuclear factor kappaB (NF-kappaB) and tumour necrosis factor alpha (TNF-alpha) production in the THP-1 monocytic cell line.

Activated protein C (APC) protects against sepsis in animal models and inhibits the lipopolysacharide (LPS)-induced elaboration of proinflammatory cytokines from monocytes. The molecular mechanism responsible for this property is unknown. We assessed the effect of APC on LPS-induced tumour necrosis factor alpha (TNF-alpha) production and on the activation of the central proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) in a THP-1 cell line. Cells were preincubated with varying concentrations of APC (200 microg/ml, 100 microg/ml and 20 microg/ml) before addition of LPS (100 ng/ml and 10 microg/ml). APC inhibited LPS-induced production of TNF-alpha both in the presence and absence of fetal calf serum (FCS), although the effect was less marked with 10% FCS. APC also inhibited LPS-induced activation of NF-kappaB, with APC (200 microg/ml) abolishing the effect of LPS (100 ng/ml). The ability of APC to inhibit LPS-induced translocation of NF-kappaB is likely to be a significant event given the critical role of the latter in the host inflammatory response.

Analysis of Variance↗
PubMed2000

Control of cellular phosphatidylinositol 4,5-bisphosphate levels by adhesion signals and rho GTPases in NIH 3T3 fibroblasts involvement of both phosphatidylinositol-4-phosphate 5-kinase and phospholipase C.

The involvement of small GTPases of the Rho family in the control of phosphoinositide metabolism by adhesion signals was examined in NIH 3T3 fibroblasts. Abrogation of adhesion signals by detachment of cells from their substratum resulted in a time-dependent decrease in the cellular level of PtdIns(4,5)P2 by approximately 50%. This effect could be mimicked by treatment of adherent cells with Clostridium difficile toxin B and toxin B-1470, which inhibit specific subsets of Rho and Ras GTPases. Detachment of cells that had been pretreated with the clostridial toxins did not cause a further reduction in PtdIns(4,5)P2 levels, suggesting that the target GTPases are integrated into the control of phosphoinositide levels by adhesion signals. The reduction in PtdIns(4,5)P2 levels could be attributed to reduced activity of the major PtdIns(4, 5)P2-producing enzyme, PtdIns4P 5-kinase. Unexpectedly, both cell detachment and toxin treatment resulted in a twofold to threefold increase in inositol phosphate production in intact cells. In lysates of these cells, in vitro phospholipase C activity was found to be elevated by 30-50%. The effects of cell detachment and toxin treatment on inositol phosphate formation could be mimicked by expression of dominant-negative N17 Rac1. Taken together, these data suggest that adhesion-controlled small GTPases of the Rho family are involved in the regulation of the cellular PtdIns(4,5)P2 levels in NIH 3T3 fibroblasts, by controlling the activities of both PtdIns4P 5-kinase and phospholipase C.

3T3 Cells↗
PubMed2000

Head to head comparison of dobutamine-transoesophageal echocardiography and dobutamine-magnetic resonance imaging for the prediction of left ventricular functional recovery in patients with chronic coronary artery disease.

AIMS: A substantial number of patients with dysfunctional but potentially viable myocardium cannot be accurately evaluated by transthoracic echocardiography due to a poor acoustic window. This study compares the diagnostic value of alternative functional imaging techniques, such as dobutamine-transoesophageal echocardiography (dobutamine-TEE) and dobutamine magnetic resonance imaging (dobutamine-MRI) for the detection of viable myocardium and the prediction of left ventricular functional recovery in patients with chronic coronary artery disease following successful revascularization procedures. METHODS AND RESULTS: Rest and low-dose (5, 10 microg dobutamine x min(-1) x kg(-1)) multiplane dobutamine-TEE and ultrafast cine-MRI studies were performed in 103 patients. Contractile recovery of an infarct region was predicted if a dobutamine contraction reserve could be assessed visually by TEE or MRI in > or =50% of infarct-related a- or dyskinetic segments. Revascularization of the infarct-related vessel was successful in 88 patients, and 4.9 +/- 0.7 months later 52 patients still had an angiographically controlled open target vessel. These patients underwent another rest MRI study to assess left ventricular functional recovery. A dobutamine contraction reserve was observed in 27/52 (52%) patients by TEE and in 26/52 (50%) patients by MRI. Functional improvement of the infarct region was diagnosed in 28/52 (54%) patients. The positive and negative predictive accuracy of dobutamine-TEE and dobutamine-MRI for the prediction of left ventricular functional recovery was not significantly different (85% vs 92%, ns and 80% vs 85%, ns). Diagnosis of a predominantly viable infarct region by TEE and MRI predicted a significant increase in left ventricular ejection fraction (TEE: 12 +/- 8% vs 2 +/- 7% P<0.001, MRI: 13 +/- 7% vs 2 +/- 7%, P<0.001) compared to infarct regions graded as scar. CONCLUSION: A qualitative visual analysis of TEE and MRI viability studies is highly accurate for the prediction of left ventricular functional recovery in patients with dysfunctional myocardium and proved to be a clinically valuable alternative if transthoracic dobutamine-echocardiography is unsuitable. To date, TEE is cardiologists' preferred choice for the assessment of myocardial viability but MRI may become significantly more attractive with increasing local availability and experience.

Aged↗
PubMed2000

Induction of apoptosis and activation of the caspase cascade by anti-EGF receptor monoclonal antibodies in DiFi human colon cancer cells do not involve the c-jun N-terminal kinase activity.

We previously reported that exposure of DiFi human colon cancer cells to the anti-epidermal growth factor (EGF) receptor monoclonal antibody (mAb) 225 resulted in apoptosis, but the mechanisms remain to be elucidated. In the present study, we investigated the effects of a panel of four anti-EGF receptor mAbs, each of which binds to different epitopes of the EGF receptor in DiFi cells, on the induction of apoptosis. We found that each of these mAbs induced apoptosis in DiFi cells. Exposure of DiFi cells to mAb 225 activated the initiation caspase-8, which was detectable between 8 and 16 h after exposure of the cells to the antibody. There was also an activation of the initiation caspase-9, which lagged a few hours behind the activation of caspase-8. Exposure of DiFi cells to mAb 225 also activated the execution caspase-3, which was accompanied temporally by evidence of cleavage of a well-characterized caspase-3 substrate, poly(ADP)ribosepolymerase (PARP). Pre-exposure of the cells to the caspase-3-specific inhibitor DEVD-CHO partially reduced the mAb 225-induced PARP cleavage and apoptosis, whereas pre-exposure of the cells to the caspase pan-inhibitor z-VAD-fmk completely inhibited mAb 225-induced apoptosis. Caspases-3, -8 and -9 were not activated in the cell lines in which mAb 225 only induced G1 phase arrest of the cell cycle. In contrast to the apoptosis of DiFi cells induced by ultraviolet irradiation, which strongly activated the c-jun N-terminal kinase-1 (JNK1) and the caspase cascade, mAb 225-induced apoptosis and activation of the caspase cascade in DiFi cells were not associated with activation of JNK1.

Adenocarcinoma↗
PubMed2000

[Molecular biology and immunohistochemical prognostic markers in head and neck squamous epithelial carcinomas].

BACKGROUND: Scientific research work of the last decade has been performed in order to investigate biological parameters of prognostic significance for head and neck squamous cell carcinoma. In contrast to other cancer types, like colon carcinoma, where tumour progression is accompanied by an almost defined sequel of gene activations and inactivations, cells of squamous cell carcinoma behave more heterogenously. METHODS: Publications concerning the most important immunohistochemical, molecular biological and cytogenetic prognostic markers in head and neck cancer have been analyzed. RESULTS: The prognostic markers discussed in this publication have been classified into the following areas: Apoptosis, cell cycle regulation, viral infections, cytokines and growth factors/growth factor receptors, angiogenesis and hypoxia, proteinases, cell-cell contacts and cell-matrix contacts, cytokeratin fragments, chromosomal rearrangements and genetically inherited susceptibility to toxic reagents. CONCLUSIONS: Significant prognostic markers are important for the clinical follow-up of patients and the choice of therapeutical approach. However, none of the factors analyzed can be used as an individual and universal prognostic marker at present.

Biomarkers, Tumor↗
PubMed2000

Late metastases of cutaneous melanoma: an analysis of 31 patients.

Analysis of data of 6298 patients with cutaneous melanoma seen at the Department of Dermatology and Allergology at the Ludwig-Maximilians University of Munich between 1977 and 1998 identified 31 patients who first experienced metastatic disease 10 or more years after surgical treatment of the primary melanoma. The mean tumor thickness in patients with late progression of disease was 1.4 mm. There was no sex predominance. Of 31 patients, 15 (48. 3%) were female and included both premenopausal and postmenopausal women at the time of initial diagnosis without any predominance. Sixteen of the 31 patients (51.6%) with late onset of progression had primary tumors located on the trunk. The prognosis after relapse was related to the site of recurrence; survival after local or regional node recurrence was often prolonged, whereas survival after distant metastases usually was limited. Survival after late recurrence did not correlate with disease-free survival. A high-risk group for late recurrence could not be identified. The data emphasize the value of continued clinical follow-up and self-examination for early detection of regional recurrences. We advocate a lifelong follow-up, also to identify other melanocytic lesions at risk (eg, dysplastic nevi, secondary or multiple melanomas).

Adult↗
PubMed2000

Risks of in-vitro production of cattle and swine embryos: aberrations in chromosome numbers, ribosomal RNA gene activation and perinatal physiology.

In cattle, in-vitro production (IVP) of embryos has become a standardized technique; however, increased frequencies of calving problems and larger calves have been reported. In swine, IVP has resulted in only a limited number of piglets. In this paper we present information on cattle and swine embryos produced in vitro by oocyte maturation, fertilization and further embryo culture to the blastocyst stage in vitro. Control in-vivo developed embryos were collected after superovulation. The cattle embryos were processed for fluorescence in-situ hybridization (FISH) with two chromosome-specific probes to detect numerical chromosome aberrations. The swine embryos were processed for transmission electron microscopy and immunocytochemistry with an antibody against RNA polymerase I [essential for ribosomal RNA (rRNA) gene transcription] in order to highlight the post-fertilization development of the nucleolus as a marker for rRNA gene activation. The FISH analyses of the cattle embryos revealed that 72% of IVP blastocysts were mixoploid, i.e. contained both diploid and polyploid cells, versus 25% in vivo. Chromosome abnormalities were observed from the 2-cell stage onwards. The immunocytochemical analyses of the swine embryos revealed that during in-vivo development, RNA polymerase I became localized to multiple foci in the developing nucleoli late during the 4-cell stage. This focal localization of RNA polymerase I was not observed in IVP embryos. In conclusion, IVP embryos may display aberrations in chromosome numbers and rRNA gene activation. The significance of these deviations for fetal and perinatal viability, however, remains unknown. The survival of most calves derived from IVP indicates that a considerable number of these embryos are able to compensate for the adverse effects of the in-vitro procedures.

Animals↗
PubMed2000

Effects of the sitting position on the distribution of blood volume in patients undergoing neurosurgical procedures.

The use of the sitting position in neurosurgery is often associated with decreased arterial pressure (MAP) and stroke volume index (SVI). A shift in blood from the intra- to the extrathoracic compartment may be responsible for this cardiovascular response. However, little is known of the amount of shift in blood volume after transfer from the supine to the sitting position. Therefore, we measured simultaneously changes in intrathoracic blood volume (ITBV) caused by a change in body position in anaesthetized patients. Measurements of cardiac index (CI), ITBV, pulmonary (PBV) and total circulating (TBVcirc) blood volumes were performed in the supine and sitting position. CI, ITBV, PBV and TBVcirc were measured using a thermodye dilution technique. Fluid input was restricted to 14 ml kg-1 before induction of anaesthesia. Change in body position caused a significant decrease in ITBV and was accompanied by a significant decrease in CI, SVI and MAP. Changes in ITBV correlated (r = 0.78) with changes in SVI. Thus a change in blood volume distribution between the intra- and extrathoracic compartment occurred after a change from the supine to the sitting position. Indicator dilution enables quantification of this shift and may be helpful in guiding fluid therapy in selected patients.

Adult↗