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M Schmidt

Publications and source records attributed to M Schmidt.

At least 91 records · Page 5Linked to original sources
PubMed2004

The dynamics of the hypothalamic-pituitary-adrenal axis during maternal deprivation.

A close contact between the dam and the litter is essential for the normal development of the hypothalamic-pituitary-adrenal (HPA) axis in rats and mice. Maternal signals, as licking and feeding, have been shown to sustain the HPA axis of the pups in a hypo-responsive state. Disruption of this mother-pup interaction by 24 h of maternal deprivation activates the otherwise quiescent stress system of the neonates, resulting in an enhanced adrenal sensitivity to adrenocorticotropic hormone (ACTH) and a decreased expression of central HPA markers, such as corticotropin-releasing hormone (CRH). However, the dynamics of these central and peripheral changes over the 24h period are largely unknown. In this study, we examined the time course of some of the central and peripheral indices of HPA activity during 24 h of maternal deprivation. We measured corticosterone and ACTH in the blood as well as CRH, mineralocorticoid and glucocorticoid receptor expression in the brain. Our results demonstrate that each of the components of the HPA axis responds to maternal deprivation at different time points following removal of the mother and with a very specific time course. The main activation of the HPA axis occurred between 4 h and 8 h of maternal absence. By contrast, during the second half of the deprivation period, negativefeedback mechanisms restrained the further increase in ACTH and corticosterone release. We conclude that maternal deprivation triggers a cascade of sequential changes at the various levels of the stress system, and that measuring only one aspect of the system at one time point does not accurately reflect the dynamic alterations of the HPA axis.

Adrenocorticotropic Hormone↗
PubMed2004

Renal clearance and daily excretion of cortisol and adrenal androgens in patients with rheumatoid arthritis and systemic lupus erythematosus.

BACKGROUND: In rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), patients demonstrate low levels of adrenal hormones. OBJECTIVE: To investigate whether increased renal clearance and daily excretion contribute to this phenomenon. METHODS: Thirty patients with RA, 32 with SLE, and 54 healthy subjects (HS) participated. Serum and urinary levels of cortisol, cortisone, 17-hydroxyprogesterone (17OHP), androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulphate (DHEAS) were measured. RESULTS: Clearance of DHEAS and DHEA was lower in patients than in HS, and clearance of androstenedione was somewhat higher in patients than in HS, but daily excretion of this latter hormone was low. Clearance of cortisol, cortisone, and 17OHP was similar between the groups. The total molar amount per hour of excreted DHEA, DHEAS, and androstenedione was lower in patients than HS (but similar for cortisol). Serum DHEAS levels correlated with urinary DHEAS levels in HS and patients, whereby HS excreted 5-10 times more of this hormone than excreted by patients. Low serum levels of adrenal androgens and cortisol in patients as compared with HS were confirmed, and proteinuria was not associated with changes of measured renal parameters. CONCLUSIONS: This study in patients with RA and SLE demonstrates that low serum levels of adrenal androgens and cortisol are not due to increased renal clearance and daily loss of these hormones. Decreased adrenal production or increased conversion or conjugation to downstream hormones are the most likely causes of inadequately low serum levels of adrenal hormones in RA and SLE.

17-alpha-Hydroxyprogesterone↗
PubMed2004

18F-FDG PET for detecting recurrent head and neck cancer, local lymph node involvement and distant metastases. Comparison of qualitative visual and semiquantitative analysis.

AIM: Assessment of the clinical value of (18)F-FDG-PET for detection of recurrent head and neck cancer, local lymph node involvement and distant metastases comparing a qualitative visual with a semiquantitative analysis (SUV values). PATIENTS, METHODS: Retrospective evaluation of 73 (18)F-FDG PET studies in 55 patients by use of a four-step qualitative visual grading system and calculation of standard uptake values in pathological lesions. Calculation of SUV values in normal regions for generating a map of physiological (18)F-FDG distribution. Correlation to histopathological findings and clinical follow-up. RESULTS: 1. Qualitative visual analysis of (18)F-FDG PET studies: a) local recurrence sensitivity 79%, specificity 97%, positive predictive value 95%, negative predictive value 85%, and diagnostic accuracy 89%; b) local metastatic lymph nodes 100%, 95%, 85%, 100%, 96%; c) distant metastases 100%, 98%, 86%, 100%, 98%, respectively. 2. Semiquantitative analysis had only little incremental, non-significant value in comparison to qualitative visual analysis for the detection of a local recurrence in two patients: a) local recurrence: sensitivity 83%, specificity 100%, positive predictive value 100%, negative predictive value 88%, and diagnostic accuracy 93%; b) local metastatic lymph nodes or c) distant metastases did not change in comparison to qualitative visual analysis. CONCLUSION: (18)F-FDG PET is an effective tool for re-staging of patients with suspected recurrence after therapy for head and neck cancer.

Carcinoma, Squamous Cell↗
PubMed2003

Oxygen and silver clusters: transition from chemisorption to oxidation.

We use the adsorption probabilities of molecular nitrogen and oxygen to study the physi- and chemisorption on small silver particles. The physisorption of nitrogen is governed by the structure of the particle surface. The sticking of oxygen additionally involves the electronic configuration of the metal cluster. At 77 K molecular oxygen sticks chemisorbed to the particles with a transfer of one electron. At temperatures above 105 K the chemisorption transforms into oxidation, invoking the dissociation of the oxygen molecule and the loss of a single oxygen atom.

Journal Article↗
PubMed2003

LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1.

We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Conversion of aliphatic 2-acetoxynitriles by nitrile-hydrolysing bacteria.

The enzymatic hydrolysis of the nitrile group of different 2-acetoxynitriles was investigated in order to obtain catalysts that chemoselectively hydrolyse nitriles in the presence of ester groups. The biotransformation of four 2-acetoxynitriles [2-acetoxybutenenitrile (ABN), 2-acetoxyheptanenitrile (AHN), 2-acetoxy-2-(2-furyl)acetonitrile (AFN), and 2-acetoxy-2,3,3-trimethylbutanenitrile (ATMB)] by different bacterial strains that synthesise nitrilases or nitrile hydratases was studied. ABN, AHN and AFN were converted by various microorganisms belonging to different bacterial genera (e.g. Pseudomonas or Rhodococcus) expressing either nitrilase or nitrile hydratase activities. In contrast, no metabolism of the sterically hindered substrate ATMB was observed. All wild-type strains investigated formed considerable amounts of cyanide and aldehydes from the 2-acetoxynitriles. This indicated the presence of esterases converting the 2-acetoxynitriles to 2-hydroxynitriles, which then spontaneously decomposed to the corresponding aldehydes and cyanide. In order to suppress unwanted side-reactions, biotransformations were performed with recombinant Escherichia coli strains that heterologously expressed nitrilase activities originating from Pseudomonas, Rhodococcus, or Synechocystis strains. The attempted conversion of the 2-acetoxynitriles to almost stoichiometric amounts of the corresponding 2-acetoxycarboxylic acids was finally achieved by using either a recombinant E. coli strain that highly overexpressed the nitrilase gene from the pseudomonad or the purified enzyme derived from this strain.

Acetonitriles↗
PubMed2003

[Thin-walled apical ventricular aneurysm associated with hypertrophic obstructive cardiomyopathy].

HISTORY AND ADMISSION FINDINGS: A 73-year-old patient presented for routine follow-up examination for pre-diagnosed hypertrophic obstructive cardiomyopathy (HOCM). The patient's history included arterial hypertension and dyspnea on exertion. INTERVENTIONS: Echocardiography revealed a large apical aneurysm, which had vastly increased in size over the past six months. Further evaluation by cardiac magnetic resonance (NMR) imaging confirmed the aneurysm and demonstrated a wall thickness of no more than 2 mm. TREATMENT AND COURSE: Due to the rapid increase in size in addition to the extremely thin wall diameter the risk of spontaneous rupture was considered high and the patient was referred to surgical therapy. Echocardiographic and NMR-findings were confirmed intraoperatively. The aneurysm was resected and the postoperative progress was uneventful. CONCLUSION: Aneurysms of the apical left ventricle can result from an underlying HOCM. In case of rapid increase of the aneurysm, aneurysmectomy should be performed.

Aged↗
PubMed2003

[Acute tongue necrosis provoked by epirubicin-cyclophosphamide treatment for invasive ductal breast cancer].

CASE: Unilateral necrosis of the tongue is an uncommon symptom of different rare diseases. Previously, it had only been described as an infrequent complication of temporal arteritis or as a side effect of therapy with ergotamine. We present a case of unilateral necrosis of the tongue in a 62-year-old woman with invasive ductal carcinoma of the breast treated with epirubicin and cyclophosphamide. RESULTS: The necrosis led to a rapid swelling of the tongue and consequently to an airway obstruction necessitating a tracheotomy. After excision of the necrosis, the swelling of the tongue and the airway obstruction subsided. DISCUSSION: Because of the temporal connection between the occurrence of the necrosis and the administration of chemotherapy, an adverse effect of the administered drugs seems most likely. However, a paraneoplastic pathogenesis cannot be completely excluded. The occurrence of unilateral necrosis of the tongue is a rare complication of the above-mentioned conditions. However, it is important to be aware of the different causes leading to this rare disease in order to initiate the right therapy.

Acute Disease↗
PubMed2003

p53 expression and resistance against paclitaxel in patients with metastatic breast cancer.

PURPOSE: Paclitaxel is an important agent in the pharmacological treatment of metastatic breast cancer. Despite its efficacy in selected patients, the majority of patients have a resistance against paclitaxel. The aim of this study was to identify the responding patients and hence prevent the other patients from ineffective treatment. Identifying these patients could spare them an ineffective treatment and could in turn characterize a subgroup of patients with a higher response rate. MATERIAL AND METHODS: Thirty-three patients with metastatic breast cancer received paclitaxel 175 mg/m(2 )either as first- (15 patients) or as second-line (18 patients) treatment. Immunohistochemistry was performed on the blocks of the primary tumors with monoclonal antibodies against p53, HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-pi, and beta-tubulin II. The expression of those factors was then correlated with the objective response to paclitaxel. RESULTS: Ten of 33 patients had an objective response to treatment. A significant correlation with the objective response was found for the expression of p53. None of the tumors with p53 expression ( n=11) responded to paclitaxel. In contrast, 10 of the 22 patients without p53 expression showed an objective response ( P=0.013). Expression of HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-pi, and beta-tubulin II did not show a correlation with the response to paclitaxel. CONCLUSION: The immunohistochemical detection of p53 characterizes patients with metastatic breast cancer unlikely to respond to paclitaxel.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Influence of energy and entropy on the melting of sodium clusters.

Energetic and entropic influences on the melting temperatures of size selected sodium clusters are experimentally separated. It is shown that the energetic difference between solid and liquid is the leading influence for the still puzzling features in the size dependence of sodium melting points. Additionally, this energy difference decreases towards smaller cluster sizes and causes steplike melting phase transitions to vanish. The entropy difference between solid and liquid has been found to be strongly correlated with the energy and causes a pronounced damping of the energetic influences.

Journal Article↗
PubMed2003

[Monitoring of the treatment of calcium-oxalate stone formers with the Bonn-Risk-Index].

Cost-effective metaphylaxis and monitoring is becoming more and more focused in the treatment of urinary stones. Therefore, medical practitioners are asked to reduce the analytical efforts necessary for evaluation and to control the actual biochemical risk of stone formation in the patients. The most common strategy available is based on chemical urinalysis and the calculation of theoretically derived risk parameters. However, this covers--in the best case--the analysis of the most prominent low molecular urinary constituents. No information about the fraction of the important macromolecular urinary components is obtained. Crystallization experiments in unprepared, native urine samples, carried out according to the Bonn-Risk-Index approach (BRI), allow the determination of a more realistic measure of a urine's crystallization risk since the entire urinary composition influences the experimental result. As only two parameters have to be analyzed, the BRI is a fast and cost-effective risk evaluation method. The results show a high selectivity between stone-formers and non-stone-forming persons. The changes in the BRI-risk of three calcium oxalate stone-formers after a 1 week stay in our hospital are presented and discussed in detail. In one of these patients, a follow up examination was performed in order to control the therapy's success and, additionally, to obtain information about the patient's compliance with the therapy. During hospitalization, the patients received a standardized and "stone-neutral" diet. All persons showed a distinct decrease in their individual crystallization risk.

Adult↗
PubMed2003

[Misdiagnosis of urinalysis due to in vivo formation of urinary stones].

The occurrence of biochemically unaltered urinalyses in patients with severe recurrent stone formation is not a rare observation in practice. The possible reasons for that phenomenon are manifold. We show that stone growth-related urinary depletion of lithogenic constituents caused by acute growth of urinary calculi in vivo can be an important reason for the observed phenomenon. The described process which can strongly influence the urinary composition occurs in any stone-bearing patient. Thus, it is strongly recommended that stone-related alterations be taken into account when interpreting the urinalyses of these patients. Based on simplified model assumptions, the extent of the expected chemical depletion effect can be calculated for any stone patient's urine sample. In two easy-to-use nomograms, we have combined the key parameters which govern the process, allowing the user a fast and easy estimation.

Adult↗
PubMed2003

Regulation of the developing hypothalamic-pituitary-adrenal axis in corticotropin releasing hormone receptor 1-deficient mice.

During postnatal development, mice undergo a so-called stress hyporesponsive period, which is characterized by low basal corticosterone levels and the inability of mild stressors to induce a corticosterone response. The stress hyporesponsiveness is in part regulated by maternal factors. Twenty-four hours of deprivation results in an activation of basal and stress-induced corticosterone and a down-regulation of corticotropin releasing hormone (CRH), mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) expression in the brain. It has been hypothesized that the CRH receptor 1 (CRHr1) may play an important regulatory role during development by mediating the effects of maternal deprivation. Using CRHr1-deficient mice we examined the role of this receptor on the maternal deprivation effects and in regulating the expression of hypothalamic-pituitary-adrenal axis-related genes. We could demonstrate that the CRHr1 is essential for the activation of the corticosterone response following maternal deprivation, most likely due to the lack of the receptor in the pituitary. Furthermore, we could show that the CRHr1 is regulating the expression of CRH and MRs. In contrast, effects of maternal deprivation during postnatal development on GRs are not mediated by this receptor.

Animals↗
PubMed2003

The postnatal development of the hypothalamic-pituitary-adrenal axis in the mouse.

The main characteristic of the postnatal development of the stress system in the rat is the so-called stress hypo-responsive period (SHRP). Lasting from postnatal day (pnd) 4 to pnd 14, this period is characterized by very low basal corticosterone levels and an inability of mild stressors to induce an enhanced ACTH and corticosterone release. During the last years, the mouse has become a generally used animal in stress research, also due to the wide availability of genetically modified mouse strains. However, very few data are available on the ontogeny of the stress system in the mouse. This study therefore describes the postnatal ontogeny of peripheral and central aspects of the hypothalamic-pituitary-adrenal (HPA) axis in the mouse. We measured ACTH and corticosterone in blood and CRH, urocortin 3 (UCN3), mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) transcripts in the brain at postnatal days 1, 2, 4, 6, 9, 12, 14 and 16. Our results show that we can subdivide the postnatal development of the HPA axis in the mouse in two phases. The first phase corresponds to the SHRP in the rat and lasts from right after birth (pnd 1) until pnd 12. Basal corticosterone levels were low and novelty exposure did not enhance corticosterone or ACTH levels. This period is further characterized by a high expression of CRH in the paraventricular nucleus (PVN) of the hypothalamus. Expression levels of GR in the hippocampus and UCN3 in the perifornical area are low at birth but increase significantly during the SHRP, both reaching the highest expression level at pnd 12. In the second phase, the mice have developed past the SHRP and were now exhibiting enhanced corticosterone basal levels and a response of ACTH and corticosterone to mild novelty stress. CRH expression was decreased significantly, while expression of UCN3 and GR remained high, with a small decrease at pnd 16. The expression of MR in the hippocampus was very dynamic throughout the postnatal development of the HPA axis and changed in a time and subregion specific manner. These results demonstrate for the first time the correlation between the postnatal endocrine development of the mouse and gene expression changes of central regulators of HPA axis function.

Adrenocorticotropic Hormone↗
PubMed2003

The process of metastasisation for breast cancer.

To investigate the process of metastasis, primary clinical data and disease events such as metastases, local recurrence and survival (median follow-up 9.4 years) from the Munich Cancer Registry from 1978 to 1996 were analysed. Since metastases, even from small tumours, may be initiated before the diagnosis of the primary tumour, the growth of the primary tumour and metastasisation may be two autonomous processes. In our data, survival following metastases was almost unrelated to primary tumour size. However, the number of M1 cases and the time to metastasisation depended on the tumour diameter at diagnosis. The time from initiation of metastases to its diagnosis was estimated as 5.8 years. The growth of metastases was almost homogeneous. However, the growth time following metastasisation-depending on the metastases-free time, receptor status and histological grade-only varied by approximately a factor of 2. Local recurrence, above all, was an indicator of metastases. Furthermore, local recurrence may also have the potential to metastasise. Excess mortality due to local recurrence was estimated up to 9.3 years after diagnosis. Our hypothesised metastases model illustrates the importance of early detection, the concept of breast-conserving therapy and additional metastases from local recurrence. It highlights the benefits of optimal local therapy of the primary tumour and the limitations of systemic therapy. It also questions the use of axilla dissection and lymph node irradiation. Its generalisation to solid tumours may help to clarify many of the current controversial debates.

Breast Neoplasms↗
PubMed2003

Immunologic characterization of the recombinant fire ant venom allergen Sol i 3.

Individuals sensitized to fire ant stings show immunoglobulin (Ig)E antibodies against the venom protein Sol i 3. We determined the full-length complementary DNA (cDNA) sequence of this protein and expressed recombinant Sol i 3 in immunogenic form. The complete cDNA of Sol i 3 was obtained by reverse transcription polymerase chain reaction (RT-PCR) and PCR + 1 reactions using gene-specific oligonucleotides, and oligonucleotides designed from the amino acid sequence of this protein. The encoding cDNA is 705 bp in length corresponding to 235 amino acids. The first 22 amino acids are a leader sequence. The protein with an added C-terminal hexahistidine tag was expressed in insect cells using a baculovirus system. The recombinant protein was secreted into the supernatant and affinity purified with a cobalt chelating resin. The recombinant fire ant venom allergen Sol i 3 showed similar IgE binding activity to the native protein in radioallergosorbent test (RAST) and RAST inhibition assays. It was produced in both a glycosylated and an unglycosylated form. A three-dimensional reconstruction of Sol i 3 was compared with the experimentally determined structure of the related allergen Ves v 5. This model is supported by results of circular dichroism spectroscopy.

Allergens↗
PubMed2003

[The role of cytokines and growth factors in fibroproliferative lung disease].

A new hypothesis of the pathogenesis of fibroproliferative lung disease suggests that fibrosis is caused by abnormal and excessive wound healing and pathologic tissue remodelling. Inflammation is possibly an epiphenomenon. Cytokines are critical players in the pathologic process and attractive targets for pharmacological intervention. TGF beta is a key profibrotic growth factor, a variety of approaches are known to modify and inhibit its activity. This article reviews the basic pathological concepts of pulmonary fibrogenesis and outlines its potential clinical benefit.

Cytokines↗