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Biomedical subjects

M Schmitz

Publications and source records attributed to M Schmitz.

At least 91 records · Page 5Linked to original sources
PubMed1997

Ki-ras oncogene and p53 tumour suppressor gene mutations in colorectal carcinomas from the European Saar-Luxembourg region are less frequent than predicted by the classic adenoma-carcinoma sequence model.

Recent investigations of colorectal cancer (CRC) have suggested that the accumulation of specific alterations in cell-growth regulating genes trigger the stage-wise progression to malignancy and that at least some of them could be useful for prognosis. In this study, the frequency, location and type of mutations of the Ki-ras proto-oncogene exons 1-2 and p53 tumour-suppressor gene exons 5-9 were analysed in colorectal carcinomas of 72 patients from the European Saar-Luxembourg region using PCR-SSCP screening and direct sequencing. The incidences of Ki-ras activating and p53 inactivating point mutations in these European samples were much lower (Ki-ras: 5 (6.9%) and p53: 13 (18.1%)) than reported for both genes in American studies (40-50% at least) (P < 1 x 10(-3)). These results suggest that other genetic mechanisms than those proposed for the classic adenoma-carcinoma sequence model can frequently underlie CRC development and that Ki-ras and p53 mutations should not be considered as universal markers for CRC.

Adenoma↗
PubMed1997

Characterization of murine monoclonal antibodies against the Ro52 autoantigen.

Immunization of BALB/c mice with purified recombinant human Ro52 protein resulted in three anti-Ro52 MoAbs termed 2E7, 4C6 and 4F11. All anti-Ro52 MoAbs specifically reacted with recombinant human Ro52 protein, and also with Ro52 protein in total extracts of all human cell lines analysed, including the epithelial cell line HeLa, the B cell line Raji, the bladder carcinoma cell line RT112, and a fibroblast cell line derived from patients with xeroderma pigmentosum. The anti-Ro52 MoAbs were able to immunoprecipitate the recombinant human Ro52 protein expressed in wheat germ extract, but failed to precipitate hY RNAs from cell extracts. The staining pattern of the MoAbs strongly differed between the RT112 cells and the fibroblast cell line. RT112 cells displayed an intense cytoplasmic staining and in addition distinct fine nuclear speckles. In contrast, in the fibroblast cell line no cytoplasmic staining but only staining of distinct nuclear speckles was observed. Using deletion mutants of Ro52 the epitopes recognized by the anti-Ro52 MoAbs 2E7, 4C6 and 4F11 were partially mapped. All three MoAbs appeared to recognize distinct epitopes, that are located in the regions of Ro52 bordered by amino acids 136-164, 208-363 and 136-190, respectively. These MoAbs can be of great use in studying the cellular processes in which the Ro52 protein is involved.

Amino Acid Sequence↗
PubMed1997

Suppression of the immune system by oral glucocorticoid therapy in bronchial asthma.

The effect of systemic glucocorticoid therapy on immune parameters was studied in patients with bronchial asthma. Patients were divided into two groups: 1) those receiving oral glucocorticoid; 2) control patients who did not receive systemic glucocorticoid treatment. The glucocorticoid dose varied between 5 and 70 mg per day. Patients had been taking oral therapy for at least 1 year. Glucocorticoid treatment was associated with an increased frequency of respiratory tract infections. Therefore, we need to define immune parameters which may predict an increased risk of infections. In this study, we analyzed several surface markers on lymphocytes and monocytes by flow cytometry. A significant reduction of the ratio of peripheral blood CD4+ to CD8+ T cells was associated with the administration of oral glucocorticoids. Furthermore, the expression of the HLA-DR molecule on monocytes was reduced in patients with systemic glucocorticoid therapy compared to control patients. Moreover, the capacity to elaborate cytokines by peripheral blood mononuclear cells upon stimulation was greatly reduced after exposure to glucocorticoids in vivo and in vitro. In addition, the humoral immune response was affected, because reduced IgG, IgM, and IgA levels were observed in patients receiving oral glucocorticoids. These results indicate that systemic glucocorticoid treatment in patients with bronchial asthma is associated with cellular and humoral immunosuppression which results in an increased risk of bacterial and viral infections.

Administration, Oral↗
PubMed1997

Expression of interleukin-5 and granulocyte-macrophage colony-stimulating factor in aspirin-sensitive and non-aspirin-sensitive asthmatic airways.

Increased numbers of eosinophils and mast cells in the bronchial mucosa are characteristic features in subjects with aspirin-sensitive asthma. Interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are involved in the activation, maturation, and perpetuation of survival of eosinophils. Immunohistochemical techniques were therefore used to study the expression of IL-5 and GM-CSF on frozen bronchial biopsies from 13 aspirin-sensitive asthmatic (ASA) and 8 non-ASA (NASA) subjects. Aspirin sensitivity was diagnosed by lysine-aspirin inhalation provocation. ASA airways demonstrated a significant 2-fold increase in the total number of submucosal inflammatory cells expressing IL-5 (p = 0.03) and approximate 4- and 2-fold increases in the numbers of mast cells expressing IL-5 and GM-CSF (p = 0.02 and p = 0.04, respectively). There was also a 4-fold increase in the number of eosinophils expressing IL-5 (p = 0.004). These results suggest a central role for the mast cell and eosinophil in regulation of the inflammatory cell infiltrate of ASA airways by secretion of the hemopoietic cytokines IL-5 and GM-CSF.

Adult↗
PubMed1997

[Vocal cord dysfunction, an important differential diagnosis of severe and implausible bronchial asthma].

BACKGROUND: For asthmatics who show-despite of all available therapeutic efforts-an unsatisfactory clinical course in- or exspiratory vocal cord dysfunctions are an important diagnostic consideration. Aside from some case reports, there is only one major study, presenting a prevalence of > 30% in subjects admitted because of refractory asthma. PATIENTS AND METHODS: The question was whether this phenomenon could also be found in our patients, mostly in- or extrinsic asthmatics. In cases suspicious for VCD or with an unexplainable asthma course, we performed videotaped laryngoscopy, including exposure to questionable provocing irritants. RESULTS: In 14 months, we detected VCD in 16 patients by laryngoscopy and spirometry at the time of severe dyspnea. Subjects were predominantly women. Our therapeutical approach included: explanation of their videotape, speech therapy, breathing techniques and psychological support. In patients, pretreated with systemic corticosteroids, the dose could be reduced remarkably. A benefit 3 month after diagnosis could be shown using a life-quality-questionnaire. CONCLUSIONS: Screening for VCD in patients with unplausible, refractory asthma and other unexplained dyspnea- or wheezing attacks is an important diagnostic consideration in order to prevent unnecessary medical treatment or drug related side-effects and to introduce a specific therapeutical concept.

Adult↗
PubMed1997

[Psychosocial aspects of chronic respiratory tract diseases (COPD): relevance and consequences for pulmonary rehabilitation].

As a part of the Davoser-Reha-Study, the significance of psychosocial aspects on the course of chronic pulmonary disease has been investigated on 414 patients (mean age = 47.1 years) with COPD (mean duration = 16 years) and a high percentage of multimorbidity (75%). Of special interest was the question, what kind of impact coping strategies do have on certain aspects of quality of life, in the sense of outcome criterias of the medical rehabilitation. Also it is not possible for the moment to draw final conclusions, because the knowledge about coping strategies and their adaptability is still very limited, the current study indicates, that some coping strategies are more supportive for adaptation than others. Positive for adaptation are strategies, which can be described as active exposition with the disease (fighting spirit, information seeking and active problem solving). Depressive coping strategies and the tendency to deny the disease seem to have a negative effect. All in all the results verify the strong necessity of taking psychosocial aspects into account for the complete treatment of chronically ill patients with COPD.

Adaptation, Psychological↗
PubMed1996

Description of RNA folding by "simulated annealing".

An algorithm is proposed which describes the thermodynamically as well as the kinetically controlled folding process of RNA. The algorithm, based on a special Monte Carlo procedure known as "Simulated Annealing", takes into account the probabilities for opening and closing of single base-pairs. Thus, the algorithm is able to reach structures and structure distributions near the global minimum of structure space, and is not restricted by the tendency to halt in local minima. Three types of structural folding processes may be analysed by this algorithm. Firstly, using thermodynamic data, structure ensembles comparable to those obtained by dynamic programming are achieved. Secondly, using kinetic data, the processes of structure formation and structural rearrangement may be simulated. Thirdly, additionally taking into account RNA polymerase chain elongation rates, the process of "sequential folding" during transcription may be described. Analysis of all types of structural folding and refolding is performed for RNA sequences related to potato spindle tuber viroid (PSTVd). The computed results are in accordance with experimental data and biological functions known for PSTVd.

Algorithms↗
PubMed1996

Development of a radioimmunoassay for European eel growth hormone and application to the study of silvering and experimental fasting.

A specific and sensitive homologous radioimmunoassay for eel (Anguilla anguilla L.) growth hormone (angGH) has been developed. The antiserum, raised against purified angGH and used at 1:20,000 final dilution, did not cross-react with eel prolactin or thyrotropin, carp gonadotropin II, bovine GH, or serum from hypophysectornized eel. The inhibition curves for eel pituitary extracts and serum were parallel to that of angGH standard. The ED50 value was between 1 and 2 ng/tube and the recovery of purified angGH added to the serum was about 100%. In immunocytochemical studies, the antiserum, used at 1:1000 dilution, specifically labeled the somatotrophs in the pituitaries of the glass, yellow, and silver eels. The GH contents were determined in the pituitaries of glass, yellow, and silver eels and in the serum at the yellow and silver stages. GH variations during the transformation of the yellow to silver eel were examined. The results indicated a decrease in GH production between the yellow and the silver eels, possibly related to the cessation of growth at the silver stage. In contrast to the situation in the naturally fasting silver eel, submitting yellow eels to 3 months of starvation (experimental fasting) greatly increased GH production. This suggests a variation in the regulation of GH according to the type of fasting (natural or experimental) and/or the stage of the fish (yellow or silver).

Anguilla↗
PubMed1996

A comparison of sevoflurance to halothane in paediatric surgical patients: results of a multicentre international study.

Induction, emergence and recovery characteristics were compared during sevoflurane or halothane anaesthetic in a large (428) multicentre, international study of children undergoing elective inpatient surgical procedures. Two hundred and fourteen children in each group underwent inhalation induction with nitrous oxide/oxygen and sevoflurane or halothane. Incremental doses of either study drug were added until loss of eyelash reflex was achieved. Steady state concentrations of anaesthesia were maintained until the end of surgery when anaesthetic agents were terminated simultaneously. Time variables were recorded for induction, emergence and the first need for analgesia in the recovery room. In addition, in 86 of the children in both groups, venous blood samples were drawn for plasma fluoride levels during and after surgery. There was a trend toward smoother induction (induction of anaesthesia without coughing, breath holding, excitement laryngospasm, bronchospasm, increased secretion, and vomiting) in the sevoflurane group with faster induction (2.1 min vs 2.9 min, P = 0.037) and rapid emergence times (10.3 min vs 13.9 min, P = 0.003). Among the children given sevoflurane, 2% developed bradycardia compared with 11% in the halothane group. Postoperatively, 46% of the children in the halothane group developed nausea and or vomiting versus 31% in the sevoflurane group (P = 0.002). Two children in the halothane group developed cardiac dysrhythmia and were dropped from the study. In addition, a child in the halothane group developed malignant hyperthermia, received dantrolene, and had an uneventful recovery. Mean maximum inorganic fluoride concentration was 18.3 microM.l-1. The fluoride concentrations peaked within one h of termination of sevoflurane anaesthetic and returned rapidly to baseline within 48 h. This study suggests that sevoflurane may be the drug of choice for the anaesthetic management of children.

Adolescent↗
PubMed1995

The human mdr1 (multidrug-resistance) gene harbours a long homopyrimidine.homopurine sequence next to a cluster of Alu repeated sequences in intron 14.

In order to identify specific DNA sequences useful as 'genetic landmarks' in the construction of a complete map of the human mdr1 (multidrug-resistance) gene, we investigated the introns in the central region. In intron 14, we identified a long stretch of a homopyrimidine.homopurine sequence most probably adopting an unconventional DNA conformation, followed by a cluster of three Alu repeated sequences in an inverted orientation. Here, we describe the structure, formation and nucleotide sequence of these DNA elements.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Repetitive DNA sequences located in the central region of the human mdr1 (multidrug resistance) gene may account for a gene fusion event during its evolution.

The mdr1 gene, first member of the human multidrug-resistance gene family, is a major gene involved in cellular resistance to several drugs used in anticancer chemotherapy. Its product, the drug-excreting P-glycoprotein, shows a bipartite structure formed by two similar adjacent halves. According to one hypothesis, the fusion of two related ancestral genes during evolution could have resulted in this structure. The DNA sequence analysis of the introns located in the region connecting the two halves of the human mdr1 gene revealed a highly conserved poly(CA).poly (TG) sequence in intron 15 and repeated sequences of the Alu family in introns 14 and 17. These repeated sequences most likely represent "molecular fossils" of ancient DNA elements which were involved in such a recombination event.

Base Sequence↗
PubMed1995

Children's anticipation of and response to colposcopic examination.

Just prior to and following general physical and colposcopic anogenital exams, 43 mothers and daughters (3-15 years), referred because of allegations of sexual abuse, were interviewed separately to determine their knowledge of and feelings about the exam. Children were not retraumatized by the examination of their anogenital anatomy. Although poorly prepared for it, children reported medical staff touch to their genitals, anus, and buttocks at a higher rate than touch to all other body locations, 84.5% versus 16%, but did not rate that touch as more painful. Children were significantly less distressed after the exam; mothers were not.

Adaptation, Psychological↗
PubMed1995

Cognitive deficit and depressive symptoms in a community group of elderly people: a preliminary study.

Since the number and proportion of old people increases worldwide, health professionals and systems should be made aware and prepared to deal with their problems. Cognitive deficit and symptoms of depression are common among the elderly, and may occur in relation to various risk factors such as health conditions and psychosocial variables. In order to study cognitive deficit and the presence of signs and symptoms of depression, 62 elderly community subjects enrolled at a Community Health Unit in Porto Alegre, southern Brazil, were interviewed. They were evaluated by means of the Mini Mental State Exam, the Montgomery-Asberg Depression rating scale, and a questionnaire on health conditions, living arrangements and social variables. Higher levels of symptoms of depression were observed among subjects exposed to major risk factors for cerebrovascular diseases (diabetes and coronary disease), while impaired cognitive performance was seen among individuals who could not count on the presence of a confidant (social network variable). The results suggest that the early identification of major risk groups among old people can help to prevent institutionalization and keep individuals in the community.

Activities of Daily Living↗
PubMed1994

Screening for sinus disease in patients with asthma: a computed tomography-controlled comparison of A-mode ultrasonography and standard radiography.

BACKGROUND: Paranasal sinus disease and bronchial asthma are frequently associated. Patients with asthma often have chronic inflammatory changes of the paranasal mucosa rather than acute bacterial sinusitis. Our aim was to compare the rankings of A-mode ultrasonography and standard radiography as routine screening procedures in the diagnostic workup of these patients. METHODS: We compared the evaluation of the maxillary sinuses by A-mode ultrasonography and standard radiographs. Computed tomography served as a gold standard in 19 patients with asthma who had no history of sinus surgery. RESULTS: Computed tomography showed at least some minimal mucosal thickening in any of the paranasal sinuses in 74% and of the maxillary sinuses in 61% of the patients. Compared with the results of computed tomography, plain-view radiography gave a specificity of 86.7% for the maxillary sinuses. Although all cases of severe mucosal thickening were detected, sensitivity for minimal mucosal hyperplasia was low, at 52.2%. In contrast, A-mode ultrasonography demonstrated a sensitivity of 70% but a specificity of only 22%. CONCLUSIONS: Even symptom-free patients with asthma show a high prevalence of at least limited mucosal thickening in the paranasal sinuses. Acute sinusitis is not a common finding. A-mode ultrasonography does not allow sufficient evaluation of this mucosal hyperplasia and is therefore not suitable for initial screening in these patients. It may prove helpful as a follow-up in selected patients with known anatomic characteristics, however, especially when antral fluid is involved. For routine screening in patients with asthma, a conventional Waters' view radiograph should be used in conjunction with direct visualization of the ostial-meatal area by fiberoptic or rigid rhinoscopy. This combination provides information about the degree of mucosal hyperplasia as well as mucosal inflammation and secretion.

Adult↗
PubMed1993

Lipidized medulloblastoma in adults.

We describe the clinical, imaging, histologic, immunohistochemical, and ultrastructural features as well as the DNA ploidy analysis of two primitive neuroectodermal neoplasms demonstrating prominent cytoplasmic lipid accumulation originating in the posterior fossa of adults. These two tumors most likely exemplify a variant of medulloblastoma with heavily lipidized cells and support the postulated pluripotentiality of primitive neuroectodermal neoplasms. Recognition of this entity as a phenotypic variant of medulloblastoma will militate against diagnostic confusion with other entities that may contain cells with lipoblastic or adipocytic differentiation.

Cerebellar Neoplasms↗