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Biomedical subjects

M Weiss

Publications and source records attributed to M Weiss.

At least 343 records · Page 19Linked to original sources
PubMed1995

DNA methylation status of the MUC1 gene coding for a breast-cancer-associated protein.

The MUC1 gene codes for protein products that are highly expressed in human breast-cancer tissue and that serve as tumor markers for disease progression. The factors contributing to the disease-specific over-expression of the MUC1 gene are under intensive investigation and are yet to be determined. A large transcribed region of the human MUC1 gene is a CpG island that consists of 60-bp tandemly repeating units, each of which contains one SmaI restriction site. The methylation status of regulatory regions, upstream to the transcriptional start site, is essential for the regulation of gene expression. We therefore evaluated whether the methylation status of the various regions of the MUC1 gene may affect its expression. Using SmaI, and its isoschizomer XmaI endonucleases, we demonstrated that in peripheral-blood leukocytes (PBL-DNA) that do not express the MUC1 gene, the repeat array is completely methylated, whereas the same sequences are entirely non-methylated in breast-tumor-tissue DNA (BT-DNA). In contrast, sequences upstream and downstream to the repeat array showed no difference in the methylation pattern in PBL-DNA and BT-DNA. Hypomethylation within the repeat array was also observed in other epithelial tissues that express the MUC1 gene at much lower levels to those seen in breast-cancer tissue. These studies demonstrate that hypomethylation of the tandem repeat array is an absolute requirement for MUC1 gene expression in epithelial tissues, although in breast-cancer tissue additional regulatory mechanisms must pertain for its over-expression.

Adenocarcinoma↗
PubMed1995

[Magnesium in cardiology].

Magnesium acts as a cofactor of numerous enzymes and is important for the maintenance of a high intracellular potassium concentration and the transmembrane action potential. Of the total magnesium content of about 1000 mmol, only 0.3% are located in plasma. Hypomagnesemia and probable magnesium deficiency are found in 7 to 11% of hospitalized patients but are only rarely accompanied by relevant clinical symptoms. Prolonged diuretic therapy and secondary aldosteronism are frequent causes of hypomagnesemia in cardiology. Intravenous magnesium is a vasodilatator and prolongs the AH interval. In animal studies magnesium has been shown to have cardioprotective and platelet-inhibiting properties. The only verified indication for intravenous magnesium is the initial treatment of torsade de pointes. Magnesium may suppress digitalis-induced tachyarrhythmias and convert paroxysmal supraventricular tachycardia and monomorphic ventricular tachycardia to sinus rhythm. Its role in the treatment of acute myocardial infarction and of ventricular arrhythmias in congestive heart failure is unclear.

Blood Platelets↗
PubMed1995

[Can obstructive sleep apnea syndrome be predicted based on anamnesis and clinical examination findings?].

The objective of this retrospective study was to determine the predictive value of a selfadministered questionnaire together with physical and laboratory examinations in establishing the diagnosis and severity of obstructive sleep apnea syndrome (OSAS). The apnea index (AI) and apnea/hypopnea index (AHI), measured by nocturnal respiratory monitoring, were matched with the 21 questions of the questionnaire as well as with physical and laboratory findings in 129 patients (average age 53 years, 80% males) referred to the sleep lab within a three-year period because of suspected OSAS. OSAS was diagnosed in 85 (66%) patients. Patients with OSAS had significantly higher body weight (BMI), but lower PaO2, lower total and vital lung capacity, as well as lower FEV1, than patients without OSAS. AI and AHI could be predicted from the BMI (R2 = 0.13) as well as the day time sleepiness (R2 = 0.11), less so by blood pressure and hemoglobin (R2 < 0.1); therefore, a predictability score could not be calculated. We conclude, that in addition to a specific questionnaire and physical and laboratory examinations, still a routine examination in a specialized sleep lab is necessary to establish the diagnosis of OSAS.

Adult↗
PubMed1995

Biologic indicators of exposure: are markers associated with oncogenesis useful as biologic markers of effect?

Radiation-induced molecular and cellular alterations play an important role in the transformation of a normal cell into a cancer cell. However, the basic molecular and cellular alterations upon exposure to ionizing irradiation are still poorly understood. Identification of such alterations would be of importance for the assessment of exposure dose, as well as for the assessment of an exposed individual's risk of developing cancer. Extensive studies of the mechanisms of oncogenesis have led to the identification of altered genes, such as proto-oncogenes and tumor suppressor genes as well as other genes intimately involved in cellular proliferation and differentiation, that are more or less frequently associated with a variety of human malignancies. It can be assumed that at least some of these mechanisms are associated with radiation-induced oncogenesis. The longevity of stem cells, particularly those of the hemopoietic system, makes them the prime target cell population to accumulate genetic alterations due to exposure to a variety of agents. Improvements in purification strategies for hemopoietic stem cells, as well as the availability of sensitive techniques such as the polymerase chain reaction (PCR) and flow cytometry analysis, should allow in-depth studies at the molecular and cellular level after exposure to physical and chemical agents.

Animals↗
PubMed1995

Catecholamines, lymphocyte subsets, and cyclic adenosine monophosphate production in mononuclear cells and CD4+ cells in response to submaximal resistance exercise.

We examined the effect of 30 min of submaximal resistance exercise on free and sulphoconjugated plasma catecholamine concentrations determined by high performance (-pressure) liquid chromatography separation, the distribution of circulating lymphocytes quantified by flow cytometry, and isoproterenol induced cyclic adenosine monophosphate (cAMP) production in mononuclear cells (MNL) and CD4+ cells. Venous blood samples were taken before, immediately after and 45 min after exercise. Resistance exercise increased free plasma adrenaline (A) and noradrenaline (NA) concentrations, whereas sulphoconjugated catecholamine concentrations remained unchanged. Exercise induced leucocytosis and lymphocytosis was predominantly manifested by an increase in the number of total lymphocytes, monocytes, CD3+, CD8+ cells and CD3- CD16/CD56+ cells. Redistribution resulted in a decrease in the CD4+:CD8+ ratio. The total number and distribution of lymphocytes returned to baseline after 45-min rest. An exercise-induced increase in the number of CD3- CD16/CD56+ cells was significantly correlated with the increase in plasma NA (r = 0.66; P = 0.035), indicating a NA dependent process of redistribution. The cAMP-production in MNL was significantly elevated after resistance exercise, when cells were stimulated with 1 mumol.1(-1) isoproterenol [pre-exercise 16.5 (SD 3.3); postexercise 21.6 (SD 9.8); 45 min postexercise 10.7 (SD 2.8)]. The cAMP production in CD4+ cells was not affected by exercise. Therefore, it is discussed whether redistribution is responsible for the exercise induced increase in cAMP production in MNL.

Adult↗
PubMed1995

Accuracy of noncompartmental pharmacokinetic parameters estimated from bolus injection and steady-state infusion data.

A Monte Carlo simulation study was carried out to examine the accuracy of parameters derived from curve moments. Impulse response (IR) and washout (WO) concentration-time curves, based on a triexponential model, were analyzed by numerical integration and regression analysis. Both designs were tested according to their robustness to measurement error and model misspecification. Performance of the methods was judged using the median error (ME) and the median absolute error (MAE) of 1000 simulations. The WO design provided better estimates of mean disposition residence time and worse estimates of the normalized variance of disposition residence times (CVD2) than its rival. At 20% measurement noise, the MAE of CVD2 was less than 13%. The WO design was much more robust to model misspecification. Numerical integration performed as good as, or better than, regression analysis. Both methods are very sensitive to tail-area error, meaning that special attention needs to be paid to this aspect of experimental design. This study demonstrates that it is possible to obtain good estimates of higher moment parameters in a well-designed experiment.

Models, Theoretical↗
PubMed1995

Hemodynamics of different degrees of right heart bypass: experimental assessment.

BACKGROUND: Although their assessment could be of the utmost importance to determine the surgical treatment for patients with univentricular hearts, differences in ventricular performance between partial and complete right heart bypass remain to be defined. METHODS: Three different degrees of right heart bypass were investigated in 5 mongrel dogs: (1) superior vena cava to both pulmonary arteries shunt (SCP); (2) inferior vena cava to both pulmonary arteries shunt (ICP); and (3) both venae cavae to both pulmonary arteries shunt (BCP). Hemodynamic studies included evaluation of the cardiac index and left atrial pressure as a function of the degree of right heart bypass. RESULTS: By maintaining the mean left atrial pressure at 5 mm Hg, cardiac indexes were 1.98 +/- 0.25, 1.67 +/- 0.29, and 1.33 +/- 0.21 L.min-1.m-2 for SCP, ICP, and BCP shunts, respectively (p = 0.001). When keeping the cardiac index constant, mean left atrial pressures were 5.2 +/- 0.8, 5.5 +/- 0.9, and 7 +/- 0.7 mm Hg for SCP, ICP, and BCP shunts, respectively (p = 0.001). CONCLUSIONS: Increasing degrees of right heart bypass are associated with a significant decrease in ventricular performance in this experimental model.

Animals↗
PubMed1995

Atrial natriuretic peptide plasma level remains unchanged in various hypertensive disorders of pregnancy.

The decreased volume of maternal extracellular fluid in preeclamptics may result in a different rate of atrial natriuretic peptide secretion and thus affect its plasma levels. Our objectives were to determine whether there was a difference in plasma levels of atrial natriuretic peptide in the various hypertensive disorders of pregnancy. Forty-nine pregnant women in the third trimester of pregnancy were evaluated: 21 with preeclampsia, 17 with chronic hypertension during pregnancy and 11 normotensives. The atrial natriuretic peptide concentration was 13.9 +/- 5.9 pg/ml, 17.8 +/- 13.5 pg/ml and 16.7 +/- 7.4 pg/ml in the preeclamptics, chronic hypertensives and normotensives, respectively. The differences between the three groups were not statistically significant. Atrial natriuretic peptide plasma levels remained stable in the various hypertensive disorders of pregnancy.

Adult↗
PubMed1995

Temperature change-induced potentiation: a comparative study of facilitatory mechanisms in aged and young rat hippocampal slices.

The effect of temperature changes in the medium on the evoked potentials of pyramidal neurons in response to the electrical stimulation of Schaffer collaterals was investigated in both young (one to two months) and aged (24-28 months) rat hippocampal slices. Temperature increase was shown to reduce, and subsequent temperature decrease to enhance, the population spike amplitude in both young and aged rats. Temperature decrease produced a long-lasting (> 30 min) and important potentiation (180%) of population spike amplitude in young but not in aged rats. Long-term post-tetanic potentiation was maintained in young but suppressed in aged rats by temperature changes. The impairment of temperature-induced potentiation in aged rats is suggested as a tool for studying promnesic drugs.

Aging↗
PubMed1995

Enhancement of neutrophil function by in vivo filgrastim treatment for prophylaxis of sepsis in surgical intensive care patients.

PURPOSE: To determine the kinetics of leukocyte counts and of oxygen radical production of neutrophils from postoperative/posttraumatic patients with or without infusion of filgrastim (recombinant human granulocyte colony-stimulating factor, rhG-CSF) as prophylaxis against sepsis. METHODS: Twenty postoperative/posttraumatic patients with a Therapeutic Intervention Scoring System (TISS) score greater than 30 were included in this study. In the 10 patients of the study group, filgrastim (1 microgram/kg/d) was infused continuously within the first 3 days and tapered to 0.5 microgram/kg/d on the following 4 days or until discharge from the surgical intensive care unit. Ten patients without administration of filgrastim served as controls. Oxygen radical production of isolated neutrophils of these patients was tested by N-formyl-methionyl-leucyl-phenylalanine (FMLP)- and zymosan-induced chemiluminescence from serial blood samples, taken until the 16th postoperative day. RESULTS: Compared with the first postoperative day, in vitro FMLP-induced neutrophil chemiluminescence was significantly increased during the following 4 postoperative days in the patients with filgrastim infusion; however, only during the first 2 postoperative days in the control group. The increase in the FMLP-induced neutrophil chemiluminescence was significantly greater (P < .05) in the study group than in the control group on the third and on the fourth postoperative day. Tapering of filgrastim by 0.5 microgram/kg/d in the study group resulted in a reduction of FMLP-induced neutrophil oxygen radical production within 48 hours. In contrast, zymosan-induced neutrophil chemiluminescence was not measurably affected in both groups. Leukocyte count of the study group significantly (P < .05) exceeded the leukocyte count of the control group from the third up to the 10th postoperative day. None of the patients treated with filgrastim developed sepsis; however, three patients within the control group did. CONCLUSIONS: Prolonged enhancement of neutrophil count and function induced by rhG-CSF may be useful in the prophylaxis of sepsis in posttraumatic/postoperative patients at high risk of sepsis.

Adolescent↗
PubMed1995

Factors associated with a positive reexcision after excisional biopsy for invasive breast cancer.

BACKGROUND: Breast-conserving therapy followed by adjuvant radiotherapy represents an alternative to mastectomy as a treatment for invasive breast cancer. When excisional biopsy has been performed outside the parent institution, reexcision is often performed, with tumor being identified in 32% to 62% of the subsequent specimens. We analyzed not only the factors associated with a positive reexcision but also those factors associated with final surgical margins that are positive for tumor. METHODS: Between 1978 and 1991, 956 female patients with American Joint Committee on Cancer clinical stage I or II breast cancer were treated with breast-conserving therapy where a total of 420 patients underwent reexcision after an initial excisional biopsy. Several factors were analyzed to determine their association with a positive reexcision, the status of the final surgical margin, and the nature of the disease present within the reexcision specimen. RESULTS: Factors that correlated with a positive reexcision in both univariate and multivariate analysis were clinical tumor size, method of detection, the pathologic status of the axillary lymph nodes, and the histologic appearance. Those factors associated with finding invasive disease at the time of reexcision were clinical tumor size, clinical presentation, and nodal status. The single factor associated with finding residual in situ disease at the time of reexcision was histologic appearance of the primary tumor. A final positive margin was associated with method of tumor detection, age of the patient, and the presence of axillary lymph node metastases. CONCLUSIONS: The most significant factors associated with a positive reexcision are clinical tumor size, method of tumor detection, pathologic nodal status, and histologic appearance. Patients with larger tumors or those that are detected by physical examination, as well as invasive lobular carcinomas, may require a more generous initial resection to achieve negative surgical margins and avoid the likelihood of reexcision.

Adult↗
PubMed1995

Radical scavenger activity of different 3',4'-dihydroxyflavonols and 1,5-dicaffeoylquinic acid studied by inhibition of chemiluminescence.

To gain more insights into structure-activity relationships, four 3',4'-dihydroxyflavonols differing in the substitution of the A and C rings and 1,5-dicaffeolyquinic acid were evaluated for their ability to inhibit chemiluminescence of human neutrophils stimulated with opsonized zymosan or FMLP as well as in an enzymatic system with H2O2 and horseradish peroxidase. It could be shown that an additional o-dihydroxy structure in the A-ring, or a 6-methoxy group, respectively, has no significant influence, thus confirming the o-dihydroxy group of the B-ring as the most important structural feature for the radical scavenger activity. It can be supposed that the main effect of the tested flavonols is based on their inhibition of myeloperoxidase, besides inhibition of enzymes involved in activating the NADPH-oxidase, and a direct reaction with oxygen radicals. Inhibition of chemiluminescence by 1,5-dicaffeoylquinic acid was in the same order as those observed with the flavonols.

Cell-Free System↗
PubMed1995

Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals.

Cataract is a major ocular disease that causes blindness in many developing countries of the world. It is well established that various factors such as oxidative stress, UV, and other toxic agents can induce both in vivo and in vitro cataract formation. However, a common cellular basis for this induction has not been previously recognized. The present study of lens epithelial cell viability suggests such a general mechanism. When lens epithelial cells from a group of 20 cataract patients 12 to 94 years old were analyzed by terminal deoxynucleotidyl transferase (TdT) labeling and DNA fragmentation assays, it was found that all of these patients had apoptotic epithelial cells ranging from 4.4 to 41.8%. By contrast, in eight normal human lenses of comparable age, very few apoptotic epithelial cells were observed. We suggest that cataract patients may have deficient defense systems against factors such as oxidative stress and UV at the onset of the disease. Such stress can trigger lens epithelial cell apoptosis that then may initiate cataract development. To test this hypothesis, it is also demonstrated here that hydrogen peroxide at concentrations previously found in some cataract patients induces both lens epithelial cell apoptosis and cortical opacity. Moreover, the temporal and spatial distribution of induced apoptotic lens epithelial cells precedes development of lens opacification. These results suggest that lens epithelial cell apoptosis may be a common cellular basis for initiation of noncongenital cataract formation.

Adult↗
PubMed1995

The influence of gonadal hormones on periodicity of obsessive-compulsive disorder.

OBJECTIVE: This paper reviews the evidence linking gonadal hormones and obsessive-compulsive disorder (OCD) symptoms. METHOD: Four case reports of the relationship between obsessive-compulsive disorder symptoms and exogenous sex hormone changes are presented. These cases are reviewed within the context of other case reports and the literature on the relationship between serotonin, gonadal hormones and OCD. RESULTS: The authors suggest that there is a relationship between onset or exacerbation of OCD and changes in gonadal hormones. CONCLUSION: Clinicians should carefully evaluate patients for exogenous and endogenous changes in gonadal hormones when evaluating onset or exacerbation of OCD.

Adult↗
PubMed1995

Purine-binding factor (nm23) gene expression in pituitary tumors: marker of adenoma invasiveness.

To determine the molecular distinction between invasive and non-invasive pituitary adenomas, we evaluated expression of the metastasizing suppressor gene, nm23, in tumors of varying stages. The nm23 gene was recently identified on the basis of reduced expression in highly metastic cancer compared with its expression in low metastatic potential tumors. Twenty-two pituitary tumors (10 nonfunctioning, 9 acromegaly, 2 prolactinomas, and 1 Cushing) were studied. H1 and H2 isoform expression of nm23 was investigated using a ribonuclease protection assay. nm23 H2 messenger ribonucleic acid expression was significantly reduced in invasive tumors and correlated highly (P = 0.0016) with cavernous sinus invasion. In these invasive tumors, sequencing of the nm23 gene did not reveal a mutation. Invasive tumors also demonstrated markedly reduced immunostaining for nm23 H2. These results show the relevance of nm23 gene expression to behavior of these benign tumors. High expression of nm23 H2 is associated with noninvasive pituitary adenomas and may restrain tumor aggression. This molecular defect distinguishing invasive from noninvasive tumors is shown to be a sensitive marker of adenoma invasiveness and may be a predictor for postoperative management plans.

Adenoma↗