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M Wald

Publications and source records attributed to M Wald.

At least 37 records · Page 2Linked to original sources
PubMed1999

Noninvasive detection of bladder cancer with the BTA stat test.

PURPOSE: We assess the sensitivity and specificity of the noninvasive BTA stat urine test for detection of primary and recurrent bladder cancer with special reference to the size, grade and stage of the tumors, and examine the effect of intravesical bacillus Calmette-Guerin treatment on the results. MATERIALS AND METHODS: A total of 250 patients recruited from 3 medical centers provided voided urine samples for the BTA stat test and cytopathological study. Of these patients 162 were monitored following resection of bladder tumors and 88 were evaluated for the first time for hematuria or irritative voiding symptoms. Each patient underwent cystoscopy. Biopsies were obtained when a bladder tumor was seen or if carcinoma in situ was suspected. The sensitivity, specificity and accuracy of the BTA stat test were compared to standard voided urine cytology. RESULTS: No tumor was found in 122 patients, primary transitional cell carcinoma was found in 71 and cystoscopy revealed recurrent tumors in 57. Overall sensitivity of the BTA stat test was 82.8% and specificity was 68.9%. Sensitivity of urine cytology was 39.8% and specificity was 95.1%. The BTA stat test detected 90.1% of the primary and 73.7% of the recurrent tumors. All patients with carcinoma in situ, high grade tumors, muscle invasive cancer and tumors larger than 2 cm. were diagnosed by the BTA stat test. CONCLUSIONS: The BTA stat test can be used as a screening test for bladder cancer in patients with hematuria or irritative voiding symptoms and for surveillance of those who have not been treated with intravesical bacillus Calmette-Guerin.

Antigens, Neoplasm↗
PubMed1998

[Bleeding gastroduodenal ulcers from the viewpoint of the surgeon].

The article has discoursed of a diagnosis and a therapy of bleeding peptic ulcer. There has been used the group of the patients admitted at The Surgical Unit of The Faculty Hospital Motol in Prague during two and half years. Urgent endoscopy and endoscopic treatment of indicated findings have been performed as a common procedures. The surgical therapy has been necessary for the part of this patients. Operation's indications, types of the operations and their timing have been discussed.

Humans↗
PubMed1998

Proteinases reduce metastatic dissemination and increase survival time in C57Bl6 mice with the Lewis lung carcinoma.

The effect of combined proteolytic enzymes, administered by the rectal route, on the metastatic process and the time of survival in C57Bl6 mice with the Lewis lung carcinoma inoculated subcutaneously was investigated. In the control group, which received no enzyme treatment, 90% of animals died of the metastatic spread of cancer by day 18 after primary tumor extirpation. In Group A, which received the multi-enzyme solution from the time of primary tumor extirpation, 30% of mice died of disseminated cancer by day 25. In Group B, which was treated with the enzymes from 6 days before primary tumor extirpation, only 10% of animals showed the metastatic process by day 15. In Group C, which received the enzymes from 24 hours after intracutaneous tumor inoculation, no metastatic dissemination was discernible. In these three groups, the enzyme treatment was carried out throughout the study. None of the control animals survived for 100 days when the study was ended. The treated groups A, B and C showed survival rate 60%, 90% and 100% of animals, respectively, by 100 days.

Administration, Rectal↗
PubMed1998

Clinical significance of tumor angiogenesis in patients with localized renal cell carcinoma.

OBJECTIVES: To determine the relationship between angiogenesis and various histopathologic features as well as clinical outcome in patients with localized renal cell carcinoma (RCC). METHODS: Microvessel density was quantified by using immunocytochemical staining of endothelial cells for factor VIII-related antigen of 36 specimens taken from patients with pathologic Stage pT1 or pT2 RCC. All patients underwent radical nephrectomy and were followed for a mean time of 97.3 months. RESULTS: No association was noted between microvessel count (MVC) and either cell type, architecture, or tumor size. Inverse correlation was noted between MVC and nuclear area (P = 0.006), nuclear elipticity (P = 0.016), nuclear roughness (P = 0.039), and histologic grade (P = 0.047). Patients having tumors with low MVC had significantly better survival rate compared with those with high MVC neoplasms (P = 0.0014, by Cox proportional hazards method). CONCLUSIONS: Despite lack of correlation with known predictors of survival, MVC provides independent prognostic information for patients with localized RCC.

Adult↗
PubMed1998

Minimally invasive pervaginam procedures for the treatment of female stress incontinence using a new pubic bone anchoring system.

The purpose of this ongoing study is to evaluate the safety and efficacy of new minimally invasive pervaginam cystourethropexy and sling procedures for the treatment of female genuine stress urinary incontinence. A total of 75 women (mean age, 52.8 years) underwent either a cystourethropexy or a sling procedure. A miniature bone anchor and a staple-like bone anchor driver were used for the fixation of periurethral tissue or a xenogenic sling to the pubic bone. With a mean follow-up of eight months, 61 patients (82%) were completely cured of stress incontinence, 10 (14%) reported a more than 50% decrease in pad usage, and 4 patients showed failure early following surgery. The exclusively pervaginam cystourethropexy and sling procedures are minimally invasive, safe, and effective. Further experience and longer follow-up are necessary to establish their role in the treatment of women with stress urinary incontinence.

Adult↗
PubMed1998

Human lymphocytes produce urocortin, but not corticotropin-releasing hormone.

Hypothalamic corticotropin-releasing hormone (CRH) is the principal regulator of the hypothalamus-pituitary-adrenal axis in mammals. In addition, immunoreactive CRH is also present at peripheral sites, where it is thought to act as a proinflammatory peptide. However, the source of peripheral CRH has remained obscure. Human lymphocytes were shown to produce immunoreactive CRH, yet the data on CRH mRNA expression in these cells are equivocal. More recently, Vaughan et al. discovered a new member of the CRH family, termed urocortin. Urocortin was shown to act through the same receptors as CRH. The current study was designed to investigate both mRNA and protein expression of CRH and urocortin in human lymphocytes. Using a commercial CRH(1-41) radioimmunoassay, we demonstrate that normal human lymphocytes and Jurkat T lymphoma cells produce significant amounts of immunoreactive peptide. However, no CRH mRNA was detectable by RT-PCR in these cells. In contrast, a band of the correct size and sequence was amplified with urocortin-specific primers. Immunocytochemical analysis of human lymphocytes using antibodies that could distinguish between CRH and urocortin revealed significant expression of urocortin but not of CRH, consistent with our RT-PCR data. We conclude that human lymphocytes produce urocortin, but not CRH.

Cells, Cultured↗
PubMed1998

Polyenzyme preparation Wobe-Mugos inhibits growth of solid tumors and development of experimental metastases in mice.

Long-term rectal administration of enzyme mixture containing papain, trypsin and chymotrypsin in the same ratio as the preparation Wobe-Mugos E (Mucos Pharma, Germany) was evaluated for their antitumor effects in C57Bl6 inbred mice inoculated with Bl6 melanoma cells. 30% of animals in the test group (3 pcs) have been cured of cancer. In the rest of animals (70%) the survival time was prolonged by 58.3% compared to the control group (from average survival time of 24 days in control group to 38 days in the test group). Based on histological and immunohistochemical evaluation a faster process of metastasizing was found in control group than in the group treated with the polyenzyme preparation. In the case of melanoma Bl6 an antimetastatic effect of the preparation was thus proved.

Animals↗
PubMed1998

[Experience with the use of criteria for evaluating the need for hospitalization in a surgery department].

Acute hospital care is the most expensive form of medical care. Some of patients hospitalized in acute hospitals could be cared for in alternative settings without compromising quality of care. The Appropriateness Evaluation Protocol (AEP) is the most widely used tool for evaluation of appropriateness of hospitalisation in acute care hospitals. We applied AEP to 189 patients admitted within 20 days to department of surgery of a teaching hospital. We have evaluated appropriateness of admission and each following day of stay up till discharge or 15th day of hospitalization. Reasons of inappropriate admissions and delayed discharges were classified and analyzed. Results of the evaluation of selected patients were subject to control by a committee of fully specialized hospital physicians. 16 (8%) of 189 admissions and 306 (27.5%) of 1114 evaluated days of stay failed the AEP criteria. These patients could be well served by lower treatment intensity in outpatient clinics, nursery homes or their own homes. Such a shift in pattern of provided care requires profound organizational changes many of which are out of reach of individual acute hospitals. Despite some limitations we find AEP a useful tool for internal utilization review. External application of AEP in a representative sample of acute care hospitals could provide important data for future development of the Czech health care system.

Health Services Misuse↗
PubMed1997

Inhibition of mineralocorticoid and glucocorticoid receptor function by the heat shock protein 90-binding agent geldanamycin.

The effects of mineralocorticoids and glucocorticoids are mediated by the intracellular mineralocorticoid glucocorticoid receptor (MR) and glucocorticoid receptor (GR), respectively. Several studies suggest that hormone binding and, thus, receptor activation depend on the association of both MR and GR with the 90-kDa heat shock protein (hsp 90). However, there are few reports analyzing the functional relevance of this association in vivo. The present study was designed to determine how the new hsp 90-binding agent geldanamycin, which was previously shown to disrupt the formation of steroid receptor/hsp complexes, interferes with MR- and GR-mediated transactivation in intact cells. We show that geldanamycin inhibits aldosterone-dependent transactivation of a mineralocorticoid-responsive reporter genes in a concentration-dependent manner. Similar effects were observed for the dexamethasone-activated GR. However, geldanamycin did not affect transcription from a retinoic acid-dependent reporter gene. Inhibition of GR-mediated transactivation was observed both in HeLa cells expressing endogenous GR and in COS-7 cells transfected with a GRa expression vector. Binding studies indicate that geldanamycin disrupts receptor function by reducing hormone binding affinity without lowering intracellular receptor protein levels. Our data support the current model of hsp 90-dependent steroid receptor activation. Furthermore, we show for the first time that MR function also depends on the interaction with hsp 90 in intact cells. Finally, we demonstrate that the function of endogenous is thought to keep the receptor protein in an inactive, yet ligand-activable state (9-17). Ligand binding induces a conformational change in the receptor molecule, which causes it to dissociate from the hsp complex, to translocate to the cell nucleus, and, finally, to interact with specific hormone response elements in the promoter regions of hormone-responsive genes (6-8). Both MR and GR bind as homodimers to identical palindromic sequences on the target DNA, termed glucocorticoid response elements (GREs) (18). The formation of GR/MR heterodimers has also been described (19,20) and may have profound functional consequences (21). The current model of MR and GR function holds that these receptors are unable to bind their respective hormones as long as they are not associated with the hsp complex (9-17). However, experimental support for this model is mainly based on in vitro work. There are few reports analyzing the functional relevance of GR/hsp interactions in mammalian cells. In the most recent study, Whitesell et al. showed that the hspE90-binding agent geldanamycin can specifically disrupt GR/hsp association, thus inhibiting glucocorticoid-mediated transcriptional activation (22). MR is even less well studied in this respect. To our knowledge, there have not been any data supporting a functional role for proper MR/hsp interaction in intact cells. In this study, we show for the first time that MR function depends on the interaction with hsp 90 in intact human cells. Furthermore, we demonstrate that geldanamycin inhibits GR-mediated transcriptional activation in two human cells lines, confirming the results by Whitesell et al. and extending them to transfected as opposed to endogenous GR.

Aldosterone↗
PubMed1997

PKC isoenzyme expression and cellular responses to phorbol ester in JEG-3 choriocarcinoma cells.

Protein kinase C (PKc) is a key regulatory enzyme involved in the transduction of extracellular growth signals to the cell nucleus. It occurs in several isoforms, the exact functional roles of which have not been established as yet. The tumor-promoting agent 12-O-tetradecanoyl-phorbol acetate (TPA) is the classic activator of PKC and modulates the activity of the activating protein-1 (AP-1) transcription factor complex via this pathway. AP-1, in turn, induces cell proliferation in many tissues. In the present study, the PKC isoenzyme expression pattern in JEG-3 choriocarcinoma cells was analyzed. The results were compared with those obtained in HEC-1B endometrium adenocarcinoma cells, which had previously been characterized in this respect. To gain insight into the possible functional consequences of different PKC expression patterns, cell proliferation rates and AP-1 activity in response to TPA in both cell lines was studied. Western blot analysis of the PKC isoenzyme expression pattern revealed that JEG-3 cells are deficient in the PKC alpha, delta, and epsilon isoforms. These isoenzymes are strongly expressed in HEC-1B cells, with the alpha and delta being constitutively active. As opposed to HEC-1B cells, JEG-3 cells did not show an enhanced proliferation rate in response to TPA. Furthermore, TPA-treated JEG-3 cells did not exhibit any change in cell shape and refractility as observed in HEC-1B cells. AP-1 activity, as determined by a transfected AP-1-luciferase reporter plasmid, was induced 10-fold by TPA in JEG-3 cells, yet only threefold in HEC-1B cells. It is concluded from these data that differential expression of a subset of PKCs, e.g., the alpha, delta, and epsilon isoforms, may serve as an indicator of the proliferative potential in response to growth factors and mitogens. Furthermore, our data indicate that the inducibility of AP-1 activity does not necessarily reflect the proliferative capacity of a given cell type in response to classical tumor promoters such as phorbol ester.

Blotting, Western↗
PubMed1997

Inhibition of mineralocorticoid activity by the beta-isoform of the human glucocorticoid receptor.

Mineralocorticoids and glucocorticoids are important regulators of electrolyte homeostasis and arterial blood pressure. Their effects are mediated by the mineralocorticoid (MR) and the glucocorticoid receptor (GR), respectively. The present study was designed to determine how the two isoforms of the human GR, the "classic" GR alpha and the non-hormone-binding GR beta, interfere with the transcriptional effects of the hormone-activated human MR. COS-7 monkey kidney cells were transfected with different mineralocorticoid-responsive reporter plasmids and a vector expressing the human MR protein. Different amounts of either control, GR alpha, or GR beta plasmid were co-transfected, and luciferase activity was measured after stimulation with aldosterone and/or dexamethasone. MR-mediated stimulation of transcription was enhanced by co-transfection of the GR alpha expression vector. In contrast, MR-mediated stimulation of transcription was strongly inhibited by co-transfection of equal amounts of the GR beta expression vector. Reverse transcription-polymerase chain reaction (RT-PCR) showed expression of both GR isoforms as well as of MR in the human kidney. These data indicate that the two isoforms of the human GR exert opposite effects on mineralocorticoid activity. We conclude that the ratio between GR alpha and GR beta can define the sensitivity of mineralocorticoid target tissues to aldosterone. Imbalances of this ratio may participate in clinical syndromes of impaired or augmented mineralocorticoid sensitivity, such as certain cases of pseudohypoaldosteronism or, possibly, primary arterial hypertension.

Aldosterone↗
PubMed1997

The role of vimentin expression in predicting the long-term outcome of patients with localized renal cell carcinoma.

OBJECTIVE: To evaluate the prognostic significance of vimentin intermediary filament expression by tumour cells in patients with renal cell carcinoma (RCC) localized to the kidney. PATIENTS AND METHODS: Thirty-nine patients with localized RCC (pT1,pT2) were assessed in a retrospective study. Tumour cells were evaluated immunohistochemically for vimentin, epithelial membrane antigen (EMA) and polyclonal cytokeratin expression. The prognosis of cases expressing positive vimentin expression in tumour cells was compared with that of cases with no expression. Additional clinical information and conventional histological grade of the tumours were also included in the survival analysis. RESULTS: Univariate analysis of patient survival and tumour recurrence showed a statistically significant association between vimentin-positive tumours and poor patient outcome; the EMA stain showed borderline significance and histological grade was significantly associated with prognosis. The combination of tumour vimentin expression and histological grade provided a better predictor of prognosis and proved to be the best independent prognosticator of survival by multivariate analysis. CONCLUSIONS: Vimentin expression by tumour cells provides important prognostic information for patients with localized RCC; the combination of vimentin expression and histological grade is a better predictor for survival than grade or vimentin expression alone.

Carcinoma, Renal Cell↗
PubMed1997

[Hemospermia].

Explore the source record for details and available documents.

Blood↗
PubMed1996

Protein kinase C (PKC) isoenzyme expression pattern as an indicator of proliferative activity in uterine tumor cells.

The protein kinase C (PKC) signal transduction pathway is the prototype of a growth factor-responsive intracellular signaling system, which is activated by various cytokines, growth factors and tumor promoters, such as the phorbol ester 12-O-tetradecanoyl-phorbol acetate (TPA). To date, a large number of different PKC isoforms has been identified, the physiological relevance of which is unknown. Moreover, the expression pattern of PKC isoforms in uterine cells has not been studied as yet. To study the functional role of differential PKC isoform expression in uterine tumor progression, we have compared the proliferative response to TPA, changes in cell morphology induced by TPA, and the PKC isoform expression pattern in two uterine tumor cell lines of different origin. The moderately differentiated endometrial HEC-1-B adenocarcinoma cell line showed a marked increase in proliferative activity and a profound morphological change in response to TPA. In contrast, TPA did not induce cell proliferation and/or morphological changes in the well-differentiated SKUT-1-B mixed mesodermal cell line. Analysis of the PKC isoform expression profile by Western blot revealed that PKC alpha, betaI, delta, epsilon, and zeta were expressed at a much higher level in HEC-1-B as compared to SKUT-1-B cells. PKC beta11 was the only isoenzyme to exhibit a higher expression level in SKUT-1-B cells. This is the first study analyzing the PKC isoform expression profile in uterine tumor cells. Our data demonstrate that the proliferative response to TPA correlates with the expression levels of the majority of PKC isoforms in these cells. Overexpression of PKC isoforms indicates a higher proliferative capacity, and may, thus, represent an important step in the pathogenesis of certain uterine malignancies.

Adenocarcinoma↗
PubMed1995

[Systemic enzyme therapy: problems of resorption of enzyme macromolecules].

Systemic enzyme therapy represents a special therapeutic approach consisting in the oral application of high doses of hydrolytic animal and plant enzyme combinations. The originally empirical method was by detailed experimental analyses and successful clinical studies transformed into a widely appreciated therapeutic method of various pathologic processes. In spite of this fact systemic enzyme therapy has been repeatedly questioned by referring to an almost hundred year old dogma claiming the unabsorbality of enzymes in the macromolecular form. The authors present arguments denying the unexceptional validity of this dogma. The histological, radiological, biochemical (chromatographical, enzymological), immunological and biological methods have convincingly proven that a part of swallowed enzymes may pass the intestinal barrier in an undamaged macromolecular form and realize their activities in the body. The most important elements able to absorb macromolecules seem to be so called "M-cells" (FAE) which cover lymphoid foci of the organized gut lymphoid tissue. Other mechanisms of enzyme resorption are under discussion. The absorbed enzymes are rapidly complexed with naturally occurring blood antiproteases. In these complexes the potential immunogenicity of enzymes is restricted and they are concentrated into pathologically affected areas of the body. Complexes in addition display important immunoregulatory activities.

Enzyme Therapy↗