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K Metze

Publications and source records attributed to K Metze.

At least 19 recordsLinked to original sources
PubMed2003

Insulin signalling pathways in aorta and muscle from two animal models of insulin resistance--the obese middle-aged and the spontaneously hypertensive rats.

AIMS/HYPOTHESIS: The aim of this study was to investigate insulin signalling pathways directly in vivo in skeletal muscle and thoracic aorta from obese middle-aged (12-month-old) rats, which have insulin resistance but not cardiovascular disease, and from spontaneously hypertensive rats (SHR), an experimental model of insulin resistance and cardiovascular disease. METHODS: We have used in vivo insulin infusion, followed by tissue extraction, immunoprecipitation and immunoblotting. RESULTS: Obese middle-aged rats and the SHR showed marked insulin resistance, which parallels the reduced effects of this hormone in the insulin signalling cascade in muscle. In aortae from obese middle-aged rats, the PI 3-kinase/Akt pathway is preserved, leading to a normal activation of endothelial nitric oxide synthase. In SHR this pathway is severely blunted, with reductions in eNOS protein concentration and activation. Both animals, however, showed higher concentrations and higher tyrosine phosphorylation of mitogen-activated protein (MAP) kinase isoforms in aortae. CONCLUSIONS/INTERPRETATION: Alterations in the IRS/PI 3-K/Akt pathway in muscle of 12-month-old rats and SHR could be involved in the insulin resistance of these animals. The preservation of this pathway in aorta of 12-month-old rats, apart from increases in MAP kinase protein concentration and activation, could be a factor that contributes to explaining the absence of cardiovascular disease in this animal model. However, in aortae of SHR, the reduced insulin signalling through IRS/PI 3-kinase/Akt/eNOS pathway could contribute to the endothelial dysfunction of this animal.

Age Factors↗
PubMed2003

Acute leukemias in Piauí: comparison with features observed in other regions of Brazil.

Differences in age and sex distribution as well as FAB (French-American-British classification) types have been reported for acute leukemias in several countries. We studied the demographics and response to treatment of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) between 1989 and 2000 in Teresina, Piau , and compared these results with reports from Brazil and other countries. Complete data concerning 345 patients (230 ALL, 115 AML) were reviewed. AML occurred predominantly in adults (77%), with a median age of 34 years, similar to that found in the southeast of Brazil but lower than the median age in the United States and Europe (52 years). FAB distribution was similar in children and adults and FAB-M2 was the most common type, as also found in Japan. The high frequency of FAB-M3 described in most Brazilian studies and for Hispanics in the United States was not observed. Overall survival for adults was 40%, similar to other studies in Brazil. A high mortality rate was observed during induction. No clinical or hematological parameter influenced survival in the Cox model. ALL presented the characteristic peak of incidence between 2-8 years. Most of the cases were CD10+ pre-B ALL. In 25%, abnormal expression of myeloid antigens was observed. Only 10% of the patients were older than 30 years. Overall survival was better for children. Age and leukocyte count were independent prognostic factors. These data demonstrate that, although there are regional peculiarities, the application of standardized treatments and good supportive care make it possible to achieve results observed in other countries for the same chemotherapy protocols.

Adolescent↗
PubMed2001

Spontaneous apoptosis in chronic lymphocytic leukemia and its relationship to clinical and cell kinetic parameters.

Chronic lymphocytic leukemia (CLL) presents considerable variability in clinical presentation as well as in its evolution. In contrast to the inhibition of apoptosis in vivo, spontaneous apoptosis after short-term culture occurs. We studied the degree of this apoptosis in vitro, and its interactions with several clinical and laboratory parameters. Apoptosis was measured by the annexin V technique. Proliferation rate was evaluated by the AgNOR (nucleolar organizer regions) technique. There were inverse correlations between the percentage of annexin V-positive cells and peripheral lymphocyte count (r = - 0.49), Rai stage (r = - 0.40), Binet stage (r = - 0.50), TTM (total tumor mass score; r = - 0.51), and percentage of cells with one AgNOR cluster (r = - 0.45). Direct correlations were found with hemoglobin values ( r = 0.34) and platelet counts (r = 0.52). The number of CD8-positive cells showed a correlation with peripheral lymphocyte count (r = 0.49). When this variable was held constant, a correlation was detected between CD8-positive cells and staging (r = -0.47), TTM (r = - 0.42), and platelet count (r = 0.67). CD4-positive lymphocytes presented a correlation only with CD8-positive lymphocytes. In a cluster analysis, it was possible to create three groups of patients with different apoptosis rates using the TTM and AgNOR values. We conclude that, with the progression of the disease, together with the increase of tumor mass and proliferation rate, there is a decrease in the susceptibility to apoptosis.

Aged↗
PubMed2001

AgNOR pattern and PCNA analysis in fine needle biopsies of liver cell carcinoma.

The aim of this study was to evaluate the prognostic and diagnostic value of AgNOR and PCNA staining mainly in fine needle biopsies of 34 liver cell carcinomas using an image analyzing system. The AgNOR number per nucleus and the relative AgNOR area, but not the PCNA index, showed a significant correlation with the histological tumor grade according to the classical and the modified Edmondson-Steiner's classification. Regarding univariate survival, only the grade of the classical Edmondson-Steiner's classification was of prognostic significance. The parameters sex, age, maximum tumor diameter, mean AgNOR number, total nuclear area and relative AgNOR area, nuclear area, PCNA index or the grade of the modified Edmondson-Steiner's classification did not reach statistical significance regarding survival. By a factor analysis, two factors could be created, which could explain together 72% of the variance of all parameters included in the study. In a linear discriminant analysis, the AgNOR variables could separate between normal liver cells and cells from high grade or low grade carcinomas in 83.7% of the cases. Therefore, we think that the AgNOR technique can be usefully applied in needle biopsies of liver carcinomas for the differential diagnosis and tumor grading.

Adolescent↗
PubMed2000

Nucleolus organizer regions (AgNORs) and total tumor mass are independent prognostic parameters for treatment-free period in chronic lymphocytic leukemia.

The aim of our study was to evaluate whether the nucleolus organizer regions (AgNOR) of circulating lymphocytes in chronic lymphocytic leukemia (CLL) could predict the duration of the stable phase (treatment-free period) of this disease. Age, sex, peripheral lymphoctes, hemoglobin, platelet count, Binet's stage, total tumor mass (TTM) and AgNOR pattern at diagnosis were assessed in 57 patients and compared with the time from diagnosis until patients fulfilled the criteria to start chemotherapy. In univariate Cox regression, Binet's stage, hemoglobin, number of peripheral lymphocytes, TTM and the percentage of lymphocytes containing one AgNOR cluster (circulating proliferative fraction) had predictive value. In the multivariate Cox model, only TTM and the percentage of cells with one AgNOR cluster were independent factors predicting the duration of the stable phase. Repetition of these analyses in 500 data sets created by bootstrap resampling confirmed the results. Summing up the percentage of lymphocytes with an AgNOR cluster and the TTM value, a simple prognostic index could be created to give information about the duration of the stable phase in CLL.

Cell Division↗
PubMed1999

Effect of Ca2+ channel blockers on arterial hypertension and heart ischaemic lesions induced by chronic blockade of nitric oxide in the rat.

The effects of the Ca2+ channel blockers diltiazem, nifedipine and amlodipine were investigated on both arterial hypertension and myocardial changes induced by chronic blockade of nitric oxide synthesis. Control male Wistar rats received Nomega-nitro-L-arginine methyl ester (L-NAME; 20 mg rat(-1) day(-1)) in the drinking water for 8 weeks; blood pressure and body weight were monitored weekly. The Ca2+ channel blockers were given concomitantly to L-NAME, as follows: diltiazem (13.5 mg rat(-1) day(-1)) and amlodipine (6.25 mg rat(-1) day(-1)) were administered in the drinking water whereas nifedipine (6.25 mg rat(-1) day(-1)) was given in the chow. Nomega-nitro-L-arginine methyl ester induced a time-dependent increase in blood pressure which was significantly attenuated by diltiazem (154+/-1.6 vs. 139+/-1.6 mm Hg, p < 0.05), nifedipine (166+/-2.7 vs. 150+/-2.1 mm Hg, p < 0.05) and amlodipine (208+/-5.8 vs. 158+/-1.8 mm Hg, p < 0.05) at the last week of the treatment. Rats treated with the L-NAME also developed myocardial ischaemia, as indicated by the increased percentage of fibrous tissue found in the left ventricles of these animals (10.9+/-0.1%, p < 0.01) when compared to control ones (6.3+/-0.1%). Neither diltiazem (14.9+/-1.2%) nor nifedipine (11.1+/-1.5%) prevented this effect whereas amlodipine (6.9+/-1.1%, p < 0.01) virtually abolished the increase in fibrous tissue induced by L-NAME. The plasma concentration of the Ca2+ channel blockers was measured by liquid chromatography coupled to mass spectrometry at two different time points (morning and afternoon). Only amlodipine treatment was able to maintain constant levels (186+/-46 ng ml(-1) in the morning and 110+/-19 ng ml(-1) in the evening) compared to nifedipine (3003+/-578 ng ml(-1) in the morning and 436+/-100 ng ml(-1) in the evening) and diltiazem (77+/-51 ng ml(-1) in the morning and not detectable in the evening). In conclusion, our results indicate that amlodipine (but not diltiazem and nifedipine) can efficiently control myocardial ischaemia in nitric oxide deficient rats, probably due to its intrinsically long half-life.

Animals↗
PubMed1999

Changes in AgNOR configurations during the evolution and treatment of chronic lymphocytic leukemia.

The evolution of the pattern of nucleolar organiser regions (AgNORs) in circulating lymphocytes during the stable phase and after chemotherapy in CLL was analysed. Peripheral blood smears were stained by the AgNOR technique at diagnosis, during observation follow-up in stable phase, or at the beginning and at the end of chemotherapy in patients with progressive disease. The changes in the AgNOR pattern were compared with those of TTM used as a tumour burden parameter. Among 52 cases that entered the study, 29 were in stable phase and 23 had progressive disease and received chemotherapy. During stable phase, the AgNORs as well as TTM remained constant. In treated patients, the relative reduction of tumour mass was correlated with a decrease in the percentage of lymphocytes containing one AgNOR cluster. The percentage of cells with one compact nucleolus before chemotherapy was inversely correlated with the relative amount of tumor reduction after treatment. We conclude that the AgNOR pattern in CLL describes the cell kinetic changes during the evolution of the disease and is a prognostic factor for tumor reduction after treatment.

Aged↗
PubMed1999

Argyrophilic nucleolar organizer region (AgNOR) technique: a helpful tool for differential diagnosis in urinary cytology.

The aim of this study was to investigate whether the AgNOR technique could be helpful for the cytologic diagnosis of neoplastic and non-neoplastic urinary tract lesions. We analysed the AgNOR pattern in urinary cytology in samples from 70 patients. In every case the average number of silver precipitations per nucleus was counted and the range between the minimum and maximum AgNOR value calculated. Furthermore we noted whether the AgNOR precipitations had a homogeneous or heterogeneous distribution. The diseases were classified in three groups: non-neoplastic lesions, low grade and high grade carcinoma. Linear discriminant analysis (with jack-knife procedure) was performed with the AgNOR parameters as independent variables. The final diagnosis of each patient had been established by histological analysis of bladder biopsies. We obtained a correct classification in 84.3% of the cases. All patients with normal or reactive lesions were correctly classified and only two cases of low grade malignancy were erroneously diagnosed as non-malignant. Five high grade neoplasms had been classified as low grade and four low grade carcinomas had been over-diagnosed as high grade neoplasms. We conclude that a combined qualitative and quantitative AgNOR analysis can be useful in the differential diagnosis of urinary cytology.

Cytodiagnosis↗