Elevated serum endostatin levels are associated with favorable outcome in acute myeloid leukemia.

BACKGROUND: Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor-derived proteases. The levels and the prognostic relevance of serum endostatin in acute myeloid leukaemia (AML) patient are not fully clear. OBJECTIVE: The aim of this study was to evaluate serum levels of endostatin in acute myeloid leukemia patients before chemotherapy and after achieving complete remission and to correlate endostatin levels with patient outcome. MATERIALS AND METHODS: Serum samples from 30 adult patients (22 males and eight females, median age 37, range 19-66 years) with AML had been taken before chemotherapy was administered. In addition 25 out of 30 patients were reinvestigated again at complete remission (CR). Ten samples from healthy normal persons of matched age and sex were evaluated as a reference control group. Serum endostatin levels were determined using enzyme linked immune sorbent assay (ELISA). Endostatin serum levels were not significantly different in the pre-treatment AML patients as compared to that in normal controls (p>0.05). In AML patients the baseline endostatin levels were significantly lower than at CR (p=0.001). RESULTS: No significant relation were detected between pre-treatment serum endostatin levels and age, peripheral blood white cell counts, platelet counts, bone marrow blast cell counts, blast cell distribution ratio or cytogenetic findings. The prognostic value of serum endostatin (sE) was also evaluated by dividing AML patients into high and low sE groups using the 75 percentile sE levels of the patients group as cutoff. The authors found that patients group in the high sE group survived for significantly longer time than those patients in the low sE group. CONCLUSION: Elevated endostatin levels at AML diagnosis is a good prognostic marker for patients' outcome. Wide scale study is recommended in order to establish the clinical value of this study.

Elevated serum endostatin levels is associated with favorable outcome in acute myeloid leukemia.

INTRODUCTION: Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor-derived proteases. The levels and the prognostic relevance of serum endostatin in AML patient is not fully clear. AIM: To evaluate serum levels of endostatin in acute myeloid leukemia patients before chemotherapy and after achieving complete remission and to correlate endostatin levels with patients outcome. MATERIALS AND METHODS: Serum samples from 30 adult patients (22 males and 8 females, median age 37, range 19-66 years) with AML had been taken before chemotherapy was administered. In addition 20 out of 30 patients were reinvestigated again at complete remission (CR). Ten samples from healthy normal persons of matched age and sex were evaluated as a reference control group. Serum endostatin levels were determined using enzyme linked immune sorbent assay (ELISA). RESULTS: Endostatin serum levels were not significantly different in the pretreatment AML patients as compared to that in normal controls (P>0.05). In AML patients the baseline endostatin levels were significantly lower than at CR (P=0.001). No significant correlation were detected between pretreatment serum endostatin levels and age, peripheral blood white cell counts, platelet counts, bone marrow blast cell counts, blast cell distribution ratio. The prognostic value of sE was also evaluated by dividing AML patients into high and low sE groups using the 75 percentile sE levels of the patients group as cutoff. The authors found that patients group in the high sE group survived for significantly longer time than those patients in the low sE group. CONCLUSIONS: Elevated endostatin levels at AML diagnosis is a good prognostic marker for patients' outcome. Wide scale study is recommended in order to establish the clinical value of this study.

Misreporting of dietary energy, protein, potassium and sodium in relation to body mass index in young Japanese women.

OBJECTIVE: Although under-reporting of dietary intake is more common in persons with a high body mass index (BMI), it is not well known whether or not misreporting is selective for different foods (and hence energy and nutrients), particularly in non-Western populations. We examined misreporting of dietary intake against biomarkers and its relation with BMI in young Japanese women. DESIGN: Cross-sectional study. SUBJECTS: A total of 353 female Japanese dietetic students aged 18-22 years (mean BMI: 21.4 kg/m(2), mean fat intake: 29.8% of energy). METHODS: Misreporting of dietary energy, protein, potassium and sodium (assessed by a self-administered diet history questionnaire) was examined against respective biomarkers (estimated energy expenditure and 24-h urinary excretion). Reporting accuracy was calculated as the ratio of reported intake to that estimated from corresponding biomarkers (complete accuracy: 1.00). RESULTS: Mean reporting accuracy of absolute intake (amount per day) varied considerably (0.86-1.14). Reporting accuracy of absolute intake decreased with increasing BMI (P for trend <0.001). However, no association was observed between reporting accuracy of energy-adjusted values and BMI (P for trend >0.15), indicating that BMI-dependent misreporting was canceled by energy adjustment. This was owing to positive correlation between the reporting accuracy of energy intake and that of absolute intake of the three nutrients (Pearson correlation coefficient: 0.49-0.67, P<0.0001). CONCLUSIONS: Although differential misreporting of absolute intake was associated with BMI, differential misreporting of energy-adjusted value was not. These findings support the use of energy-adjusted values in the investigation of diet-disease relationships among lean populations with a low-fat intake.

Prognostic relevance of circulating matrix metalloproteinase-2 in acute myeloid leukaemia patients.

Matrix metalloproteinases (MMPs) were postulated to have important implication in progression and invasiveness of many malignant disorders. On the other hand the biological role of MMP-2 in acute myeloid leukaemia (AML) is not fully clear. Serum samples from 37 adult patients with AML had been taken before chemotherapy was administered. In addition 20 out of the 37 patients were analysed again after achieving complete remission (CR). Ten samples from healthy volunteers were evaluated as the control. Total MMP-2 levels were measured using ELISA Kit obtained from R&D system. MMP-2 serum levels were significantly lower in pretreatment AML patients than that in the normal controls (p = 0.000) and in CR (p = 0.007). No significant correlations were detected between pretreatment sMMP-2 levels and FAB subtypes, peripheral blood blast cell counts, peripheral blood WBCs, bone marrow blast cell counts or blast cell distribution ratio. The prognostic value of MMP-2 was evaluated by dividing AML patients into high and low MMP-2 groups using the pretreatment median MMP-2 level of the AML group as the cut-off. The authors found that patients in the high group survived for a significantly shorter time than those patients in the lower MMP-2 group. High pretreatment levels of sMMP-2 among AML patients were associated with poor survival. Prospective studies are recommended to establish the clinical value of longitudinal sMMP-2 measurement.

Enhancing effect of taurine on CYP7A1 mRNA expression in Hep G2 cells.

Taurine has been reported to enhance cholesterol 7alpha-hydroxylase (CYP7A1) mRNA expression in animal models. However, no in vitro studies of this effect have been reported. The Hep G2 human hepatoma cell line has been recognized as a good model for studying the regulation of human CYP7A1. This work characterizes the effects of taurine on CYP7A1 mRNA levels of Hep G2 cells in a dose- and time-dependent manner. In the dose-dependent experiment, Hep G2 cells were treated with 0, 2, 10 or 20 mM taurine in the presence or absence of cholesterol 0.2 mM for 48 h. In the time-dependent experiment, Hep G2 cells were treated with 0 or 20 mM taurine for 4, 24 and 48 h with and without cholesterol 0.2 mM. Our data revealed that taurine showed time- and dose-response effects on CYP7A1 mRNA levels in Hep G2 cells. However, glycine - a structural analogue of taurine - did not have an effect on CYP7A1 gene expression. These results show that, in agreement to previous studies on animal models, taurine induces the mRNA levels of CYP7A1 in Hep G2 cells, which could enhance cholesterol conversion into bile acids. Also, Hep G2 cell line may be an appropriate model to study the effects of taurine on human cholesterol metabolism.

Thrombopoietin (TPO) levels in hepatic patients with thrombocytopenia.

Thrombocytopenia is a common problem complicating the course of liver disease. One of the postulated mechanisms in chronic liver disease is impaired production of the hormone, thrombopoietin (TPO). The aim of present study was to evaluate the role of TPO on the occurrence of thrombocytopenia. Serum TPO levels was determined by ELISA in 40 patients with liver disease (11 seropositive with hepatitis C; 10 with mixed liver cirrhosis; 19 with bilharzial hepatic fibrosis), plus 14 normal healthy subjects as a control group. The sTPO levels were unevenly distributed among the liver disease subgroups being the highest in the group with HCV (median 1232.0, range 154.7-2042.0 pg/ml) followed by the mixed cirrhosis group (556.5; 342.0-1497.0 pg/ml) and lowest among the bilharzial hepatic fibrosis group (130.0; 22.0-204.0 pg/ml) (P<0.01). While sTPO levels in HCV and cirrhotic group were significantly higher when compared to the control group (97.0; 19.0-377.0 pg/ml), those in the Bilharzial hepatic fibrosis group were not significantly elevated (P>0.05). There is significant negative correlation between sTPO levels and spleen size (R=-0.3, P=0.043); but there was no correlation with platelet count (R=0.09, P>0.05). In addition, sTPO levels were significantly higher in patients with platelet counts >or=60x10(9)/l as compared to those with platelet counts <60x10(9)/l (P=0.04). Using the receiver operating curve (ROC) at sTPO cut off value >or= vs. <368 ng/ml, most of HCV and cirrhotic patients had higher sTPO levels (81.8 and 80.0%, respectively), while all Bilharzial hepatic fibrosis group (100%) had lower sTPO levels. In conclusion, sTPO levels had no role in the occurrence of thrombocytopenia in liver disease patients and other factors appear to be more important. It also appears that the mechanism controlling sTPO levels might be different in cirrhotic patients compared to Bilharzial hepatic fibrosis patients.

Syndecan-1 in multiple myeloma: relationship to conventional prognostic factors.

Syndecan-1 (CD138) mediates myeloma cell adhesion, and loss of syndecan-1 from the cell surface may contribute to myeloma cell proliferation and dissemination and influence the prognosis in patients with multiple myeloma (MM). In order to test this hypothesis, we have evaluated syndecan-1 expression on the surface of malignant plasma cells and soluble forms of syndecan-1 in the serum of 25 newly diagnosed MM patients by flow cytometry and immunosorbent assay. Soluble syndecan-1 levels were significantly higher in MM as compared to controls (P<0.001). Cellular and soluble syndecan-1 was significantly inversely correlated (r=-0.89, P<0.001). The soluble syndecan-1 was significantly higher in non- responders to chemotherapy when compared to responders (P<0.01), and in non- survivors as compared to survivors (P<0.001). In contrast, cellular syndecan-1 expression was significantly lower in non- responders when compared to responders (P<0.01), and in non- survivors as compared to survivors (P<0.05). The levels of soluble syndecan-1 increased from stage I through stage II to stage III, whereas cellular syndecan-1 expression were decreased from high levels in stage III down to a low in stage I, with a statistically significant difference (P<0.01, P<0.05, respectively). There was a significant positive correlation between soluble syndecan-1 and plasma cell count (r=0.079, P<0.001), beta2 microglobulin (r=0.85, P<0.001), serum creatinine (r=0.84, P<0.001), C-reactive protein (r=0.082, P<0.001), alkaline phosphatase (r=0.58, P<0.05) and serum calcium (r=0.77, P<0.01) and a negative correlation with hemoglobin level (r=-0.78, P<0.01), platelets count (r=-0.82, P<0.01) and Albumin level (r=-0.64, P<0.01). Cox regression analysis using soluble syndecan-1 at mean-2SD of the controls could correctly classify patient outcome in 84.0%. The addition of beta2 microglobulin to soluble syndecan-1 increased the predictability of the patients' outcome to 96.7%. We conclude that soluble syndecan-1 levels are negatively correlated to the cellular form and that high levels of soluble syndecan-1 and lower expression of cellular syndecan-1 at diagnosis are negative prognostic factors. Assessment of soluble syndecan-1 and beta2 microglobulin at diagnosis is an independent prognostic system for MM.

Soluble hepatocyte growth factor (sHGF) and vascular endothelial growth factor (sVEGF) in adult acute myeloid leukemia: relationship to disease characteristics.

UNLABELLED: There is little understanding of the factors controlling the mobilization of blast cells from bone marrow to peripheral blood and tissues. The aim of this study was to evaluate the soluble hepatocyte growth factor (sHGF) and vascular endothelial growth factor (sVEGF) levels in newly diagnosed patients with acute myeloid leukemia (AML) and to correlate these levels with the clinico-pathological features. Sixty-three patients with AML and 15 normal controls were included in this study. The levels of sHGF and sVEGF were determined by enzyme linked immunosorbent assay at diagnosis and after remission induction chemotherapy. Our results revealed significantly increased plasma levels of sHGF and sVEGF at diagnosis when compared to both control and remission levels (P=0.000 for both). The sHGF and sVEGF levels differed between AML FAB subtypes (P=0.000). The highest concentrations were found in M5 followed by M4. SHGF and sVEGF were directly correlated with peripheral white cell counts (WBC) (r=0.836, P=0.000, r=0.718; P=0.000, respectively), but inversely correlated with blast cell distribution ratio (BCDR) (r=-0.785, P=0.000, r=-0.664, P=0.000, respectively). Moreover, both sHGF and sVEGF levels were significantly elevated in AML patients with extra-medullary infiltration as compared to those without (P=0.000, 0.006, respectively). The sHGF but not sVEGF levels were significantly elevated in patients who died compared to those who relapsed and to patients in complete remission (P=0.02, 0.08, respectively). Logistic regression analysis revealed that the sHGF level at diagnoses is a powerful predictor of the patient outcome, compared to sVEGF. IN CONCLUSION: our data support the hypothesis that angiogenic factors play a functional role in blast cell movement from the bone marrow to peripheral tissues. Assessment of sHGF at AML diagnosis is likely to be helpful in predicting patient outcome and selecting optimal therapeutic regimen.

Modulation of the expression of peroxisome proliferator-activated receptor-dependent genes through disproportional expression of two subtypes in the small intestine.

We have reported that dietary long-chain triacylglycerols (LCT) enhance the transcription of cellular retinol-binding protein, the type II (CRBPII) gene, and the liver-type fatty acid-binding protein (L-FABP) gene in the small intestine. Because the cis elements on the CRBPII gene consisting of two AGGTCA motifs separated by a single nucleotide are known to bind not only the 9-cis-retinoic acid receptor (RXR) homodimer, but also the peroxisome proliferator-activated receptor (PPAR)-RXR heterodimer, it has been implicated that the unsaturated long-chain fatty acids, as the ligands of the PPAR, might activate the transcription of the CRBPII gene, thereby making use of the RXR-response elements (RXRE and RE3) as the PPAR-response element (PPRE). In this study, we found that the PPARalpha mRNA level in the rat jejunum was elevated by dietary fat, whereas the PPARdelta mRNA level was reduced under this condition. Electrophoretic mobility-shift assay revealed that both PPARalpha-RXRalpha and PPARdelta-RXRalpha heterodimers, specifically and in a dose-dependent manner, bound to the two PPRE-like elements of the rat CRBPII gene as well as the known PPREs in the L-FABP and acyl-CoA oxidase genes. The binding of the PPARalpha-RXRalpha heterodimer to the CRBPII-RXRE, the CRBPII-RE3, and the PPREs of L-FABP, HMG-CoA synthase, and acyl-CoA oxidase was gradually diminished by the addition of increasing amounts of PPARdelta. The binding of the PPARdelta-RXRalpha heterodimer to CRBPII-RXRE, CRBPII-RE3, and other PPREs was also gradually reduced by the addition of increasing amounts of PPARalpha. Using Escherichia coli-expressed RXRalpha, we showed that the mutual competition for RXRalpha with PPARalpha and PPARdelta occurred at the protein level. These results suggest that the transcriptions of CRBPII, L-FABP, and the other PPAR-dependent genes in the small intestine may be coordinately regulated by the disproportional expression of PPARalpha and PPARdelta.

The N-terminal helix of Xenopus cyclins A and B contributes to binding specificity of the cyclin-CDK complex.

Mitotic cyclins A and B contain a conserved N-terminal helix upstream of the cyclin box fold that contributes to a significant interface between cyclin and cyclin-dependent kinase (CDK). To address its contribution on cyclin-CDK interaction, we have constructed mutants in conserved residues of the N-terminal helix of Xenopus cyclins B2 and A1. The mutants showed altered binding affinities to Cdc2 and/or Cdk2. We also screened for mutations in the C-terminal lobe of CDK that exhibited different binding affinities for the cyclin-CDK complex. These mutations were at residues that interact with the cyclin N-terminal helix motif. The cyclin N-terminal helix mutations have a significant effect on the interaction between the cyclin-CDK complex and specific substrates, Xenopus Cdc6 and Cdc25C. These results suggest that the N-terminal helix of mitotic cyclins is required for specific interactions with CDKs and that to interact with CDK, specific substrates Cdc6 and Cdc25C require the CDK to be associated with a cyclin. The interaction between the cyclin N-terminal helix and the CDK C-terminal lobe may contribute to binding specificity of the cyclin-CDK complex.

The expression of PPAR-associated genes is modulated through postnatal development of PPAR subtypes in the small intestine.

In this study, we found that the mRNA level of peroxisome proliferator-activated receptor (PPAR) alpha, but not of PPARdelta, was elevated in the jejunum during the postnatal development of the rat. Moreover, we found that the expressions of PPAR-dependent genes, such as acyl-CoA oxidase, L-FABP, and I-FABP, were also increased during the postnatal development of the small intestine. Electrophoretic mobility shift assay revealed that both the PPARalpha-9-cis-retinoic acid receptor alpha (RXRalpha) heterodimer and the PPARdelta-RXRalpha heterodimer bound to the peroxisome proliferator response element (PPRE) of acyl-CoA oxidase and L-FABP genes. The binding of the PPARalpha-RXRalpha heterodimer to the PPREs of the various genes was enhanced by the addition of PPARalpha, with a concomitant reduction of the binding of PPARdelta-RXRalpha to the PPREs. Furthermore, the binding activity of PPARalpha-RXRalpha, but not PPARdelta-RXRalpha, to the PPREs was enhanced by the addition of a PPAR ligand, WY14,643. The GAL4-PPAR-chimera reporter assay showed that WY14,643 transactivated the reporter gene through action of PPARalpha, but not through PPARdelta, in Caco-2 cells. Furthermore, oral administration of a PPAR ligand, clofibrate, during 3 consecutive days of the weanling period caused a parallel increase in the mRNA levels of these PPAR-dependent genes. These results suggest that acyl-CoA oxidase, L-FABP and the other PPAR-dependent genes in the small intestine may be coordinately modulated during postnatal development by the disproportional expression of PPARalpha over PPARdelta.

Co-ordinated induction of beta-carotene cleavage enzyme and retinal reductase in the duodenum of the developing chicks.

The developmental patterns of expression of beta-carotene cleavage enzyme activity were compared with those of retinal reductase and NAD-dependent retinol dehydrogenase activities in chick duodenum during the perinatal period. The beta-carotene cleavage enzyme activity was not detected in the duodenum before hatching, but it increased rapidly during 24 h after hatching. On the other hand, a considerable level of beta-carotene cleavage enzyme activity was observed in the liver of embryonic stages and its activity gradually rose during the perinatal period. Comparison of kinetic constants for the beta-carotene cleavage enzyme activities in the duodenum and the liver indicated that the enzyme in the duodenum possessed a lower affinity for beta-carotene than that in the liver. The retinal reductase activity was detected in the microsomes of the duodenum at the earliest time examined, i.e. day 16 of embryogenesis and its activity began to rise on the last day of embryogenesis, which was followed by a gradual increase until 1 day of age. The NAD-dependent retinol dehydrogenase activity was also seen in the microsomes of the duodenum in embryonic stages and its activity increased in parallel with the retinal reductase activity around the hatching period. These developmental inductions of beta-carotene cleavage enzyme and retinal reductase activities in the duodenum coincided with those of cellular retinol-binding protein, type II (CRBPII) and lecithin: retinol acyltransferase (LRAT). These results suggest that a co-ordinated induction mechanism should be operative for beta-carotene cleavage enzyme and retinal reductase, both of which are inevitable in the process of beta-carotene absorption and metabolism.

Isolation and characterisation of a mutation in the PMR1 gene encoding a Golgi membrane ATPase, which causes hypersensitivity to over-expression of Clb3 in Saccharomyces cerevisiae.

We screened for mutant strains of Saccharomyces cerevisiae that are sensitive to overexpression of specific cyclins, and identified mutations in two genes that caused growth inhibition in response to mild overexpression of Clb3. One was the ANP1 gene, which encodes a glycosyltransferase previously identified by a similar strategy using Clb2 instead of Clb3. This paper describes the second strain of S. cerevisiae that is hypersensitive to Clb3 expression. The gene mutated in this strain was identified as PMR1, which encodes a Ca2+-ATPase located in the Golgi membrane. The protein product of pmr1-1 was truncated at residue 409 and thus lacked the C-terminal ATPase domain. The pmr1-1 strain was hypersensitive to over-expression of Clb3, but not Cln2, Clb5 or Clb2. The lethality due to Clb3 expression in pmr1-1 could be suppressed by adding Ca2+ ions to the medium. The pmr1-1 strain proved to be defective in glycosylation, and the defects in glycosylation were exacerbated by high levels of Clb3. On induction of Clb3 expression in the pmr1-1 strain, the cells arrested at anaphase with an elongated daughter bud. We discuss possible interpretations of this synthetic lethal phenotype.

Development of the insulin-like growth factor-I assay system.

A high speed full automatic ELISA system for measurement of insulin-like growth factor-I (IGF-I) was established by using magnetic particle-linked monoclonal antibody and enzyme-labeled monoclonal antibody. A standard curve was obtained, and the effect of dilution on the assay system was investigated. An IGF-I spike recovery test of human serum samples and a study of the correlation with a radioimmunoassay system were performed, and good results were obtained from all studies. The assay range was 0.5-50 ng/ml, and the time required for the full automatic measurement was 15 minutes. This assay system will play a central role in the clinical approach to IGF-I.

Regulation of vitamin A metabolism-related gene expression.

Cellular retinol-binding protein, type II (CRBPII) is abundantly expressed in the small intestinal epithelial cells and plays a pivotal role in intestinal absorption and metabolism of retinol and beta-carotene. In the 5'-flanking region of rat CRBPII gene, two DR-1 type elements which consist of a direct repeat of the AGGTCA-like motif spaced by a single nucleotide have been identified as putative binding sites for a heterodimer of peroxisome proliferator-activated receptor (PPAR) and retinoid X-receptor (RXR). We found that CRBPII levels were elevated in the residual jejunal segment of rats subjected to jejunal bypass operation, where a concomitant increase in the apoprotein B levels occurred. This result suggested that CRBPII expression was enhanced by a condition where fat absorption was stimulated. Indeed, dietary fat (especially unsaturated fatty acids) has been shown to induce CRBPII gene expression in the jejunum. Nuclear run-on assays revealed that this increase of CRBPII mRNA levels by a high-fat diet was the result of the induction of the gene transcription through the rise in PPARalpha expression level as well as the increase in its ligand levels. Electrophoretic mobility shift assay using the DR-1 type cis-elements of CRBP II gene showed that PPARalpha-RXRalpha heterodimer was capable of binding to these elements, and that nuclear extracts from the jejunum of rats fed the high-fat diet gave greater density of retarded bands than those of rats fed a fat-free diet. We also found that the expression of PPARdelta was rather reduced by dietary fat. Thus, CRBPII gene expression is regulated predominantly by dietary fatty acids.

Regulation of the expression of carbohydrate digestion/absorption-related genes.

To explore the underlying molecular mechanism whereby nutrients modulate the expression of intestinal digestion/absorption-related genes, we have cloned the 5' flanking regions of two representing disaccharidase genes, i.e. sucrase-isomaltase (SI) and lactase-phlorizin hydrolase (LPH), and investigated whether the binding activity of putative common nuclear factor(s) binding to the cis-elements located in these regions is altered by dietary manipulations. Oro-gastric feeding of a sucrose-containing diet to rats caused parallel increases in SI mRNA and LPH mRNA levels within 3 h. Among the monosaccharides tested, fructose gave rise to the most prominent increase in the mRNA levels of SI and LPH genes, which were accompanied by a coordinate rise in the mRNA levels of two microvillar hexose transporters, i.e. SGLT1 and GLUT5. Nuclear run-on assays revealed that fructose, but not glucose, increased the transcription of SI, LPH and GLUT5. DNase I footprinting analysis of the rat LPH gene showed that the protected region conserved the same sequence as the cis-element (CE-LPH1) reported in the pig LPH gene. Electrophoretic mobility shift assay using CE-LPH1 and the related cis-element of SI gene (SIF1) revealed that nuclear extracts from the jejunum of rats fed the high-starch diet gave greater density of retarded bands than those of rats fed the low-starch diet. Force feeding a fructose diet gave rise to an increase in the binding of the dimeric nuclear protein (Cdx-2) to the SIF1 element. These results suggest that the cis-elements of CE-LPH1 and SIF1 might be involved in the carbohydrate-induced increases of the transcription of LPH and SI, presumably through a change in the expression and/or binding activity of Cdx-2.

[Relationship between the force of left atrial ejection to left ventricular function in arterial hypertension]. / Relation entre la force d'éjection auriculaire gauche et la fonction ventriculaire gauche au cours de l'hypertension artérielle.

UNLABELLED: The left atrial ejection force (LAEF), defined as that force exerted by the left atrium (LA) to accelerate the blood into the left ventricle during atrial systole, is well accepted for the evaluation of LA systolic function. The aim of this study is to determine whether LAEF is a precursor of the impairement of LV systolic function in patients with arterial hypertension (HTN). For that purpose we studied LAEF in 36 patients with HTN (av. age 58 +/- 8 years) with LV hypertrophy (Lvmi > 134 g/m2 for men and > 110 g/m2 for women). LV systolic function estimated by the fractional shortening (FSh) was 35 +/- 4% (28 to 44); 32 normal subjects (NS) were also analyzed. All subjects were submitted to echo and doppler examinations. METHODS: LAEF was obtained by the formula: 1/3 x MVA x (A-vel)2, where MVA is mitral valve area measured by 2D echo while A-vel. is the late diastolic (atrial) mitral velocity. RESULTS: 1. LAEF increased significantly with age in NS (r = 0.78) p < 0.05). Age corrected LEAF was calculated as % LEAF = (actual LAEF/normal LAEF x 100. 2. Compared to NS. % LAEF was lower in HTN (78 + 25%). 3. There was a significant inverse correlation between LAEF and LV wall thickness (r = -0.46) (p < 0.05). 4. % LAEF was 66 +/- 31% in patients with FSh < 33% and 79 +/- 25% in those with FSh > 33% (p < 0.05). 5. In HTN with the duration > 15 years, % LAEF was lower than in patients with < 15 years (62 +/- 25 vs 76 +/- 24) (p < 0.05). CONCLUSIONS: 1. LAEF is decreased in more advance stages of HTN. 2. This impairment is related to LV hypertrophy and to the duration of the disease. 3. LAEF is a sensitive precursor for LV systolic deterioration in patients with hypertension.

[Alteration of the longitudinal function of the left ventricle in hypertensives with systolic function of normal appearance]. / Altération de la fonction longitudinale du ventricule gauche chez les hypertendus avec une fonction systolique en apparence normale.

UNLABELLED: Left ventricular (LV) transverse function is often used by the echocardiography to evaluate the systolic function in arterial hypertension (HTN). It would be interesting to know whether the LV long axis systolic dysfunction may precede the abnormalities of the transverse function in hypertension (HTN). For that purpose we evaluated by echo 36 patients (24 males, 12 females) with LV concentric hypertrophic (Lvmi > 134 g/m2 for men and > 110 g/m2 for women). All subjects were free of coronary heart disease and heart failure. According to the dimensions of the LV wall chickness (WTh) the HTN were subdivided in two groups: Group 1: Wth (12-14 mm) and Group 2: WTh (> 14 mm). The patients were compared to 30 healthy persons (control group) matched for age and LV systolic function (Fractional Shortening). METHODS: LV long axis shortening was measured at the septal and lateral sides of the mitral annulus using M-mode from the apical four chamber view. RESULTS: Compared to control group, septal long axis shortening fell significantly (p < 0.05) in proportion to the degree of the wall thickness: control group: 21 +/- 2 mm. Group 1: 16 +/- 1 mm and Group 2: 14 +/- 1 mm. Lateral shortening was reduced only in the Group 2 (15 +/- 2 vs 20 +/- 2 mm) (p < 0.05). LV wall thickness correlated significantly (p < 0.05) to septal and lateral shortening respectively (r = -0.51) and (r = -0.48). CONCLUSIONS: 1. Significant impairment of LV long axis function occurs in arterial hypertension with concentric hypertrophy even with normal transverse systolic function. 2. This alteration seems to be related to the dimensions of the LV wall thickness. 3. The prognostic implication of this disorder should be investigated further.

Identification of a member of the serralysin family isolated from a psychrotrophic bacterium, Pseudomonas fluorescens 114.

An extracellular metalloprotease named No. 114 protease is one of the major secretions of a psychrotrophic bacterium, Pseudomonas fluorescens 114, the cold-adaptation mechanism of which has not been identified. In this study, we purified and cloned No. 114 protease, which is a single polypeptide having a molecular mass of 47 kDa. This protease contains a zinc-binding motif (HEXXHXUGUXH: X, arbitrary amino acid; U, bulky hydrophobic amino acid), glycine-rich repeats (GGXGXD) and no cysteine residue, which are the features specifically found in serralysin subfamily. No. 114 protease has its maximum activity at the temperature of 35-40 degrees C, which is about 20 degrees C lower than that of a serralysin from a mesophilic bacterium, Pseudomonas aeruginosa. All these results imply that No. 114 protease from this psychrophilic bacterium is a unique member of the serralysin group characterized by a low optimal temperature.