Search PubMed⌕ Search

Biomedical subjects

H Izawa

Publications and source records attributed to H Izawa.

At least 37 records · Page 2Linked to original sources
PubMed1998

Changes in size of intracellular pools of coenzyme A and its thioesters in Escherichia coli K-12 cells to various carbon sources and stresses.

Intracellular pools of three CoA molecular species of coenzyme A, CoASH, acetyl-CoA, and malonyl-CoA, in Escherichia coli K-12 cells were studied by acyl-CoA cycling method in replacement culture. The sizes and compositions of CoA pools starved for a carbon source changed within minutes after the addition of one of various carbon sources. A large acetyl-CoA pool formed after the addition of D-glucose, D-fructose, D-mannose, glycerol, or sorbitol, but there was little change when L-glucose, sucrose, maltose, succinate, or acetate was added. The beta-anomer of D-glucose was assimilated 10 times faster than the alpha-anomer. Intracellular CoA pools also changed with stress: in the pH, incubation temperature, or with osmotic stress. The sizes and compositions of CoA pools were not affected by pH changing between 4 and 8, but the breakdown of acetyl-CoA and CoASH was greater at pH 9 than at pH 4 to 8. Production of acetyl-CoA was greatest at 40 degrees C, and at 50 degrees C, an acetyl-CoA pool did not form at all and the size of the CoASH pool declined. When the organism was stressed by the addition of NaCl at concentrations of more than 0.6 M, little acetyl-CoA was produced. The total CoA pool (the sum of the concentrations of CoASH, acetyl-CoA, and malonyl-CoA) remained within the limits of 0.83-1.40 nmol/mg of dry cell weight (0.30-0.52 mM). Whenever acetyl-CoA increased, CoASH decreased. Therefore, the acetyl-CoA/CoASH ratio is an important index of facultative anaerobes that reflects the state of carbon and energy metabolism in vivo.

Acetyl Coenzyme A↗
PubMed1998

Cdk2/cdc2 expression in colon carcinogenesis and effects of cdk2/cdc2 inhibitor in colon cancer cells.

Cyclin dependent kinases propel the cell cycle in collaboration with cyclins. We have examined the expression of cdk2/cdc2 in adenoma and focal carcinoma in adenomatous tissue to explore their role in tumorigenesis of colorectum. Immunohistochemical study revealed that cdk2/cdc2 was overexpressed in a subsets of adenoma (14/50; 28.0%) but this overexpression was much more obvious in focal carcinoma (13/15; 86.7%). These results suggest that cdk2/cdc2 is remarkably upregulated together with a malignant change. In an effort to demonstrate a significant role for cdk2/cdc2 in colon cancer, we investigated growth and apoptosis with butyrolactone I, a specific inhibitor for cdk2/cdc2, using 4 colon carcinoma cell lines (HCT116, LoVo, HT29, Colo 320DM). Butyrolactone I inhibited proliferation of all colon carcinoma cell lines at 100 microM and it induced apoptosis in LoVo cell line with induction of p53. Our findings suggest that inhibition of cdk2/cdc2 may be a useful strategy against colon cancer.

4-Butyrolactone↗
PubMed1998

[PyNPase expression and cancer progression in the colorectum].

We analyzed PyNPase expression discriminating between cancer and tumor stroma of the colorectum by Western blotting using a newly developed extraction method from microdissected tissue sections fixed with buffered formalin. Analysis of 98 colorectal cancers revealed that PyNPase was as high as 70.2 +/- 18.5 unit/mg protein in the stroma fraction (SF), whereas it was 45.1 +/- 10.5 in the cancer fraction (CF) (p < 0.0001). Vessel density was correlated with PyNPase in the SF but not in the CF. In stage IIIb, 11 cases expressing a high level of PyNPase in the CF showed poorer prognosis than 10 cases with low-level PyNPase expression (p < 0.05), although the level of PyNPase expression in the SF did not affected the patients prognosis. Immunohistochemical examination indicated that PyNPase in the SF was mainly produced by macrophages (M phi), and therefore we investigated the profile of PyNPase production by M phi. In in vitro experiments PyNPase production by M phi was greatly enhanced by stimulation with OK-432, and the culture supernatant had the ability to convert 5'DFUR to 5-FU.

Antineoplastic Agents↗
PubMed1997

Adrenergic control of the force-frequency and relaxation-frequency relations in patients with hypertrophic cardiomyopathy.

BACKGROUND: Exercise-induced enhancement of the force-frequency and relaxation-frequency relations has been studied in conscious animals but not in intact diseased human hearts. METHODS AND RESULTS: We evaluated left ventricular (LV) isovolumic contraction (dP/dt(max)) and relaxation (tau) during atrial pacing and dynamic exercise in 13 patients with nonobstructive hypertrophic cardiomyopathy (HCM) and 7 control subjects to investigate the influence of exercise on the force-frequency and relaxation-frequency relations. Group A consisted of 6 patients in whom the heart rate (HR)-dP/dt(max) relation was markedly enhanced during exercise (88+/-30%) compared with during pacing (34+/-15%). Group B consisted of 7 patients in whom the HR-dP/dt(max) relation showed similar enhancement during exercise (28+/-7%) and atrial pacing (28+/-11%). There was no difference in the HR-tau (derivative method [TD] and pressure half-time method [T(1/2)]) relation between pacing and exercise in groups A and B. Both the mean maximal wall thickness and the hypertrophy score in group B were greater than in group A (27+/-5 versus 19+/-2 mm and 7+/-1 versus 5+/-1 points, respectively; both P<.01). There was no difference in the LV peak systolic pressure, end-diastolic pressure, or the plasma level of catecholamines at baseline, at 50 W of exercise, and at peak pacing between groups A and B. The HR-dP/dt(max) relation in the control group was markedly enhanced during exercise (80+/-27%) compared with during pacing (32+/-14%). The HR-tau relation in the control group was enhanced during exercise (TD, 35+/-9%; T(1/2), 34+/-8%) compared with during pacing (TD, 12+/-7%; T(1/2), 14+/-7%). CONCLUSIONS: Exercise-induced enhancement of the relaxation-frequency relation was inhibited in all HCM patients, regardless of the degree of LV hypertrophy. The patients without exercise-induced enhancement of the force-frequency relation had more severe LV hypertrophy than the patients with the enhancement, indicating that the adrenergic control of the force-frequency relation may, at least in part, depend on the severity of LV hypertrophy or the stage of HCM.

Adult↗
PubMed1997

Leukocytapheresis with leukocyte removal filter as new therapy for ulcerative colitis.

Leukocytapheresis (LCAP) with a leukocyte removal filter column was administered for 45 patients with ulcerative colitis (UC). We evaluated changes in the leukocyte count and the differential percentages during LCAP. Cytokine production was assessed from each patient's peripheral mononuclear cells or monocytes. Flow cytometry was performed to assess the removal rates of activated cells and adhesion molecule positive cells by LCAP. Clinical improvement was recognized in 35 of 45 patients during intensive LCAP therapy, and it continued throughout maintenance therapy in 32 patients (71.1%). The leukocyte count was decreased to about 40% during the first 30 min, but it increased to approximately 170% at 20 min after the completion of LCAP. The concentration of tumor necrosis factor (TNF)alpha before LCAP in the effective group was higher than it was in either the ineffective group or the control group. Its level decreased to near normal range after LCAP. In the effective group, the concentrations of interleukin (IL)-1beta, IL-2, interferon (IFN)gamma, and IL-8 were near the normal upper limits before LCAP; however, they had decreased after LCAP. The concentration of IL-4 increased after LCAP. In the ineffective group, in contrast, the concentrations had been at or near normal before the initial LCAP treatment. Flow cytometry study revealed that LCAP could remove the activated cells and adhesion molecule positive cells more effectively. The clinical improvement and the changes observed before and after LCAP therapy suggest that LCAP is able to intervene in the causal mechanism(s) of UC.

Blood Cell Count↗
PubMed1997

[Effects of halothane and sevoflurane on reversal of neuromuscular blockade induced by vecuronium in man].

To evaluate residual effects of inhalational anesthetics after reversal of neuromuscular blocking agent, neuromuscular function was monitored after halothane or sevoflurane anesthesia in thirty-seven patients (ASA physical status I or II) for elective surgery after obtaining informed consent. Electromyograph of the adductor pollicis muscle in response to train of four (TOF) stimulation was monitored throughout the study. The first twitch of TOF (T1; % of its control) and the ratio of the fourth twitch to the first twitch of TOF (T4/T1; TR) were recorded at 0, 2, 5, 10, and 15 min after reversal. The patients were divided into five groups; 1) the fentanyl group (n = 7) received fentanyl/N2O; 2) in the halothane stop group (n = 6), halothane was discontinued at least fifteen minutes before neostigmine administration; 3) in the halothane stable group (n = 7), 0.7% halothane was maintained until fifteen minutes after neostigmine; 4) in the sevoflurane stop group (n = 12), sevoflurane was discontinued fifteen minutes before the reversal; 5) in the sevoflurane stable group (n = 5), 3% sevoflurane was maintained until fifteen minutes after the reversal. Anesthesia was induced by thiopental 4 mg.kg-1 and suxamethonium 1 mg.kg-1 and the patients were intubated. After initial dose of vecuronium 0.1 mg.kg-1, the additional dose of 0.02 mg.kg-1 was administered to maintain T1 under 10% of the control value. At the end of the surgery atropine 0.015 mg.kg-1 and neostigmine 0.04 mg.kg-1 were administered to reverse vecuronium when T1 had recovered to 25% of its control. Halothane groups did not differ from fentanyl group. Recovery of T1 at 15 min was suppressed after discontinuation of sevoflurane (86.0 +/- 8.2%) in comparison with fentanyl (97.0 +/- 8.3%). Both T1 (75.4 +/- 12.2%) and TR (68.0 +/- 12.6%) at 15 min after the reversal during 3% sevoflurane inhalation were below those of the stable group. We conclude that the residual sevofulrane after discontinuation of inhalation may impair the neuromuscular transmission after the reversal of neuromuscular blockade. Neuromuscular function should be monitored after the end of anesthesia even though the patient is fully awake.

Adult↗
PubMed1997

Depressed mechanoenergetics and compensatory responses in idiopathic dilated cardiomyopathy.

The aim of this study was to clarify that the depressed mechanoenergetics in patients with idiopathic dilated cardiomyopathy (DCM) resulted from compensation for the decreased contractility. The study population consisted of eight control subjects, with normal left ventricular size and ejection fraction and 31 patients with DCM. Left ventricular end-systolic elastance (Ees), effective arterial elastance (Ea), external work (EW), and the pressure-volume area (PVA) were measured, using a dual-field volume conductance catheter equipped with a micromanometer-tipped catheter. Ea/Ees was evaluated as ventriculoarterial coupling. Normal hearts worked at almost optimal condition (defined as Ea/Ees = 1/2), while ventriculoarterial coupling was far from the optimum (Ea > Ees) in patients with DCM. Ees in patients with DCM was less than that in control subjects; however, Ea was similar in the two groups. The mismatch of Ea/Ees observed in DCM leads to depressed mechanoenergetics as a result of the compensatory response to maintain adequate blood pressure. Volume enlargement plays an important role in maintaining adequate blood pressure and cardiac output in the course of chronic deterioration of contractility.

Blood Pressure↗
PubMed1997

Dynamic exercise-induced changes in diastolic properties of the regional myocardium in hypertensive left ventricular hypertrophy.

We investigated the effect of mild exercise on global and regional diastolic function in patients with hypertensive left ventricular hypertrophy (LVH), using simultaneous measurement of micromanometric left ventricular pressure and echocardiographic indexes. Although left ventricular end-diastolic pressure (LVEDP) at rest in the hypertensive LVH group was similar to that in the control normotensive group, who had no abnormality on echocardiography or cardiac catheterization, LVEDP showed a marked increase during exercise only in the hypertensive LVH group. The pressure-dimension relation was shifted upward during exercise in all patients with hypertensive LVH. We utilized a new index of regional diastolic myocardial stiffness, KDM, which is derived from the diastolic relation between the mean wall stress and the natural logarithm of the reciprocal of wall thickness. Although KDM at rest was similar in the two groups, KDM increased significantly during exercise, both in the septum and posterior wall in patients with hypertensive LVH. The present results imply that even low-grade exercise may have deleterious effects on regional myocardial performance in patients with hypertensive LVH.

Diastole↗
PubMed1996

Mutations of the transforming growth factor beta type II receptor gene and microsatellite instability in gastric cancer.

Forty-three sporadic gastric cancers were analyzed with regard to whether mutations of simple repeated sequences in the transforming growth factor beta type II receptor (TbetaR-II) gene are associated with microsatellite instability (MSI) and gastric carcinogenesis. In 12 of the 43 cancers (28%), MSI was observed at least at 1 of the 2 microsatellite loci. Frameshift mutations of the TbetaR-II gene, all of which were 1 base deletion of 10 adenine repeats, were detected in 3 of 6 cancers, with MSI at 2 loci. However, mutations were not detected in 6 cancers, with MSI only at 1 locus and 31 cancers without MSI. Moreover, microanalysis in these cases revealed that the mutant-type alleles of TbetaR-II were invariably common in different areas within the tumor, in contrast to the markedly variable alleles of microsatellite loci. Our results suggest that frameshift mutation of the TbetaR-II gene may be a critical event associated with MSI and may contribute to carcinogenesis of the stomach. One of the possible mechanisms of escape from growth control by TGFbeta during gastric carcinogenesis could involve frameshift mutations of the TbetaR-II gene caused by DNA replication errors.

Adenine↗
PubMed1996

Assignment of the disulfide bonds in the sweet protein brazzein.

The thermostable sweet protein brazzein consists of 54 amino acid residues and has four intramolecular disulfide bonds, the location of which is unknown. We found that brazzein resists enzymatic hydrolysis at enzyme/substrate ratios (w/w) of 1:100-1:10 at 35-40 degrees C for 24-48 h. Brazzein was hydrolyzed using thermolysin at an enzyme/substrate ratio of 1:1 (w/w) in water, pH 5.5, for 6 h and at 50 degrees C. The disulfide bonds were determined, by a combination of mass spectrometric analysis and amino acid sequencing of cystine-containing peptides, to be between Cys4-Cys52, Cys16-Cys37, Cys22-Cys47, and Cys26-Cys49. These disulfide bonds contribute to its thermostability.

Amino Acid Sequence↗
PubMed1996

Synthesis and characterization of the sweet protein brazzein.

The sweet protein brazzein isolated from the fruit of the African plant, Pentadiplandra brazzeana Baillon is 2000-500 times sweeter than sucrose and consists of 54 amino acid residues with four intramolecular disulfide bonds. Brazzein was prepared by the fluoren-9-yl-methoxycarbonyl solid-phase method, and was identical to natural brazzein by high performance liquid chromatography, mass spectroscopy, peptide mapping, and taste evaluation. The D enantiomer of brazzein was also synthesized, and was shown to be the mirror image of brazzein. The D enantiomer (ent-brazzein) was devoid of any sweetness and was essentially tasteless.

Amino Acid Sequence↗
PubMed1996

Impaired response of left ventricular relaxation to exercise-induced adrenergic stimulation in patients with hypertrophic cardiomyopathy.

OBJECTIVES: We investigated the effect of adrenergic stimulation on left ventricular relaxation in patients with hypertrophic cardiomyopathy. BACKGROUND: Exercise-induced decreases in acceleration of left ventricular relaxation have been observed in patients with hypertrophic cardiomyopathy. However, data on sequential changes in left ventricular relaxation during exercise are limited. METHODS: We measured right (fluid filled) and left (high fidelity micromanometer) ventricular pressures during moderate supine ergometer exercise and during rapid right atrial pacing in four groups of patients: 9 with severe hypertrophic cardiomyopathy, 9 with moderate hypertrophic cardiomyopathy, 10 with hypertension and moderate hypertrophy and 5 control subjects. RESULTS: There was a curvilinear relation between the time constant of relaxation (tau) and heart rate in all groups during exercise. There was no difference in the slope of this relation between the two hypertrophic cardiomyopathy subgroups. Although the slope of this relation between tau and heart rate was steeper in the hypertensive than the moderate hypertrophic cardiomyopathy group (p < 0.001, analysis of covariance), the decrease in tau during right atrial pacing was similar in both groups. There were no significant differences in plasma levels of catecholamines at rest or at peak exercise among groups or in maximal heart rate during pacing. CONCLUSIONS: Pacing-induced changes in tau in hypertrophic cardiomyopathy were similar to those in hypertensive hypertrophy, but remarkable decrease in exercise-induced acceleration of tau were observed only in hypertrophic cardiomyopathy. Our results may indicate a depressed left ventricular relaxation response to exercise-induced adrenergic stimulation in hypertrophic cardiomyopathy.

Adult↗
PubMed1996

[RB gene expression in gastrointestinal tract].

pRB, the retinoblastoma tumor suppressor gene product, regulates the cell cycle at G1/S transition negatively. Many cell cycle regulators modulate pRB function through its phosphorylation status. G1 cyclins (cyclin D, E)/cyclin-dependent kinases (cdk2, 4) inactivates pRB through its phosphorylation, while p21 (WAF1) and p16 inhibit cdks. In several kinds of cancer, Rb gene alteration or functional inactivation of pRB has been reported. In esophageal cancer, loss of heterozygosity of Rb gene and cyclin D gene amplification were frequently detected. But in gastric and colorectal cancer, Rb gene loss or deletion has been shown to be rare. In this study we investigated the expression of pRB, G1 cyclins, cdks and cdk-inhibitors in adenoma-carcinoma sequence of colorectum. And we compared the phosphorylation status of pRB in colorectal normal mucosa and cancer tissue. In adenoma only cyclin D and E were overexpressed but not cdks. In cancer in adenoma pRB and cdk2 were overexpressed with high frequency, and cdk4 overexpression was detected in advanced cancer. p16 overexpression was detected in almost all cancers, but in contrast p21 overexpression was rare event. Comparative study showed that pRB-positive cancer cells also expressed both cdc2/cdk2 and cyclin E. Densitometric analysis revealed that in advanced cancer pRB was hyperphosphorylated compared with normal mucosa. These results indicate that overexpression of cyclin D/cdk4 and cyclin E/cdk2 would phosphorylate pRB, and insufficient expression of p21 may accelerate pRB inactivation.

Cell Cycle↗
PubMed1996

[Cyclin D, CDK4 and p16 expression in colorectal cancer].

G1/S transition of cell cycle is regulated by G1 cyclins/cyclin-dependent kinases (CDKs) and their inhibitors. Cyclin D/CDK4 complex phosphorylates retinoblastoma gene product and p16 inhibits CDK4 in competition with cyclin D. Aberrant expression of these proteins may deregulate cell proliferation and moreover may lead to tumor formation and progression. In this study we examined the expression of cyclin D, CDK4 and p16 in adenoma-carcinoma sequence of colorectum. Immunohistochemical staining revealed that cyclin D was overexpressed in 55 of 66 (83%) adenomas, 8 of 8 (100%) carcinomas in adenoma (CIAs), 26 of 45 (58%) advanced carcinomas and even in hyperplastic mucosa. CDK4 was overexpressed in 0 of 52 (0%) adenomas, 0 of 14 (0%) CIAs and 39 of 45 (87%) advanced carcinomas, but not in hyperplastic mucosa. p16 was overexpressed in only 5 of 52 (10%) adenomas, 10 of 14 (71%) CIA and 59 of 60 (98%) advanced carcinomas, but not in hyperplastic mucosa. And comparative study of CDK4 and p16 showed that CDK4-positive cancer cells also expressed p16. Western blot analysis also revealed that primary regions of advanced colorectal cancer tissues showed 4.61, 3.30, 1.65 and 8.03-fold overexpression on the average in cyclin D1, cyclin D2, CDK4 and p16 respectively. These results indicate that both cyclin D and CDK4 may contribute to phosphorylation of pRB. p16 overexpression would be induced as a brake at G1/S transition through pRB phosphorylation by CDK4 overexpression in advanced colorectal carcinomas.

Adenoma↗
PubMed1995

Coexpression of cdk2/cdc2 and retinoblastoma gene products in colorectal cancer.

The retinoblastoma gene (Rb gene) is a tumour-suppressor gene and its product (pRB) is known to act as a negative regulator of the cell cycle. Although lack of pRB expression resulting from gene alterations is considered to be responsible for the genesis of several human malignancies, increased expression of pRB has been demonstrated in a majority of colorectal cancer cases. In the present study, we investigated the expression of pRB as well as that of its related kinases, cdk2 and cdc2, in colorectal cancer, since these kinases have been reported to phosphorylate and inactivate pRB. Western blot analysis revealed that colorectal cancer expressed higher levels of cdk2 and cdc2 than did normal mucosa and that the ratio of the hyperphosphorylated form of pRB was higher in colorectal cancer. Furthermore, immunohistochemical studies showed that cdk2/cdc2 was expressed exclusively in the cancer cells positive for pRB. These results suggest that an increase in the expression of cdk2/cdc2 in colorectal cancer may have prevented pRB from braking the cell cycle through phosphorylation.

Blotting, Western↗
PubMed1994

Duration and extent of antianginal effects of a sustained-release formulation of nifedipine in angina.

Twenty-four patients with chronic stable exertional angina pectoris were randomized in a double-blind, placebo-controlled, crossover trial to assess the efficacy and durability of a newly developed, sustained-release formulation of nifedipine (nifedipine CC) in a single 40-mg oral dose. Symptom-limited graded treadmill exercise tests were performed just before, and at 4, 7, and 24 h after a single administration of the drug or the placebo was given. Exercise tolerance at 4, 7, and 24 h after the drug were compared with the corresponding placebo values. Data could be analysed for 19 patients. Maximal exercise time, time to the onset of angina, and time to 1 mm ST segment placebo. The average maximal exercise time was significantly increased by 72, 76, and 37 s at 4, 7, and 24 h. Rate-pressure product at rest and at peak exercise showed significant changes only at 24 h compared with placebo (both P < 0.05). The maximal increase in exercise tolerance was most marked at 7 h nifedipine CC, at which time plasma drug concentration was 99.4 +/- 14.0 ng.ml-1. Thus, in patients with chronic stable exertional angina pectoris, nifedipine CC showed a prolonged improvement in exercise tolerance up to 24 h after a single oral administration.

Angina Pectoris↗
PubMed1993

Age-related changes in left and right ventricular filling velocity profiles and their relationship in normal subjects.

To confirm age-related changes in left and right ventricular filling velocity profiles and to compare left and right ventricular filling parameters in normal subjects, we performed pulsed Doppler echocardiographic studies in 108 normal subjects (72 men and 36 women) aged 15 to 78 years. An age-related decrease in peak early velocity (E velocity), an increase in peak atrial velocity (A velocity), and augmented ratio of A velocity to E velocity (A/E) were observed in left ventricle (r = -0.71, 0.63, and 0.83, respectively). Similar age-related changes were found in right ventricle (r = -0.71, 0.54, and 0.78). Aging had a greater effect on the filling of the left ventricle than the right one (i.e., a steeper slope). The difference between left and right ventricular filling increased with advancing age. Left ventricular filling indexes exceeded those of the right ventricle. Significant correlations were observed between the right and left ventricular filling parameters (r = 0.58 to 0.90). A strong relation was noted in A/E (r = 0.90). There was no significant relation between age and left ventricular mass. The left ventricular mass appeared to have little effect on left and right ventricular filling in normal individuals. Thus in clinical studies the age-related decrease in early diastolic filling and the increased atrial filling in both left and right ventricles should be considered. The atrial contribution to ventricular filling may be more pronounced in the left ventricle than the right ventricle in older subjects.

Adult↗