Biomedical subjects

M Hamada

Publications and source records attributed to M Hamada.

At least 199 records · Page 11Linked to original sources

PubMed1996

The p53 gene is a potent determinant of chemosensitivity and radiosensitivity in gastric and colorectal cancers.

We previously reported that introduction of the wild-type p53 gene into human cancer cells with deleted p53 enhanced apoptosis induced by chemotherapy [Fujiwara et al. (1994) Cancer Res 54:2287]. This suggests that p53 status could be a potent determinant of the therapeutic efficacy of DNA-damaging cancer therapy. We analyzed 24 patients with gastric or colorectal cancer for p53 mutations and apoptotic changes in surgical specimens. Out of 11 patients with gastric cancer, 3 were treated with chemotherapeutic drugs before resection; 5 of 13 patients with colorectal cancer had 30 Gy radiation prior to surgery. p53 mutations were detected in 4 cases of gastric cancer (36.4%) and in 6 cases of colorectal cancer (46.2%) by immunohistochemical staining. The preoperative DNA-damaging therapies increased the number of apoptotic cells in wild-type-p53-expressing tumors; tumors with mutant p53, however, significantly showed fewer apoptotic cells compared with those expressing wild-type p53. The p53-inducible WAF1/CIP1 protein was immunohistochemically observed in wild-type-p53-containing tumors, whereas mutant-p53-expressing tumors expressed no detectable WAF1/CIP1. Taken together, we conclude that p53 mutations are associated with the poor response of chemotherapy and radiotherapy.

Adult↗

PubMed1996

Appendiceal mucocele with concomitant colonic cancer. Report of two cases.

PURPOSE: Mucocele of the appendix is an uncommon disorder, usually found incidentally during ultrasonography or radiographic studies. We report two cases of combined appendiceal mucocele and colonic cancer. METHODS: The two cases were analyzed for the clinicopathologic characteristics such as history, presentation, laboratory data, radiologic and endoscopic studies, pathology, and p53 immunoreactivity. RESULTS: Two patients were diagnosed with an appendiceal mucocele by ultrasound of the abdomen, together with computed tomography. Colonoscopic examination subsequently revealed synchronous colonic adenocarcinoma in both patients. Ileocecal resection following endoscopic polypectomy and a right hemicolectomy was performed for each patient. An appendiceal mucocele was histologically diagnosed as a mucinous cystadenoma. Immunohistochemical detection of abnormally high level of p53 protein was observed in colonic adenocarcinomas of both patients, whereas both appendiceal cystadenomas were negative for p53. CONCLUSIONS: To be remembered is the high frequency of concomitant gastrointestinal tumors in patients with appendiceal mucocele, especially caused by mucinous neoplasms. A total colonoscopic surveillance will afford earlier diagnosis of synchronous colonic cancers in these patients.

Adenocarcinoma↗

PubMed1996

Effects of pirenzepine on omeprazole-induced gastrin gene expression in rat antral tissues.

Pirenzepine has inhibitory effects on gastrin secretion both in vivo and in vitro. The aim of this study was to determine the mechanism responsible for the suppression of omeprazole-induced hypergastrinemia that occurs with pirenzepine treatment. The effects were measured in rats treated with oral omeprazole plus intraperitoneal pirenzepine or saline once daily for seven days in the antrum. The serum gastrin level increased significantly by more than sixfold with omeprazole treatment; additional treatment with pirenzepine suppressed this increase by 48%. Pirenzepine treatment did not change the level of gastrin mRNA but significantly increased the level of somatostatin mRNA. Combination treatment with omeprazole plus pirenzepine significantly decreased the gastrin mRNA level to half and significantly increased the somatostatin mRNA level up to 1.4-fold of the levels achieved with omeprazole treatment alone. These results suggest that the stimulatory effect of omeprazole on gastrin synthesis is partially blocked by pirenzepine via mediation of somatostatin synthesis in the antrum.

Actins↗

PubMed1996

Pneumatosis intestinalis and necrotizing enterocolitis associated with liver cirrhosis.

We report a 58-year-old woman with pneumatosis intestinalis and necrotizing enterocolitis associated with liver cirrhosis. She was receiving treatment for liver cirrhosis and hepatic failure when sudden severe right upper abdominal pain and fever developed. Abdominal radiograph disclosed pneumatosis intestinalis, involving the ascending colon, and small collections of free air along the right hemidiaphragm. The pneumatosis intestinalis appeared in both cystic and linear form. Autopsy revealed necrosis and multiple gas-filled mural cysts in the ascending colon. To our knowledge, this is the first case to be reported of pneumatosis intestinalis and necrotizing enterocolitis associated with liver cirrhosis.

Colon↗

PubMed1996

Effects of pirenzepine on omeprazole-induced hypergastrinemia and acid suppression in peptic ulcer patients.

Omeprazole effectively suppresses acid secretion, resulting in the long-term elevation of intragastric pH and serum gastrin level. Pirenzepine has been reported to inhibit gastrin secretion. This study was carried out to examine the effects of additional pirenzepine treatment on the hypergastrinemia and gastric acid suppression induced by omeprazole. Concentrations of serum gastrin and plasma somatostatin were measured in 28 peptic ulcer patients before treatment, after omeprazole treatment (20 mg/day) for 2 weeks, and after omeprazole and pirenzepine (100 mg/day) treatment for 2 weeks. The acid inhibitory effect of pirenzepine treatment in addition to omeprazole was evaluated by 24-h intragastric pH measurement in six healthy volunteers. Serum gastrin level was increased significantly, to 2.4-fold the pretreatment level, by omeprazole treatment. Additional treatment with pirenzepine suppressed serum gastrin level to 0.6-fold the omeprazole-treatment level. The serum somatostatin level was not altered significantly either by omeprazole treatment or by omeprazole and pirenzepine treatment. In healthy volunteers whose pH 3 holding time on 24-h intragastric pH monitoring was 70% by omeprazole treatment, omeprazole and pirenzepine treatment markedly increased the pH 3 holding time, to 89%. These findings suggest that pirenzepine is useful in reducing the undesirable effects of omeprazole-induced hypergastrinemia, i.e., the excessive trophic effect of omeprazole on the acid-secreting part of the stomach and the overstimulation of acid secretion. The additional pirenzepine treatment is also effective in suppressing acid secretion.

Adult↗

PubMed1996

Regression of increased left ventricular masses in elderly hypertensive patients on lisinopril as assessed by magnetic resonance imaging.

RATIONALE AND OBJECTIVES: We investigated, using magnetic resonance imaging, whether the addition of lisinopril could reduce increased left ventricular (LV) masses in hypertensive patients whose blood pressure was well controlled with nifedipine. METHODS: Fourteen hypertensive patients being treated with nifedipine and having an interventricular septum thickness of more than 12 mm were studied. Half of them were given 5 mg lisinopril, and the others were not. Short-axis images of the left ventricle from the base to the apex were obtained by a standard spin-echo pulse sequence. The entire LV mass was calculated from the area of short-axis slices of the left ventricle multiplied by slice thickness. RESULTS: Blood pressure fell slightly and almost equally in both groups. The LV mass and LV mass index showed a significant decrease in the lisinopril-treated group but not in the control group. CONCLUSION: Results demonstrate the effectiveness of lisinopril in reducing increased LV masses, at least in combination with nifedipine.

Aged↗

PubMed1996

Isolation and synthesis of novel farnesyl protein transferase inhibitors, valinoctins A and B, from Streptomyces strain MJ858-NF3.

Two novel farnesyl protein transferase inhibitors, valinoctins A (1) and B (2), were isolated from the fermentation broth of Streptomyces strain MJ858-NF3. The tentative structures of these compounds were elucidated from NMR and mass spectra as dipeptides consisting of valine and a novel amino acyl moiety. Four possible isomers of valinoctin A were synthesized, and the protected derivative of the appropriate compound was crystallized to give the relative stereochemistry of X-ray analysis. Since the valine residue of valinoctin A was determined to be the L-configuration by a chiral HPLC column, absolute configuration of valinoctin A was determined.

Animals↗

PubMed1996

Covalent binding between bucillamine derivatives and human serum albumin.

PURPOSE: To clarify the mechanism of covalent binding between human serum albumin (HSA) and drugs containing thiol groups, we studied the interactions between HSA and bucillamine (BA) and its derivatives. METHODS: To determine the concentration of HSA-drug conjugate, we used columns of N-methylpyridium polymer cross-linked with ethylene glycol dimethacrylate (4VP-Me), and analyzed the reaction between HSA and BA derivatives kinetically. Following pseudo first-order reaction kinetics, the rate constants of reduction of non-mercaptoalbumin (HNA) to mercaptoalbumin (HMA) (ka) and formation of HSA-drug conjugate (kc) were determined. RESULTS: Formation of HSA-drug conjugate was observed only for drugs containing one thiol group. In compound IV, the plots of ka and kc against pH were found to be linear. The HSA-drug conjugate was affected by various factors such as pKa, pH, temparture and the microenviroment of Cys34. The increases in ka and kc against pH were mainly due to the increase in mercaptide ion concentration. Further, fatty acid affected the microenviroment of Cys34, which increased HSA-drug formation. CONCLUSIONS: Cys34 located in a crevice on the surface of the protein plays an important role on the formation of HSA-drug conjugate. These results may be useful for elucidating the reaction mechanisms between various proteins and thiol compounds.

Cysteine↗

PubMed1996

Alteration of atrial natriuretic peptide and brain natriuretic peptide gene expression associated with progression and regression of cardiac hypertrophy in renovascular hypertensive rats.

1. We assessed the changes of atrial natriuretic peptide and brain natriuretic peptide gene expression associated with progression and regression of cardiac hypertrophy in renovascular hypertensive rats (RHR). 2. Two-kidney, one-clip hypertensive rats (6-week-old male Wistar) were made and studied 6 (RHR-1) and 10 weeks (RHR-2) after the procedure. Regression of cardiac hypertrophy was induced by nephrectomy at 6 weeks after constriction, and the nephrectomized rats were maintained further for 4 weeks (nephrectomized rat: NEP). Sham operation was performed, and the rats were studied after 6 (Sham-1) and 10 weeks (Sham-2). Atrial natriuretic peptide and brain natriuretic peptide gene expression in the left ventricle was analysed by Northern blotting. 3. Plasma atrial natriuretic peptide and brain natriuretic peptide were significantly higher in RHR-1 and RHR-2 than in Sham-1, Sham-2 and NEP. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in RHR-1 were approximately 7.2-fold and 1.8-fold higher than those in Sham-1, respectively, and the corresponding levels in RHR-2 were 13.0-fold and 2.4-fold higher than those in Sham-2, respectively. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels of NEP were normalized. Levels of atrial natriuretic peptide and brain natriuretic peptide mRNA were well correlated positively with left ventricular weight/body weight ratios. There was a significant positive correlation between the levels of atrial natriuretic peptide and brain natriuretic peptide mRNA (r = 0.86, P < 0.01). 4. We conclude that the expression of atrial natriuretic peptide and brain natriuretic peptide genes is regulated in accordance with the degree of myocardial hypertrophy and that the augmented expression of these two natriuretic peptides may play an important role in the maintenance of cardiovascular haemodynamics in renovascular hypertension.

Animals↗

PubMed1996

Fulminant hepatic failure caused by ecarazine hydrochloride (a hydralazine derivative).

The cause of fulminant hepatic failure is reported to be unknown in more than half the cases in Japan. We recently reviewed 23 cases of fulminant hepatic failure that had been treated at our hospital. The cause of disease had been regarded as unknown before this study. It was found that seven of these patients had been under ecarazine hydrochloride therapy when they developed fulminant hepatic failure. We examined the reasons why fulminant hepatic failure in these seven patients had not been previously attributed to ecarazine, and found that it could be explained by the following factors: (1) the time from the start of ecarazine therapy to the onset of hepatic failure was long; (2) in all cases, hepatic failure developed more than 10 days after the clinical recognition of hepatitis; and (3) characteristic signs of drug-induced hepatic failure such as a skin rash and positive lymphocytes stimulation test with the drug were absent in all cases. Fulminant hepatic failure in these cases could be characterized by: (1) rapid decrease in serum alanine transaminase (ALT) level after discontinuation of ecarazine, (2) prolonged jaundice despite discontinuation of ecarazine, (3) high incidence of anti-nuclear antibody (ANA) (57%), and (4) histological findings of extensive hepatocellular necrosis ranging from bridging necrosis to massive necrosis. Of the seven patients, four died of fulminant hepatic failure. These four patients had received high doses of ecarazine hydrochloride for prolonged periods. Our data suggest that there may be many cases in which the cause of fulminant hepatic failure or acute hepatitis was not previously determined that can be attributed to long-term drug therapy for chronic diseases.

Adult↗

PubMed1996

Catalytic roles of lysines (K9, K27, K31) in the N-terminal domain in human adenylate kinase by random site-directed mutagenesis.

To elucidate lysine residues in the N-terminal domain of human cytosolic adenylate kinase (hAK1, EC 2.7.4.3), random site-directed mutagenesis of K9, K27, and K31 residues was performed, and six mutants were analyzed by steady-state kinetics. K9 residue may play an important role in catalysis by interacting with AMP2-. K27 and K31 residues appear to play a functional role in catalysis by interacting with MgATP2-. In human AK, the epsilon-amino group in the side chain of these lysine residues would be essential for phosphoryl transfer between MgATP2- and AMP2- during transition state.

Adenosine Monophosphate↗

PubMed1996

Phorbol ester, but not endotoxin, desensitizes mannan-induced glycogenolysis in the perfused rat liver.

Mannan, a ligand for the mannose/N-acetylglucosamine (GlcNAc) receptor, induces suppression of oxygen consumption and increases glucose production in the perfused rat liver, and repeated infusion of mannan causes desensitization of the responses. In this study, we examined whether activation of Kupffer cells by endotoxin and phorbol ester alters the glycogenolytic responses to mannan. Infusion of lipopolysaccharide (LPS, 10 micrograms/ ml) in the perfusate failed to inhibit the responses to mannan. Intravenous administration of LPS (1 mg/kg) 6 and 24 h before perfusion did not desensitize the responses to mannan, suggesting that the responses through mannose/GlcNAc receptors in the liver are retained even after activation of Kupffer cells by LPS. In contrast, prior infusion of phorbol 12-myristate 13-acetate (PMA, 100 nM) in vitro abolished the glycogenolytic responses to subsequently infused mannan, but not that to norepinephrine (100 nM), while prior infusions of 4-alpha-phorbol 12,13-didecanoate (100 nM), A23187 (50 nM), or forskolin (1 microM) had no effect on the mannan-induced responses. H-7, an inhibitor of protein kinase C, reduced the glycogenolytic responses to mannan, while it failed to restore the desensitization. These results suggest that protein kinase C may be involved in the process of glycogenolysis by mannan, but is unlikely to be involved in the homologous desensitization of the responses.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1996

Suppressed apoptotic induction in esophageal squamous cell carcinomas expressing extensive p53 protein.

p53 protein accumulation, thought to be caused by p53 gene mutation, is closely related to poor prognosis of patients with certain types of carcinomas. The progression of esophageal squamous cell carcinoma (SCC) is also strongly suspected to depend on the p53 tumor suppressor gene. Formalin-fixed, paraffin-embedded sections were taken from 25 patients who underwent esophagectomy for SCC. Fourteen patients had no preoperative therapy (control group), while the other 11 patients received preoperative radiotherapy (radiation group). There was no difference in pathological TNM classification between the two groups. These sections were examined by immunostaining with monoclonal antibody PAb 1801 to determine the accumulation of p53 protein, and apoptotic frequency was determined by TdT mediated dUTP-biotin nick end-labeling (TUNEL). In the control group, well to moderately differentiated cases showed a significantly higher AI (apoptotic index which is the number of apoptotic cells among 1000 cancer cells. %0) (51.7+/-83.4) than poorly differentiated cases (AI=1.3+/-1.0) (P<0.05). Similar results were obtained in the radiation group. The former group included 4 cases of p53 grade 4 (p53 protein detected in over 70% of the tumor cells), and the latter included 2. Few apoptotic cells were observed in any of 6 tumor tissues. In each patient, tumor cells with accumulated p53 protein were very rare to be apoptotic. On the other hand, apoptosis was observed in tumor cells without p53 protein accumulation. Spontaneous apoptosis in esophageal SCC can be induced more easily in differentiated than in poorly differentiated cases. This tendency may be enhanced by preoperative radiotherapy. Extensive p53 protein may suppress apoptotic induction in esophageal squamous cell carcinomas.

Adult↗

PubMed1996

The 3' ends of tRNA-derived short interspersed repetitive elements are derived from the 3' ends of long interspersed repetitive elements.

Short interspersed repetitive elements (SINEs) are a type of retroposon, being members of a class of informational molecules that are amplified via cDNA intermediates and flow back into the host genome. In contrast to retroviruses and retrotransposons, SINEs do not encode the enzymes required for their amplification, such as reverse transcriptases, so they are presumed to borrow these enzymes from other sources. In the present study, we isolated a family of long interspersed repetitive elements (LINEs) from the turtle genome. The sequence of this family was found to be very similar to those of the avian CR1 family. To our surprise, the sequence at the 3' end of the LINE in the turtle genome was nearly identical to that of a family of tortoise SINEs. Since CR1-like LINEs are widespread in birds and in many other reptiles, including the turtle, and since the tortoise SINEs are only found in vertical-necked turtles, it seems possible that the sequence at the 3' end of the tortoise SINEs might have been generated by recombination with the CR1-like LINE in a common ancestor of vertical-necked turtles, after the divergence of side-necked turtles. We extended our observations to show that the 3'-end sequences of families of several tRNA-derived SINEs, such as the salmonid HpaI family, the tobacco TS family, and the salmon SmaI family, might have originated from the respective LINEs. Since it appears reasonable that the recognition sites of LINEs for reverse transcriptase are located within their 3'-end sequences, these results provide the basis for a general scheme for the mechanism by which SINEs might acquire retropositional activity. We propose here that tRNA-derived SINEs might have been generated by a recombination event in which a strong-stop DNA with a primer tRNA, which is an intermediate in the replication of certain retroviruses and long terminal repeat retrotransposons, was directly integrated at the 3' end of a LINE.

Alligators and Crocodiles↗

PubMed1996

Steady-state kinetics of Thr35 and Thr39 mutants in human adenylate kinase by site-directed mutagenesis.

Adenylate kinase (AK; EC 2.7.4.3, hAK1) catalyzes the reaction: MgATP(2-)+ AMP2- reversible MgADP-(+) ADP3-. To elucidate the catalytic and structural roles of threonine residues in human AK, Thr35 and Thr39 mutants were analyzed by steady-state kinetics. The K(m) values of T35P and T35Y were not changed for MgATP2- and AMP2-, and the kcat values were decreased by 1/39 compared to those of wild-type AK. Thr35 was suggested to be essential for catalysis. The K(m) values of T39S, T39V and T39P were increased 5.6- to 59.0-fold for AMP2-; however, the kcat values were not reduced. Although the K(m) values of T39F and T39L were unchanged, the kcat values were reduced by more than 1/57. Thr39 appears to play an important role in the binding of AMP2- and to be essential for catalysis. As noted above, a hydroxyl group of the Thr residue in human AK appears to be important.

Adenylate Kinase↗

PubMed1996

Evaluation of aortic distensibility in patients with coronary artery disease by use of cine magnetic resonance.

To evaluate the aortic wall sclerosis in patients with coronary artery disease (CAD), the authors measured the aortic distensibility (AD) at the ascending and descending aorta by using cine magnetic resonance (MR). Cine MR was performed in 15 patients with CAD and 15 normal controls (NCs). Patients with CAD had angiographically significant coronary arterial stenosis and almost normal left ventricular function. Age and sex were matched in the patients with CAD and the NCs. Ascending and descending aortic areas of transverse image were measured in the maximum and minimum frames. AD was calculated from the following formula: (max area - min area)/(min area x pulse pressure). Although systolic and diastolic blood pressures showed no significant differences between patients with CAD and NC, AD was significantly lower in patients with CAD than in the NCs in each transverse section (P < 0.05). In conclusion, it is indicated that aortic wall sclerosis is advanced in patients with CAD.

Aged↗

PubMed1996

Estimation of aortic wall sclerosis in hypertension by use of carotid pulse tracing and cine magnetic resonance.

In order to evaluate aortic wall sclerosis in hypertension, the authors studied the following two parameters of carotid pulse tracing and ascending aortic wall distensibility by using cine magnetic resonance (MR) in 15 age- and sex-matched normal volunteers (NC) (mean age, fifty-four years old) and 15 hypertensive patients (HT) (mean age, fifty-four years old). As the parameters of carotid pulse tracing, they measured the interval from aortic second heart sound to dicrotic notch (A2-DN), and the height from dicrotic notch to top/total height of carotid pulse tracing (b/a ratio). Ascending aortic distensibility was calculated from the following formula: (max area - min area)/(min area x pulse pressure). A2-DN interval was lower in HT than in NC (18.4 +/- 7.9 vs 31.5 +/- 9.2 ms, P < 0.01). The b/a ratio was lower in HT than in NC (0.34 +/- 0.07 vs 0.44 +/- 0.09, P < 0.01). Ascending aortic distensibility was lower in HT than in NC (2.08 +/- 1.37 vs 7.26 +/- 2.51 x 10(-3) mmHg(-1), P < 0.01). In conclusion, ascending aortic wall sclerosis is advanced in hypertension. A2-DN interval and b/a ratio measured by carotid pulse tracing are useful indicators in evaluating the ascending aortic wall distensibility in hypertension.

Aorta↗

PubMed1996

Morphologic and histologic characterization of cardiac myxomas by magnetic resonance imaging.

The purpose of this study was to assess the role of ECG-gated spin-echo (SE) magnetic resonance (MR) images, cine MR images, and gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced MR images for the morphologic and histologic diagnosis of atrial myxomas. Four patients with left atrial myxoma were imaged with a 1.5-T MR imager. The T1-weighted images and the cine MR images were obtained before injection of Gd-DTPA. After the injection of Gd-DTPA, the T1-weighted images were obtained again. Gd-DTPA-enhanced images of the myxomas were histologically compared with the extracted specimens. The tumors were represented more clearly on the cine MR images as low-intensity areas than on the SE images as high-intensity areas. On post-Gd-DTPA images, the 2 tumors were homogeneously enhanced and the other 2 were inhomogeneously enhanced. The locus of enhancement on post-Gd-DTPA images fitted with histologic myxoma or inflammation, and the unenhanced region reflected the necrosis or cystic changes in the specimens, respectively. The morphologic diagnosis of cardiac myxomas by MRI first should be done with SE images, and when the images are unclear, the cine MR images must be supplemented to depict the tumor clearly. Moreover, Gd-DTPA-enhanced MRI could elucidate histologic characteristics in myxomas.

Adult↗