Biomedical subjects

K Hibi

Publications and source records attributed to K Hibi.

At least 55 records · Page 3Linked to original sources

PubMed1997

Relationship between hepatic angiotensinogen mRNA expression and plasma angiotensinogen in patients with chronic hepatitis.

Recent association and linkage studies suggested that angiotensinogen may play an important role in the pathogenasis of essential hypertension. However, there is little information in human concerning a relationship between plasma angiotensinogen levels and the angiotensinogen mRNA expression in the liver, which is the main production site of angiotensinogen. Therefore, the aim of this study was to examine whether hepatic angiotensinogen gene expression determines the level of circulating angiotensinogen and the activity of the renin-angiotensin system in humans. The subjects were 36 patients with chronic hepatitis. Blood was collected from each patients for estimation of plasma renin activity, plasma angiotensinogen and angiotensin II concentrations and several parameters of liver function. In addition, total RNA was isolated from liver biopsy specimens, which were then used to measure angiotensinogen mRNA with Northern blot analysis. Levels of angiotensinogen mRNA were detected easily in the liver biopsy specimens in all of the patients. Hepatic angiotensinogen mRNA levels were positively correlated with plasma angiotensinogen levels (r=0.41, P=0.013). In contrast, hepatic angiotensinogen mRNA levels did not show any significant relationship with plasma renin activity, plasma angiotensin II concentration, histological subgroup of hepatitis, histological activity index and parameters of liver function tests. The present study demonstrated, for the first time, that hepatic angiotensinogen mRNA levels correlated with plasma angiotensinogen concentration in humans.

Adult↗

PubMed1997

Plasma angiotensinogen concentrations in obese patients.

A close relationship between obesity and hypertension has been recognized, and plasma angiotensinogen concentrations (p-AGT) have been reported to correlate with blood pressure (BP). However, little is known about AGT in obese patients with hypertension. To define the role of AGT in obese hypertension, we measured p-AGT in obese patients. The subjects were 42 obese patients diagnosed on the basis of a body mass index (BMI) of more than 25 kg/m2, and 21 sex- and age-matched nonobese patients, whose BMI was less than 25 kg/m2. The hypertensive patients had not previously received antihypertensive drugs. P-AGT (P < .05) and mean BP (P < .0001) was increased in the obese patients as compared with the nonobese patients. Positive correlations were observed between BMI and p-AGT, mean BP and p-AGT, and BMI and mean BP (all P < .05). However, after adjustment for blood pressure, p-AGT was not different between groups, and after adjustment a positive correlation remained only between BMI and mean BP. These results suggested the possible involvement of increased p-AGT in hypertension in obese patients, although this may be a secondary change to hypertension or obesity.

Adult↗

PubMed1997

Distribution of alpha 1B-adrenergic receptor mRNA expression along rat nephron segments.

Although several alpha-adrenergic receptor genes are expressed in the rat kidney, little information is available on their expression in the renal nephron segments. We investigated the distribution of alpha 1B-adrenergic receptor mRNA in rat nephron segments using reverse transcription and polymerase chain reaction (RT-PCR). The nephron segments of six- to eight-week-old male Sprague-Dawley rats were microdissected. Total RNA was prepared by the acid-guanidinium-phenol-chloroform method and used in the following RT-PCR assay. The PCR products were size-fractionated with electrophoresis, visualized with ethidium bromide staining and confirmed by Southern blot analysis. Because the PCR primers spanned an intron, the amplification product of the predicted size was considered to be from alpha 1B-adrenergic receptor cDNA and not from genomic DNA. The PCR products were detected in glomerulus (Glm), proximal convoluted and straight tubules (PCT, PST) and cortical and medullary thick ascending limbs of Henle (CTAL, MTAL). No signals were detected in cortical or medullary collecting ducts (CCD, MCD). Large signals were detected in the PCT, and PST, while small signals were found in the Glm, CTAL and MTAL. The alpha 1B-adrenergic receptor mRNA was detected for the first time in rat Glm, PCT, PST and TAL using RT-PCR. alpha 1BAR mRNA seems to be expressed in the specific sites along the nephron and may play significant roles in renal functions, although the specific physiological effects of the renal alpha 1B-adrenergic receptor are unknown.

Animals↗

PubMed1997

Alternative splicing of the FHIT gene in colorectal cancers.

In the present study, we examined the status of the FHIT gene in 112 colorectal cancer and 137 colorectal adenoma specimens. In a total of 5 specimens (4 colorectal cancers and 1 colorectal adenoma), a common smaller product was detected in addition to the normal size product. This smaller product had lost exon 4, the 5' noncoding region of the FHIT gene, owing to alternative splicing. Moreover, all of the 5 tumors with alternative splicing were located lower on the rectum than the anterior peritoneal reflection.

Acid Anhydride Hydrolases↗

PubMed1997

Modulation of tissue angiotensinogen gene expression in genetically obese hypertensive rats.

Wistar fatty rats (WFR) show obesity and obesity-related features, including hypertension. In this study, we examined the expression of angiotensinogen mRNA in a variety of tissues at different times in WFR and control Wistar lean rats (WLR). WFR were obese and hypertensive at 16 and 24 wk. Plasma renin activity and plasma angiotensinogen concentration showed age-dependent increases in WFR but decreases in WLR. Northern blot analysis showed no significant differences in the levels of hepatic and renal angiotensinogen mRNA between WFR and WLR, and the levels of fat and adrenal angiotensinogen mRNA were lower in WFR than in WLR. On the other hand, the levels of cardiac angiotensinogen mRNA at 16 and 24 wk and those of aortic angiotensinogen mRNA at 16 wk were significantly higher in WFR than in WLR. These results show that the expression of tissue angiotensinogen mRNA is regulated differently in WFR and WLR and indicate that the development of hypertension in WFR is accompanied at least temporally with increases in plasma angiotensinogen concentration as well as in cardiac and aortic angiotensinogen mRNA. Moreover, these results suggest the existence of obesity hypertension-linked and tissue-specific regulation of angiotensinogen gene expression.

Angiotensinogen↗

PubMed1997

Angiotensin-converting enzyme gene I/D polymorphism and carotid plaques in Japanese.

To clarify the role of genetic factors in atherosclerotic plaque formation in the carotid artery and magnetic resonance imaging abnormalities in the brain, we investigated the association of these abnormalities with the angiotensin-converting enzyme (ACE) genotype. One hundred sixty-nine subjects (age, 59.2+/-0.8 years, mean+/-SE) admitted to our hospital for health checkups underwent brain magnetic resonance imaging to evaluate lacunar infarction. B-mode ultrasound examinations of the carotid arteries were performed to detect atherosclerotic plaque. The I/D polymorphism of the ACE gene was determined by the polymerase chain reaction method. Multivariate regression analysis was performed to assess the effects of the following variables on the presence of plaque, mean plaque thickness, and number of plaques: fibrinogen, sex, age, body mass index, mean blood pressure, glycosylated hemoglobin, LDL cholesterol, HDL cholesterol, hematocrit, and the D allele of the ACE gene. The frequency of carotid atherosclerotic plaque was significantly (P=.034) higher in subjects with the D allele than in those without this allele. However, the frequency of lacunar stroke was similar in these groups. A multivariate regression analysis showed that the presence of plaque was independently associated with the D allele (odds ratio=3.27, P=.016). However, mean plaque thickness and the number of plaques were not associated with the D allele. The D allele of the ACE gene may be involved in the presence of carotid plaque but not in the extent of this plaque or asymptomatic lacunar stroke in Japanese subjects.

Aged↗

PubMed1997

Angiotensin-converting enzyme gene polymorphism adds risk for the severity of coronary atherosclerosis in smokers.

To investigate the relation between the angiotensin-converting enzyme (ACE) gene polymorphism and acute coronary syndromes with respect to environmental factors, we analyzed the association of genotype with the coronary angiographic findings of patients with acute myocardial infarction or unstable angina pectoris, and we examined the linkage of each genotype with established risk factors for coronary artery disease. We determined the ACE genotype in 152 Japanese patients with acute coronary syndromes and 399 healthy individuals. The genotype distributions were not different between the two groups (P=.74, chi2 test). In the former group, coronary angiograms were evaluated by criteria based on the number of diseased vessels, the number of stenotic lesions (> or = 50%), and the relative abnormal arterial portion (extent index). Although the number of stenotic lesions was higher in patients with the DD genotype than in those with the ID or II genotype (P=.006), there were no differences in the number of diseased vessels or the extent index. When only smokers were analyzed, the number of diseased vessels (P=.032), number of stenotic lesions (P=.003), and extent index (P=.019) were all higher in patients with the DD genotype than in those with the ID or II genotype. In contrast, these differences in the respective parameters did not exist in nonsmokers. The results indicate smoking-associated effects of the ACE genotype on the severity of coronary atherosclerosis.

Coronary Artery Disease↗

PubMed1997

Essential hypertension and 5' upstream core promoter region of human angiotensinogen gene.

The angiotensinogen (AGT) gene M235T variant is associated with essential hypertension and elevated plasma AGT concentrations, although the underlying mechanisms are unknown. Recent studies have suggested that AGCE 1 (human AGT gene core promoter element 1) located in the 5' upstream core promoter region (position -25 to -1) of the human AGT gene has an important part in the expression of AGT mRNA by binding with transcription factor AGCF 1 (human AGT gene core promoter element binding factor 1), and a mutation at -20 from adenine to cytosine (A-20C) increases the level of expression of this transcript. We therefore examined subjects with this mutation to study the association with increased plasma AGT concentrations and with essential hypertension. One hundred eighty-eight subjects receiving no antihypertensive medication were examined with regard to the correlation between A-20C and plasma AGT concentrations, and 234 subjects were studied with respect to the association between A-20C and essential hypertension. A-20C was determined by polymerase chain reaction-restriction fragment length polymorphism analysis with EcoOR 109I. Multiple regression analysis showed a weak but significant correlation between A-20C and plasma AGT concentrations (P=.047) and essential hypertension (P=.049). The results suggest that A-20C may underlie the increase in plasma AGT concentrations and be involved in the development of essential hypertension.

Angiotensinogen↗

PubMed1997

Angiotensin-converting enzyme gene insertion/deletion polymorphism and left ventricular hypertrophy in hemodialysis patients.

The relationships between angiotensin-converting enzyme (ACE) gene insertion (I) / deletion (D) polymorphism and left ventricular hypertrophy induced by hypertension or idiopathic hypertrophic cardiomyopathy have been studied. However, little is known about the association between this polymorphism and left ventricular hypertrophy induced by volume overload. The relationship between left ventricular hypertrophy and the ACE gene I/D polymorphism was examined in 80 maintenance hemodialysis patients (mean age: 60.1+/-1.4 years). Multivariate regression analysis showed that the left ventricular mass index calculated by M-mode echocardiography was associated with serum creatinine (p = 0.040), male gender (p = 0.027), antihypertensive drug treatment (p = 0.026), weight gain between hemodialysis (p = 0.018) and mean blood pressure after hemodialysis (p=0.010), but not with ACE I/D genotype (p = 0.69). These findings suggest that although hemodialysis patients seem to be under volume overload, ACE genotype may not be involved in their left ventricular hypertrophy. Hypertension and other factors related to renal failure are involved in the left ventricular hypertrophy in chronic hemodialysis patients.

Adult↗

PubMed1997

[Diagnosis of local recurrence of colorectal cancer, using PET and immunoscintigraphy by means of 131I or 111In anti-CEA monoclonal antibody].

The accurate and early diagnosis of the tumor in the point of the size, the location, the depth of invasion of other organs or the stages of the recurrent cancer became much more important than before, not only for the selection of the treatment method but also for the decision of the quality of the operation for preserving the function as much as possible for the quality of the life of the patient. The usefulness of positron emission tomography (PET) and immunoscintigraphy by means of 131I or 111In anti-CEA onoclonal antibody for the diagnosis of the recurrent colorectal cancer had been confirmed in clinical use of colorectal cancers. No adverse effect of this monoclonal anti-body of the mouse was seen in this studies. The differential absorption ratio (DAR) was useful indicator in PET-imaging to differentiate the true tumor tissue from the scar tissue or granulation-tissue around the tumor. Even though the imaging, structure of PET is inferior to those of CT or MRI, the imaging of PET reflects the biological character of tumor, itself and makes the more accurate diagnosis possibly by combined use with regular CT and MRI.

Adult↗

PubMed1997

Analysis of molecular heterogeneity of Dahl/Iwai salt-sensitive rats and salt-resistant rats.

Molecular evidence, using DNA fingerprint analyses, of extensive genetic heterogeneity between spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and even within some of the WKY colonies has been reported. Thus we investigated the genetic relations between Dahl S and R rats newly inbred by Dr. Iwai. Genomic DNA was isolated from the liver of four Dahl S and four Dahl R rats, digested with the restriction enzyme HinfI or AluI, and separated in 1.2% agarose gel by electrophoresis. Then, DNA fingerprinting was performed by Southern blot analysis using the human myoglobin 33.6 minisatellite probe. Bands were detected in an alkaline phosphatase reaction system. Within the same strains, there was no heterogeneity of these fingerprinting patterns. The S and R rats shared 82% of the bands in the HinfI-digested DNA and 93% of those in the AluI-digested DNA. These shared values were much greater than the reported value (54%) between SHR and WKY from Charles River Laboratories. These newly inbred Dahl S and R rats may be appropriate, although still limited, experimental animals for investigating the pathophysiology of salt-sensitive hypertension.

Animals↗

PubMed1997

Enhanced cellular proliferation and p53 accumulation in gastric mucosa chronically infected with Helicobacter pylori.

This study evaluated whether the increased risk of development of gastric carcinoma due to chronic Helicobacter pylori infection could be linked with elevated cell proliferative activity and expression of p53 and bcl-2. Forty-eight patients undergoing therapy for H pylori-positive gastroduodenal ulcers were separated into not eradicated (NE; n = 23) and eradicated (E; n = 25) groups 6 months after the treatment. Serum pepsinogen (PG) I:II ratios and histologic changes in the gastric corpus and the antrum, assessed according to the modified Sydney System, as well as epithelial cell proliferation (mitosis, Ki67, and proliferating cell nuclear antigen [PCNA]), and expression of oncoproteins (p53 and bcl-2) were examined before and at 3 months and 6 months after treatment for H pylori. Chronic persistent H pylori infection was associated with a low PG I:II ratio, increased inflammation and activity score, and elevated cell proliferation, as evidenced by the Ki67 and PCNA labeling indexes and the mitotic index in the NE group. Scattered accumulation of p53 protein continued to be observed in the NE group after treatment but was significantly decreased in the E group. We conclude that persistent H pylori infection causes gastritis, with epithelial degeneration and regeneration that result in accentuation of epithelial cell proliferation and accumulation of p53 protein, presumably heightening the genetic instability consistent with the development of carcinoma.

Adult↗

PubMed1997

[Findings of genetic changes in small intestinal carcinomas].

There is now good evidence that a series of genetic lesions in both dominant oncogenes and tumor suppressor genes are involved in the pathogenesis of human digestive tract carcinomas. Small intestinal carcinomas are very rare, accounting for only about 0.19% of all primary gastrointestinal malignant tumors in Japan, so there are few reports investigating genetic changes of small intestinal carcinoma. We analyzed 3 microsatellite loci and the status of K-ras and p53 genes isolated from tumors and surrounding normal tissue samples obtained during surgery. The polymerase chain reaction (PCR) technique used frequent genetic instability to assess differences between tumor and matched DNAs. Replication errors (RERs) were observed in 3 of the 29 cases (10%) of gastric carcinoma and in 11 of the 72 cases (15%) of colorectal carcinoma. None of the 13 (0%) esophageal carcinoma cases showed any RER, but 5 of 11 cases of small intestinal carcinoma (45%) had RERs, reflecting a significantly high incidence. None of the 11 small intestinal carcinoma cases exhibited K-ras gene mutations. Of 7 case amplified successfully by polymerase chain reaction (PCR) in exon 5-8 loci in p53 gene, 2 exhibited abnormally migrated bands in polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. It is thus clear that the genetic carcinogenesis in the small intestine is different from other parts of the digestive tract. These results suggest that genetic instability plays an important role in the pathogenesis of small intestinal carcinomas.

Adenocarcinoma↗

PubMed1997

[A case of mitochondrial cardiomyopathy with heart failure, sick sinus syndrome and diabetes mellitus: mitochondrial DNA adenine-to-guanine transition at 3243 of mitochondrial tRNA(LEU)(UUR) gene].

A 42-year-old woman with diabetes mellitus lost consciousness and was transferred to the Yokohama City University Hospital. Blood chemistry findings indicated low blood sugar levels and chest X-ray examination revealed cardiomegaly and bilateral pleural effusions. These clinical abnormalities were corrected by treatment with glucose, diuretics, angiotensin converting enzyme inhibitor and digitalis. Cardiological laboratory examinations were performed after admission. Electrocardiography revealed first degree atrioventricular block and incomplete right bundle branch block. Ultrasonography showed lower grade of ejection fraction and diffuse hypokinesis of the cardiac wall. After admission, sinus arrest suddenly occurred. The diagnosis was sick sinus syndrome. Scintigraphy using iodine-123 betamethyl-p-iodophenyl-pentadecanoic acid showed abnormal mottled defects. Coronary angiography found no significant stenosis of the coronary artery. Electron microscopy showed abnormally shaped mitochondrial accumulations in an endomyocardial biopsy specimen. Mitochondrial DNA amplification by polymerase chain reaction followed by restriction enzyme Apa I digestion revealed adenine-to-guanine transition at 3243 of the mitochondrial tRNA(LEU)(UUR) gene.

Adult↗

PubMed1997

Regulation of cardiac angiotensinogen mRNA in vivo and in vitro.

In this study, to investigate the mechanism of hypertension-associated induction of cardiac angiotensinogen in vivo and in vitro, we studied the regulation of angiotensinogen mRNA in the hearts of genetically hypertensive rats and in the rat cardiomyocytes. Levels of cardiac angiotensinogen mRNA were significantly increased in the hypertensive rats. Steady state mRNA levels for angiotensinogen mRNA in cardiomyocytes were increased by angiotensin II and mechanical stretch. The addition of an angiotensin II type 1 receptor antagonist (CV11974) and a transcriptional inhibitor (actinomycin D) completely blocked the induction of angiotensinogen mRNA by angiotensin II in cardiomyocytes. The addition of CV11974 significantly, but not completely, inhibited the induction of angiotensinogen mRNA by mechanical stretch. Actinomycin D completely blocked the induction of angiotensinogen mRNA by stretch in cardiomyocytes. An angiotensin II type 2 receptor antagonist (PD123319) and a protein synthesis inhibitor (cycloheximide) did not affect the induction. These results indicate that the expression of cardiac angiotensinogen mRNA is activated by the development of hypertensive cardiac hypertrophy, and that angiotensin II and mechanical stretch activates the angiotensinogen gene via the angiotensin II type 1 receptor-pathway in cardiomyocytes.

Angiotensinogen↗

PubMed1996

Loss of H19 imprinting in esophageal cancer.

Recent articles have reported that loss of imprinting (LOI) of the endogenous gene H19 was frequently found in lung cancer and chorio-carcinoma, common adulthood cancers. Consequently, we examined the status of genomic imprinting of H19 in 29 esophageal and 48 colorectal cancer specimens, and studied its relation to the expression of H19. Of 12 esophageal cancer specimens heterozygous for the RsaI polymorphism, 6 (50%) exhibited LOI of H19, but none of the 18 colorectal cancer specimens heterozygous for the RsaI polymorphism exhibited LOI of H19. The present study suggests that LOI of H19 may play an important role in the pathogenesis of esophageal cancer. Moreover, H19 expression was frequently abundant in both cancers, and all six esophageal cancers carried LOI with overexpressed H19. Therefore, this overexpression of H19 seems to be an important phenomenon for the development of esophageal and colorectal cancer cells.

Base Sequence↗

PubMed1996

Causes of rectal incontinence after sphincter-preserving operations for rectal cancer.

PURPOSE: Low anterior resection (LAR) is the treatment of choice for middle and high rectal tumors. Even though the rectal sphincter is preserved, some patients show a postoperative loss of rectal continence that may be recovered during follow-up. The purpose of this study was to collect clinical and manometric data before and after LAR to find possible explanations for incontinence. METHODS: Seventeen continent patients with rectal tumors located 10 cm above the anal verge were selected. Manometry was performed before and three months after surgery and when stable frequency of bowel movement was achieved (mean, 7 months). RESULTS: Immediately after the operations, 14 of 17 patients showed a certain degree of incontinence but recovered during follow-up; at the end of the study, only two patients reported minor soiling. Resting and squeeze pressures were moderately reduced after surgery and increased during the following six months without regaining preoperative levels. Rectoanal inhibitory reflex was present in 94.4 percent of patients before the operations and in 25 percent of them after surgery, but it was not associated with incontinence. Rectal sensation was significantly reduced, and its recovery was well correlated with decrease in the frequency of bowel movements. CONCLUSIONS: After LAR, there is a reduction in rectal pressures, suggesting damage to sphincter muscle fibers or innervation. There is also a reduction in rectal sensation related to loss in reservoir capacity, all of which may contribute to incontinence.

Adenocarcinoma↗

PubMed1996

[Neoadjuvant chemotherapy in high-grade advanced gastric cancer with protracted infusional 5-fluorouracil and consecutive low-dose cisplatin].

Twenty-one evaluable patients with primary gastric cancer/local invasion, liver metastasis and peritoneal metastasis were entered in a pilot study of neoadjuvant chemotherapy that used continuous 24-hour infusion 5-FU, 330 mg/m2/day plus low dose CDDP, 6 mg/m2 daily by bolus infusion d1-5. This regimen was repeated for 4 weeks. The overall response rate was 52%, including one complete and ten partial responses. The response rate of differentiated adenocarcinomas was significantly higher than that of poorly differentiated adenocarcinomas. In 15 patients (71%), gastrectomy and lymphadenectomy could be done after this regimen. chemotherapy-induced downstaging from the initial clinical stage was pathologically found in 5 patients who underwent gastrectomy. Toxicity was primarily hematologic. Leukopenia and thrombocytopenia of grade 3 or 4 occurred in 19% and 14% of patients, respectively. The patients were able to take meals during therapy and preserved good quality of life. Median survival time was 11 months for the cancers with liver metastasis and five of the 8 locally advanced cancers are alive 11 months after the therapy. This therapy was effective for patients with high-grade advanced gastric cancer.

Adenocarcinoma↗