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Biomedical subjects

I Shimizu

Publications and source records attributed to I Shimizu.

At least 19 recordsLinked to original sources

Assessment of autonomic nervous activity during gastrointestinal endoscopy: analysis of blood pressure variability by tonometry.

We continuously measured blood pressure by tonometry in 30 patients during endoscopy to determine the influence of upper gastrointestinal endoscopy on cardiac events. Patients were divided into two groups: one group treated with scopolamine butylbromide as premedication (SB group) and another group without premedication (C group). Time- and frequency domain analyses of beat-to-beat systolic blood pressure variability were performed for 128 consecutive beats. For time-domain analysis, we calculated the coefficient of variation of systolic blood pressure (CV(BP)). For the frequency domain analysis, we determined the low-frequency (LF(BP); 0.04-0.15 Hz) and high-frequency (HF(BP); 0.15-0.40 Hz) powers of the variation in systolic blood pressure and the ratio of LF(BP) to HF(BP) (LF(BP)/HF(BP)) during endoscopy. The CV(BP) and HF(BP), indicators of parasympathetic tone, increased in the early phase of endoscopy but decreased significantly in the middle and late phases compared with the pre-endoscopy value. The ratio of LF(BP)/HF(BP), an indicator of indirect sympathetic tone, increased throughout the endoscopic procedure. Moreover, premedication with scopolamine butylbromide prevents the excessive parasympathetic nervous reflex when an endoscope passes through the upper digestive tract and also brings both decreased parasympathetic tone and increased sympathetic tone at the late phase of endoscopic procedure. Our results indicate that gastrointestinal endoscopy induced an autonomic nervous abnormality, which may contribute to the occurrence of cardiac events during endoscopic procedures.

Adult

Expression of type I and type III collagens during the course of dimethylnitrosamine-induced hepatic fibrosis in rats.

AIMS/BACKGROUND: We wished to clarify the mechanisms that account for the increase in hepatic collagen accumulation during hepatic fibrosis. METHODS: The gene expression of type I and type III procollagens and matrix metalloproteinase-1 (MMP-1) was measured by Northern blot analysis; immunolocalization of both types of collagen was estimated by indirect immunohistochemical assay; and the hepatic content of collagen and malondialdehyde (MDA), a product of lipid peroxidation, were assayed in hepatic fibrosis induced in rats with a single dose of dimethylnitrosamine (DMN). RESULTS: During the experimental period, more type I procollagen mRNA was found than type III procollagen mRNA. The immunoreactive intensity of type I collagen was greater in necrotic areas near central veins 3 days after DMN treatment than it was on day 9, whereas the type III collagen immunodeposition for the latter period of the hepatic fibrosis was stronger than it was on day 3. As compared with controls, hepatic collagen content increased significantly after 3 days and continued, increasing gradually, as did type I and III procollagen mRNA levels. On day 14, fibrosis was greatest and both types of procollagen gene expression were at their highest, and type I and III procollagen mRNA levels and hepatic collagen content increased as the dosage of DMN was raised. MMP-1 mRNA levels increased early in hepatic fibrogenesis, and increased on day 14 when DMN dosages were low. Hepatic MDA levels increased rapidly for 3 days after DMN treatment, remaining significantly higher than control values and showing a significant increase even in response to low DMN doses on day 14. CONCLUSIONS: Our results suggested that fibrotic liver collagen content may make its first notable increase due in part to the balance between type I collagen and MMP-1 expression rates. Also, lipid peroxidation may be important in the mechanism of hepatofibrogenesis.

Animals

Suppressive effect of oestradiol on chemical hepatocarcinogenesis in rats.

AIMS: To examine the effects of oestradiol and testosterone on the early carcinogenic changes expressed in rat liver from the diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF), partial hepatectomy (PH) model of hepatocarcinogenesis. METHODS: Preneoplastic liver lesions were evaluated using immunohistochemical analysis of glutathione-S-transferase placental form (GST-P) expression; oestrogen and androgen receptor levels were measured by radioimmunoassay. RESULTS: Oestradiol administration to non-castrated DEN-AAF-PH treated males resulted in a decrease in the area of GST-P positive foci, while testosterone increased the serum oestradiol level and reduced the area. In males, castration alone and castration with oestradiol replacement significantly reduced the GST-P positive area, and increased the hepatic oestrogen receptor level. In DEN-AAF-PH treated females, castration with testosterone replacement was associated with a significant increase in the GST-P positive area and the hepatic androgen receptor level. CONCLUSION: These findings suggest that exogenous and endogenous oestradiol can suppress chemical hepatocarcinogenesis. It appears that oestrogen receptors may be involved in the inhibition of malignant transformation of preneoplastic liver cells, while androgens and androgen receptors are involved in hepatocarcinogenesis.

2-Acetylaminofluorene

Mutations in a hydrophilic part of the core gene of hepatitis C virus in patients with hepatocellular carcinoma in China.

We investigated the association between hepatocellular carcinoma (HCC) and the genomic characteristics of the hepatitis C virus (HCV) isolated from residents of the inshore region of the Yangtze River, an area that has one of the highest incidence of HCC in China. We determined the genomic heterogeneity of HCV, and the sequence divergence of the HCV core gene in individuals with chronic hepatitis and HCC. HCV genotype II was predominant among these isolates, which were homologous to other Chinese and Japanese HCV isolates. The rate of nucleotide substitutions in the core gene was significantly greater for isolates from HCC patients than for those from individuals with chronic hepatitis. The nucleotide substitutions were unevenly scattered along the core gene; a cluster of missense mutations was apparent in the region encoding the second hydrophilic domain of the core protein. The rate of occurrence of missense mutations per nucleotide substitution was significantly greater in this clustering variable region (CVR) of the core gene than in the remaining core gene sequence. These observations suggest that mutations in the CVR may be involved in the pathogenesis of chronic HCV infection during hepatocellular carcinogenesis.

Base Sequence

Implication of myocardial lactate metabolism during coronary artery bypass grafting.

Sixty-six consecutive patients with coronary artery disease were analysed in terms of myocardial lactate extraction during cardiac surgery. Sixteen patients had left main coronary heart disease and 50 were without such disease. Mean (s.d.) lactate extraction during empty beating in patients with and without left main coronary tract disease was -29.8(67)% and 12.0(15.3)%, respectively (P<0.001). No significant differences in lactate extraction were recognized during 15 min of reperfusion. Mean (s.d.) preoperative values of haemoglobin were 11.2(1.0) g/dl and these fell to 6.5(0.9) g/dl in an empty beating state during cardiopulmonary bypass (P<0.001). There was no significant difference between the two groups in preoperative and postoperative left ventricular stroke work index. An empty beating state before aortic clamping could induce unexpected ischaemia in the heart with left main coronary tract disease. A short duration of this ischaemic state does not influence functional recovery; however, exposing the left main coronary artery diseased heart to such a condition for long periods would be dangerous.

Blood Pressure

Detection of different quasispecies of hepatitis C virus core region in cancerous and noncancerous lesions.

The quasispecies of hepatitis C virus (HCV) core region in non-cancerous and cancerous hepatocellular carcinoma (HCC) lesions, respectively, of 7 patients with hepatocellular carcinoma were studied. Multiple fluorescence based-polymerase chain reaction (PCR)-single strand conformation polymorphism exhibited a different set and a larger number of quasispecies in cancerous portions than those in non-cancerous portions. DNA sequencing of PCR-amplified core region substantiated an accumulation of nucleotide substitutions, and a greater number of quasispecies in cancerous portions than those in non-cancerous portions. The deduced amino acid sequences disclosed that at the peptide position 45, Ser is dominant in non-cancerous lesions, and Gly in cancerous lesions, respectively. Thus, HCV in hepatocellular carcinoma includes a large number of specific quasispecies presumably due to their vigorous proliferation. A different set of quasispecies with the amino acid change is presumed to be related to the hepatocarcinogenesis.

Aged

Stimulation of albumin synthesis in rat hepatocytes by ascites from patients with cirrhosis.

Hepatocyte growth factor (HGF), identified in ultrafiltered ascites and plasma from patients with cirrhosis, enhances the DNA synthesis in adult rat hepatocytes cultured at low cell density. This study was carried out to investigate the effect of ascites and plasma from patients with cirrhosis on liver-specific functions such as albumin synthesis in adult rat hepatocytes cultured at confluent-cell density. Ultrafiltered ascites from patients with cirrhosis and its ascitic protein, partially purified by fractionation with ammonium sulfate and gel filtration on Sephadex G-200, stimulated albumin synthesis in a dose-dependent manner in the presence of 10(-8), M dexamethasone. This effect was greater than that of 10(-7) M insulin and similar to that of 10(-7) M dexamethasone, but was additive with that of insulin plus dexamethasone. The molecular weight of the ascitic factor was estimated as 100,000 to 150,000, corresponding to that of HGF purified from cirrhotic ascites. Moreover, the partially purified ascitic factor markedly stimulated DNA and protein synthesis in hepatocytes. These findings suggest that the ascitic factor may act as HGF by stimulating hepatocyte DNA and albumin synthesis in a cell density-dependent manner.

Aged

Uterine artery Doppler velocimetry in relation to trophoblast migration into the myometrium of the placental bed.

OBJECTIVE: To test the hypothesis that an abnormally high resistance in the uterine artery indicates impaired trophoblast migration into the myometrium of the placental bed. METHODS: Doppler velocimetry in the uterine artery was carried out in 43 pregnant women within 7 days before cesarean delivery and placental bed biopsy. A pathologist evaluated the placental bed biopsies histologically. Trophoblast migration was absent in 28 cases (impaired migration group) and present in 15 (migration group). Clinical characteristics were compared between these two groups. RESULTS: There was no significant difference in the mean gestational ages at delivery in the two groups, but those with impaired migration included a higher incidence of small for gestational age infants (46.4 versus 6.7%, P < .01) and a lower mean (+/- standard deviation) birth weight (1622 +/- 528 versus 2287 +/- 748 g, P < .01). The systolic-diastolic ratio (S/D) in the uterine artery was higher in the impaired migration group (2.45 +/- 0.81 versus 1.92 +/- 0.34, P < .05). The absence of migration could be deduced from the S/D of the uterine artery, with a predictive value of 92.3% when we set the cutoff value of the ratio at 2.5. CONCLUSION: The results suggest that abnormal uterine artery flow velocity waveforms may indicate impaired trophoblast migration into the myometrium of the placental bed.

Arteries

[A case of angiosarcoma with renal failure caused by recombinant interleukin-2 (rIL-2) and non-steroid anti-inflammatory drug (NSAID)].

A 77-year-old man was diagnosed to have diabetes. He was hospitalized for appetite loss, weight loss (6 kg/3 months) and right femoral pain. An abnormal shadow was noted on chest X-P. On admission, he was alert and there were no abnormal physical findings except limitation in the range of motion in the right lower extremity. His femoral pain was treated by a non-steroid anti-inflammatory drug (NSAID). Right femoral bone biopsy revealed angiosarcoma and staining for factor VIII, with negative staining for epithelial membrane antigen on enzyme assay. Therefore, he received systemic administration of recombinant interleukin-2 (rIL-2). rIL-2 was administered intravenously twice daily at a dose of 40 x 10(4) JRU. The total dosage of rIL-2 amounted to 1200 x 10(4) JRU, but renal failure deteriorated and he died on the 50th hospital day of his second admission. Combination of rIL-2 and NSAID may cause progression of nephropathy.

Aged

Inhibition of corneal ulceration by tetrapeptidyl hydroxamic acid.

The inhibitory activity of a new peptidyl collagenase inhibitor, FN-439 or tetrapeptidyl hydroxamic acid (H2N-C6H4-CO-Gly-L-Pro-D-Leu-D-Ala-NHOH), was determined against vertebrate collagenases derived from human fibroblast, human polymorphonuclear leukocyte (PMN) and tadpole skin. In addition, the effect of FN-439 in inhibiting corneal ulceration was also investigated with alkali-burned rabbit corneas. FN-439 can block the active site of collagenase, and hydroxamic acid can chelate Zn2+ which is essential for collagenase activity. Furthermore, this compound contains D-amino acids to resist nonspecific host-derived degradative enzymes. In our experiments, corneal ulceration occurred in 5 of the 9 control eyes, but in none of the 9 eyes treated with FN-439 (P < 0.01). The only cellular elements observed at the ulcerated area were PMNs and monocytes. FN-439 appeared to act against PMN collagenase. In addition, we compared the change in the concentration of FN-439 (D-peptide) and the L-form of FN-439 (L-peptide) in aqueous humor aspirated from the rabbit eyes burned with alkali. After incubation for 3 hours, the concentration of the D-peptide was decreased by 3%, while that of the L-peptide was decreased by 60%. FN-439 may be useful for treating noninfectious corneal ulcers because of its potent activity (IC50 = 1 microM) and chemical and biological stabilities.

Animals

Ribosome recycling factor (ribosome releasing factor) is essential for bacterial growth.

Ribosome releasing factor, product of the frr gene in Escherichia coli, is responsible for dissociation of ribosomes from mRNA after the termination of translation. It functions to "recycle" ribosomes and is renamed ribosome recycling factor in this paper. An E. coli strain was constructed (MC1061-2), which carried frame-shifted frr in the chromosome and wild-type frr on a temperature-sensitive plasmid. MC1061-2 is temperature-sensitive in its growth and does not segregate its frr-carrying plasmid under the plasmid incompatibility pressure. In contrast, isogenic E. coli carrying wild-type frr in the chromosome and mutated frr on the temperature-sensitive plasmid is not temperature-sensitive in its growth and segregates its plasmid from incompatible plasmids. All spontaneously formed thermoresistant colonies derived from MC1061-2 carried wild-type frr that resided either in the bacterial chromosome by re-exchange or in the plasmid, which became temperature-resistant. These observations establish that frr is an essential gene for cell growth.

Bacterial Proteins

Chronic nicotine intake decelerates aging of nigrostriatal dopaminergic neurons.

We have evaluated the effect of chronic nicotine intake on the age-associated loss of nigrostriatal dopaminergic neurons. The striatal density of dopamine (D1 and D2) receptors and DA-uptake sites decreased with age. Concomitant with these changes was a pronounced loss of many behavioral functions associated, at least in part, with dopaminergic neurotransmission. Chronic oral intake of nicotine resulted in partial restoration of the loss of receptors as well as behavioral performances. The results suggest that low doses of nicotine could have beneficial effects during aging.

Aging

Does cyclo(His-Pro) act like amphetamine?

In many pharmacologic tests, cyclo(His-Pro) (CHP) appears to act like a dopaminergic agonist and augments the actions of amphetamine (AMP). Therefore, to determine whether CHP is an AMP-like peptide, a comparison between CHP and AMP was made using four separate tests known to be AMP-responsive. These include, food intake, locomotor activity, dopamine uptake and modulation of binding sites for amphetamine and mazindol. A decrease in food intake and increase in spontaneous locomotor activity and stereotypy was observed after peripheral administration of amphetamine but not CHP. Chronic CHP administration resulted into a decrease in striatal amphetamine - and increase in mazindol-binding sites; in contrast, chronic amphetamine decreased both amphetamine - and mazindol-binding sites. These results show a clear dissociation between CHP and AMP suggesting that CHP is not an amphetamine-like peptide.

Animals

Reduced content and preserved translocation of glucose transporter (GLUT 4) in white adipose tissue of obese mice.

We investigated glucose transporters (GLUT 1 and GLUT 4) in subcellular membrane fractions of white adipose tissue (WAT) of insulin-resistant obese aurothioglucose (AuTG)- or monosodium glutamate (MSG)-treated mice. In vivo insulin stimulation (0.75 U/kg, EV) promoted, 10 min later, no significant change on glycemia of both AuTG and MSG obese mice, but control mice showed a decrease of 30% (p < 0.001). Basal GLUT 4 content in WAT of obese mice was reduced by 40% (p < 0.001) when compared to that of nonobese mice. Insulin-stimulated GLUT 4 content was significantly (p < 0.01) higher in plasma membrane fraction and lower in microsomal fraction when compared to respective basal values, in all groups. Although the absolute values of GLUT 4 were lower in membrane fractions of obese mice, the relative changes stimulated by insulin were similar among the groups. No effect of obesity or insulin stimulation was observed upon GLUT 1 content. We conclude that WAT of insulin-resistant obese AuTG- and MSG-treated mice has a decreased GLUT 4, but not GLUT 1, content, and the in vivo insulin-stimulated GLUT 4 translocation is preserved.

Adipose Tissue

Photosensitivity in the circadian hatching rhythm of the carotenoid-depleted silkworm, Bombyx mori.

Silkworms (Bombyx mori) were reared on a carotenoid-deprived artificial diet, and the carotenoid-depleted eggs of the next generation were incubated so that we could observe the effect of the depletion on the circadian rhythm of hatching. The phototactic response curves of newly hatched larvae showed that the visual photosensitivity in ocelli of larvae from the carotenoid-depleted eggs was at least 4 log units lower than that of a carotenoid-rich control group. However, the phase-shift experiment revealed that carotenoid depletion did not reduce the photosensitivity in the hatching rhythm. When the hatching rhythm was generated by exposure to a single light pulse in constant darkness, the first peak in the rhythm of the carotenoid-depleted silkworms occurred significantly earlier than that of the carotenoid-rich group, but the following second peaks of both groups were found at the same time. These results suggest that for the silkworm, carotenoid is not involved in photoreception for the hatching rhythm, but is involved in the timing of hatching.

Animals

Virological features of hepatitis C virus infection in patients with liver diseases in the inshore area of the Yangtze River.

The prevalence, genotypes, coinfection and putative core gene sequence of hepatitis C virus (HCV) were investigated in the inshore area of the Yangtze River, where hepatocellular carcinoma (HCC) is thought to be very common. Most patients with liver diseases were infected with hepatitis B virus (HBV), but the incidence of anti-HCV was very low, being 3.4% in patients with acute hepatitis, and approximately 7% in those with chronic liver diseases. The rate of coinfection with HBV and HCV in patients with HCC was 4.5%, which was similar to that in Shanghai (5.6%), but lower than that in Yangzhou (31.2%), Beijing (26.8%) and Zhejiang (28.6%). Of 124 patients with non-A, non-B (NANB) liver disease, 15 (12.1%) were positive for anti-HCV. HCV genotype analysis in 41 HCV-RNA-positive patients with liver diseases showed that genotype II was dominant (85.4%), followed by genotype III (7.3%) and II+III (7.3%). No genotype I or IV was found. The genome sequences of the HCV putative core gene from two patients with chronic hepatitis were more closely similar to those of previous isolates from Japan and China, than to that of an American isolate. These results suggest that HCV infection is not an important etiological factor for liver diseases, and that the HCV isolates in China are from the same subgroup as those in Japan.

Adult

Prevalence of HCV-antibodies and HCV-RNA in donor blood in Tokushima Prefecture.

The incidence of C100-3 among the blood specimens qualified for transfusion according to the conventional criteria was 1.1%. The incidence of C100-3 in donor blood in Tokushima Prefecture is not significantly different from that reported for all Japan. Of the donors positive for the conventional screening test and C100-3, 73.6% showed high ALT levels. For all antibodies, the incidence of HCV-RNA was very low in the donors positive for a single antibody, but was high in those positive for multiple antibodies. All of the donors showing the 3 antibodies were positive for HCV-RNA. While a test for multiple antibodies is thought to be effective for the screening of HCV, more blood needs to be discarded, having a serious cost-performance problem. The O.D. value for C100-3 and the 2nd antibody seem to be useful reference value for antibody titers.

Adolescent