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Biomedical subjects

K Ishihara

Publications and source records attributed to K Ishihara.

At least 91 records · Page 5Linked to original sources
PubMed2001

Metabolism of ipecac alkaloids cephaeline and emetine by human hepatic microsomal cytochrome P450s, and their inhibitory effects on P450 enzyme activities.

In this study, we identified the metabolites and the CYP forms that are specifically involved in emetine O-demethylation in human liver microsomes, and cleared the inhibitory potential of cephaeline and emetine on the activity of the major drug-metabolizing CYP enzymes. Incubation of emetine with human liver microsomes yielded three metabolites identified by using HPLC by comparison of the retention time with the authentic sample of cephaeline, 9-O-demethylemetine and 10-O-demethylemetine. CYP3A4 and CYP2D6 were able to metabolize emetine to cephaeline and 9-O-demethylemetine, and CYP3A4 also participated in metabolizing emetine to 10-O-demethylemetine. Cephaeline and emetine inhibited probe substrates metabolism. IC50 for cephaeline against CYP2D6 and CYP3A4 were 121 and 1000 microM, respectively. For the emetine, CYP2D6 and CYP3A4 were 80 and 480 microM, respectively. Inhibition constants (Ki) for both compounds on the CYP2D6 and CYP3A4 activities were determined by graphic analysis of Dixon plots at various concentrations. The obtained Ki values of cephaeline for CYP2D6 and CYP3A4 were 54 and 355 microM, respectively, and the values of emetine were 43 and 232 microM, respectively. We concluded that these in vitro inhibitions of cephaeline and emetine would hardly increase plasma concentrations of co-administered drugs in clinical therapy.

Chromatography, High Pressure Liquid↗
PubMed2001

A potential role of bradykinin in angiogenesis and growth of S-180 mouse tumors.

Angiogenesis is an important event in tumor growth. We evaluated the contribution of endogenous bradykinin to tumor-associated angiogenesis and tumor growth using pharmacological approaches in mice bearing sarcoma 180 cells. The weight of implanted tumors increased in parallel with increased hemoglobin contents (a parameter to evaluate angiogenesis) over a 20-day experimental period. Daily administration of bradykinin B2-receptor antagonists, Hoe140 (0.1 and 1 mg/kg per day, local injection) or FR173657 (30 mg/kg per day, p.o.), significantly suppressed the increment in angiogenesis and tumor weight, but a B1-receptor antagonist, desArg10-Hoe140 (1 mg/kgperday), did not. Administration of a plasma kallikrein inhibitor, soybean trypsin inhibitor (3 mg/site per day), significantly suppressed angiogenesis and tumor growth. In contrast, bradykinin-degrading enzyme inhibitors, captopril and phosphoramidon (500 microg/site per day), enhanced angiogenesis and increased tumor weight. Our results suggest that bradykinin, produced by plasma kallikrein or plasma kallikrein-like enzymes, promote tumor-associated angiogenesis and tumor growth in vivo.

Adrenergic beta-2 Receptor Antagonists↗
PubMed2001

Functional glucosylation of kojic acid and daidzein with the Eucalyptus membrane-associated UDP-glucosyltransferase reaction system.

Kojic acid was glucosylated to kojic acid 5- and 7-O-beta-D-glucopyranosides by cultured cells of Eucalyptus perriniana. The glucosylation was also performed effectively by the enzymatic reaction system using membrane-associated UDP-glucosyltransferase from the cells with addition of UDP-glucose. The production of the 5-O-D-glucoside occurred exclusively prior to that of the 7-O-glucoside in both systems. In the same manner, daidzein was converted to daidzin (daidzein 7-O-beta-D-glucopyranoside) by the enzymatic system. Here, we propose methods for the structural modification of phytoestrogen-related substances by enzymatic beta-glucosylation.

Journal Article↗
PubMed2001

Increased energy metabolism and suppressed body fat accumulation in mice by a low concentration of conjugated linoleic acid.

We investigated the dose-effect of the long-term intake of conjugated linoleic acid (CLA) on the energy metabolism and fat accumulation in mice. Five-week-old male Std ddY mice were fed on a diet containing none (control), 0.25%, 0.5% or 1.0% CLA for 4 or 8 weeks. The body weight was lower in the CLA groups than in the control group, and significant differences were detected between the 1.0% CLA group and the control group at both 4 and 8 weeks. The epididymal and perirenal adipose tissue weights were significantly lower in the CLA groups than in the control group. The liver weight and hepatic triglyceride values were higher in the 1.0% CLA group than in the other groups. The metabolic rate was measured after 8 weeks by using a gas analyzer. The oxygen consumption of the mice in the CLA groups was significantly higher than that of the control mice. Since there was a significant effect on the mice supplemented with 0.25% CLA, low concentration of CLA is suggested to suppress the body fat accumulation and increase the energy metabolism.

Adipose Tissue↗
PubMed2001

Capsaicin increases modulation of sympathetic nerve activity in rats: measurement using power spectral analysis of heart rate fluctuations.

We assessed the sympatho-vagal activities of the heart after administration of capsaicin by measuring the power spectral analysis in rats. There were major two frequency components of heart rate variability, which we defined as high (1.0 Hz <, HF) and low (LF, < 1.0 Hz) frequency components. Vagal blockade by atropine abolished the high frequency component, and lowered the amplitude of the low frequency component. On the other hand, under conditions of sympathetic blockade by propranolol, the low frequency component was reduced. Combined vagal and sympathetic blockade abolished all heart rate fluctuations. We analyzed the low and high frequency components by integrating the spectrum for the respective band width. The rats administered capsaicin had a higher heart rate and sympathetic nervous system index (LF/HF) than the control group of rats. These results suggest that power spectral analysis is an effective and noninvasive method for detecting subtle changes in autonomic activity in response to the intake of foods or drugs.

Animals↗
PubMed2001

Cell lineage specificity of newly raised monoclonal antibodies against gastric mucins in normal, metaplastic, and neoplastic human tissues and their application to pathology diagnosis.

The specificity of monoclonal antibodies against gastric mucins (designated as HIK1083, PGM 36, and PGM 37) was studied immunohistochemically in normal, metaplastic, and neoplastic human tissues. These antibodies labeled class III mucin-producing cells identified by paradoxical concanavalin A staining in normal stomach, duodenum (Brunner gland), biliary tract, and main pancreatic duct; in mucinous metaplasia of pancreas and gallbladder; and in adenocarcinomas of stomach (90%), bile duct (80%), gallbladder (100%), pancreas (80%), lung (100% of goblet cell type adenocarcinomas), ovary (67% of mucinous carcinomas), and uterine cervix (100% of adenoma malignum tumors). Normal and neoplastic cells of esophagus, colon, salivary gland, kidney, endometrium, breast, prostate, and liver, as well as normal small intestine, lung, and uterine cervix, were all negative. The antibodies used should be valuable for the detection of class III mucin and class III mucin-producing cells in normal, metaplastic, and neoplastic tissues.

Antibodies, Monoclonal↗
PubMed2001

Effects of inhaled corticosteroid and short courses of oral corticosteroids on bone mineral density in asthmatic patients : a 4-year longitudinal study.

BACKGROUND: It is not certain whether inhaled corticosteroid (ICS) therapy reduces bone mineral density (BMD) in asthmatic patients. In addition, the potential risk of osteoporosis associated with the rescue use of short courses of oral corticosteroids (SC-OCS) is unclear. OBJECTIVE: To evaluate the effect of inhaled beclomethasone dipropionate (BDP) and SC-OCS on BMD in asthmatic patients. DESIGN: A 4-year longitudinal study. METHOD: Lumbar BMD was measured twice by dual-energy x-ray absorptiometry at a mean (+/- SD) interval of 4.2 +/- 0.1 years in 35 asthmatic adults (15 men and 20 postmenopausal women; mean age at the second evaluation, 60.6 +/- 11.5 years) who had been treated with BDP and SC-OCS. RESULTS: The average period of BDP treatment was 7.7 +/- 2.2 years (range, 4.8 to 13.0 years) at the second evaluation. During the study period, the daily dose of BDP was 765 +/- 389 microg (range, 100 to 1,730 microg), and the frequency of SC-OCS was 1.9 +/- 2.7 courses per year (range, 0.0 to 8.9 courses per year). As a whole, lumbar BMD was unchanged during the course of the study, whereas the Z score (ie, the percentage of normal value predicted from age and sex) increased significantly. Changes in BMD and Z scores in patients receiving high doses of BDP (ie, > 1,000 microg/d; n = 9) were not significantly different from those of patients receiving lower doses (ie, 2.5 courses per year; n = 9) showed a significantly greater loss in BMD and Z score compared with those receiving sporadic courses (ie, <or= 2.5 courses per year; n = 26) (p = 0.002 and p = 0.035, respectively). CONCLUSIONS: ICS therapy per se does not affect BMD, whereas frequent SC-OCS may do so.

Absorptiometry, Photon↗
PubMed2001

Expression of cytokines and inducible nitric oxide synthase in inflamed gingival tissue.

BACKGROUND: Periodontopathic bacteria induce inflammation of periodontal tissues. The cytokines and nitric oxide released in periodontal lesions have been reported to play a protective role in bacterial infection and to relate to the process of inflammation. To clarify the relationship between colonization of periodontopathic bacteria and cytokines, we evaluated profiles of inflammatory cytokines, chemokine, anti-inflammatory cytokines, and inducible nitric oxide synthase (iNOS) and colonization by Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans, which are major pathogens of periodontitis. METHODS: mRNA expression of cytokines and iNOS in inflamed and healthy gingival tissue was determined using reverse transcription-polymerase chain reaction (RT-PCR), and the relationship between their profiles and the detection of specific bacteria was analyzed. RESULTS: The relative expression of interleukin (IL)-6 and iNOS mRNAs in periodontal lesions was significantly higher than those in healthy individuals. IL-6 mRNA expression was also significantly higher at bleeding on probing (BOP)-positive sites than at BOP-negative sites. The expressions of IL-1alpha and IL-8 increased, but IL-10 expression decreased at sites where A. actinomycetemcomitans was detected. We found no correlation between the expression of cytokine and iNOS mRNA and infection by P. gingivalis. CONCLUSIONS: The expression of IL-6 may reflect inflammation in gingival tissue, and iNOS may be involved in the inflammatory process in periodontitis. The presence of A. actinomycetemcomitans or P. gingivalis might relate to the different cytokine profiles of IL-1alpha, IL-8, and IL-10.

Actinobacillus Infections↗
PubMed2001

Cloning and characterization of a gene encoding an immunosuppressive factor from Actinobacillus actinomycetemcomitans.

Actinobacillus actinomycetemcomitans is a pathogen of localized juvenile periodontitis and adult periodontitis. Immunomodulating activity is generally thought to be important in colonization by such pathogenic bacteria. Among the proteins possessing these activities, a 14 kDa immunosuppressive factor of A. actinomycetemcomitans has been reported by Kurita-Ochiai and Ochiai (Infect Immun 64: 50-54, 1996). To evaluate this factor, we cloned and characterized the gene encoding it. The immunosuppressive factor was screened from a genomic library of A. actinomycetemcomitans using an oligonucleotide probe based on the amino acid sequence of the factor. The clone obtained, pHI13, contained a 1.5 kbp fragment. The immunosuppressive factor located in its center. Southern blot analysis showed that this factor is common among A. actinomycetemcomitans strains. The open reading frame consisted of 324 bp coding for 107 amino acid residues. The relative molecular mass of the deduced amino acid sequence was calculated to be 11,595. BLAST analysis indicated that the amino acid sequence is highly homologous with those of thioredoxins from Haemophilus influenzae (76.6%), Neisseria meningitidis (67.3%), and Pseudomonas aeruginosa (59.3%). These results suggest that the 14 kDa immunosuppressive factor characterized in this study is a thioredoxin.

Aggregatibacter actinomycetemcomitans↗
PubMed2001

Elevation of blood NAD level after moderate exercise in young women and mice.

We previously reported that the blood NAD levels are decreased by severe exercise, and administration of nicotinamide, a precursor of NAD, improves the endurance capacity of mice. In the present study, we determined whether moderate exercise changes the blood NAD levels in humans and mice. College female students exercised moderately with bike-ergometers. The blood NAD levels elevated after moderate exercise. Mice were forced to swim in a running water pool for 5 min as a moderate exercise, 15 min as a strong exercise, and until exhaustion as a severe exercise (average swimming time was 28.7 min). A 5 min swim gave a result similar to that of moderate exercise by human subjects. However, the blood NAD levels decreased after all-out exercise. The changes in whole blood tryptophan (a precursor of pyridine nucleotides) levels were similar to that in NAD. The glucose levels in whole blood and the non-esterified fatty acid levels in serum decreased according to exercising time. These data are the first demonstration of moderate exercise raising the blood NAD levels in human and mice. Elevation of the blood NAD levels may reflect changes in niacin metabolism that occur in response to exercise.

Adult↗
PubMed2001

A comparison of serum leptin concentrations in obese and normal weight Japanese women with regular menstrual cycle.

Leptin is a protein that is synthesized and secreted from adipose tissue. We examined the changes in serum leptin level during the menstrual cycle in 5 normal and 5 obese Japanese women, and compared the data with those of serum estradiol (E2) and progesterone (P4) concentrations. Serum leptin levels were highly correlated with body mass index (BMI) and percent body fat, being higher in the obese group than in the normal group. In the obese group, serum leptin level increased in the luteal phase in parallel with the rise in the serum E2 level. In the normal group, however, there was no significant change in serum level during the menstrual cycle. These results suggested that the serum leptin levels were influenced by the phase of menstrual cycle, probably through the action of E2, in different ways for obese and non-obese women.

Adult↗
PubMed2001

[Effect of fluticasone propionate at half dose of beclomethasone dipropionate divided twice daily and once daily in asthmatics inhaling beclomethasone dipropionate 800 micrograms daily or more].

We conducted a 12 weeks' single-arm prospective study comparing beclomethasone dipropionate (BDP), 1/2 doses of fluticasone propionate (FP) twice daily and the same dose of FP once daily in 47 asthmatics who had been inhaling BDP 800 mcg daily or more. Peak expiratory flow (PEF), FEV1, a symptom score and a frequency of beta 2 agonist were all significantly better in FP twice daily phase than BDP phase (329 vs. 306 L/min, 1.87 vs. 1.76 L, 3.6 vs. 6.0/week and 2.7 vs. 4.5 puffs/day, respectively). There was no significant difference in these endpoints between FP twice daily phase and FP once daily phase. FP twice daily produced better plumonary function and symptom relief than the double doses of BDP. Furthermore, FP twice daily could, at least in a short-term basis, safely be changed into the same doses of FP once daily.

Administration, Inhalation↗
PubMed2001

[Surgical treatment of hypoplastic left heart syndrome].

Hypoplastic left heart syndrome (HLHS) was previously uniformally fatal within the first month of life. The development of the Norwood stage I operation has afforded new hope to the families of newborn infants with this defect. Recent, modification of the Norwood procedure has improved the surgical results. The one-year survival rate after the Norwood procedure is from 50% to 70% in major institutions. The results of second palliation (hemi-Fontan operation or bidirectional Glenn operation) are nearly acceptable. Recently, fetal echocardiography has allowed early diagnosis of HLHS, and after a prenatal diagnosis of HLHS, couples may be offered termination of the pregnancy. It is necessary to improve the results of the Norwood stage I operation, to save more fetuses and neonates with HLHS.

Humans↗
PubMed2001

[Inhaled corticosteroids: first-line therapy in asthma].

The pathology of asthma has clarified that the inflammatory process in the pulmonary airways of the asthmatic patients determines asthma symptom activity primarily. Among the anti-inflammatory agents currently available to treat asthma, glucocorticoids are the most effective, and the topically active agents, inhaled corticosteroids (ICS) are the most efficient. In Japan, two ICS are commercially available: beclomethasone dipropionate (BDP) and fluticasone propionate(FP). Both agents have been widely used and their clinical efficacy (BDP vs FP at half the microgram dose of the BDP) are largely comparable. In order to bring asthmatic patients maximal benefits of the ICS, enhancing treatment compliance and giving educations (including how to use the ICS) are mandatory. New ICS, which have better drug delivery and be topically more potent, will be available.

Administration, Inhalation↗
PubMed2001

[A promising new treatment strategy for advanced hepatocellular carcinoma--"multi-ablation therapy" consisting of radio-frequency ablation (RFA), microwave coagulation therapy (MCT) and ethanol injection therapy (EIT)].

We introduce a new treatment strategy (multi-ablation therapy) for advanced hepatocellular carcinoma (HCC). The therapy consists of radio-frequency ablation (RFA), microwave coagulation therapy (MCT) and ethanol injection therapy (EIT). We assessed the efficacy of the therapy in 20 patients with advanced HCCs, including 10 patients with stage III and 10 patients with stage IV. The average tumor diameter was 3.6 cm (max: 6.6 cm) and the average tumor number was 3.6 (max: 11). RFA, MCT and EIT were performed in 20, 14 and 9 cases, respectively. A percutaneous, endoscopic and open approach was applied in 2, 11 and 7 cases, respectively. The average number of times treated on initial admission was 1.1. The response rate, calculated by the tumor necrosis effect, was 100%. The cumulative two-year recurrent rate in the treated sites was 33% and the 2-year cumulative survival rate was 90%. Complications were encountered in two patients (liver failure and pyothorax). Multi-ablation therapy provides an excellent prognosis for advanced HCC patients whose condition could not be controlled with conventional therapeutic modalities.

Carcinoma, Hepatocellular↗
PubMed2001

[A case of multiple liver metastases from sigmoid colon cancer effectively treated by hepatic intra-arterial administration of levoforinate and 5-fluorouracil].

A 62-year-old female patient, who was diagnosed with sigmoid colon cancer with multiple liver metastases, was admitted to our hospital. She underwent sigmoidectomy with D3 lymph node dissection on January 31, 2000. In addition to that, she received hepatic intra-arterial infusion of levoforinate (l-LV) 250 mg and 5-fluorouracil (5-FU) 500 mg for combined multiple hepatic metastases starting on postoperative day 14, and these medications were administered over 48 hours once weekly by infuser pump. The tumor diminished by 59% 2 months after the start of administration and further diminished at 4 months. PR was achieved. Cancer metastasis to the cerebellum and metastasis to the lung were detected at month 9 and month 11, respectively, but the liver metastatic tumor continued to diminish in size, ultimately becoming undetectable by CT scan at month 10. Surgery and radiotherapy were performed for the cerebellar metastasis, and intravenous administration of a combination of l-LV and 5-FU was performed systemically for the pulmonary metastatic tumor. At present, the patient receives regular outpatient treatment continuously. To our knowledge, there has been no report on the combination therapy with l-LV and 5-FU through the hepatic artery. Since good antitumor efficacy was demonstrated in the present patient, this case is described in this report together with four other cases of hepatic metastasis from colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[Complete response (CR) in a case of advanced hepatocellular carcinoma by percutaneous multi-ablation therapy].

A 56-year-old male patient was diagnosed with hepatocellular carcinoma by abdominal ultrasonography. The tumor was located in segment 7-1 and was 7 cm in diameter. Two transcatheter arterial chemoembolizations (TACE) were not effective. The patient had experienced more than ten fractures because of fibrous dysplasia of the bone. Laparotomy was very risky, so we decided to perform multi-ablation therapy. This therapy consists of percutaneous radiofrequency ablation (RFA) and percutaneous ethanol injection therapy (PEIT). PEIT was applied to the lesion where extrahepatic the Glisson's capsule was near the tumor. After two sessions with these therapies, the tumor with the surrounding liver parenchyma turned necrotic. A complete response was obtained and the patient has been disease-free for 6 months. We conclude that our multi-ablation therapy is effective for patients with advanced hepatocellular carcinoma who have therapeutic limitations because of some preoperative complications.

Carcinoma, Hepatocellular↗