Search PubMed⌕ Search

Biomedical subjects

K Imai

Publications and source records attributed to K Imai.

At least 271 records · Page 15Linked to original sources
PubMed2000

Infrequent widespread microsatellite instability in hepatocellular carcinomas.

Widespread or high-frequency microsatellite instability (MSI) due to the defective DNA mismatch repair (MMR) occurs in the majority of hereditary non-polyposis colorectal cancer and a subset of sporadic malignant tumors. The incidence of MSI and underlying DNA MMR defects have been well characterized in gastrointestinal carcinogenesis, but not in hepatocarcinogenesis. To address the issue, we analyzed 55 Japanese hepatocellular carcinomas using several indicators of DNA MMR defects, such as microsatellite analysis, loss of heterozygosity (LOH) and mutation analysis of MMR genes, methylation of hMLH1 promoter, and frameshift mutations of mononucleotide repeat sequences within possible target genes. Mutation of beta2-microglobulin gene, which is presumably involved in MSI-positive tumor cell escape from immune surveillance was also examined. Some of these analyses were also carried out in 9 human liver cancer cell lines. None of the 3 quasi-monomorphic mononucleotide markers sensitive for MSI, BAT26, BAT25, and BAT34C4 presented shortened unstable alleles in any of the carcinoma, cirrhosis, chronic hepatitis tissues, or cell lines. LOH at MMR genes was infrequent (4.4 approximately 7.1%), and no mutations were detected. Neither hMLH1 hypermethylation nor frameshift mutation in the target genes was detected. No mutations were found in beta2-microglobulin. Widespread MSI due to the defective DNA MMR appears to play little if any part in Japanese hepatocarcinogenesis.

Adult↗
PubMed2000

Association between basal serum and leptin levels and changes in abdominal fat distribution during weight loss.

The aim of this study was to evaluate the relationship between changes in abdominal fat areas and the baseline serum leptin levels of Japanese obese women during weight reduction. The study was performed on 100 obese female Japanese volunteers. We measured the BMI and abdominal fat areas (visceral, subcutaneous and total) by magnetic resonance imaging and determined the fasting serum leptin levels before and after a 3 month weight reduction program. We examined whether or not a relationship exists between the baseline leptin levels and the subsequent changes in the abdominal fat areas after a weight reduction program. Multiple linear regression analysis was performed to examine the relationship between the baseline leptin levels and changes in abdominal visceral, subcutaneous, and total fat areas, and demonstrated that the baseline leptin level was a significant predictive factor for changes in the abdominal visceral fat area in both pre and postmenopausal Japanese obese women. We thus concluded the relatively higher baseline leptin levels in Japanese obese women to be associated with a relatively smaller reduction in the amount of abdominal visceral fat after undergoing a weight reduction program.

Abdomen↗
PubMed2000

Increased glutathionyl hemoglobin in diabetes mellitus and hyperlipidemia demonstrated by liquid chromatography/electrospray ionization-mass spectrometry.

BACKGROUND: Erythrocytes contain a large amount of glutathione (GSH), which protects cells from oxidative injury. The purpose of this study was to examine whether hemoglobin (Hb) is modified with glutathione by oxidation of the thiol groups in diabetes mellitus and hyperlipidemia, and to determine the oxygen affinity of glutathionyl Hb. METHODS: Hb samples obtained from patients with type 2 diabetes, patients with hyperlipidemia, and healthy subjects were analyzed by liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS). Glutathionyl Hb was synthesized in vitro by incubating Hb with GSH. The oxygen affinity of glutathionyl Hb was determined by measuring its oxygen dissociation curve. RESULTS: We first demonstrated that the concentration of glutathionyl Hbbeta chains is markedly increased in the diabetic patients and hyperlipidemic patients compared with healthy subjects. The in vitro synthesis of glutathionyl Hb by incubation of Hb with GSH was enhanced by adding H(2)O(2), a reactive oxygen species, into the incubation solution. The glutathionyl Hb prepared in vitro by incubating Hb with GSH showed a marked increase in oxygen affinity and a marked decrease in the Hill coefficient compared with Hb incubated without GSH. CONCLUSIONS: Glutathionyl Hb may be useful as a clinical marker of oxidative stress. The increased concentrations of glutathionyl Hb with high oxygen affinity and low cooperativity in diabetes and hyperlipidemia may lead to reduced tissue oxygen delivery.

Chromatography, Liquid↗
PubMed2000

Mutations of the WASP gene in 10 Japanese patients with Wiskott-Aldrich syndrome and X-linked thrombocytopenia.

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, immunodeficiency, and eczema. X-linked thrombocytopenia (XLT) is a mild form of WAS with isolated thrombocytopenia. Both phenotypes are caused by mutation of the Wiskott-Aldrich syndrome protein (WASP) gene. In this study, we identified mutations of the WASP gene in 10 Japanese patients from 9 unrelated families with WAS/XLT. All XLT patients (n = 3) and one WAS patient had a missense mutation at the PH domain of WASP. Two WAS patients had nonsense mutations. One WAS patient had exon 8 skipping caused by one nucleotide deletion at the acceptor site of intron 7. Three WAS patients had genomic deletions; one of the three had a large genomic deletion involving exons 3 to 7. Codons 45 and 86 seem to be the hot spots of the WASP mutation, because missense mutations in these codons have been reported previously in several WAS/XLT patients in addition to the patients in this report, and patients with the same mutation show a similar clinical phenotype. All other mutations are novel, indicating that the mutations of WASP are heterogeneous. EB virus-transformed cell lines from XLT patients expressed nearly normal amounts of WASP, whereas those from typical WAS patients expressed almost undetectable amounts of WASP. We conclude that the analysis of gene mutation and protein expression of WASP are useful together in assessing the severity of WAS.

Adult↗
PubMed2000

A new concept of tumor promotion by tumor necrosis factor-alpha, and cancer preventive agents (-)-epigallocatechin gallate and green tea--a review.

The study of tumor promotion in rodent carcinogenesis using chemical tumor promoters has revealed various tumor promotion pathways, such as the 12-O-tetradecanoylphorbol-13-acetate (TPA) pathway mediated through activation of protein kinase C, and the okadaic acid pathway mediated through inhibition of protein phosphatases 1 and 2A (PP-1 and PP-2A). We previously demonstrated that application of TPA and okadaic acid induced tumor necrosis factor-alpha (TNF-alpha) gene expression in mouse skin, but that tautomycin, which is an inhibitor of PP-1 and PP-2A and not a tumor promoter on mouse skin, did not. Moreover, we found that TNF-alpha stimulated transformation of BALB/3T3 cells initiated with 3-methylcholanthrene 1,000 times stronger than did TPA (Cancer Res. 53, 1982-1985, 1993). This evidence demonstrates a link between the okadaic acid pathway and the endogenous tumor promotion pathway of TNF-alpha. Recently we presented the first evidence that tumor promotion in TNF-alpha(-/-) mice was significantly depressed compared with TNF-alpha(+/+) mice. Thus, in human carcinogenesis, we think that TNF-alpha and other inflammatory cytokines in preneoplastic lesion stimulate tumor promotion and progression of initiated cells as well as premalignant cells. The first part of this paper reports on this TNF-alpha tumor promotion pathway. In the second part, we report a promising screening method for cancer preventive agents, based on evidence that pretreatment with agents such as tamoxifen, sulindac, 1alpha, 25-(OH)2 vitamin D3, quercetin, caffeic acid phenethyl ester, and (-)-epigallocatechin gallate (EGCG) commonly inhibited TNF-alpha release from BALB/3T3 cells induced by okadaic acid. EGCG, the main constituent of Japanese green tea, and green tea itself are acknowledged cancer preventives in Japan, and this paper presents evidence of their effectiveness in both a high-risk group and the general population.

Animals↗
PubMed2000

Sesamin and episesamin induce apoptosis in human lymphoid leukemia Molt 4B cells.

The exposure of human lymphoid leukemia Molt 4B cells to sesamin and episesamin which were isolated from unroasted sesame seed oil and identified by MS, and 1H and 13C-NMR, led to both growth inhibition and the induction of programmed cell death (apoptosis). Morphological change showing apoptotic bodies was observed in the Molt 4B cells treated with sesamin and episesamin. The fragmentations by sesamin and episesamin of DNA to oligonucleosomal-sized fragments that are characteristics of apoptosis were observed to be concentration-dependent, respectively. Moreover, the amount of the DNA fragments in the sesamin-treated cells was increased from 2 days, while that in the episesamin-treated cells was elevated at 3 days after addition of the compounds. These findings suggest that growth inhibitions by sesamin and episesamin of Molt 4B cells result from the induction of apoptosis in the cells.

Antineoplastic Agents↗
PubMed2000

[The studies of hemodynamic changes and liver uptake in a combination of ATP stress test and low workload exercise test on myocardial scintigraphy].

A pharmacological adenosine-tri-phosphoric acid (ATP) stress test has been used in patients who can not perform an enough exercise stress test. However, falling blood pressure during the stress test and increased liver uptake of the tracer are often found in patients undergoing the ATP test. To prevent these phenomena, a combination of ATP stress test and low workload exercise test (ATP & EX) is proposed. The usefulness of this newly developed stress test was elucidated from two viewpoints. Firstly, the changes of hemodynamic parameters were measured in 34 patients: 17 undergoing ATP alone and 17 undergoing ATP & EX. Systolic blood pressure fell from 150 +/- 20 mmHg to 126 +/- 16 mmHg (p < 0.05) for ATP alone. However, it changed from 141 +/- 19 mmHg to 149 +/- 31 mmHg (ns) for ATP & EX. There was a significant fall in systolic blood pressure (> 30 mmHg) in 58.8% for ATP alone and 5.9% for ATP & EX (p < 0.01). Secondly, the ROI count in the liver and heart on an anterior projection image were measured in 38 patients: 11 undergoing ATP alone, 13 undergoing ATP & EX, and 14 undergoing an ergometer exercise test (EX). The ROI count in the liver at 60 minutes after tracer injection were 29.0 +/- 10.7 count/pixel, 21.4 +/- 5.2 count/pixel, 18.3 +/- 4.5 count/pixel for ATP alone, ATP & EX and EX, respectively. The activities for ATP & EX and EX were lower than that for ATP alone (p < 0.05 and p < 0.01). Thus, ATP & EX decreased the rates of the fall of systolic blood pressure and decreased liver uptake of the tracer compared with ATP alone. In conclusion, ATP & EX is a useful stress method for myocardial perfusion scintigraphy in patients who can not perform the enough exercise stress test.

Adenosine Triphosphate↗
PubMed2000

[Transient left ventricular dysfunction is still present one hour after exercise stress test: evaluation by gated SPECT with 99mTc-labeled perfusion agent].

It has been reported that quantitative gated SPECT (QGS) has revealed post-stress dysfunction of the left ventricle (LV) 30 minutes after a stress test. The purpose of this study was to determine whether post-stress dysfunction of LV is still present one hour after an exercise stress test. The subjects comprised 152 patients (124 males and 28 females, mean age 59 +/- 10 years). Exercise stress myocardial scintigraphy was performed using a one-day, stress and rest protocol. 99mTc labeled myocardial perfusion tracer, tetrofosmin, 370 MBq was injected at the end-point of a supine ergometer stress test for stress imaging. ECG gated SPECT was carried out 1 hour after injection. Three hours later, 740 MBq to 1100 MBq of 99mTc labeled myocardial perfusion tracer was injected for rest imaging. ECG gated SPECT was again performed 1 hour after injection. We divided the subjects into four groups according to the severity score of defects on the stress image and the presence or absence of fill-in; normal (NOR, n = 59), myocardial infarct (MI, n = 65), small ischemia (S-IS, n = 13) and large ischemia (L-IS, n = 15). Post-stress dysfunction is defined according to two criteria: 1) rest LVEF--post-stress LVEF > or = 5% and 2) post-stress ESV--rest ESV > or = 5 ml. The frequency of post-stress dysfunction was 3.4%, 9.1%, 23.1% and 40% in NOR, MI, S-IS and L-IS, respectively. Post-stress LV dysfunction was found to be more frequent in the large ischemia group. In conclusion, post-stress dysfunction was present 1 hour after the stress test and was more frequent in the large ischemia group.

Aged↗
PubMed2000

Hydroxyprolylserine derivatives JBP923 and JBP485 exhibit the antihepatitis activities after gastrointestinal absorption in rats.

It has been a desire to develop orally effective therapeutic agents that restore the liver function in chronic injury. Here we demonstrated that trans-4-L-hydroxyprolyl-L-serine (JBP923) and cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485), which was previously isolated from hydrolysate of human placenta, exhibit potent antihepatitis activity after their oral administration. The increase in bilirubin concentration and activities of liver cytosolic enzymes in serum caused by alpha-naphthylisothiocyanate intoxication in rats were significantly countered both after i.v. and oral administration of these dipeptides, whereas glycyrrhizin, which has been used in the treatment of chronic hepatitis, is active only after its i.v. administration. Antihepatitis activity of dipeptides results, at least partially, from their direct effect on hepatocytes because glutamic-oxaloacetic transaminase and lactate dehydrogenase activities in the medium of hepatotoxin-exposed primary cultured hepatocytes were reduced by these compounds. When comparing the plasma concentration-time profile of JBP923 after its i.v., oral, and portal vein injection, it is suggested that JBP923 is almost completely absorbed from gastrointestinal lumen, and hepatic first-pass removal is minor. JBP923 inhibited the proton-dependent transport of glycylsarcosine in brush-border membrane vesicles, suggesting that peptide transport system(s) may recognize JBP923. Thus, these dipeptides are potent antihepatitis reagents that are still active after oral administration and may be useful for clinical applications.

1-Naphthylisothiocyanate↗
PubMed2000

Pheophorbide a, a moiety of chlorophyll a, induces apoptosis in human lymphoid leukemia molt 4B cells.

The exposure of human lymphoid leukemia Molt 4B cells to pheophorbide a (PPB a), a moiety of chlorophyll a, led both to growth inhibition and induction of programmed cell death (apoptosis). The growth inhibition by PPB a was much stronger than that by chlorophyll a. Morphological change showing apoptotic bodies was observed in the Molt 4B cells treated with PPB a. The fragmentation by PPB a of DNA to oligonucleosomal-sized fragments, that are characteristics of apoptosis, was observed to be concentration- and time-dependent. These findings suggest that growth inhibition by PPB a of Molt 4B cells results from the induction of apoptosis and that PPB a, moiety of chlorophyll a, is essential for exertion of antitumor and apoptosis-inducing activity in these cells.

Apoptosis↗
PubMed2000

[Antibody treatment for cancer].

The previous pessimistic view of monoclonal antibodies as cancer therapeutics was largely influenced by the negative results of multiple clinical trials initiated shortly after the introduction of hybridoma technology. Although murine antibodies are of value in cancer therapy, their effectiveness is limited because murine monoclonal antibodies have a short survival time in humans and induce an immune response that neutralizes their therapeutic effect. Furthermore, the responses induced by murine antibodies are limited because they only weakly recruit human effector elements. To circumvent these problems, genetically engineered antibodies were produced which were mouse-human chimeric monoclonal antibodies and humanized antibodies. These antibodies combine the murine variable or hypervariable regions with the human constant or constant and variable framework regions. Numerous published studies demonstrate that erbB-2 oncogene product overexpression is a frequent cause of breast, ovarian, lung, and gastric cancers. Recently, an anti-erbB-2 humanized monoclonal antibody has been generated and used in clinical trials with high clinical response rates. We generated the anti-erbB-2 mouse-human chimeric monoclonal antibody CH401, which was able to kill cancer cells. An analysis of the mechanism of its tumor growth inhibition revealed that the cytotoxicity was induced by apoptosis. This cytotoxic mechanism is not the same a that of other anti-erbB-2 antibodies previously reported.

Animals↗
PubMed2000

[Polyarthralgia as the initial manifestation of isolated ACTH deficiency].

A 57-year-old man, employed as a taxi driver, noticed arthralgia of his fingers beginning in May 1999. He was unable to work due to the arthralgia and the accompanying general malaise and anorexia, and was thus admitted to a local hospital in July 1999. Since a diagnosis of rheumatic disease was suspected due to elevated inflammatory reactions and joint symptoms, he was referred to our hospital in September 1999. Although no joint swelling was observed, severe tenderness was present in both the fingers and wrists. His grasping power had decreased markedly and fever was intermittently observed. All autoantibodies aside from antinuclear antibody were negative. Given that hyponatremia (126 mEq/l) and fasting hypoglycemia were demonstrated, an endocrinological examination, in particular for hypopituitary-adrenal function, was performed. Both plasma and urinary cortisol concentrations were very low, and an associated low concentration of plasma ACTH (6.0 pg/ml) was noted. The ACTH circadian rhythm was absent and there was no response to the administration of corticotropin releasing hormone. All other pituitary hormones were secreted at normal levels and brain MRI revealed a normal appearance of a pituitary gland. Based on these findings, the patient was diagnosed as having isolated ACTH deficiency. Arthralgia and general malaise both improved soon after replacement of glucocorticoid, and CRP levels were normalized. Isolated ACTH deficiency should be considered in the differential diagnosis of patients suffering from polyarthralgia, given that fever and increased inflammatory reactions occasionally develop and that rheumatic symptoms are also present, as in the present case.

Adrenocorticotropic Hormone↗