Biomedical subjects

K Imai

Publications and source records attributed to K Imai.

At least 343 records · Page 19Linked to original sources

PubMed1999

The expression of p73 is increased in lung cancer, independent of p53 gene alteration.

p73 gene, a new p53 homologue, has been identified: it supposedly acts as tumour suppressor gene in neuroblastoma. To clarify whether p73 might be involved in lung carcinogenesis, we examined p73 expression in resected lung cancer and paired normal lung in 60 cases using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). We also examined p73 gene status in three representative cases using Southern blot, and p53 gene alteration in 49 cases using PCR-single-strand conformation polymorphism (PCR-SSCP) and direct sequence. In 87% of the cases (52/60) p73 expression in tumour was more than twice as high as that in paired normal lung tissues, and the difference between p73 expression in tumour and normal lung tissue was significant (P < 0.0001). However, Southern blot analysis revealed that none of the cases showed p73 gene amplification. Compared with clinicopathological characteristics, p73 expression correlates significantly with histological differences and age of patient, independently (P < 0.05). Concerning p53 gene status, 43% (21/49) showed p53 gene alteration, but there was no correlation between p73 overexpression and p53 gene alteration. Our results suggest that need for further functional analysis of the role of p73 in lung carcinogenesis.

Adult↗

PubMed1999

Selective secretion of chemoattractants for haemopoietic progenitor cells by bone marrow endothelial cells: a possible role in homing of haemopoietic progenitor cells to bone marrow.

To elucidate the mechanisms by which haemopoietic progenitor cells lodge in the bone marrow, we examined the secretion of chemoattractants for haemopoietic progenitor cells by bone marrow and lung endothelial cells. The bone marrow endothelial cells, but not lung endothelial cells, secreted chemoattractants for the haemopoietic progenitor cell line, FDCP-2, and normal haemopoietic progenitor cells. Checkerboard analysis demonstrated that the conditioned medium of the bone marrow endothelial cells had chemotactic activity and random motility-stimulating activity. The bone marrow endothelial cells expressed stromal-cell-derived factor-1 (SDF-1) mRNA and produced SDF-1 protein, whereas the lung endothelial cells did not. Adhesion of FDCP-2 cells to the bone marrow endothelial cells was partially inhibited by anti-SDF-1 antibody. These findings suggest that the chemoattractants for haemopoietic progenitor cells including SDF-1 and random motility-stimulating factor(s) selectively secreted by the bone marrow endothelial cells may contribute to the homing of haemopoietic progenitor cells to bone marrow.

Animals↗

PubMed1999

WASP is involved in proliferation and differentiation of human haemopoietic progenitors in vitro.

The 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 investigated the role of WASP in the differentiation of CD34-positive (CD34+) cells isolated from the bone marrow of patients with WAS (n = 5) or with XLT (n = 4). Megakaryocyte colony formation was significantly decreased in patients with WAS when compared with normal controls. The formation of granulocyte-macrophage colonies and erythroid bursts were also decreased in WAS patinets. In contrast, in XLT patients, formation of all these colonies was normal. However, in vitro proplatelet formation of megakaryocytes induced by thrombopoietin was markedly decreased in both XLT and WAS. Electron microscopic examination revealed that megakaryocytes obtained from WAS or XLT patients grown in vitro had abnormal morphologic features, which seemed to be caused by defective actin cytoskeletal organization, including labyrinth-like structures of the demarcation membrane system and deviated distribution of the alpha-granules and demarcation membrane system. These observations indicate that WASP is involved in the proliferation and differentiation of CD34+ haemopoietic progenitor cells probably by its participation in signal transduction and in the regulation of the cytoskeleton.

Blood Platelets↗

PubMed1999

Mechanistic findings of green tea as cancer preventive for humans.

Based on our initial work with green tea, in which repeated topical applications of (-)-epigallocatechin gallate (EGCG), the main green tea polyphenol, inhibited tumor promotion in a two-stage carcinogenesis experiment on mouse skin (Phytother Res 1, 44-47, 1987), numerous scientists have since provided so much additional evidence of the benefits of drinking green tea that it is now an acknowledged cancer preventive in Japan, and will possibly soon be recognized as such in other countries. Our work has so far produced several important results with EGCG and green tea: a wide range of target organs in animal experiments for cancer prevention, wide bioavailability of 3H-EGCG in various organs of mice, delayed cancer onset of patients with a history of consuming over 10 cups of green tea per day, and absence of any severe adverse effects among volunteers who took 15 green tea tablets per day (2.25 g green tea extracts, 337.5 mg EGCG, and 135 mg caffeine) for 6 months. This paper introduces three new findings: 1) EGCG interacted with the phospholipid bilayer membrane resulting in confirmation of the sealing effect of EGCG; 2) EGCG inhibited TNF-alpha gene expression in the cells and TNF-alpha release from the cells; 3) high consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal Stage I and II breast cancer patients, and with increased expression of progesterone and estrogen receptors among postmenopausal ones. These results provide new insights into our understanding of the mechanisms of action of tea polyphenols and green tea extract as a cancer preventive.

Antineoplastic Agents↗

PubMed1999

Flow balance between the left and right cardiac output of an eccentric roller type total artificial heart.

We have made an eccentric roller type total artificial heart (ERTAH). The ERTAH is a positive-displacement device comparable to a DeBakey roller pump. Its left and right outputs are determined by the size of its blood chambers, and the ratio of its left and right output is almost constant. We focused on an interatrial shunt to achieve left-right balance. We have conducted numerical simulation, a mock test, and an acute animal experiment to analyze left-right heart balance during ERTAH operation. Numerical simulation was performed under conditions in which the flow of the left artificial heart was fixed at 6 L/min, the flow of the right artificial heart was varied from 4.8 to 6 L/min, and the interatrial resistance was also varied. The relationship between the interatrial shunt flow rate and the output of the left and right artificial hearts was balanced when the flow of the right artificial heart was at 5.45 L/min. In a mock test, 2 DeBakey roller pumps were connected to the left and right sides of a Donovan mock circulatory system, and an interatrial shunt was created between the inlet ports of the left and right roller pumps. The interatrial resistance of the mock system was varied from 7.7, to 4.3, and to 2.9 mm Hg x min/L when the inner diameter of the interatrial shunt was 6, 8, and 10 mm, respectively. As in the mock test, 2 roller pumps were used to bypass the right and left hearts of a goat weighing 60 kg. The flow rate of the left heart was almost constant (4.7 L/min). The flow of the right heart was approximately 4.1 L/min when the interatrial shunt flow rate was zero. A leading consideration was that the left to left shunt through the bronchial arteries in this goat was approximately 0.6 L/min. In developing the ERTAH, we considered that creating an interatrial shunt between the inlet ports of the ERTAH as well as making a difference between the chamber volumes might be effective in balancing the left-right sides of the artificial heart.

Animals↗

PubMed1999

Persistent infection with chicken anaemia virus and some effects of highly virulent infectious bursal disease virus infection on its persistency.

Chicken anaemia virus (CAV) infectivity and the effect of highly virulent infectious bursal disease virus (hv IBDV) infection on CAV's infectivity were examined in chickens inoculated with CAV or inoculated dually with CAV and hv IBDV. Five chickens inoculated dually with hv IBDV at 35 days old and then with CAV at 40 days old exhibited no clinical signs of disease, but showed atrophic bursae of Fabricius when necropsied 4 weeks later. Upon examining the chickens at 7 days postinoculation (dpi) with CAV, it was found that hv IBDV infection had inhibited production of virus neutralising (VN) antibody to CAV, and that it was possible to recover CAV from plasma of these chickens. Although VN antibody to CAV appeared after 14 dpi, CAV was recovered from blood cells (BC s) at high titres ranging from 10(2.5)to 10(5.5)TCID(50)/0.1 ml, 7 to 28 dpi in IBDV -induced immunosuppressed chickens. In addition, CAV was sporadically recovered, using rectal swabs, from the dually inoculated chickens at low titers, ranging from 10(1.0)to 10(2. 0)TCID(50)/0.1 ml). In contrast, although CAV was recovered from BC s in most of the chickens inoculated with CAV alone, the titers were lower (10(1.0)to 10(2.5)TCID(50)/0.1 ml). No CAV was detected from the rectal swabs of these chickens. The results of virus recovery were confirmed by polymerase chain reaction. This study first examined the persistency of CAV in BC s and the effective enhancement of primary CAV infection as a result of immunosuppression caused by hv IBDV infection.

Anemia↗

PubMed1999

Circadian variation of hepatic glutathione S-transferase activities in the mouse.

1. The circadian variation in glutathione S-transferase (GST) activity was studied in the hepatic cytosolic fraction of the male and female mouse. A circadian variation in GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was observed in the male, the activity being higher in the light phase (07:00-19:00 h) than in the dark phase (19:00-07:00 h) during a day under normal lighting conditions. 2. The circadian variation was only existed from June to October. The difference between the lowest activity (at 01:00 h) and the highest activity (at 13:00 h) was maximum in August. 3. In both the normal and reversed light/dark cycle (lights on 07:00 and 19:00 h, respectively), reduced glutathione (GSH) content was lowest in the middle of the light period and highest in the middle of the dark period and GST activity toward 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) exhibited opposite peaks and troughs. GST activities toward CDNB and 1,2-dichloro-4-nitrobenzene (DCNB) during the normal lighting schedule was higher at 13:00 h than at 01:00 h, but no differences were observed under reversed lighting conditions. 4. A circadian variation in GST activity for CDNB and DCNB was also observed in the female in a similar manner to the male, but the variation in the activity for EPNP was not observed in the female. 5. Thus, the circadian variation of hepatic GST activities in mouse were dependent on the enzyme substrates used, and seemed to be reflected by the difference in each isozyme levels. The daily change in the hepatic GSH levels is also thought involved, at least in part, in the regulation of GST activity.

Animals↗

PubMed1999

Messenger RNA expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human hepatocellular carcinoma.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma is relatively poor because of the high rate of intrahepatic recurrences. We have previously demonstrated an association between enhanced secretion of active matrix metalloproteinases (MMPs; gelatinase A and matrilysin) and early recurrence in hepatocellular carcinoma. The aim of this study was to examine further the relationship between messenger RNA levels of metalloproteinases and their inhibitors and behavior of this carcinoma. METHODS: Messenger RNA expression of gelatinase A, gelatinase B, matrilysin and tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 were analyzed in 30 patients with hepatocellular carcinoma by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The results were contrasted with the clinicopathological data of the patients. RESULTS: Enhanced mRNA expression of gelatinase A, gelatinase B and matrilysin in tumor was observed in 20, 22 and 19 of 30 patients, respectively. Enhanced mRNA expression of gelatinase A or gelatinase B and of matrilysin showed trends toward presence of capsular invasion (P = 0.078) and intrahepatic metastasis (P = 0.064), respectively. Concomitant overexpression of gelatinase A and matrilysin was associated with portal invasion, intrahepatic metastasis and recurrence within the first postoperative year (P < 0.05). A modest increase of mRNA expression of TIMP-1 and TIMP-2 in tumor was observed in half of the patients, but did not correlate with any clinicopathological features. CONCLUSION: Our results suggest that semiquantitative RT-PCR analysis of MMPs may be helpful in disease management of patients with hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

PubMed1999

The available period and kind of exercise for increasing osteo sono assessment index in women.

PURPOSE: The purpose of this study is to determine the optimum period and kind of exercise which are more effective for increasing the calcaneus osteo sono assessment index (OSI) in adolescent women. METHODS: The subjects consisted of 600 female students aged from 19 to 21 studying at the Department of Food and Nutrition at Nakamura Gakuen University. The calcaneus OSI was measured by ultrasonic bone absorptiometry. The factors associated with an increased OSI were determined using piecewise linear regression analyses. RESULTS: Experience in performing impact-loading exercise either in junior high school or high school was found to be a significant predictive factor for increased calcaneus OSI after adjusting for age and weight. Regarding other exercise-related factors such as subjective intensity, frequency, hours at a time, and total duration of exercise, a piecewise liner regression analysis showed that a total duration of over 7 yr and a high subjective intensity of the impact-loading exercise during high school and junior high school periods caused a significant increase in the calcaneus OSI. However, the OSI decreased when the subjective intensity of the impact-loading exercise during the high school period was reported to be "very strenuous." CONCLUSIONS: Impact-loading exercise in junior high school and high school is important for increasing calcaneus OSI; however, impact-loading exercise in high school with a "very strenuous" subjective intensity was also found to possibly decrease the calcaneus OSI.

Adult↗

PubMed1999

Corynebacterium terpenotabidum sp. nov., a bacterium capable of degrading squalene.

The taxonomic status of Arthrobacter sp. Y-11T, which was described as a squalene-degrading bacterium, was investigated by chemotaxonomic and genetic methods. The strain possesses wall chemotype IV, MK-9(H2) as the predominant menaquinone, mycolic acids, and straight-chain, saturated and monounsaturated fatty acids, with considerable amounts of tuberculostearic acid. The DNA G+C content is 67.5 mol%. 16S rRNA gene sequence analysis and quantitative DNA-DNA hybridization experiments provided strong evidence that strain Y-11T represents a new species within the genus Corynebacterium, for which the name Corynebacterium terpenotabidum sp. nov. is proposed. The type strain of C. terpenotabidum is strain Y-11T (= IFO 14764T).

Base Sequence↗

PubMed1999

Risk factors for lung cancer among Northern Thai women: epidemiological, nutritional, serological, and bacteriological surveys of residents in high- and low-incidence areas.

Lung cancer incidence among Northern Thai women is one of the highest in Asia (an annual age-adjusted incidence rate of 37.4 per 100,000), and the incidence rate significantly differs by geographical districts. Therefore, we conducted a comparative study of women living in the Sarapee area, which showed the highest (crude incidence rate, 40.9), and the Chom Tong area, which had one of the lowest incidence rates (8.5) in Chiang Mai Province, despite the two areas' geographical and cultural closeness. The women in this study were either family members of lung cancer patients or their neighbors. To find clues to the etiology of lung cancer, this study used various epidemiological and biochemical approaches: interviewing on lifestyle factors, duplicate meals, chemical examination of drinking water, biochemical analysis of sera, mutagenicity test of urine, and monitoring of fungi and bacteria in the living environment. We found that tobacco smoking (Khiyo, local cigars) was less frequently observed in Sarapee (high incidence), compared with Chom Tong (low incidence), and that the history of chronic benign respiratory diseases was the most distinct event among women in Sarapee, resulting in a significantly increased percentage of those with a history of both benign respiratory diseases and tobacco smoking. This population revealed increased levels of serum tumor necrosis factor (TNF)-alpha, an endogenous tumor promoter. Furthermore, significantly increased urine mutagenicity was found to be closely associated with history of benign respiratory disease in Sarapee. The fungus which was most commonly found in the air inside houses in Sarapee was identified as Microsporum canis. Additionally, significantly increased serum concentrations of a constituent of the fungus were found in Sarapee women, compared with those in Chom Tong. Our results suggest that tobacco (Khiyo) smoking alone may not be able to explain the very high incidence of female lung cancer in Northern Thailand, and that chronic benign respiratory disease, possibly caused by the infection of fungi such as M. canis, is likely to be involved in the etiology of female lung cancer in North Thailand.

Aged↗

PubMed1999

Study on the early-onset variant of benign childhood epilepsy with occipital paroxysms otherwise described as early-onset benign occipital seizure susceptibility syndrome.

PURPOSE: We studied the early-onset variant of benign childhood epilepsy with occipital paroxysms (EVBCEOP) proposed by Panayiotopoulos, to confirm whether his five criteria are sufficient to delineate EVBCEOP as a new epileptic syndrome, as well as to predict a good outcome prospectively at the time of the first examination. SUBJECTS: The subjects were 649 children with localization-related epilepsies (LREs) observed in our hospital for >4 years. METHODS: We applied the International Classification of Epilepsies and Epileptic Syndromes to the 649 patients and identified patients who had EVBCEOP from among those with nonspecific idiopathic LRE. The inclusion criteria were to satisfy all five criteria and all but one criterion (i.e., either ictal vomiting or occipital EEG paroxysms). We were blind as to the outcomes and selected patients who satisfied the following three of the five criteria at the time of the first examination, (a) normal development before the onset, (b) epilepsy onset age between 2 and 8 years, and (c) occipital EEG foci. We attempted to determine whether the outcome can be predicted prospectively, and whether the presence or absence of ictal vomiting affects the prognosis. RESULTS: We identified 19 patients who satisfied all five criteria, 22 who exhibited all but occipital EEG foci, and 21 who exhibited all but ictal vomiting. The incidence of status convulsivus was higher in those with ictal vomiting than in those without ictal vomiting (p < 0.05). Interictal EEG performed every 6 months showed shifting and multiplication of EEG foci in 42 and 52% of all subjects, respectively. We identified 57 patients, 42 (74%) of whom were in remission by age 12 years. The number of patients who experienced remission did not differ significantly between those with (76%, n = 25) and without (72%, n = 32) ictal vomiting (p > 0.05). CONCLUSIONS: Nosologically, EVBCEOP appears to constitute the earliest form of idiopathic epileptic syndrome different from classic BCEOP. However, its clinical spectrum, ranging from the absence of ictal vomiting to a combination of extraoccipital and multifocal EEG foci, is broad, such that further prospective study is expected to reveal the exact prerequisite criteria for determining the border of this epileptic syndrome and for clarifying the clinical spectrum within this syndrome.

Adolescent↗

PubMed1999

Ictal video-EEG recording of three partial seizures in a patient with the benign infantile convulsions associated with mild gastroenteritis.

PURPOSE: In infants, benign convulsions can be triggered by febrile illness or mild diarrhea such as Rotavirus gastroenteritis. The triggering mechanism of these convulsions is still unknown. In spite of several reports concerning clinical features, the ictal EEG recordings were rarely analyzed by a video-EEG monitoring system. To reveal a clue for the triggering mechanism of these convulsions, we analyzed the correlation of clinical manifestations and the EEG discharges during the ictal events and compared with previous reports. METHODS: The ictal EEG of a cluster of three afebrile convulsions associated with mild gastroenteritis was recorded by an EEG closed-circuit TV (EEG-CCTV) monitoring system in a 6-month-old healthy female infant. RESULTS: All seizures began as complex partial seizures (CPSs), which exhibited a motionless stare with or without leftward deviation of both eyes, and evolved to secondarily generalized tonic-clonic seizures (SGTCSs) for approximately 90 s. Each of three ictal discharges began from the right occipital, right centroparietotemporal, and left occipital regions, respectively. CONCLUSIONS: Although initiating sites of ictal discharges of benign infantile convulsions associated with mild gastroenteritis (BICE) were previously reported to be variable among patients, these results indicated that those differ among seizures even in a same infant.

Cerebral Cortex↗

PubMed1999

Left atrial tachycardia after right atrial separation for chronic atrial fibrillation with atrial septal defects.

A right atrial separation procedure was performed for the ablation of chronic atrial fibrillation in four cases, concomitant with the repair of the atrial septal defect. After the operation, chronic atrial fibrillation disappeared in three of them and left atrial tachycardia occurred in the other one. Left atrial tachycardia is an arrhythmia encountered after a right atrial separation procedure.

Aged↗

PubMed1999

CpG motifs in Porphyromonas gingivalis DNA stimulate interleukin-6 expression in human gingival fibroblasts.

We suggest here that Porphyromonas gingivalis DNA may function as a virulence factor in periodontal disease through expression of inflammatory cytokine. The bacterial DNA markedly stimulated in a dose-dependent manner interleukin-6 (IL-6) production by human gingival fibroblasts. The stimulatory action was eliminated by treatment with DNase but not RNase. The stimulatory effect was not observed in the fibroblasts treated with eucaryotic DNAs. The bacterial DNA also stimulated in dose- and treatment time-dependent manners the expression of the IL-6 gene in the cells. In addition, the stimulatory effect was eliminated when the DNA was methylated with CpG motif methylase. Interestingly, a 30-base synthetic oligonucleotide containing the palindromic motif GACGTC could stimulate expression of the IL-6 gene and production of its protein in the cells. Furthermore, the synthetic oligonucleotide-induced expression of this cytokine gene was blocked by pyrrolidine dithiocarbamate and N-acetyl-L-cystine, potent inhibitors of transcriptional factor NF-kappaB. Gel mobility shift assay showed increased binding of NF-kappaB to its consensus sequence in the synthetic oligonucleotide-treated cells. Also, using specific antibody against p50 and p65, which compose NF-kappaB, we showed the consensus sequence-binding proteins to be NF-kappaB. These results are the first to demonstrate that the internal CpG motifs in P. gingivalis DNA stimulate IL-6 expression in human gingival fibroblasts via stimulation of NF-kappaB.

Acetylcysteine↗

PubMed1999

Occurrence of free D-amino acids and aspartate racemases in hyperthermophilic archaea.

The occurrence of free D-amino acids and aspartate racemases in several hyperthermophilic archaea was investigated. Aspartic acid in all the hyperthermophilic archaea was highly racemized. The ratio of D-aspartic acid to total aspartic acid was in the range of 43.0 to 49.1%. The crude extracts of the hyperthermophiles exhibited aspartate racemase activity at 70 degrees C, and aspartate racemase homologous genes in them were identified by PCR. D-Enantiomers of other amino acids (alanine, leucine, phenylalanine, and lysine) in Thermococcus strains were also detected. Some of them might be by-products of aspartate racemase. It is proven that D-amino acids are produced in some hyperthermophilic archaea, although their function is unknown.

Amino Acid Isomerases↗

PubMed1999

Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers.

BACKGROUND/AIM: Matrilysin is one of the matrix metalloproteinases that has a critical role in tumour invasion, and is often expressed in gastrointestinal cancers. The aim of this study was to examine the role of matrilysin in metastasis of human colorectal cancers. PATIENTS (SUBJECTS)/METHODS: The relation between matrilysin expression and Dukes's type was investigated immunohistochemically in 83 surgically resected colorectal cancers, including five with liver metastasis. Moreover, the effects of matrilysin on the in vivo invasive and metastatic potential of colon cancer cells transfected with matrilysin cDNA were examined after subcutaneous injection into SCID mice. RESULTS: In 46% of primary and all of metastatic liver tumours, over 10% of cancer cells were stained positively for matrilysin. The expression of matrilysin correlated significantly with the presence of nodal or distant metastases (p<0.05). In addition, matrilysin transfectants formed invasive tumours and multiple liver metastases in SCID mice, without producing any significant difference in the subcutaneous tumour growth from mock transfectants. Casein zymography showed that the invading and metastasised tumours showed conspicuous matrilysin activity, which correlated with the number of metastatic lesions (p<0.001). CONCLUSIONS: Matrilysin showed a correlation with metastasis in a cohort of 83 colorectal cancer patients and marked metastatic potentiation in human colorectal cancer xenografts, indicating that it may play a critical role in the metastatic pathway of colorectal cancers.

Animals↗

PubMed1999

Serum levels of free and total prostate-specific antigen in males with liver cirrhosis.

OBJECTIVES: We examined the serum concentrations of total and free prostate-specific antigen (PSA) from patients with liver cirrhosis to clarify the influence of liver function on serum PSA levels. METHODS: Serum concentrations of total and free PSA, as well as the free/total PSA ratio were measured in 75 male patients with histologically confirmed liver cirrhosis. As a control group, 75 age-matched healthy blood donors were studied. RESULTS: The serum levels of total PSA in liver cirrhosis patients were significantly lower than those in controls (p = 0.0004). However, the serum free/total PSA ratios in liver cirrhosis patients were significantly higher than those of controls (p < 0.0001). CONCLUSIONS: Our results suggest the absence of an obvious clearance disturbance of serum PSA as a result of severe hepatic dysfunction and offer caution against the utility of standard cutoff values of serum PSA or free/total PSA ratios in the detection and staging of prostate cancer in men with severe liver dysfunction.

Adult↗