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Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 703 records · Page 39Linked to original sources
PubMed1997

Shear-stress causes polarized change in cytoplasmic calcium concentration in human umbilical vein endothelial cells (HUVECs).

Using a newly developed, parallel-plate flow-chamber for confocal laser scanning microscopy (CLSM), we studied the distribution and temporal changes in intracellular Ca2+ concentration ([Ca2+]i) in individual HUVECs stimulated by shear-stress. In the presence of ATP, shear-stress (1-10 dyne/cm2) caused a rise in [Ca2+]i, whereas no such response was observed in the absence of ATP or in the presence of Ni2+, a nonspecific, plasma membrane Ca2+ channel blocker. These results suggest that both ATP and Ca2+ influx are essential for the increase in [Ca2+]i in response to shear stress at less than 10 dyne/cm2. Analysis of [Ca2+]i distribution revealed a repetitive intracellular 'Ca2+ wave' originating from the upstream edge of the cell in some populations of HUVECS, which was transmitted to the downstream of the cell. The polarized [Ca2+]i response induced by shear-stress might be integral to polarized cellular reactions such as remodeling of endothelial lining.

Adenosine Triphosphate↗
PubMed1997

Analysis of the cell tropism of HCV by using in vitro HCV-infected human lymphocytes and hepatocytes.

BACKGROUND/METHODS: We recently established two hepatitis C virus (HCV) replication systems, using MT-2, a human T-cell leukemia virus type I-infected human T-cell line, and PH5CH, a non-neoplastic human hepatocyte line immortalized with simian virus 40 large T antigen. These HCV replication systems were used to assess the infective potencies of seven sera containing more than 10(6) HCV genomes per ml obtained from HCV-positive blood donors. RESULTS: The results showed that these sera had different infectivities for MT-2 and PH5CH cells. One of the seven sera, 1B-1, was more infective for MT-2 cells than PH5CH cells, whereas all the sera except serum 1B-1 were more infective for PH5CH cells than for MT-2 cells. Intracellular HCV RNA could be detected at least 30 days after inoculation with three of the sera. These findings suggested that the infective potency of each serum depends on the type of target cells. To further investigate HCV replication in these cells, we examined the hypervariable region 1 (HVR1) populations of HCV recovered from both MT-2 and PH5CH cells at 8 days postinoculation. The results revealed that the shift to limited HVR1 populations from the quasi-species of HVR1 populations in both cells usually occurred within 8 days after virus inoculation. Furthermore, in two of four sera, the predominant HVR1 populations in MT-2 and PH5CH cells appeared to be different. CONCLUSION: These results suggest that HCV exhibits cell tropism.

Amino Acid Sequence↗
PubMed1997

Stimulated jitter measurements in the assessment of recovery after peripheral nerve repair.

The recording of stimulated jitter may offer a highly sensitive, quantitative method for following the recovery of neuromuscular function after peripheral nerve repair. In groups of rats, electrophysiological recording of jitter was carried out on control animals and animals which had had the sciatic nerves divided and repaired 14, 30, 60 and 90 days previously. It was found that values for jitter were highest in the early stages of regeneration and declined with time so that they were within normal limits by 90 days after repair. It is concluded that jitter measurement may be helpful as a test for the postoperative recovery of function in repaired nerves.

Animals↗
PubMed1997

Megakaryocytes derived from CD34-positive cord blood cells produce interleukin-8.

In a serum-free liquid culture, thrombopoietin (TPO) selectively stimulated the growth of megakaryocytic cells from CD34-positive cord blood cells. Using these cultured cells, we investigated cytokine production by human megakaryocytes. Day 10 megakaryocytes (2 x 10(5)) secreted > 1000 pg/ml of interleukin (IL)-8, in contrast to small amounts of IL-1beta and IL-6. A time-course study showed that the IL-8 production of megakaryocytes occurred at the late phase of the culture period. The megakaryocyte-conditioned medium had the chemotactic potential of polymorphonuclear leucocytes, which was abrogated by the addition of anti-IL-8 antibody, suggesting the secretion of biologically active IL-8. The combination of TPO and IL-1alpha was required for a significant augmentation of the IL-8 secretion. Direct evidence for IL-8 synthesis in megakaryocytes was provided by reverse transcription-polymerase chain reaction on purified CD41b+ cells and by the detection of intracellular IL-8 in CD41b+ cells. These results suggest that TPO stimulates not only the proliferation and differentiation of the progenitors capable of megakaryocytic lineage expression but also IL-8 release by the megakaryocytic cells with the aid of IL-1.

Cells, Cultured↗
PubMed1997

Murine forebrain and midbrain crest cells generate different characteristic derivatives in vitro.

Neural crest (NC) is a transient structure that gives rise to various types of tissues. Many NC cells are pluripotent in the sense that their progeny can generate more than one derivative. However, the potentiality to differentiate into certain derivatives, such as cartilage and bone, seems to be specified with respect to the neuraxial levels at which the NC generates. In order to compare the differentiation potentiality of different regions of head NC, the derivatives of forebrain and midbrain mouse NC have been investigated in vitro using explant cultures of neuroepithelial fragments. From morphology and expression of specific markers, the midbrain crest cultures obviously generated earlier and were greater in number of neuronal cells than were the forebrain ones. Moreover, collagen type II positive cells were detected in the midbrain but not in the forebrain crest cultures. Finally, pigment cells were only observed in the forebrain cultures. The results suggest that the forebrain and midbrain crest cells have a different potentiality to differentiate.

Animals↗
PubMed1997

Examining the diagnostic utility of the Fuld cholinergic deficit profile on the Japanese WAIS-R.

The diagnostic utility of the Fuld cholinergic deficit profile (Fuld, 1984) to dementia of the Alzheimer type (DAT) was evaluated on the Japanese version of the WAIS-R. Profiles were calculated for groups of subjects with DAT(n = 236), vascular dementia (n = 29), frontotemporal dementia (n = 22), and hydrocephalic dementia (n = 10). The frequency of positive profile occurrence for the subject groups was as follows: 23/236 for DAT (9.7%), 2/29 (6.9%) for vascular dementia, 2/22 (9.1%) for frontotemporal dementia, and 2/10 (20%) for hydrocephalic dementia. No significant difference in the frequency of positive profile occurrence was revealed across four types of dementia. We conclude from these findings that the Fuld profile lacks the diagnostic utility on the Japanese WAIS-R.

Adult↗
PubMed1997

Transforming growth factor-beta1 suppresses thyrotropin-induced Na+/I- symporter messenger RNA and protein levels in FRTL-5 rat thyroid cells.

Iodide transport into the thyroid catalyzed by the Na+/I- symporter (NIS), is the first and main rate-limiting step in thyroid hormone synthesis. Recently, we have demonstrated that thyrotropin (TSH) increases NIS messenger RNA (mRNA) and protein levels, as well as iodide uptake activity. Although transforming growth factor-beta1 (TGFbeta1) is known to affect thyroid cell function, it is still unclear how TGFbeta1 regulates TSH-stimulated iodide accumulation. Therefore, the effects of TGFbeta1 on TSH-stimulated NIS mRNA and protein levels were examined in FRTL-5 rat thyroid cells by Northern and Western blot analyses, and iodide uptake was assessed. Northern blot analysis revealed that TGFbeta1 suppressed TSH-stimulated NIS mRNA levels in a dose- and time-dependent manner. Western blot analysis demonstrated that TGFbeta1 suppressed TSH-stimulated NIS protein levels. TGFbeta1 also suppressed (Bu)2 cyclic adenosine monophosphate (cAMP)- and forskolin-stimulated NIS mRNA and protein levels, indicating a role for TGFbeta1 downstream of cAMP production. As predicted, TGFbeta1 inhibited TSH-stimulated iodide uptake activity. These results suggest that the inhibitory effect of TGFbeta1 on TSH-stimulated iodide uptake is at least in part due to a suppression of NIS specific transcription. Therefore, TGFbeta1 may act as an autocrine or paracrine local modulator of thyroid hormone synthesis by influencing NIS mRNA levels in the thyroid.

Animals↗
PubMed1997

Papillary adenocarcinoma of the sigmoid colon associated with psammoma bodies and hyaline globules: report of a case.

We report a case of papillary adenocarcinoma of the sigmoid colon with psammoma bodies and intracytoplasmic hyaline globules. The patient was a 59-year-old woman. The tumor showed central ulceration with smooth elevated ridges. Histologically, the tumor was composed of numerous large irregular tubular structures accompanying infolded papillary growth. The tumor cells showed cytoplasmic basophilia and prominent nuclear atypia. Psammomatous-type calcification was scattered in the tumor stroma as well as in the glandular lumina. In addition, intracytoplasmic hyaline globules of various sizes were seen in the neoplastic cells. We propose the name papillary adenocarcinoma associated with psammoma bodies and hyaline globules for this tumor. Accumulation of further cases is needed to clarify the clinical significance of this type of tumor.

Adenocarcinoma, Papillary↗
PubMed1997

Predictive factors for tumor response to systemic chemotherapy in patients with hepatocellular carcinoma.

Chemotherapy is of limited value in the treatment of hepatocellular carcinoma (HCC), since there are no established chemotherapeutic regimens proven to be effective. The aim of the present study was to determine predictive factors for tumor response to systemic chemotherapy in HCC patients. The relationship between patients' characteristics and tumor response was examined in 147 previously untreated HCC patients receiving systemic chemotherapy. Ten patients showed partial response (PR) and none showed complete response (CR). The response rate for all single anticancer agents was less than 10% and the overall response rate was 6.8%. The response rate in patients with unilateral HCC was significantly higher than in those with bilateral HCC. However, there were no responders among patients with a performance status of 2-3, ascites, a tumor occupying more than 50% of the entire liver, tumor thrombus in the main portal trunk or a serum bilirubin level of more than 2.0 mg/dl. There was a close relationship between patients' characteristics and tumor response. It is concluded that patients with fairly advanced HCC and/or poor hepatic reserve should not be given systemic chemotherapy.

Antineoplastic Agents↗
PubMed1997

Evidence for a significant role of gastrin in cysteamine-induced hypersecretion of gastric acid.

Cysteamine has been known to stimulate gastric acid secretion and to induce duodenal ulcers in rats. We investigated the role of gastrin in cysteamine-induced acid hypersecretion in the perfused rat stomach. Intravenous infusion of cysteamine (75 mg/kg/h) resulted in a significant increase in acid secretion, which was accompanied by a marked increase in the plasma gastrin concentration. The cysteamine-induced increase in gastric acid secretion was completely blocked by i.v. injection of anti-gastrin rabbit serum (500 microliters). In addition, i.v. infusion of a CCK-B/gastrin receptor antagonist (L-365,260) (1 mg/kg/h) also suppressed the cysteamine-induced increase in acid secretion. Atropine significantly, but only partially, inhibited the increase. The elevated plasma gastrin levels induced by cysteamine were unaffected by atropine and L-365,260. In conclusion, cysteamine-induced acid hypersecretion is mediated mainly by cysteamine-induced gastrin release and partially by cholinergic factors. Furthermore, gastrin release caused by cysteamine appears to be independent of cholinergic tone.

Animals↗
PubMed1997

Possibility of defense against colorectal tumor by foamy cells.

To investigate the difference between colorectal adenocarcinomas with white spots (foamy cells) and those without white spots, clinically and histopathologically, we examined 112 cases of colorectal adenocarcinomas in this study. Thirty-two cases were diagnosed as submucosal invasive adenocarcinoma and 80 as advanced adenocarcinoma. They were classified into two groups: with white spots and without white spots. Submucosal tumors and squamous epithelial-origin tumors were excluded. In each case we looked for evidence of lymph node and liver metastases. Immunoreactive staining for macrophages, foamy cells, T cells, and B cells was also performed. We found a significant difference in the incidence of lymph node metastasis between the two groups with advanced carcinoma. White spots (foamy cells) were present at some distance from carcinoma cells. We conclude that foamy cells might have a beneficial role. From a histopathological viewpoint they can be considered a possible physical defense wall, an index of immune response activation. Clinically, it is important not to overlook any lesion.

Adenocarcinoma↗
PubMed1997

Genetic analysis of the hepatitis C virus (HCV) genome from HCV-infected human T cells.

We recently established a cell culture system for the replication of hepatitis C virus (HCV) by using a human T cell leukaemia virus type I-infected cell line, MT-2, and showed that the quasi-species of the hypervariable region 1 observed in the original inoculum became homogeneous in MT-2 cells 10 days after inoculation of HCV. In this study, we obtained HCV cDNA clones covering the whole viral genome by RT-nested PCR using RNA from HCV-infected cloned MT-2C cells, which support viral replication more efficiently, at 12 days after inoculation. A total of 41 distinct HCV cDNA clones covering almost the whole viral genome were also isolated from a cDNA library derived from the original inoculum. Molecular evolutional analyses comparing the sequences of the HCV clones obtained from both sources revealed that the HCV populations became homogeneous in more than half of the compared regions. This finding suggests that limited HCV populations are able to replicate in MT-2C cells. In addition, we isolated cDNA clones containing a 3' X-tail sequence, which was recently identified as a bona fide 3' terminus of the HCV genome, in the HCV-infected MT-2C cells and confirmed that the nucleotide sequence of the 3' X-tail was highly conserved, suggesting its implication in HCV replication. Finally, on the basis of the sequences of HCV cDNA clones obtained from HCV-infected MT-2C cells, we determined the entire nucleotide sequence of the HCV genome containing the 3' X-tail as a candidate for an infectious HCV molecular clone.

Base Sequence↗
PubMed1997

Hepatitis C virus in pelvic lymph nodes and female reproductive organs.

Based on epidemiological evidence, hepatitis C virus (HCV) is thought to be involved in the etiology of not only hepatocellular carcinoma, but also lymphoproliferative diseases. In addition, our previous studies using recently developed cell culture systems that support HCV replication have indicated that HCV possesses both hepatotropism and lymphotropism. To determine whether HCV is present in extrahepatic organs, we conducted semi-quantitative reverse transcription-polymerase chain reaction for the 5' non-coding region of the HCV genome in surgical specimens (lymph nodes, ovary, uterus, peripheral blood mononuclear cells [PBMCs] and serum) from three patients with gynecological cancer. We found relatively high HCV genome titers in the lymph nodes, not in the sera, irrespective of various titers in PBMCs. These results suggest that lymph nodes may play an important role in the carrier state and the persistence of HCV infection. Moreover, contrary to expectation, high titers of the HCV genome were observed in the ovaries and the uteri, suggesting the feasibility of mother-to-infant and spouse-to-spouse transmissions of HCV.

Adult↗
PubMed1997

Evidence that expression of a mutated p53 gene attenuates apoptotic cell death in human gastric intestinal-type carcinomas in vivo.

To examine in vivo the validity of the results of experiments in vitro, we analyzed the relationship between p53 gene status and apoptotic cell death of human gastric intestinal-type adenocarcinomas. Surgical specimens were classified into two categories: 18 gastric cancers with nuclear p53 protein (A), and 17 gastric cancers without nuclear p53 protein (B). Polymerase chain reaction-single strand conformation polymorphism disclosed a shifted band that corresponded to a mutation in the p53 gene in 13 cases (72%) in category A and 3 cases (18%) in category B, the frequency being significantly higher in the former (P < 0.05). Apoptotic cells were identified from routinely stained sections and by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The TUNEL index [TI; (the number of TUNEL-positive apoptotic cells/the total number of tumor cells) x 100] was 3.8 +/- 1.4% in category A and 4.9 +/- 1.2% in category B, the value being significantly lower in the former (P < 0.05). The proliferating cell nuclear antigen index, defined similarly to the TI, was 56.4 +/- 16.3% in category A, and it was significantly higher than that in category B (P < 0.05). The immunohistochemically detected expression of p21CIP1/WAP1 did not differ between the two categories, while Bax-positive tumor cells were more frequently detected in category A. These results indicate that (1) expression of a mutated p53 gene attenuates apoptotic cell death of gastric cancer, in accordance with the previous in vitro finding that p53 gene mutation provides a possible selective advantage for tumor cell proliferation, and (2) apoptosis is related not only to expression of p53 and the stage of the cell cycle, but also to p53-independent and cell cycle-independent events.

Adenocarcinoma↗
PubMed1997

Prevalence and phylogenetic analysis of HTLV-I isolates in Cameroon, including those of the Baka Pygmy.

Our previous analysis of an HTLV-I isolate (CMR229) from a Cameroonian Pygmy demonstrated that the isolate is distinct from typical HTLV-Is of the "Central African group," which has a close similarity to HTLV-I-related simian viruses (STLV-I) in Africa. In this study, we analyzed six new HTLV-Is from Cameroon consisting of three isolates from the Pygmy and three from the Bantu to examine further the genetic features of HTLV-I in Cameroon, especially in the Pygmy. A phylogenetic tree based on the long terminal repeats (LTR) region showed that all the new HTLV-Is belong to the Central African group. On the other hand, an env-based analysis of CMR229 confirmed the previous finding derived from LTR-based analysis that CMR229 has a similarity to African STLV-Is, but is distinct from the typical Central African group of HTLV-I. This suggests that multiple interspecies transmissions from non-human primates to humans have occurred in Central Africa, resulting in the presence of two distinct HTLV-I strains in this area. In addition, it seems likely that the Pygmy harbors the heterogeneous HTLV-I strains from which the main HTLV-I population spread into the Bantu.

Base Sequence↗
PubMed1997

Medial temporal structures relate to memory impairment in Alzheimer's disease: an MRI volumetric study.

OBJECTIVES: Memory impairment is not only the earliest clinical symptom but a central and prominent feature throughout the course of Alzheimer's disease. Alzheimer related pathological alterations in the medial temporal structures may account for the memory impairments in patients with Alzheimer's disease. The aim of this study was to elucidate the role of the medial temporal structures in memory impairment caused by Alzheimer's disease. METHODS: Using high resolution MRI and a semiautomated image analysis technique, volumes of the medial temporal structures (amygdaloid complex, hippocampal formation, subiculum, and parahippocampal gyrus) were measured, and correlations between atrophy of each structure and memory dysfunction in patients with Alzheimer's disease were examined. RESULTS: Patients with Alzheimer's disease showed poor performance on verbal and non-verbal memory tests, and MRI volumetry showed a significant volume reduction of the medial temporal lobe structures. Volumes of the amygdaloid complex and of the subiculum correlated with memory performance. Stepwise regression analyses disclosed that the volume of the right amygdaloid complex specifically predicted visual memory function and to some extent verbal memory function, and that the volume of the left subiculum specifically predicted verbal memory function. Atrophy of the hippocampus did not predict severity of memory impairment. CONCLUSIONS: The presence of perihippocampal damage involving the amygdala proper, its surrounding cortex, and the subiculum further increased the severity of memory impairment attributable to hippocampal damage in Alzheimer's disease.

Adult↗
PubMed1997

PDGF-BB decreases systolic blood pressure through an increase in macrovascular compliance in rats.

The cardiovascular roles of platelet-derived growth factor (PDGF) were examined in anesthetized rats by monitoring blood pressure and in isolated blood vessels and heart preparations. Intravenous injection of PDGF-BB lowered blood pressure. The decrease in systolic pressure was greater than that in diastolic pressure, so the pulse pressure decreased. PDGF-AA and -AB, other isoforms of PDGF, did not have any effect on blood pressure. Pretreatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, shortened duration of the hypotensive effect of PDGF-BB. The administration of L-arginine with L-NAME partially prevented the effect of L-NAME. PDGF-BB relaxed aortic rings precontracted with phenylephrine with a 50% effective concentration of 3 ng/ml. In contrast, in isolated mesenteric vascular preparations, the vasodilating activity of PDGF-BB was observed only at a high concentration (>12.5 ng/ml). In isolated heart preparations, PDGF-BB had no effect on the beat rate or contractile activity. These results suggest a new role of PDGF-BB that may contribute to the regulation in circulation through the increase in macrovascular compliance mediated by NO.

Animals↗