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Biomedical subjects

I Ito

Publications and source records attributed to I Ito.

At least 55 records · Page 3Linked to original sources

Cell survival effect of activin against heat shock stress on OVCAR3.

Activin has been known as the hormone protein which regulates either cell proliferation or cell differentiation. Recently, it has also been reported that activin may have cell survival function. In this study, we have investigated, 1) the expression of inhibin subunits and activin receptors (ActRs) in ovarian carcinoma cell line (OVCAR3), 2) the binding property between activin and its receptors under the exposure to stress, and 3) the effect of activin on cell proliferation. All of inhibin subunits and ActR Ia, IIa and IIb mRNA were amplified by RT-PCR in OVCAR3. By Western blot analysis, ActR IIa and IIb proteins were detected. The binding property between activin and ActRs was analyzed with the fixed complex, using chemical cross linker. The bigger molecular weight signals, which had been shown to form the heterotrimeric complex among activin, ActR type I and ActR type II were detected after cross linking. These upper signals were apparently increased by rh-Activin and decreased by rh-Follistatin. Therefore, it was suggested that they were resultant from activin and Act-R complex. OVCAR3 was exposed to the stress (42C, 1 hour heat shock), the protein level of ActR IIa increased and ActR IIb decreased from about 3 h to 24 h after the exposure to the heat stress (HS). On the other hand, the complex between activin and ActR IIa and IIb increased from 3 h after the exposure to HS. To investigate the effect of activin and follistatin on OVCAR3 proliferation after the exposure to HS, we counted the cell number at 96 h after the treatment with activin or follistatin in the condition either with or without HS. Proliferation of the cell in the presence of HS was stimulated by rh-Activin and inhibited by rh-Follistatin. These data suggest that activin might have the function to survive and to proliferate OVCAR3, due to, at least in part the increase in its binding capacity to ActRs through either autocrine or paracrine manner.

Activin Receptors↗

Distribution and development of NMDA receptor activities at hippocampal synapses examined using mice lacking the epsilon1 subunit gene.

The effects of targeted disruption of the gene encoding N-methyl-D-aspartate (NMDA) receptor epsilon1 subunit were examined in hippocampal CA1 pyramidal cell synapses and compared with the effects in the CA3 region. The mutation resulted in the significant reduction of NMDA receptor activities at the synapses in the CA1 stratum oriens, as had been observed in the CA1 stratum radiatum which we reported before. This result was in sharp contrast to our previous observation that in the CA3 region, the epsilon1 mutation suppressed NMDA receptors at the synapses in the stratum radiatum but not in the stratum oriens. It is suggested that the subunit composition of NMDA receptors may not be determined simply by the location within a pyramidal cell, but by other factors such as properties of synaptic inputs. We also examined the postnatal development of long-term potentiation (LTP) in the CA3 region. The development of LTP at the CA3 stratum radiatum synapses closely followed the development of the epsilon1 subunit, and the epsilon1 mutation strongly suppressed this LTP, suggesting that the targeted disruption of the epsilon1 subunit may not be compensated by other epsilon subunits. The LTP at the CA3 stratum oriens synapses was not significantly affected by the mutation at any age.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Diagnosis of measles viral pneumonia in a patient with Hodgkin's disease by reverse transcription-polymerase chain reaction of serum.

We report a case of fatal measles viral pneumonia in a patient with Hodgkin's disease who had no rash. The measles viral cDNA was detected in autopsy tissue from the lung by reverse transcription-polymerase chain reaction. This method was then applied successfully to stored serum. The diagnosis of measles viral pneumonia may be improved by the application of RT-PCR using peripheral blood. Sequence analysis of amplified cDNA suggested the virus infecting this patient was a recent strain, predominantly isolated after 1980. The fatal outcome may have been due to a lack of immune response to the newer strain.

Aged↗

Etiology of community-acquired pneumonia in hospitalized patients: a 3-year prospective study in Japan.

STUDY OBJECTIVE: To compare the etiology of community-acquired pneumonia in Japan and Western countries, the causative pathogens were prospectively investigated in patients requiring hospitalization. DESIGN: Prospective study over a 3-year period. SETTING: A community general hospital in Japan. PATIENTS: Three hundred twenty-six episodes of community-acquired pneumonia in 318 patients admitted to the hospital between July 1994 and June 1997. METHODS: The microbiological diagnosis was based on the results of quantitative sputum culture, blood culture, and other invasive procedures, including transthoracic needle aspiration or bronchoscopic examination. Serologic tests for Mycoplasma pneumoniae, Chlamydia spp, Legionella spp, and viruses were also routinely performed. RESULTS: Causative pathogens were identified in 199 episodes (61%). Streptococcus pneumoniae was the most common pathogen (23%), followed by Haemophilus influenzae (7.4%), M pneumoniae (4.9%), and Klebsiella pneumoniae (4.3%). The Streptococcus milleri group and Chlamydia pneumoniae were detected in 3.7 and 3.4% of the episodes, respectively. Pneumonia due to Legionella spp was recognized in only two patients. CONCLUSIONS: The etiology of community-acquired pneumonia in Japan did not differ markedly when compared with that of Western countries except for the low incidence of Legionella pneumonia. C pneumoniae and the S milleri group, which are emerging or newly recognized pathogens, were also significant causative microorganisms.

Adolescent↗

Pulmonary Mycobacterium avium disease in a young patient with idiopathic CD4+ T lymphocytopenia.

A case of pulmonary Mycobacterium avium (M. avium) disease associated with idiopathic CD4+ T lymphocytopenia is reported. A rapidly growing pulmonary nodule was detected on a chest roentgenogram in a young man. Bronchoscopic examination revealed M. avium infection. Hematological studies showed a low CD4+ cell count in the absence of any identifiable immunodeficiency, including human immunodeficiency virus (HIV) infection. With the combination of chemotherapy and surgery, he had a good clinical outcome. Idiopathic CD4+ T lymphocytopenia should be considered in patients with unexplained opportunistic infection.

Adult↗

Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor epsilon 1 or epsilon 2 subunit.

1. We have explored the effects of targeted disruption of the N-methyl-D-aspartate (NMDA) receptor epsilon 1 or epsilon 2 subunit gene on NMDA receptor-mediated excitatory postsynaptic currents (NMDA EPSCs) and long-term potentiations (LTPs) at the two types of synapse in mouse hippocampal CA3 pyramidal neurons: those formed by the commissural/associational (C/A) and fimbrial (Fim) inputs. 2. Electrophysiological experiments were performed in hippocampal slices prepared from both wild-type and epsilon 1- or epsilon 2-disrupted mice using extracellular and whole-cell patch recording techniques. To assess the epsilon 1, epsilon 2 and zeta 1 subunit expression at cellular levels, we performed non-isotopic in situ hybridization with digoxigenin-labelled cRNA probes. 3. We could record EPSCs in response to the stimulations to either of the C/A and Fim afferents from a single CA3 pyramidal neuron. The epsilon 1, epsilon 2 and zeta 1 subunits were expressed together in individual CA3 neurons. 4. The epsilon 1 subunit disruption selectively reduced NMDA EPSCs and LTP in the C/A-CA3 synapse without significantly affecting those in the Fim-CA3 synapse, whereas the epsilon 2 subunit mutation diminished NMDA EPSCs and LTP in the Fim-CA3 synapse with no appreciable functional modifications in the C/A-CA3 synapse. 5. These results suggest that NMDA receptors with different subunit compositions function within a single CA3 pyramidal cell in a synapse-selective manner.

Animals↗

Thrombophlebitis of the inferior vena cava involving the retroperitoneum with Crohn's disease: MR demonstration.

We present a case of thrombophlebitis of the inferior vena cava (IVC) with Crohn's disease after intestinal perforation and prolonged indwelling of a catheter in the IVC. Magnetic resonance imaging demonstrated abnormal thickening and enhancement of the IVC wall. In addition, IVC thrombus formation was shown. The abnormal enhancement extended from the wall in the pericaval tissue and into the retroperitoneum, and regressed as the Crohn's disease subsided.

Adult↗

Effects of growth hormone and insulin-like growth factor-1 on protein metabolism, gut morphology, and cell-mediated immunity in burned rats.

The effects of recombinant human growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were investigated in burned rats. Sprague-Dawley rats were fed exclusively by total parenteral nutrition and were subjected to 20% third-degree scald burns. The rats were then divided into the following three groups: (1) the GH group received GH at a dose of 1 IU.kg-1.d-1 for 2d (n = 10); (2) the IGF group received IGF-1 at a dose of 4 mg.kg-1.d-1 for 2d (n = 19); and (3) the control group received saline (n = 17). Cumulative nitrogen balance increased significantly in the GH (P < 0.01) and IGF (P < 0.01) groups as compared with the control group. There were no differences in nitrogen balance between the GH and IGF groups. Blood glucose was decreased in the IGF group (P < 0.01) and increased in the GH group (P < 0.05) as compared with the control group. The intestinal villus height and wall thickness of the GH and IGF groups were significantly greater than those of the control group. Delayed-type hypersensitivity was enhanced in both the GH and the IGF groups as compared with the control group (both P < 0.01). Furthermore, the increase in the IGF group was significantly greater than that in the GH group (P < 0.05). It was concluded that both GH and IGF-1 improve protein metabolism and immune responsiveness, as well as promote proliferation of the intestinal mucosa.

Animals↗

Effects of insulin-like growth factor-1 on endotoxin translocation in burned rats receiving total parenteral nutrition.

The purpose of this study was to investigate the effect of insulin-like growth factor-1 (IGF-1) on the translocation of endotoxin from the gut of burned rats. Twenty-eight male Sprague-Dawley rats (7-wk-old) were subjected to 20% full-thickness scald burns and were divided into two groups. One group received 4 mg.kg-1.d-1 of IGF-1 (IGF-1 group, n = 14), and the other received saline (control group, n = 13). All rats were fed exclusively by total parenteral nutrition (TPN). On the second postburn day, rats were killed. The amount of endotoxin in the liver and spleen were measured. RNA from the terminal ileum was extracted, and Northern blot analyses of alpha-tubulin, beta-actin, cell division cycle-2 (cdc2), and immunoglobulin-A (IgA) were performed. Nitrogen balance was improved (p < 0.001), and the wet weight of intestine and its mucosa were increased significantly in the burned rats that received IGF-1. Gene expression of alpha-tubulin and beta-actin were not changed. Cdc2 was elevated (P < 0.05), but IgA was decreased (P < 0.05) in the IGF-1 group. Levels of endotoxin in the liver and spleen were significantly reduced (P<0.05) by the administration of IGF-1. A negative correlation between the levels of endotoxin in the liver and the weight of the intestinal mucosa was observed. In conclusion, IGF-1 improved nitrogen balance, promoted the proliferation of intestinal mucosa and reduced the translocation of endotoxin.

Actins↗

[Effects of administration of Clostridium butyricum to patients receiving long-term tube feeding].

In patients who require total parenteral or enteral nutrition the intestinal lining may atrophy and the ability to absorb nutrients may be lost. To prevent atrophy of the small intestine, we administered a suspension of Clostridium butyricum to elderly patients receiving tube feeding, and then measured the activation of serum diamine oxidase and the number, form, water content, and bacteria content of stools, indicators of intestinal structure. We found a significant increase in diamine oxidase activity and an improvement in stool condition: the number of stools per day decreased, form improved, and water content and the number of aerobic bacteria decreased significantly. These results indicate that in patients receiving long-term tube feeding, administration of Clostridium butyricum can restore condition to a near-normal state.

Aged↗

[Knockout mouse--its characteristics and application (1): NMDA receptor subunit knockout mouse].

The N-methyl-D-aspartate (NMDA) type of glutamate receptors is thought to be essential in many central actions of neurotransmitter glutamate, including learning, memory, neurodevelopment and neurodegenerative disorders. Recent molecular cloning has revealed that the NMDA receptor has multiple subunits with distinct distribution, properties and regulation. This implies that NMDA receptors are different in molecular architecture and functional properties, depending on the brain region and developmental stage. To clarify the significance of the molecular diversity of NMDA receptors in vivo, a gene-targeting technique was applied to NMDA receptor subunit genes and several strains of mutant mice lacking targeted NMDA receptor subunit molecules were created. Using these NMDA receptor subunit knockout mice, various physiological, histological and behavioral analyses were performed. In this article, after briefly reviewing recent findings, we discuss the advantages and disadvantages of the NMDA receptor subunit knockout mouse as a tool for the studies of NMDA receptors and synaptic plasticity.

Animals↗

Age-dependent reduction of hippocampal LTP in mice lacking N-methyl-D-aspartate receptor epsilon 1 subunit.

The effects of targeted disruption of the N-methyl-D-aspartate (NMDA) receptor epsilon 1 subunit gene were studied during the postnatal development of epsilon 1-disrupted mutant mice. Using the mice at the ages of 2-3, 5-6 and 9-10 weeks, we examined NMDA receptor channel-mediated synaptic currents and long-term potentiation (LTP) in CA1 pyramidal neurons of hippocampal slices. NMDA receptor channel currents, expressed as the ratios to non-NMDA receptor channel currents, decreased with the age in both wild-type and mutant mice, but the values in the mutant mice was approximately half of those of the wild-type mice at all ages examined. The LTP in the mutant mice was also reduced, but in contrast to the NMDA receptor channel currents, the extent of the reduction in the LTP was age-dependent. The reduction was marginal at the age of 2-3 weeks, and became progressively prominent to adulthood, with the potentiation being 26% of that of the wild-type mice at 9-10 weeks.

Age Factors↗

Mutations in the BRCA1 gene in Japanese breast cancer patients.

Predisposing germline mutations in the BRCA1 gene were identified recently in families with 17 q-linked breast and ovarian cancers. Using single-strand conformation polymorphism (SSCP) analysis, we examined primary breast cancers for mutations in coding exons of BRCA1 in a panel of 103 patients, of whom all either represented early-onset cases (< 35 of age), were members of multiply-affected families, and/or had developed bilateral breast cancers. Mutations were detected in tumors from four patients, all of whom had developed breast cancers bilaterally: a frame-shift due to a 2-bp deletion at codon 797; a nonsense mutation at codon 1214; and two missense mutations, one at codon 271 leading to Val-->Met substitution, and the other at codon 1150 leading to Pro-->Ser substitution. In each case the same mutation was present in constitutional DNA. The mean age of onset was 49 years among the Japanese carriers of BRCA1 mutations identified in this study, in contrast to the mean age of 35 observed among carriers of BRCA1 mutations in a similar U.S. study (Futreal et al., 1994). The evidence reported here supports a rather limited role of BRCA1 in breast carcinogenesis.

Adult↗

Regulation of follicle-stimulating hormone receptor.

The acquisition of follicle-stimulating hormone (FSH) receptors during folliculogenesis is believed to be a key event in follicle development. We have examined the effects of FSH and activin on FSH receptor mRNA in cultured rat granulosa cells. Treatment of granulosa cells with FSH resulted in transient suppression of the FSH receptor mRNA levels 2-6 h after treatment, with subsequent recovery at 24 h. We could not detect a similar effect on FSH receptor mRNA by 8-bromoadenosine 3,5-cyclic monophosphate, which continuously stimulated FSH receptor mRNA over a similar time course. On the other hand, stimulation of the protein kinase C (PKC) pathway with phorbol myristate acetate mimicked the time course of the effects of FSH on the levels of FSH receptor mRNA. Taken together, these results suggest that the cAMP cascade may increase the mRNA levels of FSH receptor and, at the same time, the other cascade, PKC, may decrease FSH receptor mRNA levels. To further investigate the role of activin in the regulation of granulosa cell function, we studied the effect of activin on FSH receptor mRNA levels. Compared to the control, treatment with activin (100 ng/ml) increased FSH receptor mRNA in a time-dependent manner with a maximum circa 4-fold increase at 24 h. Treatment of granulosa cells with activin (20-300 ng/ml) for 24 h increased FSH receptor mRNA in a dose-dependent manner to a maximum circa 4-fold increase at concentrations of 100-300 ng/ml. Although follistatin alone had no detectable effect on FSH receptor mRNA levels, combination of follistatin (0-200 ng/ml) with activin (100 ng/ml) caused a significant reduction in the levels of activin-induced FSH receptor mRNA in a dose-dependent manner.

Activins↗

[Prospective study of the etiology of community-acquired pneumonia among patients in a general hospital].

We prospectively studied the etiology of community-acquired pneumonia among all patients who were admitted to our hospital from July 1994 to June 1995. Tests for microbial pathogens including Chlamydia spp. and Legionella spp. were performed and diagnoses were made with strict criteria. A total 110 patients with 111 episodes of pneumonia were evaluated, and a pathogen was identified in 61 episodes (55%). The most common pathogen was Streptococcus pneumoniae (18%), followed by Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Mycoplasma pneumoniae, and Chlamydia spp. Infection with Legionella pneumophila was not found. Dual pathogens were identified in five episodes. Few prospective studies of the etiology of community-acquired pneumonia have been done in Japan. To prepare guidelines for the management of community-acquired pneumonia in Japan, a national study of the etiology of pneumonia is necessary.

Adult↗

Genetic diagnosis of lymph-node metastasis in colorectal cancer.

If a regional lymph node taken during surgery for colorectal cancer is found to be free of tumour on histological examination this is taken to be a good sign. However, conventional staining may not be sensitive enough. Mutant-allele-specific amplification (MASA) is a technique that can detect, at the level of an individual cell, micrometastases to lymph nodes that are histologically diagnosed as negative. To examine the prognostic significance of such genetically detectable tumour cells we screened 120 colorectal cancers from patients who had no histologically detectable lymph-node metastasis at the time of surgery for mutations in K-ras (codons 12, 13, and 61) or p53 (exons 5-8). Somatic mutations were identified by MASA in 71 tumours. We next examined preserved tissues from corresponding regional lymph nodes, using MASA to look for the specific mutation found in the primary. Of 37 patients with genetically positive lymph nodes 27 had had a tumour recurrence within 5 years of surgery; none of the 34 patients who were MASA negative for lymph node metastasis had had a recurrence. Genetic diagnosis of lymph node metastasis may be a useful prognostic factor in colorectal cancer, and it could also serve as a selective marker for intensive postoperative adjuvant chemotherapy.

Colorectal Neoplasms↗