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Biomedical subjects

Y Iwata

Publications and source records attributed to Y Iwata.

At least 91 records · Page 5Linked to original sources

Atrial septal displacement for repair of anomalous pulmonary venous return into the right atrium.

BACKGROUND: In the repair of anomalous connection of the pulmonary veins to the right atrium, the use of a baffle of pericardium to divert the pulmonary venous blood into the left atrium could cause pulmonary venous obstruction as a result of thickening of the pericardial patch. Anomalous pulmonary venous drainage to the right atrium caused by malposition of the atrial septum primum can be repaired by displacing the shifted septum primum to the normal position. METHODS: In 5 patients with total (n=2) or partial (n=3) anomalous pulmonary venous drainage into the right atrium, the septum primum was shifted toward the left atrium and the pulmonary veins drained into the anatomic right atrium despite their normal connection with the posterior wall of the left atrium. This method consisted of incision of the posterior edge of the atrial septum primum and displacement of the incised atrial septum between the anomalous pulmonary veins and both venae cavae. No patch was used. RESULTS: Postoperative echocardiography showed a wide pathway from the pulmonary veins to the left atrium with no stenotic portions. No atrial arrhythmias occurred after the operation. CONCLUSIONS: This technique may be advantageous because it allows for future growth of the route of the pulmonary venous pathway and avoids postoperative supraventricular arrhythmias.

Arrhythmias, Cardiac↗

Characterization of a calcium-dependent protein kinase of tobacco leaves that is associated with the plasma membrane and is inducible by sucrose.

The plasma membrane fraction from leaves of tobacco contains a 54-kDa protein with autophosphorylation activity, and the level of this protein increases after feeding of leaves with sucrose [Ohto and Nakamura (1995) Plant Physiol. 109: 973]. The 54-kDa autophosphorylation protein could not be released from the plasma membrane by treatment with salt or alkali but could be efficiently solubilized by 1% sodium deoxycholate (NaDOC). Ion-exchange chromatography of the NaDOC-solubilized proteins in the presence of octylglucoside separated the 54-kDa autophosphorylation protein into three peaks. The autophosphorylation activity of the 54-kDa protein in peaks I and II increased after feeding of leaves with sucrose. The 54-kDa protein in the peak II fraction was enriched about 125-fold starting from the microsomal membrane fraction. The 54-kDa protein in this fraction phosphorylated histone IIIS in a calcium-dependent manner and cross-reacted with an antibody against a calcium-dependent protein kinase (CDPK) of Arabidopsis thaliana. These results suggest that the 54-kDa protein in the peak II fraction is a novel isoform of CDPK which is associated with the plasma membrane and is inducible by sucrose.

Arabidopsis↗

Detection and sequence analysis of borna disease virus p24 RNA from peripheral blood mononuclear cells of patients with mood disorders or schizophrenia and of blood donors.

Borna disease virus (BDV) p24 RNA was detected in the peripheral blood mononuclear cells (PBMCs) of psychiatric patients and blood donors by nested reverse transcriptase PCR (RT-PCR). The prevalences of BDV p24 RNA in patients with mood disorders (4%) and schizophrenia (4%) were not significantly different from that in blood donors (2%). This finding was inconsistent with previous reports that showed either a high prevalence or absence of BDV p24 RNA in patients with psychiatric disorders. The differences in BDV p24 RNA prevalence in these studies may be due to differences in the criteria for positivity, the number of PBMCs used for RNA extraction, or the amount of RNA tested for nested RT-PCR or to laboratory contamination. Sequence analysis of BDV p24 RNA from the PBMCs of patients and blood donors showed a high nucleotide sequence conservation but definite nucleotide mutations compared with horse BDV p24 RNA sequences. In comparison with human BDV p24 RNA sequences previously reported from Japan and Germany, there were several positions with silent nucleotide mutations among these clones.

Adult↗

Increased expression of proliferating cell nuclear antigen in autoimmune hepatitis in a patient with raised serum concentration of CA19-9.

A 52 year old woman had autoimmune hepatitis and an increased concentration of serum carbohydrate antigen 19-9 (CA19-9). The origin of the raised CA19-9 was studied using immunohistochemistry. Liver biopsy section showed chronic active hepatitis with large numbers of proliferated bile ductules. Immunohistochemical analysis revealed that the proliferated bile ductule cells were positive for proliferating cell nuclear antigen (PCNA) and for CA19-9. It is speculated that the raised serum CA19-9 concentration was derived from proliferated bile ductule cells and these cells, which are positive for PCNA, may be able to produce high concentrations of CA19-9.

Bile Ducts, Intrahepatic↗

Detection of a novel nonsense mutation of the MEN1 gene in a familial multiple endocrine neoplasia type 1 patient and its screening in the family members.

We identified a novel nonsense mutation(R29X) of the MEN1 gene in a familial multiple endocrine neoplasia type 1 (MEN1) patient. Molecular analysis of the MEN1 gene was performed in the family members by a restriction digestion method. The same mutation pattern was seen in both the proband's younger brother and cousin diagnosed as MEN1, and was also observed in the son of the cousin who showed signs of normal levels of serum PTH associated with mild hypercalcemia and hypophosphatemia. These findings suggest that mutation analysis of the MEN1 gene is very useful in identifying the subclinical state of MEN1 as well as clinical MEN1.

Adult↗

[Talc pulmonary granulomatosis caused by intravenous administration of methylphenidate].

A 57-year-old man was admitted with fever and a dry cough in 1985. He had used methylphenidate intravenously for 3 years. A chest X-ray film on admission showed diffuse micronodular shadows and massive lesions in the lower lung fields bilaterally. Pulmonary granulomatosis was diagnosed histologically, but the etiology remained unclear. In 1993, the patient was readmitted because of symptom exacerbation. The micronodular shadows had extended and the bilateral, massive lesions had enlarged. Transbronchial lung biopsy revealed granulomas with crystallized foreign bodies. Electron microscopy confirmed that the foreign bodies consisted of magnesium and silicon, suggesting talc. Talc granulomatosis caused by intravenous administration of methylphenidate was subsequently diagnosed. The symptoms improved with conservative treatment, and no signs of reexacerbation have appeared.

Central Nervous System Stimulants↗

Inhibitory effects of rebamipide on ENNG-induced duodenal carcinogenesis in mice: a possible strategy for chemoprevention of gastrointestinal cancers.

Rebamipide is a potent antioxidative agent; it increases gastric mucosal PGE2 production and thus protects the gastric mucosa. We hypothesized that the mechanisms of ulcer formation could be extended to carcinogenesis and that an increase in gastric mucosal protection may result in a decrease in gastric carcinogenesis. Therefore, we assessed the inhibitory effects of rebamipide on N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) -induced carcinogenesis in mice. The percentage of tumor-bearing mice in three treatment groups--ENNG + rebamipide 20 mg, ENNG + rebamipide 50 mg, and ENNG alone--was 55%, 42%, and 67%, respectively. The incidence of tumorigenesis tended to decrease with increasing doses of rebamipide. The difference between ENNG + rebamipide 50 mg and ENNG alone was statistically significant (P < 0.05). These results suggest that rebamipide may strengthen the host defense mechanisms related to carcinogenesis in the digestive tract.

Alanine↗

[Spontaneous resolution of idiopathic spinal subdural hematoma: case report].

A 32-year-old female presented with about a week's history of dull pain in the head and neck pain. On the day of admission, she experienced a sudden onset of severe pain, extending from the occipital to the lower back region and hypesthesia and paresthesia of the right C8-Th3 dermatome. On admission, she was alert but there was a band of hypesthesia and paresthesia at the level of C8-Th3. Cervical X-ray, computed tomography scan (CT) and magnetic resonance images (MRI) of the head revealed no definite abnormalities. The peripheral blood picture was normal, and the bleeding and clotting times were in the normal range. The cerebrospinal fluid (CSF) was bloody and the CSF pressure was 220 mm H2O. An emergent 4-vessel intracranial angiography disclosed no abnormal findings. MRI and myelography revealed an intradural extramedullary lesion extending from the Th2 to the Th5 levels, ventral to the spinal cord. A T1-weighted MR image showed iso-low intensity and a T2-weighted MR image showed low intensity at these lesions. Spinal angiography revealed no abnormal vessels. In one month, spinal compression cleared gradually without surgery and her clinical symptoms disappeared about 40 days after admission. Spontaneous spinal subdural hematoma is uncommon and only 28 cases have been reported. 15 cases have been treated with surgical procedure, but spinal compression cleared spontaneously in this case. This spontaneous recovery is such a rare event that only 3 such cases have been reported in the literature. However, with the prevailing MRI, this disease will be detected more frequently in the future.

Adult↗

Characterization of Ret-Shc-Grb2 complex induced by GDNF, MEN 2A, and MEN 2B mutations.

We analyzed the intracellular signalling pathway through Ret activated by glial-cell-line-derived neurotrophic factor (GDNF), multiple endocrine neoplasia (MEN) 2A and 2B mutations. The results showed that all of them induce a signal transducing complex consisting of Ret, Shc, and Grb2 proteins. In addition, GDNF clearly activated a Ras-MAPK pathway in human neuroblastoma cells. Rat is expressed mainly as two isoforms that differ in the carboxy-terminal sequence: a long isoform (1114 amino acids) and a short isoform (1072 amino acids). The long isoform contains the consensus sequence for binding of the Shc PTB domain but not of its SH2 domain, whereas the short isoform has the consensus sequences for binding of both domains. In vitro binding assay revealed that the long isoform of the MEN2A-Ret protein and both isoforms of the MEN2B-Ret protein bound preferentially to the Shc PTB domain. On the other hand, the short isoform of MEN2A-Ret bound to the PTB and SH2 domains. In neuroblastoma cells expressing both isoforms of Ret, its activation by GDNF also resulted in the binding of both domains. GDNF and MEN 2A mutations activate Ret by inducing its dimerization, whereas the MEN 2B mutation increases Ret catalytic activity without dimerization. Our results thus suggest that Ret dimerization might be required for binding of the Shc SH2 domain to the short isoform.

3T3 Cells↗

Biological properties of Ret with cysteine mutations correlate with multiple endocrine neoplasia type 2A, familial medullary thyroid carcinoma, and Hirschsprung's disease phenotype.

We investigated the transforming activity of the ret proto-oncogene with a mutation in cysteine 609, 611, 618, 620, 630, or 634 detected in patients with multiple endocrine neoplasia type 2A (MEN 2A), familial medullary thyroid carcinoma (FMTC), or Hirschsprung's disease. Of these cysteine mutations, codon 634 mutations are known to be correlated with the development of MEN 2A, whereas codon 609, 618, or 620 mutations were detected in two-thirds of FMTCs and in several cases of Hirschsprung's disease. Analysis of a total of 18 mutant genes revealed that codon 634 mutations have the highest transforming activity. The activity of ret with a codon 609, 611, 618, or 620 mutation and with a codon 630 mutation was approximately 3- to 5-fold and 2-fold lower than that of ret with a codon 634 mutation, respectively. In addition, different amino acid substitutions for the same cysteine displayed comparable transforming activity. The expression of the cell surface form of Ret with codon 609, 611, 618, or 620 mutation was very low compared with that of Ret with codon 634 mutation, indicating that the former four mutations might impair transport of Ret to the plasma membrane, as observed for several Hirschsprung mutations affecting the Ret extracellular domain. These results thus suggest that mutations in cysteine 609, 611, 618, or 620 may have the potential to develop Hirschsprung's disease in addition to MEN 2A and FMTC.

3T3 Cells↗

Macrophage cathepsin L, a factor in the erosion of subchondral bone in rheumatoid arthritis.

OBJECTIVE: To test the hypothesis that the proteinase cathepsin L is involved in the subchondral bone lesions found in chronic rheumatoid arthritis (RA). METHODS: The medial tibial plateaus from 4 control cases and 30 patients diagnosed as having end-stage RA were examined immunochemically for cathepsin L. RESULTS: RA lesions include large groups of mononuclear cells, many of which are rich in cathepsin L. Since these mononuclear cells contained the CD68 glycoprotein and, in the electron microscope, displayed an irregular cell surface, cytoplasmic vacuoles, lysosomes, and phagosomes, they were identified as belonging to the macrophage family. The lesions were classified into 2 main patterns, both displaying these cathepsin L-rich cells, which, in at least 1 of the 2, were closely associated with bone degradation. CONCLUSION: The cathepsin L-rich macrophages are sufficiently numerous to be considered a major factor in producing the erosion of subchondral bone found in chronic RA lesions.

Adult↗

Expression of matrix metalloproteinase (gelatinase) in T1 adenocarcinoma of the lung.

The expression of matrix metalloproteinase-2 (MMP-2; 72 kDa type IV collagenase/gelatinase A) and MMP-9 (92 kDa type IV collagenase/gelatinase B) was immunohistochemically investigated in 79 T1 adenocarcinomas of the lung using non-commercial polyclonal anti-MMP-2 and -9 antibodies. Thirty-two (41%) and 22 (28%) among the 79 cases were positive in the tumor cells for MMP-2 and -9, respectively. The incidences of MMP-2 and -9 immunoreactivities were higher (64 and 45%, respectively) in poorly differentiated tumors than in well differentiated tumors (36 and 25%, respectively), and lower in bronchioloalveolar carcinoma (22 and 10%, respectively) compared with other subtypes of adenocarcinoma. The prognosis for patients with MMP-2 and/or -9 positive immunoreactivities was significantly poorer than for those with a MMP-negative tumor (P < 0.05). The degree of collagenization was divided into four grades, and tumors with a small to abundant amount of collagen (grade 2 and grade 3 fibrosis) had a higher incidence of immunoreactivity to both types of MMP. It is estimated that these expressions might be responsible for tumor invasion, metastasis, and for grade 2 and grade 3 fibrosis in T1 adenocarcinoma of the lung.

Adenocarcinoma↗

mRNA expression and cDNA sequences of beta- and gamma-sarcoglycans are normal in cardiomyopathic hamster heart.

In BIO14.6 cardiomyopathic hamster heart, the dystrophin-glycoprotein complex is disrupted and sarcoglycans are greatly reduced in abundance. We examined whether the gene expression of beta- and gamma-sarcoglycans is indeed defective in this hamster. We found that mRNA expression for these proteins and the cDNA sequences of their coding regions are identical in both normal and myopathic hamster cardiomyocytes. The results strongly suggest that defect in a currently unknown sarcoglycan-associated protein(s) is responsible for the deficiency of the sarcoglycan complex that leads to muscle cell necrosis in the myopathic hamster.

Amino Acid Sequence↗

[Sequence variability in Borna disease virus ORF II from human beings].

40 clones from five psychiatric patients and three healthy blood donors in whom Borna disease virus (BDV) ORF II fragments in PBMC were previously proved by nested RT-PCR were sequenced and compared with BDV/MDCK. There were eleven point mutations in all clones compared with reported HE80-1, but no difference between human and BDV/MDCK clones. We found specific sequence variability at nt 1701 in ten clones from two psychiatric disorder patients (T-->C) and at nt 1696 in fifteen clones from three healthy blood donors (A-->T). This result strongly suggests there are some special gene divergence in BDV derived from human beings.

Base Sequence↗

[CABG performed for LMT orifice stenosis 15 years after AVR in a case of aortitis syndrome].

The case is a 54-year-old female at age 39 years, she underwent aortic valve replacement (AVR) for aortic valve regurgitation (AR) due to aortitis syndrome at a certain hospital. At the 15th year after AVR she was diagnosed with unstable angina due to LMT orifice stenosis and underwent CABG at this hospital. A distal side of anastomosis was performed on the LAD branch seg 6, an artificial vascular patch was placed for the proximal side of anastomosis to prevent inflammation of the aortic wall from spreading to the proximal side of anastomosis. On the postoperative cardiac catheter examination, the graft was found to be patent well. In the case of CABG complicated with aortitis syndrome, stenosis and obstruction of the proximal side of anastomosis long time after surgery pose a problem. However, the method so as to perform a proximal anastomosis by placing an artificial vascular patch on the aortic wall is considered to be one of the useful means which can avoid such a problem.

Angina, Unstable↗

[Current status and problems of home parenteral nutrition for terminal cancer patients from the viewpoint of indication].

Since June 1993, we have been performing home parenteral nutrition (HPN) for end-stage cancer patients. We studied how many patients could be treated with HPN, why they were not able to be treated with HPN in the terminal stage cancer patients, 158 cases, who admitted and died in our ward from June 1993 to April 1997. Eighty-six patients (54.4%) were considered to not be indicated for HPN, due to general weakness (28 cases), dyspnea (17 cases), need for medical care other than HPN (34 cases), and inability to understand this treatment (1 case). Fifty-six patients (35.4%) were considered to have been able to be treated with HPN and could have had returned home. Fifteen patients (26.8%) were given HPN. Four cases wanted to stay in the hospital after they knew the truth and the prognosis of their disease. Another four patients became weak while preparing for HPN and could not go home. Eighty percent of patients could not to be treated with HPN because of the factors of their family. Eight patients had no family to cared for them. Twelve patients were refused to the truth of their disease. The families of 13 cases refused to accept and care for them in their home. We may conclude that co-operation among patients, their family and the medical staff is the most important factor in providing HPN for end-stage cancer patients.

Adult↗

A RING finger motif regulates transforming activity of the rfp/ret fusion gene.

The rfp/ret transforming gene was generated by DNA rearrangement which occurred during transfection of NIH 3T3 cells. The amino-terminal half of Rfp with a RING finger motif was fused to the truncated Ret receptor tyrosine kinase, leading to a transforming sequence, Rfp/Ret. In the present study, to elucidate the importance of a RING finger motif for its transforming activity, we mutated cysteine or histidine residues present in the motif that are believed to be crucial for the tertiary structure of the protein. Substitution of Cys-16, Cys-31, or His-33 markedly decreased the transforming activity of Rfp/Ret. These mutations also resulted in a striking decrease of tyrosine phosphorylation of the mutant proteins in transfectants. In contrast, mutations of Cys-118 or His-124 in the second cysteine/histidine-rich motif (called B box) of Rfp/Ret did not affect its activity. These results thus indicated that the RING finger structure is critical for the full transforming activity of Rfp/Ret.

3T3 Cells↗