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Biomedical subjects

Hiroshi Yoshida

Publications and source records attributed to Hiroshi Yoshida.

At least 19 recordsLinked to original sources
PubMed2026

Myoepithelioma-like tumor of the vulvar region shows a quiet genome and heterogeneous detectable mechanisms of SMARCB1 inactivation: Integrated analysis of two cases and review of the literature.

Myoepithelioma-like tumor of the vulvar region (MELTVR) is a rare SMARCB1-deficient mesenchymal neoplasm of adult women that can mimic malignant vulvar sarcomas, particularly epithelioid sarcoma. Although loss of SMARCB1/INI1 expression is a defining feature, the comprehensive genomic landscape of MELTVR remains poorly characterized. We report two cases of MELTVR and performed integrated histopathologic, immunophenotypic, and molecular analyses, including whole-exome sequencing (WES) with copy number assessment and targeted RNA-based fusion testing using the Archer FusionPlex Sarcoma panel. Histologically, both tumors consisted of relatively uniform epithelioid to short spindle cells in solid nests and cords within focal myxoid stroma, with complete loss of INI1 and positivity for smooth muscle markers and focal ER/EMA expression. Genomic profiling demonstrated a quiet molecular background in both cases, with low tumor mutation burden (0.45 and 1.03 mut/Mb) and no pathogenic SNVs/indels in major cancer-associated genes. One case showed a focal homozygous deletion of the SMARCB1 locus at 22q11.2, whereas the other case exhibited INI1 loss without detectable SMARCB1 mutation or copy number loss, suggesting heterogeneous mechanisms of inactivation. CDKN2A copy number remained neutral in both tumors. No canonical sarcoma-associated gene rearrangements, including EWSR1, FUS, PLAG1, or NR4A3, were identified. Together with a review of previously reported cases, these findings support MELTVR as an SMARCB1-inactivated neoplasm with low genomic complexity and highlight the diagnostic value of NGS-based profiling in excluding malignant mimics and preventing overtreatment.

Humans↗
PubMed2006

Effect of photoreceptor degeneration on RNA splicing and expression of AMPA receptors.

PURPOSE: Glutamate is the most important neurotransmitter for excitatory synapses, and its ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is widely expressed in the vertebrate retina. AMPA receptors are hetero-oligomers composed of subsets of four distinct subunits termed GluR1-4. This study was conducted to examine the developmental progression of the flip-to-flop alternative splicing switch of AMPA receptors in wild-type and rd mouse retina. METHODS: The flop:flip ratio and expression levels of GluR1-4 from postnatal day 8 (P8) to P40 were calculated using quantitative real-time polymerase chain reaction (PCR) analysis and immunoblot analysis. The time course of photoreceptor degeneration in rd mice was histologically analyzed. RESULTS: In wild-type mouse retina, the flop:flip ratio in GluR1, but not GluR2-4, dramatically increased between P16 and P20. In rd mice, photoreceptor degeneration progressed from P10 to P20. GluR1 flop:flip ratio in rd mice was normal compared with wild-type mice before P16, however, the dramatic increase between P16 and P20 was completely suppressed. The suppression in the later phase of retinal degeneration was specific to GluR1 and was not observed in GluR2-4. Moreover, the expression levels of GluR1, GluR3, and GluR4 were increased in rd mice. CONCLUSIONS: These results suggest that the inherited form of photoreceptor degeneration in rd mice contributes to the regulation of the flip-to-flop exon switch in GluR1 and the expression levels of AMPA receptors.

Aging↗
PubMed2006

Helper virus-independent trans-replication of hepatitis C virus-derived minigenome.

We have previously described a synthetic T7-driven cDNA minigenome containing the antisense sequence of luciferase gene and internal ribosome entry site of encephalomyocarditis virus flanked by 5'- and 3'-end sequences of hepatitis C virus (HCV) that contain cis-acting replication elements. Synthesis of minus-strand RNA from the artificial minigenome was determined by using Huh-7 cells harboring autonomously replicating HCV subgenome as a helper for provision of functional replication components. To further confirm and extend these studies, we investigated here whether the minigenome replication system could be reconstituted by transfection of naïve Huh-7 cells with plasmid expressing nonstructural (NS) proteins. Reporter assay and Northern blot analysis revealed that trans-expression of NS proteins from 3 to 5 resulted in high level of luciferase activity and synthesized minus-strand RNA. The analogous result was also obtained with the minigenome derived from HCV 2a, and both HCV 1b- and 2a-derived NS protein were able to support the chimeric minigenomes whose 5'- or 3'-end was replaced by the respective region of the heterologous virus. These results provide a basis for establishing the reverse genetic system that is helpful to study cis- and trans-acting factors involved in HCV RNA replication.

Cell Line, Tumor↗
PubMed2006

Cloning and sequencing of cDNA and genomic DNA encoding PDM phosphatase of Fusarium moniliforme.

PDM phosphatase was purified approximately 500-fold through six steps from the extract of dried powder of the culture filtrate of Fusarium moniliforme. The purified preparation appeared homogeneous on SDS-PAGE although the protein band was broad. Amino acid sequence information was collected on tryptic peptides from this preparation. cDNA cloning was carried out based on the information. A full-length cDNA was obtained and sequenced. The sequence had an open reading frame of 651 amino acid residues with a molecular mass of 69,988 Da. Cloning and sequencing of the genomic DNA corresponding to the cDNA was also conducted. The deduced amino acid sequence could account for many but not all of the tryptic peptides, suggesting presence of contaminant protein(s). SDS-PAGE analysis after chemical deglycosylation showed two proteins with molecular masses of 58 and 68 kDa. This implied that the 58 kDa protein had been copurified with PDM phosphatase. Homology search showed that PDM phosphatase belongs to the purple acid phosphatase family, which is widely distributed in the biosphere. Sequence data of fungal purple acid phosphatases were collected from the database. Processing of the data revealed presence of two types, whose evolutionary relationships were discussed.

Amino Acid Sequence↗
PubMed2006

Effect of transforming growth factor-beta1 on human intrahepatic cholangiocarcinoma cell growth.

AIM: To elucidate the biological effects of transforming growth factor-beta1 (TGF-beta1) on intrahepatic cholan-giocarcinoma (ICC). METHODS: We investigated the effects of TGF-beta1 on human ICC cell lines (HuCCT1, MEC, and HuH-28) by monitoring the influence of TGF-beta1 on tumor growth and interleukin-6 (IL-6) expression in ICC cells. RESULTS: All three human ICC cell lines produced TGF-beta1 and demonstrated accelerated growth in the presence of TGF-beta1 with no apoptotic effect. Studies on HuCCT1 revealed a TGF-beta1-induced stimulation of the expression of TGF-beta1, as well as a decrease in TGF-beta1 mRNA expression induced by neutralizing anti-TGF-beta1 antibody. These results indicate that TGF-beta1 stimulates the production and function of TGF-beta1 in an autocrine fashion. Further, IL-6 secretion was observed in all three cell lines and exhibited an inhibitory response to neutralizing anti-TGF-beta1 antibody. Experiments using HuCCT1 revealed a TGF-beta1-induced acceleration of IL-6 protein expression and mRNA levels. These findings demonstrate a functional interaction between TGF-beta1 and IL-6. All three cell lines proliferated in the presence of IL-6. In contrast, TGF-beta1 induced no growth effect in HuCCT1 in the presence of small interfering RNA against a specific cell surface receptor of IL-6 and signal transducer and activator of transcription-3. CONCLUSION: ICC cells produce TGF-beta1 and confer a TGF-beta1-induced growth effect in an autocrine fashion. TGF-beta1 activates IL-6 production, and the functional interaction between TGF-beta1 and IL-6 contributes to ICC cell growth by TGF-beta1.

Animals↗
PubMed2006

New methods for the management of gastric varices.

Bleeding from gastric varices has been successfully treated by endoscopic modalities. Once the bleeding from the gastric varices is stabilized, endoscopic treatment and/or interventional radiology should be performed to eradicate varices completely. Partial splenic artery embolization is a supplemental treatment to prolong the obliteration of the veins feeding and/or draining the varices. The overall incidence of bleeding from gastric varices is lower than that from esophageal varices. No studies to date have definitively characterized the causal factors behind bleeding from gastric varices. The initial episodes of bleeding from esophageal varices or gastric varices without prior treatment may be at least partly triggered by a violation of the mucosal barrier overlying varices. This is especially likely in the case of varices of the fundus. In view of the high rate of hemostasis achieved among bleeding gastric varices, treatment should be administered in selective cases. Among untreated cases, steps to prevent gastric mucosal injury confer very important protection against gastric variceal bleeding.

Balloon Occlusion↗
PubMed2006

Hypoadiponectinemia in lean lactating women: Prolactin inhibits adiponectin secretion from human adipocytes.

Adiponectin is an adipocyte-derived hormone involved in glucose, lipid and energy metabolism. A low plasma adiponectin concentration is associated with insulin resistance, obesity and atherosclerosis. In women, energy homeostasis is remarkably changed during gestation and lactation in order to supply sufficient nutrition for a fetus or newborn. In this study we aimed to elucidate the physiological impact of gestation and lactation on the plasma adiponectin levels and the influence of reproduction-related hormones on adiponectin secretion. We studied the longitudinal changes in plasma adiponectin concentration during pregnancy (1st, 2nd and 3rd trimester) and lactation (3 days and 1 month after the delivery) in lean healthy women (n = 22). The plasma adiponectin level declined slightly as the pregnancy advanced and reached its lowest level during lactation (12.25 +/- 0.182 microg/ml at early pregnancy vs. 6.88 +/- 0.375 microg/ml at 3 days postpartum, p < 0.001). In order to investigate the role of the lactogenic hormone prolactin in the decrease of plasma adiponectin levels during lactation, we further performed in vitro experiments using human primary cultured adipocytes. Western blotting of the adipocyte lysate and ELISA of the culture medium revealed that exogenous prolactin inhibited both production and secretion of adiponectin in a dose-dependent manner. Our results thus suggests that prolactin affects the regulation of maternal metabolism through suppression of adiponectin.

Adipocytes↗
PubMed2006

Postoperative bile leakage managed successfully by intrahepatic biliary ablation with ethanol.

We report a case of postoperative refractory bile leakage managed successfully by intrahepatic biliary ablation with ethanol. A 75-year-old man diagnosed with hepatocellular carcinoma underwent extended posterior segmentectomy including the caudate lobe and a part of the anterior segment. The hepatic tumor attached to the anterior branch of the bile duct was detached carefully and resected. Fluid drained from the liver surface postoperatively contained high concentrations of total bilirubin, at a constant volume of 150 mL per day. On d 32 after surgery, a fistulogram of the drainage tube demonstrated an enhancement of the anterior bile duct. Endoscopic retrograde cholangiography demonstrated complete obstruction of the proximal anterior bile duct and no enhancement of the peripheral anterior bile duct. On d 46 after surgery, a retrograde transhepatic biliary drainage (RTBD) tube was inserted into the anterior bile duct under open surgery. However, a contrast study of RTBD taken 7 mo post-surgery revealed that the fistula remained patent despite prolonged conservative management, so we decided to perform ethanol ablation of the isolated bile duct. Four mL pure ethanol was injected into the isolated anterior bile duct for ten minutes, the procedure being repeated five times a week. Following 23 attempts, the volume of bile juice reached less than 10 mL per day. The RTBD was clamped and removed two days later. After RTBD removal, the patient had no complaints or symptoms. Follow-up magnetic resonance imaging demonstrated atrophy of the ethanol-injected anterior segment without liver abscess formation.

Aged↗
PubMed2006

Myocardial infarction caused by Aspergillus embolization in a patient with aplastic anemia.

A 38-year-old Japanese man with severe aplastic anemia had invasive pulmonary aspergillosis as a complication. He was treated with amphotericin B for six weeks, but the aspergillosis did not improve. Then he experienced a fatal myocardial infarction. An autopsy revealed disseminated aspergillosis involving pericarditis and Aspergillus embolization to the coronary arteries. This led to the acute myocardial infarction. Cardiac aspergillosis is rare, but should be included within the differential diagnosis when chest pain of unknown origin occurs in an immunosuppressed patient.

Adult↗
PubMed2006

One-step palliative treatment method for obstructive jaundice caused by unresectable malignancies by percutaneous transhepatic insertion of an expandable metallic stent.

AIM: To describe a simple one-step method involving percutaneous transhepatic insertion of an expandable metal stent (EMS) used in the treatment of obstructive jaundice caused by unresectable malignancies. METHODS: Fourteen patients diagnosed with obstructive jaundice due to unresectable malignancies were included in the study. The malignancies in these patients were a result of very advanced carcinoma or old age. Percutaneous transhepatic cholangiography was performed under ultrasonographic guidance. After a catheter with an inner metallic guide was advanced into the duodenum, an EMS was placed in the common bile duct, between a point 1 cm beyond the papilla of Vater and the entrance to the hepatic hilum. In cases where it was difficult to span the distance using just a single EMS, an additional stent was positioned. A drainage catheter was left in place to act as a hemostat. The catheter was removed after resolution of cholestasis and stent patency was confirmed 2 or 3 d post-procedure. RESULTS: One-step insertion of the EMS was achieved in all patients with a procedure mean time of 24.4 min. Out of the patients who required 2 EMS, 4 needed a procedure time exceeding 30 min. The mean time for removal of the catheter post-procedure was 2.3 d. All patients died of malignancy with a mean follow-up time of 7.8 mo. No stent-related complication or stent obstruction was encountered. CONCLUSIONS: One-step percutaneous transhepatic insertion of EMS is a simple procedure for resolving biliary obstruction and can effectively improve the patient's quality of life.

Aged↗
PubMed2006

Administration of bisphosphonate for hypercalcemia associated with oral cancer.

BACKGROUND: The efficacy of treating hypercalcemia with bisphosphonate (BP) in patients with advanced oral cancer has not been fully investigated. This retrospective study evaluated the clinical course of hypercalcemic patients with and without BP treatment. METHODS: Sixteen hypercalcemic patients, most of whom had uncontrollable locoregional lesions and lung metastases, were studied. Nine patients had been given BP, and the rest had not. RESULTS: There were significant differences in age and serum ALT between the BP-treated and -untreated groups. The first administration of BP effectively and safely decreased the serum calcium level, but repeated administrations were less effective. Although the patients treated with BP survived significantly longer than the untreated subjects, the difference of the median was only about 2 weeks. CONCLUSION: The occurrence of hypercalcemia in oral cancer patients apparently implies an extremely poor prognosis, and long-term survival cannot be expected, even with BP treatment.

Adult↗
PubMed2006

Preclinical study of a "tailor-made" combination of NK4-expressing gene therapy and gefitinib (ZD1839, Iressa) for disseminated peritoneal scirrhous gastric cancer.

We evaluated the effect of a "tailor-made" chemo-gene therapy in scirrhous gastric cancer (SGC)-bearing nude mice. For this tailor-made approach, we first selected gefitinib (epidermal growth factor receptor-tyrosine kinase inhibitor)-sensitive SGC cell lines, and 5/8 cell lines demonstrated various degrees of gefitinib-sensitivity. In the highly gefitinib-sensitive NUGC-4, the biological response to NK4 (HGF antagonist/angiogenesis inhibitor) was examined. Subsequently, the composition of an NK4-expressing ternary complex (cationic lipid/nucleic acid/HMG-1, 2 protein) was optimized for maximum transfection activity in NUGC-4. Finally, mice were peritoneally coinoculated with NUGC-4 and scirrhous-associated gastric fibroblasts, NF22, on day 0. Animal models were orally administrated gefitinib (50 mg/kg/day, on days 7-28), and peritoneally NK4-expressing ternary complex (on days 14, 21 and 28). NK4-expression suppressed the gefitinib-resistance induced by the interaction between fibroblasts and SGC, and eventually, this tailor-made combination synergistically decelerated the disease progression by inhibiting proliferative, angiogenic and antiapoptotic effects in tumor tissues. On day 28, both the hemoglobin concentration (g/dl) (control (n = 8), 11.9; treated (n = 8), 17.3; p = 0.0014) and the numbers of mice in good condition (control, 2; treated, 8; p = 0.0012) were significantly greater, and the abdominal girth (mm) (control, 81.1; treated, 70.3; p = 0.0036) was significantly reduced. The median points of bloody ascite-free survival time (days) (control, 22; treated, 44; p < 0.0001) and time to euthanasia (days) (control, 36.5; treated, 56; p < 0.0001) were also significantly prolonged. This combination is a potentially useful approach to the treatment of peritoneal gefitinib-sensitive SGC dissemination.

Adenocarcinoma, Scirrhous↗
PubMed2006

Physicochemical and pharmacokinetic characterization of highly potent recombinant L-methionine gamma-lyase conjugated with polyethylene glycol as an antitumor agent.

A highly potent recombinant L-methionine gamma-lyase (METase) conjugated with polyethylene glycol (PEG) was characterized physicochemically and pharmacokinetically in vivo and in vitro. Pegylated METase (PEG-METase), which contains pyridoxal 5'-phosphate (PLP) as a cofactor in the molecule, is a potent anticancer agent that can deplete L-methionine from plasma. Although pegylation decreased its specific activity, dithiothreitol (DTT) treatment increased it over three times with the detachment of one PEG moiety modified with a cysteine residue. We can produce DTT-treated PEG-METase on a large scale in sufficient quality for therapeutic use. The superiority of DTT-treated PEG-METase was confirmed by the enhancement of L-methionine depletion and amelioration of pharmacokinetics in mice. The holoenzyme of DTT-treated PEG-METase gave a several times larger area under the plasma concentration curve than that of DTT-untreated PEG-METase, not because of an increase of the half-life but because of high specific activity. Conversely, simultaneous PLP infusion led to a greatly increased half-life of the holoenzyme. DTT-treated PEG-METase administration with PLP infusion was the most useful combination for maximizing the potency of the enzyme. We showed that serum albumin interfered with holoenzyme activity in vitro. The decrease of holoenzyme activity was dependent on the type of serum albumin. We concluded that PLP was released from PEG-METase by serum albumin in vivo and in vitro. The deleterious effect of PLP dissociation from PEG-METase could be improved by supplementing PLP and oleic acid. Their synergistic effect in preventing a decrease of the holoenzyme activity was also observed.

Animals↗
PubMed2006

Basal cell adenocarcinoma arising from the minor salivary gland in the soft palate: a case report.

Basal cell adenocarcinomas (BCACs) of the oral minor salivary gland are very rare neoplasms. We report on an 86-year-old woman with BCAC arising from the minor salivary gland in the soft palate. Histologically, the tumor was located in the submucosa and showed microinvasion into the adjacent soft tissue without encapsulation. It contained tiny tumor islands with solid and tubular patterns, as well as myxoid stroma. The neoplastic cells were basaloid cells and were composed of large pale cells and small dark cells. They were positive for alpha-smooth muscle actin, cytokeratin 14, and vimentin in the periphery of the tumor island, showing a myoepithelial differentiation. The myxoid stroma was positive for alcian blue and colloidal iron. Apical membranes of the neoplastic cells were positive for MUC1 and CEA. The present case is the 14th documented case of oral BCAC (the fifth case of palatal BCAC).

Adenocarcinoma↗
PubMed2006

Prospective trial of radiotherapy for patients 80 years of age or older with squamous cell carcinoma of the thoracic esophagus.

PURPOSE: To assess the safety and efficacy of external beam radiotherapy for elderly patients with esophageal cancer. METHODS AND MATERIALS: A trial testing external beam radiotherapy (66 Gy within 6.5 weeks) as a single-modality treatment was performed for biopsy-proven squamous cell carcinoma of the thoracic esophagus clinically staged as Stage I and IIA (T1-T3N0M0, International Union Against Cancer, 1987) in patients aged > or =80 years. RESULTS: From January 1999 through December 2002, 51 evaluable patients (35 men and 16 women) with a median age of 83 years (range, 80-91 years) were enrolled from 22 institutions. Of the 51 patients, 18 (35%) had Stage T1 and 33 (65%) had Stage T2-T3 disease. Radiotherapy could be completed in 47 patients (92%) within 43-58 days (median, 49). The actuarial incidence of Grade 3 or worse cardiopulmonary complications at 3 years was 26%, with 3 early deaths, and correlated significantly with the size of the anteroposterior radiotherapy portals. The median survival time and overall survival rate at 3 years was 30 months and 39% (95% confidence interval, 25-52%), respectively. CONCLUSION: The results of high-dose radiotherapy in octogenarians are comparable to those in younger patients, but meticulous treatment planning and quality control is required.

Aged, 80 and over↗
PubMed2006

Presence of immunounreactive albumin in the urine of diabetic patients.

Recent studies have demonstrated that conventional immunochemical assays underestimate urinary albumin concentration because of the presence of immunounreactive albumin. It has been reported that intact urinary albumin in 24-hr diabetic urine samples could be detected as total concentration (immunoreactive+immunounreactive) by an HPLC method based on size exclusion chromatography. The aim of this study was to investigate urinary albumin concentration in diabetic spot urine samples by comparing the HPLC method with several other methods. The albumin concentrations on 80 diabetic spot urine specimens were measured by turbidimetric immunoassay (TIA), high performance liquid chromatography (HPLC), and a dipstick method. In addition, they were also analyzed by reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) and native polyacrylamide gel electrophoresis (Native PAGE). The albumin concentrations derived from diabetic spot urine samples measured by the HPLC method were higher than those of the other methods except for five of 80 samples. Furthermore, the albumin concentrations analyzed by Native PAGE were higher than SDS PAGE in 61 (76.2%) of 80 samples. This study suggests the need for evaluating diabetes not only by HPLC, but also by combining it with another method.

Adult↗