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Biomedical subjects
Publications and source records attributed to I Yoshida.
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The in vitro differentiative potential of mouse parthenogenetic (PG) embryonic stem (PGES) cells were investigated in the formation of embryoid bodies (EBs). EBs derived from PGES cells retarded in growth and showed restricted differentiation compared to their fertilized counterpart. In chimeric EBs from the aggregation of PGES and fertilized ES cells, morphological examination revealed that PGES cells were reduced in their population and distributed in endodermal layer as culture periods proceeded. These findings were comparable to those in aggregation chimeras of fertilized and PG embryos, and suggest that the differentiation of PGES cells in vitro is restricted in the formation of EBs.
Murine parthenogenetic embryonic stem (ES) cell lines expressing lac Z reporter gene were isolated after co-transfection with lac Z reporter gene (pENL) and neo gene (pSTneo) to TMA-48P cell line of 129/Sv origin. Karyotype analyses showed that all of four transfected cell lines examined contained 41 chromosomes with trisomy 8. Bacterial neo transgene required for G418 selection were integrated into several chromosomes including chromosome 8. Histological studies of teratomas formed in syngenic mice and embryoid bodies grown in vitro showed that the differentiative potential remained almost identical in chromosomally normal parental cell line and its derivative cell lines trisomic for chromosome 8.
An inactive human X chromosome was introduced by microcell fusion into two mouse embryonal carcinoma cell lines, PSA1-TG8 and OTF9-63, each of which has a single X chromosome. The donor cell line was a mouse-human somatic cell hybrid, CF150, retaining one or more inactive human X chromosome(s) per cell as its only human element. Twenty hybrid clones isolated retained EC morphology and contained the intact human X chromosome(s) or its truncated derivative(s). Replication banding analysis showed that the introduced human X chromosome(s) or its derivative(s) replicated synchronously with other mouse chromosomes, suggesting reactivation of the human X chromosomal elements after transfer. Reversal of inactivation was further confirmed by the expression of five human X-linked genes repressed in CF150, although the XIST (X inactive specific transcript) gene continued to be active. The level of XIST expression in our hybrid cells was almost identical to that of parental CF150 cells. Methylation status of 5' end of the active XIST gene varied considerably from almost full methylation to unmethylation in these hybrids. Thus, mouse EC cells used in this study were capable of altering methylation status of the human XIST gene in a manner lacking consistency and unable to repress its transcription. Furthermore, we failed to obtain any positive evidence for the occurrence of X chromosome inactivation in differentiating monochromosome EC hybrids. Taken together, these findings suggest that the human X chromosome inactivation center including the XIST gene is unable to function effectively in mouse cells.
In the following report, we describe our investigation of the diagnosis and operative methods for benign tumors of the lung, in which the surgical treatment was selected due to suspicious malignancy. This study included 22 patients with benign tumors. The patients' mean age was 55 years old. The histological diagnosis was made postoperatively prior to 1985 and intraoperatively after 1986. Hamartoma was the most common of the benign tumors. In benign tumors, the preoperative diagnosis was almost the same as the postoperative one. Of the patients with benign tumors, 78% underwent lobectomy or segmentectomy prior to 1985, and none have undergone any invasive procedures since 1986. Malignant tumors are sometimes difficult to distinguish from benign tumors preoperatively. Therefore, intraoperative histological examinations are necessary in cases in which malignancy is suspected. In such cases, a smaller invasive procedure should be selected due to the possibility of the tumor being benign.
Pulmonary aspergillosis associated with old tuberculosis is generally resistant to treatment. Thus, if patients are treated only with conservative therapy, their condition continues to deteriorate due to repetitive hemoptysis, and may even become critical. Surgical treatment is required for these patients; however, it is extremely difficult to resect the lesion due to severe adhesions to the chest wall and vascular proliferation surrounding the lesion. We performed preoperative arterial embolization, achieving good results in three patients with hemoptysis caused by pulmonary aspergillosis. The feeding arteries were embolized using microcoils and/or gelatin sponges, and a lobectomy was safely carried out in all patients. We concluded that preoperative arterial embolization is a safe and effective technique to prevent massive hemorrhage occurring at the time of surgery.
We describe our technique for performing direct thoracoscopic closure of a congenital partial pericardial defect, which was successfully employed in a 15-year-old boy. This is the first such report of a procedure that is noninvasive and may therefore become the treatment of choice for patients with a small congenital pericardial defect.
Trehalose 6,6'-dimycolate (TDM), an immunomodulator, potentiates non-specific resistance in mice to influenza virus infection. When mice were injected intravenously with TDM, the striking proliferation of a minority of T-lymphocytes bearing gamma/delta T-cell receptors (gamma delta T-cells) that accumulated in granulomatous lungs was thought to be associated with the maintenance of acquired resistance to lethal influenza virus infection. To clarify the cellular basis of the defence against influenza virus, mice were depleted of gamma delta T-cells, alpha/beta (alpha beta) T-cells, or natural killer (NK) cells by in vivo administration of corresponding antibodies prior to influenza virus infection. The depletion of gamma delta T-cells significantly abrogated the augmented resistance of TDM-treated mice to infection, as did depletion of either alpha beta T-cells or NK cells. To gain insight into the functional ability of gamma delta T-cells, we evaluated the cytotoxic activity of this T-cell subset against a panel of target cell lines that were stably transfected with the influenza virus haemagglutinin (HA) gene from A/PR/8/34(H1N1) and A/Aichi/2/68(H3N2) strains. The gamma delta T-cells from TDM-treated mice showed profound cytotoxicity against the target cells expressing HA of either the H1 or H3 subtype, in a non-major histocompatibility complex-restricted manner. Taken together, these results indicate that gamma delta T-cells play a non-specific role, in conjunction with alpha beta T-cells and NK cells, in protecting mice against influenza virus infection, and that the recognition and destruction of HA-expressing target cells by the activated gamma delta T-cells is one of the steps involved in this anti-influenza virus immunosurveillance.
To evaluate the roles of cAMP degradation on hormonal actions in the kidney, we examined the segmental distribution and activities of cAMP-phosphodiesterase (PDE), a key enzyme for cAMP hydrolysis, in dissected segments of the rat nephron and characterized the isozyme compositions with subtype-specific inhibitors. Summary of the nephron distribution of PDE activities showed that cAMP-PDE activities were detected in all nephron segments and the distal convoluted tubules (DCTs) had the highest activity. Both in proximal convoluted tubules (PCTs) and medullary collecting ducts (MCDs), more than 80% of the total cAMP-PDE activities were inhibited by a nonspecific PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX). In PCTs, rolipram (type-IV PDE inhibitor) was an equally potent inhibitor of IBMX, while 8-methoxymethyl-IBMX (MM-IBMX, type-I PDE inhibitor) and cilostamide (type-III PDE inhibitor) inhibited cAMP-PDE by 35 and 57%, respectively. In MCDs, inhibition by rolipram (40%) was less than that by MM-IBMX (70%) or cilostamide (66%). Rolipram potentiated the parathyroid hormone (PTH)-induced cAMP content in PCTs most effectively. Rolipram and MM-IBMX increased the vasopressin (AVP)-stimulated cAMP content equally in MCDs. Cilostamide had no effect on the cAMP content stimulated by PTH or AVP in PCTs and MCDs. These results indicate that PDE activities were unevenly distributed along the rat nephron and cAMP-PDE was composed of at least three isoforms, namely type I, III and IV in PCTs and MCDs. Among these, type-IV PDE was responsible for hydrolysis of cAMP in PCTs, and type-I and IV PDE were responsible for that in MCDs.
We performed radiofrequency catheter ablation (RF ablation) for ventricular tachycardia (VT) in 2 patients with dilated cardiomyopathy (DCM) and 1 patient with arrhythmogenic right ventricular dysplasia (ARVD). Patient 1 had incessant VT associated with DCM. RF ablation was performed where diastolic potentials were recorded and concealed entrainment was demonstrated. VT was terminated by RF ablation. Patient 2 had drug-resistant VT associated with ARVD. RF ablation was performed where perfect pace-mapping was obtained during sinus rhythm, diastolic potentials were recorded and concealed entrainment was demonstrated. VT was terminated by RF ablation. Patient 3 had 2 morphologically distinct VTs associated with DCM. The target for RF ablation was 1 of the 2, which was a drug-resistant type. Perfect pace mapping was obtained where delayed potentials were recorded. As the current strength of pacing was reduced, the QRS complex configuration switched to the other type. This site was thought to be the common slow conduction zone for the re-entry circuit of the 2 types and RF ablation was performed at this site. In these 3 cases, VT did not recur after ablation. RF ablation is effective for the treatment of VT associated with cardiomyopathy.
Bombyxin F1 gene, a new bombyxin family gene, has been identified. The F1 gene forms a pair with bombyxin B10 gene with an opposite transcriptional orientation and the gene pair F1/B10 is located between bombyxin gene pairs B9/C1 and A7/B7 in a bombyxin gene cluster. The nucleotide sequence of the F1 gene and its deduced amino acid sequence deviate moderately from those characterized previously for the family-A, family-B, family-C, family-D, and family-E bombyxin genes; the bombyxin F1 gene and preprobombyxin F1 share no more than 62% and 53% sequence identities with other bombyxin members, respectively. Harr-plot analysis indicated that the spacer of the F1/B10 gene pair has low sequence similarity with that of other bombyxin gene pairs characterized. The bombyxin F1 mRNA in Bombyx mori brain was shown to locate in four pairs of medial neurosecretory cells, which also produce other bombyxin family mRNAs. Genomic Southern hybridization indicated that the Bombyx haploid genome contains a single copy of the family-F bombyxin gene.
During the period of 1981 and 1995, 54 patients with T4 lung cancer underwent pulmonary resection in our institutes. The actuarial survival rate of them was 30% at three years and 12% at five years. The five-year survival rate of 12 patients with complete resection was 33%. On the other hand, the five-year survival rate of 30 patients with incomplete resection was 9%. The five-year survival rates of 17 patients with N0 disease, 9 patients with N1 disease, and 22 patients with N2 disease were 13%, 40%, and 5%, respectively. There was a significant difference in survival between patients with N1 and N2 disease. Four patients survived for more than five years after the operation : two patients had invasion to the left atrium and two had a slight degree of pleural dissemination. Radical pulmonary resection may yield long-term survival in T4 lung cancer patients having invasion to the left atrium.
We report a case of testicular tumor detected by ultrasonography during the prenatal period. Ultrasonography performed at 32 weeks of gestation showed that one testis was larger than the other. The right testis was markedly enlarged at 38 weeks of gestation. The heterogeneous echo pattern of the right testis suggested a testicular tumor. Right high orchiectomy was performed 3 months after birth. Pathological findings of the tumor were teratoma with mature and immature components according to the histological classification of testicular tumor. In Japan, this is the second case diagnosed in the prenatal period using ultrasonography.
We report a rare case with rupture of thymic cyst including mediastinal hemorrhage and hemothorax. A 68-year-old man was referred to our hospital for the treatment of right hemothorax. A chest roentgenogram following thoracentesis demonstrated a widened mediastinum. Chest computed tomograms revealed a large anterior mediastinal mass extending to the right pleural cavity and bilateral pleural effusion. Digital subtraction angiography showed a normal aorta and great vessels. A median stenotomy revealed a large encysted hematoma along the thymic cyst extending from the right anterior mediastinum into the right pleural cavity and ending with rupture. Pathological examination demonstrated that the largest thymic cyst was continued to the hematoma resulting from partial destruction of its epithelial lining. To our knowledge, only five cases including our's with ruptured thymic tumors were reported, and this is the first report of ruptured thymic cyst resulting in mediastinal hemorrhage and hemothorax.
OBJECTIVE: To assess the anterior mediastinal mass in recurrent testicular cancer, with relation to thymic hyperplasia after treatment. METHODS: The anterior mediastinal regions were fully evaluated by chest computed tomography (CT) at the initial staging and after treatment in 24 of 44 patients with testicular cancer. RESULTS: One patient with stage IIB tumor had thymic hyperplasia before treatment, and one with stage III had benign thymic hyperplasia after chemotherapy with salvage surgery. Three of 4 patients who had recurrence had an anterior mediastinal mass. One had benign thymic hyperplasia confirmed by histology and 2 had metastatic tumor confirmed by histology and clinical course, in which the mass became so enlarged that it obstructed major vessels. CONCLUSION: Although the relationship of the CT finding to the response to treatment in the anterior mediastinal mass and other metastatic lesions provide some clues helpful in differentiating benign from malignant masses, surgical exploration is recommended for the patient with an indication for salvage surgery.
We reported a long-term survivor with invasive thymoma associated with myasthenia gravis. The patient underwent operations 4 times for these 13 years. At the third and fourth operation, the tumor was resected after preoperative neo-adjuvant chemotherapy with cisplatin and adriamycin, and postoperative radiotherapy was added. Her postoperative course was uneventful, and she has been alive. Our strategy for invasive thymoma is that tumors which include both primary and recurrent lesions are removed as completely as possible, and that postoperative radiotherapy is added for stage II, III and IV in Masaoka's classification, and preoperative neo-adjuvant chemotherapy for stage III and IV. We believe that these multidisciplinary treatments and long term follow-up lead good results without harm to quality of life.
Thymic size and density were studied in 23 untreated patients with Graves' disease and 38 control subjects using computed tomography. Both thymic size and density were higher in untreated patients with Graves' disease than in control subjects in the age-matched group. After treatment with antithyroid drugs, both thymic size and density were significantly reduced, with a concomitant decrease in thyrotropin receptor antibodies. PCR of human thymic cDNA using primers for human thyrotropin receptor amplified a fragment in a size expected for the receptor, and its nucleotide sequence was identical to human thyrotropin receptor cDNA in the thyroid. Northern blot analysis of human thymic poly(A)+ RNA demonstrated the presence of the full length form of thyrotropin receptor mRNA. Western blot analysis of human thymic membrane using anti-thyrotropin receptor peptide antibodies demonstrated a band of 100 kD that was also observed in the thyroid membrane. Immunohistochemistry of thymic tissue using mouse antihuman thyrotropin receptor monoclonal antibodies demonstrated the immunostaining of epithelial cells. These results indicate that thymic hyperplasia is apparently associated with Graves' disease and suggest that thymic thyrotropin receptor may act as an autoantigen that may be involved in the pathophysiology of development of Graves' disease.
We have isolated a human homologue (MEST) of the mouse mesoderm-specific transcript (Mest) gene that shares about 70% nucleotide sequence homology. Northern blot analysis showed that the MEST gene was expressed in all major fetal organs and tissues so far examined, i.e., amnion, brain, heart, lung, stomach, gut, adrenal, kidney, muscle, and liver, which does not contradict with mesoderm-specific expression. MEST was abundantly expressed in hydatidiform moles of androgenetic origin, whereas it was barely detectable in dermoid cysts of parthenogenetic origin. Thus, it seems likely that the MEST gene, mapped to 7q32 by fluorescence in situ hybridization, is maternally repressed as the mouse homologue.