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Biomedical subjects

Y Furuta

Publications and source records attributed to Y Furuta.

At least 91 records · Page 5Linked to original sources

Parthenogenetic activation of oocytes in c-mos-deficient mice.

In Xenopus the c-mos proto-oncogene product (Mos) is essential for the initiation of oocyte maturation, for the progression from meiosis I to meiosis II and for the second meiotic metaphase arrest, acting as an essential component of the cytostatic factor CSF. Its function in mouse oocytes is unclear, however, as is the biological significance of c-mos mRNA expression in testes and several somatic tissues. We have generated c-mos-deficient mice by gene targeting in embryonic stem cells. These mice grew at the same rate as their wild-type counterparts and reproduction was normal in the males, but the fertility of the females was very low. The c-mos-deficient female mice developed ovarian teratomas at a high frequency. Oocytes from these females matured to the second meiotic metaphase both in vivo and in vitro, but were activated without fertilization. The results indicate that in mice Mos plays a role in the second meiotic metaphase arrest, but does not seem to be essential for the initiation of oocyte maturation, spermatogenesis or somatic cell cycle.

Animals↗

Predictors of myocardial infarction after distal embolization of coronary vessels with percutaneous transluminal coronary angioplasty. Experience of 21 consecutive patients with distal embolization.

Of 1,855 patients with angina pectoris who underwent percutaneous transluminal coronary angioplasty (PTCA) in our hospital, 21 experienced distal embolization. Five of the patients had slow washout of contrast medium distal to the dilated stenosis accompanied by S-T segment elevation (slow-flow pattern). In the other 16 cases, a dislodged embolus was found distal to the dilated stenosis (occlusive pattern) following balloon inflation. Of the 21 patients, 8 (38%) developed acute myocardial infarction (MI). All patients with acute MI were thought to have intraluminal thrombus on angiography performed before PTCA. Interestingly, patients with recent MI or worsening angina had a significantly higher rate of acute MI (p < 0.05).

Adult↗

The significance of herpes viral latency in the spiral ganglia.

To better understand the pathogenesis of idiopathic sudden hearing loss (ISHL), the possibility of latent virus infection in the spiral ganglion cell was considered. Only few spiral ganglion cells showed positive viral antigen after systemic guinea pig-specific cytomegalovirus (GPCMV) inoculation indicating the absence of hearing loss but the possibility of a subsequent latent infection. By using a modern molecular biological technique we have detected the herpes simplex virus type-1 (HSV-1) DNA in human spiral ganglia. The concept of establishing viral latency in the spiral ganglion cells with periods of reactivation fits with the clinical picture seen in ISHL, even though the mechanism of reactivation still remains unclear.

Adult↗

Chromium-induced carcinoma in the nasal region. A report of four cases.

The carcinogenicity of chromium is well established in chromium-induced lung cancer. As of yet, however, there have been only few reports of head-and-neck cancer induced by chromium. We report four cases of carcinoma in the nasal region which seemed to be induced by chromium. All patients have worked at the same chromate factory for 19 to 32 years. The first patient has suffered from squamous cell carcinoma of the left nasal cavity, starting 11 years after his retirement. He received radiotherapy followed by surgery. A malignant fibrous histiocytoma occurred in his left upper gingiva in a previously irradiated region, 7 years after the previous treatment. Surgery and chemotherapy for palliation failed to control the tumour, and he eventually expired. The other three patients underwent lobectomy for lung cancer. In cases 2 and 3, the tumour occurred in the left nasal cavity six and ten years, respectively, each after the lobectomy. In case 4, the tumour arose from the nasopharynx 15 years after the lobectomy. These patients are alive and well without any sign of tumour. The presented cases seem to be induced by long-term exposure to chromium. We conclude that regular physical examination of chromate workers is mandatory for the early detection not only of lung cancer but also of head-and-neck cancer.

Aged↗

Fyn expression during early neurogenesis in mouse embryos.

Fyn is a member of the Src family of tyrosine kinases which are thought to play important roles in cell to cell interactions during morphogenesis. The developmental profile of Fyn expression was examined using mutant mice in which lacZ gene was introduced into this locus. The expression was characteristic in the neural system. Though at low levels, it was detected in the headfold at embryonic day (E) 7.5 and in the luminal surface of neuroectoderm along the entire neural groove at E8.5. The expression appeared regional in rhombomeres at E8.5 and E9.5. Consistent expression was also found at a low level in the notochord. The expression was high in later stages of the neural tube which consists of three layers; it was in the marginal layer but not in the germinal layer. High expression was also found in developing dorsal root filaments of neural crest origin. Non-expression in dividing neuroepithelial cells and expression in developing neural fibers appeared ubiquitous features of Fyn expression throughout the entire brain.

Animals↗

Experimental model for MDS-like myelodysplasia in transgenic mice harboring the SV40 large-T antigen under an immunoglobulin enhancer.

The SV40 large T gene under the control of immunoglobulin enhancer induced hyperproliferation of multi-lineage hematopoiesis in transgenic mice. Hence the disease has been considered to be an appropriate experimental model for MDS-like myelodysplasia, sequential pathological changes in the development of the disease are introduced in the report. Huge splenomegaly was the major gross abnormality, which developed with 100% frequency; neither hepato-renal, nor other thymico-lymphatic involvement was common. During the progressive increase in splenic weight, extensive proliferation of multi-lineage hemopoiesis was prominent, although no differences were apparent in the cellular proportions of each hematopoietic element compared with normal spleens, either in flow-cytometric analysis using markers for each subset of hematopoietic elements, or in the histological findings. In the later phases of the disease, the proliferating cell type tended to shift to a variety of single to oligo-lineage hemopoiesis, but the majority of mice still showed the presence of multi-lineage hemopoiesis; histologically, such hemopoiesis was somewhat dysplastic, but had no apparent nature of leukemic infiltration. Several transplantation-assays essentially supported the low neoplastic potential of proliferating cells even in later phase. A long-term observation was made aiming to induce more frequent transition of this abnormal hemopoiesis into a single-lineage neoplasm by transplantation of pre-onset spleen cells, as well as bone-marrow cells from transgenic mice at an early phase of the disease, into lethally irradiated C57BL/6 mice. This trial resulted in a variety of neoplastic growths in the recipients; not only was myelodysplastic hypercellularity seen, but also, single-lineage hemopoietic malignancies, such as B-cell lymphomas/leukemias, histiocytic malignancies, and even myeloid leukemias. The transition from multi-lineage myelodysplasia into single lineage hemopoiesis at some frequency is reminiscent of myelodysplastic syndromes (MDS) in humans. Higher frequency of transition into lymphoid malignancies may be due partly to the immunoglobulin enhancer used as a promoter unit. The results that the SV40 large T antigen was expressed in every proliferating cells, there was no apparent increase in multi-CSFs activity; together with the results of the transplantation assays suggest that the hyperproliferation of the cells is directly induced by the expression of SV40 large T antigen in the hemopoietic cells themselves.

Animals↗

Non-receptor tyrosine kinases in mammalian neurogenesis.

Several members of the Src family of non-receptor tyrosine kinases are expressed at high levels in embryonic neural tissues as well as in adult brain. Relatively little has been known, however, about their roles in neural development. Attempts to clarify this by production of mutant mice have been unsuccessful because of gene redundancy. We earlier isolated a new cytoplasmic protein tyrosine kinase, Csk, and showed that it inactivates uniquely all members of non-receptor tyrosine kinases in vitro. Here, we have generated Csk-deficient mouse embryos and shown that Csk is indeed an indispensable negative regulator for all non-receptor tyrosine kinases in vivo, and that regulated activity of these kinases is essential for normal development of mice at the neural stage. The signaling pathway through Src-family kinases during neurulation is also discussed.

Amino Acid Sequence↗

A novel ES cell line, TT2, with high germline-differentiating potency.

In producing mutant mice by gene-targeting and gene-trapping in embryonic stem (ES) cells, the efficient colonization of the mutant ES cells into germline is still a critical matter. We have established a new line of ES cells, TT2, from an F1 embryo between a C57BL/6 female and a CBA male. When the TT2 cells were injected into blastocysts, the colonization into each tissue was very low. However, when injected into eight-cell embryos, the cells segregated inside the blastomeres, localized in an inner cell mass of blastocysts developed 1 day later, and colonized efficiently in each tissue of the pups. The pups were disproportionately male, about half of which were composed of TT2-derived cells primarily; in more than 70% of the males, TT2-derived cells were dominant, accounting for over half of the total cells. When these males were mated, they exclusively yielded TT2-derived offspring. The germline-differentiating potency was stable during 3 weeks of culture. Twenty-one of 24 mutant clones independently isolated yielded germline chimeras, and 19 clones yielded them in a rate comparable to that of the parent cells. Thus, TT2 cells can serve as a valuable vehicle for the production of mutant mice.

Animals↗

Degeneration of skeletal and cardiac muscles in c-myb transgenic mice.

In order to reveal cellular processes sensitive to abnormal c-myb expression in vivo, transgenic mice were produced by introducing the c-myb nuclear proto-oncogene under the ubiquitous transcriptional regulatory unit of the cytoplasmic beta-actin gene. Expression of c-myb in thymus did not cause apparent abnormality, but the mice unexpectedly developed degenerative abnormalities in skeletal and cardiac muscles; this occurred predominantly in males. Expression of c-myb in skeletal muscle was correlated with an inflammation of muscle and was accompanied by vacuolar degeneration of muscle fibres, their regeneration, and lymphocyte infiltration. The identical pathological progression in cardiac muscle was associated with cardiomegaly.

Actins↗

Percutaneous angioplasty of stenosed gastroepiploic artery grafts.

OBJECTIVES: This report describes our early experience and results with percutaneous transluminal coronary angioplasty of gastroepiploic artery grafts in 12 patients. BACKGROUND: Angioplasty has been successfully performed in saphenous vein and internal thoracic artery grafts; however, experience with angioplasty in gastroepiploic artery/coronary artery bypass grafts is limited. METHODS: Balloon angioplasty was performed in 12 patients (11 men, 1 woman; mean age 58 +/- 8 years) with either total occlusion (6 patients) or severe stenosis (6 patients) of a gastroepiploic artery/coronary artery anastomosis. In seven patients, a guide wire/balloon catheter system was used through a 7F sheath inserted into the celiac trunk. In seven patients, including two who had unsuccessful wire/balloon angioplasty, an over the wire system was used through a 6.5F Cobra or 7F JR4 guide catheter, selectively inserted into the gastroduodenal artery. RESULTS: Angioplasty was successful in five (83%) of six patients with stenosis and in one of six patients with total occlusion (p = 0.08, 1 - beta = 0.68). The guide wire could not be advanced through the lesion in five patients, and the balloon catheter did not cross the lesion in one patient whose gastroepiploic artery was tortuous. Catheters exhibited better trackability and pushability when the over the wire system was used, and five of the six successes were achieved using this approach. Follow-up arteriography was performed in five patients, and all of the gastroepiploic artery grafts were patent without stenosis. CONCLUSIONS: Angioplasty can be safely performed in stenosed gastroepiploic artery grafts. An over the wire system that uses a thin balloon catheter inserted through a guide catheter in the gastroduodenal artery seems optimal.

Aged↗

Thyroplasty type I with ceramic shim.

To improve hoarseness or misswallowing caused by unilateral recurrent laryngeal nerve paralysis, medialization of paralyzed vocal cord has frequently been performed. This method includes such techniques as injection method, insertion method, and arytenoid adduction, each presenting its merits and demerits. The insertion method which can be done while monitoring the patient's voice seems advantageous in that the technique is easy to perform and generally guarantees the voice improvement. Among insertion methods, Isshiki thyroplasty type I is the one most representative as well as popularized. However, since a silicone shim is inserted in this operation, it may be accompanied by the risks of carcinogenicity, foreign body reaction, and induction of collagen disease of silicone. Therefore we planned to use a ceramic as a safe substitute instead of silicone. There has been no article reporting the use of ceramic in this type of surgery. We used a fibrin glue to fix the ceramic shim and for hemostasis, which was found very useful. Hitherto, 2 cases of unilateral recurrent laryngeal nerve paralysis underwent Isshiki thyroplasty type I using ceramic shim with satisfactory results.

Aged↗

Latent herpes simplex virus type 1 in human vestibular ganglia.

Viral infection has been considered to be a possible pathogenesis of vestibular neuronitis, and reactivation of the herpes simplex virus (HSV) is one of the most likely causes. However, it remains unknown whether the human vestibular ganglia contain latent HSV. We examined 26 vestibular ganglia from autopsied adults in search of HSV type 1 (HSV-1). To detect HSV-1, we used polymerase chain reaction (PCR), in situ hybridization and immunohistochemical staining. HSV DNA was detected in 6 of 10 vestibular ganglia using the PCR method. However, the latency-associated transcript (LAT) of HSV-1 was negative in all of the 16 vestibular ganglia examined. No HSV antigen was detected in any of the ganglia. These results indicate that HSV-1 is latently infected in the human vestibular ganglia, and that LAT is transcribed weakly or not at all.

Adult↗

MDS-like experimental myelodysplasia: multilineage abnormal hematopoiesis in transgenic mice harboring the SV40 large T antigen under an immunoglobulin enhancer.

The SV40 large T gene under the control of immunoglobulin enhancer induced hyperproliferation of multilineage hematopoiesis in transgenic mice. Huge splenomegaly was the major gross abnormality; mice were rather anemic, and neither leukoerythroblastosis nor invasion into tissues such as liver, kidneys or lymph nodes was common. In the latter phases of the disease, the proliferating cell type tended to shift to a variety of single-lineage hematopoiesis, but the majority of mice still showed the presence of multilineage hematopoiesis; such cells were somewhat dysplastic but low in neoplastic potential. A long-term observation by transplantation of the hematopoietic cells into lethally irradiated C57BL/6 mice resulted in a variety of neoplastic growths in the recipients; not only was myelodysplastic hypercellularity seen, but also single-lineage hematopoietic malignancies such as B cell lymphomas/leukemias, histiocytic malignancies and even myeloid leukemias. The disease bore the proliferative feature solely in the spleen and bone marrow, and the transition from multilineage myelodysplasia into single-lineage hematopoiesis at some frequency is reminiscent of myelodysplastic syndromes (MDS) in humans. The results that the SV40 large T antigen was expressed in every proliferating cell, and that there was no apparent increase in any colony-stimulating cytokine(s), together with the results of the transplantation assays, suggested that the hyperproliferation of the hematopoietic cells was a direct consequence of the expression of SV40 large T antigen in these cells themselves.

Animals↗

Detection of human papillomavirus DNA in carcinomas of the nasal cavities and paranasal sinuses by polymerase chain reaction.

The authors retrospectively searched for human papillomavirus (HPV) types 16 and 18 in 60 cases of carcinoma arising from the nasal cavities (NC) and paranasal sinuses (PS) by using the polymerase chain reaction (PCR) on DNA extracted from formalin-fixed, paraffin-embedded tissues. In cases of SCC (n = 49), the authors also compared the clinical features of patients with HPV-positive and HPV-negative results to determine the clinical significance of HPV. HPV 16 and 18 were detected in 7 of the 49 cases (14%) of SCC. In the other histologic types of carcinoma (n = 11), neither HPV 16 nor HPV 18 was detected. No significant differences in the clinical features were observed between patients with SCC with HPV-positive and HPV-negative results. The results suggest that HPV 16 and 18 are implicated in the pathogenesis of SCC arising from the NC and PS. However, the presence of HPV is not related to local progression, occurrence of metastases, or the prognosis of the patients.

Adult↗

Clinical significance of the epidermal growth factor receptor gene in squamous cell carcinomas of the nasal cavities and paranasal sinuses.

The authors retrospectively analyzed epidermal growth factor receptor (EGFR) gene amplification in 49 cases of squamous cell carcinoma (SCC) arising from the nasal cavities (NC) and paranasal sinuses (PS) by using slot-blot analysis of DNA extracted from formalin-fixed, paraffin-embedded tissues. Also, the relationship between the results of gene analysis and the clinical features of the patients was studied to investigate the clinical significance of the EGFR in SCC of the NC and PS. Amplification of the EGFR gene was detected in 5 of the 49 cases (10%). No significant difference was observed between EGFR gene amplification and the presence of lymph node metastases, local recurrence, or prognosis. This suggests that EGFR gene amplification is not related to the local progression or metastasis of the SCC in the NC and PS. In addition, it appears that amplification of the EGFR gene is not a prognostic indicator for SCC in the NC and PS.

Adult↗

Molecular characterization of a JC virus (Sap-1) clone derived from a cerebellar form of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by polyomavirus JC (JCV). In the majority of cases of PML the cerebrum is mainly affected (cerebral PML) but on rare occasions lesions are restricted to the cerebellum and brain stem (cerebellar PML). We report a rare cerebellar PML case which occurred in a Japanese patient undergoing prolonged hemodialysis treatment. To understand the molecular basis of the viral tissue tropism, we molecularly cloned JCV DNA and compared it with those of cerebral PML. Of ten clones analyzed nine showed identical fragment patterns after digestion with various restriction endonucleases, and we designated these clones Sap-1. It could be shown that the basic structures of the regulatory regions are similar between Sap-1 and isolates from cerebral PML. Restriction endonuclease mapping analysis was used to examine the genetic relationship between Sap-1 and urine-derived isolates containing the archetypal regulatory sequence. We found that Sap-1 was genetically related to an archetypal JCV isolate in Japan.

Base Sequence↗