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T Shinagawa

Publications and source records attributed to T Shinagawa.

At least 19 recordsLinked to original sources
PubMed2003

Origin-associated features of chondrocytes in mouse Meckel's cartilage and costal cartilage: an in vitro study.

Using a cell culture method, we histochemically and immunohistochemically investigated whether chondrocytes deriving from different origins, such as Meckel's or costal cartilages, express similar phenotypic characteristics. Chondrocytes isolated enzymatically from Meckel's and costal cartilages of 17-day embryonic mice both actively proliferated and formed cartilage nodules consisting of toluidine blue-positive proteoglycans and type II collagen. Both deposited calcified cartilaginous matrix as revealed by alkaline phosphatase (ALPase) activity and alizarin red staining throughout 3 weeks in culture. Immunostaining for osteopontin (OP), osteocalcin (OC), and osteonectin (ON) revealed that chondrocytes from both cartilages were positive for their proteins, but type I collagen was detected only in cells transforming from Meckel's chondrocytes late in the culture. Electron microscopy demonstrated that although costal and Meckel's chondrocytes had typical chondrocytic features during 2 weeks in culture, Meckel's chondrocytes transformed into osteocytic cells that produced thick, banded type I collagen fibrils. In contrast, costal chondrocytes maintained typical hypertrophic morphology throughout the final stage of culture. The present study suggests that Meckel's chondrocytes derived from neural crest-ectomesenchyme retain osteogenic potential, and differ from costal chondrocytes originating from mesoderm.

Alkaline Phosphatase↗
PubMed2002

Maternal plasma adenosine and endothelin-1 levels in twin gestation complicated by preeclampsia.

The aim of this study was to evaluate the relationship between the vascular resistance in uterine arteries and the maternal release of adenosine and endothelin-1 in twin gestations with and without preeclampsia. Uterine artery Doppler velocimetry and maternal arterial blood sampling were performed in 14 women with normal singleton gestation, nine women with singleton gestation with preeclampsia, eight women with dichorionic twin gestation without preeclampsia and six women with dichorionic twin gestation with preeclampsia at 28-34 weeks' gestation. In normal singleton gestations, the average maternal uterine arteries pulsatility index (PI), plasma adenosine and endothelin-1 levels were 0.64+/-0.07, 0.34+/-0.11 micromol/l and 1.29+/-0.31 pg/ml, respectively. In preeclamptic singleton gestations, increased vascular resistance in the uterine arteries (PI: 0.85+/-0.14, P<0.05) and the elevation of maternal arterial plasma adenosine (0.48+/-0.14 micromol/l, P<0.05) and endothelin-1 levels (1.91+/-0.55 pg/ml, P<0.05) were observed. In the normal twin gestation group, the average maternal vascular resistance of the uterine arteries (PI: 0.55+/-0.09) was lower than that in the normal singleton gestation group, while the average plasma adenosine levels (0.47+/-0.12 micromol/l) were higher than that in normal singleton gestation. On the other hand, significant increased plasma endothelin-1 concentrations (1.87+/-0.42 pg/ml) were observed in the preeclamptic twin gestation groups without changes in plasma adenosine levels or vascular resistance of uterine arteries. Our results indicate the presence of different mechanisms for the pathogenesis of preeclampsia between twin and singleton gestations.

Adenosine↗
PubMed2001

Increased susceptibility to tumorigenesis of ski-deficient heterozygous mice.

The c-ski proto-oncogene product (c-Ski) acts as a co-repressor and binds to other co-repressors N-CoR/SMRT and mSin3A which form a complex with histone deacetylase (HDAC). c-Ski mediates the transcriptional repression by a number of repressors, including nuclear hormone receptors and Mad. c-Ski also directly binds to, and recruits the HDAC complex to Smads, leading to inhibition of tumor growth factor-beta (TGF-beta) signaling. This is consistent with the function of ski as an oncogene. Here we show that loss of one copy of c-ski increases susceptibility to tumorigenesis in mice. When challenged with a chemical carcinogen, c-ski heterozygous mice showed an increased level of tumor formation relative to wild-type mice. In addition, c-ski-deficient mouse embryonic fibroblasts (MEFs) had increased proliferative capacity, whereas overexpression of c-Ski suppressed the proliferation. Furthermore, the introduction of activated Ki-ras into c-ski-deficient MEFs resulted in neoplastic transformation. These findings demonstrate that c-ski acts as a tumor suppressor in some types of cells. The level of cdc25A mRNA, which is down regulated by two tumor suppressor gene products, Rb and Mad, was upregulated in c-ski-deficient MEFs, whereas it decreased by overexpressing c-Ski in MEFs. This is consistent with the fact that c-Ski acts as a co-repressor of Mad and Rb. These results support the view that the decreased activities of Mad and Rb in ski-deficient cells at least partly contribute to enhanced proliferation and susceptibility to tumorigenesis. Human c-ski gene was mapped to a region close to the p73 tumor suppressor gene at the 1p36.3 locus, which is already known to contain multiple uncharacterized tumor suppressor genes.

Animals↗
PubMed2001

The Ski protein family is required for MeCP2-mediated transcriptional repression.

DNA methylation is essential for development in the mouse and plays an important role in inactivation of the X chromosome and genomic imprinting. MeCP2 is the founder member of a family of methyl-CpG-binding proteins. MeCP2 directly binds to the co-repressor mSin3, which interacts with class I histone deacetylase, recruiting them to methyl-CpG regions to suppress transcription. Here, we report that MeCP2 directly binds to two co-repressors, c-Ski and N-CoR, in addition to mSin3A, and that the c-Ski, which is encoded by the c-ski proto-onocogene, is required for MeCP2-mediated transcriptional repression. The two regions of c-Ski, including the C-terminal coiled-coil region, interact with the transcriptional repression domain in the center of the MeCP2 molecule. The immunostaining signals for c-Ski and MeCP2 overlap in the nuclear heterochromatin region, suggesting the co-localization of the two proteins. The degree of transcriptional repression mediated by a Gal4-MeCP2 fusion protein was abrogated by overexpression of the putative dominant negative form of c-Ski. Furthermore, injection of antibodies against c-Ski and Sno almost completely abolished the transcriptional repression mediated by the Gal4-MeCP2 fusion protein. These results suggest that the ski gene family is involved in methyl CpG-mediated transcriptional repression.

Blotting, Western↗
PubMed2001

Carbon-carbon bond formation by electrophilic addition at the central carbon of the mu-eta(3)-allenyl/propargyl ligand on the Pd-Pd bond.

The mu-eta(3)-allenyl/propargyldipalladium complexes were synthesized by the reaction of the corresponding eta(1)-allenyl- or eta(1)-propargylpalladium complexes with Pd(2)(dba)(3). The X-ray diffraction analysis indicates that the dinuclear complex has a unique structure, in which two palladium, three carbon, two phosphorus, and one halogen atoms are in the same plane. These dinuclear complexes react with electrophiles, such as HCl or AcCl, at the central carbon of the mu-eta(3)-allenyl/propargyl ligand to give the mu-eta(3)-vinylcarbenedipalladium complexes. Intramolecular reaction proceeded smoothly to give cyclization products quantitatively. Addition of a catalytic amount of a palladium(0) complex dramatically accelerated the carbon-carbon bond formation. The MO calculations on the mu-eta(3)-allenyl/propargyl complexes indicated that the reaction proceeds via orbital control.

Journal Article↗
PubMed2001

Role of PML and PML-RARalpha in Mad-mediated transcriptional repression.

Fusion of the promyelocytic leukemia (PML) protein to the retinoic acid receptor-alpha (RARalpha) generates the transforming protein of acute promyelocytic leukemias. PML appears to be involved in multiple functions, including apoptosis and transcriptional activation by RAR, whereas PML-RARalpha blocks these functions of PML. However, the mechanisms of leukemogenesis by PML-RARalpha remain elusive. Here we show that PML interacts with multiple corepressors (c-Ski, N-CoR, and mSin3A) and histone deacetylase 1, and that this interaction is required for transcriptional repression mediated by the tumor suppressor Mad. PML-RARalpha has the two corepressor-interacting sites and inhibits Mad-mediated repression, suggesting that aberrant binding of PML-RARalpha to the corepressor complexes may lead to abrogation of the corepressor function. These mechanisms may contribute to events leading to leukemogenesis.

Animals↗
PubMed2001

Moyamoya disease complicated with renal artery stenosis and nephrotic syndrome: reversal of nephrotic syndrome after nephrectomy.

A 7-year-old boy with moyamoya disease developed sustained hypertension, nephrotic syndrome, hyperreninemia, and occlusion of the right renal artery. After right nephrectomy, hyperreninemia and hypertension improved. Proteinuria was resolved after nephrectomy, in parallel with the decrease in plasma renin activity. Moyamoya disease can cause nephrotic-range proteinuria, which is caused hemodynamically by hyperreninemia.

Child↗
PubMed2001

Final height and growth hormone secretion after bone marrow transplantation in children.

Growth hormone (GH) deficiency has been regarded as a principal determinant for growth failure following bone marrow transplantation (BMT). We herein analyzed final height and GH secretion in the patients who received BMT during childhood. The study on final height in 30 patients (23 males; 19 with malignant disease) who underwent BMT before or at the onset of puberty showed the following findings: (1) Final height SD score (SDS) significantly decreased compared to pretreatment height SDS. (2) Patients who underwent BMT before the age of 10 years showed significantly greater reduction in height SDS compared to those who received after the age of 10 years. (3) The type of disease or a difference in preconditioning regimen did not influence the outcome of growth. (4) No patient showed GH deficiency. The study on GH secretion included 71 patients who had been followed for more than 5 years and who underwent insulin tolerance test more than twice following BMT. Thirteen patients experienced poor GH response at least once. Two of these patients had poor GH response repeatedly. In conclusion, children who undergo BMT at younger age have a higher risk of growth failure, and GH deficiency is not a major contributing factor for growth impairment following BMT.

Adolescent↗
PubMed2000

The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice.

The Ski and Sno oncoproteins are components of a macromolecular complex containing the co-repressor N-CoR/SMRT, mSin3 and histone deacetylase. This complex has been implicated in the transcriptional repression exerted by a number of repressors including nuclear hormone receptors and Mad. Further more, Ski and Sno negatively regulate transforming growth factor-beta (TGF-beta) signaling by recruiting this complex to Smads. Here we show that loss of one copy of sno increases susceptibility to tumorigenesis in mice. Mice lacking sno died at an early stage of embryogenesis, and sno was required for blastocyst formation. Heterozygous (sno(+/-)) mice developed spontaneous lymphomas at a low frequency and showed an increased level of tumor formation relative to wild-type mice when challenged with a chemical carcinogen. sno(+/-) embryonic fibroblasts had an increased proliferative capacity and the introduction of activated Ki-ras into these cells resulted in neoplastic transformation. The B cells, T cells and embryonic fibroblasts of sno(+/-) mice had a decreased sensitivity to apoptosis or cell cycle arrest. These findings demonstrate that sno acts as a tumor suppressor at least in some types of cells.

Animals↗
PubMed2000

Small bowel obstruction in early pregnancy treated by jejunotomy and total parenteral nutrition.

BACKGROUND: Small bowel obstruction in early pregnancy increases maternal and fetal morbidity and mortality and might be diagnosed mistakenly as hyperemesis gravidrum. Prompt diagnosis and therapy is essential. CASE: A 29-year-old primigravida was admitted at 13 weeks' gestation with small bowel obstruction. After jejunotomy, total parenteral nutrition was given until oral intake was resumed completely 1 month after surgery. She was discharged with no complications and the rest of her pregnancy and delivery were uneventful. CONCLUSION: Small bowel obstruction in early pregnancy should be diagnosed expeditiously and can be treated with jejunotomy and total parenteral nutrition.

Adult↗
PubMed2000

Japanese familial patients with male-limited precocious puberty.

Familial male-limited precocious puberty (FMPP) is a rare disease caused by constitutively activating mutations in the luteinizing hormone receptor (LH-R) gene. In the present study, we analyzed the LH-R gene in members of a Japanese FMPP family. Two males of the family were affected and had a heterozygous M398T mutation; one patient developed pubertal signs as early as 2 years of age, and the other at 6 years of age. Both patients had elevated serum testosterone levels and prepubertal gonadotropin secretions. The father of the latter patient carried the M398T mutation, but lacked history of precocious puberty. Thus, phenotypic differences were observed in the three males with the same LH-R mutation belonging to the same family. In summary, we have described a Japanese family with FMPP.

Child, Preschool↗
PubMed2000

Mechanism for the development of ovarian cysts in patients with congenital lipoid adrenal hyperplasia.

OBJECTIVE: Although ovarian cysts commonly occur in patients with congenital lipoid adrenal hyperplasia (CLAH), the mechanism of development remains to be determined. To clarify the pathogenesis of the ovarian cysts, endocrinological examinations were performed in patients with CLAH. METHODS: The subjects were three Japanese CLAH patients. Basal body temperature, serum and urinary gonadotropin levels, serum and/or urinary ovarian hormones and mutations of the steroidogenic acute regulatory protein (StAR) gene were examined. RESULTS: The basal body temperature was not biphasic in any patient. Basal LH levels were high in all CLAH patients and markedly responded to LH-releasing hormone in two patients. Urinary gonadotropin analysis revealed repetitive LH surges in the menstrual cycles of the CLAH patients. No increase in the urinary pregnanediol suggested anovulation in all patients, and bilateral ovarian cysts were found in two of the subjects. Examination of the StAR gene revealed a frameshift mutation 840delA at codon 238, a nonsense mutation Q258X at codon 258, a homozygotic mutation at Q258X, and a compound heterozygotic mutation with 251insG and Q258X. CONCLUSIONS: We concluded that the development of ovarian cysts may be derived from continued anovulation in CLAH patients. Elevated LH levels may be explained by increased sensitivity of the anterior pituitary to circulating estrogen.

Adolescent↗
PubMed1999

Histochemical and immunohistochemical analysis of the mechanism of calcification of Meckel's cartilage during mandible development in rodents.

It is widely accepted that Meckel's cartilage in mammals is uncalcified hyaline cartilage that is resorbed and is not involved in bone formation of the mandible. We examined the spatial and temporal characteristics of matrix calcification in Meckel's cartilage, using histochemical and immunocytochemical methods, electron microscopy and an electron probe microanalyser. The intramandibular portion of Meckel's cartilage could be divided schematically into anterior and posterior portions with respect to the site of initiation of ossification beneath the mental foramen. Calcification of the matrix occurred in areas in which alkaline phosphatase activity could be detected by light and electron microscopy and by immunohistochemical staining. The expression of type X collagen was restricted to the hypertrophic cells of intramandibular Meckel's cartilage, and staining with alizarin red and von Kossa stain revealed that calcification progressed in both posterior and anterior directions from the primary centre of ossification. After the active cellular resorption of calcified cartilage matrix, new osseous islands were formed by trabecular bone that intruded from the perichondrial bone collar. Evidence of such formation of bone was supported by results of double immunofluorescence staining specific for type I and type II collagens, in addition to results of immunostaining for osteopontin. Calcification of the posterior portion resembled that in the anterior portion of intramandibular Meckel's cartilage, and our findings indicate that the posterior portion also contributes to the bone formation of the mandible by an endochondral-type mechanism of calcification.

Alkaline Phosphatase↗
PubMed1999

Relapsing polychondritis diagnosed by Tc-99m MDP bone scintigraphy.

PURPOSE: Relapsing polychondritis is a generalized recurring disease of cartilage that involves joints, trachea, bronchi, laryngeal cartilages, costal cartilages, and cartilages of the ear and nose. It is associated with autoimmune diseases, including Hashimoto disease in some cases. METHODS: The authors evaluated a 29-year-old man with relapsing polychondritis who had symptoms and signs of a common cold for 2 months and anterior chest pain near the sternum for 1 month. RESULTS: After the diagnosis, the authors found that the patient had a history of thyroid therapy for hyperthyroidism 15 years before. Tc-99m MDP bone scintigraphy performed to evaluate anterior chest pain showed diffusely increased accumulation of radioactivity in all costocartilages and sternoclavicular joints. Based on that information, relapsing polychondritis was diagnosed. Ga-67 citrate scintigraphy was preformed to determine the optimum biopsy site of the cartilage. The diagnosis was histologically supported by the results of the open biopsy. CONCLUSIONS: In this case, Tc-99m MDP bone scintigraphy was useful for diagnosing relapsing polychondritis, and Ga-67 citrate scintigraphy was helpful in determining the biopsy site.

Adult↗
PubMed1999

Conservative management of a case of placenta praevia percreta.

Pregnancies complicated by placenta praevia and a history of caesarean section are associated with increased risk of placenta percreta (1). Placenta praevia percreta sometimes involves the bladder or other pelvic organ, invasion leading to genital bleeding or haematuria (2, 3). Bladder injury or uncontrollable profuse haemorrhage occasionally occurs in such patients during surgery. Examination of placental invasion is necessary as this clinical condition is severe. Treatment of placental myometrium invasion is required to prevent uncontrollable profuse haemorrhage during surgery. We present a multiparous patient who was diagnosed prenatally with placenta praevia percreta using magnetic resonance imaging (MRI) and who was treated conservatively with a good prognosis.

Adult↗