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N Hoshi

Publications and source records attributed to N Hoshi.

At least 19 recordsLinked to original sources
PubMed2006

Both N-terminal and C-terminal regions of steroid sulfatase are important for enzyme activity.

Steroid sulfatase (STS) is localized in the endoplasmic reticulum and catalyzes desulfation of 3beta-hydroxysteroid sulfates. X-linked ichthyosis (XLI) is an inherited skin disorder caused by deficiency of STS enzyme activity. We previously reported a case in which XLI with a one-base change in the STS gene and variation in amino acid Q560P developed. In this study, we performed molecular analysis to determine the importance of terminal regions of STS and the effect of mutant STS on STS enzyme activity. To examine the effect of terminal truncated STS on the enzyme activity, N- and C-terminal truncated STS expression vectors were transfected into COS-1 cells. The activity of truncated STS lacking the N-terminal regions declined, and the activity of C-terminal-truncated STS declined with extension of the truncated C-terminal region. Although the results of pulse-chase experiments showed that a one-base mutant STS (Q560P) and C-terminal-truncated STS (deltaC2 (1-559)) had no effects on protein synthesis and degradation, the mutant STS and C-terminal-truncated STS have dominant negative effect on STS enzyme activity when the STS mutant or truncated STS protein and a wild-type STS protein coexist in cells. Results of coprecipitation of the truncated STS with an STS-FLAG fusion protein showed that STS formed a dimer conformation in cells. In this study, we have shown that both the N-terminal region and C-terminal region are important for STS enzyme activity. The C-terminal mutant has a dominant negative effect on wild-type STS.

Amino Acids↗
PubMed2001

Endometrioid adenocarcinoma arising from adenomyosis: report and immunohistochemical analysis of an unusual case.

A case of endometrioid adenocarcinoma arising from adenomyosis is reported. The patient was a 53-year-old woman who complained of vulvar itching. Smear cytology of the endometrium revealed adenocarcinoma. Magnetic resonance imaging of the pelvis revealed a lesion with a slightly high intensity in the uterine fundus on a T2-weighted image. Semiradical total hysterectomy and bilateral adnexectomy were performed, followed by chemotherapy. Histologically, the lesion in the uterine fundus was composed mostly of adenocarcinoma with stromal invasion. There were many adenomyotic foci in and around the carcinoma, including some showing transition to adenocarcinoma. There was no malignant finding in the normally situated endometrium. The carcinoma invaded in the myometrium, involving the uterine serosa, but no dissemination to the peritoneal cavity was found. The carcinoma was, therefore, considered to be endometrioid adenocarcinoma arising from adenomyosis. Immunohistochemistry showed expression of p53 oncoprotein and Ki-67 antigen in the carcinoma cells. The value of immunohistochemistry in predicting prognosis is discussed.

Adenocarcinoma↗
PubMed2001

Cyclic ADP-ribose as a potential second messenger for neuronal Ca2+ signaling.

Cyclic ADP-ribose (cADPR), a known endogenous modulator of ryanodine receptor Ca2+ releasing channels, is found in the nervous system. Injection of cADPR into neuronal cells primarily induces a transient elevation of intracellular Ca2+ concentration ([Ca2+]i), and/or secondarily potentiates [Ca2+]i increases that are the result of depolarization-induced Ca2+ influx. Acetylcholine release from cholinergic neurons is facilitated by cADPR. cADPR modifies K+ currents or elicits Ca2+-dependent inward currents. cADPR is synthesized by both membrane-bound and cytosolic forms of ADP-ribosyl cyclase in neuronal cells. cADPR hydrolase activity is weak in the membrane fraction, but high in the cytoplasm. Cytosolic ADP-ribosyl cyclase activity is upregulated by nitric oxide/cyclic GMP-dependent phosphorylation. Stimulation of muscarinic and beta-adrenergic receptors activates membrane-bound ADP-ribosyl cyclase via G proteins within membranes of neuronal tumor cells and cortical astrocytes. These findings strongly suggest that cADPR is a second messenger in Ca2+ signaling in the nervous system, although many intriguing issues remain to be addressed before this identity is confirmed.

ADP-ribosyl Cyclase↗
PubMed2001

Lens culinaris agglutinin-reactive alpha-fetoprotein, an alternative variant to alpha-fetoprotein in prenatal screening for Down's syndrome.

BACKGROUND: Three serum tests, alpha-fetoprotein (AFP), human chorionic gonadotrophin and unconjugated oestriol, are now widely used for screening for Down's syndrome. Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) is a variant of alpha-fetoprotein with alpha1-->6 fucose appended to the reducing terminal N-acetylglucosamine. It is the most prominent AFP detected in the serum of patients with hepatocellular carcinoma. METHODS: We investigated microheterogeneities of the carbohydrate chain on AFP in fetal liver tissues, amniotic fluids and maternal sera obtained from pregnancies with Down's syndrome using lectin affinity electrophoresis with four lectins. The percentages of AFP-L3 in maternal sera from 22 Down's syndrome and 227 unaffected pregnancies were determined. RESULTS: Unlike the case with AFP concentration, the percentage of AFP-L3 in maternal serum and amniotic fluid was similar, and apparently not influenced by membrane permeability. Knowing the percentage of AFP-L3 in maternal serum was effective for discriminating between Down's syndrome-affected pregnancies and unaffected pregnancies. The percentage of AFP-L3 in maternal serum identified 55% of Down's syndrome cases with a 5% false-positive rate. CONCLUSIONS: AFP-L3 should be an effective replacement for AFP in prenatal Down's syndrome screening.

Adult↗
PubMed2001

Myofibrosarcoma of the bone: a clinicopathologic study.

Myofibroblastic tumors are fairly recently established soft tissue neoplasms. Although most of them appear to be benign, myofibrosarcoma of the soft tissue, seemingly their malignant counterpart, have been reported. We describe the clinicopathologic and radiologic features of four cases of myofibrosarcoma arising from the bone. All but one of the patients were women ranging in age from 60 to 71 years. Two tumors occurred in the metaphyses of distal femurs and the others arose in the iliac bones. On radiologic examination all tumors exhibited well-demarcated lytic destructive lesions without periosteal reaction. Two tumors were localized in the bone, whereas the other two extended into surrounding soft tissues. Histologically, all tumors were composed principally of a mixture of a cell-rich fascicular area and a hypocellular fibrous area. In the former area tumor cells had rather eosinophilic spindle-shaped wavy cytoplasm and were arranged in interlacing fascicles and small storiform patterns with variable numbers of inflammatory cells. Tumors occasionally showed prominent pleomorphism, and large cells with hyperchromatic nuclei were seen. In contrast, hypocellular areas had various features, including collagenous, hyalinous scar-like and rarely keloid-like areas. Focal coagulation necroses were present in all but one tumor. Immunohistochemically, the tumors were positive for vimentin, muscle actin (HHF35), alpha-smooth muscle actin, calponin, and desmin, whereas all of them were negative for high molecular weight caldesmon. On follow-up there was one fatal case with distant metastases, whereas the clinical courses of other cases after wide resection were excellent. Myofibrosarcoma of the bone has distinctive histopathologic features, which should be distinguished from those of other bone tumors with myoid differentiation.

Actins↗
PubMed2001

Signal transduction from bradykinin, angiotensin, adrenergic and muscarinic receptors to effector enzymes, including ADP-ribosyl cyclase.

Muscarinic acetylcholine receptors in NG108-15 neuroblastoma x glioma cells, and beta-adrenergic or angiotensin II receptors in cortical astrocytes and/or ventricular myocytes, utilize the direct signaling pathway to ADP-ribosyl cyclase within cell membranes to produce cyclic ADP-ribose (cADPR) from beta-NAD+. This signal cascade is analogous to the previously established transduction pathways from bradykinin receptors to phospholipase Cbeta and beta-adrenoceptors to adenylyl cyclase via G proteins. Upon receptor stimulation, the newly-formed cADPR may coordinately function to upregulate the release of Ca2+ from the type II ryanodine receptors as well as to facilitate Ca2+ influx through voltage-dependent Ca2+ channels. cADPR interacts with FK506, an immunosuppressant, at FKBP12.6, FK506-binding-protein, and calcineurin, or ryanodine receptors. cADPR also functions through activating calcineurin released from A-kinase anchoring protein (AKAP79). Thus, some G(q/11)-coupled receptors can control cADPR-dependent modulation in Ca2+ signaling.

ADP-ribosyl Cyclase↗
PubMed2001

Pseudosarcomatous myofibroblastic tumor and myosarcoma of the urogenital tract.

OBJECTIVE: Pseudosarcomatous myofibroblastic tumors (PMTs) of the urogenital tract are rare but distinctive lesions. Despite their benign behavior, they are frequently misinterpreted as leiomyosarcomas and rhabdomyosarcomas in preoperative biopsies and even in resected specimens because of their atypical spindle-cell features. Precise diagnosis of PMTs is important to avoid unnecessary radical therapy. We analyzed urogenital myoid tumors to clarify which of their characteristics are useful for the differential diagnosis. METHODS: We evaluated 7 urogenital myoid tumors consisting of 3 PMTs, 2 leiomyosarcomas, and 2 rhabdomyosarcomas. We studied the expression of various immunohistochemical muscle-cell markers including desmin, muscle-specific actin, alpha-smooth muscle actin, high-molecular-weight caldesmon, and myogenin. RESULTS: Desmin, muscle-specific actin, and alpha-smooth muscle actin were noted variably in all tumor types, whereas high-molecular-weight caldesmon was expressed only in leiomyosarcomas, and myogenin was expressed only in rhabdomyosarcomas. CONCLUSION: High-molecular-weight caldesmon and myogenin are useful for differentiating urogenital PMTs from myosarcomas.

Actins↗
PubMed2000

Novel mutation (E113X) of antithrombin III gene (AT3) in a woman with gestational recurrent thrombosis.

A 35-year-old Japanese woman with a low level (42-54%) of blood antithrombin (AT) III, experienced two induced abortions due to deep venous thrombosis at 8 weeks of gestation (GW) and cerebral thrombosis at 10 GW. The present pregnancy was successfully managed with intravenous administration of AT III (6,000-8,000 U/wk). Analysis of polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) for exons 3A and 4 of the AT III gene (AT3) using her DNA revealed extra expansion bands with altered migration. The DNA sequencing demonstrated novel mutations in exon 3A of AT3: a G to T substitution at nucleotide position 5333 in codon GAG for Glu 113, causing a stop codon (E113X), and an A to T substitution at position 5338 in codon AAA for Lys 114, forming Asn (K114N). These novel mutations, especially E113X, in AT3 may be related to recurrent thrombosis in the pregnancy.

Abortion, Induced↗
PubMed2000

PCR diagnosis of X-linked ichthyosis: identification of a novel mutation (E560P) of the steroid sulfatase gene.

X-linked ichthyosis (XLI) is an inherited skin disorder due to deficiency of steroid sulfatase (STS) activity. XLI has been diagnosed by assaying STS activity in placenta or lymphocytes of patients after birth. Most patients have a large deletion of the STS gene, generated by inaccurate recombination at the STS locus. However, point mutations in the STS gene have been reported in some patients with complete STS deficiency. In a new case of STS deficiency, we identified an STS missense mutation, Glu560Pro or E560P. This new point mutation suggests that the C-terminal region of the STS enzyme is important for STS enzymatic function. Hum Mutat 15:296, 2000.

Amino Acid Substitution↗
PubMed2000

Dumb-bell-type teratoma in the lumbar spine.

We report a case of a lumbar teratoma in a 50-year-old woman. The teratoma showed a dumb-bell-type expansion at the level of the left L3/4 foramen with massive erosion of the L3 vertebral body. MRI revealed inhomogeneous signal changes in the tumor, which were histologically compatible with a mixture of bone, muscle, fat, and cyst containing sebaceous material. Complete resection of the tumor and spinal arthrodesis with pedicle screw fixation was necessary to obtain stability of the affected spinal segment.

Bone Screws↗
PubMed2000

Factor XII deficiency in women with recurrent miscarriage.

Congenital thrombophilia is known to cause significant maternal complications, and possibly has an adverse effect on normal fetal development. The aim of this study was to assess the prevalence of factor XII (FXII) deficiency in women with a history of recurrent miscarriage. Two hundred and forty-one consecutive Japanese women with a history of two or more recurrent miscarriages were prospectively assessed for their etiology by conventional screening methods. Seven women were found to have reduced FXII activity (19. 2-46.1%) and prolonged activated partial thromboplastin time (33. 3-51.3 s). Of these 7 women, 6 had experienced early pregnancy losses, while 1 woman had experienced repeated mid-trimester fetal losses with coincidental gestational thrombocytopenia. In 241 women with a history of recurrent miscarriage, the prevalence of FXII deficiency was 2.9%.

Abortion, Spontaneous↗
PubMed2000

Fatty acid synthase is expressed mainly in adult hormone-sensitive cells or cells with high lipid metabolism and in proliferating fetal cells.

Animal fatty acid synthase (FAS) is a homodimer protein which synthesizes long-chain fatty acids and is rich in liver, brain, breast, and lung. However, the precise cellular localization of FAS in human tissues has not been elucidated. Immunohistochemistry with a new antibody to human FAS revealed that in adult human tissues FAS is distributed mainly in cells with high lipid metabolism (adipocytes, corpus luteum, hepatocytes, sebaceous glands, and Type II alveolar cells), in hormone-sensitive cells (anterior pituitary, apocrine gland, breast, endometrium, prostate, seminal vesicle, and adrenal cortex), and in a subset of epithelial cells of duodenum and stomach, colon absorptive cells, cerebral neurons, basket cells of cerebellum, decidua, uroepithelium, and epidymis. In fetal cells at 20 weeks of gestation, FAS was mainly present in proliferative epithelial cells of the digestive and respiratory systems, proximal renal tubules, adrenocortical cells, and mesenchymal and hematolymphoid cells. Staining was significant in nonproliferating cells, as observed in adult, and in sympathetic ganglion cells, Leidig cells of testis, and Langhans cells of chorionic villi. FAS is maintained in hormone-sensitive cells and/or cells active in lipid metabolism in the adult and is expressed in proliferating cells in the fetus, suggesting active fatty acid synthesis for energy utilization or membrane lipids.

Adipocytes↗
PubMed2000

Aneuploidy of sex chromosomes in basal cell carcinoma: its clonality and involvement in the development of carcinogenesis.

Although basal cell carcinoma (BCC) is a major skin cancer, the mechanism of carcinogenesis with regard to cytogenetic abnormalities has not been fully investigated. In the present study, we carried out cytogenetic analyses of 18 patients (9 male and 9 female) with BCC. Aneuploidy was seen by Q-banding method in more than half of the cases and was mostly loss of the sex chromosome. We also performed FISH to the interphase nuclei of various tissues and short-term cultured BCC cells. The frequency of sex chromosomal aneuploidy was significantly higher in all samples from BCC patients (peripheral blood lymphocytes, non-lesional tissues, BCC tumor tissues and cultured BCC cells) than in age-matched normal controls. In addition, we analyzed clonality of BCC tissues using a human androgen receptor gene assay and found uniparental pattern of inactive X-chromosomes. This indicates that BCC cells were monoclonal in origin and the development of BCC might be correlated with sex chromosomal aneuploidy, which acquired accumulation of genetic mutations.

Adult↗
PubMed1999

12-Lipoxygenase overexpression in rodent NG108-15 cells enhances membrane excitability by inhibiting M-type K+ channels.

1. 12-Lipoxygenase produces 12-hydroperoxy acid from arachidonic acid released from membrane phospholipids. To elucidate the role of the enzyme in neuronal functions, mouse neuroblastoma x rat glioma hybrid NG108-15 cells were permanently transfected with the cDNA for human 12-lipoxygenase. 2. The number of action potentials evoked by depolarizing current steps in a current-clamp mode was strikingly increased in 12-lipoxygenase-expressing NG108-15 cells as compared with the wild-type cells which hardly had the enzyme activity. 3. In the transformed cells, the M-type voltage-dependent K+ current was significantly reduced with little or no change in other ion channel currents. 4. Treatment of the transformed cells with a 12-lipoxygenase inhibitor recovered the action potential frequency and the M-current amplitude to the control level. 5. These results indicate that 12-lipoxygenase and/or its metabolites target K+ channels and upregulate the membrane excitability, and thereby modulate neuronal signalling.

Action Potentials↗
PubMed1999

Recent trends in the prevalence of Down syndrome in Japan, 1980-1997.

The aims of the present study were to determine recent trends in the prevalence of Down syndrome (DS) in Japan, and to determine whether recent changes in demographic and social habits and access to prenatal diagnosis have influenced the livebirth rates of DS. Livebirth statistics indicate that the birth rate in Japan has decreased for women in their 20s and has increased for those in their 30s and 40s. During an 18-year period between 1980 and 1997, 1,299 consecutive DS infants were born among a total of 2,232,694 births, a rate corresponding to approximately 10% of all births in Japan over the same period. The increasing risk of DS with advancing maternal age was confirmed. The overall prevalence was 5.82 DS births per 10,000 livebirths (8.3-9.7 per 10,000 after correction according to the estimated ascertainment ratio: 60-70%). The prevalence rate by year of child birth represents a statistically significant increase (P = 0.001). In conclusion, recent trends in the prevalence of DS in Japan from 1980 to 1997 failed to show a consistent tendency to decrease, probably because of the concomitant increase in pregnancy in advanced maternal age.

Birth Rate↗
PubMed1999

Membranocystic lesion in lumbar yellow ligament.

STUDY DESIGN: An examination of surgical cases of membranocystic lesions in the lumbar yellow ligament between the fourth and fifth lumbar vertebrae. OBJECTIVES: To report the incidence and pathogenesis of membranocystic lesions of the yellow ligament in surgical specimens. SUMMARY OF BACKGROUND DATA: The membranocystic lesion has been observed not only in membranous lipodystrophy, but also in other conditions. However, there has been no report concerning this lesion in the yellow ligament. METHODS: Forty-four yellow ligaments excised in surgery were histologically reviewed. In eight cases, S-100 expression was investigated. In two cases, ultrastructural findings were examined. RESULTS: Membranocystic lesions were present in 8 (18%) of the 44 cases. The cases with the lesions had undergone surgery for spondylolisthesis (4 cases), sequestration-type disc herniation (2 cases), postradiation status (1 case), and spinal stenosis (1 case). Histologically, in all 8 cases, fibrosis was present around the lesion. In 5 of the 8 cases, chondrocytes were observed adjacent to the lesion, and nuclei positive for S-100 protein were observed in 4 cases. Nuclei of chondrocytes adjacent to the lesion also were positive for S-100 protein. Ultrastructurally, irregularly shaped cystic spaces surrounded by an electron-dense membranous structure, which were identical to those of membranous lipodystrophy, were observed. CONCLUSIONS: These results suggest that degeneration of the chondrocytes has a causal relationship to the formation of membranocystic lesions in the yellow ligament.

Adolescent↗