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Biomedical subjects

S Wakatsuki

Publications and source records attributed to S Wakatsuki.

At least 37 records · Page 2Linked to original sources
PubMed1999

Fas ligand-induced apoptosis of hepatocytes in natural killer cell leukaemia.

Neoplastic natural killer (NK) cells overexpress Fas ligand (FasL), which may cause damage of Fas-bearing tissues. We report a patient with NK cell leukaemia who developed liver injury after pharyngitis. The NK leukaemic cells expressed functional FasL. In addition to soluble FasL, serum levels of interleukin-6 and interferon-gamma were increased dramatically when liver injury was aggravated. Moreover, hepatocytes expressed Fas and apoptotic hepatocytes were detected in the portal areas. These findings are consistent with the notion that inflammatory cytokines enhance the sensitivity to FasL and trigger apoptosis of hepatocytes in NK cell malignancies.

Adult↗
PubMed1999

Characterization of a novel fungal protein, p15, which induces neuronal differentiation of PC12 cells.

In our previous paper, we reported that a 15 kDa protein (p15) produced by a fungus, genus Helicosporium, enhanced NGF-induced neurite outgrowth from PC12 cells. Here we further characterized the actions of p15. The complete amino acid sequence of p15 was determined and it was shown to be a hydrophilic protein composed of 118 amino acid residues with two intramolecular disulfide bridges. p15-induced neurite outgrowth was blocked by the depletion of extracellular Ca(2+) in the culture medium and was significantly inhibited by L-type Ca(2+) channel inhibitor nicardipine. p15 stimulated Src kinase and MAPK activities, and neurite outgrowth was not observed in srcDN2, a dominant negative c-src(K295R)-expressing cell line, and was significantly reduced in RasN17-expressing cells. These results suggest that p15 stimulates neurite outgrowth through the potentiation of L-type Ca(2+) channels, thereby activating the Src-Ras-MAPK cascade.

Amino Acid Sequence↗
PubMed1999

Bladder neck suspension using percutaneous bladder neck stabilization to the pubic bone with a bone-anchor suture fixation system: A new extraperitoneal laparoscopic approach.

A 39-year-old woman with type 1 genuine stress urinary incontinence was treated using a novel extraperitoneal laparoscopic bladder neck suspension procedure with a bone-anchor suture fixation system. Operative time and blood loss were 2.5 and 50 g, respectively. The patient showed a remarkable improvement on chain cystography and in subjective and objective well-being with no complications, even 12 months after surgery. Extraperitoneal laparoscopic bladder neck suspension using the bone-anchor suture fixation system is an easy and feasible procedure.

Adult↗
PubMed1999

Biclonal lymphoplasmacytic immunocytoma associated with Crohn's disease.

A 33-year-old man with a 4-year history of Crohn's disease presented with marked ascites and an abdominal tumor. Two M-protein peaks, immunoglobulin (Ig) G-kappa and IgA-kappa, were detected in the serum. Neoplastic lymphoplasmacytic cells were infiltrated in the bone marrow and ascites. Histological examination of the abdominal tumor showed marked proliferation of lymphoplasmacytic cells that were positive for either IgG or IgA. Moreover, DNA sequences of the expressed IgG and IgA genes were different in the complementarity-determining region 3. These results suggest that chronic inflammation in Crohn's disease contributes to the simultaneous development of biclonal lymphoplasmacytic immunocytoma of the small intestine.

Abdominal Neoplasms↗
PubMed1999

[A case of tracheobronchopathia osteoplastica discovered incidentally by hypoxemia following the operation].

An 85-year-old woman was found to have tracheobronchopathia osteoplastica incidentally following an operation for left breast cancer. She entered the ICU because of impaired sputum expectoration and hypoxemia. For the purpose of bronchial toilet, bronchofiberscopy was performed under general anesthesia. Numerous nodular elevated lesions were found on all sides of trachea and lobar bronchi except at the membranous part. Transbronchial forceps biopsy showed squamous metaplasia of the mucosa and formation of lamellar bone in the submucosal tissue. The diagnosis was finally confirmed as tracheobronchopathia osteoplastica from these two findings. Although anesthesiologists rarely encounter this disease in their daily practice, it is necessary to keep tracheobronchopathia osteoplastica in their mind as an airway disease.

Aged↗
PubMed1998

ID14 'Quadriga', a Beamline for Protein Crystallography at the ESRF.

The ESRF undulator beamline ID14 'Quadriga' is dedicated to monochromatic macromolecular crystallography. Using two undulators with 23 mm and 42 mm periods and a minimum gap of 16 mm installed on a high-beta section, it will provide high-brilliance X-ray beams at around 13.5 keV, as well as a wide tuneability between 6.8 and 40 keV. Based on the Troika concept, this beamline has four simultaneously operating experimental stations: three side stations, EH1, EH2 and EH3, using thin diamond crystals, and an end station, EH4, with a fast-scan double-crystal monochromator. Station EH3 has a kappa-diffractometer, and an off-line Weissenberg camera with a large 80 x 80 cm active area combined with a 2048 x 2048 CCD detector. During data collection the image plates are placed and removed by a robot located inside the hutch using a cassette system. After data collection the image plates are scanned with an off-line drum scanner. Station EH4 is designed for MAD applications, including Xe K-edge anomalous experiments, and is equipped with a 2048 x 2048 CCD detector on a pseudo 2theta arm. A common graphical user interface and a database will be available to cover all aspects of data collection, including strategy optimization. First results on the performance of the optics elements and initial crystallographic results are presented.

Journal Article↗
PubMed1998

Crystal structure of troponin C in complex with troponin I fragment at 2.3-A resolution.

Troponin (Tn), the complex of three subunits (TnC, TnI, and TnT), plays a key role in Ca2+-dependent regulation of muscle contraction. To elucidate the interactions between the Tn subunits and the conformation of TnC in the Tn complex, we have determined the crystal structure of TnC (two Ca2+ bound state) in complex with the N-terminal fragment of TnI (TnI1-47). The structure was solved by the single isomorphous replacement method in combination with multiple wavelength anomalous dispersion data. The refinement converged to a crystallographic R factor of 22.2% (Rfree = 32.6%). The central, connecting alpha-helix observed in the structure of uncomplexed TnC (TnCfree) is unwound at the center (residues Ala-87, Lys-88, Gly-89, Lys-90, and Ser-91) and bent by 90 degrees. As a result, TnC in the complex has a compact globular shape with direct interactions between the N- and C-terminal lobes, in contrast to the elongated dumb-bell shaped molecule of uncomplexed TnC. The 31-residue long TnI1-47 alpha-helix stretches on the surface of TnC and stabilizes its compact conformation by multiple contacts with both TnC lobes. The amphiphilic C-end of the TnI1-47 alpha-helix is bound in the hydrophobic pocket of the TnC C-lobe through 38 van der Waals interactions. The results indicate the major difference between Ca2+ receptors integrated with the other proteins (TnC in Tn) and isolated in the cytosol (calmodulin). The TnC/TnI1-47 structure implies a mechanism of how Tn regulates the muscle contraction and suggests a unique alpha-helical regulatory TnI segment, which binds to the N-lobe of TnC in its Ca2+ bound conformation.

Amino Acid Sequence↗
PubMed1998

Adrenocortical tumor in a patient with familial adenomatous polyposis: a case associated with a complete inactivating mutation of the APC gene and unusual histological features.

Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary disorder caused by a germline inactivating mutation of the adenomatous polyposis coli (APC) gene. Patients with FAP sometimes develop various extracolonic manifestations including adrenocortical neoplasms. We present a 14-year-old boy with FAP who had an adrenocortical tumor with atypical histopathologic features, ie, sex-cord-like differentiation. Immunohistochemical studies of adrenal 4 binding protein (Ad4BP) and steroidogenic enzymes showed the capacity of these tumor cells to produce steroids. Genetic analysis of the tumor disclosed a two-hit mutation in APC: a germline 5-base pair deletion accompanied by a loss of the normal allele. Because there were no reports of genetic alterations in adrenocortical tumors developed in FAP patients, we examined 10 sporadic adrenal tumors (four carcinomas and six adenomas) for mutations in APC. However, no mutations were found in these 10 sporadic adrenal tumors. These results suggest that mutation of APC is also responsible for some fraction of the adrenocortical tumors: the tumor in this case is included.

Adenoma↗
PubMed1998

Etiological analysis of focal nodular hyperplasia of the liver, with emphasis on similar abnormal vasculatures to nodular regenerative hyperplasia and idiopathic portal hypertension.

Pathological studies were performed on 23 cases of focal nodular hyperplasia (FNH) under the hypothesis that FNH is a hyperplastic lesion caused by abnormal vasculatures of portal tracts within the nodule. For a comparison of the histological features of portal tracts, nodular regenerative hyperplasia (NRH), idiopathic portal hypertension (IPH), chronic hepatitis and so-called normal liver were used as control tissues. Extranodular areas of FNH nodules were also examined. Clinical data were briefly summarized. Most of the portal tracts within FNH nodules showed various abnormal findings, such as dilatation and/or stenosis of portal vein, muscular thickening of arterial wall with dilated or stenotic lumina, lymphocyte infiltration, and bile ductule proliferation. However, portal vein thrombi were not found. These findings were not thought to represent compensatory reaction to portal vein thrombosis. Similar abnormal features were also observed in extranodular areas of FNH although to a milder degree. These abnormal features resembled those of NRH and IPH. Moreover, the characteristic scar-like tissues within FNH nodules were proved to be abnormally large portal tracts including large feeding arteries, portal veins and bile ducts. It has been believed that septa and scar-like tissue within FNH nodules are not portal tracts and that arterial malformation independent of portal tracts are related to the development of FNH. In addition, venous structures within FNH modules have until now not been considered to be portal veins. However, this study revealed that severe anomaly of portal tracts including portal veins and hepatic arterial branches existed in FNH nodules. Moreover, portal tracts in extranodular areas were also abnormal. Clinically, only one patient had a history of oral contraceptives. Based on these findings, congenital anomaly of the portal tracts histologically resembling the abnormal portal tracts of NRH and IPH may be related to the pathogenesis of FNH.

Adult↗
PubMed1998

Matching the crystallographic structure of ribosomal protein S7 to a three-dimensional model of the 16S ribosomal RNA.

Two recently published but independently derived structures, namely the X-ray crystallographic structure of ribosomal protein S7 and the "binding pocket" for this protein in a three-dimensional model of the 16S rRNA, have been correlated with one another. The known rRNA-protein interactions for S7 include a minimum binding site, a number of footprint sites, and two RNA-protein crosslink sites on the 16S rRNA, all of which form a compact group in the published 16S rRNA model (despite the fact that these interactions were not used as primary modeling constraints in building that model). The amino acids in protein S7 that are involved in the two crosslinks to 16S rRNA have also been determined in previous studies, and here we have used these sites to orient the crystallographic structure of S7 relative to its rRNA binding pocket. Some minor alterations were made to the rRNA model to improve the fit. In the resulting structure, the principal positively charged surface of the protein is in contact with the 16S rRNA, and all of the RNA-protein interaction data are satisfied. The quality of the fit gives added confidence as to the validity of the 16S rRNA model. Protein S7 is furthermore known to be crosslinked both to P site-bound tRNA and to mRNA at positions upstream of the P site codon; the matched S7-16S rRNA structure makes a prediction as to the location of this crosslink site within the protein molecule.

Anticodon↗
PubMed1998

Identification and characterization of porcine NP-190, a novel protein that is specifically expressed in the axonal membrane during the embryonic period.

To identify and analyze the function of proteins expressed in the growth cones, we have screened monoclonal antibodies raised against the preparation of the growth cone particles derived from fetal porcine brains and found a novel neuronal antigen, termed NP-190. Biochemical characterization of NP-190 demonstrated that it was an integral membrane protein with an apparent molecular weight of 190 kDa and that it was mainly expressed in fetal brains. Homologous antigens with molecular weights of 200 and 170 kDa were also identified in the fetal brain extracts of chickens and rats, respectively. Immunoblot experiments of brain extracts from chickens and rats in various stages of development indicated that the expression of NP-190 homologs was developmentally regulated; it began to appear and increased in the embryonic stage, then decreased to very low level in the adult brains. Immunostaining of cultured primary of neurons from the embryonic day 18 rat cerebral cortex demonstrated that rat NP-190 homolog localized in the cell bodies, axons and growth cones, but not in dendrites. Partial amino acid sequence analysis of affinity-purified NP-190 from fetal porcine brains demonstrated that it was a novel protein. These results suggest that NP-190 plays a distinct role in brain development.

Amino Acid Sequence↗
PubMed1998

Histiocytic sarcoma of the spleen associated with hypoalbuminemia, hypo gamma-globulinemia and thrombocytopenia as a possibly unique clinical entity--report of three cases.

We report three patients with histiocytic sarcoma of the spleen associated with severe hypoalbuminemia, hypo gamma-globulinemia and thrombocytopenia. After the clinical diagnosis of splenic tumor of unknown origin was made, all three patients underwent splenectomy. The histiocytic origin of the tumor was confirmed histopathologically and immunohistochemically using a panel of antibodies. In contrast to malignant histiocytosis (MH), which typically reveals severe generalized clinical manifestations and a rapidly fatal course caused by the disseminated proliferation of neoplastic histiocytes, these patients were asymptomatic or showed only mild clinical symptoms for a long period of time until the recurrence was detected by which time the tumor cells had already spread to other organs. All three cases were characteristically associated with hypoalbuminemia, hypo gamma-globulinemia and thrombocytopenia, which returned to normal after splenectomy. Splenic histiocytic sarcoma with the features described here may represent a unique clinical entity, distinct from MH.

Adult↗
PubMed1998

Hepatosplenic gamma delta T-cell lymphoma associated with hepatitis B virus infection.

Hepatitis B virus (HBV) infection has been implicated in the development of hepatocellular and hematopoietic malignancies. We describe a patient with chronic hepatitis B who developed hepatosplenic gamma delta T-cell lymphoma. A 45-year-old woman presented with marked hepatosplenomegaly and hepatic failure during the course of chronic hepatitis B. Peripheral blood examination revealed 57% abnormal lymphoid cells which expressed the gamma delta T-cell receptor. The cytogenetic analysis of tumor cells showed an abnormal karyotype; 47, XX, -13, +2mar in all 20 metaphases examined. A clonal rearrangement of the T-cell receptor genes was demonstrated by Southern blot analysis, showing monoclonal expansion of tumor cells. A liver biopsy specimen showed fibrosis of the portal areas and sinusoidal infiltration of tumor cells. HBV infection was documented by the presence of IgG anti-HBc and anti-HBs antibodies in serum. Although HBV-DNA was not detected in tumor cells by polymerase chain reaction analysis, there is a possibility that proliferation of gamma delta T cells in response to HBV infection played a role in the pathogenesis of hepatosplenic gamma delta T-cell lymphoma.

Chronic Disease↗
PubMed1998

The crystal structure of troponin C in complex with N-terminal fragment of troponin I. The mechanism of how the inhibitory action of troponin I is released by Ca(2+)-binding to troponin C.

Troponin (Tn), the complex of three subunits (TnC, TnI, and TnT), plays a key role in Ca2+ dependent regulation of muscle contraction. To elucidate the interactions between the Tn subunits and the conformation of TnC in the Tn complex, we have determined the crystal structure of TnC in complex with the N-terminal fragment of TnI (TnI1-47). The structure was solved by single isomorphous replacement method in combination with multiple wavelength anomalous dispersion data. The refinement converged to a crystallographic R-factor of 22.2% (R-free = 32.6%). The central, connecting alpha-helix observed in the structure of uncomplexed TnC (TnCfree) is unwound at the center and bent by 90 degrees. As a result, the TnC in the complex has a compact globular shape with direct interactions between the N- and C-lobes, in contrast to the elongated dumb-bell shaped molecule of uncomplexed TnC. The 31-residue long TnI1-47 alpha-helix stretches on the surface of TnC and stabilizes its compact conformation by multiple contacts with both TnC lobes. The amphiphilic C-terminal end of the TnI1-47 alpha-helix is tightly bound in the hydrophobic pocket of the TnC C-lobe through 38 van der Waals interactions. The results indicate the major difference between integrated (TnC) and isolated (calmodulin) Ca2+ receptors. The TnC/TnI1-47 structure suggests the model for a novel regulatory TnI segment bound to TnC and implies the mechanism of how Tn regulates the muscle contraction.

Animals↗
PubMed1997

Alternative splicing of GTBP in normal human tissues.

GTBP is one of the functional homologues of the bacterial mismatch repair gene mutS, whose product forms a heterodimer with hMSH2 to bind to the mismatched region of double-stranded DNA. We determined the expression of the GTBP gene and found that two forms of the transcripts were ubiquitously expressed in normal human tissues. These transcripts, termed GTBP-N and GTBP-ALT, were generated by the alternative splicing machinery. These two transcripts share 3172 bp from the translation initiation codon that codes for 1057 amino acids. GTBP-ALT lacked a region that codes for a highly conserved region between GTBP-N, hMSH2, and hMSH3 in their C-termini.

Actins↗
PubMed1997

Immunotherapy of multiple myeloma with a monoclonal antibody directed against a plasma cell-specific antigen, HM1.24.

Multiple myeloma remains an incurable malignancy because of marked resistance of tumor cells to conventional chemotherapeutic agents. Alternative strategies are needed to solve these problems. To develop a new strategy, we have generated a monoclonal antibody (MoAb), which detects a human plasma cell-specific antigen, HM1.24. In this report, we evaluated the in vivo antitumor effect of unconjugated anti-HM1.24 MoAb on human myeloma xenografts implanted into severe combined immunodeficiency (SCID) mice. Two models of disseminated or localized tumors were established in SCID mice by either intravenous or subcutaneous injection of human myeloma cell lines, ARH-77 and RPMI 8226. When mice were treated with a single intraperitoneal injection of anti-HM1.24 MoAb 1 day after tumor inoculation, the development of disseminated myeloma was completely inhibited. In mice bearing advanced tumors, multiple injections of anti-HM1.24 MoAb reduced the tumor size and significantly prolonged survival, including tumor cure, in a dose-dependent manner. The proliferation of cultured human myeloma cells was inhibited in vitro by anti-HM1.24 IgG-mediated complement-dependent cytotoxicity, but not by the antibody alone. Moreover, spleen cells from SCID mice mediated antibody-dependent cell cytotoxicity against RPMI 8226 cells. These results indicate that anti-HM1.24 MoAb can be used for immunotherapy of multiple myeloma and related plasma cell dyscrasias.

Animals↗