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Biomedical subjects

H Katayama

Publications and source records attributed to H Katayama.

At least 37 records · Page 2Linked to original sources

Assessment of risk of infection due to Cryptosporidium parvum in drinking water.

The risk of infection of Cryptosporidium via drinking water was assessed using Monte Carlo simulation with the field survey data of the Sagami River watershed. The levels of Cryptosporidium in this river were found to follow the lognormal distribution. From the counted data, the median level of the Miyayama sampling point was estimated to be 5.7 oocysts per 100L. To calculate the annual risk of infection due to Cryptosporidium in drinking water, the Cryptosporidium level of Miyayama sampling point was used as the water source of the waterworks. The 95% percentile of the annual risk of infection was found to be 10(-2.60). If the daily risk was eliminated when the level of Cryptosporidium in treated water exceeded 1 oocyst per 20L, the 95% percentile of the annual risk was reduced by about 1 log. To reduce the 95% value of the annual risk lower than 10(-4), the risk of days with levels of Cryptosporidium in treated water exceeding 1 oocyst per 80L should be eliminated.

Animals↗

Interaction and feedback regulation between STK15/BTAK/Aurora-A kinase and protein phosphatase 1 through mitotic cell division cycle.

STK15 is an Aurora/Ipl-1 related serine/threonine kinase that is associated with centrosomes and induces aneuploidy when overexpressed in mammalian cells. It is well known that phosphorylation and dephosphorylation of kinases are important for regulation of their activity. But mechanisms by which STK15 activity is regulated have not been elucidated. We report that STK15 contains two functional binding sites for protein phosphatase type 1 (PP1), and the binding of these proteins is cell cycle-regulated peaking at mitosis. Activated STK15 at mitosis phosphorylates PP1 and inhibits PP1 activity in vitro. In vivo, PP1 activity co-immunoprecipitated with STK15 is also reduced. These data indicate that STK15 inhibits PP1 activity during mitosis. Also, PP1 is shown to dephosphorylate active STK15 and abolish its activity in vitro. Furthermore, we show that non-binding mutants of STK15 for PP1 are superphosphorylated, but their kinase activities are markedly reduced. Cells transfected with these non-binding mutants manifest aberrant chromosome alignment during mitosis. Our results suggest that a feedback regulation through phosphorylation/dephosphorylation events between STK15 kinase and PP1 phosphatase operates through the cell cycle. Deregulation of this balance may contribute to anomalous segregation of chromosomes during mitotic progression of cancer cells.

Aurora Kinase A↗

A novel monoclonal antibody recognizes a previously unknown subdivision of the habenulo-interpeduncular system in zebrafish.

The habenulo-interpeduncular system is an evolutionarily conserved structure found in the brain of almost all vertebrates. We prepared a monoclonal antibody (6G11) which very specifically recognizes only a part of this system. 6G11 is a monoclonal antibody prepared from a neuronal membrane protein in adult zebrafish brain. In western blot analysis of the adult zebrafish brain, the antibody recognized a 95 kDa protein, and the class of the antibody was determined to be IgM. The 6G11 antigen was not detected in zebrafish muscle, intestine, testis or ovary. A group of neurons stained by the 6G11 antibody was located in the caudomedial part of the zebrafish habenula. The 6G11-immunopositive neurons extended their axons into the fasciculus retroflexus (FR). One group of immunopositive neurons projected toward the interpeduncular nucleus (IPN), especially to the intermediate and the central subnucleus (type 1 neuron). The other group projected to the ventral midline at the level of the raphe nucleus; these axons passed ipsilaterally beside the IPN and converged in the ventral midline under the raphe nucleus (type 2 neuron). Both type 1 and type 2 fibers are relatively minor components of the FR. Little has previously been known about this topological pattern in any species. The 6G11 monoclonal antibody could be a useful tool for expanding knowledge of the habenulo-interpeduncular system.

Animals↗

A 28 kDa protein of the Bacillus thuringiensis serovar shandongiensis isolate 89-T-34-22 induces a human leukemic cell-specific cytotoxicity.

A 28 kDa protein that exhibits cytocidal activity specific for human leukemic T (MOLT-4) cells was purified from proteinase K-digested parasporal inclusion of a Bacillus thuringiensis serovar shandongiensis isolate. The N-terminal sequence of the protein was identical with that of the 32 kDa protein, regarded as a protoxin, of the inclusion proteins. The median effective concentration of this protein was 0.23 microg/ml against MOLT-4 cells and its specific activity was 7.9 times greater than that of the whole inclusion proteins. The 28 kDa protein induced necrosis-like cytotoxicity against MOLT-4 cells and the cytopathic effect with the passage of time was characterized by cell swelling, nuclear membrane isolation and chromatin condensation.

Antineoplastic Agents↗

Improvement of in-gel digestion protocol for peptide mass fingerprinting by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

High-sensitivity, high-throughput analysis of proteins for proteomics studies is usually performed by polyacrylamide gel electrophoresis in combination with mass spectrometry. However, the quality of the data obtained depends on the in-gel digestion procedure employed. This work describes an improvement in the in-gel digestion efficiency for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) analysis. A dramatic improvement in the coverage of tryptic peptides was observed when n-octyl glucoside was added to the buffer. Whole cell extracted proteins from S. cerevisiae were separated by two-dimensional gel electrophoresis and stained with silver. Protein spots were identified using our improved in-gel digestion method and MALDI-TOFMS. In addition, the mass spectra obtained by using the matrix alpha-cyano-4-hydroxycinnamic acid (CHCA) were compared with those obtained using 2,5-dihydroxybenzoic acid (DHB). The DHB matrix usually gave more peaks, which led to higher sequence coverage and, consequently, to higher confidence in protein identification. This improved in-gel digestion protocol is simple and useful for protein identification by MALDI-TOFMS.

Electrophoresis, Gel, Two-Dimensional↗

Fibroblast growth factor receptor 3 lacking the Ig IIIb and transmembrane domains secreted from human squamous cell carcinoma DJM-1 binds to FGFs.

The fibroblast growth factor receptors (FGFRs) are a family of transmembrane tyrosine kinases that play a key role in cell growth and tumorigenesis in response to FGFs. FGFR complexity is increased by the existence of additional isoforms generated by alternative mRNA splicing. We identified that the transcript FGFR3DeltaTM, an alternatively spliced isoform of FGFR3 lacking exons encoding the C-terminal half of Ig III (IIIb) and transmembrane domains, is expressed in the human squamous carcinoma cell line DJM-1. To determine whether FGFR3DeltaTM has the potential to be secreted, we analyzed the protein expression in CHOK1 cells transfected with FGFR3DeltaTM cDNA and DJM-1 cells. Western blot analysis revealed that FGFR3DeltaTM protein was secreted, N-glycosylated, and dimerized by an intermolecular disulfide bond. Cross-linking experiments showed that FGF1 and FGF2 were able to bind to FGFR3DeltaTM, suggesting that the loss of the Ig IIIb domain may confer upon FGFR3DeltaTM the ability to bind to FGF2.

Alternative Splicing↗

Use of electron microscopic evaluation for the diagnosis of adrenal cortical carcinoma in fine needle aspiration cytology: a case report and review of the literature.

Bilateral adrenal tumors were detected in a 72-year-old man who had a history of hepatic inflammatory pseudotumor. Computet tomography (CT)-guided fine needle aspiration cytology (FNAC) of the adrenal glands was performed. The cytologic findings were similar to the previous diagnosis of "inflammatory pseudotumor" in the liver. However, the origin of some aggregated large atypical cells observed in the adrenal FNAC specimens was not known. Immunocytochemically, these large atypical cells were positive for vimentin and negative for cytokeratin and chromogranin A. An electron-microscopic study showed that these large atypical cells contained mitochondria with tubulovesicular cristae and smooth endoplasmic reticulum arranged in whorled and laminated patterns, and these findings confirmed diagnosis of primary adrenal cortical carcinoma. The histopathological diagnosis of the resected bilateral adrenal tumor was adrenal cortical carcinoma. The patient died 7 months after surgery, with recurrence of the bilateral adrenal cortical carcinoma and extensive metastases. A diagnosis of primary adrenal cortical carcinoma with extensive metastases was finally demonstrated by autopsy. Retrospectively, the previous liver tumor was determined to be a metastatic lesion.

Adrenal Cortex Neoplasms↗

Inspiratory pressure-volume curves at different positive end-expiratory pressure levels in patients with ALI/ARDS.

BACKGROUND: In lung protective strategy, positive end-expiratory pressure (PEEP) slightly higher than the Pflex (the airway pressure corresponding to the lower inflection point (LIP) on the inspiratory pressure-volume (P-V) curve measured with ZEEP) is generally recommended. However, this method to determine optimal PEEP lacks a theoretical background and there is no clinical report that investigated how the P-V relationship would be with such PEEP. Therefore, we measured inspiratory P-V curves at different PEEP levels to increase our knowledge about the inspiratory P-V curve with PEEP. METHODS: In eight consecutive patients with ALI/ARDS, inspiratory P-V curves were repeatedly measured at different PEEP levels by low flow inflation technique and LIP was assessed in all inspiratory P-V curves. Afterwards, the minimum PEEP level at which LIP was not identifiable (PEEP(LIP)(-)) was determined and the relationship between Pflex and PEEP(LIP)(-) was investigated. RESULTS: Pflex and PEEP(LIP)(-) could be determined in all patients. Pflex was 9.4+/-2.0 cmH2O (range: 7 to 12 cmH2O) and PEEP(LIP)(-) was 7.9+/-1.6 cmH2O (range: 5 to 10 cmH2O) (mean+/-SD, P=0.0877). PEEP(LIP)(-) was lower than the Pflex in five patients, and significantly lower than the Pflex + 2 cmH2O (P=0.0024). CONCLUSION: From the analysis of inspiratory P-V curves at different PEEP levels, PEEP 2 cmH2O higher than the Pflex may not be necessary to prevent cyclic collapse and reopening of alveoli, at least in some ALI/ARDS patients. Further studies are needed to confirm this preliminary result.

Adolescent↗

Identification of a silent pituitary somatotropic adenoma based on a paradoxic response of growth hormone on a thyrotropin-releasing hormone or gonadotropin-releasing hormone provocation test.

Preoperative endocrinologic identification and surgical removal of a silent somatotropic adenoma among patients with either amenorrhea or galactorrhea, or both, are beneficial for the restoration of menstruation and ovulation. Paradoxic rises of serum growth hormone in either a thyrotropin-releasing hormone or a gonadotropin-releasing hormone provocation test and high serum growth hormone levels were noted in the 3 patients with a silent somatotropic adenoma.

Adenoma↗

Histopathological analyses of silent pituitary somatotroph adenomas using immunohistochemistry, in situ hybridization and confocal laser scanning microscopic observation.

To characterize the morphological and functional aspects of silent somatotroph adenomas with paradoxical responses of GH in TRH or GnRH provocation tests, which are considered to be a useful strategy for endocrinological identification of silent somatotroph adenomas, we examined three silent somatotroph adenomas histopathologically. The adenomas were investigated by immunohistochemistry, including the highly sensitive catalyzed signal amplification system, the non-radioisotopic in situ hybridization method, and confocal laser scanning microscopy. GH production and GH-immunopositive secretory granules in the adenoma cells were demonstrated histopathologically, and the adenomas were interpreted as being densely granulated somatotroph adenomas. Endocrinological identification of silent somatotroph adenomas in combination with paradoxical responses of GH in TRH or GnRH provocation tests may elucidate the increasing number of silent somatotroph adenomas that have been regarded as mammotroph or clinically inactive adenomas. One should be aware of the differences between the previously reported silent somatotroph adenomas, most of which are sparsely granulated somatotroph adenomas, a somatotroph adenomas with paradoxical and the silent somatotroph adenomas, most of which are sparsely granulated somatotroph adenomas, and the silent somatotroph adenomas with paradoxical responses of GH in TRH or GnRH provocation tests, which are densely granulated somatotroph adenomas.

Adenoma, Chromophobe↗

Clinical experience with iomeprol in myelography and myelo-CT: clinical pharmacology and double-blind comparisons with iopamidol, iohexol, and iotrolan.

RATIONALE AND OBJECTIVES: To evaluate iomeprol, a new nonionic iodinated contrast medium, as a contrast agent for myelography and to compare it with iopamidol, iohexol, and iotrolan. METHODS: An extensive clinical program was conducted on more than 600 patients to assess iomeprol's pharmacokinetics, tolerability, safety, and efficacy after intrathecal injection. RESULTS: Pharmacokinetics study results showed that after intrathecal administration iomeprol is completely absorbed from the cerebrospinal fluid compartment; once absorbed into the systemic circulation, it is rapidly excreted, unmetabolized, by glomerular filtration. Dose-finding studies showed that the opacification produced by iomeprol depends on the injected dose. Although a dose-dependent increase in efficacy was observed, no differences in neurotolerability and safety were detected between the doses tested. Doses of iomeprol greater than 3 g I did not cause a greater incidence of adverse events and produced significantly better contrast efficacy. Comparative clinical trials showed that iomeprol and iopamidol, iohexol, and iotrolan always provided adequate opacification of the subarachnoid space, both in conventional myelography and myelo-CT, with adequate delineation of normal structures and pathologic processes. No serious adverse events occurred up to a total dose of 4.5 g I. No differences between the agents with regard to tolerance, adverse events, and effects on vital signs, physical examination, and neurologic examination were observed. CONCLUSIONS: Iomeprol is safe and effective and can be recommended for myelography and myelo-CT.

Adult↗

Iomeprol: current and future profile of a radiocontrast agent.

RATIONALE AND OBJECTIVES: To review the safety and efficacy profiles of iomeprol by examining the most indicative comparative clinical studies of iomeprol with widely used low-osmolar ionic or nonionic contrast agents, and to illustrate the recent development in iomeprol liposomal formulations for liver imaging and intravascular enhancement. METHODS: Randomized, double-blind, comparative studies were performed of iomeprol versus iopamidol, iopromide, ioxaglate, iopentol, iodixanol, ioversol, and iohexol. In all studies, safety controls included pre- and postadministration physical examinations, monitoring of vital signs, electrocardiography, clinical laboratory investigations, and 24- or 72-hour postadministration monitoring of patients for adverse events. Technically adequate images were rated for diagnostic efficacy by masked assessors. RESULTS: Iomeprol showed similar safety and diagnostic efficacy compared with the nonionic monomers iopamidol, iohexol, and ioversol, and no statistically significant differences were observed. No differences in diagnostic efficacy between iomeprol and iopromide were observed, but in one study on 1,200 patients, the incidence of adverse events and adverse reactions was significantly higher with iopromide than with iomeprol. Iomeprol caused significantly less heat/pain than iopentol in one study; it showed similar safety and tolerability to the nonionic dimer iodixanol, the two agents causing no or modest, superimposable pain and heat sensation at injection and showing similar renal tolerability after intra-arterial injection. A comparison of iomeprol versus ionic dimer ioxaglate in 2,000 patients undergoing percutaneous coronary interventions showed that the incidence of thrombus-related events was similar with the two agents, but ioxaglate caused a significantly higher incidence of allergy-like reactions. First results with iomeprol-containing liposomal formulations show that these agents may facilitate the CT assessment of intrahepatic malignancies and CT angiography procedures. CONCLUSIONS: The overall results of numerous randomized, double-blind, comparative clinical studies in a variety of indications show that the diagnostic efficacy of iomeprol solutions does not differ significantly from that of the low-osmolar contrast media available on the marketplace when similar iodine strengths are used, although iomeprol may have better tolerability and safety than the ionic dimer and some of the nonionic monomers in selective applications. First results obtained with iomeprol-containing liposomal formulations are promising and may foster additional clinical testing.

Animals↗

Comparison of gadobenate dimeglumine with gadopentetate dimeglumine for magnetic resonance imaging of liver tumors.

RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (Gd-BOPTA) with gadopentetate dimeglumine (Gd-DTPA) for magnetic resonance imaging of the liver. METHODS: The contrast agent Gd-BOPTA or Gd-DTPA was administered at a dose of 0.1 mmol/kg to 257 patients suspected of having malignant liver tumors. Dynamic phase images, spin-echo images obtained within 10 minutes of injection, and delayed images obtained 40 to 120 minutes after injection were acquired. All postcontrast images were compared with unenhanced T1-weighted and T2-weighted images obtained immediately before injection. A full safety assessment was performed. RESULTS: The contrast efficacy for dynamic phase imaging was moderately or markedly improved in 90.9% (110/121) and 87.9% (109/124) of patients for Gd-BOPTA and Gd-DTPA, respectively. At 40 to 120 minutes after injection, the cor- responding improvements were 21.7% (26/120) and 11.6% (14/121) for spin-echo sequences and 44.5% (53/119) and 19.0% (23/121) for breath-hold gradient-echo sequences, respectively. The differences at 40 to 120 minutes after injection were statistically significant (P < 0.02). Increased information at 40 to 120 minutes after injection compared with information acquired within 10 minutes of injection was available for 24.0% (29/121) of patients with Gd-BOPTA and for 14.5% (18/124) of patients with Gd-DTPA (P < 0.03). Adverse events were seen in 4.7% (6/128) and 1.6% (2/127) of patients receiving Gd-BOPTA and Gd-DTPA, respectively. The difference was not statistically significant. CONCLUSIONS: The efficacy of Gd-BOPTA is equivalent to that of Gd-DTPA for liver imaging during the dynamic phase and superior during the delayed (40-120 minutes) phase of contrast enhancement. Both agents are safe for use in magnetic resonance imaging of the liver.

Adult↗

Determination of pyrimidine dimers in Escherichia coli and Cryptosporidium parvum during UV light inactivation, photoreactivation, and dark repair.

UV inactivation, photoreactivation, and dark repair of Escherichia coli and Cryptosporidium parvum were investigated with the endonuclease sensitive site (ESS) assay, which can determine UV-induced pyrimidine dimers in the genomic DNA of microorganisms. In a 99.9% inactivation of E. coli, high correlation was observed between the dose of UV irradiation and the number of pyrimidine dimers induced in the DNA of E. coli. The colony-forming ability of E. coli also correlated highly with the number of pyrimidine dimers in the DNA, indicating that the ESS assay is comparable to the method conventionally used to measure colony-forming ability. When E. coli were exposed to fluorescent light after a 99.9% inactivation by UV irradiation, UV-induced pyrimidine dimers in the DNA were continuously repaired and the colony-forming ability recovered gradually. When kept in darkness after the UV inactivation, however, E. coli showed neither repair of pyrimidine dimers nor recovery of colony-forming ability. When C. parvum were exposed to fluorescent light after UV inactivation, UV-induced pyrimidine dimers in the DNA were continuously repaired, while no recovery of animal infectivity was observed. When kept in darkness after UV inactivation, C. parvum also showed no recovery of infectivity in spite of the repair of pyrimidine dimers. It was suggested, therefore, that the infectivity of C. parvum would not recover either by photoreactivation or by dark repair even after the repair of pyrimidine dimers in the genomic DNA.

Animals↗

A recombinant molt-inhibiting hormone of the kuruma prawn has a similar secondary structure to a native hormone: determination of disulfide bond arrangement and measurements of circular dichroism spectra.

In crustaceans, molt-inhibiting hormone (MIH) is presumed to regulate molting through suppressing synthesis and/or secretion of ecdysteroids by the Y-organ. Recently, a recombinant MIH of the kuruma prawn Penaeus japonicus was produced in E. coli. To approximate the secondary structure of native and recombinant MIH of P. japonicus containing six cysteine residues, the arrangements of disulfide bridges in both MIHs were determined by characterizing their enzymatic digests, and their circular dichroism spectra were measured. The arrangements of disulfide bonds in both MIHs were determined to be identical, and they were linked between Cys7 and Cys44, Cys24 and Cys40, and Cys27 and Cys53. The circular dichroism spectra of both MIHs were very close, and demonstrated that they were rich in a-helix. a-Helix contents in native and recombinant MIHs were calculated to be 49.3% and 46.0%, respectively. All these results strongly suggested that the recombinant MIH was folded in the same manner as the native MIH.

Animals↗

Expression and localization of basic fibroblast growth factor and its mRNA in solitary fibrous tumor.

Solitary fibrous tumors (SFTs) represent a distinct neoplasm that should be included in the differential diagnosis of spindle-cell neoplasms of the soft tissue. Basic fibroblast growth factor (bFGF or FGF-2) is a mitogenic and angiogenic polypeptide produced by diverse cell types, including the cells derived from normal tissue and neoplastic lesions. In this study, the expression of bFGF, vimentin, CD 34, c-kit (or CD 117), desmin, S-100 protein, and alpha-smooth muscle actin (alpha-SMA) in SFTs, hemangiopericytomas (HPC), gastrointestinal stromal tumors (GIST), and dermatofibrosarcoma protuberans (DFSP) were evaluated to assess their usefulness in the differential diagnosis of these lesions. The expression of bFGF mRNA was also examined in SFTs by in situ hybridization (ISH) using a digoxigenin-labeled bFGF oligonucleotide probe. All the SFTs, GISTs and DFSPs exhibited strong and diffuse immunoreactivity for CD34 and vimentin, and were completely negative for desmin, S-100 protein and alpha-SMA. The HPCs were positive for vimentin, but negative for CD34. In all the SFTs, strong and diffuse nuclear immunostaining was observed with bFGF antibody, contrasting with the negative staining observed in the majority of the HPCs, GISTs, and DFSPs. The bFGF mRNA was also expressed in the SFT cells. The constitutive expression of the bFGF in the SFT widens the spectrum of available markers for these tumors, providing a useful addition to their differential diagnosis in difficult cases, and contributing to the understanding of their histogenesis and molecular pathogenesis.

Adult↗

Epstein-Barr virus associated diffuse large B-cell lymphoma complicated by autoimmune hemolytic anemia and pure red cell aplasia.

A 53-year old man with systemic lymphadenopathy and hepatosplenomegaly was diagnosed with diffuse large B cell-lymphoma after inguinal lymph node biopsy. Anemia was noted, direct and indirect Coombs tests were positive, and the haptoglobin level was low. However, the bone marrow aspirate revealed erythroid aplasia. Co-existing autoimmune haemolytic anemia (AIHA) and pure red cell aplasia (PRCA) were diagnosed. In situ hybridization with Epstein-Barr virus (EBV) encoded small RNA (EBER) showed positive findings in lymphoma cells. Southern blot hybridization revealed immunoglobulin heavy chain gene rearrangement and a clonal EBV terminal repeat, indicating monoclonal proliferation of EBV in infected B cells. The patient was treated with CHOP, resulting in a complete remission (CR). AIHA and PRCA subsided after 3 courses of chemotherapy. In conclusion, this case demonstrates not only the association of B-cell lymphoma with autoimmune disorders but also the involvement of EBV in these conditions.

Anemia, Hemolytic, Autoimmune↗