Biomedical subjects
Publications and source records attributed to H Hashimoto.
Inhibitory activities of various cyclic sulfonium compounds including salacinol against several glycosidases were studied and some compounds showed significant inhibition. The sulfonium ion structure was found to be essential for the inhibitory activity. Specific inhibition of salacinol toward rice alpha-glucosidase was ascribed to the tether arm.
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Proliferating cell nuclear Ag (PCNA) occurs as a component of multiprotein complexes during cell proliferation. We found the complexes to react with murine anti-PCNA mAbs, but not with anti-PCNA Abs in lupus sera. The complexes were purified from rabbit thymus extract by affinity chromatography using anti-PCNA mAbs (TOB7, TO17, and TO30) and analyzed by ELISA, immunoprecipitation, immunoblotting, and HPLC gel filtration. That PCNA was complexed with other proteins was demonstrated by its copurification with a group of proteins excluded by an HPLC G3000 SW column. Although immunoblot analysis showed the mAbs to react exclusively with the 34-kDa PCNA polypeptide, they nonetheless immunoprecipitated the same group of proteins, confirming the interaction of the isolated PCNA with other proteins. Anti-PCNA sera, including AK, which reacts with biologically functional sites on PCNA, did not react with complexed PCNA, but did react with it once it was dissociated from the complexes. PCNA complexes in turn reacted with murine anti-DNA mAbs, as well as with Abs against p21, replication protein A, DNA helicase II, cyclin-dependent kinases 4 and 5, and topoisomerase I. These findings suggest that the PCNA complexes purified using anti-PCNA mAbs comprise the "protein machinery" for DNA replication and cell cycle regulation. They also suggest that anti-PCNA mAbs are useful tools with which to characterize the protein-protein interactions within PCNA complexes, as well as the autoimmune responses to proteins interacting with PCNA, which may shed light on the mechanisms of autoantibody production in lupus patients.
The crystal structure of family B DNA polymerase from the hyperthermophilic archaeon Pyrococcus kodakaraensis KOD1 (KOD DNA polymerase) was determined. KOD DNA polymerase exhibits the highest known extension rate, processivity and fidelity. We carried out the structural analysis of KOD DNA polymerase in order to clarify the mechanisms of those enzymatic features. Structural comparison of DNA polymerases from hyperthermophilic archaea highlighted the conformational difference in Thumb domains. The Thumb domain of KOD DNA polymerase shows an "opened" conformation. The fingers subdomain possessed many basic residues at the side of the polymerase active site. The residues are considered to be accessible to the incoming dNTP by electrostatic interaction. A beta-hairpin motif (residues 242-249) extends from the Exonuclease (Exo) domain as seen in the editing complex of the RB69 DNA polymerase from bacteriophage RB69. Many arginine residues are located at the forked-point (the junction of the template-binding and editing clefts) of KOD DNA polymerase, suggesting that the basic environment is suitable for partitioning of the primer and template DNA duplex and for stabilizing the partially melted DNA structure in the high-temperature environments. The stabilization of the melted DNA structure at the forked-point may be correlated with the high PCR performance of KOD DNA polymerase, which is due to low error rate, high elongation rate and processivity.
STUDY DESIGN: A case report. OBJECTIVES: To illustrate a rare case of synovial sarcoma arising within a peripheral nerve. SUMMARY OF BACKGROUND DATA: A synovial sarcoma arising within a peripheral nerve is very unusual. Only five cases of primary synovial sarcoma within a peripheral nerve have been reported. This is the first case with involvement of the nerve root. The authors diagnosed the tumor arising within the S1 nerve root as synovial sarcoma using cytogenetic analysis that detected the chimeric SYT/SSX gene. METHODS: In addition to the immunohistochemical study, a reverse transcription-polymerase chain reaction (RT-PCR) assay was conducted for the SYT-SS10 fusion gene using archival formalin-fixed paraffin-embedded tumor specimens. RESULTS: Computed tomography scan, magnetic resonance imaging performed before surgery, and the intraoperative findings showed that the tumor was embedded within the S1 nerve root. Although the histologic findings were suggestive of a malignant peripheral nerve sheath tumor, the results of the cytologic study confirmed its diagnosis of synovial sarcoma. CONCLUSION: Primary intraneural synovial sarcoma, although rare, must be distinguished from malignant peripheral nerve sheath tumor. The molecular assay of the detection of the SYT/SSX fusion gene is useful to make a definite diagnosis of monophasic synovial sarcoma.
PURPOSE: A B-flow sonographic technique was recently developed to provide direct visualization of blood flow with gray-scale sonography. Compared with color Doppler sonography, B-flow imaging has wideband resolution and a high frame rate. The purpose of this study was to evaluate the usefulness of B-flow sonography for visualizing blood flow in hepatic vessels and tumor vascularity in patients with liver cirrhosis or hepatocellular carcinoma (HCC). METHODS: Twenty-five patients with liver cirrhosis, including 15 with HCC, were studied by B-flow and color Doppler sonography. Blood-flow detection rates in portal veins and hepatic arteries and tumor vascularity in HCC were analyzed, and the 2 methods were compared. RESULTS: Using B-flow, blood flow was visualized in the portal vein in 23 (92%) of 25 patients and was visualized in the hepatic artery separately from the portal vein in 9 (36%) of 25 patients. The blood-flow signals were visualized only within vessels, never "bleeding" outside the vessel's lumen. Blood flow in the portal vein was observed with color Doppler sonography in all 25 patients, but the hepatic artery was never clearly separated from the portal vein. Vascularity within the HCC tumor was detected in 9 (60%) of 15 nodules with B-flow imaging, and fine arteries flowing into the tumor were observed in 6 nodules. Color Doppler sonography detected blood flow in 13 (87%) of the 15 HCC nodules. CONCLUSIONS: Blood flow in hepatic vessels and tumor vessels of HCC were visualized with B-flow sonography. B-flow sonography is a potentially useful technique for the evaluation of liver vascularity and intratumoral vessels.
The diagnosis of fibrosarcoma has become relatively rare since the recognition and definition of certain adult spindle-cell sarcomas, such as monophasic synovial sarcoma, malignant peripheral nerve sheath tumour (MPNST), and malignant fibrous histiocytoma (MFH). Although most adult fibrosarcomas occur within intra- or inter-muscular fibrous tissues, some originate from superficial soft tissues (superficially located adult fibrosarcomas) (SAFs). Recently, the COL1A1-PDGFB chimeric gene resulting from a reciprocal translocation, t(17;22), and/or a supernumerary ring chromosome, r(17;22), has been identified, not only in conventional dermatofibrosarcoma protuberans (DFSP) but also in areas of DFSP with progression to fibrosarcoma (so-called fibrosarcomatous transformation) (FS-DFSP). Since many SAFs are clinically and histologically similar to DFSP or FS-DFSP, this study postulated that the two groups may be interrelated histogenetically. To test this hypothesis, a reverse transcription-polymerase chain reaction (RT-PCR) assay was conducted to determine whether COL1A1-PDGFB fusion transcripts could be detected in six cases of SAF, using archival formalin-fixed, paraffin-embedded tissues. COL1A1-PDGFB fusion transcripts were detected in four of six SAFs, whereas no such fusion transcripts could be amplified in five deep-seated fibrosarcomas, eight congenital/infantile fibrosarcomas or 28 other spindle-cell tumours and tumour-like lesions. These results show that at least some cases of SAF are genetically similar to DFSP and FS-DFSP, suggesting that some SAFs originate from DFSP or involve similar pathogenetic mechanisms.
BACKGROUND: Reports of morphometric analysis using computerized digitized images of fine needle aspirates of breast cancer are rare. We aimed to evaluate whether quantitative morphometric estimations of cytological nuclear features could be used for preoperative prediction of the risk of recurrence as well as chemosensitivity. METHODS: Seventy consecutive breast cancer patients were treated with preoperative chemotherapy (Doxifluridine 800 mg/body/day, orally) for 4 weeks and subsequently they underwent surgery. Using Papanicolaou-stained cytological materials, computerized morphometric analyses were performed. Mean nuclear area (NA) was measured and the coefficient of variation of NA (NACV) was calculated as the quantitative parameter of nuclear atypism. NA and NACV were compared with prognostic factors (tumor size, histological grade, hormone receptor status, nodal status, and ploidy status), and with the response to the chemotherapy. RESULTS: NA and NACV were significantly associated with hormone receptor status and ploidy status (p<0.05). NACV correlated with histological grade (p<0.05). Neither NA nor NACV were associated with tumor size and nodal status. Patients with high NACV (>35%) had lower rates of disease-free survival (p<0.05) than those with low NACV (< or =35%). Responders to preoperative chemotherapy had statistically larger NA, higher NACV and higher S-phase fraction at the time of diagnosis compared with non-responders (p<0.001, p<0.0005, and p<0.05 respectively). CONCLUSIONS: Morphometric analysis of preoperative fine needle aspirates reflects important clinical information, such as the risk of recurrence, and particularly, chemosensitivity.
Proliferative kinetics of parathyroid cells in secondary hyperparathyroidism (HPT) are still unknown. We examined the histopathological changes and proliferative activity of parathyroid cells in spontaneously hypercholesterolemic (SHC) rats that exhibit secondary HPT and in normal Sprague Dawley (SD) rats from 3 weeks to 32 weeks of age. Proliferative activity [proliferating cell nuclear antigen(PCNA) labeling index], evaluated by means of immunohistochemical examination of PCNA, declined in SD rats with age from 10.8% at 3 weeks of age to 0.15% at 32 weeks of age. In SHC rats, a PCNA labeling index of 11.6% declined to 3.12% at 14 weeks of age and rebounded to 6.15% at 26 weeks of age. Parathyroid glands increased in size as determined by the maximum cross-sectional area, but in SHC rats, the increase was significantly greater, paralleling the progression of renal dysfunction, and at 32 weeks they were almost three times larger than in SD rats. Parathyroid hormone (PTH) levels in SHC rats also rose sharply after 20 weeks and reached 611 pg/ml at 32 weeks, while PTH in SD rats remained unchanged at approximately 110 pg/ml. This study showed that in the course of developing HPT in SHC rats, there is a large increase in the size of the parathyroid gland, a concomitant increase in PTH levels, and a PCNA labeling index that is higher than in normal SD rats.
Myocardial ischemia initiates an acute inflammatory response, in which polymorphonuclear leukocytes (PMNs) are major participants. We investigated whether increased PMN activity in the peripheral blood is a marker for high-grade coronary artery stenosis in patients with angina pectoris. PMN activity was examined in 45 patients by measuring the luminol-dependent chemiluminescence (CL) response of the peripheral blood upon addition of phorbol myristate acetate (PMA). The CL of patients with angiographic filling delay was 1.6-fold higher than in patients without delay (480+/-54 vs. 302+/-33 counts/PMN, P<0.01). The CL of patients with a filling delay of the left anterior descending artery (LAD) was 1.7-fold higher than in patients without an LAD filling delay (537+/-79 vs. 317+/-27 counts/PMN, P<0.01). With the CL cut-off at 400 counts/PMN, the sensitivity and specificity for detecting an angiographic filling delay of the LAD were 69 and 75%, respectively. These data indicate that PMN activity in the peripheral blood is increased with the presence of a flow-limiting coronary lesion showing an angiographic filling delay. Measuring PMN activity may be a useful approach to assess indications for and timing of angiography and/or adjunctive invasive therapies in patients with angina pectoris.
Various types of organic compounds have been detected in Jupiter, Titan, and cometary coma. It is probable that organic compounds were formed in primitive Earth and Mars atmospheres. Cosmic rays and solar UV are believed to be two major energy sources for organic formation in space. We examined energetics of organic formation in simulated planetary atmospheres. Gas mixtures including a C-source (carbon monoxide or methane) and a N-source (nitrogen or ammonia) was irradiated with the followings: High energy protons or electrons from accelerators, gamma-rays from 60Co, UV light from a deuterium lamp, and soft X-rays or UV light from an electron synchrotron. Amino acids were detected in the products of particles, gamma-rays and soft X-rays irradiation from each gas mixture examined. UV light gave, however, no amino acid precursors in the gas mixture of carbon monoxide, nitrogen and nitrogen. It gave only a trace of them in the gas mixture of carbon monoxide, ammonia and water or that of methane, nitrogen and water. Yield of amino acid precursors by photons greatly depended on their wavelength. These results suggest that nitrogen-containing organic compounds like amino acid precursors were formed chiefly with high energy particles, not UV photons, in Titan or primitive Earth/Mars atmospheres where ammonia is not available as a predominant N-source.
Infection associated with an indwelling catheter is a representative type of biofilm infection occurring in the urinary tract. Since the most effective way to control this intractable infection is the prevention of bacterial attachment and subsequent biofilm formation on the catheter, the importance of catheter materials and anti-bacterial coating cannot be underestimated. The difference in the degree of bacterial attachment among standard catheter materials, the efficacy of silver-coating of catheters in preventing infection and the potency and effectiveness of a new lecithin/silver coating are discussed.
This study compared the effects of cholera toxin (CTX) and pertussis toxin (PTX) on the actions of sodium fluoride (NaF) and those of aluminum fluoride (AlF3) on cell proliferation and differentiation, as well as tyrosine phosphorylation level of mitogen activated protein kinase (MAPK) in human bone cells. NaF and AlF3 each significantly stimulated the proliferation of human TE85 osteosarcoma cells, increased cellular alkaline phosphatase (ALP) activity, and increased MAPK tyrosine phosphorylation level. CTX completely blocked the bone cell anabolic activities of both NaF and AlF3. While PTX (2 ng/ml) inhibited the bone cell actions of NaF, it had no significant effect on those of AlF3. Both CTX and PTX completely blocked the stimulatory action of AlF3 on MAPK tyrosine phosphorylation, but neither toxin had an effect on the action of NaF on MAPK tyrosine phosphorylation. In conclusion, PTX and CTX had contrasting effects on the anabolic bone cell actions of NaF and AlF3 actions. These findings argue against the hypothesis that the osteogenic activity of NaF is mediated via the formation of AlF3 in human TE85 osteosarcoma cells.
This concise review describes the current status of research into how carotenoids function in bacterial photosynthesis. This is illustrated by reference to very recent studies on both the photoprotective and antenna functions of carotenoids. The major remaining open questions on the detailed molecular mechanisms involved in these reactions are highlighted.
A polymorphism in high-affinity receptor of TNF (TNFR2) gene, Met196Arg, was reported to be associated with systemic lupus erythematosus (SLE) in Japanese, whereas the association could not be found in Europeans at all and this represents an apparent discrepancy. The association, then, should be tested in other populations to clarify the possible involvement, if any, of the TNFR2 polymorphism in SLE or other related autoimmune diseases. The purposes of this study were to examine the TNFR2 polymorphism in Japanese patients with SLE and to investigate its association with other autoimmune diseases accompanied by vasculitis, mixed connective tissue disease, Buerger's disease, and Takayasu's arteritis. We found no association at all between the TNFR2 polymorphism and any autoimmune diseases including SLE in Japanese.
Phosphodiesterase (PDE) III exists in airway smooth muscles. In addition, PDEIII inhibitors have been suggested to relax airway smooth muscle by increasing intracellular cAMP concentrations. We report a successful use of olprinone, a PDEIII inhibitor, for treatment of an asthmatic attack. A 15-year-old male patient treated with oral theophylline 400 mg x d(-1) was anesthetized with propofol, fentanyl and ketamine for knee joint surgery. Immediately after tracheal intubation, an asthma attack occurred with peak airway pressure (Paw)>40 cmH2O. Thus, propofol 20 mg was additionally given to increase anesthetic depth, and Paw gradually decreased to 30 cmH2O. In addition, we started monitoring bronchial cross-sectional area using a superfine fiberoptic bronchoscopic method previously reported. However, as Paw did not further decrease for 30 min, olprinone was intravenously infused (10 microg x kg(-1) x 10 min(-1) + 0.3 microg x kg(-1) x min(-1), total 5 mg). Olprinone infusion rapidly decreased peak Paw from 30 cmH2O to 24 cmH2O and increased bronchial cross-sectional area by 50%. These findings suggest that olprinone produced bronchodilation.
BCMA (TNFRSF17), along with TACI, has recently been demonstrated to be a receptor for BLyS (TNFSF13B). Recent studies indicated substantial role of BLyS signaling pathway for systemic lupus erythematosus (SLE). In the present study, we made an attempt to screen for polymorphisms of human BCMA, and to test their possible association with SLE and rheumatoid arthritis (RA). Two single nucleotide polymorphisms (SNPs) were detected within the coding sequence, both of which were synonymous substitutions. In addition, two SNPs within the promoter, two SNPs in the 5'-untranslated region (UTR), one SNP and one single nucleotide deletion in the 3'UTR and four rare variations were detected. From the combination of the polymorphisms, it was elucidated that four major haplotypes account for most of the genotypes in the Japanese population. Association with SLE and RA was not detected, although a slight tendency for the increase of BCMA.03 in SLE was observed (P = 0.089). These results indicated that human BCMA is conserved with respect to the amino acid sequence, and evidence for association with SLE and RA was not observed.
We report two cases in which visualization of the segmental branch of the hepatic portal vein with the colour Doppler ultrasonography (US) technique was useful for the early diagnosis of veno-occlusive disease. The change in blood flow in the segmental branch of the portal vein occurred 5 and 6 d before the clinical criteria were fulfilled in the two cases. Reverse flow in the segmental branch began partially in the liver at first, and then spread to the whole liver several days later. All the US findings in both cases disappeared after thrombolytic therapy.