Search PubMed⌕ Search

Biomedical subjects

K Hiramatsu

Publications and source records attributed to K Hiramatsu.

At least 19 recordsLinked to original sources
PubMed2006

Proposal of a new staging and grading system of the liver for primary biliary cirrhosis.

AIMS: To define a new histological staging and grading system for primary biliary cirrhosis (PBC), to provide more information reflecting clinical laboratory data and the prognosis to hepatologists. METHODS AND RESULTS: First, 17 histological lesions of PBC were scored in 188 needle liver biopsy specimens. Factor analysis yielded three independent groups of factors: factor 1 (fibrosis, fibrous piecemeal necrosis, orcein-positive granules, bile plugs, Mallory bodies, feathery degeneration, bile duct loss and atypical ductular proliferation); factor 2 (portal inflammation, eosinophilic infiltration, lymphoid follicles, epithelioid granulomas, interface hepatitis and chronic cholangitis); and factor 3 (interface hepatitis, lobular hepatitis, acidophilic bodies and pigmented macrophages). The eight findings of factor 1, but not factors 2 and 3, were significantly correlated with clinical laboratory data and scores in the Mayo Clinic's prognostic model. Factor 1 lesions may reflect histological progression (staging), while factor 2 and 3 lesions may relate to necroinflammatory activity (grading). Then, we devised a staging and grading system using three lesions (bile duct loss, fibrosis and orcein-positive granules) from factor 1 and three from factors 2 and 3 (chronic cholangitis, interface hepatitis and lobular hepatitis). CONCLUSION: This new system might provide more pathological information on PBC patients for hepatologists.

Biopsy, Needle↗
PubMed2006

[Evaluation of aortic valve replacement involving small severely calcified aortic annulus in elderly patients].

We performed aortic valve replacement in 24 patients aged over 70 with small calcified valves. The surgical management of such patients remains controversial as the extensive calcification compromises implantation. Hence, we used an ultrasonic debridement instrument to remove calcium and selected a small prosthesis with the largest possible orifice without enlargement of the aortic annulus. Echocardiography showed significant reductions in left ventricular mass index compared with preoperative values. Early and mid-term prognosis has been relatively good.

Aged↗
PubMed2005

Augmentation of the bactericidal activities of human cathelicidin CAP18/LL-37-derived antimicrobial peptides by amino acid substitutions.

OBJECTIVE: Mammalian myeloid and epithelial cells express various peptide antibiotics (such as defensins and cathelicidins) that contribute to the innate host defense against invading micro-organisms. Among these, human cathelicidin CAP18/LL-37 (L1-S37) possesses potent antibacterial activities against Gram-positive and Gram-negative bacteria. In this study, to develop peptide derivatives with improved bactericidal actions, we utilized the amphipathic 18-mer peptide (K15-V32) of LL-37 as a template, and evaluated the activities of modified peptides. METHODS: Antibacterial activities of the peptides (0.022 approximately 4.4 microM corresponding to 0.1 approximately 10 microg/ml) were assessed by alamarBlue assay using Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli and Pseudomonas aeruginosa as target organisms. Furthermore, the membrane-permeabilization activities of the peptides were examined by using E. coli ML-35p as a target. RESULTS: By substituting E16 and K25 with two L residues, the hydrophobicity of the peptide (18-mer LL) was increased, and by further substituting Q22, D26 and N30 with three K residues, the cationicity of the peptide (18-mer LLKKK) was enhanced. Among peptide derivatives, 18-mer LLKKK exhibited the most potent antibacterial actions against S. aureus (methicillin-resistant and -sensitive), S. pneumoniae, S. pyogenes, E. coli and P. aeruginosa, and possessed the most powerful membrane-permeabilizing activities against E. coli ML-35p at the effective concentrations (p <0.05, 18-mer LLKKK vs. 18-mer LL, 18-mer K15-V32 and LL-37). CONCLUSIONS: Bactericidal activities of the amphipathic human CAP18/LL-37-derived 18-mer peptide can be augmented by modifying its hydrophobicity and cationicity, and 18-mer LLKKK is the most potent among peptide derivatives with therapeutic potential for Gram-positive and Gram-negative bacterial infections.

Amino Acid Substitution↗
PubMed2005

Structural comparison of ten serotypes of staphylocoagulases in Staphylococcus aureus.

Staphylocoagulase detection is the hallmark of a Staphylococcus aureus infection. Ten different serotypes of staphylocoagulases have been reported to date. We determined the nucleotide sequences of seven staphylocoagulase genes (coa) and their surrounding regions to compare structures of all 10 staphylocoagulase serotypes, and we inferred their derivations. We found that all staphylocoagulases are comprised of six regions: signal sequence, D1 region, D2 region, central region, repeat region, and C-terminal sequence. Amino acids at both ends, 33 amino acids in the N terminal (the signal sequences and the seven N-terminal amino acids in the D1 region) and 5 amino acids in the C terminal, were exactly identical among the 10 serotypes. The central regions were conserved with identities between 80.6 and 94.1% and similarities between 82.8 and 94.6%. Repeat regions comprising tandem repeats of 27 amino acids with a 92% identity on average were polymorphic in the number of repeats. On the other hand, D1 regions other than the seven N-terminal amino acids and D2 regions were less homologous, with diverged identities from 41.5 to 84.5% and 47.0 to 88.9%, respectively, and similarities from 53.5 to 88.7% and 56.8 to 91.9%, respectively, although the predicted prothrombin-binding sites were conserved among them. In contrast, flanking regions of coa were highly homologous, with nucleotide identities of more than 97.1%. Phylogenetic relations among coa did not correlate with those among the flanking regions or housekeeping genes used for multilocus sequence typing. These data indicate that coa could be transmitted to S. aureus, while the less homologous regions in coa presumed to be responsible for different antigenicities might have evolved independently.

3' Flanking Region↗
PubMed2004

A single treatment with microcapsules containing a CXCR4 antagonist suppresses pulmonary metastasis of murine melanoma.

Biodegradable poly D,L-lactic acid (PLA, molecular weight: ca. 5000) microcapsules containing a CXCR4 antagonist (4F-benzoyl-TE14011) were prepared (4F-benzoyl-TE14011-PLA), and their anti-metastatic activity was evaluated in mice. A single subcutaneous administration of 4F-benzoyl-TE14011-PLA significantly reduced the number of colonies formed by pulmonary metastasis of B16-BL6 melanoma cells expressing CXCR4. The same dose of 4F-benzoyl-TE14011 in a single or a series of treatments affected little. The substance 4F-benzoyl-TE14011 dose-dependently suppressed B16-BL6 cell growth. In the cells cultured with SDF-1, a more potent suppression was observed. 4F-Benzoyl-TE14011 was rapidly released from 4F-benzoyl-TE14011-PLA for an initial period, both in vitro and in vivo. A steady release was thereafter observed. Therefore, this drug release profile might contribute to prevention of melanoma metastasis at the steps involving the migration and cell growth. These results also show that a sustained drug release formulation could be a useful drug delivery system for CXCR4 antagonists.

Animals↗
PubMed2002

Diminution of early insulin response to glucose in subjects with normal but minimally elevated fasting plasma glucose. Evidence for early beta-cell dysfunction.

AIM: Systematic analysis of beta-cell function in Japanese health examinees. METHODS: In 938 Japanese health examinees (627 men and 311 women, mean age and body mass index, 54.0 years and 23.6 kg/m2, respectively), plasma specific insulin was measured at fasting and during a 75-g oral glucose tolerance test. The subjects were stratified into six groups based on fasting plasma glucose < or = 5.1 mmol/l, 5.2-6.0 mmol/l, 6.1-6.9 mmol/l, 7.0-7.8 mmol/l, 7.9-8.7 mmol/l, and > or = 8.8 mmol/l as the 1st, 2nd, 3rd, 4th, 5th and 6th groups, respectively. RESULTS: Distribution of fasting insulin showed a very modest 'inverted U' shape, with the peak in the 5th group. Progressive increase from the 1st toward the 5th group was significant. In contrast, the ratio of change in insulin to change in glucose from 0 to 30 min during the glucose tolerance test was greatest in the 1st group and progressively declined in the groups with higher fasting glycaemia. Difference in the ratio was most striking and highly significant between the 1st and 2nd groups. Distribution of the insulin to glucose ratio of subjects with normal glucose tolerance significantly overlapped with that of untreated patients with diabetes. CONCLUSIONS: In a Japanese population, (i) beta-cell starts to deteriorate during normoglycaemia with a minimal elevation of fasting plasma glucose, and (ii) there are glucose-tolerant subjects with beta-cell dysfunction.

Adolescent↗
PubMed2002

[Extracardiac fontan procedure in adult: report of a case].

We report a case of a 28-year-old female who underwent an extracardiac Fontan procedure. The subject was diagnosed as an atrioventricular septal defect (Rastelli classification: type C), a double outlet right ventricle, pulmonary artery stenosis, a hypoplasty of left ventricle, total anomalous venous return (Darling: Ib + IIb), and atrial flutter. She underwent a Blalock shunt and an aorto-pulmonary shunt at the ages of 3 and 9 years, respectively. Under a total CPB, an extracardiac total cavo-pulmonary connection (TCPC), using a 26 mm Hemashield graft, was completed. The postoperative course was uneventful. The complicated atrial anatomy and atrial arrhythmia indicated TCPC in this adult patient.

Adult↗
PubMed2001

Adrenomedullin and proadrenomedullin N-terminal 20 peptide induce histamine release from rat peritoneal mast cell.

Adrenomedullin (ADM)-induced histamine release from rat peritoneal mast cells was investigated. We compared the ability of full-length ADM to induce histamine release to the fragments ADM-(1-25) and ADM-(22-52), as well as proadrenomedullin N-terminal 20 peptide (PAMP). ADM (10(-8) to 10(-5) M) and PAMP (10(-8) to 10(-5) M) dose-dependently increased histamine release from peritoneal mast cell preparations. The effect of ADM-(1-25) was similar to ADM, whereas ADM-(22-52) did not show any effects. These data suggest the relative importance of the ADM C-terminal fragment, which contains a six-membered ring structure. Histamine release, induced by ADM, was significantly and dose-dependently inhibited by the addition of ADM-(22-52) (10(-5) M), Ca(2+) (0.5 to 2.0 mM), and benzalkonium chloride (3 to 7 microM), a selective inhibitor of Gi type G proteins. In contrast, PAMP (10(-5) M)-induced histamine release was not inhibited by Ca(2+). These results suggest that ADM induce histamine release via a putative ADM receptor in a manner sensitive to Gi-protein function and extracellular Ca(2+) concentration, and that PAMP might produce its effect by a different mechanism than ADM.

Adrenomedullin↗
PubMed2001

Development of specific CXCR4 inhibitors possessing high selectivity indexes as well as complete stability in serum based on an anti-HIV peptide T140.

We previously reported a truncated polyphemusin peptide analogue, T140, which efficiently inhibits infection of target cells by T-cell line-tropic strains of HIV-1 (X4-HIV-1) through its specific binding to a chemokine receptor, CXCR4. We have found that T140 is not stable in feline serum due to the cleavage of the C-terminal Arg,(14) indispensable for anti-HIV activity. On the other hand, a C-terminally amidated analogue of T140, TZ14004, has been found to be completely stable in incubation in the serum for 2 days. The C-terminal amide is thought to be needed for stability in serum. However, TZ14004 does not have fairly strong anti-HIV activity, but has relatively strong cytotoxicity, probably due to an increase by +1 charge from total +7 charges of T140. In our previous study, the number of total +6 charges seemed to be a suitable balance between activity and cytotoxicity. In this study, we have conducted a double-L-citrulline (Cit)-scanning study on TZ14004 based on the C-terminally amidated form in due consideration of the total net charges in the whole molecule to find novel effective CXCR4 inhibitors, TN14003 ([Cit(6)]-T140 with the C-terminal amide) and TC14012 ([Cit(6), D-Cit(8)]-T140 with the C-terminal amide), which possess high selectivity indexes (SIs) and complete stability in feline serum.

Animals↗
PubMed2001

Whole genome sequencing of meticillin-resistant Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is one of the major causes of community-acquired and hospital-acquired infections. It produces numerous toxins including superantigens that cause unique disease entities such as toxic-shock syndrome and staphylococcal scarlet fever, and has acquired resistance to practically all antibiotics. Whole genome analysis is a necessary step towards future development of countermeasures against this organism. METHODS: Whole genome sequences of two related S aureus strains (N315 and Mu50) were determined by shot-gun random sequencing. N315 is a meticillin-resistant S aureus (MRSA) strain isolated in 1982, and Mu50 is an MRSA strain with vancomycin resistance isolated in 1997. The open reading frames were identified by use of GAMBLER and GLIMMER programs, and annotation of each was done with a BLAST homology search, motif analysis, and protein localisation prediction. FINDINGS: The Staphylococcus genome was composed of a complex mixture of genes, many of which seem to have been acquired by lateral gene transfer. Most of the antibiotic resistance genes were carried either by plasmids or by mobile genetic elements including a unique resistance island. Three classes of new pathogenicity islands were identified in the genome: a toxic-shock-syndrome toxin island family, exotoxin islands, and enterotoxin islands. In the latter two pathogenicity islands, clusters of exotoxin and enterotoxin genes were found closely linked with other gene clusters encoding putative pathogenic factors. The analysis also identified 70 candidates for new virulence factors. INTERPRETATION: The remarkable ability of S aureus to acquire useful genes from various organisms was revealed through the observation of genome complexity and evidence of lateral gene transfer. Repeated duplication of genes encoding superantigens explains why S aureus is capable of infecting humans of diverse genetic backgrounds, eliciting severe immune reactions. Investigation of many newly identified gene products, including the 70 putative virulence factors, will greatly improve our understanding of the biology of staphylococci and the processes of infectious diseases caused by S aureus.

Animals↗
PubMed2001

Impaired suppression of processing in schizophrenic patients suggested by ERPs obtained in a selective attention task.

In the present study, we focused on the ability of suppression of processing in schizophrenic patients, using event-related potentials (ERPs) recorded during a selective attention task. During the task, subjects were required to focus on one ear, counting deviant stimuli, those deviating in duration from a sequence of standard stimuli. We compared amplitude data of two positive components differing in latency elicited by standard stimuli, which reflect suppression of stimulus processing, between schizophrenic patients and normal controls. Significant between-group differences were obtained specifically in the right ear attended condition, suggesting impaired suppression of processing in schizophrenics mediated in the left hemisphere.

Adult↗
PubMed2001

Monocyte chemotactic protein-1, -2, and -3 are distinctively expressed in portal tracts and granulomata in primary biliary cirrhosis: implications for pathogenesis.

The monocyte chemotactic proteins (MCPs) form a distinct structurally related subclass of C-C chemokines. MCPs select specific target cells due to binding to a distinct set of chemokine receptors and because of their effects on monocytes, and may participate in the process of granuloma formation during bacterial and/or mycobacterial infections. The aetiology of primary biliary cirrhosis (PBC) is still unclear, although bacterial infection and autoimmune processes have been implicated. In this study, the expression of three of the most potent monocyte chemoattractants, MCP-1, -2, and -3, was examined in patients with PBC and the data were compared with results for other liver diseases including primary sclerosing cholangitis (PSC), chronic viral hepatitis C, hepatic sarcoidosis, and normal liver. MCP-1 was expressed mainly in biliary epithelial cells of all liver specimens, irrespective of the cause of disease. Some mononuclear leukocytes in the portal tract expressed MCP-1 in all the disease groups examined and there were no significant differences in frequency between these groups. In contrast, more than 80% of PBC livers showed MCP-2- and MCP-3-positive mononuclear leukocyte infiltration in portal tracts, particularly around the bile ducts, whereas such cells were far less frequent in the other disease groups or in normal livers. Epithelioid granulomata of PBC patients contained MCP-2- and MCP-3-positive cells at their edge. In double staining experiments, more than 60% of the MCP-positive mononuclear cells co-expressed CD68, suggesting that a proportion of MCP-2- and MCP-3-positive cells are derived from monocytes. These monocytes expressing MCP-2 and MCP-3 may be responsible for the chemotactic activity of more monocytes. Such an expression pattern of MCP-1, -2 and -3 in portal tracts seems to be distinctive for PBC. This pattern underlines the importance of MCP-1, -2, and -3 in the recruitment of monocytes and possibly T lymphocytes into portal tracts, around the injured bile ducts, and into epithelioid granulomata in PBC. The data further implicate bacterial materials derived from bile in the overall pathogenesis of PBC.

Adult↗
PubMed2001

Frequent molecular identification of Campylobacter but not Helicobacter genus in bile and biliary epithelium in hepatolithiasis.

Bacterial infection of the biliary tree and bile stasis may be causally related to hepatolithiasis, but which bacterial species are involved and their roles in the pathogenesis of hepatolithiasis have not been ascertained. Recently, the Helicobacter genus was detected in human bile and biliary mucosal samples by molecular techniques, and its association with several biliary diseases has been suggested. The Campylobacter genus, which is closely related to the Helicobacter genus, has also recently been identified as causative of human gastrointestinal diseases. This study attempted to elucidate whether Helicobacter and/or Campylobacter bacteria are present in bile samples and biliary mucosal specimens from hepatolithiasis patients and whether they are involved in the pathogenesis of hepatolithiasis. The 16S rRNA gene of the Helicobacter and of the Campylobacter genus was examined by polymerase chain reaction in DNA samples extracted from bile and/or microdissected biliary epithelium from 69 patients with hepatolithiasis and control patients with choledocholithiasis, cholecystolithiasis, and normal gall bladders. The Helicobacter genus was detected in 1 of 8 (13%) biliary epithelial samples in hepatolithiasis and 1 of 10 (10%) bile samples in choledocholithiasis. The Campylobacter genus was detected in 3 of 14 (21%) bile samples and 5 of 8 (63%) epithelial samples in hepatolithiasis, and in 2 of 15 (13%) bile samples and 1 of 8 (13%) epithelial samples in cholecystolithiasis. The detection rate for Campylobacter in biliary epithelium of hepatolithiasis was significantly higher than in the bile or biliary epithelium of control groups (p<0.05). By a phylogenetic analysis based on nucleotide sequences, the Campylobacter genuses detected in hepatolithiasis were clustered with C. rectus or C. showae. The frequent detection of the Campylobacter 16S rRNA gene in bile, and especially in biliary epithelium of hepatolithiasis, suggests a pathogenetic relationship with Campylobacter infection.

Aged↗
PubMed2001

Choledochal cyst and benign stenosis of the main pancreatic duct.

We report here the first case of choledochal cyst associated with a benign stenosis of the cephalic part of the main pancreatic duct. The pancreatic ductal stenosis was associated with a protein plug located upstream of the stenosis. Preoperatively, it was not possible to rule out a localized intraductal pancreatic tumor, and a pylorus-preserving pancreaticoduodenectomy was performed. This association has not been described previously, and gives new insights into the pathogenesis of acute pancreatitis associated with choledochal cyst.

Adult↗
PubMed2001

Increased expression of WAF1 in intrahepatic bile ducts in primary biliary cirrhosis relates to apoptosis.

BACKGROUND/AIMS: In primary biliary cirrhosis (PBC), the intrahepatic small bile ducts are selectively damaged by immune attacks, followed by progressive loss mainly due to apoptosis. Compared to the intercellular signaling such as the CD95/CD95 ligand interaction, little is known about alterations in intracellular cell cycle regulatory proteins and genotoxic damage in this apoptotic process. WAF1 is a potent and reversible inhibitor of cell cycle progression at both the G1 and G2 checkpoint and upregulated WAF1 induces irreversible G1 arrest and apoptosis. Transcriptional activation of the WAF1 gene is induced by the upregulated p53 in response to DNA damage. In this study, the cell cycle regulatory process of apoptosis in PBC was examined with respect to expression of WAF1. METHODS: Immunostaining for WAF1 and p53 was performed using 11 liver sections of PBC and 26 control livers. In addition, Ki67, apoptosis (TUNEL-positive), and human telomerase RNA (hTR) were also detected. RESULTS: WAF1 was expressed in the nuclei of several epithelial cells in most damaged bile ducts in PBC but infrequently or rarely in controls. Some of these cells were also positive for p53, while the remainder were not. Ki67 immunostaining and TUNEL disclosed that the bile ducts in PBC showed increased cell division as well as enhanced apoptosis. Immunostaining of Ki67 and TUNEL staining showed that WAF1-positive cells were not proliferating, while some WAF1-positive cells were undergoing apoptosis. Moreover, the bile ducts lacked hTR expression, implying progressive shortening of telomeres during increased cell divisions. CONCLUSIONS: It seems possible that in PBC, expression of WAF1 on biliary epithelial cells relates to the apoptosis. p53 may be involved in this upregulation. This may be due to physiological upregulation of WAF1 and p53 in response to genotoxic damage such as oxidative stress associated with cholangitis, suggesting other processes than CD95/CD95 ligand interaction in biliary epithelial apoptosis in PBC.

Aged↗
PubMed2001

Scavenger cells with gram-positive bacterial lipoteichoic acid infiltrate around the damaged interlobular bile ducts of primary biliary cirrhosis.

BACKGROUND/AIMS: Gram-positive bacterial DNA is frequently detectable in gallbladder bile of primary biliary cirrhosis (PBC) patients. To advance these findings, lipoteichoic acid (LTA) of gram-positive bacteria with high antigenicity was examined in liver specimens and bile from PBC patients and controls. METHODS: LTA was examined by Western blotting in the gallbladder bile from 15 PBC, 11 cholecystolithiasis and six normal subjects, and by immunohistochemistry in liver specimens from 16 PBC, six primary sclerosing cholangitis (PSC), eight chronic viral hepatitis C (CVH-C) and five normal subjects. RESULTS: In the gallbladder bile, there was no significant difference in the positive rate of LTA between PBC and controls. LTA-containing mononuclear cells were frequently detected in the portal tracts, particularly around the bile ducts and in hepatic sinusoids in PBC, while they were infrequent or occasional in control livers. These LTA-containing cells were sinusoidal endothelial cells and Kupffer cells, and portal monocytes, which frequently expressed scavenger receptor class B type 1. CONCLUSIONS: LTA derived from bacterial fragments may reach the bile, not only in the diseased state but also under normal conditions. Such LTA may be involved in the development and progression of portal tract lesions, particularly bile duct lesions, in PBC.

Adult↗
PubMed2001

The emergence and evolution of methicillin-resistant Staphylococcus aureus.

Significant advances have been made in recent years in our understanding of how methicillin resistance is acquired by Staphylococcus aureus. Integration of a staphylococcal cassette chromosome mec (SCCmec) element into the chromosome converts drug-sensitive S. aureus into the notorious hospital pathogen methicilin-resistant S. aureus (MRSA), which is resistant to practically all beta-lactam antibiotics. SCCmec is a novel class of mobile genetic element that is composed of the mec gene complex encoding methicillin resistance and the ccr gene complex that encodes recombinases responsible for its mobility. These elements also carry various resistance genes for non-beta-lactam antibiotics. After acquiring an SCCmec element, MRSA undergoes several mutational events and evolves into the most difficult-to-treat pathogen in hospitals, against which all extant antibiotics including vancomycin are ineffective. Recent epidemiological data imply that MRSA has embarked on another evolutionary path as a community pathogen, as at least one novel SCCmec element seems to have been successful in converting S. aureus strains from the normal human flora into MRSA.

Bacterial Proteins↗