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Hiroyuki Kobayashi

Publications and source records attributed to Hiroyuki Kobayashi.

At least 181 records · Page 10Linked to original sources
PubMed2002

Clinical evaluation of serum levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases as predictors of progressive fibrosis in postoperative biliary atresia patients.

BACKGROUND/PURPOSE: The authors analyzed serum Metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in postoperative biliary atresia (POBA) patients to evaluate their usefulness for assessing progressive fibrosis. METHODS: The authors measured serum MMPs (-1,2) and TIMPs(-1,2) using respective one-step sandwich enzyme immunoassays in 36 POBA patients (mean age, 12.3 +/- 6.5 years) and 13 age-matched controls. POBA patients were classified into 3 groups; group I: n = 12; normal liver function test (LFT); group II: n = 15; elevated LFT, anicteric; and group III: n = 9; elevated LFT, icteric. RESULTS: Serum MMP-2 levels were higher in all BA groups(especially in group II and III) compared with controls (P <.01). However, MMP-1 in all POBA patients groups (especially in group II and III) was significantly decreased compared with controls (P <.01). There was no statistical difference between mean values for serum TIMP-1 and TIMP-2 in all POBA patients compared with controls. CONCLUSIONS: Serum MMPs levels might be useful for predicting the progress of fibrosis and the functional reserve in POBA patients with documented deterioration in liver function caused by fibrosis. Our finding that TIMPs do not rise as cirrhosis progresses and this imbalance may be a causal factor for the excessive accumulation of extracellular matrix, which, in turn, may contribute to the progression of fibrosis in BA.

Adolescent↗
PubMed2002

Levels of circulating antiinflammatory cytokine interleukin-1 receptor antagonist and proinflammatory cytokines at different stages of biliary atresia.

BACKGROUND/PURPOSE: Antiinflammatory cytokine (interleukin [IL]-1ra) and proinflammatory cytokines (tumor necrosis factor [TNF]- alpha and IL-6) appear to play important roles in the pathophysiology of liver disease. In this study, the authors attempt to identify the roles of IL-1ra, IL-6, and TNF-alpha at different stages in postoperative biliary atresia (POBA) patients. METHODS: Serum concentrations of IL-1ra, IL-6, and TNF-alpha were measured in 34 POBA patients and 25 healthy controls using specific enzyme-linked immunosorbent assays (ELISA). POBA patients were classified into 5 groups: group I (n = 21), less than 3 years old; Ia, stable; Ib, mild liver dysfunction; Ic, severe liver dysfunction. Group II (n = 13), (more than 3 years old); IIa, stable; IIb, variable liver dysfunction. RESULTS: For IL-1ra differences between controls and groups Ib, Ic, and IIa were statistically significant (P <.01), and for IL-6, differences between controls and groups Ia, Ib, Ic, and IIb were statistically significant (P <.01). Groups Ib and Ic (less than 3 years old subjects) had the highest levels in this series. Serum TNF-alpha was not detected in any groups. CONCLUSION: The relationship between serum levels of IL-6 and IL-1ra may be predictive of prognosis with respect to the progression of fibrosis in POBA patients.

Adolescent↗
PubMed2002

Intraoperative endosonography enhances laparoscopy-assisted colon pull-through for high imperforate anus.

PURPOSE: The authors used ultrasonographic endoprobes during laparoscopy-assisted colon pull-through (LACPT) for the repair of high imperforate anus to confirm the pull-through canal was surrounded symmetrically by pelvic floor muscles. METHODS: Six patients with high imperforate anus were treated by LACPT (mean age at LACPT, 8.2 months). An endoscopic (12-MHz, 2.5-mm in diameter) and proctoscopic (7.5-MHz, 12-mm in diameter) probe were inserted into the proposed route of dissection intraoperatively to measure the thickness of the surrounding muscle tissue at at least 3 levels: the external anal sphincter, the levator ani muscle sling, and the intervening muscle complex. RESULTS: The average thickness of the external anal sphincter was 2.3 +/- 0.4 mm anteriorly, 2.4 +/- 0.4 mm on the left, 2.4 +/- 0.5 mm posteriorly, and 2.6 +/- 0.6 mm on the right. The average thickness of the muscle complex was 2.3 +/- 0.6 mm anteriorly, 2.2 +/- 0.5 mm on the left, 2.1 +/- 0.4 mm posteriorly, and 2.2 +/- 0.5 mm on the right. The average thickness of the left crus of the levator ani muscle was 1.8 +/- 0.3 mm, the right crus was 1.9 +/- 0.4 mm, and the rim located posterior to the rectum was 2.0 +/- 0.3 mm. No statistically significant difference was found between the measurements taken at each level. CONCLUSION: Intraoperative endosonography during LACPT can greatly enhance the precision of positioning the pull-through canal.

Anus, Imperforate↗
PubMed2002

Laparoscopy-assisted suction colonic biopsy and intraoperative rapid acetylcholinesterase staining during transanal pull-through for Hirschsprung's disease.

BACKGROUND: It is crucial to identify the exact level of transition to normal ganglion cells in instances of Hirschprung's disease. This report describes a technique for laparoscopy-assisted suction colonic biopsy during transanal pull-through. METHODS: Laparoscopy-assisted suction colonic biopsy (SCBx) was used in 12 patients with Hirschsprung's disease affecting the rectosigmoid. Average age was 4.4 +/- 2.1 months with a mean operative weight 6.2 +/- 1.0 kg. The pull-through was performed as the primary operative procedure in 11 patients. Using a 2-team approach (laparoscopic team and transanal team), the site was chosen for transanal suction biopsy and marked externally by the laparoscopic team with a silver clip. Biopsies were processed for ganglion cells and rapid AChE technique. RESULTS: There were no biopsy-induced perforations. Abnormal biopsies were repeated more proximally until ganglion cells were observed. Transanal pull-through was performed and an open full-thickness biopsy performed to confirm the presence of ganglion cells. All procedures were performed successfully. CONCLUSIONS: Laparoscopy-assisted SCBx can be used successfully in patients with Hirschsprung's disease affecting the rectosigmoid (80% of cases). The technique, when used with rapid AChE staining, provides accurate identification of the level of normoganglionosis.

Acetylcholinesterase↗
PubMed2002

[A case of Nocardia farcinica pneumonia treated with sulfamethoxazole-trimethoprim monitoring its serum concentration].

A 75-year-old male suffered from interstitial pneumonia in December 2000 and treated with predonisolone. The treatment was effective, and the dosage of predonisolone had been gradually tapered. In January 2001, when the dosage was 30 mg/day, he complained of cough and yellowish sputum. The chest X-ray and CT revealed bilateral infiltrations with cavities. He was treated with cefozopram and fluconazole. However, there were no improvements. The sputa of the 2nd, 3rd, 6th and 8th hospital days showed the presence of gram-positive branched rods, which were identified as Nocardia farcinica. Therefore, the treatment was changed to sulfamethoxazole-trimethoprim. During the treatment, serum concentration of sulfamethoxazole was repeatedly measured, and kept over 60 microgram/ml. He was swiftly recovered after the start of sulfamethoxazole-trimethoprim. This case was supposed to be the seventh one of N. farcinica pneumonia in Japan, and the measurement of the concentration of sulfamethoxazole was useful to determine its dosage.

Aged↗
PubMed2002

Effects of olopatadine, a new antiallergic agent, on human liver microsomal cytochrome P450 activities.

Olopatadine, a new histamine H(1) receptor-selective antagonist, is a tricyclic drug containing an alkylamino moiety. Some compounds containing a similar alkylamino group form a cytochrome p450 (p450) -iron (II)-nitrosoalkane metabolite complex [metabolic intermediate complex (MIC)], thereby causing quasi-irreversible inhibition of the p450. There was concern that olopatadine might also form MICs, therefore, the present investigation was undertaken to explore this possibility. We identified the enzymes catalyzing olopatadine metabolism and investigated the effect of olopatadine on human p450 activities. During incubation with human liver microsomes in the presence of a NADPH-generating system, olopatadine was metabolized to two metabolites, M1 (N-monodemethylolopatadine) and M3 (olopatadine N-oxide) at rates of 0.330 and 2.50 pmol/min/mg protein, respectively. Troleandomycin and ketoconazole, which are both selective inhibitors of CYP3A, significantly reduced M1 formation but specific inhibitors of other p450 isozymes did not decrease M1 formation. Incubation of olopatadine with cDNA-expressed human p450 isozymes confirmed that M1 formation was almost exclusively catalyzed by CYP3A4. The formation of M3 was enhanced by N-octylamine and was inhibited by thiourea. High specific activity of M3 formation was exhibited by cDNA-expressed flavin-containing monooxygenase (FMO)1 and FMO3. Olopatadine did not inhibit p450 activities when it was simultaneously incubated with substrates for different p450 isozymes. Also, p450 activities in human liver microsomes were unaffected by pretreatment with olopatadine or M1. Furthermore, spectral analysis revealed that neither olopatadine nor M1 formed an MIC. Therefore, it is unlikely that olopatadine will cause drug-drug interactions involving p450 isozymes.

Animals↗
PubMed2002

Animal model of Mycoplasma pneumoniae infection using germfree mice.

We have attempted to establish a gnotobiotic mouse model monoassociated with Mycoplasma pneumoniae following single or repeated infection to examine the mechanism of pathogenesis following M. pneumoniae infection. M. pneumoniae inoculated into germfree mice colonized equally well at 10(5) CFU/lung in both single infection and repeated infection. In histopathological observation, repeatedly infected mice showed pneumonia with mild infiltration of mononuclear cells and macrophages. Antibody titers against M. pneumoniae rose in the repeatedly infected mice but not in the singly infected mice. The percentage of CD4-positive, CD8-positive, and CD25-positive lymphocytes infiltrated in the lung was increased in the repeatedly infected mice. In contrast, the lymphocyte subset in the spleen was not significantly different among mock-, singly, and repeatedly infected mice. In the study of cytokine productivity of spleen cells, production of interleukin (IL)-4 and IL-10 was significantly increased and that of gamma interferon was remarkably increased in the mice following repeated infection. These results indicate that a gnotobiotic mouse model monoassociated with M. pneumoniae was established and that immune mechanisms might be involved in the pathogenesis in pneumonia following M. pneumoniae infection.

Animals↗
PubMed2002

Smoldering myeloma associated with zonisamide treatment.

A 39-year-old man was found to have hyperproteinemia after being treated with zonisamide for 10 years. Laboratory examination revealed a serum M-protein which consisted of IgG (lambda) and an increased number of plasma cells in the bone marrow, resulting in a diagnosis of smoldering myeloma. Considering his age, zonisamide was suspected to play an etiologic role in the occurrence of smoldering myeloma. Zonisamide was changed to sodium valproate. Subsequently the M-protein did not increase over 13 months. When zonisamide is used, the monitoring of serum levels of M-protein and patterns of gammaglobulin is warranted.

Adult↗
PubMed2002

Glucagon is required for early insulin-positive differentiation in the developing mouse pancreas.

The embryonic pancreas is thought to develop from pluripotent endodermal cells that give rise to endocrine and exocrine cells. A key guidance mechanism for pancreatic development has previously been found to be epithelial-mesenchymal interaction. Interactions within the epithelium, however, have not been well studied. Glucagon is the earliest peptide hormone present at appreciable levels in the developing pancreatic epithelium (embryonic day [E]-9.5 in mouse). Insulin accumulation begins slightly later (E11 in mouse), followed by a rapid accumulation during the "second wave" of insulin differentiation ( approximately E15). Here we found that blocking early expression and function of glucagon, but not GLP-1, an alternate gene product of preproglucagon mRNA, prevented insulin-positive differentiation in early embryonic (E11) pancreas. These results suggest a novel concept and a key role for glucagon in the paracrine induction of differentiation of other pancreatic components in the early embryonic pancreas.

Animals↗
PubMed2002

A novel therapeutic technology of specific RNA inhibition for acute promyelocytic leukemia: improved design of maxizymes against PML/RARalpha mRNA.

Targeting of PML/RARalpha using a loss of function strategy in acute promyelocytic leukemia (APL) is a direct therapeutic approach for patients and may be the basis of future gene therapy for this leukemia. To achieve this, we designed specific maxizymes, novel allosterically controllable ribozymes, against both short and long PML/RARalpha isoforms. The maxizyme has sensor arms that can only recognize target sequences, and it can form a cavity that captures catalytically indispensable Mg2+. We deleted 1 base nucleotide in the Mg2+-binding pocket designed MzPRT50 and MzPRK55. The distance from the PML/RARalpha junction site to the center of effectors is only 2 bases, and there are 8 and 9 complementary bases in their inactive forms, respectively. Both maxizymes specifically cleaved PML/RARalpha mRNA but not wild-type RARalpha mRNA in a cell-free system. Modification of the sequence of the Mg2+-binding pocket will be important in designing the sequence-specific maxizymes against oncogenic genes.

Cell-Free System↗
PubMed2002

[cDNA microarray technology as a laboratory examination method: a gene expression profiling test for analysis of drug resistance in tumor cells].

cDNA microarray technology permits the simultaneous measurement of the expressions of thousands of genes. The technology is now an indispensable research tool in molecular biology, and the challenge is its development and usage as clinical diagnostic tools. cDNA microarray can be used to identify gene expression profiles in tumor cells which correlate strongly with the treatment responsiveness such as drug resistance and clinical outcome of the disease despite similar phenotypes. For the introduction of cDNA microarray into laboratory examination, many issues need to be resolved. Design of a diagnostic array must be developed with defined sequences based on interpretation of huge quantities of data from experimental arrays to predict treatment responsiveness. Assay quality must be improved in terms of detection sensitivity, reproducibility, and linear dynamic range for RNA quantitation. Generally available instruments, which are much less expensive and more practical, need to be developed. Along with the improvement of the assay as a laboratory examination method, cDNA microarray will facilitate the integration of diagnosis and therapeutics, and the introduction of individual medicines.

Clinical Laboratory Techniques↗
PubMed2002

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2000)].

From October 2000 to September 2001, we collected the specimen from 410 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various anti-bacterial agents and antibiotics and patients' characteristics. Of 499 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 493 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 73, Haemophilus infiuenzae 99, Pseudomonas aeruginosa (non-mucoid) 64, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 25, Moraxella subgenus Branhamella catarrhalis 21, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 53.8%. Vancomycin and arbekacin had the most potent activities against MRSA as observed in 1999. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 38.4% being consistent with that in 1999 (34.7%). PRSP accounted for 11.0% of the total, being more than that in 1999 (3.0%). Carbapenems had strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 73 strains at 0.125 microgram/ml. Generally, all drugs had strong activities against H. influenzae with MIC80s of 8 micrograms/ml or less. The drug that had the strongest activity against H. infiuenzae was levofloxacin, which inhibited the growth of 94 of the 99 strains at 0.063 microgram/ml. Tobramycin had a strong activity against P. aeruginosa (both mucoid and non-mucoid) with MIC80 of 1 microgram/ml. The mucoid strain was little isolated (14 strains) but the susceptibilities to all drugs were better than the non-mucoid strain. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and the MIC80S were 2 micrograms/ml or less. Particularly, cefpirome, cefozopran, and levofloxacin had strong bactericidal activities against K. pneumoniae with MIC80s of 0.125 microgram/ml, and cefotiam, second-generation cephems, also had a favorable activity being MIC80 of 0.25 microgram/ml. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or less. The drug having the strongest activity was imipenem and levofloxacin inhibiting all 21 strains at 0.063 microgram/ml. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (44.4%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 38.0% and 31.7% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (18.3%) and S. pneumoniae (16.1%). In contrast, H. infiuenzae (20.4%) and P. aeruginosa (both mucoid and non-mucoid: 16.7%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from all the patients were S. pneumoniae (24.3%) and H. infiuenzae (26.7%). The frequency of isolated S. pneumoniae tended to decrease with the increase in the number of administration days while that of isolated H. infiuenzae did not. The frequency of isolated P. aeruginosa tended to increase with the duration of administration. The isolated bacteria were comparable between the patients already treated with penicillins and cephems. In the patients treated with aminoglycosides, macrolides, and quinolones, P. aeruginosa was most frequently isolated (33.3 to 40.0%).

Anti-Bacterial Agents↗
PubMed1997

Influence of macrolides on mucoid alginate biosynthetic enzyme from Pseudomonas aeruginosa.

OBJECTIVE: The long-term administration of erythromycin (EM), clarithromycin (CAM) or azithromycin (AZM) has generally resulted in a favorable outcome for patients with diffuse panbronchiolitis (DPB) infected with mucoid Pseudomonas aeruginosa. To elucidate the mechanism involved, the influence of macrolides on mucoid alginate production by P. aeruginosa was investigated in vitro. METHODS: The macrolides used in this study were EM with a 14-membered ring, AZM with a 15-membered ring, midecamycin (MDM) with a 16-membered ring, and CP-4305, which has had mycarose removed from MDM, The effects of macrolides on mucoid P. aeruginosa were investigated by quantitative assay of alginate production and inhibition of guanosine diphospho-D-mannose dehydrogenase activity. RESULTS: After incubation with EM, AZM and CP-4305, the structural material of P. aeruginosa biofilm was distorted, and the enzymatic activity of GDP-D-mannose dehydrogenase, the most important enzyme in mucoid alginate biosynthesis, was inhibited. However, these effects were not observed with the 16-membered macrolide MDM. CONCLUSIONS: The basic mechanism of clinical efficacy seen characteristically in 14- or 15-membered macrolides for patients with airway biofilm disease depends on the ability of such macrolides to inhibit alginate production by P. aeruginosa. Furthermore, this suggests that the inhibitory effect observed with 14-, 15- and 16-membered macrolides may depend on the sugar chain connected with the macrolide ring.

Journal Article↗
PubMedDate not supplied

Expression of IL-6 receptor in pancreatic cancer: involvement in VEGF induction.

BACKGROUND: Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic growth factors and its expression is correlated with MVD (microvascular density) in malignant tumors, including pancreatic adenocarcinoma. On the other hand, serum interleukin-6 (IL-6) is elevated in many patients with pancreatic cancer in accordance with their disease progression. In this study, we examined whether IL-6 and its receptors have any involvement in the induction of VEGF in pancreatic cancer. MATERIALS AND METHODS: Two human pancreatic cancer cell lines were examined for the induction of VEGF after treatment with IL-6. Thirty-two pancreatic cancer surgical specimens were stained immunohistochemically with VEGF, IL-6 and IL-6 receptor antibodies. RESULTS: CFPAC-1 cells expressed IL-6 receptor whereas AsPC-1 cells rarely expressed it. IL-6 treatment induced VEGF expression significantly and dose-dependently in CFPAC-1 cells, while it did not change in AsPC-1 cells. The intensity of VEGF expression in CFPAC-1 also increased time-dependently with IL-6 treatment. In 32 surgical pancreatic cancer tissues, 19 (59%) stained positive for VEGF and 26 (87%) positive for IL-6 receptor beta subunit. The correlation between IL-6 receptors and VEGF was significant (p = 0.0002 and p = 0.0019) while less correlation was seen between IL-6 and VEGF (p = 0.1937). CONCLUSION: Our results suggest that IL-6 is likely to take part in VEGF expression in both paracrine and autocrine fashion in pancreatic cancer. Induction of VEGF seems to be regulated by the extent of the IL-6 receptor expression on cancer cells.

Aged↗
PubMedDate not supplied

Possible involvement of TNF-alpha in left ventricular remodeling in hemodialysis patients.

BACKGROUND: Tumor necrosis factor (TNF)-alpha causes hypertrophic as well as negative inotropic effects on cardiac myocytes. Circulating TNF-alpha levels are reported to be elevated in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). We investigated whether increased circulating TNF-alpha is associated with left ventricular remodeling against pressure and/or volume overload in HD patients with or without diabetes mellitus. METHODS: Echocardiography and the measurement of plasma TNF-alpha and B-type natriuretic peptide (BNP) concentrations, one of the parameters indicating left ventricular wall stress, were performed on 176 ESRD patients undergoing maintenance HD (88 non-diabetic and 88 diabetic patients). RESULTS: The mean plasma TNF-alpha concentrations were high, but did not differ between non-diabetic and diabetic patients (9.8 +/- 4.3 pg/mL vs. 9.9 +/- 5.4 pg/mL). In non-diabetic patients, plasma TNF-alpha concentration correlated positively with interventricular septal wall thickness (IVST) and relative left ventricular wall thickness (rLVWT), and inversely with left intraventricular dimensions, but did not correlate with left ventricular mass index (LVMI). In contrast, in diabetic patients, plasma TNF-alpha concentration correlated positively with plasma BNP concentration (r=0.821, p=0.0001) and left intraventricular dimensions, and inversely with rLVWT (r=-0.407, p=0.0001) and left ventricular fractional shortening (r=-0.445, p=0.0001). CONCLUSIONS: Circulating TNF-alpha is possibly involved in concentric left ventricular remodeling in non-diabetic HD patients, whereas it is associated with eccentric left ventricular remodeling against sustained pressure and/or volume overload in diabetic HD patients.

Diabetic Nephropathies↗