Search PubMed⌕ Search

Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 73 records · Page 4Linked to original sources
PubMed2001

Intraductal papillary components in invasive ductal carcinoma of the pancreas are associated with long-term survival of patients.

Most patients with pancreatic ductal carcinoma have a poor prognosis. However, in certain cases, 5-year survival can be achieved after surgical resection. Analysis of the pathologic findings associated with good survival rates will assist in identifying the optimum treatment. The clinicopathologic features of 67 patients who underwent surgical resection of ductal adenocarcinoma of the pancreas between 1990 and 1996 were reviewed and correlated with survival rates. There were 42 men and 25 women, with a mean age of 62.1 years (range, 44 to 82 years). The mean greatest diameter of the tumor was 4.3 cm (range, 1.5 to 11 cm). Nineteen patients (29.4%) survived more than 3 years, and 9 (13.2%) survived more than 5 years after surgical resection. The intraductal papillary component (IDPC) of the carcinoma was the main focus of the pathologic observations. IDPC was defined as intraductal papillary proliferative lesions seen in the tumor nodule with proliferative cells consistent with carcinomatous cellular atypia. IDPC was clearly present (++) in 24 patients and vaguely present (+) in 9 patients. Using the Mantel-Cox test, a statistically significant correlation was found between the presence of IDPC (either + or ++) and postoperative patient survival (P =.002). IDPC is a morphologic feature associated with longer patient survival and should be taken into consideration in assessing the pathway of tumor progression.

Adult↗
PubMed2001

Expression of mRNA for DNA methyltransferases and methyl-CpG-binding proteins and DNA methylation status on CpG islands and pericentromeric satellite regions during human hepatocarcinogenesis.

To evaluate the significance of alterations in DNA methylation during human hepatocarcinogenesis, we examined levels of mRNA for DNA methyltransferases and methyl-CpG-binding proteins and the DNA methylation status in 67 hepatocellular carcinomas (HCCs). The average level of mRNA for DNMT1 and DNMT3a was significantly higher in noncancerous liver tissues showing chronic hepatitis or cirrhosis than in histologically normal liver tissues, and was even higher in HCCs. Significant overexpression of DNMT3b and reduced expression of DNMT2 were observed in HCCs compared with the corresponding noncancerous liver tissues. DNA hypermethylation on CpG islands of the p16 (8% and 66%) and hMLH1 (0% and 0%) genes and methylated in tumor (MINT) 1 (6% and 34%), 2 (24% and 58%), 12 (21% and 33%), 25 (0% and 5%), and 31 (0% and 23%) clones, and DNA hypomethylation on satellites 2 and 3 (18% and 67%), were detected in noncancerous liver tissues and HCCs, respectively. There was no significant correlation between the expression level of any DNA methyltransferase and DNA methylation status. Reduced expression of DNA repair protein, MBD4, was significantly correlated with poorer tumor differentiation and involvement of portal vein. Slightly reduced expression of MBD2 was detected in HCCs, and the expression of MeCP2 was particularly reduced in HCCs with portal vein involvement. These data suggest that overexpression of DNMT1 and DNMT3a, DNA hypermethylation on CpG islands, and DNA hypomethylation on pericentromeric satellite regions are early events during hepatocarcinogenesis, and that reduced expression of MBD4 may play a role in malignant progression of HCC.

Adult↗
PubMed2001

Inhibition of intrahepatic metastasis of human hepatocellular carcinoma by Rho-associated protein kinase inhibitor Y-27632.

Intrahepatic metastasis is one of the most important prognostic factors for patients with hepatocellular carcinoma (HCC). Cell motility mediated by Rho- and p160 Rho-associated coiledcoil forming protein kinase (p160ROCK) signaling pathways has recently been shown to play a critical role in intrahepatic metastasis in human HCC. Furthermore, the stable introduction of dominant-negative p160ROCK into Li7 cells resulted in a reduced metastatic rate in mice with severe combined immunodeficiency (SCID). To investigate whether the specific p160ROCK inhibitor, Y-27632, could also inhibit intrahepatic metastasis, the effect of Y-27632 on the cell motility and intrahepatic metastasis of Li7 was investigated. Y-27632 markedly blocked actin reorganization and motility of Li7 cells mediated by lysophosphatidic acid (LPA). Y-27632 was administered continuously into the peritoneal cavity using a micro-osmotic pump, together with orthotopic implantation of Li7 cells into the liver of SCID mice. Phosphate-buffered saline (PBS) alone was administered as the control. The incidence of mice with metastatic nodules decreased in the Y-27632-treated group. The primary tumor volume at the site of injection was smaller in the Y-27632-treated group compared with the control group, but the difference was not statistically significant. Histologically, control tumors showed infiltrative growth into the sinusoidal area at the tumor boundary, whereas Y-27632-treated tumors showed expansive growth and low invasiveness. These findings confirm the importance of the Rho/p160ROCK signaling pathway in intrahepatic metastasis of human HCC, and indicate that Y-27632 may be useful for the prevention of intrahepatic metastasis of human HCC.

Actins↗
PubMed2001

Localization and role of endothelin-1 and endothelin receptors in the human Fallopian tube.

The present experiments were designed to investigate the localization and role of endothelin-1 (ET-1) and endothelin receptors (ET(A) and ET(B)) in human Fallopian tubes obtained from patients in the follicular phase. Immunohistochemical studies revealed the predominant localization of ET-1 and of ET(B) receptors in the tubal epithelium and also within the muscle layer to a lesser degree. ET(A) receptors were dominant within the muscle layer. Scatchard plot analysis of the [(125)I]ET-1 binding also revealed the localization of ET(A) and ET(B) receptors on the Fallopian tubal membrane. A dissociation equilibrium constant of 34.6 +/- 3.3 pmol/l and a maximum binding site concentration of 1137.0 +/- 239.1 fmol/mg protein were obtained from the Scatchard plot analysis. Treatment of Fallopian tubal strips with ET-1 produced a tonic contraction which was inhibited by an ET(A) antagonist but not by an ET(B) antagonist. However, the increase in frequency and decrease in amplitude of rhythmic contractions caused by ET-1 were modulated by the ET(B) antagonist but remained unaffected by the ET(A) antagonist. These results suggest that ET-1 modulates the motility of the Fallopian tube through excitation of ET(A) and/or ET(B) receptors and possibly plays some role in oocyte capture.

Adult↗
PubMed2001

Effects of prenatal rubratoxin-B exposure on behaviors of mouse offspring.

The effects of prenatal rubratoxin-B (RB) exposure on 8 behavioral parameters in JCL:ICR mice were assessed. Pregnant mice were injected intraperitoneally with 0.1 or 0.2 mg/kg/day of RB dissolved in propylene glycol water solution on days 7-9 (Group A) or 10-12 (Group B) of gestation. Controls received the vehicle similarly on days 7-12 of gestation. Before weaning, the offspring of both sexes were examined to test their the surface righting reflex (5 days of age), cliff avoidance response (6 days), negative geotaxis response (7 days), and swimming development (8, 10, and 12 days). After weaning, male animals were examined using the rotarod test (6 weeks of age), the open-field test (7 weeks), the shuttle-box-avoidance-learning test (9 weeks), and the water E-maze test (10 weeks). The preweanling offspring in the 0.2 mg/kg-B group showed significantly lower success rates and longer response times than controls in the cliff-avoidance response. In swimming development, the offspring in the 0.2 mg/kg B group had significantly lower scores than controls for swimming angle at 10 and 12 days of age. The avoidance learning of the mice in all RB-exposed A and B groups was significantly poorer than that of controls. These results indicate that prenatal exposure to RB produced a delay of early response development and impaired learning ability in the offspring of mice exposed to RB during middle pregnancy.

Animals↗
PubMed2001

The pharmacokinetics of epidural ropivacaine in infants and young children.

UNLABELLED: The pharmacokinetic variables of ropivacaine were characterized after epidural bolus injection in pediatric patients. The subjects, 7 infants (aged 3-11 mo) and 11 young children (aged 12-48 mo), received 1.7 mg/kg of ropivacaine via a lumbar epidural catheter. Total plasma concentrations of ropivacaine measured over 24 h were assayed by high-pressure liquid chromatography, and pharmacokinetic modeling was performed by Nonlinear Mixed Effects Modeling analysis. The median peak venous plasma concentrations (C(max)) in infants and young children were 610 microg/L (interquartile range [IQR], 550-725 microg/L) and 640 microg/L (IQR, 540-750 microg/L), respectively. The median times to maximum plasma ropivacaine concentration (T(max)) were 60 min (IQR, 60-120 min) in infants and 60 min (IQR, 30-90 min) in young children. There were no statistical differences between median values of C(max) and T(max) between infants and young children. The calculated clearance (CL) in infants was 4.26 mL x min(-1) x kg(-1) (9% coefficient of variation), and in young children it was 6.15 mL x min(-1) x kg(-1) (11% coefficient of variation). The CL for infants was significantly less than the CL for young children (P < 0.01). The volume of distribution was estimated to be 2370 mL/kg (9% coefficient of variation) for both young children and infants. No systemic toxicity was observed in either group. IMPLICATIONS: This study revealed that the pharmacokinetic variables of lumbar epidural bolus ropivacaine in pediatric patients aged 3 to 48 mo are similar to those of adults, except that drug clearance was less in infants compared with older children.

Algorithms↗
PubMed2001

Abdominal pain in patients with resectable pancreatic cancer with reference to clinicopathologic findings.

Abdominal and/or back pain is one of the most common symptoms in patients with pancreatic cancer. However, the cause of the pain and the clinicopathologic features of patients with pain have not been fully elucidated. We retrospectively determined the factors related to preoperative abdominal and/or back pain in 95 patients with resectable pancreatic cancer. Pancreatic tumor size, invasion of the intrapancreatic nerves, invasion of the anterior pancreatic capsule, and lymph node metastasis were determined to be variables related to the pain. Pancreatic tumor size, invasion of anterior pancreatic capsule, and lymph node metastasis were also variables significantly correlating to pain intensity. Survival also correlated with pain intensity: the median survival periods were 29 months in patients without pain, 19 months in those with mild pain, and 9 months in those with severe pain who required analgesics. Larger pancreatic tumors, invasion of the intrapancreatic nerves, and invasion of the anterior pancreatic capsule may cause abdominal and/or back pain in patients with resectable pancreatic cancer. This study also suggests clinical implications of the pain intensity as a prognostic factor in patients with resectable pancreatic cancer.

Abdominal Pain↗
PubMed2001

Simultaneous measurement of plasma ropivacaine and bupivacaine concentrations by HPLC with UV detection.

The authors developed a high-performance liquid chromatography (HPLC) assay for the simultaneous determination of plasma ropivacaine and bupivacaine concentrations using ultraviolet (UV) detection and a simple solid-phase extraction procedure. The absolute retention times of ropivacaine, bupivacaine, and the internal standard pentycaine were 1.9, 3.0, and 5.6 minutes, respectively. The assay had a linearity of 2000 ng/mL, a sensitivity of 5 ng/mL, an average recovery of 98%, and an average day-to-day imprecision of <10% for both drugs. A patient correlation study (n = 23) using this HPLC method and an established gas chromatographic assay revealed a slope of 1.01, an intercept of -10.6 ng/mL, and a correlation coefficient of 0.99 for ropivacaine; and a slope of 0.96, an intercept of 14.7 ng/mL, and a correlation coefficient of 0.99 for bupivacaine. Of the 60 different drugs tested, only quinidine and lidocaine extracted but did not interfere with the measurement of the drugs of interest. The authors conclude that the method described here is ideally suited for the therapeutic monitoring of plasma ropivacaine and bupivacaine concentrations.

Amides↗
PubMed2001

Rapid detection and quantification of five periodontopathic bacteria by real-time PCR.

The quantity of periodontopathic bacteria in plaque samples is an important determinant for understanding the etiologic role of bacteria. The real-time PCR method was used to detect and quantify periodontopathic bacteria, such as Actinobacillus actinomycetemcomitans, Bacteroides forsythus, Porphyromonas gingivalis, Treponema denticola, and Treponema socranskii, in saliva and subgingival plaque samples. There was good agreement between the results of conventional PCR and real-time PCR methods. Using the LightCycler system we were able to determine the amount of periodontopathic bacteria within an hour. The real-time PCR method was linear for samples containing from 10(3) to more than 10(8) cells (r2 = 0.999). The application of the real-time PCR method should be useful in the rapid detection and quantification of periodontopathic bacteria in clinical samples.

Actinobacillus↗
PubMed2001

PCR detection method of Clostridium scindens and C. hiranonis in human fecal samples.

Clostridium scindens and C. hiranonis have high bile acid 7alpha-dehydroxylating activity. Direct PCR and nested PCR with the specific primers for C. scindens and C. hiranonis were developed and tested for the detection of them in human fecal samples. Nested PCR detected C. scindens in all samples, but direct PCR detected it in 27 of 34 samples. Regarding C. hiranonis, nested PCR detected it in only 18 of 34 samples although nested PCR has a high level of sensitivity. Nested PCR was a specific and sensitive method for the detection of C. scindens and C. hiranonis in fecal samples.

Adult↗
PubMed2001

Characterization of the Lactobacillus casei group and the Lactobacillus acidophilus group by automated ribotyping.

A total of 91 type and reference strains of the Lactobacillus casei group and the L acidophilus group were characterized by the automated ribotyping device Riboprinter microbial characterization system. The L. casei group was divided into five (C1-C5) genotypes by ribotyping. Among them, the strain of L. casei ATCC 334 was clustered to the same genotype group as most of L. paracasei strains and L casei JCM 1134T generated a riboprint pattern that was different from the type strain of L. zeae. These results supported the designation of L. casei ATCC 334 as the neotype strain, but were not consistent with the reclassification of L. casei JCM 1134T as L. zeae. The L. acidophilus group was also divided into 14 (A1-A11, B1-B3) genotypes by ribotyping. L. acidophilus, L. amylovorus, L. crispatus and L. gallinarum generated ribotype patterns that were distinct from the patterns produced by L. gasseri and L. johnsonii. This result confirmed previous data that the L. acidophilus group divided to two major clusters. Five strains of L. acidophilus and two strains of L. gasseri were correctly reidentified by ribotyping. Most strains belonging to the L. casei group and the L. acidophilus group were discriminated at the species level by automated ribotyping. Thus this RiboPrinter system yields rapid, accurate and reproducible genetic information for the identification of many strains.

Humans↗
PubMed2001

Involvement of c-Src in carcinoma cell motility and metastasis.

Carcinoma cells exhibit dysfunction / dysregulation of cell adhesion systems that correlates with their abilities to migrate, invade, and metastasize. Here we show that the tyrosine kinase c-Src is required for motility and metastasis of two carcinoma cell lines. Adherent KYN-2 cells having a high level of c-Src kinase activity become scattered, extend lamellipodia, and exhibit high motility. Expression of a dominant-negative mutant form of c-Src caused formation of stress fibers and focal adhesions, and markedly reduced motility. HCT15 cells extended lamellipodia and became scattered in response to lysophosphatidic acid stimulation in parallel with transient activation of c-Src, which was inhibited by expression of a dominant-negative mutant form of c-Src or treatment with a specific Src kinase inhibitor. Furthermore, implantation of dominant-negative c-Src transfectants into the peritoneal cavity of SCID mice resulted in reduced peritoneal dissemination compared with control transfectants. These findings indicate that c-Src activation is critically involved in carcinoma cell migration and metastasis.

Adenocarcinoma↗
PubMed2001

[Evaluation of an HIV screening assay kit for the combined detection of anti-HIV-1/2 antibodies and HIV p24 antigen].

We have evaluated a new HIV screening assay kit (Genscreen HIV Ag-Ab) for the HIV antigen-antibody combined test by comparing with two HIV antigen-antibody combined assay kits (VIDAS HIV DUO, Enzygnost HIV integral). Genscreen HIV Ag-Ab is a microwell plate enzyme immunoassay for the detection of HIV infection, based on the detection of anti-HIV-1/2 antibodies and HIV p24 antigen in human serum or plasma. In this study, 90 samples of HIV-1 antibody positive sera and 670 samples of HIV negative sera were examined. The sensitivity was 100% and the specificity was 99.7%. All of HIV-1 group M sera (subtypes A to G and B/D), HIV-1 group O sera and HIV-2 sera in worldwide HIV performance panel-302 were positive with Genscreen HIV Ag-Ab. Ten commercially available HIV-1 seroconversion panels were tested to evaluate sensitivity of three HIV antigen-antibody combined assay kits. Genscreen HIV Ag-Ab detected infection at the same bleeds as VIDAS HIV DUO in 8 of 10 seroconversion panels and 1 to 2 bleeds earlier than Enzygnost HIV integral in 5 of 10 seroconversion panels. However, VIDAS HIV DUO indicated false negative on 5th bleed in panel BB (PRA952). The result of the specimen was positive on 3rd bleed, equivocal on 4th bleed, negative on 5th bleed and again positive on 6th bleed. All of these specimens were positive by Genscreen HIV Ag-Ab. Therefore, Genscreen HIV Ag-Ab that shorten the window period is a useful and reliable for HIV screening test, especially in case of primary infection.

AIDS Serodiagnosis↗
PubMed2001

[A case of leptospirosis infected in Borneo Island, Malaysia].

We report a case of leptospirosis infected in Sabah, Borneo island, Malaysia. The case is 25-year-old male who had participated in the EcoChallenge Sabah 2000 Expedition Race, a multisport event held during August 20 to September 3, 2000 at various sites in Sabah in Malaysian Borneo. He developed a high fever and headache on September 7, and he was admitted to our hospital on September 9. On admission he also had conjunctivitis and myalgias. Laboratory findings on admission revealed leukocytosis with left shift, slightly elevated transaminase levels, high CRP levels and proteinuria. Plasmodium spp. were negative on blood smears, and no bacteria were isolated from blood and feces cultures. We performed the laboratory tests for leptospirosis, based on the information about the probable leptospirosis outbreak among athletes who participated in the EcoChallenge Race, however both Leptospira antigens and antibodies were negative at that time. We diagnosed leptospirosis clinically because he manifested persistent symptoms, and minocycline 100 mg b.i.d. was administered intravenously resulting in excellent efficacy. Serum antibody tests by microscopic agglutination test (MAT) at convalescent stage revealed significant increased antibodies against Leptospira interrogans serovar hebdomadis, and the diagnosis of leptospirosis was confirmed. Infectious diseases have been global and it is important to have information concerning worldwide infectious disease situations as much as possible for accurate diagnosis.

Adult↗
PubMed2001

[Acute exacerbations due to Streptococcus pneumoniae in chronic lower respiratory tract infections during long-term macrolide therapy].

In Japan, long-term 14-membered macrolide administration is chosen as a first line therapy against chronic lower respiratory tract infections (CLRTIs) such as diffuse panbronchiolitis, bronchiectasis and chronic bronchitis. However, sometimes acute exacerbations occur in these cases, even if therapy is effective. We investigated 18 episodes of CLRTIs exacerbations that were caused by Streptococcus pneumoniae during long-term macrolides therapy from 1991 to 1999 to clarify the clinical features and prevalence of antimicrobial resistance in S. pneumoniae. Exacerbations did not occur only in winter season, but also in other seasons. Among 18 episodes of exacerbation, only 7 episodes (39%) revealed infiltration in chest roentogenogram and few episodes revealed marked elevations of inflammation markers in laboratory data. Intermediate resistance or resistance rates of S. pneumoniae isolated from sputum or transtracheal aspiration were 100% to erythromycin, 67% to clindamycin or minocycline, 11% to ampicillin, and 0% to cephazoline or imipenem. Coresistance to erythromycin, clindamycin and minocycline was seen in a half of the episodes. Resistance was not correlated with the duration of macrolides administration. All episodes were mainly treated with beta-lactam agents or fluoroquinolones and cured successfully. These findings suggest that acute exacerbations in CLRTIs caused by S. pneumoniae during long-term macrolides therapy do not reveal severe clinical aspects and can be treated successfully at present, but attention should be paid to the trend of antibiotic susceptibility in S. pneumoniae.

Adolescent↗
PubMed2001

[Pathogenetic study on bronchopulmonary infections in 1,416 patients by transtracheal aspiration method].

We have performed transtracheal aspiration (TTA) in 1,416 patients, who were suspected to have bronchopulmonary infection, in order to collect non-contaminated specimens directly from the lower airway. The overall isolation rates in 1,416 TTA were 68.7% for any microorganisms. Aerobes had a high incidence but many kinds of microorganisms were associated with bronchopulmonary infections. Haemophilus influenzae was the major pathogen in patients with acute bronchitis. Streptococcus pneumoniae was the most important pathogen and mycoplasma was often isolated in patients with community-acquired pneumonia. Major pathogens of nosocomial pneumonia consisted of alpha-streptococcus spp., anaerobes and Pseudomonas aeruginosa. Anaerobes were isolated from transtracheal aspirates in 20 of 33 episodes of lung abscesses. H. influenzae and P. aeruginosa were the main persistent pathogens and H. influenzae, S. pneumoniae and anaerobes were important exacerbated pathogens in patients with chronic lower respiratory tract infection. S. pneumoniae was isolated more from TTA than expectorated sputa. Oropharyngeal flora bacteria were easily isolated in the culture of expectorated sputa. We assessed the final diagnosis or causative factor in 443 patients whom no microorganism was isolated from transtracheal aspirates. The final diagnosis was infectious diseases in 52 patients (11.7%) and non-infectious diseases in 80 patients (18.1%), respectively. The causative factor was unsuited TTA sample in 81 patients (18.3%), preceding antimicrobial chemotherapy in 95 patients (21.4%) and unknown in 135 patients (30.5%), respectively. The pathogenesis of bronchopulmonary infections is complex and various microorganisms are associated with pathogens of bronchopulmonary infections. Therefore, we should accurately diagnose the pathogens in patients with bronchopulmonary infections. TTA is one of the useful methods that we can accurately detect the respiratory pathogens.

Adolescent↗