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Biomedical subjects

Kaoru Kobayashi

Publications and source records attributed to Kaoru Kobayashi.

At least 91 records · Page 5Linked to original sources
PubMed2004

Preoperative ultrasonographic examination for lymph node metastasis: usefulness when designing lymph node dissection for papillary microcarcinoma of the thyroid.

Papillary microcarcinoma has an excellent prognosis after surgical treatment, but how to dissect the lymph nodes remains an open question. In this study, we investigated whether modified radical neck dissection (MND) affected the lymph node recurrence-free survival (LN-RFS) rate for 590 patients with papillary microcarcinoma and recurrence in the lateral compartment who underwent surgery in our hospital between 1993 and 2001. MND was performed in 316 patients, and metastasis in lateral compartment was preoperatively detected on ultrasonography in 67. These 67 patients showed significantly worse LN-RFS (p = 0.0038) than the remaining 249 patients without preoperatively detectable lateral node metastasis. Of the 523 patients (590 minus the 67 patients) whose lateral node metastasis was not detected preoperatively, 249 underwent MND; the remaining 274 patients did not. There was no significant difference in LN-RFS between these two groups. Our preliminary data suggest that with papillary microcarcinoma: (1) MND is not necessary in patients without lateral node metastasis detected on ultrasonography preoperatively, and (2) patients with preoperatively detected lateral node metastasis are more likely to develop recurrence in the lymph nodes so careful MND should be performed.

Adolescent↗
PubMed2004

A bowl-shaped fullerene encapsulates a water into the cage.

The sequential carbon-carbon bond cleaving reactions of the diketone derivative of C60 with o-phenylenediamine give a novel bowl-shaped fullerene bearing a 20-membered ring orifice. The product reversibly encapsulates a water molecule into the fullerene cage for the first time.

Fullerenes↗
PubMed2004

Ca at C82 isomers: computed temperature dependency of relative concentrations.

Relative concentrations of nine isomers of Ca at C82 derived from the C82 isolated-pentagon-rule satisfying cages are computed in a wide temperature interval. The computations are based on the Gibbs energy constructed from partition functions supplied with molecular parameters from density functional theory calculations. Five structures show significant populations at higher temperatures: C2v > Cs > C2 > C3v > Cs. The computed relative stabilities agree well with available observations.

Journal Article↗
PubMed2004

Lanthanum endohedral metallofulleropyrrolidines: synthesis, isolation, and EPR characterization.

Lanthanum endohedral metallofulleropyrrolidines have been synthesized for the first time through addition of an azomethine ylide to La@C(82)-A in toluene. It was found that the addition reaction is very efficient and, to some extent, regioselective. Two major endohedral metallofulleropyrrolidines, a monoadduct and a bisadduct of La@C(82)-A with abundance ratio of approximately 1:0.4, have been isolated by HPLC chromatography and characterized by mass spectrometry, UV/Vis-NIR absorption, and EPR spectroscopy. The electronic structure of La@C(82)-A has been modified slightly upon monoaddition and significantly upon bisaddition of the pyrrolidines.

Journal Article↗
PubMed2004

Uncoupling of flow and metabolism induced by sodium nitroprusside in rat cerebral cortex.

The effects of sodium nitroprusside (SNP) on cerebral blood flow and glucose metabolism were investigated by the microinfusion of SNP into rat cerebral cortex. A significant enhancement in glucose metabolism, as measured using [14C]deoxyglucose (DG), was observed throughout widespread areas of the cerebral cortex within 1 h of microinjection of 50 nmol/microl SNP. Using a kinetic analysis, the increase in glucose metabolism was found to be due to an increase in the phosphorylation of [14C]DG in the brain. On the other hand, regional cerebral blood flow, as measured using [14C]iodoantypirine, was not significantly altered by the SNP infusion. No significant cell death was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining 1 h after the SNP infusion. The uncoupling of flow and metabolism was almost completely prevented by pretreatment with an NMDA antagonist, MK-801. However, pretreatment with MK-801 did not prevent the SNP-induced neural cell death detected 6 h after the SNP infusion. These results suggest that the SNP-induced uncoupling of flow and metabolism was not directly related to neural cell death in the cerebral cortex.

Animals↗
PubMed2004

Cribriform-morular variant of papillary thyroid carcinoma: clue to early detection of familial adenomatous polyposis-associated colon cancer.

The cribriform-morular variant (CMV) of papillary thyroid carcinoma (PTC) is a rare histologic subtype of PTC that shows a combination of growth patterns including cribriform and spindle cell areas. The thyroid cancer with this unique histology was originally reported in patients with familial adenomatous polyposis (FAP), although it was later found in patients without polyposis as well. Because of its rarity, its clinical features are not clear. We reviewed seven patients with CMV-PTC who were found among 4194 patients with PTC in our pathology files between June 1991 and March 2003. The prevalence of CMV was 0.16% among all PTCs. We invited these patients to our hospital so we could obtain a detailed family history and recommend colonoscopic examination and germline APC gene analysis. Two patients without subjective symptoms had polyposis of the colon and colon cancers. Germline APC gene mutations were found in both patients. The father of a patient who refused the invitation was revealed to have undergone surgery for colon polyposis. In the remaining four patients, neither polyposis nor APC gene mutation was found. Common clinical features included a young age (mean 25 years), predominance of females, circumscribed tumors, negative node metastasis, and no recurrence of the thyroid cancer after surgery. Two of the three patients with colon polyposis had bilateral multiple thyroid tumors, whereas the remaining four (without polyposis) had a solitary tumor. The histopathology of CMV in patients with PTC should arouse a suspicion of FAP, especially if there are multiple tumors. This finding can lead to early detection of colon cancer.

Adenomatous Polyposis Coli↗
PubMed2004

Papillary microcarcinoma of the thyroid: how should it be treated?

We previously demonstrated that (1) most papillary microcarcinomas can be followed without surgical treatment and (2) when surgery is performed, patients with lateral lymph node metastasis detected on preoperative ultrasonography (US) are more likely to develop recurrence. In this study, we further investigated the application of these strategies. To date, we have observed 211 patients (average follow-up 47.9 months). In more than 70% of these patients the tumor size did not increase during the follow-up period. There were no clinicopathologic features linked to tumor enlargement except in tumors > or = 7 mm, which tended to enlarge in patients followed for 4 years. To evaluate not only whether observation can continue but also how to dissect the lymph nodes optimally at surgery, US diagnosis for lateral node metastasis is essential because the presence of US-diagnosed lateral metastasis is an even stronger predictive marker for recurrence than the presence of pathologically confirmed node metastasis. The positive predictive value (PPV) was 80.6% for US but reached 100% if fine-needle aspiration biopsy (FNAB) of nodes or FNAB-thyroglobulin measurement is added. Furthermore, carcinomas occupying the upper region of the thyroid more frequently showed US-diagnosed and pathologically confirmed lateral metastasis, and those measuring > or = 7 mm were more likely to show pathologically confirmed lateral metastasis. These findings suggest that, for papillary microcarcinoma: (1) US-diagnosed lateral metastasis is a strong marker predicting a worse relapse-free survival; (2) FNAB of nodes and FNAB-thyroglobulin measurement are useful tools for evaluating lymph node metastasis; and (3) careful US evaluation for lateral metastasis is necessary in patients with a tumor measuring > or = 7 mm or that is located in the upper region of the thyroid both during observation and preoperatively.

Adult↗
PubMed2004

Prognosis after reoperation for local recurrence of papillary thyroid carcinoma.

PURPOSE: To investigate the factors associated with a favorable prognosis after reoperation for local recurrent papillary thyroid carcinoma (PTC), we reviewed 45 patients who underwent surgery for first local recurrence of PTC. METHODS: We divided the patients into two groups. Group A (n = 28) had no second recurrence, and group B (n = 17) had second local recurrence after surgery for recurrence. RESULTS: The mean follow-up period after reoperation was 56.9 months. The mean age at the time of reoperation in group A was significantly lower than that in group B, at 48.1 years versus 62.3 years, respectively (P = 0.0007). The mean age at the time of the initial operation in group A was also significantly lower than that in group B, at 40.1 years versus 55.1 years, respectively (P = 0.0006). Patients with recurrent tumors only outside the area dissected at the initial operation (n = 27) had a better outcome than those with recurrence within the dissected area (n = 18; P = 0.0127). Patients who underwent systematic partial or modified neck dissection (n = 36) had a better outcome than those who underwent only simple local resection (n = 9; P = 0.0169). CONCLUSION: For local recurrent PTC, systematic neck dissection is recommended over local resection of recurrent tumors.

Adult↗
PubMed2004

Analysis of approach to therapy for chronic liver disease in an HCV hyperendemic area of Japan.

In 1990, we conducted an epidemiological study of 509 residents in a hepatitis C virus (HCV) hyperendemic area in Japan. The purpose of the present study was to examine the approach to therapy for liver diseases accompanied by HCV and hepatitis B virus (HBV) infections among the surviving residents in the town after 12 years. Fifty-three with HCV or HBV infections among 385 people who resided in the town were clearly analyzed in 2002. The number of persons diagnosed with the liver diseases was as follows: HCV-related asymptomatic healthy carrier (1), past history of HCV infection (15), chronic hepatitis C (22), HCV-related liver cirrhosis (6), HCV-related hepatocellular carcinoma (HCC) (5), and HBV-related asymptomatic healthy carrier (4). HCC was detected in residents who did not have periodic regular hospital checkups. Only 19% of the 53 inhabitants consulted liver medical specialists, and 75% (3/4) who received interferon therapy received treatment from a liver medical specialist. It is necessary to provide continuous medical treatment to HCV carriers, minimizing difference in treatment quality in different medical institution. An efficient HCV medical checkup and a program of subsequence health management are important problems to be solved for improved health care.

Journal Article↗
PubMed2004

A technique for making a diagnostic and surgical template.

Implant-supported restorations can restore function and esthetics provided that the implants are placed in the predetermined location and properly angulated. This article describes the fabrication of a diagnostic template incorporating a silicone radiopaque marker as a guide for achieving 3-dimensional evaluation of bone without artifacts using computed tomography. The diagnostic template may be easily transformed into a surgical template by removing the silicone marker.

Dental Implantation, Endosseous↗
PubMed2004

Comparative study of intra-articular irrigation and corticosteroid injection versus closed reduction with intermaxillary fixation for the management of mandibular condyle fractures.

OBJECTIVE: To evaluate the clinical outcome of a modified conservative treatment protocol involving intra-articular irrigation and corticosteroid injection into the superior joint compartment (SJC) of patients with fresh mandibular condyle fractures. Study design A total of 26 consecutive unilateral fresh condylar fractures in 26 patients were divided into the intra-articular irrigation (IR) group (14 patients, 14 joints) and the conventional conservative treatment (CC) group (12 patients, 12 joints). In the IR group, the SJCs of the fractured joints were irrigated with saline solution and injected dexamethazone sodium, followed by conventional rehabilitation. In the CC group, patients were treated by closed reduction with intermaxillary fixation (IMF) for 2 weeks, followed by conventional rehabilitation. Clinical outcome at 1 month, 3 months, 6 months, and 1 year after injury was determined by clinical examination of jaw motion, joint pain, and occlusal changes. The posttreatment results were compared with the pretreatment baseline data. Between-group differences in clinical parameters were analyzed. RESULTS: There were significant between-group differences in the range of mandibular motion at 1 month and 3 months after injury (1 month, P=.0022; 3 months, P=.0022). In the IR group, joint pain was well relieved from the early stage of treatment. Occlusal changes were found in 1 patient in the IR group and 4 patients in the CC group at 1 year after injury. CONCLUSIONS: The modified treatment protocol involving intra-articular irrigation and corticosteroid injection into the SJC is a more effective and quick-acting modality than conventional closed reduction with IMF for functional recovery and control of clinical symptoms of patients with unilateral fresh condylar fractures.

Adult↗
PubMed2004

Maspin expression is directly associated with biological aggressiveness of thyroid carcinoma.

Maspin belongs to the serpin superfamily and has been identified as a tumor suppressor because it inhibits cell motility, invasion, and angiogenesis. However, its physiological activity in carcinoma tissues seems to differ according to the origin of the carcinoma. In this study, we investigated maspin expression in thyroid neoplasms originating in follicular cells by means of immunohistochemistry. Neither normal follicular cells nor stromal cells expressed maspin. Follicular adenomas were all negative for maspin, but 12.5% of follicular carcinomas and 30.5% of papillary carcinomas were positive for it. However, the staining pattern was only focal in all positive specimens except for one and maspin-expressing cells were present mainly at the edge of carcinoma nests. Widely invasive follicular carcinomas tended to be more frequently positive for maspin than minimally invasive ones. In papillary carcinoma, maspin expression was directly linked to stage, tumor size, and extrathyroidal invasion. Papillary and follicular carcinomas involving lesions with solid, trabecular, or scirrhous growth patterns (poorly differentiated carcinoma as designated by Sakamoto et al.) expressed maspin in significantly higher incidence than those with pure papillary or follicular patterns. Furthermore, 48.2% of anaplastic (undifferentiated) carcinomas diffusely expressed maspin, and the rest were completely negative. These findings indicate that, in contrast to other carcinomas, maspin expression is directly associated with the biological aggressiveness of thyroid carcinoma. Further studies regarding the function of maspin in this carcinoma are required.

Cysteine Proteinase Inhibitors↗
PubMed2004

Pharmacogenetic roles of CYP2C19 and CYP2B6 in the metabolism of R- and S-mephobarbital in humans.

OBJECTIVES AND METHODS: We assessed the relationship between the metabolism of R- and S-mephobarbital (MPB) and genetic polymorphisms of cytochrome P450 (CYP) 2C19 and CYP2B6. Nine homozygous extensive metabolizers (homo-EMs, 2C19*1/2C19*1) of CYP2C19, ten heterozygous EMs (hetero-EMs, 2C19*1/2C19*2, 2C19*1/2C19*3) and eleven poor metabolizers (PMs, 2C19*2/2C19*2, 2C19*3/2C19*3, 2C19*2/2C19*3) recruited from a Japanese population, received an oral 200 mg-dose of racemic MPB. Blood and urine samples were collected, and R-MPB, S-MPB and the metabolites, phenobarbital (PB) and 4'-hydroxy-MPB, were measured. Each subject was also genotyped for CYP2B6 gene. RESULTS: The mean area under the plasma concentration-time curve (AUC) of R-MPB was 92-fold greater in PMs than in homo-EMs. R/S ratios for AUC of MPB were much higher in PMs than in EMs (homo- and hetero-). The cumulative urinary excretion of 4'-hydroxy-MPB up to 24 h postdose was 21-fold less in PMs than in homo-EMs. The metabolic ratio of AUCPB/(AUCS-MPB + AUCR-MPB) was higher in PMs than in EMs (homo- and hetero-). In addition, this metabolic ratio was lower in the carriers of CYP2B6*6 compared with that in its non-carriers. CONCLUSIONS: Our results indicate that the 4'-hydroxylation of R-MPB is mediated via CYP2C19 and that the rapid 4'-hydroxylation of R-MPB results in a marked difference in the pharmacokinetic profiles between R-MPB and S-MPB in the different CYP2C19 genotypic individuals. In addition, a minor fraction of the interindividual variability in PB formation from MPB may be explainable by the CYP2B6*6 allele.

Adult↗
PubMed2004

Catalytic roles of CYP2C9 and its variants (CYP2C9*2 and CYP2C9*3) in lornoxicam 5'-hydroxylation.

The effects of allelic variants of CYP2C9 (CYP2C9*2 and CYP2C9*3) on lornoxicam 5'-hydroxylation were studied using the corresponding variant protein expressed in baculovirus-infected insect cells and human liver microsomes of known genotypes of CYP2C9. The results of the baculovirus expression system showed that CYP2C9.3 gives higher K(m) and lower V(max) values for lornoxicam 5'-hydroxylation than does CYP2C9.1. In contrast, K(m) and V(max) values of CYP2C9.1 and CYP2C9.2 for the reaction were comparable. Lornoxicam 5'-hydroxylation was also determined in liver microsomes of 12 humans genotyped for the CYP2C9 gene (*1/*1, n = 7; *1/*2, n = 2; *1/*3, n = 2; *3/*3, n = 1). A sample genotyped as *3/*3 exhibited 8- to 50-fold lower intrinsic clearance for lornoxicam 5'-hydroxylation than did samples genotyped as *1/*1. However, the values for intrinsic clearance for *1/*3 were within the range of values exhibited by samples of *1/*1. In addition, no appreciable differences were observed in kinetic parameters for lornoxicam 5'-hydroxylation between *1/*1 and *1/*2. In conclusion, this study showed that lornoxicam 5'-hydroxylation via CYP2C9 was markedly decreased by the substitution of Ile359Leu (CYP2C9.3), whereas the effect of the substitution of Arg144Cys (CYP2C9.2) was nonexistent or negligible. Additional in vivo studies are required to confirm that individuals with homologous CYP2C9*3 allele exhibit impaired lornoxicam clearance.

Alleles↗
PubMed2004

Key structural features of ligands for activation of human pregnane X receptor.

The ligand-binding domain of human pregnane X receptor (hPXR) is highly hydrophobic and flexible, allowing promiscuity in accepting structurally diverse ligands. However, little information is available regarding the critical substituents of compounds involved in the activation of hPXR. The aim of this study was to determine the structure-activity relationships for hPXR-mediated transactivation by barbiturates, hydantoins, and macrolide antibiotics. Most of the barbiturates studied (mephobarbital, pentobarbital, phenobarbital, etc.) activated hPXR. However, barbital, which has a low hydrophobic moiety at the 5-position, and primidone, which has no carbonyl moiety at the 2-position, did not activate hPXR. Therefore, a hydrophobic moiety at the 5-position and a hydrogen-bond acceptor being sufficiently separated from the phenyl-ring are responsible for activation of hPXR by barbiturates. In the case of hydantoins, only mephenytoin and ethotoin, which have an alkylchain at the R1-position, strongly activated hPXR at 300 microM. Phenytoin and 5-(4-methylphenyl)-5-phenylhydantoin, which contain a phenyl or methylphenyl group at both R2- and R3-positions, also activated hPXR, whereas 5-(4-hydroxyphenyl)-5-phenylhydantoin did not activate the receptor. These results suggest that the presence of an alkyl-chain at the R1-position and the presence of bulky and hydrophobic moieties at both R2- and R3-positions are important factors for activation of hPXR by hydantoins. In the case of macrolide antibiotics, troleandomycin, but not oleandomycin, showed significant activation of hPXR. Therefore, triacetate esterification of oleandomycin might increase the hydrophobicity and enhance the activation of hPXR. These findings suggest that hydrophobicity of the ligand and adequate distance between the hydrogen-bond acceptor and the hydrophobic group are important for hPXR activation.

Anti-Bacterial Agents↗
PubMed2004

S100A4 expression is an early event of papillary carcinoma of the thyroid.

OBJECTIVES: S100A4 is a calcium-binding protein related to the metastatic potential of carcinoma. In order to elucidate its contribution to the progression of thyroid carcinoma, we investigated S100A4 expression in various thyroid neoplasms. METHODS: We immunohistochemically examined S100A4 expression in 195 cases of thyroid neoplasms. RESULTS: Although S100A4 was absent in normal follicular cells and follicular adenoma, S100A4 was positive in all 115 cases of papillary carcinoma examined, including 58 microcarcinomas. However, a significant relationship could not be established between S100A4 expression and clinicopathological features of papillary carcinoma. In follicular carcinoma, the widely invasive type expressed S100A4 more frequently than the minimally invasive type (p = 0.0028). In anaplastic carcinoma, S100A4 was expressed in 61.9% of cases, but the incidence was significantly lower (p < 0.0001) than that in papillary carcinoma. CONCLUSIONS: These findings suggest that (1) S100A4 plays a constitutive role in papillary carcinoma and (2) S100A4 may be a useful marker for early the detection of this carcinoma.

Adenocarcinoma, Follicular↗
PubMed2004

A novel single nucleotide polymorphism (SNP) of the CYP2C19 gene in a Japanese subject with lowered capacity of mephobarbital 4'-hydroxylation.

We sequenced all nine exons and exon-intron junctions of the cytochrome P450 2C19 (CYP2C19) gene from a Japanese subject with a lowered capacity of CYP2C19-mediated 4'-hydroxylation after an oral administration of mephobarbital. We found a novel single nucleotide polymorphism (SNP) of CYP2C19 gene as follows: SNP, 040110MoritaJ001; GENENAME: CYP2C19; ACCESSION NUMBER: NT_030059.8; LENGTH; 25 bases; 5'-GAGGGCCTGGCCC/TGCATGGAGCTGT-3'. The SNP (168946C>T) induced an amino acid alteration (Arg442Cys) located in exon 9 close to the heme-binding region of CYP2C19, which may result in the decrease in the catalytic properties of CYP2C19. A new allele having this SNP was designated as CYP2C19*16.

Amino Acid Sequence↗