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Biomedical subjects

K Tokuda

Publications and source records attributed to K Tokuda.

At least 19 recordsLinked to original sources
PubMed2001

Invariant chain expression in gastric cancer.

Invariant chain (Ii) is a chaperone molecule that inhibits the binding of endogenous antigens to HLA class II. The tumor cell with overexpressed Ii chain is thought to escape attacking cytotoxic lymphocytes by suppressing the host immune. However, the relationship between Ii expression by the tumor and clinicopathological factors in gastric cancer remains unclear. We studied 126 patients with gastric cancer who had undergone curative gastrectomy at Kagoshima University Hospital between 1988 and 1997. In order to detect Ii and HLA-DR expression by tumor cells, immunohistochemical staining with anti-CD74 and anti-HLA-DR antibodies were performed by avidin-biotin peroxidase complex method. The 126 patients studied were divided into two groups based on Ii expression. Ii and HLA-DR were expressed both on the surface and in the cytoplasm of tumor cells and tumor infiltrating lymphocytes. A total of 48 patients were identified as Ii positive, while the remaining 78 patients were Ii negative. Ii expression negatively correlated with the depth of invasion of the tumor as well as the patients' clinical stage. Ii expression was negatively correlated with HLA-DR expression. Patients with Ii negative expression had significantly better surgical outcomes than those with Ii positive expression (P<0.05). Ii expression in gastric cancer affected surgical outcome and Ii expression was negatively correlated with depth of invasion and HLA-DR expression. Ii expression in gastric cancer may be a prognostic factor related to suppressive effects on host immune responses to tumor cells.

Adult↗
PubMed2001

Simultaneous electroanalysis of peroxyacetic acid and hydrogen peroxide.

The electrochemical behavior of peroxyacetic acid (PAA) in the presence of hydrogen peroxide (H2O2) has been investigated using cyclic voltammetry and hydrodynamic techniques [rotating disk electrode (RDE) voltammetry and rotating ring-disk electrode (RRDE) voltammetry]. The results have been analyzed aiming at simultaneous electroanalysis of both species. Glassy carbon and gold electrodes were used for this investigation. It was found that the reduction of PAA, as well as H2O2, is highly sensitive to the electrode material; for example, at 100 mV s-1, the reduction peak potentials of PAA were 0.2 and -1.1 V at gold and glassy carbon electrodes, respectively. The well-separated steady-state limiting currents were obtained using a gold electrode for the reduction of both PAA and H2O2 and also a well-defined one for the oxidation of H2O2. On the basis of the RDE experiments, good calibration curves were obtained for both species over a wide range of their concentrations, for PAA and H2O2 in the range of 0.36 to 110 and 0.11 to 34 mM, respectively. The simultaneous and selective electroanalysis of PAA and H2O2 in their coexistence is demonstrated for the first time.

Journal Article↗
PubMed2001

Electroanalytical applications of cationic self-assembled monolayers: square-wave voltammetric determination of dopamine and ascorbate.

Gold electrodes modified with cationic self-assembled monolayers (SAMs) of 2,2'-dithiobisethaneamine (CYST) and 6,6'-dithiobishexaneamine (DTH) were used for the simultaneous determination of dopamine (DA) and ascorbate (AA). The cationic SAM modified electrodes have several advantages over the bare electrode for the oxidation of AA. A very large (approximately 450 mV) decrease in the overpotential for the oxidation of AA when compared with the bare electrode has been observed at the cationic monolayer-modified electrode. The electrostatic interaction of negatively charged AA with the monolayer shift the oxidation peak potential of AA to less positive potential and enhances the peak current. On the other hand, the positively charged DA is repelled from the monolayer and the oxidation potential shifts to more positive potential when compared to the bare electrode. The electrochemical oxidation of AA at the mixed monolayer of CYST and diethyl disulfide (DEDS) supports the influence of cationic terminal group of the monolayer on the oxidation of AA. Since the oxidation of AA occurs well before the oxidation potential of DA is reached, the homogeneous catalytic oxidation of AA by the oxidized DA has been advantageously eliminated at the monolayer-modified electrode. The cationic self-assembled monolayers successfully detect DA in the presence of high concentration of AA. The sensitivity of the electrode modified with CYST monolayer was found to be 0.036 and 0.021 microA/microM towards AA and DA, respectively.

Ascorbic Acid↗
PubMed2001

Protective effects of fluvastatin against reactive oxygen species induced DNA damage and mutagenesis.

Oxidative stress may be an important factor in the development of diabetic complications. Advanced glycation end-products have drown attention as potential sources of oxidative stress in diabetes. We investigated the protective effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on oxidative DNA damage from reactive oxygen species or advanced glycation end-products in vitro, as well as effects of main fluvastatin metabolites and other inhibitors of the same enzyme, pravastatin and simvastatin. Protective effects were assessed in terms of the DNA breakage rate in a single-stranded phage DNA system in vitro. DNA was exposed to either reactive oxygen species or advanced glycation end-products. Fluvastatin and its metabolites showed a strong protective effect comparable to those seen with thiourea and mannitol, though pravastatin and simvastatin did not exert clear protective effects. Furthermore, fluvastatin reduced the mutagenesis by reactive oxygen species or advanced glycation end-products in Salmonella typhimurium test strains. Both pravastatin and simvastatin still lacked protective activity. Fluvastatin and its metabolites protect against oxidative DNA damage and may reduce risk of consequent diabetic complications.

Bacteriophages↗
PubMed2001

Surgical maneuvers enhance molecular detection of circulating tumor cells during gastric cancer surgery.

OBJECTIVE: To evaluate the relation between the presence of cancer cells in blood according to the time course during a surgical procedure and liver metastases in patients with gastric cancer. SUMMARY BACKGROUND DATA: Several studies have reported on the detection of circulating cancer cells in blood by reverse transcriptase-polymerase chain reaction (RT-PCR). However, few reports have examined the relation between molecular detection of circulating cancer cells according to the time course during a surgical procedure and blood-borne metastases. METHODS: Blood samples from 57 patients with gastric cancer were obtained from the portal vein, peripheral artery, and superior vena cava before and after tumor dissection. After total RNA was extracted from each blood sample, carcinoembryonic antigen (CEA)-specific RT-PCR was performed. RESULTS: CEA-mRNA was detected in the blood of 21 (36.8%) of the 57 patients. CEA-mRNA was not detected in the blood obtained from 15 healthy volunteers and 15 patients with benign disease. The positive rate increased in proportion to the depth of tumor. The incidence of positive CEA-mRNA did not differ among the various sites of blood sampling. The appearance of circulating cancer cells was related to the surgical maneuver. A significant relation was found between the detection of CEA-mRNA and blood-borne metastases. CONCLUSIONS: A high incidence of positive CEA-mRNA was found in the blood during gastric cancer surgery. Surgical maneuvers are a possible cause of hematogenous metastasis. The authors found that patients with positive CEA-mRNA had a high risk of blood-borne metastasis even after curative resection.

Aged↗
PubMed2001

Clinical importance of preoperative carcinoembryonic antigen and carbohydrate antigen 19-9 levels in gastric cancer.

Although serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are commonly measured before surgery for gastric carcinoma, this clinical significance is not fully understood. We evaluated a total of 549 patients with gastric cancer who underwent gastrectomy. Levels of CEA and CA19-9 were measured preoperatively in all patients. We retrospectively analyzed correlations between CEA or CA19-9 and clinicopathologic features, and estimated the prognostic utility of the tumor markers by analyzing clinicopathologic characteristics of the carcinoma as a function of seropositivity or negativity of the antigens in combination or by raising the levels. The positivity rates of CEA (> or =5 ng/mL) and CA19-9 (> or =37 U/mL) were 19.5% and 18%, respectively. Serum CEA and CA19-9 positivity significantly correlated with depth of invasion, hepatic metastasis, and curativity. Forty-nine patients positive for both CEA and CA19-9 had significantly higher frequencies of lymph node metastasis, deeper invasion by the tumor, lower rates of curative resection (p < 0.01), and higher rates of hepatic metastasis (p < 0.05) than 377 patients with normal levels of CEA and CA19-9. Surgical outcomes of patients who were CEA- and CA19-9-positive were poorer than those of patients with normal CEA and CA19-9 levels (p < 0.01). Significant correlation was found between serum CEA and CA19-9 level (p < 0.001, r = 0.24). Doubling the threshold level of serum positivity to 10 ng/mL (CEA) and 74 U/mL (CA19-9) improved the prognostic value of these factors. However, multivariate analysis using Cox's hazards model revealed that only CEA positivity using the doubled threshold value (10 ng/mL) (p = 0.04, hazard ratio = 1.7), nodal involvement (p = 0.01, hazard ratio = 1.9), and depth of invasion (p = 0.02 hazard ratio = 1.5) significantly predicted prognosis. Carcinoembryonic antigen positivity using the doubled threshold level (10 ng/mL) was an important prognostic factor in patients with gastric cancer.

Aged↗
PubMed2001

[Surgery for acoustic neurinoma treated by gamma-knife radiosurgery: a case report].

A 52-year-old woman had a history of left hearing loss for 5 years. An acoustic neurinoma with 3.2 cm in diameter was diagnosed and treated with gamma-knife radiosurgery (19 Gy of marginal dose) 1 year and 4 months ago. She developed headache, nausea, and visual disturbance 1 month prior to admission. Slight left facial palsy appeared after radiosurgery. Magnetic resonance imaging demonstrated the tumor with central necrosis in the left cerebellopontine angle cistern, increasing in size to 3.5 cm in diameter, and hydrocephalus. Tumor removal was performed incompletely, because of the fibrous appearance of the tumor and severe adherence with the surrounding cerebellar tissue. Facial palsy did not worsen after surgery. Since the hydrocephalus was not resolved, a right ventriculo-peritoneal shunt was inserted. The clinical course in this case suggests that tumor removal followed by radiosurgery was an approximately effective treatment for large acoustic neurinoma.

Female↗
PubMed2000

Clinical impact of intratumoral natural killer cell and dendritic cell infiltration in gastric cancer.

Intratumoral natural killer cells (NKC) and dendritic cells (DC) may affect the clinical features of various gastrointestinal cancers. However, the relationship between intratumoral NKC and DC remains unclear. We examined 169 patients with gastric cancer who underwent gastrectomy at Kagoshima University Hospital. Immunohistochemical staining of CD57 and S-100-protein was performed to evaluate NKC and DC infiltration, respectively. A total of 25 areas containing pericancerous tissue were selected for determining the number of NKC and DC under high power microscopy (x400). Patients were classified into two groups according to NKC and DC population. Intratumoral lymphocytic infiltration was also calculated in 15 areas with a high power (x400) objective. The degree of NKC and DC infiltration was gradually decreased according to the progression of nodal involvement. Patients with many NKC infiltration had a lower positivity of lymph node metastasis and lymphatic invasion than patients with little NKC infiltration. DC infiltration was also negatively correlated with depth of invasion, lymph node metastasis and curativity. DC infiltration was positively correlated with lymphocytic infiltration (P=0.01. r=0.6). The 5-year survival rates of patients with many NKC infiltration and patients with DC many infiltration were 75 and 78%, respectively, both of which were significantly better than that of patients with little NKC and DC infiltration (P<0.05). NKC may be activated without DC or intratumoral lymphocytes. Intratumoral NKC may act as an independent immunologic effector against tumor cells, unlike DC.

CD57 Antigens↗
PubMed2000

Prognostic value of intratumoral natural killer cells in gastric carcinoma.

BACKGROUND: Natural killer (NK) cells are a group of effector cells that act nonspecifically against tumor cells. The correlation between intratumoral NK cell infiltration and clinicopathologic features remains unclear. METHODS: The authors selected 146 patients with gastric carcinoma who underwent gastrectomy at Kagoshima University Hospital between 1985-1995. Immunohistochemical staining with the CD57 antibody was performed for the evaluation of NK cell infiltration. A total of 25 areas containing CD57 positive cells were selected and the number of NK cells were counted (magnification, x200). The patients were divided into 2 groups: patients with a high level of NK infiltration (n = 39) (>25 NK cells/25 high-power fields [HPF]) and patients with a low level of NK infiltration (n = 107) (<25 NK cells/25 HPF). Intratumoral lymphocytic infiltration also was counted in 25 areas at a magnification of x200. Patients were classified into a high infiltrating lymphocyte (IL) group (n = 69) (>150 cells/HPF) and a low IL group (n = 77) (<150 cells/HPF). The Kaplan-Meier curve was used to analyze surgical outcome. Multivariate analyses were performed to evaluate prognostic factors. RESULTS: Patients with a high level of NK infiltration had a higher rate of early gastric carcinoma, fewer metastases to the lymph nodes (P < 0.01), and less lymphatic invasion (P < 0.05) than patients with a low level of NK infiltration. NK cell infiltration also was found to correlate with depth of invasion, clinical stage, and venous invasion. There was no correlation between NK cells and lymphocytic infiltration (P = 0.07; correlation coefficient = 0.15). The 5-year survival rate of patients with a high rate of NK infiltration was 78%, which was significantly better than that of patients with a low level of NK infiltration (P < 0.01). Multivariate analysis did not show NK cell infiltration to be a significant prognostic factor. Combination analysis of the number of NK cells and lymphocytic infiltration was shown to be an independent prognostic factor (P = 0.02; hazard ratio = 1.32). CONCLUSIONS: Patients with a high level of NK infiltration were found to have a better prognosis than those with a low level of NK infiltration. Combination analysis with lymphocytic infiltration may provide useful information regarding the immunologic condition of patients with gastric carcinoma.

Adult↗
PubMed2000

Synthesis, characterization, and chiral properties of CoIII2AgI3 pentanuclear, CoIII4ZnII4 octanuclear, and CoIII mononuclear complexes with aza-capped hexadentate-N3S3 thiolate ligands: crystal structures of.

The reaction of an S-bridged Co2(III)Ag3(I) pentanuclear complex, [Ag3[Co(aet)3]2][BF4]3 (aet = NH2CH2CH2S-), with paraformaldehyde in basic acetonitrile, followed by adding aqueous ammonia, produced an aza-capped Co2(III)-Ag3(I) complex, [Ag3[Co(L)]2]3+ ([1]3+) (L = N(CH2NHCH2CH2S-)3). The crystal structure of [1]3+ was determined by X-ray crystallography. [1][PF6]3 x H2O, empirical formula C18H44Ag3Co2F18N8OP3S6, crystallizes in the tetragonal space group 142m with a = 13.012(1) A, c = 24.707(2) A, and Z = 4. In [1]3+ the two aza-capped [Co(L)] units are linked by three Ag(I) atoms, such that the two Co(III) atoms are encapsulated in a macrobicyclic metallocage, [Ag3(I)(L)2]3-. [1]3+ was converted to an aza-capped Co4(III)Zn4(II) octanuclear complex, [Zn4O[Co(L)]4]6+ ([2]6+), by reaction with I- in the presence of Zn2+ and ZnO in water. The crystal structure of [2]6+ was also determined by X-ray crystallography. [2][PF6]6 x 8H2O, empirical formula C36H100Co4F36N16O9P6S12Zn4, crystallizes in the monoclinic space group P2(1/n) with a = 14.33(7) A, b = 25.67(10) A, c = 24.83(6) A, beta = 101.3(3) degrees , and Z = 4. In [2]6+ each of four [Co(L)] units is bound to each trigonal Zn3(II) face of the tetrahedral [Zn4(II)O]6+ core, such that each Co(III) atom is encapsulated in a macrobicyclic [Zn4(II)O(L)] fragment. Treatment of [2]6+ with a basic aqueous solution resulted in a cleavage of the Zn-S bonds to produce an aza-capped Co(III) mononuclear complex, [Co(L)] ([3]), from which [1]3+ is readily reproduced by the reaction with Ag+ in water. All the reactions were found to proceed with retention of the absolute configuration (delta or lambda) of the Co(III) chiral centers; deltadelta-[1]3+, deltadeltadeltadelta-[2]6+, and A-[3] were derived from deltadelta-[Ag3[Co(aet)3]2]3+. The contributions to circular dichroism (CD) from the triple helicity in [1]3+, besides from the asymmetric N and S donor atoms and the Co(III) chiral centers in [1]3+ and [2]6+, were estimated by comparing the CD spectra of deltadelta-[1]3+, deltadeltadeltadelta-[2]6+, and delta-[3].

Journal Article↗
PubMed2000

Acquired hypothyroidism in a very young infant with Omenn's syndrome.

A very young male infant with Omenn's syndrome had acquired hypothyroidism that was most likely caused by autoimmune thyroiditis. The hypothyroidism appeared at 3 months of age. These 2 rare conditions have not previously been reported occurring together. This case suggests that autoimmune thyroiditis may be another abnormal finding in Omenn's syndrome.

Follow-Up Studies↗
PubMed2000

Improvement in corrected QT dispersion by physical training and percutaneous transluminal coronary angioplasty in patients with recent myocardial infarction.

The aim of the present study was to assess whether physical training and percutaneous transluminal coronary angioplasty (PTCA) improve the corrected QT (QTc) dispersion in patients with recent myocardial infarction (MI). Twenty-four patients with recent MI were allocated to one of 3 groups: training (n = 8), PTCA (n = 7) or controls (n = 9). Physical training as well as PTCA decreased QTc dispersion, whereas QTc dispersion increased in the control group. Changes in QTc dispersion after physical training or PTCA were inversely correlated with exercise-induced ST depression at the baseline test. These observations suggest that physical training, as well as PTCA, could improve QTc dispersion and electrical instability in patients with recent MI, possibly due to improvement of myocardial ischemia.

Aged↗
PubMed2000

[Changes in the antibacterial activity of chemotherapeutic agents (especially carbapenems) for 10 species of clinical isolates between 1994 and 1996. Surveillance group of the sensitivities of clinical isolates to antibacterial agents].

During October and December of each year of from 1994 to 1996, 3,849 strains of 10 species of bacteria were isolated from clinical materials in 21 institutions nationwide. The minimum inhibitory concentrations (MICs) for these bacteria of four carbapenems (imipenem [IPM], panipenem [PAPM], meropenem [MEPM], and biapenem [BIPM]) and other representative antibacterial agents were measured to investigate annual changes in antibacterial activity. Carbapenems showed potent activity against methicillin-sensitive S. aureus (MSSA), S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, S. marcescens, and the B. fragilis group, with the activity being stable. However, these drugs showed weak activity against methicillin-resistant S. aureus (MRSA) and P. aeruginosa. The antibacterial activity (MIC90) against the tested organisms generally remained stable. Particularly, there was annual improvement of the MIC90 values of IPM and BIPM for S. pneumoniae, as well as the values of IPM and PAPM for H. influenzae, and those of IPM, PAPM, and BIPM for S. marcescens. On the other hand, the activity of carbapenems (including IPM) against MRSA was not necessarily strong, but there was annual improvement of MIC90 values.

Bacteria↗
PubMed2000

Intranodal antitumor immunocyte infiltration in node-negative gastric cancers.

The status and role of immunocytes and dendritic cells in regional lymph nodes in patients with gastric cancer are examined in this study. Forty-nine patients with gastric cancer who underwent curative resection were enrolled in the present study. These patients had no lymph node metastases according to a histological examination. The infiltration of natural killer (NK) cells, dendritic cells, and MIB-1-positive immunocytes was investigated. Based on the Japanese Classification of Gastric Carcinoma, regional lymph nodes were divided into three compartments: (a) compartment 1 (lymph node station numbers 1-6); (b) compartment 2 (lymph node station numbers 7-12); and (c) compartment 3 (lymph node station numbers 14 and 16). Dendritic cells and MIB-1-positive immunocytes infiltrated compartment 1 lymph nodes in increased numbers compared with the lymph nodes of compartments 2 or 3 (P < 0.05). Conversely, intranodal NK cell infiltration did not differ significantly among the three compartments. The incidence of intranodal dendritic and MIB-1-positive cell infiltration in patients with submucosal gastric cancer was significantly higher than in patients with tumors that invaded beyond the muscularis propria. The decreased expression of these immunological markers correlated well with recurrent disease, regardless of tumor depth. The immunocyte level is higher in lymph nodes near the primary tumor (compartment 1) than in those that are distant from the tumor (compartments 2 and 3). This pertains to all three markers, i.e., NK, dendritic, and MIB-1-positive cells. Unlike dendritic and MIB-1-positive cells, intratumoral infiltration of NK cells did not correlate well with either lymph node compartment or the depth of tumor invasion. The degree of NK cell infiltration may be directly associated with antitumor effects, especially in compartment 1. A decrease in all three markers is associated with tumor recurrence.

Adult↗
PubMed1999

A complete deficiency of coagulation factor XIII A-subunit due to a novel compound heterozygote of Ser 413 Leu missense and an nt 389 (ins G) frameshift mutation.

Coagulation factor XIII consists of two A- and two B-subunits, and either gene mutation can cause a complete deficiency. In a newborn patient with persistent bleeding from the umbilical cord stump, the plasma A-subunit protein was not detectable. Direct PCR sequencing revealed an nt 389 (ins G) frameshift mutation in exon 4 resulting in a new stop codon and a Ser 413 Leu missense mutation in exon 10 in either allele. His mother and father were heterozygous for the nt 389 (ins G) and the Ser 413 Leu, respectively, with about 50% reduction of the plasma A-subunit proteins. In all family members examined only those with either mutation showed the reduced subunit A protein levels. Thus, this complete deficiency of factor XIII was due to a novel compound heterozygous mutation in the A-subunit gene.

DNA Transposable Elements↗
PubMed1999

[Survey of the sensitivities of clinical isolates to antibacterial agents (annual report)].

Research groups were formed in 21 institutions nationwide to investigate carbapenem resistance. The activities of various antibacterial agents, principally carbapenems, were tested against clinical isolates collected from these institutions. The broth microdilution method was used to determine the minimum inhibitory concentrations (MIC) of 17 antibacterial agents for 1,241 strains of 11 bacterial species isolated at all institutions between October and December 1996. The results were as follows: Carbapenems exhibited strong antibacterial activities against MSSA and Streptococcus pneumoniae and showed low activities against MRSA. Their activities against Enterococcus faecalis were comparable to that of ampicillin and piperacillin. The carbapenems showed high activities against Haemophilis influenzae, Escherichia coli, Klebsiella pneumoniae. Enterobacter cloacae. Serratia marcescens and Bacteroides fragilis group. Their activities were greater than that exhibited by other beta-lactam antibacterial agents, but some resistant strains of Serratia marcescens were detected. The antibacterial activity of carbapenems against Pseudomonas aeruginosa was comparable to that of CAZ, and there were some resistant strains.

Carbapenems↗