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Biomedical subjects

K Yamazaki

Publications and source records attributed to K Yamazaki.

At least 253 records · Page 14Linked to original sources

[Pharmacological study of weekly docetaxel in patients with metastatic breast cancer].

A pharmacological comparison of weekly administrations of docetaxel (TXT) and standard/conventional TXT was carried out among patients with metastatic breast cancer. Fifteen patients were enrolled in this study of weekly TXT (TXT: 40 mg/body/week x 3 with 1 week interruptions in 10 patients) and standard TXT (TXT: 60 mg/m2/3 weeks in 5 patients). The median dose intensity (DI) of weekly TXT (20.63 mg/m2/week) was similar to that of standard TXT, and the median relative dose intensity (RDI) of weekly TXT was 0.98. The median area under the plasma concentration-time curve (AUC) of weekly TXT (1.20 micrograms.h/ml) was smaller than that of standard TXT (1.87 micrograms.h/ml). Therefore, there were remarkable decreases in both median percent of decrease in neutrophil counts and grade 3, 4 neutropenia with weekly TXT. These pharmacological data show that weekly TXT is a well-tolerated and feasible schedule for the treatment of metastatic breast cancer.

Adult↗

[A case of AIDS-associated primary CNS lymphoma difficult to differentiate from toxoplasmic encephalitis by clinical symptoms, neuroimages, and therapeutic responses].

We reported a 24-year-old Thai woman who developed primary CNS lymphoma (PCNSL) associated with acquired immunodeficency syndrome. It was difficult to distinguish PCNSL from toxoplamic encephalitis in this case by clinical symptoms, findings of CT and MRI, and therapeutic responses for toxoplasmosis. It is important to make a definite diagnosis of PCNSL by brain biopsy to treat appropriately, because this disorder could be fatal if it is not treated by corticosteroid, radiation, or other proper methods.

Adult↗

[The efficacy and limitation of hepatic arterial infusion chemotherapy for colorectal liver metastases].

We investigated the efficacy and limitation of hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. In terms of prophylactic HAI following curative resection of liver, the 5-year disease-free survival of HAI group (12 g of 5-FU administered in 6 weeks) was 66.7%, whereas that of randomly selected control group was 20.0%. The difference was statistically significant (p = 0.045). Recurrent disease was confirmed in three cases of HAI group (one in liver) and in 8 patients of the control group (6 in liver). However, the overall survival was not significantly different between the groups. Thus, the short-term HAI of 5-FU is effective in decreasing the recurrence of disease. As for the treatment of unresectable liver metastases, some patients received HAI of 5-FU (1,000-1,500 mg/w) showed prolonged survival with partial remission of the disease. However, the 1-, 2-, and 3-year cumulative survival of HAI group (n = 27) was 69.3, 34.1 and 11.4%, respectively, against 61.3, 22.6 and 9.4%, respectively, in the transarterial embolization (TAE) group (n = 31). Therefore it is important to estimate the effect in the early phase of HAI, and aggressively continue the treatment in selected patients for whom it is suitable.

Administration, Oral↗

[Positron emission tomography for detection of lymph node metastases in lung cancer].

Although radiography, computed tomography (CT), and magnetic resonance imaging are still the methods of choice for the study of lung cancer, they have certain limitations in the evaluation of mediastinal lymph node metastases. Positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) has recently emerged as a practical and useful imaging modality in patients with lung cancer. We evaluated the usefulness of FDG-PET in the detection of mediastinal lymph node metastases and then compared the findings with the results of CT by region based on the histological diagnosis. For FDG-PET, the sensitivity, specificity and accuracy were 93%, 76%, and 98%, respectively, whereas, for CT, this was 65%, 87%, and 82%, which showed significant differences. FDG-PET is significantly more accurate than CT in lymph node staging of lung cancer, and also can improve the diagnostic accuracy in distant metastases.

Fluorodeoxyglucose F18↗

Single tottering mutations responsible for the neuropathic phenotype of the P-type calcium channel.

Recent genetic and molecular biological analyses have revealed many forms of inherited channelopathies. Homozygous ataxic mice, tottering (tg) and leaner (tgla) mice, have mutations in the P/Q-type Ca2+ channel alpha1A subunit gene. Although their clinical phenotypes, histological changes, and locations of gene mutations are known, it remains unclear what phenotypes the mutant Ca2+ channels manifest, or whether the altered channel properties are the primary consequence of the mutations. To address these questions, we have characterized the electrophysiological properties of Ca2+ channels in cerebellar Purkinje cells, where the P-type is the dominant Ca2+ channel, dissociated from the normal, tg, and tgla mice, and compared them with the properties of the wild-type and mutant alpha1A channels recombinantly expressed with the alpha2 and beta subunits in baby hamster kidney cells. The most striking feature of Ca2+ channel currents of mutant Purkinje cells was a marked reduction in current density, being reduced to approximately 60 and approximately 40% of control in tg and tgla mice, respectively, without changes of cell size. The Ca2+ channel currents in the tg Purkinje cells showed a relative increase in non-inactivating component in voltage-dependent inactivation. Besides the same change, those of the tgla mice showed a more distinct change in voltage dependence of activation and inactivation, being shifted in the depolarizing direction by approximately 10 mV, with a broader voltage dependence of inactivation. In the recombinant expression system, the tg channel with a missense mutation (P601L) and one form of the two possible tgla aberrant splicing products, tgla (short) channel, showed a significant reduction in current density, while the other form of the tgla channels, tgla (long), had a current density comparable to the normal control. On the other hand, the shift in voltage dependence of activation and inactivation was observed only for the tgla (long) channel. Comparison of properties of the native and recombinant mutant channels suggests that single tottering mutations are directly responsible for the neuropathic phenotypes of reduction in current density and deviations in gating behavior, which lead to neuronal death and cerebellar atrophy.

Animals↗

Differential regulation of mouse uncoupling proteins among brown adipose tissue, white adipose tissue, and skeletal muscle in chronic beta 3 adrenergic receptor agonist treatment.

Uncoupling proteins (UCPs) are inner mitochondrial membrane transporters that dissipate the proton gradient, releasing stored energy as heat, without coupling to other energy-consuming processes. Therefore, the UCPs are thought to be important determinants of the metabolic efficiency. To elucidate relationships between the UCPs expressions and insulin sensitivity improvement, we treated KK-Ay mice with beta 3 adrenergic receptor agonist for 21 days and examined the changes of the UCPs mRNA expressions in various tissues. Chronic treatment of a specific beta 3 adrenergic receptor agonist, CL316,243 (0.2 mg/kg body weight/day s.c.) markedly increased the expressions of uncoupling protein 1 (UCP1), uncoupling protein 2 (UCP2), and uncoupling protein 3 (UCP3) by 14-fold, 6-fold, and 16-fold, respectively, in the brown adipose tissue (BAT). The UCP1 and UCP3 mRNA expressions in the white adipose tissue (WAT) were also increased by 12-fold and 9-fold, respectively, but the UCP2 mRNA expression was not changed in this tissue. Interestingly, the UCP2 and UCP3 mRNA expressions were strikingly decreased in the skeletal muscle and heart. Particularly, the UCP3 mRNA expression level in the skeletal muscle was dropped to 10% of that of the saline-treated control mice, indicating that the UCPs mRNA expressions are regulated in tissue-specific ways. The concentrations of plasma insulin and circulating free fatty acid (FFA) were significantly decreased, suggesting that they correlate with the reductions of the UCP2 and UCP3 mRNA expressions in the skeletal muscle and heart. It has been thought that the UCP1 and UCP3 mRNA expressions in the BAT and WAT are mainly controlled by the hypothalamus via the sympathetic nervous system, while the levels of insulin, FFA or both may play important roles in the control of the UCP2 and UCP3 mRNA expressions in the skeletal muscle an heart.

Adipose Tissue↗

Intracellular accumulation of thallium as a marker of cisplatin cytotoxicity in nonsmall cell lung carcinoma: an application of inductively coupled plasma mass spectrometry.

BACKGROUND: Thallium-201 (201Tl) scintigraphy has been used to detect malignant pulmonary disease. The mechanism of Tl influx in tumor cells is believed to be similar to that of cisplatin (CDDP) mediated by sodium- and potassium-activated adenosine triphosphatase (Na-K ATPase), and the Na-K ATPase activity may determine the cellular CDDP accumulation and sensitivity to CDDP. The objective of this study was to determine the accumulation of CDDP and Tl in vitro by using inductively coupled plasma mass spectrometry (ICP-MS), a new analytic technique for detecting ultra trace elements, and to evaluate the correlations between cellular CDDP and Tl accumulation, between CDDP 50% inhibitory concentration (IC50) values and cellular CDDP accumulation, and between CDDP IC50 values and cellular Tl accumulation. METHODS: Eight nonsmall cell lung carcinoma (NSCLC) cell lines were used (five adenocarcinomas and three squamous cell carcinomas). The cell lines were exposed to CDDP or Tl for 1 hour, and the resulting cellular accumulation of platinum and Tl was determined by ICP-MS. CDDP IC50 values were determined by a soluble tetrazolium/formazan assay. RESULTS: The authors were able to measure cellular CDDP and Tl accumulation precisely, and heterogeneity in the cellular accumulation of CDDP and Tl existed among the NSCLC cell lines. A significant inverse correlation was observed between CDDP IC50 values and the cellular accumulation of both CDDP and Tl. CONCLUSIONS: ICP-MS is suitable for the determination of cellular CDDP and Tl accumulation in NSCLC cell lines. Cellular Tl accumulation determined by ICP-MS may reflect CDDP cytotoxicity rather than cellular CDDP accumulation.

Adenocarcinoma↗

Cloning of mouse uncoupling protein 3 cDNA and 5'-flanking region, and its genetic map.

Brown adipose tissue and skeletal muscle are important sites of non-shivering thermogenesis. It has been known that UCP1 and UCP2 function as the main effector of the thermogenesis: the former is expressed exclusively in brown adipose tissue, whereas the latter is distributed widely. Recently, the third UCP homologue was discovered in humans, which was designated as UCP3. We now report molecular cloning of full-length mouse UCP3 cDNA and its 5'-flanking genomic region. The mouse UCP3 cDNA sequence predicted a 308-amino acid protein, and the overall identity between the mouse and human UCP3 proteins was 85.6%. The mouse UCP3 amino acid sequence was 54.7% and 73.1% identical to the mouse UCP1 and UCP2, respectively. Expression of the mouse UCP3 was found to be abundant in skeletal muscle and somewhat less abundant in heart, but was minimally expressed in other critical organs. The sequences of 5'-flanking regions of the mouse UCP1 and UCP3 were very different, resulting in different distributions of putative transcriptional factor binding sites. The differences could reflect tissue-specific expression of the UCPs. The mouse Ucp3 gene was mapped near Ucp2 on chromosome 7, suggesting that the Ucp2 and Ucp3 are clustered genes. This region is boundary of synteny between human chromosome 11q13 and 11p15. As Solanes et al. reported that both human UCP2 and UCP3 genes are assigned to chromosome 11q13, the region where the mouse Ucp2 and Ucp3 are localized is syntenic to human chromosome 11q13.

Amino Acid Sequence↗

Solution structure of thermostable cytochrome c-552 from Hydrogenobacter thermophilus determined by 1H-NMR spectroscopy.

The solution structure of a thermostable cytochrome c-552 from a thermophilic hydrogen oxidizing bacterium Hydrogenobacter thermophilus was determined by proton nuclear magnetic resonance spectroscopy. Twenty structures were calculated by the X-PLOR program on the basis of 902 interproton distances, 21 hydrogen bonds, and 13 torsion angle constraints. The pairwise average root-mean-square deviation for the main chain heavy atoms was 0.91 +/- 0.11 A. The main chain folding of the cytochrome c-552 was almost the same as that of Pseudomonas aeruginosa cytochrome c-551 that has 59% sequence identity to the cytochrome c-552 but is less thermostable. We found several differences in local structures between the cytochromes c-552 and c-551. In the cytochrome c-552, aromatic-amino interactions were uniquely formed between Arg 35 and Tyr 32 and/or Tyr 41, the latter also having hydrophobic contacts with the side chains of Tyr 32, Ala 38, and Leu 42. Small hydrophobic cores were more tightly packed in the cytochrome c-552 because of the occupancies of Ala 5, Met 11, and Ile 76, each substituted by Phe 7, Val 13, and Val 78, respectively, in the cytochrome c-551. Some of these structural differences may contribute to the higher thermostability of the cytochrome c-552.

Amino Acid Sequence↗

Cloning of 5'-flanking region and a polymorphic CTT trinucleotide repeat within 5'-untranslated region of mouse R-type calcium channel alpha1-subunit (Cchra1) gene, and its genetic mapping.

The 5'-flanking region of the mouse R-type calcium channel (Cchra1) gene was cloned, and a transcriptional start point (tsp) was determined by rapid amplification of 5'-cDNA end (5'RACE) method. The putative promoter region of the gene contained no obvious TATA or CCAAT element in the expected positions, but multiple putative binding sites for transcriptional factors, such as Sp1, AP-1, AP-2, AP-3, EGR-1, EGR-2, NF-kappaB and HIP1, were detected. We found the existence of a tandem CTT trinucleotide repeat within the 5'-untranslated region (UTR) of the gene, and its polymorphism between C57BL/6J and Mus spretus. Using this polymorphism, the Cchra1 was mapped to the region of chromosome 1 where the synteny to human chromosome 1q was conserved.

Amino Acid Sequence↗

Effect of maternal deprivation on N-acetyltransferase activity rhythm in blinded rat pups.

It has been reported that the rhythms of infant rats synchronize with the mother's rhythm until the light-dark cycle comes and has strong effects on their endogenous clocks. We found that periodic maternal deprivation (PMD) was able to cause a phase shift of serotonin N-acetyltransferase (NAT) in neonatal blinded rat pups. PMD in which contact with the mother was allowed for only 4 h caused a phase shift of NAT rhythm, irrespective of the timing of contact with the mother in a day. Acute single mother deprivation caused an excess of NAT activity for more hours than usual and contact with the mother prevented such an excessive response. Mother deprivation may act as a cold stress, since artificial warming of pups gave the same results as contact with the mother. When the pups were artificially warmed by a heater during a 1-week deprivation period, a flat 24-h pattern of NAT was observed. The mechanism causing a phase shift of NAT activity rhythm of rat pups may be complicated.

Animals↗

Flow cytometric assays to detect platelet activation and aggregation in device-implanted calves.

Cardiovascular device development often relies upon large-animal models to assess blood biocompatibility prior to initiating clinical trials. Unfortunately, the amount of information gleaned from such trials is limited by simple assays that do not take full advantage of immunotechnological advances that increasingly are applied in clinical studies. Thus we have developed and tested new flow cytometric techniques for measuring circulating activated bovine platelets and platelet microaggregates. Monoclonal antibodies (MAbs) raised against both activated and quiescent bovine platelets were incubated with control and PMA-or ADP-stimulated whole blood. Selected MAbs detected activated bovine platelets and platelet microaggregates in vitro with flow cytometry. Five calves implanted with one of two designs of nonpulsatile ventricular-assist devices (VADs) were followed with these assays prior to and during VAD implantation. Circulating activated bovine platelets and microaggregates increased after implantation in all animals and, alternatively, remained elevated or returned toward preimplant levels. Platelet activation percentages as detected temporally by three MAbs were correlated with one another, and platelet activation was correlated with microaggregate formation. In summary, these new methods for the sensitive measurement of circulating activated bovine platelets and microaggregates may provide valuable information for the development and assessment of future cardiovascular device designs.

Adenosine Diphosphate↗

A sweat-gland tumor metastasizing to the axilla: report of a case.

Sclerosing sweat-duct carcinoma is a rare malignancy of the skin. We herein present the case of a 68-year-old Japanese man who developed sclerosing sweat-duct carcinoma 2 years after undergoing local excision of a primary tumor in his right arm. Firm nodules appeared in the right axilla, which were revealed by surgical resection to be metastases. This rare tumor grows slowly but usually metastasizes to the regional lymph nodes, whereupon they are often associated with a poor prognosis. As the effectiveness of chemotherapy and radiotherapy against this neoplasm remains unclear, we recommend that the disease should initially be aggressively treated by surgery, which would also be indicated for any metastatic lesions.

Adenocarcinoma↗

Age-dependent changes in metallothionein levels in liver and kidney of the Japanese.

Samples of liver, renal cortex, and medulla were obtained from 55 forensic autopsies (0- to 95-yr-old Japanese). Metallothionein (MT) was determined by the Ag-hem or Cd-hem method. Zinc (Zn), copper (Cu), and cadmium (Cd) were determined by atomic absorption spectrophotometry. The mean levels of MT were 250 micrograms/g in the liver, and 394 micrograms/g (cortex) and 191 micrograms/g (medulla) in the kidney. Age-dependent changes were observed in both the liver and kidney. In the liver, MT level decreased during infancy and increased thereafter with age. Similar age-dependent changes in the levels of Zn and Cu were observed. In the kidney cortex, MT level increased with age, although no correlation was found after middle age. The levels of Cd and Zn also increased with age until middle age; however, they decreased thereafter. These results suggest that age-dependent changes in renal MT levels are associated with accumulation of Cd.

Adolescent↗

[Blood conservation effect and safety of shed mediastinal blood autotransfusion after cardiac surgery].

Autotransfusion of shed mediastinal blood after cardiac surgery has been used to reduce risks related to homologous blood transfusions. To document the efficacy and safety of autotransfusion, we compared clinical findings of 80 patients receiving shed mediastinal blood (autotransfusion group) with those of the control group of 52 patients. The amount of the autotransfusion was limited to 800 ml, given the potentially harmful effects of shed blood transfusion. The mean transfused shed volume was 314 +/- 236 ml (S.D.). The serum levels of FDP-E, D-dimer and TAT after autotransfusion were higher in the autotransfusion group than in the control group (p = 0.01, p = 0.0004, p = 0.001, respectively). However, postoperative blood loss and the rate of reexploration for bleeding were similar in the two groups. The patients receiving blood products were fewer in the autotransfusion group than those in the control group (21% vs 44%; p = 0.005). Autotransfusion did not increase postoperative complications, including infection. Thus, although autotransfusion of mediastinal shed blood has the potential to affect hemostasis, unless the amount of autotransfusion exceeds 800 ml, it appears that this method is clinically safe and effective as a mean of blood conservation.

Blood Transfusion, Autologous↗

Efficacy of single-voided urine metanephrine and normetanephrine assay for diagnosing pheochromocytoma.

Urinary catecholamines (CAs) and their metabolites are usually measured during the process of diagnosing pheochromocytoma (pheo), but a 24-hour urine collection is not convenient for outpatients. Since 1987 we have utilized "spot" urine metanephrine (MN) and normetanephrine (NMN) assays for management of patients with pheo or adrenal incidentaloma. MN and NMN were measured by radioimmunoassay in 82 patients with surgically proved pheo and 15 patients with incidentaloma. In 10 patients with pheo, MN and NMN were measured with fractional every-3-hour urine samples, which were accumulated and then measured as a 24-hour urinary specimen. Fractions of 3-hour MN and NMN excretion were constant (MN 98.5 +/- 9.6%, NMN 97.6 +/- 10.8%; 24-hour MN and NMN 100%). The average levels of MN and NMN in patients with pheo were 6801 ng/mg creatinine (Cr) (range 93-88,248, median 1426) and 5627 ng/mg Cr (range 219-31,528, mean 3190), whereas the MN and NMN levels in patients with incidentaloma were 123 ng/mg Cr (range 36-246, mean 133) and 251 ng/mg Cr (range 84-472, mean 220), respectively. When we selected a cutoff value for MN + NMN of 1000 ng/mg Cr, the sensitivity was 97.6% and the specificity 100% for diagnosing pheo. When the standard was set as > 500 ng/mg Cr for either MN or NMN, both the sensitivity and specificity were 100%. The assay for MN and NMN is simple and effective, not only for screening but for diagnosing pheo and managing incidentaloma.

Adrenal Gland Neoplasms↗