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K Takami

Publications and source records attributed to K Takami.

At least 55 records · Page 3Linked to original sources
PubMed1998

Immunohistochemical p53 protein status in nonsmall cell lung cancer is a promising indicator in determining in vitro chemosensitivity to some anticancer drugs.

BACKGROUND AND OBJECTIVES: The tumor suppressor oncogene p53 abnormalities have been closely associated with resistance or sensitivity of cancer cells to some chemotherapeutic agents. We examined the association between p53 protein status in nonsmall cell lung cancer (NSCLC) and in vitro chemosensitivity to several chemotherapeutic agents. METHODS: Using 146 surgically resected specimens of NSCLC, p53 status was immunohistochemically evaluated, and in vitro chemosensitivity to 5-fluorouracil (5-Fu), cisplatin (CDDP), mitomycin C (MMC), etoposide (VP-16), doxorubicin hydrochloride (ADM), and vindesine sulfate (VDS) was examined by a collagen gel-droplet embedded culture drug sensitivity test (CD-DST, Int J Oncol, 1997;11:449). RESULTS: Sixty-five of 146 materials (45%) showed immunohistochemically abnormal p53 protein accumulation in >10% of cancer cells within the tumor tissue, being regarded as p53+, whereas 81 (55%) were to p53-, in which no or less than 10% positive immunostaining cancer cells were detected. By CD-DST, the incidence of chemosensitive, borderline, and resistant p53- materials (N=81) to 5-Fu was 37%(N=30), 14%(N=11), and 49%(N=40), whereas that of p53+ materials (N=65) was 20%(N=13), 6%(N=4), and 74%(N=48), respectively, showing that p53- materials were significantly more sensitive to 5-Fu than p53+ materials (P=0.011), especially in the adenocarcinoma type. As similar borderline association between p53 protein status and in vitro chemosensitivity was also shown in ADM (P=0.078), but not in other chemoagents. CONCLUSIONS: Immunohistochemically detected p53 protein status in NSCLC patients may be a promising indicator in determining in vitro chemosensitivity to some anticancer drugs, especially 5-Fu and ADM.

Adult↗
PubMed1998

Analysis of zebrafish Mhc using BAC clones.

Although major histocompatibility complex (Mhc) genes have been identified in a number of species, little is yet known about their organization in species other than human and mouse. The zebrafish, Danio rerio, is a good candidate for full elucidation of the organization of its Mhc. As a step toward achieving this goal, a commercially available zebrafish BAC library was screened with probes specific for previously identified zebrafish class I and class II genes, as well as for genes controlling the proteasome subunits LMP7 and LMP2. Restriction maps of the individual positive clones were prepared and the Mhc (LMP7) genes localized to specific fragments. The total length of genomic DNA fragments with Mhc genes was approximately 1700 kilobases (kb) (200 kb of fragments bearing class I loci and 1500 kb of fragments bearing class II loci). One of the two class I loci (Dare-UCA) is closely associated with the LMP7 locus; the second class I locus (Dare-UAA) is more than 50 kb distant from the UCA locus and has no LMP genes associated with it. None of the class II genes are linked to the class I or the LMP genes. All six of the previously identified class II B genes and one of the three class II A genes were found to be present in the BAC clones; no new Mhc loci could be identified in the library. Each of the six previously identified class II B loci was found to be borne by a separate group of BAC clones. The Dare-DAB and -DAA loci were found on the same clone, approximately 15 kb apart from each other. An expansion of DCB and DDB loci was detected: the zebrafish genome may contain at least five closely related DCB and two closely related DDB loci which are presumably the products of relatively recent tandem duplication. These results are consistent with linkage studies and indicate that in the zebrafish, the class I and class II loci are on different chromosomes, and the class II loci are in three different regions, at least two of which are on different chromosomes.

Animals↗
PubMed1998

Effects of troglitazone on hepatic and peripheral insulin resistance induced by growth hormone excess in rats.

It is well known that short-term growth hormone (GH) administration in humans and animals induces insulin resistance and glucose intolerance. The purpose of the present study was to clarify whether troglitazone, a new insulin-sensitizing drug of the thiazolidinedione class, counteracts the insulin antagonistic effects of recombinant human (rh) GH on glucose metabolism in rats. Male Wistar rats weighing 184 to 226 g were treated either with rhGH (n = 8) or rhGH plus troglitazone (n = 8). rhGH (20 IU/kg body weight/d) was given by subcutaneous injection twice daily for 2 days. Troglitazone was given at 100 mg/kg/d orally for 5 days before and 2 days during rhGH. Saline was injected to the control rats (n = 7). Euglycemic clamp studies with an insulin infusion rate of 8 mU/kg/min were performed in these rats after an overnight fast. Hepatic glucose output (HGO), glucose infusion rate (GIR), and glucose disappearance rate (GDR) were measured. Fasting levels of plasma glucose (6.6 +/- 0.1, 6.1 +/- 0.3, 6.5 +/- 0.2 mmol/L), insulin (187.5 +/- 24.1, 206.4 +/- 24.1, 182.3 +/- 31.0 pmol/L), and serum free fatty acid (FFA) (1.58 +/- 0.18, 1.43 +/- 0.16, 1.61 +/- 0.25 mEq/L) were comparable among rats treated with rhGH, rhGH plus troglitazone, and controls, respectively. Basal HGO was also comparable among the three treatment groups. HGO was suppressed significantly during the hyperinsulinemic glucose clamp in control rats, but not in rhGH rats. When troglitazone was coadministered with rhGH, suppressibility of HGO during the glucose clamp was comparable to that of controls. GIR (13.5 +/- 4.5 v 24.1 +/- 4.1 mg/kg/min) and GDR (18.1 +/- 5.8 v 30.3 +/- 5.2 mg/kg/min) were decreased by rhGH treatment compared with control values. They returned to normal levels in rats treated with both rhGH and troglitazone (GIR, 22.4 +/- 5.9; GDR, 24.7 +/- 7.1). From these results, it is evident that rhGH treatment impaired insulin's ability to suppress HGO and stimulate peripheral glucose utilization. Troglitazone could block the insulin antagonistic effects of GH on hepatic glucose output and peripheral glucose utilization.

Administration, Oral↗
PubMed1998

Effects of troglitazone on dexamethasone-induced insulin resistance in rats.

Troglitazone, a thiazolidinedione derivative, has been shown to counteract insulin resistance in obesity and non-insulin-dependent diabetes mellitus (NIDDM). To test its effects on dexamethasone-induced insulin resistance, we measured hepatic glucose production (HGP) and the insulin-stimulated glucose disposal rate (Rd) by a euglycemic-hyperinsulinemic glucose clamp technique coupled with 3-3H-glucose infusion in male Wistar rats treated with low-dose dexamethasone ([LoDex] 0.05 mg/kg/d, n = 7), high-dose dexamethasone ([HiDex] 0.1 mg/kg/d, n = 7), or dexamethasone plus troglitazone (LoDex + T, n = 8; HiDex + T, n = 6). Dexamethasone was injected subcutaneously for 4 days. Troglitazone was administered orally at 20 mg/d for 3 days before and for 4 days along with the dexamethasone treatment. The glucose clamp study was performed after an overnight fast in chronically catheterized conscious rats with a continuous insulin infusion of 57.4 pmol/kg/min. Basal HGP was comparable among the control (45.8 +/- 2.1 micromol/kg/min, n = 7), LoDex (47.9 +/- 4.7 micromol/kg/min), LoDex + T (46.0 +/- 2.6 micromol/kg/min), and HiDex + T (54.7 +/- 3.4 micromol/kg/min) groups. It increased about twofold in the HiDex group (80.1 +/- 5.2 micromol/kg/min, P < .05 v control). Under hyperinsulinemia, HGP was suppressed to a similar level in the control (11.3 +/- 8.8 micromol/kg/min), LoDex (10.2 +/- 8.4 micromol/kg/min), and LoDex + T (7.8 +/- 7.9 micromol/kg/min) groups. The suppressive effect of insulin on steady-state HGP during the clamp was impaired in HiDex (63.7 +/- 9.7 micromol/kg/min, P < .05) and HiDex + T (64.0 +/- 6.5 micromol/kg/min, P < .05). Rd decreased 27% in LoDex (81.5 +/- 5.8 micromol/kg/min, P < .05) and 36% in HiDex (71.3 +/- 9.4 micromol/kg/min, P < .05) compared with the controls (111.4 +/- 7.4 micromol/kg/min). Troglitazone prevented the decrease in Rd in LoDex + T (102.6 +/- 5.7 micromol/kg/min), but not in HiDex + T (67.0 +/- 6.4 micromol/kg/min). These results indicate that the development of peripheral insulin resistance was prevented by troglitazone in LoDex rats. Troglitazone may be a useful drug to treat steroid-induced diabetes.

Animals↗
PubMed1998

Myoepithelioma of the lung: report of two cases and review of the literature.

Myoepithelial tumors occur mainly in the salivary glands, the sweat glands or the breast, but uncommonly in the lung. Herein, we describe two cases of myoepithelioma of the lung. Both patients were 58-year-old men, in whom the tumors were located in the right-upper bronchus and in the left-upper bronchus, respectively, with endobronchial growth pattern. Surgery was performed, but metastasis occurred into the forearm and hip muscles in the former case, and into the liver in the latter. Histologically, the tumor in the former was a spindle-plasmacytoid type, and that in the latter was a plasmacytoid type in part with squamous differentiation. Based on histochemical, immunohistochemical and ultrastructural analyses, both were compatible with myoepithelioma. The clinicopathological uniqueness of this neoplasm is discussed, together with a review of reports of this disease in the literature.

Fatal Outcome↗
PubMed1998

Genetic variation of mitochondrial cytochrome b genes among the subspecies of koala, Phascolarctos cinereus.

A conserved DNA region among the subspecies of koala, of mitochondrial cytochrome b gene, was employed to analyze the genetic variation among 3 available subspecies of koala. This conserved sequence, 307 bp DNA, was sequenced using polymerase chain reaction and direct DNA sequencing technique. Substitutions in the nucleotide sequences were observed, with which koalas can be divided into 3 DNA haplotypes subspecies, but the molecular data provided inconsistency with current classification of the 3 subspecies of koala.

Amino Acid Sequence↗
PubMed1998

[Does induction therapy followed by surgery improve the survival rate in limited-stage small-cell lung cancer patients?].

Small-cell lung cancer (SCLC) is distinguished from non-small cell lung cancer (NSCLC) by its rapid tumor doubling time, high growth fraction, and early development of widespread metastases. Surgery alone offers the best chance for long-term survival in selected patients with stage I SCLC. Most patients with limited SCLC (stage I-IIIa) are treated with "comprehensive therapy" combined with chemotherapy, radiotherapy (thoracic radiotherapy and/or prophylactic cranial irradiation), and surgery. Although the efficacy of surgery in the control of local disease is well established, to date no report has shown better survival rates in patients who receive induction therapy when compared with patients receiving postoperative chemotherapy. However, studies of induction therapy include more patients with advanced-stage cancer than do studies of post-operative chemotherapy. Thus the final role of induction therapy followed by surgery must await the results of future prospective, randomized trials conducted by large cooperative study groups.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

[Simultaneous operation of lung cancer accompanied with aortic arch aneurysm: report of a case].

We report a simultaneously operated case of a 68-year-old man with lung cancer accompanied with aortic arch aneurysm. Preoperative staging CT for lung cancer incidentally demonstrated another lesion in the para-aortic arch area, which was suspected to be rather a pleural or intrapulmonary lesion by enhanced CT and MRI. However, this lesion was intraoperatively diagnosed as a cystic small sized-aneurysm. After a left upper lobectomy with lymph node dissection for lung adenocarcinoma (T2N0) was performed, this aneurysm was tightly wrapped using PTFE felt during the course of one operation. The difficulty of peroperative diagnosis by CT and MRI for small sized-aneurysm is discussed, and surgical stragety for lung cancer accompanied with such an aortic aneurysm is also commented.

Adenocarcinoma↗
PubMed1998

Distinct characteristics of transcellular transport between nicotine and tetraethylammonium in LLC-PK1 cells.

To clarify the mechanisms of the renal tubular secretion of nicotine, we studied transport of nicotine in the kidney epithelial cell line LLC-PK1. The transcellular transport of nicotine from the basolateral side to the apical side of the LLC-PK1 monolayers grown on membrane filters was much greater than that of tetraethylammonium. The basolateral-to-apical transport of nicotine was stimulated by lowering the pH of the apical side, accompanied by a decrease in the accumulation of nicotine. The accumulation of nicotine from the basolateral side was inhibited by unlabeled nicotine, cotinine, tetraethylammonium, cimetidine and quinidine. The uptake of nicotine across the apical membrane was inhibited by unlabeled nicotine and quinidine but not by tetraethylammonium or cimetidine. Pretreatment with p-chloromercuribenzene sulfonate caused a decrease in the transcellular transport of tetraethylammonium but not of nicotine. These results suggest that nicotine undergoes vectorial transport from basolateral side to the apical side of LLC-PK1 monolayers in a H+ gradient-dependent manner, corresponding to the secretion in the renal tubules. Nicotine transport in LLC-PK1 cells could be mediated by a transport system that is distinct from the transport system for tetraethylammonium.

4-Chloromercuribenzenesulfonate↗
PubMed1998

[Surgical treatment of T3N0M0 non-small cell lung cancer].

From January 1982 to June 1995, 45 patients underwent operation at our department for T3N0M0 non-small cell lung cancer. Tumors invaded chest wall in 38 patients (parietal pleura in 17, subpleural fat tissue in 10, and rib in 11), diaphragm in 3, mediastinum in 3, and pericardium in 1. Extrapleural dissection was performed in 17 patients and en bloc resection of chest wall and lung was performed in 21. Complete resection was possible in 43 patients (96%). Operative mortality was 2.2%. The actuarial overall 5-year survival rate was 63% for the patients with parietal pleura invasion, 45% for those with subpleural invasion, 45% for those with rib invasion, and 56% for those with diaphragm, mediastinal pleura or pericardial invasion. Recurrence at the resected margin was observed in 5 patients with chest wall invasion (subpleural tissue in 3, rib in 2) and 1 with diaphragmatic invasion. In conclusion, we recommend an en bloc resection of the chest wall with enough surgical margin for peripheral tumors firmly adherent to the parietal pleura.

Adult↗
PubMed1997

Linkage of LMP, TAP, and RING3 with Mhc class I rather than class II genes in the zebrafish.

The LMP2 and LMP7 genes code for subunits of the proteasome, a multimeric enzymatic complex that degrades proteins into peptides. The two subunits replace corresponding constitutively expressed subunits during the immune response. Some of the peptides generated by the proteasome in the cytosol are transported by the products of the TAP1 and TAP2 genes into the lumen of the endoplasmic reticulum and are loaded onto the assembling MHC class I molecules. In mammals, the LMP2, LMP7, TAP1, and TAP2 genes reside in the class II region of the Mhc, closely linked to the RING3 gene. In the present study we identified, cloned, and sequenced the LMP, TAP2, and RING3 genes of the zebrafish, Danio rerio. We identified variants of these genes and used them in a segregation analysis of haploid embryos derived from heterozygous mothers. The analysis revealed that in zebrafish, the LMP2, LMP7, TAP12, and RING3 loci are closely linked but, in contrast to mammals, the LMP/TAP/RING3 cluster resides not in the Mhc class II but in the class I region. We also confirmed that in the zebrafish, the class I and class II regions are not linked to each other. In this species, therefore, the LMP/TAP/RING3 genes are clustered with the class I genes on a chromosome that apparently does not contain any class II genes. The linkage of LMP/TAP/RING3/class I may be the original and the LMP/TAP/RING3/class II a derived arrangement of these genes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Expression of presenilin-1 and -2 mRNAs in rat and Alzheimer's disease brains.

Recently, new genetic linkages have been identified for early-onset familial Alzheimer's disease (AD). Mutations have been found in the presenilin (PS)-1 (S182) gene on chromosome 14 and the PS-2 (STM2/E5-a) gene on chromosome 1. We have investigated the distribution of gene expression of both presenilins in normal rat brain, and in human control and AD cases using in situ hybridization histochemistry. In normal rat brain, intense PS-1 mRNA expression was observed predominantly in neurons, particularly hippocampal pyramidal and dentate granular neurons and cerebellar Purkinje and granular neurons. The distribution of intensely expressing PS-2 mRNA cells was similar to that of PS-1, but additional groups in the brain stem and cortex were identified. Faint but significant mRNA expression of both PS genes was detected in white matter. In control human cases, the same neuronal cell types as seen in rat brain expressed both PS mRNAs in the hippocampus and cerebellum. In AD cases, the expression of both mRNAs was markedly decreased in the hippocampus but not in the cerebellum. In addition, PS-2 hybridization showed increased mRNA expression in astrocyte-like cells in affected areas of AD cases. The present data indicate that the PS genes may play important roles in specific neurons in normal brain, and that the decreased expression in neurons in sporadic AD brain may bear some relationship to the pathogenesis.

Alzheimer Disease↗
PubMed1997

Csk overexpression reduces several monokines and nitric oxide productions but enhances prostaglandin E2 production in response to lipopolysaccharide in the macrophage cell line J774A.1.

The catalytic activity of src-family protein tyrosine kinases (src-PTK) is suppressed when a C-terminal tyrosine is phosphorylated by an intracellular PTK, C-terminal Src kinase (Csk). In the present report, to study the regulatory functions of the Csk in cells of monocyte/macrophage lineage, we transfected a eukaryotic expression vector containing rat csk cDNA in a macrophage cell line, J774A.1, and examined alterations of the response to lipopolysaccharide (LPS) in the transfectants which overexpressed Csk. Csk overexpression resulted primarily in a down-regulation of Fgr activity, an src-PTK expressed in J774A.1, and hyperphosphorylation of several cellular proteins of 35, 57, 66, 97 and 120-130 kDa. Furthermore, in these Csk transfectants, production of interleukin (IL)-1alpha, IL-6, tumor necrosis factor-alpha, and nitric oxide (NO) following LPS stimulation were reduced compared with those in parental J774A.1 or J774A.1 transfected with the vector alone. The extent of reduction paralleled the amounts of Csk proteins expressed in the Csk-transfected J774A.1. The reduced NO production in these cells was associated with low levels of mRNA of inducible NO synthetase. On the other hand, an enhancement of prostaglandin E2 production was observed in the Csk-transfected J774A.1 cells upon stimulation with LPS, which appeared to result from the high level of prostaglandin-H synthetase in the transfectants. The present findings indicate that overexpression of Csk has differential effects on the regulation of production of chemical mediators and monokines, probably via modulation of signal transduction downstream of LPS-mediated signals.

Animals↗
PubMed1997

MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation.

MDM2 is an oncoprotein that inhibits p53 tumour-suppressor protein. Amplification of the MDM2 gene and overexpression of its protein have been observed in some human malignancies, and these abnormalities have a role in tumorigenesis through inactivation of p53 function. To determine the clinicopathological and prognostic value of MDM2 abnormalities in non-small-cell lung cancer (NSCLC), MDM2 gene amplification and its protein expression status were analysed in surgically resected materials. MDM2 gene amplification was detected in only 2 (7%) of the 30 tested patients. MDM2 protein was found immunohistochemically in a total of 48 (24%) of the 201 patients. MDM2 protein was slightly frequently observed in patients with adenocarcinoma, but its presence or absence was not associated with clinicopathological factors such as T-factor, N-factor, stage, tumour size, differentiation or p53 protein status. Overall, MDM2-positive patients tended to have a better prognosis (P = 0.062). In particular, among immunohistochemically p53-negative patients (n = 110), those with positive MDM2 protein expression showed significantly better prognosis (P = 0.039) and, in a multivariate analysis, MDM2 protein status was a favourable prognostic factor (P = 0.037). In contrast, among p53-positive patients (n = 91), there was no difference in prognosis depending on MDM2 protein status. Thus, in the NSCLC patients studied, MDM2 gene amplification was a minor event, but expression of its protein, which was often observed immunohistochemically, was a favourable prognostic marker, especially among patients without p53 protein accumulation. Further study is needed to determine how MDM2 protein expression results in a better prognosis.

Adult↗
PubMed1997

A detailed analysis of the role of K-ras gene mutation in the progression of colorectal adenoma.

To elucidate the role of ras gene mutations during the early stage of colorectal tumour progression, K-ras gene mutations were analysed in 32 benign adenomas and 36 adenomas with focal carcinoma in the colorectum by microscraping of histologically pure regions from tissue sections, polymerase chain reaction-restriction fragment length polymorphism and in part by direct sequencing. Several regions were scraped out and analysed when an adenoma contained areas with different grades of dysplasia. The frequencies of K-ras gene mutation in mild dysplasia, moderate dysplasia and focal carcinoma were 19% (7/36), 51% (25/49) and 39% (14/36) respectively. The K-ras gene status was heterogeneous in 4 of the 11 benign adenomas from which multiple samples were obtained, and mutations were always found in the regions with more advanced dysplasia in these adenomas. Thirteen of the 36 adenomas with focal carcinoma showed heterogeneity of mutations between the adenoma region and the focal carcinoma. Seven of which had mutations only in the adenoma region. These findings indicated that the K-ras gene mutations occur during the late stage of adenoma progression and may confer a more advanced morphological phenotype of adenoma, but these mutations are not mainly involved in malignant transformation from adenoma to carcinoma.

Adenoma↗