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Biomedical subjects

K Kozaki

Publications and source records attributed to K Kozaki.

At least 55 records · Page 3Linked to original sources
PubMed1999

Prognostic significance of elevated cyclooxygenase 2 expression in primary, resected lung adenocarcinomas.

Recently, we demonstrated that elevated expression of cyclooxygenase 2 (COX-2) is frequently seen in a specific type of lung cancer, i.e., adenocarcinoma, and is possibly associated with its invasion and metastasis. Here, the prognostic significance of elevated COX-2 expression was evaluated in a cohort of 130 adenocarcinoma patients who had consecutively undergone potentially curative resections. Immunohistological examination showed the presence of tumor cells with markedly increased COX-2 immunoreactivity in 93 of 130 (72%) cases. No relationship was found between the increase in COX-2 expression and clinical outcomes when the entire cohort was considered (P = 0.099). Reasoning that the influence of the increase in COX-2 expression may have been obscured by the clinical and molecular pathogenetic complexities in cases with an advanced disease, we also separately analyzed the prognostic significance of increased COX-2 expression after stratification according to the disease stage. A significant relationship between elevated COX-2 expression and shortened patient survival was observed only in a cohort of patients with stage I disease (P = 0.034). These findings suggest that an increase in COX-2 expression may be clinically significant for the prognosis of patients undergoing surgical resection of early-stage adenocarcinomas and, thus, warrant further conclusive studies involving a larger cohort.

Adenocarcinoma↗
PubMed1999

[Application of measuring 99mTc-MAG3 plasma clearance based on one-compartment model (MPC method) to renal transplantation].

Measurement of 99mTc-MAG3 plasma clearance (CLmag) based on one-compartment model (MPC method) was applied to renal transplantation and evaluated for the factors which might affect the calculated results, especially concerning renal depth. Correlation coefficient of CLmag between MPC method using real renal depth and Russell or Bubeck single sampling method was good (r = 0.852 or 0.876, respectively). Regression equation between MPC method and Russell method was y = 1.044x - 3.0 and was more closer to y = x than that between MPC method and Bubeck method. CLmag of MPC method calculated by estimated renal depth from the abdominal thickness was also similar to that by real renal depth. Even if the fixed renal depth, 4 cm, was applied, the coefficient and regression equation between MPC method and Russell method were r = 0.884 and y = 1.004x - 10.2. In conclusion, MPC method is applicable to the evaluation of renal transplants. Though measuring renal depth is best, calculation with fixed renal depth of 4 cm might be practically acceptable.

Adult↗
PubMed1998

Detailed deletion mapping suggests the involvement of a tumor suppressor gene at 17p13.3, distal to p53, in the pathogenesis of lung cancers.

The short arm of chromosome 17 is one of the most frequently affected chromosomal regions in lung cancers, while there is solid evidence that the p53 gene at 17p13.1 is a target for frequent 17p deletions. In the present study, we re-evaluated 17p deletions in lung cancers by conducting a detailed analysis of the minimum deleted region(s) on 17p with reference to the p53 gene status in each 100 primary lung cancer cases. In addition to the p53 locus at 17p13.1, the presence of an independent, commonly deleted region(s) at 17p13.3 was identified. Furthermore, loss of heterozygosity (LOH) at 17p13.3 was shown to be even more frequent than that at 17p13.1 and it appeared to occur in the absence of p53 mutation and/or 17p13.1 deletion. These results suggest that in addition to the p53 gene at 17p13.1, an as yet unidentified tumor suppressor gene(s) residing at 17p13.3 might play a role in lung carcinogenesis possibly in an earlier phase than the p53 gene. This would warrant future studies to identify the putative tumor suppressor gene at 17p13.3 in order to gain a better understanding of the molecular pathogenesis of this fatal disease.

Adenocarcinoma↗
PubMed1998

Estrogen attenuates endothelin-1 production by bovine endothelial cells via estrogen receptor.

To investigate the mechanism underlying the antiatherogenic effect of estrogen, we examined the role of estrogen in the regulation of endothelin-1 (ET-1) production by cultured bovine carotid arterial endothelial cells. Treatment of the cells with 17beta-estradiol dose dependently inhibited gene expression and peptide secretion of ET-1. This inhibitory effect of 17beta-estradiol was more marked when ET-1 production was stimulated by transforming growth factor-beta1. Simultaneous addition of ICI 182,780, a pure estrogen receptor antagonist, completely blocked the effect of 17beta-estradiol, indicating that 17beta-estradiol acted via estrogen receptor. These results suggest that reduced ET-1 production by endothelial cells may be involved in the vasoprotective effect of estrogen.

Animals↗
PubMed1998

Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas.

Cyclooxygenase (COX)-2 expression was immunohistochemically examined in 59 human lung cancers as well as in normal and premalignant lung specimens. In contrast to scattered weak reactivity seen in normal peripheral airway epithelial cells, markedly up-regulated COX-2 expression was detected in about one-third of atypical adenomatous hyperplasias and carcinoma in situ specimens, and a significant increase in COX-2 expression was observed in 70% of invasive adenocarcinoma cases. Interestingly, the proportion of adenocarcinoma cells with marked COX-2 expression was much greater in lymph node metastases than in the corresponding primary tumors. In contrast, small cell carcinomas showed virtually negligible expression, and squamous cell carcinomas showed infrequent and low expression. These findings suggest that an increase in COX-2 expression may be associated with the development of adenocarcinomas and possibly with acquisition of an invasive and metastatic phenotype.

Adenocarcinoma↗
PubMed1998

Cytokine-induced expression of parathyroid hormone-related peptide in cultured human vascular endothelial cells.

Parathyroid hormone-related peptide (PTHrP) is a potent vasodilatory peptide whose expression has been demonstrated in various tissues. The present study was undertaken to examine the regulation of PTHrP expression in cultured endothelial cells derived from human umbilical vein. Immunoradiometric assay revealed that the amount of PTHrP in the conditioned medium was increased by both tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) in both a time- and a dose-dependent manner. The induction of PTHrP mRNA was also observed, with a peak after 2 hours of incubation with both TNF-alpha and IL-1beta. Angiotensin II, endothelin-1, and arginine vasopressin had no affect on PTHrP production. Our results suggest that PTHrP produced in vascular endothelial cells in response to cytokines may modulate vascular function as a local factor.

Cells, Cultured↗
PubMed1998

Isolation, purification, and characterization of a collagen-associated serpin, caspin, produced by murine colon adenocarcinoma cells.

A 45-kDa serpin secreted by a murine colon adenocarcinoma cell line, colon26, was isolated, purified, and characterized. It was found to bind specifically to type I collagen with high affinity and to type III collagen with lower affinity. Immunohistochemical studies of murine embryonic tissues showed a specific distribution of this collagen-associated serpin, named caspin, in relation to the formation of bone, cartilage, teeth, and basement membrane. The expression of caspin in high and low lung metastatic subclones of colon26 cell lines was inversely correlated with their metastatic capacity: low lung metastatic cells secreted higher amounts of caspin than their high lung metastatic counterparts. Caspin also demonstrated high homology with human pigment epithelium-derived factor/early population doubling level cDNA-1, which reportedly induces neuronal differentiation of human retinoblastoma cells and is expressed in association with G0 growth arrest. These findings suggest that caspin/pigment epithelium-derived factor/early population doubling level cDNA-1 is a novel factor that might play a crucial role in embryogenesis and tumor metastasis through binding to the extracellular matrix.

Amino Acid Sequence↗
PubMed1998

Elevated expression of PDI family proteins during differentiation of mouse F9 teratocarcinoma cells.

We investigated the expression of protein disulfide isomerase family proteins (PDI, ERp61, and ERp72) in mouse F9 teratocarcinoma cells during differentiation induced by treatment with retinoic acid and dibutyryl cAMP. Each member of this family was expressed at a constitutive level in undifferentiated F9 cells. During differentiation of F9 cells to parietal or visceral endodermal cells the protein level of all these enzymes increased, although the extent of this increase in both protein and mRNA levels varied among the enzymes. Certain proteins were found to be coimmunoprecipitated with PDI, ERp61, and ERp72 in the presence of a chemical crosslinker. Type IV collagen was significantly coprecipitated with PDI whereas laminin was equally coprecipitated with the three proteins. Furthermore, 210 kDa protein characteristically coprecipitated with ERp72. Thus, the induction of PDI family proteins during the differentiation of F9 cells and their association with different proteins may implicate specific functions of each member of this family despite the common redox activity capable of catalyzing the disulfide bond formation.

Animals↗
PubMed1998

Amino-terminal fragment (1-34) of parathyroid hormone-related protein inhibits migration and proliferation of cultured vascular smooth muscle cells.

We investigated the effects of amino-terminal fragment (1-34) of parathyroid hormone-related protein [PTHrP-(1-34)] on the migration and proliferation of vascular smooth muscle cells (VSMCs). Cultured VSMCs (5-9th passage) obtained from the aortas of male Wistar rats were used in this study. Migration of VSMCs was assessed using a modified Boyden's chamber. Proliferation of VSMCs was evaluated by measuring [3H]thymidine incorporation and counting cell numbers. PTHrP-(1-34) inhibited 10% fetal bovine serum (FBS)-induced increase in migration of VSMCs (61% of control at 1 micromol/l) in a concentration-dependent manner. PTHrP-(1-34) also inhibited 5% FBS-induced increase in [3H]thymidine incorporation (37% of control at 1 micromol/l) and cell number of VSMCs (33% of control at 1 micromol/l) in a concentration-dependent manner. Parathyroid hormone (PTH)-(1-34) inhibited the migration and DNA synthesis of VSMCs to a similar extent. PTHrP-(7-34), a PTH/PTHrP receptor antagonist, significantly inhibited these effects of PTHrP and PTH. PTHrP-(1-34) also inhibited platelet-derived growth factor-BB (5 ng/ml)-induced migration and DNA synthesis of VSMCs. These findings suggest that PTHrP-(1-34) inhibits the migration and proliferation of VSMCs through PTH/PTHrP receptors.

Animals↗
PubMed1998

The impairment of flow-mediated vasodilatation in obese men with visceral fat accumulation.

BACKGROUND: Obesity has been reported to be associated with coronary artery disease and other atherosclerotic diseases. Recently, evidence has accumulated indicating that intra-abdominal visceral fat accumulation contributes to atherogenesis; however, the mechanism underlying this remains to be determined. This study was undertaken to elucidate whether intra-abdominal visceral fat accumulation impairs vascular endothelial function in obese men. METHODS AND RESULTS: Thirty-eight obese men (body mass index (BMI) > or = 26.0), aged 19-64 y (mean age 37.6 +/- 1.8 y) and 23 age-matched non-obese subjects were examined. According to the ratio of the maximum thickness of preperitoneal fat to the minimum thickness of subcutaneous fat (Pmax/Smin) obtained by longitudinal ultrasound scanning in the subxiphoid region in obese men, we divided obese subjects into two categories; visceral (Pmax/Smin > or = 1; n=23) and subcutaneous type (Pmax/Smin < 1; n=15). To investigate endothelial function, we performed ultrasound measurement of the brachial artery diameter non-invasively both at rest and during reactive hyperaemia in the muscle distal to the brachial artery which causes endothelium-dependent vasodilatation. The brachial diameter change was also measured after sublingual administration of nitroglycerin, which causes endothelium-independent vasodilatation. Flow-mediated diameter (D) increase (%FMD; deltaD/D x 100), in the subjects with visceral type obesity (3.09 +/- 0.43%) was significantly lower than those of the subjects with subcutaneous type obesity and non-obese subjects (7.90 +/- 0.51%, 8.91 +/- 0.44%, respectively, P < 0.01). The magnitude of endothelium-independent vasodilatation by nitroglycerin was similar in all groups. On multiple regression analysis, the Pmax/Smin showed a significant inverse correlation with %FMD. CONCLUSIONS: The subjects with visceral type obesity, rather than those with the subcutaneous type, are associated with impaired flow-mediated endothelium-dependent vasodilatation of the brachial artery.

Adipose Tissue↗
PubMed1998

The herbal medicine Sho-saiko-to inhibits growth and metastasis of malignant melanoma primarily developed in ret-transgenic mice.

Sho-saiko-to is the most popular herbal medicine in Japan. We investigated the anti-tumor and anti-metastatic effects of Sho-saiko-to and its chemically defined ingredients on the primary skin melanoma that developed in a metallothionein-I (MT)/ret transgenic mouse line and on a melanoma cell line (Mel-ret), which was derived from a primary tumor developed in a MT/ret transgenic mouse. In vitro, Sho-saiko-to suppressed the growth of Mel-ret cells more strongly than any single ingredient of Sho-saiko-to, although baicalin as one of several ingredients tested also suppressed it significantly. In vivo, Sho-saiko-to (i) significantly (p < 0.02) prolonged the onset of tumor development (1.5 mo), (ii) definitely retarded the transition to malignancy, (iii) significantly decreased the incidence of distant metastasis to brain (p < 0.002), kidney (p < 0.05), and liver (p < 0.05) at the malignant stage, and (iv) significantly (p < 0.02) prolonged life span (2.6 mo). Moreover, Sho-saiko-to and baicalin down-regulated the matrix metalloproteinase-2 and -9 expression levels, and upregulated their inhibitor expression level in both the primary tumors and Mel-ret cells. In conclusion, Sho-saiko-to displayed anti-tumor and anti-metastatic effects on melanoma with regulation of the balance of matrix metalloproteinase and tissue inhibitor of the matrix metalloproteinase levels.

Animals↗
PubMed1998

Molecular analysis of a Myc antagonist, ROX/Mnt, at 17p13.3 in human lung cancers.

The chromosome region 17p13 is known to be frequently deleted in lung cancers. We recently showed the presence of an independent, commonly deleted region at 17p13.3, suggesting that in addition to p53 at 17p13.1 an as-yet-unidentified tumor suppressor gene may reside in this telomeric region. Interestingly, the chromosomal location of a recently isolated novel myc antagonist gene, termed ROX/Mnt, coincides exactly with the centromeric border of the commonly deleted region at 17p13.3 in lung cancers. In conjunction with the generally acknowledged roles of myc genes in the pathogenesis of lung cancers, these findings led us to investigate whether ROX/Mnt is altered in lung cancers. Despite an extensive search for alterations in 52 lung cancer specimens. somatic mutations of ROX/Mnt could not be identified. We conclude that ROX/Mnt itself is not a frequent target for 17p13.3 deletions in lung cancers and that further explorations are required to identify the putative tumor suppressor gene at 17p13.3.

Amino Acids↗
PubMed1998

Activin/follistatin and atherosclerosis--a review.

Activin-A, a member of the TGF-beta superfamily, has a variety of important biological functions. Concerning Møs, we demonstrated that MSR which has a key role in disposing of modified LDL is downregulated by activin-A. This leads to a decrease in binding, cell association, and degradation of Ac-LDL, resulting in the inhibition of foam cell formation. Follistatin, presumably by blocking the effect of intrinsic activin-A, upregulates MSR expression, thereby promoting Ac-LDL disposal and foam cell formation. Because both activin-A and MSR are induced during Mø differentiation, these results suggest that MSR expression is suppressed by simultaneous production of activin-A in an autocrine manner. In addition to Møs, activin-A and follistatin exert influences on SMCs and ECs. Examination of in vivo expression of activin-A and follistatin revealed that they are present in various atherosclerotic lesions, including human coronary arteries, suggesting that they are locally produced. Activin-A and follistatin are produced by Møs, SMCs, and ECs in vitro. Thus, the activin-A/follistatin system plays an important role in the development of atherosclerosis.

Activins↗
PubMed1998

Role of machine perfusion preservation in kidney transplantation from non-heartbeating donors.

The shortage of kidneys for transplantation is a universal problem. If the viability of the kidney can be assured, organ procurement from non-heartbeating donors will be greatly enhanced. This study evaluates the usefulness of machine perfusion preservation parameters as an index of kidney graft viability. We report our experience with 77 non-heartbeating donor kidneys preserved with machine perfusion technique. Sixty-eight grafts demonstrated excellent perfusion (mean flow 0.79 ml/min/g) with low vascular resistance (55.4 mmHg/ml/min/g). Early graft function occurred in all of these kidneys. Nine kidneys demonstrated poor perfusion (mean flow 0.35 ml/min/g) and elevated pressures with high vascular resistance (132.5 mmHg/ml/min/g). Four kidneys with poor perfusion and elevated pressures was discarded after perfusion. The four mates of these discarded at our center were primarily non-functional when transplanted at another transplant center. All five of the poorly perfused kidneys experienced primary non-function. We conclude that the use of quantitative values of perfusion flow (> 0.4 ml/min/g) and no increased pressure pattern allow safe utilization of grafts from non-heartbeating donors and can predict early postoperative function.

Graft Survival↗