Biomedical subjects

K Maruyama

Publications and source records attributed to K Maruyama.

At least 73 records · Page 4Linked to original sources

PubMed2001

Angiotensin II signaling and HB-EGF shedding via metalloproteinase in glomerular mesangial cells.

BACKGROUND: Angiotensin II (Ang II) has been implicated in the development of glomerulosclerosis by stimulating fibronectin (FN) synthesis. The processing and release of heparin binding-endothelin growth factor (HB-EGF) are activated by protein kinase C (PKC) and Ca2+ signaling. We studied the roles of HB-EGF and endothelial growth factor (EGF) receptor (EGFR) in Ang II-induced FN expression using mesangial cells. METHODS: Mesangial cells were prepared from mouse kidneys by the explant method and cells were used at passages 4 and 5. RESULTS: Ang II stimulated FN mRNA levels dose-dependently with a maximal increase (3.4-fold) after 12 hours of incubation. This action was completely inhibited by PKC inhibitors and slightly blocked by Ca2+ chelating agents. FN mRNA accumulation by Ang II was abolished by tyrosine kinase inhibitors, a specific inhibitor for EGFR (AG1478) and extracellular signal-regulated kinase (ERK) inactivation. Addition of neutralizing anti-HB-EGF antibody, as well as pretreatment with heparin or the metalloproteinase inhibitor batimastat abolished induction of FN expression by Ang II. In mesangial cells stably transfected with a chimeric construct containing HB-EGF and alkaline phosphatase (ALP) genes, ALP activity in incubation medium was rapidly increased by Ang II (1.7-fold at 0.5 min) and reached a 4.1-fold increase at two minutes. Ang II phosphorylated EGFR (maximal at 2 min) and ERK (maximal at 8 min) in a PKC- and metalloproteinase-dependent manner. Ang II stimulated the expression and release of transforming growth factor-beta (TGF-beta) via EGFR-mediated signaling, and the released TGF-beta also contributed to Ang II-mediated FN expression via EGFR transactivation. CONCLUSIONS: Ang II-mediated FN expression was regulated by autocrine effects of HB-EGF and TGF-beta, suggesting a novel paradigm for cross-talk between Ang II and growth factor receptor signaling pathways.

Angiotensin II↗

PubMed2001

Hypothalamic appetite-regulating neuropeptide mRNA levels in cachectic nude mice bearing human tumor cells.

We previously reported that the human melanoma cell line, SEKI, induces severe weight loss in nude mice. In the present study, we examined the expression of weight-regulating neuropeptide mRNAs in the hypothalamus of this cancer cachectic model by using a sensitive quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method and in situ hybridization. mRNA levels of neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH) in the whole hypothalamus were elevated significantly in the SEKI mice as compared with control mice. In situ hybridization showed that NPY and CRH mRNA were upregulated in the arcuate nucleus and the paraventricular nucleus, respectively. There were no significant differences in melanin-concentrating hormone (MCH), orexin (OX), and cholecystokinin mRNA levels between the SEKI and control mice. These results suggest that the NPYergic system is functioning in the rodent model of cancer cachexia; however, the role of the CRHergic system in energy homeostasis remains to be elucidated. This is the first report of the hypothalamic neuropeptide response to cachexia-inducing human cells.

Animals↗

PubMed2001

Growth curve analyses in selected duck lines.

1. Growth patterns of male ducks from 4 lines (lines A, B, C and D) selected for market weight were analysed and compared to growth patterns of ducks in the respective line 7 generations earlier. Growth curves were analysed using procedures derived from the Weibull sigmoidal function and the linear-linear relative growth rate model and simple allometry. 2. The ducks were fed ad libitum under 24-h lighting throughout the experiment. At weekly intervals from the time of hatch through 70 d of age, 16 ducks from each line were killed to determine body, carcase, breast-muscle, leg and thigh-muscle, and abdominal fat weights. 3. Line A was the heaviest line, followed by line B, line C and line D. However, body weight, carcase weight and breast-muscle weight at 49 d of age were not significantly different between lines A and B. After 7 generations of selection, the breast-muscle yield was increased to >19% and the abdominal fat percent was reduced to <1.4% in all lines. 4. The Weibull growth curve analysis of body weight showed an increase in the asymptotes during selection, while the age of the inflection point remained constant in all lines (21.3 to 26.0 d). For breast-muscle growth, ducks reached the inflection point 12.8 to 14.3 d later than for body weight. Between line A and line B, asymptotes for body weight, asymptotes for breast-muscle weight and allometric growth coefficients of breast muscle and leg and thigh muscles from 14 to 49 d were not significantly different. 5. The relative growth rate model discriminated body and breast-muscle growth patterns of line A and line B. The initial decline in the relative body growth rate was less and the time to reach the transition was longer in line A than line B. On the other hand, the initial decline in the relative breast-muscle growth rate was greater in line A than line B.

Abdomen↗

PubMed2001

Response of hypothalamic NPY mRNAs to a negative energy balance is less sensitive in cachectic mice bearing human tumor cells.

We selected three human cancer cell lines [human melanoma (SEKI), human melanoma (G361), and human neuroepithelioma (NAGAI)] that have an ability to develop cancer cachexia syndrome with and without accompanying anorexia and examined the hypothalamic levels of mRNAs for neuropeptide Y (NPY), melanin-concentrating hormone, and orexin. The body weight of sham-operated mice continued to increase, while mice of all tumor-bearing groups lost weight. Competitive reverse transcription-polymerase chain reaction analysis showed that, regardless of feeding status, NPY mRNA levels were elevated in all tumor-bearing mice compared with sham-operated mice, although to a lesser degree than weight-matched pair-weight mice. Melanin-concentrating hormone and orexin mRNA in the hypothalamus followed the same pattern as NPY, although most of the differences did not reach statistical significance. These results support the notion that the response of NPY mRNA to a negative energy balance is less sensitive in these rodent models of cancer cachexia.

Animals↗

PubMed2001

Monitoring of deep brain temperature in infants using multi-frequency microwave radiometry and thermal modelling.

In this study we present a design for a multi-frequency microwave radiometer aimed at prolonged monitoring of deep brain temperature in newborn infants and suitable for use during hypothermic neural rescue therapy. We identify appropriate hardware to measure brightness temperature and evaluate the accuracy of the measurements. We describe a method to estimate the tissue temperature distribution from measured brightness temperatures which uses the results of numerical simulations of the tissue temperature as well as the propagation of the microwaves in a realistic detailed three-dimensional infant head model. The temperature retrieval method is then used to evaluate how the statistical fluctuations in the measured brightness temperatures limit the confidence interval for the estimated temperature: for an 18 degrees C temperature differential between cooled surface and deep brain we found a standard error in the estimated central brain temperature of 0.75 degrees C. Evaluation of the systematic errors arising from inaccuracies in model parameters showed that realistic deviations in tissue parameters have little impact compared to uncertainty in the thickness of the bolus between the receiving antenna and the infant's head or in the skull thickness. This highlights the need to pay particular attention to these latter parameters in future practical implementation of the technique.

Body Temperature↗

PubMed2001

Alcohol and aldehyde dehydrogenase gene polymorphisms and oropharyngolaryngeal, esophageal and stomach cancers in Japanese alcoholics.

Alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) gene polymorphisms play roles in ethanol metabolism, drinking behavior and esophageal carcinogenesis in Japanese; however, the combined influence of ADH2 and ALDH2 genotypes on other aerodigestive tract cancers have not been investigated. ADH2/ALDH2 genotyping was performed on lymphocyte DNA samples from Japanese alcoholic men (526 cancer-free; 159 with solitary or multiple aerodigestive tract cancers, including 33 oropharyngolaryngeal, 112 esophageal, 38 stomach and 22 multiple primary cancers in two or three organs). After adjustment for age, drinking and smoking habits, and ADH2/ALDH2 genotypes, the presence of either ADH2*1/2*1 or ALDH2*1/2*2 significantly increased the risk for oropharyngolaryngeal cancer [odds ratios (ORs), 6.68 with ADH2*1/2*1 and 18.52 with ALDH2*1/2*2] and esophageal cancer (ORs, 2.64 and 13.50, respectively). For patients with both ADH2*1/2*1 and ALDH2*1/2*2, the risks for oropharyngolaryngeal and esophageal cancers were enhanced in a multiplicative fashion (OR = 121.77 and 40.40, respectively). A positive association with ALDH2*1/2*2 alone was observed for stomach cancer patients who also had oropharyngolaryngeal and/or esophageal cancer (OR = 110.58), but it was not observed for those with stomach cancer alone. Furthermore, in the presence of ALDH2*1/2*2, the risks for multiple intra-esophageal cancers (OR = 3.43) and for esophageal cancer with oropharyngolaryngeal and/or stomach cancer (OR = 3.95) were higher than the risks for solitary intra-esophageal cancer and for esophageal cancer alone, but these tendencies were not observed for ADH2*1/2*1 genotype. Alcoholics' population attributable risks due to ADH2/ALDH2 polymorphisms were estimated to be 82.0% for oropharyngolaryngeal cancer and 63.9% for esophageal cancer.

Adult↗

PubMed2001

Node-positive mucosal gastric cancer: a follow-up study.

BACKGROUND: Lymph node metastasis from mucosal gastric carcinoma is rare and the prognosis of the patients has seldom been reported. METHODS: Forty-five patients with node-positive mucosal gastric cancer were studied. They accounted for 2.5% of 1770 patients with mucosal gastric cancer who underwent gastrectomy with lymphadenectomy at the National Cancer Center Hospital, Tokyo. The clinicopathological features were studied and the current clinical status was sought. RESULTS: The majority of patients (87%) were treated with D2 lymphadenectomy. The metastasis was confined to the perigastric nodes (pN1 by Japanese classification) in 30 patients (67%). The number of positive nodes was less than seven (pN1 by TNM) in 42 patients (93%). Two patients had para-aortic nodal metastasis. The median follow-up period was 11 years. Four patients died of definite or possible recurrent disease and the disease-specific 5- and 10-year survival rates were 95 and 89%, respectively. CONCLUSIONS: Although nodal metastasis is an important prognostic factor for gastric cancer, the prognosis was excellent as long as the primary tumor was confined to the mucosa and was treated with gastrectomy and lymphadenectomy.

Adenocarcinoma↗

PubMed2001

DNA electrochemical sensor using osmium complex.

The [Os(DA-bpy)2DPPZ]2+ complex (DPPZ; dipyrido [a:2',3'-c] phenazine, DA-bpy; 4,4'-diamino-2,2'-bipyridine) had a lower half-wave potential (E1/2) of 147 mV (vs. Ag|AgCl) and higher binding affinity with DNA (binding constant, K = 3.1 x 10(7) M-1) than those of DPPZ type metal complexes. With a single stranded DNA (ssDNA) immobilized gold electrode, the hybridization signal (delta I) of the [Os(DA-bpy)2DPPZ]2+ complex was linear in the concentration range of 1.0 pg ml-1-0.12 microgram ml-1 for the targeted DNA with a regression coefficient of 0.999. The detection limit was 0.1 pg ml-1. The 400 bp yAL3 gene was also detected with good sensitivity and selectivity using the [Os(DA-bpy)2DPPZ]2+ complex.

Biosensing Techniques↗

PubMed2001

Alcohol and the pancreas.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The presentations were (1) Phenotypic alteration of myofibroblast during ethanol-induced pancreatic injury: its relation to bFGF, by Masahiko Nakamura, Kanji Tsuchimoto, and Hiromasa Ishii; (2) Activation of pancreatic stellate cells in pancreatic fibrosis, by Paul S. Haber, Gregory W. Keogh, Minoti V. Apte, Corey S. Moran, Nancy L. Stewart, Darrell H.G. Crawford, Romano C. Pirola, Geoffrey W. McCaughan, Grant A. Ramm, and Jeremy S. Wilson; (3) Pancreatic blood flow and pancreatic enzyme secretion on acute ethanol infusion in anesthetized RAT, by H. Nishino, M. Kohno, R. Aizawa, and N. Tajima; (4) Genotype difference of alcohol-metabolizing enzymes in relation to chronic alcoholic pancreatitis between the alcoholic in the National Institute on Alcoholism and patients in other general hospitals in Japan, by K. Maruyama, H. Takahashi, S. Matsushita, K. Okuyama, A. Yokoyama, Y. Nakamura, K. Shirakura, and H. Ishii; and (5) Alcohol consumption and incidence of type 2 diabetes, by Katherine M. Conigrave, B. Frank Hu, Carlos A. Camargo Jr, Meir J. Stampfer, Walter C. Willett, and Eric B. Rimm.

Alcohol Drinking↗

PubMed2001

Roentgenographic evaluation of ossification and calcification of the lumbar spinal canal after intradiscal betamethasone injection.

There have been reports of lumbar spinal canal ossification and calcification after triamcinolone intradiscal injection therapy. Our objective was to observe the roentgenographic changes after betamethasone intradiscal injection therapy for lumbar disc diseases. The subjects were 183 patients (498 discs; 130 men and 53 women) who underwent discography and betamethasone intradiscal injection therapy and were followed for a mean of 5 years and 7 months. Ossification and calcification appeared de novo (three patients, three discs) or enlarged (four patients, five discs) in the outer layer of the posterior annulus fibrosus or posterior longitudinal ligament in eight discs among seven patients (3.8%). The incidence and degree of ossification and calcification in our patients were significantly lower than those reported in previous studies, and a long time elapsed before ossification and calcification appeared or enlarged. Intradiscal injection of betamethasone did not appear to confer any incremental relative risk for lumbar spinal canal ossification and calcification based on review of follow-up roentgenographs.

Adolescent↗

PubMed2001

Warning from Nagano: increase of vulvar hematoma and/or lacerated injury caused by snowboarding.

BACKGROUND: On the basis of the number of women snowboarders whose vulvar injuries we have recently treated, we believe that the cases of vulvar hematoma and lacerated injuries caused by snowboarding have been increasing. To analyze the causal relation between snowboarding and vulvar injuries, we investigated how women were injured during snowboarding. METHODS: During the last three ski-ing seasons at the five hospitals near the ski resorts in Nagano Prefecture, Japan, the clinical charts of all patients with vulvar injuries during snowboarding were reviewed for the number of patients treated, the condition of the patients at diagnosis, and the characteristics of vulvar injuries. All patients were also asked by phone about how their vulvar injury was caused during snowboarding. RESULTS: The number of patients with vulvar injuries during the last three seasons was 16, 14, and 35, respectively. The types of vulvar injuries included hematoma in 33 (51%) patients, hematoma with lacerated injury in 17 (26%), and lacerated injury in the remaining 15 (23%). Of the 65 patients, 45 (69%) needed surgical treatment. Characteristically, 54 (88%) patients were injured when they tumbled onto the binding of the snowboard at the same time that one foot was left off the board and the binding was not turned down but left erect. CONCLUSION: It is important for women snowboarders to realize that in snowboarding there are dangers that may cause vulvar injuries. The prevention of such injuries requires that the binding should be turned down when the foot is left off the board and that snowboarders should try not to tumble onto the board.

Adolescent↗

PubMed2001

Phage display cloning and characterization of monoclonal antibody genes and recombinant Fab fragment against the CD98 oncoprotein.

The Fab gene of anti-CD98 heavy chain (h.c.) monoclonal antibody (mAb) HBJ127 was cloned and expressed as a recombinant Fab (rFab) fragment by means of a phage display system. The variable heavy and light chain genes of HBJ127 were found to be derived from VOx-1 and IgVk8-30 germline, respectively. Extensive somatic mutation was found in the heavy chain complementarity determining region 2. rFab fragment was purified homogeneously from crude bacterial lysates by Ni-chelate chromatography in a yield of 71.4 mg from 100 ml of culture. rFab fragment was reactive with the cell surface of CD98-positive cells irrespective of tissues of origin, but not with CD98-negative cells. The recognition site of the rFab fragment was identical to that of mAb since the binding of rFab fragment to HeLaS(3) cells was completely inhibited by pretreatment with an excess of mAb. The relative affinity values of rFab fragment and mAb were found to be 0.11 x 10(8) and 0.35 x 10(8) M(-1), respectively. Three-fold lower affinity of rFab fragment may be due to the difference of valency of the antibody preparation. Cell growth inhibition in vitro by rFab fragment preincubated with anti-Fab suggests that the rFab fragment produced by cloned gene-bearing Escherichia coli was identical to the Fab part of HBJ127 mAb. These results show that a small fragment with antigen binding activity similar to that of the parent mAb can easily be prepared by using a phage display system. To our knowledge, this is a first report of the production of anti-CD98 h.c. rFab fragment.

Amino Acid Sequence↗

PubMed2001

Salivary glands and lesions: evaluation of apparent diffusion coefficients with split-echo diffusion-weighted MR imaging--initial results.

The authors investigated the feasibility of performing diffusion-weighted (DW) magnetic resonance (MR) imaging with split acquisition of fast spin-echo signals (hereafter, split echo) for the assessment of salivary glands and salivary lesions. Eighteen patients without salivary disease and 10 patients with Sjögren syndrome, chronic parotitis, or focal salivary masses underwent split-echo and echo-planar DW MR imaging. DW MR images and apparent diffusion coefficient maps of the salivary gland had higher quality with split-echo rather than with echo-planar DW MR imaging.

Adult↗

PubMed2001

The orphan nuclear receptor NOR-1 interacts with the homeobox containing protein Six3.

Neuron-derived orphan receptor 1 (NOR-1) is a member of the NGFI-B subfamily within the nuclear receptor superfamily. In order to identify cofactors that associate with NOR-1 in the fetal forebrain, we tested a yeast two-hybrid system with the NOR-1 cDNA fragment lacking a transactivating domain as a bait. By screening of the rat fetal brain embryonic day 17 library, a rat homologue of Six3 was identified as an associated protein. We demonstrated that NOR-1 interacted with Six3 in yeast and in vitro, and the association was required for the DNA binding and AF2 domains of NOR-1. Regarding the other members of the family (NGFI-B and RNR-1), association with Six3 was not observed in yeast. In addition, cotransfection experiments with Six3 and NOR-1 indicated that Six3 had a negative activity against the transactivation by NOR-1 through the NBRE response element in a dose-dependent manner. The overlap in expression of NOR-1 and Six3 was mainly detected in the rat fetal forebrain on embryonic day 18. Thereafter, the expression of both genes diminished rapidly. These results suggest that a dimer consisting of a homeobox containing protein Six3 and transcriptional factor NOR-1 might regulate gene expression during the late stage of the fetal forebrain development. This study provides, after the association of Ftz and Ftz-F1 in Drosophila, another example of a dimer formation of a homeobox protein and an orphan nuclear receptor.

Amino Acid Sequence↗

PubMed2001

Methylprednisolone accelerates the resolution of glomerulonephritis by sensitizing mesangial cells to apoptosis.

Glucocorticoid has long been used to treat patients with glomerulonephritis because it ameliorates mesangial cell proliferation and proteinuria, in part by suppressing nuclear factor-kappa B (NF-kappaB) activation, which regulates the transcription of various pro-inflammatory genes. Recent evidence shows that NF-kappaB activation increases the resistance to TNF-alpha-induced apoptosis in mesangial cells. We examined glomerular cell proliferation and apoptosis along with NF-kappaB activation in the Thy-1.1 nephritis model. We also evaluated TNF-alpha-induced apoptosis in cultured mesangial cells. Methylprednisolone treatment ameliorated mesangial hypercellularity in Thy-1.1 nephritis by decreasing proliferating cells and increasing apoptosis in the glomeruli. These effects were associated with suppressed NF-kappaB activation. This in vitro study revealed that treatment with methylprednisolone and TNF-alpha induced cultured mesangial cell apoptosis. These results suggest that methylprednisolone may accelerate the resolution phase of Thy-1.1 nephritis in part by sensitizing mesangial cells to apoptosis.

Animals↗

PubMed2001

Long-term inhalation of high-dose nitric oxide increases intraalveolar activation of coagulation system in mice.

Inhalation of nitric oxide (NO) is useful for the treatment of patients with pulmonary hypertension. However, the potential toxicity of inhaled NO is still unclear. Coagulation activation plays an important role in lung injury. We assessed the effect of low- and high-dose inhaled NO on the coagulation system in the intraalveolar space of mice. The animals were assigned to five groups (n = 6): [RA] group, mice exposed to fresh air alone; [RA+2 ppm NO] group, fresh air and 2 ppm NO; [RA+40 ppm NO] group, fresh air and 40 ppm NO; [RA+2 ppm NO+O(2)] group, fresh air, 2 ppm NO and O(2); and [RA+40 ppm NO+O(2)] group, fresh air, 40 ppm NO and O(2). Each group was treated for 3 wk. Lung specimens of [RA+40 ppm NO] and [RA+40 ppm NO+O(2)] groups showed significant nitrotyrosine immunoreactivity. BALF concentrations of total protein, thrombin and soluble tissue factor were significantly increased in mice of [RA+40 ppm NO] and [RA+40 ppm NO+O(2)] groups compared with [RA] group. However, BALF concentrations of total protein, thrombin, and soluble tissue factor were not significantly increased in mice of [RA+2 ppm NO] and [RA+2 ppm NO+O(2)] groups compared with [RA] group. Lung tissue factor mRNA expression was higher in the high-dose NO group than in the low-dose NO group. NO donor increased significantly tissue factor activity on alveolar epithelial cells. This study has shown for the first time that long-term inhalation of high, but not low, concentration of NO may activate the clotting system by increasing the lung expression of tissue factor.

Administration, Inhalation↗

PubMed2001

Vascular smooth muscle cell phenotypes in primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is associated with specific structural alterations, including cellular intimal thickening, intimal fibrosis, and plexiform lesions. To determine the phenotypes of smooth muscle cells (SMCs) in such lesions, the authors conducted an immunohistochemical analysis of lung tissues from two patients with PPH, using two antimuscle actin antibodies, HHF35 and CGA7, and two anti-SMC myosin heavy chain markers, anti-SM1 and anti-SM2 antibodies and related antibodies. Cells that stained positive (+) with HHF35, CGA7, anti-SM1, and anti-SM2 were considered to be SMCs of a mature state. Conversely, those that stained positive with HHF35 and anti-SM1, but weakly positive (+/-) or negative (-) with CGA7 and anti-SM2, were considered to be SMCs exhibiting an immature state. Cellular intimal thickening was composed of SMCs of an immature phenotype (HHF35+, CGA7+/-, SM1+, SM2+/-), accompanied by the expression of fibronectin and the presence of macrophages; intimal fibrosis contained mature SMCs (HHF35+, CGA7+, SM1+, SM2+); and plexiform lesion consisted of proliferative endothelial cells (von Willebrand factor-positive cells, proliferating cell nuclear antigen-positive cells) and underlying immature SMCs (HHF35+, CGA7-, SM1+, SM2-) associated with fibronectin expression and macrophage infiltration. These findings suggest that smooth muscle cells with specific phenotypes may contribute to the development of specific vascular lesions in primary pulmonary hypertension.

Actins↗

PubMed2001

Purification and characterization of an esterase from Micrococcus sp. YGJ1 hydrolyzing phthalate esters.

An esterase hydrolyzing phthalate esters has been purified from Micrococcus sp. YGJ1. The enzyme, a monomeric protein (Mr = 56 kDa) with a pI of 4.0, hydrolyzes various aliphatic and aromatic carboxylesters. The medium chain (C3-C4) esters are the most preferred substrates. The enzyme is inhibited by HgCl2 and p-chloromercuribenzoate but not by phenylmethylsulfonyl fluoride.

Dibutyl Phthalate↗