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Biomedical subjects

K Yasuda

Publications and source records attributed to K Yasuda.

At least 289 records · Page 16Linked to original sources

[The value of serum C-reactive protein as a survival determinant in patients with advanced non-small-cell lung cancer].

We retrospectively reviewed the information in our data base concerning 127 patients with advanced non-small-cell lung cancer. Seventeen pretreatment clinical variables including serum C-reactive protein (CRP) were analyzed to determine the factors related to survival using Cox's proportional hazards model. Univariate analysis revealed that eleven explanatory variables were significant. In multivariate statistical technique for those variables, six were selected as significant factors. The highest hazard ratio was observed in the serum CRP (3.82). The other factors were therapy (2.52), serum lactate dehydrogenase (2.41), serum total protein (2.20), white blood cell counts (1.98) and performance status (1.80). Median survival times estimated by the Kaplan-Meier procedures in patients with normal CRP (CRP < 0.2 mg/dl) and high positive CRP (CRP > or = 3.0 mg/dl) were 24.9 months and 3.7 months, respectively. These results suggest that serum CRP is an independent survival determinant in advanced non-small-cell lung cancer.

Adult↗

[Coronary artery bypass grafting for a patient with effort angina pectoris and apical hypertrophic cardiomyopathy: case report].

A sixty-five year old man, known to have had apical hypertrophic cardiomyopathy (APH) since 1981, presented worsening of angina pectoris. Severe triple coronary artery disease was diagnosed and referred to our department for surgery. He underwent quintruple coronary artery bypass grafting (CABG) with left internal thoracic artery, left radial artery and saphenous veins. The cardiac index increased from 2.9 to 3.4 l/[symbol: see text]/m2 postoperatively. To our knowledge, this was the second case of CABG for APH in the world.

Aged↗

Laparoscopic splenopexy for adult wandering spleen: sandwich method with two sheets of absorbable knitted mesh.

Wandering spleen is a rare entity with a constant danger of splenic torsion leading to splenomegaly and infarction, which requires surgery. The authors describe a 30-year-old woman with intermittent left hypochondralgia and back pain with wandering spleen, who was successfully treated with a new method of laparoscopic splenopexy. In this procedure, two sheets of absorbable knitted mesh were used to sandwich the detorsed spleen. The procedure is feasible and less invasive, without impaired splenic function, and is applicable even for adult splenomegalic wandering spleen.

Absorbable Implants↗

[A case report of TS-1 in a patient with advanced gastric cancer].

TS-1 is an oral anticancer drug that produces biochemical modulation. TS-1 is composed of FT (tegafur), CDHP (gimestat, which inhibits 5-FU degradation enzyme), and Oxo (otastat potassium, which reduces 5-FU gastrointestinal toxicities), in a molar ratio of 1:0.4:1. We administered TS-1 to a 68-year-old female gastric cancer patient, after distal gastrectomy (Stage IV, cur C). As a result of abdominal CT, the diameter of metastatic lymph node increased before and after surgery, and before TS-1 (45 x 35 mm), but it was reduced after 1 course of TS-1 (37 x 25 mm), 2 courses of TS-1 (35 x 20 mm), 3 courses of TS-1 (30 x 20 mm), 4 courses of TS-1 (30 x 20 mm), and 6 months after 4 courses of TS-1 (20 x 20 mm). The reduction rate is 74.6%. The value of CA125 was reduced 74.4 to 8.6 after TS-1. Anorexia and back pain, which occurred after operation, disappeared after TS-1. There was no side effect over grade 3.

Aged↗

Clinical significance of cathepsin E in pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma.

BACKGROUND: It has been reported that cathepsin E (CTSE) is a non-secretory and intracellular aspartic proteinase found in the superficial epithelial cells of the stomach and that it is also expressed in pancreatic ductal adenocarcinoma. We evaluated the diagnostic value of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma compared with that of CA19-9, carcinoembryonic antigen (CEA) and K-ras mutations. METHODS: One hundred and one patients (25 with pancreatic ductal adenocarcinoma and 76 with chronic pancreatitis) were examined for the diagnostic significance of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma. Forty of 101 patients (15 with pancreatic ductal adenocarcinoma and 25 with chronic pancreatitis) were examined to compare the diagnostic value of various tumor markers in the pancreatic juice, namely CA19-9, CEA, K-ras mutations and CTSE. RESULTS: The detection frequency of CTSE was significantly higher in patients with pancreatic ductal adenocarcinoma (64.0%) than in patients with chronic pancreatitis (7.9%; chi2 = 34.76; P < 0.0001). The sensitivity, specificity and diagnostic accuracy of CTSE in the pancreatic juice for pancreatic ductal adenocarcinoma was 66.7, 92.0 and 82.5%, respectively. These values were more efficient in comparison with those of CA19-9, CEA and K-ras mutations. The main cause of the detection failure of CTSE in pancreatic ductal adenocarcinoma was obstruction of the main pancreatic duct. Sensitivity was 85.7% in patients without obstruction of the main pancreatic duct. CONCLUSIONS: Cathepsin E in the pancreatic juice is a novel marker for a definitive diagnosis of pancreatic ductal adenocarcinoma.

Adult↗

Neonatal repair of anomalous origin of the right pulmonary artery from the ascending aorta. A case report and review in the literature.

A seven-day-old neonate presented with respiratory distress and an early diagnosis was achieved through the echocardiographic studies which successfully visualized an anomalous origin of the right pulmonary artery arising from the ascending aorta. Subsequently a surgical correction with direct anastomosis of the right pulmonary artery to the main pulmonary trunk was accomplished in the neonatal period. The English literature in the last two decades is reviewed to discuss the characteristics, the diagnosis and treatment of neonatal cases with anomalous origin of the right pulmonary artery arising from the ascending aorta.

Angiography↗

Biological response to expandable metallic stents implanted into the portal vein. A histomorphometric study.

BACKGROUND: This study was undertaken to investigate the biological response to an expandable metallic stent implanted in the canine portal vein with a special reference to the histomorphometric contribution of cellular and acellular elements to the intimal and medial growth. METHODS: In 11 dogs, the Gianturco Z stent was placed into the portal vein and was harvested at intervals of 4 (n=6) and 12 weeks (n=5). In 6 dogs, the normal portal vein was harvested and used as a control. The specimens were subjected to histomorphometric examination. RESULTS: Mean intimal/medial thickness and total intimal/medial area significantly increased progressively by 12 weeks. Collagen intimal/medial area also significantly increased progressively by 12 weeks, while smooth muscle intimal/medial area significantly increased at 4 weeks but did not change from 4 weeks to 12 weeks. Collagen density tended to increase at 4 weeks and significantly increased at 12 weeks, while smooth muscle density significantly decreased at 4 weeks and continued to decrease at 12 weeks. CONCLUSIONS: The total area or mean thickness of the intima and media of the stented portal vein continued to increase by 12 weeks after stent placement. This phenomenon appeared to be due to proliferation of smooth muscle cells followed by accumulation of collagen.

Animals↗

Arterial thoracic outlet syndrome with embolic cerebral infarction. Report of a case.

Cerebral embolism is a very rare but recognized manifestation of arterial complications of thoracic outlet syndrome, and is associated with retrograde embolization in the cerebral arteries. We herein report a case of embolic brain infarction due to arterial thoracic outlet syndrome while discussing the etiology, diagnosis, and surgery.

Cerebral Infarction↗

Location of tumor and distribution of lymph node metastasis in gastric cancer: lesser curve or greater curve.

BACKGROUND: The aim of this study was to clarify the relationship between the location of tumor and distribution of lymph node metastasis in node-positive gastric cancer. Pathologic findings of tumors in which location of tumors or positive nodes was confined within the lesser or greater curve were evaluated, and candidates of limited resection were assessed. METHODS: A total of 211 patients with node-positive gastric cancer treated by D2 or D3 gastrectomy was studied. Location, size, gross type, and histologic type of tumors, presence or absence of serosal, lymphatic, and vascular invasions, and status of lymph node metastasis were investigated. Tumors were divided into lesser curve tumors, greater curve tumors, and others; and lymph node metastases were classified as lesser curve metastasis, greater curve metastasis, and both curves metastasis. RESULTS: Lesser or greater curve tumors were featured by small size, negative serosal invasion, negative vascular invasion, metastasis confined to the perigastric nodes, and number of positive nodes less than seven. Cases of lesser or greater curve metastasis were featured by tumor location within the lesser or greater curve, small size, grossly superficial type, negative serosal invasion, negative lymphatic invasion, and number of positive nodes less than seven. When size of lesser or greater curve tumors was less than 4 cm, lymph node metastasis was mostly restricted to the same lesser or greater curve. CONCLUSION: Among node-positive gastric cancers, tumors located within the lesser or greater curve were characterized by small size, negative serosal invasion, and a few metastases confined to the perigastric lymph nodes. When tumor size was less than 4 cm and tumor invasion was not into serosa, lesser or greater curve tumors rarely extend into lymph nodes along the other curve. Limited resection or less invasive treatment is acceptable for such small gastric cancers along the lesser or greater curve.

Gastrectomy↗

Separate cis-acting DNA elements control cell type- and tissue-specific expression of collagen binding molecular chaperone HSP47.

HSP47 is a collagen-binding heat shock protein and is assumed to act as a molecular chaperone in the biosynthesis and secretion of procollagen. As the synthesis of HSP47 is closely correlated with that of collagen in various cell lines and tissues, we performed a promoter/reporter assay using HSP47-producing and nonproducing cells. 280 base pairs (bp(s)) of upstream promoter were shown to be necessary for the basal expression but not to be enough for the cell type-specific expression. When the first and the second introns were introduced downstream of this 280-bp region, marked up-regulation of the reporter activity was observed in HSP47-producing cells but not in nonproducing cells. This was confirmed in transgenic mice by staining the lacZ gene product under the control of the 280-bp upstream promoter and the introns. Staining was observed in skin, chondrocytes, precursor of bone, and other HSP47/collagen-producing tissues. A putative Sp1-binding site at -210 bp in the promoter, to which Sp3 and an unidentified protein bind, was shown to be responsible for this up-regulation when combined with the introns. However no difference in the binding to this probe was observed between HSP47-producing and nonproducing cells. The responsible region for cell type-specific up-regulation was found to be located in a 500-bp segment in the first intron. On electrophoresis mobility shift assay using this 500-bp probe, specific DNA-protein complexes were only observed in HSP47-producing cell extracts. These results suggest that two separate elements are necessary for the cell type-specific expression of the hsp47 gene; one is a putative Sp1-binding site at -210 bp necessary for basal expression, and the other is a 500-bp region within the first intron, required for cell type-specific expression.

3T3 Cells↗

Vitellogenin-6 is a major carbonylated protein in aged nematode, Caenorhabditis elegans.

Recently we found that protein carbonyl content increases with age in wild-type as well as long- and short-lived Caenorhabditis elegans nematodes in inverse correlation with life span (Adachi et al., J. Gerontol. 53A, B240-B244, 1998; Yasuda et al., J. Gerontol. 54A, B47-B51, 1999). In the present study, we investigated carbonyl modification of individual proteins in young and old wild-type nematodes by two-dimensional immunoblot using antibodies against 2, 4-dinitrophenylhydrazones. A protein with apparent molecular weight of 110 kDa was found to be a major carbonylated protein in aged animals. Amino acid sequence of peptide fragments of the protein was identical to that of vitellogenin-6, a yolk protein synthesized in and secreted from the intestine during egg-laying stage. Although the function(s) of the protein in aged nematodes is unclear, we suggest that the protein may have a role to protect other cellular components from oxidation because of its metal binding capacity.

Age Factors↗

Regulation of lens fiber cell differentiation by transcription factor c-Maf.

To elucidate the regulatory mechanisms underlying lens development, we searched for members of the large Maf family, which are expressed in the mouse lens, and found three, c-Maf, MafB, and Nrl. Of these, the earliest factor expressed in the lens was c-Maf. The expression of c-Maf was most prominent in lens fiber cells and persisted throughout lens development. To examine the functional contribution of c-Maf to lens development, we isolated genomic clones encompassing the murine c-maf gene and carried out its targeted disruption. Insertion of the beta-galactosidase (lacZ) gene into the c-maf locus allowed visualization of c-Maf accumulation in heterozygous mutant mice by staining for LacZ activity. Homozygous mutant embryos and newborns lacked normal lenses. Histological examination of these mice revealed defective differentiation of lens fiber cells. The expression of crystallin genes was severely impaired in the c-maf-null mutant mouse lens. These results demonstrate that c-Maf is an indispensable regulator of lens differentiation during murine development.

Animals↗

Molecular and histological evaluation of pancreata from patients with a mitochondrial gene mutation associated with impaired insulin secretion.

A mutation in mitochondrial DNA, which was originally identified in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), can be associated with a subtype of diabetes mellitus. To determine the molecular and histological basis of impaired insulin secretion in the subjects with this mutation, we studied autopsy pancreata specimens from eight subjects diagnosed as having MELAS. The 3243 bp mutation was identified in seven out of eight pancreata examined. Immunohistochemical studies demonstrated a reduction in total islet mass, and in the numbers of both B and A cells. No evidence of insulitis or apoptosis was found. These data suggested that the 3243 bp mutation may cause the reduction of islet cells, mainly through mechanisms other than autoimmune destruction.

Adolescent↗

Rate of detection of lymph node metastasis is correlated with the depth of submucosal invasion in early stage gastric carcinoma.

BACKGROUND: Gastric carcinoma invading the submucosa is often accompanied by lymph node metastasis. However, the relation between the depth of submucosal invasion and the status of metastasis has not been investigated. The objective of this study was to clarify the relation between lymph node status and the histologic features of gastric carcinoma invading the submucosa. METHODS: The histopathology of 118 patients who underwent gastrectomy and lymph node dissection for gastric carcinoma invading the submucosa was examined. These pT1 tumors with invasion of the submucosa were confirmed by histologic examination of the resected specimens. Tumor size, depth of submucosal invasion, histologic type, and macroscopic type were investigated in association with presence or absence of and anatomic level of lymph node metastasis. RESULTS: Among the 118 patients, 16 (14%) had lymph node metastasis, and the status of metastasis significantly correlated with tumor size and depth of submucosal invasion. The frequency of metastasis to perigastric lymph nodes and extragastric lymph nodes was 0% and 0% for < or =1-cm tumors, 5% and 1% for 1- to 4-cm tumors, and 46% and 15% for >4-cm tumors, respectively. There was no lymph from a node metastasis in tumors with less than 300 microm of submucosal invasion. The frequency of lymph node metastasis for tumors with 300-1000 microm and >1000 microm of submucosal invasion were 19% and 14%, respectively. CONCLUSIONS: Tumor size and depth of submucosal invasion serve as simple and useful indicators of lymph node metastasis in early stage gastric carcinoma. Optimal lymph node dissection levels are as follows: 1) local resection (D0) for lesions < or =1 cm, 2) limited lymph node dissection (D1) for 1- to 4-cm lesions, and 3) radical lymph node dissection (D2) for lesions >4 cm. When submucosal invasion of a locally resected tumor is more than 300 microm, additional gastrectomy and lymph node dissection are necessary.

Adenocarcinoma↗

The Gln27Glu beta2-adrenergic receptor variant is associated with obesity due to subcutaneous fat accumulation in Japanese men.

The Trp64Arg beta3-adrenergic receptor (AR) variant is associated with visceral obesity probably due to decreased lipolysis in visceral fat (H. Kim-Motoyama et al., Diabetologia 40, 469-472, 1997). Functional alteration of beta2AR may also change fat distribution. We investigated the influence of the Gln27Glu beta2AR variant upon obesity and fat distribution. We screened 278 unrelated Japanese men and detected 249 wild-type Gln27 homozygotes, 28 Gln27/Glu27 heterozygotes, and one mutant Glu27 homozygote. The frequency of mutant Glu27 allele was significantly higher in obese subjects than in nonobese/intermediate subjects (0.11 vs 0.04, P = 0. 004). The Gln27/Glu27 heterozygotes had a significantly higher mean age-adjusted body-mass index (BMI) and mean age-adjusted subcutaneous fat area assessed by CT scan than the wild-type homozygotes but not the mean age-adjusted visceral fat areas. In summary, we have found that in Japanese men the Gln27Glu beta2AR variant is associated with obesity due to subcutaneous fat accumulation.

Adipose Tissue↗

Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds.

Much progress has been made in understanding limb development. Most genes are expressed equally and in the same pattern in the fore- and hindlimbs, which nevertheless develop into distinct structures. The T-box genes Tbx5 and Tbx4, on the other hand, are expressed differently in chick wing (Tbx5) and leg (Tbx4) buds. Molecular analysis of the optomotor blind gene, which belongs to the same family of transcription factors, has revealed that this gene is involved in the transdetermination of Drosophila wing and leg imaginal discs. In addition, expression of Tbx5 and Tbx4 correlates well with the identity of ectopic limb buds induced by fibroblast growth factor. Thus, it is thought that Tbx5 and Tbx4 might be involved in determining limb identity. Another candidate is the Pitx1 gene, which encodes a bicoid-type homeodomain transcription factor that is expressed in leg buds. Here we determine the importance of these factors in establishing limb identity.

Animals↗

Identification of a photoreceptor cell-specific nuclear receptor.

Nuclear receptors comprise a large and expanding family of transcription factors involved in diverse aspects of animal physiology and development, the functions of which can be modulated in a spatial and temporal manner by access to small lipophilic ligands and/or the specificity of their own localized expression. Here we report the identification of a human nuclear receptor that reveals a unique proximal box (CNGCSG) in the DNA-binding domain. The conservation of this feature in its nematode counterpart suggests the requirement for this type of P box in the genetic cascades mediated by nuclear receptors in a wide variety of animal species. The expression of this receptor, PNR (photoreceptor-specific nuclear receptor), appears strongly restricted in the retina, exclusively in photoreceptor cells. In human cell lines, PNR expression was observed in Y79 retinoblastoma along with other photoreceptor marker genes such as CRX. Among vertebrate receptors, PNR shares structural kinship with an orphan receptor TLX, and despite distinct differences in the DNA binding domain, PNR is able to recognize a subset of TLX target sequences in vitro. Analyses of the human PNR gene revealed its chromosomal position as 15q24, a site that has recently been reported as a susceptible region for retinal degeneration. These data support a role for PNR in the regulation of signalling pathways intrinsic to the photoreceptor cell function.

Amino Acid Sequence↗

Effect of tumor necrosis factor-alpha on insulin signal transduction in rat adipocytes: relation to PKCbeta and zeta translocation.

Although much evidence has been accumulated suggesting that tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance, the precise mechanism involved is still unclear. Recently, it has been reported that insulin-induced glucose uptake is mediated by activation of second messengers such as insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and diacylglycerol (DG)-protein kinase C (PKC). We have examined the effect of TNF-alpha on insulin-induced glucose uptake and activations of tyrosine kinase, IRS-1, PI3K and PKC in rat adipocytes. Pretreatment with 0.1-100 nM TNF-alpha for 60 min resulted in a significant decrease in 10 nM insulin- or 1 microM 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced [3H]2-deoxyglucose uptake without affecting basal glucose uptake. 10 nM insulin-stimulated activation of tyrosine kinase, IRS-1 and PI3K was suppressed by preincubation with 0.1-10 nM TNF-alpha for 60 min. 10 nM TNF-alpha pretreatment also suppressed 10 nM insulin- and 1 microM TPA-induced increases in membrane-associated PKCbeta and PKCzeta. Furthermore, 10 nM TNF-alpha, by itself, altered PKCbeta translocation from the membrane to cytosol. These results suggest that TNF-alpha inhibits insulin-stimulated activation of both the tyrosine kinase-IRS-1-PI3K-PKCzeta pathway and DG-PKC pathway. Finally, TNF-alpha contributes to insulin resistance in rat adipocytes.

Adipocytes↗