Biomedical subjects

T Nakata

Publications and source records attributed to T Nakata.

At least 109 records · Page 6Linked to original sources

PubMed1998

The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3.

The MLK (mixed lineage) ser/thr kinases are most closely related to the MAP kinase kinase kinase family. In addition to a kinase domain, MLK1, MLK2 and MLK3 each contain an SH3 domain, a leucine zipper domain and a potential Rac/Cdc42 GTPase-binding (CRIB) motif. The C-terminal regions of the proteins are essentially unrelated. Using yeast two-hybrid analysis and in vitro dot-blots, we show that MLK2 and MLK3 interact with the activated (GTP-bound) forms of Rac and Cdc42, with a slight preference for Rac. Transfection of MLK2 into COS cells leads to strong and constitutive activation of the JNK (c-Jun N-terminal kinase) MAP kinase cascade, but also to activation of ERK (extracellular signal-regulated kinase) and p38. When expressed in fibroblasts, MLK2 co-localizes with active, dually phosphorylated JNK1/2 to punctate structures along microtubules. In an attempt to identify proteins that affect the activity and localization of MLK2, we have screened a yeast two-hybrid cDNA library. MLK2 and MLK3 interact with members of the KIF3 family of kinesin superfamily motor proteins and with KAP3A, the putative targeting component of KIF3 motor complexes, suggesting a potential link between stress activation and motor protein function.

14-3-3 Proteins↗

PubMed1998

Early gastric cancer associated with synchronous liver metastasis and portal tumorous embolism: report of a case.

We report herein the first known case of early gastric cancer with synchronous liver metastasis forming a portal tumorous embolism. A 62-year-old man was found to have multiple liver tumors and a portal tumorous embolism by ultrasonography. A gastroscopy subsequently showed Borrmann type III-like gastric cancer in the antrum. His carbohydrate antigen (CA) 19-9 level was elevated to 8280 U/ml, but the alpha-fetoprotein level was within normal limits. A laparotomy revealed multiple liver metastasis and subpyrolic lymph-node enlargement; a distal partial gastrectomy with group 1 lymph-node dissection for the gastric cancer in the antrum, and cannulation of the proper hepatic artery for postoperative chemotherapy were performed. Histopathologically, the cancer was found to be a medullary type well-differentiated adenocarcinoma. Subpyrolic lymph node metastasis was noted, but cancer invasion was localized to only the mucosal and submucosal layers of the stomach. Thus, the patient was diagnosed as having early gastric cancer. Adjuvant chemotherapy given through the cannula suppressed further elevation of CA19-9 levels, and a total of 26 Gy irradiation to a liver tumor, which had caused ascites by pressing on the inferior vena cava, diminished the ascites. The patient was able to remain at home with treatment for 7 months after radiation therapy, but finally died of cancer with jaundice 13 months after his operation. Therefore, although adjuvant chemotherapy and radiation therapy contributed to improving his quality of life, it could not prolong survival.

Adenocarcinoma↗

PubMed1998

Sequential percutaneous microwave coagulation therapy for liver tumor.

BACKGROUND: Percutaneous microwave coagulation therapy (PMCT) is effective for small liver tumors. To enhance the radicality of PMCT, we developed a sequential coagulation technique. METHODS: After inserting the first guide-needle under sonography, multiple needles were placed through a disk-type introducer that was devised to guide needle puncture at regular intervals, and microwaves were irradiated. Six patients, including 4 with hepatocellular carcinoma and 2 with liver metastasis, underwent this technique for tumors of 15 to 80 mm in diameter. RESULTS: This technique can coagulate an area up to 60 mm in diameter in one session. Insertion of multiple needles, ranging from 2 to 11, was successful without complications. Three patients undergoing curative PMCT developed no tumor recurrence. The other 3 received incomplete PMCT due to the large size and location of the tumor. CONCLUSIONS: This preliminary study indicates the efficacy of this technique to facilitate and secure PMCT in selected patients with liver tumors.

Carcinoma, Hepatocellular↗

PubMed1998

Enteric absorption of FK 506: estimation by a block liver perfusion technique in rats.

This perfusion model enables a pharmacokinetic study of enteral absorption and hepatic metabolic rate simultaneously. FK 506 is absorbed mainly via the proximal small intestine and metabolized rapidly by the liver during single passage. These results may lead to further analyses of absorption and metabolism of FK 506 under various conditions.

Animals↗

PubMed1998

Unique association of pheochromocytoma with contralateral nonfunctioning adrenal cortical adenoma.

A 57-year-old woman complaining of hypertensive attacks associated with headache and palpitation was admitted to our hospital for examination of bilateral adrenal tumors in 1985. After right pheochromocytoma was diagnosed, right adrenalectomy was performed. The left adrenal tumor was small; thus, the left adrenal tumor was preserved to avoid adrenal insufficiency, although left adrenal pheochromocytoma could not be denied. In 1995, she was referred to our clinic again because of recurrent headache and palpitation, and enlargement of the left adrenal tumor. Although pheochromocytoma was suspected again, the enlarged left adrenal turned out to be a nonfunctioning cortical adenoma. This case was interesting, not only because of difficulty in identifying the left adrenal tumor, but also because of the rare coexistence of a pheochromocytoma and a nonfunctioning adrenal cortical tumor.

Adrenal Cortex Neoplasms↗

PubMed1998

Identification of a new commonly deleted region within a 2-cM interval of chromosome 11p11 in breast cancers.

Allelic loss has been observed on the short arm of chromosome 11 in a variety of human cancers. We have examined 184 breast cancers for allelic loss anywhere in chromosome 11p, using 15 well-spaced microsatellite markers. Allelic loss was observed in 86 cases (47%) and a new commonly deleted region 2-cM in length was identified at 11p11 between loci D11S986 and D11S1313, in addition to a 12-cM region of a common deletion at 11p15.5. A significant association was found between allelic loss on 11p15.5 and LOH on 11p11 and the loss of progesterone receptors.

Autoradiography↗

PubMed1998

A furanoid labdane diterpene from Potamogeton nodosus.

A new furanoid diterpene, 15,16-epoxy-12-oxo-8(17), 13(16), 14-labdatrien-20,19-olide (1) was isolated from an ethanolic extract of Potamogeton nodosus. Its structure was elucidated by the usual spectroscopic methods, including 2D NMR techniques. Compound 1 was found to exhibit moderate inhibitory activity against a number of both Gram-positive and Gram-negative bacteria.

Anti-Bacterial Agents↗

PubMed1998

Cloning and expression of an alpha-2,8-polysialyltransferase (STX) from Xenopus laevis.

Polysialic acid (polySia) is a carbohydrate structure found on neural cell adhesion molecules (N-CAM). Two polysialyltransferases (polySiaTs) that catalyze synthesis of polySia have been described, and designated PST-1/PST/ST8SiaIV and STX/ST8SiaII. We cloned a polySiaT (xSTX) from a nonmammalian vertebrate, Xenopus laevis . xSTX had 80% amino acid similarity to the rat STX. This clone induced polySia expression when transfected into polySia-negative COS-1 cells. Northern blot analysis of whole embryos at different stages of development revealed that xSTX mRNA was most abundantly expressed in premetamorphic stages. The relative level of xSTX and N-CAM mRNAs was also examined and found to change in parallel to the extent of polysialylation on N-CAM. In adult tissues, the expression of xSTX mRNA was restricted to brain, eye and heart, which also expressed polySia. These results suggest that xSTX is the major enzyme responsible for the synthesis of polysialylated N-CAM in embryos at certain stages of development and also in adult tissues.

Amino Acid Sequence↗

PubMed1998

Augmented response of endothelin-A and endothelin-B receptor stimulation in coronary arteries of hypertensive hearts.

To determine whether the vasoconstrictor response to endothelin-1 (ET-1) is altered in coronary vessels of hypertensive hearts and the role of ETA and ETB receptors in these responses to ET-1, the vasoconstrictor response to ET-1 in coronary vessels was measured with or without ETA and ETB receptor antagonists. In isolated hearts of spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat, the coronary perfusion pressure was measured on a Langendorff apparatus with constant pressure (75 mm Hg). Coronary perfusion resistance (CPR) (mm Hg/ml/min/g) was calculated. ET-1 elicited dose-dependent increases of CPR in both normotensive and SHR rat hearts. However, the responses were significantly greater in SHR than those of WKY. Pretreatment with the ETA antagonist FR139317 and the ETB antagonist BQ788 inhibited CPR increases with ET-1 infusion. However, vasoconstrictor responses to ET-1 were still greater in SHR than in WKY after FR139317 or BQ788 infusion. These findings suggest that the augmented vasoconstrictor response of coronary artery to ET-1 is mediated by both ETA and ETB receptors. These changes may contribute to the impaired coronary circulation in hypertension.

Animals↗

PubMed1998

Blockade of angiotensin II receptors inhibits the increase in blood pressure induced by insulin.

To elucidate whether hyperinsulinemia increases blood pressure by increasing sympathetic outflow via the activation of the central angiotensin system, insulin was infused into urethane-anesthetized rats intravenously (i.v.) or intracerebroventricularly (i.c.v.) under euglycemic conditions. Infusion (i.v.) of insulin elicited pressor effects in a dose-dependent manner (13, 20, and 40 mU/min). Although depressor responses to i.v. injections of hexamethonium were significantly greater in insulin-infused than in saline-infused rats, i.v. captopril and d(CH2)5Tyr(Me)-arginine vasopressin did not show any differences between the groups. Infusions (i.c.v.) of insulin (8 mU/10 microl) also induced cardiovascular acceleration and augmented the depressor response to i.v. hexamethonium in insulin-infused rats. The i.c.v. pretreatment with the angiotensin II antagonist losartan inhibited the pressor responses to both the i.c.v. and i.v. infusion of insulin. These results suggest that the increase in blood pressure induced by euglycemic hyperinsulinemia is elicited by sympathetic activation and that hyperinsulinemia stimulates the angiotensin system in the brain to increase sympathetic nerve activity.

Angiotensin II↗

PubMed1998

Multiplex mutation screening of the BRCA1 gene in 1000 Japanese breast cancers.

To detect BRCA1 mutations in Japanese breast cancer patients, we screened 1,000 unselected primary cancers for mutations in exon 11, which accounts for 61% of the entire BRCA1 coding sequence. Using a method based on multiplex single-strand conformational polymorphism (SSCP) analysis of multiple restriction fragments generated by restriction-enzyme digestion of amplified DNA, we identified eight mutations. All eight were germline mutations; four of them were non-sense mutations or small deletions resulting in premature stop codons, and the other four were missense mutations. The Japanese carriers of these mutant BRCA1 alleles had developed breast cancers at ages ranging from 45 to 62, five of them bilaterally.

Aged↗

PubMed1998

A pure antiestrogen, ICI 182,780, stimulates the growth of tamoxifen-resistant KPL-1 human breast cancer cells in vivo but not in vitro.

The critical mechanisms responsible for antiestrogen resistance have not yet been elucidated. We previously established a breast cancer cell line, KPL-1, derived from a patient with recurrent disease which appeared under tamoxifenadministration. In a previous study, we suggested that this cell line is estrogen receptor (ER)-positive but tamoxifen-resistant. In the present study, the effects of a pure antiestrogen, ICI 182,780, on this cell line were investigated. Although tamoxifen inhibited neither cell growth nor estradiol-stimulated transcriptional activity in vitro, ICI 182,780, significantly inhibited both of them. Tamoxifen and ICI 182,780 were then administered to female nude mice bearing KPL-1 tumors. Tamoxifen had no effect on tumor growth, but ICI 182,780 unexpectedly stimulated it (p = 0.022). Estradiol tended to inhibit tumor growth (p = 0.198). Immunohistochemical analysis revealed that ICI 182,780 significantly increased the Ki6-labeling index (p<0.001) but estradiol decreased it (p = 0.035). To explore the possible mechanisms of these phenotypes, the mRNA levels of ER-alpha,ER-beta, transforming growth factor-beta1, fibroblast growth factor (FGF)-1 and FGF-4 in KPL-1 cells were compared with those in other ER-positive human breast cancer cell lines by reverse-transcription polymerase chain reaction. FGF-1 was overexpressed only in KPL-1 cells. This cell line is the first breast cancer cell line to be growth-stimulated by ICI 182,780 in vivo. Paracrine interaction between tumor cells and stromal cells mediated by growth factors, such as FGF-1, might be a key factor to explain the unique hormone responsiveness of KPL-1 cells.

Animals↗

PubMed1998

Ischemic and non-ischemic myocyte damage and antimyosin monoclonal imaging.

Antimyosin monoclonal antibody is a specific marker of impaired sarcolemmal integrity resulting not only from ischemia but also from non-ischemic myocardial injury, such as infection, inflammatory, or immunologic reactions, and alcohol or drug intoxication. In addition, antimyosin accumulation has been demonstrated in some forms of cardiomyopathy with unknown as well as known etiologies. Antimyosin positivity appears to indicate precisely the extent of myocardial necrosis and to reflect cardiac dysfunction in an acute stage of active myocardial damage caused by ischemia and inflammation. However, the correlation is not necessarily good in the chronic stages of the disease or in idiopathic cardiomyopathic hearts; in other words, cardiac antimyosin uptake can be detected even in myocardial tissue with a normal histologic appearance independent of the presence of inflammatory responses, myocyte necrosis, or functional or morphologic deterioration. Thus, antimyosin is useful not only for detecting and quantifying acute myocardial necrosis but also for specifically identifying ongoing or latently progressing myocardial degeneration and sarcolemmal disruption, which will certainly lead to myocardial necrosis. These characteristics may contribute to the early detection of myocardial damage and lead to the investigation of pathophysiologic mechanisms. Further progress in immunologic and radiolabeling techniques is necessary for better specificity and less antigenicity against humans in antimyosin monoclonal antibody imaging.

Animals↗

PubMed1998

Rheumatoid arthritis associated with renal amyloidosis and crescentic glomerulonephritis.

A 43-year-old woman with rheumatoid arthritis (RA), renal amyloidosis and crescentic glomerulonephritis had severe abdominal pain, melena and progressive renal failure. Autopsy findings revealed vasculitis of small and middle size of vessels and there was a deposition of amyloid in the small intestines. Although there were no findings of vasculitis in the kidney, amyloid deposition was noticed and 70-80% of glomeruli showed a crescentic formation. No immunological abnormality was found in glomeruli. Although the immunological mechanisms of crescentic glomerulonephritis were not necessarily eliminated, amyloid deposition may play a role in crescent formation.

Acute Kidney Injury↗

PubMed1998

[Successful removal of an infected pacemaker electrode adhered to the tricuspid valve].

A 77-year-old male suffered from pacemaker lead infection with pacing failure. Because he had a severe fever, we performed an interventional removal procedure with the help of a lead removal kit. However, the tip of the lead could not be withdrawn via the right internal jugular vein because it adhered tightly to the tricuspid valve. Two days later, we proceeded with an open removal procedure under cardiopulmonary bypass. The lead could be removed without any complication, and no inflammation was observed postoperatively. We report the case and discuss the indications and limitations of both the interventional and open methods.

Aged↗

PubMed1998

Outcome significance of thallium-201 and iodine-123-BMIPP perfusion-metabolism mismatch in preinfarction angina.

UNLABELLED: The relevance of brief antecedent ischemia to preservation of myocyte viability and cardiac function is still controversial in humans. Dysfunctioning but viable myocardium shows impaired fatty acid metabolism despite restored coronary perfusion. We asked whether preinfarction angina might be related to preservation of cell viability and better functional recovery in comparison with impaired fatty acid metabolism. METHODS: Tomographic imagings with thallium and beta-methyl-p-iodophenyl penta-decanoic acid (BMIPP) were performed in 32 patients with first acute myocardial infarction who received primary coronary angioplasty: 20 patients with preexisting angina before infarction (Group A) and 12 without (Group B). Thallium and BMIPP abnormalities were quantified as a severity index by a polar map. Regional function was quantified by ventriculography and followed up. RESULTS: Despite no significant difference in coronary risk factors, cardiac function and angiographic findings, the thallium severity index was significantly lower than that of BMIPP (62+/-45 versus 96+/-59) in Group A but not in Group B (104+/-65 versus 115+/-68); the thallium severity index in Group A was significantly lower than that in Group B, but there was no significant difference in BMIPP abnormality between them. The BMIPP severity index correlated significantly with that of thallium in both groups. However, the regression line in Group A shifted downward and was statistically different compared with that in Group B. Regional function at an acute stage was significantly improved from 107+/-31 to 70+/-31 s.d./chord during follow-up in Group A but not in Group B (109+/-62 versus 106+/-52). The ratio of the thallium severity index to that of BMIPP at an acute stage was significantly related to improved regional wall motion during follow-up in the reperfused patients (y=-53x + 65, r=0.667). CONCLUSION: Preinfarction angina preserves myocyte viability relative to fatty acid metabolism, resulting in augmented perfusion-metabolism mismatch and functional improvement in patients undergoing successful reperfusion, indicating cardioprotective effects of preinfarction angina.

Aged↗

PubMed1998

[Involvement of glucose metabolism abnormalities and insulin resistance in atherosclerotic coronary artery disease: semiquantitative coronary angiography study].

Insulin resistance is known to be important in the aggravation of established coronary risk factors, but it is unclear whether insulin resistance might cause coronary artery disease as diabetes mellitus. To evaluate the relationship between insulin resistance and coronary atherosclerosis, the angiographic semiquantitative score of coronary atherosclerosis was investigated in 216 patients (175 males, 41 females) with coronary artery disease and the varying degrees of glucose metabolism including insulin resistance. Insulin resistance was estimated by plasma insulin level at 120 min after the 75g oral glucose tolerance test. Patients were divided into 3 groups according to the levels of glucose metabolism: 37 patients with treated diabetes mellitus, 48 with glucose intolerance and non-treated diabetes, and 131 with normal glucose tolerance. Multivessel disease was more frequently seen in the treated diabetes group (67.6%) than in the glucose intolerance and non-treated diabetes groups (43.8%) and in the normal glucose tolerance group (40.5%). The severity of coronary artery stenosis (8.5 +/- 3.9 vs 7.6 +/- 3.7 vs 6.6 +/- 3.7) and calcification (6.5 +/- 6.3 vs 3.3 +/- 3.3 vs 4.0 +/- 4.8) were significantly higher in the treated diabetes group than in other groups. Distal coronary lesions were significantly more frequent in the treated diabetes group (61.1% vs 17.6% vs 27.4%) than in other groups. Half of the patients in the normal glucose tolerance group had hyperinsulinemia. Multivessel disease was significantly more frequent in the insulin resistant subgroup than in the insulin non-resistant subgroup (59.4% vs 25.0%, p = 0.011). The severity of coronary artery stenosis was significantly higher in the insulin resistant subgroup than in the insulin non-resistant subgroup (8.6 +/- 3.9 vs 5.6 +/- 3.0, p < 0.001), but the severity of coronary artery calcification was not significant. Distal coronary lesions showed a tendency to increase in the insulin resistant subgroup (37.5% vs 12.0%, p = 0.081). These results suggest that insulin resistance is an important risk factor for coronary artery disease in patients with normal glucose tolerance, and is related to the severity and multiplicity of coronary atherosclerosis as in patients with diabetes.

Blood Glucose↗

PubMed1997

Correlation of Allelic Losses and Clinicopathological Factors in Primary Breast Cancers.

Human breast cancers frequently show allelic loss or loss of heterozygosity (LOH) at apecific chromosomal regions. To understand the possible role of these genetic alterations in tumor development and progression, we examined LOH at loci on chromosomal arms 1p, 3p. 11p, 13q, 16q, 18q, and 22q in 140 to 246 cases of primary breast cancers and compared it with lymph node metastasis, histological type, tumor stage, estrogen receptor (ER) and progesterone receptor (PgR) status. LOH at 1p22-31 correlated with lymph node metastasis and a tumor size of greater than 2 cm. LOH at 13q12-14 and 18q21 were most frequently observed in tumors of the solid-tubular type. LOH at 1p34-36 was more frequent in tumors of the scirrhous and solid-tubular types than in other less aggressive histological types. Furthermore, a significant association was observed between LOH at 3p14-21, 11p11-15 and 13q12-14 and the absence of progesterone receptors. These results suggest that some clinical characteristics of breast cancers are determined by loss of tumor supperssor genes present at specific chromosomal regions.

Journal Article↗