Biomedical subjects
Publications and source records attributed to J Yamamoto.
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The primary structure of nucleoside diphosphate (NDP) kinase from spinach leaves has been deduced from its cDNA sequence. A lambda gt 11 cDNA library derived from spinach leaves was screened using an antibody against NDP kinase I, which we previously purified to electrophoretic homogeneity (T. Nomura, T. Fukui, and A. Ichikawa, 1991, Biochim. Biophys. Acta 1077, 47-55). The cDNA sequences of positive clones contained the amino acid coding region (444 base pairs) for NDP kinase I as well as 5' and 3' noncoding regions of 33 and 361 base pairs, respectively. The cDNAs hybridized to a 1.1-kb mRNA. NDP kinase I contains 148 amino acid residues with a molecular mass of 16,305, which is in excellent agreement with that of the purified enzyme (16 kDa). Homology was found between the sequence of spinach NDP kinase I and those of the rat, Myxococcus xanthus, and Dictyostelium discoideum NDP kinases, as well as the human Nm23-gene product and the awd protein of Drosophila melanogaster.
The present study established that 2',3'-cyclic-nucleotide 3'-phosphodiesterase doublet common to mammalian brain originates from an alternative splicing. Peptides specific to the predicted larger translation product were synthesized and antisera against these peptides were prepared. Immunostaining of SDS/PAGE blots showed that the antisera react with the larger protein, but not with the smaller protein, of 2',3'-cyclic-nucleotide 3'-phosphodiesterase doublet in all mammals studied.
It is essential to detect section planes during hepatectomy, notably for limited resections in cirrhotic patients. The authors describe a technical artifice, the use silicon-impregnated compresses, to help in the peroperative ultrasonographic detection of these section planes.
In the preceding paper (Kawai, H. et al. (1992) Biochim. Biophys. Acta 1133, 172-178), we reported that in mastocytoma P-815 cells dexamethasone and 12-O-tetradecanoylphorbol-13-acetate (TPA) synergistically enhanced the de novo synthesis of L-histidine decarboxylase (HDC). Here we found that Ca2+ acted synergistically with cAMP in the induction of HDC mRNA and HDC activity in mastocytoma P-815 cells, and that the mechanism underlying the enzyme induction by Ca2+ plus cAMP was distinguishable from that by dexamethasone plus TPA. Ca2+ ionophore A23187, itself having no significant activity, markedly enhanced the induction of HDC activity by N6,O2'-dibutyryl cAMP (db cAMP) or cAMP-inducible prostaglandins such as PGE1, PGE2 and PGI2 in the presence of the phosphodiesterase inhibitor, Ro201724. However, A23187 had little effect on increases in HDC activity induced by other known stimulants, such as TPA, dexamethasone and sodium butyrate. These results suggest that A23187 has a specific effect on the induction of HDC activity due to an increased level of cAMP. The finding that both A23187 and cAMP enhanced HDC activity suggests that both Ca2+/calmodulin and cyclic nucleotide dependent protein kinase play essential roles in the process of enhancement of HDC activity. To examine this possibility, we studied the effects of W-7, an inhibitor of calmodulin, removal of extracellular Ca2+, and H-8, an inhibitor of cAMP-dependent protein kinase, on the enhancing activity of A23187 plus db cAMP. The enhancement of HDC activity by A23187 plus db cAMP was inhibited by W-7, removal of extracellular Ca2+, and H-8. The increase in HDC activity was due to the de novo synthesis of the enzyme, since it was suppressed by the addition of cycloheximide or actinomycin D, and was well correlated with the marked accumulation of a 2.7 kilobase HDC mRNA. Furthermore, the mechanism underlying the induction of HDC by db cAMP plus A23187 is distinguishable from that in the case of dexamethasone plus TPA, since preexposure to dexamethasone plus TPA for 12 h, for a plateau level to be reached, did not affect the subsequent increase in HDC activity due to db cAMP plus A23187.
The pharmacokinetics of temocapril hydrochloride, a novel prodrug-type angiotensin-I converting enzyme (ACE) inhibitor, has been studied in patients with mild (Group II) to severe (Group III) renal insufficiency in comparison with subjects with normal renal function (Group I). The pharmacokinetic parameters of the active diacid metabolite, including Cmax, AUC and half-life (t1/2), showed only slight changes between the three groups: AUC (0-inaffinity) was significantly larger in Group III than Group I, and t1/2 tended to be prolonged in Group III, but the change was not significant. The urinary recovery of the diacid was significantly decreased in Group III. (Group I, 28.1%, Group II, 21.6%, Group III, 12.8%). Compared with other ACE inhibitors, which are mainly excreted through the kidney, the plasma concentration of the active diacid metabolite was hardly influenced by renal function. It was speculated that lowering of the dose of temocapril might be recommended only in patients with severe renal insufficiency.
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The inhibitory effects of ticlopidine and acetylsalicylic acid (ASA) on thrombus formation in rat mesenteric microvessels were studied. The results were compared with the effect of the drugs on platelet aggregation in citrated whole blood. He-Ne laser-induced thrombus formation in arterioles and in venules was significantly inhibited by 100 mg/kg ticlopidine. In contrast, a higher dose of ASA (300 mg/kg) was needed to inhibit thrombus formation and the effects of ASA were observed only in arterioles and not in venules. In addition, although the inhibition by ASA in arterioles was not strong it followed a dose-dependent manner, suggesting that the differential effect of ASA on platelets and endothelium may not be evident in vivo. Ticlopidine and ASA strongly inhibited ADP-induced whole blood platelet aggregation, but not collagen- or thrombin-induced platelet aggregation.
Poly-L-lysine with molecular masses of 3.3-290 kDa increased the amidolytic activities of leukocyte elastase and cathepsin G at low concentration, but had little effect on the activities of pancreatic elastase, alpha-chymotrypsin, plasmin and thrombin. Highly purified cathepsin G was obtained from column of EAH Sepharose 4B or Suc-L-Tyr-D-Leu-D-Val-pNA-Sepharose (affinity chromatography) by elution with poly-L-lysine solution (0.4 mg/ml, molecular weight (MW.) 290000 or 2.2 mg/ml, MW. 3300). Leukocyte elastase, adsorbed to Suc-L-Tyr-D-Leu-D-Val-pNA-Sepharose, was not eluted with poly-L-lysine solution. The amino acid composition of purified cathepsin G has been determined.
Thirty-two benign hepatic lesions, which were resected because of a diagnosis of malignancy, were reviewed to demonstrate the characteristics of the problem and to consider the best course of management. The preoperative diagnoses included 21 hepatocellular carcinomas, six metastases and five others. As the final diagnosis, hemangioma and focal nodular hyperplasia were the two major lesions mimicking malignancy, accounting for seven and six patients, respectively. Four of seven hemangiomas were atypical, with a considerable amount of fibrosis. Focal nodular hyperplasia and adenoma were misdiagnosed as hepatocellular carcinoma among other malignancies. Two instances each of necrotic tissue and hemangioma were diagnosed as metastatic carcinoma. The lesions that were studied had main features, including a diameter of less than 4 centimeters in 23 patients, evident discrepancy among the roentgenologic diagnoses in 25 patients and no rapid increase in size in 28 patients. Four of nine needle biopsies performed gave false-positive results and did not always provide adequate information. It was concluded that 15 of the 32 patients, who satisfied the aforementioned three criteria, could have been observed more carefully. However, in the other 17 patients, surgical intervention was considered justified because of an indication of a higher likelihood of a real malignancy.
BACKGROUND: To find the rational surgical strategy for the treatment of intrahepatic cholangiocarcinoma (ICC), clinical features of ICC were studied in 20 patients who underwent hepatic resection in the National Cancer Center Hospital from 1980 to 1990. METHODS: According to the morphologic pattern, we classified the ICCs into two subcategories, mass-forming and infiltrating, which correlated with their biologic behavior. RESULTS: Of 10 patients who underwent hepatectomy for mass-forming ICC, three survived more than 5 years without recurrence. The 1-, 3-, and 5-year survival rates were 59.3%, 44.4%, and 44.4%, respectively. Of 10 patients who underwent hepatectomy for infiltrating ICC, one survived more than 5 years without recurrence. The 1-, 3-, and 5-year survival rates were 72.0%, 27.0%, and 27.0%, respectively. The pathologic findings and recurrences indicated that the salient feature of the mass-forming type was its tendency for intrahepatic metastasis especially near a main lesion, and of the infiltrating type was the infiltrative spread via Glisson's capsule and hilar lymph nodal metastasis. CONCLUSIONS: An anatomic and extensive liver resection should be performed for mass-forming ICC, whereas a hepatectomy with excision of the extrahepatic bile duct and hilar lymph nodal dissection is recommended for infiltrating ICC.
A new strategy for the treatment of hepatic malignancy located deep in the cirrhotic liver is reported. A 66-year-old man, who had a 3 cm hepatocellular carcinoma in the cranial part of the caudate lobe, underwent an isolated caudate lobectomy. By transecting along the interlobar plane and opening the hepatic hilus anteriorly, we resected almost the entire caudate lobe without loss of the remaining liver parenchyma.
Result of hepatic resection in 150 patients with hepatocellular carcinoma (HCC) harboring up to three lesions smaller than 3cm in diameter (PEI candidates) and 144 patients with multiple lesions (TAE candidates) was studied. In PEI candidates, associated liver diseases were liver cirrhosis in 108 patients (72%) and chronic hepatitis in 41 (27.3%). Survival rates at 1-, 3- and 5-years were 98.0%, 83.5% and 61.4%, respectively. Prognosis of the patients with a well-differentiated solitary lesion was particularly good. In TAE candidates, 1-, 3- and 5-years survival rates were 98.5%, 57.8% and 33.7%, respectively. Half of the patients were considered to have multicentric disease, and their prognosis was better than that with intrahepatic metastases. Surgical resection is recommended as a primary treatment of HCC when the patients are feasible for surgery even if nonsurgical treatments are possible. Further study is required to establish the proper indication for nonsurgical procedures as a primary treatment of HCC in patients who are candidates of surgery.
To evaluate the extent and characteristics of infarct areas, we performed indium-111 monoclonal antimyosin Fab (InAM), thallium-201 (TL) and Tc-99m pyrophosphate (PYP) imagings in 17 patients with acute myocardial infarction, and tried to find out the mechanism that causes difference of these imagings. In each study, the extent scores as an index of the infarct area were obtained by single photon emission computed tomography (SPECT), and comparisons were made between the results obtained. The overlap between InAM and TL imagings obtained by SPECT was evaluated. Location, severity, extent and patterns of accumulation were compared between InAM and PYP with both planar image and SPECT. The extent scores of InAM correlated well with those of TL (r = 0.73, p < 0.01). However, the overlap of both methods was recognized in 8 of 17 patients, in whom wall thickness of the infarct area as obtained by echocardiography was well preserved. The left ventricular regional asynergy was mild in 6 of these 8 patients. Coronary angiography showed poor or no collateral circulation in these cases. Although there were generally close correlations of the extent scores between InAM and PYP, discrepancy was noted in 2 cases for location; 2 for severity, 5 for extent, and 3 for patterns of accumulation. These differences may be attributed to the timings of imaging, coronary reperfusion and different mechanisms of accumulation. In conclusion, the extent of acute myocardial infarction obtained by InAM correlates well with those obtained by TL and PYP, with some exceptions.
A patient with ulcerative colitis developed skin pigmentation and diffuse pulmonary shadowing without respiratory symptomatology, while taking sulfasalazine. The clinical picture and radiological abnormalities disappeared spontaneously on discontinuation of the drug. Histopathological studies from specimens taken by transbronchial biopsy showed bronchiolitis obliterans with fibrosing alveolitis. Sulfasalazine-induced lung disorder is an extremely rare entity which must be considered in all ulcerative colitis patients while on sulfasalazine therapy, despite the absence of pulmonary symptomatology.
The prognosis for ductal cancer of the pancreas is extremely poor. Diagnosis of pancreatic cancer in the earlier stages has become possible by taking note of early symptoms, mild abdominal pain, back pain, anorexia, diabetes and obstructive jaundice. Presently, measurements of amylase in serum and urine, serum elastase-1, serum CA 19-9 and US are usually used for screening patients with the symptoms. Furthermore, for correct diagnosis, intensive study by US, dynamic CT, ERCP, MRI, cytological examination and CEA of pancreatic juice, endoscopic pancreatoscopy and endoscopic ultrasonography are used. The results of surgical treatment for resectable pancreatic cancer are not generally favorable. Extended pancreatic resection (pancreatoduodenectomy, total pancreatectomy or distal pancreatectomy) with en bloc dissection of the lymph nodes has been performed for patients with invasive cancer. However, local recurrence and distant metastasis usually occurred after surgery. It seems difficult to cure pancreatic cancer by surgery alone. To improve the prognosis of resectable pancreatic cancer, multimodality treatment with intraoperative radiation therapy and chemotherapy is performed and a better outcome is achieved.