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Biomedical subjects

N Harada

Publications and source records attributed to N Harada.

At least 577 records · Page 32Linked to original sources

[Early determination of the effect of preoperative TAE by observation of serum AFP changes in patients with hepatocellular carcinoma].

Serum Alpha-fetoprotein (AFP) was assessed several times after preoperative TAE on 18 patients with hepatocellular carcinoma, and postoperatively the resected specimens were examined histopathologically. Changes in AFP level after TAE showed five typical patterns: AFP continued to rise in spite of treatment (non-effective type); AFP shows regular and equal increases and decreases (undulating type); AFP showed an increase after initially decreasing (increasing after decreasing type); AFP decreased gradually to normal levels (gradually decreasing type); and AFP decreased along a half-value period line to normal levels (half-value period type). These AFP patterns were intimately related to necrosis rate of tumor and other factors such as tumor size and existence of daughter tumors. Even when the AFP level decreased to 1/2 one week after TAE, the tumor showed only about 70% necrosis. Only when the AFP level fell into 1/4 of the original level after one week we could expect complete necrosis. Immuno-histological findings revealed AFP-producing cells in carcinoma but not in necrotic cells. It seems therefore, that the immuno-histological technique is uneffective in determining the viability of tumor cells.

Carcinoma, Hepatocellular↗

Adenosquamous carcinoma of the liver.

Two cases of adenosquamous carcinoma of the liver are presented. In one case, the carcinoma probably arose in the left hepatic duct, whereas in the other, it probably developed from a liver cyst. Only 10 other such tumors have been reported in the literature. Analysis of these cases indicates that the prognosis etiology of adenosquamous carcinoma may be similar to that of intrahepatic bile duct carcinoma. The prognosis for this tumor is very poor. Operation seems not to be an effective treatment, but radiation therapy may be of some use. Several terms, such as adenosquamous, adenoacanthoma, and mucoepidermoid carcinoma, have been used for carcinomas containing both adenomatous and squamous elements. We discuss the etiology and the origin of this rare liver tumor and conclude that the term adenosquamous carcinoma is the most apt.

Adenocarcinoma↗

Leiomyoblastoma of the greater omentum. A case report and review of literature.

A case of leiomyoblastoma of the greater omentum, occurring in a 36-year-old man was described. Leiomyoblastoma of the omentum is extremely rare and only 6 cases have been reported in the Japanese and English literature up to date. According to the review of these cases, including the present case, 1) females were affected more frequently than males, and the age ranged from 36 to 76 years; 2) leiomyoblastoma was usually a large tumor which caused abdominal fullness and pain, and occasionally complicated with anemia and bloody ascites; 3) mitosis was rare, and there was no sign of metastasis and recurrence. Finally the morphological criteria and clinical parameters of malignancy in leiomyoblastoma were discussed.

Adult↗

Sensory axonal dysfunction in the upper and lower limb of diabetic patients and its relation to diabetic retinopathy.

We studied the sensory and motor potentials of the median and posterior tibial nerves and sural nerves in 20 insulin-treated diabetic patients, aged 21-71 years, with a known duration of 1 month to 25 years. Individual levels of sensory velocity were within normal range or slightly reduced in diabetic patients. However, the reductions of sensory potential amplitude were obvious in the sural nerve. No relation was found between sensory amplitude and either known diabetic duration or retinal diabetic changes. These results suggest that axonal degeneration of sensory fibers cannot easily be corrected in comparison to the slight changes caused by segmental demyelination.

Adult↗

Cystadenoma and cystadenocarcinoma of the liver: localization of carcinoembryonic antigen.

Cystadenomas and cystadenocarcinomas of the liver are rare tumors. The distribution of carcinoembryonic antigen (CEA) in two cystadenomas and a cystadenocarcinoma was examined immunohistochemically by the peroxidase-labeled antibody method, at the light microscopic level. In the cystadenomas and areas consisting of benign-appearing cells in the cystadenocarcinoma, CEA was localized to the luminal surfaces of the glandular cells appearing as thin linear stains. In malignant epithelial cells forming nests and daughter cysts of the cystadenocarcinoma, CEA was demonstrated throughout the cytoplasm, in a diffuse pattern. Thus, the immunohistochemical localization of CEA may be helpful in the diagnosis of borderline lesions and in determining the distribution of benign and malignant epithelium in cystadenocarcinomas. The etiology, clinical features, pathology and treatment of these rare tumors are discussed.

Adult↗

Mucus-secreting presacral cyst--a case report.

A mucus-secreting presacral cyst was found in a 49-year-old woman who complained of dysuria. A routine rectal digital examination revealed a retrorectal mass. Diagnostic imaging demonstrated a large presacral cystic tumor. The cyst was removed through a transsacral approach. Histologically, the cyst membrane consisted of squamous and columnar mucus-secreting epithelium, and was diagnosed as a mucus-secreting presacral cyst.

Cysts↗

Expression of synthetic human-lysozyme gene in Saccharomyces cerevisiae: use of a synthetic chicken-lysozyme signal sequence for secretion and processing.

A multicopy plasmid was constructed to direct the synthesis and secretion of human lysozyme (HLY) in Saccharomyces cerevisiae. This plasmid contains a synthetic chicken-lysozyme signal sequence (SIG) and a synthetic HLY structural gene, both inserted between the yeast GAL10 promoter and 2 mu plasmid FLP (flip-flop recombination gene) terminator. The resulting plasmid directed the expression of the hybrid pre-lysozyme, with most of the HLY activity secreted into the culture medium and extracellular periplasmic space. The HLY activity in the culture medium increased with cell growth. The yeast accurately processed the hybrid precursor at the junction between the chicken SIG and the coding sequence downstream, yielding mature HLY. HLY purified from the culture medium was homogeneous and displayed specific activity identical to that of authentic HLY.

Animals↗

Collective review of small carcinomas of the pancreas.

To determine problems involved in the treatment and diagnosis of pancreatic cancer, a collective study of small carcinoma of the pancreas (2 cm or less in diameter) was performed. One hundred six cases were collected and analyzed. The results were as follows: In small carcinoma of the pancreas, the resectability rate was 99.0% and the operative mortality rate was 4%. Only 44% of the patients belonged to Stage I, and 14% belonged to Stage III or IV. Lymph node involvement, capsular invasion, retroperitoneal invasion, and vascular invasion were found in 30, 20, 12, and 9% of the patients, respectively. The postoperative cumulative 5-year survival rate was 30.3%, and that of Stage I was 37.0%. A small-sized tumor of the pancreas is not always an early carcinoma, but a tumor in Stage I may be regarded as an early carcinoma. Percutaneous transhepatic cholangiography and endoscopic retrograde cholangiopancreatography were the main diagnostic indicators in cases with and without jaundice, respectively. There was no specific single serum test for detecting small pancreatic cancer.

Adult↗

Establishment of an assay system for the detection of translated materials of T-cell-replacing factor mRNA in Xenopus oocytes.

We established an assay system for detecting T cell-replacing factor (TRF) activity of translated materials in Xenopus oocytes of poly (A)-positive mRNA extracted from a T cell hybrid cell line, B151K12 (B151) which constitutively produces TRF. Since it was difficult to detect TRF activity of the translated products of B151-mRNA, partly because of low TRF activities, we developed the following two systems. First, RNA was prepared from B151 cells stimulated with phorbol myristate acetate and calcium ionophore A23187 because such stimulations augmented TRF production by approximately three to five-fold. Second, interleukin 2 (IL-2, 125 U/ml) was added to the culture of BCL1 cells to detect a small amount of TRF-active materials since IL-2 synergizes with a suboptimal dose of TRF to induce IgM secretion in TRF-responding BCL1 cells (chronic B cell leukemic cells). Here we describe TRF activity of translation products of B151-mRNA in Xenopus oocytes. B151-TRF mRNA was detected in the fractions sedimented between 15 and 18S by analysis using sucrose density gradient centrifugation.

Animals↗

Cardiovascular effects of NPK-1886, a new dihydropyridine compound with calcium entry blocking activity.

The cardiovascular effect of NPK-1886 (NPK), a novel photostable dihydropyridine compound, was studied by comparing it with that of nifedipine (Nif). In normal Wistar rats (NWR), systolic blood pressure was only slightly depressed by NPK or Nif, while in three types of hypertensive rats (i.e., spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR) and DOCA-saline-induced hypertensive rats (DOC-Na-R)), the hypotensive potency of NPK was more than or equal to that of Nif. The effectiveness of NPK on the normal and hypertensive models was in the following order: DOC-Na-R, RHR, SHR, NWR. Coronary perfusion flow in Langendorff's heart was increased almost the same extent by NPK and Nif. On isolated rabbit aortic strips, the antagonistic potencies of NPK, like those of Nif, were greater for calcium than for norepinephrine, serotonin and angiotensin II. The negative ino- and chronotropic potency of NPK in isolated guinea-pig right atria was less than that of Nif. The slow membrane action potentials of guinea-pig papillary muscle were suppressed by NPK, but less than by Nif, with manifestations of a reduction of Vmax and AP-duration. These results indicate that NPK has a potent hypotensive effect on hypertensive models and a weaker cardiac inhibition. The general toxicity of NPK was lower than that of Nif.

Action Potentials↗

[The effects of protein and amino acids on DNA synthesis in regenerating liver].

In order to estimate the effects of protein and amino acids on regenerating liver, the induction of enzymes involved in synthesis of DNA was studied in rats fed protein free diet. In the regenerating livers of rats of the protein free diet, increase of liver weight and DNA content were stopped 48 hours after hepatectomy, and induction of DNA synthesizing enzymes such as dCMP deaminase, ribonucleotide reductase, and thymidine kinase were depressed and shortened. On the other hand, induction of protein or RNA synthesizing enzymes such as polyamine, ornithine decarboxylase, and tyrosine aminotransferase were not depressed by protein deprivation. The results indicate that protein deprivation inhibits the DNA synthesizing enzymes specifically, and regenerating liver cells can not enter S phase of cell cycle. When rats were maintained solely by total parenteral nutrition after hepatectomy, amino acids were essential for induction of DNA synthesizing enzymes. In particular, induction of these enzymes were regulated by 7 amino acids include Val, Leu, Ile, Met, Trp, Phe, and Thr, and most of these plasma amino acid levels were depressed after hepatectomy. By administration of amino acids for 12 hours just after hepatectomy, the DNA synthesizing enzymes were almost normally induced. This suggests that amino acids administration just after hepatectomy is effective to induce the DNA synthesizing enzymes for hepatic regeneration.

Amino Acids↗

Sexual dimorphism of testosterone 15 alpha-hydroxylase mRNA levels in mouse liver. cDNA cloning and regulation.

A cDNA library was constructed from 129/J female mouse liver poly(A)+ RNA immunoenriched for testosterone 15 alpha-hydroxylase (P-450(15)alpha) in the expression vector pUC9. Fifteen clones coding for P-450(15)alpha were identified by duplicate colony hybridization to nick-translated cDNAs synthesized from immunoenriched or depleted poly(A)+ RNA. Recombinant plasmid p 15 alpha-29 contained the largest cDNA (1.6 kilobases) and cross-hybridized strongly with all other clones. cDNAs representing two different transcripts were identified based on restriction map analysis. Clones p 15 alpha-29 and p 15 alpha-15 have identical internal restriction fragments generated by ClaI, BamHI, and StuI digests, but p15 alpha-15 has unique PstI and HindIII sites located within 150 base pairs of each other. This suggests P-450(15)alpha is transcribed from two genes. Northern hybridization of poly(A)+ RNA with nick-translated p15 alpha-29 or p15 alpha-15 showed a single size mRNA of 2.1 kilobases. The level of P-450(15)alpha mRNA was 6.6 times higher in 129/J female than in male mice. The difference between P-450(15)alpha mRNA levels in females and males was positively correlated with P-450(15)alpha protein detected by anti-P-450(15)alpha and testosterone 15 alpha-hydroxylase activity in microsomes. Sexual dimorphism in hepatic testosterone 15 alpha-hydroxylase activity is shown to result from differential mRNA regulation in females and males.

Animals↗

Characterization of testosterone 16 alpha-hydroxylase (I-P-450(16) alpha) induced by phenobarbital in mice.

Cytochrome P-450 (I-P-450(16) alpha), which is associated with phenobarbital-induced testosterone 16 alpha-hydroxylation activity, was purified from livers of phenobarbital-treated female 129/J mice on the basis of the specific hydroxylation activity in fractions eluted from columns of octylamino-Sepharose 4B, hydroxylapatite, DEAE-Bio-Gel A, and isobutyl-Sepharose 4B. The specific cytochrome P-450 content of the purified I-P-450(16) alpha fraction was 12.4 nmol/mg of protein, and it had an apparent molecular weight of 54K. The specific activity of reconstituted testosterone 16 alpha-hydroxylation activity with the purified I-P-450(16) alpha fraction was 6-8 nmol min-1 (nmol of cytochrome P-450)-1. Rabbit antibody raised against the purified I-P-450(16) alpha fraction inhibited nearly 100% of the 16 alpha-hydroxylation activity in liver microsomes of phenobarbital-treated female 129/J mice but did not affect hepatic microsomal 16 alpha-hydroxylation activity of untreated male and female 129/J mice at all. In hepatic microsomes of phenobarbital-treated male 129/J mice, 70% of the 16 alpha-hydroxylation activity, at most, was catalyzed by I-P-450(16) alpha, and the residual 30% of the activity was catalyzed by C-P-450(16) alpha. The increase of I-P-450(16) alpha by phenobarbital was due to de novo synthesis of I-P-450(16) alpha, and this induction was not sexually regulated in 129/J mice. Anti-C-P-450(16) alpha [Harada, N., & Negishi, M. (1984) J. Biol. Chem. 259, 12285-12290] did not inhibit the 16 alpha-hydroxylation catalyzed by I-P-450(16) alpha; thus, I-P-450(16) alpha and C-P-450(16) alpha are immunochemically distinct isozymes of testosterone 16 alpha-hydroxylase.

Animals↗

Kinetic isotope effects on cytochrome P-450-catalyzed oxidation reactions: full expression of the intrinsic isotope effect during the O-deethylation of 7-ethoxycoumarin by liver microsomes from 3-methylcholanthrene-induced hamsters.

The intrinsic primary deuterium isotope effect for the O-deethylation of 7-ethoxycoumarin has been estimated by the Northrop method [D. B. Northrop (1977) in Isotope Effects on Enzyme-Catalyzed Reactions (Cleland, W. W., O'Leary, M. H., and Northrop, D. B., eds.), pp. 122-152, University Park Press, Baltimore] for the microsomal cytochrome P-448 system from 3-methylcholanthrene-induced hamster livers. The intrinsic isotope effect (Dk = 5.5) was found to be equivalent to the observed deuterium isotope effect, demonstrating that the isotope effect for this reaction was fully expressed by this cytochrome P-448 system. These data unequivocally demonstrate that C-H bond cleavage is the rate-limiting step in the overall reaction catalyzed by this system. The decrease in the rate of product formation, occurring as a consequence of deuterium substitution, resulted in a reduction in the quantity of substrate metabolized but was not accompanied by the change in regiospecificity observed in previous studies with a hepatic cytochrome P-448 isozyme purified from 3-methylcholanthrene-induced rats. These data demonstrate that the catalytic site of the hamster isozyme(s) offers more constraints to 7-ethoxycoumarin reorientation than does the catalytic site of the rat liver isozyme.

Animals↗