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Biomedical subjects

S Okuda

Publications and source records attributed to S Okuda.

At least 307 records · Page 17Linked to original sources

[Cell kinetic study of human gastric cancers--using an in vitro 3H-thymidine labeling method].

For the purpose of investigating cell the kinetics of human gastric carcinoma, the distribution of 3H-thymidine labeled cells and the labeling index were evaluated in biopsy specimens obtained from 52 patients with gastric cancer, using an in vitro labeling technique. Adenocarcinomas were scattered with labeled cells, while in carcinoid speciners labeled cells were confined to the periphery of tumor cell nests. Characteristically, small-sized cells were exclusively labeled with 3H-thymidine in signet-ring cell carcinomas but signet-ring cells bearing a large amount of mucin were not. Thus signet-ring cells could be regarded as cells in a differentiated condition which have lost their prolife-rating capability. The labeling index of gastric cancers ranged from 10 to 20% in most cases although it varied greatly from case to case (2.2-40.8%). The values of the labeling index were correlated with neither the degree of histological differentiation, macrascopic appearance nor the depth of mural invasion of carcinomas.

Adenocarcinoma↗

Necrotizing vascular lesions in spontaneously hypertensive rats with nephrotic syndrome: hypercoagulability as a contributory factor.

Heymann nephritis was induced in rats with spontaneous hypertension (group HN), and renal lesions were investigated at the twentieth and thirty-sixth week. An identical group given antihypertensive drugs (group HN-AH), an identical group given anticoagulant drugs (group HN-AC), and a nonimmunized control group of spontaneously hypertensive rats (controls) were also examined. Massive proteinuria, hypoalbuminemia, and hyperlipidemia were present in groups with induced Heymann nephritis (HN, HN-AH, and HN-AC). Coagulation studies demonstrated a shortening of prothrombin time, an increase in serum fibrinogen and thrombocytes, and a reduction of antithrombin III in the groups HN and HN-AH. Necrotizing lesions were observed only in group HN and without further elevation in blood pressure. Intravascular thrombosis was prominent at the twentieth week, and marked fibrinoid necrosis appeared at the thirty-sixth week. These vascular lesions were not observed in the HN-AH, HN-AC, and control groups. Thus, a state of hypercoagulability in addition to high blood pressure probably contributes to the genesis of necrotizing vascular lesions in spontaneously hypertensive rats with nephritis.

Animals↗

Cerulenin resistance in a cerulenin-producing fungus. III. Studies on active-site peptides of fatty acid synthetase from Cephalosporium caerulens.

Active-site peptides of acetyl transferase, condensing enzyme and acyl carrier protein in the neighborhood of the prosthetic group, 4'-phosphopantetheine, of Cephalosporium caerulens fatty acid synthetase were investigated. The enzyme was reacted with [14C]acetyl-CoA or [14C]iodoacetamide. 14C-Labeled enzyme was digested with pepsin, trypsin or both. 14C-Labeled peptides were isolated by several purification procedures. The amino acid sequence of the active site of condensing enzyme was determined to be Tyr-Gln-Val-Glu-Ser-Cys-Pro-Ile-Leu-Glu-Gly-Lys and that of acetyl transferase was Phe-Ser-Gly-Ala-Thr-Gly-His-Ser-Gln-Gly. The amino acid composition around the 4'-phosphopantetheine-carrying serine was determined to be Asx2, Thr, Ser, Glx3, Gly2, Ala, Ile, Leu3, and Lys. When these active-site peptides were compared with those of Saccharomyces cerevisiae synthetase, a high degree of homology was observed in the active-site peptides of the acetyl transferase and acyl carrier protein domains. However, that of the condensing enzyme domain gave lower homology. These findings may support the assumption that the low reactivity of cerulenin with C. caerulens synthetase is a consequence of the structure of the condensing enzyme domain.

Acetyl Coenzyme A↗

2,3-diamino-2,3-dideoxy-D-glucofuranurono-6,3-lactam from the hydrolysate of Pseudomonas aeruginosa P14 lipopolysaccharide.

An unknown amino sugar, U-7, which had been detected in the hydrolysate of the polysaccharide fraction (F-A) of Pseudomonas aeruginosa P14 lipopolysaccharide, was isolated from the hydrolysate of whole cells of this micro-organism and converted into the N-acetyl derivative (U-7NAc). On the basis of i.r.-absorption spectrometry, 13C-n.m.r. and 1H-n.m.r. spectroscopy and mass spectrometry, the structure of compound U-7NAc was identified as 2-acetamido-3-amino-2,3-dideoxyhexofuranurono-6,3-lactam. The configuration of compound U-7NAc was then unequivocally identified as 2-acetamido-3-amino-2,3-dideoxy-D-glucofuranurono-6,3-lactam by comparing the synthetic and natural compounds. Compound U-7 and synthetic 2,3-diamino-2,3-dideoxy-D-glucofuranurono-6,3-lactam showed the same behaviour on chromatography. G.l.c.--mass-spectral analyses of fraction F-A and synthetic 2,3-diacetamido-2,3-dideoxy-D-glucuronic acid after methanolyses and trimethylsilylations showed the presence of the same derivative. It was concluded that the amino sugar U-7 was produced from the 2,3-diacetamido-2,3-dideoxy-D-glucuronic acid residue present in fraction F-A.

Chemical Phenomena↗

Significance of carcinoembryonic antigen levels and cytology of pure pancreatic juice in diagnosis of pancreatic cancer.

The diagnostic accuracies of measurement of carcinoembryonic antigen (CEA) and analysis of the cytologic characters of pure pancreatic juice were assessed in 16 control subjects, 20 patients with pancreatitis and 22 patients with pancreatic cancer. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation using a duodenofiberscope after intravenous administration of secretin. The pancreatic fluid was centrifuged and the supernatant was used for CEA assay, while the cell pellet was examined cytologically. Abnormally high CEA levels in the pure pancreatic juice were significantly more frequent in patients with pancreatic cancer; an increased CEA concentration in the pancreatic juice was found in 68.2% of the patients. The location of the cancer had no influence on the CEA level of the pancreatic juice, but the level tended to be high when the tumor had distant metastases. Positive cytologic findings were obtained in specimens of pure pancreatic juice of 68.2% of the patients with pancreatic cancer. Positive cytologic results were more frequent in patients with carcinoma of the head of the pancreas than in those with carcinoma of the body or tail, and those with localized tumors had the lowest yield of positive cytologic results. For sensitive tests, it was necessary to collect pure pancreatic juice containing no contrast medium. High CEA levels and positive cytological results were significantly more frequent in pancreatic juice obtained 10 to 20 minutes after secretin stimulation than in those collected immediately after stimulation. Correct diagnosis of malignancy was made by CEA assay alone or by cytological examination alone in 68.2% of the patients examined, while a combination of these methods raised the diagnostic rate to 86.4%.

Adenocarcinoma↗

Cytologic examination and CEA measurement in aspirated pancreatic material collected by percutaneous fine-needle aspiration biopsy under ultrasonic guidance for the diagnosis of pancreatic carcinoma.

Diagnostic accuracy of the cytologic examination or CEA measurement in pancreatic fluid obtained by percutaneous fine-needle aspiration biopsy under ultrasonic guidance, was investigated in 26 patients with histologically proven carcinoma of the pancreas, and the incidence of positive results of cytology and CEA assay were compared in pancreatic fluid obtained by percutaneous fine-needle aspiration biopsy and by endoscopic cannulation of the ampulla of Vater in the same 19 patients. Positive cytologic findings were observed in the fluid obtained by percutaneous aspiration biopsy of 88.5% of the patients with pancreatic carcinoma. The location of the cancer had no influence on the cytology, but positive results were more frequent in patients with distant metastases than in those with localized tumor or locally invasive carcinoma. Positive cytologic results were obtained in the pancreatic fluid obtained by endoscopic cannulation from the ampulla of Vater of only 15.8% of the patients examined by both methods, but percutaneous fine-needle aspiration biopsy significantly increased the diagnostic rate. In the specimens obtained by aspiration biopsy, tumor cells were much more abundant and easily recognizable. When cytologic examination does not provide any evidence of malignancy, measurement of CEA levels in pancreatic fluid is probably useful. Combination of the cytology and CEA assay of the specimens obtained by percutaneous fine-needle aspiration biopsy of the pancreas increased the diagnostic rate to 100%.

Adenocarcinoma↗

Sinus Pericranii.

Two cases of sinus pericranii are reported. X-ray films, taken with the direct injection of contrast medium into the extracranial blood cavity, made visualization of the intracranial venous systems possible in both cases. The pericranial blood sinuses were totally removed and communications through the osseous holes were closed with bone wax. The pericranial blood sinuses, surrounded by connective tissues, were located mainly in the subgaleal and supraperiosteal space. The literature is reviewed.

Adult↗

Age-related changes in the acid-secreting area in patients with duodenal ulcer.

The extent of, and age-related changes in, the acid-secreting area in patients with duodenal ulcer were compared with those in patients with gastric ulcer and healthy subjects. Studies were made by the endoscopic Congo red test developed in our clinic. The incidence of a large acid-secreting area was significantly higher in patients with duodenal ulcer than in normal subjects or patients with gastric ulcer. Although the incidence of a large acid-secreting area decreased with age in patients with gastric ulcer and in normal subjects, an extensive acid-secreting area was found in patients with duodenal ulcer, irrespective of age. In endoscopic follow-up studies, shrinkage of the acid-secreting area was observed in 18.8% of the healthy subjects and 31.9% of the patients with gastric ulcer, but in only 2.4% of the patients with duodenal ulcer.

Adult↗

Diagnosis of minute cancers by the endoscopic Congo red--methylene blue test.

The clinicopathological features of minute cancers of the stomach were investigated, and the accuracy of diagnosis of minute cancers by routine endoscopic examinations and by the endoscopic Congo red - methylene blue test were compared. From 1959 to 1979, 56 minute cancer were found in 54 patients. Minute cancers are defined as those of less than 5 mm in the longest diameter. None involved the muscularis propria, but when minute cancers, especially the depressed type, were more than 4 mm in diameter, cancer cells were frequently found to invade the submucosa. Therefore, minute cancers must be diagnosed as early as possible. A correct diagnosis of minute cancers was made in only 25.0% of the cases by routine endoscopic examinations. But with the Congo red--methylene blue test the diagnostic rate was raised significantly to 75.0%. In this test, tumors are seen as areas in which the dyes become bleached to white, in sharp contrast to the unaffected mucosa. This test is more accurate than other methods for diagnosis of minute cancers, because the target area can be biopsied with greater accuracy.

Adenocarcinoma↗

Studies on the metabolism of unsaturated fatty acids. XII. Reaction catalyzed by 2,4-dienoyl-CoA reductase of Escherichia coli.

Incorporation of deuterium atoms from deuterium-labeled NADPH and 2H2O during the reaction catalyzed by 2,4-dienoyl-CoA reductase of Escherichia coli (E. coli) was investigated. When trans-2,cis-4-decadienoyl-CoA was incubated with 4R- or 4S-[4-2H1]NADPH in the presence of purified 2,4-dienoyl-CoA reductase, no deuterium was detected in the reaction product by gas chromatography-mass spectrometry after derivatization to its pyrrolidine amide. On the other hand, when the dienoyl-CoA was incubated in the presence of NADPH and the reductase in 2H2O, two deuterium atoms were incorporated: One deuterium atom was located at the C-4 position of trans-2-decenoate, and the other at the C-5 position. The UV and shorter wavelengths of the visible spectrum of the reductase solution revealed that the reductase contained flavin as a prosthetic group. Therefore it is considered that a hydrogen atom of NADPH was first transferred to the flavin moiety of the reductase, and then the hydrogen atom was rapidly exchanged for one in the medium before its direct transfer to the substrate.

Catalysis↗

An enzymic cycling method for the determination of free fatty acids with acyl-CoA synthetase and acyl-CoA hydrolase.

A method for measuring free fatty acids by enzymic cycling is described. Free fatty acids are converted to acyl-CoAs by acyl-CoA synthetase, then the acyl-CoAs are hydrolyzed back to the free fatty acids by acyl-CoA hydrolase in a cyclic fashion. The amounts of AMP produced during this cyclic reaction are determined from the absorbance at 340 nm in the presence of AMP deaminase and glutamate dehydrogenase. This method is sensitive to as low as 0.1 nmol of free fatty acids, and the standard curve is linear up to 1.0 nmol. This method shows a broad specificity for long-chain fatty acids (C12--C20) and the recoveries of fatty acids added to bacterial cell-free extracts are more than 90%.

AMP Deaminase↗

Milbemycins, a new family of macrolide antibiotics. Studies on the biosynthesis of milbemycins alpha 2, alpha 4 and D using 13C labeled precursors.

The biosynthetic origins of the carbon skeleton of milbemycins alpha 2, alpha 4 and D were studied. 13C Labeled antibiotics, milbemycins alpha 2, alpha 4 and D, were isolated from the culture broth of Streptomyces hygroscopicus subsp. aureolacrimosus strain Au-3 after feeding [1-13C]acetate, [1-13C]-propionate, [3-13C]propionate, [1-13C]isobutyrate, DL-[2-13C]valine and L-[methyl-13C]methionine, and 13C NMR spectra of the antibiotics thus obtained were measured. It was revealed that the carbon skeleton, except for carbon 25, of milbemycins alpha 2, alpha 4 and D are derived from seven acetate units and five propionate units. It was also shown that the methyl, ethyl and isopropyl groups at carbon 25 in milbemycins alpha 2, alpha 4 and D are derived from acetate, propionate and isobutyrate or DL-valine, respectively, and the methyl carbon of the methoxy group at carbon 5 in milbemycins alpha 2 and alpha 4 was enriched by L-[methyl-13C]methionine.

Acetates↗

Influence of hypertension on the progression of experimental autologous immune complex nephritis.

In order to determine the influence of hypertension on the progression of chronic glomerulonephritis, we studied the renal lesions in Heymann nephritis (autologous immune complex nephritis) produced in SHR. Nephritic SHR treated by AHD, normal SHR, nephritic WKYR, and normal WKYR served as controls. Induction of Heymann nephritis did not alter the blood pressure in either SHR or WKYR as compared with each untreated control group. Administration of AHD normalized the blood pressure of SHR. Proteinuria, hypoproteinemia, hypercholesterolemia, and reduction in body weight were significantly greater in nephritic SHR than in nephritic SHR treated by AHD or nephritic WKYR, whereas BUN and serum creatinine were unchanged in all the nephritic rats. Histological findings such as glomerular basement membrane thickening, IgG and C3 deposits along capillary walls, and subepithelial electron-dense deposits were similar in all nephritic groups. Glomerular sclerosis and tubulointerstitial changes were more marked in nephritic SHR than in the other nephritic groups. Severe vascular thickening and necrosis, intravascular thrombosis, and perivascular cell infiltration were frequently observed in nephritic SHR. These lesions are characteristic of malignant hypertension. However, they were not found in control SHR, which maintained elevation of blood pressure equivalent to that of nephritic SHR throughout the study. It was concluded that hypertension may aggravate nephritic manifestations such as proteinuria, hypoproteinemia, and hypercholesterolemia but not excretory renal function and that the hypertensive vascular lesions are augmented by Heymann nephritis.

Animals↗

Carcinoembryonic antigen in the bile in patients with pancreatic and biliary cancer. Correlation with cytology and percutaneous transhepatic cholangiography.

The level of carcinoembryonic antigen (CEA) in the bile of 17 patients with benign pancreatic and biliary diseases and 50 patients with pancreatic and biliary cancer were determined by enzyme immunoassay. The bile specimens were obtained at the time of percutaneous transhepatic cholangiography. The bile was centrifuged and the supernatant was used for CEA measurement, while the cell pellet was examined cytologically. High CEA values in the bile were significantly more frequent in patients with pancreatic and biliary cancer than in those with benign pancreatic or biliary diseases; increased CEA concentrations in the bile were observed in 76.0% and 60.0%, respectively, of all the patients and of the patients with localized cancer. The location of the cancer had no influence on the bile CEA level, but the CEA levels in the bile tended to be high when the tumor had distant metastases, or when the biliary tract was completely obstructed. Although patients with pancreatic and biliary cancer had a high CEA value in the bile significantly more frequently, bile CEA measurement is not sufficient to distinguish an individual patient with pancreatic or biliary cancer from those with other disease, since the overlap between the values is too great, and therefore, additional examinations are required. Correct diagnosis of malignancy were made by cytological examination alone, by bile CEA assay alone and visual examination of dye in the biliary tract alone in 72.0, 76.0, and 88.0% respectively, of the patients examined, while the combination of these methods raised the diagnostic rate to 100%.

Bile↗

Endoscopic diagnosis of early gastric cancer by the endoscopic Congo red-methylene blue test.

The endoscopic Congo red test combined with dyeing with methylene blue was performed in 85 patients with early gastric cancer (94 lesions). Results revealed that gastric cancer bleached the Congo red and methylene blue sprayed over their surface and this appeared in sharp contrast to the red-colored mucosa of unaffected areas. Grossly, polypoid and flat types, and histologically differentiated adenocarcinomas bleached the dyes more frequently and more intensely than depressed and undifferentiated adenocarcinomas. Thus the spread of cancerous growth could be judged rather accurately and so the target area could be reached by biopsy in cases where there were few if any visual signs of abnormality.

Adenocarcinoma↗