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Biomedical subjects

M Iwai

Publications and source records attributed to M Iwai.

At least 235 records · Page 13Linked to original sources

[A case of coexisting primary malignant lymphoma and adenocarcinoma of the stomach].

Reports of the presence of two histologically different neoplasms in one organ are still unusual. We experienced a rare case of coexisting primary malignant lymphoma and adenocarcinoma of the stomach. A 66-year-old woman was admitted in April 1983 because of weight loss and epigastralgia. Several examinations including gallium scan, upper GI endoscopy, biopsy and touch cytology of the stomach, were performed, and she was diagnosed as having primary malignant lymphoma (noncleaved, large cell type) of the stomach. After the administration of 20 mg of vincristine, 6,000 mg of cyclophosphamide, 1,000 mg of prednisolone and 150 mg of Adriamycin, she improved to complete remission in August 1983. In February 1984, she received gastrectomy because of stenosis of the esophagogastric junction. Microscopic examination of the ulcerated lesion at esophagogastric junction revealed moderately differentiated tubular adenocarcinoma infiltrating to the subserosa. Despite chemotherapy, peritonitis carcinomatosa developed, and the patient died of cachexia in July 1984.

Adenocarcinoma↗

Endogenous type-C viral expression during lymphoma development in irradiated NFS mice.

The expression of the type-C retrovirus and the virus-related components in NFS mice were examined during preleukemic and leukemic phases after fractionated whole-body X irradiation. The NFS mice were highly susceptible to induction of thymoma by fractionated X irradiation. The leukemic tissues were negative for infectious type-C virus, as detected by both the XC-plaque test and mink S+ L- focus-inducing assays, but contained a substantially higher level of viral-specific RNA-dependent DNA polymerase activity and a major core protein p30 than the corresponding tissues from unirradiated age-control mice. In the preleukemic phase, the amount of p30-related antigen increased transiently in spleen. The leukemic cell lines established from radiation-induced lymphomas produced particulate entities with a buoyant density of about 1.15 g/ml. These virus-like particles lacked in vitro infectivity to mouse cells and mink lung cells and leukemogenicity in syngeneic mice. The p30-related antigens of these particles were immunologically similar to that of xenotropic virus derived from NZB mouse.

Animals↗

[Retrospective study of short survival cases in hepatocellular carcinoma after transcatheter arterial embolization therapy].

Twenty-two patients with hepatocellular carcinoma were treated with transcatheter arterial embolization therapy. In the six who died within about a month, serum albumin and Ch-E were lower, and total bilirubin and ICG R15 were higher than in the other cases. In four of them, more than 50% of the liver was occupied by tumor, and tumor thrombosis were found in the portal trunk or bilateral first portal branch. Five patients died of hepatic failure followed by upper gastrointestinal bleeding. One died of cachexia. The causes of short survival were 1) severe liver cirrhosis, 2) portal obstruction, 3) large tumor, 4) widespread TAE, 5) retrograde flow of gelfoam.

Adult↗

[Alteration of blood coagulation and fibrinolysis after transcatheter arterial embolization of hepatocellular carcinomas].

Alteration in blood coagulation and fibrinolysis were observed serially after TAE 37 times by measuring PT, APTT, FDP, fibrinogen, AT III, plasminogen, and alpha 2-macroglobulin. Immediately after TAE, PT and APTT were prolonged, Fbg AT III, alpha 2-M, and platelets decreased, and FDP increased. These changes within 24 hours suggested that coagulation activities were accelerated, and fibrinolysis followed. Within four weeks after TAE, PT and APTT became most prolonged one to three days after, while AT III, Plg, and alpha 2-M became lowest on the third to seventh days. It is suggested that these decrease were mainly due to suppressed production resulting from damage of the residual liver.

Antineoplastic Agents↗

Immunohistochemical and electron microscopic observations of nevic corpuscle.

Nevic corpuscle in the pigmented nevus was studied under light microscopy in comparison with Meissner corpuscle of the human sole skin in order to determine its ontogenesis. No nerve fibers within nevic corpuscle but coiled fibers in Meissner corpuscle could be demonstrated by Bodian stain. Presence of S-100 protein in the pigmented nevus and Meissner corpuscle was observed under light microscopy utilizing peroxidase-antiperoxidase immunohistochemical staining. S-100 protein was more evident in nevic corpuscles than in Types A and B intradermal nevus cells. Meissner corpuscle showed moderate stainability for S-100 protein. Ultrastructural study revealed that the nevic corpuscle was composed of the laminated cells with flattened cytoplasmic processes but lacked peripheral nerve endings such as axons, characteristically shown in Meissner corpuscle. No melanogenic activity of nevic corpuscle was observed. These morphological and histochemical findings of nevic corpuscle did not enable us to give definite conclusion on its ontogenesis.

Female↗

Studies on pharmacological activation of human serum immunoglobulin G by chemical modification and active subfragments. III. Mechanism of anti-ulcerous action of alkylated light chain (Fr. I-L).

The effects of a new anti-ulcer agent Fr. I-L, a reduced and carboxamide-methylated light chain of human immunoglobulin G, on defensive factors in gastric mucosa were studied. Fr. I-L increased the mucopolysaccharide contents (hexosamine, uronic and sialic acids) in the gastric mucosa of intact rats and inhibited the decrease of mucopolysaccharide contents in the gastric mucosa of rats with phenylbutazone-induced gastric ulcers. The activation of the biosynthesis of mucopolysaccharides by Fr. I-L was suggested by tracing the incorporation of 35SO4(2-) into the gastric mucosa. The administration of aspirin or phenylbutazone caused an increase of mucopolysaccharase activity in the gastric mucosa and the concomitant administration of Fr. I-L blocked the elevation of the enzyme activities. Fr. I-L also showed inhibitory activities on the local fibrinolysis and lipid peroxidation in the gastric mucosa.

Animals↗

Pharmacokinetic study of the enterohepatic circulation of acetaminophen glucuronide in rats.

A pharmacokinetic model of the enterohepatic circulation of acetaminophen glucuronide was investigated in rats with particular attention to a lag time between biliary excretion and reabsorption. The plasma drug data obtained after acetaminophen glucuronide injection into the various sites of the gut confirmed that there is a lag time in the enterohepatic circulation and that the lag time is due to the intestinal transit period of the conjugate to the site of the hydrolysis. The value of the lag time was fairly close to that reported previously in the rat. Based on the result, a compartment model with periodic trigonometric function for the enterohepatic circulation was built up and the urinary excretion data were fitted to this model. Same parameters which are considered to be common to other glucuronide conjugates were in good agreement with those reported previously, indicating that the model and those values are useful to study the enterohepatic circulation for glucuronides of other compounds in the rat.

Acetaminophen↗

[A light and electron microscopic studies of müllerian adenofibroma of the uterus].

Müllerian adenofibroma composed of both histologically benign epithilia and benign mesenchyme is considered to be a rare entity of mixed müllerian tumor. A case of müllerian adenofibroma of the uterus was studied by light and electron microscopy. Light microscopically, the cleft-like glands lined by single-layered columnar or cuboidal epithelial cells were distributed in the proliferation of surrounding fibroblast-like mesenchymal cells. Mitotic figures of mesenchymal cells were less than 1--2 in 10 high power fields, and no nuclear atypia or heterologous elements were observed. Electron microscopically, the epithelial cells had well-developed mitochondria, r-ERs, tonofilaments in the cytoplasm, and short microbilli or cilia protruding into the lumen. In the mesenchyme, two types of cells were observed. One was spindle-shaped cells resembling fibroblasts, and the other was cells resembling immature smooth muscle cells. The histological and ultrastructural features of müllerian adenofibroma were felt to resemble those of müllerian adenosarcoma, which may pursue a clinically malignant course. These findings suggest that müllerian adenofibroma and adenosarcoma may be in the common spectrum of mixed müllerian tumor.

Adenofibroma↗

Mode of invasion, bleomycin sensitivity, and clinical course in squamous cell carcinoma of the oral cavity.

Forty patients with squamous cell carcinoma of the oral cavity were treated with bleomycin prior to undergoing surgery. The degree of the clinical effect of bleomycin and the postoperative clinical course of each case were estimated from the viewpoint of correlation with the mode of invasion. A strong correlation was found among the mode of invasion, bleomycin sensitivity, and clinical course. A slight effect of bleomycin and poor prognosis existed in the group with a diffuse invasion of mode of invasion, while the greatest effect of bleomycin and good clinical course were achieved in the group with a well-defined tumor-host borderline.

Adult↗

Pharmacokinetic study of the fate of acetaminophen and its conjugates in rats.

Pharmacokinetic studies of the fate of acetaminophen and its major metabolites, acetaminophen sulfate (AS) and acetaminophen glucuronide (AG), were made in rats. The rates of conjugate formation were calculated by deconvolution. The Michaelis-Menten equation gave maximum velocity and Michaelis constant (Km) values of 4.92 mumol/min/kg and 109 microM for AS formation, and 2.76 mumol/min/kg and 915 microM for AG formation. However, AG formation showed approximately first-order behavior in the present dose range because of its large Km value. The disposition of acetaminophen could be described by a two-compartment model with simultaneous first-order and Michaelis-Menten type elimination kinetics for AS formation. Curve fitting of the data based on this model was successfully done for doses of up to 1058 mumol/kg, suggesting that sulfation proceeds without depletion of sulfate in the blood at least up to this dose. The disposition of AS could be described by a two-compartment model and was apparently dose-independent over an 8-fold dose range. Although a slight dose dependence in the elimination of AG was suggested over a 16-fold dose range, for the purpose of the present study, it was assumed that the disposition of AG is approximately linear. The excretion of AS in the bile was negligibly small, whereas a considerable amount of AG was excreted into the bile. The results following intraduodenal injection of AS or AG indicated that AS or AG was hydrolyzed by the microflora and the liberated acetaminophen was reabsorbed, confirming enterohepatic circulation of the conjugates. This was consistent with the urinary metabolite excretion patterns observed after acetaminophen injection in normal and bile fistula rats. Based on the kinetic parameters obtained, the plasma concentrations of AS and AG after acetaminophen injection were simulated, and a fairly good agreement was obtained between calculated and observed values at the dose of 264.6 mumol/kg. Although the urinary metabolite excretion pattern differs from that of humans, the kinetic parameters obtained for rats were similar to those for humans in some respects, suggesting that the rat might be useful as a model animal to predict human data.

Acetaminophen↗

Immunocytochemical investigation of alpha-fetoprotein-positive cells in hepatocarcinogenesis and hepatomas induced by 3'-ME-DAB.

AFP-positive cells during 3'-Me-DAB hepatocarcinogenesis and in hepatomas induced by 3'-Me-DAB were observed by the light microscope immunoperoxidase method, and the location of AFP-immunoreaction products in hepatocytes was determined by the electron microscope immunoperoxidase method. Simultaneously serum concentrations of AFP were measured by radioimmunoassay. Serum concentrations of AFP during hepatocarcinogenesis showed a biphasic pattern, and proliferation of cholangiolar cells in the periportal areas was associated with the first peak of serum AFP in the early stage of hepatocarcinogenesis. AFP-containing cells in the late stage were distributed in clusters in the peripheral areas of hyperplastic nodules. The clusters were composed of two different types of AFP-positive cells, one atypical in shape and structure and the other preserving the structure of hepatic cords. In neoplasms, a heterogeneous AFP immunoreaction was recognized in hepatoma cells. In non-neoplastic nodules, cholangiofibrosis surrounded by AFP-positive cholangiolar cells developed. Ultrastructural immunoperoxidase studies revealed immunoreaction products of AFP on the membrane of r-ER, outer nuclear membrane, s-ER and Golgi complex in hepatocytes of hyperplastic nodules as well as of hepatocellular carcinoma cells. It is suggested that cholangiolar cells detected in hepatocarcinogenesis may form proliferating bile ductules, and the appearance of a cluster in association with AFP in hyperplastic nodules supports the hypothesis that some hyperplastic nodules with clusters of AFP-positive cells are important cell populations which may develop into hepatocellular carcinoma.

Animals↗

Increase in the activity of Rhizopus delemar lipase on water-soluble esters by its binding with phosphatidylcholine.

Rhizopus (Rh.) delemar (ATCC 34612) C-lipase was found to exhibit a slight activity towards water-soluble esters. The hydrolytic reaction of this lipase on alpha-naphthyl acetate was competitively inhibited by the presence of olive oil or Tween 80. This finding showed that both substrates, insoluble triglyceride and water-soluble ester, were hydrolyzed at the same site on the enzyme. The activities on water-soluble esters (alpha-naphthyl acetate, beta-naphthyl acetate, methyl acetylsalicylate and Tween 80) increased on binding of lipase with phosphatidylcholine (PC), although the activity on olive oil did not change. The increase in activity on water-soluble esters was due to the increase in the Vmax for its hydrolysis. It appears that local structural change of the catalytic site on lipase occurred on binding of PC to the lipase molecule and resulted in an increase in the activity on water-soluble esters. The temperature dependence of the hydrolysis of water-soluble esters demonstrated that the activation energy was lowered on binding of PC to the lipase molecule, and this resulted in an increase in the activity.

Binding Sites↗

Studies on pharmacological activation of human serum IgG by chemical modification and active subfragments. I. Induction of anti-ulcerogenic activity by chemical cleavage of interchain disulfide bonds in human IgG and properties of active subfragments.

Commercially available human IgG (native IgG) was passed through a DEAE cellulose column. Two fractions (Fr. I and Fr. II), responding equally against the anti-human IgG antibody were obtained. The carboxamide-methylated H and L chains from both fractions showed remarkable inhibitory activities on both the gastric ulceration and the gastric juice secretion in pylorus-ligated rats. The carboxamide-methylated L chain of rat IgG was also effective, while none of the human native IgG, Fr. I or Fr. II showed any effect. The reduction and the following alkylation of the interchain disulfide bonds were necessary for the induction of the biological activities of human IgG. Sulfonation of human IgG failed to induce the activities. Although the gastric acid secretion was clearly reduced by the administration of Fr. I-L (alkylated L chain of Fr. I), the gastric mucosal blood flow was not affected.

Alkylation↗

Studies on pharmacological activation of human serum IgG by chemical modification and active subfragments. II. Inhibitory effects of carboxamide-methylated L chain from human serum IgG on various ulcer models and its inhibition mechanism.

In view of the strong inhibitory effects of the carboxamide-methylated L chain (Fr. I-L) from human IgG on gastric ulceration and juice secretion, we carried out various experiments to clarify the mechanism of its action and obtained the following results. Fr. I-L inhibited the gastric ulceration induced by phenylbutazone or aspirin in rats, but no appreciable effect was observed on stress or acetic acid ulceration. The distribution of 14C-labelled Fr. I-L increased particularly in the stomach mucous membrane of rats after the intravenous or intraperitoneal administration. The hexosamine content in the gastric mucous membrane, reduced by the treatment with phenylbutazone, aspirin or pylorus-ligation, was recovered by the administration of Fr. I-L to an intact level. The high total of hexosamine levels found in the gastric juice after aspirin treatment or pylorus-ligation were decreased by the injection of Fr. I-L or cimetidine. The histochemical observation revealed that the concomitant administration of Fr. I-L with phenylbutazone or aspirin prevented the abolishment of Hematoxylin-Eosin, Periodic Acid Schiff and Alcian Blue staining polysaccharides from the stomach epithelial cells.

Animals↗

Inhibitory effects of unsaturated fatty acids of trans-2-C10:1 to trans-2-C16:1 several C18:n and C20:n on gastric secretion and experimental ulceration in rats.

Among various unsaturated fatty acids which were examined in this experiment, trans-2-tridecenoic acid was found to be a potent inhibitor on gastric secretion in rats (i.p. or i.d.). Therefore, the effects of trans-2-tridecenoic acid on several experimental ulcerations in rats were examined. At the dose of 10 mg/kg, trans-2-tridecenoic acid significantly decreased the ulcer index in pylorus-ligated rats; aspirin-, phenylbutazone-, histamine- and stress-induced ulcerations were also significantly inhibited at the dose of 25 mg/kg. Finally, effects of trans-2-tridecenoic acid on hexosamine and sialic acid contents in the gastric mucous were examined. In intact or phenylbutazone-induced ulcerated rats, trans-2-tridecenoic acid increased the sialic acid levels in the gastric mucous at the dose of 25 mg/kg. The decreased hexosamine content in the gastric mucous by phenylbutazone treatment was recovered by the administration of trans-2-tridecenoic acid.

Animals↗