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J Sano

Publications and source records attributed to J Sano.

At least 55 records · Page 3Linked to original sources

Methylation and expression of human pepsinogen genes in normal tissues and their alteration in stomach cancer.

In normal human tissues, pepsinogen A mRNA was expressed only in the fundic mucosa of the stomach, whereas pepsinogen C mRNA was expressed in all regions of the stomach mucosa and also in the proximal duodenal mucosa. The distributions of these mRNAs were consistent with those of pepsinogens A and C in the gastroduodenal mucosa. Methylation analysis of DNAs from normal tissues with methylation-sensitive restriction enzymes, HpaII and HhaI, revealed that pepsinogen A and C genes are hypomethylated in tissues producing pepsinogens A and C, suggesting a role of DNA methylation in the regulation of the differential expression of the genes for the two human pepsinogens during normal differentiation. In stomach cancer tissues and cancer cell lines, the expressions of the pepsinogen genes were decreased or lost, in good accordance with their pepsinogen productions. No gross structural changes of the pepsinogen genes were observed in these cancers, but the methylation patterns of the pepsinogen genes were found to be altered in different ways in different cancers. The functional significance of the altered methylation is unknown; however, these results suggest that considerable heterogeneity of the methylation patterns occurs in human stomach cancers.

Blotting, Northern↗

A case of epilepsy characterized by spike-wave stupor followed for long period.

A 34-year-old housewife with nonconvulsive status epilepticus was followed up for 20 years since the initial fit. She maintained some contact with reality during the stupor and recalled the episode to some extent, while the EEG showed continuous spike-wave complexes. During the clinical course, the main type of seizures was spike-wave stupor, of which the maximum frequency was several times a week in the hospital and the duration was many minutes to several hours, and also secondarily generalized convulsive seizures occurred approximately once a month. The lasting control of spike-wave stupor was not achieved in spite of the various medications for the long follow-up period. The ictal EEGs of spike-wave stupor always showed the frontal origin. The meaning of the term "nonconvulsive status epilepticus" in this case was briefly discussed.

Adult↗

Effects of KF-14363 on liver fibrosis in rats with chronic liver injury induced by carbon tetrachloride.

The present study examined the effects of (1-[(2-thiazolin-2-yl)amino]-acetyl-4-(1,3-dithiol-2-ylidene)-2,3, 4,5- tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) on liver fibrosis in rats with chronic liver injury induced by carbon tetrachloride (CCl4). Liver injury in male rats was induced by repeated administration of CCl4 at 0.5 ml/kg twice a week. The progression of liver fibrosis was checked in the 4th, 6th, 8th and 10th weeks using the relative amount of hepatic 4-hydroxy proline (4-hyp) to total proteine as an index of hepatic collagen. The relative amount of hepatic 4-hyp in these rats exceeded significantly that in rats not administered CCl4 by the 4th week. This progressed in proportion to the duration of CCl4 administration. In groups concurrently administered KF-14363 at 30 and 100 mg/kg/d from the 5th or 8th week of the CCl4 administration, the relative amount of hepatic 4-hyp was found to be lower in the 10th week than at the start of the KF-14363 administration. The inhibition of liver fibrosis was also observed histopathologically. The concurrently co-administration with CCl4 or KF-14363 at 30 and 100 mg/kg for 2 or 5 weeks inhibited the increases in serum transaminases and alkaline phosphatase induced by CCl4. The results show that KF-14363 inhibits liver fibrosis in a dose dependent fashion in rats with progressive liver injury.

Alkaline Phosphatase↗

The significance of low serum pepsinogen levels to detect stomach cancer associated with extensive chronic gastritis in Japanese subjects.

Serum pepsinogen levels were measured in 137 stomach cancer patients and compared with those of 288 normal cancer-free subjects. The serum pepsinogen levels of stomach cancer patients, especially pepsinogen I and the pepsinogen I/pepsinogen II ratio were significantly lower than those of normal controls and correlated well with the extent of chronic gastritis associated with the cancerous stomach. These results were in good accordance with the results of previous studies indicating that the cancer derived from the stomach where chronic gastritis/intestinal metaplasia is extensive. The high sensitivity and specificity of this non-invasive serum test to detect chronic gastritis suggested the possibility of its application to the mass screening of stomach cancer.

Adenocarcinoma↗

In situ localization of pepsinogens I and II mRNA in human gastric mucosa.

Localization of pepsinogens I and II mRNA in the human gastric mucosa was investigated by an in situ hybridization method using digoxigenin-labeled cDNA probes. Gastric fundic mucosa from healthy volunteers, which was stained with digoxigenin-labeled pepsinogens I and II cDNA probes, showed positive staining in the cytoplasm of both chief cells and mucous neck cells. In contrast, gastric antral mucosa stained with the pepsinogen I cDNA probe showed no positive reaction in the surface mucous cells or pyloric glands. On the other hand, the pyloric glands were stained positively with the pepsinogen II cDNA probe and the staining appeared to be identical to that obtained with the antipepsinogens I and II monoclonal antibodies using the avidin-biotin-peroxidase complex technique. These results are consistent with those of previous studies that have employed immunochemical and immunohistochemical techniques.

DNA↗

Pepsinogens I and II in gastric cancer: an immunohistochemical study using monoclonal antibodies.

Monoclonal antibodies were used to examine the immunohistochemical expression of pepsinogens I and II in 31 early and 76 advanced gastric cancers. Of the 107 carcinomas studied, 19 contained pepsinogen II and only 3, found exclusively in pepsinogen II-positive cases, contained pepsinogen I. Gastric cancer produces pepsinogen II more frequently than pepsinogen I, and production of the latter is significantly associated with the former. Histologically, there were 54 intestinal-type and 53 diffuse-type cancers. The former produced pepsinogen II more frequently than the latter. In the diffuse type, the four pepsinogen II-positive cases were found exclusively in females. Although the pepsinogen expression was independent of the macroscopic features in advanced gastric cancer, it was found that the protruded-type early gastric cancer produced pepsinogen II more frequently than the depressed type. Incidences of pepsinogen positivity were not different between early and advanced gastric cancers or between cancers with or without lymph node metastasis, suggesting that production of pepsinogen is independent of tumor growth.

Aged↗

Intensified IgA mesangial deposits after administration of sheep anti-type IV collagen serum in mice.

Sheep anti-type IV collagen serum was intravenously administered to male mice of the BALB/c, C3H and ddY strains, and their kidneys were morphologically studied monthly for 10 months thereafter. By immunofluorescence, the sheep IgG was seen to have immediately become conjugated to the glomeruli, mainly in a mesangial pattern. Successively, autologous mouse C3 and IgG appeared with the same type of distribution. Within 3 to 4 months after the start of the experiment, mouse IgA also appeared in the mesangium, especially in ddY mice. The intensity and frequency of mesangial IgA deposition and the serum IgA level increased with time in this strain. BALB/c and C3H mice also showed the same tendency of mesangial IgA deposition, although to a lesser degree. In summary, it was concluded that mesangial IgA deposition was due to non-immunological local trapping, on the basis of the results obtained by ELISA analysis of the sera and renal eluate. Although the ddY mouse is known to show spontaneous mesangial IgA deposition associated with a high serum IgA level with aging, these characteristics were much accelerated and intensified by this antiserum treatment. The relation of this observation to the pathogenesis of human IgA nephritis is discussed.

Animals↗

Foamy cells associated with phagocytosis of glutaraldehyde-treated red blood cells and red cell membranes.

In order to clarify the mechanism for the formation of foamy cells (macrophages with foamy appearance) associated with increased erythrophagocytosis, we tried to reproduce these cells in mice by subcutaneous injection of intact red blood cells (RBCs), OsO4-treated RBCs (Os-RBCs), glutaraldehyde-treated RBCs (G-RBCs), or isolated red cell membranes, and time-course observation was done by light and electron microscopy. Foamy cells were induced by the latter two methods. Within the macrophages, G-RBCs were fragmented into spherules by newly formed small vacuoles, and with time these spherules lost their hemoglobin content transforming into small vacuoles with translucent matrix. In most of these vacuoles, red cell membrane structure was discernible adjacent to the phagocytic vacuole. Such macrophages containing abundant small vacuoles appear foamy in light microscopy. Foamy cells induced by injection of red blood cell membranes were positive for lipid stains and contained abundant laminated membrane structures in electron microscopy. These results suggest that the foamy cells related with increased erythrophagocytosis are heterogeneous with respect to their pathogenesis and cellular inclusions, and proteinaceous constituents resistant to intracellular digestion are also responsible for the occurrence of foamy cells.

Animals↗

[An outbreak of Trichophyton mentagrophytes infection in a rat breeding stock and its successful control].

An outbreak of dermatophytosis by Trichophyton mentagrophytes infection was observed in a breeding stock of the Wistar-Imamichi rat. Typical cutaneous lesions such as alopecia and hyperkeratosis due to the fungus were observed in 10% and 44% of adult females, and males respectively. No infection was seen in infant, even in those fostered by infected females. By 3 repeated cultivations of the hair, T. mentagrophytes was isolated from 107 (90.7%) of 118 rats clinically diagnosed as dermatophytosis. In order to maintain the original stock, the usual wholesale slaughter program was avoided and the following control measures were taken. After sacrificing all rats with the cutaneous lesions, the breeding colony was transferred temporarily to a separate animal room. The resulting vacant room was then disinfected 3 times with 10% formalin, followed by spraying with 3% sodium propionate solution 3 month later. The progenies from the non-infected mothers were dipped into 3% sodium propionate solution and transferred back into the disinfected animal room for re-colonization. Frequent sterilization of all equipment with iodophor, balsam and formalin was carried out. The room sterilized monthly with iodophor and 70% alcohol. Daily observation of all rats and monthly screening by culture test was done thereafter. As a result, no infection has been detected 4 month after recolonization, except for the 3 rats which were sacrificed immediately after detection. On the basis of the culture test and clinical observation, no infection was observed in the treated rat colony for the next five following years. Therefore, the effectiveness of these procedures of the eradication of T. mentagrophytes infection from a rat colony was shown to be quite reliable.

Animals↗

Activation of collagen synthesis in primary culture of rat liver parenchymal cells (hepatocytes).

An increase in collagen synthesis by hepatic parenchymal cells (hepatocytes) was observed during 8 days in primary culture by the quantification of total [3H]hydroxyproline as a marker of total collagen synthesis and the ratio of [3H]hydroxyproline in the high-molecular-weight fraction to total [3H]hydroxyproline as a marker of collagen degradation after incubation of the cells with [3H]proline for 24 h. Type analysis of the collagen produced by the cells after 8 days in culture showed the presence of type I and type III collagens in addition to the components corresponding to type IV and type V (alpha A and alpha B) collagens. Only the latter two types were found in the collagens produced by the cells after 2 days in primary culture. The purity of the hepatocytes inoculated was 97%, and the majority of the contaminating small cells were erythrocytes. The rate of serum albumin synthesis, which is a typical function of the hepatocytes, was constant or increased during the culture period. Immuno-electron microscopic observation indicated the production of type I collagen by the hepatocytes after 8 days in primary culture. These results are explained only by the activation of collagen synthesis in the day-8 hepatocytes in primary culture.

Animals↗

Biochemical and immunohistochemical studies on the scirrhous carcinoma of human stomach.

Tumor mass of the stomach from patients with scirrhous carcinoma was analyzed biochemically and immunohistochemically to elucidate whether or not infiltrating carcinoma cells are directly responsible for overproductions of collagen in the lesion. Collagen content per unit transverse section of the tumor was two to four times higher than the normal. Of particular interest was that the contents of hyaluronic acid and chondroitin sulfate were five to ten times higher than the normal, suggesting that cells in the lesion of the tumor are in an actively proliferating stage. Immunohistochemical observations using type-specific anti-collagen antibodies and anti-carcinoembryonic antigen antibody revealed that type IV collagen was diffusely distributed through the tumor stroma of submucosa and fragmented regions of muscle layer, along with dense fibrous components composed of type I and type III collagens. Stroma cells in the lesion were often stained with antibody to type IV collagen. In contrast, carcinoma cells were with antibody to type I collagen, but not with antibodies to type III and type IV collagen. Quantitative analysis of the collagen production by isolated stroma cells and undifferentiated (KATO-III) and highly differentiated (MKN-28) carcinoma cells in culture in the presence and absence of a combination of the conditioned medium of these cells has shown that the scirrhous carcinoma of stomach results from the "stroma reaction" of stroma cells induced by infiltrating malignant epithelium.

Adenocarcinoma, Scirrhous↗

[Locked-in syndrome with bilateral midbrain infarcts--report of an autopsy].

A case of "Locked-in" syndrome with bilateral midbrain infarcts was reported. A 51-year-old man had a memory disturbance and a change of his personality after head trauma, and then became rapidly "Locked-in" state. He was quadriplegic and bulbar paralytic, but ocular movements were preserved. Left VAG showed the narrowing of the basilar artery and there was a striking anastomosis between the SCA and PICA. Neuropathological findings were as the following; 1) The lateral two third of bilateral cerebral peduncles were extensively infarcted. 2) There were contusion of the left frontal orbital surface and the ischemic infarction of the left frontal white matter. 3) Two small infarcted lesions were found in the ventral pons without involving the pyramidal tracts. 4) Additional findings were retrograde degeneration of the medial nucleus of the left thalamus from the left frontal orbital lesion, and were loss of the Purkinje cells and neurons of pontine nucleus from the infarction of the middle cerebellar peduncle. Tegmentum of the midbrain, pons and medulla were preserved, which was considered to be due to the anastomosis of the SCA and PICA. Bilateral midbrain infarcts are responsible lesions in this case and it seems that "Locked-in" state is not synonymous with the "Ventral pontine syndrome".

Cerebral Cortex↗

Cloverleaf skull syndrome. An autopsy case and review of literature.

An autopsy case of cloverleaf skull deformity associated with hydrocephalus, systemic skeletal malformation including facial dysostosis, fused elbow, syndactyly of the toes, odd digits and striking anomaly of tracheal cartilage is presented. Extra-skeletal abnormalities included covered anus, dermal sinus and the absence of corpus callosum and the septum pellucidum. Several basal skull deformity appeared to be a primary morphologic alteration associated with premature closure of the specific sutures, which terminally resulted in life-threatening hydrocephalus. Histological investigation showed the abnormalities of endochondral ossification in the cartilage at the epi- and meta-physis of the fused elbows. In addition, electron microscopical study revealed unusual fat droplet-containing chondrocytes even in the resting and multiplicative phase. Association of the tracheal anomaly with this syndrome was disclosed in this case. Generalized bone and cartilage abnormalities not only in the skeletal system but also in the internal organs strongly suggest that this disorder involves generalized osteocartilagenous system. The present case makes a total of 14 cases of the cloverleaf skull syndrome reported in the Japanese literatures to date. Major clinical and pathologic findings of these cases were summerized.

Abnormalities, Multiple↗

Immunohistochemical localization of type I, III and IV (basement membrane) collagens in the liver.

The tissue distribution of type I, III and IV (basement membrane) collagens in normal human and bovine livers was examined by indirect immunofluorescence microscopy, by using type-specific rabbit antibodies to individual types of bovine collagen. Type I and III collagens were found to distribute in the interstitium of portal tracts as thick fiber bundles and in perisinusoidal spaces as thin fibers like reticulin fibers, both in human and bovine livers. No significant distribution differences of type I and III collagens in the livers was observed under the experimental conditions employed, indicating that both collagens are involved in in vivo collagen, fibrillogenesis in the tissue, regardless of the sizes of collagen fibers, as in the skin (Conn. Tiss. Res. 7: 157-163, 1980). Type IV collagen, when examined with bovine liver, was located in hepatic arteries, portal veins and bile ducts of portal tracts, and was also distributed in the perisinusoidal spaces in a linear fasion.

Animals↗

Immunohistochemical localization of type I, II, III, and IV collagens in the lung.

Type specific rabbit antibodies to bovine type I, II, III, and IV (basement membrane) collagens showing no cross-reaction with other types of collagen were prepared by cross-adsorption and diethylaminoethyl-cellulose chromatography. The antibodies to bovine type I and III collagens showed a high cross-reaction with the corresponding human collagens, but those to type II and IV collagens did moderate and no cross-reactions with human type II and IV collagens, respectively. By using these antibodies, tissue distribution of various types of collagen in normal bovine lung was examined by indirect immunofluorescence microscopy. both type I and III collagens were found to distribute widely in the interstitium of bronchial tree, bronchial lamina propria and of interlobules as well as alveolar nipples and adventitia of pulmonary arteries. Type II collagen was located only in bronchial cartilage. The tissues mainly stained for type III collagen were the alveolar interstitium (also stained faintly for type I collagen) and the intima and media of the arteries. Type IV collagen was located in a membranous fashion in alveolar septa and bronchial smooth muscles and subepithelial layers as well as capillaries and the intima and media of arteries.

Animals↗