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Biomedical subjects

I Okayasu

Publications and source records attributed to I Okayasu.

At least 127 records · Page 7Linked to original sources

HPV type 16 in conjunctival and junctional papilloma, dysplasia, and squamous cell carcinoma.

AIMS: To clarify the role of human papillomavirus (HPV) infection in the development of papilloma, dysplasia, squamous cell carcinoma, and basal cell epithelioma arising from the eyelids, including the tunica conjunctiva palpebrum (conjunctiva), its junction to epidemis of eyelid skin (junction), and eyelid skin. METHODS: Sixteen cases of papilloma, four of dysplasia, four of squamous cell carcinoma, and 12 of basal cell epithelioma were examined using formalin fixed and paraffin embedded samples. Detection of HPV-DNA was performed by PCR-RFLP and in situ hybridisation (ISH) methods. RESULTS: HPV-16 was detected in 12/16 papillomas (75%), 2/4 dysplasias (50%), and 1/4 squamous cell carcinomas (25%) but in none of the basal cell epitheliomas. No other HPV subtypes were found. ISH assay showed positive signals in only two cases of dysplasia and squamous cell carcinoma. The mean age of HPV-16 positive dysplasia and squamous cell carcinoma cases (81.7 years) was significantly higher than that of HPV-16 positive papilloma cases (p < 0.01). CONCLUSIONS: Based on the presence of HPV-16 in both benign and malignant lesions and the age distribution, it seems likely that HPV-16 alone may be incapable of causing development of conjunctival and junctional dysplasia and squamous cell carcinoma, and that any correlation between the papilloma-squamous cell carcinoma sequence and HPV infection may be due to rare events.

Adult↗

Changes in bacterial phagocytosis of macrophages in experimental ulcerative colitis.

We previously reported that numerous macrophages which phagocytosed dextran sulfate sodium were observed to have accumulated in the mucosal lesions and in the spleen in experimental ulcerative colitis induced in mice with dextran sulfate sodium. In this paper, we investigated the bacterial phagocytic ability of macrophages which were isolated from spleens of mice treated with 3% dextran sulfate sodium for 6 months. In this model, the number of phagocytosed bacteria (Listeria monocytogenes) and the phagocytic index were significantly decreased. The phagocytic ability of splenic macrophages obtained from nontreated mice was also evaluated by incubating with dextran sulfate sodium in vitro, and adding bacteria. The number of phagocytosed bacteria and the phagocytic index were also significantly decreased. These observations suggest that the decrease in bacterial phagocytosis in this model by macrophages that phagocytosed dextran sulfate sodium indicates a decline of the mucosal defense system to bacteria.

Animals↗

Histopathological and immunohistochemical analysis of adenomatous hyperplasia and hepatocellular carcinoma: cellularity, thickness of cell cord, and Ki-67 proliferative activity.

To characterize adenomatous hyperplasia (AH) and hepatocellular carcinoma (HCC), and to establish their histopathological differences, morphometrical and immunohistochemical analyses, namely, cellularity, thickness of cell cord, and Ki-67 labeling index (Ki-67 LI) were done on surgically obtained hepatic lesions from patients with positive serum antibody against HCV. The hepatic lesions analyzed include chronic active hepatitis (CAH) (11 specimens), regenerative nodules of liver cirrhosis (LC) (29), AH (11), small HCC Edmondson's Grade I (GI) (19), GII (26), GIII (14). The results showed that AH has relatively high cellularity, and significantly greater thickness of cell cord than LC; whereas, HCC GI has significantly higher cellularity and Ki-67 LI than AH. From the data of these markers, and from the absence of conspicuous structural atypism, AH is considered to be in a different category from HCC GI. The premalignant potential of AH is supported only by its high incidence of coexistence adjacent to HCC GI or GII(6/11). Most lesions of HCC seem to develop from the liver tissue having a background of CAH or LC without passing through AH. Focal fatty changes are frequently observed within lesions of both AH and HCC GI (5/11, 8/19). When non-fatty regions of AH and HCC GI are compared, with respect to their markers, particularly Ki-67 LI, as well as the structural atypism, such as microacinus formation and pseudoglandular structure, and invasive growth into the surrounding liver parenchyma, HCC GI can be diagnosed as an early or well-differentiated malignant lesion.

Adenoma↗

Racial and age-related differences in incidence and severity of focal autoimmune thyroiditis.

To determine possible racial and age-related differences of focal autoimmune thyroiditis between white and black Americans, autopsy material from American subjects was evaluated for incidence and severity of chronic lymphocytic thyroiditis. The overall incidence of lymphocytic infiltration in thyroid sections from subjects aged more than 20 years was 41.4% in white females, 20% in white males, 17.4% in black females, and 8.5% in black males. An increase to 54.8% in incidence of thyroiditis from the first decade onward was noted in white females older than 80 years of age. Age did not cause a remarkable increase in incidence of thyroiditis in white males, in black females, or black males. The susceptibility to chronic thyroiditis in American white males and females was almost the same as that of British white males and females. The incidence of thyroiditis in black females and males was similar to that in Japanese females and males. These findings showed clear racial differences in susceptibility to chronic thyroiditis.

Adult↗

Focal hepatocellular necrosis and portal lymphocytic infiltration of the liver in chronic alcoholics: histopathological study of 40 liver biopsies.

Forty liver biopsies of hepatitis B surface antigen negative chronic alcoholics were histologically studied to assess the influence of hepatitis C virus (HCV)-infection. A moderate degree of focal hepatocellular necrosis and/or portal lymphocytic infiltration (FHN-PLI) was observed in 28% of the specimens, being especially prevalent in advanced cases of fibrosis and cirrhosis, and significantly correlated with HCV-infection. Eleven of these cases were examined in detail: HCV-infection was detected in eight and lymphocytic infiltration was apparent in the portal area, accompanied by formation of lymph follicles. The FHN-PLI was ascribed to alcoholic hepatitis in two HCV-negative cases and was concluded to be of unknown etiology in the remaining one HCV-negative case. This study thus indicated that over two-thirds of cases of chronic hepatitis in alcoholics can be attributed to HCV-infection, with the remainder being at least partly related to alcoholic hepatitis. The prevalence of alcohol-induced chronic hepatitis based on immunopathological findings was unclear, but was probably less frequent than previously reported.

Adult↗

[Establishment and characterization of strain KE-39 derived from human gastric cancer].

We succeeded in establishing a human gastric carcinoma cell line (KE-39) from oncocytes obtained from the primary focus of a 77-year-old male stomach cancer patient. From a histopathological point of view the gastric carcinoma was a poorly differentiated adenocarcinoma exhibiting a funicular from and a structure with a solid vesicular focus. The oncocytes adhered to glass and proliferated in cell clusters, with a doubling time of about 38.4 hours. Upon transplantation of the cancer cells into nude mice, no visible tumors were found, but from a histological point of view poorly differentiated adenocarcinoma similar to the primary focus was found in all cases. With immunological staining they were found to be positive for anti-CEA antibody and anti-CA19-9 antibody, but negative for anti-ICAM-1 antibody. KE-39 is a cell line which was established from the primary focus, and it was reported in the belief that it is a useful cell line, upon the investigation of its cancer metastasis mechanism and cytological characteristics.

Adenocarcinoma↗

Three novel synthetic retinoids, Re 80, Am 580 and Am 80, all exhibit anti-angiogenic activity in vivo.

In a previous study, we demonstrated that retinoic acid or a synthetic retinoid, Ch 55 ((E)-4-[3-(3,5-di-tert-butylphenyl)-3-oxo-1-propenyl]benzoic acid), significantly affects in vivo angiogenesis, on the basis of our working hypothesis that a cell differentiation modulator could also exhibit anti-angiogenic activity. In the present study, three novel synthetic retinoids, Re 80 (4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl- 2- naphthalenyl)-1-propenyl]benzoic acid), Am 580 (4-[(5,6,7,8-tetrahydro- 5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]benzoic acid) and Am 80 (4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl] benzoic acid), whose cell differentiation-modulating effects are roughly comparable to or more potent than that of Ch 55, which was the most effective angiostatic retinoid identified previously, were examined. Their anti-angiogenic effects were tested in an in vivo assay system involving chorioallantoic membranes of growing chick embryos. They were all found to exert dose-dependent anti-angiogenic effects in the picomolar range. Their rank order for inhibitory potency was Re 80 > Am 580 > Am 80, the ID50 values being 6.3, 23 and 28 pmol/egg, respectively. These results indicate that treatment involving these three novel synthetic retinoids might have potential therapeutic efficacy in various angiogenesis-dependent disorders, including solid tumors, psoriasis, rheumatoid arthritis and diabetic retinopathy.

Animals↗

Characterization of resistance to murine experimental autoimmune thyroiditis: duration and afferent action of thyroglobulin- and TSH-induced suppression.

Genetically susceptible mice develop experimental autoimmune thyroiditis (EAT) after immunization with mouse thyroglobulin (MTg). Earlier studies have shown that resistance to EAT induction can be activated by two regimens, pretreatment with deaggregated MTg (dMTg) or with thyroid-stimulating hormone (TSH). With both protocols, suppression is linked to a > or = 2-3 day increase in circulatory MTg level and is mediated by CD4+ suppressor T cells (Ts). To assess the duration of suppression, CBA (H-2k) mice were injected with dMTg or infused with TSH via an osmotic pump for 3-4 days and then challenged with MTg + adjuvant at intervals up to 73 days for dMTg-pretreated mice or up to 94 days for TSH-pretreated mice. Suppression was measurable for at least 73 days after injected dMTg. TSH-induced suppression was also long-lasting; resistance was strong 38 days after TSH infusion and was still measurable on Day 66. The Thy-1+, CD4+ Ts which transfer MTg-induced suppression were further characterized by treatment with I-J antibodies plus complement prior to transfer. This treatment abolished the transfer of suppression which acts in the afferent phase to interfere with EAT induction. The capacity of Ts to suppress the efferent phase of EAT was assessed in vitro and in vivo. Cells from dMTg-pretreated mice did not block the in vitro proliferative response of MTg-primed cells to MTg, nor did these cells, when left intact in situ, reduce the severity of disease produced by the adoptive transfer of thyroiditogenic cells. Similarly, TSH-induced suppression was ineffective in preventing adoptively transferred EAT. Since suppression, which correlates with a temporary increase of circulatory MTg, occurs only at the afferent phase of active immunization, these findings lend support to our earlier hypotheses that circulatory MTg serves a physiologic role in maintaining normal self-tolerance by sustaining low levels of Ts activation and that additional rise above baseline increases and prolongs resistance to EAT induction.

Animals↗

Occurrence of dysplasia and adenocarcinoma after experimental chronic ulcerative colitis in hamsters induced by dextran sulphate sodium.

In this study, long term dextran sulphate sodium administration was studied to ascertain whether colorectal carcinoma could be produced in patients with long standing ulcerative colitis. Simultaneously, changes in the intestinal microflora were analysed. Low grade to high grade dysplasia was seen in three of the five hamsters treated with 1% dextran sulphate sodium solution for 100 days, while no dysplasia was detected in the eight animals concomitantly treated with metronidazole, an antianerobic microbial agent, which prevents colonic ulceration. In these two groups, none of the animals developed colorectal cancer over 100 day period. In a group treated for 180 days, seven of the eight animals had dysplasia, and one had two adenomas. Furthermore, four of the eight animals had adenocarcinoma in the transverse colon; they were protruding well differentiated adenocarcinoma in one and non-protruding lesions infiltrating into the musclaris propria in three. The three non-protruding infiltrating adenocarcinomas were classified to be well differentiated adenocarcinoma in one and mucinous adenocarcinoma in two, resembling the type of cancer which complicates ulcerative colitis in man.

Adenocarcinoma↗

Multiple carcinoid tumors of the stomach with hypergastrinemia.

A 42-yr-old woman presented with multiple carcinoid tumors in her stomach and a markedly elevated serum gastrin level. Total gastrectomy was performed, and 22 small carcinoid tumors were found in the gastric fundus and body. A high serum gastrin level was revealed in the gastric drainage veins; still more gastrin was detected in the carcinoid tumors by the immunohistochemical method, and many secretory granules were found in the tumor cells with an electron microscope. The fundic gland showed marked atrophy, and there was some conglobation of endocrine cells (ECL cells). This case suggests a hypothetic sequence of anacidity due to atrophic gastritis----hypergastrinemia----proliferation of ECL cells----multiple carcinoids. A search of the Japanese literature revealed that 26 cases of multiple carcinoid tumors in the stomach have been reported so far, and most of them support this hypothesis.

Adult↗

Is focal chronic autoimmune thyroiditis an age-related disease? Differences in incidence and severity between Japanese and British.

The incidence of chronic lymphocytic thyroiditis in autopsy material from Japanese and British subjects was evaluated. Lymphocytic infiltration in representative thyroid sections from 1826 Japanese cases collected from four different institutions was analysed. The overall incidence of lymphocytic infiltration was significantly higher in females (22.2 per cent) than in males (13.9 per cent). In females, the incidence reached 23.2 per cent in the fourth decade and showed no increase with age thereafter. The overall incidence of lymphocytic infiltration in thyroid sections from 810 British cases was 42.5 per cent in females and 19.4 per cent in males; an increase in the incidence of thyroiditis from the sixth decade onwards was noted in British females, the figure reaching 50.0 per cent in those aged over 70 years. These findings suggest possible racial differences in susceptibility to chronic thyroiditis. The disorder is not necessarily related to age, increasing severity of disease with age being found only in British females.

Adult↗

A high frequency of detection of Helicobacter pylori in whitish exudate of gastric ulcer.

Helicobacter pylori has been implicated in the pathogenesis of chronic gastritis and peptic ulcer. However, no report to date has been made on the presence of H. pylori in the whitish exudate of peptic ulcers. We examined the biopsy specimens of 52 patients (42 men and 10 women, aged 29-78, not taking steroids or nonsteroid antiinflammatory drugs), and evaluated the frequency of detecting the organism in the whitish exudate of gastric ulcers in comparison with that in the ulcer border, gastric fundic gland, and pyloric gland using microaerobic culture and acridine-orange stain. H. pylori was detected in high rates: 38 (73%) of 52 cases by culture, and 50 cases (96%) by staining of the whitish exudate, 42 (81%) of 52 cases by culture, and 46 cases (88%) by staining of the ulcer border. The frequency for the other regions were 81% by culture and 90% by staining of the fundic gland, and 81 and 90% of the pyloric gland, respectively. Of all sites studied by the staining method, H. pylori was detected at the highest frequency in the whitish exudate. The fact that many H. pylori live in the whitish exudate of gastric ulcer, suggests a causal relationship between H. pylori and gastric ulcer.

Acridine Orange↗

A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice.

Acute and chronic experimental ulcerative colitis models were produced in mice by providing them with drinking water containing synthetic dextran sulfate sodium. Mice that developed acute colitis showed signs of diarrhea, gross rectal bleeding, and weight loss within 6-10 days after ingesting 3%-10% dextran sulfate sodium. On postmortem examination, multiple erosions and inflammatory changes including crypt abscesses were found on the left side of the large intestine. Mice that developed chronic colitis showed signs of erosions, prominent regenerations of the colonic mucosa including dysplasia, shortening of the large intestine, and frequent formation of lymphoid follicles after 5 administration cycles, where each cycle was composed of 7 days' consumption of drinking water containing 5% dextran sulfate sodium followed by 10 days' consumption of distilled water. The population of intestinal microflora, Bacteroides distasonis and Clostridium spp., increased significantly in mice with acute and chronic ulcerative colitis. Further, morphological studies suggest that the administered dextran sulfate sodium was partially phagocytized by macrophages in the colonic mucosa.

Acute Disease↗

DNA analysis of periampullary cancers.

The nuclear DNA content in 71 cases of periampullary cancer (27, cancer of the head of the pancreas (Ph); 24, cancer of the ampulla of Vater (A); and 20, cancer of the inferior common bile duct (Bi] was measured cytofluorometrically using the archival paraffin-embedded specimens of the primary lesions. They were analyzed in relation to prognosis, tumor size, histological differentiation, lymph node metastasis, lymphatic invasion, venous invasion, perineural invasion, and growth pattern. The results show that "Ph" has more unfavorable prognosis compared with the other two and it has more DNA content under the same conditions such as tumor from 2.1 to 4 cm in its greatest dimension, well differentiated adenocarcinoma, with or without lymph node metastasis, with or without venous invasion, with lymphatic invasion, with perineural invasion, and in the intermediate growth pattern between expansive and infiltrative. In conclusion, this study demonstrates a close correlation between the DNA content and prognosis and the significant clinical value of DNA analysis for predicting the prognosis in patients of periampullary cancer.

Adenocarcinoma↗

Long-term observation and effect of age on induction of experimental autoimmune thyroiditis in susceptible and resistant mice.

After induction of experimental autoimmune thyroiditis (EAT) in mice, long-term observation on both the severity of thyroiditis and antibody formation against mouse thyroglobulin (MTg) was carried out over a period of 18 months. In EAT-susceptible strains (CBA, C3H/Anf), both the severity of thyroiditis and MTg antibody production continued for a long term. In EAT-resistant mice (BALB/c), thyroiditis remained minimal, if present, and the low antibody response to MTg became negligible. On the other hand, aging had a prominent effect on the EAT induction in susceptible mice; both MTg antibody response and thyroid infiltration were markedly reduced. These data were well correlated with reduced antibody formation against sheep red blood cells. Young and old mice were further compared as donors or recipients in adoptive transfer of concanavalin A-stimulated cells. Lymph node cells from either young or old MTg-immunized mice transferred appreciable thyroiditis to normal young and old recipient mice. However, similarly treated spleen cells from MTg-immunized old mice responded more poorly to in vitro stimulation with mitogens or MTg and transferred thyroiditis to very few normal young or old mice.

Aging↗

Selective and persistent deposition and gradual drainage of iodized oil, Lipiodol in the hepatocellular carcinoma after injection into the feeding hepatic artery.

The selective and long-term deposition of iodized oil in the hepatocellular carcinoma (HCC) and its gradual drainage were clinicopathologically analyzed in 13 cases. All patients were Japanese and had an intrahepatic arterial injection of Lipiodol (LIP) mixed with Mitomycin C. The comparison among the follow-up computerized tomography (CT) findings, the observation of the soft x-ray radiogram, and histopathologic studies of the surgical or autopsy materials revealed that the selective deposition of LIP in HCC lasted for a long term, particularly in cases treated by LIP combined with transcatheter arterial embolization (TAE). Also revealed was an extremely gradual decrease of LIP from the HCC. It was thus postulated that, mainly, the accumulated macrophages surrounding LIP around the necrotic cancer tissue and, partially, the intrahepatic lymphatic system itself contributed to this drainage. Further, in histologic sections with lipid staining, x-ray microanalysis proved that the lipid droplets in the cancer tissue included highly concentrated iodine, as a deposition of LIP.

Carcinoma, Hepatocellular↗

[The immunohistochemical localization of CA 15-3 in human breasts and their tumors].

The tissue distribution of CA 15-3, a breast carcinoma associated antigenic determinant, has been investigated by an avidin-biotin immunoperoxidase technique in the human breasts and in their tumors. In cases of scirrhous carcinoma, positive stainings for CA 15-3 were observed in almost all carcinoma cells. In cases of solid-tubular carcinomas and papillotubular carcinomas, the reaction was various and there was no correlation between the distribution of CA 15-3 and the clinical stage. Apical staining was recognized in both solid-tubular and papillotubular carcinomas, in benign breast tumors, and in normal breast tissues. CA 15-3 appears to be related to the degree of differentiation of the breast tissue.

Adenocarcinoma↗