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Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 829 records · Page 46Linked to original sources

A new murine model of autoimmune orchitis induced by immunization with viable syngeneic testicular germ cells alone. I. Immunological and histological studies.

Experimental autoimmune orchitis (EAO) was produced in C3H/He mice with as high as 100% incidence by two or three s.c. injections of 1 x 10(7) viable syngeneic testicular germ cells (TC) without resorting to adjuvants, Bordetella pertussis vaccine, or other immunological manipulations. On day 40 after the first injection of TC, the lesions induced were characterized by interstitial infiltration of inflammatory cells and severe hypospermatogenesis in the testis with resulting whole organ atrophy and, in contrast, by a complete lack of epididymitis. Immunological studies revealed that this form of immunization caused both delayed-type hypersensitivity and humoral antibody responses to syngeneic TC. We compared the susceptibilities to the induction of this type of EAO among six different strains of inbred mice comprising A/J, AKR, BALB/c, C3H/He, C57BL/6 and DBA/2 mice. All strains except for DBA/2 mice developed lesions of EAO to a greater or lesser extent, and severe disease was induced with high frequency in two strains, C3H/He and A/J. As this murine model of EAO can be induced without the use of Freund's complete adjuvant and B. pertussis vaccine, it is simply 'autoimmune' in nature and may provide new ways for further investigation into the immunological mechanisms which regulate deleterious autoimmune reactions to germ cell antigens leading to the male infertility.

Animals↗

Absorbed dose estimates in positron emission tomography studies based on the administration of 18F-labeled radiopharmaceuticals.

Absorbed doses were estimated after intravenous administration of 18F-labeled radiopharmaceuticals in Positron Emission Tomography (PET) studies. These radiopharmaceuticals, [18F]-2-Fluoro-2-Deoxy-D-Glucose (FDG), 6-[18F]Fluoro-L-Dopa (FDOPA) and 18F-5-Fluorodeoxyuridine (FdUR), are used in clinical research at the Cyclotron and Radioisotope Center of Tohoku University. Radiopharmaceutical biokinetic values were measured in humans or extrapolated from animal experiments. Selective organ uptake and rapid clearance of activity from the blood were observed. High activity in the bladder contents of humans was found. Calculations were made by the MIRD method, modified to account for the differences in physique and organ mass between the Caucasian Reference Man and the Japanese one. The bladder wall receives the highest dose (more than 1.23 x 10(-1) mGy/MBq) when any of these compounds are administered. Other organs receiving high doses are the heart, brain and kidneys from FDG; the kidneys and pancreas from FDOPA, and the kidneys and small intestine from FdUR. These organs received absorbed doses of more than 2.7 x 10(-2) mGy/MBq. Effective dose equivalents of 2.4 x 10(-2), 2.6 x 10(-2) and 3.3 x 10(-2) mSv/MBq were estimated in the intravenous administration of 18F-FDG, 18F-FDOPA and 18F-FdUR, respectively.

Adult↗

Circulating activated T cell subsets in autoimmune thyroid diseases: differences between untreated and treated patients.

To investigate the relationships between lymphocyte subsets and thyroid function, peripheral blood lymphocytes were analysed with cell surface antigens of activated (HLA-DR+) T, helper T (CD4+ 2H4-, CD4+ 4B4+) and suppressor-inducer T (CD4+ 2H4+, CD4+ 4B4-) cells subsets in 56 patients with Graves' disease, 16 patients with Hashimoto's thyroiditis, 7 patients with typical subacute thyroiditis and 2 patients with the thyrotoxic phase of autoimmune thyroiditis. Both patients with Graves' disease and Hashimoto's thyroiditis had increased percentages of HLA-DR+ T (Ia+ CD3+) cells as well as HLA-DR+ helper-inducer T (Ia+ CD4+) cells, which seemed to be independent of treatments. The percentage of HLA-DR+ suppressor-cytotoxic T (Ia+ CD8+) cells was increased in euthyroid or hypothyroid patients with Graves' disease following treatment, but was normal in hyperthyroid patients. The percentages of Ia+ CD4+ cells and Ia+ CD8+ were also increased in patients with thyroiditis, whereas these abnormal values normalized in the remission phase. These findings suggest that an increase in Ia+ CD4+ cells characteristically occurs during immune system activation in patients with hyperthyroid Graves' disease, Hashimoto's thyroiditis and the thyrotoxic phase of subacute thyroiditis, whereas the activated CD8+ cells in Graves' disease are induced by antithyroidal therapy.

Adolescent↗

A new murine model of autoimmune orchitis induced by immunization with viable syngeneic testicular germ cells alone. II. Immunohistochemical findings of fully-developed inflammatory lesion.

Previous studies demonstrated that experimental autoimmune orchitis (EAO) was produced in C3H/He mice with very high incidence by two or three subcutaneous injections of viable syngeneic testicular germ cells, without the use of any adjuvants or immunopotentiators and that the disease induced was characterized by a complete lack of epididymitis despite a definite orchitis with hypospermatogenesis. In this report, immunohistochemical characterization of immune cells in the fully-developed orchitic lesion was carried out using monoclonal antibodies and immunoperoxidase staining. Thy-1.2+ cells, Mac-1+ cells, B220+ cells and cytoplasmic Ig-bearing cells in the lesion were estimated to be approximately 30, 15, 20 and 30% of all inflammatory cells, respectively. Major phenotype of T cells in the lesion was CD4+ (approximately 85%) with the remainder (approximately 15%) being CD8+. The percentages of cytoplasmic IgG-, IgA- and IgM-bearing cells were estimated as approximately 35, 60 and 5% of all cytoplasmic Ig-bearing cells, respectively. Deposits of immunoglobulins and third component of complement were identified on the basement membrane of the seminiferous tubules, interstitium between the tubules, vessel endothelium and degenerated germ cells in the lesion. Circulating antibodies directed against the acrosomal portion of germ cells were detected in IgG and IgM classes but not in IgA class. Inflammatory cells (including macrophages, B cells and, probably, activated T cells) in the lesion were Ia+, but Leydig cells, Sertoli cells and germ cells did not stain for Ia at all.

Animals↗

[The role of extensive Denkers operation in combined therapy for maxillary sinus carcinoma].

We had a total of 372 patients with maxillary carcinoma in the period from 1972 to 1983. 108 patients were treated with 50Gy irradiation, intraarterial infusion of 2000 mg 5-FU and extensive Denker's operation in combination. 222 patients were treated with 50 Gy. irradiation and intraarterial infusion of 2000 mg 5-FU. The remaining 42 patients were treated with radio-therapy alone. The 5-year survival in these three groups was 48%, 43%, and 17%, respectively. The cumulative local control of the two former groups was 51%, and 33%, respectively. Total maxillectomy was performed as a second treatment only in 24 of 108 patients (22%) of the first group. Nine of them survived for 5 years and 15 died. On the other hand, 84 of 108 patients not treated with total maxillectomy consisted of 41 five year survivors and 43 deads. From the above, we believe that extensive Denker's operation plays a role to increase success rate of initial treatment, decrease in the necessity of total maxillectomy and improve survival rate, but its indication is limited.

Carcinoma, Squamous Cell↗

Vaccine effect of intact metacestodes of Taenia crassiceps against T. taeniaeformis infection in rats.

Wistar rats inoculated intraperitoneally with 10 viable metacestodes of Taenia crassiceps without adjuvant once on day 0 showed strong resistance to challenge with 200 eggs of T. taeniaeformis on day 30. When rats were killed one month after challenge, there were 80.4% and 46.1% reductions in the number of cystic and total metacestodes of T. taeniaeformis in the liver, respectively. When five rats were killed 16 months after challenge, they showed almost complete immunity against the challenge, with 99.4% and 91.1% reductions in the number of cystic and total metacestodes, respectively. There were only a few degenerated, pin-point metacestodes of T. taeniaeformis in the liver of all five rats; one harbored one cystic metacestode as well. However, there were no such reductions in rats injected initially with cyst fluid antigens of T. crassiceps with Freund's complete adjuvant. An additional experiment was carried out using 500 eggs of T. taeniaeformis in order to confirm the vaccine effect against higher egg dose. There were 96.6%, 87.9%, 83.9%, and 79.3% reductions in the number of cystic metacestodes in rats initially inoculated with 10 viable, 10 formalized, and 10 frozen metacestodes, and injected with sodium deoxycholate-solubilized metacestode antigens, respectively. It is strongly suggested that rats singly dosed with 10 viable or non-viable, intact metacestodes of T. crassiceps without adjuvant became highly resistant to challenge infection with eggs of T. taeniaeformis, which resulted in almost no cystic metacestode establishment.

Animals↗

[A case of recurrent hepatocellular carcinoma after hepatic resection surviving over five years by hepatic arterial infusion of lipiodol-anticancer drug suspension].

A 63-year-old male with four intrahepatic recurrences of surgically resected hepatocellular carcinoma was admitted to our hospital in June 1985. He underwent lateral segmentectomy of the liver in November 1983. Pathologic finding of Edmondson II with liver cirrhosis had been confirmed by the operative specimen. Sizes of four recurrent tumors were assessed by CT as 3.5 x 2.2 cm, 2.6 x 2.2 cm, 2.2 x 2.2 cm and 2.2 x 2.2 cm, respectively. During five years until July 1990, the patient was treated with hepatic arterial infusion of Lipiodol-anticancer drug suspension eight times (total 5-FU 900 mg, ADM 77 mg, MMC 73 mg, and Lipiodol 36 ml) and hepatic arterial chemoembolization of MMC microcapsules one time. In addition, two hepatic arterial infusions of CDDP (total 70 mg) were given and 5-FU (total 10 g) was administered intravenously. Partial response (PR) was obtained for 19 months. Hepatic arterial infusion of Lipiodol-anticancer drug suspension was given only once every 6 months, and he maintained a good quality of life for over four and half years. The man died in July 1990. In general, multiple intrahepatic recurrence of surgical resected hepatocellular carcinoma has a poor prognosis. Therefore it was considered that hepatic arterial infusion of this drug brought about the relatively long survival of more than five years.

Antineoplastic Combined Chemotherapy Protocols↗

[Toxic reduction and superior therapeutic effects on peritoneal carcinomatosis of etoposide particles suspended in oil in mice].

Two dosage forms of etoposide diluted by saline solution (Etp-sol) and etoposide particles suspended in oil (Etp-oil) were examined for the toxicity and therapeutic effects when injected intraperitoneally (ip) in mice. The 50% lethal dose (LD50) values for two weeks observation were 135 mg/kg in Etp-oil and 108 mg/kg in Etp-sol. Two days after intraperitoneal transplantation of 10(6) cells/mouse of P388 leukemia to CDF1 male mice, etoposide was injected intraperitoneally in the form of Etp-oil or Etp-sol. In the mice receiving 20mg/kg of etoposide, 11 of 19 mice given Etp-oil and 3 of 20 given Etp-sol survived to day 60. In the mice receiving 80 mg/kg of etoposide, 1 in 20 treated with Etp-oil and 8 of 20 treated with Etp-sol died from by the toxicity.

Animals↗

Multistage carcinogenesis of liver-fluke-associated cholangiocarcinoma in Thailand.

In northeast Thailand, the traditional habit of eating ground, raw freshwater and salt-fermented fish on a daily basis results in a local population repeatedly exposed to both liver fluke (Opisthorchis viverrini) infection and consuming nitrosamine-contaminated food from early in life. Epidemiological studies have revealed a coincident high prevalence of cholangiocarcinoma in this region and we have demonstrated in animal models that dietary contamination with nitrosamines and Opisthorchiasis are strong predisposing factors for cholangiocarcinogenesis. Thus all Syrian golden hamsters receiving a combination of subcarcinogenic doses of dimethylnitrosamine (DMN) and infection with flukes developed cholangiocarcinomas, while chemical administration or fluke infection alone did not cause cancer. Synergistic induction by chemical carcinogens and liver fluke infection was found to be related to levels of exposure to both. In this two-stage carcinogenesis model, nitrosamines are considered to act as genotoxicants exerting carcinogenic effects, while the liver flukes are assumed to play epigenetic roles. In our studies of biliary pathology related to worm burden in humans we found that while most of the subjects had worms, only a minority (25%) demonstrated a pathology of adenomatous hyperplasia, which is believed to predispose bile ducts to subsequent development of carcinomas, indicating the possible role of flukes as promoters. Biliary changes in nontumorous areas of hepatectomy specimens, including fibrosis (with or without adenomatous hyperplasia) which is found in most cases, and dysplasia in the fibrotic ducts indicate a conversion event in carcinogenesis: other factors may be required to aggravate the simple proliferation lesion so that they subsequently change to carcinomas. Furthermore, commonality in tumor phenotypes and expressions of ras p21 in both fluke related and non-fluke-related cholangiocarcinomas suggest that some similar mechanisms might be operating, at least in the relatively late stages of this multistage carcinogenesis involving the bile ducts.

Adenoma, Bile Duct↗

Measurement of D2 dopamine receptor-specific carbon-11-YM-09151-2 binding in the canine brain by PET: importance of partial volume correction.

Carbon-11-YM-09151-2 binds highly selectively to D2 dopamine receptors in the brain. Using this ligand, D2 dopamine receptor density (Bmax) and affinity (Kd) in canine striatum were measured. After administering various doses of the ligand in nine experiments, regional uptake was followed by repeated PET scanning for up to 80 min. D2 dopamine receptor specific binding at equilibrium was defined as striatal minus occipital activity after partial volume correction. Bmax and Kd were estimated by Scatchard analysis to be 40.3 pmole/ml of tissue and 22.9 nM, respectively. When a low mass dose of the ligand was administered, the bound-to-free ligand ratio in the striatum at equilibrium was consistent with the Bmax/Kd value obtained from the Scatchard analysis. The present study demonstrates the importance of partial volume correction and the Bmax/Kd measurement in a single PET study with carbon-11-YM-09151-2.

Animals↗

Clinical studies on hemorrhagic fever with renal syndrome found in Nagoya City University Medical School.

This study refers to the clinical features of 11 cases of hemorrhagic fever with renal syndrome (HFRS) which was prevalent in Nagoya City University Medical School. The clinical course was divided into two parts: the febrile stage and the polyuria stage. Symptoms such as lumbago, muscular pain, general malaise and anorexia disappeared along with a fall of fever. The incubation period of this disease was estimated to be about three weeks. Polyuria, proteinuria, gastric complication and impairment of liver function seemed to be some of clinical features of this disease. There was no HFRS patient with severe renal failure in our cases. The presence of disseminated intravascular coagulation (DIC) was confirmed in 3 of these 11 cases. Therefore, it was suggested that hemorrhagic tendency of this disease might be attributed to DIC. From our experiences, the most important factor for the treatment of the severe case was the earliest detection whether they were complicated by DIC or not. If they were suspected of DIC, it could be necessary to start treatment for DIC as soon as possible. Prophylactic measures for HFRS in our animal facility could contribute to the prevention of this disease.

Blood Cell Count↗

Immune mechanism facilitating clearance of Trypanosoma gambiense by IgG3 antibody from infected host.

The aggregation of trypansomes, immune adherence to macrophage and protection against infection of Trypanosoma gambiense are associated with IgG3 antibody. IgG3-mediated clumping trypanosomes are readily dissociated by the aid of complement to become free. Dissociation of the clumped trypanosomes in the equivalence area released approximately fifty percent of previous bound surface antigens. These antigens were capable of binding again to new IgG3 antibody. Experiments indicated that complement deposition altered functionally bivalent IgG3 antibody in the immune complex into a univalent one. Such event in the presence of complement is of great advantage to the infected host in killing pathogens in vivo, as it allows more antibodies to attach to surface antigens and subsequently initiate complement activity.

Animals↗