Biomedical subjects
Publications and source records attributed to T Tsujimura.
The authors report a case of an epidermoid in the quadrigeminal cistern in a 40-year-old female who presented with headache and nausea. According to the literature, epidermoids are rarely found in the quadrigeminal cistern. Additional unusual features in this case were the absence of a capsule and T1-weighted magnetic resonance images suggestive of both solid (less intense) and fluid (more intense) components.
For the purpose of assessing the anti-tumor effect of UFT in metastatic liver cancer, blood futraful (FT), 5-fluorouracil (5-FU) and uracil levels and their distribution in tissue (cancer lesion, etc.) following oral UFT administration were examined in 10 surgically treated cases of metastatic liver cancer secondary to cancer of the large intestine and 4 cases of metastatic liver cancer secondary to stomach cancer. Liver tissue 5-FU distribution following UFT treatment was excellent. 5-FU concentration in liver cancer lesion was 0.164 +/- 0.128 micrograms/g, which was markedly higher than the minimal effective tissue concentration for 5-FU (0.050 micrograms/g). 5-FU level in normal tissue of the organ with primary cancer was significantly lower than that in the tumor-affected tissue of the same organ, while no difference in 5-FU level was noted between cancer-affected and normal tissues of the liver. Tissue 5-FU level in both primary and metastatic cancer lesions was significantly higher than the simultaneously determined blood 5-FU level. Histological findings of cancer-affected liver did not differ between different UFT dose levels, but degeneration of cancer cells was severe in some cases given high doses of UFT.
Poorly controlled NOD spontaneously diabetic mice were proven to have significantly less plasma and testicular testosterone than well-controlled diabetic mice (489 +/- 15 ng/dl and 3.89 +/- 0.79 micrograms/100 g tissue, vs. 176 +/- 24 and 9.00 +/- 1.24, respectively), and these in turn had significantly less than NOD non-diabetic control mice. These data were consistent with our previous observation of a decrease in total plasma and testicular testosterone levels in streptozotocin diabetic rats. A greater difference between total plasma testosterone levels and free testosterone levels was found in streptozotocin diabetic rats (17 +/- 4 ng/dl vs. 91 +/- 7 ng/dl) than in control rats (660 +/- 141 vs. 352 +/- 77). Fat droplets, depicting blocked testosterone synthesis, were found in the testicular Leydig cells of streptozotocin diabetic rats and disappeared with insulin treatment. No difference was found among plasma total testosterone concentrations in people in different stages of diabetes, as had been previously reported. However, human diabetic males, free of complications but poorly controlled, had less free testosterone than those without complications but well controlled (18.0 +/- 2.0 pg/ml vs. 22.8 +/- 1.3), who in turn had significantly less than age-matched controls (25.3 +/- 1.1 pg/ml). These data suggest gonadal dysfunction in diabetes mellitus.
Five hundred and nineteen patients with follicular center cell (FCC) tumors in Osaka, Japan were selected for study from 1000 patients with non-Hodgkin's lymphoma (NHL). They were admitted to hospital during 1964-1987, which was divided into three periods 1964-1972 (I), 1973-1979 (II), and 1980-1987 (III) to examine the time trend of FCC tumors. The median age of patients rose from 51 to 55 years of age with an increase in female and extranodal disease patients. The frequency of nodal FCC tumors among all nodal NHL increased from 37.5 to 51.5% (P less than 0.05), but that of extranodal types decreased from 82.9 to 56.8% (P less than 0.01), although the total number showed little change. When the cases were categorized as diffuse type and follicular type, the diffuse type predominated through the period in both nodal and extranodal sites. The frequencies of follicular type among all NHL were 10.2, 6.3, and 8.4% during the periods I, II and III, respectively. These results showed that follicular lymphoma was a minor constituent of NHL in Japan compared to Western countries, and the frequency did not increase from 1964 to 1987. The frequency of FCC tumors in the present series was rather higher than that in Western countries, therefore it is concluded that FCC tumors in Japanese have much less potential for forming a follicular structure than those in patients from Western countries.
Human tumor cell strains having different activities of O6-alkylguanine-DNA alkyltransferase (ATR) were transplanted into nude mice and chemotherapeutic responses of tumor xenografts were compared after intraperitoneal injection of the anti-tumor drug 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). The tumor strains used were four Mer+ strains possessing high ATR activity and three Mer- strains lacking this activity. Included in these Mer+ strains was a clone 5'dD which expresses the Escherichia coli ATR in Mer- HeLa cells and thus shows the Mer+ phenotype. All the Mer- tumor xenografts were much more sensitive than tumors of Mer+ strains, including the clone 5'dD; after the highest ACNU dose (three injections of 50 mg/kg), some Mer- tumors disappeared completely and the growth of other tumors was severely retarded, whereas all Mer+ tumors continued to grow. These results demonstrate that ATR activity in tumor cells is a major determinant of tumor response to ACNU, and further suggest that measurement of ATR activity in biopsy specimens may provide a useful guide to predict the response to chemotherapy.
An extrarenal malignant rhabdoid tumor arising from soft parts in the prepubic region of a 37-year-old man is described. This case appears to be unusual with regard to its location and age at onset. To our knowledge, the patient is the oldest recorded in whom such a lesion has arisen. Histologically, the tumor consisted of an admixture of polygonal and elongated cells with abundant eosinophilic cytoplasm frequently containing hyaline-like globules. Ultrastructurally, these cytoplasmic inclusions were compatible with intermediate filaments. Immunohistochemical staining disclosed keratin (non-squamous epithelial type) and epithelial membrane antigen positivity. These characteristic features were identical to malignant rhabdoid tumor of the kidney seen in infants and young children. This extrarenal malignant rhabdoid tumor showed an aggressive clinical course, although its exact histogenesis was unclear.
T cell-depleted C3H/He or (C57BL/6xC3H/He)F1 (B6C3F1) mice were prepared by adult thymectomy and injection of antithymocyte serum, followed 3 wk later by lethal x-irradiation and bone marrow reconstitution. When these T cell-depleted mice were not injected or injected i.v. with normal spleen and lymph node cells treated with either anti-Thy-1, -L3T4 or -Lyt-2 antibody plus C or C alone, none of the groups of mice developed thyroiditis. In contrast, the adoptive transfer of normal cells treated with anti-Lyt-1 plus C resulted in high incidence of the production of antithyroglobulin antibody and the induction of typical thyroiditis lesion. The thyroid was the sole organ involved, because neither typical inflammatory lesion in other organs nor autoantibody such as anti-DNA antibody was detected in mice that exhibited thyroiditis. Analyses of surface phenotypes of cells required for inducing thyroiditis by the adoptive transfer revealed that an appreciable percentage of Lyt-1 dull T cells remained after the treatment of normal lymphoid cells with anti-Lyt-1 plus C. Almost all of these Lyt-1 dull T cells expressed magnitudes of L3T4 or Lyt-2 Ag comparable to those detected on Lyt-1 bright T cells. More important, the induction of thyroiditis was almost completely prevented by either in vitro or in vivo elimination of Lyt-1 dull L3T4+(bright) but not of Lyt-1 dull Lyt-2+(bright) T cells. These results indicate that Lyt-1 dull L3T4+ T cells existing in normal healthy individuals have potential to induce typical thyroiditis which is associated with the production of antithyroglobulin autoantibody, and that the activation and/or function of this T cell subset is regulated by the Lyt-1 bright T cell population coexisting in normal lymphoid cell population.
To investigate the prognostic value of histologic and clinical factors in lymphomas of the gastrointestinal (GI) tract, the clinicopathologic findings in 56 Japanese patients with GI lymphomas were reviewed. They included 37 patients with gastric and 19 with intestinal lymphomas. The male to female ratio was 2.7:1 in gastric and 11:1 in small intestinal lymphomas. Histologically, all but one of intestinal lymphomas were high-grade lymphomas. Gastric lymphomas comprised 47% of low-grade and 53% of high-grade tumors. Significant factors for favorable prognosis identified by Cox's multivariate analysis were female sex, the presence of reactive lymphoid hyperplasia (RLH) in the primary site, early stage of disease, gastric lymphomas, and low-grade histologic type. The important role of chronic lymphocytic infiltration for development of gastric lymphoma was suggested by the high incidence of RLH and the intermediate lymphocytic type of lymphoma.
A study using monoclonal antibodies was made to evaluate the immunohistochemical localization of S-100 protein subunits alpha and beta in a total of 41 mixed tumours and adenomas of sweat gland origin. Normal eccrine glands showed positive staining for S-100 alpha in the secretory portion and in epithelial cells located in the transitional area from the coiled duct to the intraepidermal duct, as well as granular deposition of S-100 beta at the luminal surface of the secretory coil and duct. The myoepithelial cells were negative for S-100 alpha and beta. In mixed tumours, the tumour cells were round or oval in shape and displayed markedly positive staining for S-100 alpha and slightly positive or negative staining for S-100 beta. S-100 alpha staining in clear cell tumours was typically more intense than in any other sweat gland tumour. It is possible that clear cell tumours may arise from the transitional area of sweat glands. Spindle cell tumours displayed on abundance of S-100 alpha subunits but little S-100 beta. Occasional spindle cells located in the outer layer of tubular structures within tumours gave positive S-100 alpha staining. This result was different from that seen in pleomorphic salivary adenomas. Cells having undergone chondroidal changes revealed a positive S-100 reaction.
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A case of plasma cell dyscrasia with polyneuropathy and endocrine disorder is reported. Clinically, polycythemia vera, gynecomastia, pigmentation of the skin, hepatosplenomegaly, renal enlargement and severe polyneuropathy in the lower extremities were recognized. The peculiarity of this case was polycythemia vera that had been present for several years before manifestation of the clinical symptoms. Microscopically, retroperitoneal lymph nodes showed angio-follicular lymphoid hyperplasia and plasma cell infiltration in the interfollicular region. By means of the avidin-biotin-peroxidase complex method, plasma cells were positive for lambda light chain, IgA and IgG. Severe segmental demyelination and slight axonal atrophy were found in a sural nerve biopsy.
We report on an autopsy case of cholangiocarcinoma associated with Caroli's disease. A 38-year-old woman was admitted to our hospital suffering from epigastralgia. A diagnosis of Caroli's disease was made after CT, US, and ERCP testing. Because of diffuse intrahepatic bile duct dilatation, the patient was treated with antibioticus. In August 1985, her CA 19-9 level was 3,800 U/ml. This data suggested the development of a carcinoma secondary to Caroli's disease, but no tumor in the liver had been detected in the US and CT examinations. The patient died on February 1, 1986, of hepatorenal failure, approximately seven years after her first admission. An autopsy revealed diffuse dilatation of the intrahepatic bile duct (Caroli's disease) with a cholangiocarcinoma.
A case of placental-site trophoblastic tumor arising in the uterus is reported. The patient, a 34-year-old female, complained of irregular menstruation. Under the diagnosis of a tumor in the uterus or the ovary, a simple total hysterectomy and right adnexectomy were performed. Histologically, the tumor cells, which were large, polygonal or rounded in shape, had infiltrated into the myometrium in clusters or singly. Immunohistochemically, most of the tumor cells were positive to hPL. Further, hCG also was present in some tumor cells, though only weakly. Because of these findings, this case was diagnosed as a placental-site trophoblastic tumor (PSTT).
A case of primary signet ring cell carcinoma of the urinary bladder is reported. A 52-year-old man was admitted with the complaint of gross hematuria. Cystoscopy showed non-papillary tumor on the right lateral wall. Abdominal CT, Ga scintigraphy, upper gastrointestinal series and barium enema, revealed no signs of a tumor other than the bladder carcinoma. The routine hematologic and chemistry profiles showed no abnormalities except for the serum level of carcinoembryonic antigen elevated to 210 ng/ml. Total cystectomy and right nephroureterectomy with left cutaneous ureterostomy was performed and the surgical specimen showed adenocarcinoma of the bladder. The patient died 5 months after the operation, and autopsy was performed. No tumors were found on the mucosa of the whole digestive tracts or pancreas. This case might be of primary adenocarcinoma originated from the bladder. The literature on the differential diagnosis of the cases reported as bladder adenocarcinoma are reviewed briefly.
Lymphoproliferative diseases involving the nasal cavity and paranasal sinuses are uncommon and show complex histology, which make our understanding of the disease inadequate. In the present study, clinicopathologic findings, especially prognostic factors, in 42 patients with such diseases were reviewed. Histologically these cases were divided into ordinary lymphoma (23 cases) and a disease pattern that frequently showed a polymorphous picture containing large atypical cells with a non-lymphoid appearance (19 cases). The latter was termed midline malignant reticulosis (MMR) according to Kassel's classification. Clinically 'MMR' showed greater incidence of early onset of disease and higher male preponderance than ordinary lymphoma. The most common presenting symptom was nasal obstruction in both diseases. Favourable prognostic factors assessed by Cox's multivariate analysis were ordinary lymphoma (vs MMR), stage I disease, absence of ulceration in the lesions, and a tendency for local tumor formation.
Histological changes in 56 patients with recurrent soft tissue sarcomas (STS) were analysed. The original tumors included 23 malignant fibrous histiocytomas, five liposarcomas, four leiomyosarcomas, four synovial sarcomas, four neurogenic sarcomas, four dermatofibrosarcomas and 12 other assorted tumor types. The histological features of the recurrent tumors which underwent changes included increased cellularity, an increased number of mitotic figures, extension of sclerotic areas and the appearance of a storiform pattern; these were found in 30%, 43%, 41% and 29% of cases, respectively. No case showed a histological change from one subtype to another. A follow-up study revealed increased cellularity and mitotic counts in the recurrent tumors to be signs of an unfavorable prognosis.
Immunosuppressive acidic protein (IAP), a substance purified from cancer ascitic fluid, is released into the culture medium of macrophages and neutrophils, and is supposed to suppress an immune function of the host. Elevation of serum IAP in cancer patients has been reported. In the current study, presence of IAP in proliferating diseases of macrophage was examined. Macrophages in reactive proliferation, histiocytosis X, and neoplastic proliferation gave positive reaction for IAP. Diffuse cytoplasmic staining was usual, but dot-like or globular and surface staining also were observed. Proliferating cells in malignant fibrous histiocytoma were more sensitively stained by IAP than by other ordinary used markers for macrophage. These findings provide useful information to understand the mechanism of elevation of serum IAP in cancer patients.
We have constructed a truncated E. coli O6-methylguanine methyltransferase (MT) gene (ada gene) to express the MT activity for O6-methylguanine and O4-methylthymine but not for methylphosphotriester in human cells and transferred it into Mer- HeLa MR cells. The transfectant cells expressed the truncated E. coli MT were resistant to alkylating agents as same as the transfectant cells with the intact ada gene in cell killing, sister-chromatid exchange induction and host-cell reactivation of adenovirus 5. These results strongly suggest that methylphosphotriester may not contribute to the biological effect of alkylating agents in human cells.