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Biomedical subjects

S Sugihara

Publications and source records attributed to S Sugihara.

At least 19 recordsLinked to original sources

The morphologic transition in hepatocellular carcinoma. A comparison of the individual histologic features disclosed by ultrasound-guided fine-needle biopsy with those of autopsy.

In hepatocellular carcinoma (HCC), it has been strongly suggested that as the tumor increases in size, foci of less-differentiated malignant tissues arise in the well-differentiated tumor and increase until they replace the well-differentiated tumor tissues. It has also been suggested that tumor growth is attributed to such dedifferentiation. In the current study, the individual histologic features of ultrasound-guided fine-needle biopsy specimens, taken from 12 small HCC in an early stage, were compared with those of autopsy to confirm the dedifferentiation of HCC. In all 12 cases, autopsy was performed 6 months or more after the initial biopsy. Dedifferentiation was demonstrated in 9 of 12 cases (75.0%). Most of the biopsy specimens from minute HCC were well-differentiated. All tumors that had been well-differentiated when evaluated by biopsy were found to have become moderately differentiated at autopsy. This comparative study confirmed the dedifferentiation of HCC with tumor growth.

Aged

[Experimental study of water jet angioplasty].

A newly invented angioplasty by using water jet energy was investigated for evaluating its safety and effectiveness in 3 dogs. The water jet was produced from a small tip nozzle (0.2 mm in diameter) of catheter by injecting 20 ml of diluted contrast medium. By using this method recanalization of femoral arterial occlusion produced by fresh thrombi was achieved in all 3 dogs. Post recanalization angiography showed no apparent small vessel occlusions. Injection apart more than 5 mm from the inner surface of human aorta provoked no apparent changes histopathologically. Water jet angioplasty may be useful in treating vascular occlusive disease.

Animals

Adenomatous hyperplasia in the vicinity of small hepatocellular carcinoma.

The nodular lesions seen in the noncancerous areas of the 80 consecutively resected small hepatocellular carcinoma associated with cirrhosis were pathomorphologically studied. A total of 51 nodular lesions were found, and they were classified into the following four groups: large regenerative nodule (30 nodules), adenomatous hyperplasia (12 nodules), atypical adenomatous hyperplasia (4 nodules) and adenomatous hyperplasia containing cancerous foci (5 nodules). Grossly, all large regenerative nodules were well demarcated, but some of the adenomatous hyperplasia group were vaguely nodular. Atypical adenomatous hyperplasia and adenomatous hyperplasia containing cancerous foci accounted for 43% of the adenomatous hyperplasia group found in the vicinity of the 16 resected hepatocellular carcinoma (20%) out of 80 cases. The mean size (+/- S.D.) of the adenomatous hyperplasias containing cancerous foci, 15.8 +/- 2.2 mm, was significantly larger than 10.1 +/- 2.6 mm of the adenomatous hyperplasias p less than 0.01). All adenomatous hyperplasias containing cancerous foci and 75% of the atypical adenomatous hyperplasias demonstrated a marked fatty change, but none of the large regenerative nodules were accompanied by any fatty changes. This study demonstrated the morphological transition from adenomatous hyperplasia to hepatocellular carcinoma that was suggestive of multistep hepatocarcinogenesis. As a result, it is predicted that approximately 20% of all hepatocellular carcinomas may have the potential for being of multicentric origin and that approximately 40% of adenomatous hyperplasias may undergo malignant transformation, but it is difficult to estimate the exact number of incidences. The presence of varying degrees of fatty change may be one of the significant morphological markers for a malignant transformation from adenomatous hyperplasia to hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma

Suppression of pulmonary granulomatous inflammation by immunomodulating agents.

We demonstrated previously that macrophages and macrophage-derived cytokines including lymphocyte-activating factors (LAFs) play a critical role in lung granuloma formation in mice and that granulomas sizes correlated with LAF activity in the lesions. In the present study, we examined the effects of D-penicillamine (D-Pc), 2-acetylthiomethyl-3-(4-methyl-benzoyl)propionic acid (KE-298) and dexamethasone (Dex) on dextran bead-induced lung granulomas in mice. KE-298 is a newly synthesized compound containing sulfur (S) similar to D-Pc. Large granulomas developed, which reached peak intensity within 3 days and declined in size thereafter. Aqueous lung extracts of the mice contained high levels of LAF that were correlated with granuloma sizes. The lesions and local LAF activity were inhibited by administration of these agents. The most potent inhibitor was Dex. The suppressive effect of KE-298 was similar to that of D-Pc. These results suggest that suppression of granulomas may be attributed to inhibition of LAF activity/synthesis by these agents.

Animals

The inhibitory effect of the combination of antineoplaston A-10 injection with a small dose of cis-diamminedichloroplatinum on cell and tumor growth of human hepatocellular carcinoma.

The inhibitory effects of a combination of Antineoplaston A-10 Injection with a small dose of cis-diamminedichloroplatinum (CDDP) on cell and tumor growth was tested in vitro and in vivo settings. A human hepatocellular carcinoma cell line (KIM-1) was used for the cell growth and transplanted tumor growth studies. In the cell growth study, one-hour exposure of KIM-1 cells to CDDP in the medium at concentrations of 0.5, 1.0, and 2.0 micrograms/ml inhibited cell growth dose-dependently. Continuous exposure of cultured cells to Antineoplaston A-10 Injection at concentrations of 4, 6, and 8 mg/ml also inhibited tumor growth dose-dependently. The combination of 0.5 microgram/ml CDDP and 6 mg/ml A-10 Injection inhibited cell growth more than did each agent individually. Electron microscopic study showed well-maintained organelle structures in Antineoplaston A-10 Injection-treated cells compared to CDDP-treated cells. alpha-Fetoprotein (AFP) production by 10(4) cells in 48 h increased in the A-10 Injection-treated and A-10 Injection+CDDP-treated groups as the concentration of these agents increased. In the tumor growth study, daily administration of Antineoplaston A-10 Injection 75 mg with once a week administration of 20 micrograms of CDDP for 5 weeks inhibited transplanted tumor growth in athymic mice after 33 days of treatment, while administration of 75 mg of A-10 Injection or 20 or 60 micrograms of CDDP alone showed no significant inhibition of tumor growth.

Animals

Pathomorphologic study of pale bodies in hepatocellular carcinoma.

Pathomorphological and immunohistochemical studies were conducted on cases of hepatocellular carcinoma (HCC) with pale bodies (PB). HCC containing PBs was seen in 6 (5.7%) of 106 consecutively resected HCC cases. It was of interest that varying degrees of sclerotic change were found in 4 of the 6 cases and a certain correlation between PBs and sclerotic change of HCC tissue was suggested. Histologically, PBs were identified as a pale amorphous substance with a distinct margin and most of PBs occupied the entire cytoplasm of the cancer cells. PBs were practically negative for periodic-acid Schiff, and were also negative for phosphotungstic acid hematoxylin and orcein stains. Ultrastructurally, PBs were found to be a mass of granular or fibrillar materials having a single-layered limiting membrane, and dilated rough endoplasmic reticular (rER) were also found in the vicinity of PBs, suggesting the presence of a close relationship between rough endoplasmic reticula and PBs. Most PBs were found to be strongly positive for anti-fibrinogen antibody and some of them were weakly positive for anti-albumin, but were solely negative for other antibodies such as anti-HBs antigen, anti-alpha-1-antitrypsin, and anti-ferritin. According to those findings, PBs were thought to be fibrinogens accumulating in cystic rER due to a defective intracellular transport or an excretion disturbance.

Aged

Inflammatory cytokines and enzymes in synovial fluid of patients with rheumatoid arthritis and other arthritides.

Cytokines and lysosomal enzymes, which are produced by inflammatory cells, play a role in inflammation. We have found that synovial fluid (SF) in rheumatoid and septic arthritis contained a large number of white blood cells (WBCs) and high levels of cytokines and enzymes, while in contrast the SF of osteoarthritis and traumatic arthritis did not contain significant amounts. Measurements of WBCs, cytokines and enzymes in SF are useful for evaluating clinical disease activity. Assays for WBCs and enzymes are simple and rapid when compared to those for cytokines.

Adult

Clinical study of malignant tumors originating in the pelvic region.

We evaluated the surgical problems encountered during treatment of 14 patients with malignant tumors originating in the pelvic region at our department. The tumor involved the iliac bone in 6 patients, the ischial bone in 2, the pubic bone in 2, and the gluteal region in 4. Invasion to the sacrum was observed in 7 patients. Twelve patients underwent surgical procedures consisting of intralesional resection in 6, marginal resection in 3, and wide margin resection in 3. Six of the 7 patients with sacral invasion developed local recurrence. Two patients with chondrosarcoma and one with parosteal osteosarcoma survived for 4 or more years, but the mean survival period in those with high grade malignant tumors was 11 months. These findings indicate the difficulties encountered in the treatment of malignant pelvic tumors.

Adolescent

Gadolinium-DTPA enhanced magnetic resonance imaging of bone and soft tissue sarcomas in comparison with pathological findings.

We compared gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced T1-weighted images (T1-Gd) with the histopathological findings in 13 patients with bone or soft tissue sarcomas. Signal intensity of the viable tumor tissue was increased in T1-Gd in 92% of the patients. The necrotic or cystic areas in the tumor were not enhanced, rendering them distinctly. The degree of enhancement of the edematous area around the tumor was similar to or more marked than that of the tumor in 54% of the patients. Area showing inflammatory cells infiltration and edematous areas in the tumor tissue were also enhanced. Thus, the effect of preoperative chemotherapy in tumor tissues other than necrotic and cystic areas tended to be underestimated in T1-Gd. Its effect should be comprehensively evaluated based on not only T1-Gd but also T2-weighted images and findings of other imaging techniques.

Antineoplastic Agents

Radiological long-term follow-up of grafted xenogeneic bone in patients with bone tumors.

Radiological findings on the fate of grafted Kiel bone implants for the treatment of bone tumors were evaluated in 25 lesions. The mean follow-up period was 14.8 years, ranging from 5 to 21.8 years. We classified the radiological findings into 4 grades; Excellent (4 lesions), Good (14 lesions), Fair (2 lesions), and Poor (5 lesions). All cases of the Poor grade were polyostotic fibrous dysplasia. The younger the patient at the time of the operation, the more rapidly Kiel bone grafts tended to be incorporated. The grafted bone can become enmeshed in the structure of the recipient bed (Good or Excellent grades) within 10 years in most cases, except in polyostotic fibrous dysplasia.

Adolescent

Sclerosing hepatocellular carcinoma with hypercalcemia--a case report.

A case of sclerosing hepatocellular carcinoma (SHCC) with hypercalcemia was reported. Clinical studies revealed a tumor at the liver hilum with invasion into the bile duct. Light microscopy of the tumor disclosed a moderately differentiated hepatocellular carcinoma (HCC) of the trabecular type with diffuse fibrous stroma. Abundant dense granules were observed in the cytoplasm of the tumor cells with electron microscopy. The elevated serum calcium (13.9 mg/dl) returned to the normal range after resection of the tumor.

Carcinoma, Hepatocellular

Tumor-targeted chemotherapy with lipid contrast medium and macromolecular anticancer drug (SMANCS) for renal cell carcinoma.

Twenty-five patients with renal cell carcinoma were treated with a lipophilic macromolecular drug, poly(stylene-co-maleic acid)-conjugated neocarzinostatin (SMANCS) dissolved in lipid contrast medium (Lipiodol). The drug was injected by catheterizing the renal artery and another feeding artery in 24 patients, and in the common hepatic artery in 1 patient with metastases to the liver after a radical nephrectomy. The procedure of selective arterial administration of 3-20 mg/mL of SMANCS/Lipiodol was simple to perform and was required once every two to three weeks. Total dose of SMANCS for each patient varied from 3 to 57 mg. Both SMANCS and Lipiodol accumulated more selectively in tumor than in any other tissue and remained in the neovasculature and extracapillary space for a long time. CT pattern of the remaining oil contrast medium in the tumor was characterized by the high-density area localized mainly in the periphery of the tumor around the central necrosis. When hyperviscosity Lipiodol (Lipiodol HV) was used as lipid contrast medium, it remained more persistently in the tumor and disappeared more slowly than Lipiodol. Moreover, the pronounced anticancer effect was recognized when SMANCS/Lipiodol HV was administered compared with only SMANCS/Lipiodol. Severe side effects, such as myelosuppression, unendurable pain, paralytic ileus, etc., were not observed. This targeting chemotherapy may be of great significance for advanced renal cell carcinoma.

Adult

Enzyme-induced aggregation and disaggregation of tumor cells via the cell surface glycocalyx in association with deoxyribonucleic acid.

Serine proteases cause aggregation of the rat ascites tumor cell lines AH-130, AH-109A and YS in vitro, and the tumor cell aggregates are dissolved by treatment with DNase I. We previously demonstrated that these events played a critical role in the augmentation or reduction of experimental blood-borne metastasis of these cell lines. In the present study, the ultrastructural features of this protease-dependent aggregation were analysed. Transmission and scanning electron microscopy revealed that after the protease treatment each tumor cell was surrounded by a thin membranous (sleeve-like) structure. This sleeve-like structure was stained with ruthenium red to an intensity similar to the cell surface of the control. Adjacent cells became attached to each other with microvilli via this fine structure. Immuno-electron microscopy revealed DNA antigen as dense patches on the sleeve-like structure or as faint and diffuse deposits on the outer surface of the cells by indirect immunoperoxidase staining using an anti-DNA monoclonal antibody. Both the sleeve-like structure and immunopositive deposits disappeared after treatment with DNase I. Neither cell viability nor the normal ultrastructure of their organelles was influenced by the enzyme treatment. These results indicate that serine protease-induced tumor cell aggregation is due to cellular contact via the sleeve-like structure, which probably originates from the cell surface glycocalyx in association with DNA molecules of unknown origin.

Animals

[DNA ploidy in submucosal cancer of the stomach and its relationship to lymph node metastasis].

The relationship between DNA ploidy and lymph node metastasis was determined in 40 cases of gastric cancer confined to the submucosa (with lymph node metastasis 20 cases and without 20 cases). The DNA ploidy patterns were classified as follows: Type D, Type A1 and Type A2. Of the 20 cases with lymph node metastasis, 1 was Type D, 7 were Type A1 and 12 were Type A2. The likelihood of lymph node metastasis was 12.5% (1/8) for Type D, 43.8% (7/16) for Type A1 and 75.0% (12/16) for Type A2. It is concluded that although gastric cancer confined to the submucosa is classified as early one, analysis of DNA content places such tumors with lymph node metastasis into the advanced cancer category.

DNA, Neoplasm

Intermediate filament expression in non-neoplastic pituitary cells.

Fifty-one non-neoplastic human pituitary glands, including examples with Crooke's hyalinization or amyloidosis, were examined by an immunoperoxidase method using antibodies to keratin, vimentin, neurofilaments (NFs), glial fibrillary acidic protein (GFAP), desmin, actin, S-100 protein and a variety of pituitary hormones. It was confirmed that most of the epithelial cells in the pituitary gland express keratin immunoreactivity. These cells included endocrine cells in the anterior lobe, endocrine cells and squamous metaplastic cells in the pars tuberalis, columnar and ciliated epithelia forming follicular structures and salivary-type epithelium in the pars intermedia, and anterior lobe cells infiltrating the posterior lobe. This study also demonstrated that keratin and NFs may be co-expressed in endocrine cells in the pituitary anterior lobe, that keratin, vimentin and GFAP may be co-expressed in the epithelial cells forming cyst-like follicle in the pars intermedia, and that vimentin and GFAP may be co-expressed in folliculo-stellate cells and pituicytes. In addition, the GFAP and S-100 protein-negative high columnar epithelium in the pars intermedia tended to be positive for adrenocorticotropic hormone and melanocyte stimulating hormone, while the low columnar epithelium with the co-expression of GFAP and S-100 protein was negative for pituitary hormones.

Amyloidosis

Intermediate filament expression in pituitary adenomas.

Seventy-five formalin-fixed and 18 alcohol-fixed pituitary adenomas were studied immunohistochemically using antibodies to keratin, vimentin, neurofilaments (NFs), glial fibrillary acidic protein, desmin, actin, S-100 protein and a variety of pituitary hormones. The pituitary adenoma cells were positive for keratin, vimentin and NFs (68 kDa and 160 kDa) and in a few instances there was co-expression of these three types of intermediate filaments (IMFs). The pattern of keratin-specific staining showed diffuse cytoplasmic or patchy paranuclear reactivity and of NF- or vimentin-specific staining showed fibrillar or patchy paranuclear reactivity. The patchy staining seemed to decorate the fibrous body. There was no correlation between the distribution of IMFs and pituitary hormones in pituitary adenomas except that melanocyte-stimulating-hormone-positive reactivity was limited to the NF-positive adenomas. The pattern of IMF staining did not depend on hormone production in adenomas.

APUD Cells

Electron microscopic observations on the morphogenesis of renal cell carcinoma induced in rat kidney by dimethylnitrosamine and N-(3,5-dichlorophenyl)succinimide.

Renal cell carcinoma was induced in rats by p.o. administration of dimethylnitrosamine, 500 ppm daily, followed by N-(3,5-dichlorophenyl) succinimide (NDPS), 5000 ppm daily. Fine structural changes of the proximal convoluted tubule cells were observed by sequential examinations of the kidney cortices at 3, 5, 12, and 24 weeks after drug administration. Early prominent structural changes of the cells induced by dimethylnitrosamine alone were the appearance of microspherules in nucleoli and of numerous lamellar bodies on the membrane structure of the cells. With the addition of NDPS, the cells exhibited edematous cytoplasm that, in contrast to the relatively intact nuclear structure, contained numerous bodies small vesicles and dark mitochondria, with markedly disarranged microvilli. After prolonged treatment with these drugs, some of the cells showed regenerating features, while others became necrotic. In the former case, large clear nuclei appeared with enlarged nucleoli containing a large amount of granular components. Ribosomes in the cytoplasm also increased in number in accordance with nucleolar changes, and edema in cytoplasm and microvilli markedly decreased. However, a considerable number of vesicles still remained in some cells. Mitochondria decreased in number and showed pleomorphism and relatively high electron density. At 24 weeks, when clear cell carcinoma was induced, the cells in the cancer tissue exhibited a variety of features in their nuclei and cytoplasm. Some cells showed intact nuclear structure and dark cytoplasm containing a large number of vesicles; others had large round clear nuclei with enlarged nucleoli and clear cytoplasm containing no vesicles. Among these cells were mixed populations of large clear cells, showing a structure similar to the cells at 12 weeks, 2.e., to nodular hyperplastic cells. The starting point of malignant transformation seemed to be 1 week after treatment with NDPS (i.e., cells at 5 weeks) and, or the precancerous stage, at 12 weeks. These results suggest that the proximal convoluted tubule cells previously damaged by dimethylnitrosamine treatment were marked for mutation and were transformed to cancer cells by additional treatment with NDPS in such a way as to disturb the permeability of the membrane system of the cell and to condense chromatin fibers.

Adenocarcinoma