[Experimental periodontitis induced by crown margin extension in dogs (author's transl)].
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Biomedical subjects
Publications and source records attributed to F Takayama.
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A patient with secondary thyroid lymphoma who complained of a neck mass was presented. Multiple nodules were detected in both lobes of the thyroid gland, which appeared as homogeneous hypoechoic masses on ultrasonogarphy (US), low-density masses on computed tomography (CT), and areas of increased uptake on gallium-67 scintigraphy. The residual thyroid gland was normal. Surgery established a diagnosis of secondary thyroid lymphoma with no coexistent Hashimoto's thyroiditis but with cervical node involvement by lymphoma. Radiologic evidence of normal residual thyroid gland in a patient with thyroid lymphoma may be a sign of secondary thyroid lymphoma.
PURPOSE: We reviewed the radiologic and clinical data in patients with metastatic disease to the thyroid gland and assessed the role of radiologic techniques in this disorder. METHOD: The findings on US (n = 11), CT (n = 7), MRI (n = 6), palpation or US-guided fine needle aspiration (FNA) biopsy, and clinical records were reviewed in 11 cases of pathologically verified metastatic tumors of the thyroid gland. RESULTS: Five patients had palpable thyroid nodules and six had nonpalpable nodules discovered incidentally with imaging procedures. Three patients had no known malignancies at the time of diagnosis of thyroid tumors. Correct diagnosis was obtained in 10 of the 11 cases with FNA biopsy. Thyroid metastases were detected in all of the cases with US and MRI and six of the seven cases with CT. Thyroid metastases were solitary (n = 5) or multiple (n = 6), and about half of them measured <2 cm in diameter. These tumors typically had well defined margins and no calcification and sometimes had cystic portions. Multiple nodules within the same patient were radiologically quite similar to each other. On US, metastases appeared as hypoechoic or markedly hypoechoic areas without halo, on CT as low density areas, and on MRI as areas of varying signal intensities. Half of the metastases showed hypointensity on either T2-weighted images or gadolinium-enhanced T1-weighted images. The tumors involved lymph nodes in 10 cases and other remote organs in 5. Level I or II or parotid nodes were involved in six cases. CONCLUSION: These radiologic features may alert clinicians to a possibility of metastatic thyroid cancer. US combined with US-guided FNA biopsy is suitable for early diagnosis of metastases to the thyroid gland.
PURPOSE: We studied the prevalence of spontaneous extensive necrosis in the nodes of patients with non-Hodgkin lymphomas and assessed the clinical significance of this finding. METHOD: CT and MRI performed before initiation of radiation or chemotherapy were reviewed in 60 consecutive patients with non-Hodgkin lymphomas to evaluate the presence or absence of spontaneous extensive necrosis in the lymphomatous nodes. The results were correlated with histopathologic grading, stages of lymphomas, maximal axial diameters of the lesions, International Prognostic Index (IPI), age, and serum lactate dehydrogenase (LDH) levels. We then performed Kaplan-Meier analysis of disease-free survival using each factor. RESULTS: Extensive necrotic nodes that appeared as rim-enhanced masses on enhanced CT or MR images were found in 15 patients (25%), of whom 10 patients had pathologic verification. The patients with necrosis had significantly higher stages (Stage II or higher), greater IPI (IPI of > or = 2), and higher serum LDH levels than those without necrosis (p = 0.001, p = 0.005, and p = 0.005, respectively). With the Kaplan-Meier method, a statistically significant difference was noted for serum LDH levels (p = 0.015) and IPI (p = 0.021) but not for extensive necrosis (p = 0.600). CONCLUSION: Spontaneous extensive necrosis in lymphomatous nodes is not a rare event. This finding may have a prognostic significance for patients with non-Hodgkin lymphomas.
We recently demonstrated that indoxyl sulfate is a stimulating factor for the progression of chronic renal failure (CRF). In this study we determined whether the urine or serum levels of indoxyl sulfate are related to the progression rate of CRF in undialyzed uremic patients. Fifty-five CRF patients with a serum creatinine of >2 mg/dl who had not been treated with an oral sorbent (AST-120) were randomly enrolled in the study. We measured the serum and urine levels of indoxyl sulfate, and estimated the recent progression rate of CRF as the slope of the reciprocal serum creatinine versus time (1/S-Cr-time) plot. The mean urinary amount of indoxyl sulfate in the patients was 60 mg/day. Those with indoxyl sulfate urine levels of >60 mg/day had a significantly faster progression rate of CRF than those with <60 mg/day. Especially, those patients with indoxyl sulfate urine levels of >90 mg/day had the highest CRF progression rate and those with indoxyl sulfate urine levels of <30 mg/day had the slowest CRF progression rate. Urinary indoxyl sulfate had a significantly negative correlation with the slope of the 1/S-Cr-time plot. However, the serum level of indoxyl sulfate or the ratio of serum indoxyl sulfate to creatinine was not significantly correlated with the slope of the 1/S-Cr-time plot. In conclusion, high urine levels of indoxyl sulfate are related with a rapid progression of CRF in undialyzed uremic patients. Thus, urinary indoxyl sulfate is one of the clinical factors that affect CRF progression.
Dopamine dose-dependently reduced the viable cell number of both human salivary gland tumor HSG and oral squamous cell carcinoma HSC-2, HSC-4, and NA cells. CoCl2 significantly reduced both the cytotoxic activity and radical intensity of dopamine (determined by ESR spectroscopy). Dopamine produced DNA fragments (demonstrated by TUNEL method) and induced degradation of cytokeratin by activated caspase in HSG cells (detected by an immunocytochemical method, using a specific M30 monoclonal antibody). FACS analysis demonstrated that dopamine induced DNA fragmentation, a biochemical hallmark of apoptosis, in human promyelocytic leukemia HL-60 cells. The addition of catalase did not prevent the apoptosis-inducing activity of dopamine, reducing the possibility of the involvement of H2O2 for dopamine-induced apoptosis. Dopamine transiently induced p38 mitogen-activated protein kinase (MAP kinase) phosphorylation. However, an inhibitor of p38 MAP kinase phosphorylation, SB203680, failed to inhibit the dopamine-induced apoptosis. These data suggest that p38 phosphorylation at an early stage may not be a causative event for apoptosis.
Biological activities of two granulocyte-colony stimulating factor (G-CSF) preparations with (Lenograstim) or without (Filgrastim) sugar moiety were compared. Both G-CSF preparations similarly enhanced the N-Formyl-Met-Leu-Phe-induced-migration of human peripheral blood polymorphonuclear cells, but did not significantly affect the proliferation of human oral tumor cell lines (HSC-2, HSG). However, Lenograstim induced cytotoxicity (accompanied by the production of cytoplasmic vacuoles and large DNA fragments) in human promyelocytic leukemic cells HL-60, more potently than Filgrastim. Lenograstim, but not Filgrastim, enhanced the cytotoxic activity of sodium ascorbate. In contrast to Lenograstim, Filgrastim was degraded gradually, but too slowly to explain its lower biological activity. These data suggest that the carbohydrate moiety in G-CSF might confer unique biological activities.
A total of 150 chemically-defined natural and synthetic polyphenols (flavonoids, dibenzoylmethanes, dihydrostilbenes, dihydrophenanthrenes and 3-phenylchromen-4-ones), with molecular weights ranging from 224 to 824, were investigated for cytotoxic activity against normal, tumor and human immunodeficiency virus (HIV)-infected cells. They showed higher cytotoxic activity against human oral squamous cell carcinoma HSC-2 and salivary gland tumor HSG cell lines than against normal human gingival fibroblasts HGF. Many of the active compounds had a hydrophilic group (hydroxyl group) in the vicinity of a hydrophobic group (prenyl, phenyl, methylcyclohexene or methylbenzene moiety), similar to isoprenoid-substituted flavones. Substitution of hydrophobic group (prenyl or geranyl group) did not significantly change the cytotoxic activity of flavanones, isoflavans, chalcones or 5-hydroxy-3-phenoxychromen-4-ones. However, the prenylation(s) of an isoflavone and a 2-arylbenzofuran significantly enhanced the cytotoxic activity. Agarose gel electrophoresis showed that active components induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells, but not in HSC-2 cells. Most of the polyphenols failed to reduce the cytophathic effect of HIV infection in MT-4 cells.
Hydroquinone (HQ) dose-dependently reduced the viable cell number of oral tumor cell lines (HSC-2, HSG). HQ induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells, but not in HSC-2 nor HSG cells. Cytotoxic activity of HQ was slightly reduced by catalase, but was enhanced by superoxide dismutase, suggesting the possible involvement of hydrogen peroxide in HQ-induced cytotoxicity. This was supported by slight increase or decrease of cytotoxicity of HQ in the presence of Cu2+ and Fe3+, respectively. Lower concentrations of sodium ascorbate, ascorbic acid and ascorbic acid 6-palmitate reduced both the radical intensity and cytotoxic activity of HQ, more efficiently than ascorbic acid 2,6-dipalmitate, in contrast to the cytotoxic action of these ascorbates at higher (millimolar) concentrations. Popular antioxidants such as N-acetyl-L-cysteine and cysteine also reduced the radical intensity and cytotoxic activity of HQ. The present study suggests that cytotoxic activity of HQ is generated by radical-mediated oxidation mechanism.
Three steroidal saponins showed higher cytotoxicity against human oral squamous cell carcinoma cell lines (HSC-2), as compared with normal human gingival fibroblasts HGF. Tumor specificity of saponins exceeded that of tannins and flavonoids. Agarose gel electrophoresis showed that saponins failed to induce internucleosomal DNA fragmentation, but produced large DNA fragments in both HSC-2 cells and human promyelocytic leukemic HL-60 cells. In contrast to epigallocatechin gallate or gallic acid, cytotoxic activity of saponins was not significantly affected by metals (Co2+, Cu2+, Fe3+) nor by antioxidants (sodium ascorbate, N-acetyl-L-cysteine, catalase). Furthermore, saponins did not produce radicals (detected by ESR spectroscopy) nor oxidation potential (measured by NO monitor). These data suggest that an oxidation-mediated mechanism is not involved in the cytotoxicity induced by steroidal saponins.
Cytotoxic activity of 9 polyprenylalcohols and 6 vitamin K2 derivatives (MK-1 to MK-6) with various lengths of prenyl units was investigated. Among these compounds, geranylgeraniol with 4 prenyl units, and MK-2 with 2 prenyl units, showed the highest cytotoxic activity against human oral tumor cell lines (HSC-2, HSG), without induction of internucleosomal DNA fragmentation. Higher molecular weight compounds showed selective cytotoxicity against tumor cell lines than normal human gingival fibroblasts HGF. ESR spectroscopy showed that all polyprenylalcohols did not produce radical, nor scavenged O2- generated by hypoxanthine and xanthine oxidase reaction, and only slightly enhanced the radical intensity of sodium ascorbate. Vitamin K2 derivatives scavenged O2- more efficiently, but did not produce radical (except MK-3) and only slightly modified the ascorbate radical intensity. Cytotoxic activity of these compounds might be affected by the molecular weight, hydrophobicity, van der Waals area and stabilization of hydration of the molecule.
Five steroidal saponins from Camassia leichtlinii showed higher cytotoxicity against human oral squamous cell carcinoma cells HSC-2, as compared to normal human gingival fibroblasts HGF. The tumor specificity of saponins varied considerably from sample to sample, but was generally higher than that of tannins, flavonoids and prenylated compounds such as geranylgeraniol and vitamin K2 (MK-2). Agarose gel electrophoresis showed that the saponins failed to induce internucleosomal DNA fragmentation, but produced large DNA fragments in HSC-2 cells, whereas two saponin samples (compounds 1 and 5) induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells. In contrast to epigallocatechin gallate or gallic acid, the cytotoxic activity of saponins was not significantly affected by metals (Co2+, Cu2+, Fe3+) or by antioxidants (sodium ascorbate, N-acetyl-L-cysteine, catalase). Furthermore, the saponins did not produce radicals (detected by ESR spectroscopy) nor oxidation potential (measured by NO monitor). These data suggest that an oxidation-mediated mechanism is not involved in the cytotoxicity induced by the steroidal saponins.