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Biomedical subjects

D Yoshida

Publications and source records attributed to D Yoshida.

At least 19 recordsLinked to original sources

Development and assessment of morphologic criteria for diagnosing gastric cancer using confocal endomicroscopy: an ex vivo and in vivo study.

BACKGROUND AND STUDY AIMS: The Confocal Endomicroscopy System (Optiscan Pty Ltd. and Pentax Corp.) is a newly developed imaging tool that uses laser light and optical technology to visualize living tissue at the cellular level. Digital images of cells magnified 1000-fold appear in real time on a computer screen, which enables immediate detection of changes in cellular structure without the need for a biopsy. The aim of this study was to assess the features of the cellular architecture of cancerous tissue that can be used in the differential diagnosis of cancerous tissue and normal mucosa using this system's image-processing software. PATIENTS AND METHODS: A total of 27 gastric cancers were examined ex vivo using confocal endomicroscopy. A fluorescent contrast agent, acriflavine, was applied topically to normal and to cancerous mucosa. In vivo imaging of the gastric mucosa after intravenous injection of fluorescein sodium was also performed in nine patients with gastritis or gastric cancer. RESULTS: The nuclear area in the ex vivo specimens was calculated using Scion Image software. The mean nuclear area of cancer cells was found to be significantly larger than that of normal cells in 18/27 gastric cancers (67 %). The mean nuclear area of the cancers tended to be larger than that of normal mucosa, especially in cases of differentiated adenocarcinoma. In more than half the cases, it was possible to diagnose malignancy automatically using confocal endomicroscopy and image-processing software without the need for biopsy and pathological examination. In vivo imaging of cancerous lesions showed irregularity in cellularity and vascularity. CONCLUSION: The ability of this imaging device to differentiate between normal tissue and cancerous tissues gives it potential value as a new screening tool for early detection of malignancy.

Adenocarcinoma↗

A case of pleomorphic xanthoastrocytoma presenting with massive tumoral hemorrhage.

Pleomorphic xanthoastrocytoma has been generally conceived to be in a benign nature, showing a relatively favorable prognosis. Apoplectic attack attributable by massive hemorrhage in this distinct form of the supratentorial glioma is an exceedingly rare event. A 61-year-old female presented with a sudden onset of generalized tonic--clonic convulsion. CT and MRI disclosed the presence of a tumor composing of massive intra-tumoral hemorrhage filling the cyst associated with mural nodule in the left frontotemporal lobe. At surgery, the subpial mass involving hematoma was well marginated and slightly adherent to the dura mater. It could be removed totally and proved to be a pleomorphic xanthoastrocytoma. The unusual hemorrhagic presentation of this typically benign entity is extremely rare and is thought to be intra-tumoral bleeding in this case, since subarachnoid hemorrhage was absent.

Astrocytoma↗

Chronological analysis of physiological T2* signal change in the cerebrum during breath holding.

The purpose of this study was to examine which physiological factors affect cerebral T2* signal intensity (SI) during breath holding (BH) (apnea after inspiration and breathing after expiration) in normal volunteers. We examined SI changes caused by anoxic gas inhalation, by respiratory movements, and by BH. High-speed echo planar images (EPI) showed changes in SI that could be divided into five phases. Reports indicate that SI changes induced by BH are due to the effects on the magnetic susceptibility of deoxygenated hemoglobin (deoxyhemoglobin (dHb)) and to hypercapnia, but these reports could not fully explain the observed five phases. In addition to deoxyhemoglobin susceptibility and hypercapnia, we found that respiratory movements play a third critical role in modifying SI by affecting blood flow into the region of interest (ROI), as judged from right carotid artery flow. Consequently, we propose that the physiological SI changes induced by BH are derived from blood oxygenation, hypercapnia, and respiratory movements.

Adult↗

Novel approach to analysis of in vitro tumor angiogenesis with a variable-pressure scanning electron microscope: suppression by matrix metalloproteinase inhibitor SI-27.

Degradation of basement membrane by metalloproteinases (MMP) is a critical step in tumor angiogenesis. To evaluate in vitro angiogenesis, several models have been employed, including bovine cornea, fenestrated rat brain, Matrigel, and others. These models did not provide quantitative analysis of capillary formation. The current study aimed for a novel approach to in vitro assay of angiogenesis with a "wet scanning electron microscope (SEM)" to investigate suppression of tumor angiogenesis by the MMP inhibitor, SI-27. The effects of noncytotoxic concentrations of SI-27 (1-100 microM) were determined on nonmitogenic vascular endothelial growth factor (VEGF) (10 ng/ml)-mediated cell motility and in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). Activities of MMP and tissue inhibitor of metalloproteinase (TIMP) were determined by enzyme-linked immunosorbent assay (ELISA). Subsequently, the inhibitory effect of SI-27 was examined on in vitro angiogenesis stimulated by supernatants of human glioma cell lines (U87MG, U251MG, or U373MG). In vitro angiogenesis was quantitatively analyzed with a variable-pressure SEM. Cell motility and in vitro angiogenesis by HUVECs were significantly increased by VEGF along with elevated MMP-1 and -2 activity, whereas SI-27 significantly suppressed VEGF-mediated in vitro angiogenesis and inactivated both MMP-1 and MMP-2, but not inhibited cell motility. The angiogenesis promoted by glioma supernatants showed a significant reduction in the presence of SI-27. SI-27, a novel MMP inhibitor, inhibited tumor angiogenesis in vitro. It can be anticipated to prevent tumor growth through its angiosuppressive effect. Quantitative analysis with a variable-pressure SEM is a novel approach to in vitro angiogenesis assay.

Angiogenesis Inhibitors↗

Suppression of matrix metalloproteinase-2 and -9 mediated invasiveness by a novel matrix metalloproteinase inhibitor, BE16627B.

Cell invasion is a nature of malignant gliomas, demeriting to many efforts of the treatment. Matrix metalloproteinase (MMP) is acknowledged as a key factor in this complicated process. The aim of this study was to investigate whether inhibition of MMP activity in malignant glioma cells could be achieved by a novel agent, BE16627B (BE). Malignant glioma cell lines, U87MG, U251MG, and U373MG, were employed to evaluate inhibitory effect on zymogram, type IV collagenolysis assay, and haptoinvasion assay for 24 h exposure of BE, following preliminar

Antineoplastic Agents↗

The bleb formation of the extracellular pseudopodia; early evidence of microtubule depolymerization by estramustine phosphate in glioma cell; in vitro study.

Estramustine phosphate (EMP) is an anti-microtubule agent that depolymerizes microtubules and also causes apoptosis of glioma cells. Both of these pharmacological actions have been previously studied within the same cytotoxic range of EMP concentrations. The purpose of this study was to investigate which of these two phenomena occurred before the other. A preliminary MTT assay was done to distinguish non-cytotoxic (0.005-0.1 microM) and cytotoxic (0.5-10 microM) of EMP for BT4C cells. To investigate apoptotic changes, transmission electron microscopy (TEM), DNA laddering, and in situ endo-labeling (TUNEL) method were employed. A chemotaxis assay was used to assess cell motility. Scanning electron microscopy and TEM immunocytochemistry with an anti-beta tubulin antibody were applied to detect morphological changes of the microtubules. Suppression of cell motility by cytotoxic doses of EMP (0.5-10 microM) group was attributed by the cyto-reductive effect, relating to apoptosis. At 0.01-0.1 microM (non-cytotoxic doses), EMP did not indue apoptosis. At these concentrations, TEM and immunohistochemistry revealed the formation of blebs on the tip of the pseudopodia that contained abnormally depolymerized microtubules, a finding that was not observed at a low temperature or during cell migration. Cell chemotaxis was significantly inhibited by cytostatic EMP doses (0.05 and 0.1 microM). Bleb formation of the pseudopodia might be evidence of the abnormal disassembly of microtubules by cytostatic EMP concentrations, prior to the induction of apoptosis. In glioma cells EMP probably initiates apoptosis by causing the depolymerization of microtubules. Inhibition of cell motility by cytostatic doses of EMP could be beneficial to support other therapies.

Animals↗

Induction of apoptosis by estramustine phosphate mediated by phosphorylation of bcl-2.

Estramustine phosphate (EMP) is an anti-microtubule agent that induces apoptosis of glioma cells. We investigated whether EMP caused apoptosis through the alkylating effect of its nitrogen mustard component or by phosphorylation of bcl-2 like other anti-microtubule agents in normal human astrocyte and human malignant glioma cell lines. Apoptosis was seen in glioma cells treated either with nitrogen mustard or EMP and expression of bcl-2 mRNA was not changed by exposure to the drug. An immunoprecipitation study only found phosphorylation bcl-2 in glioma cells exposed to EMP and not in cells exposed to nitrogen mustard. These results indicate that induction of apoptosis in glioma cells by EMP is mediated by phosphorylation of bcl-2.

Antineoplastic Agents, Alkylating↗

Drug-induced apoptosis by anti-microtubule agent, estramustine phosphate on human malignant glioma cell line, U87MG; in vitro study.

The drug effect of estramustine phosphate (EMP), an anti-microtubule agent on human glioma cells has been studied with the focus being mainly its cytotoxity or its targeting of organelles. However, the pharmacological knowledge of estramustine with respect to its cytotoxity and mechanism is limited. To acquire such knowledge, the present study investigates the ability of EMP to induce apoptosis in a human malignant glioma cell line. Transmission electron microscope (TEM) images were examined to monitor periodic changes. Agarose gel electrophoresis was also examined. Cellular DNA fragmentation ELISA was performed to investigate the DNA fragmentation rates and an MTT assay was studied to evaluate the ID50. A TEM study revealed condensing and fragmentation of the chromatin. Laddering of the bands was observed in all EMP exposure groups in agarose gel electrophoresis. DNA fragmentation in all EMP groups began at 0.5 h following an exposure with EMP and increased in a dose- and time-dependent manner as revealed by DNA ELISA fragmentation. ID50 at 24 h was 5.0 microM according to the MTT assay, a value close to 4.8 microM of ID50 was revealed by the DNA fragmentation assay. None of the above mentioned changes was observed in the control group. These results indicated that EMP caused a drug-induced apoptosis in the human malignant glioma cell line, U87MG.

Antineoplastic Agents, Alkylating↗

Suppression of cell invasion on human malignant glioma cell lines by a novel matrix-metalloproteinase inhibitor SI-27: in vitro study.

Matrix metalloproteinase (MMP) has come to be highlighted by its close relation to the cell invasion of gliomas. Suppression of MMP activity in malignant glioma cells would be meriting to local delivery of genes or chemotherapeutic agents. In this study, we employed a novel MMP inhibitor, SI-27 to investigate inhibition of cell invasiveness in human malignant glioma cell lines, U87MG, U251MG, and U373MG. We evaluated with zymogram, reverse zymogram, and cell invasion assay after exposure of SI-27 for 24 h followed by preliminary MTT assay to find non-cytotoxic dose range, 5, 10, 50, 100 microg/ml compared with non-treatment group as the control. Common to three glioma cell lines, zymogram disclosed that expressions of MMP-2 and -9 were suppressed in a dose-dependent fashion, meanwhile those of tissue inhibitor of MMP (TIMMP) in reverse zymogram were not. The numbers of invading cells through Boyden chamber were significantly reduced in a dose-dependent manner, while those with 5 microg/ml were not diminished common to those three lines. In conclusion, dose concentration ranging 10-100 microg/ml of SI-27 inhibited MMP-2 and -9 mediated cell invasiveness in malignant glioma cell lines. This is the first report for chemotherapeutic effect of SI-27 on glioma cells.

Brain Neoplasms↗

Intracranial malignant meningioma with abdominal metastases associated with hypoglycemic shock: a case report.

A thirty-year-old male with an intracranial malignant meningioma, first diagnosed 9 years ago, with three recurrences was admitted with a hypoglycemic shock. The blood glucose level was 17 mg/dl, requiring treatment with high doses of intravenous and oral dextrose for improvement. A large metastatic tumor in the liver was noted. All hormones and peptides influencing blood glucose levels were in their normal levels. Chemo-embolization and injection of anti-cancer drugs was employed in the management of the metastatic tumor. Positron emission tomography was performed to measure the glucose metabolism of the abdominal tumor and it indicated that glucose consumption within the tumor was much elevated than the surrounding abdominal organs. Hypoglycemia secondary to primary hepatoma or islet-cell cancer has been frequently described, but a complication of metastatic meningioma is an exceedingly rare event. Elevated glucose consumption within the tumor might be addressed as one of the reasons for hypoglycemia, not due to the elevated serum levels of insulin or IGF, but due to the closely related blood glucose level.

Abdominal Neoplasms↗

[Preliminary study of calculating cerebral arterial blood oxygen saturation using MRI].

To assess whether cerebral arterial blood oxygen saturation (SaO2) can be calculated by EPI, we examined the relationship between peripheral SaO2 and T2+ signal intensity (SI) changes in the brain in three normal subjects, using 1.5 Tesla MRI. To decrease SaO2, hypoxia was induced by 100% helium-gas inhalation (60 sec). SI declined as SaO2 decreased during helium inhalation, while rapid recovery of SI to the baseline was noted with recovery from hypoxia. The differential effective transverse relaxation rate was closely correlated with SaO2 (r > 0.94). Consequently, using MRI, we were able to calculate arterial SaO2.

Cerebral Arteries↗

Scintigraphic prediction of resistance to radiation and chemotherapy in patients with lung carcinoma: technetium 99m-tetrofosmin and thallium-201 dual single photon emission computed tomography study.

BACKGROUND: Various prognostic markers for lung carcinoma have been proposed, but to the authors' knowledge none is noninvasive and convenient for clinical use. The current study examined the utility of several radiotracers for the prediction of multidrug resistance (MDR) and radioresistance in patients with lung carcinoma. METHODS: Thirty patients with untreated lung carcinoma underwent a dual isotope single photon emission computed tomography (SPECT) scan at 10 minutes and 120 minutes after the injection of technetium-99m ((99m)Tc)-tetrofosmin ((99m)Tc-TF) (370 megabecquerels [MBq]) and thallium-201 ((201)TlCl) (111 MBq). Retention of each tracer was evaluated semiquantitatively. Using radiation and chemotherapy (cisplatin plus etoposide), the patients either were treated sequentially (n = 12) or concurrently (n = 18). The relation between therapeutic response and retention of each tracer was analyzed. The detectability of radioresistance was examined. RESULTS: In patients treated with sequential therapy, the response to radiation was predicted by (99m)Tc-TF retention, whereas (201)Tl retention was found not to be predictive. Regardless of whether the sequential or concurrent protocol was applied, 14 of 18 tumors with high (99m)Tc-TF retention (>/= 15%) exhibited a favorable response to chemoradiotherapy whereas all 12 tumors with low (99m)Tc-TF retention (</= 15%) did not respond to the therapy. In contrast, (201)Tl retention was not found to be a predictive factor. CONCLUSIONS: The employed SPECT method is a useful tool for the in vivo prediction of radioresistance, P-glycoprotein (P-gp), and non-P-gp MDR in lung carcinoma. Low (99m)Tc-TF retention serves as a strong predictor of therapeutic resistance. High (99m)Tc-TF retention implies a favorable response. (201)Tl did not appear to be a predictive factor but is required for localization of the lesion on SPECT imaging.

Aged↗

Cavernous hemangioma of the skull in a neonate.

Cavernous hemangiomas rarely occur in the calvarium and most commonly present in middle-age. Although a congenital vascular disorder can theoretically cause a diploic lesion in any age group, a calvarial cavernous hemangioma has not been reported in newborn. A 4-month-old male infant presented with a large left parietal mass that had been present since birth. Total resection was performed. Pathological examination revealed a cavernous hemangioma developing within the diploic space adjacent to prior hemorrhages. Surgery was performed in this case because of the size and persistence of the lesion. Removal of tumors of a benign nature from the calvarium can be done safely. Cavernous hemangioma of the skull in a neonate should be considered as one of the differential diagnoses in the case of suspected ossified cephalohematoma.

Hemangioma, Cavernous↗

Extraosseous metastases of hepatocellular carcinoma detection and therapeutic assessment with Tc-99m PMT SPECT.

Owing to recent advances in imaging technology and radiologic intervention, survival rates in patients with hepatocellular carcinoma have improved markedly. However, such prolonged survival has resulted in an increase in extrahepatic metastases. Tc-99m (Sn)-N-pyridoxyl-5-methyltryptophan (Tc-99m PMT), developed for hepatobiliary scintigraphy, has been used to visualize extrahepatic metastases, with most related reports limited to osseous metastases. The authors report two cases of hepatocellular cancer presenting as a hypopharyngeal metastasis and intraperitoneal dissemination along the tract of a fine-needle biopsy. Lesions undetectable on planar imaging could be visualized by Tc-99m PMT SPECT.

Aged↗

Dual-isotope SPECT diagnosis of a skull-base metastasis causing isolated unilateral hypoglossal nerve palsy.

We describe a 48-year-old female with an isolated unilateral hypoglossal nerve palsy caused by a skull base metastasis from breast cancer. The patient had a medical history of conservative breast therapy for breast cancer. Although the cause of such a neurological deficit includes various pathologies, the reports focusing on metastatic tumor have been limited in number. Radiologic investigation showed a mass involving both the right hypoglossal canal and the clival edge. Swelling of the hypoglossal nerve was observed in views including its canal. Three-dimensional CT images demonstrated the tumor protruding from the enlarged external orifice of the hypoglossal canal. In the present report we mentioned a nuclear medicine procedure to visualize and characterize the small, abnormal tissue in the skull base. Dual-isotope SPECT confirmed an abnormal uptake of 99mTc-HMDP around the hypoglossal canal and a 201Tl-positive elongated lesion running along the hypoglossal nerve.

Cranial Nerve Diseases↗

Suppression of matrix metalloproteinase-2-mediated cell invasion in U87MG, human glioma cells by anti-microtubule agent: in vitro study.

Because microtubules are important components of cell motility and intracellular transport, it is reasonable to propose that the depolymerizing effect of an antimicrotubule agent, estramustine, on glioma microtubules would modulate cell invasiveness. To determine whether matrix metalloproteinases, key factors in cell invasion, are affected by exposure to estramustine, a cell proliferation assay, a zymogram, a collagenolysis assay and a haptoinvasion assay were used in this study. The zymogram revealed that an activated (62 kDa) form of matrix metalloproteinase-2 diminished with increasing estramustine concentrations. The collagenolysis assay demonstrated approximately 2.5- to 21-fold lower rates of enzymatic activity suppressed by estramustine in a dose-dependent manner at estramustine concentrations of 1, 5, and 10 microM, compared with the control group. On the haptoinvasion assay, no statistically significant difference was seen in the 0.5 microM estramustine group, whereas 1-10 microM estramustine groups revealed significant suppression of invasion from 6 to 24 h in a dose-dependent manner. The results suggest that estramustine suppresses the invasion of U87MG cells in vitro using the decreasing available matrix metalloproteinase-2, an effect caused by the disassembly of microtubules. Suppression of the infiltrative capacity of malignant glioma cells could be of significant value in the treatment of this disease.

Antineoplastic Agents, Alkylating↗

Dual isotope SPECT in malignant Jacod's syndrome.

A case is presented of metastatic tumor causing Jacod's syndrome: total ophthalmoplegia, blindness, and trigeminal neuralgia. Abnormal soft tissue invading the orbital apex, anterior clinoid process, and cavernous sinus was difficult to assess by CT and MRI, but dual-isotope SPECT including Tc-99m HMDP bone imaging and Tl-201 tumor imaging strongly suggested that the cause of this rare syndrome was a small metastatic tumor. Although the therapeutic effect was also difficult to assess by anatomic imaging alone, dual-isotope SPECT after radiation therapy showed a decline of tumor viability.

Aged↗