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Biomedical subjects

J Yoshida

Publications and source records attributed to J Yoshida.

At least 217 records · Page 12Linked to original sources

Nitric oxide metabolites in the cisternal cerebral spinal fluid of patients with subarachnoid hemorrhage.

OBJECTIVE: To investigate nitric oxide (NO) metabolism after subarachnoid hemorrhage (SAH). METHODS: We measured the concentrations of the NO metabolites, nitrite and nitrate, in cerebrospinal fluid (CSF) obtained from the cisternal drainage of patients with SAH. Studies were performed for 31 patients who had undergone surgical obliteration of bleeding aneurysms within 3 days of their hemorrhage. The concentrations of nitrite and nitrate in the CSF were measured for 14 days using a nitrate/nitrite kit and samples that were obtained on a daily basis from the cisternal drainage. RESULTS: Compared with the control values in the CSF (2.6 +/- 0.4 mumol/L, n = 14) obtained from patients with hemifacial spasm, trigeminal neuralgia, or nonruptured aneurysms, the concentrations of nitrite and nitrate in the CSF were significantly elevated in the acute stage of SAH and remained elevated. The concentration of NO metabolites may correlate with the amount of bleeding, inasmuch as the values in patients in Fisher Group 3 (n = 25) were higher than those in patients in Fisher Group 2 (n = 6). The concentration of nitrate was higher than that of nitrite, suggesting that NO in the subarachnoid space is mainly absorbed by hemoglobin and degraded to nitrate. No differences were demonstrated in patients treated with high doses of methylprednisolone (n = 17) compared with those treated with usual-dose steroids (n = 14). Steroids are known to prevent the formation of inducible NO synthase mediated by inflammatory cytokines. CONCLUSION: NO metabolism in the brain is stimulated after SAH. Nitrate is the dominant NO metabolite in CSF after SAH. The involvement of inducible NO synthase in the pathophysiology of NO metabolism after SAH was not clearly suggested based on the present data.

Adult↗

Intracellular hyperthermia for cancer using magnetite cationic liposomes: ex vivo study.

Heating properties of magnetite cationic liposomes (MCL) were investigated in ex vivo experiments using implanted cell pellets. The cell pellets, which consisted of rat glioma T9 cells into which MCL had been incorporated in a petri dish, were implanted subcutaneously in the left femoral region of female F344 rats. The rats were placed in a magnetic field generating coil and irradiated with an alternating magnetic field (384 Oe, 118 kHz) for 60 min. The cell pellets were heated to over 43 degrees C by MCL in the magnetic field, but other body parts of the rats were not heated. After 3 cycles of magnetic heating, all glioma cells were killed and no tumor take was observed.

Animals↗

Retroviral introduction of the p16 gene into murine cell lines to elicit marked antiproliferative effects.

The p16 gene is a candidate tumor suppressor, because mutation of the gene has been reported in many transformed cell lines and some primary tumor tissues. We have examined this possibility in murine cell lines (NIH3T3 and RSV-M) which lack p16 gene expression. Full-length human p16 cDNA was obtained from a HeLa cell line using polymerase chain reaction amplification. We constructed two separate retrovirus vectors carrying this p16 cDNA. First, we transduced the p16 cDNA into the murine cell lines using a retrovirus vector harboring the neomycin-resistance gene. The p16 gene-transduced cells formed no colonies after selection with G418, in contrast to the vector-transduced cells. Next, we used another retrovirus vector that expresses both the p16 cDNA and the Lac Z gene, which enabled us to distinguish affected cells from unaffected ones. Proliferation of the p16 gene-transduced cells was markedly inhibited and morphological change in the cells was also observed. Thus, we concluded that the p16 gene has an antiproliferative effect on the cell cycle and that the loss of its function may play a major role in dysregulated proliferation of the cells.

3T3 Cells↗

Abducens nerve neurinoma--case report.

A 61-year-old female presented with an abducens nerve neurinoma manifesting as diplopia and facial numbness. The tumor was totally removed, and the exact origin was confirmed intraoperatively. Neuroradiological imaging and clinical history are frequently insufficient to obtain an accurate preoperative diagnosis of intracranial neurinoma.

Abducens Nerve↗

Enzyme immunoassay of glioma cell tenascin secretion and augmentation by tumor necrosis factor-alpha.

Expression of tenascin, an extracellular matrix glycoprotein, was measured in glioma cell lines using a newly established enzyme immunoassay. Secreted tenascin was found at concentrations greater than 800 ng/ml in eight of 14 glioma, three small cell lung carcinoma, two melanoma, and one sarcoma cell lines. The remaining six glioma and other carcinoma cell lines, and cell lines originating from normal tissues demonstrated low levels or no secretion into the supernatant. The glioma cell line, U-251-MG nu/nu, which has almost 100% transplantability in nude mice, had the highest expression level of tenascin among the glioma cell lines examined. Even low secretor glioma cell lines released high concentrations of tenascin, detectable by assaying the NP-40 solubilized cell lysates. Flow cytometric analysis revealed that tenascin was located on both the cell surface and primarily in the cytoplasm of glioma cells. When the glioma cell lines were exposed to tumor necrosis factor-alpha (TNF-alpha), levels of secreted tenascin increased between 36% and 380%, whereas transforming growth factor-beta induced only minimal changes. These results suggest that glioma cell lines may be classified according to the degree of tenascin secretion/expression: high secretor type, low secretor type, and non-expressing type. The increase in tenascin secretion by TNF-alpha suggests that the expression of tenascin in glioma growth and development may be mediated through a cytokine network.

Animals↗

Antitumor activity of recombinant human tumor necrosis factor-alpha (rH-TNF alpha) and liposome-entrapped rH-TNF alpha.

The antitumor activities of recombinant human tumor necrosis factor-alpha (rH-TNF alpha) and liposome-entrapped rH-TNF alpha were evaluated in various glioma cell lines and a rat brain T9 gliosarcoma model. rH-TNF alpha had a direct cytotoxic activity against various glioma cell lines in vitro, and indirect cytotoxic activity against gliosarcoma (T9) in vivo. Liposome-entrapped rH-TNF alpha had increased direct cytotoxic activity in vitro, and against experimentally induced brain tumors in vivo. The effects in vivo were probably due to vascular damage of the tumor vessels as shown by histological examination and activation of cytotoxic macrophages as shown in vitro. These results indicate that the general or local administration of liposome-entrapped rH-TNF alpha may become a useful adjunct treatment for malignant brain tumor.

Animals↗

Effect of glycerol on blood flow distribution in tumoral and peritumoral brain tissue.

The effect of glycerol on blood flow in tumoral and peritumoral tissue was measured in 32 patients with brain tumor, 17 gliomas and 15 meningiomas. Blood flow before and after the administration of glycerol was measured by stable xenon-enhanced computed tomography. The tumor part of glioma was significantly hypoperfused. In contrast, the tumor part of meningioma was significantly hyperperfused. Peritumoral edema of both glioma and meningioma was hypoperfused. After the administration of glycerol, blood flow increased in all regions except for the tumor part of glioma. Vascular responses to glycerol may be different in these two tumor types. The steal phenomena of blood flow might occur in cases of glioma.

Adolescent↗

Xanthogranulomatous cholecystitis versus gallbladder cancer: clinical differentiating factors.

Xanthogranulomatous cholecystitis (XC) is occasionally difficult to differentiate from gallbladder cancer and mandates efforts to avoid extensive operations. We studied the clinical factors to differentiate XC from cancer. Subjects were a consecutive series of 10 patients with XC and 10 with carcinoma, all of whom radiologically showed thickened gallbladder walls. As opposed to cancer, XC was typified by invisible gallbladders on cholangiography (1), the presence of cholelithiasis (P = 0.01) (2), and, intraoperatively, an aspirate of pus or nothing (P < 0.01) (3). To diagnose XC against gallbladder cancer, (1) and (2) in combination and (3) demonstrated an accuracy of 82.4% and 85.0 per cent, respectively. Clinically, XC can be distinguished from gallbladder cancer by cholangiography, calculous findings, and a gallbladder aspirate of pus or nothing.

Aged↗

Differential flotation centrifugation study of hepatitis C virus and response to interferon therapy.

Hepatitis C virus (HCV) appears to circulate in various forms such as native virion, immune complexes, and nucleocapsids during chronic infections. To determine the association of the physicochemical properties of HCV and its response to interferon therapy in patients with chronic hepatitis C, we examined pretreatment serum samples from 43 patients with HCV RNA who had received interferon therapy, using differential flotation centrifugation in a NaCl solution with a density of 1.063 g/ml. After centrifugation, the ratio of HCV RNA in the top and bottom fractions was determined by the polymerase chain reaction and expressed as T/B. Patients with a sustained response to IFN therapy were found to have higher T/B ratios than transient responders who relapsed after treatment (P < 0.01) and nonresponders (P < 0.01). With regards to HCV genotypes, patients with genotype 1b had higher T/B ratios in the sustained response group than in the nonsustained response groups (P = 0.001), but patients with genotype 2 had a similar distribution of T/B among the 3 response groups (not significant). These findings indicate that the physicochemical properties of HCV affect the effectiveness of interferon therapy, particularly in patients with genotype 1b.

Adult↗

[Gene therapy for brain tumors].

Patients with glioma(which constitute 33% of all brain tumor cases) still have a poor prognosis, especially in the case of malignant(anaplastic astrocytoma and glioblastoma). This poor prognosis is related to the fact that malignant glioma cells aggressively infiltrate into normal brain tissues, making total removal of the tumor impossible. The median survival time of glioblastoma patients is less than 2 years, despite multimodality treatment with extensive surgical resection and adjuvant therapies using radiation and immunochemotherapy. In order to overcome this formidable neoplasm, the effectiveness of molecular neurosurgery using gene therapy has been investigated since 1992. In this paper, the current state of gene therapy for malignant brain tumors are described, and the future direction of this fascinating approach is discussed.

Brain Neoplasms↗

[A case of traumatic cardiac contusion accompanied by the rupture of pericardium].

We experienced a case of traumatic cardiac contusion accompanied by the rupture of the pericardium after multiple blunt trauma sustained in a traffic accident. A 26-year-old woman who had suffered from blunt chest and abdominal trauma was admitted to our hospital, being unconscious with multiple severe injuries including pelvic fracture, bilateral hemothorax, and multiple fractures in the extremities. The patient was in a shock status. We performed the transcatheter arterial embolization of the internal iliac arteries to control the bleeding, when aortography showed that the contrast media extravasated toward the left thoracic cavity. Immediately, an operation for blunt chest trauma was performed. Blood was flooding out of the ruptured pericardium because of the contusion of myocardium. The postoperative course was uneventful. Blunt chest trauma is usually accompanied by multisystem injury. Therefore, it is imperative to determine the priority of treatment based on preoperative examination in patients having multiple injuries.

Abdominal Injuries↗

Splenic B-cell activation in lipopolysaccharide-non-responsive C3H/HeJ mice by lipopolysaccharide of Porphyromonas gingivalis.

Porphyromonas gingivalis 381 lipopolysaccharide (LPS) definitely exhibited mitogenic activity in purified B-cells, separated from spleens of LPS-responsive C3H/HeN mice and LPS-non-responsive C3H/HeJ mice by using a magnetic cell sorting system. The mitogenic activity induced by P. gingivalis LPS was incompletely inhibited by polymyxin B. P. gingivalis LPS also induced a higher production of interleukin-6 (IL-6) in splenic B-cells of C3H/HeN mice as compared with Escherichia coli LPS. Furthermore, P. gingivalis LPS, but not E. coli LPS, induced definite IL-6 production in C3H/HeJ mice. P. gingivalis LPS increased tyrosine, serine/threonine phosphorylation of proteins with various major induced bands in splenic B-cells of both C3H/HeN and C3H/HeJ mice. Additionally, radioiodinated P. gingivalis LPS, similarly to E. coli LPS, bound to a 73-kDa protein on C3H/HeJ as well as C3H/HeN B-cells. Thus P. gingivalis LPS may activate B-cells of C3H/HeJ as well as C3H/HeN mice via the LPS-specific binding protein on the cells.

Acute-Phase Proteins↗

Suppression of CD44 expression decreases migration and invasion of human glioma cells.

We have reported high expression of CD44H in human glioma cells. To investigate the role of CD44H in the invasion of human glioma, we established a CD44-anti-sense-gene-expression glioma cell line named U-251A1. The expression of CD44H in the G-418-selected U-251A1 cells was reduced to 20% of that in the parental U-251SP cells, as determined by flow-cytometry analysis. We first examined the migratory responses of U-251A1 cells in vitro by time-lapse video-microscopic sparse cell-migration assay on hyaluronic acid or on chondroitin 6 sulfate. U-251A1 cells did not show significant differences in motility on any substrate, while U-251SP and other CD44H-positive cells showed dose-dependent increase of migration specifically on hyaluronic acid. To examine the physiologic function of CD44H in gliomas in vivo, U-251A1 and its control cells, U-251S1, which retain CD44-sense-expression vector, were injected stereotactically into the brains of nude mice. U-251A1 cells were localised in the region of the injection site, with relatively well demarcated borders between tumour and brain tissue, while the control cells demonstrated a cell-infiltration pattern. Our data suggest that CD44H may be required for infiltration of glioma cells through its interaction with hyaluronic acid, a major component of the brain extracellular matrix.

Animals↗

Nucleotide sequences of the hepatitis C virus core region in patients without anti-core antibody.

Second-generation assays for detection of hepatitis C virus (HCV) infection that include reactivity of antibodies to core, NS3, NS4 are used because of their high sensitivity. Among these antibodies, anti-core antibody seems to be the most sensitive. However, there are some patients without anti-core antibodies, although HCV RNA is detectable by reverse transcription-polymerase chain reaction and branched DNA assay. The mechanism for the absence of anti-core antibody on its own is unclear. We therefore determined the nucleotide and deduced amino acid sequences of the core region obtained from two anti-core antibody-negative patients with HCV RNA (genotype 1b) and compared them with those of four anti-core antibody-positive patients and a previously reported sequence. Amino acids spanning 1-47, which seemed to exist in major B cell epitopes, were found to be completely conserved among these patients. Furthermore, the predictive binding motif to HLA DR4 (a.a 81-90) was completely conserved in both of the anti-core antibody-negative patients. There were various mutations in the residual amino acids spanning 49-108, but specific mutations could not be found in anti-core antibody-negative patients. These data indicate that the absence of anti-core antibody in two patients is not due to the presence of some formerly unknown viral variants, but due to a possible defect in the host's immune system.

Amino Acid Sequence↗

Changes in hepatitis C virus quasispecies and density populations in patients before and after interferon therapy.

Some chronic hepatitis C patients show sustained response to interferon (IFN) therapy despite viremia. This condition seems to be related to the density populations of hepatitis C virus (HCV) [Kanto et al. (1995): J Med Virol 46:230-237]. To investigate further the relationship between alanine aminotransferase (ALT) levels after IFN therapy and the HCV density populations, we undertook differential flotation centrifugation of HCV and single strand conformation polymorphism targeted the hypervariable region (HVR) of E2 glycoprotein, which seems to be related to the density populations. Sera were obtained serially from 12 patients who had undergone IFN therapy (six sustained responders with viremia, six nonresponders). During the follow-up after interferon therapy, the HVR heterogeneities changed in 9 of the 12 patients. The remaining three patients whose heterogeneities did not changed persistently showed normal ALT. The changes in HVR heterogeneities were less pronounced in the sustained responders with viremia than in nonresponders; however, their density populations were prominently high in both responders. In two cases, changes in HVR heterogeneities and increase in low-density virion were observed before the hepatitis flare-up. These data indicate that HVR quasispecies show more relation to ALT levels after IFN therapy than HCV density populations and that the changes in the HVR sequences and HCV density populations may be associated with ALT elevation in some patients.

Adult↗