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Biomedical subjects

J Yoshida

Publications and source records attributed to J Yoshida.

At least 55 records · Page 3Linked to original sources

Targeting hyperthermia for renal cell carcinoma using human MN antigen-specific magnetoliposomes.

Magnetoliposomes (MLs) conjugated with an antibody fragment to give specificity to a tumor were applied to hyperthermia for cancer. The Fab' fragment of the G250 antibody, which binds to MN antigen on many types of human renal cell carcinoma, was cross-linked to N-(6-maleimidocaproyloxy)-dipalmitoyl phosphatidylethanolamine (EMC-DPPE) in liposomal membrane. The targetability of the G250-Fab' fragment-conjugating MLs (G250-FMLs) was investigated using the mouse renal cell carcinoma (mRCC) and MN antigen-presenting cell, MN-mRCC. The amount of G250-FMLs uptake reached 67 pg / cell against MN-mRCC cells in an in vitro experiment using plastic dishes and this value was about 6 times higher than that in the case of MLs. In an in vivo experiment using MN-mRCC-harboring mice, 1.5 mg of the FMLs per carcinoma tissue accumulated (tumor weight was 0.19 g), which corresponded to approximately 50% of the total injection. This value was 27 times higher than that of the MLs. After injection of the FMLs, mice were exposed to intracellular hyperthermia using alternating magnetic field irradiation. The temperature of tumor tissue increased to 43 degrees C and the growth of the carcinoma was strongly arrested for at least 2 weeks. These results indicate the G250-FMLs could target renal cell carcinoma cells in vitro and in vivo, and are efficiently applicable to the hyperthermic treatment of carcinoma.

Animals↗

Relation between brain displacement and local cerebral blood flow in patients with chronic subdural haematoma.

OBJECTIVES: To evaluate the relation between brain displacement, clinical signs and symptoms, and local cerebral blood flow (lCBF) in patients with chronic subdural haematoma (CSDH). METHODS: Forty five patients (age range 58-87 years, mean 71.9 (SD 8.4)) with unilateral CSDH were studied. Patients were categorised into three groups: I, headache (n=16); II, paresis (n=14); and III, mental change (n=15). T1 weighted MR images were obtained in all patients preoperatively. Quantitative values of maximum haematoma thickness, midline shift, and brain rotation angle were measured on axial and coronal MR images. In 21 patients, lCBF was measured by Xe enhanced CT. Values for lCBF were obtained in selected regions of interest in the frontal cortex, thalamus, and hemisphere on both the haematoma and contralateral sides. RESULTS: The lCBF reduction in the ipsilateral frontal cortex showed the best linear correlation with haematoma thickness (r=0.57), whereas the reduction in the ipsilateral thalamus had the most significant correlation with pineal shift (r=0.65) and third ventricle incline (r=0.67). In patients with paresis, lCBF decreased significantly on the ipsilateral side of both the frontal cortex and thalamus (p<0.05), whereas patients with mental change showed a significant reduction of lCBF on both sides of the thalamus (p<0.01) and in the ipsilateral frontal cortex (p<0.01). CONCLUSIONS: The lCBF reduction and clinical symptoms correlated well with local brain displacement in patients with CSDH. The lCBF in the central cerebral area including the thalamus was reduced in patients with clinical signs. The mental changes found were thought to derive from mild impairment of consciousness due to upper brain stem displacement.

Aged↗

Respiratory alkalosis does not alter NOx concentrations in human plasma and erythrocytes.

To test the hypothesis that NOx (NO and NO, metabolites of NO) accumulates in red blood cells (RBC) in response to changes in PCO(2) and bicarbonate (HCO) concentration in blood, we examined the effect of changes in PCO(2) and HCO induced by hyperventilation in healthy adults on partitioning of NOx in whole blood. NOx in hemolysate was measured by a high-performance liquid chromatography-Griess system equipped with a C(18) reverse phase column to trap hemoglobin, which enables determination of whole blood NOx concentration and calculation of NOx concentration in RBC with high accuracy and reproducibility. NOx concentration in RBC was lower than that in plasma, and equilibrium between plasma and RBC was achieved rapidly after addition of NO. Changes in PCO(2) and HCO by hyperventilation failed to influence NOx concentrations in both plasma and RBC. Plasma NOx concentrations correlated with whole blood NOx and RBC NOx concentrations. Our results indicate that changes in PCO(2) or HCO induced by hyperventilation do not influence NOx compartmentalization in plasma and RBC.

Adult↗

Cerebral blood flow, glucose metabolism and tunel-positive cells in the development of ischemia.

Few in vivo studies were available about the relation between cerebral blood flow, glucose metabolism and the appearance of apoptotic cells in the development of cerebral infarct. To investigate this, we measured local cerebral blood flow (lCBF), local cerebral metabolic rate in glucose (lCMRglc), and histopathology in transient focal cerebral ischemia in the rat. A unilateral middle cerebral artery occlusion (MCAO) was induced for 2 h in Wistar-ST rats (n = 42). A histopathological study with hematoxylin-eosin staining and the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method was performed. lCBF was measured by means of the (14)C-iodoantipyrine autoradiography technique during MCAO (n = 6), and 1, 22 and 70 h after reperfusion. lCMRglc was also measured by autoradiography with (14)C-2-deoxyglucose in the animals 22 h after reperfusion. These parameters were assessed in each region of interest: the ischemic core, boundary zones (BZ-I and BZ-II) and remote area. The boundary zones were defined as the area based on TUNEL positivity (more than 5/field) at 22 h after reperfusion (BZ-I) and at 70 h after reperfusion (BZ-II). In the BZ-I, lCBF was decreased to 18% of the control during MCAO, and lCBF and lCMRglc showed 44 and 62% of the control, respectively, 22 h after reperfusion. In this area, TUNEL-positive cells increased at 22 h, then markedly decreased 70 h after reperfusion. In the BZ-II, lCBF decreased to 39% of the control during MCAO, then returned to about 90% of the control 22 h after reperfusion. lCMRglc was maintained near its normal range (82% of the control) 22 h after reperfusion. Histopathology of BZ-II was normal 22 h after reperfusion. The TUNEL positivity of neurons in our study was assumed to be a marker of apoptotic cells. Our data suggested that the apoptotic process plays an important role in the maturation of a cerebral infarct. Both lCBF and lCMRglc were maintained with only a mild reduction in the predisposing phase of apoptosis, suggesting that sufficient blood supply and glucose metabolism are required to promote the process of apoptosis.

Animals↗

Efficacy of adjuvant therapy with procarbazine, MCNU, and vincristine for oligodendroglial tumors.

An adjuvant chemotherapy regimen consisting of procarbazine, MCNU, and vincristine (PMV) was evaluated for the treatment of malignant oligodendroglial tumors. Ten patients with histologically proven oligodendroglial tumors were treated with PMV therapy and the effectiveness was assessed using magnetic resonance imaging. Four patients with primary tumors underwent PMV after radiation therapy, and six patients with recurrent tumors were treated using PMV only. Tumor response was defined as radiological evidence of mass size change after completion of three courses of PMV. Complete or partial responses (more than 50% reduction in tumor mass) were noted in six patients, and tumor growth stabilized in four patients. In particular, inhibition of tumor growth using PMV was achieved in three patients with recurrent oligodendroglial tumors, despite the initial response after chemoradiation therapy (interferon-beta, MCNU, radiation) or nitrosourea chemotherapy (ACNU, MCNU). This PMV regimen (a modified PCV regimen using drugs available in Japan) is effective for treating malignant oligodendroglial tumors despite recurrence after other initial treatment procedures.

Adult↗

Vasodilatory effect of basic fibroblast growth factor in isolated rat cerebral arterioles: mechanisms involving nitric oxide and membrane hyperpolarization.

Basic fibroblast growth factor (bFGF), a potent mitogen, acutely dilates cerebral blood vessels and may be effective in reducing cerebral infarction. However, the vasodilatory mechanism, which may involve nitric oxide (NO), is not completely understood. This study investigated whether membrane hyperpolarization is also involved in this mechanism. Membrane potential (MP) of smooth muscle cells and vessel diameter of isolated intracerebral arterioles were simultaneously measured following extraluminal application of bFGF in rats. The involvement of NO and adenosine triphosphate-sensitive potassium (KATP) channels in bFGF-induced vasodilation and membrane hyperpolarization was evaluated using specific inhibitors, NG-monomethyl-L-arginine (L-NMMA, 10(-4) M) and glibenclamide (GB, 10(-5) M), respectively. The resting MP was recorded at a mean value of -31.9 +/- 4.5 mV. bFGF (1 to 1000 ng/ml) produced significant vasodilation and hyperpolarization. Treatment with L-NMMA caused vasoconstriction and significantly attenuated bFGF-induced vasodilation without affecting membrane hyperpolarization. In the presence of GB, the membrane potential was significantly depolarized but the vessel diameter was only marginally reduced, so bFGF-induced membrane hyperpolarization was inhibited while arteriolar dilation was attenuated. These results suggest that bFGF-induced vasodilation is mediated by a mechanism involving both NO and membrane hyperpolarization, and that membrane hyperpolarization is caused by the activation of KATP channels.

Adenosine Triphosphate↗

Time course of expression of three nitric oxide synthase isoforms after transient middle cerebral artery occlusion in rats.

The involvement of nitric oxide synthase (NOS) in ischemia was evaluated by detecting the expression of neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) by the immunohistochemical method in the rat model of middle cerebral artery (MCA) occlusion. Transient MCA occlusion (2 hours) was induced in 32 male Wistar rats by extracranial insertion of a 3-0 nylon thread through the internal carotid artery into the MCA. Animals were killed at 0, 6, 24, 72, and 168 hours after MCA occlusion (n = 6, 6, 8, 6, and 6, respectively). The brains were fixed with periodate-lysine-paraformaldehyde, frozen, and sectioned. Sections were stained with polyclonal antibody against nNOS, eNOS, and iNOS. Each section was evaluated by microscopic observation (x100). The number of nNOS-positive neurons was 41.6 +/- 5.8 (mean +/- SD) in the control hemisphere. nNOS was upregulated in the ischemic hemisphere (88.3 +/- 18.9), especially in the border zone at 6 hours after MCA occlusion. However, the number decreased to 36.4 +/- 3.6 and 26.3 +/- 7.3 in the ischemic hemisphere after 72 and 168 hours, respectively. eNOS immunoreactivity was present in the endothelium of major vessels at each time point. eNOS was not detected in the microvessels before ischemia, but faint staining was found in the endothelium at 6 hours after MCA occlusion. Immunostaining became more intense thereafter. Faint iNOS immunoreactivity was seen in the microvessels at 6 hours after MCA occlusion. Macrophages in the ischemic core and astrocytes in the border zone showed immunoreactivity to iNOS at 72 and 168 hours after MCA occlusion. Three types of NOS must be related to different stages of ischemic brain damage. nNOS may be neurotoxic in ischemia in the early phase, like iNOS in the late phase. On the other hand, eNOS seemed to be neuroprotective in all stages. These observations suggest the necessity for tailored therapeutic intervention against NOS isoforms at each stage in patients with ischemic stroke.

Animals↗

Endovascular trapping of giant serpentine aneurysms by using Guglielmi detachable coils: successful reduction of mass effect. Report of two cases.

Giant serpentine aneurysms (GSAs) are defined as partially thrombosed giant aneurysms with persistent serpentine vascular channels. Surgical management of these rare lesions is difficult because of their large size, complex structure, and unique hemodynamics. The authors report two cases of patients harboring GSAs with mass effect, which were managed effectively with endovascular treatment. The first patient was a 48-year-old man who presented with left homonymous hemianopsia caused by a GSA involving the terminal portion of the right internal carotid artery. The second patient, a 10-year-old boy, presented with tetraparesis from compression of the cervicomedullary junction by a GSA of the right vertebral artery. In each case, after confirming collateral flow by temporarily occluding the proximal artery, the aneurysm was trapped by placement of Guglielmi detachable coils at the sites at which the serpentine channels entered and exited the aneurysm. The midportion of each channel was isolated completely without packing, to maximize resorption of the devascularized mass. Mass effect and clinical symptoms rapidly improved in both cases, with no associated morbidity. We recommend endovascular trapping as a safe and effective therapeutic option for GSAs.

Carotid Artery Diseases↗

Recurrence of a neurenteric cyst with malignant transformation in the foramen magnum after total resection. Case report.

A 53-year-old man presented with recurrence of a neurenteric cyst with malignant transformation in the foramen magnum 3.5 years after total resection of the original tumor had been reported. For 2 years following the initial surgery, the patient had been in good condition, but then underwent ventriculoperitoneal shunt placement for intracranial hypertension. At the time there was no evidence of recurrence of the tumor on magnetic resonance (MR) images. One and one-half years later, he presented with headache and anorexia. A massive recurrent tumor was identified on MR images. The tumor was severely adhesive to the brainstem, cranial nerves, and vessels, allowing only partial resection. Histological examination of tumor specimens obtained during the first and second craniotomies indicated a malignant change from a typical neurenteric cyst with a one-layer epithelium in the first specimen to an adenocarcinoma with papillary proliferation in the second. The results of various immunohistochemical studies of the first specimen were typical of those of a neurenteric cyst. The second specimen displayed stronger staining of carbohydrate 19-9 and carcinoembryonic antigens than the initial specimen. The percentage of Ki-67 antigen (MIB-1)-positive cells increased from 0% in the first specimen to 6.7% in the second. To the authors' knowledge this is the first case in which malignant transformation has been demonstrated after total resection of a neurenteric cyst in the foramen magnum.

Adenocarcinoma, Papillary↗

[Perspectives on postgenome medicine: Gene therapy for brain tumors].

Recent development of therapeutic modalities in neurosurgery has brought about dramatic improvement for prognosis of brain tumors. Nevertheless, malignant glioma is one of the most formidable neoplasms in humans. According to a report by the Committee of Brain Tumor Registry of Japan, five-year relative survival rate of malignant gliomas is less than 10%. Malignant gliomas grow aggressively infiltrating into the surrounding normal brain tissue. So that total surgical resection is impossible. The tumors respond to radiation and chemotherapy, however, the efficiency has sustained transiently. The advert of new strategies for the treatment of malignant gliomas has long been awaited. We have developed a cytokine gene therapy for malignant glioma since about 10 years ago. Here, we introduce both suicide gene therapies and immune gene therapies including our case(IFN-beta gene therapy).

Brain Neoplasms↗

[Adjuvant GM-CSF cytokine gene therapy for breast cancer].

UNLABELLED: The aim of this study was to examine the enhancement of antitumor immunity of irradiated granulocyte macrophage-colony-stimulating factor (GM-CSF) gene-transduced mouse breast cancer cells. METHODS: BALBMC mouse were vaccinated subcutaneously with saline or irradiated mouse breast cancer cells, BALBMC (1 x 10(6)/mouse), infected or not infected with recombinant adenovirus harboring GM-CSF gene on day-7. Mice were injected with parental cells (1 x 10(5)/mouse) on day 0. RESULTS: No mice vaccinated with irradiated GM-CSF producing BALBMC cells developed a tumor during the observation period of up to 16 weeks, whereas 100% of mice injected with saline developed a tumor. CONCLUSION: Our study demonstrates the feasibility of this immunotherapeutic approach as a novel adjuvant cancer therapy after surgery for breast cancer.

Animals↗

[Docetaxel was effective as neoadjuvant chemotherapy for patients after failure of trans-arterial neoadjuvant chemotherapy with CEF in 2 cases of advanced breast cancer].

Docetaxel was effective as a second line neoadjuvant chemotherapy after failure of cyclophosphamide, epirubicin and 5-FU (CEF) in 2 cases of breast cancer. In Case 1, 4 cycles of trans-arterial neoadjuvant chemotherapy of docetaxel showed a PR effect after failure of 2 cycles of trans-arterial neoadjuvant chemotherapy with CEF. This patient died of pleuritis carcinomatosa 18 months after surgery for breast cancer (latissimus dorsi muscle myocutaneous flap after radical mastectomy). In Case 2, 6 cycles of neoadjuvant venous drip infusion of docetaxel resulted in a CR effect after failure of 2 cycles of transarterial neoadjuvant chemotherapy with CEF. This patient is alive and disease-free 27 months after the operation for breast cancer (same operation as for Case 1). Docetaxel was effective as neoadjuvant chemotherapy for patients after failure of trans-arterial neoadjuvant chemotherapy with CEF.

Aged↗

[Bis]

[formula: see text] The generation of (2-PyMe2Si)2CHLi was easily accomplished by the deprotonation of (2-PyMe2Si)2CH2 using n-BuLi in Et2O. Thus generated (2-PyMe2Si)2CHLi was found to react with a variety of aldehydes and ketones to give the corresponding vinylsilanes in extremely high yields with complete stereoselectivities.

Journal Article↗

Increased expression of cyclooxygenase-2 protein in rat lung tumors induced by N-nitrosobis(2-hydroxypropyl)amine.

Expression of cyclooxygenase (COX)-2 protein in preneoplastic and neoplastic lung lesions induced by the administration of 2000 ppm of N-nitrosobis(2-hydroxypropyl)amine (BHP) in the drinking water to Wistar male rats, was examined immunohistochemically. The majority of alveolar/bronchiolar adenomas (ADs) and all adenocarcinomas (ADCs) examined, stained positive or strongly positive for COX-2. In contrast, only a minority of alveolar/bronchiolar hyperplasias demonstrated immunoreactivity and half of the squamous cell carcinomas examined, were only weakly positive. Western blotting analysis also revealed expression of COX-2 protein in the resected ADs and ADCs. These results clearly indicate up-regulated expression of COX-2 in lung neoplastic lesions, particularly ADs and ADCs, induced by BHP in rats.

Adenocarcinoma, Bronchiolo-Alveolar↗

Combined effects of adeno-associated virus vector and a herpes simplex virus mutant as neoplastic therapy.

BACKGROUND AND OBJECTIVES: Although surgical therapy for pancreatic cancer has not been successful, new gene therapies, such as adeno-associated virus (AAV) vectors hold promise for treating cancer. However, expression of AAV vectors alone is insufficient for adequate effects in vivo for cancer therapy. We describe a novel therapy using the combined herpes simplex virus-ICP6 deletion mutant (ICP6delta) and AAV vector. METHODS: We investigated ICP6delta and AAV regarding kinetics and dose-response relationships of LacZ expression in vitro. We studied the expression of LacZ in vivo using subcutaneous pancreatic cancer tumors (SW1990) in nude mice. RESULTS: In vitro, ICP6delta enhanced the expression of AAV; 24 hr following inoculation there was more expression with AAV plus ICP6delta than with AAV plus KOS, and a multiplicity of infection (MOI) of 0.5 was the optimal titer of ICP6delta to support maximal expression of AAV. In vivo, there was much higher expression of LacZ in mice injected with AAV-LacZ plus ICP6A than with AAV-LacZ alone. CONCLUSIONS: ICP6delta enhances expression of AAV-vector in vitro and in vivo. These results suggested that combined therapy have potential for human cancer.

Adenoviruses, Human↗

NO(x) contamination in laboratory ware and effect of countermeasures.

Contamination of various types of laboratory wares with NO(x) (NO(-)(2) and NO(-)(3)) was assessed systematically and the effect of extensive washing as a countermeasure was evaluated. Mean NO(x) contamination arising from a model procedure for NO(x) determination in plasma was 0.93 microM (range, 0.35-1.49 microM). The major source of contamination included conical tubes (54.8%) and pipette tips used for transfer of solution (12.3-16.3%). Except for soft glassware, most NO(x) contamination could be washed out by pure water. Although NO(x) contamination in respective laboratory wares could be reduced below detection levels by extensive washing, summation of the contamination through the model procedure could not be completely abolished (but the effect of washing persisted at least 10 days). Heavy contamination was noted in glassware (especially soft glass) and ultrafiltration units, which was difficult to remove. Several types of vacuum blood sampling tubes contained various levels of NO(x). Our results indicated that a small but significant amount of contamination remained in laboratory ware even after extensive washing, and that it is advisable to avoid the use of glassware (soft glass), ultrafiltration units, and vacuum blood sampling tubes during the processing of clinical sampling for the measurement of NO(x).

Blood Specimen Collection↗

Clinicopathological study of oligodendroglial tumors: the effectiveness of interferon beta, ACNU/MCNU, and radiation (IAR/IMR) for anaplastic tumors.

The retrospective clinicopathological characteristics of oligodendroglial tumors were investigated in patients who underwent surgery, radiotherapy, and/or chemotherapy. Regarding oligodendroglioma and oligoastrocytoma without malignancy, patients who had undergone radiation therapy at a total dose of 40-50Gy had relatively long postoperative survival. Of these 15 patients, 6 showed signs of recurrence, and after additional treatment, 5 patients are still alive. On the other hand, regarding anaplastic oligodendroglial tumors, patients with anaplastic oligoastrocytoma responded well to combination chemotherapy with interferon beta, nitrosourea derivatives (ACNU/ MCNU), and radiation therapy (referred to as IAR/IMR) and survived longer than patients with anaplastic oligodendroglioma. In conclusion, patients with oligodendroglial tumors could survive longer by treatment involving surgery and radiotherapy. As for malignancy, cases of anaplastic oligoastrocytoma could be effectively treated by adjuvant therapy using IAR/IMR after surgery, but in cases of anaplastic oligodendroglioma, the response to IAR/IMR was not good, and another strategy of treatment should be recommended.

Adolescent↗

Hemopneumothorax and hemoperitoneum in a case with large cell carcinoma of the lung.

Hemopneumothorax and hemoperitoneum coincide rarely in nontraumatic cases. Here, a 70-year-old male presented a left axillary lymph node and was diagnosed as having metastatic squamous cell carcinoma. Under the same diagnosis, another lesion developed in the right femur and was resected. One year later, computed tomography detected another tumor in the left adrenal gland. Shortly afterwards, left pneumothorax developed and a chest operation revealed hemopneumothorax due to a ruptured cavitary form of large cell carcinoma. The serum showed a human chorionic gonadotropin-beta level of 1,100 ng/ml. At three-months later, he died of hemoperitoneum. The autopsy demonstrated hepatic metastases and a ruptured adrenal metastasis; microscopy showed marked trophoblastic and squamous cell changes in these organs. This patient was unique in that the rupture of the pulmonary and the adrenal lesions caused clinical manifestation.

Aged↗