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Biomedical subjects

T Wakabayashi

Publications and source records attributed to T Wakabayashi.

At least 163 records · Page 9Linked to original sources
PubMed1996

Intracellular hyperthermia for cancer using magnetite cationic liposomes: in vitro study.

'Magnetite cationic liposomes (MCL)' were developed as a means to generate intracellular hyperthermia. Affinity of the MCL to glioma cells was ten times higher than that of magnetite 'neutral' liposomes due to the electrostatic interaction based on the positive charge of the MCL. Heat generation of the MCL was studied using agar phantoms and small pellets of rat glioma cells. When a high-frequency magnetic field, 118 kHz, 384 Oe was applied to glioma cells in the presence of MCL, the glioma cell pellet of 80 microl (5.4 mm in diameter) was heated to over 43 degrees C and all the cells died after 40 min irradiation owing to the hyperthermic effect. The terminal temperature of the cell pellet was proportional to the pellet volume when other parameters were constant. It thus appears that the MCL can heat a tumor of more than 80 microl in volume to above 42 degrees C.

Adsorption↗
PubMed1996

[The role of catalase in histologic changes of acute experimental pancreatitis].

We produced acute biliary reflux pancreatitis by an injection of auto-bile in 31 young mongrel dogs. We divided into control group (n = 10), catalase administration group (B1 group, n = 17) and no-administration group (B2 group, n = 14). We studied the histologic changes of the brain tissue in those groups. There was no significant difference in the survival rate between group B1 and B2. In the histologic findings, ischemic cell changes were dominant in both groups within one month, but after 3 or 6 months after operation in group B2, satellitosis and/or neuronophagia was recognized as the irreversible changes. The lipid peroxides level was significant high in group B2. Consequentially, it is natural to think that the production of free radicals have been inhibited by catalase and the histologic changes in the brain in group B1 have been light.

Acute Disease↗
PubMed1996

Detection of K-ras point mutation at codon 12 in pure pancreatic juice collected 3 years and 6 months before the clinical diagnosis of pancreatic cancer.

We report herein a patient with K-ras point mutation at codon 12 that had been detected in pure pancreatic juice (PPJ) obtained 3 yr and 6 months before he was diagnosed with pancreatic cancer (PC). In this 73-yr-old man, PC was diagnosed by ERCP, which showed obstruction of the main pancreatic duct (MPD) at the borderline area between the body and tail of the pancreas. Distal pancreatosplenectomy was performed, and an advanced PC at the tail of the pancreas with a few metastatic nodules in the liver was confirmed. Retrospectively, a K-ras point mutation at codon 12 from GGT (glycine) to GAT (aspartic acid) was detected in the PPJ collected endoscopically 3 yr and 6 months earlier, as well as in the PPJ when PC was diagnosed and in the resected tumor tissue. Reevaluation of pancreatography from the ERCP performed at that time revealed a very mild stenotic lesion of the MPD, speculated to be a PC at a very early stage, at the body-tail border, but it was difficult to diagnose this lesion as a PC, based only on this morphological study. Accordingly, we believe that this is an interesting and valuable clinical case, indicating that K-ras mutation can precede clinical evidence, and its determination in PPJ could be a useful genetic test calling for a careful and extensive clinical investigation for early detection of PC.

Adenocarcinoma↗
PubMed1996

Gene therapy against an experimental glioma using adeno-associated virus vectors.

The efficacy of gene therapy for glioma was examined using adeno-associated virus (AAV)-based vectors to deliver genes to experimental tumors in mice. Stereotactic injection of 2 x 10(5) U-251SP human glioma cells into the brains of nude mice produced tumors of 19.06 +/- 1.79 mm2 17 days after injection. Employing a high titer preparation of AAV vector containing the gene for beta-galactosidase (AAV-lacZ), dose-dependent transduction of U-251SP cells was seen in vitro. When 1.6 x 10(10) AAV-lacZ particles were directly injected into tumors in vivo, 30-40% of the cells along the needle track expressed beta-galactosidase. Transduction of U-251SP cells in vitro with an AAV vector containing a bicistronic gene encoding both herpes simplex thymidine kinase and human interleukin-2 (AAV-tk-IRES-IL2) rendered them sensitive to the cytocidal effects of ganciclovir (GCV) and IL-2 was produced in a dose-dependent manner. Cocultures of AAV-tk-IRES-IL2 transduced cells and nontransduced cells proved highly sensitive to GCV indicating the contribution of the bystander effect. Stereotactic delivery of 6 x 10(10) AAV-tk-IRES-IL2 particles into day 7 tumors in nude mice followed by administration of GCV for 6 days, resulted in a 35-fold reduction in the mean volume of tumors compared with controls. Normal brains did not suffer from any toxic effect of the administration of AAV-tk-IRES-IL2 and GCV. These results indicate that high titer AAV vector treatment may be safe and effective for in vivo gene therapy of human brain tumors.

Animals↗
PubMed1996

Development of a target-directed magnetic resonance contrast agent using monoclonal antibody-conjugated magnetic particles.

We developed a novel magnetic resonance (MR) imaging contrast agent, MAb-magnetite, that was prepared by covalently linking polyethylene glycol-coated magnetite to a monoclonal antibody specific for a human glioma cell-surface antigen. When MAb-magnetite was injected intravenously into tumor-bearing nude mice at a dose of 100 mumol Fe/kg body weight, a 50% decrease in the T2 signal intensity of the tumor was observed, immediately following administration and continued for 48 h. Microscopic observation of the tumor tissue demonstrated localization of MAb-magnetite in cancer cells. These results suggest that MAb-magnetite is a promising agent for MR imaging of neoplasms.

Animals↗
PubMed1996

[Bronchiolitis obliterans organizing pneumonia (BOOP) after allogeneic bone marrow transplantation].

We report a patient who underwent allogeneic bone marrow transplantation for ALL. The patient presented low grade fever, cough and dyspnea at day 3 after after bone marrow transplantation. Imaging studies showed bilateral patchy infiltrates on chest X-ray and chest CT. Though treated by antibiotics, chest auscultation recognized marked bilateral inspiratory crackles. Transbronchial lung biopsy performed on day 34 showed bronchiolitis obliterans and an organizing interstitial pneumonia. The patient was treated with methylprednisolone and follow up computed tomography findings improved.

Administration, Oral↗
PubMed1995

Unilateral Multicentric Breast Carcinoma Studied by Whole Mammary Gland Serial Sectioning.

The incidence and clinicopathologic features of unilateral multicentric breast cancer (UMBC)were studied by mammary gland serial sectioning in 116 cases of clinically defined monocentric breast cancer (MONBC) examined histopathologically at the Nagano Cancer Detection Center. UMBC was defined as: 1) histopathologically discontinuous tumors each with an intraductal spread, 2)at least one tumor-free section separating two tumors, and 3) a large primary tumor and other small secondary tumors. UMBC was detected in 23 of 116 cases (19.8%), all with one secondary tumor. Primary and secondary tumors were located in the same quadrant in 34.8% and in different ones in 65.2%. The secondary tumors were < 5 mm in size in 56.5%. Secondary tumors, averaging 8.3 mm in size and 25.5 mm in distance from the primary tumor, were almost exlcusively noninvasive carcinomas, including 15 (65.4%) noninvasive ductal carcinomas and several special types. The primary and secondary tumors were of the same histologic type in 3 of 23 cases. UMBC patients averaged 6 years younger than MONBC patients, and the incidence of UMBC tended to be higher in younger patients (P<0.1). UMBC tended to occur more frequently in quadrant B with an average histologic tumor size significantly smaller than that in MONBC (P <0.01). The histologic types of the primary tumor in UMBC and MONBC were similar, with common types predominant. Lymph node metastases tended to be slightly more frequent in MONBC. This high incidence of UMBC calls for careful attention when considering breast conserving therapy.

Journal Article↗
PubMed1995

Studies on urea synthesis in the liver of rats treated chronically with ethanol using perfused livers, isolated hepatocytes, and mitochondria.

Changes in urea synthesis in the liver of rats treated with 32% ethanol in the drinking water for up to 6 months were studied using perfused livers, isolated hepatocytes, and mitochondria. Results obtained from ethanol-treated rats are summarized as follows: (1) the mitochondria of the hepatocytes of rats treated with ethanol for 2 months or longer became enlarged to various degrees, (2) the levels of ammonia in the serum remained within a normal range, while those in liver tissue were elevated compared with the control, (3) urea synthesis from ammonia in perfused livers was decreased markedly, while that from citrulline remained in the normal range, (4) the activities of carbamyl phosphate synthetase (CPS; EC 2.7.2.5) and ornithine transcarbamylase (OTC; EC 2.1.3.3) in mitochondria were unchanged compared with those of the control, and (5) the levels of ATP in liver tissue and the ability of mitochondria to synthesize ATP were decreased markedly compared with the control. Both the level of ATP in the hepatocytes and the synthesis of urea from ammonia by perfused livers of rats treated with ethanol were resistant to externally added ethanol, while those of control animals were severely affected. These results suggest that the intracellular level of ATP is intimately related to urea synthesis in both control and ethanol-treated animals, and lowered levels of ATP may be a key factor in the suppression of urea synthesis in ethanol-treated animals.

Adenosine Triphosphate↗
PubMed1995

Axonal degeneration promotes abnormal accumulation of amyloid beta-protein in ascending gracile tract of gracile axonal dystrophy (GAD) mouse.

The GAD mouse is a spontaneous neurological mutant with axonal dystrophy in the gracile tract of the medulla oblongata and spinal cord. The immunoreactivity of amyloid precursor protein (APP-IR) and amyloid beta-protein (A beta P-IR) was examined in the gracile tract and the dorsal root ganglia of normal and GAD mice. The mice were studied at 4, 9, 18, and 32 weeks of age. These periods correspond clinically to the initial, progressive, critical, and terminal stages of the disease, respectively. The APP-IR in both axons and glial cells was already accentuated to a higher level as early as 4 weeks of age in the gracile nucleus of GAD mouse. Similarly there was increase in APP-IR of GAD mouse in the dorsal root ganglia. Almost all of the primary neurons in the dorsal root ganglia at the lumbar cord level of GAD mouse revealed stronger APP-IR than those of normal mouse throughout all stages. The cells showing immunoreactivity for amyloid beta-protein became positive in axons and glial cells in the gracile nucleus by approximately the 9th week, and followed by an increase of A beta P-IR in order of the cervical, thoracic and lumbar spinal cords. These results suggest that the initial feature in GAD mouse is an accumulation of amyloid precursor protein induced by axonal dystrophy which then leads to a deposition of amyloid beta-protein within the cytoplasm of both axons and glial cells in the gracile tract.

Amyloid beta-Protein Precursor↗
PubMed1995

Three-dimensional structure of the kinesin head-microtubule complex.

Kinesin is a microtubule (MT)-associated 'motor' molecule fundamental to organelle transport. Recently, various kinesin superfamily members (KIFs) have also been identified and suggested as being responsible for the transport of specific organelles. Kinesin is a heterotetramer composed of two heavy chains and two light chains. The heavy chains form two globular heads, a rod and a fan-like tail completed by the light chains. The globular head, which is composed of approximately 340 amino-terminal residues of the heavy chain, includes both ATP-binding and MT-binding domains, and its recombinant protein also has these properties. To improve the understanding of the mechanism of force generation by an MT-based molecular motor, kinesin, we report here the three-dimensional structure of the complex of a recombinant kinesin head and MTs, as revealed by helical reconstruction from cryo-electron micrographs. A kinesin head is a globular teardrop-like structure binding to the ridge of one protofilament of MTs. We have determined the polarity of the structure of the complex of MTs and the kinesin head in relation to MT polarity.

Animals↗
PubMed1995

Antithrombotic activity of a symmetrical triglyceride with eicosapentaenoic acid and gamma-linolenic acid in guinea pig mesenteric microvasculature.

The antithrombotic effect of a synthetic symmetrical triglyceride having eicosapentaenoic acid (EPA) at positions 1 and 3, and gamma-linolenic acid (GLA) at position 2 was investigated. Administration of the triglyceride significantly increased thrombus formation time and thrombotic occlusion time induced by light irradiation and a fluorescent dye in guinea pigs after 14 days administration compared to that of soybean oil. The antithrombotic effect of the triglyceride was similar to that of EPA ethyl ester. Administration of the triglyceride increased GLA, dihomo-gamma-linolenic acid (DGLA) and EPA contents in plasma and the liver, and the ratio of DGLA to arachidonic acid. These results might be responsible for this antithrombotic effect.

8,11,14-Eicosatrienoic Acid↗
PubMed1995

Staging, scoring and grading of medulloblastoma. A postoperative prognosis predicting system based on the cases of a single institute.

Although recently survival of some medulloblastoma patients increased remarkably, it remains a serious diagnosis in others. In order to predict the postoperative prognosis in patients treated for medulloblastoma, a new staging, scoring and grading system was developed. Sixty-six patients operated on microsurgically between 1975 and 1990 at a single neurosurgical center were fully followed-up. No patient was excluded due to a poor postoperative course. Completion of commonly used radiotherapy protocols was attempted in all patients. Survival of patients was evaluated by the Kaplan-Meier method. The following 5 parameters were selected to define subgroups: patients' age, tumour location and histology, degree of resection and presence or absence of metastases. Patients older than 10 years had a better prognosis than individuals aged 10 or less (p < 0.01), patients with lateral tumours had a better prognosis than patients with midline tumours with brain stem infiltration (p < 0.05), patients with complete tumour resection had a more favourable prognosis than individuals with subtotal (p < 0.01) or partial resection (p < 0.001), patients without metastases at the time of diagnosis had a better prognosis than individuals without such evidence (p < 0.001), patients with the desmoplastic tumour variant had a better prognosis than patients with classical tumour histology (p < 0.01). According to the prognosis of a distinct subgroup, scoring points were distributed which correlated with the degree of inter-subgroup significances. The sum of a single patient's scoring points was called the total score. Based on this score, three groups of prognosis were distinguished.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

A super long-acting LH-RH analogue induces regression of hypothalamic hamartoma associated with precocious puberty.

We treated a 1-year-old female with a hypothalamic hamartoma and precocious puberty with leuprolide acetate depot, a super long-acting hormone-releasing hormone analogue (Tap-144-SR; [D-Leu6-[des-Gly10-NH2] LH-RH ethylamide acetate). The infant's major symptoms were genital bleeding and gynaecomastia. The LH-RH analogue (30 micrograms/kg) was injected subcutaneously once every 4 weeks. Clinical and laboratory manifestations of precocious puberty showed marked improvement. A follow-up after 16 months of treatment, the size of the tumour decreased significantly and remained unchanged for 2 years of further follow-up. To the best of our knowledge, this is the first hypothalamic hamartoma case in whom a decrease of tumour size under treatment with LH-RH analogue has been documented. But, because diagnosis of hamartoma is only based on neuroradiological and not on histological examinations, the possibility of a gangliocytoma cannot be excluded with certainty.

Delayed-Action Preparations↗
PubMed1995

Cerulein-induced acute pancreatitis diminished vitamin E concentration in plasma and increased in the pancreas.

Redistribution of vitamin E in the rat body was studied during acute pancreatitis induced by two intraperitoneal doses of cerulein 40 micrograms/kg of body weight at 1-hr intervals. Hyperamylasemia (2064 +/- 521 vs 6419 +/- 129 U/dL) and pancreatic edema (pancreatic water content, 71 +/- 1.2% vs 78 +/- 2%) were observed. In this model the increased level of lipid soluble fluorophore was also observed (274 +/- 18 vs 120 +/- 9.0 relative fluorescence per g dry wt). Parallel with these changes was a decrease in the level of vitamin E in the serum and an increase in the pancreas. The concentration of vitamin E in the pancreas after 6 h was 162 +/- 8.5 ng/mg dry mass vs 128.1 +/- 6.1 ng/mg dry mass in control animals. The effect of heparin on vitamin E redistribution induced by acute pancreatitis was also investigated. It was found that heparin at a dose of 100 U/kg body mass prevents the drop of the vitamin E level in the serum as well as the increases in the concentration in the pancreas tissue. It was concluded that acute pancreatitis induced redistribution of vitamin E in the rat body. Moreover, we studied the effects of heparin treatment on oxidative stress in the pancreas tissue. Acute pancreatitis caused an increase in lipofuscin accumulation, and a decrease in protein sulfhydryl groups in citrate synthetase (CS) and in malate dehydrogenase (MDH) activity. Heparin treatment that protected vitamin E accumulation in the pancreas tissue did not influence the changes in the level of lipofuscin and proteins sulfhydryl.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

Proposal of alignment-independent classification of electron microscopic images with helical symmetry and its application to reconstituted thin filaments os skeletal muscle.

A new method to classify noisy images of filaments with helical symmetry was developed and applied to cryo-electron microscopic images of skeletal muscle thin filaments. In this method, images are transformed to minimum data sets which are independent of the relative view parameters, such as rotation of a three-dimensional object around the axis of helical symmetry, translation along an axis and operation to make a filament upside down, and classified by a principal component analysis. By this method, atypical data can be identified without aligning procedures, and small structural changes and polymorphic variation are expected to be detected objectively.

Actin Cytoskeleton↗
PubMed1995

Endoscopic MRI: preliminary results of a new technique for visualization and staging of gastrointestinal tumors.

BACKGROUND AND STUDY AIMS: The principle of endoscopic ultrasonography--introducing the transducer of an external imaging method, such as ultrasonography, in combination with an endoscope into the gastrointestinal tract for higher-resolution imaging--has also been applied to magnetic resonance imaging (MRI). We report here on our preliminary experience with a new method of endoscopic MRI in the upper gastrointestinal tract. PATIENTS AND METHODS: Endoscopic MRI was performed in 32 patients with esophageal (n = 8) or gastric diseases (n = 24), mostly tumors (n = 26). Most cancers were at an advanced stage (T3/T4). A prototype MRI endoscope connected to a 1.5 tesla MRI scanner was used. The accuracy of endoscopic MRI in visualizing and staging gastrointestinal lesions was assessed. RESULTS: The normal gastrointestinal wall consisted of three layers, and tumors were visualized as having a low signal intensity on both T1- and T2-weighted sequences. Destruction of the wall layers was found to be characteristic of malignancy. Sufficient images were obtained in seven of eight esophageal cases (88%), but in only 14 of 24 gastric cases (58%). In patients in whom adequate visualization was achieved, the endoscopic MRI results of local and regional staging were consistent with surgical, histopathological, CT and/or EUS results in all six esophageal cancer cases and in 89% (T stage) and 56% (N stage) of the nine patients with gastric cancer. CONCLUSIONS: These preliminary results of endoscopic MRI are the first to be reported in the English literature. They show the potential of the method for local and regional staging, three-dimensional visualization of lesions being a potential advantage. Further technical improvements are expected.

Diagnosis, Differential↗