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Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 37 records · Page 2Linked to original sources

Various imaging modalities for the detection of salivary gland lesions: the advantages of 201Tl SPET.

The aim of this study was to compare dual-isotope (99Tc(m) and 201Tl) SPET imaging with computed tomography (CT) and magnetic resonance imaging (MRI) in the differentiation of various lesions of the major salivary glands. Twenty-two patients underwent dual-isotope SPET imaging, of whom 12 also had CT and 15 also had an MRI study. The uptake ratio and retention index for 99Tc(m) and 201Tl were calculated by drawing regions of interest on the involved and normal glands. Both CT and MRI were interpreted by two radiologists. All malignant tumours were detected by all three modalities. Warthin's tumours were detected by dual-isotope SPET imaging; however, MRI failed to differentiate Warthin's tumour from pleomorphic adenoma. Of 13 other benign tumours, dual-isotope SPET correctly diagnosed 12. Of 16 tumours showing a cold defect on the 99Tc(m) images, parametric analysis with 201Tl gave an accuracy of 94%, whereas CT gave an accuracy of 70-90%. MRI was 73-91% accurate in differentiating between benign (Warthin's) and malignant tumours. We believe that dual-isotope SPET imaging (99Tc(m) and 201Tl), together with semi-quantitative analysis, is the method of choice for differentiating between various lesions of the major salivary glands.

Adenolymphoma↗

Peripheral airway findings in chronic obstructive pulmonary disease using an ultrathin bronchoscope.

The authors performed bronchoscopic examination using an ultrathin bronchoscope to determine the characteristics of the peripheral airways in chronic obstructive pulmonary disease (COPD). The study population comprised 13 healthy control subjects, 10 patients with chronic bronchitis without airflow limitation, and 20 patients with COPD. The COPD patients were divided clinically into 10 with chronic bronchitis and 10 with pulmonary emphysema. The peripheral airways were examined using an ultrathin bronchoscope. In chronic bronchitis, peripheral airways of the 11th or 12th generation showed a high frequency of obstruction and mucosal changes such as granulation. In pulmonary emphysema, the peripheral airways frequently showed a net-like appearance of the bronchial epithelium and obstruction at the 11th or 12th generation. Morphological changes of the small airways in chronic obstructive pulmonary disease can be detected by an ultrathin bronchoscope, and this method is likely to be useful for investigating the small airways in vivo.

Adult↗

Multiseptate gallbladder with cholelithiasis diagnosed incidentially in an elderly patient.

A 70-year-old woman with rheumatoid arthritis was admitted to our hospital because of gastric ulcers. Abdominal echography incidentally revealed that the patient's gallbladder was multiseptate, an extremely rare anomaly. The diagnosis was confirmed by endoscopic retrograde cholangiography. This is the 26th case of multiseptate gallbladder in the world literature, but the patient is the oldest yet recorded with this condition. Furthermore, unlike most patients with multiseptate gallbladder, she had no biliary symptoms with concomitant cholelithiasis.

Aged↗

Regression of gastric mucosa-associated lymphoid tissue lymphoma with reduced telomerase activity after eradication of Helicobacter pylori.

Recently, telomerase activity has been demonstrated in a large number of malignant tumors whereas its activity is not detected in most normal somatic cells suggesting its role in the immortalization process. Here we report the first investigation of telomerase activity in a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Elevated telomerase activity was detected in biopsy specimens of the lymphoma. After eradication of Helicobacter pylori, the level of telomerase activity returned to normal with histological regression of the lymphoma. The telomerase activity was associated with the disease activity of the gastric MALT lymphoma after eradication therapy in the present case.

Aged↗

[Clinical evaluation of rhG-CSF in patients with neutropenia induced by chemotherapy for multiple myeloma].

A randomized controlled study of patients with multiple myeloma was performed to evaluate the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rhG-CSF:KW-2228) in treating neutropenia induced by chemotherapy, and its influence on the dose intensity of, and response rate to, chemotherapy. As a rule, 3 courses of chemotherapy at intervals of 4 weeks were administered both to the untreated and KW-2228-treated groups. Among 98 eligible patients evaluated for neutrophil recovery, a markedly reduced duration of neutropenia was observed during each course in the KW-2228 treated group. No significant difference distinguished the two groups in terms of incidence or duration of infection. However, febrile neutropenia appeared only in the untreated group. There was no significant difference in terms of response rate or dose intensity. However, only patients in the untreated group withdrew from the study due to protracted neutropenia. These results demonstrated that KW-2228 is effective and safe, and has a significant effect on the acceleration of neutrophil recovery in patients with neutropenia induced by chemotherapy for multiple myeloma, and is useful for the completion of chemotherapy regimens.

Adolescent↗

Efficacy of a new formulation of lenograstim (recombinant glycosylated human granulocyte colony-stimulating factor) containing gelatin for the treatment of neutropenia after consolidation chemotherapy in patients with acute myeloid leukemia.

The efficacy and safety of a new formulation of lenograstim (recombinant glycosylated granulocyte colony-stimulating factor) prepared by switching the stabilizer from human serum albumin (HSA) to gelatin was investigated for the treatment of neutropenia after consolidation chemotherapy in patients with acute myeloid leukemia (AML). The results obtained in the study using the gelatin-containing formulation (gelatin-lenograstim) were retrospectively compared to those obtained from a placebo-controlled double-blind randomized study (AML-DBT) using the HSA-containing formulation (HSA-lenograstim). The median time of neutrophil recovery to > or = 1000/mm3 was significantly shorter in the gelatin-lenograstim group (14 days) than in the placebo group (21 days, P = .0001), and there was no significant difference between the gelatin-lenograstim group and the HSA-lenograstim group (14.5 days of AML-DBT, P = .5462). The incidences of febrile neutropenia were significantly reduced in the gelatin-lenograstim group (24/43, 55.8%) compared to the placebo group (58/64, 90.6%, P < .0001). The incidence of fever and antibiotic use was also significantly lower in the gelatin-lenograstim group (69.8% and 83.7%, respectively) than in the placebo group (92.2%, P = .0034, and 96.9%, P = .0285, respectively). However, between the 2 groups there were no differences in the number of patients who had infectious episodes. No serious adverse drug reactions ascribed to gelatin-lenograstim were encountered. These results demonstrate that gelatin-lenograstim exerted beneficial effects in the acceleration of neutrophil recovery and in the reduction of fever, febrile neutropenia, and antibiotic use, and its efficacy was equivalent to HSA-lenograstim. Therefore, we concluded that the gelatin-lenograstim formulation, which offers no risk of virus contamination and can be stored at room temperature, is more beneficial than the HSA-lenograstim formulation.

Acute Disease↗

[A case report of pulmonary nocardiosis successfully treated with a combination of sulfamethoxazole-trimethoprim (ST) and sparfloxacin].

We encountered a case of pulmonary nocardiosis that responded dramatically to combined ST and sparfloxacin treatment. A 55-year-old woman presented with fever, cough and yellowish sputum. She had been under treatment with oral prednisolone (15 mg per day) since July 1997 after a diagnosis of Evans syndrome. A high fever of 39.8 degrees C was noted on January 30, 1998. The patient was hospitalized for bloody sputum, bilateral hypochondriac pain and evidence of infiltrative opacities in the left lower lobe on chest radiography. Bacterial pneumonia was suspected, and she was treated with piperacillin, but her clinical symptoms did not improve. Sputum culture and serologic examination failed to lead to a definitive diagnosis. Nocardia farcinica was isolated by culturing tissue obtained by CT-guided transcutaneous pulmonary biopsy, leading to a diagnosis of pulmonary nocardiosis. The results of an MIC test for antimicrobial agents led to treatment with a combination of ST and sparfloxacin, and the clinical symptoms improved. These clinical observations suggest that, when pneumonia is diagnosed in patients who have been receiving oral steroids for a prolonged period, pulmonary nocardiosis should be considered in the differential diagnosis to enable selection of appropriate antimicrobial agents.

Anti-Infective Agents↗

Development of membrane properties of rat neocortical neurons studied in organotypic cocultures.

Development of membrane properties of layer IV neocortical neurons, which receive thalamic inputs, and other layer neurons, which receive cortical inputs, were studied in organotypic cocultures of a rat visual cortical slice with either a block of the lateral geniculate nucleus or another cortical slice. In all types of cells, the membrane time constant, input resistance and spike width decreased markedly with days in culture whereas maximum rate of rise of the spike increased. Except for layer V/VI neurons, spike height and resting potentials also tended to increase during development. These changes were more prominent in superficial neurons regardless of afferent connectivity. The results suggest that the membrane properties of cortical neurons develop primarily based on laminar specificity.

Action Potentials↗

Effects of ion channel modulators in the influx and efflux of Tc-99m-MIBI.

Possible involvement of cell membrane ion transport systems in the uptake and extrusion of Tc-99m-MIBI was investigated by using various buffers with or without Na+ and Ca++, and ion transport inhibitors in a tumor cell line. The ion transport modulators dimethyl amiloride (DMA), verapamil, flunarizine and monensin were used. The uptake of Tc-99m-MIBI was significantly increased in all buffers containing either Na+ or Ca++ alone or none of them. There was significantly increased uptake of Tc-99m-MIBI especially in buffers without Na+. Verapamil, a L-type Ca++ channel blocker, increased Tc-99m-MIBI uptake in all buffers. Flunarizine, which inhibits Na+/ Ca++ channels, caused significantly increased accumulation of Tc-99m-MIBI only in buffer containing both Na+ and Ca++. Monensin, a sodium ionophore, significantly increased uptake of Tc-99m-MIBI. DMA, a potent Na+/H+ antiport inhibitor, significantly inhibited the uptake of Tc-99m-MIBI in all buffers. In conclusion, Tc-99m-MIBI behaves like Na+ during its uptake and extrusion. Extrusion of Tc-99m-MIBI may involve both verapamil- and flunarizine-sensitive pathways.

Adrenal Cortex Neoplasms↗

Bone marrow stroma from refractory anemia of myelodysplastic syndrome is defective in its ability to support normal CD34-positive cell proliferation and differentiation in vitro.

We examined the supportive function of stromal cells from patients with refractory anemia (RA) of myelodysplastic syndrome (MDS) on CD34-positive hematopoietic cell proliferation and differentiation using a long-term bone marrow culture (LTMC) system. Primary marrow stromal cells were obtained from 11 MDS RA patients and 12 healthy volunteers, and freshly prepared CD34-positive bone marrow cells from a normal subject were inoculated onto the stroma. There seems to be three broad patterns of hematopoietic cell growth in the LTMCs. In one group, hematopoietic cells were maintained at near normal levels (type A). In the second group, the number of hematopoietic cells increased within the first 5-10 days of culture, but declined to low levels at 15-20 days of culture as compared with normal control (type B). In the third group, the incidence of hematopoietic cells steadily declined from the beginning of the culture (type C). Furthermore, apoptotic change of hematopoietic cells was very frequently observed in cultures with the type C stroma, which were especially defective for supporting CD34 + cell proliferation and differentiation. The expression of CD95 on hematopoietic cells was induced by the type C stroma, however, production of fas ligand by the stromal cells was not observed. These findings suggest a lack of hematopoietic supportive function in some cases of MDS RA and also indicate that there is heterogeneity of stromal function among MDS RA patients.

Adult↗

A new method for magnetoencephalography: a three-dimensional magnetometer-spatial filter system.

A novel three-dimensional magnetometer-spatial filter system was developed to study human brain activity with high spatiotemporal resolution. The system combines the high temporal resolution of magnetoencephalography with the high spatial resolution achieved by using three-dimensional magnetometers and spatial filters to measure the direction and intensity of magnetic fields generated during brain activity. Simulation and phantom studies indicate that the system is capable of mapping current sources of magnetic fields with a spatial resolution comparable to that of any other brain functional imaging technique while maintaining millisecond temporal resolution. Application of this system to the human brain resolved magnetoencephalographic responses evoked by motion stimuli on a millisecond scale into responses occurring in visual cortical areas V1, V2/3 and V5. It also revealed signals related to contextual modulation in V1 and V2/3. This system provides a new way of studying the dynamics of human brain function.

Brain↗

Altered spatial patterns of functional thalamocortical connections in the barrel cortex after neonatal infraorbital nerve cut revealed by optical recording.

In rodents, the somatosensory cortex has a cell aggregation cluster termed the barrel, reflecting a whisker vibrissa, and this barrel formation is disrupted by infraorbital nerve cut at birth. In the present study, we prepared thalamocortical slice preparations from rats that received infraorbital nerve cut either at birth or at postnatal day (P) 7 and those from normal rats, recorded the optical response reflecting neural excitation in the somatosensory cortex with a voltage-sensitive dye (RH482) and compared the optical responses from lesioned rats with those from normal rats. In normal rats at P10, the optical response elicited electrically by thalamic stimulation propagated to the cortex, and then several patchy clusters appeared in layer IV. The size and location of these patchy responses precisely matched either barrels identified by cytochrome oxidase staining or terminal arbors of thalamocortial axons stained with biotinylated dextran amine. In contrast, at P10 in P0-lesioned rats, clusters having a wider horizontal width but smaller amplitude than those seen in normal rats appeared in layer IV. Correspondingly, neither cytochrome oxidase staining nor biotinylated dextran amine labeling of thalamocortical axons showed any barrel-like clusters or glomerular axon terminals. Likewise, at P5-P6, the tangential width of clusters in layer IV were larger than that in normal rats. At P10 in P7-lesioned rats, small cluster-matched barrels were seen in the optical response as well as in normal rats. These results suggest that P0 infraorbital nerve cut interrupted segregation of functional synapses into the barrels and retarded the maturation of thalamocortical transmission.

Animals↗

Increase in glutamate-aspartate transporter (GLAST) mRNA during kanamycin-induced cochlear insult in rats.

Kanamycin (KM)-induced changes in expression of the gene for glutamate-aspartate transporter (GLAST) in the rat cochlea were analyzed by Northern blotting. With the administration of KM (600 mg/kg/day) once daily for 20 days, the expression of GLAST mRNA gradually increased and reached a peak on day 20. Although the expression of GLAST mRNA remained at a high level until 12 days after the completion of the KM treatment, it then fell to the normal level within 2 months. Such KM treatment resulted in loss of both inner and outer hair cells and a concomitant profound permanent threshold shift. The present findings suggest that during KM administration, high concentrations of extracellular glutamate released by collapsing hair cells induced GLAST mRNA expression. Increased GLAST mRNA might play an important role in the prevention of the secondary death of spiral ganglion neurons from glutamate neurotoxicity.

ATP-Binding Cassette Transporters↗

The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes.

The Wilms' tumor gene, WT1, is a tumor marker for leukemic blast cells. The WT1 expression levels were examined for 57 patients with myelodysplastic syndromes (MDS) (refractory anemia (RA), 35; RA with excess of blasts (RAEB) 14; RAEB in transformation (RAEB-t), six; and MDS with fibrosis, two) and 12 patients with acute myeloid leukemia (AML) evolved from MDS. These levels significantly increased in proportion to the disease progression of MDS from RA to overt AML via RAEB and RAEB-t in both bone marrow (BM) and peripheral blood (PB). WT1 expression levels in PB significantly correlated with the evolution of RAEB or RAEB-t to overt AML within 6 months. Therefore, WT1 expression levels in PB were superior to those in BM for early prediction of the evolution to AML by means of quantitation of the WT1 expression levels. Furthermore, WT1 expression in PB of patients with overt AML evolved from MDS was significantly decreased by effective chemotherapy or allogeneic stem cell transplantation and became undetectable in long-term survivors. These results clearly showed that WT1 expression levels are a tumor marker for preleukemic or leukemic blast cells of MDS and thus reflect the disease progression of MDS. Therefore, monitoring of WT1 expression levels has made continuous assessment of the disease progression of MDS possible, as well as the prediction of the evolution of RAEB or RAEB-t to overt AML within 6 months. The results also showed that quantitation of WT1 expression levels is useful for diagnosis of minimal residual disease of MDS with high sensitivity, thus making it possible to evaluate the efficacy of treatment for MDS.

Adult↗

Vitamin K2 induces apoptosis of a novel cell line established from a patient with myelodysplastic syndrome in blastic transformation.

We have previously reported that vitamin K2 (VK2) has a potent apoptosis inducing activity toward various types of primary cultured leukemia cells including acute myelogenous leukemia arising from myelodysplastic syndromes (MDS). We established a novel cell line, designated MDS-KZ, from a patient with MDS in blastic transformation, and further investigated the effects of VK2 using this novel cell line. MDS-KZ shows complex chromosomal anomaly including -4, 5q-, -7, 13q+, 20q-, consistent with that seen in the original patient. Culture of MDS-KZ cells in RPMI1640 medium containing 10% FBS lead to steady but very slow proliferation with a doubling time of 14 days. However, the cellular growth rate was significantly accelerated in the presence of various growth factors such as granulocyte colony-stimulating factor, stem cell factor, granulocyte-macrophage colony-stimulating factor, interleukin-3, and thrombopoietin. Most of the cultured cells show the morphological features of myeloblasts. They are positive for CD7, CD33, CD34, CD45, CD117, and HLA-DR. However, about 10% of the cells are more mature metamyelocytes and neutrophils with various dysplastic characteristics such as pseudo-Pelger nuclear anomaly and hypersegmentation, suggesting a potential for differentiation in this cell line. As previously reported for cultured primary leukemia cells, exposure to VK2, but not to VK1, resulted in induction of apoptosis of MDS-KZ cells in a dose-dependent manner (IC50: 5 microM). In addition, VK2 treatment induced down-regulation of BCL-2 and up-regulation of BAX protein expression with concomitant activation of caspase-3 (CPP32). A tetrapeptide functioning as antagonist of caspase-3, Ac-DEVD-H, suppressed the VK2-induced inhibition of cell growth, suggesting that caspase-3 is, at least in part, involved in VK2-induced apoptosis. These observations suggest that the MDS-KZ cell line can serve as a model for the study of the molecular mechanisms of VK2-induced apoptosis.

Aged↗