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Biomedical subjects

M Umeda

Publications and source records attributed to M Umeda.

At least 145 records · Page 8Linked to original sources
PubMed1997

Molecular and biochemical characterization of a proteasome subunit from rice and carrot cells.

Proteasomes function mainly in the ATP-dependent degradation of proteins that have been conjugated with ubiquitin. We isolated a cDNA clone for a rice protein that exhibited high homology to subunit C2 of proteasomes. Southern blot analysis revealed that the corresponding gene was present as a single copy in the rice genome. After fractionation of a crude extract from cultured cells, a 35-kDa protein that cross-reacted with antibodies against the C2 subunit was recovered in the peak fraction of both 20 S and 26 S complexes. The same antibodies cross-reacted with two proteins in seedlings, one of which was the same as that detected in cultured cells. The level of the protein was reduced in roots under conditions of high salinity. The 35-kDa protein was not detected in the nuclei of rice of carrot cells. However, during somatic embryogenesis of carrot cells, the C2 subunit was found in the nucleus at the globular stage, and it gradually disappeared in the period from the heart to the torpedo stage. Cells at the globular stage are proliferating rapidly, thus, it is possible that proteasomes are associated with the proliferation of plant cells.

Amino Acid Sequence↗
PubMed1997

THP-COPBLM (pirarubicin, cyclophosphamide, vincristine, prednisone, bleomycin and procarbazine) regimen combined with granulocyte colony-stimulating factor (G-CSF) for non-Hodgkin's lymphoma in elderly patients: a prospective study.

THP-COPBLM including pirarubicin (THP), which is thought to be less toxic than doxorubicin, was used to treat non-Hodgkin's lymphoma (NHL) and the remission rate and adverse effects were studied in 26 patients older than 70 years. Complete remission (CR) was achieved in 19 patients (73.1%) and partial remission in three (11.5%). Classified by stages, CR was achieved in seven out of nine stage II patients and 12 out of 17 stage III, IV patients. The 2-year survival rate was 60.3%. Grade 3 or higher adverse effects included leukopenia in eight patients (30.8%), anemia in three (11.5%), thrombocytopenia in two (7.7%) and nausea/vomiting in 1 (3.8%). The THP-COPBLM regimen appears useful for the treatment of NHL in elderly patients. The regimen was seldom associated with gastrointestinal symptoms and cardiotoxicity. Despite the administration of granulocyte colony-stimulating factor (G-CSF), however, the white blood cell count decreased in many patients, suggesting the necessity for further study of this regimen to modify the dose of THP.

Aged↗
PubMed1997

Inhibition of tumor promoter activity toward mouse fibroblasts and their in vitro transformation by tissue inhibitor of metalloproteinases-1 (TIMP-1).

Tissue inhibitor of metalloproteinases-1 (TIMP-1), a natural inhibitor of matrix metalloproteinases (MMPs), is known to inhibit invasion and metastasis of tumor cells. In the present study we examined anti-tumor promoter activity of TIMP-1 and its effect on in vitro cell transformation using BALB/3T3 cells in low serum culture medium. In the dye transfer assay the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) continuously blocked gap-junctional intercellular communication (GJIC) of BALB/3T3 cells in confluent phase. TIMP-1 did not prevent transient inhibition of GJIC induced by TPA, but it quickly restored the reduced GJIC level to the control level. The recovery of GJIC was dependent on the concentration of TIMP-1 from 1 to 1000 ng/ml. In an in vitro two-stage transformation assay in which BALB/3T3 cells were treated with 0.5 microg/ml N-metyl-N'-nitro-N-nitrosoguanidine as initiator and 100 ng/ml TPA as promoter, TIMP-1 at concentrations > 10 ng/ml inhibited the focus formation of transformed cells by approximately 60%. TIMP-2 and a synthetic MMP inhibitor showed a similar inhibitory activity on in vitro cell transformation. Furthermore, zymographyic analysis showed that TPA treatment of BALB/3T3 cells induced secretion of gelatinase B and stromelysin-1 into the culture medium. These results indicate that TIMP-1 and TIMP-2 have inhibitory activity on in vitro transformation of cells. It seems likely that TPA-inducible MMPs are involved in carcinogenesis and TIMPs have a protective role against carcinogenesis in vivo.

3T3 Cells↗
PubMed1997

Localization of the phosphatidylserine-binding site of glyceraldehyde-3-phosphate dehydrogenase responsible for membrane fusion.

In this study, we demonstrated that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a phosphatidylserine (PS)-binding protein and localized the putative PS-binding site involved in the membrane fusion induced by this enzyme. In an attempt to identify the PS-binding proteins, we raised polyclonal antibodies against a 15-amino-acid synthetic peptide (amino acid residues 390-403 of phosphatidylserine decarboxylase), which was shown to bind specifically to PS. One polyclonal antibody, designated aPSD-2, crossreacted with GAPDH, and its binding to GAPDH was inhibited by PS but not by other phospholipids such as phosphatidylethanolamine and phosphatidylinositol. Kinetic analysis of GAPDH binding to phospholipid membranes by measuring surface plasmon resonance showed that GAPDH associated with the phospholipid membrane containing PS rapidly (k[on] =2.8 X 10(4) M(-1) X s[-1]) and dissociated extremely slowly (k[off]=5.9 X 10(-5) s[-1]), giving a low dissociation constant (KD=2.6nM). GAPDH bound less effectively to membranes without PS with a dissociation constants of 0.2 microM. GAPDH-induced vesicle fusion was also inhibited by aPSD-2, suggesting that this antibody recognizes the putative PS-binding site on GAPDH involved in the enzyme-induced membrane fusion. Chemical fragmentation of GAPDH with cyanogen bromide followed by separation and sequence analysis of the reactive peptide resulted in the identification of a single reactive peptide with the sequence of amino acid residues 45-103 of GAPDH. Analysis of aPSD-2 binding to synthetic peptides derived from the corresponding region localized the antibody-binding site to amino acid residues 70-94 of GAPDH. Both the 25-amino-acid synthetic peptide (amino acid residues 70-94 of GAPDH) and polyclonal antibody raised against this peptide inhibited GAPDH-induced membrane fusion, suggesting that these amino acid residues play a crucial role in this membrane fusion process.

Amino Acid Sequence↗
PubMed1997

Evaluation of long-term daily administration of oral low-dose etoposide in elderly patients with relapsing or refractory non-Hodgkin's lymphoma.

Etoposide produces reversible inhibition of topoisomerase II, leading to cleavage of DNA, and thereby has an antitumor effect. This mechanism suggests that the longer treatment is continued, the greater the antitumor effect will be. In the present study, both therapeutic and adverse effects of long-term treatment with low-dose oral etoposide were studied in 29 patients aged > or = 65 years with non-Hodgkin's lymphoma (NHL) for whom standard chemotherapy was not effective or refractory. These patients received etoposide at a dose of 50 mg/d for as long as possible. Treatment was continued until white blood cell count decreased to < or = 2,000/microL or the platelet count decreased to < or = 5 x 10(4)/microL. According to the World Health Organization (WHO) criteria of therapeutic effects, 6 (20.7%) of the 29 patients achieved complete remission and 13 patients (44.8%) had partial remission, for a response rate of 65.5%. Adverse effects of > or = grade 3 included leukopenia in 24 patients (82.8%) and anemia in 7 (24.1%). Granulocyte colony-stimulating factor (G-CSF) was given in combination with etoposide to eight patients because of leukopenia (granulocyte count < or = 1,000/microL). In view of the excellent subjective tolerance, low incidence of serious adverse effects, and good activity, single agent oral etoposide given continuously over prolonged periods represents a useful treatment for elderly patients with NHL.

Administration, Oral↗
PubMed1997

Investigation of morphological change of lateral and midline fluid percussion injury in rats, using magnetic resonance imaging.

OBJECTIVE: Investigating the time course of morphological changes in experimental traumatic brain injury (TBI) in vivo helps to clarify the mechanism of TBI and develop new therapeutic modalities. We examined the morphological changes in experimental TBI, using magnetic resonance imaging (MRI) in a rat model. METHODS: We produced lateral fluid percussion injury (LFP) and midline fluid percussion injury (MFP) in rats, using the Yamaki fluid percussion device. The rats were divided into four groups: LFP, MFP, sham LFP, and sham MFP. MRI was performed with a 4.7-T magnetic resonance apparatus 2 days and 90 days after the induction of injury. T1-, T2-, and T2- weighted images were obtained using a surface coil. RESULTS: Hemorrhage, contusion, and brain edema in LFP models were detected on the 2nd day after injury, and the necrotic tissue was absorbed and replaced by cerebrospinal fluid on the 90th day. In MFP animals, we detected a small hemorrhage in the corpus callosum with minimal brain edema around the hemorrhage on the 2nd day after injury, and on the 90th day, enlarged ventricles and cisterns were observed, indicating brain atrophy. CONCLUSION: MRI, therefore, is useful for plotting morphological changes in experimental TBI in vivo. We report the novel and clinically important finding of brain atrophy after experimental TBI.

Animals↗
PubMed1997

Hemorrhagic and nonhemorrhagic stroke: diagnosis with diffusion-weighted and T2-weighted echo-planar MR imaging.

PURPOSE: To determine if diffusion- and T2-weighted echo-planar magnetic resonance (MR) imaging can be used to detect acute hemorrhagic stroke and to differentiate hemorrhagic from nonhemorrhagic stroke. MATERIALS AND METHODS: A total of 118 examinations (diffusion- and T2-weighted MR imaging) in 19 patients with 27 nonhemorrhagic strokes and in six patients with seven hemorrhagic strokes were performed. The ratios of apparent diffusion coefficient and of signal intensity on T2-weighted MR images in lesions to those in contralateral control areas were calculated. RESULTS: Decreased ADC was shown in lesions of acute (0-3 days) hemorrhagic stroke, as well as in lesions of acute nonhemorrhagic stroke. Hypointense areas were seen on T2-weighted MR images in patients with acute hemorrhagic stroke, in contrast to normal to increased signal intensity in those with acute nonhemorrhagic stroke. Apparent diffusion coefficient tended to remain decreased in hemorrhagic stroke lesions even 100 days after onset, in contrast to the increased coefficient in nonhemorrhagic stroke lesions at the late chronic stage (31 days or older). CONCLUSION: Diffusion- and T2-weighted echo-planar MR imaging can be used to detect and distinguish between acute hemorrhagic and nonhemorrhagic stroke.

Acute Disease↗
PubMed1997

[Effectiveness of prolonged oral therapy with low-dose etoposide in patients aged 85 years and over with non-Hodgkin's lymphoma].

Individualizing the doses of cancer chemotherapy agents and progress in supportive therapy have improved the prognosis for elderly patients with non-Hodgkin's lymphoma. Prolonged hospitalization elderly patients has adverse effects, which include dementia, difficulty in walking, and depression. We treated 10 elderly patients (> or = 85 years) with non-Hodgkin's lymphoma as outpatients with oral etoposide, 25 mg or 50 mg daily for as long as possible, or until the white blood cell count decreased to < or = 2,000/microliter or the platelet count decreased to < or = 5 x 10(4)/microliter. Complete remission was achieved in 4 patients and partial remission in 4; the median duration of survival was 19 months. Adverse effects included leukopenia in 1 patient (< or = 1,000 cells/microliter), thrombocytopenia in 1 patient (< or = 5 x 10(4) cells/microliter), and anorexia in 1 patient. These results indicate that prolonged oral administration of low-dose etoposide is effective and safe for the treatment of non-Hodgkin's lymphoma in elderly patients. This outpatient chemotherapy caused no serious adverse reactions.

Administration, Oral↗
PubMed1997

[Doxorubicin-induced myocardial damage in elderly patients with hematologic malignancies].

Cardiac function was evaluated in 53 elderly patients with hematologic malignancies who were being treated with doxorubicin (DXR). The left ventricular ejection fraction was measured by radionuclide angiocardiography, the washout rate by 123I-MIBG myocardial SPECT, the extent and severity scores by 123I-BMIPP myocardial SPECT, and the frequency of premature ventricular contractions by Holter electrocardiography. 1) In some patients, both the washout rate and the extent and severity scores were abnormally high before treatment. 2) Because the washout rate correlated with the total dose of DXR, it may be an early indicator of cardiac sympathetic nervous dysfunction. 3) The left ventricular ejection fraction correlated with the extent and severity scores, but not with the washout rate or with the frequency of premature ventricular contractions. 4) The washout rate correlated with the frequency of premature ventricular contractions. These data show that elderly patients had abnormal cardiac function even before treatment with DXR; that cardiac sympathetic dysfunction and cardiac mitochondrial dysfunction developed at total DXR doses of 250 to 300 mg/m2 or higher; and that the left ventricular ejection fraction was less than or equal to 50% in many patients. Consequently, when DXR is used to treat elderly patients, multimodal evaluation of cardiac function is necessary to detect cardiotoxicity and to determine the optimal total dose and the optimal dosage.

Aged↗
PubMed1997

[Usefulness of THP-COPBLM therapy in elderly patients with non-Hodgkin's lymphoma].

We studied the remission rate and adverse effects in THP-COPBLM therapy consisting of pirarubicin (THP), which is said to be less cardiotoxic than doxorubicin. Subjects were 21 non-Hodgkin's lymphoma (NHL) patients older than 70 years of age. Of 21 patients, complete remission (CR) was achieved in 16 patients (76.2%) and partial remission in 2 patients (9.5%). Classified by stages, CR was achieved in 5 out of 6 patients in stage II, 7 out of 8 in stage III and 4 out of 7 in stage IV. Two-year survival rate was 61.5%. Adverse effects were observed in 7 patients (33.3%) with grade 3 or above leukocytopenia, 2 (9.5%) with thrombocytopenia and 1 (4.8%) with gastrointestinal symptoms. However, no abnormality in EKG was found, and the left ventricular ejection fraction in echocardiography did not differ before and after therapy. One patient each developed pneumonia and sepsis when they had granulocytopenia. THP-COPBLM therapy seemed useful in treatment of elderly patients with NHL. There were few adverse effects such as gastrointestinal symptoms or cardiotoxicity. However, leukocytopenia was observed in many patients despite combined use of G-CSF, suggesting the dose and administration method of THP should be studied further.

Aged↗
PubMed1997

AML1a but not AML1b inhibits erythroid differentiation induced by sodium butyrate and enhances the megakaryocytic differentiation of K562 leukemia cells.

AML1 may play a role in growth and differentiation of cells along erythroid and/or megakaryocytic lineages, because a significant level of the AML1 gene is expressed in these cells. We overexpressed AML1a (without the transcription-activating domain) and AML1b (with the domain) proteins in K562 leukemia cells, which can be induced to differentiate into hemoglobin-producing cells and megakaryocytes. The AML1a-transfected K562 cells had a reduced capacity to differentiate in the presence of sodium n-butyrate but not in the presence of other inducers, such as hemin, 1-beta-D-arabinofuranosylcytosine, and herbimycin A. The AML1 antisense oligodeoxynucleotide but not the sense oligomer recovered its differentiation-inducing capacity in the presence of butyrate. On the other hand, AML1b conferred a similar differentiation-inducing capacity upon K562 cells transfected with vector alone. AML1a expression was associated with enhanced sensitivity to megakaryocytic differentiation induced by phorbol ester. These results provide evidence that AML1 proteins play a role in erythroid and megakaryocytic differentiation.

Antigens, CD↗
PubMed1997

[Theory and clinical application of functional MRI: 3D-functional brain mapping].

Functional magnetic resonance imaging (fMRI) was performed using a clinical 1.5 T MR scanner. Normal volunteers and patients with several neurological disorders were studied with somatosensory stimulation using sponge at right hand and visual stimulation using checkerboard pattern. Both fMR images by gradient echo echo planar imaging and three dimensional gradient echo images were studied. Reconstructed 3 dimensional functional brain mapping was superimposed on 3D anatomical images. Apparent signal increase was observed at contra lateral sensorimotor cortex and secondary sensory cortex with sponge stimulation. In the case of left homonymous hemianopia due to cerebral infarction, increasing signal was only observed surrounding left calcarine fissure by using stimulation of all visual field. In conclusion, fMRI and 3-D functional brain mapping has extremely high potentiality to examine pathophysiology of various neurological disorders.

Brain↗
PubMed1997

[Functional brain mapping in motor task and somatosensory stimulation using echo planar MRI].

Functional brain mapping was performed with a 1.5T clinical MRI apparatus. Single shot gradient echo echo-planar imaging (EPI) sequence was employed. Normal volunteers were studied with the task of grasping hand or opposition of fingers at the frequency of 3 Hz, median nerve electro-stimulation, pure somatosensory stimulation by roller for acupuncture. Apparent signal increase was observed at contralateral sensorimotor cortex with motor task. Signal changes delayed about 5 seconds compared with the start and the cessation of the task, which may suggest that regional changes of CBF and blood oxygen level in capillary and/or in venule lag behind electrical excitation. It was hard to detect the activated area with median nerve electro-stimulation. On the other hand, roller stimulation provoked distinct activated areas at contralateral sensorimotor cortex. The activated areas caused by the roller stimulation and the motor task coincided entirely, which suggests the possibility of the intermixed localization of primary areas of motor and somatosensory. It was also clearly demonstrated that the activated area was broader with quick (3 Hz) and complicated motor task (finger opposition) than with slow (1Hz) and simple motor task (hand grasping).

Adult↗
PubMed1997

[Principles and clinical applications of diffusion weighted echo planar MR imaging].

The ultrafast capability of echo planar imaging(EPI) made diffusion-weighted MRI (DWI) measurements practical, without the need of head fixation and without the need to exclude patients unable to hold still. The DW hyperintensity and reduced apparent diffusion coefficient(ADC) were observed in all hyperacute strokes, initially at 2.5 hours. In contrast to decreased ADC within 10 days and DW hyperintensity within 30 days, ADC was increased without DW hyperintensity in chronic stage. This suggests that DWI can discriminate between acute and chronic strokes. Furthermore, DWEPI and T2-weighted EPI were also be useful to detect and distinguish acute hemorrhagic stroke from nonhemorrhagic stroke. This review highlighted the promising technique of DWEPI to examine stroke patients in routine clinical practice.

Animals↗
PubMed1997

[Detection of pulsated blood flow by cine mode 3D angiography].

The phase contrast(PC) has an advantage to get an information about flow speed of blood along the gradient axis. The cine mode 3D-PC MRA was performed by a 1.5T clinical MR system(GE; Signa) using multi-slices gradient echo sequence with ECG gating and velocity-encoding gradient along three orthogonal axes. The cine mode 3D-PC data in three axes was constructed from 10 cardiac phases, respectively. The black and white cine mode 3D-PC MRA enabled to get an information of blood flow speed. The color MRA, in which flow direction was assigned with RGB colors, enabled to observe flow orientation of blood. Furthermore, the flow speed vector in each pixel showed a detail flow information in the intravascular space.

Basilar Artery↗
PubMed1997

[Mapping of cerebral metabolism on cerebral disorders using multi-slice proton magnetic resonance spectroscopic imaging].

Multi-slice proton magnetic resonance spectroscopic imaging(MRSI) was performed using a 1.5 T clinical MR apparatus. Normal volunteer and several kinds of cerebral disorders were examined using following parameters; Tr/Te = 2.3 s/280 ms, slice thickness/gap/slices = 15/3.5 mm/4, 32 phase encoding and 24 cm FOV. Every 4 slice images of NAA, Cr, Cho and Lip/Lac were obtained in about 34 minutes. In control cases, images of Cr and Cho showed very high intensity at cerebellum comparing with cerebrum. This means high concentration or changes of relaxation times of both Cr and Cho. In cerebral infarction and brain tumor, though NAA images showed no signal intensity, Cr and Cho images showed small iso-or mild high-signal intensity areas. These findings suggest neuronal loss and gliosis or tumor growth in the lesions. In conclusion, MRSI has extremely high potential to evaluate metabolism of brain and cerebral disorders.

Aspartic Acid↗
PubMed1997

[Prognostic factors of follicular lymphoma treated with combination chemotherapy].

This study investigated 72 patients (12.4%) with follicular lymphoma among 582 patients with non-Hodgkin's lymphoma admitted to our department. Treatment achieved complete remission (CR) in 83.3% of the follicular lymphoma patients, with an overall 5-year survival rate of 63.7%. The 5-year survival rate was 76.9% for the 60 patients who achieved CR, and this rate was significantly higher than that for patients who achieved only partial remission (PR) (p < 0.01). The 5-year survival rate was 40% with the CHOP regimen and 74.3% with the COP-BLAM regimen. The 3-year survival rate for biweekly COP-BLAM was 88.4%. The 5-year disease free survival rate for patients who achieved CR was 80.5%. The rate reached a plateau after 42 months, and the same survival was maintained for more than 10 years. These results suggest that intensive chemotherapy is effective even against follicular lymphoma. The 5-year survival rate for patients who achieved PR, suggesting the importance of the response to initial chemotherapy.

Adult↗