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Biomedical subjects

M Umeda

Publications and source records attributed to M Umeda.

At least 217 records · Page 12Linked to original sources

[The effects of COP-BLAM regimen with G-CSF for intermediate and high grade non-Hodgkin's lymphoma].

G-CSF was used concomitantly with the COP-BLAM regimen, and its therapeutic results and adverse effects were evaluated. A total of 104 patients with untreated non-Hodgkin's lymphoma (NHL), including 22 in stage II, 52 in stage III and 30 in stage IV. Seventy five patients had diffuse large cell type, 18 diffuse medium cell type, and 11 diffuse mixed cell type. The treatment consisted of the COP-BLAM regimen based on the method of Laurence et al., was performed every 3 weeks. Complete remission was achieved in 98 out of 104 patients (94.2%), and the 4-year survival rate was 82.4%, while at the time of evaluation the median observation period was 26 months. The survival time was significantly prolonged in patients with low LDH values, B-cells, stage II or low CRP values. The COP-BLAM regimen with concomitant G-CSF administration achieved a high remission rate and reduced the frequency of infections. Almost all of the patients could be treated in 21-day cycle and this appeared to be effective for treatment with increased dose intensity.

Adolescent↗

[Chemotherapy with concomitant IFN treatment in three HBV carriers (mutant strain) with malignant lymphoma].

Intensive multidrug chemotherapy with concomitant IFN was performed in three hepatitis B virus (HBV) carriers with malignant lymphomas. All of the patients were HBsAg+, HBsAb-, HBcAb+, HBeAg- and HBeAb+ (mutant strain+). HBV-DNA polymerase (DNA-P) was normal at the beginning of chemotherapy, and complete response was achieved with CO-BLAM chemotherapy (without PDN) in all cases. In case 1, a slight elevation of DNA-P and normal GOT and GPT was observed after IFN-alpha was started during the third course. IFN-alpha was administered twice a week. In case 2, elevation of DNA-P and normal GOT and GTP were noted at the end of the 5th course, then daily IFN-alpha was started. In case 3, daily IFN-alpha was started during the 3rd course because of elevation of DNA-P. It was possible to prevent severe liver damage by administering IFN immediately after the elevation of DNA-P, since DNA-P elevation is noted before GOT and GPT elevation. The detection of the HBV mutant strain could be helpful in the treatment of HBsAg+ and HBeAb+ patients. In all of three patients, DNA-P, serum GOT and GPT normalized quickly after the administration of IFN-alpha. Severe hepatitis did not develop.

Aged↗

[Current imaging techniques in multiple myeloma].

The detection of skeletal involvement in multiple myeloma (MM) is often difficult. Plain radiographs have a very low yield in depicting skeletal lesions when they are confined to the bone marrow. The major advantage of bone scintigraphy is the ability to evaluate the entire skeletal system and to detect the bone lesions with a single examination. However it is well known that the false negative bone scan may occur frequently in MM. The advantage of magnetic resonance imaging (MRI) is the availability to detect myeloma foci within the spine, particularly early epidural involvement and spinal cord compression due to fracture. MRI is becoming increasingly routine in the work-up of patients with MM. Further investigations are required for the improved assessment of therapeutic response, correct diagnosis of diffuse bone marrow infiltration and distinction between pathologic and osteoporotic compression fractures.

Humans↗

[Bone lesions in multiple myeloma].

The etiology and pathophysiology of bone lesions in multiple myeloma (MM) and the new treatment for bone lesions in MM are mentioned in this report. The osteoclastic activating factors (OAF) include lymphotoxin (TNF-beta), interleukin 1, tumor necrosis factor (TNF-alpha) and several other cytokines. MM patients with multiple bone lesions have low bone density and low serum 1,25-hydroxyvitamin D level. The measurement of bone mineral density using dual-energy X-ray absorptiometry is useful to evaluate the bone lesions in MM. New diphosphates, which strongly inhibit the activity of osteoclasts, are now expected to be effective in the treatment of bone lesions in MM.

Bone and Bones↗

Transport and metabolism of glutathione isopropyl ester in cerebrospinal fluid.

The transport of glutathione (GSH) or glutathione isopropyl ester (GSH isopropyl ester) to the cerebrospinal fluid (CSF) in rats was estimated by levels of GSH or GSH isopropyl ester and their metabolites in CSF 30 min after the intravenous administration of GSH or GSH isopropyl ester (300 mg/kg). Although the CSF uptake of GSH isopropyl ester was almost equal to that of GSH as evidenced by about a two-fold increase in the amount of non-protein sulfhydryl groups in CSF, the sum of GSH isopropyl ester and GSH concentrations in the CSF after GSH isopropyl ester treatment was increased by 32% compared with saline-treated controls. On the other hand, treatment with GSH had no significant increase in GSH levels in CSF but increased its metabolite levels, such as cysteinyl-glycine and cysteine. GSH isopropyl ester was less metabolized than GSH. GSH isopropyl ester had low affinity to purified gamma-glutamyl transpeptidase, a key enzyme for metabolism of GSH in the choroid plexus, supporting the finding that GSH isopropyl ester is more stable than GSH in CSF. These results are compatible with our previous report (Yamamoto et al. (1993) showing that the protective action of GSH isopropyl ester against cerebral ischemia was greater than that of GSH in rats. GSH isopropyl ester may be a useful agent which protects the brain from the damage associated with oxygen-related toxicities by increasing GSH levels in the CSF.

Animals↗

[Assessment of cardiac toxicity by 123I-MIBG myocardial SPECT in elderly non-Hodgkin lymphoma patients treated with COP-BLAM and G-CSF].

COP-BLAM chemotherapy with concomitant G-CSF was performed on patients 65 or older with non-Hodgkin's lymphoma (NHL), and cardiac sympathetic disorders due to the chemotherapeutic agents were studied using 123I-MIBG (metaiodobenzylguanidine) myocardial SPECT (single photon emission CT). The results showed no correlation between the ejection fraction due to echocardiography and the total dose of adriamycin (ADR). However, there was a positive correlation between the total dose of ADR and the washout rate, and the possibility of cardiac sympathetic disorders caused by ADR was suggested.

3-Iodobenzylguanidine↗

Identification of one- and two-chain forms of trypsinogen 1 produced by a human gastric adenocarcinoma cell line.

It has previously been reported that two kinds of human gastric adenocarcinoma cell lines (STKM-1 and MKN28) secrete a trypsin-like enzyme. In this study, four molecular forms of the enzyme (26, 25, 24 and 23 kDa on non-reducing SDS/PAGE) were purified from the serum-free conditioned medium of STKM-1 cells. Analysis of N-terminal amino acid sequences showed that the 26 kDa protein was a two-chain form of trypsinogen 1 which had been produced by proteolytic cleavage of the Arg107-Val108 bond of trypsinogen 1, and the 24 kDa protein was the one-chain form of trypsinogen 1. The 25 and 23 kDa proteins were the activated forms of the two-chain and one-chain trypsinogen 1 respectively. Isoelectric focusing gave pI values of 6.3 and 6.6 for the 26 kDa two-chain form and the 24 kDa one-chain form of trypsinogen 1 respectively. Comparison of the proteolytic activities indicated that the one-chain trypsin 1 had amidolytic activity about four times higher than that of the two-chain enzyme.

Adenocarcinoma↗

Natural autoantibody against apolipoprotein A-I. Detection and characterization of the monoclonal antibody established from normal unimmunized BALB/c mice.

During the course of studying the immunogenicity of soybean lipids, we observed frequent production of the mAbs that bind to apolipoprotein A-I (apoA-I) when spleen cells from unimmunized normal BALB/c mice were employed for fusion. Of the 986 colonies from six fusions, 38 (3.9% of the total) were directed against apoA-I and 13 mAbs (IgM) were established for further analysis. The following lines of evidence indicate that this family of mAb may form a novel family of natural autoantibodies against apoA-I: 1) The mAbs were shown to bind effectively to high density lipoprotein from various species, including BALB/c mouse, and immunoblotting analyses revealed that the mAbs bound specifically to the 28-kDa protein of high density lipoprotein. 2) The 28-kDa protein was purified to homogeneity and identified as apoA-I by amino acid sequence analyses and by its cross-reactivity with a xenogenic anti-apoA-I mAb (clone A/11). 3) Differing from the xenogenic anti-apoA-I mAb, the present mAb did not bind to native apoA-I, whereas an effective binding was observed only when the apoA-I had formed a complex with neutral lipids containing polyunsaturated fatty acids such as trilinoleoylglycerol and 5-cholesten-3 beta-ol 3-linoleate. 4) Sera from unimmunized BALB/c mice had readily detectable Abs against apoA-I and the majority of the serum autoantibodies were of the IgA and IgM isotype. 5) The anti-apoA-I mAbs displayed a functional heterogeneity in their reactivity with polyanionic substances and some of the mAbs established showed an extensive cross-reaction with polyanionic substances such as ssDNA and cardiolipin.

Animals↗

Monoclonal antibody to phosphatidylserine inhibits Na+/K(+)-ATPase activity.

A monoclonal IgG, directed to phosphatidylserine (PS1G3), partially (40-50%) inhibited Na+/K(+)-ATPase activity (forward running reaction cycle) without affecting the K0.5 values for Na+,K+ and MgATP. The Hill or interaction coefficients (nH) for Na+ and K+ for this reaction were reduced from 3.0 to 1.6 and from 1.6 to 0.8, respectively. The K(+)-stimulated p-nitrophenylphosphatase activity (p-NPPase), which is a partial reaction sequence of the Na+/K(+)-ATPase system (but in the backward running mode), was inhibited more strongly (about 70%) due to an increase in K+/substrate antagonism. In this system K0.5 and nH values for both p-nitrophenyl phosphate (p-NPP) and K+ were increased by the mAb. At the maximally inhibitory concentration of PS1G3 the Vmax of the p-NPPase was also reduced. Partial reactions, which were inhibited by PS1G3, are: (1) the Na(+)-activated phosphorylation (non-competitive vs. Na+), (2) the Rb+ occlusion (competitive vs. Rb+). Partial reactions not harmed by PS1G3 are: (3) the K(+)-dependent dephosphorylation, (4) the K(+)-dependent E1 + K+<-->E2K transition. We conclude that PtdSer is involved in cation occlusion, possibly by forming part of the access gate.

4-Nitrophenylphosphatase↗

Gelatinase A and APP.

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Amyloid Precursor Protein Secretases↗

Anti-idiotypic monoclonal antibody recognizes a consensus recognition site for phosphatidylserine in phosphatidylserine-specific monoclonal antibody and protein kinase C.

In order to elucidate the molecular mechanisms responsible for the specific lipid-protein interactions, we have undertaken structural and idiotypic analyses of a monoclonal antibody, PS4A7, which binds specifically to phosphatidylserine (PS). Here we showed that one of the anti-idiotypic monoclonal antibodies raised against PS4A7 cross-reacted extensively with protein kinase C (PKC) and inhibited the activation of the enzymatic activity. The binding of the anti-idiotypic antibody to PKC was inhibited specifically by PS, but not by other phospholipids including 1,2-diacyl-sn-glycero-3-phospho-D-serine or 1,2-diacyl-sn-glycero-3-phospho-L-homoserine. In contrast, the binding of the anti-idiotypic mAb to the enzyme was significantly enhanced in the presence of either diacylglycerol or sphingosine. These findings indicate that the PS-specific monoclonal antibody and PKC share a consensus structure which is responsible for the specific interaction with PS and both diacylglycerol and sphingosine may induce a similar conformational change which exposes the PS-specific binding site of the enzyme.

Amino Acid Sequence↗

Cell adhesion activity of a 30-kDa major secreted protein from human bladder carcinoma cells.

Human bladder carcinoma cell line EJ-1 secreted a protein of 30 kDa as a major component. This protein was purified from the serum-free conditioned medium of EJ-1. Its N-terminal amino acid sequence was identical to that of fibroblast-derived endothelial cell growth factor (f-ECGF), but there were differences in their amino acid compositions and isoelectric points. The 30-kDa protein showed no effect on the growth of bovine capillary endothelial cells, but it promoted the attachment and spreading of rat liver cell line BRL and human umbilical vein endothelial cell line ECV-304. These results suggest that the 30-kDa protein, tentatively named "tumor-derived adhesion factor (TAF)", may be related with the aberrant cell adhesion of cancer cells.

Amino Acid Sequence↗

Nucleotide sequence of a rice cDNA similar to a maize NADP-dependent malic enzyme.

We have isolated a rice cDNA clone that is homologous to the gene for the maize NADP-dependent malic enzyme (EC 1.1.1.40; NADP-ME). The deduced amino acid sequence coded for by the cDNA indicates a high level of homology to chloroplast type NADP-ME, including a transit peptide with pronounced hydrophobic properties at the amino terminus. Northern blot analysis indicates that the expression of this gene is regulated by external stress such as submergence.

Amino Acid Sequence↗

Isolation and expression analysis of two rice genes encoding the major intrinsic protein.

We isolated two rice cDNAs (rMip1 and rTip1) which are homologous to the genes encoding the major intrinsic protein (Mip) (soybean nod-26 and Arabidopsis gamma-Tip), respectively. Expression of rTip1 in shoots and roots of rice seedlings was enhanced by water stress, salt stress and exogenous ABA. rMip1 was expressed only in shoots. Although mRNA level of rMip1 in shoots was induced to a small extent by exogenous ABA, it did not show any increase under water or salt stress over the course of 12 h. On the basis of the differential expression patterns and evolutional distinctions, it is suggested that the possible channel proteins encoded by rMip1 and rTip1 genes may function in different transport systems.

Abscisic Acid↗

Isolation and characterization of a rice cDNA similar to the S-phase-specific cyc07 gene.

We isolated a rice cDNA clone (T151) which encodes an open reading frame of 262 amino acids. This clone is similar to the S-phase-specific cyc07 gene of Catharanthus roseus. Expression of this gene is much higher in callus than in seedlings and regulated by external stresses such as high osmotic pressure, salinity, low temperature and submergence.

Amino Acid Sequence↗