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Biomedical subjects

M Umeda

Publications and source records attributed to M Umeda.

At least 379 records · Page 21Linked to original sources
PubMed1989

Effects of inhaled cadmium on breathing in the mouse.

Effects of intranasally administered cadmium (3.67 micrograms Cd approximately 36.7 mg per mouse) on breathing were investigated in mice under pentobarbital anesthesia. Cd levels found in the respiratory tract were dependent on the amount administered. Cd mainly caused degeneration and desquamation of the bronchial epithelium and pulmonary congestion, while the carrier solvent had no effects. On the other hand, the carrier solvent decreased respiratory frequency and enhanced its amplitude. These effects were absent 24 h later. However, Cd strongly affected respiration; frequency and amplitude were decreased and recovery at 24 h was not complete at the higher concentrations. These effects by Cd on respiration were dependent on the concentration of administered Cd and the Cd level in lung. Therefore, these results suggest that intranasally administered Cd has inhibitory effects on mouse respiration, perhaps owing to its acute toxicity to pulmonary tissues.

Administration, Inhalation↗
PubMed1989

[Treatment with a new preparation using peplomycin emulsion in hydroxypropylcellulosum. Analysis of immediate response in sixty-two patients with bladder cancer].

To 62 vesical tumor patients, 30 ml of a HPC-PEP mixed solution was infused into the urinary bladder. The HPC-PEP solution was prepared by adding 15 ml of 2% hydroxypropylcellulosum (HPC) to 15 ml of peplomycin (PEP)/physiological saline solution in which 90 mg PEP had been dissolved. Accordingly, a total of 30 ml of the mixed solution was used. On day 7 after treatment, a clinical evaluation was made through endoscopic observation and urine cytodiagnosis. The results of the evaluation were expressed by assigning appropriate grades for the improvements made. As for the overall clinical effects, 10 patients demonstrated excellent improvement (CR) but 26 patients exhibited no improvement (NC). The overall clinical efficacy for all cases was 58%. When the evaluation was made according to severity (T1, T2, or T3), the results were as follows: of 43 T1 patients, 9 patients were judged CR, and 23 patients were PR; and of 15 T2 patients, 1 patient was CR and 3 patients were PR. However, all T3 patients were NC. The clinical efficacy for the T1 and T2 groups was 74.4% and 26.4%, respectively. A significant difference was observed between the T1 group and the T2 and T3 groups (p less than 0.05). Evaluation made according to the degree of histopathological differentiation (G1, G2 and G3) demonstrated the following results: of 23 G1 cases, 6 cases were CR, 9 cases were PR; of 32 G2 cases, 4 cases were CR and 16 cases were PR; and of 7 G3 cases, only 1 patient was found to be PR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Studies of enzymuria and proteinuria: Report 2; Relationship between glomerular filtration rate and urinary enzymuria and proteinuria].

Urinary splitting enzymes and proteins including N-acetyl-b-D-glucosanimidase (NAG), beta 2 microglobulin (beta 2MG), and alpha 1 microglobulin: (alpha 1MG), which are established to be useful in the evaluation of renal dysfunction, especially renal tubular impairment, were measured to determine the extent of renal tubular impairment in relation to the degree of glomerular dysfunction in patients with renal deterioration. In healthy volunteers, urinary NAG, alpha 1MG and beta 2MG levels were 3.5 +/- 1.4 (mean +/- SD) U/g creatinine, 2.5 +/- 2.0 mg/l and 88 +/- 75 micrograms/l, respectively. While serum beta 2MG level (SBMG; microgram/ml) was between 2.0 and 2.9, among the patients with renal dysfunction, NAG, alpha 1MG and BMG levels showed 8.6 +/- 5.5, 9.8 +/- 5.8 and 785 +/- 1,264, respectively, and further elevated to 10.1 +/- 5.0, 16.5 +/- 0.7 and 525 +/- 440, respectively with a SBMG level over 3.0. Thus glomerular function was deteriorated, urinary alpha 1MG level elevated to significantly higher with a parallel to renal dysfunction. In patients with more severe renal dysfunction, the corresponding urinary NAG and alpha 1MG levels became significantly higher. However, urinary beta 2MG level was significantly higher in patients with moderate renal dysfunction compared to healthy volunteers only when SBMG level was more than 2.0. Therefore, it was more valuable to measure urinary alpha 1MG with NAG or beta 2MG at SBMG level of less than 1.9 and to determine urinary NAG and alpha 1MG at greater than 2.0. These results indicated that the measurement of the levels of urinary splitting enzymes and proteins is valuable in the evaluation of proximal tubular impairment, even when the degree of glomerular impairment is minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1989

[Growth factors produced by rat glioma cells: activities of transforming growth factors].

Growth factors contained in cultured medium of rat glioma C6 cells (C6 cells) were examined mainly for the activity of transforming growth factors (TGFs). Cultured medium of C6 cells was dialyzed against acetic acid, lyophilized and chromatographed by gel-permeation method, the fractions were assayed by soft agar colony formation, iodine 125 (125I)-epidermal growth factor (EGF)-binding competition and incorporation of tritium-thymidine. Two nontransformed cell lines, clonal NRK49F and BALB/3T3 A 31-1-1 (3T3) cells, were used as indicator cells for the soft agar colony assay. 3T3 cells were also used for the incorporation of tritium-thymidine. EGF receptor-rich A 431 cells were used for 125I-EGF-binding competition assay. The activity of alpha-type TGFs was examined by soft agar colony formation of NRK49F cells and inhibition of EGF-binding to A 431 cells since TGF alpha has sequence homology with EGF and binds to EGF receptors on the cell membrane, while the activity of beta-type TGFs was examined by soft agar colony formation of 3T3 cells and NRK 49 F cells with the addition of EGF. High level of activities of both TGF alpha and TGF beta were detected in 14,000 to 45,000 daltons, and also high level of the activity of DNA synthesis was detected at the same molecular weight. These results suggest that C6 cells produce TGF alpha and TGF beta as well as platelet-derived growth factors (PDGFs)-analogue. Since amplification of EGF receptor gene has been demonstrated in glioma, TGF alpha released by glioma may provide autocrine stimulation through the binding to the amplified EGF receptors. TGF beta is known to increase EGF receptors on the cell membrane. TGF beta has been demonstrated not only to stimulate but also inhibit cell proliferation under certain circumstances.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Relationship between Ara-C sensitivity of leukemic-colony forming units (L-CFU) and [3H] deoxycytidine suicide test of L-CFU].

Ara-C sensitivity test and suicide tests of L-CFU using [3H] deoxycytidine (dCyd) and [3H] thymidine (TdR) were performed in patients with acute nonlymphocytic leukemia (ANLL) and with chronic myeloid leukemia in blastic crisis (CML-BC). We found a correlation between ara-C sensitivity and the [3H] dCyd suicide test of L-CFU (p less than 0.001); and between ara-C sensitivity and the [3H] TdR suicide test (p less than 0.05). These results suggest that the [3H] dCyd suicide test reflects the degree of activity of ara-C metabolism in L-CFUs.

Adult↗
PubMed1989

[Comparative clinical study of single and combination therapy of human lymphoblastoid interferon (HLBI) with 5-FU in the treatment of advanced renal cell carcinoma].

A clinical trial using human lymphoblastoid interferon (HLBI) was done on patients with advanced renal cell carcinoma to compare the efficacy of monotherapy with that of combined administration with a 5-fluorouracil (FU) agent. A total of 24 patients with definitely diagnosed advanced renal cell carcinoma were enrolled in either of the HLBI treatments. Principally, the daily intramuscular injection of 3 million units of HLBI was done for 4 consecutive days and thereafter followed by twice of weekly injections. The combined agent used in the present study was 300 or 600 mg of 5-fluorouracil agent given orally. The efficacy of HLBI was evaluated according to direct assessment standard of chemotherapy to a solid tumor expelled by the committee of Japanese health and welfare ministry. Of 11 patients who received monotherapy, 3 had a partial response rate of 27.3 percent. While only one of 13 patients having received combined HLBI administration with oral 5-FU tablets showed a partial response with a response rate of 7.7 percent. A total of 4 patients partially responded to either HLBI treatment with a subsequent response of 16.7 percent. Partial response implied reduction of lung metastatic foci in 3 patients and primary lesion in one patient. There was observed untoward fever-up in all patients with HLBI injections which was relieved with acquired tachyphylaxis owing to repeated injections. Otherwise minimal adverse effects were temporary elevation of liver transaminase in 4 and leucopenia in 2 patients during the HLBI treatment both of which eventually returned to the normal level without discontinuation of HLBI therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Sequences of the VH and VL regions of murine monoclonal antibodies against 3-fucosyllactosamine.

Many mAb that bind the carbohydrate antigenic determinant 3-fucosyl-lactosamine (3-FL), Gal beta 1-4[Fuc alpha-3]GlcNAc-R have been raised in BALB/c mice, and we are studying the structure and regulation of these antibodies. In this report, we present the first information about their amino acid sequences and the Ig gene segments used to encode them. V regions of the H and L chains of three anti-3-FL antibodies, PMN6, PMN29, and PM81, were sequenced by a combination of mRNA and amino acid sequencing. The L chain sequences of PMN6 and PM81 antibodies indicate that their VK and JK regions are encoded by VK24B and JK1 germ-line genes, respectively. The nucleotide and amino acid sequences of the H chains suggest that the three anti-3-FL antibodies are encoded by the VH441 gene segment of the X24 VH family, and this conclusion was supported by Southern filter hybridization with VH441 and JH3-JH4 probes. PMN29 has at least 11 amino acid substitutions, which is an unusually large amount of somatic mutation for an IgM antibody. Previous analyses of BALB/c genomic libraries with VHX24 and VH441 probes make it unlikely that this VH family contains additional germ-line genes, but this possibility cannot be excluded. All three antibodies use the DQ52 and JH4 gene segments. The single VH and VL gene segments used to encode the anti-3-FL antibodies is in contrast to the multiple VH and VL segments used by antibodies against other carbohydrate Ag such as alpha 1-6 dextran and group A streptococcal carbohydrate. VH441 also encodes the VH regions of antibodies against galactan and levan (beta 2-6 fructosan). The similarities among VH segments of antibodies against 3-FL, levan, and galactan, and the striking differences in their CDR3 sequences, suggest that CDR3 plays an important role in the formation of the Ag binding site. The use of a single VH segment from the smallest VH gene family by antibodies against at least three different carbohydrate determinants is noteworthy. It raises the possibility that the amino acid sequence encoded by VH441 has some general structural features that make it particularly well adapted for binding to carbohydrate sequences.

Amino Acid Sequence↗
PubMed1988

Production and characterization of monoclonal antibodies that bind to phosphatidylinositol 4,5-bisphosphate.

We established a series of monoclonal antibodies (MAbs) that bound to phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] which is confidently believed to play an important role in cellular signal transduction. We used complement dependent liposome lysis assay for screening MAbs and antibodies that bind to PI(4,5)P2 but not to phosphatidylinositol 4-monophosphate [PI(4)P] were selected. The reactivity of the MAbs was analyzed by complement dependent liposome lysis assay, enzyme-linked immunosorbent assay (ELISA) and inhibition of liposome lysis by soluble haptens. The MAbs exhibited three distinct reactivity profiles measured by three different assay systems and the results obtained from three typical MAbs designated AM-2, AM-7 and AM-212 are described. On liposome lysis assay, all three MAbs were highly specific with PI(4,5)P2 and no cross-reaction with other acidic phospholipids such as PI(4)P, phosphatidylinositol (PI), phosphatidic acid (PA), phosphatidylserine (PS), phosphatidylethanolamine (PE) and cardiolipin (CL) was observed. All three MAbs were able to react with as low as 0.1 mol% of PI(4,5)P2 embedded in the liposomal membrane. On ELISA, AM-2 and AM-212 bound only to PI(4,5)P2 and did not cross-react with other acidic phospholipids including PI(4)P. In contrast, AM-7 showed considerable binding to other phospholipids such as PI(4)P, PA and PE on ELISA. The reactivities of the MAbs with water soluble haptens such as inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] were examined by inhibition of liposome lysis. Among three clones examined, only AM-212 showed considerable reactivity with Ins(1,4,5)P3 while also showing weak cross-reactivity with fructose 1,6-diphosphate and inositol 1,4-bisphosphate. No cross-reaction with other structural analogs such as inositol 1-monophosphate and inositol 2-monophosphate was observed.

Animals↗
PubMed1988

Cytotoxic and mutagenic effects of emodin on cultured mouse carcinoma FM3A cells.

Employing a suspension culture of a mouse mammary carcinoma cell line, FM3A cells, the cytotoxicity and induced mutagenicity of emodin (EM) were examined and compared with those of 2-hydroxy-emodin (2-OH-EM), which was identified as an active form of EM in the Ames/microsomes assay. EM was cytotoxic to FM3A cells in concentrations of 1-10 micrograms/ml, and induced 6-thioguanine-resistant (6TGr) mutation. 2-OH-EM was a little more toxic than EM, but induced little mutation.

Animals↗
PubMed1988

Specific binding of mitochondrial protein precursors to liposomes containing cardiolipin.

In vitro synthesized precursors of several mitochondrial proteins, including P-450(SCC), adrenodoxin, and malate dehydrogenase, bound to liposomes prepared from mitochondrial phospholipids, but not to those from microsomal phospholipids. When liposomes were prepared from various pure phospholipids, adrenodoxin precursor was bound only to the liposomes that contained cardiolipin. The liposomes containing other phospholipids did not show the binding affinity for the precursor. The binding was observed only with the precursor peptides of adrenodoxin and malate dehydrogenase, and their mature forms were not bound to the liposomes. The binding of the precursors was dependent on the concentration of cardiolipin in the liposomes. Liposomes containing various cardiolipin derivatives with modified polar head groups showed very different binding affinity for adrenodoxin precursor, suggesting the importance of the structure of the polar head of the cardiolipin molecule. Two or three positively charged amino acid residues in the extension peptide of P-450(SCC) precursor were replaced by neutral amino acid residues by site-directed mutagenesis. The mutated P-450(SCC) precursors did not bind to the liposomes containing cardiolipin. The results indicated that mitochondrial protein precursors have specific affinity for cardiolipin, and the affinity was due to the interaction between the extension peptides of the precursors and the polar head of the cardiolipin molecule.

Adrenodoxin↗
PubMed1988

Monoclonal antibodies against rat platelet phospholipase A2.

Monoclonal antibodies which bind specifically to rat platelet phospholipase A2 have been raised. None of them bound to exocrine phospholipase A2 derived from pancreas or snake venom. All antibodies recognized the conformational structure of rat platelet phospholipase A2 supported by intramolecular disulfide bonds, since the reactivity between the antibodies and the enzyme was lost in the presence of 2-mercaptoethanol. One of them, designed MB5.2, inhibited the activity of the platelet phospholipase A2 in a dose-dependent manner. A kinetic study revealed that antibody MB5.2 apparently competed with the substrate for the active site of the enzyme. The other antibodies, designed MD7.1 and ME6.1, inhibited the binding of the enzyme to heparin. The distribution of phospholipases A2 bearing a similar determinant to rat platelet phospholipase A2 was investigated by immunoprecipitation of the enzyme activity or by an immunoblot technique. Among rat tissues, cross-reactivity was observed with phospholipases A2 from spleen, lung, and bone marrow. Extracellular phospholipase A2 detected in the peritoneal cavity of casein-treated rat was also recognized by these antibodies. Furthermore, antibody MD7.1 cross-reacted with rabbit and guinea pig platelet phospholipases A2.

Animals↗
PubMed1988

Homogeneous liposome lysis assay for determination of anti-streptolysin O antibody titer in serum.

We developed a liposome lysis assay for determining anti-streptolysin O antibodies (ASO) in human sera involving the use of carboxyfluorescein-entrapped multilamellar liposomes. This assay system was based on the inhibition of streptolysin O-induced liposome lysis by ASO. Briefly, after incubation of a given amount of streptolysin O with ASO for 30 min at 37 degrees C, carboxyfluorescein-entrapped liposomes composed of egg yolk phosphatidylcholine and cholesterol in a molar ratio of 1:1 were added to the mixture to determine the residual streptolysin O activity. Liposome lysis, detected as carboxyfluorescein release from the liposomes, was inversely proportional to the ASO titer. The results of within-run and between-run precision studies indicated that the liposome lysis assay is accurate and gives reproducible data. Bilirubin, hemoglobin, and triglycerides did not interfere with the liposome lysis assay. The ASO titers of 100 patient sera, evaluated by our new method and the Rantz-Randall method, showed good correlation.

Antistreptolysin↗
PubMed1988

Secretion of a novel cell-adhesive protein distinct from fibronectin by mouse L.P3 cells growing in protein- and lipid-free synthetic medium.

Several cell lines growing in protein- and lipid-free synthetic medium secreted cell-adhesive protein(s) into the medium. The conditioned medium (CM) of one of these cell lines, mouse L.P3, showed the highest cell attachment-promoting activity (CPA) among them. Cell-adhesive protein(s) in the CM of L.P3 cells (L.P3-CM) were separated into two types by sequential affinity column chromatography employing gelatin-Sepharose 4B and heparin-Sepharose 4B. One was a gelatin- and heparin-binding cell-adhesive protein (GCP), and was identified as a cellular form of mouse fibronectin. The other was a gelatin-non-binding and heparin-binding cell-adhesive protein (GNCP). The CPA of GNCP preparation was effective for the cell-attachment and spreading of both epithelial and fibroblastic cells. The CPA of GNCP preparation was not blocked by the antiserum and scarcely inhibited in the presence of the synthetic cell attachment-promoting peptide Gly-Arg-Gly-Asp-Ser-Pro, a competitive inhibitor of fibronectin. This suggests that the structure of the cell-attachment site of GNCP is different from that of fibronectin. The GNCP preparation showed little cross-reactivity with anti-mouse laminin antiserum in enzyme-linked immunosorbent assay (ELISA). These results demonstrate the possibility that GNCP in L.P3-CM is a novel cell-adhesive protein distinct from fibronectin or laminin. The secretion of the two types of cell-adhesive proteins by L.P3 cells is discussed.

Animals↗
PubMed1988

[Acute reversible cataract due to nitrocompounds in Japanese quail (Coturnix coturnix japonica)].

The present study was designed to examine the usefulness of the Japanese quail as an experimental model of cataractogenic activity. Chemicals, 2, 6-dibromo-4-nitro-phenol (2, 6-D), 2, 4-dinitroanisole (2, 4-DA), and 2, 4-dinitrophenol (2, 4-D; for the positive control), were administered singly through an oral route to 2-week old male Japanese quails to investigate the reversibility of cataracts. A single administration of 2, 4-D (36 and 43 mg/kg) produced reversible cataract in 14 of 16 animals (87.5%). This cataract was seen 1 or 2 hours after treatment and continued for 1 to 12 hours. Treatment with 2, 6-D (20 and 25 mg/kg) and 2, 4-DA (120 and 150 mg/kg) caused cataracts in 7 of 11 (63.6%) and 8 of 8 surviving animals (100%), respectively. Cataracts produced by 2, 6-D and 2, 4-DA, which were observed from 1 and 2 to 4 hours after the treatment, continued for 6 to 15 and 1 to 13 hours, respectively. Mortalities in the 25 mg/kg group of 2, 6-D, 120 mg/kg and 150 mg/kg group of 2, 4-DA were found in 2 of 5 animals, 1 of 5 animals and 5 of 9 animals, respectively. These results indicate that the Japanese quail is useful as an animal model to evaluate toxicity to the eye and cataractogenesis.

Acute Disease↗
PubMed1988

Heterogeneity of primary malignant melanomas in oral mucosa: an analysis of 43 cases in Japan.

In contrast to Caucasians, Japanese people have a relatively high incidence of malignant melanoma in the oral cavity and volar-subungual skin. The classification of oral melanoma has not been established. We report 7 new cases of oral melanoma, with a review of 36 cases, published in Japan, between 1970 and 1984. Most of the cases reviewed have radial growth phases, and their gross and microscopic features seem to correspond to those of acral lentiginous melanoma of the skin. However, 1 of our cases and 3 previously reported cases of oral nodular melanoma suggest the presence of melanoma heterogeneity in the oral cavity.

Adult↗
PubMed1988

Transforming growth factors in urine from patients with primary brain tumors.

Urine specimens obtained from 19 patients with primary brain tumors were examined for the activity of transforming growth factors (TGF's). Urine was assayed for TGF's by soft agar colony formation and iodine-125 (125I)-epidermal growth factor (EGF)-binding competition. Two nontransformed cell lines, clonal NRK49F and BALB/3T3 A31-1-1 cells, were used as indicator cells for the soft agar colony assay, while EGF receptor-rich A431 cells were used for 125I-EGF-binding competition assay. Urine samples were dialyzed against acetic acid, then lyophilized, prepared with gel-permeation chromatography, and assayed. All 19 patients and a control group of healthy individuals showed high levels of alpha-type TGF's with low molecular weight (4 to 8 kD) in all urine samples. In addition, alpha-type TGF's of high molecular weight (20 to 50 kD) were detected at high levels in urine from all 10 patients with high-grade astrocytoma; at intermediate levels in urine from one of two patients with low-grade astrocytoma and from two of four patients with meningioma; and at low levels in urine from one of two patients with low-grade astrocytoma, from two of four patients with meningioma, from one patient with oligodendroglioma, from two patients with neurinoma, and from all healthy control individuals. The high level of alpha-type TGF's with high molecular weight detected in urine from patients with high-grade astrocytoma could be useful as a tumor marker.

Adult↗
PubMed1988

Local antibody production and immune complex formation in rats experimentally infected with Angiostrongylus cantonensis.

The systemic humoral immune responses and tissue localization of worm-antigen, antibodies (IgG), and complement (C3) were examined in rats experimentally infected with Angiostrongylus cantonensis. While the worms remained in the subarachnoid space, it was infiltrated with plasma cells and lymphoid cells containing IgM and IgG. When the infiltration of these cells became more pronounced, the serum antibody titer began to increase. At the same time, deposits of IgM, IgG, and C3 were found in the glomeruli of the kidney. A number of eggs were observed in the lungs, enclosed in granulomatous tissues. Infiltrates of plasma cells including IgM and IgG, and deposits of IgM, IgG, and C3 were detected around the eggs and in the granulomatous tissues. A marked increase in serum antibody was observed. A. cantonensis larvae induce local antibody (IgM and IgG) production in the central nervous system prior to an increase of serum antibody titer. Measurement of cerebrospinal fluid antibody titer at an early stage of infection may confirm infection. The larvae showed no evidence of damage in spite of marked local antibody production in the central nervous system. The eggs in the lungs stimulated both local and systemic antibody production, and immune complexes were formed in the lung and the circulatory system. Immune complexes may participate in the formation of granuloma.

Angiostrongylus↗