Search PubMed⌕ Search

Biomedical subjects

M Abe

Publications and source records attributed to M Abe.

At least 757 records · Page 42Linked to original sources

Effect of monoclonal antibody CD4 on glomerulonephritis of ddY mice, a spontaneous animal model of IgA nephropathy.

Immunopathological studies were performed to determine whether the glomerular injuries in ddY mice, a model for IgA nephropathy (Berger's disease), are influenced by treatment with a rat monoclonal antibody (mAb) to murine CD4 molecules. The ddY mice were initially treated with intravenous injections, followed by weekly intraperitoneal injections of mAb CD4. Flow cytometry analysis showed that there was a marked decrease in the number of CD4+ T cells. In immunofluorescence, the mean intensity of IgA deposits in the renal glomerular mesangial areas and capillary walls of the treated ddY mice was significantly lower than that in saline-treated control mice of comparable ages. Glomerular mesangial expansion in the treated mice was milder than that found in the saline control mice. However, no significant differences in the level of serum IgA, urinary protein, and average number of intraglomerular cells between the treated and control ddY mice were observed. Thus, it appears that although CD4+ T cells control the amount of IgA deposits in glomeruli, other factors may be involved in the evolution of IgA nephropathy in ddY mice.

Animals↗

Role of the latent TGF-beta binding protein in the activation of latent TGF-beta by co-cultures of endothelial and smooth muscle cells.

Transforming growth factor beta (TGF-beta) is released from cells in a latent form consisting of the mature growth factor associated with an aminoterminal propeptide and latent TGF-beta binding protein (LTBP). The endogenous activation of latent TGF-beta has been described in co-cultures of endothelial and smooth muscle cells. However, the mechanism of this activation remains unknown. Antibodies to native platelet LTBP and to a peptide fragment of LTBP inhibit in a dose-dependent manner the activation of latent TGF-beta normally observed when endothelial cells are cocultured with smooth muscle cells. Inhibition of latent TGF-beta activation was also observed when cells were co-cultured in the presence of an excess of free LTBP. These data represent the first demonstration of a function for the LTBP in the extracellular regulation of TGF-beta activity and indicate that LTBP participates in the activation of latent TGF-beta, perhaps by concentrating the latent growth factor on the cell surface where activation occurs.

Animals↗

The mechanism for the activation of latent TGF-beta during co-culture of endothelial cells and smooth muscle cells: cell-type specific targeting of latent TGF-beta to smooth muscle cells.

Transforming growth factor-beta (TGF-beta) is secreted in a latent form and activated during co-culture of endothelial cells and smooth muscle cells. Plasmin located on the surface of endothelial cells is required for the activation of latent TGF-beta (LTGF-beta) during co-culture, and the targeting of LTGF-beta to the cellular surface is requisite for its activation. In the present study, the cellular targeting of LTGF-beta was examined. We detected the specific binding of 125I-large LTGF-beta 1 isolated from human platelets to smooth muscle cells but not to endothelial cells. A mAb against the latency-associated peptide (LAP) of large LTGF-beta 1 complex, which blocked the binding of 125I-large LTGF-beta 1 to smooth muscle cells, inhibited the activation of LTGF-beta during co-culture. The binding of 125I-large LTGF-beta 1 could not be competed either by mannose-6-phosphate (300 microM) or by the synthetic peptide Arg-Gly-Asp-Ser (300 micrograms/ml). These results indicate that the targeting of LTGF-beta to smooth muscle cells is required for the activation of LTGF-beta during co-culture of endothelial cells and smooth muscle cells. The targeting of LTGF-beta to smooth muscle cells is mediated by LAP, and the domain of LAP responsible for the targeting to smooth muscle cells may not be related to mannose-6-phosphate or an Arg-Gly-Asp sequence, both of which have been previously proposed as candidates for the cellular binding domains within LAP.

Amino Acid Sequence↗

Novel immunization protocol and ELISA screening methods used to obtain and characterize monoclonal antibodies specific for human light chain variable-region subgroups.

We have developed a novel immunization protocol for the production of a panel of high-affinity murine monoclonal antibodies (MoAbs) that are specific for each of the major human kappa and lambda light chain variable-region (VL) subgroups. Mice were injected with heat-precipitated human Bence Jones proteins or VL-related fragments emulsified in monophosphoryl lipid A (MPL) and trehalose dimycolate (TDM) at two- to four-week intervals over a seven-month period. A unique direct capturing enzyme-linked immunosorbent assay (ELISA) employing biotinylated monoclonal light chains was designed to select optimally immunized animals for hybridoma preparation and to screen culture supernatants for high-affinity anti-VL MoAbs. These methods have led to the generation of MoAbs that by ELISA react specifically with each of the four V kappa subgroups--V kappa I, V kappa II, V kappa III, and V kappa IV or five V lambda subgroups--V lambda I, V lambda II/V, V lambda III, V lambda IV, and V lambda VI. These reagents have been used successfully to establish, on the basis of VL subgroup, the monoclonal nature of serum or urinary immunoglobulins as well as those found in the cytoplasm or on the cell surface of monoclonal plasma cell or B-lymphocyte populations, respectively. The availability of anti-VL subgroup-specific MoAbs will facilitate the immunodiagnosis and study of patients with multiple myeloma, AL amyloidosis, and related B-cell proliferative disorders.

Amyloidosis↗

Production and immunodiagnostic applications of antihuman light chain monoclonal antibodies.

Hybridomas producing antihuman light chain monoclonal antibodies (MoAbs) were derived from fusion of SP2/O mouse myeloma cells with splenic lymphocytes from mice repeatedly immunized with purified kappa- and lambda-type Bence Jones proteins representative of the major V kappa (V kappa I, V kappa II, V kappa III, V kappa IV) and V lambda (V lambda I, V lambda II/V, V lambda III, V lambda IV, V lambda VI) subgroups or gene families. Monoclonal antibodies were obtained that had specificity for constant-region (CL) determinants common to all kappa or lambda light chains (C kappa and C lambda, respectively) as well as for variable-region (VL) epitopes unique to each of the V kappa or V lambda subgroups. The capability of these reagents to recognize CL and VL determinants on monoclonal immunoglobulin (Ig) molecules was demonstrated in fluid-phase antigen-capturing enzyme-linked immunosorbent assay (ELISA), solid-phase ELISA, and immunoblotting. In addition, these antilight chain MoAbs were used to establish immunocytochemically the kappa or lambda type and VL-subgroup nature of light chains expressed by the cytoplasmic Ig of monoclonal plasma cell and surface Ig of B-lymphocyte populations, respectively. These antibodies facilitated the immunohistochemical detection and characterization of light-chain-associated amyloid (AL amyloid) and other types of light-chain-related tissue deposits. Furthermore, the anti-CL-specific MoAbs were used to measure serum and urinary Ig kappa and Ig lambda concentrations. Quantification of Bence Jones protein excretion, even in the presence of other urinary proteins, was possible using the highly sensitive anti-C kappa and anti-C lambda MoAbs reactive only with free light chains. The ability to identify and characterize, through the use of these antihuman light chain MoAbs, light-chain-related epitopes at the protein, cellular, and tissue level has clinical importance in the diagnosis and treatment of patients with monoclonal plasma cell and related B-cell immunoproliferative diseases.

Amyloidosis↗

Alteration of radiosensitivity of quiescent cell populations in solid tumors irradiated with X-rays twice at various intervals.

5-Bromo-2'-deoxyuridine (BUdR) was injected into SCC VII or EMT6/KU tumor-bearing mice intraperitoneally to label all the proliferating tumor cells. First, the mice were irradiated with X-rays at a dose of 10 Gy, followed by a dose of 0-20 Gy at 0, 12, 24 or 48 h later. During the interval, no BUdR was injected. Immediately after the second irradiation, the tumors were excised and trypsinized. The micronucleus (MN) frequency in cells without BUdR labeling was determined by means of incubation with cytochalasin-B (a cytokinesis-blocker) and immunofluorescence staining for BUdR. When the tumors were not pretreated with BUdR before the first irradiation, the MN frequency in all tumor cells was determined. To determine the labeling indices of SCC VII and EMT6/KU tumors at the time of the second irradiation, each group also included mice that were continuously administered BUdR until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the first irradiation. The MN frequency of all tumor cell populations obtained immediately after the second irradiation decreased in proportion to the increase in interval time. However, in both tumor systems, the MN frequency of unlabeled cell populations, which could be regarded as quiescent cells in the tumors at the time of the first irradiation, was raised with increase in the interval time. In addition, the labeling index at the second irradiation was higher than that at the first irradiation. These findings support the occurrence of recruitment from quiescent to proliferating state during fractionated irradiation.

Animals↗

Frontal lobe tumor associated with late-onset seizure and psychosis: a case report.

This is a report of a 55-year-old woman with a 6-year history of uncontrollable complex partial seizure and severe delusion. A computed tomography (CT) brain scan showed a nonenhanced low density area with an ill-defined mass located at the right frontal lobe. Magnetic resonance imaging (MRI) demonstrated an area of hyperintensity on T2-weighted images. After a tumorectomy, the patient gradually recovered from the seizures and delusion. A histological diagnosis showed a mixed oligoastrocytoma or dysembryoplastic neuroepithelial tumor (DNT). The clinical and pathological features of the tumor as well as its relation to psychosis were discussed.

Biopsy↗

Contact sensitivity and cross-reactivity of budesonide.

5 cases of allergic contact dermatitis due to budesonide are described. We studied the antigen determinant structures in these cases by applying patch tests with several substances related to budesonide. 2 cases showed cross-reactions to both amcinonide and prednisolone acetate. The antigen determinant structure is also discussed.

Adult↗

Nosocomial outbreak of Pseudomonas cepacia respiratory infection in immunocompromised patients associated with contaminated nebulizer devices.

From May 1990 to August 1991, 36 patients admitted to the Department of Internal Medicine in a medical school hospital with hematological malignancies or solid tumors, developed respiratory tract colonization with Pseudomonas cepacia. Sixteen (44.4%) of these patients developed pneumonia, and four (11.1%) died of respiratory failure due to P. cepacia pneumonia. Extensive survey of the hospital environment as well as equipment showed that nebulizer devices used by the patients for inhalation were contaminated with P. cepacia. Phenotypic characteristics, (production of hemolysin and extracellular enzymes [lipase, lecithinase and protease]), the Analytical Profile Index 20 NE pattern, and the pattern of DNA fingerprinting by pulse-field gel electrophoresis in clinically isolated strains and strains derived from nebulizer devices were compared. The strains of P. cepacia obtained from patients in the Department of Internal Medicine were indistinguishable from each other and also from those isolated from nebulizer devices, but were different from those isolated from patients in other departments at the same time. These results demonstrated that the outbreak of P. cepacia respiratory colonization in immunocompromised patients was a nosocomial acquisition, and probably occurred by transmission through contaminated nebulizer devices.

Adolescent↗

[Epidemiological study on nosocomial infection of Pseudomonas cepacia by plasmid analyses].

In order to clarify the usefulness of plasmid analyses in epidemiological study, plasmid DNA profiles, restriction fragment patterns of chromosomal DNA analysed by pulsed-field gel electrophoresis (PFGE), and patterns of extracellular products were performed in twenty-four nosocomial strains of Pseudomonas cepacia isolated at the Kagawa Medical School Hospital. Fifteen strains were obtained from 15 patients admitted in A ward, three strains were obtained from nebulizer devices used in A ward, 5 strains were obtained from 5 patients admitted in B ward, and 1 strain was obtained from a patient admitted in C ward. Three different patterns which differed from ward to ward were clearly distinguished by PFGE patterns and patterns of extracellular products. On the other hand, plasmid DNA profiles were different in some strains obtained from B ward. These results suggested that plasmid analyses combined with other typing methods are useful in more precise epidemiological analysis on nosocomial infection of P. cepacia.

Burkholderia cepacia↗

Effects of the molecular weight of hyaluronic acid and its action mechanisms on experimental joint pain in rats.

OBJECTIVES: It has been shown previously that hyaluronic acid (HA) has an analgesic action on bradykinin induced pain in the knee joints of rats. This study further clarifies the effects of the molecular weight of HA and its mechanism of action in the same model using HA of molecular weight 800 to 2.3 x 10(6) daltons and a bradykinin antagonist. METHODS: Bradykinin and the test HA preparations were given to rats by intra-articular injection, and the severity of pain was evaluated by a change in the walking behaviour. RESULTS: HA with a molecular weight greater than 40 kilodaltons produces analgesic effects with a simultaneous or earlier injection. The ID50 values of HA with molecular weight 40, 310, 860, and 2300 kilodaltons were greater than 2.5, 0.6, 0.07, and 0.06 mg/joint respectively. The duration of the analgesic effect of 860 and 2300 kilodalton HA was 72 hours at 10 mg/ml, whereas that of 310 kilodalton HA was short, being undetectable after 24 hours. The analgesic action of HA of 860 kilodaltons was not changed by pretreatment with four saccharide HA and inhibited by pretreatment with HA larger than six to eight saccharides, capable of binding to HA receptors. Further, HA did not interfere with the analgesic action of the bradykinin antagonist, indicating that HA does not directly bind with bradykinin receptors. CONCLUSIONS: HA with a molecular weight of greater than 40 kilodaltons produced an analgesic effect, and HA of 860 and 2300 kilodaltons produced high and long-lasting analgesia. These effects of HA appear to be caused by the interaction between HA and HA receptors.

Animals↗

Coexistence of morphea and systemic sclerosis.

While the association of morphea and systemic sclerosis (SSc) is considered to be a rare condition, we observed well-demarcated sclerotic skin changes indistinguishable from morphea in 9 of 135 SSc patients who visited our clinic during the last decade. We consider this rate of incidence (6.7%) to be high enough to consider morphea to be one of the skin involvements of SSc. There was a significantly (p < 0.01) higher incidence of morphea in males (3 of 5) than in females (6 of 130). Only 3 of 111 SSc patients positive for antinuclear antibody (ANA) also showed morphea, whereas 6 of 9 patients negative for ANA showed morphea (p < 0.01). Although the mechanism underlying the development of morphea in SSc patients remains unknown, our observations suggest a heterogeneous pathogenesis related to SSc gender and ANA type.

Adult↗

In vivo effect of lipopolysaccharide on alveolar and peritoneal macrophages of rats: superoxide anion generation and 5-lipoxygenase metabolism of arachidonic acid.

Influences of the intravenous administration of Escherichia coli lipopolysaccharide, 3 mg/kg, on the production of superoxide anion (O2-) and 5-lipoxygenase metabolites of arachidonic acid (AA) were evaluated in alveolar macrophages (AM) and peritoneal macrophages (PM) on days 1 and 3 after injection. The dose selected was that found to induce a significant leakage of [125I]bovine serum albumin in the pulmonary vasculature. AM obtained 1 day after LPS injection generated smaller amounts of O2- on stimulation with C5a but generated similar amounts with wheat germ lectin (WGA) or AA compared with control AM. This result suggested a prior complement activation. On day 3, on the contrary, their production of O2- significantly exceeded that by control AM with either of the three stimuli. PM collected on day 1 after LPS injection generated a significantly greater amount of O2- on stimulation with either WGA or AA than did control PM. The amount of O2-, however, decreased from day 1 to day 3. AM collected 1 day after the injection of LPS generated significantly more leukotriene B4 (LTB4) and 5-HETE on stimulation with A23187 alone and in combination with AA than did the cells from untreated rats. Such activities returned to the control levels in the AM collected on day 3. In contrast, the PM collected on day 1 produced amounts of LTB4 and 5-HETE similar to those of the control PM, but the cells on day 3 produced significantly more LTB4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

High concentration of carboxypeptidase M in lungs: presence of the enzyme in alveolar type I cells.

The presence of high concentrations of membrane-bound carboxypeptidase M in human, baboon, dog, and rat lung was established by employing a variety of techniques. The activity of the enzyme in the membrane-enriched fractions of human, baboon, dog, and rat lung, measured with fluorescent dansyl substrate (DNS-Ala-Arg), was 198, 261, 484, and 153 nmol/h/mg protein, respectively. This activity in the lung was much higher than that found in the heart, liver, or kidney. The enzyme, optimally active around neutral pH, was completely inhibited by 10 microM 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid and was activated by 1 mM CoCl2 to 170%. Antibody to human carboxypeptidase M immunoprecipitated the solubilized carboxypeptidase from human (98%), baboon (81%), and dog (88%) lung membrane fractions. Carboxypeptidase M is attached to lung membranes by a phosphatidylinositol glycan anchor; thus, it is released with bacterial phospholipase C. Membrane fractions from cultured human pulmonary arterial endothelial cells also contained high carboxypeptidase M activity (254 nmol/h/mg protein). A Northern blot of poly(A)+ RNA from various human tissues showed the presence of a high level of carboxypeptidase M mRNA in human lung and placenta. Finally, immunohistochemistry, employing purified antibody to the enzyme, revealed in fluorescent light microscopy that carboxypeptidase M is present in alveolar type I pneumocytes and in macrophages in apparently lower concentration. In contrast, type II alveolar epithelial cells gave negative results. Because carboxypeptidase M cleaves a variety of active peptides (e.g., bradykinin, anaphylatoxins), it may protect the alveolar surface from the effects of these peptides. In addition, carboxypeptidase M could be a marker enzyme for type I cells.

3-Mercaptopropionic Acid↗

Measurement of cardiac chamber volumes by cine magnetic resonance imaging.

Cardiac chamber volumes (both atria and ventricles) in 19 healthy volunteers were measured noninvasively by cine magnetic resonance imaging (MRI). First, cardiac localization was determined from the coronal image by 0.5-T superconducting magnetic imager. Then, transaxial ECG gated multislice spin echo images were obtained from the bottom to the top of the heart. In the last step, cine MRI was performed at each level of all these transaxial spin echo MR images involving the heart. Each cardiac chamber volume at the same phase was calculated by adding chamber areas in each anatomic section multiplied by slice thickness. Left ventricular (LV) end-diastolic volume (EDV) 132.0 +/- 26.9 mL) and LV end-systolic volume (ESV) (47.8 +/- 13.9 mL) were smaller than right ventricular (RV) EDV (141.1 +/- 24.8 mL) and RVESV (57.0 +/- 12.6 mL), respectively (p < 0.01). LV stroke volume (84.3 +/- 17.9 mL) was equivalent to RV stroke volume (84.2 +/- 17.6 mL) (r = 0.91, p < 0.01). Left atrial (LA) and right atrial (RA) maximal volumes were 75.8 +/- 15.4 mL and 84.4 +/- 18.7 mL, respectively. LA minimal volume (37.5 +/- 10.7 mL) was smaller than RA minimal volume (47.8 +/- 12.2 mL). These values measured by cine MRI are satisfactory and cine MRI will be a useful method of determining cardiac chamber volumes, especially atrial volumes.

Adult↗