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Biomedical subjects

T Doi

Publications and source records attributed to T Doi.

At least 37 records · Page 2Linked to original sources
PubMed1992

[Intracellular killing mechanisms of alveolar macrophages against Mycobacterium avium complex].

To clarify the intracellular killing mechanisms of alveolar macrophages against Mycobacterium avium complex, effects of cytokines on O2- and NO2- production from normal and BCG-induced alveolar macrophages were studied. Intracellular growth of M. avium complex was inhibited in the alveolar macrophages stimulated by TNF, but not IFN. Enhancement of O2- production by normal alveolar macrophages stimulated by cytokines, was associated with the inhibition of intracellular growth of M. avium complex. However, when NO2- production by the alveolar macrophages was enhanced by the stimulating of IFN or IFN+TNF, in the presence L-arginine in the culture medium, their defense activity against M. avium complex decreased.

Animals↗
PubMed1992

[Traumatic dislocation of the testis].

Dislocation of the testis is a rare injury, with only 73 cases having been reported in Japan. We herein add 6 cases. Lately, accidents involving teenage patients, primarily involving motorcycles, have been increasing. Closed reduction is recommended, but it was successful only 5 of 73 cases. The results of testicular biopsies suggest that early surgical management is required when closed reduction is unsuccessful.

Accidents, Traffic↗
PubMed1992

[Inhibition of Cls activity by methylprednisolone].

From a clinical study it was found that serum ClINH activity increased 6 hours after methylprednisolone (MP) pulse therapy in all the patients we studied with connective tissue diseases. Furthermore plasma ClINH-Cls complex decreased after pulse therapy. These phenomena lead us to investigate the effect of MP on Cls. 1) When a constant amount of Cls (8 micrograms/ml) was incubated with several concentrations of MP (2-50 mg/ml), the Cls activity of consuming C4 hemolysis was inhibited by MP in a dose-dependent manner. 2) MP inhibited consumption of C2 as well as C4 by Cls in a dose-dependent manner, even when MP had been removed by dialysis following incubation with Cls. These experimental data suggested that the trace amounts of Cls generated by immune complexes could be inhibited by long circulation of MP even at low concentrations in vivo, and resulted in a decrease of ClINH consumption and ClINH-Cls complex formation. These results indicated that the inhibition of Cls activity is one of the most important mechanisms in the process of the anti-inflammatory effect of MP in vivo.

Complement C1 Inactivator Proteins↗
PubMed1992

[Application of transgenic model in renal research].

In the present report, we have used transgenic models to analyze the role of growth factors in the development of glomerulosclerosis. All peptides inducing a growth response do not lead to glomerulosclerosis, however, several transgenic models including growth hormone, transforming growth factor-a or SV 40T antigen developed progressive glomerulosclerosis, which was associated with glomerular hypertrophy. Evidence obtained from these transgenic models suggests that glomerulosclerosis may be related to a dysregulation of glomerular cell growth and a synthesis of extracellular matrix components by resident glomerular cells.

Animals↗
PubMed1992

[Complement system in status asthmatics--analysis of anti-complementary effects induced by methylprendisolone].

Complement system was investigated in 7 patients with status asthmatics treated with large doses of methylprednisolone (MPS). Complement hemolytic activities, complement protein profile, complement fragments and circulating immune complexes were measured before, 3 and 8 hours after and 14 days after MPS administration. MPS normalized C4 and C1INH activities 6 hours after administration. MPS also decreased ACH50 6 hours after administration and D activity 3 and 6 hours after, but these activities recovered to their previous normal range within 14 days. P and H were decreased at each measurement time, and C1s was transiently decreased 6 hours after MPS administration. Complement fragment iC3b was increased at each measurement time, but fragment Bb tended to be decreased 14 days after MPS administration. The increment of anaphylatoxin C3a recovered to normal 14 days after MPS administration. In vitro experiments, MPS inhibited D and C1s activation directly, and decreased the decay of B and C4. Inhibition of C1s might also increase C1INH activity clinically. These results clarified that the alternative complement pathway was activated, and suggested that the C1 bypass pathway might be also activated in status asthmatics. It was further considered that these anti-complementary effects induced by MPS, brought about an improvement in asthmatic symptoms. Studies to identify the complement activators continued, and circulating immune complexes may possibly be one of those agents activating complement cascade.

Adult↗
PubMed1992

Crossed cerebellar hypoperfusion in unilateral major cerebral artery occlusive disorders.

We evaluated regional blood flow and oxygen metabolism in the cerebral and cerebellar cortices of 15 patients with unilateral major cerebral artery occlusive disorders with PET. These patients showed a cortical blood flow asymmetry in middle cerebral artery distribution. Only subcortical abnormalities were detected on computed tomography. Nine patients showed crossed cerebellar hypoperfusion, a reduction in contralateral cerebellar blood flow, while six did not. No difference in the degree of cerebral blood flow asymmetry existed between the two patient groups. However, oxygen metabolism asymmetry was more pronounced and was more closely matched to blood flow asymmetry in patients with crossed cerebellar hypoperfusion. These findings suggest that a major cause of cerebral cortical blood flow reduction is reduced metabolic demand in patients with crossed cerebellar hypoperfusion. Crossed cerebellar hypoperfusion may have clinical significance as a reflection of the cerebral metabolic state on blood flow images.

Adult↗
PubMed1992

Lymphangioma of the upper extremity.

Lymphangioma of the upper extremity is rare; its treatment is unstandardized. We reviewed five female and one male patient with cavernous lymphangioma of the hand and forearm. Each of them underwent at least one surgical procedure. Five patients had satisfactory results with cosmesis and hand function. Satisfactory results are expected in those treated initially in early childhood, as most lymphangiomas tend to increase gradually in size and infiltrate previously uninvolved normal tissues.

Arm↗
PubMed1991

Sub-piconewton force fluctuations of actomyosin in vitro.

A new system has been developed for measuring the forces produced by a small number (less than 5-150) of myosin molecules interacting with a single actin filament in vitro. The technique can resolve forces of less than a piconewton and has a time resolution in the submillisecond range. It can thus detect fluctuations of force caused by individual molecular interactions. From analysis of these force fluctuations, the coupling between the enzymatic ATPase activity of actomyosin and the resulting mechanical impulses can be elucidated.

Actins↗
PubMed1991

Glomerulosclerosis in mice transgenic for growth hormone. Increased mesangial extracellular matrix is correlated with kidney mRNA levels.

Mice transgenic for growth hormone (GH) develop progressive glomerulosclerosis. The compositions of kidney extracellular matrix (ECM) and ECM mRNA were examined. The glomerulosclerotic areas in GH mice contained types I and IV collagen, laminin, and basement membrane heparan sulfate proteoglycan (HSPG), which increased with age. The type IV collagen, laminin B2, and HSPG mRNA levels in GH mice, measured by a solution hybridization RNase protection assay, were increased over normal littermates. These findings suggest that the accumulation of ECM components in the glomeruli of GH mice is regulated at the transcriptional level and that glomerulosclerosis is, in part, due to the excess production of ECM rather than simply a reduction in its turnover. The glomerular lesions in GH mice resemble diabetic nephropathy and may allow further dissection of the molecular basis of certain forms of glomerulosclerosis.

Aging↗
PubMed1991

Intracranial metastasis of a choroid plexus papilloma originating in the cerebellopontine angle region: a case report.

The authors present a rare case in which a choroid plexus papilloma originating in the left cerebellopontine angle region metastasized and formed a space-occupying lesion in the right temporal region. A 46-year-old woman with choked disks presented with two separate mass lesions in the right temporal and the left cerebellopontine angle regions. Magnetic resonance imaging exhibited the relationship between the tumors and the surrounding structures. To our knowledge, no case has been reported in which a choroid plexus papilloma originating in the cerebellopontine angle region formed a space-occupying lesion in the right temporal region.

Brain Neoplasms↗
PubMed1991

Transcriptional regulation of the rat platelet factor 4 gene: interaction between an enhancer/silencer domain and the GATA site.

We used various segments of the 5' upstream region of the rat platelet factor 4 (PF4) gene coupled to the human growth hormone gene and heterologous promoters to identify domains which are critical for tissue-specific expression. Transient expression experiments with rat bone marrow cells and other cell lines revealed a complex interplay between a core promoter domain from -97 to the transcriptional start site and an enhancer/silencer domain from -448 to -112. The core promoter contains a GATA site at -31 to -28 whose mutation to TATA or AATA decreases tissue specificity and moderately affects expression in megakaryocytes as well as a positively acting subdomain from -97 to -83 whose removal decreases overall transcription without affecting tissue specificity. The enhancer/silencer domain possesses three positively acting subdomains from -380 to -362, -270 to -257, and -137 to -120 as well as a negatively acting subdomain at -184 to -151 which is able to reduce overall transcription but has no effect on tissue specificity. The subdomain from -380 to -362 is most critical in restricting gene expression driven either by the PF4 promoter or by a heterologous promoter to the megakaryocytic lineage. The subdomains from -270 to -257 and -137 to -120 function together with the subdomain from -380 to -362 to somewhat increase tissue specificity. Simultaneous mutation of the GATA site and deletion of either the whole enhancer/silencer domain or the subdomain from -380 to -362 or -137 to -120 reduce transcription in megakaryocytes by 10- to 30-fold. On the basis of the above-described results, we propose that the megakaryocyte-specific enhancer/silencer domain and the GATA site are responsible for high-level expression of the PF4 gene in a lineage-specific manner.

Animals↗
PubMed1991

Analysis of IgG immune complexes in sera from patients with membranous nephropathy: role of IgG4 subclass and low-avidity antibodies.

The levels of circulating immune complexes (CIC) were determined using an anti-C3d binding assay in patients with various types of glomerulonephritis (GN). It was found that IgG class CIC were positive in 20% (7/35) of patients with idiopathic membranous nephropathy (MN) and in 80% (8/10) of patients with lupus glomerulonephritis (LN). Of these patients, IgG4 subclass CIC were observed more frequently in 29% of MN and 60% (3/5) of minimum change nephrotic syndrome, and, with less amounts, in 10% (1/10) of membranoproliferative GN (MPGN) and 20% (2/10) of IgA nephropathy. On the other hand, the patients with LN showed a lower positivity (30%) of IgG4-CIC as compared with that of IgG-CIC. In the comparison of mean levels, only MN patients showed significantly higher value than normal individuals (p less than 0.05). In patients with MN, the CIC of the other IgG subclasses (IgG1, IgG2, IgG3) were not significantly elevated and their positivities were low (9-11%). The study on the salt-dependent dissociability of CIC, which is considered to reflect the avidity of antibodies in CIC, showed that the IgG-CIC of 11 of 15 patients with MN were dissociable to various extents even at the physiological concentration. These findings suggested that IgG4 subclass specificity and low avidity may be pathogenic characteristics of IgG-CIC in certain populations of patients with MN.

Antibody Affinity↗
PubMed1991

Relationship of intraglomerular coagulation and platelet aggregation to glomerular sclerosis.

In order to investigate the relationship between intraglomerular coagulation and glomerular sclerosis, the distribution of fibrin-related antigen (FRA) in glomeruli without extracapillary lesions was examined by immunoperoxidase microscopy in 80 patients with IgA nephropathy (IgA-N). A total of 302 glomeruli were examined, including 20 with global sclerosis, 31 with segmental sclerosis (SS glomeruli), and 251 nonsclerosed glomeruli. In the nonsclerotic areas of SS glomeruli, the deposition of FRA was significantly greater than in the nonsclerosed glomeruli. In the nonsclerosed glomeruli FRA was mainly found in the mesangium, while in the nonsclerotic areas of SS glomeruli FRA was not only present in the mesangium but also in the endothelium of the glomerular capillary loops. FRA-positive microclots were also often observed attached to the endothelium of the capillaries of the nonsclerotic areas of SS glomeruli. Cross-linked FRA was also observed in the endothelium of the same capillaries using the monoclonal antibody DD3B6/22. Deposition of von Willebrand factor (vWF) was greater in the endothelium than in the mesangium in the same areas. Aggregated platelets adhering to the glomerular capillary walls in these areas were frequently detected using the monoclonal antibody P2. Such distribution of platelets and vWF showed that the endothelium of the nonsclerotic areas of SS glomeruli was more severely damaged than that of nonsclerosed glomeruli. These findings suggest that endothelial cell damage might activate the intraglomerular coagulation, which might be one of the factors in the development of global glomerular sclerosis.

Antigens, Human Platelet↗
PubMed1991

[Kinetics of immune complex deposition and influence of decomplementation on their clearance in cationized antigen induced acute serum sickness].

Using a murine acute serum sickness model caused by cationized bovine gamma-globulin (CBGG), the histological findings, accumulation of CBGG in the organs and the effect of decomplementation for the clearance of immune complex (IC) were investigated. The accumulation of CBGG increased in the lungs in the presence of anti-CBGG antibody 1 hour after injection of CBGG, but did not change in the kidneys. This suggests that CBGG forms IC in situ in the kidneys, and that circulating IC accumulates in the lungs. Decomplementation did not influence the uptake of CBGG immediately after challenge but delayed the clearance of CBGG in the kidneys, lungs, liver and spleen. A beneficial role of the complement system in the clearance of IC even for those formed in situ was recognized. Histological changes, cellular infiltration and microvascular destruction, evoked in the lungs in this experimental model immediately after challenge, were not seen in the kidney, suggesting the different modes of complement activation in these organs.

Animals↗
PubMed1991

Tissue distribution, intracellular localization, and in vitro expression of bovine macrophage scavenger receptors.

Macrophage scavenger receptors are trimeric membrane proteins implicated in the pathologic deposition of cholesterol in atherogenesis. The authors have studied the tissue distribution and intracellular localization of bovine scavenger receptors using monoclonal antibovine receptor antibody IgG-D2. The receptor proteins were detectable in macrophages of various organs and tissues, particularly Kupffer cells, alveolar macrophages, and macrophages in the spleen and lymph nodes. In the brain, perivascular macrophages were immunoreactive with IgG-D2. Fibroblasts, endothelial cells, smooth muscle cells, and dendritic cells such as epidermal Langerhans cells, interdigitating cells, or follicular dendritic cells, however, showed no immunoreactivity to IgG-D2. Immunoelectron microscopy showed localization of reaction products for these receptors on the cell surface, vesicles, and endosomes of macrophages. Transient expression of bovine scavenger receptors on cultured cells shows that scavenger receptors are mainly expressed in the endoplasmic reticulum, nuclear envelope, and Golgi apparatus of nonmacrophage cells and moved to the cell surface and endosomes of macrophagelike cells. These results indicate that efficient intracellular transport of scavenger receptors in macrophages is mediated by a macrophage-specific transport system.

Acetic Anhydrides↗
PubMed1991

[Complement fragments in patients with bronchial asthma].

In this study, we investigated the pharmacological reactions induced by ibudilast to the complement system with the aim of clarifying the functional relation of the complement system to allergic reactions and pathology in patients with bronchial asthma. Complement hemolytic activities (CH50 and ACH50), complement profile, anaphylatoxins (C3a and C5a) and complement fragments (Bb, iC3b and C4d) were measured in 20 patients with bronchial asthma. One of antiasthmatic activities induced by ibudilast was concluded to be brought about though inactivation of the alternative complement pathway working on type III allergic reaction. Ibudilast increased the complement fragment Bb in the patients' plasma with the fairly controlled bronchial asthma. This increase in circulating Bb was suspected to be a result of inactivation of intermediate complement complexes, for example C3b.Bb.P, because the amounts in plasma of C3 and C5 showed no changes, while those of factor, B, P, H and I were decreased by ibudilast administration in patients with fairly controlled bronchial asthma. This antiasthmatic ability of ibudilast was restrained in those patients whose peripheral leukocytopenia was advanced before ibudilast administration, and in those whom ibudilast did not provoke an increase in the plasma level of iC3b, or did not prevent the serum level of C5 from increasing. In those unfairly controlled cases, enough anaphylatoxins, especially C5a might be produced to make the margination of peripheral neutrophils to the lung and increase CR3 on neutrophils binding with iC3b.

Adult↗
PubMed1991

Atomic structure of a pyrimidine-dimer specific excision-repair enzyme from bacteriophage T4.

T4 endonuclease V is an enzyme responsible for the first step of a pyrimidine-dimer specific excision-repair process. The three-dimensional structure of this enzyme has been determined at 1.6A resolution by X-ray crystallography. The enzyme consists of one single compact domain classified into the all alpha structure. This single domain possesses two distinct catalytic activities, a pyrimidine-dimer glycosylase and an apurinic/apyrimidinic endonuclease. The backbone of the enzyme represents a unique folding scheme incompatible with close packing of alpha-helices. The refined structure suggests possible residues that participate in interactions with DNA.

Amino Acid Sequence↗