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Biomedical subjects

T Matsubara

Publications and source records attributed to T Matsubara.

At least 379 records · Page 21Linked to original sources

A macrophage phenotype for a constitutive, class II antigen-expressing, human dermal perivascular dendritic cell.

A previously uncharacterized population of class II antigen-bearing dendritic cells that are intimately associated with the dermal microvasculature was identified in normal human skin using a double-label, indirect immunofluorescence technique. The only other major HLA-DR positive dermal cell type noted in these studies, the dermal microvascular endothelial cell (DMVEC), appeared to express lesser amounts of HLA-DR region gene product than did this dermal perivascular dendritic cell (DPDC). These DPDC were particularly common around small vessels in the superficial vascular plexus of the papillary dermis and were distinct from the mast cell, another cell type normally seen in a similar location. Phenotypic and ultrastructural studies have determined that the DPDC is more closely related to the monocyte/macrophage lineage than the dendritic cell lineage. The perivascular location and phenotype of this cell distinguishes it from other previously described constitutive dermal cell types such as the classic "histiocyte," veiled cell, and dendrocyte. The relatively rich expression of all three major HLA-D region gene products by this dermal perivascular dendritic macrophage would suggest that it could play a significant role in the immunobiology of the dermal microvascular unit.

Antigen-Presenting Cells↗

Inhibition of human endothelial cell proliferation in vitro and neovascularization in vivo by D-penicillamine.

To investigate the effects of D-penicillamine (D-Pen) on angiogenesis, we have studied the effects of this drug on in vitro proliferation of human endothelial cells (EC) and in vivo corneal neovascularization. D-Pen, in the presence of copper sulfate, suppressed tritiated thymidine ([3H]TdR) incorporation into EC in a dose-dependent manner. Significant inhibition was observed with D-Pen concentrations attainable in the serum and tissues of treated patients. Neither D-Pen nor copper ion alone significantly affected [3H]TdR incorporation into EC. The inhibition by D-Pen and copper was blocked by catalase (CAT) or horseradish peroxidase but not by boiled CAT or SOD. When rabbits were daily injected intravenously with D-Pen at the per kilogram dosage administered to rheumatoid patients, neovascularization as quantitated by the proliferation of corneal new blood vessels was significantly inhibited. These results suggest that hydrogen peroxide generated by D-Pen and copper exerts a pronounced antiangiogenic effect through inhibition of EC proliferation. It is, therefore, considered that D-Pen may suppress rheumatoid synovitis by reducing the number of small blood vessels available for the emigration of chronic inflammatory cells, and the proliferation of the synovial tissue.

Catalase↗

Studies on oxacephem antibiotics: comparison of the effects of 1-oxa and 1-thia cephalosporins on blood coagulation activities and vitamin K metabolism in rats.

Oxacephem antibiotics have been developed to increase the antibacterial activity of cephem antibiotics, but the effect of 1-oxygen replacement of cephem antibiotics on blood coagulation activities is not yet known. Therefore, latamoxef (LMOX), flomoxef (FMOX) and their 1-S congeners were examined for their effects on prothrombin time, activated partial thromboplastin time, plasma prothrombin and Factor VII levels, plasma and liver descarboxyprothrombin (PIVKA-II) levels, and liver microsomal vitamin K epoxide reductase activities in rats kept on a vitamin K-deficient diet. Under the vitamin-deficient states, LMOX, FMOX and their 1-S congeners inhibited the vitamin K epoxide reductase, although the effect of FMOX or its congener was much less than that of LMOX, and they decreased the blood clotting activities in rats fed a vitamin K-deficient diet. However, no difference was found in these effects between LMOX and its 1-S congener or between FMOX and its 1-S congener. This result suggests that the 1-oxygen replacement of cephem antibiotics is not responsible for the hypoprothrombinemic effect of the antibiotics.

Animals↗

Species and sex differences in the inhibitory action of the corticosteroid alclometasone dipropionate on the hepatic drug-metabolizing system.

The effect of successive administration of the corticosteroid alclometasone dipropionate (ACM) on the hepatic drug-metabolizing system was examined using male and female rats. Although some pharmacological changes such as increases in plasma enzyme activity, lipid level and protein concentration appeared similarly in ACM-treated male and female rats, the activities of 7-alkoxycoumarin O-dealkylase, especially the O-depropylation activity, decreased dose-dependently by ACM administration only in male rats. ACM did not affect the hepatic drug-metabolizing activity in female rats and mice of both sexes. Also, ACM did not inhibit androgen-independent aniline hydroxylase activity even in male rats. The time course of changes of the drug-metabolizing system in male rats showed a rapid decrease in cytochrome P-450 content and O-depropylation activity following successive treatments with ACM, but there was a slow onset in the decreases of the O-demethylation and O-deethylation activities of 7-alkoxycoumarin. When ACM was withdrawn, the O-demethylation and O-deethylation activities rapidly returned to their control levels, while recovery of the O-depropylation activity was slow. These results suggested that ACM inhibits the hepatic drug-metabolizing enzyme activity associated with a specific form(s) of androgen-dependent cytochrome P-450 in male rats.

Animals↗

Effect of TRK-100, a prostacyclin analogue, on endotoxin-induced enhancement of blood coagulation in rats.

TRK-100 (0.03, 0.1 and 0.3 mg/kg, p.o.), a chemically stable analogue of prostacyclin, dose-dependently prevented blood coagulation and glomerular fibrin deposition which were enhanced by 4 hr infusion of endotoxin (100 mg/kg) in rats. In addition, TRK-100 suppressed the generation of endotoxin-induced tissue thromboplastin like activity in cultured human endothelial cells.

Administration, Oral↗

A case of atrial septal defect combined with hypertension and left ventricular hypertrophy. Left ventricular failure induced by balloon occlusion and the effect of nifedipine.

A 46 year old woman with hypertension and left ventricular hypertrophy accompanied by an atrial septal defect is reported. Hemodynamic changes induced by balloon occlusion and concomitant nifedipine were studied. Left ventricular failure appeared after balloon closure of the defect. Nifedipine decreased the increment in left ventricular end-diastolic pressure induced by balloon occlusion. After the reduction of systemic vascular resistance, the ratio of intracardiac shunt flow was still larger. Surgical closure of the defect was performed and the postoperative course was good with the use of vasodilators.

Blood Pressure↗

Recanalization of experimental thrombotic arterial occlusion by radiofrequency thermal angioplasty: an angioscopic observation.

The efficacy of radiofrequency (RF) angioplasty for recanalization of arterial thrombosis was assessed angioscopically in five dogs. A thrombus was induced by balloon injury of the left femoral artery. Within two hr, thrombi led to total occlusion of the artery in three dogs, subtotal occlusion in one, and about 70% obstruction in one. A metal-tipped catheter, with a tip size of 2.0 mm x 5.7 mm, was advanced into the thrombus and RF at 13.56 MHz was delivered repeatedly with gradually increased energies. The arterial lumina were recanalized or enlarged in all dogs. The thrombus surface had a shaggy appearance, and were dark (charring), or mixed dark and white in color. There were relatively large variations in the energies required; 140 J in one, 200 J in two and 250 J in two. The present results suggest that thrombotic arterial occlusion, such as acute occlusion complicating balloon angioplasty, can be treated with RF thermal angioplasty. Angioscopy provided detailed information about thrombus surfaces. The variations in required energies indicate the inability to control the thermal effect by energy settings alone. A more sophisticated method such as measurement of tip temperature will be able to overcome this difficulty.

Angioplasty, Balloon↗

Vitamin K-reversible hypoprothrombinemia in rats: comparison of hypoprothrombinemic changes in various strains of rats caused by vitamin K deficiency and antibiotic treatment.

Hypoprothrombinemic changes were compared in rats fed various vitamin K-deficient diets. Changes such as prolongation of prothrombin time and activated partial thromboplastin time, decrease in plasma levels of prothrombin and clotting factor VII, and increase in plasma descarboxyprothrombin, appeared in rats maintained on vitamin K-deficient diet, but in rats on ordinary diet (vitamin K-sufficient diet). As the development of hypoprothrombinemia was not significantly different among animals fed various vitamin K-deficient diets, the blood coagulation parameters were concluded to be regulated only by the vitamin K level. Following the development of hypoprothrombinemia, hemorrhaging in various organs was detected in vitamin K-deficient rats, with strain differences in the severity of hemorrhage; Fischer and Wistar strains were more sensitive than the Sprague Dawley strain. Administration of a beta-lactam antibiotic, latamoxef (LMOX), to vitamin K-deficient rats led to enhancement of the hypoprothrombinemic conditions, but LMOX-associated changes in plasma enzyme levels were not detected.

Animals↗

[Allergen tests with midge allergens in Moriyama City, located on the south coast of Lake Biwa].

The main species of midge which emerge from the Lake Biwa, the biggest lake in Japan, are Tokunagayusurika akamusi (TA) and Chironomus pulmons. In order to determine how the existence of Lake Biwa affects the positivity to allergen tests with midge allergens, randomly selected asthmatic patients were examined by skin test and RAST. Out of 129 patients, 35 (27%) were positive to scratch tests with an extract of Chironomus yoshimatsui (CY). Out of 64 patients, 16 (25%) were positive to TA RAST and 12 (19%) were positive to CY RAST. The positive rate of skin tests was highest in the patients aged between 20 and 39. The positive rate of TA RAST was not significantly higher than the rates reported in other districts of Japan.

Adolescent↗

[Study on the clinical usefulness of RAST using insect and mite allergen discs].

In order to examine the usefulness of mite and insect RAST, RAST was carried out on 79 asthmatic patients using mite, cockroach, mosquito and larval chironomid midge (Chironomus thummi thummi, CTT) allergen discs supplied from Pharmacia AB, and discs of two species of adult chironomid midge (Tokunagayusurika akamusi, TA and Chironomus yoshimatsui, CY in Japan) which were prepared in our laboratories. The results were as follows. 1) The positive rate of RAST in 65 randomly selected asthmatic patients was 62% in the case of mite, 25% for TA, 20% for CY, 14% for cockroach, 11% for CTT, 8% for silk and 6% for mosquito. The positive rates of silk and mosquito RAST were low. However, these RAST seemed to be clinically useful when patients were positive to these RAST. 2) The rate of coincidence between skin test and RAST was 86.5% in the case of mite and 30% in the case of silk. The rate of coincidence between prick test using adult CY and RAST using larval CTT was 46.5%. 3) The positive rate of larval CTT RAST was about half that of adult TA or adult CY. However, larval CTT RAST seemed clinically useful when patients were positive to the RAST, because all the patients who were positive to larval CTT RAST were also positive to both adult TA and CY RAST. 4) A significant correlation was found among the three kind of chironomid midge RAST and also between cockroach RAST and any of the three kinds of chironomid midge RASTs.

Allergens↗

Rapid methods to visualize Y-specific repeated DNA sequences in cytological preparations.

We described rapid methods to detect Y-specific repeated DNA sequences in cytological preparations using in situ hybridization. A human Y chromosome specific DNA probe with an insert equivalent to that in pHY2.1 was labelled with [alpha-32P]dCTP or photobiotin, and hybridized to chromosome preparations. Signals were visualized specifically on Y chromosomes after 1 day's autoradiography or a couple of hours treatment with streptavidin alkaline phosphatase/BCIP/NBT. These methods are useful for molecular confirmation of Y-autosomal translocations.

DNA↗

[Serum interleukin-2 receptor in patients with Kawasaki disease].

Serum levels of soluble interleukin 2 receptor (IL-2R) were determined by a sandwich enzyme immunoassay in 42 patients during the acute phase and in 30 at the convalescent phase of Kawasaki disease, 5 with streptococcal infection, 13 with anaphylactoid purpura, 7 with various vasculitis and also in 16 healthy children. In addition, we analysed the population of peripheral blood mononuclear cells in 18 of 42 patients with KD using a fluorescence-activated cell sorter. Serum IL-2R levels in patients with KD were increased in the acute phase and return to the normal range in the convalescent phase. The increased serum IL-2R levels during the acute phase correlated with the percentage of peripheral blood helper/inducer T cells among the mononuclear cells. Serum IL-2R levels were increased in patients with measles who were examined as the infectious disease (viral) controls. However, serum IL-2R levels were increased neither in patients with anaphylactoid purpura nor in other diseases with vasculitis. These results suggest that immunological activation accompanied by the release of IL-2R from helper T cells in KD is similar measles virus infection and differs from vasculitis.

Cell Separation↗

In vivo effects of beta-lactam antibiotics and heterocyclic thiol compounds on vitamin K-dependent carboxylation activity and blood coagulation factors in vitamin K-deficient rats.

The in vivo effects of heterocyclic thiol compounds, corresponding to the 3'-position substituents of several beta-lactam antibiotics, on blood coagulation factors and on liver microsomal gamma-glutamylcarboxylation (gamma-carboxylation) activity were evaluated in rats maintained on a vitamin K-deficient diet. These rats, when compared to normal control animals, exhibited hypoprothrombinemic changes: prolongation of both prothrombin time and activated partial thromboplastin time, decreases in factor VII and plasma prothrombin, and increases in PIVKA II (descarboxyprothrombin) both in plasma and liver. They also displayed a marked increase in liver microsomal gamma-carboxylation activity. These blood coagulation variables could be altered markedly by administering various heterocyclic thiol compounds to the vitamin K-deficient rats, although these compounds did not inhibit gamma-carboxylation activity in an assay system using phylloquinone. A similar pattern of alteration was observed when some beta-lactam antibiotics were administered. Increased microsomal gamma-carboxylation activity in antibiotic-treated vitamin K-deficient rats was normalized by the administration of vitamin K, concomitant with the recovery of blood coagulation variables to the normal range. The results indicate that antibiotic-induced hypoprothrombinemia in vivo is not caused by inhibition of enzymes of the gamma-carboxylation system, such as vitamin K reductase and gamma-glutamylcarboxylase, but is related to the endogenous vitamin K level.

Animals↗

Suppression of human fibroblast proliferation by D-penicillamine and copper sulfate in vitro.

We examined the effect of D-penicillamine (DP) and copper sulfate (CuSO4) on human fibroblast proliferation in vitro. DP plus CuSO4 inhibited both basal and interleukin-1 (IL-1)-induced tritiated thymidine incorporation into fibroblasts in a dose- and time-dependent manner. Significant inhibition was observed at the level of 60 microM in the presence of 4 microM CuSO4. At this range of concentrations, which is attained in serum and in tissues of treated patients, DP alone or CuSO4 alone did not affect fibroblast proliferation. Similar inhibition was observed with various thiols in the presence of copper, but not with disulfides such as DP disulfide or oxidized glutathione. Inhibition of fibroblast DNA synthesis induced by DP and CuSO4 was reversed by the simultaneous addition of catalase or horseradish peroxidase, but not by boiled catalase or superoxide dismutase. The inhibition by DP and CuSO4, therefore, may be attributable to hydrogen peroxide produced by these 2 agents. DP, in the presence of CuSO4, did not affect IL-1 secretion from human peripheral mononuclear phagocytes. These observations indicate that hydrogen peroxide produced by DP plus CuSO4 inhibits IL-1-induced fibroblast proliferation by directly affecting fibroblasts, without alteration of IL-1 secretion from mononuclear phagocytes. Thus, DP may play a role in inhibiting the growth of rheumatoid pannus and excessive collagenation in scleroderma by direct inhibition of fibroblast proliferation.

Cell Division↗

Low-dose gold compounds inhibit fibroblast proliferation and do not affect interleukin-1 secretion by macrophages.

We examined the effect of low concentrations of gold compounds on the proliferation of human fibroblasts. Gold sodium thiomalate (GST) inhibited both basal and interleukin-1-induced tritiated thymidine incorporation into fibroblasts in a dose- and time-dependent manner. Significant inhibition was observed at the level of 5 micrograms/ml GST, and greater than 50% inhibition was attained at 10 micrograms/ml. These concentrations are attainable in the serum of treated patients. Similar inhibition was observed when less than 1 micrograms/ml auranofin, which is also within a serum-attainable range, was added. Low concentrations of GST (0-10 micrograms/ml) did not affect interleukin-1 secretion from lipopolysaccharide-stimulated human mononuclear phagocytes (M phi) when assessed by both human fibroblast and C3H/HeJ mouse thymocyte proliferation assays. When M phi precultured for 48 hours with GST (0-10 micrograms/ml) were added to the fibroblast culture in the presence or absence of lipopolysaccharide, there was no significant inhibition of M phi-induced DNA synthesis of fibroblasts. In contrast, when fibroblasts were precultured with GST (0-10 micrograms/ml) for 48 hours and freshly separated M phi were added, significant inhibition was observed in M phi-induced fibroblast proliferation at 5 micrograms/ml. These results suggest that low concentrations of GST directly cause a reduction of fibroblast proliferation, but do not affect the capability of M phi for induction of fibroblast proliferation. Therefore, gold compounds may play a role in the inhibition of the growth of rheumatoid pannus by direct inhibition of fibroblast proliferation.

Auranofin↗

Phase I clinical studies of 7432-S: effect of 7432-S on platelet aggregation and blood coagulation.

The effects of 7432-S, a new oral cephalosporin antibiotic, on platelet functions and vitamin K-dependent blood coagulation parameters were studied in human volunteers and animals. Although the ADP- and collagen-induced aggregations of human and animal platelets were inhibited in vitro by extremely high concentrations of 7432-S, the inhibitory effect of 7432-S was weaker than that of latamoxef or cefotaxime. When administered orally to human volunteers or animals, 7432-S caused no inhibition of platelet aggregation. Its administration also caused no change in prothrombin time and activated partial thromboplastin time both in human volunteers and in rats. The conclusion reached was that the new oral antibiotic 7432-S does not affect platelet functions and blood coagulation.

Adenosine Diphosphate↗

Human placenta gangliosides.

Gangliosides extracted from human placenta were composed of four major components (G1-G4), which were purified by silica beads column chromatography. The structures of these gangliosides were analyzed by exoglycosidase treatments, 400 MHz proton magnetic resonance spectroscopy and gas chromatography-mass spectrometry and were concluded to be as follows: (Formula: see text). Gangliosides containing more than 10 sugar residues were observed in addition to the above four major components. But ganglio-series gangliosides were undetectable in the placenta.

Amino Sugars↗