Search PubMed⌕ Search

Biomedical subjects

K Hirohata

Publications and source records attributed to K Hirohata.

At least 55 records · Page 3Linked to original sources
PubMed1989

Inhibition of in vitro vascular endothelial cell proliferation and in vivo neovascularization by low-dose methotrexate.

Neovascularization in the rheumatoid synovium plays an important role in the propagation of rheumatoid synovitis because the emigration of mononuclear cells and the growth of pannus are critically dependent on the development of small blood vessels. Inhibition of local vascular endothelial cell (EC) proliferation, which is essential for growth of these vessels, therefore, would have the potential to suppress rheumatoid inflammation. We investigated the effects of methotrexate (MTX), low doses of which are commonly administered to rheumatoid arthritis patients, on DNA synthesis by human umbilical vein EC in vitro and on rabbit corneal neovascularization in vivo. MTX inhibited both basal and EC growth factor-stimulated tritiated deoxyuridine (3H-UdR) incorporation into EC in a dose-dependent manner. Significant inhibition was observed at a concentration of 5 x 10(-9) M, which is that attained in the serum of treated patients. Neovascularization in vivo was also suppressed by low-dose intramuscular injections. These results suggest that MTX has an antiangiogenic effect, and may suppress rheumatoid inflammation through the reduction of synovial small blood vessels responsible for mononuclear cell infiltration and proliferation of synovial tissue.

Animals↗
PubMed1989

An electron microscopic study of the changes observed in osteocytes under ischemic conditions.

The purpose of this study was to observe the process of ischemia in osteocytes using light and electron microscopy and to compare the changes in these ischemic osteocytes with those in other types of osteocytes (i.e., degenerative osteocytes in physiological states, steroid-induced lipid-accumulating osteocytes) that have been previously reported. Five female Japanese white rabbits were used in this study. Osteochondral chips were taken from one side of the femoral condyle, covered with Millipore filters, and then inserted into the other side of the knee joint. These tissues were examined after 12 h and after 2, 5, 8, and 14 days of ischemia under both light and electron microscopy. Under light microscopy, osteocytes and lacunae were classified into four types: normal osteocyte, pyknotic osteocyte, pale osteocyte, and empty osteocyte lacuna. The number of each type of osteocyte (or lacuna) in a settled area was counted. The ratio of normal osteocytes decreased significantly (p less than 0.001) after the second day of ischemia. Pyknotic osteocytes increased at 12 h (p less than 0.01) and 2 days (p less than 0.001) of ischemia. On the fifth day of ischemia, the percentage of pale osteocytes reached a peak. This was followed by a gradual increase in the number of empty lacunae. On the fourteenth day of ischemia, empty lacunae constituted greater than 40% of the cell types. When viewed by electron microscopy, these necrotic osteocytes were similar to the degenerative osteocytes that have been observed in physiological states and apparently different from lipid-accumulating osteocytes. The results suggested that there could be at least two types of necrotic processes in osteocytes that eventually lead to cell death.

Animals↗
PubMed1989

Histopathology of femoral head osteonecrosis in rheumatoid arthritis: the relationship between steroid therapy and lipid degeneration in the osteocyte.

To investigate the pathology of osteonecrosis of the femoral head (ON) in patients with rheumatoid arthritis (RA), we examined 26 hips clinically and histologically. In this study, we diagnosed ON by both the radiological evidence of femoral head collapse, with or without narrowing of the joint space, and by histological evidence of extensive areas of bone necrosis with surrounding reparative new bone. Thus 14 hips were diagnosed as ON, and 12 hips were not. All of the patients with ON had a history of steroid medication. The frequency of lipid-containing osteocytes observed in the subchondral area of the femoral head significantly correlated with the occurrence of ON (P less than 0.05). In electron micrographs, these osteocytes showed degenerative features, with their nuclei pressed towards one side of the cell by plump fatty droplets (fatty degeneration). In patients with RA, there was a significant correlation between the appearance of lipid-containing osteocytes and steroid medication (P less than 0.05). No relationship existed between the severity of RA synovitis and the occurrence of ON. These data suggest that ON in rheumatoid hips may relate to the administration of a steroid and the fatty degeneration of osteocytes.

Aged↗
PubMed1989

Human epidermal growth factor for the stratification of synovial lining layer and neovascularisation in rheumatoid arthritis.

Immunohistochemical study showed selective localisation of human epidermal growth factor (hEGF) to the synovial lining layer. Although the synovial lining layer of the rheumatoid, osteoarthritic, and traumatic joints was hEGF positive, hEGF staining was especially dense at the rheumatoid synovial lining layer; the staining increasing linearly according to the degree of stratification of the lining layer (r = 1). Human epidermal growth factor was ultrastructurally localised to cytoplasm, especially to rough endoplasmic reticulum, of the synovial lining fibroblast-like (type B) cell. Only the cell surface of macrophage-like (type A) cells was hEGF positive. When different histological variables were compared with each other a positive correlation was found between hEGF staining of the synovial lining layer and the degree of neovascularisation of rheumatoid synovium (r = 0.72). Although some lymphocytes were weakly hEGF positive, neovascularisation did not correlate with the extent of lymphocyte infiltration or of hEGF staining of lymphocytes. Lymphocyte infiltration or hEGF staining of lymphocytes did not correlate with hEGF staining of the synovial lining layer, whereas the lymphocyte infiltration correlated positively with the extent of perivascular accumulation of lymphocytes (r = 0.89). These findings suggest that (a) hEGF is synthesised by and secreted through endoplasmic reticulum and Golgi apparatus from the synovial lining type B cell; (b) hEGF is at least partially responsible for the pathogenesis of stratification of the rheumatoid synovial lining layer, and perhaps of neovascularisation of the rheumatoid synovium, whereas it is not responsible for lymphocyte accumulation to the rheumatoid synovium.

Arthritis, Rheumatoid↗
PubMed1989

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↗
PubMed1989

Inflammatory cell changes in haversian canals. A possible cause of osteoporosis in rheumatoid arthritis.

We studied the morphology of the haversian canals in the osteopenic cortical bone of the medial femoral neck from patients with rheumatoid arthritis and compared the findings with those in patients with osteoarthritis and with uncomplicated coxa valga. In the rheumatoid bone, the diameters of the canals were larger and many more contained osteoclasts. Fewer haversian canals showed only lining cells than in the osteoarthritic or coxa valga patients. In bone from rheumatoid patients, especially in canals with osteoclasts, small blood vessels were frequently lined by tall endothelial cells with an infiltration of mononuclear cells. These morphological differences are discussed with reference to the possible mechanisms of loss of cortical bone in rheumatoid arthritis and other conditions.

Adolescent↗
PubMed1989

[Establishment and characterization of human lung cancer cell line (KUM.LK-2)].

Human lung cancer cell line, named KUM.LK-2 was established from xenograft implanted in nude mice and maintained for 43 months. And serially transplanted in nude mice. This line has the following biological characters. 1) Spontaneous lung metastases are made in nude mice inoculated subcutaneously. 2) This line can produce some kinds of proteases, like as tissue type plasminogen activator, urokinase type plasminogen activator and collagenase. 3) KUM.LK-2 has the ability of platelet aggregation.

Adenocarcinoma↗
PubMed1989

Effect of intramedullary bone cement fixation on fracture healing.

The effect of bone cement implanted in the marrow cavity on the fracture healing process was assessed in rabbits with an experimentally induced transverse fracture of the tibia. In the cement treated animals external callus formation occurred slowly, due to poor bone-forming capacity of the endosteum and a failure to form a bridge at the fracture site. Numerous resorption cavities then occurred in the cortical bone. The microangiogram revealed a lack of blood supply from the marrow in the cement treated group. Thus, the histological changes were probably due to obstruction of the marrow blood supply to cortical and endosteal bone.

Animals↗
PubMed1989

Interaction of macrophages with rheumatoid articular cartilage.

These experiments investigated the in vitro interaction of macrophages and rheumatoid articular cartilage. When rheumatoid articular cartilage samples were incubated with normal peripheral blood mononuclear cells (PBM) for 1 hour or 12 hours in vitro, there were large numbers of PBM attached to the articular surface, and some PBM invaded the cartilage during the 12 hour incubation period. Conversely, in cartilage from osteoarthritic and normal subjects in the control, only a few PBM were attached to the articular surface after incubation with PBM. Under electron microscopic observation, macrophages were tightly attached to the surface and within the eroded cartilage. Light and electron microscopic observation with immuno-peroxidase staining of the rheumatoid cartilage surfaces showed the deposition of immunoglublins adjacent to the attached macrophages, suggesting the presence of immune-complexes as chemoattractants. These results suggest that macrophages in a rheumatoid joint may play an important role in the formation of pannus, resulting in the destruction of cartilage to interact with immune-complexes trapped in the superficial region of the rheumatoid articular cartilage.

Arthritis, Rheumatoid↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

Lipid microspherules in synovial fluid of patients with pigmented villonodular synovitis.

We describe 2 patients with pigmented villonodular synovitis. In both patients, synovial fluids (SF) were characterized by the presence of abundant, strongly birefringent lipid microspherules, which appeared as Maltese crosses and were found both inside foam cells and free in the SF. Histologically, the synovial membranes showed pigmented villonodular synovitis, with aggregation of foam cells containing abundant lipid microspherules in their cytoplasm. Observation of numerous birefringent lipid microspherules and foam cells in SF may be a clue to the diagnosis of pigmented villonodular synovitis.

Adult↗
PubMed1988

The restoration of proliferation and differentiation of peripheral blood mononuclear non-adherent cells into immunoglobulin-secreting cells by autologous synovial adherent cells from patients with rheumatoid arthritis.

The ability of enzyme-dissociated synovial adherent cells (SAC) obtained from patients with active rheumatoid arthritis to restore the proliferation and differention of peripheral blood mononuclear non-adherent cells (NAC) into immunoglobulin-secreting cells (ISC) was investigated. Autologous combinations of cells were used in this study to eliminate allogeneic reactions. Peripheral blood NAC, prepared by glass adherence and leucine methylester treatment to remove monocytes, almost completely lost their capacity to proliferate and differentiate into ISC in response to pokeweed mitogen. The response of NAC was restored by adding 12.5% of 'fresh SAC', which was obtained by glass-adherence after an overnight culture of non-rosette forming, enzyme-dissociated rheumatoid synovial cells. Although the response was also restorable by adding more than 25% fresh SAC, this was less satisfactory than adding 12.5% SAC. 'Old SAC', obtained by glass-adherence after 7 days culture of enzyme-dissociated synovial cells, did not restore the response of NAC. Immunohistochemical studies showed that 55% of fresh SAC and 3% of old SAC expressed HLA-DR antigens. When 100 units/ml of interferon gamma was present, 25% of old SAC remained HLA-DR-positive and some of these cells retained a dendritic morphology after 7 days culture. The results indicate that rheumatoid synovia contain macrophage-like cells that can effectively support the ultimate differentiation of lymphocytes to ISC.

Antibody-Producing Cells↗
PubMed1988

Knee arthroscopy using local anesthetic.

The purpose of this study was to examine the effectiveness and safety of local anesthetics (a mixture of lidocaine and bupivacaine) in knee arthroscopy. Local anesthetic agents were shown to be effective and safe, based on chart review and measurement of blood levels of the anesthetic drugs.

Adult↗
PubMed1988

Bone and joint lesions associated with pustulosis palmaris et plantaris. A clinical and histological study.

We have reviewed 41 patients with pustulotic arthro-osteopathy (PAO), all having both the typical skin rash of pustulosis palmaris et plantaris and bone lesions. The most common bones affected were the clavicle, sternum and ribs. Changes in the clavicle started, not as an enthesopathy, but with periosteal bone formation, indicative of a bone marrow disorder. About 30% of the patients also had lesions in the spine, sacroiliac region or the peripheral joints. Bone and joint lesions followed a variable and intermittent clinical course over a long period of time. Biopsies in eight cases showed similar inflammatory changes in skin, bone and synovium, with infiltration of lymphocytes and polymorphonuclear leucocytes. This suggests that there is a common pathogenesis in the three tissues.

Adolescent↗