Biomedical subjects

S Kokubun

Publications and source records attributed to S Kokubun.

At least 19 recordsLinked to original sources

PubMed2000

Changes with age in proteoglycan synthesis in cells cultured in vitro from the inner and outer rabbit annulus fibrosus. Responses to interleukin-1 and interleukin-1 receptor antagonist protein.

STUDY DESIGN: Proteoglycan synthesis was examined in cells isolated from the inner and outer annulus fibrosus of young and old rabbits. Their responses to interleukin-1 alpha and interleukin-1 receptor antagonist protein were investigated. OBJECTIVES: To evaluate the age-related changes and the anatomically related differences in the function of intervertebral disc cells. SUMMARY OF BACKGROUND DATA: Proteoglycan content in the human intervertebral disc decreases with age. Age-related changes in intervertebral disc cell function, however, have not been fully investigated. METHODS: Japanese white rabbits aged 2 months (young group) and 3 years (old group) were used. The inner and outer layer of the annulus fibrosus were separated. The proteoglycan synthesis and release were measured in cells cultured with or without human recombinant interleukin-1 alpha and interleukin-1 receptor antagonist protein. RESULTS: The proteoglycan synthesis significantly decreased and the release rate significantly increased in the old rabbits, compared with the young ones. In the inner annulus, the inhibition of proteoglycan synthesis due to interleukin-1 alpha was greater in the old rabbits than in the young ones. In the old rabbits, interleukin-1-induced inhibition was more pronounced in the inner annulus than in the outer annulus. Interleukin-1 receptor antagonist protein suppressed inhibition of proteoglycan synthesis by interleukin-1 alpha in the two layers in both age groups. CONCLUSIONS: Both the decline in proteoglycan synthesis and the increased cell sensitivity to interleukin-1 alpha with age may contribute to the degradation of discs. The increase in cell response to interleukin-1 alpha in the inner annulus of rabbits may explain why the inner annulus and nucleus pulposus degrade earlier than the outer annulus in human discs. Interleukin-1 receptor antagonist protein could be useful in inhibiting the degradation of the disc.

Age Factors↗

PubMed1999

Enhanced beta-receptor-mediated vasorelaxation in hypoxic porcine coronary artery.

To investigate the beta-adrenoceptor-mediated responses in hypoxic coronary arteries, we studied the effect of isoproterenol (Iso) on isolated porcine coronary arteries contracted with endothelin-1 in media aerated with 0, 5, 7.5, and 95% O(2). The concentration-response curve of Iso was significantly shifted to the left by hypoxia (0 and 5% O(2)). In oxygenated and hypoxic arteries, 3 x 10(-8), 10(-6), and 10(-5) M Iso significantly increased the contents of cAMP. However, there was no difference in the increases of cAMP content induced by 3 x 10(-8) M Iso between oxygenated and hypoxic arteries. The content of cAMP induced by high concentrations of Iso (10(-6) and 10(-5) M) was significantly larger in hypoxic than in oxygenated arteries. Furthermore, the potentiation by hypoxia of the Iso-induced vasorelaxation was inhibited by glibenclamide and depolarization by KCl, but not by removal of endothelium and indomethacin. The vasodilatory response to forskolin and dibutyryl cAMP was unaffected by hypoxia. We conclude that activation of the ATP-sensitive K(+) channel may account for the potentiation of the response to Iso in hypoxic coronary arteries.

Animals↗

PubMed1999

Clinical use of etodolac for the treatment of lumbar disc herniation.

This paper reports a non-comparative multicentre study designed to assess the usefulness of a non-steroidal anti-inflammatory agent--etodolac--for the treatment of lumbar disc herniation. The efficacy and safety of etodolac were evaluated based on the changes of symptoms and signs of the patients, including the following parameters: low back pain, leg pain and tingling, gait, the straight-leg-raising test, sensory disturbance, motor disturbance, restriction of activities of daily living (ADL), urinary bladder function, and patients' impressions at each hospital on the initial day, and at one week and two weeks after the start of administration of etodolac, in a total of 88 patients. The overall improvement was noted as a 'marked' in 5% and 13%, 'moderate' or better in 31% and 54%, 'slight' or better in 82% and 84%, 'no change' in 12% and 9%, and 'aggravated' in 6% and 7%, at one and two weeks after administration, respectively. The only adverse drug reaction reported was stomach pain in one of the 81 patients. It can be concluded that etodolac is an effective and well-tolerated non-steroidal anti-inflammatory agent in the treatment of lumbar disc herniation.

Activities of Daily Living↗

PubMed1999

c-Myc protein in the rabbit growth plate. Changes in immunolocalisation with age and possible roles from proliferation to apoptosis.

Growth plates taken from five- to 20-week-old Japanese white rabbits were immunostained for c-Myc protein. This was localised both in the proliferating zone and upper hypertrophic zone at five weeks, whereas after ten weeks it was found mostly in the lower hypertrophic zone. The proliferating chondrocytes tended to show nuclear staining and the hypertrophic cells cytoplasmic staining, although the terminal hypertrophic chondrocytes sometimes expressed the protein in their nuclei. In the younger rabbits, c-Myc co-localised with proliferating cell nuclear antigen, whereas in the hypertrophic zone of older rabbits, it was present in some chondrocytes the nuclei of which also contained DNA breaks. Our study suggests that, in the rabbit growth plate, c-Myc is associated with different cellular processes, depending on the age and the developmental stage of the chondrocytes.

Aging↗

PubMed1999

Localization of PDK-1 mRNA in the brain of developing and adult rats.

Gene expression for 3-phosphoinositide-dependent protein kinase-1 (PDK-1) in developing and adult rat brains was examined by in situ hybridization histochemistry. In embryonic days, the mRNA was evident throughout the entire neuraxis. The expression remained evident throughout the entire gray matters until postnatal day 7, and thereafter it decreased overall in the mantle and ventricular zones except for the cerebellar Purkinje and granule cell layers, the olfactory and hippocampal neuronal layers. The pattern of this gene expression is similar to those of for protein kinase B and class I phosphoinositide 3-kinases.

3-Phosphoinositide-Dependent Protein Kinases↗

PubMed1999

Fibrous dysplasia arising from the calcaneus.

A case of an 18-year-old woman with fibrous dysplasia arising in the calcaneus, which is extremely rare, is reported, with the emphasis placed on differential diagnosis from low-grade central osteosarcoma. She had a severe pain in her left ankle after sprain. Plain radiographs showed a radiolucent lesion measuring 6.3 x 2.5 cm with a sclerotic margin in the left calcaneus. CT scans showed a well-defined lytic lesion with disruption of the lateral cortex and an ossification or calcification in its center. On MR imaging, the lesion had isointensities and high intensities on T1 and T2 weighted images, respectively, but its central portions showed lower intensities both on T1 and T2 weighted images. The lesion was enhanced with gadolinium except for the central portions. The specimen obtained by open biopsy consisted of fibrous tissue and foci of irregular woven bone. None of the nuclear atypia, mitoses, longitudinal stream of bone or invasive nature of growth was detected. The diagnosis of fibrous dysplasia was histologically made. The lesion was curetted and packed with autogenous bone chips. No evidence of recurrence was noted postoperatively.

Adolescent↗

PubMed1999

Nonselective cationic currents activated by acetylcholine in swine tracheal smooth muscle cells.

Membrane currents in isolated swine tracheal smooth muscle cells were investigated using a pipette solution containing BAPTA-Ca2+ buffer and Cs+ as the major cation. With a pipette solution containing 100 nM free Ca2+, acetylcholine (ACh; 1-100 microM), in a concentration-dependent manner, activated a current without inducing shortening of cells, although neither 1 mM histamine nor 1 microM leukotriene D4 activated the current (n = 7, n is the number of cells). The effect of 100 microM ACh was suppressed by pretreatment with 100 microM atropine (n = 6) or intracellular application of preactivated pertussis toxin at a concentration of 0.1 microg x mL(-1) (n = 8). Genistein (0.1-100 microM), in a concentration-dependent manner, suppressed the activation of the inward current by 100 microM ACh, whereas it did not significantly suppress that of the outward current (n = 6-8). With a pipette solution containing 50 nM free Ca2+, outward current, but not inward current, was activated by 100 microM ACh (n = 10). When the pipette solution had free Ca2+ concentrations greater than 50 nM, the inward current together with the outward current was activated. The ratio between the amplitude of the inward and outward currents was significantly increased as the free Ca2+ concentration in the pipette solution increased. The steady-state activation curve of the ACh-activated current with the 50 nM free Ca2+ pipette solution was fitted by a single Boltzmann distribution (Vh = +69.8 mV, k = -11.9 mV, n = 10). The activation time constant became smaller as the membrane potential was more depolarized (164.3+/-5.9 ms at +40 mV to 92.4+/-6.3 ms at +120 mV, n = 10). The reversal potential was not significantly changed by reducing extracellular Cl- concentration to one-tenth of the control (n = 8), suggesting that the current is a nonselective cationic current. These results suggest that ACh activates an outward nonselective cationic current via pertussis toxin-sensitive G-protein(s) coupled with muscarinic receptors. Involvement of genistein-sensitive tyrosine kinase in the activation process of the current is unlikely.

Acetylcholine↗

PubMed1998

Radiological and laboratory features of infantile cortical hyperostosis. A case report.

We describe a boy aged nine months with infantile cortical hyperostosis in association with cystic fibrosis. Symmetrical periosteal thickening was present in the clavicles, ribs, femora, humeri, ulnae and radii. Periosteal hyperostosis of the humerus developed in association with an increase in the levels of serum alkaline phosphatase a month before the appearance of hyperirritability and soft tissue swelling about the hip joints. The condition gradually resolved during the following eight months.

Alkaline Phosphatase↗

PubMed1998

The long-term efficacy and tolerability of the new anti-inflammatory agent zaltoprofen in rheumatoid arthritis.

This paper reports on a non-comparative multicentre study designed to assess the usefulness of the non-steroidal anti-inflammatory agent zaltoprofen in the long-term treatment of rheumatoid arthritis. The efficacy and safety of zaltoprofen in the long-term treatment of rheumatoid arthritis were evaluated on the bases of changes of symptoms and presentation signs in the patients including the following: averaged bilateral grip strength, blood sedimentation rate, the duration of morning stiffness, joint pain for Lansbury scoring, restriction of activities of daily living (ADL) and pain score, and on patients' impressions at each hospital on the first day of attendance and then at 6 and 12 months after the start of administration of zaltoprofen, in a total of 46 patients. Overall improvements were recorded as 'marked' in 9%, 'moderate' or better in 60%, 'slight' or better in 80%, 'no change' in 17% and 'worse' in 3%, after 12 months' treatment. The overall safety was recorded as 'safe' in 86% and 'almost safe' or better in 97% after 12 months' treatment. On the basis of these results it can be concluded that, in the long-term treatment of rheumatoid arthritis, zaltoprofen is a well-tolerated and safe non-steroidal anti-inflammatory agent.

Adult↗

PubMed1998

Changes in the expression of Fas, osteonectin and osteocalcin with age in the rabbit growth plate.

Chondrocytes of the growth plate are generally assumed to undergo apoptosis, but the mechanisms which induce this cell death are not known. The Fas receptor is a mediator of the apoptotic signal in some systems. We studied its expression in situ in growth plates of rabbits aged from five to 20 weeks. In addition, we investigated the immunolocalisation in the growth plates of the bone proteins, osteonectin and osteocalcin, and the changes in their expression with age. The Fas-positive chondrocytes were found mostly in the hypertrophic zone, as were the osteonectin-positive and osteocalcin-positive cells. The percentage of Fas-positive cells increased with age whereas little change was found in the number of osteonectin-positive and osteocalcin-positive chondrocytes. Many of the Fas-positive chondrocytes were also TUNEL-positive. This strongly suggests that apoptosis in the growth plate is mediated through the Fas system. Double immunostaining for osteocalcin and Fas showed that not all hypertrophic chondrocytes were of the same cell type. Some chondrocytes stained for osteocalcin only, others for Fas only, while some were positive for both.

Aging↗

PubMed1998

Thoracic myelopathy in the Japanese: epidemiological and clinical observations on the cases in Miyagi Prefecture.

Surgeries for thoracic myelopathy for 7 years in a northeastern prefecture (population, 2.26 million) and surrounding areas were reviewed. Eighty-one residents in the prefecture were operated on. The annual operation rate per one million people was 5.1. The rate corresponded to 9% of that reported for cervical myelopathy in the same prefecture. The mean age at operation was 55 years. Fifty-five patients (68%) were male and 26 (32%), female. Twenty-eight % of the patients had preoperative periods longer than two years, and 23% had severe disabilities. Anterior decompression was performed in 27%, posterior decompression in the others. The postoperative recovery rate averaged 48%. The lowest rate was 31% in patients with a preoperative duration of more than 2 years (p < 0.05). Sixty-four % of the patients had ossification of the ligamentum flavum; 20%, posterior spur; 19%, disc herniation; 16%, ossification of the posterior longitudinal ligament; 1%, calcification of the ligamentum flavum; 1%, degenerative spondylolisthesis. Seventy-nine % had one of the above spinal factors and 21% had two.

Adult↗

PubMed1998

Myositis ossificans in the tip of the thumb: a case report.

A case of a myositis ossificans occurring in the distal portion of the finger is reported. An 18-year-old female noticed a small nodule in the tip of the left thumb for 11 months. Plain radiographs showed calcified shadow and there was a radiolucent zone between the mass and the distal phalanx. The excised mass was diagnosed as myositis ossificans. To our best knowledge, there has been no report of a myositis ossificans in the tip of the finger in literature.

Adolescent↗

PubMed1998

Periosteal ganglion of the radius: a case report.

We report a case of 43-year-old female with a periosteal ganglion arising in the right radius. Plain radiographs showed thick and sparse spicula with shallow and irregular cortical erosion, which suggested periosteal ganglion. Magnetic resonance (MR) imaging revealed a well circumscribed homogeneous lesion with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. No apparent enhancement observed after gadolinium injection suggested that the lesion was cystic. At operation, gelatinous material was removed together with the spicula, the surface of the cortex and the overlying periosteum. There was no clinical evidence of recurrence after three years of surgical treatment. MR imaging was thought to be useful to confirm the diagnosis of periosteal ganglion.

Adult↗

PubMed1997

Flow cytometrical and genotypic analysis of primary non-Hodgkin's lymphoma of bone.

Primary malignant lymphoma of bone presents both diagnostic and therapeutic problems. No previous study has addressed the use of flow cytometry in the immunophenotypic evaluations of bone lymphomas. A 41-year-old Japanese female presented with a large lytic lesion in the right femur. Biopsies from the lesion were examined by light microscopy, immunohistochemistry, 3-color flow cytometry and Southern blotting. Microscopic examination showed a diffuse, noncleaved large cell lymphoma. The lymphoid cells were positive for mature B cell antigens and the phenotype was: CD5-, CD10-, CD19+, 20+, CD22+, IgG+, IgA-, IgM-, kappa-, lambda+, CD1-, CD2-, CD3-, CD4-, CD7-, CD8-. Southern blot analysis revealed rearranged bands on both heavy- and lambda light-chain genes, in contrast to germline configuration on T cell antigen receptor (beta, gamma and delta) genes. Flow cytometry, in conjunction with morphologic and other molecular techniques, can provide a rapid and accurate means of diagnosing primary lymphoma of bone. In addition, the capabilities of flow cytometry to assess cell properties/constituents can be utilized in detailed analysis of adhesion molecules and activation antigen which may lead to better prediction of the prognosis of this group of lymphomas, and may provide further important data for the therapeutic decision making process.

Adult↗

PubMed1997

The signalling pathway which causes contraction via P2-purinoceptors in rat urinary bladder smooth muscle.

1. The signalling pathway which causes contractions to adenosine 5'-O-2-thiodiphosphate (ADPbetaS) and alpha,beta-methylene adenosine 5'-diphosphate (alpha,beta-Me ADP) was investigated in rat urinary bladder smooth muscle by measuring isotonic tension. 2. The responses to 10 microM alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-Me ATP) in 0 and 3.6 mM Ca2+ were 5.9+/-1.3 (n=10) and 122.2+/-6.4 (n=8) % respectively of those obtained in 1.8 mM Ca2+, whereas those to 100 microM ADPbetaS were 34.6+/-3.3 (n=8) and 96.8+/-7.2 (n = 8) %, in 0 and 3.6 mM Ca2+, respectively. In both experimental conditions, the responses to the two agonists expressed as % of the control responses were significantly different (P<0.01). 3. Indomethacin at high concentrations (>1 microM) decreased the responses to alpha,beta-Me ATP (10 microM), ADPbetaS (100 microM) and alpha,beta-Me ADP (100 microM). However, no significant difference was obtained between the responses to all the agonists at 30 microM indomethacin. 4. 2-Nitro-4-carboxphenyl n,n-diphenylcarbamate (NCDC) at concentrations between 1 microM and 100 microM concentration-dependently decreased the responses to ADPbetaS (100 microM) and alpha,beta-Me ADP (100 microM) and almost completely inhibited them at 100 microM. Although the responses to alpha,beta-Me ATP (10 microM) were also inhibited by the drug, at 50 and 100 microM NCDC the responses to alpha,beta-Me ATP were significantly larger than those to ADPbetaS and alpha,beta-Me ADP (P<0.01). 5.NCDC 100 microM significantly inhibited the KCl-induced contraction to 65.9+/-4.9% (n=6) of the control (P<0.01). 6. It is suggested that the contraction via ADPbetaS-sensitive receptors in the rat urinary bladder smooth muscle mainly depends on Ca2+ ions liberated from intracellular Ca2+ stores, though the contribution of Ca2+ ions from the extracellular space cannot be neglected. The release of Ca2+ ions from stores is mainly mediated by the production of inositol trisphosphate (IP3) via the activation of phospholipase C.

Adenosine Diphosphate↗

PubMed1997

Clinical evaluation of indomethacin-containing patches for osteoarthritis and extremity trauma.

Seventy-eight patients, aged 12-87 years, with osteoarthritis or extremity trauma, attached one indomethacin patch (containing 96 mg indomethacin) to the most symptomatic site twice daily. The final overall treatment outcome was excellent in 52% of the osteoarthritic patients and in 82% of the trauma patients, good in 27% and 13%, and fair in 3% and 0%, respectively. Side effects were reported by 4% of the patients. It is concluded that indomethacin-containing patches were effective and well-tolerated for the treatment of osteoarthritis and extremity trauma.

Administration, Cutaneous↗

PubMed1997

Apoptosis and proliferation of growth plate chondrocytes in rabbits.

The growth plates of the femoral head of Japanese white rabbits aged 5, 10, 15 and 20 weeks were stained for apoptotic and proliferating chondrocytes using the TUNEL and PCNA antibody staining techniques. Both TUNEL- and PCNA-positive chondrocytes were detected in all of the specimens. The positive ratios of both stainings were calculated for the whole plate and for the resting, proliferating and hypertrophic zones. The highest ratios in both stainings occurred in the hypertrophic zone in all age groups. With growth, the TUNEL-positive ratio increased whereas the proliferating ratio decreased. We suggest that the increase in chondrocytic death by apoptosis and the decrease in cell proliferation potential led to closure of the growth plate.

Aging↗

PubMed1997

The effect of extracellular Ca2+ on responses to purinoceptor agonists in cultured swine tracheal smooth muscle cells.

The effects of extracellular Ca2+ ions on purinergic responses were examined in swine tracheal smooth muscle cells (TSMCs) in primary culture. ATP (1 microM to 1 mM) and alpha, beta-methylene adenosine 5' triphosphate (alpha, beta-Me ATP) (100 microM and 1 mM) concentration-dependently increased [Ca2+]i in the presence and the absence of extracellular Ca2+. Responses to ATP (10 microM to 1 mM) in the presence of extracellular Ca2+ were significantly larger than those in its absence (n=8), whereas those to alpha, beta-Me ATP were not significantly different between the presence (n=7) and the absence (n=8) of extracellular Ca2+. Responses to ATP (1 mM) at extracellular Ca2+ concentration ([Ca2+]o) of 10 and 5 mM were significantly larger than that at extracellular EGTA concentration ([EGTA]o) of 1 mM (p< 0.01, n=5), whereas the responses to alpha, beta-Me ATP (1 mM) at 10 and 5 mM [Ca2+]o were significantly smaller than that at [EGTA]o of 1 mM (p<0.05, n=5). Increasing [Ca2+]o to 5 mM after the application of either 1 mM ATP (n=4) or 1 mM alpha, beta-Me ATP (n=4) in the absence of extracellular Ca2+ (1 mM [EGTA]o) further increased [Ca2+]i, though the increases in [Ca2+]i by agonists in 1 mM [EGTA]o had been already maximal. Incubating cells for 300 s in 5 mM [Ca2+]o before the application of ATP (1 mM) significantly increased the response to the drug than that obtained by incubating cells for 6 sec in 5 mM [Ca2+]o before the drug application (p< 0.01, n=4). However, alpha, beta-Me ATP (1 mM) induced similar responses by incubating cells for 30 or 300 s in 5 mM [Ca2+]o to that by incubating them for 6 s. These results suggest that the effect of alpha, beta-Me ATP in swine TSMCs in primary culture is mainly through Ca2+ release and that its effect on Ca2+ entry is smaller than other nucleotides.

Adenosine Triphosphate↗