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Biomedical subjects

T Kurokawa

Publications and source records attributed to T Kurokawa.

At least 19 recordsLinked to original sources
PubMed1992

Osteoclasts express high levels of p60c-src, preferentially on ruffled border membranes.

Expression of p60c-src, the normal cellular counterpart of the transforming protein of Rous sarcoma virus (RSV), p60v-src, was examined in mouse and rat authentic osteoclasts and mouse osteoclast-like multinucleated cells (MNCs) formed in vitro. In co-cultures of mouse osteoblastic cells and spleen cells, the expression of p60c-src strikingly increased on day 5 in parallel with the appearance of MNCs in the presence of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3). Immunohistochemical examination confirmed the high level expression of p60c-src in both mouse authentic osteoclasts and MNCs. Electron microscopic examination revealed that p60c-src was primarily localized on ruffled border membranes and vacuoles, but not on the clear zone in rat authentic osteoclasts. These results suggest that p60c-src is important in osteoclastic bone resorption.

Animals↗
PubMed1992

Thrombolytic and pharmacokinetic properties of an immunoconjugate of single-chain urokinase-type plasminogen activator (u-PA) and a bispecific monoclonal antibody against fibrin and against u-PA in baboons.

Targeting of plasminogen activators to the fibrin component of a thrombus with the use of monoclonal antibodies (MA) directed against human fibrin may enhance their thrombolytic potency and fibrin-specificity. The thrombolytic and pharmacokinetic properties of rscu-PA/MA-FU1-74, an immunoconjugate of recombinant single-chain urokinase-type plasminogen activator (rscu-PA) and a bispecific MA directed against u-PA and against the beta-chain of human fibrin (MA-FU1-74), were investigated in baboons with a [125I]fibrin-labeled autologous blood clot in the femoral vein. Continuous intravenous infusion of rscu-PA/MA-FU1-74 (1:1.2 molar ratio) over 2 hours showed a fivefold increased thrombolytic potency (lysis per unit dose) over that of unconjugated rscu-PA, as evidenced both by a higher maximal rate of lysis (380% +/- 68% v 78% +/- 25% lysis per mg u-PA equivalent of compound administered per kg body weight, P less than .001), and by a lower dose at which the maximal rate of lysis occurs (0.19 +/- 0.03 v 0.82 +/- 0.10 mg compound per kg body weight, P less than .001). The specific thrombolytic activity (percent lysis per unit steady-state plasma u-PA antigen level) was lower for rscu-PA/MA-FU1-74 than for rscu-PA, as shown by both a lower maximal rate of lysis (60% +/- 13% v 220% +/- 22% lysis per microgram/mL u-PA antigen level in plasma, P less than .001) and a higher plasma antigen level at which maximal lysis is achieved (1.2 +/- 0.17 v 0.20 +/- 0.01 microgram/mL, P less than .001). The thrombolytic potency of rscu-PA/MA-UK1-3, an immunoconjugate of rscu-PA with the parental anti-u-PA antibody was similar to that of unconjugated rscu-PA. Clot lysis was achieved without systemic fibrinogen or alpha 2-antiplasmin consumption, and with a minor transient prolongation of the bleeding time. After the end of the infusions, u-PA-related antigen disappeared from plasma in a biphasic manner, with an initial half-life of 3.3 +/- 0.4 minutes for rscu-PA, 13 +/- 1 minutes for rscu-PA/MA-FU1-74, and 13 +/- 1 minutes for rscu-PA/MA-UK1-3, with corresponding plasma clearances of 340 +/- 28, 10 +/- 1, and 37 +/- 4 mL/min, respectively (mean +/- SEM). rscu-PA/MA-FU1-74 has a fivefold higher thrombolytic potency than unconjugated rscu-PA, as a result both of fibrin targeting by the specific idiotype of the antibody and of a slower plasma clearance.

Animals↗
PubMed1992

Ossification of the ligamentum flavum in the thoracolumbar spine of young adults report of two cases.

Ossification of the ligamentum flavum in the thoracolumbar spine is rare in young adults. We report two cases in 22 year old males who required surgical treatment. The first patient was obese and hyperinsulinaemic. He had a compression myelopathy below T11 due to extensive posterior ossification. The second patient had an osteoid osteoma of the right pedicle of T11 with ossification of the adjacent ligamenta flava. Both patients benefited from surgical decompression of the spine.

Adult↗
PubMed1992

Tay-Sachs disease: progression of changes on neuroimaging in four cases.

The neuroradiological findings in four patients with Tay-Sachs disease are described in three phases of the clinical course. The basal ganglia and cerebral white matter show low density on computed tomography and high signal intensity on T2-weighted magnetic resonance imaging in the initial phase. The caudate nuclei are characteristically enlarged and protrude into the lateral ventricles in the first and second phases. The cerebral white matter shows low density on the CT which varies in extent from the second to third phases, and the whole brain becomes atrophic in the last phase. Thus, central nervous system involvement in the disease may begin in basal ganglia as well as in cerebral white matter.

Atrophy↗
PubMed1992

Increased bone volume and reduced bone turnover in vitamin D-replete rabbits by the administration of 24R,25-dihydroxyvitamin D3.

To study the effect of a large dose of 24R,25(OH)2D3 on bone metabolism, we treated vitamin D-replete rabbits with the agent for eight weeks. Fifteen rabbits 20 weeks of age were divided into three groups of five animals each. Group I received only the vehicle; groups II and III were given the agent at doses of 10 micrograms/kg/d, and 100 micrograms/kg/d, respectively. Through the dosing period, serum calcium, phosphorus, alkaline phosphatase, and creatinine levels were not altered. By the end of the experiment, serum 1,25(OH)2D or serum 25(OH)D levels did not change, nor did the PTH level. Serum 24,25(OH)2D levels for groups I, II, and III were 5.25 +/- 3.40, 76.16 +/- 19.90 (p less than .01), and 199.0 +/- 30.90 (p less than .01) ng/ml, respectively. The bone mineral content (BMC) significantly increased in group III. The percentages of BMC increase in group III over group I were 14.5% on the femur, 34.1% (p less than .01) on the sixth lumbar vertebra, and 23.3% (p less than .05) on the seventh lumbar vertebra. A marked increase of bone mineral densities in the cancellous bone-rich regions was seen in group III. Bone histomorphometry on the seventh lumbar vertebra demonstrated that both the eroded surface and the osteoclast number were reduced and the surfaces indicating bone formation such as the osteoid surface and the tetracycline double labeled surface were also reduced. However, both the osteoid thickness and the mineral apposition rate increased and the mineral formation rate at the tissue level remained approximately equal to that in the control.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗
PubMed1992

Congenital focal muscle dysplasia in the lower extremities from probable abnormal innervation: a case report.

A two-year-seven-month-old girl with pes equinovarus congenita, muscle hypotonia and weakness limited to the lower extremities is presented. Upon admission to our hospital, she could stand with support but could not walk alone. Serum creatine kinase level was normal and the electromyogram was nondiagnostic. The muscle CT disclosed an almost total absence of bilateral vastus lateralis and medialis, rectus femoris and gastrocnemius muscles. The biopsied vastus lateralis muscle was almost completely replaced by fat tissue, and a small amount of muscle tissue showed uniform type 1 fiber and an aggregate of atrophic fibers in one fascicle. Because of an absence of progressive muscle weakness and neurogenic EMG findings, the authors conclude that the muscle pathology was due to the congenital anomalous condition of probable abnormal innervation to developing muscles.

Child, Preschool↗
PubMed1992

Elevated fibrinopeptide A (FPA) in patients with Lesch-Nyhan syndrome.

The detection of elevated fibrinopeptide A (FPA) level in a patient with the Lesch-Nyhan syndrome complicated with cerebral infarction prompted us to examine FPA level in 3 other patients with the syndrome. FPA level significantly increased in all patients. Fibrinopeptide B beta 15-42 (FPB beta 15-42) level was increased in two, and both beta-thromboglobulin (beta TG) and platelet factor 4 (PF4) levels were elevated in one patient. These results suggest coagulation abnormalities in patients with Lesch-Nyhan syndrome.

Adolescent↗
PubMed1992

The effect of dobutamine on hepatic blood flow and oxygen supply-uptake ratio during enflurane nitrous oxide anesthesia in humans undergoing liver resection.

Liver surgery is often accompanied by hepatic hypoperfusion and hypoxia, and it is controversial whether catecholamines increase hepatic blood flow and oxygen supply. The effects of 3 micrograms.kg-1.min-1 dobutamine on hepatic circulation and oxygen balance were examined in patients anesthetized with enflurane, nitrous oxide, and oxygen for liver surgery. Dobutamine did not cause a significant increase in hepatic arterial blood flow. However, total hepatic blood flow and portal venous blood flow were increased, resulting in an increase in hepatic oxygen delivery (HDO2). The increase in HDO2 was not associated with an improvement of hepatic oxygen supply-uptake ratio, since hepatic oxygen uptake (HVO2) also increased. After hepatectomy, the increases in portal venous blood flow and HDO2 were not accompanied by an increase in HVO2. The stimulation of hepatocellular oxygen metabolism by dobutamine and depressed responsiveness of adrenoceptors on hepatocytes in which metabolism was already augmented are the likely explanation for the different reactions before and after hepatectomy.

Adult↗
PubMed1992

Quantitation of three-dimensional deformity of idiopathic scoliosis.

Three-dimensional deformities in vertebrae of patients with idiopathic scoliosis were analyzed quantitatively using three-dimensional computed tomography. To evaluate the deformities, the vertebral lordosis and scoliosis were defined clearly. An average lordosis of 7.9 degrees and an average scoliosis of 6.8 degrees were calculated in 40 vertebrae near the top of the thoracic curve in 10 subjects with adolescent idiopathic scoliosis. Lordosis is characteristic of idiopathic scoliosis. Three-dimensional deformities in scoliotic patients cannot be represented precisely using the Cobb angle. A new technique for quantifying the three-dimensional deformities must be established.

Adolescent↗
PubMed1992

The role of calcium metabolism abnormalities in the development of ossification of the posterior longitudinal ligament of the cervical spine.

To study the role of calcium metabolism in the development of ossification of the posterior longitudinal ligament of the cervical spine, 39 patients with affected cervical spines were investigated using an oral calcium tolerance test and followed by cervical spinal radiography to evaluate disease progression. The average follow-up was 6 years. The patients were divided into two groups according to their responsiveness to an oral calcium load: a group of 14 patients with decreased calciuric responses and another group of 25 with normal responses. The incidence of the development of cervical ossification of the posterior longitudinal ligament in the decreased-response group was significantly higher than that in the normal group. Because these patients were managed operatively by laminoplasty, however, the incidence was low irrespective of their calciuric responses. These results suggest that the development of cervical ossification of the posterior longitudinal ligament is associated with decreased intestinal calcium absorption but that treatment with laminoplasty alters the mechanical environment of the cervical spine (eg, range of motion of the cervical spine is limited). The development of cervical ossification of the posterior longitudinal ligament may be controlled by this procedure.

Aged↗
PubMed1992

Immunohistochemical demonstration of bone morphogenetic protein-2 and transforming growth factor-beta in the ossification of the posterior longitudinal ligament of the cervical spine.

To clarify the mechanism of ossification of the posterior longitudinal ligament, immunohistochemical localization of bone morphogenetic protein-2 and transforming growth factor-beta was examined using surgical specimens of ligament tissues from an affected patient. Two polyclonal antibone morphogenetic protein-2 antibodies and an anti-human transforming growth factor-beta antibody were used as primary antibodies. Bone morphogenetic protein-2 and transforming growth factor-beta were present in ossified matrix and chondrocytes of adjacent cartilaginous areas of ossification of the posterior longitudinal ligament. Although immunostaining with antibone morphogenetic protein-2 antibodies also was observed in mesenchymal cells with fibroblastic features in the immediate vicinity of the cartilaginous areas, no staining could be detected with anti-human transforming growth factor-beta antibody in these cells. The presence of these factors were specific for the ossified ligament because no immunostaining was observed after using antibodies in the posterior longitudinal ligament at unossified levels from the same patient. It is suggested that bone morphogenetic protein-2 and transforming growth factor-beta play important roles in the development of ossification of the posterior longitudinal ligament and that bone morphogenetic protein-2 may act as an initiating factor in the development of ossification of the posterior longitudinal ligament by stimulating differentiation of mesenchymal progenitor cells. Transforming growth factor-beta may stimulate bone formation at a later stage of the process of ectopic ossification.

Aged↗
PubMed1992

Rotation vector, a new method for representation of three-dimensional deformity in scoliosis.

Rotation vector for three-dimensional deformity, a new concept in scoliosis, is presented. This vector quantifies three-dimensional deformity in scoliosis. Rotation vectors are calculated between pairs of end plates. Any three-dimensional malalignments (scoliosis, lordosis [or kyphosis] and rotation) existing between a pair of end plates should be cancelled perfectly by rotating one end plate against the other about an axis represented by the rotation vector. A rotation vector suggests how the deformity in scoliosis should be corrected three-dimensionally.

Adolescent↗
PubMed1992

Beneficial effects of cyclosporine on postischemic liver injury in rats.

The discovery of cyclosporine has had a significant impact on preventing the rejection of transplanted organs in humans. In this study, we present another positive aspect of cyclosporine. Rats were pretreated with cyclosporine (10 mg/kg, i.v.), or untreated. After 2-hr ischemia or 1 hr of reperfusion following 2-hr ischemia, livers were isolated and liver adenine nucleotide concentrations were determined. Liver mitochondria were prepared and their function was estimated polarographically. Leakage of AST, ALT, LDH, and adenine nucleotides into the hepatic vein just after reperfusion was also measured. Cyclosporine treatment did not affect ischemia-induced mitochondrial dysfunction, nor did it prevent the associated decrease in adenosine triphosphate concentration. However, treatment with cyclosporine accelerated the recovery of mitochondrial function and of tissue adenosine triphosphate concentrations. Cyclosporine treatment also mitigated leakage of AST, ALT, LDH, and adenine nucleotides after reperfusion. These results indicate that cyclosporine shows a potent protective effect on ischemia-reperfusion-related liver injury.

Adenine Nucleotides↗
PubMed1992

The effects of gamma-glutamylcysteine ethyl ester, a prodrug of glutathione, on ischemia-reperfusion-induced liver injury in rats.

This study was designed to clarify the effects of changes in liver tissue glutathione (GSH) concentration on postischemic liver injury together with the effects of gamma-glutamylcysteine ethyl ester (GCE), a prodrug of GSH, and GSH. Rats were pretreated with GSH (50 mg/kg, i.v.), or GCE (50 mg/kg, i.v.), or untreated. In each rat, liver was isolated, and liver mitochondria were prepared after 2 h of ischemia or 1 h of reperfusion following 2 h of ischemia. Mitochondrial function was measured polarographically. Liver adenine nucleotide concentrations were also determined using high-performance liquid chromatography. Liver tissue GSH, an oxidized form of glutathione (GSSG) concentrations, and activities of GSH peroxidase and GSSG reductase were determined enzymatically. Liver hypoxanthine and xanthine concentrations were determined by HPLC. Liver tissue concentration of lipid peroxide was measured. Leakages of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and adenine nucleotides into the hepatic vein after reperfusion were also measured. Administration of GCE improved the recovery of mitochondrial function and maintained tissue GSH concentration concomitantly. Increases in liver lipid peroxide concentration after reperfusion, and leakage of liver cell enzymes and adenine nucleotides were mitigated by administration of GCE. Administration of GSH itself failed to maintain tissue GSH concentration and had no protective effects. From these results, it is concluded that in the postischemic process, free radical formation might be enhanced, and the radical scavenging system deteriorated. To enhance the radical scavenging system is a possible maneuver to prevent radical-related cell damage associated with reperfusion, because pharmacological reduction of breakdown of ATP to hypoxanthine and xanthine seems to be difficult. GCE maintained liver GSH concentrations and mitigated postischemic liver injury, concomitantly. Clinical use of GCE might be recommended.

Adenine Nucleotides↗
PubMed1992

Polyoxyethylene-modified superoxide dismutase reduces side effects of adriamycin and mitomycin C.

Polyoxyethylene-modified superoxide dismutase (SOD-POE) is a newly developed long-acting superoxide dismutase. Adriamycin (ADR) and mitomycin C (MMC) generate superoxide, which contributes to their cytocidal effects or side effects. We examined whether SOD-POE could prevent the side effects induced by superoxide generated by antitumor agents, and the following results were obtained. SOD-POE did not influence the antitumor effects of ADR and MMC either in vitro or in vivo, but prevented the toxic death of BALB/c, nu/nu male mice caused by overdoses of ADR or MMC. As for its effective sites, SOD-POE prevented a decrease in the specific activity of rotenone-sensitive NADH-ubiquinone oxido-reductase (complex I) in heart muscle mitochondrial respiratory chain function in BALB/c male mice administered 10 mg/kg ADR, and prevented damage to the sarcoplasmic reticulum and mitochondria of mouse heart muscle by ADR as observed by electron microscopy. Furthermore, SOD-POE prevented bone marrow suppression induced by MMC in Donryu rats. The above results suggest that combination chemotherapy with SOD-POE would make it possible to increase the maximum permissible doses of antitumor agents, improving the efficacy of these agents.

Animals↗
PubMed1992

Partial seizures in two cases of metachromatic leukodystrophy: electrophysiologic and neuroradiologic findings.

This report concerns two cases of metachromatic leukodystrophy presenting partial seizures. One was a 2-year-old boy with a late infantile type and the other a 17-year-old girl with a juvenile type. The former had tonic-clonic seizures on the left with concomitant twitching of the left side of the face and adversive conjugate deviation of the eyes. After a while, his interictal sleep electroencephalogram (EEG) showed spikes in the right central area. The second case had hemiconvulsions on the right side, consisting mainly of tonic flexion of the upper limb followed by clonic flexions, and accompanied by adversive conjugate deviation of the head and eyes. Her ictal EEG showed rhythmic 6- to 7-Hz wave bursts in the left frontal area. To this date, no report has given a detailed discussion of the type of seizures and ictal EEG in metachromatic leukodystrophy. In addition, there have been few detailed reports of magnetic resonance imaging (MRI) in the juvenile type. It is interesting that typical partial seizures were observed in a hereditary metabolic disorder characterized by diffuse demyelination of the white matter, and the pathophysiology is discussed here mainly in relation to MRI findings of the case with the juvenile type.

Adolescent↗