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Biomedical subjects

A Fujiwara

Publications and source records attributed to A Fujiwara.

At least 37 records · Page 2Linked to original sources

Modulation of doxorubicin sensitivity by cyclosporine A in hepatocellular carcinoma cells and their doxorubicin-resistant sublines.

BACKGROUND AND AIMS: Cyclosporine A (Cys) and verapamil (Ver) sensitize multidrug-resistant (MDR) cells to various anticancer drugs by interacting with membrane glycoproteins involved in the drug efflux. In the present study, we assessed the effect of Cys on the modulation of doxorubicin (DOR) sensitivity in hepatocellular carcinoma (HCC) cell lines, and their DOR-resistant sublines. METHODS: The sensitivity to DOR and the chemosensitizing effects of Cys were assessed by using two human HCC cell lines, PLC/PRF/5 and Hep-3B, and their DOR-resistant sublines, PLC/DOR and 3B/DOR. The expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated protein (MRP) mRNA in these cells were detected by using a RT-PCR. The HCC cell lines grown in individual wells of 24-well plates were incubated with DOR that were sequentially diluted in culture medium in combination with 5 micromol/L Cys for 24 h. The cell viability in each well was measured by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: The mRNA of MDR1 and that of MRP were readily detectable in the HCC cell lines by RT-PCR. When 5 micromol/L Cys was added to the culture, the 50% inhibiting concentration (IC50) of DOR was reduced from 0.93 +/- 0.29 microg/mL to 0.32 +/- 0.10 microg/mL in PLC/PRF/5, and from 0.25 +/- 0.07 microg/mL to 0.09 +/- 0.04 microg/mL in Hep-3B. Furthermore, in the presence of 5 micromol/L Cys, the IC50 of DOR was reduced from 48.63 +/- 17.04 microg/mL to 0.49 +/- 0.14 microg/mL in PLC/DOR, and from 4.60 +/- 1.22 microg/mL to 0.15 +/- 0.06 microg/mL in 3B/DOR. The amounts of PCR products of MDR1 mRNA in PLC/DOR and 3B/DOR were greater than those in PLC/PRF/5 and Hep-3B, respectively. CONCLUSIONS: In HCC, the amplification of MDR1 mRNA is probably the main mechanism underlying acquired DOR resistance. Cyclosporine is also indicated to be highly active in potentiating the anticancer activity of DOR in HCC cells and their DOR-resistant sublines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Orientation and osteoarthritis of the lumbar facet joint.

Several studies have shown an association between sagittal orientation of the facet joint and degenerative spondylolisthesis. There is currently no information available on the association between orientation of the facet joint and osteoarthritis. This study examined the association between orientation and osteoarthritis of the lumbar facet joints. One hundred eleven consecutive patients underwent plain radiography and magnetic resonance imaging. These patients were divided into two groups: No Degenerative Spondylolisthesis Group (98 patients) and Degenerative Spondylolisthesis Group (13 patients). In the No Degenerative Spondylolisthesis Group, segments with higher grades of osteoarthritis showed more sagittal orientation of the facetjoints at the L3-L4 and L4-L5 levels. The facet joint was oriented significantly more sagittally in the Degenerative Spondylolisthesis Group than in the No Degenerative Spondylolisthesis Group at the L4-L5 and L5-S1 levels. The severity of facet joint osteoarthritis was significantly higher in the Degenerative Spondylolisthesis Group than in the No Degenerative Spondylolisthesis Group at the L3-L4, L4-L5, and L5-S1 levels. A significant association was found between sagittal orientation and osteoarthritis of the lumbar facet joints, even in patients without degenerative spondylolisthesis. Facet joint osteoarthritis, rather than spondylolisthesis, is the pathoanatomic feature that is associated with sagittal orientation of the facet joints in patients with degenerative spondylolisthesis.

Aged↗

Therapeutic effects of azathioprine in combination with low-dose prednisolone in patients with intractable autoimmune hepatitis type 1.

This study evaluated the effects of azathioprine in combination with low-dose prednisolone in the management of patients with intractable autoimmune hepatitis. Thirteen patients with intractable autoimmune hepatitis who had an incomplete or arrested response to conventional prednisolone therapy, or who relapsed during prednisolone maintenance therapy were additionally administered 50 or 100 mg/day of azathioprine in combination with prednisolone. This regimen reliably induced complete remission in 12 of 13 patients, and these 12 remained in remission during the follow-up period with maintenance therapy of 50 mg/day of azathioprine in combination with 5 mg/day of prednisolone. The findings of the current study indicate that the azathioprine and low-dose prednisolone combined therapy may offer a satisfactory alternative therapy for patients with intractable autoimmune hepatitis who have an incomplete or arrested response to conventional prednisolone therapy, or who relapse during prednisolone maintenance therapy.

Adult↗

Intracerebral hematoma due to ruptured nontraumatic middle meningeal artery aneurysm--case report.

A 77-year-old woman suddenly lost consciousness and presented with right hemiparesis. Computed tomography showed a large subcortical hematoma in her left frontal lobe associated with subarachnoid hemorrhage. The first impression was hemorrhage due to a ruptured aneurysm of the middle cerebral or the internal carotid artery on the left. Left internal carotid angiography showed no aneurysm or vascular anomaly, but back flow of contrast medium into the external carotid artery disclosed two saccular aneurysms arising from the anterior branch of the left middle meningeal artery (MMA). Emergent surgical intervention confirmed that the hematoma was due to ruptured MMA aneurysm. Nontraumatic MMA aneurysm should be recognized as a possible causative lesion of intracranial hemorrhage despite the extremely low incidence. External carotid angiography should be performed in patients with intracranial hemorrhage in whom no vascular cause can be detected in the internal carotid system.

Aged↗

The effect of disc degeneration and facet joint osteoarthritis on the segmental flexibility of the lumbar spine.

STUDY DESIGN: A biomechanical and imaging study of human cadaveric spinal motion segments. OBJECTIVE: To investigate the effect of both disc degeneration and facet joint osteoarthritis on lumbar segmental motion. SUMMARY OF BACKGROUND DATA: Spinal degeneration includes the osteoarthritic changes of the facet joint as well as disc degeneration. Disc degeneration has been reported to be associated with spinal motion. The association of facet joint osteoarthritis with lumbar segmental motion characteristics and the combined influence of disc degeneration and facet osteoarthritis has not yet been investigated. METHODS: A total of 110 lumbar motion segments (52 female, 58 male) from 44 human lumbar spines were studied (mean age = 69 years). Magnetic resonance images were used to assess the disc degeneration from Grade I (normal) to Grade V (advanced) and the osteoarthritic changes in the facet joints in terms of cartilage degeneration, subchondral sclerosis, and osteophytes. Disc height, endplate size, and facet joint orientation and width also were measured from the computed tomographic images. Rotational movements of the motion segment in response to the flexion, extension, lateral bending, and axial rotational moments were measured using a three-dimensional motion analysis system. RESULTS: Female motion segments showed significantly greater motion (lateral bending: P < 0. 001, flexion: P < 0.01, extension: P < 0.05) and smaller endplate size (P < 0.001) than male ones. The segmental motion increased with increasing severity of disc degeneration up to Grade IV, but decreased in both genders when the disc degeneration advanced to Grade V. In male segments, the disc degeneration-related motion changes were significant in axial rotation (P < 0.001), lateral bending (P < 0.05), and flexion (P < 0.05), whereas female segments showed significant changes only in axial rotation (P < 0.001). With cartilage degeneration of the facet joints, the axial rotational motion increased, whereas the lateral bending and flexion motion decreased in female segments. In male segments, however, motion in all directions increased with Grade 3 cartilage degeneration and decreased with Grade 4 cartilage degeneration. Subchondral sclerosis significantly decreased the motion (female: axial rotation, P < 0. 05; extension, P < 0.05 vs.- male:flexion,P < 0.05). Severity of osteophytes had no significant association with the segmental motion. CONCLUSION: Axial rotational motion was most affected by disc degeneration, and the effects of disc degeneration on the motion were similar between genders. Facet joint osteoarthritis also affected segmental motion, and the influence differed for male and female spines. Further studies are needed to clarify whether the degenerative process of facet joint osteoarthritis differs between genders and how facet joint osteoarthritis affects the stability of the spinal motion segment.

Cadaver↗

Wound healing acceleration of a novel transforming growth factor-beta inducer, SEK-1005.

The studies were carried out to elucidate the effect of a novel cyclic peptide, SEK-1005 (C(45)H(70)N(8)O(13)), on wound healing. SEK-1005 (4-10 microg/wound) applied topically significantly accelerated the healing of a full-thickness wound on the dorsal skin of a rat. In a healing-impaired mouse, the peptide (2-10 microg/wound) had more potent activity, exerting an effect comparable to that of basic fibroblast growth factor (FGF). However, SEK-1005 (0.1-100 ng/ml) scarcely promoted the proliferation of cultured fibroblasts (NIH3T3 cells) while basic FGF (0.2-5 ng/ml) showed marked mitogenic activity. SEK-1005 (2-10 microg/wound) significantly increased the topical production of transforming growth factor (TGF)-beta1, a cytokine that is known to accelerate wound healing. This activity was closely correlated with the wound-repairing effect. From the above, SEK-1005 can be considered as a new type of wound healing agent with potent TGF-beta1-inducing activity.

3T3 Cells↗

Anti-inflammatory action of a novel peptide, SEK-1005, isolated from a Streptomyces.

The pharmacological activity of a novel cyclic peptide (SEK-1005: C(45)H(70)N(8)0(13)) isolated from Streptomyces nobilis was studied in rats during the development of inflammation. SEK-1005 (0.1-0.5 mg/kg, i.p.) suppressed the passive Arthus reaction and the carrageenin-induced oedema. A steroidal anti-inflammatory drug, prednisolone (10 mg/kg, i.p.), also was effective on both inflammations. However, indomethacin (5 mg/kg, i.p.), a cyclooxygenase inhibitor, was less effective on the passive Arthus reaction. Also interesting was that the SEK-1005 effect showed its maximum level after a 24-h lag period and that its effect, as well as the prednisolone effect, was reduced by the treatment with a protein synthesis inhibitor, cycloheximide. SEK-1005 and prednisolone also showed marked protection against the adjuvant-induced arthritis, but failed to prevent the tuberculin response. These findings indicate that SEK-1005 is a new type of non-steroidal anti-inflammatory agent with an action similar to that of prednisolone.

Animals↗

The interspinous ligament of the lumbar spine. Magnetic resonance images and their clinical significance.

STUDY DESIGN: A preliminary study of magnetic resonance features of the interspinous ligament in degenerative lumbar spine. OBJECTIVES: To classify the magnetic resonance imaging features of the interspinous ligaments in relation to the patient's age, disc degeneration, and radiographic instability. Magnetic resonance imaging also was correlated with the histologic findings of the interspinous ligaments. SUMMARY OF BACKGROUND DATA: As reported, rupture of the interspinous ligament frequently is found in the degenerative lumbar spine. However, little information is available in the literature on imaging assessment of the interspinous ligament in degenerative lumbar disorders. METHODS: In this study, 24 interspinous ligaments at L1-L2 or L2-L3 from 15 patients with nondegenerated discs were selected to represent normal magnetic resonance features of the interspinous ligament, and 38 patients with the mean age of 49 years underwent functional radiography and magnetic resonance imaging. The magnetic resonance features of the interspinous ligament were classified into five categories according to their signal intensities: Type 1A (low intensity on T1- and T2-weighted images without hypertrophy of the spinal process); Type 1B (same signal pattern as in Type 1A with hypertrophy of spinal process); Type 2 (low intensity on T1- and high intensity on T2-weighted images); Type 3 (high intensity on T1-weighted images); and Type 4 (others). Seven patients with variable patterns of the interspinous ligament were selected to undergo histologic examinations. RESULTS: Of the interspinous ligaments considered normal, 80% were classified as Type 1A. There were 14 Type 1A, 30 Type 1B, 19 Type 2, 16 Type 3, and 20 Type 4 ligaments. The mean age and disc degeneration grade of the patients with the Type 1B ligaments was significantly higher. Instability was found to be associated with Type 2 interspinous ligaments (7 of 19), whereas instability rarely was noted in Types 1A (1 of 14) and 1B (1 of 30) ligaments. The histologic examination revealed that chondrometaplasia and necrotization of fiber bundle predominated in Type 1B, proliferation of cells and vascular invasion in Type 2, fatty degeneration in Type 3 ligaments. CONCLUSIONS: The magnetic resonance imaging characteristics may be helpful in assessing normal or pathologic changes in the interspinous ligaments.

Adolescent↗

Substance P-immunoreactive neurons in the rostromedian area of the midbrain send axons to the lower spinal cord in the chicken.

Substance P-immunoreactivity in neurons projecting to the spinal cord was examined using retrograde tract-tracing method combined with immunohistochemical techniques in chickens. Many small substance P-immunoreactive neurons were densely clustered in the midline area in the rostral midbrain, the rostromedian area (80% of the neurons in the rostromedian area). Some of these substance P-immunoreactive neurons in the rostromedian area (about 20% of substance P-immunoreactive neurons) were retrogradely labeled by small injections of wheat germ agglutinin conjugated horseradish peroxidase into the central part of the lumber segments including the intermediomedial nucleus, suggesting the projections from the rostromedian area to the lower spinal preganglionic regions. From the present data and mammalian previous studies, it was suggested that the midline area in the midbrain has fiber connections with the regions related autonomic functions, and all of which exhibit substance P-immunoreactivity.

Animals↗

Relationship between ATP level and respiratory rate in sea urchin embryos.

In sea urchin embryos, the rate of respiration, as a result of electron transport through the mitochondrial respiratory chain, was enhanced after hatching without any change in the intrinsic capacity of electron transport in mitochondria. The increase in respiratory rate after hatching was accompanied by an evident decrease in intracellular adenosine triphosphate (ATP) concentration without any change in intracellular levels of adenosine diphosphate (ADP) and adenosine monophosphate (AMP). Adenosine triphosphate is proposed to fortify acceptor control of respiration at high concentrations and to reduce the respiratory rate even in the presence of ADP, the acceptor. The relationships between the respiratory rate and intracellular ATP concentration in embryos were the same as those in mitochondria isolated from embryos, obtained in the presence of ADP at the same concentration as in the embryos. Probably, the respiratory rate is enhanced after hatching because of the decrease in the level of ATP. In embryos kept in a medium containing adenosine, intracellular ATP concentration increased especially after hatching, without any change in the ADP level, and the respiratory rate after hatching was made as low as the rate expected, based on the relationships obtained on isolated mitochondria. The respiratory rate in embryos probably depends on intracellular ATP concentration, irrespective of the developmental stage in early development.

Adenosine Triphosphate↗

Changes in the activities of protein phosphatase type 1 and type 2A in sea urchin embryos during early development.

In the eggs and embryos of sea urchins, the activity of protein phosphatase type 2A (PP2A) increased during the developmental period between fertilization and the morula stage, decreased after the prehatching blastula stage and increased again after hatching. The PP2A activity changed keeping pace with alteration to the activities of cAMP-dependent protein kinase (A kinase), Ca2+/calmodulin-dependent protein kinase (CaM kinase) and casein kinase. Probably, PP2A contributes to the quick turning off of cellular signals because of protein phosphorylation. The activity of protein phosphatase type 1 (PP1) was not detectable up to the morula stage and appreciably increased thereafter. In the isolated nucleus fraction, specific activities of PP1 and PP2A were higher than in whole embryos at all stages in early development. Exponential increase in the number of nuclei because of egg cleavage probably makes PP1 activity detectable in whole embryos after the morula stage. In isolated nuclei, the activities of PP1 and PP2A appreciably decreased after hatching, whereas the activities of A kinase, Ca2+/phospholipid-dependent protein kinase (C kinase) and CaM kinase, as well as casein kinase, became higher. In nuclei, cellular signals caused by protein phosphorylation after hatching do not seem to be turned off by these protein kinases so quickly as before hatching. The PP1 and PP2A in nuclei also seem to contribute to the elimination of signal noise.

Animals↗

The relationship between disc degeneration, facet joint osteoarthritis, and stability of the degenerative lumbar spine.

Degenerative processes in the disc and facet joints affect the stability of the motion segment. The exact relations among disc degeneration, facet joint osteoarthritis, and the kinematics of the motion segment are not well defined in the literature. Magnetic resonance imaging and functional radiography of the lumbar spine were analyzed to examine the relations among segmental instability, facet joint osteoarthritis, and disc degeneration in patients with degenerative disorders of the lumbar spine. Seventy consecutive patients (mean age, 46 years) had both magnetic resonance imaging and flexion and extension radiographs of the lumbar spine. The lumbar instability was classified into abnormal tilting on flexion, rotatory instability in the sagittal plane, and translatory instability. Translatory instability was subdivided into anterior, posterior, and anteroposterior translatory instability. Disc degeneration as seen on T2-weighted sagittal images was classified into five grades. Facet joint osteoarthritis as seen on axial T1-weighted images was divided into four grades. This study revealed that the kinematics of the lumbar motion segment are affected by disc degeneration and facet joint osteoarthritis. Abnormal tilting movement on flexion and anteroposterior translatory instability both had negative associations with facet joint osteoarthritis. However, anterior translatory instability was positively associated with disc degeneration and facet joint osteoarthritis. Rotatory instability in the sagittal plane and posterior translatory instability were not associated with disc degeneration and facet joint osteoarthritis.

Adolescent↗

Anatomy of the iliolumbar ligament.

Information is lacking in the literature on the precise anatomy of the iliolumbar ligament and its individual differences. The morphologic pattern, length, and width of the iliolumbar ligament were determined in 56 embalmed lumbosacral spines from human cadavers. It was possible to classify the iliolumbar ligament into two groups: Type A (74 ligaments), in which anterior and posterior ligaments had separate courses; and Type B (32 ligaments), in which anterior and posterior ligaments moved together as one band. The angle of the posterior iliolumbar ligament in Type A was oriented significantly more posteriorly than that in Type B. The posterior iliolumbar ligament was significantly shorter and oriented more posteriorly in male anatomic specimens than in female ones.

Aged↗

Stimulatory release of hepatic lipase activity from rat hepatocytes by ruthenium red.

Ruthenium Red (RuR; ruthenium oxychloride ammoniated) stimulated the release of hepatic lipase (HTGL) activity from primary cultured rat hepatocytes into medium in a time- and dose-dependent manner. The RuR-stimulated release of HTGL activity was suppressed by tyrosine kinase (TK) inhibitors (ST-638 and biochanin A). The activity of partially purified TK preparation from hepatocytes was found to be increased by incubation with RuR. In addition, treatment of the hepatocytes with H-89, a potent inhibitor of cAMP-dependent protein kinase (PKA), decreased the stimulatory release of HTGL activity by RuR. Moreover, cAMP content in RuR-incubated hepatocytes was rapidly increased, and activation of PKA was observed. The RuR-stimulated release of HTGL activity is also inhibited by uncouplers and glycosylation inhibitors. In addition, incorporation of [3H]leucine into protein was increased in the present of RuR. Under marked inhibition of protein synthesis by cycloheximide, RuR still showed a full effect on the release of HTGL activity. These results suggest that RuR stimulates the release of HTGL activity through mechanisms of action involving TK- and PKA-activating pathways, which require a metabolic energy-sensitive process rather than elevation of enzyme molecule synthesis.

Animals↗

The developmental study on lamination of the optic tectum in relation to the retinotectal projection in chicks and chick embryos.

The tectal lamination was investigated in the central part of the chick embryonic tectum. Two and 5 layers were observed above the neuroepithelium (NE) on embryonic day 6 (E6) and E8, respectively. Optic fibers extended on the surface of the tectum by E8. On E10-11, the outer tectum was composed of 2 layers, that is, a fibrous layer forming the optic fiber layer on the tectal surface and a cellular layer showing the gradient of cell density. In the inner tectum, the lamination was almost completed. On E12-13, the outer tectal layers, which showed the gradient of cell density, was divided into dark and light cellular layers. The dark cellular layer was divided into 2 layers on E14-15 and further into 4 layers (layer C-F in chick) on E18. On the other hand, the light cellular layer did not change until E18, but finally, it was divided into 2 layers (layer A and B in chick) by E20. Optic fibers reached the bottom of the outer tectum by E14 showing different densities of terminals. Stratification by optic fibers was going to step into the final stage on E18. On E20, laminations according to cytoarchitectural features and the optic fiber terminals were substantially completed. In the tectum affected by destruction of the contralateral embryonic eye (E4), some cellular layers were incompletely discriminated by differences of cell density.

Animals↗

Autoantibodies against oxidized low-density lipoprotein correlate with Achilles tendon xanthomas.

Although there is increasing evidence for anti-oxidized low-densitiy lipoprotein (LDL) autoantibodies in human sera, their diagnostic utility remains controversial. We examined the difference in autoantibody titers between patients with Achilles tendon xanthoma and control subjects. Fifteen hyperlipidemic patients with Achilles tendon xanthoma (group A+) and 94 hyperlipidemic patients without Achilles tendon xanthoma (group A-) were studied. Quantification of anti-oxidized LDL and anti-native LDL autoantibodies was performed using an ELISA method. To calculate antibody titers, we used the ratio between the spectrophotometric reading of anti-oxidized LDL and anti-native LDL wells. Using oxidized LDL that was purified by gel-permeation chromatography as antigen, immunoglobulin G level differed significantly between groups A+ and A- (p < 0.01). In contrast, using native and oxidized LDL as antigens without chromatographical purification revealed no significant difference between the two groups. Furthermore, immunoglobulin autoantibody titer did not correlate with age, body mass index, total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, or triglyceride in the entire group of subjects. Thus, immunoglobulin G autoantibody values appear to correlate with Achilles tendon xanthoma.

Achilles Tendon↗

[Three approaches to surgical treatment of traumatic disruption of the thoracic aorta].

Traumatic disruption of the thoracic aorta is said to occur most often near the aortic isthmus because of the mechanisms of aortic injury. Between November 1990 and August 1999, we encountered eight cases of surgical treatment for traumatic injury of the thoracic aorta combined with multi-system injury. In some cases, the injury was located near the aortic isthmus; in such cases, we selected surgical options that made use of three different approaches, namely, media sternotomy, posterolateral left thoracotomy, and anteroaxillal thoracotomy. Each approach has advantages and disadvantages. In selecting an appropriate approach, it is not only necessary to consider the various features of the approach itself, but it is also necessary to consider other factors, such as the assisting apparatus in use, the effects of other injuries sustained by perioperative positioning, safety measures against accidental bleeding during surgery, deployment of the operative field, and potential complications after surgery.

Adolescent↗