Biomedical subjects

T Ochi

Publications and source records attributed to T Ochi.

At least 55 records · Page 3Linked to original sources

PubMed2000

Rheumatoid arthritis synovial stromal cells inhibit apoptosis and up-regulate Bcl-xL expression by B cells in a CD49/CD29-CD106-dependent mechanism.

Inflammatory sites, such as rheumatoid arthritis (RA) synovial tissue, contain large numbers of activated B cells and plasma cells. However, the mechanisms maintaining B cell viability and promoting their differentiation are not known, but interactions with stromal cells may play a role. To examine this, purified human peripheral B cells were cultured with a stromal cell line (SCL) derived from RA synovial tissue, and the effects on apoptosis and expression of Bcl-2-related proteins were analyzed. As a control, B cells were also cultured with SCL from osteoarthritis synovium or skin fibroblasts. B cells cultured with medium alone underwent spontaneous apoptosis. However, B cells cultured with RA SCL cells exhibited less apoptosis and greater viability. Although SCL from osteoarthritis synovium and skin fibroblasts also rescued B cells from apoptosis, they were less effective than RA SCL. B cell expression of Bcl-xL was markedly increased by RA SCL in a contact-dependent manner, whereas B cell expression of Bcl-2 was unaffected. Protection of B cells from apoptosis and up-regulation of Bcl-xL by RA SCL were both blocked by mAbs to CD106 (VCAM-1), but not CD54 (ICAM-1). Furthermore, cross-linking of CD49d/CD29 (very late Ag-4) on the surface of B cells rescued them from apoptosis and up-regulated Bcl-xL expression. These results indicate that SCL derived from RA synovial tissue play a role in promoting B cell survival by inducing Bcl-xL expression and blocking B cell apoptosis in a CD49d/CD29-CD106-dependent manner.

Adult↗

PubMed2000

Decorin antisense gene therapy improves functional healing of early rabbit ligament scar with enhanced collagen fibrillogenesis in vivo.

Injured ligaments heal with scar tissue, which has mechanical properties inferior to those of normal ligament, potentially resulting in re-injury, joint instability, and subsequent degenerative arthritis. In ligament scars, normal large-diameter collagen fibrils have been shown to be replaced by a homogenous population of small collagen fibrils. Because collagen is a major tensile load-bearing matrix element and because the proteoglycan decorin is known to inhibit collagen fibrillogenesis, we hypothesized that the restoration of larger collagen fibrils in a rabbit ligament scar, by down-regulating the proteoglycan decorin, would improve the mechanical properties of scar. In contrast to sense and injection-treated controls, in vivo treatment of injured ligament by antisense decorin oligodeoxynucleotides led to an increased development of larger collagen fibrils in early scar and a significant improvement in both scar failure strength (83-85% improvement at 6 weeks; p < 0.01) and scar creep elongation (33-48% less irrecoverable creep; p < 0.03) under loading. This is the first report that in vivo manipulation of collagen fibrillogenesis improves tissue function during repair processes with gene therapy. These findings not only suggest the potential use of this type of approach to improve the healing of various soft tissues (skin, ligament, tendon, and so on) but also support the use of such methods to better understand specific structure-function relationships in scars.

Animals↗

PubMed2000

Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: A novel neuronal marker of nerve injury.

Activating transcription factor 3 (ATF3), a member of ATF/CREB family of transcription factors, is induced in a variety of stressed tissue. ATF3 regulates transcription by binding to DNA sites as a homodimer or heterodimer with Jun proteins. The purpose of this study was to examine the expression and regulation of ATF3 after axonal injury in neurons in dorsal root ganglia (DRG) and spinal cord. In naive rats, ATF3 was not expressed in the DRG and spinal cord. Following the cut of peripheral nerve, ATF3 was immediately induced in virtually all DRG neurons and motoneurons that were axotomized, and the time course of induction was dependent on the distance between the injury site and the cell body. Double labeling using immunohistochemistry revealed that the population of DRG neurons expressing ATF3 included those expressing c-jun, and in motoneurons ATF3 and c-jun were concurrently expressed after axotomy. In contrast to c-jun, ATF3 was not induced transsynaptically in spinal dorsal horn neurons. We conclude that ATF3 is specifically induced in sensory and motoneurons in the spinal cord following nerve injury and should be regarded as an unique neuronal marker of nerve injury in the nervous system.

Activating Transcription Factor 3↗

PubMed2000

[Humeral lengthening and deformity correction].

Nine patients with achondroplasia and one patient with Apert syndrome underwent the surgical lengthening of both humerus and simultaneous correction of both associated bone deformity. An unilateral external fixator was applied to the lateral aspect of the humerus with four half-pins and percutaneous predrilling osteotomy was performed at the apex of flexion deformity of the bone. During the waiting period before distraction, the flexion deformity of the distal humerus was corrected using an additional external fixator. Slow gradual distraction was subsequently carried out at a rate of 0. 25 mm every 6 hours. The average lengthening was 8 cm (range 7.5 to 9 cm), the overall treatment time 312 days (range 192 to 406 days), and the average healing index 39.0 days/cm. The average correction of the elbow flexion deformity was 20 degrees. We believe this treatment is useful to improve the function of the arms and the activity of daily living for the patients with bilateral short humeri.

Achondroplasia↗

PubMed2000

Prostaglandin E1 improves hepatic encephalopathy produced by ischaemia-reperfusion liver injury in rats.

OBJECTIVE: To investigate the action of prostaglandin E1 on hepatic encephalopathy. DESIGN: Prospective, randomised, controlled animal study. SETTING: University animal laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: After passive avoidance learning, acute liver failure was induced by occlusion of the left portal vein and the hepatic artery for 90 min. Then memory retention was evaluated 48 h later. The effects of prostaglandin E1 on memory retention were examined in animals treated with the agent systemically (intravenous injections with prostaglandin E1 twice before and after surgery, 20 microg/kg each time) and animals treated with the agent topically (intracerebroventricular injection with prostaglandin E1, 0.1 microg/h for 48 h beginning at liver ischaemia). MEASUREMENTS AND RESULTS: Marked damage was found on plasma analysis in animals subjected to liver ischaemia, and the memory retention was also impaired. Intravenous administration of prostaglandin E1 improved both the liver injury and memory retention. However, intracerebroventricular administration of prostaglandin E1 alleviated neither. CONCLUSION: These findings show that prostaglandin E1 contributes to the amelioration of hepatic encephalopathy by improving liver function.

Alprostadil↗

PubMed2000

MR findings of necrotic lesions and the extralesional area of osteonecrosis of the femoral head.

OBJECTIVE: To investigate the MR findings of necrotic lesions and the extralesional area of osteonecrosis of the femoral head (ONFH) for each of the radiological stages. DESIGN AND PATIENTS: Forty-nine hips in 29 patients (15 female, 14 male; mean age 38 years, range 17-59 years) were imaged using a 1.0-T superconducting magnet. T2-weighted spin echo pulse sequences (T2WI), spoiled gradient recalled echo pulse sequences (SPGR) and fat suppression SPGR (FS-SPGR), followed by Gd-DTPA enhanced fat suppression SPGR (Gd-FS-SPGR), were all obtained with the aid of a TORSO surface coil. RESULTS AND CONCLUSIONS: While a normal fat intensity area with a low-intensity band on SPGR (band pattern) was seen in 16 of 16 stage 1 (100%), nine of 11 stage 2 (82%), four of 17 stage 3 (24%), and none of five stage 4 hips, all hips showed peripheral rim enhancement on Gd-FS-SPGR (100%). This enhancement band on Gd-FS-SPGR corresponded to histological findings of necrotic trabecular bone, repaired marrow, and fibrous reparative tissue. Bone marrow edema was also clearly demonstrated as a diffuse, high-intensity area outside this enhancement band on Gd-FS-SPGR in two stage 2 (18%), 12 stage 3 (71%), and one stage 4 hip (20%). In cases at stage 2 or more advanced stages with homogeneous or inhomogeneous low intensity on nonenhanced MRI, the reparative process both inside and outside the necrotic lesion, including bone marrow edema, was detected clearly on contrast-enhanced MRI.

Adolescent↗

PubMed2000

Congenital transverse deficiency of the tibia and fibula: a report of two cases.

We report two similar, but unrelated, patients with congenital bilateral partial deficiencies of the tibia and fibula associated with intact feet. In both patients, the tibia and fibula were absent on initial radiographs, while the femur and the tarsal bones were well developed and there was bilateral teratologic dislocation of the hips. Ultrasound and magnetic resonance imaging (MRI) studies suggested the presence of cartilaginous remnants of the tibia and fibula. There were multidirectional instabilities in the knees and ankles. The clinical and radiological features of these cases are distinct from those of congenital longitudinal deficiency of the tibia, in which the fibula is always preserved, and from longitudinal deficiency of the fibula, in which the tibia is present and the foot is usually involved. We suggest that the bilateral partial deficiencies of the tibia and fibula associated with the intact foot and teratologic dislocation of the hips is a single-entity disorder, possibly categorized as an intercalary transverse deficiency of the lower limb.

Abnormalities, Multiple↗

PubMed2000

Matrix metalloproteinases in patients with osteoarthritis of the hip.

In 78 patients undergoing a total hip replacement we examined the production of matrix metalloproteinases (MMP) by the fibroblasts from the connective tissue of the acetabulum; we then correlated these findings with clinical and radiological characteristics of the same patients. In 53 patients only MMP-2 was produced; in 15 cases MMP-1, -2 and -3 were present; and in 10 cases not only MMP-1, -2, -3 but also MMP-9. Significant differences among the clinical and radiological parameters were found in the 3 subsets. A positive correlation between the production of MMP-9 and a rapid destruction of the hip joint was found.

Adolescent↗

PubMed2000

Bone marrow CD34+ progenitor cells from rheumatoid arthritis patients support spontaneous transformation of peripheral blood B cells from healthy individuals.

We show that bone marrow (BM) CD34+ progenitor cells from rheumatoid arthritis (RA) patients have the capacity to support spontaneous transformation of peripheral blood B cells. CD34+ cells purified from BM blood from eight RA patients and eight osteoarthritis (OA) patients were expanded with granulocyte/macrophage colony stimulating factor (GM-CSF) for 4-6 weeks. GM-CSF-stimulated BM CD34+ cells from three of eight RA patients, but none from seven OA patients, gave rise to spontaneous transformation of highly purified B cells of Epstein-Barr virus (EBV)-seronegative healthy donors. GM-CSF-stimulated BM CD34+ cells from four of six RA patients and from one of four OA patients also supported the spontaneous transformation of peripheral blood B cells from EBV-seropositive healthy donors. All the transformed B cell lines were positive for EBV-DNA as determined by PCR. Neither GM-CSF-stimulated BM CD34+ cells alone nor highly purified B cells alone gave rise to spontaneously transformed B cell lines. These results suggest that the capacity of BM CD34+ cells to support survival of B cells might contribute to the pathogenesis of RA by sustaining abnormal B cell responses.

Antigens, CD19↗

PubMed2000

Pathology of femoral head collapse following transtrochanteric rotational osteotomy for osteonecrosis.

We investigated the pathology of femoral head collapse following transtrochanteric anterior rotational osteotomy. Six femoral heads were obtained during total hip arthroplasty some 2-12 years after osteotomy. In all cases, the preoperatively necrotic lesions exhibited mostly osteonecrosis with accumulation of bone marrow cell debris and trabecular bone with empty lacunae, although repair tissue such as granulation tissue and appositional bone formation were observed in limited areas in some cases. In the transposed intact articular surface of the femoral head, osteoarthritic changes such as fissure penetration to the subchondral bone and osteophyte formation were commonly observed. In newly created subchondral areas at weight-bearing sites, trabecular thickness and the number of trabecular bones had decreased, with few osteoblasts, osteoclasts, and osteocytes being present, resulting in a coarse lamellar structure of the trabecular bone. These findings suggest that transposed areas in cases of failure consist mostly of low-turnover osteoporotic lesions which could cause collapse of the femoral head.

Adult↗

PubMed2000

Therapeutic effect of transtrochanteric rotational osteotomy and hip arthroplasty on quality of life of patients with osteonecrosis.

We reviewed 37 patients with avascular necrosis of the femoral head (ANF). There were 23 men and 14 women with a mean age of 36 years at the time of the operation. The duration of follow-up was 9 years. Twenty patients had undergone transtrochanteric rotational osteotomy (TRO) and 17, hip arthroplasties. Assessment of their quality of life (QoL) was performed using the Rosser Index Matrix for disability and distress. Concerning TRO, the mean preoperative and postoperative QoL scores were 0.944 and 0.957, respectively. Twelve patients exhibited increases and 7 patients decreases in their scores. Regarding the arthroplasty, the mean preoperative and postoperative QoL scores were 0.949 and 0.998, respectively. All patients showed increases in QoL scores after arthroplastic surgery. Concerning heavy manual work, all five of those patients returned to their preoperative occupations. These findings suggest that hip arthroplasty has more reliable therapeutic effects than TRO on QoL improvement for patients with ANF.

Adult↗

PubMed2000

Immunohistochemical detection of cathepsin D, K, and L in the process of endochondral ossification in the human.

Cathepsins D, K, and L were immunolocalized in tissue undergoing endochondral ossification in the human. Cathepsins D, K, and L were localized in osteoclasts and chondroclasts attached to bone matrix and cartilage matrix, respectively. Cathepsins D and L were immunostained in chondrocytes. Immunolocalization of cathepsin D was limited to hypertrophic chondrocytes adjacent to the osteochondral junction. In contrast, cathepsin L was immunolocalized in both proliferating and hypertrophic chondrocytes. In the bone marrow space, cathepsins D, K, and L were localized in multinucleated cells. Cathepsin D was diffusely detected in mononuclear bone marrow cells which were negative for cathepsins K and L. The present findings indicated that cathepsins K, D, and L were associated with the process of endochondral ossification in the human, and suggested that these cathepsins share roles in bone and cartilage turnover in the human.

Bone Marrow↗

PubMed2000

Identification of 142 single nucleotide polymorphisms in 41 candidate genes for rheumatoid arthritis in the Japanese population.

Single-nucleotide polymorphisms (SNPs) can make an important contribution to our understanding of genetic backgrounds that may influence medical conditions and ethnic diversity. We undertook a systematic survey of genomic DNA for SNPs located not only in coding sequences but also in non-coding regions (e.g., introns and 5' flanking regions) of selected genes. Using DNA samples from 48 Japanese patients with rheumatoid arthritis (RA) as templates, we surveyed 41 genes that represent candidates for RA, screening a total of 104 kb of DNA (30 kb of coding sequences and 74 kb of non-coding DNA). Within this 104 kb of genomic sequences we identified 163 polymorphisms (1 per 638 bases on average), of which 142 were single-nucleotide substitutions and the remainder, insertions or deletions. Of the coding SNPs, 52% were non-synonymous substitutions, and non-conservative amino acid changes were observed in a quarter of those. Sixty-nine polymorphisms showed high frequencies for minor alleles (more than 15%) and 20 revealed low frequencies (<5%). Our results indicated a greater average distance between SNPs than others have reported, but this disparity may reflect the type of genes surveyed and/or the relative ethnic homogeneity of our test population.

Alleles↗

PubMed2000

A technique of percutaneous multidrilling osteotomy for limb lengthening and deformity correction.

We have recently developed a technique of per-cutaneous multidrilling osteotomy for limb lengthening and deformity correction. The bone is drilled percutaneously, using a special drill guide, and osteotomy is accomplished by connecting the multiple drill holes with a small chisel. The bone segments are subjected to slow progressive distraction with an external fixation device. We have lengthened 33 limbs in 22 patients with congenital or post-traumatic limb shortening and/or bone deformities. All the patients underwent the proposed lengthening and/or correction of the bone deformities through a single-treatment procedure. None of the lengthened segments resulted in nonunion. This technique can prevent undesirable bone cracks and preserve soft tissue around the osteotomy site, and is also applicable to other fields of orthopedic surgery.

Adolescent↗

PubMed2000

Optimizing femoral anteversion and offset after total hip arthroplasty, using a modular femoral neck system: an experimental study.

To investigate the effectiveness of a modular femoral neck system, consisting of two neutral and four types of retroverted necks for the correction of femoral anteversion and offset in total hip arthroplasty, an experimental study was carried out, using sawbones with four different angles of femoral anteversion (16 degrees, 34 degrees, 47 degrees, and 59 degrees ). With the neutral neck, reconstruction of the preoperative anteversion and offset in the normal femur was achieved. While the 15 degrees retroverted long neck was effective for the mildly or moderately anteverted femur, this retroverted neck showed insufficient correction for the severely anteverted femur. This modular neck system proved to be useful for correction of the medial component of femoral offset in femora with anteversion of less than 47 degrees. For patients with greater anteversion, a feature which is rarely seen in the clinical situation, femoral necks with a greater degree of retroversion may be useful.

Arthroplasty, Replacement, Hip↗

PubMed2000

A novel type X collagen gene mutation (G595R) associated with Schmid-type metaphyseal chondrodysplasia.

Metaphyseal chondrodysplasia of the Schmid type (MCDS) is a skeletal dysplasia affecting the long bone metaphyses; it is characterized by short stature, bowlegs, and coxa vara. The spine is generally not involved. Here we report a novel missense mutation of the type X collagen gene in a sporadic case of MCDS. The mutation was a heterozygous single base-pair transition of G-to-A at nucleotide 1783, which predicted a substitution of glycine by arginine at codon 595 (G595R) in the carboxyl-terminal noncollagenous domain. Interestingly, another mutation of the same codon, in which glycine is substituted by glutamic acid (G595E), was previously reported to cause spondylometaphyseal dysplasia (SMD), another group of skeletal dysplasias with involvement of the spine in addition to the long tubular bones. The novel G595R mutation identified in the present study supports the concept of type X collagenopathy.

Adolescent↗

PubMed2000

The spinal antinociceptive effect of FR140423 is mediated through kyotorphin receptors.

We investigated the antinociceptive effect of a novel anti-inflammatory and analgesic drug, 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyraz ole (FR140423), in the tail-pinch test in mice, and evaluated the mechanism of action of FR140423 using L-leucyl-L-arginine (Leu-Arg), a kyotorphin (endogenous Met-enkephalin releaser) receptor antagonist, L-NG-nitroarginine methylester (L-NAME), an inhibitor of nitric oxide (NO) synthase, and methylene blue (MB), an inhibitor of activation of guanylate cyclase. Oral administration of FR140423, at doses of 5-80 mg/kg, produced a dose-dependent antinociceptive effect with an ED50 value of 18 mg/kg. This antinociception was reversed by intrathecal (i.t.) (10 microg/mouse), but not by intracerebroventricular (i.c.v.) (100 microg/mouse), injection of Leu-Arg. Moreover, the antinociceptive effect of i.t. injection of FR140423 with an ED50 value of 3.7 microg/mouse was completely antagonized by co-administered Leu-Arg 10 microg/mouse. However, L-NAME (2000 mg/kg s.c.) and MB (200 mg/kg s.c.) did not antagonize the antinociception of FR140423. These findings suggest that FR140423 plays a role in nociceptive modulation in the spinal cord, being antinociceptive via the kyotorphin-Met-enkephalin pathway but not via the peripheral NO-cyclic GMP pathway.

Analgesics, Opioid↗

PubMed2000

Left ventricular mass and atrial volume determined by cine magnetic resonance imaging in essential hypertension.

To evaluate the relationship between left atrial volume determined by cine magnetic resonance imaging and progression of left ventricular hypertrophy (LVH), left atrial volume and echocardiographic left ventricular mass (LVM) were measured in 30 hypertensive patients (15 without LVH and 15 with LVH) and 10 normotensive control subjects. We also evaluated the effects of antihypertensive therapy on the cardiac chamber volumes and LVM in hypertensive patients. The cardiac chamber volumes and LVM were indexed by body surface area. Although there were no significant differences in left ventricular chamber volumes among the three groups, both maximum and minimum left atrial volume indexes, and the LVM index were greater in hypertensive patients with LVH than in the other two groups. The LVM index was correlated with maximum left atrial volume index (r = 0.74, P < .0001), and minimum left atrial volume index (r = 0.76, P < .0001), respectively. Furthermore, in multivariate models, the LVM index was significantly correlated with maximum left atrial volume index. In hypertensive patients with LVH, both maximum and minimum left atrial volume indexes, and the LVM index significantly reduced after treatment. The percent of changes in maximum left atrial volume index after treatment was significantly correlated with the percent of changes in LVM index after treatment. In conclusion, our data indicate that LVH is an independent determinant of left atrial enlargement, and both LVH and left atrial enlargement may be reversed by some effective therapeutic interventions.

Antihypertensive Agents↗