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Biomedical subjects

Kozo Nakamura

Publications and source records attributed to Kozo Nakamura.

At least 37 records · Page 2Linked to original sources

Effect of GDF-5 on ligament healing.

The effects of growth and differentiation factor-5 (GDF-5) on ligament healing were studied using a gap injury model of the medial collateral ligament in rat knee joints. The administration of GDF-5 once at the time of surgery significantly improved the mechanical properties of the femur-ligament-tibia complex. At 3 weeks after surgery, 30 microg of GDF-5 improved the ultimate tensile strength of the complex by 41%, and the stiffness by 60%, compared with the vehicle control (p < 0.05 for both; Fisher's PLSD test). The observation with a transmission electron microscopy revealed that GDF-5 increased the diameter of collagen fibrils in the repair tissue, which was considered to be a possible mechanism for the positive result in the biomechanical testing. Quantitative PCR and in situ hybridization revealed enhanced type I procollagen expression by GDF-5, and the PCR analysis also revealed that the GDF-5 treatment reduced the expression of type III procollagen relative to type I procollagen. The PCR analysis further showed that the expression of decorin and fibromodulin was relatively reduced against type I procollagen by the growth factor, which was considered to be responsible for the increase of collagen fibril diameter in the repair tissue. No adverse effects were observed, and the use of GDF-5 was considered a promising approach to facilitate ligament healing.

Animals↗

Factors associated with mortality following hip fracture in Japan.

Various factors have been reported to increase the risk of death following hip fracture. However, our review of the literature indicates that previous studies were generally performed based on a rough classification of comorbidities. In this study, comorbidities were classified in detail, and the risk of death following hip fracture was investigated. Four hundred and eighty patients with hip fracture were enrolled. The patients' comorbidities and walking ability before injury were investigated using their own or their family's reports or their medical history, and the residences where the subjects were taken after discharge were recorded. Subsequently, the patients or their family were interviewed about whether they were alive or dead on January 1, 2002, by mail or telephone. A survival curve was drawn based on the Kaplan-Meier method. Cox proportional hazards regression models were used to determine the risk factors for death. An expected mortality rate for the Japanese population from 1991 to 2002 was obtained from a life table published by the Ministry of Health, Labour, and Welfare and compared to our observed mortality. The 1-year survival rate following hip fracture was 88.5%, which was a little lower than the expected survival rate. In subsequent years, the survival rate was lower than the expected survival rate. Being male and/or having a trochanteric fracture were risk factors for death. Patients who walked with a walker or other support or were nonambulatory before injury had an increased risk of death. Among the comorbidities, dementia, diabetes mellitus, and a history of gastrectomy or colonectomy were risk factors for death. Among the complications, pneumonia during hospitalization was a risk factor for death.

Body Mass Index↗

Decreased activities of daily living and associations with bone loss among aged residents in a rural Japanese community: the Miyama Study.

The present study aimed to clarify frequencies of decreased activities of daily living (ADL) and associations with rate of bone loss among inhabitants more than 60 years old in Miyama, a rural community in Japan. A cohort of 1543 inhabitants aged 40-79 years was established according to Miyama resident registrations in 1989. Men (n = 50) and women (n = 50) from each of two age strata between 60 and 79 years (N = 200) were selected from this cohort, and bone mineral density (BMD) of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry in 1990 (initial survey) and again in 1993, 1997, and 2000. Difficulties involving ADL were surveyed at every follow-up study. Of the 200 initial participants, 124 (57 men, 67 women; 62.0%) completed all BMD measurements and answered all items about ADL in the follow-up survey. The following items were investigated as a general indication of changes to ADL: reaching objects on a high shelf or cupboard (reaching); washing and drying the body (washing body); washing hair over a washbasin (washing hair); sitting for 1 h on a hard chair (sitting); raising the torso from a lying position in bed (raising); standing continuously for 30 min (standing); taking socks on and off the feet (taking socks); bending down from a seated position and picking up a small object at the side of the chair (bending); lifting heavy objects (lifting); and running 100 m without stopping (running). Among ADL items, the most frequent difficulties in men involved running (50.0%), followed by raising (30.6%), standing (27.1%), sitting (24.7%), and reaching (16.5%). In women, difficulties involved running (67.0%), followed by lifting (36.3%), standing (33.1%), reaching (30.8%), and sitting (23.6%). To evaluate relationships between decreased ADL and changes in BMD, annual rates of change for BMD at the lumbar spine and femoral neck were compared to changes for each ADL item (2 grade decrease; 1 grade decrease; or no change). Analysis of covariance (ANCOVA) was then performed on decreased ADL and annual bone changes after adjustment for age, concomitant disease (previous fractures, gastrectomy, diabetes mellitus, and renal dialysis at initial survey). In men, annual rates of change in BMD at the femoral neck over 10 years were significantly correlated with decreased abilities in bending (P = 0.046; R2 = 0.10). In women, annual rates of change in BMD at the lumbar spine over 10 years were significantly correlated with decreased abilities in reaching (P = 0.007; R2 = 0.25), and lifting (P = 0.014, R2 = 0.27), and those at the femoral neck were significantly correlated with decreased abilities in lifting (P = 0.001, R2 = 0.33).

Activities of Daily Living↗

Incidence and prognostic factors of Japanese breast cancer patients with bone metastasis.

BACKGROUND: Few previous studies have analyzed the incidence of bone metastases in a defined population of Japanese breast cancer patients and their prognosis after chemotherapy. METHODS: This is a retrospective cohort study. We investigated 695 patients who underwent surgery for breast cancer. The strategy of adjuvant therapy was as follows. Patients with both estrogen receptors (ERs) and progesterone receptors (PgRs) had endocrine therapy as initial adjuvant therapy (n = 239). Patients with neither ERs nor PgRs had chemotherapy. When metastasis to other organs, including bone, was identified, patients received chemotherapy. The survival rates after surgery and after the onset of bone metastasis, as well as the incidence of bone metastasis, were calculated. We also evaluated the prognostic and predictive factors. RESULTS: Bone metastases developed in 148 of 695 patients. All 148 received chemotherapy, and 121 of them developed spinal metastases. The 5-year survival rate after bone metastases was 26.1%. Prognostic factors for bone metastases were visceral metastases and PgR status. Cord compression was observed in 17 of the 148 patients, with the thoracic spine being the most common. The 1-year survival rate for patients with bone metastases who received chemotherapy was 66.3%, whereas that of patients with paralysis after spinal metastases was 17.6%. Within 6 months of the development of spinal cord compression, 70.6% of the patients died. CONCLUSIONS: We reported the incidence and prognostic factors for a defined population of Japanese breast cancer patients with bone and spinal metastases. Our results suggest that the expected survival time for patients with paralysis who received adequate endocrine therapy or chemotherapy is generally poor. However, to detect a predictive factor of long survival after paralysis and establish the indications for surgery, a comparative study among large groups of patients with paralysis and with different backgrounds is necessary.

Adult↗

Endoscopic anterior cruciate ligament reconstruction using a computer-assisted fluoroscopic navigation system.

BACKGROUND: During anterior cruciate ligament (ACL) reconstruction, placement of the reconstructed ligament affects the clinical results. To accomplish accurate and reproducible placement of the tibial bone tunnel, we employed a fluoroscopic navigation system for endoscopic ACL reconstruction. In this study, preciseness of the tibial tunnel placement was evaluated, and the advantages and disadvantages of this navigation system for endoscopic ACL reconstruction are discussed. METHODS: Altogether, 16 knees of 16 patients who had undergone ACL reconstruction using this system (navi group) were evaluated regarding the positioning of the tibial tunnel against Blumensaat's line using X-p and the route of the graft by magnetic resonance imaging (MRI). Another 16 knees of 16 patients who underwent endoscopic ACL reconstruction without the navigation system were the controls (control group). RESULTS: At the 1-year follow-up, maximally extended lateral knee X-p revealed that the anterior edge of the tibial tunnel and Blumensaat's line were almost aligned and that roof impingement was avoided; the T2-weighted MR images showed that the graft was placed close to and parallel to the intercondylar roof in all the knees of the navi group. The ratio of the distance between Blumensaat's line and the anterior edge of the tibial tunnel at the level of the tibial plateau to the anteroposterior width in fully extended true lateral radiographs was 2.7% +/- 3.4% in the navi group and 8.4% +/- 7.4% in the control group. CONCLUSIONS: The computer-assisted fluoroscopic navigation system improves accuracy and decreases dispersion of the tibial tunnel placement against Blumensaat's line in single-bundle ACL reconstruction. This innovative device renders the reconstruction procedure more reliable, eliminating the problem of skeletal variation among patients. However, the function of this navigation system for femoral tunnel placement is insufficient at present. Further refinement of the system is necessary, and the method of application requires improvement.

Adolescent↗

Clinical use of a newly developed calcium phosphate cement (XSB-671D).

BACKGROUND: Several kinds of thermally processed hydroxyapatite have been commonly used for bone defects due to bone diseases or fractures instead of autologous bone grafts. However, these materials do not change in form during surgery and are not absorbed over a long period. To overcome this disadvantage, calcium phosphate bone cements (CPCs) have been developed and are already in use in clinical cases. These materials have merit in that to be formed in situ they are injectable and absorbable, but there are still problems with their handling and their hardening properties. A newly developed CPC called XSB-671D hardens earlier and is more resistant to body fluids than other CPCs. The purpose of this article is to verify the effectiveness, safety and usefulness of this CPC (XSB-671D) as a bone defect filler. METHODS: We conducted clinical trials at five medical institutions based on a unified protocol in a total of 75 cases (30 males, 45 females). We observed the postoperative constitutional symptoms and local symptoms of the filling sites. The effectiveness of this material was evaluated by radiographs of the filled sites, and blood and urine were examined to evaluate any adverse effects. RESULTS: The ratio of the cases determined to be "effective" or "better" among the 74 cases we found qualified was 97.3%, and XSB-671D was confirmed to be a highly effective material with beneficial effects of biocompatibility and osteoconduction as a bone defect filler. Additionally, there were no adverse effects caused by XSB-671D except one local skin reaction, which disappeared 2 weeks later; its safety was also thus verified. CONCLUSIONS: We conclude that effective, safe treatment is possible using XSB-671D in cases requiring filling of a bone defect as well as those with serious osteoporosis.

Adult↗

Skin behavior during leg lengthening in patients with achondroplasia and hypochondroplasia: a short-term observation during leg lengthening.

BACKGROUND: Although distraction osteogenesis is a recently established method of limb lengthening, it is not well known how soft tissues behave during bone lengthening. Because skin is tissue that can be easily and directly observed, we analyzed skin extension during limb lengthening to study the condition of soft tissues. METHOD: We examined three achondroplastic and two hypochondroplastic patients who underwent bilateral tibial lengthening with unilateral bone lengtheners. To analyze skin extension during leg lengthening, the bilateral skin surface was marked in a latticework pattern, starting 10 cm proximal to the knee joint down to 10 cm distal to the ankle joint, with black ink. The longitudinal length and the area of lattices, and the circumferential length of legs were measured. RESULTS: We found that: (1) the longitudinal extension of the skin during leg lengthening occurs not only in the bone lengthening portion between fixator pins but also around the knee or ankle joints; (2) circumferential length of legs was decreased, and soft tissue volume also does not increase in proportion to the increase in leg length. Soft tissue volume started to increase in the central region of the legs after a 30% increase in leg length was obtained, resulting in the 10% increase in the volume at the end point. CONCLUSIONS: These data suggest that soft tissue extension precedes soft tissue neogenesis at least during the initial period of leg lengthening, possibly based on its viscoelastic properties. After a 30% increase in leg length is obtained, soft tissue neogenesis takes place in the central region of the leg.

Achondroplasia↗

Risk factors for knee osteoarthritis in Japanese men: a case-control study.

Risk of knee osteoarthritis (OA) was assessed in a population-based case-control study of Japanese men. The study covered three health districts in Wakayama and Osaka prefectures, Japan. Subjects were male individuals >or=45 years old diagnosed radiographically with knee OA, and who did not display any established causes of secondary OA. Controls selected randomly from the general population were individually matched to cases for age, sex, and residential district. Subjects were interviewed using structured questionnaires to determine medical history, physical activity, socio-economic factors, and occupation. Interviews were obtained from 37 cases and 37 controls. In univariate analysis, heaviest weight in the past and physical work such as factory, construction, agricultural, or fishery work as the principal occupation significantly raised the risk of male knee OA (P<0.05). Odds ratios (OR) were determined using conditional logistic regression analysis mutually adjusted for potential risk factors using the results of univariate analysis. Heaviest weight in the past (OR 6.01, 95% confidence interval (CI) 1.18-30.5, P<0.05), past knee injury (OR 6.25, 95% CI 1.13-34.5, P<0.05), and physical work as the principal occupation (OR 6.20, 95% CI 1.40-27.5, P<0.05) represented independent factors associated with knee OA after controlling for other risk factors. Physical work is associated with knee OA, demonstrating the influence of working activity on the development of OA. The present study suggests that risk factors for knee OA in men resemble those in women.

Aged↗

Encapsulation of chondrocytes in photopolymerizable styrenated gelatin for cartilage tissue engineering.

We have developed a photopolymerizable styrenated gelatin that can cross-link through polymerization induced by irradiation with visible light. The purpose of this study was to investigate the feasibility of using photopolymerizable styrenated gelatin as a cell carrier in chondrocyte transplantation. As visible light activates camphorquinone added as a photoinitiator, free radicals induce the polymerization of the gelatin macromer; the styrenated gelatin then becomes cross-linked. Rabbit articular chondrocytes were cultured in styrenated gelatin hydrogels and also in collagen gels as a control. After being cultured in the gels, the cells were collected from both gels and counted. Reverse transcriptase-polymerase chain reaction, histological examination, and quantification of the synthesized glycosaminoglycan were performed. On average, 26% of the embedded cells were collected from the gelatin hydrogel immediately after the crosslinking reaction. The surviving chondrocytes expressed the mRNA of type II collagen and aggrecan core protein and produced a cartilaginous matrix throughout the gelatin after 3 weeks. A slightly insufficient accumulation of the matrix was found in the internal region of the gelatin hydrogels, suggesting that less permeability for nutrients due to the high concentration and closely packed structure resulted in less cell viability. Although some limitations became evident, these results indicate that it may be possible to use photopolymerizable styrenated gelatin as a cell carrier in chondrocyte transplantation.

Animals↗

2006 Frank Stinchfield Award: grafting of biocompatible polymer for longevity of artificial hip joints.

Aseptic loosening induced by wear particles from the polyethylene liner is likely the most common cause of long-term total hip arthroplasty failure. We developed a novel hip polyethylene liner with the surface graft of a biocompatible phospholipid polymer, 2-methacryloyloxyethyl phosphorylcholine (MPC), and previously reported the grafting decreased the short-term production of wear particles and the subsequent bone resorptive responses. For clinical application, we investigated the stability of the 2-methacryloyloxyethyl phosphorylcholine grafting during sterilization and the wear resistance of the sterilized liner during longer loading comparable to clinical usage. Radiographic spectroscopy confirmed the stability of the 2-methacryloyloxyethyl phosphorylcholine polymer on the liner surface after the gamma irradiation. We used a hip wear simulator up to 1 x 10(7) cycles to test sterilized cross-linked polyethylene liners with and without 2-methacryloyloxyethyl phosphorylcholine grafting. The 2-methacryloyloxyethyl phosphorylcholine grafting markedly decreased the friction, the production of wear particles, and the wear of the liner surface. These data suggest a marked improvement in the wear resistance of the polyethylene liner by the 2-methacryloyloxyethyl phosphorylcholine grafting for clinically relevant periods after sterilization, indicating 2-methacryloyloxyethyl phosphorylcholine grafting is a promising technology for extending longevity of artificial hips.

Gamma Rays↗

Age-related changes in histogram pattern of anterior horn cells in human cervical spinal cord.

The purpose of the present study was to clarify age-related changes in histograms of spinal anterior horn cells. The study examined Rexed lamina IX of the C7 spinal cord segment in 22 men who had died of non-spinal disease (age range, 0-85 years). First, we confirmed that the size of nucleoli exhibited a linear relationship to the diameter of spinal anterior horn cells by preparing histograms of nucleoli. Second, this formula was used to create histograms of cervical anterior horn cells. Results were as follows: (i) diameter of nucleoli ranged from 2.0 microm to 6.0 microm; (ii) in each subject, no changes were seen in histogram patterns among ventral, intermediate, dorsal and overall sections; (iii) at < or =20 years of age, histograms displayed a single peak for the diameter of nucleoli at about 4.0-4.5 microm; (iv) at 21-60 years of age, histograms displayed two peaks, at about 3.5-4.0 microm and 5.0-5.5 microm; and (v) at 61-85 years of age, histograms displayed a single peak at about 5.0-5.5 microm.

Adolescent↗

Molecular mechanism of the life and death of the osteoclast.

The life span of osteoclasts is critically regulated by various cytokines, and therapeutics such as bisphosphonates act directly on osteoclasts and induce apoptosis of the cells. This article will focus on the molecular mechanism of osteoclast apoptosis and summarize the recent advances in this field with an emphasis on the role of intracellular signaling pathways.

Animals↗

Signaling axis in schwann cell proliferation and differentiation.

Recent progress in molecular biology has markedly expanded our knowledge of the molecular mechanism behind the proliferation and differentiation processes of Schwann cells, the myelin-forming cells in peripheral nervous systems. Intracellular signaling molecules participate in integrating various stimuli from cytokines and other humoral factors and control the transcriptional activities of the genes that regulate mitosis or differentiation. This article provides an overview of the roles played by the intracellular pathways regulating Schwann cell functions. In Schwann cell proliferation, cyclic adenosine monophosphate signals and mitogen-activated protein kinase pathways play pivotal roles and may also interact with each other. Regarding differentiation, myelin formation is regulated by various cytokines and extracellular matrix molecules. Specifically, platelet-derived growth factor, neuregulin, and insulin-like growth factor-I all are classified as ligands for receptor-type tyrosine kinase and activate common intracellular signaling cascades, mitogen-activated protein kinase pathways, and phosphatidylinositol-3-kinase pathways. The balance of activities between these two pathways appears crucial in regulating Schwann cell differentiation, in which phosphatidylinositol-3-kinase pathways promote myelin formation. Analysis of these signaling molecules in Schwann cells will enable us not only to understand their physiological development but also to innovate new approaches to treat disorders related to myelination.

Animals↗

[Interactions of chondrocytes and osteoblasts during endochondral bone formation].

During endochondral bone formation, mesenchymal condensations, chondrocyte differentiation and proliferation, termination of proliferation, hypertrophic differentiation, and replacement by bone occur sequentially. This sequence is spatially represented by the structure of the growth plate of the embryo, and reflects the evolution of bone. Endochondral bone formation is mainly regulated by the interactions of chondrocytes and osteoblasts; a variety of signals are implicated in this regulation. The roles of factors regulating chondrocyte proliferation and hypertrophy including the Sox trio, PTH related peptide (PTHrP), Indian hedgehog (Ihh), the runt-related transcription factor (Runx) family, fibroblast growth factor receptor 3 (FGFR3) and bone morphogenetic protein (BMP) and other factors including hypoxia-inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) will be discussed.

Animals↗