Bone regeneration and Mesenchymal stem cells

Bone marrow mesenchymal stem cells have been considered to differentiate into cells in bone, cartilage, tendon, muscle, and fat. Further analyses revealed that these cell also give rise to myocardial cells, oval cells and nerve cells, indicating high plasticity of these cells. Recent researches have been focused to utilize these cells to regenerate not only bone but also the life-maintaining major organs. As a cell source for the future regeneration of multiple organs, regeneration of the bone marrow is critical and thus studies on the process of bone marrow regeneration will benefit not only bone physiology field alone but also that of many other organs.     

Response of rabbit skeletal muscle to tibial lengthening

Background Experimental and clinical studies have provided knowledge regarding osteogenesis during limb lengthening. However, response of skeletal muscle to limb lengthening is not fully understood, especially as concerns histogenesis. We studied the morphological response of rabbit skeletal muscle to limb lengthening. In this study, we investigated proliferation of satellite cells, responsible for generation of new myonuclei, during limb lengthening. Methods Tibialis anterior muscles of young and adult rabbits were subjected to lengthening at a rate of 0.mm twice per day for 20 days. After lengthening, muscle wet weight was measured to assess skeletal muscle growth, then proliferating cell nuclear antigen was measured. Immunostaining was performed to analyze proliferating cells in the proximal, middle, and distal portions of the muscle belly and the musculotendinous junction. Results Muscle wet weight increased significantly after lengthening both in adult (0.4g) and young (0.1g) rabbits. Satellite cells showed proliferation in response to lengthening. In adult rabbits, satellite cell proliferation increased along the entire lengthened muscle to a similar degree (from 7.1% in the middle portion to 8.6% in the musculotendinous junction). In young rabbits, proliferation was greater in the musculotendinous junction (4.8%) than that in other muscle portions (2.3% in the middle and distal portions, and 2.4% in the proximal portion). In adult rabbits, the rate of increase in satellite cell proliferation was 1780% in the middle portion to 2860% in the musculotendinous junction, whereas the rate was between 210% in the middle portion and 290% in the distal portion in young rabbit. The rate of increase in cell proliferation by lengthening was higher in adult muscle than that in young muscles as well as satellite cell proliferation. Conclusion These findings indicate that limb lengthening promotes muscle growth in both young and adult rabbits.     

Correlations between both the expression levels of inflammatory mediators and growth factor in medial perimeniscal synovial tissue and the severity of medial knee osteoarthritis

An enhanced expression of the inflammatory mediators in the perimeniscal synovium in knee osteoarthritis (OA) has been suggested to contribute to progressive cartilage degeneration. However, whether the expression levels of these molecules correlated with the severity of OA still remained unclear. Medial perimeniscal synovial samples were obtained from 23 patients with Kellgren-Lawrence (K/L) grades 2 to 4 of medial knee OA. Immunohistochemical analysis of the synovium revealed that the MMP-1, COX-2 and IL-1β expression of the patients with K/L 4 to be significantly reduced in comparison to those with either K/L 2 or 3, while the TGF-β expression showed the opposite. The synovial expression of MMP-1 and IL-1β showed a significant negative correlation with the severity of OA, while that of TGF-β again showed the opposite. In conclusion, although synovial inflammation remained active, the MMP-1, COX-2 and IL-1β expression in synovium decreased depending upon the severity of OA, while the TGF-β expression increased.     

Congenital-idiopathic superficial femoral artery aneurysm in a 7-year-old child

Superficial femoral artery aneurysm in children is distinctly uncommon, and usually results from infection, vasculitis, connective tissue disorder, or trauma. We report a 7-year-old girl who had multiple fusiform aneurysms of the right superficial femoral artery, with no evidence of related disorders. The patient successfully underwent aneurysm resection and femoral artery reconstruction with autogenous saphenous vein. Histologic examination revealed intimal thickening with fibroplasia without severe inflammatory infiltrates or cystic medial necrosis, suggesting a congenital-idiopathic arterial aneurysm. Three years after the procedure, the saphenous vein graft is fully patent and the patient is in good condition.     

Effect of acute hepatic failure on the hepatic first‐pass effect of 5‐fluorouracil in rats

Objectives In cancer chemotherapy for hepatocellular carcinoma, 5‐fluorouracil is widely used and has typically been given by intrahepatic arterial (i.a.) infusion to increase treatment efficacy and reduce systemic toxicity. 5‐Fluorouracil is eliminated primarily by the liver and so the hepatic first‐pass effect after intrahepatic arterial administration of 5‐fluorouracil may be lower in patients with hepatic failure, and systemic toxicity may not be reduced. In this study, we have investigated the effect of acute hepatic failure on the first‐pass effect of 5‐fluorouracil in rats. Methods Experimental acute hepatic failure was induced by treatment with carbon tetrachloride (CCl₄). 5‐Fluorouracil was infused for 15 min into the hepatic artery or the saphenous vein of rats at a dose of 1.25 mg/kg. Key findings Hepatic availability in 50% CCl₄‐treated (severe hepatic failure) rats was higher than in controls. Conclusions The hepatic first‐pass effect after intrahepatic arterial administration of 5‐fluorouracil was lower in severe hepatic failure. Therefore, the reducing effect of the systemic toxicity after intrahepatic arterial administration may be lower in severe hepatic failure.     

Changes of fiber type ratio and diameter in rabbit skeletal muscle during limb lengthening

 Changes in the fiber-type ratio and diameter during limb lengthening in 10 adult rabbits were studied using histochemical techniques. Changes in the ratio and diameter of muscle fibers (classified as type 1, 2A, or 2B fibers) in tibialis anterior muscles were examined after 20% gradual distraction of the tibia. There was an increase in the number of type 1 fibers and a decrease in type 2B fibers after tibial lengthening. Moreover, the average diameter of the type 1 fibers increased, whereas that of the type 2B fibers decreased. The diameters of muscle fibers measured immediately after completion of the lengthening showed a tendency to recover to normal levels within 1 month; however, the ratio profile of the muscle fibers changed both immediately and 1 month after lengthening. The above results demonstrate that stretched skeletal muscle adapts differently to bone lengthening according to the type of muscle fibers present, resulting in qualitative changes in the fiber-type profile. Received: February 1, 2002 / accepted: August 26, 2002 Acknowledgments. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan. Offprint requests to: H. Yamazaki, 4-21-2 Kurakuen, Nishi-nomiya 662-0088, Japan     

Homologous recombination inquiry through ovarian malignancy investigations: JGOG3025 Study

The Cancer Genome Atlas (TCGA) network has clarified that ~50% of high-grade serous ovarian cancers show homologous recombination deficiency (HRD). However, the frequency of HRD in Japanese patients with ovarian cancer remains unclear. We aimed to identify the frequency of HR-associated gene mutations in Japanese patients with ovarian cancer. The JGOG3025 study is a multicenter collaborative prospective observational study involving 65 study sites throughout Japan. We recruited 996 patients who were clinically diagnosed with ovarian cancer before surgery from March 2017 to March 2019, and 701 patients were eligible according to the criteria. We used frozen tumor tissues to extract DNA and performed next-generation sequencing for 51 targeted genes (including 29 HR-associated genes) in 701 ovarian cancers (298 high-grade serous cases, 189 clear cell cases, 135 endometrioid cases, 12 mucinous cases, 3 low-grade serous cases, and 64 others). HRD was defined as positive when at least one HR-associated gene was mutated. The frequencies of HRD and tumor BRCA1/2 mutations were 45.2% (317/701) and 18.5% (130/701), respectively, in the full analysis set. Next, we performed multivariate Cox proportional hazards regression analysis for progression-free survival (PFS) and overall survival (OS). Advanced-stage ovarian cancer patients with HRD had adjusted hazard ratios of 0.72 (95% CI, 0.55–0.94) and 0.57 (95% CI, 0.38–0.86) for PFS and OS, respectively, compared with those without HRD (p = 0.016 and 0.007). Our study demonstrated that mutations in HR-associated genes were associated with prognosis. Further studies are needed to investigate the prognostic impact of each HR-associated gene in ovarian cancer.     

Medical emergency education using emergency care simulators in the School of Pharmaceutical Sciences

Clinical pharmacy training III (bedside training) in the School of Pharmaceutical Sciences, Kyushu University of Health and Welfare is intended to train pharmacists who can also cope with medical emergencies. Therefore we produced original scenarios that provide experience of various medical emergencies using emergency care simulators. As a result, these simulators enabled students to experience dealing with various medical emergencies such as cardiopulmonary resuscitation, automated external defibrillation (AED), adrenalin administration, and oxygen inhalation. In addition, a survey on the necessity for and the degree of the understanding of training contents associated with emergency care simulators was performed before and at the end of clinical training. After clinical training, the necessity for and the degree of the understanding of these training contents significantly increased (p<0.01). The introduction of emergency care simulators into clinical pharmacy training provides experience of not only cardiopulmonary resuscitation but also the treatment procedures as well as observation of improvement in the pathological condition after drug administration, which increases pharmacists' awareness of patient needs in drug therapy. Therefore these simulators are helpful for pharmacy education aiming at improving pharmacists' pharmaceutical care ability.     

Rolipram plus Sivelestat inhibits bone marrow-derived leukocytic lung recruitment after cardiopulmonary bypass in a primate model

Journal of Artificial Organs - Cardiopulmonary bypass (CPB) recovery is complicated by lung inflammation from bone marrow (BM)-derived polymorphonuclear leukocytes (PMNs) and monocytes (MO)....