Anatomical study of the articular branches innervated the hip and knee joint with reference to mechanism of referral pain in hip joint disease patients

Introduction : Referred pain in the anterior knee joint is the most common symptom in hip disease patients. The development of referred pain is considered to be related to dichotomizing peripheral sensory fibers. However, no gross anatomical findings identify any dichotomizing fibers innervating both the hip and knee joints. We dissected the femoral and obturator nerves in human cadavers to investigate the distribution of the articular branches in the hip and knee joints. Fourteen embalmed left lower limbs from 14 Japanese adult cadavers (five from females, nine from males, average age 73.8 ± 14.1 years) were observed macroscopically. The articular branches of the femoral and obturator nerves were dissected at the anterior margin of the groin toward the thigh region. After dissections of the articular nerves of the hip joints, the femoral and obturator nerves were exposed from proximally to distally to identify the articular nerves of the knee joints. The branching pattern of the articular branches in the hip and knee joints was recorded. In six of 14 limbs (42.9%), the femoral nerve supplied articular branches to the anteromedial aspect of both the hip and knee joints. These articular branches were derived from the same bundle of femoral nerve. These gross anatomical findings suggested that dichotomizing peripheral sensory fibers innervate the hip and knee joints and these could relate to the referred pain confirmed in the anterior knee joints of patients with hip disease. Clin. Anat. 31:705–709, 2018. © 2018 Wiley Periodicals, Inc.     

Blockade of Rho/Rho-associated coiled coil-forming kinase signaling can prevent progression of hepatocellular carcinoma in matrix metalloproteinase-dependent manner

Aim:  There is growing evidence that the Rho/Rho-associated coiled coil-forming kinase (ROCK) signaling pathway is upregulated in tumors and plays a key role in cancer invasion and metastasis. Our aim was to test the anticancer effects of Rho/ROCK inhibitor, Y-27632, including possible mechanisms in a highly-metastasizing hepatocellular carcinoma (HCC) mouse model on its secretion of matrix metalloproteinase (MMP) and tumor progression.
Methods:  Following orthotopic implantation of CBO140C12 HCC tumor fragments into the liver of mice, the mice were randomly assigned to a Y-27632-treated group or control group. After treatment for 4 weeks, specimens were obtained to evaluate tumor size, metastases, and immunohistochemical findings. In vitro , we examined the effects of Y-27632 and RhoC siRNA on MMP-2 and -9 expressions, invasiveness, and apoptosis in cultured tumor cells.
Results:  Both RhoA and RhoC were upregulated in HCC-bearing livers, and Y-27632 significantly inhibited not only tumor growth and intrahepatic metastasis ( P  < 0.05), but also tumoral MMP-9 expression. Moreover, Y-27632 treatment resulted in large necrotic areas in tumors. In vitro , Y-27632 and RhoC siRNA reduced MMP-2 and -9 expressions, as well as the chemotactic migration of tumor cells dose-dependently, and increased apoptosis eight times.
Conclusion:  Y-27632 suppresses progression and limits the intrahepatic metastasis of established HCC. This could be linked to the decreased MMP expression and induction of apoptosis in tumor cells. Rho signaling may prove to be a productive target in anticancer therapy.     

Targeted mutations of the juxtamembrane tyrosines in the Kit receptor tyrosine kinase selectively affect multiple cell lineages

Loss-of-function mutations in the murine dominant white spotting/c-kit locus affect a diverse array of biological processes and cell lineages and cause a range of phenotypes, including severe anemia, defective pigmentation, sterility, mast cell deficits, a lack of interstitial cells of Cajal, spatial learning memory deficits, and defects in peripheral nerve regeneration. Here we show that tyrosine residues 567 and 569 in the juxtamembrane (Jx) domain of the murine Kit receptor tyrosine kinase are crucial for the function of Kit in melanogenesis and mast cell development, but are dispensable for the normal development of erythroid, interstitial cells of Cajal and germ cells. Furthermore, adult mice lacking both tyrosines exhibit splenomegaly, dysregulation of B-cell and megakaryocyte development, and enlarged stomachs. Analysis of signal transduction events induced by the mutant receptors after ligand stimulation indicates that Jx tyrosine mutations diminish receptor autophosphorylation and selectively attenuate activation of extracellular signal-regulated kinase/mitogen-activated protein kinases. Together, these observations demonstrate that the Jx domain of Kit plays a cell-type specific regulatory role in vivo and illustrate how engineered mutations in Kit can be used to understand the complex biological and molecular events that result from activating a receptor tyrosine kinase.     

Increased reactive oxygen species and anti-oxidative response in mitochondrial cardiomyopathy.

A 60-year-old woman was admitted for treatment of congestive heart failure. She had been diagnosed with diabetes mellitus when she was 23 years old, and she began to go deaf when she was 34 years old. She showed symptoms of heart failure at age 51 and was diagnosed with hypertrophic cardiomyopathy. Echocardiography showed progressive diffuse hypokinetic motion of the left ventricle and the left ventricular hypertrophy had gradually regressed. A mitochondrial transition mutation, A3243G, was detected in her peripheral leukocytes (9%) and in those of her 27-year-old son, who also has diabetes and deafness. Electron microscopy of an endomyocardial biopsy specimen showed proliferation and swelling of the mitochondria, and significant generation of reactive oxygen species (ROS), as well as marked induction of heme oxygenase-1, which is an adaptive enzyme to oxidative damage, were also observed in the myocardial tissue. These observations were more prominent than in other patients with heart failure of different etiology, which suggests that the increased ROS generation and anti-oxidative response were involved in the development of the mitochondrial cardiomyopathy.     

A retrospective study of the preventive effect of transarterial chemotherapy for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy

A major problem in treating hepatocellular carcinoma (HCC) is intrahepatic recurrence after partial hepatectomy, despite the relatively early detection now possible due to recent developments in non-invasive diagnostic modalities. The present study evaluated the usefulness of preventive therapy for intrahepatic recurrence of HCC. In order to suppress intrahepatic recurrence in HCC patients at high risk of recurrence after tumor removal, we performed preventive transarterial chemotherapy in 23 such patients. Doxorubicin, at a dose of 0.5 mg/kg body weight, was administered, via a catheter inserted at the junction of the common hepatic artery and the gastroduodenal artery, every 2 weeks for the first 2 months, and every month thereafter for at least 1 year. The control group consisted of 30 patients with similar risk of recurrence who underwent partial hepatectomy during the same period without receiving transarterial preventive therapy. The 1-, 2-, 3-, and 5-year cumulative cancer-free survival rates in patients who received transarterial preventive chemotherapy after partial hepatectomy were 87.0%, 47.1%, 21.2%, and 21.2%, respectively, compared to 53.3%, 30.0%, 20.0%, and 13.3%, respectively, in the control group (P<0.05). The 1-, 2-, 3-, and 5-year cumulative overall survival rates were 95.7%, 81.2%, 58.4%, and 48.7%, respectively, in the preventive chemotherapy group, compared to 70.0%, 49.4%, 41.7%, and 19.5%, respectively, in the control group (P<0.05). Thus, the present study demonstrates the limited but significant effect of preventive transarterial chemotherapy for the intrahepatic recurrence of HCC after partial hepatectomy.     

Morphological divergence in the curvature of human femoral diaphyses: Tracing the central mass distributions of cross-sections

The diaphysis of the human femoral bone has a physiological anterior curvature; additionally, there is a curvature to the medial side or lateral side. In addition to compression stress from gravity during standing, walking, and running, these bones are continuously exposed to complex stresses from the traction forces of the various strong muscles attached to them. The femoral diaphysis is subjected to these mechanical stresses, and the direction and size of its curvature are defined according to Wolff's law and the mechanostat theory of Frost. The purpose of this study was to quantitatively evaluate the curvature of the femoral diaphysis in Japanese skeletons by determining the curve connecting the central mass distributions (CMD) of cross-sectional images. A total of 90 right femora (46 males and 44 females) were randomly selected from modern Japanese skeletal specimens. Full-length images of these bones were acquired using a clinical computed tomography scanner. The range between the lower end of the lesser trochanter and the adductor tubercle of each femur was divided at regular intervals to obtain ten planes, and nine levels were analyzed. The CMD curve was determined by connecting the CMDs of each of the nine cross-sections. First, the CMD of a cross-section in each of the nine slices was calculated, and the nine trajectories were superimposed from above. Then, by converting the shape of the entire CMD curve to superimpose the coordinates of the endpoint on the starting point, a closed arc representing the curvature of the femur was determined. For both males and females, the patterns varied from mostly medial to largely lateral curvature. The size of the curvature also varied for individuals. By analyzing only the coordinates of the vertex of the CMD curve of each femoral bone, the outlines of the diaphyseal curvatures could be recognized. The femora were thereby divided into two groups: medial bending and lateral bending. Considering males and females together, the number in the lateral-curvature group (n = 51) was larger than that in the medial-curvature group (n = 39). Moreover, the average age of the lateral-curvature group was significantly higher than that of the medial-curvature group (p < 0.05). In males, with an increase in the cortical bone proportion of the cross-sectional area, the anterior vertex of diaphyseal bending tended to be more prominent. This cortical proportion was significantly higher in the medial-curvature groups than in the lateral-curvature group (p < 0.01). The phenomena observed in this study may be related to pathophysiologies such as atypical fractures of the femur and osteoarthritis of the knee joints.     

First experience of efficacy and radiation exposure in 320-detector row CT fluoroscopy-guided interventions

Objective:We investigated the efficacy and exposure to radiation in 320-detector row computed tomography fluoroscopy-guided (CTF-guided) interventions.Methods:We analysed 231 320-detector row CTF-guided interventions (207 patients over 2 years and 6 months) in terms of technical success rates, clinical success rates, complications, scanner settings, overall radiation doses (dose–length product, mGy*cm), patient doses of peri-interventional CT series, and interventional CT (including CTF), as a retrospective cohort study. The relationships between patient radiation dose and interventional factors were assessed using multivariate analysis.Results:Overall technical success rate was 98.7% (228/231). The technical success rates of biopsies, drainages, and aspirations were 98.7% (154/156), 98.5% (66/67), and 100% (8/8), respectively. The clinical success rate of biopsies was 93.5% (146/156). All three major complications occurred in chest biopsies. The median total radiation dose was 522.4 (393.4–819.8) mGy*cm. Of the total radiation dose, 87% was applied during the pre- and post-interventional CT series. Post-interventional CT accounted for 24.4% of the total radiation dose. Only 11.4% of the dose was applied by CTF-guided intervention. Multilinear regression demonstrated that male sex, body mass index, drainage, intervention time, and helical scan as post-interventional CT were significantly associated with higher dose.Conclusion:The 320-detector row CTF interventions achieved a high success rate. Dose reduction in post-interventional CT provides patient dose reduction without decreasing the technical success rates.Advances in knowledge:This is the first study on the relationship between various interventional outcomes and patient exposure to radiation in 320-detector row CTF-guided interventions, suggesting a new perspective on dose reduction.