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.     

Assessment of Hounsfield unit in the differential diagnosis of odontogenic cysts

Objectives:The purpose of this study was to evaluate the usefulness of Hounsfield unit (HU) assessment with multislice-CT in the differentiation of radicular cysts (RCs), dentigerous cysts (DCs) and odontogenic keratocysts (OKCs).Methods:In total, 307 odontogenic cysts (RCs, DCs and OKCs) were included in this study. Cysts with lesion diameter <10 mm, cysts with artefacts affecting measurement of HU values, cysts involving infection and recurrent cysts were regarded as exclusion criteria. Images were acquired in three different types of CT scanners: Aquilion ONE, Discovery CT750 HD and SOMATOM Definition Flash. Differences in HU values among scanners and among types of odontogenic cysts were assessed using one-way analysis of variance; multiple comparisons were performed post hoc, using the Tukey–Kramer honestly significant difference test.Results:In total, 164 cysts were analysed in this study (64 RCs, 57 DCs and 43 OKCs). Regardless of the type of lesion, the Aquilion ONE scanner demonstrated a significant difference in HU value, compared with the Discovery CT750 HD scanner. Regardless of CT scanner model, HU values significantly differed between DCs and OKCs (p < 0.0001), as well as between OKCs and RCs (p < 0.0001).Conclusions:HU values were found to vary among CT scanners and should always be associated with other lesion imaging features while interpreting and elaboration diagnostic hypothesis. Notably, the results suggested that OKCs might be able to be differentiated from DCs and RCs by using HU values.     

Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome

Perlman syndrome is a rare, autosomal recessive overgrowth disorder. Recently, the deletion of exon 9 and other mutations of the DIS3L2 gene have been reported in patients; however, the mechanism behind this deletion is still unknown. We report the homozygous deletion of exon 9 of DIS3L2 in a Japanese patient with Perlman syndrome. We identified the deletion junction, and implicate a non-allelic homologous recombination (NAHR) between two LINE-1 (L1) elements as the causative mechanism. Furthermore, the deletion junctions were different between the paternal and maternal mutant alleles, suggesting the occurrence of two independent NAHR events in the ancestors of each parent. The data suggest that the region around exon 9 might be a hot spot of L1-mediated NAHR.     

Promotion of Transplanted Bone Marrow-derived Cell Migration into the Periodontal Tissues due to Orthodontic Mechanical Stress

Background: Bone marrow-derived cells (BMCs) have abilities of cell migration and differentiation into tissues/organs in the body and related with the differentiation of teeth or periodontal tissue including fibroblasts. Then, we examined the effect of orthodontic mechanical stress to the transplanted BMC migration into periodontal tissues using BMC transplantation model.Material and Method: BMC from green fluorescence protein (GFP) transgenic mice were transplanted into 8-week-old female C57BL/6 immunocompromised recipient mice, which had undergone 10 Gy of lethal whole-body-irradiation. Five mice as experimental group were received orthodontic mechanical stress using separator between first molar (M1) and second molar (M2) 1 time per week for 5 weeks and 5 mice as control group were not received mechanical stress. The maxilla with M1 and M2 was removed and was immunohistochemically analyzed using a Dako Envision + Kit-K4006 and a primary anti-GFP-polyclonal rabbit antibody. Immunohistochemically stained was defined as positive area and the pixel number of positive area in the periodontal tissue was compared with the previously calculated total pixel number of the periodontal tissue.Results: The immunohistochemistry revealed that GFP positive cells were detected in the periodontal tissues, both in the experimental and control specimens. The ratio of pixel number in the examination group showed 5.77 ± 3.24 % (mean ± SD); and that in the control group, 0.71±0.45 % (mean ± SD). The examination group was significantly greater than that of control group (Mann-Whitney U test: p<0.001).Conclusion: These results suggest that orthodontic mechanical stress accelerates transplanted BMC migration into periodontal tissues.     

A Survey of the FAERS Database Concerning the Adverse Event Profiles of α1-Adrenoreceptor Blockers for Lower Urinary Tract Symptoms

Purpose: Current guidelines recommend α1-adrenoreceptor blockers (A1Bs) for treating lower urinary tract symptoms suggestive of benign prostatic hyperplasia, but their adverse effects can be problematic. In this study, reports submitted to the US Food and Drug Administration Adverse Event Reporting System (FAERS) between 1997 and 2011 were reviewed to assess the safety profiles of A1Bs.Methods: After deleting duplicated submissions and revising arbitrary drug names, reports involving A1Bs for male patients were analyzed. Data mining algorisms were used for the quantitative detection of signals, where a signal represents an association between a drug and an adverse event or a drug-associated adverse event, including the proportional reporting ratio, reporting odds ratio, information component given by a Bayesian confidence propagation neural network, and empirical Bayes geometric mean.Results: The total number of reports used was 1,260,182. Signal scores suggested the associations of alfuzosin, doxazosin, tamsulosin, and terazosin with dizziness/vertigo, orthostatic hypotension, erectile dysfunction, ejaculation dysfunction (EjD), thirst/dry mouth, and constipation; however, reports on naftopidil, silodosin, and urapidil were not enough to compare with the other 4 A1Bs. Signal scores for EjD were higher for tamsulosin, and those for dizziness/vertigo were lower for doxazosin than for the other 3 drugs.Conclusions: Tamsulosin-associated EjD, which was found in clinical studies, was reproduced in this analysis with markedly higher signal scores, and these results strongly suggest the necessity of well-organized clinical studies on A1B-associated adverse events.     

A Single Case of Single-Port Access Laparoscopic Appendectomy During the Puerperium

Laparoscopic appendectomy is now widely practiced for the treatment of acute appendicitis. As result of increased demand for minimally invasive surgery, single-incision access was introduced and is being performed in various abdominal surgeries. Conventional laparoscopic appendectomy (LA) is gradually being performed in pregnant women. A 33-year-old woman was referred to our department at 39 weeks and 1 day of gestation due to abdominal pain. She was aware of her gastroepiploic pain even after the delivery. Though it was past 2 days, she was not recovering from right lower abdominal pain, so she was transferred to the Department of Gynecology at our hospital on the same day. Although an antibiotic was administered, the right abdominal pain did not improve, and she was referred to our department from the Department of Gynecology. We performed single-port LA (SP-LA). The total operation time was 63 minutes, and the estimated blood loss was 0 mL. She was discharged with no complications on postoperative day 7. We report our initial experience with single-port LA (SP-LA) using the glove technique for treatment of acute appendicitis in a postpartum woman. SP-LA using the glove technique was performed successfully during the puerperium without prolongation of operation time. This approach is less invasive, offers a much better cosmetic result than with conventional methods, and can be performed safely and at low cost.Key words: PLA (single-port laparoscopic appendectomy), PuerperiumThe advantages of laparoscopic appendectomy (LA) over open appendectomy (OA) are widely known and include decreased pain, shorter convalescence, and earlier return to work. Especially, LA is advantageous for treating acute appendicitis in pregnant women. Because the appendix of a pregnant woman is shifted from its normal position, OA may leave a larger operative scar than normal. In recent years, efforts of laparoscopic surgeons have resulted in a reduction in both the diameter of the access ports and the number of ports needed.¹ In addition, natural orifice transluminal endoscopic surgery (NOTES) is being developed as another form of minimally invasive surgery.² As a part of this process, the single-incision laparoscopic surgery (SILS) technique is presently being developed for various laparoscopic surgeries.³ SILS is a virtually scarless technique in which the single-port access site is hidden in the umbilicus. We think that the primary advantage of single-port laparoscopic appendectomy (SP-LA) is the superior cosmetic result compared with multi-port access LA. We report a very rare case in which SP-LA was performed to treat acute appendicitis during the puerperium. This approach is less invasive, offers a much better cosmetic result than with conventional methods, and can be performed safely and at low cost.     

Retardation of skeletal development and cervical abnormalities in transgenic mice expressing a dominant-negative retinoic acid receptor in chondrogenic cells

Skeletal formation is a fundamental element of body patterning and is strictly regulated both temporally and spatially by a variety of molecules. Among these, retinoic acid (RA) has been shown to be involved in normal skeletal development. However, its pleiotropic effects have caused difficulty in identifying its crucial target cells and molecular mechanisms for each effect. Development of cartilage primordia is an important process in defining the skeletal structures. To address the role of RA in skeletal formation, we have generated mice expressing a dominant-negative retinoic acid receptor (RAR) in chondrogenic cells by using the type II collagen α1 promoter, and we have analyzed their phenotypes. These mice exhibited small cartilage primordia during development and retarded skeletal formation in both embryonic and postnatal periods. They also showed selective degeneration in their cervical vertebrae combined with homeotic transformations, but not in their extremities. The cervical phenotypes are reminiscent of phenotypes involving homeobox genes. We found that the expression of Hoxa-4 was indeed reduced in the cartilage primordia of cervical vertebrae of embryonic day 12.5 embryos. These observations demonstrate that endogenous RA acts directly on chondrogenic cells to promote skeletal growth in both embryonic and growing periods, and it regulates the proper formation of cervical vertebrae. Furthermore, RA apparently specifies the identities of the cervical vertebrae through the regulation of homeobox genes in the chondrogenic cells. Great similarities of the phenotypes between our mice and reported RAR knockout mice revealed that chondrogenic cells are a principal RA target during complex cascades of skeletal development.     

Junctional adhesion molecule-A deficiency increases hepatic ischemia-reperfusion injury despite reduction of neutrophil transendothelial migration

The endothelial receptors that control leukocyte transmigration in the postischemic liver are not identified. We investigated the role of junctional adhesion molecule-A (JAM-A), a receptor expressed in endothelial tight junctions, leukocytes, and platelets, for leukocyte transmigration during hepatic ischemia-reperfusion (I/R) in vivo. We show that JAM-A is up-regulated in hepatic venular endothelium during reperfusion. I/R-induced neutrophil transmigration was attenuated in both JAM-A-/- and endothelial JAM-A-/- mice as well as in mice treated with an anti-JAM-A antibody, whereas transmigration of T cells was JAM-A independent. Postischemic leukocyte rolling remained unaffected in JAM-A-/- and endothelial JAM-A-/- mice, whereas intravascular leukocyte adherence was increased. The extent of interactions of JAM-A-/- platelets with the postischemic endothelium was comparable with that of JAM-A+/+ platelets. The I/R-induced increase in the activity of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and sinusoidal perfusion failure was not reduced in JAM-A-/- mice, while the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL)-positive hepatocytes was significantly higher. Thus, we show for the first time that JAM-A is up-regulated in hepatic venules and serves as an endothelial receptor of neutrophil transmigration, but it does not mediate leukocyte rolling, adhesion, or platelet-endothelial cell interactions. JAM-A deficiency does not reduce I/R-induced microvascular and hepatocellular necrotic injury, but increases hepatocyte apoptosis, despite attenuation of neutrophil infiltration.