Left Atrial Contribution to Left Ventricular Filling in Patients with Mitral Stenosis: Combined Analysis of Transmitral and Pulmonary Venous Flow Velocities

We recorded transmitral and pulmonary venous flow velocities using transthoracic continuous-wave and transesophageal pulsed Doppler echocardiography, respectively, in 36 patients with mitral stenosis who were in sinus rhythm to investigate the left atrial contribution to left ventricular filling in mitral stenosis. The mitral valve area was determined by transthoracic two-dimensional short-axis echocardiography. Patients were classified as having mild stenosis (± 1.5 cm², n = 17) or moderate stenosis (< 1.5 cm², n = 19). The mean pulmonary capillary wedge pressure and left atrial maximal diameter were significantly larger, and left atrial volume change during atrial contraction was significantly smaller in the moderate group than in the mild group. The percent left atrial contribution to left ventricular filling, estimated from the transmitral flow velocity, the peak atrial systolic velocity, and the percent ratio of left atrial systolic regurgitation to left atrial filling, estimated from the pulmonary venous flow velocity, were significantly lower in the moderate group than in the mild group. The percent left atrial contribution to left ventricular filling, the peak atrial systolic velocity, and the percent ratio of left atrial systolic regurgitation to left atrial filling were positively correlated with the mitral valve area and negatively correlated with the mean pulmonary capillary wedge pressure. These results suggest that the left atrial contribution to left ventricular filling in patients with mitral stenosis in sinus rhythm decreases as the severity of valve stenosis increases, and that analysis of the atrial systolic waves of the transmitral and pulmonary venous flow velocities provides important information for evaluation of left atrial systolic performance in patients with mitral stenosis.     

Antibiotic susceptibility of glutaraldehyde-tolerant Mycobacterium chelonae from bronchoscope washing machines

BACKGROUND: Contamination of bronchoalveolar lavage fluid is a major problem in the world. Although 2% glutaraldehyde (GA) is widely used as a disinfectant for bronchoscope cleaning, recently, GA-tolerant mycobacteria have been isolated, which makes this problem more complicated. METHODS: We studied the susceptibility to GA and antibiotics of mycobacteria isolated from bronchoscope washing machines in our hospital. We also studied the minimum inhibitory concentrations of GA and antibiotics with pump inhibitors. RESULTS: Twenty-nine mycobacteria were isolated, of which 26 were Mycobacterium chelonae. Among 18 isolates of M chelonae, excluding 8 isolates in which some results were not reproducible, 50% (9 of 18) were 2% GA-tolerant. One hundred percent (9 of 9) of the GA-tolerant isolates and 11% (1 of 9) of the GA-sensitive isolates were either resistant or intermediately resistant to 2 or 3 classes of antibiotics. Efflux pump inhibitors did not influence the susceptibility to GA and antibiotics. CONCLUSIONS: It was suggested that there might be an association of GA tolerance with antibiotic resistance in M chelonae. There may a different mechanism(s) other than that involving efflux pumps with regard to GA tolerance and antibiotic resistance in M chelonae. When bronchoscopy-related mycobacterial infections are suspected, physicians and clinical microbiologists should exercise care in handling GA-tolerant mycobacteria, which may be resistant to multiple antibiotics.     

Decreased calcitonin gene-related peptide expression in the dorsal root ganglia of TNF-deficient mice in a monoiodoacetate-induced knee osteoarthritis model

Background: The detailed mechanisms of knee osteoarthritis (OA) pain have not been clarified, but involvement of inflammatory cytokines such as tumor necrosis factor-alpha (TNF) has been suggested. The present study aimed to investigate the more detailed neurological involvement of TNF in joint pain using a TNF-knockout mouse OA model. Methods: The right knees of twelve-week-old C57BL/6J wild and TNF-deficient knockout (TNF-ko) mice (n=15, each group) were given a single intra-articular injection of 10 µg monoiodoacetate in 10 mL sterile saline. The left knees were only punctured as the control. Evaluations were performed immediately after the injection (baseline) and at 7, 14, and 28 days after the injection with a subsequent intra-articular injection of neurotracer into both knees. The animals were evaluated for immunofluorescence of the lumbar dorsal root ganglia (DRG) innervating the knee joints. The injected knees were observed macroscopically and mouse pain-related behaviors were scored. Results: Macroscopic observation showed similar knee OA development in both wild and TNF-ko mice. Calcitonin gene-related peptide (CGRP, a neuropeptide identified as a inflammatory pain-related biomarker) was significantly increased in DRG neurons innervating OA-induced knee joints with significantly less CGRP expression in TNF-ko animals. Pain-related behavior scoring showed a significant increase in pain in OA-induced joints, but there was no significant difference in pain observed between the wild and TNF-ko mice. Conclusions: The result of the present study indicates the possible association of TNF-alpha in OA pain but not OA development.     

Horizontal impaction of primary mandibular bilateral central incisors identified in 2-year-8-month-old girl

A girl aged 2 years and 8 months came to our clinic for consultation with regard to unerupted primary mandibular bilateral central incisors. An intraoral examination revealed that the teeth had not emerged into the oral cavity and showed a tooth crown morphology similar to that of the primary mandibular incisors, which appeared in the lingual submucosal area outside of the mandibular dental arch. Periapical radiographs demonstrated that the tooth crowns of both affected teeth were severely displaced to the lingual side. Computed tomography examinations were performed to clarify the three-dimensional positions of the affected teeth and their permanent successors, which revealed that the affected teeth were located in their estimated positions and had a standard root morphology. In addition, the permanent successors, which had not initiated root formation, were located close to the affected teeth. We decided to postpone extraction of the affected teeth and perform periodical examinations until the roots of the permanent successors are sufficiently formed. At the age of 2 years and 10 months, the edge of the tooth crown of the primary mandibular left central incisor was found emerged into the oral cavity. According to her parents, the patient did not complain of the emerging edge and no abnormal conditions were observed around the tooth.     

Mechanisms of Tumor Development and Anti-angiogenic Therapy in Glioblastoma Multiforme

Despite advances in surgical and medical therapy, glioblastoma multiforme (GBM) remains a fatal disease. There has been no significant increase in survival for patients with this disease over the last 20 years. Tumor vasculature formation and glioma cell invasion along the white matter tracts both play a pivotal role in glioma development. Angiogenesis and invasion are the major factors believed to be responsible for treatment resistance in tumors, and a better understanding of the glioma invasion and angiogenesis mechanisms will lead to the development of potential new treatments. In this review, we focus on the molecular characteristics of angiogenesis and invasion in human malignant glioma. We discuss bevacizumab and cilengitide, which are used to inhibit angiogenesis in GBM.     

Traumatic unilateral temporomandibular joint dislocation overlooked for more than two decades

Forward dislocation of the temporomandibular joint commonly can be easily diagnosed and successfully reduced by manual repositioning. In this report, we discuss a rare case of prolonged temporomandibular dislocation that had persisted for more than 20 years because the otolaryngologist and dentist had missed the dislocation. This patient underwent open reduction and mandibular joint plasty with preoperative orthodontic therapy. It is possible that strong pain and mouth-closing disability may gradually remit and only deviated mandibular prognathism like malocclusion may persist. Therefore, abnormal occlusion warrants careful attention to temporomandibular joint dislocation.     

Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence

Despite their high degree of genomic similarity, reminiscent of their relatively recent separation from each other ( approximately 6 million years ago), the molecular basis of traits unique to humans vs. their closest relative, the chimpanzee, is largely unknown. This report describes a large-scale single-contig comparison between human and chimpanzee genomes via the sequence analysis of almost one-half of the immunologically critical MHC. This 1,750,601-bp stretch of DNA, which encompasses the entire class I along with the telomeric part of the MHC class III regions, corresponds to an orthologous 1,870,955 bp of the human HLA region. Sequence analysis confirms the existence of a high degree of sequence similarity between the two species. However, and importantly, this 98.6% sequence identity drops to only 86.7% taking into account the multiple insertions/deletions (indels) dispersed throughout the region. This is functionally exemplified by a large deletion of 95 kb between the virtual locations of human MICA and MICB genes, which results in a single hybrid chimpanzee MIC gene, in a segment of the MHC genetically linked to species-specific handling of several viral infections (HIV/SIV, hepatitis B and C) as well as susceptibility to various autoimmune diseases. Finally, if generalized, these data suggest that evolution may have used the mechanistically more drastic indels instead of the more subtle single-nucleotide substitutions for shaping the recently emerged primate species.     

Associations Between hOGG1 Ser326Cys Polymorphism and Increased Body Mass Index and Fasting Glucose Level in the Japanese General Population

Background

Evidence suggests that Ser326Cys, a genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1), is associated with insulin resistance and type 2 diabetes; however, the underlying mechanism is unclear. Recently, an animal study showed a significant association between the hOGG1 genotype and obesity, although evidence for such an association in humans is limited. The purpose of this study was to examine the association between the hOGG1 genotype and body mass index (BMI) and fasting blood glucose (FBG) levels.

Methods

Cross-sectional analysis was conducted using the baseline survey data from a Japan Multi-Institutional Collaborative Cohort Study, which included 1793 participants aged 40–69 years. The hOGG1 polymorphism was detected using a multiplex polymerase chain reaction-based invader assay. Multiple linear regression, analysis of covariance, and logistic regression were used to control for confounding variables.

Results

The Cys allele was significantly associated with increased BMI, FBG level, and total cholesterol (TC) level, even after adjustment for gender, age, energy intake, alcohol, smoking, physical activity, and family history of diabetes. An association with BMI was still observed after further adjustment for FBG and TC, but not for the study area (Amami or the mainland). The Cys/Cys genotype was significantly more prevalent in the participants with higher BMI (>27.5 kg/m²). However, the impact of genotype decreased and significance disappeared after adjusting for the study area.

Conclusions

The present results suggest that the study area being inside Japan confounds the association between hOGG1 genotype and obesity.Key words: human 8-oxoguanine glycosylase 1 (hOGG1), obesity, body mass index (BMI), fasting blood glucose (FBG), polymorphism, study area