Assessment of the calcification of the nuchal ligament and osteophytes of the cervical spine in obstructive sleep apnoea subjects and snorers.

The previous reports suggest that obstructive sleep apnoea (OSA) is related to metabolic syndrome, mineral metabolism disorders and cardiovascular disease. In addition, a possible relationship between obesity and the calcification of ligaments has been implied. However, the potential link between OSA and the calcification of ligaments has not been directly studied. In this present study, to investigate the potential link between OSA and the calcification of ligaments, we examined the prevalence of the calcification of ligaments in OSA patients and the relationship between these findings and OSA severity. Eighty consecutive patients (60 males, 20 females) diagnosed as OSA or a heavy snorer based on full-night polyso-mnography were retrospectively recruited from May 2006 to July 2008. Each patient underwent cephalometric imaging examination before the arrangement of an oral appliance. One calibrated observer (YS) reviewed the cephalometric images for the presence of calcification of the nuchal ligament and osteophytes of the cervical spine. The prevalence of calcification of the nuchal ligament in OSA patients and snorers was 46.3% (males: 52%, females: 30%) There was a significant positive correlation between the severity of OSA (AHI) and the calcification of the nuchal ligament before and after adjusting for BMI. The prevalence of the calcification of the nuchal ligament in OSA subjects and snorers was higher than in previous studies with non-OSA subjects. In addition, it is suggested that the severity of OSA correlates with the presence of calcification of the nuchal ligament.

Cervical curvature variations in patients with infraocclusion.

The purpose of this study was to observe the variations of cervical curvature in patients with infraocclusion, and to compare this with the controls. In this study, the infraocclusion criteria were defined with the Pr-id as <17 mm on the cephalometric image. The subjects were 32 patients with infraocclusion, and 28 controls which matched the distribution for gender and age. The six points of inquiry were as follows: (i) cervical vertebra height, (ii) neck alignment, (iii) ratio of lower facial height, (iv) vertical dimension of occlusion, (v) cervical angle and (vi) occlusal angle. In over 90% of the patients with infraocclusion, the cervical curvature was classified as straight or kyphosis. Conversely, in 36% of the control subjects, the cervical curvature was classified as lordosis. There was a weak positive correlation between the vertical dimension of occlusion and the cervical curvature in all subjects. In the control group, there was a significant and strong positive correlation between the age and cervical curvature, and a strong negative correlation between age and cervical angle and occlusal angle. Conversely, in the patients with infraocclusion, age was only correlated with the ratio of lower facial height. The prevalence of non-lordosis in the patients with infraocclusion was higher in comparison with the control group in our study, and the previous large-scale study of Japanese. However, there was merely a weak positive correlation between the cervical curvature and the vertical dimension of occlusion.

Immune response to cytolethal distending toxin of Aggregatibacter actinomycetemcomitans in periodontitis patients.

BACKGROUND AND OBJECTIVE: Cytolethal distending toxin (CDT) is a genotoxin produced by Aggregatibacter actinomycetemcomitans. In spite of its association with pathogenesis, little is known about the humoral immune response against the CDT. This study aimed to test whether subgingival colonization and humoral response to A. actinomycetemcomitans would lead to a response against CDT. MATERIAL AND METHODS: Sera from periodontally healthy, localized and generalized aggressive periodontitis and chronic periodontitis subjects (n = 80) were assessed for immunoglobulin G titers to A. actinomycetemcomitans serotypes a/b/c and to each CDT subunit (CdtA, CdtB and CdtC) by ELISA. A. actinomycetemcomitans subgingival levels and neutralization of CDT activity were also analyzed. RESULTS: Sera from 75.0% localized and 81.8% generalized aggressive periodontitis patients reacted to A. actinomycetemcomitans. A response to serotype b was detected in localized (66.7%) and generalized aggressive periodontitis (54.5%). Reactivity to A. actinomycetemcomitans correlated with subgingival colonization (R = 0.75, p < 0.05). There was no correlation between A. actinomycetemcomitans colonization or response to serotypes and the immunoglobulin G response to CDT subunits. Titers of immunoglobulin G to CdtA and CdtB did not differ among groups; however, sera of all generalized aggressive periodontitis patients reacted to CdtC. Neutralization of CDT was not correlated with levels of antibodies to CDT subunits. CONCLUSION: Response to CdtA and CdtB did not correlate with the periodontal status of the subject in the context of an A. actinomycetemcomitans infection. However, a response to CdtC was found in sera of generalized but not of localized aggressive periodontitis subjects. Differences in response to CdtC between generalized and localized aggressive periodontitis subjects indicate that CDT could be expressed differently by the infecting strains. Alternatively, the antibody response to CdtC could require the colonization of multiple sites.

Genetic diversity and toxic activity of Aggregatibacter actinomycetemcomitans isolates.

INTRODUCTION: Very little is known of the diversity and expression of virulence factors of serotypes of Aggregatibacter actinomycetemcomitans. Toxic activity on Chinese hamster ovary (CHO) cells and cdt and ltx genotyping were evaluated in A. actinomycetemcomitans serotypes. METHODS: Forty-one A. actinomycetemcomitans isolates were analysed for CHO cell growth inhibition. Genotyping was performed by polymerase chain reactions specific to the ltx promoter region, serotype-specific and cdt region and by sequencing of cdtB. RESULTS: cdtABC was detected in 40 strains. Analysis of the cdtA upstream region revealed 10 cdt genotypes. Toxicity to CHO cells was detected for 92.7% of the isolates; however, no correlation between the toxic activity and the cdt genotype was detected. Serotype c was more prevalent among Brazilian samples (68.0%). Four serotype b isolates from subjects with aggressive periodontitis were associated with high leukotoxin production and exhibited moderate to strong toxic activity in CHO cells, but were classified in different cdt genotypes. High levels of toxicity in CHO cells were not associated with a particular serotype; 57.1% of serotype a isolates presented low toxicity to CHO cells whereas the highly toxic strains belonged to serotypes b and c. Sequencing of cdtB revealed a single nucleotide polymorphism of amino acid 281 but this was not related to the toxic activity in CHO cells. CONCLUSION: Differences in prevalence of the low and highly cytotoxic strains among serotypes reinforce the hypothesis that serotype b and c isolates of A. actinomycetemcomitans are more virulent than serotype a strains.

A case of obstructive sleep apnoea with anterior cervical osteophytes.

Osteophytes of the cervical spine are usually seen in elderly adults. When prominent, they have been blamed for dysphagia, cough, dysphonia and dyspnoea. This paper reports on an obstructive sleep apnoea (OSA) patient with cervical spinal osteophytes, one cause of airway obstruction. A 75-year-old male complained of pronounced snoring. The diagnosis was mild OSA, apnoea hypopnoea index was 9.4. Patient reported no restrictions in neck movements, experiences of neck pain or neck trauma. Previously, patient underwent a tonsillectomy due to discomfort in the pharyngeal region. A lateral cephalometric image was taken to observe airway before oral appliance therapy. The image revealed the presence of large osteophytes or sclerotic enthesopathy, lying on anterior surfaces from the fourth to seventh cervical vertebrae. A computed tomography (CT) image revealed the relationship of airway position to the spine. In the reconstructed three-dimensional (3D) image, the airway appeared displaced to the right of the craniomandiblar bone, with the hyoid bone similarly displaced in a manner to that of the airway. The spine also appeared displaced to the left side ofcraniomandiblar bone. Additionally, the 3D image revealed calcification of the stylohyoideum ligament and ligamentum nuchae. This present case highlights the necessity of CT examination for OSA patients. There were several ligament calcifications in the head and neck region. Cervical spine osteophytes, as a component of Forestier's or cervical spine disease, have been associated with dysphagia and dysphonia. It was reported that bilateral vocal cord paralysis was caused by osteophytes compressing the post-cricoid area of larynx.

Relationship Between Stress Coping Mechanisms and Depression in Kidney Transplant Recipients.

BACKGROUND: It has been reported that transplant recipients are exposed to physical and psychosocial stresses even after transplant surgery and exhibit psychological disorders such as depression. PURPOSE: In this study, we extracted trends concerning how recipients of kidney transplants cope with stress, and we also examined how they cope with depression and its countermeasures. METHOD: We administered questionnaire surveys to 109 kidney transplant recipients. These included items on personal attributes, medical information, depression, and stress-coping type scales. Statistical analysis was performed using factor analysis and multiple regression analysis. RESULTS: Fifteen out of 109 (13.8%) were found to be high-risk patients for depression based on responses to the questionnaire using the depression scale. We extracted 2 factors of stress-coping type, namely Factor 1, "Directly coping with the problem," of patients who try to directly resolve the problem in a positive manner and Factor 2, "Stress-release while avoiding the problem," for those who relieve their feelings in response to the stress without resolving the problem itself. When multiple regression analysis was conducted with the depression scale as the dependent variable and the stress-coping factor as the independent variable, Factor 1 tended to be associated with reduced depression and Factor 2 with increased depression. CONCLUSIONS: Results showed that to improve the mental health of those who receive kidney transplants, it is necessary to examine the depression and stress-coping types of such patients at an early stage and carry out education on stress-coping, focusing on resolving the actual problem.

Inhibition of interferon-gamma-induced nitric oxide production in endotoxin-activated macrophages by cytolethal distending toxin.

INTRODUCTION: Cytolethal distending toxin (CDT) is a DNA-targeting agent produced by certain pathogenic gram-negative bacteria such as the periodontopathogenic organism Aggregatibacter actinomycetemcomitans. CDT targets lymphocytes and other cells causing cell cycle arrest and apoptosis, impairing the host immune response and contributing to the persistence of infections caused by this microorganism. In this study we explored the effects of CDT on the innate immune response, by investigating how it affects production of nitric oxide (NO) by macrophages. METHODS: Murine peritoneal macrophages were stimulated with Escherichia coli sonicates and NO production was measured in the presence or not of active CDT. RESULTS: We observed that CDT promptly and significantly inhibited NO production by inducible nitric oxide synthase (iNOS) in a dose-dependent manner. This inhibition is directed towards interferon-gamma-dependent pathways and is not mediated by either interleukin-4 or interleukin-10. CONCLUSION: This mechanism may constitute an important aspect of the immunosuppression mediated by CDT and may have potential clinical implications in A. actinomycetemcomitans infections.

Work-related psychosocial factors and metabolic syndrome onset among workers: a systematic review and meta-analysis.

BACKGROUND: Work-related psychosocial factors have been associated with metabolic syndrome. However, no systematic reviews or meta-analyses have evaluated this association. METHODS: A systematic literature search was conducted, using PubMed, Embase, PsycINFO, PsycARTICLES and the Japan Medical Abstracts Society. Eligible studies included those that examined the previously mentioned association; had a longitudinal or prospective cohort design; were conducted among workers; provided sufficient data for calculating odds ratios, relative risks or hazard ratios with 95% confidence intervals; were original articles in English or Japanese; and were published no later than 2016. Study characteristics, exposure and outcome variables and association measures of studies were extracted by the investigators independently. RESULTS: Among 4,664 identified studies, 8 were eligible for review and meta-analysis. The pooled risk of adverse work-related stress on metabolic syndrome onset was significant and positive (RR = 1.47; 95% CI, 1.22-1.78). Sensitivity analyses limiting only the effects of job strain and shift work also indicated a significant positive relationship (RR = 1.75; 95% CI, 1.09-2.79; and RR = 1.59; 95% CI, 1.00-2.54, P = 0.049 respectively). CONCLUSION: This study reveals a strong positive association between work-related psychosocial factors and an elevated risk of metabolic syndrome onset. The effects of job strain and shift work on metabolic syndrome appear to be significant.

3D fibre architecture of fibre-reinforced sand.

The mechanical behaviour of fibre-reinforced sands is primarily governed by the three-dimensional fibre architecture within the sand matrix. In laboratory, the normal procedures for sample preparation of fibre-sand mixtures generally produce a distribution of fibre orientations with a preferential bedding orientation, generating strength anisotropy of the composite's response under loading. While demonstrating the potential application of X-ray tomography to the analysis of fibre-reinforced soils, this paper provides for the first time a direct experimental description of the three-dimensional architecture of the fibres induced by the laboratory sample fabrication method. Miniature fibre reinforced sand samples were produced using two widely used laboratory sample fabrication techniques: the moist tamping and the moist vibration. It is shown that both laboratory fabrication methods create anisotropic fibre orientation with preferential sub-horizontal directions. The fibre orientation distribution does not seem to be affected by the concentration of fibres, at least for the fibre concentrations considered in this study and, for both fabrication methods, the fibre orientation distribution appears to be axisymmetric with respect to the vertical axis of the sample. The X-ray analysis also demonstrates the presence of an increased porosity in the fibre vicinity, which confirms the assumption of the "stolen void ratio" effect adopted in previous constitutive modelling. A fibre orientation distribution function is tested and a combined experimental and analytical method for fibre orientation determination is further validated.

Inhibition of corneal inflammation by an acylated superoxide dismutase derivative.

Superoxide radicals and their metabolite(s) have been postulated to play an important role in the pathogenesis of inflammation. Hence, superoxide dismutase (SOD) has been used to reduce tissue injury caused by reactive oxygens. However, protection of the cornea and other ocular tissues from oxygen toxicity could not be achieved by administering SOD presumably due to its unfavorable in vivo behavior. To scavenge superoxide radicals on the outer surface of corneal epithelial cells, the authors synthesized an acylated SOD derivative (AC-SOD) by linking capric acid. When instilled into rabbit eyes, a significant amount of AC-SOD remained bound to the corneal surface for a fairly long time. Intracorneal injection of lipopolysaccharide (LPS) triggered infiltration of polymorphonuclear leukocytes (PMNs) to the cornea and induced severe keratitis. Topical administration of AC-SOD to the LPS-treated cornea markedly inhibited the infiltration of PMNs and suppressed the occurrence of keratitis. Under identical conditions, topically administered SOD was rapidly removed by tears and, hence, did not inhibit LPS-induced keratitis. When the number of PMNs in the systemic circulation was reduced by intravenous administration of hydroxyurea, LPS-induced keratitis was inhibited markedly. These results indicate that superoxide radicals and circulating PMNs might play a critical role in LPS-induced keratitis.

The subsite structures of guanine-specific ribonucleases and a guanine-preferential ribonuclease. Cleavage of oligoinosinic acids and poly I.

In order to estimate the size of the active site of guanylic acid specific RNases (RNase T1 from Aspergillus oryzae and RNase St from Streptomyces erythreus) and guanine-preferential RNase (RNase Ms from A. saitoi), the depolymerization reaction of oligoinosinic acid, (Ip)nI greater than p, having various chain lengths was studied. The kinetic parameters for depolymerization of oligoinosinic acids, (pKm, log V and log V/Km) by the three RNases increased with increase of the chain length of the substrates, and became almost constant at n = 2 or more. Thus, the size of the active site of RNase T1, RNase St, and RNase Ms was estimated to be three nucleotides in length.

Japanese monozygotic twins with familial amyloidotic polyneuropathy (FAP) (ATTR Val30Met).

Twenty-nine-year-old twin brothers having the amyloidogenic transthyretin (ATTR) Val30Met gene developed the clinical symptoms of familial amyloidotic polyneuropathy (FAP) in 1995. The twins had the same educational background and lived in the same district. FAP manifestations were similar in both cases, although electromyographic examinations revealed sensorimotor polyneuropathy in No. 1 and sensory polyneuropathy in No. 2. DNA analysis revealed that they were monozygotic twins. In addition to environmental factors, genetic factors may play an important role in determining the onset of FAP.

Analysis of transthyretin amyloid fibrils from vitreous samples in familial amyloidotic polyneuropathy (Val30Met).

The aim of the present study was to analyze the forms of wild type and mutated monomeric transthyretin (Val30Met) in the amyloid fibrils of patients with familial amyloidotic polyneuropathy by electrospray ionization mass spectrometry (ESI-MS). The solubility of amyloid fibrils from the vitrectomized samples was examined to determine the appropriate solution for ESI-MS. ESI-MS analysis revealed that heterozygotic Val30Met amyloid fibrils contained 14.6 +/- 7.5% normal TTR. In all samples, 3 different types of variant ATTR could be identified: Full length ATTR, and -57, and -157 (or 156) Da from ATTR Val30Met were found. The two peaks showing -57, and -157 (or 156) Da from ATTR Val30Met corresponded to the -Gly, and -Gly-Pro sequences of ATTR Val30Met from the N-terminal. The results illustrate the heterogeneity of ATTR amyloid deposits and this method may be very useful for analyzing amyloid fibrils in ATTR related amyloidosis.

Synthesis, solution structure, binding activity, and cGMP activation of human guanylin and its disulfide isomer.

Guanylin is a recently isolated peptide consisting of 15 amino acid residues with four cysteines, which may form two intramolecular disulfide bridges, and stimulates intestinal membrane guanylate cyclase. The position of the disulfide linkages of guanylin was predicted from its structural similarity to a heat stable enterotoxin which is thought to be responsible for secretory diarrhoea. Both guanylin, with disulfide positions 4-12 and 7-15, and its disulfide isomer, with disulfides positions 4-15 and 7-12, were chemically synthesized by the solid-phase method and purified. Two specific disulfides were selectively formed and confirmed by sequencing, mass spectrometry and high-performance liquid chromatography in combination with enzymatic cleavage. The structure of both isomers has been investigated in solution by 1H nuclear magnetic resonance spectroscopy. Guanylin exists as a mixture of two stable conformations which have compact spiral structures, from comparison with literature data. In contrast, the disulfide isomer of guanylin shows only a single conformation with an elongated curved plate-like structure. Binding assays were performed using labelled guanylin with membranes obtained from rat jejunum. Both disulfide isomers were investigated by the cGMP assay. Both binding and cGMP assays indicated that the relevant form of disulfide bridges in the intact guanylin was as predicted.

Outcome of liver transplantation for transthyretin amyloidosis: follow-up of Japanese familial amyloidotic polyneuropathy patients.

Since 1990, liver transplantation for familial amyloidotic polyneuropathy (FAP) has been carried out world-wide, and the outcome of the procedure seems to be promising. FAP is inherited systemic disease caused by mutated transthyretin. The most common cause is the valine to methionine substitution at position 30 (Met30). We have developed a scoring system for FAP Met30 that takes into account a variety of clinical symptoms of the disease. Six patients with FAP Met30 underwent extensive examinations according to our scoring system before and after transplantation. All patients survived the procedure and are alive after transplantation. Improvements of sensory and autonomic disturbances were observed during the initial 12 months after the procedure only, thereafter the patients' status remained unchanged. Following transplantation, no improvement of motor function and visceral organ damage were observed, but the modified body mass index improved in four of six patients after the operation. These results suggest that liver transplantation of FAP patients stops the progress of the disease, and that minor improvements are noted in several patients after the procedure. However, transplantation should be performed early after the onset of the disease in order to preserve the patients' functional status.

Hepatic arterial infusion chemotherapy with continuous low dose administration of cisplatin and 5-fluorouracil for multiple recurrence of hepatocellular carcinoma after surgical treatment.

To date, conventional treatments for multiple intrahepatic recurrence of hepatocellular carcinoma (HCC) after surgery are unsuccessful. The aim of this retrospective study was to evaluate the prognostic effectiveness of a new infusion chemotherapy of cisplatin (CDDP) and 5-fluorouracil (5-FU) via hepatic artery for HCC with multiple intrahepatic recurrence. Fifty-two patients, who had postoperative multiple recurrence of HCC (more than 3 tumors), were enrolled in this study. Thirty-one patients were treated by hepatic arterial infusion chemotherapy via a subcutaneously implanted injection port. A one-week course of this treatment consisted of daily administration of cisplatin (10 mg for 1 h on days 1-5) and subsequent daily administration of 5-fluorouracil (250 mg for 5 h on days 1-5). Three to six sequential one-week courses were performed (the CDDP,5-FU group). Twenty-one patients underwent conventional interventional therapies including transcatheter arterial chemoembolization, lipiodolization (the conventional group). The complete response rate and the effective response rate in the CDDP,5-FU group were 29.0% and 71.0%, respectively. The 5-year survival rate in this group was 45.7%, which was significantly better than that in the conventional group. Based on multivariate analysis, CDDP,5-FU hepatic arterial infusion chemotherapy was found to be significant in prolonging survival, and this treatment achieved favorable therapeutic results for multiple recurrence of HCC. As part of a multidisciplinary approach this treatment is expected to improve the prognosis of patients with advanced HCC.

Ocular manifestations of familial amyloidotic polyneuropathy type I: long-term follow up.

AIMS: To obtain precise information on ocular manifestations of familial amyloidotic polyneuropathy (FAP) type I, the incidence of five main ocular manifestations--abnormal conjunctival vessels (ACV), keratoconjunctivitis sicca (KCS), pupillary abnormality, vitreous opacity, and glaucoma, were compared through long term follow up. METHODS: Ocular examinations were performed in 37 FAP type I patients (Met30) from once to 12 times over a period of 1 to 12 years and 7 months. RESULTS: The following incidences were observed on initial examination of each patient with FAP: ACV in 75.5%, pupillary abnormalities in 43.2%, KCS in 40.5%, glaucoma in 5.4%, and vitreous opacity in 5.4%. All ocular manifestations increased with the progression of FAP, and the incidence of ACV reached 100% during follow up: this may be helpful in the diagnosis of FAP. CONCLUSION: Since no precise statistical ocular study on FAP with long term follow up has been performed, this report may provide important information to help elucidate the mechanism of the amyloid distributing process in the amyloid targeted organs of FAP and to provide the natural course of ocular manifestations of FAP.

Effect and distribution of intravenously injected 125I-guanylin in rat kidney examined by high-resolution light microscopic radioautography.

125I-guanylin was injected intravenously into rats, and their kidney and intestinal tract were processed for light microscopic radioautography using semithin sections to examine the binding sites. Various doses of unlabeled guanylin were also injected to examine the morphological effects of guanylin on the kidney. Dense labeling of silver grains due to 125I-guanylin were observed only in the kidney. In the cortex, silver grains were localized on the luminal side of the proximal tubules at 5-30 min. In the medulla, silver grains appeared at the basal side of the collecting ducts, capillaries and loops of Henle after 5 min. Silver grains then accumulated in the cytoplasm of the collecting ducts after 10 min, and disappeared after 30 min. The cell height of the inner medullary collecting ducts (IMCD) decreased and their luminal spaces increased dose-dependently 5 min after the injection of both labeled and unlabeled guanylin. These structural changes returned to control levels within 30 min. These results indicate a high density localization of guanylin receptors on the luminal surface of proximal tubules in the renal cortex and also rapid excretion of guanylin through the IMCD. The morphological changes of the IMCD suggest a diuretic effect of guanylin.

Immunocytochemical evidence for CDD/ANP-like peptides in strands of myoendocrine cells associated with the ventricular conduction system of the rat heart.

Immunohistochemical investigations with different antisera against cardiodilatin 99-126 or alpha atrial natriuretic polypeptide revealed the presence of cardiac hormones not only in the atria of rats but also in strands of myoendocrine cells located in subendocardial regions of the ventricular septum. The localization of CDD-IR (cardiodilatin immunoreactivity) in the ventricle is associated with the location of the conduction system in the rat. The significance of the morphological relationship between cardiodilatin and the conduction system of the rat heart is discussed.

Treatment of a Japanese patient with familial amyloidotic polyneuropathy with orthotopic liver transplantation.

A 28-year-old male patient with familial amyloidotic polyneuropathy (FAP) underwent a liver transplantation from a heart-beating cadaveric donor in Sweden. He had suffered from the disease for 2.5 years. It took 5.5 hours to carry out the operation without blood transfusion. After the liver transplantation, serum amyloidgenic variant transthyretin (TTR) levels became extremely low and diarrhea stopped after the 7th day. On day 13, the patient was discharged from the hospital and one month after the transplantation, his general condition remained quite good. This is the first case of a Japanese patient with congenital metabolic disorders as well as FAP to receive a liver transplantation from a heart-beating cadaveric donor.