Perforation of the temporomandibular joint disc: cadaveric anatomical study.

The aim of this human cadaveric study was to investigate the relationship between temporomandibular joint disc perforation and bony changes of the mandibular condyle. Overall, 135 cadaveric mandibles were used (69 male, 66 female; all White). Mean age at death was 78.7 years. Perforation of the disc was investigated. Differences in the area of the perforation according to the different types of bony change (erosion, flattening, osteophyte) were evaluated. Perforation of the disc was observed in 34.8% of all mandibles, occurring unilaterally in 53.2% of cases and bilaterally in 46.8%. The prevalence of perforation was 16.4% in cadavers <80 years old (67 heads) and 52.9% in those ≥80 years old (68 heads) (P < 0.001). Osteophyte formation was always identified along with other bony changes (21.7%) and never in isolation. The area of the perforation was significantly larger in the groups with bony changes (one, two, or three changes) than in the 'no bony change' group. The group with osteophyte formation showed a significantly larger perforated area than the group without osteophyte formation; likewise, the group with flattening showed a significantly larger perforated area than the group without flattening. Osteophytes and flattening are probably secondary bony changes that occur following disc perforation. Based on this study, disc perforation should be suspected when these findings are identified on imaging.

Verification of the influence of the arrangement of implants on the load distribution (a well-known figure by Rangert).

The purpose of this study is to evaluate the effects of the number and the placement of implants on load distribution for multiple implants with three-dimensional geometric analysis, and to verify the well-known conceptual figure by Rangert. Three teeth missing in left mandibular region was geometrically modelled in clinically simulated situation. Two implants placement as 'control', 'cantilever', 'three-implants' and 'offset placements' were analyzed with geometric analysis. The cantilever received 180-182% load of control, that is, almost same to the result by Rangert (200%). Three implants received 59-65% load of control, that is, almost same to the result by Rangert (67%). Offset arrangement received 59-65% load of control, that is, larger than the result by Rangert (40%). It was concluded that the influence of the arrangement of implants on the load distribution presented in the conceptual figure by (Rangert BR, Sullivan RM & Jemt TM, J Oral Maxillofac Implants. 1997;12:360) was verified except for the effects of the offset arrangement.

Purification and identification of lactoperoxidase in milk basic proteins as an inhibitor of osteoclastogenesis.

A milk protein fraction with alkaline isoelectric points (milk basic protein, MBP) inhibits both bone resorption and osteoclastogenesis for in vitro models. We previously identified bovine angiogenin as a component of MBP that inhibits bone resorption. However, purified angiogenin had no effect on osteoclastogenesis, suggesting that MBP contains unidentified component(s) that inhibit osteoclast formation. In this study, we purified lactoperoxidase (LPO) as the predominant inhibitor of osteoclastogenesis in MBP. The LPO treatment downregulated levels of reactive oxygen species in osteoclasts. Signaling by receptor activator of NF-kappa-B ligand/receptor activator of NF-kappa-B (RANKL/RANK) was downregulated in LPO-treated cells, and, in particular, the ubiquitination of tumor necrosis factor receptor associate factor 6 (TRAF6) and activation of downstream signaling cascades (JNK, p38, ERK, and NFκB) were suppressed. Ultimately, LPO treatment led to decreased expression of c-Fos and NFAT2. These results suggest that MBP contains at least 2 components that independently suppress bone resorption through a unique mechanism: angiogenin inhibits bone resorption and LPO inhibits RANKL-induced osteoclast differentiation. These data explain many of the positive aspects of milk consumption on bone health.

Graduate and undergraduate geriatric dentistry education in a selected dental school in Japan.

Geriatric dentistry and its instruction are critical in a rapidly ageing population. Japan is the world's fastest-ageing society, and thus, geriatric dentistry education in Japan can serve as a global model for other countries that will soon encounter the issues that Japan has already confronted. This study aimed at evaluating geriatric dental education with respect to the overall dental education system, undergraduate geriatric dentistry curricula, mandatory internships, and graduate geriatric education of a selected dental school in Japan. Bibliographical data and local information were collected. Descriptive and statistical analyses (Fisher and chi-squared test) were conducted. Japanese dental schools teach geriatric dentistry in 10 geriatric dentistry departments as well as in prosthodontic departments. There were no significant differences found between the number of public and private dental schools with geriatric dentistry departments (P = 0.615). At Showa University School of Dentistry, there are more didactic hours than practical training hours; however, there is no significant didactic/practical hour distribution difference between the overall dental curriculum and fourth-year dental students' geriatric dental education curriculum (P = 0.077). Graduate geriatric education is unique because it is a 4-year PhD course of study; there is neither a master's degree programme nor a certificate programme in geriatric dentistry. Overall, both undergraduate and graduate geriatric dentistry curricula are multidisciplinary. This study contributes to a better understanding of geriatric dental education in Japan; the implications of this study include developing a clinical/didactic curriculum, designing new national/international dental public health policies, and calibrating the competency of dentists in geriatric dentistry.

Diagnostic accuracy of cardiac metaiodobenzylguanidine scintigraphy in Parkinson disease.

BACKGROUND AND PURPOSE: To estimate the diagnostic accuracy of cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigram for detection of Parkinson disease. METHODS: A cross-sectional study with index test of MIBG scintigram and reference standard of U.K. Parkinson's Disease Brain Bank Criteria was performed in 403 patients. Ratio of cardiac-to-mediastinum MIBG accumulation was determined at 20 min (early H/M) and 4 h (late H/M). Area under the receiver-operator characteristic (ROC) curve, sensitivity and specificity in detecting Parkinson disease were analyzed. Accuracy was analyzed in a subgroup of patients with disease duration of 3 years or less. RESULTS: Area under the ROC curve was 0.89 using either early or late H/M as a diagnostic marker (95% CI 0.85-0.92 for early H/M and 0.86-0.93 for late H/M). Sensitivity and specificity were 81.3% (76.1-85.8%) and 85.0% (77.7-90.6%) for early H/M and 84.3% (79.3-88.4%) and 89.5% (83.01-94.1%) for late H/M. In the subgroup with duration of 3 years or less, the ROC curve area, sensitivity, and specificity were 0.86 (0.79-0.92), 76.0% (64.8-85.1%), and 83.9% (71.7-92.4%) for early H/M and 0.85 (0.78-0.92), 73.3% (61.9-82.9%), and 87.5% (75.9-94.8%) for late H/M. CONCLUSION: Although diagnostic accuracy of cardiac MIBG scintigram is high, it is limited because of insufficient sensitivity in patients with short duration.

Estimation of the area under the curve for mycophenolic acid in adult renal transplant patients with concomitant tacrolimus using a limited sampling strategy.

OBJECTIVES: The aim of this study was to develop a limited sampling strategy (LSS) for monitoring the use of mycophenolic acid (MPA) in maintenance therapy with tacrolimus (TCL) in renal transplant patients. METHODS: Eighteen adult patients receiving a first transplant were investigated. All patients were treated with a combination of TCL, steroid and mycophenolate mofetil (MMF). Besides the predose trough concentration (C(0)), whole blood samples were taken for measurement of the MPA concentration at 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 h for a 14-point 12-h pharmacokinetic (PK) profile. Using stepwise linear regression analysis, an abbreviated area under the concentration time curve (AUC) was calculated using all 14, and any combination of sampling points to give an estimating equation with up to three predictors. RESULTS: The equation derived from C(2), C(7) and C(12,) for AUC estimation: AUC = (2.05 x C(2)) + (8.51 xC(7)) + (2.29 x C(12)) + 4.24. was found to be optimal. Using this formula, there was an excellent correlation between the estimated 3-point AUC and AUC(0-12 h). To assess the agreement between the abbreviated methods and the full PK profile, we plotted the average AUC of the abbreviated estimates and the full PK profile. This Bland-Altman analysis indicated good agreement to within +/-2 SD and a prediction variability of 7.56 microg x h/mL. CONCLUSION: Our proposed three-sampling-point estimate of AUCs is clinically acceptable. However, the sampling times are inconvenient for outpatients, and is recommended only for monitoring MMF treatment of inpatients with suspected toxicity or at high risk of organ rejection.

Successful endovascular occlusion of an aneurysm of the cervical vertebral artery associated with neurofibromatosis-1.

A 30 year old female with a fusiform aneurysm of the cervical vertebral artery causing nerve root compression and associated with neurofibromatosis-1 was successfully treated with endovascular methods which resolved the mass effect. This is the first report demonstrating the reduction of the mass effect of an aneurysm on a cervical nerve root with endovascular treatment by using MR neurography.

Frequent beta-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm.

Significance of Wnt signaling with beta-catenin mutations on solid-pseudopapillary neoplasm (SPN) of the pancreas was studied by immunohistochemistry and molecular analysis. On immunohistochemistry, all 18 SPNs tested showed diffuse cytoplasmic/nuclear positivity for beta-catenin. Upon direct DNA sequencing of exon 3 of the beta-catenin gene, 15 (83%) of the 18 SPNs showed 1-bp missense mutation in codons 32 (5 cases), 33 (3 cases), 34 (3 cases), 37 (3 cases), and 41 (1 case). Immunoreactivity for cyclin D1, one of the intranuclear targets of beta-catenin complexes, was found in tumor cells of more than half the tumor cells of all of the 18 SPNs. The present study strongly suggested a significant role of Wnt signaling, mostly associated with beta-catenin mutations in the tumorigenesis of SPN.

Integrated genomic and functional analyses reveal glyoxalase I as a novel metabolic oncogene in human gastric cancer.

Chromosomal abnormalities are good guideposts when hunting for cancer-related genes. We analyzed copy number alterations of 163 primary gastric cancers using array-based comparative genomic hybridization and simultaneously performed a genome-wide integrated analysis of copy number and gene expression using microarray data for 58 tumors. We showed that chromosome 6p21 amplification frequently occurred secondary to ERBB2 amplification, was associated with poorer prognosis and caused overexpression of half of the genes mapped. A comprehensive small interfering RNA knockdown of 58 genes overexpressed in tumors identified 32 genes that reduced gastric cancer cell growth. Enforced expression of 16 of these genes promoted cell growth in vitro, and six genes showing more than two-fold activity conferred tumor-forming ability in vivo. Among these six candidates, GLO1, encoding a detoxifying enzyme glyoxalase I (GLO1), exhibited the strongest tumor-forming activity. Coexpression of other genes with GLO1 enhanced growth-stimulating activity. A GLO1 inhibitor, S-p-bromobenzyl glutathione cyclopentyl diester, inhibited the growth of two-thirds of 24 gastric cancer cell lines examined. The efficacy was found to be associated with the mRNA expression ratio of GLO1 to GLO2, encoding glyoxalase II (GLO2), another constituent of the glyoxalase system. GLO1 downregulation affected cell growth through inactivating central carbon metabolism and reduced the transcriptional activities of nuclear factor kappa B and activator protein-1. Our study demonstrates that GLO1 is a novel metabolic oncogene of the 6p21 amplicon, which promotes tumor growth and aberrant transcriptional signals via regulating cellular metabolic activities for energy production and could be a potential therapeutic target in gastric cancer.

Mediastinoscopic extended thymectomy for pediatric patients with myasthenia gravis.

BACKGROUND: Extended thymectomy is indicated for children with myasthenia gravis (MG) when drug-resistance or dependence is seen. We have employed a technique for mediastinoscopic extended thymectomy (MET) on children with MG. METHOD: A total of 14 children underwent MET at Kanagawa Children's Medical Center between 2005 and 2013. A mediastinal operation field was made by a V-shaped hook infrasternally to extirpate the thymus with adipose tissue around the thymus. RESULTS: The operation time and the amount of blood loss were 182±44 minutes and 34±43 ml, respectively. Postoperative complications, in the form of transient paralysis of the right recurrent nerve, occurred in 2 patients. The median length of postoperative hospital stay was 4.5 days. After MET, 6 patients achieved complete remission and 7 patients achieved steroid dose reduction, but no improvement was seen in 1 patient. CONCLUSIONS: This procedure offers the advantage of good surgical access for dissection around the bilateral phrenic nerves in extended total thymectomy, while achieving good cosmetic results.

Clinical study of niceritrol on serum lipids in the treatment of hyperlipidemia.

The effects of niceritrol, a nicotinic acid derivative, on the levels of HDL-cholesterol (HDL-Ch) and a mixture of VLDL- and LDL-Ch (VLDL- + LDL-Ch) were studied in hyperlipidemic patients. Serum total cholesterol (sTC) and serum triglyceride (sTG) were significantly reduced during niceritrol administration. Lipoprotein electrophoresis showed that niceritrol increased the alpha:beta ratio. HDL-Ch showed a significant increase of 12.5% by the 16th week of therapy. This increase was more marked in patients with lower pre-treatment HDL-Ch levels and significant in patients whose pre-treatment sTG levels were in excess of 200 mg/dl. Females displayed higher pre-treatment HDL-Ch levels (38.5 mg/dl) than males (30.6 mg/dl). However, niceritrol increased HDL-Ch significantly in both groups. At 16 weeks, the VLDL- + LDL-Ch level showed a significant decrease of 9.2%; the HDL-Ch:VLDL + LDL-Ch and HDL-CH:sTC ratios were significantly increased throughout niceritrol administration. Niceritrol is thought to be effective in preventing the development and progression of atherosclerosis because it raises the level of anti-atherogenic HDL-Ch and lowers the level of atherogenic VLDL- + LDL-Ch.

Monoclonal antibodies to human chorionic gonadotropin and their application to two-site sandwich radioimmunoassay.

Monoclonal antibodies were prepared against human chorionic gonadotropin (HCG). One monoclonal antibody recognized a conformational determinant expressed only on native HCG molecule and another monoclonal antibody had the specificity for the epitopes located on the beta-subunit of HCG. Monoclonal antibodies reacting with different antigenic determinants on the HCG molecule were used to develop a simplified 2-site sandwich radioimmunoassay in which one monoclonal antibody was immobilized and another labeled with 125iodine. This assay was highly specific for HCG and there was no cross-reactivity with alpha, beta-subunit of HCG, luteinizing hormone and follicle stimulating hormone.

Attenuation of ischemia and reperfusion injury of canine livers by inhibition of type II phospholipase A2 with LY329722.

BACKGROUND: Membrane phospholipid breakdown, caused by ischemia and reperfusion (I/R) of the liver, releases free fatty acids including arachidonic acids and lysophospholipids, which serve as precursors of various inflammatory lipid derivatives. Phospholipase A2 (PLA2) is a key enzyme that initiates this reaction. In this study, we tested our hypothesis that a type II PLA2 inhibitor, LY329722, could attenuate hepatic I/R injury caused by a 2-hr total hepatic vascular exclusion (THVE) in dogs. METHODS: Eighteen beagle dogs, subjected to a 2-hr THVE, were divided into three groups. Group 1 (n=6) was untreated and served as a control group. LY329722 was administered to animals in group 2 (n=6) intravenously (0.2 mg x kg(-1) x hr(-1)) for 60 min before ischemia, and to animals in group 3 (n=6) for 60 min starting 15 min before reperfusion (0.2 mg x kg(-1) x hr(-1)). Animal survival, systemic and splanchnic hemodynamics, hepatic tissue blood flow, liver functions, energy metabolism, hepatic venous thromboxane B2 and endothelin-1 levels, phospholipid levels and tumor necrosis factor-a mRNA expression in liver tissue, and histopathologic findings were evaluated. RESULTS: Two-week animal survival was 33% (two of six) in group 1, and 100% (six of six) in groups 2 and 3. LY329722 improved systemic and splanchnic hemodynamics, hepatic tissue blood flow, and energy metabolism, reduced liver enzyme, thromboxane B2, and endothelin-1 release, prevented hepatic phospholipid degradation and tumor necrosis factor-alpha mRNA expression, and lessened histopathologic damage and the number of neutrophil infiltrating into the liver tissue. CONCLUSION: The present study demonstrated that a type II PLA2 inhibitor, LY329722, attenuated hepatic I/R injury caused by a 2-hr THVE model in dogs.

Lightning injury as a blast injury of skull, brain, and visceral lesions: clinical and experimental evidences.

The present study attempts to better understand the mechanism of injuries associated with direct lightning strikes. We reviewed the records of 256 individuals struck by lightning between 1965 and 1999, including 56 people who were killed. Basal skull fracture, intracranial haemorrhage, pulmonary haemorrhage, or solid organ rupture was suspected in three men who died. Generally these lesions have been attributed to current flow or falling after being struck. However, examination of surface injuries sustained suggested that the true cause was concussion secondary to blast injury resulting from vaporization of water on the body surface by a surface flashover spark. To investigate this hypothesis, an experimental model of a lightning strike was created in the rat. Saline-soaked blotting paper was used to simulate wet clothing or skin, and an artificial lightning impulse was applied. The resultant lesions were consistent with our hypothesis that the blast was reinforced by the concussive effect of water vaporization. The concordance between the clinical and experimental evidence argues strongly for blast injury as an important source of morbidity and mortality in lightning strikes.

Regional distribution of sultopride and sulpiride in rat brain measured by radioimmunoassay.

Sensitive and specific radioimmunoassays for both sultopride and sulpiride were developed. Using these radioimmunoassays, the regional distributions of sultopride and sulpiride in rat brain after intraperitoneal administration were investigated. Although relatively small amounts of both drugs were detected in the brain, sultopride appears to pass the blood-brain barrier more easily than sulpiride. Relatively high concentrations of sultopride were seen in hypothalamus, striatum, the mesolimbic area and hippocampus, while sulpiride accumulated mainly in brain areas such as hypothalamus, medulla oblongata and cerebellum, where the blood-brain barrier is less effective. Both drugs seem to be concentrated by the pituitary and pineal body. These differences between sultopride and sulpiride in penetration to the brain may depend on their different lipid solubilities, since sultopride has a higher lipid solubility compared with sulpiride.

Characteristics of [3H]sultopride binding to rat brain.

The binding of [3H]sultopride, a benzamide drug, to rat brain was investigated in vitro. Specific [3H]sultopride binding was observed in dopaminergic regions: striatum, nucleus accumbens, olfactory tubercle, substantia nigra, frontal cortex and anterior pituitary. Specific [3H]sultopride binding to striatum was saturable and had one high affinity binding site with a KD of 5.8 nM and a total density of receptors 25.7 pmol/g. [3H]Sultopride binding was stereoselectively displaced by (-)- and (+)-sultopride. Inhibition studies indicated that all neuroleptic drugs and dopamine were capable of displacing sultopride from its binding sites. A highly significant correlation was observed between IC50 values against [3H]sultopride and those against [3H]spiperone binding. Specific [3H]sultopride binding was highly dependent on the presence of sodium ions. The results suggest that the characteristics of sultopride binding sites seem to be similar to those of the D2-receptor labeled by spiperone and haloperidol. The sultopride binding site was highly dependent on the presence of sodium ions and may thus be characterized as a sodium-dependent D2-receptor.

Effect of suramin on 125I-insulin-like growth factor-I binding to human meningiomas and on proliferation of meningioma cells.

Suramin, a polyanionic compound, has been shown to inhibit the binding of various growth factors to cell surface receptors. The effects of suramin on 125I-insulin-like growth factor (IGF)-I binding to human meningioma tissues and IGF-I-induced deoxyribonucleic acid (DNA) synthesis in cultured meningioma cells were examined using the quantitative receptor autoradiographic method and 3H-thymidine incorporation, respectively. Suramin inhibited specific 125I-IGF-I binding to meningioma tissue sections in concentration-dependent manner, with a 50% inhibiting concentration (IC50) of 8.7 +/- 0.5 x 10(-5) M. The addition of 10(-3) M suramin to the incubation buffer potently dissociated 125I-IGF-I previously bound to meningioma tissue as a function of time (dissociation half-life (T1/2) 6.8 minutes). After preincubation of tissue sections with 10(-3) M suramin for 120 minutes, there was no inhibition of the subsequent 125I-IGF-I binding to meningiomas. Suramin inhibited the IGF-I-induced incorporation of 3H-thymidine into meningioma cells in a dose-dependent manner, with an IC50 of 4.6 +/- 1.4 x 10(-5) M. The growth rate of meningioma cells (determined 4 days after seeding) was reduced by 10%, 20%, and 50% of the control culture in the presence of 10(-6), 10(-5), and 10(-4) M suramin, respectively. These results suggest that suramin interferes with IGF-I binding to meningioma tissue and inhibits proliferation of cells, at least partially by preventing IGF-I-induced DNA synthesis and probably by interacting with IGF-I directly rather than with its binding sites.

Open pergolide treatment of tricyclic and heterocyclic antidepressant-resistant depression.

BACKGROUND: Recently, a dopamine hypothesis of depression was put forward, and several studies have demonstrated that direct and indirect dopamine agonists have antidepressant effects. METHODS: Using Clinical Global Impressions, we evaluated the efficacy of 4-week treatment of pergolide as an antidepressant adjuvant involving 20 unipolar depressed patients who were refractory to standard treatment with antidepressants. RESULTS: One patients (5%) were very much improved, seven (35%) much improved, four (20%) minimally improved, six (30%) no change or worse, and two (10%) not assessed. There was no significant difference in any clinical factors between the pergolide responder and non-responder group. LIMITATIONS: This study was a non-blind open trial, and pergolide was added to tricyclic and heterocyclic antidepressants. CONCLUSION: Pergolide may be useful as an antidepressant adjuvant, suggesting a potential role for dopamine-2 stimulation in the antidepressant response.

Expression of a functional endothelin (ETA) receptor in human meningiomas.

Endothelin (ET) receptor subtypes (ETA and ETB) in human meningiomas were characterized using quantitative receptor autoradiography. A single class of high-affinity 125I-ET-1 binding sites was localized in all meningioma tissue studied (dissociation constant: 2.4 +/- 0.3 nM, maximum binding capacity: 319 +/- 66 fmol/mg (mean +/- standard error of the mean for 13 tumors)). Unlabeled ET-1 showed a strong affinity for 125I-ET-1 binding to tissue sections of the tumors with a 50% inhibiting concentration (IC50) of 2.9 +/- 0.7 x 10(-9) M, whereas ET-3 showed a much lower affinity (IC50: 8.4 +/- 2.5 x 10(-6) M). Sarafotoxin S6c, a selective agonist for the ETB receptor, could not compete for 125I-ET-1 binding to meningiomas. Endothelin-1 significantly stimulated deoxyribonucleic acid (DNA) synthesis in a dose-dependent manner in cultured human meningioma cells. In contrast, no significant stimulation of DNA synthesis occurred with an S6c concentration up to 10(-7) M. Pretreatment of the meningioma cells with pertussis toxin, a bacterial toxin that adds adenosine 5'-diphosphate-ribose to the alpha subunit of guanine nucleotide binding (G) proteins such as Gi or G(o), induced a concentration-dependent reduction in ET-stimulated DNA synthesis in meningioma cells, but did not affect the epidermal growth factor-induced DNA synthesis. These observations suggest that the ETA receptor is predominantly expressed in human meningioma tissue and that ET may act as a growth factor on the meningioma cells by interacting with the ETA receptor and by pertussis toxin-sensitive mechanisms.

Simple determination of mycophenolic acid in human serum by column-switching high-performance liquid chromatography.

A column-switching high-performance liquid chromatographic analysis was established to monitor the serum concentration of mycophenolic acid, the active metabolite from mycophenolate mofetil administered for the prophylaxis of acute organ rejection in renal transplantation. The system consisted of two pumps for solvent delivery, a column-switching valve, a precolumn, and a reversed-phase analytical column. The present method enabled us to determine MPA by injecting serum samples directly into HPLC without any pretreatment. The mobile phases with different amounts of organic solvent were delivered to the precolumn and analytical column by separate lines, and samples were applied to the precolumn. The column switching valves were switched automatically following the processes for the elimination of protein and the drug analysis. The peak heights of MPA were linearly related to the concentrations (r=0.999) in the range of 0.1-20 micro g/ml, and the limit of quantification was 0.1 micro g/ml (S/N ratio=3). This method was accurate and reproducible on the basis of the results of recovery (94.0-98.0%) and small coefficient of variations of intra and inter-assay (less than 8.3%).