Evaluation of non-Gaussian model-based diffusion-weighted imaging in oral squamous cell carcinoma: comparison with tumour functional information derived from positron-emission tomography.

AIM: To evaluate and compare diffusion-weighted imaging (DWI) parameters derived from a non-Gaussian fitting model and positron-emission tomography (PET) parameters derived from 18F-fluoromisonidazole-PET (FMISO-PET) in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Primary sites were evaluated prospectively in 18 patients. DWI was performed using six b-values (0-2,500). Diffusion-related parameters of kurtosis value (K), the kurtosis-corrected diffusion coefficient (DK), diffusion heterogeneity (α), distributed diffusion coefficient (DDC), the slow diffusion coefficient (Dslow), and the apparent diffusion coefficient (ADC) were calculated from four diffusion-fitting models. Maximal standardised uptake values (SUVmax), mean standardised uptake values (SUVmean), and the tumour-to-muscle ration (TMR) of the SUV value were calculated for FMISO-PET. Spearman's correlation coefficient was used to evaluate the correlation between each non-Gaussian diffusion model parameters and PET parameter. RESULTS: There was moderate correlation between FMISO-PET SUVmax and Dslow (ρ=-0.45, p=0.06). In addition, there was good correlation between TMRmax and five non-Gaussian diffusion model parameters (K: ρ=0.65, p=0.004, DK: ρ=-0.72, p=0.0008, DDC: ρ=-0.75, p=0.0003, ADC: ρ=-0.74, p=0.0005, and Dslow: ρ= -0.65, p=0.003), and between TMRmean and five non-Gaussian model parameters (K: ρ=0.64, p=0.005, DK: ρ=-0.61, p=0.007, DDC: ρ=-0.63, p=0.005, ADC: ρ=-0.61, p=0.007, and Dslow: ρ=-0.56, p=0.015). CONCLUSION: Non-Gaussian diffusion model parameters can be related to tumour hypoxia.

Arsenic trioxide induces down-regulation of gp46 via protein oxidation: proteomics analysis of oxidative modified proteins in As2O3-treated HTLV-1-infected cells.

Adult T-cell leukemia (ATL) is a severe chemotherapy-resistant malignancy associated with prolonged infection by the human T cell-lymphotropic virus 1 (HTLV-1) retrovirus. Epidemiology studies strongly indicate that an increase in HTLV-1 virus load is an important factor during the onset of ATL. Therefore, inhibition of the growth/transmission of HTLV-1 infected cells is a promising strategy in preventing the disease. In our previous study, we revealed that arsenic trioxide (As2O3), a drug used to treat acute promyelocytic leukemia (APL), exerts an inhibitory effect on syncytium formation between HTLV-1 infected cells and HeLa cells via suppression of HTLV-1 envelope protein gp46 expression at low concentrations. In this study, we analyze the mechanism of action of As2O3 using a proteomics approach. Our results suggest that down-regulation of gp46 might be related to As2O3-induced oxidation of the 71-kDa heat shock cognate protein (HSC70) and the 78-kDa glucose-regulated protein (BiP/GRP78). We postulate that AS2O3 exerts an inhibitory effect on HTLV-1 virus transmission via down-regulation of gp46-production, which might be caused by oxidative modification of various proteins such as chaperones.

Creation of an improved mutant TNF with TNFR1-selectivity and antagonistic activity by phage display technology.

Tumor necrosis factor-alpha (TNF), which binds two types of TNF receptors (TNFR1 and TNFR2), regulates the onset and exacerbation of autoimmune diseases such as rheumatoid arthritis and Crohn's disease. In particular, TNFR1-mediated signals are predominantly related to the induction of inflammatory responses. We have previously generated a TNFR1-selective antagonistic TNF-mutant (mutTNF) and shown that mutTNF efficiently inhibits TNFR1-mediated bioactivity in vitro and attenuates inflammatory conditions in vivo. In this study, we aimed to improve the TNFR1-selectivity of mutTNF This was achieved by constructing a phage library displaying mutTNF-based variants, in which the amino acid residues at the predicted receptor binding sites were substituted to other amino acids. From this mutant TNF library, 20 candidate TNFR1-selective antagonists were isolated. Like mutTNF, all 20 candidates were found to have an inhibitory effect on TNFR1-mediated bioactivity. However, one of the mutants, N7, displayed significantly more than 40-fold greater TNFR1-selectivty than mutTNF. Therefore, N7 could be a promising anti-autoimmune agent that does not interfere with TNFR2-mediated signaling pathways.

Relations between anterior disc displacement and maxillomandibular morphology in skeletal anterior open bite with changes to the mandibular condyle.

In this study we investigated the relation between anterior disc displacement (ADD) and maxillomandibular morphology in skeletal anterior open bite with changes to the mandibular condyle. Thirty female patients (60 joints) with both conditions were evaluated. Magnetic resonance imaging of the temporomandibular joint (TMJ) was used to diagnose both ADD and changes to the mandibular condyle (erosion, osteophyte, and deformity). The relations among ADD, changes to the mandibular condyle, and maxillomandibular morphology were examined statistically. Changes to the mandibular condyle had a higher score than sym anterior open bite, the deviated side in asymmetric anterior open bite, and the non-deviated side. The score for disc displacement on the non-deviated side was lower than both the sym side and the deviated side. Unilateral changes to the mandibular condyle and unilateral disc displacement were not apparent in sym anterior open bite, but a unilateral non-displaced disc was seen only on the asymmetric side. Mandibular condylar changes were significantly more common on the deviated, than on the non-deviated, side. The SNB angle was significantly smaller, and the ANB, GZN, and SN-mandibular plane angles were significantly larger in sym anterior open bite. Overjet, ANB angle, GZN angle, and SN-MP angle were significantly larger, and the SNB angle was significantly smaller, in the presence of ADD without reduction and mandibular condylar deformity. We conclude that the prevalence of ADD without reduction and changes to the mandibular condyle were related to mandibular asymmetry and mandibular morphology in anterior open bite. This retrospective study suggests that ADD without reduction and mandibular condylar bone changes may be related to the progression of skeletal class II open bite and mandibular asymmetry in cases of skeletal open bite.

Static bone cavity in the condylar neck and mandibular notch of the mandible.

This study presents the radiographic findings of two cases of static bone cavity in the inferior aspect of the condylar neck and mandibular notch of the mandible. On plain CT, a soft tissue mass was observed in each cavity. The submandibular gland and the other glands were not found in each cavity. On contrast-enhanced CT, the soft tissue in the cavity in the inferior aspect of the condylar neck had marked linear enhancement and dilated vasculature structure was observed in the cavity. On the contrast-enhanced MRI, the soft tissue in the cavity of the mandibular notch had marked enhancement and flow void was detected in the cavity. In the inferior aspect of the condylar neck, the cavity size had enlarged radiographically over a period of three years. Vascular lesions were found in the cavity located in the inferior aspect of the condylar neck and mandibular notch of the mandible by both CT and MRI. The vascular lesion might explain the enlargement of the static bone cavity.

Incidence of anterior disc displacement without reduction of the temporomandibular joint in patients with dentofacial deformity.

The aim of this study was to investigate the incidence of anterior disc displacement without reduction (ADDwoR) of the temporomandibular joint (TMJ) in patients with dentofacial deformity. Eighty-eight female patients (176 joints) with skeletal class III malocclusion and 33 female patients (66 joints) with skeletal class II malocclusion, with or without anterior open bite and asymmetry, were evaluated. Magnetic resonance imaging (MRI) of the TMJ was used to diagnose ADDwoR. A statistical analysis was performed to examine the relationship between ADDwoR and skeletal structure. ADDwoR was present in 37 of the 66 joints (56.1%) in class II compared to 34 of the 176 joints (19.3%) in class III (P<0.05). In class III, ADDwoR was significantly more common in joints with mandibular asymmetry (24/74; 32.4%) than in joints with open bite (9/62; 14.5%) and joints with open bite and without mandibular asymmetry (1/38; 2.6%). In class II, ADDwoR was significantly less common in joints with mandibular asymmetry and without open bite (1/8; 12.5%). ADDwoR was only observed on the deviated side in both class III and class II with mandibular asymmetry. The prevalence of ADDwoR differed according to the dentofacial morphology.

Efinaconazole: Developmental and reproductive toxicity potential of a novel antifungal azole.

Efinaconazole is a new triazole antifungal for topical treatment of onychomycosis. The reproductive and developmental toxicity of efinaconazole was characterized in fertility and early embryonic development (rat), embryo-fetal development (rat and rabbit), and peri/post-natal development (rat) studies in accordance with current ICH guidances. In the fertility study, maternal reproductive toxicity was noted as estrous cycle prolongation (NOAEL=5mg/kg/day) but there were no male reproductive effects even in the presence of paternal toxicity (NOAEL=25mg/kg/day). Rat embryo-fetal and perinatal pup lethality was the most sensitive (NOAEL=5mg/kg/day) efinaconazole developmental toxicity and was noted at maternally toxic doses. Efinaconazole did not affect rabbit embryo-fetal development at maternally toxic doses (NOAEL=10mg/kg/day). No malformations were induced by efinaconazole in rats or rabbits. When compared with systemic exposures observed in onychomycosis patients, embryo-fetal toxicity in rats was noted at high (>100-fold) multiples of systemic exposure.

Changes in dietary fiber intake among Japanese in the 20th century: a relationship to the prevalence of diverticular disease.

In view of the fact that Japanese dietary patterns have been undergoing rapid "Westernization," in part characterized by decrease in fiber, we assessed dietary and crude fiber content in the Japanese diet using food consumption tables for the period from 1911 to 1980, and studied the trend in the reported prevalence of diverticular disease of the colon. Fiber content declined in diphasic pattern: the first decline, which probably had started in the late 19th century, progressed until the Second World War. Although records during the war period were unavailable, the high fiber content of the Japanese diet in the period immediately after the war reflects the tendency to supplement rice with more fiber-rich cereals, and to increase the amount of rice through reduced polishing during the war time. The second decline in fiber content in the Japanese diet, which started in the 1950s and progressed throughout the period of "high economic growth," was mainly due to the decrease in cereal consumption. The changes in crude fiber content in the Japanese diet after the Second World War resemble the pattern of rapid decline noted in the United States during the 1930s to the 1950s. The prevalence of diverticular disease in both countries also shows sudden steep upward turns during the period between 1930 and 1950 in the United States and the late 1970s in Japan, suggesting the presence of threshold level(s) of fiber intake for the effective prevention of diverticular disease. The prevalence of diverticular disease is still relatively low in Japan. However, if the current dietary trend continues, it may rise to a level currently found in the "Western" countries in the coming few decades.

Regional differences of metabolism in human masseter muscle by two-dimensional 31P-chemical shift imaging.

Many reports have demonstrated significant region-dependent differences in the fiber-type composition of the human masseter muscle. Therefore, it is considered that there is intramuscular heterogeneity of metabolic activity in the muscle. The present study was carried out, with two-dimensional Chemical Shift Imaging, to detect differences between the deep and superficial parts of the human masseter muscle at rest. Masseter muscle from 11 volunteers, from 20 to 27 years old, was examined, and characteristic spectra of the inorganic phosphate (Pi), phosphocreatine (PCr), and alpha-, beta-, and gamma-adenosine triphosphate (ATP) from each part of the muscles were obtained. In this study, the deep and superficial parts of the masseter muscle were distinguished by the existence of aponeurosis. The Pi/PCr, PCr/beta-ATP, and Pi/beta-ATP ratios as well as the pH in the deep and superficial parts were calculated from the peak spectra. Compared with the deep part, the Pi/PCr of the superficial part was lower (p < 0.05) and the PCr/beta-ATP was higher (p < 0.01). The Pi/beta-ATP and pH showed no significant differences between the two parts. The results indicate that the superficial part of the masseter muscle contains more PCr than the deep part, and this may be related to functional differences between these two parts. In future examinations of the metabolic activity of the human masseter muscle, the deep and superficial parts must be measured separately.

Nicotine attenuates stress-induced changes in plasma amino acid concentrations and locomotor activity in rats.

It is known that stressor stimuli (both systemic and processive) and nicotine activate central nervous system. Surprisingly, numerous studies have demonstrated an increase in nicotine self-administration among smokers when exposed to stress in order to reduce the stress-related tension. Therefore, in the present study, we decided to investigate the influence of nicotine on both behavioral (i.e., on locomotor activity) and metabolic (i.e., on the level of amino acids in the plasma) changes following water immersion restraint stress in rats. As expected, the stress produced evident decline in locomotor activity of the rats (p < 0.001) and in the levels of all plasma amino acids studied (p < 0.05). Nicotine alone also significantly reduced locomotor activity (p < 0.05) and the levels of some plasma amino acids. However, when administered to rats subjected to water immersion and restraint, nicotine attenuated both stress-induced decrease in locomotor activity (p < 0.05) and in some plasma amino acids. Thus, this study demonstrated that the mode of action of nicotine is strongly dependent on the level of initial brain activity, which provide new evidence for arousal-modulation model of nicotine action.

Neural activities during replacement of blood with fluorocarbon emulsion.

Exchange transfusion of the blood with fluorocarbon (FC) emulsion was conducted in the cat ventilated spontaneously with high oxygen tension gas, and responses of various neural activities to this replacement were studied. Animals survived in good physiological condition, at hematocrit values of less than 5%, more than 3 hours after the end of the FC transfusion. Electroencephalographic activity and afferent impulses of the carotid sinus nerve increased and sympathetic renal nerve activities decreased compared with the control activities before the replacement, indicating no impairment in the reflexogenic control of the respiratory and circulatory systems. Moreover, the amplitudes of the sensory evoked cortical potentials increased with lower hematocrit values during FC treatment. However, early components of auditory brain stem responses did not increase as markedly compared with the cortical responses. We concluded that the general condition of the animals and the neural responses examined were well preserved after FC emulsion exchange transfusion.

Comparison of magnetic resonance imaging and gross findings regarding masseter muscle aponeuroses in cadavers.

OBJECTIVES: The main objective of this study was to compare the actual distribution and thickness of aponeuroses in cadavers with the distribution and thickness as determined by means of magnetic resonance imaging for the sake of evaluating magnetic resonance imaging as a diagnostic modality for assessing masseter muscle aponeuroses. STUDY DESIGN: The aponeuroses of 26 masseter muscles from 13 intact cadavers were examined by magnetic resonance imaging. RESULTS: The ratio of concordance between gross findings and magnetic resonance imaging findings was 99.0%, although depiction of thin parts of the aponeuroses on magnetic resonance imaging was poor. CONCLUSIONS: Magnetic resonance imaging was useful as a diagnostic modality in the assessment of masseter muscle aponeuroses. Aponeuroses were distributed throughout almost the entire masseter muscle, although almost no aponeuroses were seen below the lower half of the anterior margin. This was thought to be a characteristic finding of masseter aponeuroses.

Analyses of muscular activity, energy metabolism, and muscle fiber type composition in a patient with bilateral masseteric hypertrophy.

Hyperwork of the masseter muscles due to habitual parafunction is thought to induce masseteric hypertrophy (so called work hypertrophy). However, the causes underlying this disease are not yet fully understood. Recently, we had a patient with bilateral masseteric hypertrophy, and we performed a partial excision of the masseter muscles. In this patient's case, we examined muscular activity, energy metabolism, and fiber type composition of the masseter muscles using electromyograms (EMG), 31P-magnetic resonance spectroscopy (MRS), and enzyme-histochemistry. The EMG showed no hyperactivity, and the 31P-MRS showed normal energy spectral patterns and PCr contents of the masseter muscles. The fiber type composition, however, in the muscles in this case was very different from that in muscles with "work hypertrophy" and also that in normal masseter muscles: 1. Loss of type IIB fibers; 2. Increases in type IIA and in type IM & IIC fibers; and 3. Decrease in type I fibers. The findings suggest that this is not a case of work hypertrophy but a case of compensatory hypertrophy possibly due to a lack of high-tetanus-tension type IIB fibers.

[A case of ureteral malacoplakia in a hemodialysis patient].

A case of ureteral malacoplakia in a hemodialysis patient is reported. A 64-year-old woman suffering from macrohematuria, was diagnosed as having a right ureteral tumor by means of computerized tomography and antegrade pyelography. Right nephroureterectomy with bladder cuff resection was performed. Pathological examination indicated malacoplakia; multiple Michaelis-Gutmann bodies were found. The patient did well postoperatively and was discharged without further complications. This case appears to be the twenty-first report of ureteral malacoplakia in the world.

Vacuum phenomenon in non-open fracture of the mandibular condyle: report of three cases.

Gas in the joint space was observed in three patients with condylar fracture who were referred for CT examinations of the mandible. CT showed that the condylar fractures were non-open fractures. The gas was only observed in the intrajoint capsule of the temporomandibular joint (TMJ). Follow-up CT, 4 days after the initial CT, showed that the gas in the joint space was absorbed in one of three cases. In the non-open condylar fractures, the gas collection in the TMJ was considered to be a vacuum phenomenon due to the intact joint capsule of the TMJ on CT.

CT and MRI findings of intraosseous schwannoma of the mandible: a case report.

We report the radiographical findings of a rare case of intraosseous schwannoma of the mandible. The tumour that presented as a unilocular, well-defined, radiolucent lesion on plain radiography was located in the molar region. On CT, the tumour was a well-demarcated mass with no periosteal reaction and no destruction of the bone cortex. Destructive changes in the cortical wall of the mandibular canal by the tumour were observed on CT, but no evidence of dilatation and shift in the inferior mandibular canal was seen. MR imaging revealed that the mandibular canal was encased by the tumour as a solid mass without cystic parts. The signal intensity of the tumour was non-specific on MRI. Characteristics of intraosseous schwannoma in the mandible are the encasement of the canal by a well-demarcated tumour without periosteal reaction and the destruction of mandibular bone cortex. The destructive change of the inferior mandibular canal can be observed on CT and MRI. However, a biopsy is necessary to make the final diagnosis because of the non-specificity of the findings.

Static bone cavity of the mandible: Computed tomography findings with histopathologic correlation.

PURPOSE: To review computed tomography (CT) findings of histopathologically examined static bone cavities in order to determine whether an additional pathogenesis may play a role in this disease. MATERIAL AND METHODS: Four patients with histopathologically examined static bone cavities were included in this retrospective study. Location, appearance of bone remodeling, tissue characteristics, and contrast enhancement of the cavity were assessed on CT images. CT findings were then compared with the histopathological findings. RESULTS: Static bone cavity was found in the lingual molar region in three patients and in the lingual cuspid region of the mandible in one patient. Both fatty and soft tissues were present in the cavities of all four patients. Attenuation of the soft tissue in the cavities was found to be different from that of the submandibular gland. The soft tissue showed enhancement with contrast-enhanced CT in three patients. For all patients, the histopathologic content of the static bone cavity included fat, soft tissue, and abnormal vasculature. The thickened vein wall in the abnormal vasculature was observed. Aberrant tissue of the submandibular gland was not found in any of the static bone cavities. CONCLUSION: Contrast enhancement of the soft tissue on the contrast-enhanced CT images suggests the presence of vasculature in the cavities. Histopathological examination confirmed the presence of fatty tissue and dilated abnormal vessels, and the absence of salivary gland tissue in the cavities. These findings show that vascular structures are prominent in tissues found in static bone cavities.