Type 1 interferon signature and cytotoxic T lymphocyte activation targeted against sweat ducts in inflammatory acquired idiopathic generalized anhidrosis.

BACKGROUND: Acquired idiopathic generalized anhidrosis (AIGA) leads to heat intolerance due to the loss or reduction in thermoregulatory sweating over an extensive area of the body. The pathomechanism of AIGA is still unclear but is believed to be autoimmune. OBJECTIVES: We investigated the clinical and pathological features of inflammatory AIGA (InfAIGA) and noninflammatory AIGA (non-InfAIGA) within the skin. METHODS: We compared anhidrotic and normohidrotic skin samples from 30 patients with InfAIGA and non-InfAIGA, as well as skin samples of melanocytic nevus as a negative control. We conducted morphometric analysis and immunohistochemical analysis of cell types and expression of inflammatory molecules (TIA1, CXCR3 and MxA). MxA expression was used as a proxy for type 1 interferon activity. RESULTS: We found that tissue samples from patients with InfAIGA exhibited inflammation within the sweat duct and atrophy of the sweat coil, whereas patients with non-InfAIGA exhibited only atrophy of the sweat coil. Cytotoxic T lymphocyte infiltration and MxA expression were only observed in the sweat ducts of patients with InfAIGA. CONCLUSIONS: InfAIGA is associated with increased sweat duct inflammation and sweat coil atrophy, whereas non-InfAIGA is only associated with sweat coil atrophy. These data suggest that inflammation leads to epithelial destruction of sweat ducts associated with the sweat coil atrophy and subsequent loss of function. Non-InfAIGA may be regarded as a postinflammatory state of InfAIGA. These observations indicate the contribution of both type 1 and type 2 interferons to sweat gland injury. The mechanism involved is similar to the pathomechanism of alopecia areata (AA).

Steatohepatitic hepatocellular carcinoma: imaging findings with clinicopathological correlation.

AIM: To evaluate the clinicopathological and computed tomography (CT) and magnetic resonance imaging (MRI) findings of steatohepatitic hepatocellular carcinoma (SH-HCC). MATERIALS AND METHODS: Clinicopathological and radiological features were evaluated in 20 patients with SH-HCC. The diagnosis of SH-HCC was made histologically if the tumour had four of the following five characteristics: steatosis (>5% tumour cells), ballooning, Mallory-Denk bodies, interstitial fibrosis, and inflammation. All patients underwent dynamic CT and MRI. CT and MRI images were reviewed for morphological features including tumour size, presence, and distribution of fat, and patterns and degree of contrast enhancement. RESULTS: Obesity, hypertension, and history of heavy alcohol intake were common clinical findings observed in 10 (50%), 13 (65%), and 11 (55%) of the 20 patients, respectively. Steatosis and steatohepatitis were pronounced in the background liver in 12 (60%) and 10 (50%) patients, respectively. SH-HCC was moderately differentiated in 18 patients (90%) and well differentiated in two (10%). Pathologically, steatohepatitic features were diffuse in 12 (60%) of the 20 tumours and focal in eight (40%). Tumour size and the percentage of intratumoural steatosis were not correlated (r=0.17, p=0.47). On CT, 16 (80%) patients showed arterial phase enhancement and delayed washout. On MRI, 16 (80%) of 20 tumours showed prominent fatty deposition (10 diffusely, six focally) with arterial phase enhancement. CONCLUSIONS: SH-HCC is likely to show prominent fatty deposits with arterial phase enhancement on CT and MRI. A hypervascular lesion with prominent fatty change should raise the diagnostic suspicion of SH-HCC.

Spheroid culture enhances osteogenic potential of periodontal ligament mesenchymal stem cells.

OBJECTIVE AND BACKGROUND: Human periodontal ligament mesenchymal stem cells (hPDLMSCs) are reported to be responsible for homeostasis and regeneration of periodontal tissue. Although hPDLMSCs are commonly cultured in monolayers, monolayer cultures have been reported as inferior to 3-dimensional cultures such as spheroids, which are spherical clusters of cells formed by self-assembly. The aim of this study was to examine the osteogenic phenotype of spheroids of hPDLMSCs, compared with monolayer cultures of hPDLMSC, in vitro and in vivo. MATERIAL AND METHODS: Spheroids were formed using microwell chips that were tagged with polyethylene glycol. Mesenchymal stem cell (MSC) markers in hPDLMSC spheroids were examined by flow cytometer. Real-time polymerase chain reaction analysis was examined to measure the expressions of stemness markers and osteogenesis-related genes in monolayer and spheroid-cultured hPDLMSCs. Immunofluorescence analysis was performed to confirm protein expressions of stemness markers in PDLMSC spheroids. Nodule formation assay, alkaline phosphatase (ALP) activity assay and transplantation assay in a mouse calvarial defect model were performed to confirm the osteogenic potential of hPDLMSC spheroids. To elucidate the mechanism of spheroid culture enhanced osteogenesis in hPDLMSCs with osteoinductive medium (OIM), a small interfering RNA (siRNA) assay targeted with secreted frizzled-related protein 3 (SFRP3) was examined. The levels of SFRP3 expression in monolayer and spheroid-cultured hPDLMSCs with OIM were measured by real-time polymerase chain reaction and western blotting analysis. ALP gene expression and ALP activity were examined in SFRP3-deficient hPDLMSC spheroids. RESULTS: The hPDLMSC spheroids expressed MSC markers, which were similar to hPDLMSCs grown in monolayer cultures. Intriguingly, the protein and mRNA expressions of transcription factors that regulate "stemness" were significantly increased in hPDLMSC spheroids, compared with hPDLMSCs in monolayer cultures. Nodule formation by hPDLMSCs was significantly increased in spheroid cultures grown with OIM, compared with monolayer-cultured hPDLMSCs. ALP activity and expression of osteogenesis-related genes were also significantly enhanced in hPDLMSC spheroids, compared with monolayer cultures. Treatment with hPDLMSC spheroids significantly enhanced new bone formation in a murine calvarial defect model, compared with hPDLMSCs in monolayer culture. Finally, to elucidate mechanisms by which spheroid culture enhances ALP activation in hPDLMSCs grown with OIM, an siRNA assay was used to manipulate expression of SFRP3, a Wnt signaling antagonist. Knockdown of SFRP3 suppressed ALP gene expression in hPDLMSCs grown in OIM; further, it suppressed ALP activity in spheroid culture. These data suggest that the enhancement of osteogenic potential in hPDLMSC spheroids is regulated through SFRP3-mediated ALP activation. CONCLUSION: Spheroid cultures of hPDLMSCs may be a novel and useful tool in regenerative medicine.

Degranulation and shrinkage of dark cells in eccrine glands and elevated serum carcinoembryonic antigen in patients with acquired idiopathic generalized anhidrosis.

BACKGROUND: Acquired idiopathic generalized anhidrosis (AIGA) is characterized by anhidrosis/hypohidrosis without other autonomic and neurological dysfunctions. Pathologically, AIGA is considered to usually present no significant morphological alterations in eccrine glands, the secretory portion which consists of clear cells, dark cells, and myoepithelial cells. AIGA patients recently have been reported to show high serum concentrations of carcinoembryonic antigen (CEA). OBJECTIVE: Our aim is to reveal morphological abnormalities of dark cells and investigate their relationship with serum CEA. METHODS: We performed comparative analysis of eccrine glands between sweat-preserved and non-sweating skin in four AIGA patients. Serum CEA concentrations in 22 cases with AIGA were measured with healthy volunteers. Furthermore, we semiquantitatively investigated dermcidin, FoxA1 and CEA expression in eccrine glands of 12 cases with AIGA and 5 cases with non-AIGA. RESULTS: Marked degranulation and shrinkage of dark cells consistently occurred in AIGA. Furthermore, high serum CEA concentrations were found in 14 of 22 AIGA patients (over 60%), but serum CEA levels were not correlated with CEA expression in eccrine glands. Dermcidin expression in dark cells apparently decreased in AIGA patients, severely in those with high serum CEA and moderately in those with low serum CEA, while well-preserved expression was found in non-AIGA subjects. CONCLUSION: Our study suggests morphological damage and molecular dysregulation of dark cells, leading to impairment of their functions in AIGA patients. Severely damaged dark cells correspond to high serum CEA. Accordingly, these pathological changes in eccrine dark cells may be involved in anhidrosis/hypohidrosis of AIGA.

Gingival epithelial cells support osteoclastogenesis by producing receptor activator of nuclear factor kappa B ligand via protein kinase A signaling.

BACKGROUND AND OBJECTIVE: Periodontal disease is dental plaque-induced inflammatory disease of the periodontal tissues that results in bone loss in the affected teeth. During bone resorption, receptor activator of nuclear factor kappa B ligand (RANKL) is an essential factor that regulates osteoclastogenesis. Recently, we found that gingival epithelial cells (GECs) in periodontal tissue produce RANKL, the expression of which is regulated by tumor necrosis factor-α and protein kinase A signaling. In this study, we asked whether RANKL-producing GECs induce bone marrow macrophages (BMMs) to form osteoclasts in a co-culture system. MATERIAL AND METHODS: Ca9-22 GECs and osteoclast precursor BMMs were co-cultured with or without the protein kinase A signaling activator forskolin or inhibitor H89 to examine whether the RANKL-producing GECs could be induced to form osteoclasts, as determined using a pit formation assay. RESULTS: Osteoclasts formed spontaneously in co-cultures of Ca9-22 cells and BMMs, even in the absence of RANKL. The cells were cultured on bone slices for 14 d, at which time resorption pits were observed. Forskolin treatment significantly increased osteoclast numbers in these co-cultures, but forskolin alone did not induce osteoclast formation by BMMs. CONCLUSION: GECs producing RANKL are able to support osteoclastogenesis in an in vitro co-culture system using GECs and BMMs, in a process promoted by forskolin.

Clinical efficacy of dual-phase scanning using (68)Ga-DOTATOC-PET/CT in the detection of neuroendocrine tumours.

AIM: To investigate whether delayed scanning at approximately 90 minutes post-injection of (68)Ga-labelled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide (DOTATOC) had any clinical benefits regarding the evaluation of neuroendocrine tumours (NETs), relative to conventional combined positron-emission tomography (PET) and computed tomography (CT) at 60 minutes post-injection. MATERIALS AND METHODS: Fifty-four patients who underwent DOTATOC-PET/CT for suspected or known NETs were retrospectively reviewed. PET/CT was performed twice at approximately 60 and 90 minutes post-injection. For visual analysis, a five-point grading scale (0: definitely normal to 4: definitely abnormal) was used, and grade 3-4 lesions were regarded as positive. For quantitative analysis, the time course of the maximum standardised uptake value (SUVmax) in each lesion and the mean SUV of physiological uptake in the liver were evaluated. RESULTS: Of the 54 patients, 43 had a total of 132 lesions. In interpreting the early images, there were four grade 3 lesions, and the remaining 128 lesions were grade 4. All 132 lesions were grade 4 in the delayed images. SUVs and tumour-to-liver ratios for hepatic lesions were slightly higher in delayed scanning than in early scanning (SUV, 26.8±21.2 versus 28.2±21.2 [p<0.01]; tumour-to-liver ratio, 5.9±4.5 versus 6.2±4.6 [p<0.01]), which did not affect the detection rate. Additionally, bone and peritoneal metastases had slightly higher SUVs at delayed imaging (p<0.05), but there was no difference in diagnostic performance. No significant difference in the SUVs for pancreatic lesions and primary sites in the bowel were observed between the early and delayed scans. CONCLUSION: Delayed scanning may be helpful for improving diagnostic confidence in some cases, although it provided no specific merits for diagnostic accuracy in detecting primary or metastatic NETs.

Specific muscle-tendon architecture in elite Kenyan distance runners.

The Achilles tendon moment arm (MA_AT) and foot lever ratio (FLR) can play important roles for force production and movement economy during locomotion. This notion has become more relevant, and suggestion has been given that the Kenyan runners belonging to the world elite would have specific anatomical, mechanical, and functional properties in their lower limbs and that this feature could be responsible for their high running economy. The present study aimed to characterize the AT of elite Kenyan distance runners as compared with Japanese ones, and to examine the potential relationship with their running performance. Ultrasonography was used to measure AT cross-sectional area and AT soleus and gastrocnemius lengths. MA_AT and FLR were calculated from the position of anatomical landmarks using sagittal plane photographs. MA_AT was significantly longer and the FLR lower in Kenyans than in Japanese. Independently of the group, the running performance was positively related to the MA_AT (r = 0.55, P < 0.001) and negatively to the FLR (r = -0.45, P = 0.002). These results suggest that longer MA_AT and lower FLR could be advantageous in elite Kenyan runners, by contributing to effective endurance running performance in a protective and economical way.

Preoperative routine evaluation of bilateral adrenal glands by endoscopic ultrasound and fine-needle aspiration in patients with potentially resectable lung cancer.

BACKGROUND AND STUDY AIMS: The aim of the current study was to assess the detection rate of the right adrenal gland and the diagnostic ability of endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) for the diagnosis of adrenal metastasis in potentially resectable lung cancer. PATIENTS AND METHODS: This retrospective cohort study included a consecutive series of 150 patients undergoing EUS/EUS - FNA for staging of lung cancer. The detection rate of the right adrenal gland by EUS and the diagnostic accuracies of computed tomography (CT), positron emission tomography-CT (PET-CT), and EUS/EUS - FNA for the diagnosis of adrenal metastasis were evaluated. RESULTS: The right adrenal gland was visualized by EUS in 131 patients (87.3 %); the left adrenal gland was visualized in all patients. Findings suggestive of metastasis in either one of the adrenal glands or in both were observed in 6 patients (4.0 %) by CT, in 5 patients (3.3 %) by PET-CT, and in 11 patients (7.3 %) by EUS. EUS - FNA was performed simultaneously in the 11 patients, and in 4 patients the diagnosis of metastasis was established. The accuracy for the diagnosis of adrenal metastasis was 100 % for EUS/EUS - FNA, 96.0 % for CT, and 97.0 % for PET-CT (P = 0.1146). CONCLUSIONS: As well as the left adrenal gland, the right adrenal gland was also usually visible by EUS. EUS/EUS - FNA provided an accurate diagnosis of adrenal metastasis, although the prevalence of adrenal metastasis was relatively low in these patients with potentially resectable lung cancer.

Muscle-tendon interaction and EMG profiles of world class endurance runners during hopping.

The present study examined the muscle-tendon interaction of ten international level Kenyan runners. Ultrasonography and kinematics were applied together with EMG recordings of lower limb muscles during repetitive hopping performed at maximal level. The ten Kenyans had longer gastro Achilles tendon at rest (p < 0.01) as compared with ten control subjects matched in height. Conversely, the stretching and shortening amplitudes of the tendinous tissues of the medial gastrocnemius (MG) muscle were significantly smaller in the Kenyans than in controls during the contact phase of hopping. This applied also to the fascicle length changes, which were smaller and more homogeneous among Kenyans. These limited musculo-tendinous changes resulted in higher maximal hopping height and in larger power despite their reduced body weight. The associated finding of a greater shortening to stretching ratio of the MG tendinous tissues during contact could imply that the Kenyan MG muscle-tendon unit is optimized to favor efficient storage and recoil of elastic energy, while operating at optimal muscle fascicle working range (plateau region).

Combined endobronchial and endoscopic ultrasound-guided fine needle aspiration for mediastinal nodal staging of lung cancer.

BACKGROUND: Recently, transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been evaluated for mediastinal nodal staging (N staging) of lung cancer, as this technique is less invasive than mediastinoscopy and possibly more accurate than 18F-fluorodeoxyglucose positron emission tomography with computed tomography (PET-CT). However, EUS-FNA does not provide access to pretracheal and hilar lymph nodes. More recently, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been introduced as a novel technique for accessing pretracheal and hilar lymph nodes. Although the combined endoscopic approach of EUS-FNA and EBUS-TBNA is presumably more accurate than PET-CT, only a few reports have quantitatively evaluated its diagnostic ability. Therefore, we prospectively assessed the diagnostic yield of this combined endoscopic approach for mediastinal N staging of lung cancer. METHODS: A consecutive series of 120 patients with suspected resectable lung cancer on CT findings underwent PET-CT and combined EUS-FNA/EBUS-TBNA. The accuracy and other diagnostic indices of the combined approach in mediastinal N staging were compared with those of PET-CT. RESULTS: Among the enrolled patients, a final pathological N stage was established in 110 patients. The accuracy of the combined approach using EUS-FNA and EBUS-TBNA was significantly higher than that of PET-CT (90.0 % vs. 73.6 %; P < 0.0001). The sensitivity, specificity, and positive and negative predictive values were respectively 71.8 %, 100 %, 100 %, and 86.6 % for the combined approach vs. 47.4 %, 87.5 %, 66.7 %, and 75.9 % for PET-CT. CONCLUSIONS: The combined endoscopic approach using EUS-FNA and EBUS-TBNA provided excellent diagnostic performance. Therefore, this approach is strongly recommended before surgery or mediastinoscopy to avoid futile thoracotomy and surgical intervention.

Magnetic resonance diffusion-weighted imaging in the characterization of pancreatic mucinous cystic lesions.

AIM: The aim of the study was to evaluate the utility of diffusion-weighted imaging (DWI), including apparent diffusion coefficient (ADC) measurement, in order to differentiate mucinous cystic neoplasms (MCNs) from intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. MATERIALS AND METHODS: Fifty cases of IPMN with a total of 62 lesions, and eight cases of MCN, were retrospectively selected for the study. The cases of IPMN were selected using multimodality clinical or histopathological criteria, while all MCN lesions were histopathologically proven. DWI was carried out using b values of 500 and 1000s/mm(2). Visual assessment was performed by two radiologists who used two categories (low-iso or high signal intensity). ADC values of the lesions were also calculated. Fisher's exact test and the Mann-Whitney U test were used for statistical analysis. RESULTS: All IPMN lesions demonstrated low-iso signal intensities compared with the pancreatic parenchyma on DWI. Two of the MCN lesions demonstrated low-iso signal intensities, and six lesions demonstrated high signal intensities. The ADC values for IPMNs (mean 2.9 ± 0.024 × 10(-3)mm(2)/s) were significantly higher than those for MCNs (mean 2.1 ± 0.30 × 10(-3)mm(2)/s). ROC analysis showed an optimal cut-off value of 2.4 × 10(-3)mm(2)/s for differentiating between the two types of lesions, providing a sensitivity of 98% and a specificity of 88%. CONCLUSION: The results of the present study suggest that ADC values in mucinous cystic lesions of the pancreas can be advantageous for their characterization into IPMN and MCN.

MHC-restricted minimal regulatory circuit initiated by a class II-autoreactive T cell clone.

The in vivo administration of a self-class II-reactive Th clone MS202 derived from C3H into syngeneic mice resulted in the suppression of both primary and early secondary antibody responses against T cell-dependent antigens. The suppression was due to the generation of antigen-nonspecific Ts cells in the recipient, as the splenic T cells from the mice treated with MS202 were able to strongly suppress the in vitro secondary antibody response of primed syngeneic spleen cells. The dose-response curve of suppression indicated the generation of an effector type Ts that directly suppressed Th. The surface phenotype of Ts was Ly-1+,2-, L3T4+, I-J-. The presence of Ly-1+,2+ T cells was not required to induce the suppression. The suppression was strictly restricted to H-2k, as F1 Ts cells were able to suppress the response of C3H but not of B6 B cells helped by the same F1 Th cells. The experiments with chimeric mice indicated that the direct target of Ts is an MHC-restricted Th but not a B cell or APC. The results indicate the existence of a minimal regulatory circuit where an MHC-restricted Th induces a preprogrammed Ts that in turn directly suppresses Th with the same MHC-restriction specificity. The induction of and suppression by Ts appeared to be due to the direct recognition of MHC restriction sites of Th cells.

High-affinity receptor-mediated internalization and degradation of interleukin 2 in human T cells.

Receptor-mediated internalization and degradation of IL-2 were investigated in cell lines carrying human T cell leukemia/lymphoma (lymphotrophic) virus type I (HTLV-I) and PHA-treated normal PBL. The HTLV-I-carrying cell lines ILT-Yan and TL-Mor, and the PBL expressed both high- and low-affinity IL-2-R. However, another HTLV-I-carrying T cell line, MT-1, expressed mainly low-affinity receptors. Greater than 50% of the IL-2 bound to high-affinity receptors was internalized within 10 min when these cells were incubated at 37 degrees C. The internalized IL-2 was rapidly degraded and the products were excreted into the culture fluid. The t1/2 of IL-2 degradation in these cells was estimated as 60-80 min at 37 degrees C. The internalization and degradation of IL-2 were both temperature dependent. Light-microscopic autoradiography with 3H-labeled IL-2 confirmed the internalization of IL-2, and suggested that some IL-2 might be carried to the nucleus.

A novel type of cell death of lymphocytes induced by a monoclonal antibody without participation of complement.

A monoclonal antibody, RE2, raised by immunizing a rat with cell lysate of a mouse T cell clone, was found to directly kill interleukin 2-dependent T cell clones without participation of serum complement. Fab fragments of RE2 had no cytolytic activity, while the cross-linking of Fab fragments with anti-rat immunoglobulin reconstituted the cytotoxicity. The cytotoxicity was temperature dependent: the antibody could kill target cells at 37 degrees C but not at 0 degrees C. Sodium azide, ethylenediaminetetraacetic acid, and forskolin did not affect the cytolytic activity of RE2, while the treatment of target cells with cytochalasin B and D completely blocked the activity. This suggested that the cell death involves a cytoskeleton-dependent active process. Giant holes on the cell membrane were formed within 5 minutes after the treatment with RE2, as observed by scanning electron microscopy. There was no indication of DNA fragmentation nor swelling of mitochondria during the cytolysis, suggesting that the cell death is neither apoptosis nor typical necrosis. The antibody also killed T cell lymphomas and T and B cell hybridomas only when these cells were preactivated with concanavalin A, lipopolysaccharide, or phorbol myristate acetate. Preactivated peripheral T and B cells were sensitive to the cytotoxicity of RE2, while resting T and B cells were insensitive. These results provide evidence for a novel pathway of cell death of activated lymphocytes by membrane excitation.

Electron localization near the Mott transition in the organic superconductor κ-(BEDT-TTF)2Cu[N(CN)2]Br.

The effect of disorder on the electronic properties near the Mott transition is studied in an organic superconductor κ-(BEDT-TTF)2Cu[N(CN)2]Br, which is systematically irradiated by x rays. We observe that x ray irradiation causes Anderson-type electron localization due to molecular disorder. The resistivity at low temperatures demonstrates variable range hopping conduction with Coulomb interaction. The experimental results show clearly that the electron localization by disorder is enhanced by the Coulomb interaction near the Mott transition.

Dermoscopic features of nonpigmented eccrine poromas in association with their histopathological features.

BACKGROUND: Nonpigmented eccrine poromas (EPs) occasionally mimic various skin tumours, but their dermoscopic features have not been clarified. OBJECTIVES: To evaluate the dermoscopic features of nonpigmented EPs in association with their histopathological features. METHODS: Retrospective analysis of the dermoscopic features of 10 histopathologically proven cases of nonpigmented EP at the Department of Dermatology, Shinshu University Hospital (Matsumoto, Japan). RESULTS: Specific features in vascular structures were observed in five of 10 nonpigmented EPs. Three cases showed a polymorphous vascular pattern: two cases of a combination of hairpin and dotted vessels, and one case of a combination of hairpin, dotted and linear-irregular vessels. In addition, there were two cases of monomorphous vascular pattern: one case of linear-irregular vessels, and one case of hairpin vessels. We did not observe arborizing, crown or comma vessels. Comedo-like openings, milia-like cysts, cerebriform pattern and ulceration were observed in one case each. Furthermore, nine of 10 cases showed the characteristic feature, described as well-circumscribed reddish globule/lacuna-like structures with separation of mesh bands, which were reminiscent of frog eggs aggregation. This characteristic feature on dermoscopy was explained by the histopathological features of horizontal sections at a depth of 300-400 µm from the surface. Island-shaped oedematous stroma with numerous microvessels, which were surrounded by poroid cells in mesh-like forms, were seen. CONCLUSIONS: Vascular structures and 'frog eggs-like appearance' are important features on dermoscopic examination of nonpigmented EP. Further studies are required to evaluate their diagnostic accuracy to differentiate nonpigmented EP from other tumours.

Fertilization of sea urchins needs magnesium ions in seawater.

When sea urchin eggs were inseminated in seawater free of magnesium, the fertilization rate was very low. Spermatozoa that had been treated with egg jelly to induce the acrosome reaction also failed to fertilize eggs in seawater free of magnesium. These results indicate that magnesium is indispensable for some process or processes at fertilization, such as membrane, fusion or sperm penetration.

Delta 9-tetrahydrocannabinol-induced catalepsy-like immobilization is mediated by decreased 5-HT neurotransmission in the nucleus accumbens due to the action of glutamate-containing neurons.

Delta(9)-tetrahydrocannabinol (THC) has been reported to induce catalepsy-like immobilization, but the mechanism underlying this effect remains unclear. In the present study, in order to fully understand the neural circuits involved, we determined the brain sites involved in the immobilization effect in rats. THC dose-dependently induced catalepsy-like immobilization. THC-induced catalepsy-like immobilization is mechanistically different from that induced by haloperidol (HPD), because unlike HPD-induced catalepsy, animals with THC-induced catalepsy became normal again following sound and air-puff stimuli. THC-induced catalepsy was reversed by SR141716, a selective cannabinoid CB(1) receptor antagonist. Moreover, THC-induced catalepsy was abolished by lesions in the nucleus accumbens (NAc) and central amygdala (ACE) regions. On the other hand, HPD-induced catalepsy was suppressed by lesions in the caudate putamen (CP), substantia nigra (SN), globus pallidus (GP), ACE and lateral hypothalamus (LH) regions. Bilateral microinjection of THC into the NAc region induced catalepsy-like immobilization. This THC-induced catalepsy was inhibited by serotonergic drugs such as 5-hydroxy-L-tryptophan (5-HTP), a 5-HT precursor, and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), a 5-HT receptor agonist, as well as by anti-glutamatergic drugs such as MK-801 and amantadine, an N-methyl-d-aspartate (NMDA) receptor antagonist. THC significantly decreased 5-HT and glutamate release in the NAc, as shown by in vivo microdialysis. SR141716 reversed and MK-801 inhibited this decrease in 5-HT and glutamate release. These findings suggest that the THC-induced catalepsy is mechanistically different from HPD-induced catalepsy and that the catalepsy-like immobilization induced by THC is mediated by decreased 5-HT neurotransmission in the nucleus accumbens due to the action of glutamate-containing neurons.

The yield of endoscopic ultrasound-guided fine needle aspiration for histological diagnosis in patients suspected of stage I sarcoidosis.

BACKGROUND AND STUDY AIM: Sarcoidosis is a systemic disorder of unknown cause that is characterized by a pathological hallmark, noncaseating granuloma. Bilateral hilar lymphadenopathy (BHL) is a major clinical feature, but it is sometimes difficult to exclude other diseases, especially in cases where there are no pulmonary abnormalities (stage I). Bronchoscopic transbronchial biopsy is currently a popular method by which to obtain pathological material, but its diagnostic power is insignificant. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), also attempted recently, makes the sampling of pathological material easier and better, but the diagnoses are still based on cytological findings. Our study aimed to evaluate the yield of transesophageal EUS-FNA for histological confirmation of stage I sarcoidosis. METHODS: The study was a prospective comparative study to investigate the diagnostic sensitivities of FNA cytology and FNA histology. Subjects were consecutive patients with BHL without lung lesions on chest radiographs or chest CT who were referred to our hospitals between December 2003 and April 2006. Transesophageal EUS-FNA was performed with 19-gauge needles instead of the conventional 22-gauge needles. RESULTS: Forty-one patients were included in this study, and both histological and cytological materials were obtained successfully by EUS-FNA in all patients. Histopathological examination of the FNA sample showed noncaseating granuloma in 34 (94.4%) of the 36 patients with a final diagnosis of sarcoidosis. In contrast, only 28 of the 36 (77.8%) were diagnosed as having sarcoidosis on the basis of cytological findings. The difference was statistically significant (P = 0.0444). CONCLUSION: FNA histology is better suited than FNA cytology to establishing the diagnosis of stage I sarcoidosis, and EUS-FNA with a 19-gauge needle plays a important role in this process.

Pathological fracture of the mandible resulting from osteomyelitis successfully treated with only intermaxillary elastic guiding.

Treatment of mandibular pathological fractures differs according to etiology. Closed reduction with intermaxillary fixation is usually performed when fractures occur as a result of osteomyelitis. Here is reported a case of pathological fracture of the mandible resulting from osteomyelitis that was successfully treated with intermaxillary elastics only.