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In search and rescue activities, unmanned aerial vehicles (UAV) should exploit sound information to compensate for poor visual information. This paper describes the design and implementation of a UAV-embedded microphone array system for sound source localization in outdoor environments. Four critical development problems included water-resistance of the microphone array, efficiency in assembling, reliability of wireless communication, and sufficiency of visualization tools for operators. To solve these problems, we developed a spherical microphone array system (SMAS) consisting of a microphone array, a stable wireless network communication system, and intuitive visualization tools. The performance of SMAS was evaluated with simulated data and a demonstration in the field. Results confirmed that the SMAS provides highly accurate localization, water resistance, prompt assembly, stable wireless communication, and intuitive information for observers and operators., Competing Interests: The authors declare no conflict of interest.

B-cell activating factor (BAFF) promotes the survival and adhesion of multiple myeloma (MM) cells. Tabalumab (LY2127399) is an anti-BAFF monoclonal antibody. This phase 1, multicenter, open-label, nonrandomized, dose-escalation study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of tabalumab in combination with bortezomib and dexamethasone in Japanese patients with relapsed or refractory MM (RRMM). Sixteen patients received intravenous i.v. tabalumab 100 mg (Cohort 1, n = 4) or i.v. tabalumab 300 mg (Cohort 2, n = 12) in combination with oral dexamethasone 20 mg/day and i.v. or s.c. bortezomib 1.3 mg/m(2) . All patients had treatment-emergent adverse events (TEAE) possibly related to study treatment; the most common TEAE were thrombocytopenia (81.3%), lymphopenia (43.8%) and increased alanine aminotransferase (43.8%). Two (20.0%) dose-limiting toxicities were observed, both in Cohort 2 (tabalumab 300 mg), which was below the predefined cutoff for tolerability (<33%). The pharmacokinetics of tabalumab were similar when bortezomib was coadministered i.v. versus s.c. The overall response rate was 56.3%, suggesting that the combined treatment was effective. In conclusion, combined treatment with these three agents was well tolerated in this population of Japanese patients with RRMM. The study was registered at www.clinicaltrials.gov (NCT01556438)., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Chronic kidney disease (CKD), characterized by senile inflammation, is a risk factor for cardiovascular disease. Conduit artery function and small artery structure relate to cardiovascular disease. We examined the correlations, determinants and interrelationships of arterial indices in association with CKD in a cross-sectional study of 139 patients (60% male; mean age 44 years) with CKD (stages 3-5, 39%) who underwent a renal biopsy. Conduit artery function and small artery sclerosis were assessed by brachial artery flow-mediated dilatation (FMD) and semiquantitative evaluation of small artery intimal thickening (SA-IT), respectively. The estimated glomerular filtration rate correlated with FMD (r=0.31, P=0.0002) and inversely correlated with SA-IT (r=-0.54, P<0.0001). Multiple regression analysis showed that FMD was inversely correlated with SA-IT and vice versa. In addition, high-sensitivity C-reactive protein (hs-CRP) was significantly correlated with SA-IT, but not FMD. Multiple logistic analysis revealed that higher hs-CRP concomitant with decreased FMD was further associated with the risk of severe SA-IT compared with their individual effects. These findings suggest that both conduit artery and small artery disease develop with mutual interaction in parallel with decreased kidney function. Coexistence of inflammation and conduit artery dysfunction may be closely related to renal small artery sclerosis in patients with CKD.

A 61-year-old man who was being treated with hemodialysis (HD) for end-stage renal disease presented with symptoms of severe congestive heart failure (CHF). Removing excess intravascular fluid during HD was difficult due to the patient's chronic hypotension induced by severe left ventricular (LV) dysfunction. The application of adaptive servo-ventilation (ASV) increased the patient's cardiac output and blood pressure during HD, thus resulting in the effective removal of excess intravascular fluid. Therefore, ASV may be effective for treating CHF in HD patients with LV dysfunction and chronic hypotension.

Clinical studies suggest that colonic luminal hydrogen sulfide (H(2)S), produced by sulfate-reducing bacteria or through other pathways, might be involved in the pathogenesis of inflammatory bowel disease (IBD). Nonetheless, this hypothesis has been poorly investigated by basic studies using laboratory animals. We thus focused on two enzymes, cystathionine-gamma-lyase (CSE) that generates H(2)S from l-cysteine, and rhodanese that directly or indirectly detoxifies H(2)S, particularly in relation to the colitis induced by dextran sulfate sodium (DSS) in mice. CSE was a major H(2)S-forming enzyme in colonic and renal homogenates from mice and rats, and the rhodanese activity was also detectable in both tissues. Colitis-related symptoms including decreased body weight gain, diarrhea, hematochezia and shortening of colon length were observed in the mice drinking DSS. Those symptoms were not or only slightly attenuated by repeated administration of a CSE inhibitor. CSE activity and protein levels in the colonic tissue did not notably change in the mice with colitis. In contrast, the activity and protein/mRNA levels of rhodanese in the colon, but not kidney, significantly decreased nearly in parallel with the development of colitis, followed by elevation of rhodanese activity in red blood cells (RBCs). These data show that rhodanese, but not CSE, is associated with DSS-induced colitis in mice, leading to a hypothesis that impaired detoxification of H(2)S due to down-regulation or suppression of colonic rhodanese is involved in IBD. The delayed enhancement of rhodanese activity in RBCs, a possible compensative event, might be available as a disease marker for IBD., (2009 Elsevier Ireland Ltd.)

Irritable urological symptoms with gross hematuria and bilateral lumbar pain developed when the patient received penicillin G for endocarditis. These symptoms were followed by renal insufficiency. A contrast-enhanced abdominal computed tomography (CT) scan revealed a thickened bladder wall, bilateral hydroureter and hydronephrosis, suggesting hemorrhagic cystitis complicated with urinary tract obstruction. Urine culture was negative. After discontinuation of penicillin G, all symptoms subsided and renal function recovered; hence, penicillin G seems to have been associated with hemorrhagic cystitis and acute kidney injury. Positive findings in the drug lymphocyte stimulation test (DLST) for penicillin G were consistent with this diagnosis.

Cardiac involvement is a rare complication with thromboangiitis obliterans (TAO). We report a 29-year-old man with TAO accompanied with non-ischemic dilated cardiomyopathy. He had no history of heart disease, but echocardiogram demonstrated diffuse hypokinesis and dilated left ventricle. Coronary angiography revealed no organic stenotic lesion. For limb salvage, he was treated with granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cell (PBMNC) implantation on his right leg. Not only ischemic leg symptoms, but also plasma level of BNP and (123)I-metaiodobenzylguanidine scintigraphic parameters improved after 24 weeks. G-CSF-mobilized PBMNC implantation could be an effective approach to treating non-ischemic cardiomyopathy.

Hydrogen sulfide (H(2)S), an endogenous gasotransmitter, modulates various biological events such as inflammation in the mammalian body. The present study investigated possible involvement of H(2)S in peripheral nociceptive processing. Intraplantar (i.pl.) administration of NaHS, a H(2)S donor, produced prompt hyperalgesia in rats, accompanied by expression of Fos in the spinal dorsal horn. The H(2)S-evoked hyperalgesia was blocked by 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB), an oxidizing agent, or ethosuximide and mibefradil, T-type Ca(2+) channel inhibitors. L-Cysteine, an endogenous source for H(2)S, given i.pl., also elicited hyperalgesia, an effect being abolished by DL-propargylglycine (PPG) and beta-cyanoalanine (BCA), inhibitors of cystathionine-gamma-lyase, a H(2)S synthesizing enzyme. PPG and/or BCA partially inhibited the hyperalgesia induced by i.pl. lipopolysaccharide, an effect being reversed by i.pl. NaHS. In the patch-clamp study using undifferentiated NG108-15 cells that express T-type, but not other types, of Ca(2+) channels, NaHS enhanced the currents through the T-type channels, an effect being blocked by DTNB. Thus, H(2)S appears to function as a novel nociceptive messenger through sensitization of T-type Ca(2+) channels in the peripheral tissues, particularly during inflammation.

Camostat mesilate, an orally available proteinase inhibitor, is clinically used for treatment of pancreatitis. Given recent evidence that pancreatic proteinases including trypsin and/or proteinase-activated receptor-2 (PAR2) might be involved in pancreatic pain, we examined if camostat mesilate could suppress spinal Fos expression, a marker for neuronal activation, following specific application of trypsin to the pancreas, and pancreatitis-related referred allodynia. Trypsin, administered into the pancreatic duct, caused delayed expression of Fos proteins in the superficial layer of the bilateral T8 and T9 spinal dorsal horns in rats. The trypsin-induced spinal Fos expression was completely abolished by oral pre-administration of camostat mesilate at 300 mg/kg. After hourly repeated (6 times in total) administration of caerulein, mice showed typical symptoms of pancreatitis, accompanied by mechanical allodynia in the upper abdomen (i.e., referred hyperalgesia/allodynia), as assessed by use of von Frey filaments. Camostat mesilate at 100-300 mg/kg, given orally twice before the 1st and 4th doses of caerulein, abolished the pancreatitis-related abdominal allodynia, while it partially prevented the inflammatory signs. The same doses of camostat mesilate, when administered once after the final dose of caerulein, also revealed significant anti-allodynic effect. These data suggest that camostat mesilate prevents and/or depresses pancreatitis-induced pain and/or referred hyperalgesia/allodynia, in which proteinases including trypsin would play a critical role.

Proteinase-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, can be activated not only by PAR1-activating peptides (PAR1APs) based on the N-terminal cryptic tethered ligand sequence but also by an N-palmitoylated (Pal) peptide, Pal-RCLSSSAVANRSKKSRALF-amide (P1pal-19), based on the intracellular loop 3 of PAR1, designated pepducin, in human platelets or PAR1-transfected cells. The present article evaluated the actions of P1pal-19 and also the shorter peptide, Pal-RCLSSSAVANRS-amide (P1pal-12), known as a possible PAR1 antagonist, in multiple cells/tissues that naturally express PAR1. P1pal-19 as well as a PAR1AP, TFLLR-amide, evoked cytosolic Ca(2+) mobilization in cultured human lung epithelial cells (A549) and rat gastric mucosal epithelial cells (RGM1). P1pal-19 and TFLLR-amide, but not a PAR2-activating peptide, SLIGRL-amide, caused delayed prostaglandin E(2) formation in RGM1 cells. P1pal-19, like TFLLR-amide, produced endothelial NO-dependent relaxation in rat aorta and epithelial prostanoid-dependent relaxation in mouse bronchus. The P1pal-19-induced relaxation remained constant even after desensitization of PAR1 with TFLLR-amide in either tissue. P1pal-19 failed to mimic the contractile effects of TFLLR-amide in the endothelium-denuded preparations of rat aorta or superior mesenteric artery and the rat gastric longitudinal smooth muscle strips. P1pal-12 partially inhibited the vasorelaxation caused by TFLLR-amide and P1pal-19, but not SLIGRL-amide, in the rat aorta. Our data thus indicate that P1pal-19 is capable of mimicking the effects of PAR1APs in the endothelial and epithelial, but not smooth muscle, cells/tissues, and suggest that P1pal-12 may act as a PAR1 antagonist in the vascular endothelium.

A high plasma aldosterone concentration (PAC) is known to be associated with poor outcome in patients with cardiac disease. However, the prognostic value of PAC in chronic hemodialysis (HD) patients is unknown. In 1996 we examined 128 hypertensive patients treated with antihypertensive drugs, excluding angiotensin-converting enzyme inhibitors, who were undergoing chronic HD (ages 61.8+/-13.8 years, 62% male), and for whom PAC (ng/dl) data were obtained. We followed up these patients until November 2003. During the follow-up period, 30 patients died. About half of all patients (48%) had PAC values above the normal range. We assigned the 128 patients to a lower (<22.9) or higher (> or = 22.9) PAC group according to the median baseline PAC. The survival rate as calculated by the Kaplan-Meier method was 90.6% in the higher PAC group and 62.5% in the lower PAC group (p=0.003). In multivariate analysis, serum potassium and plasma renin activity were independent determinants of PAC. Cox proportional hazards analysis, with adjustment for other variables including diabetes, showed that lower PAC was independently predictive of death. The adjusted hazard ratio (95% confidence interval) of the lower PAC group was 2.905 (1.187-7.112, p=0.020). The significance of PAC became marginal by adjustment with albumin or potassium. These results indicate that higher PAC is common, but not associated with an increase in total and cardiovascular deaths among hypertensive patients undergoing chronic HD. The association between lower PAC and poor survival may be driven by volume retention and/or lower potassium.

Bisphosphonates, pyrophosphate analogues, known as inhibitors of bone resorption, appear to cause analgesia in certain clinical painful situations. To detect clinically relevant analgesic property of etidronate, a non-aminobisphosphonate, we examined and characterized its antiallodynic effect in the rat with adjuvant-induced arthritis, in comparison with alendronate, an aminobisphosphonate, as determined by the von Frey test. Repeated systemic administration of etidronate at 10-40 mg/kg/day suppressed the adjuvant-induced mechanical allodynia in rat hindpaw, an effect reaching a plateau in approximately 10 days. Systemic or intraplantar (i.pl.) administration of ATP-sensitive K+ (K+ ATP) channel inhibitors, glibenclamide and/or tolbutamide, completely reversed the antiallodynic effect of etidronate within 1h in the arthritic rats, without affecting the nociceptive scores in naïve or arthritic animals that had not received etidronate. Alendronate, administered repeatedly, also revealed similar glibenclamide-reversible antiallodynic effect. In contrast, the antiallodynic effect of repeated systemic indomethacin was resistant to i.pl. glibenclamide in the arthritic rats. Repeated administration of etidronate or alendronate only slightly attenuated the adjuvant-evoked hindpaw edema. Among K+ ATP channel subunits, mRNAs for Kir6.1, SUR1, SUR2A and SUR2B were abundant in rat dorsal root ganglia, while Kir6.2 mRNA was poor. Our data demonstrate that repeated etidronate as well as alendronate exhibits antiallodynic activity in arthritic rats, which might be clinically relevant, and suggest involvement of K+ ATP channels in the underlying mechanisms.

Intracolonic (i.col.) administration of the PAR2-activating peptide (PAR2AP) SLIGRL-NH2 slowly develops visceral hypersensitivity to i.col. capsaicin in ddY mice. Thus, we further analyzed roles of PAR2 in colonic hypersensitivity, using the novel potent PAR2AP, 2-furoyl-LIGRL-NH2 and PAR2-knockout (KO) mice. In ddY mice, i.col. 2-furoyl-LIGRL-NH2 produced delayed (6 h later) facilitation of capsaicin-evoked visceral nociception, an effect being much more potent than SLIGRL-NH2. Such effects were mimicked by i.col. trypsin. In wild-type (WT), but not PAR2-KO, mice of C57BL/6 background, i.col. PAR2 agonists caused delayed facilitation of sensitivity to capsaicin. The PAR2-triggered visceral hypersensitivity was abolished by a bradykinin B2 receptor antagonist, HOE-140. Our data thus provide ultimate evidence for role of PAR2 in colonic hypersensitivity, and suggest involvement of the bradykinin-B2 pathway.

1 Proteinase-activated receptor-2 (PAR2), a receptor activated by trypsin and tryptase, is abundantly expressed in the gastrointestinal tract including the C-fiber terminal, and might play a role in processing of visceral pain. In the present study, we examined and characterized the roles of PAR2 in pancreatitis-related abdominal hyperalgesia/allodynia in mice. 2 Caerulein, administered i.p. once, caused a small increase in abdominal sensitivity to stimulation with von Frey hairs, without causing pancreatitis, in PAR2-knockout (KO) mice, but not wild-type (WT) mice. 3 Caerulein, given hourly six times in total, caused more profound abdominal hyperalgesia/allodynia in PAR2-KO mice, as compared with WT mice, although no significant differences were detected in the severity of pancreatitis between the KO and WT animals. 4 The PAR2-activating peptide, 2-furoyl-LIGRL-NH(2), coadministered repeatedly with caerulein six times in total, abolished the caerulein-evoked abdominal hyperalgesia/allodynia in WT, but not PAR2-KO, mice. Repeated doses of 2-furoyl-LIGRL-NH(2) moderately attenuated the severity of caerulein-induced pancreatitis in WT animals. 5 Our data from experiments using PAR2-KO mice provide evidence that PAR2 functions to attenuate pancreatitis-related abdominal hyperalgesia/allodynia without affecting pancreatitis itself, although the PAR2AP applied exogenously is not only antinociceptive but also anti-inflammatory.

Receptor-activating peptides for protease-activated receptors (PARs) 1 or 2 enhance gastric mucosal blood flow (GMBF) and protect against gastric mucosal injury in rats. We thus examined and characterized the effects of PAR-1 and PAR-2 agonists on the isometric tension in isolated rat gastric artery. The agonists for PAR-2 or PAR-1 produced vasodilation in the endothelium-intact arterial rings, which was abolished by removal of the endothelium. The mechanisms underlying the PAR-2- and PAR-1-mediated relaxation involved NO, endothelium-derived hyperpolarizing factor (EDHF) and prostanoids, to distinct extent, as evaluated by use of inhibitors of NO synthase, cyclo-oxygenase and Ca2+-activated K+ channels. The EDHF-dependent relaxation responses were significantly attenuated by gap junction inhibitors. These findings demonstrate that endothelial PAR-1 and PAR-2, upon activation, dilate the gastric artery via NO and prostanoid formation and also EDHF mechanisms including gap junctions, which would enhance GMBF.

We characterized the tracheal and bronchial relaxation caused by proteinase-activated receptor-2 (PAR-2) activation in ddY mice and/or in wild-type and PAR-2-knockout mice of C57BL/6 background. Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-NH(2)) and Thr-Phe-Leu-Leu-Arg-amide, PAR-2- and PAR-1-activating peptides, respectively, caused relaxation in the isolated ddY mouse trachea and main bronchus. The relaxation was abolished by specific inhibitors of cyclooxygenase (COX)-1, COX-2, mitogen-activated protein kinase kinase (MEK), and p38 MAP kinase. The MEK and p38 MAP kinase inhibitors did not affect prostaglandin E(2)-induced relaxation. Inhibitors of cytosolic Ca(2+)-dependent phospholipase A(2) (PLA), Ca(2+)-independent PLA(2), diacylglycerol lipase, tyrosine kinase, and protein kinase C exhibited no or only minor inhibitory effects on the PAR-mediated relaxation. Trypsin, a PAR-2 activator, and 2-furoyl-Leu-Ile-Gly-Arg-Leu-amide, a potent PAR-2-activating peptide, in addition to SLIGRL-NH(2), caused airway relaxation in wild-type C57BL/6 mice, as in ddY mice. In PAR-2-knockout mice, the peptide effects were absent and the potency of trypsin decreased. Desensitization of PAR-2 and/or PAR-1 greatly suppressed the relaxant effect of trypsin. The bronchial and tracheal tissues displayed distinct sensitivities toward trypsin and the PAR-2-activating peptides. Our data indicate an involvement of both COX-1 and COX-2, and the MEK-extracellular signal-regulated kinase and p38 MAP kinase signaling pathways in the PAR-2- and PAR-1-triggered relaxation of mouse airway tissue, and substantiate a role for PAR-2 in regulating both the trachea and bronchial responsiveness in the mouse lung.

To develop potent and metabolically stable agonists for protease-activated receptor-2 (PAR-2), we prepared 2-furoylated (2f) derivatives of native PAR-2-activating peptides, 2f-LIGKV-OH, 2f-LIGRL-OH, 2f-LIGKV-NH(2), and 2f-LIGRL-NH(2), and systematically evaluated their activity in PAR-2-responsive cell lines and tissues. In both HCT-15 cells and NCTC2544 cells overexpressing PAR-2, all furoylated peptides increased cytosolic Ca(2+) levels with a greater potency than the corresponding native peptides, although a similar maximum response was recorded. The absolute potency of each peptide was greater in NCTC2544, possibly due to a higher level of receptor expression. Furthermore, the difference in potency between the 2-furoylated peptides and the native peptides was enhanced when evaluated in the rat superior mesenteric artery and further increased when measuring PAR-2-mediated salivation in ddY mice in vivo. The potency of 2f-LIGRL-NH(2), the most powerful peptide, relative to SLIGKV-OH, was about 100 in the cultured cell Ca(2+) signaling assays, 517 in the vasorelaxation assay, and 1100 in the salivation assay. Amastatin, an aminopeptidase inhibitor, augmented salivation caused by native peptides, but not furoylated peptides. The PAR-2-activating peptides, including the furoylated derivatives, also produced salivation in the wild-type C57BL/6 mice, but not the PAR-2-deficient mice. Our data thus demonstrate that substitution of the N-terminal serine with a furoyl group in native PAR-2-activating peptides dramatically enhances the agonistic activity and decreases degradation by aminopeptidase, leading to development of 2f-LIGRL-NH(2), the most potent peptide. Furthermore, the data from PAR-2-deficient mice provide ultimate evidence for involvement of PAR-2 in salivation and the selective nature of the 2-furoylated peptides.

Objective: Protease-activated receptors (PARs) 1 and 2 are expressed in various blood vessels including rat aorta, modulating vascular tone. We investigated the roles of PAR-1 and PAR-2 in vasomotor modulation in rat superior mesenteric artery., Methods and Results: Effects of the PAR-2-activating peptide Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-amide) and the PAR-1-activating peptide Thr-Phe-Leu-Leu-Arg-amide (TFLLR-amide) on isometric tension were examined in isolated rat superior mesenteric artery or aorta. Both SLIGRL-amide and TFLLR-amide caused relaxation in the precontracted rat aortic rings. The latter peptide, but not the former, produced contraction in the resting rings. NG-nitro-L-arginine methyl ester (L-NAME), but not apamin/charybdotoxin known to block the endothelium-derived hyperpolarizing factor (EDHF) pathway, abolished the relaxation and facilitated the contraction. In the precontracted rat superior mesenteric artery, SLIGRL-amide, but not TFLLR-amide, elicited endothelium-dependent relaxation, which was only partially inhibited by L-NAME with and without indomethacin. The residual relaxation was abolished by apamin/charybdotoxin. Carbenoxolone, a gap junction inhibitor, significantly attenuated the SLIGRL-amide-evoked, EDHF-dependent relaxation, although neither 17-octadecynoic acid, a P450 epoxygenase inhibitor, nor catalase, a hydrogen peroxide scavenger, revealed inhibitory effects. The residual response resistant to carbenoxolone was unaffected by ouabain/BaCl2. In the resting artery, TFLLR-amide, but not SLIGRL-amide, produced only slight contraction, which was dramatically facilitated by combination of L-NAME and apamin/charybdotoxin or by removal of the endothelium., Conclusions: Our data suggest that, in rat superior mesenteric artery, endothelial PAR-2, upon activation, causes relaxation via both NO and EDHF pathways, and that activation of muscular PAR-1 exhibits potential contractile activity that is largely masked by NO and EDHFs pathways triggered by endothelial PAR-1. Gap junctions might be involved in the EDHF mechanisms in this artery.

A survey of the Japanese literature revealed 28 well-documented cases of central carcinoma of the jaws. There was no sex predominance and the mandible was the site of involvement in 26 cases. The most common initial symptom was local swelling, which was followed in order of frequency by spontaneous pain, paraesthesia of the lower lip, discomfort, loosening of teeth and trismus. On clinical examination, local swelling which was often accompanied by variable symptoms was an almost constant finding. Radiographic appearance varied from unilocular to worm-eaten type radiolucencies which were often surrounded by indistinct margins on close examination. Radical surgery, combined with irradiation and/or chemotherapy was the principal treatment in most cases, but there were 4 cases in which the lesions were simply excised under a tentative diagnosis of cyst; local recurrence was noted in 5 cases. Regional lymph node metastasis and lung metastasis were observed in 8 and 2 cases, respectively. No definite conclusion was drawn with regard to the prognosis because of the short follow-up period. Histologically, epidermoid carcinoma was most frequently seen, but odontogenic cyst was confirmed to be the site of origin in 3 cases only.

A huge chondrosarcoma of the mandible (80 X 95 X 100 mm in size) with extension into the infratemporal fossa is described. The tumour was successfully treated by surgical removal and postoperative irradiation. A survey of the Japanese literature revealed 23 cases of chondrosarcoma with involvement of the mandible. The tumours occurred equally in males and females whose mean age was 38 years. The molar region was the site of predilection. The most common symptom was swelling and it was accompanied by pain in 7 cases and paraesthesia in 5 cases. Radiographically, the lesions were quite variable and with the exception of 3 cases in which information was not available, they consisted of a combination of irregular radiopacity and radiolucency in 9 cases, whereas the predominant feature was radiopacity in 6 cases and radiolucency in 4 cases. There was no radiographical abnormality in 2 cases. Root resorption of adjacent teeth was noted in 3 of 6 cases where information existed. Computed tomography was thought to be quite valuable in determining the nature and extent of the tumour. Although an elevation of serum alkaline phosphatase was observed in our case, results of laboratory tests were mostly of no diagnostic significance. Surgical removal was employed in 22 cases alone or in conjunction with irradiation and/or chemotherapy. Of 14 cases on whom information was available, local recurrence occurred in 6 cases in which radiotherapy was not given and distant metastasis in 2 of 10 cases on whom information was available. Of 20 patients on whom information was available on the postoperative course, 7 patients died 5 months to 6 years after the primary treatment.

The clinical, radiographic and histological characteristics of the calcifying odontogenic cyst were studied in 23 well-documented cases in the Japanese literature. The cysts occurred equally in males and females whose mean age was 21 years. The appeared as a painless swelling with cortical expansion and involved the maxilla three times more often than the mandible. There was no report of the lesion involving the soft tissues. Radiographically, the lesions were unilocular in most cases and contained aggregates or dispersed foci in the radiolucencies which were diagnosed as odontomes in 5 cases. Unerupted teeth and root resorption of the adjacent teeth were noted in approximately half of the cases. Except for one case, they were simply enucleated under a diagnosis of cyst or odontome and recurrence was encountered in no case. The excised specimens consisted of cystic sacs mostly containing calcified materials with or without tooth-like structures which were histologically diagnosed as odontomes in 10 cases. An intimate relationship between the cysts and the unerupted teeth was observed in 4 out of 10 cases. The pathogenesis of the lesion is discussed.

Two cases of cystic ameloblastoma are described in which the diagnosis was established after marsupialization. Although the clinical and radiographic findings strongly suggested the diagnosis of ameloblastoma, the initial incisional biopsy specimens consisted of cystic walls lined with squamous epithelium which showed in both cases no evidence of ameloblastic proliferation. Marsupialization could be a diagnostic aid in these cases since relief of intracystic pressure may trigger regeneration of a solid mass of tumour in a monocystic ameloblastoma with cells possessing potentiality for spontaneous proliferation.

We studied whether the DNA contents may be useful in the differential diagnosis of glandular tumors in the maxillofacial regions. In 25 of these tumors, the DNA contents were measured by microspectrophotometry, using 4 normal salivary glands as controls. We found that: (1) DNA histgram patterns were useful in differential diagnosis only in special cases. (2) The criteria were based on our decision and these tumors were classified into 3 types (a) Benign, (b) Low-grade malignant, (c) High-grade malignant. Our classification seemed to offer an objective means for differentiating between Benign & Malignant tumors of these types.

An unusual case with an aggressive destructive granulomatous lesion of the maxilla is reported. Although the possibility of infection and neoplasm could be ruled out, a definite diagnosis could not be established even by repeated biopsies which showed the lesion to be a non-specific inflammatory process. Since Wegener's granulomatosis was most unlikely, the patient was treated by radiotherapy which caused rapid remission of the lesion with no sign of recurrence after 4 years. The clinical and histological findings as well as the responsiveness to the treatment were most indicative of idiopathic midline destructive disease. Effective management of lethal midline granuloma of unknown aetiology is discussed.

An unusual case of ameloblastoma that underwent malignant change and metastasis during recurrence is described. The primary tumor of the mandible and two independent recurrent lesions found in the base of the coronoid process and in the mandibular notch were cystic ameloblastoma of follicular type, with no histological evidence off malignancy. The second recurrence developed in the soft tissues on the medial aspect of the ascending ramus and consisted of a large solid tumor mass with poorly differentiated ameloblastoma cells, which were seen clustered in blood vessels in close apposition to tumor nests. Apparently these metastasized to the temporal bone in five months. The metastatic tumor was composed of atypical follicles packed with undifferentiated hyperchromatic cells with nuclear atypia and abundant mitoses. The histological diagnosis was malignant ameloblastoma. The cerebral lesion that developed in the skull base, possibly by direct extension of the second recurrent tumor, was also regarded as malignant because of its rapidity and aggressive growth and its high sensitivity to radiotherapy.