Search

To determine whether temporal subtraction (TS) CT obtained with non-rigid image registration improves detection of various bone metastases during serial clinical follow-up examinations by numerous radiologists. Six board-certified radiologists retrospectively scrutinized CT images for patients with history of malignancy sequentially. These radiologists selected 50 positive and 50 negative subjects with and without bone metastases, respectively. Furthermore, for each subject, they selected a pair of previous and current CT images satisfying predefined criteria by consensus. Previous images were non-rigidly transformed to match current images and subtracted from current images to automatically generate TS images. Subsequently, 18 radiologists independently interpreted the 100 CT image pairs to identify bone metastases, both without and with TS images, with each interpretation separated from the other by an interval of at least 30 days. Jackknife free-response receiver operating characteristics (JAFROC) analysis was conducted to assess observer performance. Compared with interpretation without TS images, interpretation with TS images was associated with a significantly higher mean figure of merit (0.710 vs. 0.658; JAFROC analysis, P = 0.0027). Mean sensitivity at lesion-based was significantly higher for interpretation with TS compared with that without TS (46.1% vs. 33.9%; P = 0.003). Mean false positive count per subject was also significantly higher for interpretation with TS than for that without TS (0.28 vs. 0.15; P

Manufacturing meltblown nonwoven fabrics requires special grades of resin with very low viscosity, which are not dealt with so much on market and cost quite high compared to the standard grades. We propose a high-shear rate processing method that can quickly and easily produce such low-viscosity resin from the commercial one without using organic peroxides. In this method, we apply high-shear stress to molten resin by using a high-shear extruder, which is a single screw extruder with high screw rotation speed, and the resin is thermally decomposed of its shear-induced heat which is quickly generated. We found that polypropylene with a value of melt flow rate over a thousand, which was required for the meltblown process, was produced from the standard grade with the high-shear extruder at the screw rotation speed of 3600 min−1 and the barrel temperature over 300 ∘C. Using the degradated polypropylene, a meltblown nonwoven fabric sheet was successfully fabricated. We also developed a numerical simulator of the high-shear extruder which can handle a wide range of the screw rotation speed and barrel temperature by the Nusselt number modulated with the operational conditions. The experimental values of the zero-shear viscosity and temperature at the exit of the extruder agreed well with the simulation results. Our high-shear rate processing method will enable us to quickly and easily produce various meltblown nonwoven fabric sheets at low costs.

To develop and evaluate a deep learning-based algorithm (DLA) for automatic detection of bone metastases on CT.This retrospective study included CT scans acquired at a single institution between 2009 and 2019. Positive scans with bone metastases and negative scans without bone metastasis were collected to train the DLA. Another 50 positive and 50 negative scans were collected separately from the training dataset and were divided into validation and test datasets at a 2:3 ratio. The clinical efficacy of the DLA was evaluated in an observer study with board-certified radiologists. Jackknife alternative free-response receiver operating characteristic analysis was used to evaluate observer performance.A total of 269 positive scans including 1375 bone metastases and 463 negative scans were collected for the training dataset. The number of lesions identified in the validation and test datasets was 49 and 75, respectively. The DLA achieved a sensitivity of 89.8% (44 of 49) with 0.775 false positives per case for the validation dataset and 82.7% (62 of 75) with 0.617 false positives per case for the test dataset. With the DLA, the overall performance of nine radiologists with reference to the weighted alternative free-response receiver operating characteristic figure of merit improved from 0.746 to 0.899 (p.001). Furthermore, the mean interpretation time per case decreased from 168 to 85 s (p = .004).With the aid of the algorithm, the overall performance of radiologists in bone metastases detection improved, and the interpretation time decreased at the same time.• A deep learning-based algorithm for automatic detection of bone metastases on CT was developed. • In the observer study, overall performance of radiologists in bone metastases detection improved significantly with the aid of the algorithm. • Radiologists' interpretation time decreased at the same time.

To compare observer performance of detecting bone metastases between bone scintigraphy, including planar scan and single-photon emission computed tomography, and computed tomography (CT) temporal subtraction (TS). Data on 60 patients with cancer who had undergone CT (previous and current) and bone scintigraphy were collected. Previous CT images were registered to the current ones by large deformation diffeomorphic metric mapping; the registered previous images were subtracted from the current ones to produce TS. Definitive diagnosis of bone metastases was determined by consensus between two radiologists. Twelve readers independently interpreted the following pairs of examinations: NM-pair, previous and current CTs and bone scintigraphy, and TS-pair, previous and current CTs and TS. The readers assigned likelihood levels to suspected bone metastases for diagnosis. Sensitivity, number of false positives per patient (FPP), and reading time for each pair of examinations were analysed for evaluating observer performance by performing the Wilcoxon signed-rank test. Figure-of-merit (FOM) was calculated using jackknife alternative free-response receiver operating characteristic analysis. The sensitivity of TS was significantly higher than that of bone scintigraphy (54.3% vs. 41.3%, p = 0.006). FPP with TS was significantly higher than that with bone scintigraphy (0.189 vs. 0.0722, p = 0.003). FOM of TS tended to be better than that of bone scintigraphy (0.742 vs. 0.691, p = 0.070). Sensitivity of TS in detecting bone metastasis was significantly higher than that of bone scintigraphy, but still limited to 54%. TS might be superior to bone scintigraphy for early detection of bone metastasis. • Computed tomography temporal subtraction was helpful in early detection of bone metastases. • Sensitivity for bone metastasis was higher for computed tomography temporal subtraction than for bone scintigraphy. • Figure-of-merit of computed tomography temporal subtraction was better than that of bone scintigraphy.

To assess whether temporal subtraction (TS) images of brain CT improve the detection of suspected brain infarctions. Study protocols were approved by our institutional review board, and informed consent was waived because of the retrospective nature of this study. Forty-two sets of brain CT images of 41 patients, each consisting of a pair of brain CT images scanned at two time points (previous and current) between January 2011 and November 2016, were collected for an observer performance study. The 42 sets consisted of 23 cases with a total of 77 newly developed brain infarcts or hyperdense artery signs confirmed by two radiologists who referred to additional clinical information and 19 negative control cases. To create TS images, the previous images were registered to the current images by partly using a non-rigid registration algorithm and then subtracted. Fourteen radiologists independently interpreted the images to identify the lesions with and without TS images with an interval of over 4 weeks. A figure of merit (FOM) was calculated along with the jackknife alternative free-response receiver-operating characteristic analysis. Sensitivity, number of false positives per case (FPC) and reading time were analyzed by the Wilcoxon signed-rank test. The mean FOM increased from 0.528 to 0.737 with TS images (p < 0.0001). The mean sensitivity and FPC improved from 26.5% and 0.243 to 56.0% and 0.153 (p < 0.0001 and p = 0.239), respectively. The mean reading time was 173 s without TS and 170 s with TS (p = 0.925). The detectability of suspected brain infarctions was significantly improved with TS CT images. • Although it is established that MRI is superior to CT in the detection of strokes, the first choice of modality for suspected stroke patients is often CT. • An observer performance study with 14 radiologists was performed to evaluate whether temporal subtraction images derived from a non-rigid transformation algorithm can significantly improve the detectability of newly developed brain infarcts on CT. • Temporal subtraction images were shown to significantly improve the detectability of newly developed brain infarcts on CT.

Temporal subtraction of CT (TS) images improves detection of newly developed bone metastases (BM). We sought to determine whether TS improves detection of BM by radiology residents as well. We performed an observer study using a previously reported dataset, consisting of 60 oncology patients, each with previous and current CT images. TS images were calculated using in-house software. Four residents independently interpreted twice the 60 sets of CT images, without and with TS. They identified BM by marking suspicious lesions likely to be BM. Lesion-based sensitivity and number of false positives per patient were calculated. Figure-of-merit (FOM) was calculated. Detectability of BM, with and without TS, was compared between radiology residents and board-certified radiologists, as published previously. FOM of residents significantly improved by implementing TS (p value

In our previous study, we developed a computer-aided diagnosis (CADx) system using imaging findings annotated by radiologists. The system, however, requires radiologists to input many imaging findings. In order to reduce such an interaction of radiologists, we further developed a CADx system using derived imaging findings based on calculated image features, in which the system only requires few user operations. The purpose of this study is to check whether calculated image features (CFT) or derived imaging findings (DFD) can represent information in imaging findings annotated by radiologists (AFD). We calculate 2282 image features and derive 39 imaging findings by using information on a nodule position and its type (solid or ground-glass). These image features are categorized into shape features, texture features and imaging findings-specific features. Each imaging finding is derived based on each corresponding classifier using random forest. To check whether CFT or DFD can represent information in AFD, under an assumption that the accuracies of classifiers are the same if information included in input is the same, we constructed classifiers by using various types of information (CTT, DFD and AFD) and compared accuracies on an inferred diagnosis of a nodule. We employ SVM with RBF kernel as classifier to infer a diagnosis name. Accuracies of classifiers using DFD, CFT, AFD and CFT $$+$$ AFD were 0.613, 0.577, 0.773 and 0.790, respectively. Concordance rates between DFD and AFD of shape findings, texture findings and surrounding findings were 0.644, 0.871 and 0.768, respectively. The results suggest that CFT and AFD are similar information and CFT represent only a portion of AFD. Particularly, CFT did not contain shape information in AFD. In order to decrease an interaction of radiologists, a development of a method which overcomes these problems is necessary.

We aimed to describe the development of an inference model for computer-aided diagnosis of lung nodules that could provide valid reasoning for any inferences, thereby improving the interpretability and performance of the system. An automatic construction method was used that considered explanation adequacy and inference accuracy. In addition, we evaluated the usefulness of prior experts’ (radiologists’) knowledge while constructing the models. In total, 179 patients with lung nodules were included and divided into 79 and 100 cases for training and test data, respectively. F-measure and accuracy were used to assess explanation adequacy and inference accuracy, respectively. For F-measure, reasons were defined as proper subsets of Evidence that had a strong influence on the inference result. The inference models were automatically constructed using the Bayesian network and Markov chain Monte Carlo methods, selecting only those models that met the predefined criteria. During model constructions, we examined the effect of including radiologist’s knowledge in the initial Bayesian network models. Performance of the best models in terms of F-measure, accuracy, and evaluation metric were as follows: 0.411, 72.0%, and 0.566, respectively, with prior knowledge, and 0.274, 65.0%, and 0.462, respectively, without prior knowledge. The best models with prior knowledge were then subjectively and independently evaluated by two radiologists using a 5-point scale, with 5, 3, and 1 representing beneficial, appropriate, and detrimental, respectively. The average scores by the two radiologists were 3.97 and 3.76 for the test data, indicating that the proposed computer-aided diagnosis system was acceptable to them. In conclusion, the proposed method incorporating radiologists’ knowledge could help in eliminating radiologists’ distrust of computer-aided diagnosis and improving its performance.

The glucocorticoid dexamethasone inhibited the production of the rat cytokine-induced neutrophil chemoattractant CINC/gro, a counterpart of human melanoma growth-stimulating activity that belongs to the interleukin-8 (IL-8) family, in the normal rat kidney epithelial cell line NRK-52E stimulated with interleukin-1 beta (IL-1 beta), lipopolysaccharide, or tumor necrosis factor alpha. The accumulation of CINC/gro mRNA induced by these activators was also decreased comparably by dexamethasone. A nuclear run-on assay revealed that dexamethasone decreased the IL-1 beta-induced transcription of the CINC/gro gene. The half-life of CINC/gro mRNA transcripts did not change significantly after exposure to dexamethasone, suggesting that this glucocorticoid acts mainly at the transcriptional level. Transfection with luciferase expression vectors containing 5'-deleted and mutated CINC/gro gene sequences demonstrated that the 5'-flanking region containing the NF-kappa B binding site is involved in the IL-1 beta- and dexamethasone-induced activation and repression of the CINC/gro gene expression, respectively. Furthermore, a tandem repeat of the NF-kappa B sequence in the CINC/gro gene conferred the inducibility by IL-1 beta and suppression of luciferase activity by dexamethasone. In an electrophoretic mobility shift assay, dexamethasone diminished the IL-1 beta-induced formation of NF-kappa B complexes, which consisted of p65 and p50. Western blotting revealed that dexamethasone inhibited the IL-1 beta-induced translocation of p65 from the cytoplasm into the nucleus, while the nuclear level of NF-kappa B p50 remained almost unchanged. In addition, the degradation of I kappa B-alpha induced by IL-1 beta was not inhibited by dexamethasone. These results indicated that the suppression of the CINC/gro gene transcription by glucocorticoid occurs through the impairment of NF-kappa B activation, possibly by interference with the translocation of NF-kappa B p65 from the cytoplasm into the nucleus, thereby suppressing transactivation of the CINC/gro gene.

A clinicopathological study in 229 patients with postoperative maxillary cysts (POMC)(unilateral: 215 cases. bilateral: 14 cases) is described.The patients were treated at our hospital between 1979 and 1989. The age of the patients ranged from 18 to 72 years, and their average age was 45.2 years. The chief complaints of these patients were swelling and pain, and POMC were diagnosed based on clinical, radiologic and histopathologic findings.The patients were surgically treated by the following procedures: 1) extirpation of cysts (35 cases), 2) marsupialization to the inferior meatus (120 cases), and 3) radical operation according to the Caldwell-Lucs, method (88 cases).Histopathologic examination revealed various patterns of the cyst wall, including ciliated, cuboidal, squamous, and columnar epithelium, as well as a mixture of two or three kinds of these epithelial cells.Radiological examination using contrast media revealed that the from of cysts was either ovoid or irregular.One of the 243 cases showed recurrence. In this case, there was no passage between the cystic and nasal cavity. These findings suggest that sufficient marsupialization to the nasal cavity is important to ensure a favorable outcome.

The pharmacological properties of a structurally novel kappa-opioid receptor agonist, (3R)-3-(1-pyrrolidinylmethyl)-4-[(1S)-5,6-dichloro-1-indancarbo nyl]- tetrahydro-1,4-thiazine hydrochloride (R-84760), were examined. In an opioid receptor binding assay with a guinea pig brain membrane fraction, R-84760 showed a 5 times higher affinity for the kappa-opioid receptor than CI-977, the most potent reference kappa-opioid receptor agonist, and selectivity of R-84760 for the kappa-opioid receptor was higher than that of U-69593, a highly selective kappa-opioid receptor agonist. R-84760 was functionally 2.5 times more potent than CI-977 as a kappa-opioid receptor agonist in rabbit vas deferens. Subcutaneously administered R-84760 had an antinociceptive effect in the phenylquinone writhing test in mice and its potency was 5-846 times higher than those of CI-977, U-50488, morphine, pentazocine and butorphanol. On oral administration, R-84760 was 20-2077 times more potent than the same reference drugs. The antinociceptive effect of R-84760 was not antagonized by naloxone in a dose at which naloxone antagonized the effect of morphine, but on the other hand nor-binaltorphimine antagonized the effect of R-84760 at a dose which did not affect the effect of morphine. R-84760 and the reference kappa-opioid receptor agonists produced sedative and diuretic effects in mice with the same order of potency as for the antinociceptive effect. Tolerance to the antinociceptive effect of R-84760 barely developed, and naloxone-induced jumping tests for morphine-like physical dependence of R-84760 gave negative results.

The effects of CS-518 (sodium 2-(1-imidazolylmethyl)-4,5-dihydrobenzo[b]thiophene-6-carboxylate), a thromboxane A 2 synthase inhibitor, on eosinophil accumulation and activation were investigated in an experimental asthmatic guinea pig model and several cellular models. In the in vivo studies, CS-518 inhibited the biphasic eosinophil accumulation in the bronchoalveolar lavage fluid, potently in the early phase, but less potently in the delayed phase. On the other hand, even at the lower dose, CS-518 completely inhibited the hypodensity of eosinophils in the delayed phase. In the in vitro studies, CS-518 suppressed thromboxane A 2 production and potentiated prostaglandin I 2 production from guinea pig eosinophils. Moreover, CS-518 and prostaglandin I 2 suppressed chemotaxis, peroxidase release and superoxide generation in guinea pig eosinophils. In addition, the present studies provide further support for the possibility that thromboxane A 2 and prostaglandin I 2 , which are produced in bronchoalveolar tissue and within eosinophils, are involved in modulation of eosinophil function and suggest that CS-518 is a potent inhibitor of eosinophil activation.

Potent chemotactic activity for neutrophils was detected in rat inflammatory exudate induced by a subcutaneous injection of lipopolysaccharide in a carboxymethyl-cellulose suspension. We purified and characterized chemoattractants from the exudate by the following procedures: carboxymethyl-Sephadex C-25 ion-exchange chromatography; G3000SW gel-filtration chromatography; preparative reverse-phase high-pressure liquid chromatography; rechromatography on reverse-phase HPLC. Two chemotactic factors were purified and their N-terminal amino acid sequences were determined. One factor was a protein in which the first 20 N-terminal amino acids were identical to those of rat cytokine-induced neutrophil chemoattractant (CINC), a counterpart of human gro/melanoma growth-stimulating activity (MGSA). The other factor was highly similar to mouse macrophage inflammatory protein 2 (MIP-2). Mouse MIP-2, a chemotactic factor for neutrophils, is a member of the interleukin-8 family; however the protein we purified had higher similarity to human gro/MGSA than to human interleukin-8. These results indicate that, in rats, chemotactic factors for neutrophils induced by lipopolysaccharide stimulation are not counterparts of interleukin-8, but are gro/CINC-related peptides.

Rat cytokine-induced neutrophil chemoattractant (CINC) is a member of the IL-8 family, and its human counterpart is gro/MGSA but not IL-8. We ascertained that chemically synthesized CINC was comparable to native CINC/gro with regard to chemotactic activity for rat neutrophils and studied the effect of synthesized CINC/gro on circulating leukocytes in microvascular vessels of rat mesentery. Exposure of rat mesentery to 10(-8)M authentic CINC/gro induced neutrophil adherence to and extravasation from postcapillary venules (PCVs) but not from capillaries or arterioles. CINC/gro concentrations as low as 10(-10) M were effective in causing neutrophil adherence. Neutrophils adhered to thin PCVs (mean diameter, approximately 25 microns) after exposure to CINC/gro for 15 min. The mean diameters of the PCV with adherence of neutrophils after exposure to CINC/gro for 30 and 60 min were 37 and 43 microns, respectively. The diameters of PCV with extravasation of neutrophils also increased in a time-dependent manner. The starting position of adherence of neutrophils was approximately 25-50 microns away from the upper junction of two vessels and remained virtually unchanged during exposure to CINC/gro for 60 min. However, the distance from the start to the end of neutrophil adherence increased in a time-dependent manner. The effect of CINC/gro on adherence and extravasation of leukocytes was neutrophil specific since other leukocytes such as lymphocytes and monocytes were not identified among the adherent and extravasated leukocytes.

The effect of loxoprofen-Na, a novel non-steroidal anti-inflammatory drug with a prodrug property, on prostaglandin (PG) levels in the inflammatory tissue was investigated with a carrageenin-induced pleurisy model in rats. The intrapleural injection of carrageenin caused a marked increase in the levels of PGE2 and 6-keto-PGF1 alpha in the pleural exudate up to 3 hr after the injection. When [14C]PGE2 was injected into the cavity 2 hr after the carrageenin injection, the PG rapidly disappeared from the cavity (T 1/2 = 5 min). Thus, the PG level determined in the inflammatory exudate represents PG produced in the inflammatory tissue. Loxoprofen-Na, administered orally 2 hr after the carrageenin injection, dose-dependently inhibited the increase in the levels of PGs in the exudate 1 hr after administration (ID50 = 0.07 mg/kg for PGE2 and 0.10 mg/kg for 6-keto-PGF1 alpha). Indomethacin also inhibited PG production, but was less effective (ID50 = 0.24 mg/kg for PGE2 and 0.47 mg/kg for 6-keto-PGF1 alpha). Similar results were obtained 3 hr after the administration of these drugs (ID50 of PGE2 production = 0.14 mg/kg for loxoprofen-Na and 0.28 mg/kg for indomethacin). The time-course analysis of the effect of loxoprofen-Na showed that this drug had more immediate and stronger inhibitory activity than indomethacin. The relative potencies of suppression of protein leakage and leukocyte infiltration correlated well with the inhibition of PG production, but higher doses were needed for an obvious anti-inflammatory effect. The active metabolite (SRS trans-OH) of loxoprofen-Na determined in the inflammatory exudate 1 hr after oral administration of 0.2 and 2 mg/kg of loxoprofen-Na was 0.05 and 0.25 micrograms/mL, respectively. The concentration was sufficient to suppress PG production in the exudate, because the IC50 of the SRS trans-OH for PG production in vitro with leukocytes was 0.02 microgram/mL (0.01 microM). The potency of the SRS trans-OH metabolite to inhibit PGE2 production in leukocytes was about 20 times stronger than that of the parent compound and 3 times stronger than that of indomethacin.

A case of exostosis at the inferior border of the mandible was reported. The patient was a 66-year-old woman who complained chiefly of painless swelling at the inferior border of the left mandible. Physical examination disclosed a firm and hard mass, adhering to the inferior surface of the mandible. Roentogenograms of the mandible disclosed a cylindric, radiopaque appearance, which extended outward beyond the normal inferior border of the left mandible. The clinical diagnosis was exostosis. Surgical removal of the bony mass was done under local anestl-esia. The bony mass was about 6 mm in diameter and 12 mm in length. Its histopathological diagnosis was also exostosis. Generally, exostosis is not a rare disease, but such cylinder shaped exostosis occurring at the inferior border of the mandible as seen in this case was extremely rare. And we could not find out the cause of the lesion in this case.The patient was last seen about two years after the operation and no evidence of further trouble was found clinically and roentogenologically at that time.

Pycnodysostosis first described by Aoike (1954) and named by Marouteaux and Lamy (1962), is a rare skeletal bone disease. This disease is characterized by dwarfism, failure of closure of cranial sutures, obliquity of mandibular angle and defects of the terminal phalanges.A rare case of pycnodysostosis in 42 year-old woman complicated with maxillary and mandibular osteomye-litis for a long time was reported. This patient suffered severe osteomyelitis following a tooth extraction because of extremely high bone density and abnormal dentition. We discussed the treatment of osteomyelitis associated with pycnodysostosis.

The anti-asthmatic effects of CS-518 (sodium 2-(1-imidazolylmethyl)-4,5-dihydrobenzo[b]thiophene-6-carboxylate), a specific thromboxane A2 (TXA2) synthase inhibitor, were investigated in the ovalbumin-sensitized guinea pig asthmatic model. Although CS-518 slighly inhibited (about 25%) whole bronchoconstriction, it significantly inhibited the antigen-induced bronchoconstriction mediated by slow-reacting substance of anaphylaxis (SRS-A), which was not reduced by chlorpheniramine, a histamine H1 antagonist. On the other hand, indomethacin, a cyclooxygenase inhibitor, potentiated the SRS-A-mediated constriction. CS-518 strongly, and indomethacin slightly, suppressed the leukotriene D4-induced bronchoconstriction. CS-518 clearly inhibited the antigen-induced airway hyperresponsiveness, but this compound had no effect on the airway hyperresponsiveness induced by U-46619, a TXA2-mimetic agent, and propranolol. These results suggest that CS-518 suppresses the development of bronchoconstriction and airway hyperresponsiveness in asthmatic models by inhibition of TXA2 synthesis with the concomitant increase in bronchodilating prostaglandins such as prostaglandin E2 and prostaglandin I2.

A series of hindered phenolic 1,3-benzoxathioles were prepared and investigated for biological properties. Many compounds had lipid peroxide-lowering, antisuperoxide inhibiting, Slow-reacting Substance of Anaphylaxis (SRS-A) inhibiting, and 5-lipoxygenase inhibiting activities. Among them, 5-hydroxy-4,6,7-trimethyl-2-propyl-1,3-benzoxathiole and 3-(5-hydroxy-4,6,7-trimethyl-1,3-benzoxathiol-2-yl)propanol were most potent in SRS-A inhibiting and 5-lipoxygenase inhibiting activities, respectively, and were selected for further development as candidate drugs for the treatment of asthma

This report was undertaken to reveal the process of changes occuring in the alveolar clefts secondarily transplanted with fresh autogenous particulate cancellous bone and marrow of iliac bone, the frequency of the bone bridge formation in the alveolar cleft, and the time of bone bridging after the operation.The subjects were 87 cases with alveolar clefts, which consisted of 14 cleft lip and alveolus, 55 unilateral cleft lip and palate, and 18 bilateral cleft lip and palate. The average age at the time of bone grafting was 13 years 0 month with a range from 8 years 5 months to 22 years 1 month. The materials used in this investigation were periapical and occlusal radiographs taken before and after the bone grafting.The information obtained was summarized as follows:1. The frequency of the bone bridge formation in the alveolar clefts by one year postoperatively was 84.9% as a whole, and it had a tendency to decrease as the patients age increased.2. The bone bridge formation was completed from three to six months in the majority of the cases, and the average bone bridging time was 5. 4 months after the operation. The completion of the bone bridge formation was likely to delay, as the time of operation was later.3. No significant relation was observed between rate of successful bone formation in the clefts and the sex of the patient or the type of clefts.

In this paper, a 16 year old male case of odontogenic myxofibroma with peculiar calcareous substances in the lower left molar region and mandibular ramus was reported. He had suffered from a swelling without pain in this region. Radiographic examination revealed a multilocular and radiolucent lesion containing a mandibular third molar and uncertain cloudy radiopaque shadows. Boundary of the lesion was radiographically comparatively clear. Extraction of the second molar and removal of the tumor were performed under general anesthesia. The tumor was 6.5×3. 5×4.0cm in size, trancelucent and light brown color, smooth surfaced with soft consistency and cystic lumens containing viscoid fluid.Thin calcareous substances were scattered in the tumor.Microscopically, the tumor consisted of dense fibrous connective and myxomatous tissues. Tumor cells were stellate or spindle shaped, but mitotic figure was not seen. The tumor contained numerous peculiar calcareous substances which varied in size and were of unknown origin. The tumor was diagnosed odontogenic myxofibroma because of the existence of epithelial islands of odontogenic origin and continuation between dental sac of the embedded third molar and tumor tissue. No recurring after treatment.

[(Cycloalkylmethyl)phenyl]acetic acid derivatives and related compounds were synthesized to test their antiinflammatory and analgesic activities. Some of the compounds in this series were found to have good activity in the carrageenan edema test. Among them, sodium 2-[4-[(2-oxocyclopentyl)methyl] phenyl]propionate dihydrate (15) and 2-[4-[(2-oxocyclohexylidene)methyl]phenyl]propionic acid (13b) showed potent analgesic and antiadjuvant arthritis activities with excellent antipyretic properties.

Secondary bone grafting of alveolar clefts has been performed in 109 cleft palate patients, 55 boys and 54 girls, using the autogenous particulate cancellous bone and marrow of the iliac bone. The patients age range was 8 years 2 months to 28 years 8 months, with a mean age of 12 years 11 months.Before the bone grafting, any malocculusion of the maxillary segments were corrected with orthodontic treatment. Operation was done with simultaneous correction of alveolar clefts and oral-nasal fistulas.The incision made along the clefts margin of the labial site, mucoperiosteal flap was developed.Mucoperiosteum of the fistula was dissected and separated the palatal and nasal portion with scissors. The mucoperiosteum were closed with stiches in each.At this point, nasal and palatal layers of mucoperiosteum had been created. Cancellous bone and marrow were packed into any spaces, and placed in the area of the alar base. After an adequate osseous form was obtained, the labial mucoperiosteum was undermined and relaxed, and closed with stiches. But, the cases of great oral-nasal fistulas, labial sulcus flap used closure of the labial and palatal portion of oral-nasal fistula.Secondary bone grafting of alveolar clefts has following benefits to cleft palate patients.1) Stabilization of the maxillary segment.2) Closure of oral-nasal fistulas.3) Support of the slumping alar base of the nose.4) Restoration of alveolar process and dental arch.5) Provision of bone support for unerupted canine.These advantages of secondary bone grafting were results of short term observation, but, in the future, long term observation is necessary.

The development of immune response in rats directed toward EL4 cells, after the injection of EL4 cells suspended in a saline/oil emulsion, was enhanced by the incorporation of Mycobacterium into the saline/oil emulsion; the incorporation of type II collagen into the saline-acetic acid/oil emulsion in concentrations ranging from 0.5-25 micrograms/ml had no apparent effect on the development of immune response. The incorporation of type II collagen into the saline-acetic acid/oil emulsion at higher concentrations (100 micrograms and 1.0 mg/ml) significantly suppressed both the humoral and the cell-mediated immune response. Pretreatment of rats with the maximal subarthritiogenic dose of complete Freund's adjuvant prevented the development of arthritis in response to a subsequent injection of an arthritogenic dose of the same adjuvant, but had no effect on the development of type II collagen-induced arthritis. These observations suggest that adjuvant arthritis and the type II collagen-induced arthritis are distinctly different diseases.

ラット後肢足に火傷をつくり，それに重ねて熱刺激を加えて惹起させた炎症性終痛によるラットの症状を指標とし，新しい鎮痛薬試験法を考案した．ラット後肢足をエーテル麻酔下に57DCの熱湯に5秒間浸して火傷を作成し，2ないし4時間後に40°Cの温湯に5秒間の刺激を重ねてその火傷足に加える．再加熱直後，ラットは通常火傷足を床につけずに持ち上げるかまたは舐める行動を示す．この行動を終痛反応と規定し，再加熱後の30秒間に示される痔痛反応の時間を計測する．痛みの程度はこの終痛反応時間で表示した．火傷2時間後に疹痛反応を明瞭に示すラットを選別して投薬し，疹痛反応時間の抑制百分率ならびにID50値(50%の抑制率を与える薬用量)で薬効を表示した．この方法の特長は指標とする反応が疹痛知覚に起因している可能性が大きく，それが鎮痛薬によってのみ特異的に抑制されること，下熱鎮痛薬の鎮痛作用を抗炎症作用あるいは下熱作用の影響をうけずに測定し得ること，ならびに疹痛反応の観察に際し惹起熱刺激を与える時間と反応観察時間とを分離したことにより被検動物に加えられる通常でない環境因子を除去し得ることなどで，従来の鎮痛試験法より特異性が大きいと推察される．この方法によって測定された下熱鎮痛薬の有効性の順位は，indomethacin>flufenamic acid>mefenamic acid>bimetopyrol>ibuprofen>phenylbutazone>aminopyrine>mepirizole>aspirinであった．

On cardiovascular systems, oxazolazepam caused slight hypotension and depression of heart rate in larger doses but no significant effects on respiration, ECG and responses to autonomic drugs. These effects were weaker than those by chlordiazepoxide. On isolated organs, oxazolazepam exhibited more effect than chlordiazepoxide. Other effects, such as miosis, hypothermia, constipation and physical dependence liability were less demonstrated by oxazolazepam than by chlordiazepoxide. Emetic, antiinflammatory and diuretic actions were not seen by these drugs. Subacute toxicity by oxazolazepam for 5 weeks was definitely less than by chlordiazepoxide.

The severity of type II collagen-induced arthritis was found to correlate with the serum titers of anti-type II collagen antibody, but not with cell-mediated immunity to type II collagen. In contrast, no significant levels of either the humoral or the cell-mediated immunity to type II collagen were found in rats with Freund's complete adjuvant-induced arthritis. Pre-treatment of young rats with an oily preparation of type II collagen prevented the development of arthritis in these animals in response to a subsequent injection of oily preparation of type II collagen, but had no effect on the development of arthritis in response to a subsequent injection of Freund's complete adjuvant. It is concluded that while an immune response directed toward the injected type II collagen is responsible for the development of type II collagen arthritis, it does not play an important role in the induction of Freund's adjuvant-induced arthritis.

[(Cycloalkylmethyl)phenyl]acetic acid derivatives and related compounds were synthesized to test their antiinflammatory and analgesic activities. Some of the compounds in this series were found to have good activity in the carrageenan edema test. Among them, sodium 2-[4-[(2-oxocyclopentyl)methyl] phenyl]propionate dihydrate (15) and 2-[4-[(2-oxocyclohexylidene)methyl]phenyl]propionic acid (13b) showed potent analgesic and antiadjuvant arthritis activities with excellent antipyretic properties.

The immunomodulatory properties of RS-2131, 2-[4-(2-oxocyclohexylidenemethyl)phenyl]propionic acid, were studied using normal and autoimmune mice. RS-2131 suppressed the Arthus-type footpad reaction in BALB/c mice when administered orally at the time of immunization with sheep red blood cells, in contrast to indomethacin. This drug also suppressed the direct plaque-forming cell response against sheep erythrocytes in BALB/c mice. Under the same experimental conditions, the percentage ratio of Lyt 2+ cells to Thy 1.2+ cells were increased in the spleen cells. When used in non-immunized normal BALB/c mice, however, RS-2131 produced no effect on the ratio of Lyt 2+ cells to Thy 1.2+ cells in the spleen cells and on the percent distribution of T lymphocyte subsets. In MRL/Mp-lpr/lpr (MRL/lpr) mice, which have been known as a model of autoimmune disease, Lyt 2 cells in the thymus and the lymph node increased on oral treatment with RS-2131. These findings suggest that this drug may induce suppressor T cells only when the immune response in host animals is increased and then results in inhibition of immune responses in mice.