Immunohistochemical evaluation of cartilage-derived morphogenic protein-1 and -2 in normal human salivary glands and pleomorphic adenomas

Cartilage-derived morphogenic protein (CDMP)-1 and -2 belong to the bone morphogenetic protein (BMP) family in the transforming growth factor (TGF)-beta superfamily. CDMP-1 and CDMP-2 were reported to play essential roles in limb cartilage and limb-joint formation in developing mice. Although pleomorphic adenoma of the salivary glands is an epithelial tumor, it frequently shows ectopic cartilaginous formation. These findings suggested that CDMP-1 and -2 may play essential roles in chondroid formation in salivary pleomorphic adenoma. To evaluate this hypothesis, we examined the expression and localization of CDMP-1 and -2 immunohistochemically in 20 normal human salivary glands and 35 pleomorphic adenomas. CDMP-1 was immunolocalized in the striated ducts and the intercalated ducts in the normal salivary glands. CDMP-1 was immunolocalized in the cuboidal neoplastic myoepithelial cells around the chondroid areas of the pleomorphic adenomas, whereas these molecules were not localized in the spindle-shaped neoplastic myoepithelial cells of the myxoid element or the lacuna cells of the chondroid element in these tumors. CDMP-2 was expressed neither in normal salivary glands nor any of the elements of the pleomorphic adenomas. Type-II collagen and aggrecan were immunolocalized throughout the matrix around the lacuna cells of the chondroid element, whereas type-X collagen was not immunolocalized in any epithelial or stromal elements, including the chondroid elements. Aggrecan was deposited not only on the chondroid matrix, but also on the myxoid stroma and intercellular spaces of the tubulo-glandular structures, whereas chondromodulin-I was deposited on the chondroid matrix. These results indicated that the cuboidal neoplastic myoepithelial cells around the chondroid areas expressed CDMP-1 and suggested that this molecule may play a role in the differentiation of neoplastic myoepithelial cells in pleomorphic adenoma. The phenotype of the lacuna cells was similar to that of mature to upper hypertrophic chondrocytes of the authentic cartilage. In conclusion, pleomorphic adenoma expressed CDMP-1 but not CDMP-2.     

Fermented grain products, production, properties and benefits to health

Fermented foods such as Japanese traditional food “miso (fermented soy bean paste)” have been shown to be rich source of micronutrients with the potential to prevent various human diseases. We have introduced effects of a new dietary supplement of fermented grain foods mixture containing extracts from wheat germ, soybeans, rice bran, tear grass, sesame, wheat, citrus lemon, green tea, green leaf extract and malted rice under the trade name of antioxidant biofactor (AOB). Chemical analysis of AOB shows the presence of various phenolic compounds (catechins, rutin, genistin, daidzin, etc.). AOB has strong antioxidant properties and additional biological effects, which might be of importance in context with the prevention of degenerative diseases. This paper focuses on the effect of supplementing AOB in various animal models and humans.     

Role of small airways in asthma: investigation using high-resolution computed tomography

BACKGROUND: Small airways may have an important role in asthma but are more difficult to assess pathologically than central airways. Computed tomographic indices of lung density are assumed to reflect air trapping and may be a useful noninvasive measure of small airways disease, but their pathophysiological relevance remains undetermined. OBJECTIVE: To evaluate lung density on high-resolution computed tomography and examine its correlations with clinical and physiologic variables in 29 patients with stable asthma. METHODS: Both lungs were scanned at full-inspiratory and full-expiratory phases to quantify percentage of lung field occupied by low attenuation area (LAA%; < -960 Hounsfield units) and mean lung density. Asthma severity, pulmonary function, methacholine airway sensitivity and reactivity, and sputum eosinophil counts were evaluated. RESULTS: The mean lung density increased and LAA% decreased in all patients at expiratory phase compared with inspiratory phase. The inspiratory density indices and expiratory mean lung density correlated only with FEV(1)/forced vital capacity (FVC). Expiratory LAA% correlated more strongly than other variables with FEV(1)/FVC and with indices of peripheral airflow obstruction. Expiratory/inspiratory ratios of LAA% and mean lung density correlated, the former more strongly, with disease severity, residual volume/total lung capacity, and airway sensitivity, as well as with indices of global (FEV(1) and FEV(1)/FVC) and peripheral airflow obstruction. CONCLUSION: Expiratory/inspiratory high-resolution computed tomography is useful for assessing small airways disease in asthma. Small airways involvement is associated with airflow obstruction, airway hypersensitivity, and more severe disease. CLINICAL IMPLICATIONS: Small airways are an important therapeutic target in asthma.     

Effect of Hammerhead Ribozyme against Human Thymidylate Synthase on the Cytotoxicity of Thymidylate Synthase Inhibitors

One of the resistance mechanisms to folate-based thymidylate synthase (TS) inhibitors is the increase in TS activity in tumor cells. Human B lymphoblastoid cell line (W1L2) was made resistant to a lipophilic non-polyglutamatable TS inhibitor (ZM249148), and the subline (W1L2:R179) showed a 20-fold increase in TS enzyme activity with concomitant overexpression of TS mRNA. To overcome the resistance, we designed a ribozyme that can cleave the CUC sequences in a triple tandemly repeated sequence of TS mRNA. Expression of this ribozyme in W1L2:R179 cells transfected with Epstein Barr virus-based expression vector resulted in sensitization to TS inhibitors concomitantly with a decrease of TS expression. The ribozyme expressed in transfectants was shown to be functional in cleaving artificial TS RNA in vitro.     

Accumulation of photosensitizer ATX-S10 (Na) in experimental corneal neovascularization

PURPOSE: To determine the most appropriate time for laser irradiation to produce selective occlusion of new corneal vessels by photodynamic therapy (PDT) with a new photosensitizer, ATX-S10(Na). METHODS: The time course of the plasma levels of ATX-S10(Na) and the degree of dye accumulation in the corneal neovascularization after intravenous administration was determined in rabbit eyes. Plasma concentration of ATX-S10(Na) was analyzed by a spectrophotometer. The amount of ATX-S10(Na) in the new corneal vessels was measured by nitrogen-pulsed laser spectrofluorometry. Frozen sections of neovascularized cornea and iris were observed by fluorescence microscopy. RESULTS: Plasma ATX-S10(Na) concentration was highest 5 minutes after dye injection and rapidly decreased and reached almost zero at 24 hours, indicating its prompt excretion from the body. The amount of ATX-S10(Na) in the new corneal vessels as measured by nitrogen-pulsed laser spectrofluorometry increased and reached maximal level at 2 to 4 hours. Under fluorescence microscopy, the dye was more abundantly localized in the wall of new corneal vessels than in the normal tissue at 2 to 4 hours. CONCLUSION: These results indicate that laser irradiation between 2 and 4 hours after dye injection is appropriate for selective PDT with ATX-S10(Na) for the occlusion of new corneal vessels.     

Successful treatment of a huge meningeal hemangiopericytoma using Preoperative Autologous Transfusion and Hemodilutional Autologous Transfusion: case report

We report successful operations for a meningeal hemangiopericytoma using sufficient amounts of Preoperative Autologous Transfusion (PAT) and Hemodilutional Autologous Transfusion (HAT). A 23-year-old woman with amenorrhea and bilateral visual field disturbance was found to have a huge intracranial tumor. MRI showed a well-enhanced cystic mass in the left middle fossa, suprasellar, intrasellar, sphenoidal sinus, and cavernous sinus. Preoperatively, the tumor was thought to be a cystic pituitary tumor or meningioma. Surgical removal was planned in three steps. The first operation was carried out via the transsphenoidal approach. Total blood loss was 1348 ml and 2 MAP infusion were required to control bleeding. Histopathological diagnosis was hemangiopericytoma. After preparation of PAT 400 ml and HAT 800 ml, we carried out the second partial removal operation mainly via the interhemispheric approach. Total blood loss was 1829 ml and required autologous transfusion only. After preparation of PAT 1200 ml and HAT 400 ml, the last total removal operation was carried out mainly via the pterional and subtemporal approach. Total blood loss was 1813 ml and required autologous transfusion only. We needed 2 MAP infusion in the first operation, but were able to perform total removal successfully without homologous blood transfusion because a sufficient amount of PAT and HAT had been prepared preoperatively. Hemangiopericytoma required postoperative radiation therapy to avoid local recurrence. After successful removal of the tumor surgically, postoperative radiation therapy was able to be carried out efficiently.     

Usefulness of self-expandable metallic stent with an antireflux mechanism as a palliation for malignant strictures at the gastroesophageal junction

BACKGROUND: Patients with unresectable malignant gastroesophageal strictures often are troubled with reflux esophagitis after stent placement. METHODS: A self-expandable metallic stent (SEMS) without an antireflux mechanism was placed in seven patients with unresectable malignant gastroesophageal strictures (group A), and SEMS with an antireflux mechanism was placed in five patients (group B). After we obtained monitoring systems, two patients in group A and all the patients in group B underwent measurement of bilirubin and pH in the esophagus using a 24-h bilirubin and pH monitor. RESULTS: The mean percentage of total time less than 0.14 for use of the bilirubin absorbance unit was 12.4% in group B and 64.0% in group A. The mean percentage of total time for a pH less than 4 was 2.9% in group B and 37.8% in group A. CONCLUSION: The placement of SEMS with the antireflux mechanism can be effective not only for palliation of gastroesophageal stricture, but also for prevention of reflux.     

A selective plasmin inhibitor, trans-aminomethylcyclohexanecarbonyl-L-(O-picolyl)tyrosine-octylamide (YO-2), induces thymocyte apoptosis

The treatment of rat thymocytes with YO-2, a novel inhibitor of plasmin, resulted in an increase in DNA fragmentation. DNA fragmentation was also induced by another YO compounds such as YO-0, -3, -4 and -5. These YO compounds are the inhibitor of plasmin activity. On the other hand, YO-1, -6 and -8 that hardly inhibit plasmin activity had no effect on DNA fragmentation. Analysis of fragmented DNA from thymocytes treated with YO-2 by agarose gel electrophoresis revealed that the compound caused internucleosomal DNA fragmentation. In addition, judging from a laser scanning microscopy, annexin V-positive and propidium iodide-negative cells were increased by the treatment of the cells with the compound. Moreover, chromatin condensation was observed in thymocytes treated with the compound. These results demonstrated that YO-2 induces thymocyte apoptosis. There seemed to be some correlation between the apoptosis induced by YO compounds and their plasmin inhibitory effect. However, because the other protease inhibitors including pepstatin A, leupeptin, AEBSF, DFP and E-64-d did not affect DNA fragmentation, YO compounds are likely to have unique mechanism on plasmin or to show the effect on the other plasmin-like proteases. The plasmin inhibitory activity may have an important role in YO-2-induced apoptosis. Furthermore, the stimulations of caspase-8, -9 and -3-like activities were observed in thymocytes treated with YO-2. These results suggest that YO-2 induces thymocyte apoptosis via activation of caspase cascade.     

Sleep habits of students attending elementary schools,and junior and senior high schools in Akita prefecture

It is widely accepted that students in Japan sleep fewer hours than what they actually need. However, epidemiological data on sleep habits among students are scarce. The sleep habits and related problems among 1650 students in Akita prefecture were studied. The results revealed that schoolchildren attending elementary schools seemed to sleep for a sufficient number of hours, whereas students attending junior or senior high schools were not sleeping enough. In particular, approximately half of the students attending senior high schools answered that they slept 6 h or less on weekdays and nodded off during classes more than twice a week.     

Effects of somatosensory cortical stimulation on expression of c-Fos in rat medullary dorsal horn in response to formalin-induced noxious stimulation

We examined the effects of epidural electrical stimulation of primary (SI) and secondary (SII) somatosensory cortex on expression of c-Fos protein in rat medullary dorsal horn neurons (Vc; trigeminal nucleus caudalis) in response to formalin-induced noxious stimulation. Epidural electrical stimulation (single pulse, 0.2 msec duration at 10 Hz) was applied to the left facial region SI or SII at three different stimulus intensities, 0.1, 0.5, and 1.0 mA for 60 min 0 or 2 hr after bilateral injection of formalin into the lower lip. SII stimulation at 1.0 mA immediately after injection of formalin, significantly decreased the number of Fos-positive cells in the right VcI/II by 32.4%. There was no significant change in the number of Fos-positive cells in the VcIII/IV. SII stimulation at 0.5 and 1.0 mA 2 hr after injection of formalin, significantly decreased the number of Fos-positive cells in the right VcI/II by 47.9% and 40.8%, but significantly increased the number of Fos-positive cells in the right VcIII/IV by 178.8% and 324.3%, respectively. In contrast, SI stimulation had no effect on expression of c-Fos in Vc. Possible direct corticotrigeminal projections were labeled anterogradely by injection of WGA-HRP into the SI and SII. In the Vc, labeled terminals were distributed mostly in the contralateral medial half of VcIII/IV and medullary reticular nucleus dorsalis but rarely in VcI/II. These results suggest that activation of SII-medullary fibers suppress nociceptive information from the oro-facial regions.