Search

To improve the cytocompatibility of mineral trioxide aggregate (MTA) cement and its ability for reparative dentin formation, the effect of adding choline dihydrogen phosphate (CDHP), which is reported to be biocompatible, to MTA cement was investigated. The L929 cell proliferation showed that the addition of CDHP improved cell viability. The addition of CDHP shortened the setting time of MTA cement, with a significant decrease in consistency above 0.4 g/mL. Diametral tensile strength of the set cement was improved by the addition of 0.4 g/mL CDHP. Solubility was judged to be within the range of clinical application. The spontaneous precipitation of low crystalline hydroxyapatite was examined by immersing the set cement in phosphate buffer saline, and it was found that the ability of the cement with 0.4 g/mL of CDHP was significantly improved compared with that of the cement without CDHP.

Objectives: Dental caries and periodontal diseases are significant health concerns in developing nations. This study assessed the impact of a comprehensive oral health education program on adolescent girls in rural Kenya., Methods: Eighty-seven girls aged 13-18 years attending school in rural Nanyuki, Kenya, were enrolled in the study. The comprehensive program included personalized oral hygiene training, education and health advocacy coaching. Dental caries, gingival inflammation and dental plaque biofilm were assessed at baseline, 1- and 2.5-year post-implementation., Results: The intervention was highly effective in arresting pre-existing carious lesions and preventing the formation of new ones in this population. The data revealed that there was a significant remineralization of incipient caries lesion, as shown by decreases in modified ICCMS™ scores from baseline to 1-year post-implementation. From baseline to the 2.5-year post-implementation assessment, only six new carious lesions developed. Dental plaque biofilm was reduced by 83.6%, and gingival inflammation was reduced by 81.6%., Conclusion: A comprehensive oral health program, which included behavioural awareness and educational approaches, resulted in significant positive oral health outcomes in caries, dental plaque biofilm and gingival inflammation., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A 65-year-old woman presented with a flat elevated lesion of about 1cm in the cecal diverticulum during a lower gastrointestinal endoscopy that was performed previously by another physician during a medical checkup. The patient was referred to our department for resection. Considering the risk of perforation owing to the diverticular lesion, positive nonlifting sign, and Group 5 diagnosis on the previous biopsy, EMR with over-the-scope clip (OTSC) (EMRO) was selected, and complete resection was achieved without complications.

A 51-year-old woman with edema of the lower extremities and exertional dyspnea was admitted to our hospital. Enhanced CT revealed thrombi of the pulmonary artery and a gallbladder tumor. After anticoagulation therapy was started on her, anemia and jaundice progressed; thus, endoscopic retrograde cholangiopancreatography(ERCP)was performed on suspicion of bleeding from a gallbladder tumor. We performed cholecystectomy in emergency to control the anemia due to hemorrhage. Oxygenation suddenly worsened intraoperatively, maintaining her blood pressure became difficult, and the patient decompensated. The histopathological diagnosis was gallbladder mucinous carcinoma with severe lymphatic invasion. Although an autopsy was not performed, pulmonary artery embolism derived from a tumor embolus was the suspected cause of the sudden change of the clinical course.

A 70-year-old woman was admitted to a local hospital because of anal pain during defecation. Anoscopy revealed an anal mass lesion, and the patient was referred to our hospital. Colonoscopy revealed an anal canal tumor with ulceration, and biopsy showed squamous cell carcinoma. The patient was treated with chemoradiotherapy(chemotherapy with capecitabine plus mitomycin C and 54 Gy radiation in the anal region)and achieved complete response. However, metastatic recurrence was detected in a lymph node in the hepatic hilar region. We administered an S-1/CDDP combination chemotherapy (5 courses). For 3 years and 5 months since the initial treatment, the patient survived with no signs of recurrence. We report a rare case of long-term survival with S-1/CDDP for distant metastasis of anal canal squamous cell carcinoma after chemoradiotherapy.

We prepared hydroxyapatite (HAp) bone grafts by the setting reaction of calcium phosphate cement, and investigated the effects of the porosity and crystallinity on the osteoconductivity and bioresorbability. We examined the effect of the water-mixing ratio, pressure, and post-heat treatment temperature during preparation on the crystallite size and porosity of the HAp blocks. The quantity of protein adsorption increased with increasing porosity and specific surface area (SSA) of the HAp blocks, whereas the initial cell attachment was similar despite the different porosities and crystallinities. In in vitro dissolution tests with a pH 5.5 buffer, which mimics an osteoclast-created Howship's lacuna, both the porosity and SSA of the HAp blocks affected the solubility; most likely due to the increased contact area with the buffer. Thus, HAp blocks prepared by the setting reaction of calcium phosphate cement could be applicable for bioresorbable HAp bone grafts because of the high porosity and SSA.

Advancements in dental cements have considerably improved their bond strengths. However, high bond strength often makes the removal of restorations difficult. Thus, smart dental cements that show controllable bond strength are required. A conventional resin-modified glass-ionomer-cement demonstrated a significant reduction in the bond strength after current application. However, for this system, the ions in the cement are released into the oral cavity, resulting in a reduction of the electrical conductivity and in losses of the expected on-demand debonding property. Herein, the effects of immersion in 0.9 and 15% NaCl solutions on the electrical conductivity and debonding properties were investigated. The cement immersed in 0.9% NaCl solution from 1 to 28 days maintained similar bond strength reductions after current application, whereas that in 15% NaCl solution initially showed no bond strength reduction after 1 day but exhibited an increase in the bond strength reduction after immersion for 28 days.

An 87-year-old man had a self-extracted percutaneous endoscopic gastrojejunostomy tube (PEG-J tube) and underwent PEG-J replacement. He vomited 2 days after the replacement, and bowel bleeding occurred 5 days after the replacement. Therefore, he presented to our hospital. A simple abdominal computed tomography scan showed a target sign in the jejunum on the anus side rather than on the PEG-J tube tip portion, resembling intussusception. We confirmed mucosa necrosis in the intussusception by small-diameter endoscopy and attempted internal treatment. However, resistance was so strong that the internal treatment was difficult;therefore, he underwent a jejunal resection. Although diarrhea and dumping syndrome are common PEG-J complications, there have been few reports of intussusception caused by PEG-J. We report a case of adult-onset intussusception, which was thought to be caused by long-term PEG-J implantation.

The enhancement in the bonding strength of advanced dental cements has enabled long-lasting dental restorations. However, the high bonding strength can cause difficulty in removing these restorations. Therefore, "smart" dental cements with simultaneous strong bonding and easy on-demand debonding ability are required. A resin-modified glass-ionomer-cement (RMGIC) with an ionic liquid (IL) has demonstrated significant reduction in the bonding strength with current application (CA). This research investigates the effect of immersion in distilled water on the electric conductivity and bonding strength of RMGIC with and without an IL and CA. The RMGIC without the IL exhibited significant electric conductivity after immersion, and a significant decrease in bonding strength with CA. In comparison, the electric conductivity after immersion and the decrease in bonding strength with CA were greater for RMGIC with the IL. Thus, the feasibility of smart dental cements capable of electrically debonding-on-demand is indicated.

A 68-year-old man underwent partial colectomy and double-barrel colostomy for an obstructive colon cancer of the splenic flexure at another hospital 10 years before. He was referred to us with an examination of anemia pointed out in human dock. Lower gastrointestinal endoscopy revealed the tumor occupied the remnant descending colon. We performed remnant left hemicolectomy and diagnosed as triple colon cancers. Six months after the initial operation, he was admitted to us with the chief complaints of abdominal fulness and vomit. Abdominal CT and radiologic enteroclysis after decompression used the ileus tube revealed complete stenosis at the small intestine. We performed surgery with a suspicion of obstruction of the small intestine. The tumor, 5 cm in diameter, occupied the jejunum was detected, and partial resection of the jejunum was performed. Histologically, the tumor was diagnosed as solitary metastasis of jejunum.

A 68-year-old woman was referred to our hospital due to widespread purpura on her legs. A diagnosis of IgA vasculitis was made based on the findings of a skin biopsy. However, after being admitted to our hospital, abdominal pain and lower gastrointestinal hemorrhaging developed. The purpura disappeared gradually, whereas the abdominal pain migrated and persisted. Treatment with prednisolone was initiated, and the clinical course improved temporarily. However, her severe abdominal symptoms recurred while, in addition, the intestinal tract lesions migrated after the prednisolone dosage was tapered. Therefore, intravenous high-dose methylprednisolone was administered followed by oral steroids. The dose was thereafter carefully tapered, and the steroid dose reduction was successful with this treatment. We herein report the clinical course of the case along with a review of the relevant literature.

With improvement of bonding strength of recent dental cement, it is difficult nowadays to remove restorations without excessive force or vibration to tooth, occasionally resulting in damage of dentin, enamel, and dental root. Therefore, "smart" dental cement indicating strong bonding and easy debonding-on-demand simultaneously is required. In this research, resin-modified glass-ionomer-cement containing an ionic-liquid, tris(2-hydroxyethyl)methylammonium methylsulfate was produced, and the shear bonding strength before and after direct current application were evaluated. The prototype cement containing 15 to 20 mass% ionic-liquid indicated simultaneously no significant reduction of shear bonding strength from that of the original cement not containing ionic-liquid, and significant reduction of bonding strength to approximately 20% of that of the original cement after direct current application of more than 2 mmC/mm 2 . The prototype cement in this research demonstrated that the concept of smart dental cement electrically debonding-on-demand is feasible.

Aims: This study evaluated whether optical frequency domain imaging (OFDI) could identify various coronary calcifications and accurately measure calcification thickness in comparison with histopathology., Methods and Results: A total of 902 pathological cross-sections from 44 coronary artery specimens of human cadavers were examined to compare OFDI and histological images. Histological coronary calcification was classified into four different types: (i) superficial dense calcified plates, (ii) deep intimal calcification, (iii) scattered microcalcification, and (iv) calcified nodule. The thickness of calcification was measured when both the leading and trailing edges of calcification were visible on OFDI. Of the 902 histological cross-sections, 158 (18%) had calcification: 105 (66%) were classified as superficial dense calcified plates, 20 (13%) as deep intimal calcifications, 30 (19%) as scattered microcalcifications, and 3 (2%) as calcified nodules. Superficial dense calcified plates appeared as well-delineated heterogeneous signal-poor regions with sharp borders on OFDI. Deep intimal calcifications could not be identified on OFDI. Scattered microcalcification appeared as homogeneous low intensity areas with indiscriminant borders. Calcified nodule, a high-backscattering protruding mass with an irregular surface, also appeared as a low intensity area with a diffuse border. The ROC analysis identified calcium thicknesses <893 µm as cut points for the prediction of measurable calcification (72% sensitivity and 91% specificity, area under the curve = 0.893, P < 0.001)., Conclusion: Our study demonstrated the potential capability of OFDI to characterize various types of coronary calcifications, which may contribute to the understanding of the pathogenesis of coronary atherosclerosis., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Sporadic mast cell neoplasms and gastrointestinal stromal tumors (GISTs) often have various types of somatic gain-of-function mutations of the c-kit gene which encodes a receptor tyrosine kinase, KIT. Several types of germline gain-of-function mutations of the c-kit gene have been detected in families with multiple GISTs. All three types of model mice for the familial GISTs with germline c-kit gene mutations at exon 11, 13 or 17 show development of GIST, while they are different from each other in skin mast cell number. Skin mast cell number in the model mice with exon 17 mutation was unchanged compared to the corresponding wild-type mice. In the present study, we characterized various types of mast cells derived from the model mice with exon 17 mutation (KIT-Asp818Tyr) corresponding to human familial GIST case with human KIT-Asp820Tyr to clarify the role of the c-kit gene mutation in mast cells. Bone marrow-derived cultured mast cells (BMMCs) derived from wild-type mice, heterozygotes and homozygotes were used for the experiments. Immortalized BMMCs, designated as IMC-G4 cells, derived from BMMCs of a homozygote during long-term culture were also used. Ultrastructure, histamine contents, proliferation profiles and phosphorylation of various signaling molecules in those cells were examined. In IMC-G4 cells, presence of additional mutation(s) of the c-kit gene and effect of KIT inhibitors on both KIT autophosphorylation and cell proliferation were also analyzed. We demonstrated that KIT-Asp818Tyr did not affect ultrastructure and proliferation profiles but did histamine contents in BMMCs. IMC-G4 cells had an additional novel c-kit gene mutation of KIT-Tyr421Cys which is considered to induce neoplastic transformation of mouse mast cells and the mutation appeared to be resistant to a KIT inhibitor of imatinib but sensitive to another KIT inhibitor of nilotinib. IMC-G4 cells might be a useful mast cell line to investigate mast cell biology.

Chronic intussusception, defined as intussusception continuing over 14 days, is rare in children. We herein report a case of chronic ileocolic intussusception caused by the transmural infiltration of diffuse large B cell lymphoma in a 14-year-old boy. The patient had been suffering from anorexia and intermittent abdominal pain for 5 weeks, during which his body weight decreased by around 7 kg. Upon admission to our hospital, ultrasonography and enhanced computed tomography (CT) of the abdomen showed ileocolic intussusception. A retrospective examination of abdominal CT led us to suspect that the intussusception had initially appeared 5 weeks before admission, presumably coinciding with the beginning of the patient's abdominal symptoms. Since hydrostatic reduction was unsuccessful, laparotomy was performed, which showed unreducible ileocolic intussusception with a marked edematous ileum and mesentery. Ileocecal resection without lymph node dissection was carried out, and a histological examination of the resected specimen revealed the transmural infiltration of diffuse large B-cell lymphoma of the terminal ileum. The patient's postoperative course was uneventful, and adjuvant chemotherapy was administered. This case illustrates the diagnostic challenges of confirming 'chronic' intussusception in older children.

We report a case of a 49-year-old Japanese man, who was admitted to our hospital because of severe dyspnea. He was found to have severely low serum folate and megaloblastic anemia, which was at first suspected to cause his dyspnea. It was assumed that severely low serum folate might be related to his malnutrition, probably caused by habitual alcohol consumption. He died in several days because of acute respiratory distress syndrome. Autopsy revealed diffuse alveolar damage (DAD) in the lungs and systemic lymph node swelling by EBV-positive diffuse large B-cell lymphoma, in addition to megaloblastic anemia in the bone marrow. Together with histological hemophagocytosis and high level of serum iron and ferritin, DAD was considered to be caused by hypercytokinemia triggered by the presence of EBV-positive diffuse large B-cell lymphoma. On the other hand, pathological findings suggestive of habitual alcohol consumption were not apparent. We considered that low serum folate in this case was not by the low intake but by increased consumption of folate by rapid progression of the lymphoma.

The great majority of gastrointestinal stromal tumors (GISTs) have gain-of-function mutations of the c-kit gene, which encodes KIT receptor tyrosine kinase. Most of the mutations are located at exon 11, but some are at exon 9 or at other exons. Mutation types at exon 11 vary, while most mutations at exon 9 are a particular duplication of Ala502Tyr503 (KIT-Dup-Ala502Tyr503). Recently a duplication of Ser501Ala502 (KIT-Dup-Ser501Ala502) at exon 9 has been reported in two cases of pediatric mastocytosis and one case of adult mast cell leukemia. Although KIT-Dup-Ser501Ala502 had not been reported in GISTs, we found two GIST cases possessing the mutation in 45 GIST cases with exon 9 c-kit gene mutations, among a total of approximately 500 GIST cases examined. In this report, we briefly summarize clinicopathological findings of the two cases, and characterize the biology of the mutation. When autophosphorylation of KIT-Dup-Ser501Ala502 was examined by transient transfection of c-kit cDNA with Dup-Ser501Ala502 into CHO-K1 cells, KIT-Dup-Ser501Ala502 was ligand-independently activating. The inhibitory effect of selective tyrosine kinase inhibitors, imatinib and nilotinib, on KIT-Dup-Ser501Ala502 was examined and compared with that of KIT-Dup-Ala502Tyr503. Imatinib efficiently inhibited constitutive activation of KIT-Dup-Ser501Ala502 at a concentration of 0.1 μM, whereas it inhibited that of KIT-Dup-Ala502Tyr503 at a concentration of 10 μM. Constitutive activation of KIT-Dup-Ser502Ala503 was not inhibited by nilotinib even at a concentration of 10 μM but that of KIT-Dup-Ala501Tyr502 was almost completely inhibited at a concentration of 1 μM. The results suggest that imatinib and nilotinib could be more effective on GISTs with KIT-Dup-Ser501Ala502 than those with KIT-Dup-Ala502Tyr503. In fact, a patient with KIT-Dup-Ser501Ala502 showed long-term stable disease with administration of the usual dose of 400 mg imatinib. Although mutation sites of KIT-Dup-Ser501Ala502 and KIT-Dup-Ala502Tyr503 are closely located, imatinib- and nilotinib-sensitive KIT-Dup-Ser501Ala502 are distinguishable from KIT-Dup-Ala502Tyr503.

During upper endoscopic screening, a 71-year-old asymptomatic woman was found to have a small, yellowish, superficial elevated lesion in the upper third of her stomach, without any signs of atrophic mucosa. The patient underwent endoscopic follow-up once a year for approximately five years; however, changes in the tumor were barely detectable. Endoscopic mucosal resection was performed, and a histological examination confirmed the diagnosis of gastric adenocarcinoma with chief cell differentiation (GA-CCD). GA-CCD is rare; therefore, its clinicopathological features remain unknown. This case suggests that only barely detectable endoscopic changes may be observed in GA-CCD during long-term follow-up.

We found a novel type germline mutation at exon 11 of the c-kit gene, which results in a substitution of Tyr to Cys at codon 553 of the c-kit gene product (KIT-Tyr553Cys), in a 68-year-old female patient with multiple gastrointestinal stromal tumors (GISTs). In the present study, we carried out mutational analysis in her family members to determine the carriers and characterized the mutation by introducing the corresponding mutation (murine KIT-Tyr552Cys) into expression vector possessing murine c-kit cDNA. Mutational analysis of peripheral blood leukocytes of her family members revealed that a 44-year-old son had the same mutation, but at present he had neither apparent symptoms nor images of multiple GISTs. By transfection with the expression vector possessing the murine mutant c-kit cDNA, interleukin-3-dependent Ba/F3 murine lymphoid cells started growing autonomously without any growth factors, indicating that the mutation was considered to be of gain-of-function. Imatinib, a small molecule of tyrosine kinase inhibitor, effectively inhibited autophosphorylation of KIT-Tyr552Cys. Nilotinib, another small molecule of the KIT inhibitor, also effectively inhibited autophosphorylation of KIT-Tyr552Cys. In fact, proliferation of Ba/F3 cells expressing KIT-Tyr552Cys was effectively inhibited by both imatinib and nilotinib. These findings indicate that the novel type human KIT-Tyr553Cys mutation is the cause of the present familial and multiple GISTs, and that both imatinib and nilotinib might effectively inhibit the growth of GISTs developing in the patients of this family.

Sodium alginate oligosaccharides (NaAOs) consisting of a mixture of eight oligosaccharides have previously been reported to lower blood pressure. We investigated in this study the excretion of NaAOs into the urine or feces, and attempted to elucidate the mechanism for lowering blood pressure by using isolated mesenteric arteries from the rabbit. The recovery rate of P8, which is the main component of NaAOs, was 5.2% and 58.9% over 48 hours in the urine and feces, respectively. The mechanism for lowering blood pressure appeared to be NaAOs having calcium antagonist activity, especially voltage-operated calcium channels. Our results suggest that NaAOs are substantially excreted into the feces, although some of them may be absorbed internally, exerting antagonist activity towards the calcium channels, especially voltage-operated calcium channels.

Using the in situ measurements of the surface potential built across the evaporated liquid crystalline 4-n-pentyl-4'-cyanobiphenyl (5CB) films on metal electrodes with different work functions, we studied the cooperative molecular field effect (CMFE) that assists carrier injection from electrodes and the induced orientational reordering in evaporated liquid crystalline molecules on metals. The surface potential increased, and then became constant after the 5CB monomolecular layer was formed. It was shown that the CMFE accompanying orientational reordering accounts for the metal work function dependence of the surface potential. Finally, the orientational reordering is discussed in terms of the anchoring energy.

In order to prepare a series of N-acetylheparosan (NAH)-related oligosaccharides, bacterial NAH produced in Escherichia coli strain K5 was partially depolymerized with heparitinase I into a mixture of even-numbered NAH oligosaccharides, having an unsaturated uronic acid (DeltaUA) at the non-reducing end. A mixture of odd-numbered oligosaccharides was derived by removing this DeltaUA in the aforementioned mixture by a 'trimming' reaction using mercury(II) acetate. Each oligosaccharide mixture was subjected to gel-filtration chromatography to generate a series of size-uniform NAH oligosaccharides of satisfactory purity (assessed by analytical anion-exchange HPLC), and their structures were identified by MALDITOF-MS, ESIMS, and 1H NMR analysis. As a result, a microscale preparation of a series of both even- and odd-numbered NAH oligosaccharides was achieved for the first time. The developed procedure is simple and systematic, and thus, should be valuable for providing not only research tools for heparin/heparan sulfate-specific enzymes and their binding proteins, but also precursor substrates with medical applications.

Diabetic neuropathy is a very common complication of diabetes mellitus, and animal studies have contributed tremendously to its understanding. The aim of this study was to estimate the neuropathic alterations in the Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human type 2 diabetes mellitus. For this purpose, four groups of animals were used: untreated OLETF rats, sucrose-fed for 2 months OLETF rats, untreated Long-Evans Tokushima Otsuka (LETO) nondiabetic rats as genetic controls of OLETF, and sucrose-fed LETO rats. All were examined at baseline, at the end of the sucrose treatment, and during a washout period. The following parameters were evaluated: motor nerve conduction velocity (MNCV), sensitivity to noxious thermal and mechanical stimuli using the tail-flick (TF) and tail-pressure (TP) tests, and blood glucose (BG) and HbA1c levels. Our results showed that BG and HbA1c were significantly higher in OLETF rats when compared with those in control LETO rats. Sucrose caused remarkable increase of BG and HbA1c in the OLETF rats, but not in the sucrose-fed LETO rats. MNCV and thermal nociception significantly decreased in OLETF rats in their 10th month, while the values of the TP test did not differ compared with those from LETO rats. Sucrose administration significantly decreased the MNCV, and increased the pain threshold evaluated by the TF and TP tests, compared with those in the control OLETF rats. The studied parameters were not significantly altered in sucrose-fed LETO rats. In conclusion, our findings show that signs of diabetic neuropathy appear late in the individual development of the OLETF rats, and MNCV and thermal nociception are selectively affected in this strain. Sucrose deteriorated the diabetic state, decreased MNCV, and caused thermal and mechanical hypoalgesia., (2006 Prous Science.)

1. Stroke-prone spontaneously hypertensive rats (SHRSP) are a strain of rat that exhibit severely high blood pressure and stroke attacks at an early age, but their heart function in vitro has seldom been studied in detail. Although the activity of the sympathetic nervous system is known to increase after myocardial ischaemia, there is little information about the cardiac release of noradrenaline (NA) associated with heart function after ischaemia in SHRSP. The aim of the present study was to examine heart function and cardiac NA release after ischaemia in SHRSP. 2. Isolated hearts of 4- and 8-month-old SHRSP and age-matched Wistar-Kyoto (WKY) rats were perfused in a working heart preparation and were subjected to 30 min ischaemia followed by 30 min reperfusion. Heart function and coronary flow were monitored throughout the experiment. Coronary effluent was collected for determination of NA using high-performance liquid chromatography coupled with electrochemical detection. 3. Under baseline conditions, cardiac output of 4-month-old SHRSP was slightly but significantly decreased compared with that of WKY rats (P < 0.05), although coronary flow was maintained normally at this age. Eight-month-old SHRSP showed a further impairment of systolic heart function, with lower coronary flow and higher coronary vascular resistance under baseline conditions. Elevated left ventricular end-diastolic pressure was evident in SHRSP at both ages before ischaemia. Heart function was severely damaged after 30 min global ischaemia in SHRSP from both age groups. Stroke-prone spontaneously hypertensive rats also showed lower coronary flow and higher coronary vascular resistance during reperfusion. 4. Coronary NA was not detectable in WKY rats or SHRSP at 4 months of age under baseline conditions. In 8-month-old SHRSP, pre-ischaemic NA release was significantly higher than that in age-matched WKY rat controls. The concentration of NA in the coronary effluent of SHRSP during reperfusion was also significantly higher than that of WKY rats at both ages. 5. These data demonstrate that SHRSP have early impairment of both systolic and diastolic heart function compared with WKY rats. Severe damage of heart function and coronary flow after ischaemia in SHRSP was accompanied with an increased release of NA, which may play a harmful role in heart function impairment in SHRSP after ischaemia.

Background: Non-adrenergic, non-cholinergic (NANC) relaxation evoked by electrical field stimulation (EFS) has been observed in the urethra, with nitric oxide (NO) considered the agent most probably mediating this effect. However, Burnstock's purinergic hypothesis suggests that ATP and related purine compounds are neurotransmitters in NANC relaxation, although the physiological and pharmacological effects of ATP and related purine compounds in the urethra have been little studied., Methods: The effects of ATP and related purine compounds, NG-nitro-L-arginine (NOARG; an inhibitor of nitric oxide synthesis from L-arginine), calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal polypeptide (VIP) on relaxation and smooth muscle tension induced by electrical field stimulation (EFS) were studied in isolated male rabbit circular urethral smooth muscle (functional study). In addition, the outflow of ATP elicited by EFS was measured using the luciferase technique (superfusion study). All experiments were performed in the presence of guanethidine (3 x 10(-3) mol/L) and atropine (10(-6) mol/L)., Results: In preparations contracted with U46619, a prostaglandin peroxidase inhibitor, ATP had almost no effect on EFS-induced relaxation; however, suramin, a non-selective P2Y-purinoceptor antagonist, and NOARG each markedly attenuated this relaxation in a concentration-dependent manner. ATP and related purine compounds (adenosine, AMP and ADP) each reduced U46619-induced tonic contraction in a concentration-dependent manner. The potencies of the relaxant effects of ATP and these purine compounds were almost the same. In preparations contracted with U46619, CGRP and substance P had no effect on tonic contraction, but VIP reduced tonic contraction in a concentration-dependent manner. In the superfusion study, the outflow of ATP into the superfusate was markedly increased by EFS. When NOARG or prazosin was added to the superfusate, the increase in outflow of ATP was unchanged, but when suramin was added to the superfusate, no increase in outflow of ATP was observed., Conclusions: These findings suggest that P2Y-purinoceptors exist in the male rabbit urethra, and that ATP and related purine compounds may play a role in non-adrenergic, non-cholinergic neurotransmission. Consequently, the pathways mediating urethral relaxation by ATP, NO and VIP may be different.

Novel dioxane nucleosides having two bases, 2(R)-(5-fluorouracil-1-yl)-5(R)-hydroxymethyl-3(R)-(uracil-1-yl)-1,4-dioxane (7a) and 2(S)-(5-fluorouracil-1-yl)-5(R)-hydroxymethyl-3(R)-(uracil-1-yl)-1,4-dioxane (7b) were synthesized from uridine to develop a new category of nucleoside for therapeutic use. Some derivative of precursors of the nucleoside were also synthesized and several compounds synthesized were tested antitumor activity using human gastric cancer cell lines in culture.

1. The effects of chronic NG-nitro-L-arginine (LNA) feeding on the endothelial function in isolated coronary arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto (WKY) rats were studied. 2. A diet containing LNA (0.02%) was given to male SHRSP and WKY at 6 weeks of age and the coronary arteries were dissected on the 10th day of feeding. 3. In the SHRSP and WKY fed the LNA-free diet, acetylcholine (ACh) relaxed the precontracted ring segments of the coronary artery with intact endothelium in a dose-dependent manner. The reactivity was stronger in the WKY than in the SHRSP. However, the ACh-induced relaxation after the LNA-feeding was significantly stronger in the coronary arteries from the WKY than in those from the SHRSP. 4. The relaxation induced by the calcitonin gene-related peptide (CGRP) was endothelium-dependent and endothelium-independent. The degree of the response in the rats fed the LNA-containing diet was not significantly different from that in the rats fed the LNA-free diet. 5. The vasodilator response induced by sodium nitroprusside (SNP) was dose-dependent and similar in the rats fed the LNA containing diet and the LNA-free diet. 6. These findings indicate that chronic LNA feeding markedly impaired the endothelial nitric oxide formation in the coronary artery from young SHRSP.

Background: The objective of this study is to analyze the adrenoceptor and calcitonin-gene related peptide receptor in the isolated striated urethral sphincter from a male rabbit., Methods: The striated urethral sphincter preparations were suspended in 2ml tissue chamber filled with Krebs Ringer solution, and the changes of isometric twitch contraction induced by electrical field stimulation (EFS-contraction) were recorded in the presence of 3-isobutyl-1-methyl-xanthine (IBMX, 10(-5) M)., Results: The EFS-contraction was almost completely attenuated by tetrodotoxin (TTX, 10(7) M), vecronium (10(-4) M) and suxamethonium (10(-4) M). Norepinephrine (NE, 10(-8) M-10(-4) M) did not affect the EFS-contraction, but increased the tonic contraction in a dose-dependent manner. The tonic contractions induced by NE was significantly blocked by phentolamine (10(-6) M). Clonidine (10(-7) M), yohimbin (10(-7) M) and propranolol (10(-9) M-10(-6) M) did not affect the EFS-contraction. Isoproterenol (10(-9) M-10(-6) M) did not reduce the carbachol (10(-5) M) induced tonic contraction. Calcitonin-gene related paptide (CGRP, 10(-7) M-3 x 10(-6) M) did not affect the EFS-contraction and did not increase the tonic contraction., Conclusion: These results suggested that alpha 1-adrenoceptors of the striated urethral sphincter play a role to modulate the resting tension level, but alpha 2-adrenoceptors, beta-adrenoceptors and CGRP receptors play no role in this regard.

A case of traumatic bilateral medial longitudinal fasciculus (MLF) syndrome is reported. An 18-year-old man who had been struck on the occipital region in a traffic accident was admitted to our center. On admission, the consciousness evaluated by the Japan Coma Scale was 30. Skull X-ray film revealed a linear skull fracture of the left occipital bone. CT scan showed subdural hematoma in the right frontotemporal region, contusion of bilateral frontal lobes and the left cerebellar hemisphere, subarachnoid hemorrhage, and pneumoce phalus. Two weeks after the injury, his consciousness improved and he was diagnosed as having bilateral MLF syndrome. Barbiturate, dehydration and steroid therapy were added to for intracranial hemorrhage. One month later, MLF syndrome improved and he was discharged without any neurological deficit.

The relaxant effects of calcitonin gene-related peptide (CGRP) and other drugs were compared in basilar artery rings obtained from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). In addition, the relaxant effect of CGRP on basilar arteries from spontaneously hypertensive rats (SHR) was examined. Relaxation induced by CGRP was independent of the presence of endothelium, and it was markedly increased in SHRSP when compared to WKY. In contrast, acetylcholine-induced relaxation was endothelium-dependent and did not differ between the two groups. Enhanced CGRP-induced relaxation was also found in SHR when compared to WKY. However, the relaxant response was greater in SHRSP than in SHR. No significant differences were found in the relaxation induced by isoproterenol, forskolin, dibutyryl cyclic AMP, and 3-isobutyl-1-methylxanthine in endothelium-rubbed arteries of WKY and SHRSP. These results suggest that CGRP produces endothelium-independent relaxation in the rat basilar artery, and that the enhanced CGRP-induced relaxation found in SHRSP may not be associated with alterations of vasodilation mediated by cyclic AMP.

Phenylephrine-induced oscillatory contractions in rabbit mesenteric arteries were investigated in vitro. Adrenergic, cholinergic, or histamine antagonists as well as cyclooxygenase and lipoxygenase inhibitors had no effect on this phenylephrine-induced oscillation. The removal of extracellular calcium ions or treatment with a calcium antagonist reduced the amplitude and frequency of the oscillation. Removal of the endothelium or treatment with inhibitors of the synthesis or the target enzyme of endothelium-derived relaxing factor (EDRF) also reduced the amplitude and frequency of the oscillation. In a perfusion bioassay, the perfusate from an endothelium-intact arterial segment induced oscillation of an endothelium-denuded arterial ring recipient. These results suggest that phenylephrine-induced oscillation is mediated by an endothelium-derived factor such as EDRF and depends on the influx of extracellular calcium ions.

The fourth heart sound was clearly recorded by using the signal averaging method. Furthermore, the simultaneous recording of the Doppler signal with the fourth heart sound was performed. Thus, it was demonstrated that the Doppler signal started after the P wave and followed by the fourth heart sound. In 2 cases, the effect of the double Master's test and taking a bath was studied on the computer averaged phonocardiogram. After the exercise, the amplitude of the fourth heart sound was increased, whereas after taking a bath it was almost unchanged. The above results show that the simultaneous recordings of a computer averaged phonocardiogram and Doppler signal that is associated with cardiac activity can greatly facilitate the interpretation of small vibrations such as the fourth heart sound.

A possible mechanism of infertility by Cd was investigated from the standpoint of influence of Cd on the contractile responses of isolated seminal vesicle from guinea pigs to K, acetylcholine, noradrenaline, Ba and Ca by using the Magnus method. Cd inhibited the contractile responses to the contractile agents tested in a dose-dependent manner. Cd showed the preferential inhibition against the contractile responses to K and Ca. The inhibitory effect of Cd on the contractile responses to noradrenaline and acetylcholine was hardly removed. The effect of Cd was inhibited by the thiol compounds, glutathione and thiola. The active mechanism of Cd was discussed in relation to Ca mobilization.