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Biomedical subjects

Y Endo

Publications and source records attributed to Y Endo.

At least 19 recordsLinked to original sources

Alveolar cleft osteoplasty using tissue-engineered osteogenic material.

The use of tissue-engineered osteogenic material comprising platelet-rich plasma and autologous mesenchymal stem cells isolated, expanded and induced to osteogenic potential in bone augmentation procedures as a replacement for autologous bone grafts, offers predictable results with minimal donor-site morbidity. This material was applied for an alveolar cleft osteoplasty of a 9-year-old female patient. Serial computed tomograms showed the regenerated bone extending from the cleft walls after 3 months and bridging the cleft after 6 months, with 79.1% of the grafted region after 9 months at the time when the canine and lateral incisor in the affected side erupted in the reconstructed alveolar ridge.

Alveolar Process↗

Ubiquitous mitochondrial creatine kinase downregulated in oral squamous cell carcinoma.

In this study, we performed two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionisation time of fly mass spectrometry to identify the protein(s) associated with the development of oral squamous cell carcinomas (OSCCs) by comparing patterns of OSCC-derived cell lines with normal oral keratinocytes (NOKs), and found that downregulation of ubiquitous mitochondrial creatine kinase (CKMT1) could be a good candidate. Decreased levels of CKMT1 mRNA and protein were detected in all OSCC-derived cell lines examined (n=9) when compared to those in primary normal oral keratinocytes. Although no sequence variation in the coding region of the CKMT1 gene with the exception of a nonsense mutation in exon 8 was identified in these cell lines, we found a frequent hypermethylation in the CpG island region. CKMT1 expression was restored by experimental demethylation. In addition, when we transfected CKMT1 into the cell lines, they showed an apoptotic phenotype but no invasiveness. In clinical samples, high frequencies of CKMT1 downregulation were detected by immunohistochemistry (19 of 52 (37%)) and quantitative real-time RT-PCR (21 of 50 (42%)). Furthermore, the CKMT1 expression status was significantly correlated with tumour differentiation (P<0.0001). These results suggest that the CKMT1 gene is frequently inactivated during oral carcinogenesis and that an epigenetic mechanism may regulate loss of expression, which may lead to block apoptosis.

Apoptosis↗

Overexpression of stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis.

Stathmin is an intracellular phosphoprotein that is overexpressed in a number of human malignancies. Our previous study using proteomic profiling showed that significant upregulation of stathmin occurs in oral squamous-cell carcinoma (OSCC)-derived cell lines. In the current study, to determine the potential involvement of stathmin in OSCC, we evaluated the state of stathmin protein and mRNA expression in OSCC-derived cell lines and human primary OSCCs. A significant increase in stathmin expression was observed in all OSCC-derived cell lines examined compared to human normal oral keratinocytes. In immunohistochemistry, 65% of the OSCCs were positive for stathmin, and no immunoreaction was observed in corresponding normal tissues. Real-time quantitative reverse transcriptase-polymerase chain reaction data were consistent with the protein expression status. Moreover, stathmin expression status was correlated with the TNM stage grading. Furthermore, we found a statistical correlation between the protein expression status and disease-free survival (P=0.029). These results suggest that expression of stathmin could contribute to cancer progression/prognosis, and that stathmin may have potential as a biomarker and a therapeutic target for OSCC.

Aged↗

Primary erythrocytosis in a Japanese black calf: a case report.

An 8-month-old Japanese Black heifer with severe erythropoietic symptoms was subjected to clinical, histological and cytological examinations. During the 1 month clinical observation period, severe increases in RBC count, packed cell volume and haemoglobin concentration were observed. The plasma erythropoietin (Epo) concentration of the heifer (20.7 mIU/ml) was similar to that observed in normal control heifers. Blood gas examinations of the arterial and venous blood revealed low levels of partial pressure O(2) (PaO(2)), partial pressure CO(2) (PaCO(2)) and O(2) saturation (SaO(2)), while the blood pH was within the normal range. Gross lesions could not be detected. However, microscopic observation revealed severe proliferation of erythroblasts in the bone marrow and in the spleen without evidence of neoplastic changes. Based on these clinical and pathological examinations, we diagnosed the heifer as being the first case of primary erythrocytosis in Japanese Black cattle.

Animals↗

Carbohydrate-binding specificities of mouse ficolin A, a splicing variant of ficolin A and ficolin B and their complex formation with MASP-2 and sMAP.

Ficolins are a group of proteins mainly consisting of collagen-like and fibrinogen-like domains and are thought to play a role in innate immunity via their carbohydrate-binding activities. Two types of ficolins have been identified in mice, ficolin A, and ficolin B. However, their structure and function are not fully understood. In this study, we isolated the cDNA encoding a novel variant of ficolin A having a shorter collagen-like domain and a longer gap sequence, which was generated from the ficolin A gene by alternative splicing. We delineated the structure and function of mouse ficolins, including this splicing variant, by preparing the respective recombinants. Recombinant ficolin A, its splicing variant, and ficolin B showed multimeric structures and revealed binding to both N-acetylglucosamine and N-acetylgalactosamine. Interestingly, ficolin B specifically recognized sialic acid residues. Ficolin A and its variant, but not ficolin B, bound to mannose-binding lectin (MBL)-associated serine protease-2 (Masp-2) and small MBL-associated protein (smap), and the resulting complexes showed a potent complement activating capacity. In addition, smap competed with Masp-2 in association with ficolin A and its variant, and inhibited the complement activation by the ficolin A (or ficolin A variant)/MASP-2 complex, indicating its regulatory role in the lectin pathway. These results suggest that ficolin A and its variant function as recognition molecules of the lectin pathway, and ficolin B plays a distinct role through its unique carbohydrate-binding specificity.

Adaptor Proteins, Signal Transducing↗

Feeding with powdered diet after weaning affects sex difference in acetylcholine release in the hippocampus in rats.

We have reported in the past that female rats fed a powdered diet showed better spatial learning and memory functions than female rats a fed pelleted diet. In the present study, we examined the effects of feeding with powdered diet on acetylcholine release in the hippocampus in both sexes of rats. After weaning (3 weeks of age), rats were fed either standard pelleted diet or powdered diet, and after maturation (9-12 weeks of age), they were used in an in vivo microdialysis study, in which no eserine (a cholinesterase inhibitor) was added to the perfusate. The dialysate was collected from the dorsal hippocampus at 20-min intervals under freely moving conditions for more than 24 h. Acetylcholine in the dialysate was measured by high performance liquid chromatography. As we reported previously, the acetylcholine release showed a clear daily rhythm in both sexes, and males showed significantly greater acetylcholine release in the hippocampus than females in rats fed pelleted diet. Conversely, in rats fed powdered diet, no sex difference in the acetylcholine release was observed, since feeding with powdered diet significantly increased the acetylcholine release only in females. To further examine the number of cholinergic neurons in the medial septum and horizontal limb of the diagonal band of Broca, immunocytochemistry for choline acetyltransferase was performed in both sexes of rats fed either standard pelleted diet or powdered diet. However, neither sex nor feeding conditions affect the number of choline acetyltransferase immunoreactive cells in the areas. These results suggest that powdered diet after weaning enhances spontaneous acetylcholine release in the hippocampus in female rats without changes in the number of cholinergic neurons in the areas. It is possible that this effect of feeding contributes to improve the performance in spatial learning and memory functions in female rats fed powdered diet.

Acetylcholine↗

Aberrant expression of RAB1A in human tongue cancer.

This study was designed to identify specific gene expression changes in tongue squamous cell carcinomas (TSCCs) compared with normal tissues using in-house cDNA microarray that comprised of 2304 full-length cDNAs from a cDNA library prepared from normal oral tissues, primary oral cancers, and oral cancer cell lines. The genes identified by our microarray system were further analysed at the mRNA or protein expression level in a series of clinical samples by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis and imuunohositochemistry. The microarray analysis identified a total of 16 genes that were significantly upregulated in common among four TSCC specimens. Consistent with the results of the microarray, increased mRNA levels of selected genes with known molecular functions were found in the four TSCCs. Among genes identified, Rab1a, a member of the Ras oncogene family, was further analysed for its protein expression in 54 TSCCs and 13 premalignant lesions. We found a high prevalence of Rab1A-overexpression not only in TSCCs (98%) but also in premalignant lesions (93%). Thus, our results suggest that rapid characterisation of the target gene(s) for TSCCs can be accomplished using our in-house cDNA microarray analysis combined with the qRT-PCR and immunohistochemistry, and that the Rab1A is a potential biomarker of tongue carcinogenesis.

Aged↗

Inhibition of inflammatory and bone-resorption-inhibitory effects of alendronate by etidronate.

Among the bisphosphonates (BPs), the aminobisphosphonates (aminoBPs) have much stronger bone-resorption-inhibitory activities (BRIAs) than nonaminobisphosphonates (nonaminoBPs). However, aminoBPs have inflammatory effects. We previously reported that in mice: (i) all aminoBPs tested (10-40 micromol/kg) induced various inflammatory reactions (including induction of histidine decarboxylase), whereas clodronate (a non-aminoBP) (10-160 micromol/kg) inhibited these reactions; and (ii) a clear sclerotic line (tentatively called the BP line) was detectable in the tibia by radiography a few weeks after a single injection of either alendronate (a typical aminoBP) (1.6 micromol/kg) or clodronate (160 micromol/kg), and this BP-line formation (a marker for the BRIAs of BPs) was not reduced in mice given both alendronate and clodronate. In this study, using this murine model, we compared clodronate, etidronate (another typical non-aminoBP), alendronate, etidronate + alendronate, and clodronate + alendronate in terms of their inflammatory effects and/or BP-line formation. For BP-line formation, 480 micromol/kg etidronate was needed (single injection). At 160 micromol/kg, etidronate inhibited the histidine decarboxylase induction, but not the other inflammatory reactions induced by alendronate. However, etidronate (unlike clodronate) also inhibited alendronate-induced BP-line formation (even at 40 micromol/kg). Etidronate (160 micromol/kg) also inhibited the physicochemical changes in the tibia induced by six, weekly injections of alendronate. Therefore, depending on the dose, etidronate can inhibit alendronate's inflammatory actions and its BRIA. These results, together with those reported previously, suggest that a strategy utilizing clodronate (but not etidronate) plus an aminoBP might prevent or reduce the inflammatory side effects induced by aminoBPs while preserving their powerful BRIAs. We discuss the mechanisms underlying the antagonism between aminoBPs and non-aminoBPs.

Alendronate↗

Primary care in the treatment of functional gastrointestinal symptoms in Japan: prescription preferences and impression of results.

BACKGROUND: Functional gastrointestinal (GI) disorders are common in primary care. However, proper pharmacological approaches have not yet been established. The reason for a lack of proper approaches may be attributable to the lack in clarity of their pathogenesis and pathophysiology. Meta-analysis of pharmacological approaches to functional GI disorders failed to identify the solid cluster of patients' symptoms. AIM: The aim of this study is to assess the perspective of primary care doctors concerning prescriptions for functional GI symptoms, evaluate the efficacy of the drugs prescribed, and the need for medication for these symptoms. METHOD: Questionnaires were sent to primary care doctors, and a total of 149 responses were obtained. Efficacy of each medication was evaluated by the number of doctors favouring the category, and the respective impressions of prescriptions given. RESULTS: Symptoms of heartburn were well controlled by anti-secretory drugs (H2RAs and PPIs), while appetite loss and abdominal gurgling were not controlled by any medications. CONCLUSIONS: This survey reveals differences in need for various prescription drugs in functional GI symptoms.

Abdominal Pain↗

Atrophy rate in medial temporal lobe during progression of Alzheimer disease.

OBJECTIVE: To establish the progression of brain atrophy rates in patients with a known date of onset of Alzheimer disease (AD). METHODS: Each of 18 subjects had two high-resolution T1-weighted three-dimensional MRI examinations. The two MRIs were coregistered and the annual rate of brain tissue atrophy was derived both for the entire brain and regionally for the left and right medial temporal lobe (MTL). Time since onset (TSO) of AD, defined as the interval between the date of onset and the midpoint of MRI dates, ranged from -2.9 to 4.2 years. RESULTS: In patients with AD, TSO was a correlate of the atrophy rate for both the left MTL (R2 = 0.58, p = 0.001) and right MTL (R2 = 0.30, p = 0.03). When serial measurements were applied to a control group of 21 cognitively normal elderly subjects, MTL atrophy rate classified the group membership (AD vs normal cognition) with an accuracy of 92.3%. CONCLUSION: Increased annual atrophy rate in the medial temporal lobe is a potential diagnostic marker of the progression of Alzheimer disease.

Aged↗

Bottle choice tests for oxidized oil in rats.

Bottle choice tests in rats are useful for the study of fat appetite. However, little is known about the feeding behavior of rats toward oxidized oil. In this study, 24-h two-bottle choice tests were performed in male Sprague-Dawley (SD) rats for 5 days. When rats were given a choice between thermally oxidized oil and fresh oil, they ingested more fresh oil. A choice test between vapor-added fresh oil and fresh oil showed that rancid flavor is involved in the avoidance of oxidized oil. Results with deodorized oxidized oil indicated that a nonvolatile product also influenced choice. In conclusion, rats could distinguish oxidized oil from fresh oil and preferred fresh oil.

Adult↗

Platelet responses and anaphylaxis-like shock induced in mice by intravenous injection of whole cells of oral streptococci.

Intravenous injection of lyophilized whole cells of various oral streptococcal strains into muramyldipeptide (MDP)-primed C3H/HeN mice induces rapid anaphylactoid shock. Here we examined the mechanism underlying this shock. In non-primed mice, Streptococcus intermedius K-213K (SiK213) and Streptococcus constellatus T21 (ScT21) produced little or no sign of shock. In MDP-primed mice, SiK213 caused lethal shock, while ScT21 only had a weak effect. SiK213 induced decreases in blood platelets and 5-hydroxytryptamine (5HT) preceding the shock, while the effects of ScT21 were weak. The SiK213-induced 5HT decrease and shock were reduced by a complement-C5 inhibitor. These results suggest that (i). streptococcal bacterial cells can induce rapid platelet responses, (ii). complement-dependent degradation of platelets may be involved in streptococcus-induced shock, (iii). the streptococcus-induced platelet degradation or degranulation may occur largely in the systemic circulation, and (iv). platelets may play a role not only in infectious diseases caused by gram-negative bacteria, but also in diseases caused by gram-positive bacteria.

Acetylmuramyl-Alanyl-Isoglutamine↗

Efficacy of argon plasma coagulation in nonvariceal upper gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: Various methods of endoscopic hemostasis have been described. However, few reports have investigated the efficacy of argon plasma coagulation (APC) in the treatment of upper gastrointestinal bleeding. The aim of this study was to evaluate the efficacy of APC in various types of upper gastrointestinal bleeding. PATIENTS AND METHODS: The present study was designed as a prospective and observational study. A total of 254 consecutive patients with upper gastrointestinal bleeding (excluding variceal bleeding) were primarily treated using APC. If it was difficult to achieve complete hemostasis with APC alone, injection of a hypertonic saline-epinephrine solution and clipping were carried out. The initial hemostasis rate, rate of recurrent bleeding after APC, permanent hemostasis rate, and mean procedure time were evaluated. RESULTS: Initial hemostasis with APC alone was achieved in 193 of the 254 patients (75.9 %). With the assistance of other methods as well, initial hemostasis was achieved in 253 patients (99.6 %). Among the 193 patients treated with APC alone, recurrent bleeding was observed in 11 cases (11 of 193, 5.7 %). With one exception, these cases of recurrent bleeding were controlled with APC alone again; permanent hemostasis was thus ultimately achieved with APC alone in 192 of the 254 patients (75.5 %). The mean procedure time was 8 min. No complications (such as perforation) were observed with the APC treatment. CONCLUSIONS: These data indicate that APC is a safe, quick, and effective method of treating various types of nonvariceal upper gastrointestinal bleeding and that it can be a powerful tool for endoscopic hemostasis.

Adult↗

Identification of the novel canine CYP1A2 1117 C > T SNP causing protein deletion.

The pharmacokinetics of YM-64227 (4-cyclohexyl-1-ethyl-7-methylpyrido[2,3-d]-pyrimidine-2-(1H)-one), a novel and selective phosphodiesterase type 4 inhibitor, was characterized in beagle dogs. Based on the plasma parent drug to major hydroxylated metabolite ratio, 21 dogs were phenotyped as 16 extensive metabolizers (EM) and five poor metabolizers (PM). Nucleotide sequences of CYPs 1A2, 2B11, 2C21, 2D15, 2E1 and 3A12 were investigated in the EM and PM dogs. A CYP1A2 1117 C>T single nucleotide polymorphism was found, which resulted in an amino acid change from an Arg codon to a stop codon at position 373. All dogs phenotyped as PM were T/T homozygous, whereas EMs were C/C homozygous and C/T heterozygous. In Western blotting of liver microsomes, CYP1A protein expression was detected in the C/C and C/T types, but not in the T/T type. Of 65 dogs genotyped using genome DNA, the frequencies of the C and T alleles were 0.61 and 0.39, respectively, suggesting approximately 15% of the dogs would not express the CYP1A2 protein. The findings provide a coherent explanation for the inter-individual variability in the pharmacokinetics of CYP1A2 substrate drugs in dogs.

Alleles↗

Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome.

BACKGROUND AND AIMS: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. METHODS: Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of alphahCRH (10 micro g/kg). RESULTS: ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of alphahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. alphahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by alphahCRH. CONCLUSION: Peripheral administration of alphahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.

Abdominal Pain↗

Effects of weekly administrations of alendronate+clodronate on young mouse tibia: localized action at the proximal growth plate.

Alendronate (A), a typical aminobisphosphonate (aminoBP), has a strong bone-resorption-inhibitory activity (BRIA). However, like other aminoBPs it has inflammatory side effects. In contrast, the BRIA of clodronate (C), a non-aminoBP, is much weaker, and in animal experiments it suppresses aminoBP-induced inflammatory reactions. In the present study, we examined the effects of weekly administrations of A (1.6 micro mol/kg) + C (160 micro mol/kg) on the tibias in young mice and compared them to those induced by A or C alone. Radiophotography showed that A increased bone density at a selective site in the tibia. Indeed, one week after the final injection of A (given alone), clear sclerotic lines (tentatively called BP-lines) were visible at sites corresponding to the location of the growth plate at the time of the each injection. C also produced BP-lines, although they were weaker than those produced by A. Combined administration of A and C produced similar BP-lines as seen in mice given A alone. These results together with other physicochemical effects of A on the tibia suggest that (1) each injection of A and C inhibits bone resorption selectively and transiently at the tibial growth plate in young mice, although minor effects on other sites cannot be excluded, and (2) the combination of A and C keeps still a strong BRIA. Our findings may suggest a strategy for the prevention or reduction of some inflammatory side effects of A or other aminoBPs.

Alendronate↗