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    Purpose: We investigated the significance of CD24 and CD44 expression for predicting responses to chemotherapy and prognosis in primary breast cancer patients. Patients and Methods: Diagnosis of breast cancer was confirmed by core needle biopsy, and immunohistochemical studies were performed. Preoperatively, patients received anthracyclinecontaining chemotherapy. Expression of CD44 and CD24 was assessed immunohistochemically and the relationship with chemotherapy response and with prognosis was analyzed. Results : Between 2001 and 2004, 139 women were enrolled in this study. In the correlation analysis, CD24 expression was negatively associated with pathological response to chemotherapy (p=0.0003). A machine learning technique with an alternating decision tree (ADTree) showed that four logical rules are involved in predicting the response depending on the combination of CD24, HER2, tumor stage, CD44, progesterone receptor, and patient age. In the survival analysis, patients having CD44 (++) showed a significantly favorable prognosis as compared with others (p=0.0002). A multivariate analysis showed that CD44 expression had an independent prognostic value (p<0.001). Conclusion : We found a significant correlation between CD44 expression and prognosis and between CD24 expression and response to chemotherapy. CD24 and CD44 expressions would be useful predictive markers, although further studies are needed.departmental bulletin pape

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    Volatile sulfur compounds (VSCs), which are major sources of oral malodor, are produced by putrefactive activities of bacteria. Saliva provides easily degradable protein substrates, and most proteins are glycosylated. We hypothesized that oral malodor would be associated with enhanced proteolysis or deglycosylation in saliva. The purpose of this study was to evaluate properties of glycoproteins in saliva and assess their association with VSC levels. Subjects were 88 patients who visited “the Fresh Breath Clinic”, Dental Hospital, Tokyo Medical and Dental University. They were classified into malodor (n = 67) and non-malodor (n = 21) groups. After collecting saliva, the amounts of the total proteins and carbohydrate were determined. Molecular size distributions of salivary proteins/glycoproteins were analyzed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The amount of the total salivary proteins was significantly higher in the malodor group. Major proteins/glycoproteins observed in SDS-PAGE analyses showed similar distributions between the two groups. In the malodor group, the salivary protein concentrations were positively correlated with the CH3SH levels (p < 0.05), and the carbohydrate contents were negatively correlated with the H2S levels (p < 0.05). These results indicated the possibility that salivary proteins/glycoproteins might be related to the malodor generation.departmental bulletin pape

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    oai:tmdu.repo.nii.ac.jp:00000100Background: To determine the prevalence andclinical features of strabismus in patients withpathologic myopia.Methods: Medical records of a total of 636 highlymyopic patients were retrospectively reviewed.Pathologic myopia was defined as sphericalequivalent (SE) of at least -8D, or axial length>26.5 mm in patients older than 9 years, <-4D inthose younger than 5 years, <-6D in those agedfrom 6 to 8 years. Myopic refractive degree, axiallength measurements, best-corrected visual acuityand eye position were then analyzed.Results: Among 636 patients with pathologicmyopia, 520 (81.8%) had orthophoria, 85 (13.4%)had exotropia and 31 (4.9%) had esotropia at neardistance. At long distance, 499 (86.5%) hadorthophoria, 51 (8.8%) had exotropia and 27(4.7%) had esotropia. Vertical heterotropia wasseen in 103 patients (16.2%). The mean axiallength was significantly longer and the mean agewas higher in esotropia than orthophoria and inpatients with vertical heterotropia than withoutvertical heterotropia. There were 16 patients withmyopic strabismus fixus or acquired progressiveesotropia.Conclusions: This study confirmed the relativelyhigh prevalence of horizontal and verticalstrabismus in patients with pathologic myopia.departmental bulletin pape

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    Background: Some kinds of incisions have been reportedin skin- or nipple-sparing mastectomy, butfew reports have described the advantages anddisadvantages of each incision. This study wasconducted to compare the lateral horizontal incisionwith the lateral vertical incision in bothmastectomies, in terms of hypertrophic scarring,breast envelope necrosis, nipple-areola necrosis.Material and Methods: We performed a retrospectiveanalysis of patients who underwent skin- ornipple-sparing mastectomy using lateral horizontalor lateral vertical incisions with immediate breastreconstruction. All data were obtained retrospectivelyfrom databases, operation records and postoperativepictures. We compared the frequency ofhypertrophic scarring and breast envelope necrosisbetween lateral horizontal and lateral verticalincision groups by using Pearson's chi-square test.For nipple-sparing mastectomy, we also investigatednipple-areola necrosis.Results and Conclusions: One hundred fiftycases were analyzed and identified as 89 lateralhorizontal incision cases and 61 lateral verticalincision cases. Mastectomy comprised SSM in49 cases and NSM in 101 cases. Hypertrophicscarring was significantly less frequent withlateral vertical incisions (1.6%) than with lateralhorizontal incisions (14.6%) (P =0.007). Nosignificant differences were seen in terms ofbreast envelope necrosis, nipple-areolar necrosis.departmental bulletin pape

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    This study investigated the efficacy of hyperbaric oxygen therapy (HBOT) as a secondary treatment for patients with idiopathic sudden sensorineural hearing loss (ISSNHL) in the subacute and chronic phases. Forty-eight ISSNHL patients (HBOT group) who had received primary conventional treatment within 4 weeks after onset and underwent HBOT between 4 and 20 weeks post-onset were retrospectively compared with 44 ISSNHL patients (control group) with primary conventional treatment alone. Mean hearing gain was slight, with gains of 5.2 ± 8.9 dB in the HBOT group and 2.0 ± 7.6 dB in the control group. However, no significant difference was recognized between the two groups. In the HBOT group, no significant difference was observed in hearing gain among patients with HBOT initial time at 4-7, 8-11, 12-15 or 16-20 weeks after onset. Meanwhile, hearing gain was significantly higher in patients with profound hearing loss than in the other patients. We conclude that the effectiveness of secondary HBOT for ISSNHL patients in either subacute or chronic phase remains unproven, and thus, the decision administer HBOT should be made with caution.departmental bulletin pape

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    Background-Chronic endemic dental fluorosis is a malformation of teeth caused by excessive ingestion of fluoride during period of tooth development. Apatite crystallites and collagen fibrils determine the caries susceptibility related properties of dentine. Information relating the effect of dental fluorosis with dentine crystallite and collagen structure is currently unavailable. This study examined structural aberrations of apatite crystallites and collagen fibrils in human fluorosed dentine. Method- Superficial dentine of thirty six normal (Thylstrup-Fejerskov index - 0) and thirty six severely fluorosed (Thylstrup-Fejerskov index - 7 to 9) extracted human molars from individuals living in an area which is endemic for dental fluorosis were morphologically analyzed using transmission electron microscopy with selected area electron diffraction and dynamic force microscopy. Results- A statistically significant enlargement in the size of crystallites was found in fluorosed dentine (p<0.05). These crystallites were not homogenously arranged. Selected area electron diffraction revealed a lower density of crystallites in fluorosed dentine. Randomly distributed collagen fibrils showed a less complex lay out in contrast to normal dentine tissue. Conclusion- Ultrastructure aberrations of the dentine explain the caries susceptibility of the tissue and suggest the necessity of special approach in dental caries treatment for patients with chronic severe endemic dental fluorosis.departmental bulletin pape

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    Airway smooth muscle cells (ASMCs) have been reported to express Toll-like receptors (TLRs) and take part in the pathogenesis of asthma exacerbation. Though TLRs were found to activate epidermal growth factor receptor (EGFR) in airway epithelial cells, little is known about the association of TLR ligands with EGFR signaling pathways in ASMCs. Using primary cultured ASMCs from Brown Norway rats, TLR4, eotaxin, and RANTES mRNA were examined by real-time quantitative RT-PCR after stimulation with the TLR4 ligand, lipopolysaccharides (LPS). The concentration of RANTES protein in culture supernatant was measured by ELISA. The effect of EGFR signaling inhibitors on RANTES expression was examined as well. Phosphorylation of EGFR after stimulation was examined by Western Blotting. Rat ASMCs expressed TLR4 and eotaxin, and LPS upregulated RANTES production. The EGFR tyrosine kinase inhibitor AG1478, the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, and the matrix metalloproteinase (MMP) inhibitor GM6001 inhibited RANTES expression induced by LPS. LPS phosphorylated EGFR. TLR4 activation can induce RANTES expression via EGFR transactivation and PI3K/Akt pathway in rat ASMCs. MMP-induced EGFR proligand cleavage and ligand binding to EGFR seem to be involved in this pathway. These findings may be critical in the pathogenesis of asthma exacerbation by airway infection.departmental bulletin pape

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    HER2 oncoprotein plays an essential role in breast cancer growth and differentiation. Determination of HER2 status contributes not only to predicting survival but also to selecting the patients for anti-HER2 therapy. HER2 protein expressed in human cancer cells often contains variant forms as well as the full-length wild-type form. In the present study, we investigated the subcellular localization of HER2 protein in 1053 primary breast cancer tissues. HER2 protein was stained by various immunohistochemical methods and studied by immunoelectron microscopy to confirm the intracellular localization. Thirty-four of 1053 specimens showed cytoplasmic staining of the intracellular domain of HER2 protein by the HercepTest® and CB-11. In contrast, no immunoreactivity to the antibodies against the extracellular domain was observed. None of the 34 specimens showed amplification of the HER2 protein by fluorescence in situ hybridization. Subsequently, we studied the association of the cytoplasmic expression of HER2 with neuroendocrine differentiation. Interestingly, all 34 specimens had some positive signals of neuroendocrine markers such as synaptophysin, chromogranin A, neuron-specific enolase, and CD56. Although the result is preliminary, it warrants further study on the role of the cytoplasmic variant form of HER2 in breast cancer growth, particularly in the aspect of neuroendocrine differentiation.departmental bulletin pape

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    We report a 24-month-follow-up study of argon plasma coagulation of the inferior turbinate (APC) in patients with perennial nasal allergy. This was a retrospective study, in which 41 patients with perennial allergic rhinitis were treated by inferior turbinate reduction using APC. The grades of nasal stuffiness, rhinorrhea, sneezing and the daily activity impairment caused by these nasal symptoms were evaluated before and then 6, 9, 12, 15, 18, 21, and 24 months after APC, using a questionnaire graded on a four-point scale according to the Severity Criteria of Symptoms of Nasal Allergy issued by the Japanese Society of Allergology. Both nasal stuffiness and any daily activity impairment significantly improved 6 months after APC. Twenty four months after APC, 8/10 (80%) of the patients reported mild or no stuffiness and 9/10 (90%) of the patients reported mild or no daily activity impairement. Neither rhinorrhea nor sneezing were significantly improved during this study. Of the 41 patients 18 (43.9%) received no additional treatment. A second APC treatment was administered to 10/41 (24.4%) patients during follow-up period. Additional conservative medications were needed in 15/41 (36.6%) patients. Among the patients uncontrolled by conservative medical treatment, inferior turbinate reduction using APC provides significant relief in a 24-month-follow-up from nasal stuffiness and daily activity impairment.departmental bulletin pape

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    We have proposed a concept that prolonged rhythmic gum chewing causes a suppressed nociceptive flexion reflex via the serotonergic (5- HT) descending inhibitory pathway. However, the mechanism of activation of the 5-HT system by gum chewing remains undetermined. Several human and animal studies have reported that a direct connection exists between the prefrontal cortex (PFC) and 5-HT neurons in the dorsal raphe nucleus; therefore, we hypothesized that activation of the PFC region might be responsible for augmented 5-HT activity. To evaluate this hypothesis, oxygenated hemoglobin (oxyHb) and deoxygenated hemoglobin concentrations in the PFC were measured in the PFC during a 20-min time period of gum chewing using 24-channel nearinfrared spectroscopy. A significant increase in oxyHb level was observed in the ventral part of PFC compared with the dorsal part of PFC. We confirmed the previous results in that the nociceptive flexion reflex was significantly suppressed and the 5-HT level in blood was significantly increased following prolonged gum chewing. These results support the hypothesis that activation of the ventral part of PFC during gum chewing evokes augmented activity of 5-HT neurons in the dorsal raphe nucleus, which in turn suppress nociceptive responses.departmental bulletin pape

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