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Kenji Kondo

Publications and source records attributed to Kenji Kondo.

At least 19 recordsLinked to original sources
PubMed2007

Methimazole-induced cell death in rat olfactory receptor neurons occurs via apoptosis triggered through mitochondrial cytochrome c-mediated caspase-3 activation pathway.

The administration of methimazole is known to induce cell death in rat olfactory receptor neurons (ORNs). We investigated whether this injury occurs via apoptosis or through necrosis and whether it involves the extrinsic or intrinsic pathway. Rats were intraperitoneally injected with vehicle (control) or 300 mg/kg methimazole. The experimental animals were also administered vehicle or a caspase-3 or caspase-9 inhibitor 30 min earlier. The administration of methimazole induced cell death predominantly in the mature ORNs and partially reduced olfactory sensitivity in the rats; the injured cells were TUNEL-positive and showed a nuclear staining pattern. This insult induced cytochrome c release from the mitochondria and a significant increase in the immunoreactivity of activated caspase-3 and caspase-9 as well as that of cleaved poly-ADP-ribose-polymerase; in addition, it caused a significant increase in the fluorogenic activity of caspase-3 and caspase-9. However, it did not affect the immunoreactivity of activated caspase-8 or the fluorogenic activity of caspase-8. Pretreatment with a caspase-3 or caspase-9 inhibitor nearly completely prevented the morphologic, biochemical, and functional changes induced by methimazole. These findings suggest strongly that methimazole-induced cell death in rat ORNs is predominantly apoptosis; moreover, the majority of this apoptotic cell death is triggered through mitochondrial cytochrome c-mediated caspase-3 activation pathway, and both caspase-3 and caspase-9 inhibitors can prevent methimazole-induced cell death in the ORNs.

Animals↗
PubMed2006

Age-related changes in cell density and the proliferation rate of olfactory ensheathing cells in the lamina propria of postnatal mouse olfactory mucosa.

We investigated age-related changes in the distribution and proliferation of olfactory ensheathing cells (OECs) in postnatal mouse olfactory mucosa. In contrast to reported data on other glial cell types in the peripheral and central nervous systems, OEC cell density in the olfactory nerve bundles in the lamina propria remained almost constant from 10 days through 16 months of age. Electron microscopy of the nerve bundles revealed that axon packing density also was constant during that period. These findings suggest that the ratio of the number of OECs to the unit length of the olfactory neuron axons ensheathed by them does not change markedly throughout the lifetime of mice in an undisturbed condition. By contrast, OEC proliferative density decreased rapidly in the 10-day to 1-month-old period, showing a significant difference, and for the rest of life remained at low level, similar to previous values reported for other glial cell types.

Aging↗
PubMed2006

Effects of adacolumn selective leukocytapheresis on plasma cytokines during active disease in patients with active ulcerative colitis.

AIM: To investigate the relationship between ulcerative colitis (UC) clinical activity index (CAI) and circulating levels of IL-1ra, IL-10, IL-6 and IL-18. METHODS: Blood levels of IL-1ra, IL-10, IL-6 and IL-18 were measured in 31 patients with active UC, the mean CAI was 11.1, ranging from 5-25; and 12 healthy individuals as controls. Patients were given granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn. Leucocytes which bear the FcgammaR and complement receptors were adsorbed to the column leucocytapheresis carriers. Each patient could receive up to 11 GMA sessions over 8 wk. RESULTS: We found strong correlations between CAI and IL-10 (r = 0.827, P < 0.001), IL-6 (r = 0.785, P < 0.001) and IL-18 (r = 0.791, P < 0.001). IL-1ra was not correlated with CAI. Following GMA therapy, 24 of the 31 patients achieved remission and the levels of all 4 cytokines fell to the levels in healthy controls. Further, blood levels of IL-1ra and IL-10 increased at the column outflow and inflow at 60 min suggesting release from leucocytes that adhered to the carriers.

Adolescent↗
PubMed2006

Supporting cell proliferation after hair cell injury in mature guinea pig cochlea in vivo.

In cold-blooded animals, lost sensory hair cells can be replaced via a process of regenerative cell proliferation of epithelial supporting cells. In contrast, in mammalian cochlea, receptor (hair) cells are believed to be produced only during embryogenesis; after maturity, sensory or supporting cell proliferation or regeneration are thought to occur neither under normal conditions nor after trauma. Using bromodeoxyuridine (BrdU) as a proliferation marker, we have assessed cell proliferation activity in the mature organ of Corti in the cochlea of young guinea pigs following severe damage to the outer hair cells induced by kanamycin sulfate and ethacrynic acid. Although limited, we have found BrdU-labeled nuclei in the regions of Deiters cells when BrdU is given for 3 days or longer. When BrdU is given for 10 days, at least one labeled nucleus can be observed in the organ of Corti in approximately half of the ears; proliferating cells typically appear as paired daughters, with one nucleus being displaced away from the basement membrane to the position expected of the hair cells. Double-staining with antibodies to cytokeratin, vimentin, and p27 have shown that the BrdU-labeled nuclei are located in cells phenotypically similar to Deiters cells. Most of the uptake of BrdU occurs 3-5 days following ototoxic insult, and the number of BrdU-labeled cells does not decrease until 30 days following insult. These findings indicate that Deiters cells in the mature mammalian cochlea maintain a limited competence to re-enter the cell cycle and proliferate after hair cell injury, and that they can survive at least for 1 month.

Animals↗
PubMed2006

Immunohistochemical and genetic features of gastric and metastatic liver gastrointestinal stromal tumors: sequential analyses.

Metastatic gastrointestinal stromal tumors (GIST) have an extremely poor prognosis; however, their immunohistochemical and genetic features have not been assessed satisfactorily and the mechanisms responsible for their high malignant potential remain unclear. We examined the immunohistochemical differences between gastric GIST and metastatic lesions in the liver of four patients who had undergone a postgastrectomy hepatectomy for metachronous liver metastases. We also carried out genetic analysis of the tumors in three of the four cases. In all cases, the immunoreactivity profiles, including KIT (CD117), CD34, smooth muscle actin (SMA), desmin, S-100 and vimentin, were similar between the gastric and metastatic tumors, but the Ki67 labeling index in the metastatic GIST was higher than that of the primary GIST. Interestingly, in the case who had received neoadjuvant imatinib therapy before gastrectomy, its therapeutic effect was observed in most of the primary lesion, with the exception of a specific small area with high cellularity. Genetic analysis revealed no acquired mutations in the c-kit or PDGFRA genes in the metastatic lesions in any of the patients, but loss of heterozygosity (LOH) of the c-kit gene was observed mainly in the metastatic tumors in two of the three cases. Furthermore, in the case of neoadjuvant imatinib therapy, LOH of the c-kit gene was shown in the high cellularity area in the primary lesion and metastatic liver GIST. It is suggested that LOH of the c-kit gene is an important event that leads to imatinib resistance and metastatic progression of GIST. In conclusion, both gastric and metastatic GIST had almost the same immunohistochemical features, except for their proliferative activity, and LOH of the c-kit gene played an important role in the process of liver metastasis.

Aged↗
PubMed2006

Identification of medicinal Atractylodes based on ITS sequences of nrDNA.

Dried rhizomes of five species of Atractylodes (A. japonica, A. macrocephala, A. lancea, A. chinensis, and A. koreana), Compositae, have been used as crude drugs mainly for the treatment of stomach disorders and for their diuretic properties in Chinese and Japanese traditional medicines. The identification of the botanical origins of these crude drugs is generally difficult from their morphological and chemical features only. In this study, for identification with more reliable, nuclear ribosomal DNA (nrDNA), internal transcribed spacer (ITS) regions of five species of medicinal Atractylodes were sequenced. As a result, specific ITS genotypes were recognized by each species. The four species (A. japonica, A. macrocephala, A. lancea, and A. chinensis) prescribed in Chinese and Japanese Pharmacopoeias as botanical origins of crude Atractylodes drugs could be distinguished by their ITS sequences because they had difference genotypes on the ITS sequences. However, the genotype of A. koreana was the same as that of A. chinensis. Additionally, hybrids between A. lancea and A. chinensis were also recognized as nucleotide additives on their ITS sequences. In this study, several morphological characteristics were researched by their genotype, too. As this result, the hybrids recognized from the genetic analysis had intermediate morphological characteristics between A. lancea and A. chinensis. It was also recognized that A. lancea and A. chinensis except for their hybrids were significant differences. It is therefore suggested that ITS sequences of nrDNA would be useful for the identification of the crude drugs derived from Atractylodes species and their interspecific hybridizations.

Atractylodes↗
PubMed2005

Decrease of reactive-oxygen-producing granulocytes and release of IL-10 into the peripheral blood following leukocytapheresis in patients with active ulcerative colitis.

AIM: To investigate the clinical efficacy of leukocytapheresis (LCAP) in patients with active ulcerative colitis (UC), and to elucidate the mechanisms by determining the changes in the cytokine levels in the peripheral blood and of the functions of the peripheral blood leukocytes in these patients. METHODS: The subjects were 19 patients with active UC, with a mean clinical activity index (CAI) of 9.2. The LCAP was conducted using Cellsorba E. In each session of LCAP, 2-3 L of blood at the flow rate of 30-50 mL/min was processed. The treatment was carried out in approximately 1-h sessions, once a week, for 5-10 wk. Blood samples for determination of the cytokine levels were collected from the inflow side of the column (site of dehematization; at the start of LCAP) and outflow side of the column (at the end of LCAP). Blood samples for the determination of reactive-oxygen-producing cells were collected from the peripheral blood before and after LCAP. RESULTS: LCAP resulted in clinical improvement in all the 19 patients of UC recruited for this study. Remission (CAI: < or = 4) was noted in 15 (79%) of the 19 patients. The blood level of the pro-inflammatory cytokine IL-6 was found to be decreased following treatment by LCAP, and the level of the anti-inflammatory cytokine IL-10 at the outflow side of the LCAP column was found to be significantly elevated as compared to that at the inflow side of the column. The reactive-oxygen-producing granulocytes in the peripheral blood of UC patients was increased as compared to that in healthy persons and the increase was found to be decreased following treatment by LCAP. CONCLUSION: LCAP exerted a high therapeutic efficacy in patients with active UC. Our findings suggest that LCAP is associated with enhanced production of the inhibitory cytokine IL-10 to indirectly inhibit the functions of the inflammatory leukocytes, and that inflammation is also considerably attenuated by the direct removal of reactive-oxygen-producing neutrophils from the peripheral blood.

Adult↗
PubMed2005

Correlation between microtia and temporal bone malformation evaluated using grading systems.

OBJECTIVE: To evaluate the relationships between temporal bone abnormalities and the severity of microtia in Japanese patients using objective grading systems. DESIGN: Retrospective case series study conducted between 1992 and 2003. SETTING: Academic, tertiary care, referral medical center. PATIENTS: One hundred forty-two ears of 109 Japanese patients (85 male and 24 female patients; mean age, 12.8 years [range, 2-36 years]) with microtia. MAIN OUTCOME MEASURES: The severity of microtia was classified according to Marx classification. Developmental abnormalities of the temporal bone were evaluated by a computed tomographic (CT) scoring system modified after the system used by Jahrsdoerfer and colleagues, using high-resolution CT scans of the temporal bone. Correlations between the scores obtained from these 2 grading systems were evaluated using a nonparametric statistical method. RESULTS: Male preponderance and incidence of bilateral cases of approximately 30% were observed in our Japanese patients with microtia. There was no significant difference in the severity of microtia between unilateral and bilateral cases. The mean +/- SEM total points in the CT scoring system (full marks, 10) was 7.9 +/- 0.4 for grade I microtia, 6.6 +/- 0.6 for grade II, and 6.4 +/- 0.3 for grade III; the total points correlated inversely with the microtia grade. Development of the auricle correlated significantly with aeration in the middle ear spaces but not with ossicular development or formation of the oval/round windows. Proportion of acceptable surgical candidates according to the CT scoring system (>5 points) was 79% for grade I microtia, 52% for grade II microtia, and 65% for grade III microtia. CONCLUSION: The principle "the better developed the auricle, the better developed middle ear" was confirmed in Japanese patients with microtia; however, even with grade II/III microtia, more than half of the patients were considered suitable for atresia surgery.

Abnormalities, Multiple↗
PubMed2005

Cyclooxygenase-2 regulates the degree of apoptosis by modulating bcl-2 protein in pleomorphic adenoma and mucoepidermoid carcinoma of the parotid gland.

CONCLUSION: These results suggest that COX-2 and bcl-2 protein were overexpressed and that apoptosis was reduced in MEC compared to PMA, and that COX-2 may regulate the degree of apoptosis by modulating bcl-2 protein in PMA and MEC. OBJECTIVE: Cyclooxygenase (COX)-2 plays a crucial role in tumorigenesis and overexpression of COX-2 in vitro accompanied by overexpression of bcl-2 protein has been shown to reduce apoptosis. The purpose of this study was to verify that COX-2 regulates the degree of apoptosis by modulating bcl-2 protein in benign and malignant parotid gland tumors. : We examined archival formalin-fixed, paraffin-embedded tissue sections of 10 pleomorphic adenomas (PMAs) and 10 mucoepidermoid carcinomas (MECs) by immunostaining with anti-COX-2, anti-bcl-2 and anti-single-stranded DNA (ssDNA) antibodies. Labeling indices of the three antibodies were calculated using computer-assisted image analysis. RESULTS: Labeling indices (mean+/-SD) of anti-COX-2 antibody in PMA and MEC were 2.05+/-1.30 and 11.2+/-2.95, respectively (p < 0.001), those of anti-bcl-2 antibody were 2.00+/-1.28 and 9.68+/-4.05, respectively (p < 0.001) and those of anti-ssDNA antibody were 8.06+/-2.54 and 2.08+/-1.47; respectively (p <0.001). Correlation coefficients between the labeling indices of anti-COX-2 antibody and anti-bcl-2 antibody, anti-bcl-2 antibody and anti-ssDNA antibody and anti-COX-2 antibody and anti-ssDNA antibody were 0.88, -0.75 and -0.76, respectively (p <0.001).

Adenoma, Pleomorphic↗
PubMed2005

Loss of FHIT expression in squamous cell carcinoma and premalignant lesions of the larynx.

The tumor suppressor gene FHIT (fragile histidine triad) at chromosomal position 3p14.2 is altered by deletions in human tumors. The frequency and specificity of its inactivation vary among carcinomas, but few articles have referred to premalignant lesions such as dysplasia. We studied the expression of FHIT in a series of squamous cell carcinomas and premalignant lesions of the larynx. We observed 36 laryngeal carcinoma biopsy specimens and 70 dysplasia biopsy specimens. We studied FHIT expression in carcinoma and dysplasia with the immunohistochemical ABC (avidin-biotinylated peroxidase complex) method. Loss of FHIT protein was observed in 42% of the squamous cell carcinomas and 23% of the premalignant lesions. There was no significant difference among the three grades of dysplasia in FHIT expression. These findings of loss of FHIT protein expression, not only in squamous cell carcinoma, but also in premalignant lesions, indicate that FHIT alterations play an important role in the early events of carcinogenesis.

Acid Anhydride Hydrolases↗
PubMed2004

Mechanism of combined injuries of the posterior cruciate ligament and the posterolateral ligament while wake boarding.

BACKGROUND: We encountered a case involving posterior cruciate ligament (PCL) and posterolateral ligament injuries of the knee due to a noncontact injury while wake boarding. The moment of injury was recorded on a home video. CASE REPORT: Based on our analysis of the video, the mechanism of injury was considered to be a combination of varus stress and internal rotation of the lower leg that induced tearing of the posterolateral ligaments. Subsequently, tearing of the PCL in the midsubstance occurred due to increased flexion of the knee.

Adult↗
PubMed2004

The role of the external auditory canal in the development of the malleal manubrium in humans.

OBJECTIVE: To determine if the external auditory canal (EAC) plays a role in the induction and proper positioning of the malleal manubrium in humans. STUDY DESIGN: Retrospective study between 1994 and 2002. SETTING: Academic, tertiary care referral medical center. Patients Fifty-five ears of 50 patients with congenital atresia (n = 47) or stenosis (n = 8) of the EAC, for which meatoplasty was performed at the University hospital between 1994 and 2002. MAIN OUTCOME MEASURES: The presence of the manubrium was examined during surgery, and the corre-lation between the presence of the manubrium and the grade of the microtia was evaluated. RESULTS: The manubrium was identified in all ears with EAC stenosis, whereas it was absent in all ears with EAC atresia. No correlation was observed between manubrium formation and auricular deformity. CONCLUSIONS: Our results demonstrated a close relationship between the formation of the EAC and that of the malleal manubrium in humans. This is consistent with the recent findings in knockout mice. This information is useful for surgical intervention in cases of congenital EAC anomalies.

Adolescent↗
PubMed2004

Actions of subtype-specific purinergic ligands on rat spiral ganglion neurons.

In a previous study we showed that, in rat spiral ganglion neurons (SGNs), the adenosine 5'-triphosphate (ATP)-evoked currents were a combination of the activation of ionotropic receptors (the first fast current) and the activation of metabotropic receptors which secondarily opened non-selective cation channels. These two conductances imply the involvement of different receptor subtypes. In the present study, we tested three subtype-specific purinergic ligands: alpha,beta-methylene ATP (a;pha,beta-meATP) for P2X receptors, uridine 5'-triphosphate (UTP) for P2Y receptors and 2'-3'-O-(4-benzoylbenzoyl) ATP (Bz-ATP) for P2Z (P2X(7)) receptors. Application of 100 microM alpha,beta-meATP did not trigger any significant change in membrane conductance, while the SGNs were responsive to ATP. Pressure application of UTP (100 microM, 1 s) evoked an inward current averaging 344+/-169 pA at a holding potential of -50 mV. The conductance developed after a latency averaging 1.5+/-0.6 s, took 4-6 s to peak and reversed slowly within 15-30 s. The current-voltage curve reversed near 0 mV, suggesting a non-selective cation conductance, like the second component of the ATP conductance. Bz-ATP evoked an inward current which developed without latency, was sustained during ligand application and was rapidly inactivated at the end of application: the same characteristics as the first component of the ATP-evoked current. The Bz-ATP conductance reversed around -10 mV, indicating also a non-selective cation conductance. These results suggest that, in SGNs, ATP acts via two different receptor subtypes, ionotropic P2Z receptors and metabotropic P2Y receptors, and that these two receptor subtypes can assume different physiological roles.

Adenosine Triphosphate↗
PubMed2004

Overexpression of ErbB-2 protein in human middle ear cholesteatomas.

OBJECTIVE: The purpose of this study is to verify the hypothesis that ErbB-2 protein is overexpressed in human middle ear cholesteatomas and to elucidate the relationship between overexpression of ErbB-2 protein, cell proliferation, and apoptosis. STUDY DESIGN: Prospective review of 20 patients between 2001 and 2003 with middle ear cholesteatoma. METHODS: Middle ear cholesteatoma matrix and retroauricular skin were immunostained with anti-ErbB-2, Ki-67, and single-stranded DNA (ssDNA) antibody. The distribution of immunoreactivity to these antibodies and labeling indices were compared between cholesteatoma and retroauricular skin. RESULTS: In matrix of middle ear cholesteatoma, ErbB-2 and ssDNA were expressed in the keratinocytes of all layers and Ki-67 was expressed in the keratinocytes of the basal, lower spinous, and occasionally granular layer. In retroauricular skin, ErbB-2 and Ki-67 were expressed in the keratinocytes of the basal and occasionally lower spinous layer and ssDNA was expressed in the keratinocytes of all layers. Labeling indices against anti-ErbB-2, Ki-67, and ssDNA antibody were significantly greater in cholesteatoma as compared with retroauricular skin. CONCLUSIONS: In cases of cholesteatoma, ErbB-2 protein was overexpressed and cell proliferation and apoptosis of keratinocytes were accelerated. ErbB-2 protein could modulate terminal differentiation and apoptosis in the keratinocytes of all layers in cholesteatoma matrix and cell proliferation in the keratinocytes of the basal and lower spinous layer in normal skin.

Adolescent↗
PubMed2004

Immunohistochemical localization of histamine receptor subtypes in human inferior turbinates.

Histamine is an important chemical mediator in allergic rhinitis and plays an important role in eliciting the nasal symptoms of the disorder. However, the immunohistochemical localization of histamine receptor subtypes (H1R, H2R, H3R, and H4R) in human nasal mucosa is unknown. There are also no prior studies of H3R and H4R in human nasal mucosa. The objective of this study was to examine the distribution of histamine receptor subtypes in the human inferior turbinates by an immunohistochemical method. H1R was localized primarily in the epithelium, vessels, and nerves. H2R was localized primarily in the epithelium and the glands. H3R and H4R were clearly distributed on the nerves. In addition, H1R, H3R, and H4R were clearly localized on the same nerves. This result indicates that H1R, H3R, and H4R adjoin and regulate each other in the same nerves. All histamine receptor subtypes may play some role in patients with allergic rhinitis.

Adult↗
PubMed2004

Elevated expression of cyclooxygenase-2 in adenocarcinoma of the parotid gland: insights into malignant transformation of pleomorphic adenoma.

Pleomorphic adenoma, the most common type of tumor of the parotid gland, may transform into a malignant tumor. In the current study, we investigated whether the expression of cyclooxygenase-2 (COX-2) is elevated in adenocarcinoma as compared to pleomorphic adenoma. Ten pleomorphic adenomas and 10 adenocarcinomas were examined. The tumor specimens were immunohistochemically stained with antibodies against COX-2 and Ki-67. The labeling indices of COX-2 in pleomorphic adenoma and adenocarcinoma were 6.0% +/- 4.1% and 16.1% +/- 4.6%, respectively, and those of Ki-67 in pleomorphic adenoma and adenocarcinoma were 0.77% +/- 0.62% and 6.9% +/- 6.6%, respectively. The labeling indices of both COX-2 and Ki-67 were significantly greater (p < .001) in adenocarcinoma than in pleomorphic adenoma. Together with the biological effects of COX-2, these results suggest that overexpression of COX-2 plays a crucial role in the pathogenesis of malignant transformation of pleomorphic adenoma in the parotid gland.

Adenocarcinoma↗
PubMed2004

[Two cases of recurrent gastric cancer treated by combined chemotherapy of TS-1 and low-dose cis-platinum].

We report 2 patients with recurrent gastric cancer treated by combined chemotherapy of TS-1 and low-dose cis-platinum (TS-1/LCDDP). Who both obtained long-term survival while maintaining good QOL. Case 1: A 60-year-old man underwent total gastrectomy for gastric cancer (pT3, pN2, Stage III B). Three months after surgery, multiple liver metastases were identified, for which TS-1/LCDDP therapy (TS-1 100 mg/body/day, CDDP 10 mg/body/week; 1 course for 4 weeks) was started without hospitalization. After CR was obtained after 4 courses, an additional 4 courses were carried out. At present, 1 year and 11 months have passed since the initial treatment, and CR has been maintained. Regarding adverse events, only grade-1 pigmentation was observed. Case 2: A 65-year-old man with gastric cancer (pT3, pN1, Stage III A) underwent distal gastrectomy. One year after surgery, CT showed both multiple liver and pulmonary metastases. Twelve courses of TS-1/LCDDP therapy have been carried out for 2 years and 4 months. Therapeutic effect was NC, but the patient was able to tolerate the treatments as an outpatient without any subjective symptoms. Leukopenia (grade 2), pigmentation, stomatitis and nausea (grade 1) were observed. Both patients received TS-1/LCDDP therapy as outpatients with good QOL and performance status (0). Recently, chemotherapy for recurrent cancer has been focusing on long-term survival and maintenance of QOL, instead of tumor shrinkage. These results suggest that TS-1/LCDDP treatment is useful as a first-line chemotherapy for patients with recurrent gastric cancer.

Aged↗