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Biomedical subjects

Keiichi Ichimura

Publications and source records attributed to Keiichi Ichimura.

At least 19 recordsLinked to original sources
PubMed2006

Nasal dermoplasty for Japanese hereditary hemorrhagic telangiectasia.

OBJECTIVE: While generally considered an effective treatment for moderate to severe epistaxis in hereditary hemorrhagic telangiectasia (HHT), nasal dermoplasty (ND) has not been well established in Japan. This prompted the present Japanese assessment of clinical efficacy and patient satisfaction following this procedure. METHODS: Retrospective analysis of clinical records of 15 patients with HHT undergoing ND between August 1991 and May 2004 and survey of these patients as to postsurgical conditions. Main outcome measures were skin graft "take" frequency after surgery (all patients), reported patient satisfaction (eight recent patients), and reported volume and frequency of epistaxis after versus before surgery (eight recent patients). RESULTS: Graft take rate was 100%. Most patients experienced reduced frequency and volume of bleeding. One patient required an additional operation, total closure of the external nares, 2 years later. Overall patients felt satisfied with ND, experiencing less nasal obstruction than expected. CONCLUSIONS: ND is effective in Japanese patients with moderate and severe nasal bleeding from HHT, reducing their risk of bleeding.

Adolescent↗
PubMed2006

[Fluticasone propionate aqueous nasal spray for the treatment of chronic sinusitis with eosinophil].

Chronic sinusitis with eosinophils easily recurs after endoscopic sinus surgery. The condition is usually complicated by asthma, and many eosinophils are present in the sinus mucosa. One conservative treatment method is the administration of glucocorticoids locally or systematically. To evaluate the efficacy and tolerability of intranasal fluticasone propionate for the treatment of chronic sinusitis with eosinophils, seven patients with chronic sinusitis with eosinophils were treated over a 12-week period using a fluticasone propionate aqueous nasal spray (800 microg per day in each nostrilz). The Symptons of 7 patients, especially nasal discharge and nasal obstructions, improved and an expanded air space was observed on paranasal CT images. The percent of drug systemically available after intranasal administration varied by less than 1% for intranasal fluticasone propionate. Therefore, even if intranasal fluticasone propionate is administerved at double the usual dose, it is unlikely to cause systemic side effects. Fluticasone propionate aqueous nasal spray at double the usual dose is effective for the treatment of chronic sinusitis with eosinophils.

Administration, Intranasal↗
PubMed2006

Acute sensorineural hearing loss and vertigo in a young adult with congenital plasminogen disorder.

A 19-year-old Japanese man exhibiting acute right sensorineural hearing loss and vertigo was referred to the Jichi Medical School Hospital in June 1994. Although he had no history of recurrent thrombosis and no family history of thrombosis, he had undergone reconstruction of a right foot joint fracture 4 months earlier. Screening studies for plasminogen activity demonstrated 10% of normal plasminogen activity and his plasminogen was diagnosed as "plasminogen Tochigi" by the gene analysis using restriction enzyme Fnu4HI. The patient's hearing returned to normal with administration of heparin, and he was prescribed warfarin for the prevention of thrombosis until October 1995. There was no recurrence of hearing loss during seven years of follow-up. The cause of this patient's hearing loss is believed to be associated with consumption of the already low levels of plasminogen as a result of his surgery as well as congenital plasminogen disorder.

Acute Disease↗
PubMed2006

Temporal bone histopathologic abnormalities associated with mitochondrial mutation T7511C.

OBJECTIVES: We previously reported a mitochondrial T7511C mutation in the tRNA gene in a Japanese family with nonsyndromic hearing loss (HL). However, the temporal bone histopathology associated with T7511C has not been reported. The aim of the present study is to report histopathologic findings of a temporal bone from a patient in the Japanese family with this mutation. STUDY DESIGN: Single case study. METHODS: A temporal bone was obtained from the right ear of a male subject with progressive HL from 5 years of age and who died at 60 years of age from cerebral infarction. The bone was embedded, sectioned, and stained with hematoxylin-eosin for light microscopic study. Graphic reconstruction of the cochlea was performed using the method described by Schuknecht to determine loss of the stria vascularis and neurosensory elements including hair cells and spiral ganglion neurons. RESULTS: The most significant histopathologic finding was severe loss of spiral ganglion cells in all turns of the cochlea. Severe loss of neuronal filaments in Rosenthal's canal was also observed. The organ of Corti showed scattered loss of inner and outer hair cells in the basal turn. Partial atrophy of the stria vascularis was observed in all turns of the cochlea. CONCLUSION: Our results suggest that severe loss of spiral ganglion cells was the main cause of sensorineural HL associated with the T7511C mutation.

Atrophy↗
PubMed2006

[Development of new surgical tools, Q-PAL and HP-Jet for endoscopy only used unilateral transnasal approach for pituitary adenomas].

UNLABELLED: The aim of this study is to present surgical techniques and results of endoscope-assisted transnasal approach (TNA) for pituitary adenomas. It is a new alternative for Hardy's surgery (TSS). We performed TNA assisted by only endoscope through single nostril. METHOD: We enter the sphenoid sinus directly through the natural ostium and ablate neither the nasal septum nor the vomer bone. We found the hardest problem of this method resides in its deep and narrow working space which obstructs usage of two tools at same time. To overcome this problem we developed two surgical tools, Q-PAL and HP-Jet. Q-PAL is combination of PAL and suction. We place flexible PAL wire electrode through suction tube so as PAL tip protrudes from suction tip. This eliminates coagulation smoke which otherwise disturbs surgeons view. HP-Jet is a combination of a suction tool and an irrigator. The irrigator is connected to syringe containing saline. Saline is injected manually from tip bursting up tumor tissue with its jet pressure. It is safe and effective instrument suitable for extirpation of rather fragile tissue like adenomas existing in deep and blind spaces. CASES: Since 2004 we have operated on 16 patients using endoscopic TNA. Eight were non-functioning adenomas, and 8 functioning. RESULTS: Results of surgery were compared with those of 10 cases operated by TSS. More than 70% removal of adenoma was achieved in 75% of cases with TNA, but in only 71% with TSS. Postoperative CSF rhinorrhea was seen in one case. Four cases showed postsurgical transient diabetes insipidus. We had no case with postsurgical infection. With the help of instruments having multiple functions in single probe such as Q-PAL and HP-Jet, we can execute endoscopic TNA more smoothly and more safely.

Adenoma↗
PubMed2006

[Only used unilateral transnasal approach applied endoscopic sinus surgery for pituitary adenomas].

Endoscope-assisted transnasal approach (TNA) for pituitary adenoma is a new alternative for Hardy's surgery (TSS). We performed TNA using only an endoscope through unilateral nostril. In our approach to sphenoid sinus, we apply method of endoscopic sinus surgery (ESS-TNA). We enter the sphenoid sinus directly through the natural ostium and do not brake the nasal septum nor vomer bone. Since September 2004 we had operated on 12 patients by endoscopic TNA. Six were non-functioning adenomas, and 6 were functioning adenomas. We are first to open the ethomoid sinus to make the space for middle concha to be displaced laterally. Secondary, we widen the natural ostium of the sphenoid sinus, retracting the middle concha laterally. The results were compared with those in 10 cases by TSS operated in our institute. Adenoma removal more than 80% was achieved in 58% by endoscopic TNA whereas in 50% by TSS. We had no case with postsurgical infection. Transient DI occurred in 4 cases and 1 case showed permanent. CSF rhinorrhea was seen in the case having small empty sellae in front of adenoma. For this case, we packed the fat tissue at the floor of the sella with endoscope under local anesthesia to close the fistula. Three cases that had hemianopsia before surgery showed the recovery postoperatively. In 6 functional adenoma, postoperative endocrinological examinations showed normalization in 3 cases and improvements in 3 cases. Postsurgical hospitalization days were 11.4 by endoscopic TNA whereas 15.4 by TSS. Our method showed same or better results than TSS in the removal rate and complication rate whereas the postoperative duration of nasal packing and hospitalization days were shorter than TSS.

Adenoma↗
PubMed2005

Protection of plasminogen activator inhibitor-1-deficient mice from nasal allergy.

This study was performed to clarify the relationship between fibrinolytic components and the pathology of allergy, particularly that during the development of nasal allergy and nasal tissue changes. Intranasal OVA challenge after sensitization by i.p. administration of OVA induced a higher level of excess subepithelial collagen deposition in wild-type (WT) C57BL/6J mice than in plasminogen activator inhibitor (PAI)-1-deficient (PAI-1(-/-)) mice. The excess PAI-1 induction in the nasal mucosa and higher level of active PAI-1 in the nasal lavage fluid of WT-OVA mice compared with those in WT-control mice suggested that the decrease of proteolytic activity inhibits the removal of subepithelial collagen. The frequency of sneezing, nasal rubbing, nasal hyperresponsiveness, production of specific IgG1 and IgE in the serum, and production of IL-4 and IL-5 in splenocyte culture supernatant increased significantly in WT-OVA mice. In PAI-1(-/-) mice, these reactions were absent, and specific IgG2a in serum and IFN-gamma in splenocyte culture medium increased significantly. Histopathologically, there were marked goblet cell hyperplasia and eosinophil infiltration into the nasal mucosa in WT-OVA mice, but these were absent in PAI-1(-/-) mice. These results indicate that the immune response in WT-OVA mice can be classified as a dominant Th2 response, which would promote collagen deposition. In contrast, the Th2 response in PAI-1(-/-) mice was down-regulated, and the immune response shifted from Th2-dominant reaction to a Th1-dominant one. Taken together, these findings suggest that PAI-1 plays an important role not only in thrombolysis but also in immune response.

Animals↗
PubMed2005

Maternally inherited nonsyndromic hearing loss is associated with the T7511C mutation in the mitochondrial tRNASerUCN gene in a Japanese family.

We report here the characterization of a Japanese family with maternally transmitted nonsyndromic hearing loss. Fourteen of 21 matrilineal relatives in this family exhibited early or late-onset/progressive but noncongenital hearing impairment with a wide range of severity, ranging from severe to normal hearing. The age-of-onset varies from 3 to 30 years. Sequence analysis of the complete mitochondrial genome in one matrilineal relative of this family revealed the presence of T7511C mutation and other variants. However, the levels of heteroplasmy of T7511C mutation did not correlate with the severity and age-of-onset of hearing loss in this family. Furthermore, none of other mtDNA variants are evolutionarily conserved and implicated to have significantly functional consequence. The absence of the ND1 T3308C and tRNA(Ala) T5655C mutations in this Japanese family but the presence of these mtDNA mutations in an African family with a high penetrance seems to account for different penetrance between two pedigrees. Incomplete penetrance in this family indicates the involvement of modulatory factors in the phenotypic expression of hearing impairment associated with the T7511C mutation. Here, two known variants G79A and G109A in the GJB2 gene were identified in the hearing-impaired and normal hearing matrilineal relatives of this Japanese family. However, the lack of correlation in the severity and age-of-onset in hearing impairment with homozygous or heterozygous G79A or G109A or combination of both variants in the GJB2 gene in those subjects with hearing impairment and normal hearing indicates that those variants of GJB2 gene may not be a modifier of the phenotypic effects of the T7511C mutation in those subjects. Thus, the phenotypic variability in this family is due to the involvement of other modifier factor(s).

Age of Onset↗
PubMed2005

Specific and efficient transduction of Cochlear inner hair cells with recombinant adeno-associated virus type 3 vector.

Recombinant adeno-associated virus (AAV) vectors are of interest for cochlear gene therapy because of their ability to mediate the efficient transfer and long-term stable expression of therapeutic genes in a wide variety of postmitotic tissues with minimal vector-related cytotoxicity. In the present study, seven AAV serotypes (AAV1-5, 7, 8) were used to construct vectors. The expression of EGFP by the chicken beta-actin promoter associated with the cytomegalovirus immediate-early enhancer in cochlear cells showed that each of these serotypes successfully targets distinct cochlear cell types. In contrast to the other serotypes, the AAV3 vector specifically transduced cochlear inner hair cells with high efficiency in vivo, while the AAV1, 2, 5, 7, and 8 vectors also transduced these and other cell types, including spiral ganglion and spiral ligament cells. There was no loss of cochlear function with respect to evoked auditory brain-stem responses over the range of frequencies tested after the injection of AAV vectors. These findings are of value for further molecular studies of cochlear inner hair cells and for gene replacement strategies to correct recessive genetic hearing loss due to monogenic mutations in these cells.

Adenovirus E1 Proteins↗
PubMed2005

[Systemic effects of intranasal steroid drops in patients with dysosmia].

PURPOSE: To evaluate the systemic effects of intranasal steroid drops in patients with dysosmia. CASES AND METHODS: Intranasal steroid drops were administered for 12 weeks to 23 patients with dysosmia, and their plasma cortisol and adrenocorticotropic hormone (ACTH) values were measured before and after treatment. Improvement in dysosmia was judged based on the standerd olfactory test and the patients' symptoms. RESULTS: The post-treatment plasma cortisol levels ranged from 0.1 to 25.0 microg/dl (5.4 +/- 5.9 microg/dl), and the posttreatment plasma ACTH levels ranged from 5.0 to 55.0 pg/ml (13.8 +/- 11.7 pg/ml). After treatment, the 23 cases were divided into two groups: 14 cases (60.9%) with a decline in cortisol and/or ACTH level, and 9 patients (39.1%) with normal plasma cortisol and ACTH levels. Improvement in dysosmia was found in 4 patients (28.6%) in the former group and 4 patients (44.4%) in the latter group. The difference in percentage of patients who improved was not significant between the groups. CONCLUSIONS: We conclude that the direct topical effect of intranasal steroid drops on the olfactory mucosa may have been the principal reason for the improvement in the patients' dysosmia.

Administration, Intranasal↗
PubMed2004

Expression profiles of fibrinolytic components in nasal mucosa.

Components of the fibrinolytic pathway contribute to diverse pathways in many tissues, in addition to their well-recognized role in degradation of fibrin clots. In this study of nasal mucosa, we investigated the presence of mRNA of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor-1 (PAI-1), and plasminogen activator inhibitor-2 (PAI-2) using reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization, and compared these results with their localization in immunostained tissues. According to real-time RT-PCR results, t-PA, u-PA, PAI-1, and PAI-2 mRNA were noted in human nasal mucosa. Particularly, expression of u-PA and PAI-1 mRNA was significantly high in allergic nasal mucosa in comparison with normal mucosa. t-PA mRNA was detected in endothelial cells and epithelium in normal nasal mucosa. t-PA mRNA was detected in mucous cells of allergic submucosal glands, but not in normal glands. In allergic rhinitis, u-PA and PAI-2 mRNA were detected in mucinous cells and epithelium, and PAI-1 mRNA was detected in serous cells and epithelium. Expression of u-PA and PAI-1 mRNA in normal nasal tissues was decreased in contrast to that in allergic nasal tissues. u-PA staining was observed in mucous cells of allergic submucosal glands and the staining pattern of PAI-2 was similar to that of u-PA. PAI-1 was present in serous cells of submucosal glands from allergy samples, while epithelial cells were almost devoid of stain. In contrast, with allergy, immunohistochemical staining of t-PA was negative in submucosal glands, though positive in endothelial cells and epithelium. However, the expression of t-PA mRNA in allergic nasal mucosa was noted in mucous cells. In fibrin autography of nasal discharge, u-PA was markedly activated in the allergic patient. These results suggest that t-PA synthesized in mucous cells is promptly secreted and modifies watery nasal discharge in allergic rhinitis, and that u-PA activity may help the passage of large amounts of rhinorrhea by also reducing its viscosity. A lot of cellular infiltration (eosinophils in particular) was recognized in allergic nasal mucosa. It is most likely that the modifications in expression of PAs and PAIs are due to the local release of cytokines or growth factors from these inflammatory and immune cells.

Fibrinolysis↗
PubMed2004

Rosai-Dorfman disease revealed in the upper airway: a case report and review of the literature.

Rosai-Dorfman disease (RDD) is a systemic disease and its etiology is not well understood. It is a very rare but established disease. We report a case of RDD diagnosed in the upper airway that became a life-threatening condition because of the stricture of the subglottic space. A 49-year-old female complained of nasal obstruction, hoarseness and lacrimation. After evaluation following by fiberscopic examination and CT scanning of the head and neck, sinusitis and laryngeal masses were detected. Endoscopic sinus surgery and endolaryngeal microsurgery were performed simultaneously. The masses in the nasal cavity and larynx showed the same histological findings. Proliferative large histiocytes with voluminous clear cytoplasm and rounded nuclei, and lymphophagocytosis known as emperipolesis are the characteristic features of RDD. In this case, extranodal manifestations in the subglottic space gradually emerged postoperatively. Tracheotomy was performed to ensure an airway and prevent suffocation. An extensive treatment is not required in most patients with RDD, however, some patients who have extranodal manifestations involving the airway may detoriorate into a life-threatening condition.

Biopsy↗
PubMed2004

Increased nasal patency caused by smoking and contraction of isolated human nasal mucosa.

In this study, we investigated the effects of smoking and nicotine, an important constituent of cigarettes, on the nasal patency using acoustic rhinometry (AR) and an in vitro bioassay technique. In the AR study, the nasal cavity volume of volunteers classified into two groups, smoking and nicotine chewing gum groups, was measured. The nasal cavity volumes immediately after smoking and 5 minutes after smoking significantly increased compared with that before smoking (P < 0.05), whereas the nasal cavity volume after chewing a nicotine gum was unchanged compared with that before chewing the gum. An in vitro study showed significant nicotine-induced contraction of the human nasal mucosa (50.2 +/- 14.0% noradrenaline-induced contraction: n = 10). The threshold nicotine level that can induce human nasal mucosa contraction was 3.0 x 10(-7) M. Prazosin (10(-6) M) inhibited nicotine-induced contraction incompletely (20.5 +/- 7.5% of noradrenaline-induced contraction n = 5). These results indicate that smoking increases nasal patency and that nicotine induces contraction of the human nasal mucosa. The nicotine-induced contraction is likely mediated, at least in part by alpha1-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed2004

Topoisomerase inhibitors enhance the cytocidal effect of AAV-HSVtk/ganciclovir on head and neck cancer cells.

Adeno-associated virus (AAV) is a non-pathogenic virus with a single-strand DNA genome. AAV vectors have several unique properties suited for gene therapy applications. However, an obstacle to their application is a low efficiency of transgene expression, mainly due to a limited second-strand synthesis. Previously, we reported that gamma-rays enhanced the transduction efficiency and cytocidal effect of AAV vector harboring the herpes simplex virus-thymidine kinase (AAVtk) and ganciclovir (GCV) system. In the present study, we investigated whether topoisomerase inhibitors (etoposide and camptothecin) enhance the AAV vector-mediated transgene expression and the killing effect by AAVtk/GCV system. The enhancement of transgene expression was observed in a concentration-dependent manner on human laryngeal carcinoma cells (HEp-2 cells) and HeLa cells. Southern analysis confirmed that etoposide enhanced the double-strand synthesis of the AAV vector genome in HEp-2 cells and HeLa cells. The cells were efficiently killed by AAVtk/GCV system, as expected. More importantly, both etoposide and camptothecin augmented the cytocidal effect of the AAVtk/GCV system. These findings suggest that the combination of AAV-mediated suicide gene therapy and treatment with topoisomerase inhibitors may have synergistic therapeutic effects in the treatment of cancers.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Apolipoprotein E -491 promoter polymorphism is an independent risk factor for Alzheimer's disease in the Chinese population.

Polymorphisms at positions -491, -427 and -219 in the promoter region of the Apolipoprotein E APOE gene have been variously reported to confer an increased risk of developing Alzheimer's disease (AD) independent of the effect of epsilon 2, 3 or 4 alleles in exon 4. In order to assess APOE promoter polymorphisms as independent risk factors in AD we have compared results in 183 definite or probable AD cases with 133 controls. We assayed markers at sites -491, -427, -219, and +113 in APOE gene and a polymorphic Hha1 site in the nearby APOC1 gene. We found that APOE promoter polymorphisms and APOC1 insertion alleles were significantly associated with AD. However, after stratification for epsilon 4 allele, only the A allele at -491 in APOE remained significantly associated with AD. The effects of the other markers depended almost entirely upon linkage disequilibrium with epsilon 4 allele, and only trends remained when cases and controls were stratified for the presence or absence of epsilon 4 allele. This occurred irrespective of whether markers were examined separately or together as haplotypes. So in the Chinese population only APOE -491 promoter alleles confer significant risk of AD independent of epsilon 4 status.

Aged↗
PubMed2003

Foreign bodies in the aerodigestive tract in pediatric patients.

OBJECTIVE: To investigate pediatric foreign body cases in the aerodigestive tract, and to elucidate the characteristic problems in Japan. METHODS: A total of 310 pediatric patients (age 15 or below), gathered from two medical university hospitals (University of Tokyo and Jichi Medical School), were included in this study. Data were collected by retrospective chart review and were statistically analyzed. RESULTS: Two-year-olds were the most common patients, and the range from age 1 to age 4 included 67.7% of all the patients. The most involved sites were the nose (39.4%) and the pharynx (38.4%), followed by the esophagus (12.9%) and the trachea-bronchi (6.5%). Fish bones and toys were the representative foreign bodies (30.7 and 13.6%, respectively). Other foreign bodies often encountered included coins, food, candy, peanuts and nuts, and batteries. The type of foreign body was closely related to the site in which foreign bodies were lodged: 77.3% of foreign bodies in the pharynx were fish bones, and toys were the most common impacted foreign body in the nose. In the esophagus, representative impacted foreign bodies were coins (35.7%), but disk-type battery ingestion has been increasing in recent years. Although most foreign bodies in the esophagus were safely removed, one case of a disk-type battery had a serious sequela. In the trachea-bronchi, peanuts, food, cotton, and coins were impacted. A rigid bronchoscope was basically used to remove foreign bodies, but in some cases, a fine flexible endoscope, with a channel for fiber forceps, was useful, because it could be inserted into narrow bronchi. Advance of a flexible endoscope will make it an excellent tool for diagnosis and management of the trachea-bronchial foreign body. CONCLUSIONS: Fish bones in the pharynx, which were closely related to Japanese eating habits, and toys in the nose, were the typical foreign bodies encountered in this study. In the esophagus, an increased incidence of disk-type battery ingestion has become a serious problem in recent years. Since prevention is the most essential way to manage foreign body cases, feedback from studies to public education should be encouraged.

Adolescent↗
PubMed2003

Results of orbital preservation for advanced malignant maxillary sinus tumors.

OBJECTIVE: The purpose of the study was to examine the oncological and functional outcomes of multimodality therapy for patients with advanced malignant maxillary sinus tumors that invaded the orbit. STUDY DESIGN: Retrospective study. METHODS: The medical records of 26 patients with orbital invasion were retrospectively analyzed. The patient group consisted of 16 men and 10 women, with a median age of 58 years. The mean follow-up period was 73 months. The most common disease was squamous cell carcinoma. Seven patients had nodal disease. All patients underwent simultaneous combined therapy consisting of conservative surgery through a sublabial incision, radiotherapy, and regional chemotherapy. Patients with nodal disease were treated with either irradiation or selective neck dissection. RESULTS: The 5- and 10-year overall survival rates were 68% and 51%, respectively. The 5- and 10-year local control rates were 66% and 51%, respectively. Overall survival rates and local control rates were significantly worse in patients with disease other than squamous cell carcinoma. Local control rates were significantly worse in patients with orbital apex disease than in patients without orbital apex disease. All 26 patients, despite orbital involvement, retained their orbital contents. Nineteen of these patients demonstrated adequate ocular function. CONCLUSIONS: Combined therapy with conservative surgery, radiotherapy, and regional chemotherapy is an effective method for local control and preservation of ocular function. However, performing orbital conservation procedure in patients with disease other than squamous cell carcinoma and with orbital apex disease must be considered carefully.

Adult↗