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Biomedical subjects

K Ichimura

Publications and source records attributed to K Ichimura.

At least 73 records · Page 4Linked to original sources
PubMed1999

Low p27 expression correlates with poor prognosis for patients with oral tongue squamous cell carcinoma.

BACKGROUND: p27, a cyclin-dependent kinase inhibitor, regulates progression from G1 to S phase. There have been a few clinical reports of low p27 expression associated with poor survival among patients with cancer; however, there have been no reports of such an association in cases of head and neck cancer. The authors investigated whether p27 expression in patients with oral tongue squamous cell carcinoma was associated with their prognosis. METHODS: Ninety-four patients with oral tongue squamous cell carcinoma were analyzed. The authors performed p27 immunohistochemistry on all patients and Western blot analysis on 19 available patients. Cox proportional hazards regression analysis that included gender, history of smoking and alcohol usage, presence of multiple primary cancers, stage, histologic grade, and p27 status was used to identify the multivariate predictive value of prognostic factors. RESULTS: Twenty-six patients had high p27 expression (> or =50% tumor cell nuclei positive), and 68 patients had low p27 expression (<50%) by immunohistochemistry. In those with low p27 expression, N(+) and advanced T (T3 or T4) were significantly higher than in those with high p27 expression (P = 0.02 and 0.04). The 5-year survival rate in the low p27 group was 44%, whereas that in the high p27 group was 68%, indicating a significant difference (P = 0.04). p27 expression was inferred from Western blot analysis, and an arbitrary quantity (<1, 1-5, or > or =5) from the ratio of tumor to normal tissue density was used to characterize, resulting in 8 (42%), 3 (16%), and 8 (42%) patients in the low (<1-fold), intermediate (1-5-fold), and high (> or =5-fold) groups, respectively. Results of immunohistochemical analysis for p27 were significantly correlated with those of Western blot analysis (P = 0.02). Multivariate analysis revealed that low intensity of p27 expression and advanced stage (Stage III or IV) were predictors of reduced survival (P = 0.02 and 0.001). CONCLUSIONS: Low p27 expression was associated with increasing lymph node metastasis and stage of tumor and resulted in a poor prognosis for patients with oral tongue squamous cell carcinoma. p27 is apparently a significant predictor of survival.

Actins↗
PubMed1999

Treatment of life-threatening huge atrial myxoma: report of two cases.

We herein report two patients with left atrial myxoma who needed an emergency operation. Case 1 was a 48-year-old woman who was injured in a traffic accident and underwent an operation for a right leg fracture. Just after the operation she developed cardiac and respiratory arrest with complaints of chest pain. She was successfully resuscitated and diagnosed to have a left atrial myxoma by echocardiography. Emergency surgery was performed and a giant left atrial myxoma was thus removed from the atrial septum. Case 2 was a 54-year-old housewife who was transferred to our department under the diagnosis of a left atrial myxoma by echocardiography. She complained of dyspnea and chest discomfort. By angiography, the tumor was seen to be partially incarcerated at the diastolic phase. A huge myxoma was removed from the atrial septum which was secured by a patch closure. Cardiac echocardiography can help rule out left atrial myxoma if it is highly suspected. As early surgical mortality is low and the long-term results are good, we strongly believe that patients with cardiac myxoma should be operated on as early as possible, once a diagnosis is made.

Echocardiography↗
PubMed1999

A group of schwannomas with interstitial deletions on 22q located outside the NF2 locus shows no detectable mutations in the NF2 gene.

Schwannomas are tumors arising mainly at cranial and spinal nerves. Bilateral vestibular schwannoma is the hallmark of neurofibromatosis type2 (NF2). The NF2 gene has been cloned and comprehensive analysis of its mutations in schwannomas shows that up to 60% of tumors carry inactivating mutations. Thus, the genetic mechanism behind the development of more than 40% of schwannomas without NF2 mutations is unknown. We have therefore studied tumor tissue from 50 human schwannomas by allelotyping and have found chromosome 22 deletions in over 80% of the cases. We detected 14 cases (27%) that revealed partial deletions of one copy of chromosome 22, i.e., terminal and/or interstitial deletions. We sequenced the NF2 gene in seven of these tumors and detected only one case with mutations. The deletion mapping of chromosome 22 in tumors with partial deletions indicates that several regions, in addition to the NF2 locus, harbor genes involved in schwannoma tumorigenesis. Our findings suggest that heterogeneity in the mechanisms leading to the development of schwannomas probably exists. These findings are in agreement with the recent analysis of schwannomas from familial and sporadic cases of schwannomatosis and point to a possible role of an additional gene, which, in cooperation with the NF2 tumor suppressor, causes schwannomas.

Adolescent↗
PubMed1999

Isolation and characterization of Neurospora crassa nucleoside diphosphate kinase NDK-1.

We have previously reported that phosphorylation of a 15-kDa protein increased after blue-light irradiation in Neurospora crassa. In this study, the 15-kDa protein was purified using four columns; DEAE-cellulose, Blue-Sepharose, SP-Sepharose and Mono Q. The 15-kDa protein was shown to be homologous with nucleoside diphosphate kinase by amino acid sequencing and was also shown to possess nucleoside diphosphate kinase activity. A gene encoding N. crassa nucleoside diphosphate kinase, ndk-1, was isolated from the mycelial cDNA and genomic libraries. The deduced amino acid sequence of NDK-1 was identical to that of the 15-kDa protein. Northern blot analysis suggested that WC-1 and WC-2, the key factors of blue-light signal transduction in N. crassa, did not regulate NDK-1 at the transcriptional level. NDK-1 also showed rapid autophosphorylation activity and protein kinase activity against myelin basic protein with a Km value of 0.36 mM. These results suggest that NDK-1 acts as a signal transducer by phosphorylating proteins.

Amino Acid Sequence↗
PubMed1999

Mutational profile of the PTEN gene in primary human astrocytic tumors and cultivated xenografts.

The genetic abnormality most frequently identified in glioblastomas is loss of alleles on chromosome 10. We have performed a comprehensive study of the PTEN tumor suppressor gene on 10q23, including loss of heterozygosity (LOH) analysis, multiplex PCR, mutation analysis, and reverse transcription PCR (RT-PCR). In total, 151 glioblastomas, 41 anaplastic astrocytomas, 15 astrocytomas, and 13 glioma cell lines were analyzed as well as 23 xenografts derived from primary glioblastomas, which allows a comparison of the PTEN gene status in primary tumors versus xenografts. Homozygous deletions were found in 7% of the glioblastomas and 40% showed mutation of a single retained allele. This mutation frequency is higher than reported previously. The large number of mutations identified allows the presentation of a mutational profile along the coding sequence. The majority of mutations appear to affect conserved residues or structurally conserved regions. PTEN alterations were selected for in xenografts, and there is evidence that they may even facilitate establishment of xenografts. No alterations were found in astrocytomas and only 5% of anaplastic astrocytomas had mutations. Thus, loss of wild type PTEN represents one of the major abnormalities associated with astrocytic tumor progression to glioblastoma and provides a strong selective growth advantage when cultivating glioblastoma tissue in xenografts. No correlation with EGFR amplification was evident.

Alleles↗
PubMed1999

Prefabricated free jejunal transfer: a new reconstructive technique for high pharyngeal defects.

A new method that uses a prefabricated free jejunal transfer has been applied to three cancer patients with pharyngoesophageal defects with a high pharyngeal deficit extending up to the nasopharynx. In this method, the jejunum harvested in the usual manner is divided into two segments with a single vascular pedicle. Its distal segment is used to reconstruct the cervical esophagus, and its proximal segment is turned over to create a mucosal patch to cover the high pharyngeal defects. The two segments are then co-apted in a side-by-side anastomosis. The esophagus can be reconstructed in a naturally straight shape without a curved portion or blind loop formation, thus leading to good swallowing function. In our series, all grafts survived well and there was no complication directly related to jejunal transfer. All patients could tolerate a soft diet without difficulty. This method is easy to perform and applicable to any shape or size of very high pharyngeal defects that cannot be reconstructed properly by other methods. Although patients with an advanced hypopharyngeal cancer usually have a poor prognosis, this technique allows a better quality of life for a probable short life span.

Aged↗
PubMed1999

[Endoscopic sinus surgery for unilateral chronic sinusitis].

Functional endoscopic sinus surgery has become an increasingly popular treatment for chronic sinusitis. This approach is aimed at re-establishment of ventilation and mucociliary clearance of the sinuses. However, some otolaryngologists believe that the Caldwell-Luc procedure should be routinely used for unilateral chronic sinusitis, because it is often associated with the maxillary sinus carcinomas. To evaluate the state of endoscopic sinus surgery for the diagnosis and treatment of unilateral chronic sinusitis, we analyzed the cases of 39 patients with unilateral chronic sinusitis who underwent endoscopic sinus procedures. These patients were unresponsive to appropriate antibiotic management for more than 6 months. Generally, endoscopic ethmoidectomy and antrostomy were performed with preservation of the middle turbinate. After the ostium was enlarged, the maxillary sinus was cleaned and carefully inspected for the presence of associated neoplasms using 30 and 70 degree endoscopes. Preoperative computed tomography (CT), postoperatve pathologic diagnosis, fiberscopic findings of the maxillary sinus, and symptomatic improvement were evaluated. Three patients had CT evidence of bone destruction of the lateral nasal wall. Pathological diagnosis demonstrated that three patients had maxillary sinus mycoses caused by Aspergillus species, one patient had inverted papilloma, and the other 35 patients had chronic sinusits. No associated malignancy was found. Eighty-one percent of the patients had almost normal endoscopic findings of the maxillary sinus by postoperative fiberscopic examination 4 to 8 months following surgery. With an average follow-up of 26 months, 88% of the patients were judged as having significantly improved in their presenting complaints of mucopurulent rhinorrhea, nasal obstruction, and facial pain. The results of this series suggest that endoscopic sinus surgery is an effective procedure for the diagnosis and treatment of unilateral chronic sinusitis.

Adult↗
PubMed1999

Severe phenotype of neurofibromatosis type 2 in a patient with a 7.4-MB constitutional deletion on chromosome 22: possible localization of a neurofibromatosis type 2 modifier gene?

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder predisposing to multiple neoplastic lesions with the hallmark of schwannoma arising at the eighth cranial nerve. NF2 shows a distinct clinical variability, with a mild and a severe form of the disease. The NF2 gene is mutated in constitutional DNA of affected patients from NF2 families and in sporadic cases. Comprehensive mutation analyses in patients with severe and mild phenotypes revealed mutations in only 34%-66%. In the remaining fraction, the genetic mechanism behind the development of NF2 is unknown. Analyses of germline mutations do not provide a conclusive explanation for the observed clinical heterogeneity of NF2. It can therefore be hypothesized that other factors, e.g., modifier gene(s), contribute to the development of a more severe NF2 phenotype. We report a mentally retarded patient with the severe form of NF2 who displays a 7.4 million base pair deletion on chromosome 22. We performed a full genetic characterization of this case using heterozygozity analysis of 41 markers from chromosome 22, detailed FISH mapping of deletion breakpoints, allelotyping of all other chromosomes, and sequencing of the NF2 gene in tumor DNA. Two genomically large deletions similar in size (700-800 kb), which encompass the entire NF2 gene, have been reported previously in mildly affected NF2 patients. The centromeric breakpoints of these deletions were similar to the centromeric breakpoint in the present case. However, the deletion in our patient extends over a much larger distance toward the telomere of 22q. Our results support the existence of NF2 modifier gene(s) and suggest that such a putative locus maps to a 6.5-MB interval on 22q, between D22S32 and the MB gene.

Adult↗
PubMed1999

How to manage patients with hard-to-recognize postnasal drip?

Postnasal drip (PND), commonly regarded as a phenomenon wherein nasal fluid drips into the pharynx, is one of the main symptoms of chronic sinusitis and other nasal lesions. This definition is controversial, however, because some patients have PND with no evidence of fluid either in the oropharynx or around the choanae. Among 220 patients in whom PND was diagnosed at the University of Tokyo Hospital between January 1996 and December 1997, 19 (8.6%) had hard-to-recognize PND on routine examination. Through careful observation, responsible lesions could be identified in all patients with hard-to-recognize PND. Seven patients had latent chronic sinusitis, 5 had nasopharyngeal lesions, such as Tornwaldt's cyst and inflammation, 3 had "old man's PND", 2 had "reflux PND", and 2 had polyps around the sphenoid ostium. Five patients received no treatment. In the other patients, medical therapy, mainly long-term treatment with low doses of macrolides, now regarded as a standard regimen for intractable chronic sinusitis in Japan, was effective in alleviating symptoms regardless of the cause.

Body Fluids↗
PubMed1998

Molecular cloning and characterization of three cDNAs encoding putative mitogen-activated protein kinase kinases (MAPKKs) in Arabidopsis thaliana.

We isolated three Arabidopsis thaliana cDNA clones (ATMKK3, ATMKK4 and ATMKK5) encoding protein kinases with extensive homology to the mitogen-activated protein kinase kinases (MAPKKs) of various organisms in the catalytic domain. ATMKK3 shows high homology (85% identity) to NPK2, a tobacco MAPKK homologue. ATMKK4 and 5 are closely related to each other (84% identity). Phylogenetic analysis showed that the plant MAPKKs constitute at least three subgroups. The recombinant ATMKK3 and ATMKK4 were expressed as a fusion protein with glutathione S-transferase (GST) in Escherichia coli. Affinity purified GST-ATMKK3 and GST-ATMKK4 proteins contained phosphorylation activity, which shows that both the ATMKK3 and ATMKK4 genes encode functional protein kinases. Northern blot analysis revealed that the ATMKK3 gene expressed in all the organs. The levels of ATMKK4 and 5 mRNAs were relatively higher in steins and leaves than in flowers and roots. We determined the map positions of the ATMKK3, 4 and 5 genes on Arabidopsis chromosomes by RFLP mapping using P1 genomic clones.

Amino Acid Sequence↗
PubMed1998

Isolation of ATMEKK1 (a MAP kinase kinase kinase)-interacting proteins and analysis of a MAP kinase cascade in Arabidopsis.

In plants, a number of MAP kinase (MAPK), MAPK kinase (MAPKK), and MAPKK kinase (MAPKKK) homologues have been reported. However, there have been no reports of protein-protein interactions between these kinases or molecular analysis of MAPK cascades in higher plants. To analyze a possible MAPK cascade in Arabidopsis thaliana, we took two molecular approaches. One is the two-hybrid screening of ATMEKK1 (a MAPKKK)-interacting proteins; the other is an analysis of physical and functional interactions among isolated MAPK, MAPKK, and MAPKKK homologues from Arabidopsis. In two-hybrid screening using ATMEKK1 as bait, we isolated a novel MAPKK homologue, ATMKK2, a MAPK homologue, ATMPK4, and an unknown protein. ATMKK2 has high sequence similarity with MEK1 (a MAPKK) in Arabidopsis. Based on yeast two-hybrid analysis, we detected protein-protein interactions between ATMEKK1 and ATMKK2/MEK1 (MAPKKs), between ATMKK2/MEK1 and ATMPK4 (a MAPK), and between ATMPK4 and ATMEKK1. ATMPK4 and ATMKK2/MEK1 interacted with two distinct regions of ATMEKK1, the N-terminal regulatory domain and the C-terminal kinase domain, respectively. Coexpression of ATMEKK1 increased the ability of two closely related MAPKKs, ATMKK2 and MEK1, to complement a growth defect of the yeast pbs2 mutant. Coexpression of ATMPK4 and MEK1 complemented a growth defect of the yeast mpk1 and bck1 mutants. By contrast, other combinations of MAPKs and MAPKKs did not suppress these yeast mutations. These results suggest that ATMEKK1, ATMKK2/MEK1, and ATMPK4 may constitute a MAP kinase cascade.

Alanine↗
PubMed1998

Identification of a possible MAP kinase cascade in Arabidopsis thaliana based on pairwise yeast two-hybrid analysis and functional complementation tests of yeast mutants.

A possible MAP kinase (MAPK) cascade of Arabidopsis thaliana was identified on the basis of both yeast 2-hybrid analysis and complementation analysis of yeast mutants. Specific protein-protein interactions between ATMPK4 (a MAPK) and MEK1 (a MAPKK) and interactions between MEK1 and ATMEKK1 (a MAPKKK) were detected by using the 2-hybrid system. A growth defect of the yeast mpk1delta mutant was reversed by coexpression of ATMPK4 and MEK1. Coexpression of the N-terminal deletion form of ATMEKK1 increased the ability of MEK1 to suppress a growth defect of the yeast pbs2delta mutant. These results suggest that ATMPK4, MEK1, and ATMEKK1 may interact with each other and constitute a specific MAPK cascade in Arabidopsis. This is the first demonstration of a possible MAPK cascade in plants.

Arabidopsis↗
PubMed1998

Genetic alterations in the retinoblastoma protein-related p107 gene in human hematologic malignancies.

Genetic alterations in the p107 gene, a close relative of the retinoblastoma tumor suppressor gene, have never been identified in human malignancies. When we searched for such alterations in human hematologic malignancies by Southern blot analysis, 2 of 21 cell lines and 1 of 88 primary disorders had genomic alterations within the gene. Particularly, an altered p107 gene in a diffuse-large B-cell lymphoma cell line, KAL-1, harbored an intragenic deletion of about 15 kbp leading to the expression of an altered p107 mRNA devoid of 819 nucleotides of the coding sequences, which predicts to encode an approximately 87-kDa protein. This cell line was found to express solely a p107 derivative of 84 kDa by immunoblotting analysis. These results suggest that alterations in the p107 gene are probably related to a limited subset of human hematologic malignancies.

Gene Deletion↗
PubMed1998

Distinct patterns of deletion on 10p and 10q suggest involvement of multiple tumor suppressor genes in the development of astrocytic gliomas of different malignancy grades.

Deletions of chromosome 10 are the most frequent genetic abnormality in glioblastomas. Several commonly deleted regions have been proposed; however, they are not coincident. We have deletion mapped chromosome 10 in 198 astrocytic gliomas using 53 microsatellite markers. Two commonly deleted regions on 10p were identified, one of which lies between D10S594 and D10S559 and the other between D10S1713 and D10S189. Most of 10q deletions were large and included a region distal to D10S554. Four glioblastomas of 122 had patterns suggestive of homozygous deletions at D10S541, a locus close and distally located to the PTEN/MMAC1 gene. Losses of alleles were found not only in glioblastomas (93%) but also in anaplastic astrocytomas (66%) and in astrocytomas (35%). Most glioblastomas lost one entire chromosome 10, while astrocytomas preferentially lost only 10p. The data suggest that a number of tumor suppressor genes on chromosome 10, in addition to PTEN/MMAC1, may be associated with astrocytic glioma development.

Astrocytoma↗
PubMed1998

Analysis of tumor recurrence following anterior skull base surgery.

In order to elucidate the predictive factors for tumor recurrence following skull base surgery and the significance of salvage surgery in cases of recurrence, we retrospectively surveyed the incidence, site, and time of local recurrences in 20 patients who underwent either anterior or anterolateral skull base surgery for malignant tumors invading the anterior cranial fossa between 1989 and 1995 at the University of Tokyo Hospital. Nineteen patients underwent total resections of malignancies, with recurrences and/or metastases occurring in 13. Local recurrences occurred at the skull base in 5 patients (group A), outside the skull base in 4 patients (group B), and in both locations in 2 patients (group C). The mean time interval between surgery and recurrence was 29 months in group A, and 4.2 months in groups B and C. The local recurrence-free rates were 51% at 1 year and 34% at 5 years. Both brain and/or dural invasion and a microscopic positive surgical margin were proven to be predictive factors for tumor recurrences. The 3-year local recurrence-free rate was 20% in patients with dural invasions and 83% in those without. The incidence of recurrence-free patients was 79% in cases with negative margins, with no patient being recurrence-free in positive cases. All recurrences found more than 6 months after the initial surgery resulted in patients being salvaged successfully by a second operation.

Adolescent↗
PubMed1998

Dumbbell type jugular foramen meningioma extending both into the posterior cranial fossa and into the parapharyngeal space: report of 2 cases with vascular reconstruction.

Two cases with huge dumbbell type jugular foramen meningioma with extension into the parapharyngeal space are reported. A well co-ordinated surgical strategy for total resection to this high risk tumour with neurosurgeons, otolaryngologists and plastic surgeons is mandatory to minimise operative complications. Both of our patients presented with a cervical mass and lower cranial nerve palsies, and had huge dumbbell type masses extending from the posterior cranial fossa through the jugular foramen to the parapharyngeal space, encasing the cervical internal carotid artery. Gross total resection of the tumours was successfully achieved by basically a 2-stage operation. In the first stage, posterior fossa tumours were removed by the transjugular approach, combined with the petrosal approach in one case. In the second stage, cervical tumours were removed along with the cervical carotid artery by the transcervical and/or transmandibular approach, followed by vascular reconstruction from the ipsilateral carotid artery to the middle cerebral artery using saphenous vein graft. From these experiences, we recommend this 2-stage operation for large dumbbell type meningiomas extending to the infratemporal/parapharyngeal space. The intracranial tumour is removed at the first operation. The extracranial portion is resected at the second, and if necessary, the involved cervical carotid artery is resected and simultaneous revascularisation using saphenous vein graft is performed with a vascularised free muscle graft. This strategy could maximise the functional preservation on the one hand, and minimise the surgical risk, such as postoperative infection, on the other.

Adult↗
PubMed1998

A preliminary report: clinical effects of otic solution of ofloxacin in infantile myringitis and chronic otitis media.

Patients with infantile myringitis or chronic otitis media may refuse treatment when antibiotics are to be administered orally. The present study was undertaken to treat myringitis and chronic otitis media with an otic solution of non-ototoxic ofloxacin in 21 children aged 0-15 years. They consisted of eight normal children, four children operated on for microtia, and nine so-called handicapped children mainly with advanced hearing impairment and retardation in mental development, or eight children with myringitis and 13 children with chronic suppurative otitis media. Otic solution of ofloxacin was instilled into the ear twice daily, in the morning and evening, for 7 days or more, the treatment time being 10 min. With the causative pathogen completely eradicated in 14 patients and the bacterial count reduced in three patients and unchanged in two patients, the results of treatment with ofloxacin may be considered to be excellent.

Anti-Infective Agents↗