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Biomedical subjects

Y Takeshima

Publications and source records attributed to Y Takeshima.

At least 19 recordsLinked to original sources

[Intralobar pulmonary sequestration with high level of serum CEA; report of a case].

We reported a case of intralobar pulmonary sequestration with a high level of the serum CEA. A 53-year-old woman whose chief complaint was cough was admitted to our hospital. Enhanced chest computed tomography (CT) revealed the mass in the left lower lung, lymph-nodes swelling, and the aberrant artery. Magnetic resonance angiography (MRA) conformed the aberrant artery from the descending aorta. The level of serum CEA elevated at 9.6 ng/ml. Left lower lobectomy was performed. A diagnosis of intralobar pulmonary sequestration (Pryce type II) was established in this case. Histopathologically, the peribronchial epithelial cells in pulmonary sequestration showed weak positive for anti-CEA monoclonal antibody. Postoperative course was uneventful and the serum CEA level was 3.5 ng/ml in the normal range at the postoperative 17th day.

Bronchopulmonary Sequestration↗

Gene amplification and protein expression of EGFR and HER2 by chromogenic in situ hybridisation and immunohistochemistry in atypical adenomatous hyperplasia and adenocarcinoma of the lung.

AIMS: To investigate the importance of gene amplification and EGFR (epidermal growth factor receptor) and HER2 protein expression during the progression of adenocarcinoma of the lung. METHODS: EGFR and HER2 gene amplification was examined in atypical adenomatous hyperplasia (AAH), bronchioloalveolar carcinoma (BAC), and adenocarcinoma with mixed subtypes (MX) by chromogenic in situ hybridisation (CISH), and protein expression was examined by immunohistochemistry using paraffin wax embedded tissues. RESULTS: EGFR and HER2 gene amplification was found in four and two of 86 cases, respectively, and was detected only in the invasive components of MX. EGFR and HER2 protein expression was seen in 24 and 18 of 86 cases, respectively. EGFR and HER2 proteins were not expressed in AAH but were expressed in one BAC case each. EGFR and HER2 proteins were expressed in 23 and 17 of 55 adenocarcinomas with MX. EGFR and HER2 protein expression was seen more often in the invasive components than in the BAC components of MX, and increased significantly as lesions progressed from AAH to BAC, early MX, and overt MX. Because EGFR and HER2 protein expression was frequently seen without gene amplification, other mechanisms apart from gene amplification may be associated with protein expression. CONCLUSIONS: EGFR and HER2 gene amplification may be a late event and EGFR and HER2 protein expression may be associated with the development of adenocarcinoma of the lung.

Adenocarcinoma↗

[Mucoepidermoid carcinoma with high level of serous carcinoembryonic antigen; report of a case].

We reported a case of mucoepidermoid carcinoma with a high level of the serum CEA. A 38-year-old woman was admitted because of abnormal chest shadow. Bronchoscopy revealed polypoid tumor occluding the lumen of right B3 bronchus. Bronchoscopic biopsy suggested a diagnosis of tubular adenocarcinoma. Chest computed tomography (CT) confirmed the mass in the right upper lung field and the swelling of right bronchial lymph node. The CEA level of serum elevated at 12.4 ng/ml. A right upper and middle lobectomy with mediastinal lymph nodes dissection was performed on August 26, 2003. Histopathologically, the polypoid tumor was a low grade mucoepidermoid carcinoma with partially extrabronchial extension. However, no lymph nodes metastasis were noted. The cytoplasms of about 45% of tumor cells showed positive for anti-CEA monoclonal antibody. Pathological stage was IB (T2N0M0). Seventeen months has passed with no evidence of recurrence and the CEA level of serum was in the normal range.

Adenocarcinoma↗

[Pulmonary pleomorphic carcinoma].

Pleomorphic carcinoma is a rare primary pulmonary malignancy. We report 2 surgical cases of pulmonary pleomorphic carcinoma. The first case was a 71-year-old male. Chest computed tomography (CT) showed a rapidly growing tumor with irregular density. Transbronchial lung biopsy revealed the tumor to be malignant. Left lower lobectomy was performed. Pathological diagnosis was pleomorphic carcinoma (pT2N2M0, stage IIIA). He died 8 months after surgery due to brain metastasis and mediastinal lymph node metastasis. The second case was a 74-year-old male who complained of bloody sputum. Chest CT showed a tumor with cavity in the right middle lobe. Brushing cytology under bronchofiberscopy revealed atypical cell. Right middle lobectomy and partial resection of the right lower lobe were performed. Pathological diagnosis was also pleomorphic carcinoma (pT2N0M0, stage IB). He has no findings of recurrence nor metastasis 15 months after the operation.

Aged↗

Rescue of dystrophin mRNA of Duchenne muscular dystrophy by inducing exon skipping.

Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease, and its victims usually succumb in their twenties. Many studies, including investigations into gene-replacement therapy, have been conducted in a search for a treatment for DMD, and the most promising treatment to date is rescue of mutant dystrophin mRNA by induction of exon skipping. On the basis of results from the molecular analysis of dystrophin Kobe, we propose a treatment for DMD in which antisense oligonucleotides induce exon skipping to edit out-of-frame dystrophin mRNA into in-frame, thereby converting severe DMD to a milder form. Here we review the progress of development of this alternative treatment, with a special focus on dystrophin Kobe.

Dystrophin↗

Analysis of dystrophin mRNA from skeletal muscle but not from lymphocytes led to identification of a novel nonsense mutation in a carrier of Duchenne muscular dystrophy.

Dystrophin mRNA expressed in peripheral lymphocytes of individuals with X-linked Duchenne muscular dystrophy (DMD) has been used as a source material for mutation analysis. Here we present the first report of failure of isolation of nonsense dystrophin mRNA in lymphocytes but success in skeletal muscle in a female carrier of DMD. The mutation responsible for dystrophin-negative muscle fibers of the carrier was analysed by direct sequencing of the reverse transcription PCR product of dystrophin mRNA. In her peripheral lymphocytes, no nucleotide change was detected in the 14 kb long mRNA. Remarkably, a novel nucleotide change of C1682T in exon 12, changing glutamine codon to stop codon (Q492X) was found to be present in her skeletal muscle. This change was heterozygous. Analysis of her genomic DNA disclosed heterozygous C and T nucleotides at nt 1682, confirming the genomic origin of the nonsense mutation. Although dystrophin cDNA prepared from lymphocytes was sequenced again after subcloning, mutation-retaining clone could not be isolated. This lymphocyte-specific disappearance of nonsense mRNA strongly suggested tissue-specific skewing of X-inactivation. However, both paternal and maternal dystrophin alleles were shown to be equally expressed in lymphocytes as well as in muscle, indicating no skewing of X-inactivation in lymphocytes. We concluded that the dystrophin mRNA of the DMD carrier was destabilized in lymphocytes. Our results indicated that analysis of mRNA in lymphocytes is not enough for exact carrier diagnosis of Duchenne muscular dystrophy.

Adult↗

The auditory evoked magnetic fields to very high frequency tones.

We studied the auditory evoked magnetic fields (AEFs) in response to pure tones especially at very high frequencies (from 4000 Hz to 40,000 Hz). This is the first systematic study of AEFs using tones above 5000 Hz, the upper audible range of humans, and ultrasound. We performed two experiments. In the first, AEFs were recorded in 12 subjects from both hemispheres under binaural listening conditions. Six types of auditory stimulus (pure tones of five different frequencies: 4000 Hz, 8000 Hz, 10,000 Hz, 12,000 Hz, 14,000 Hz, and a click sound as the target stimulus) were used. In the second experiment, we used 1000 Hz, 15,000 Hz, and two ultrasounds with frequencies of 20,000 Hz and 40,000 Hz. The subjects could detect all stimuli in the first experiment but not the ultrasounds in the second experiment. We analyzed N1m, the main response with approximately 100 ms in peak latency, and made the following findings. (1) N1m responses to the tones up to 12,000 Hz were clearly recorded from at least one hemisphere in all 12 subjects. N1m for 14,000 Hz was identified in at least one hemisphere in 10 subjects, and in both hemispheres in six subjects. No significant response could be identified to ultrasounds over 20,000 Hz. (2) The amplitude of the N1m to the tones above 8000 Hz was significantly smaller than that to 4000 Hz in both hemispheres. There was a tendency for the peak latency of the N1m to be longer for the tones with higher frequencies, but no significant change was found. (3) The equivalent current dipole (ECD) of the N1m was located in the auditory cortex. There was a tendency for the ECD for the tones with higher frequencies to lie in more medial and posterior areas, but no significant change was found. (4) As for the interhemispheric difference, the N1m amplitude for all frequency tones was significantly larger and the ECDs were estimated to be located more anterior and medial in the right hemisphere than the left. The priority of the right hemisphere, that is the larger amplitude, for very high frequency tones was confirmed. (5) The orientation of the ECD in the left hemisphere became significantly more vertical the higher the tones. This result was consistent with previous studies which revealed the sensitivity of the frequency difference in the left hemisphere. From these findings we suggest that tonotopy in the auditory cortex exists up to the upper limit of audible range within the small area, where the directly air-conducted ultrasounds are not reflected.

Acoustic Stimulation↗

Predictive factors for long-term survival in patients with intrahepatic cholangiocarcinoma.

BACKGROUND: In order to elucidate the predictive factors for long-term survival in patients with intrahepatic cholangiocarcinoma (ICC), we evaluated 7 patients who survived for more than 5 years (5-year survivors). METHODS: We examined the clinicopathologic and biologic factors of the 5-year survivors, and these findings were then compared with those in 20 patients who died within 5 years after surgery (control group). RESULTS: In the 5-year survivors, the gross appearance of the tumors included a mass-forming (MF) type in 5 cases, an intraductal growth (IG) type in 1, and another type (microcarcinoma with hepatolithiasis) in 1. No case demonstrated a periductal infiltrating (PI) type. Except for 1 case with an IG type tumor, no lymph node metastasis was seen in any patients. All of the 5-year survivors were classified from stage I to III, and all also underwent a curative resection. The clinicopathologic factors demonstrating significant differences between the 5-year survivors and the control group included the gross type of the tumor, lymph node involvement, the surgical margin, curability, and pTNM stage. CONCLUSION: The predictive factors for long-term survival in patients with ICC are thus suggested to include not only tumor staging and curability, but also lymph node metastasis and the gross type of the tumors.

Actuarial Analysis↗

Extra-abdominal desmoid tumor presenting as an intrathoracic tumor: case report and literature review.

A case of an extra-abdominal desmoid tumor presenting as an intrathoracic tumor (intrathoracic desmoid tumor) in a 46-year-old woman is reported. The tumor originated in the left chest wall and protruded into the left pleural cavity. Simple resection was carried out. The tumor, measuring 13 x 9 x 7 cm, was solid, gray-tan in color, and covered with parietal pleura. Histologically, the tumor was composed of a hypocellular arrangement of spindle-shaped cells with a fibromyxoid background. In some areas, keloid-like hyalinized collagen fibers proliferated, and a perivascular hypercellular area was seen. Immunohistochemical analysis showed that the cytoplasms of the tumor cells were strongly positive for vimentin, and some tumor cells were positive for alpha-smooth muscle actin, but all tumor cells were negative for CD34. These findings were consistent with the characteristics of an intrathoracic desmoid tumor. The differential diagnoses, in particular solitary fibrous tumor and tumors with a myofibroblastic nature, are discussed.

Actins↗

Immunohistochemical study of Ki-67 (MIB-1), p53 protein, p21WAF1, and p27KIP1 expression in benign, atypical, and anaplastic meningiomas.

Histologic grading of meningiomas has prognostic and clinical therapeutic implications. Meningiomas were histologically classified into 3 different World Health Organization grades. Grade II, an atypical meningioma, was defined by major and various minor histologic criteria. However, these histologic criteria sometimes are not fulfilled, and other criteria are necessary. We studied and analyzed the immunohistochemical expression of MIB-1, p53, p21WAF1, p27KIP1 proteins in 146 cases of meningiomas, including 109 benign, 27 atypical, and 10 anaplastic meningiomas. Most of the benign meningiomas expressed low MIB-1 labeling index (mean, 1.5%), and fewer cases had p53 protein expression. In contrast, the anaplastic meningiomas had a high labeling index of MIB-1 (mean, 19.5%) and always expressed p53 protein, with a mean labeling index of 6.3%. The atypical meningiomas had MIB-1 and p53 labeling indexes in the range between benign and anaplastic meningiomas, with mean labeling indexes of 8.1% and 3.5%, respectively. These expressions were statistically significant among benign, atypical, and anaplastic meningiomas (P <.001). We conclude that the immunohistochemistry of MIB-1 and p53 protein will be valuable in discriminating atypical meningiomas from benign or anaplastic meningiomas, at least in histologically borderline cases. In addition, we also found direct correlation of p21 and inverse correlation of p27 expressions in meningiomas with increasing histologic grade and proliferative index.

Aged↗

Heterogeneous genetic alterations in ovarian mucinous tumors: application and usefulness of laser capture microdissection.

Histologic observation of ovarian mucinous tumors suggests that there is a multistep transition through the accumulation of genetic alterations. We analyzed loss of heterozygosity (LOH) and replication error (RER) on TP53 and D17S855 as well as K-ras point mutations of the heterogeneous histologic areas of the same tumor in 26 cases of ovarian mucinous tumor. The laser capture microdissection (LCM) technique has been applied to the study of K-ras point mutation in 10 cases. As for genetic alterations for LOH or RER on TP53 and D17S855, 2 (1 borderline tumor and 1 carcinoma) of 14 cases and 4 (1 borderline tumor and 3 carcinomas) of 12 cases, respectively, showed genetic heterogeneities in different histologic areas. Six (2 borderline tumors and 4 carcinomas) of 18 cases showed heterogeneity of K-ras point mutation in the different histologic areas of the same tumor, and 5 (1 cystadenoma with Brenner tumor component, 2 borderline tumors, and 2 carcinomas) of 10 cases showed heterogeneous K-ras mutation pattern in the same tumor when the LCM technique was used. Atypical areas tended to show K-ras point mutations frequently. Out of 3 cases of mixed mucinous cystadenoma and Brenner tumor, 1 case showed K-ras point mutation in the Brenner tumor area but not in the area of mucinous cystadenoma. These preliminary results suggest that a subset of ovarian mucinous tumors occur through multistep carcinogenesis and show that LCM is useful for molecular pathologic studies.

Adult↗

[Investigation on zoonosis by disseminating questionnaire to members of medical associations in Kobe and Fukuoka].

With the purpose of studying the involvement of physicians to zoonosis, investigation on the consciousness was performed by disseminating a questionnaire to members of Medical Associations of Kobe City (2,584 members) and Fukuoka City (1,814 members). From the members in Kobe, 1,165 replies were collected (answer ratio: 45.1%) and 774 replies from the members in Fukuoka (answer ratio: 42.7%). About 70-80% of all physicians answering the questionnaire stated that they had examined the patients with infectious diseases at a ratio of less than 10% to a total of patients examined. Among them, 70% of the doctors had asked the patients as to whether or not the patients were keeping pet animals or had traveled overseas recently when infectious diseases was suspected. There were 738 doctors (38.1%) (1,355 cases), who had suspected or made definitive diagnosis on 15 diseases of zoonosis as stipulated in the new Infectious Disease Control Law for the recent 5 years. In all, 365 doctors (18.9%) examined the patients who were suspected to have had an infection from pet animals. The causative animals primarily included dogs, cats, and birds such as parakeet, while monkeys, tortoises, etc. were found in several cases. About one half of the physicians felt that the cases of infectious diseases and zoonosis would increase in the future. In the entry of free opinions relating to the effective measures for the prevention of zoonosis, 712 physicians (39.8%) entered 1,050 proposals. The details of these proposals were: 444 proposals on "administrative measures". 244 on the need of "education" to citizens, and 201 on the importance of "medical management". About 80% of the physicians replied that they would cooperate for the secondary investigation. It appears that the physicians place much expectation on adequate measures against zoonosis. Namely, they expect much on the establishment of a reliable network, i.e. the network of administrative authorities--physicians--veterinarians--pet animal suppliers--pet animal keepers.

Animals↗

In vivo histological changes occurring in hydroxyapatite cranial reconstruction--case report.

Histological changes were observed in a hydroxyapatite plate and hydroxyapatite granules used to repair a craniotomy defect and removed after 2 years and 9 months of use. The hydroxyapatite plates and granules had completely fused to the cranium, with new bone formation on the dural side extending in a three-dimensional matrix along the pores with the Haversian system in the center. New bone formation was less extensive under the artificial dura than under normal dura. This finding suggests that the dura has the ability to promote bone formation. A new vessel was found along the interconnecting pores. The interconnecting pores allow osteoconduction in the hydroxyapatite plate, so new bone formation can progress. Hydroxyapatite has osteoconduction properties and is biocompatible, so gains strength in vivo through new bone formation, and is the ideal material for artificial bones. Factors important to achieving good bone formation after cranial reconstruction surgery include presence of the dura, and pore size approximate to the Haversian system (100-500 microns) and interconnecting pores in the hydroxyapatite plate.

Adult↗

Purine-rich exon sequences are not necessarily splicing enhancer sequence in the dystrophin gene.

Purine-rich sequences within exons are proposed to promote proper splicing as splicing enhancers. In order to test this supposition in the dystrophin gene, which is characterized by the large size of its introns, purine-rich sequences from three exons (exons 43, 46 and 53) were examined for their splicing enhancer activity by using a Drosophila doublesex pre-mRNA. The most powerful activating effect on upstream intron splicing was seen with a sequence from exon 43. A sequence from exon 53 showed relatively low activity, whilst that from exon 46 had little effect. To characterize the splicing enhancer sequences in exons 53 and 46 further, entire exons were divided into 30nt fragments that were examined separately for their splicing enhancer activity. In exon 53, two fragments located at the 5' and 3' ends, respectively, had strong splicing enhancer activity, although they were not the most purine-rich regions of the exon. In contrast, all of the fragments derived from exon 46 had little activity. These results suggest that different exons in the dystrophin transcript are subject to different mechanisms of control by the splicing machinery.

Animals↗