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Biomedical subjects

T Nagashima

Publications and source records attributed to T Nagashima.

At least 19 recordsLinked to original sources

Synthesis and characterization of xylan-coated magnetite microparticles.

This work evaluates an experimental set-up to coat superparamagnetic particles in order to protect them from gastric dissolution. First, magnetic particles were produced by coprecipitation of iron salts in alkaline medium. Afterwards, an emulsification/cross-linking reaction was carried out in order to produce magnetic polymeric particles. The sample characterization was performed by X-ray powder diffraction, laser scattering particle size analysis, optical microscopy, thermogravimetric analysis and vibrating sample magnetometry. In vitro dissolution tests at gastric pH were evaluated for both magnetic particles and magnetic polymeric particles. The characterization data have demonstrated the feasibility of the presented method to coat, and protect magnetite particles from gastric dissolution. Such systems may be very promising for oral administration.

Administration, Oral↗

Analyses of the factors influencing bone graft infection after delayed cranioplasty.

BACKGROUND: Several factors influencing bone graft infection after delayed cranioplasty are analyzed in order to reduce the occurrence of infection. METHODS: For about 10 years, from March 1995 to February 2005, delayed cranioplasty was performed for 206 cases. The cases comprised 124 males and 82 females. Age distribution of the patients ranged from 6 months to 79 years old. The mean postoperative follow-up period was 1834 days. Autogenous bone, which was preserved in 100% ethanol at -20 degrees C and autoclaved before operation, was used in 54 patients. Polymethylmethacrylate (PMMA) was used in 55 patients. Custom-made PMMA was used in 3 patients. Custom-made titanium mesh was used in 77 patients. Custom-made ceramics (Alumina-ceramics 10 cases and hydroxyapatite 7 cases) was used in 17 patients. FINDINGS: Autoclaved and autogenous bone graft and PMMA have a significantly high rate of graft infection. Titanium mesh has the significantly lowest rate of graft infection. Alumina-ceramic has a merit that it has sufficient strength, however the number of cases using custom-made ceramics including alumina-ceramic was relatively small, and thus we cannot find significant differences in infection rate compared with that of other materials. There was no statistically significant difference in the bone graft infection rate among four categories of preceding diseases; cerebrovascular diseases, head trauma, infectious diseases, and brain tumour. CONCLUSION: Autoclaved and autogenous bone grafts and PMMA have a significantly higher rate of graft infection. Titanium mesh has the significantly lowest rate of graft infection.

Adolescent↗

[Pleomorphic lung cancer; a clinicopathologic study].

Pulmonary pleomorphic carcinoma is a comparatively rare histologic type of lung carcinoma, and the incidence among all lung carcinomas has been reported to be 0.4%. We reported our experience with 8 patients who had been diagnosed as pulmonary pleomorphic carcinoma, and discussed clinicopathologically the preoperative diagnosis and treatment. In 2 of 8 patients, preoperative transbronchial lung biopsy revealed spindle cell component, highly suggesting pulmonary pleomorphic carcinoma. All patients underwent surgical treatment and 2 of then had incomplete resections because of intrathoracic disseminations or carcinomatous pericarditis. Pathological findings showed invasions into the surrounding thoracic organs such as the chest wall, pericardium, adjacent pulmonary lobe or mediastinal pleura in 5 cases, intrapulmonary metastasis of the same lobe in 3 and lymph node involvement in 3. Recurrence occurred in 6 patients immediately after the operation. Although the preoperative diagnosis of biphasic tumor such as pulmonary pleomorphic carcinoma is difficult, it is possible to suspect the diagnosis when sarcomatous components were detected by preoperative biopsy. The efficacy of chemotherapy and radiotherapy have not been established yet, and thus we would like to emphasize that surgery might be the treatment of choice.

Adult↗

[Collision cancer of squamous cell carcinoma and small cell carcinoma of the lung; report of a case].

We report a rare case of a primary collision cancer in the lung consisting of squamous cell carcinoma and small cell carcinoma. A 65-year-old man with an abnormal shadow in the right S6 was diagnosed as squamous cell carcinoma by transbronchial lung biopsy. A right lower lobectomy with mediastinal lymph node dissection was performed. The pathological stage of squamous cell carcinoma was IIIA (T2N2M0). The other element diagnosed by pathological examination was small cell carcinoma of which pathological stage was IA (T1N0M0). Each element was clearly distinguished and touched each other. Following the operation, the patient received systemic chemotherapy against small cell carcinoma with cisplatin and irinotecan hydrochloride for 1 course, and cisplatin and etoposide for 3 courses. Since the prognosis of collision cancer is generally reported to be influenced by more advanced element of cancer, the prognosis of the present case is suspected to be dependent on the squamous cell carcinoma.

Aged↗

[Surgical resection of T3 and T4 lung cancer].

Lung cancer invading neighboring anatomical structures such as the chest wall, pericardium, diaphragm, and left atrium are categorized as T3 or T4, which is regarded as locally advanced lung cancer. The purpose of this study was to evaluate results of surgical treatment of T3-4N0-2M0 non-small cell lung cancer according to involved organs. From 1981 to April 2005, 148 patients with lung cancer invading neighboring organs were surgically treated in our hospital. The 5-year survival was 41.4% in all cases. According to 5-year survival of clinical characteristics, the chest wall (parietal pleura) group (45.5%) had a significantly better prognosis compared with the left atrium (0%, p = 0.03) and diaphragm (0%, p = 0.04) groups. T3N0 (50.3%), IIB (55.4%), IIIA (44.6%), and complete resection groups (49.0%) showed a significantly better prognosis compared with T3N2 (27.9%, p = 0.01), III B (0%, p < 0.0001), and incomplete resection groups (13.9%, p < 0.0001), respectively. These results indicate that the prognosis of patients with N2 disease or incomplete resection remains poor in regardless with the type of involved organs.

Adult↗

Quantitative analysis of hyperosmotic and hypothermic blood-brain barrier opening.

Hyperosmotic opening of the blood-brain barrier (BBB) by mannitol is being used to enhance drug transport in human brains. Recently, cooling of the solution has been reported to have potential to open the BBB. However, the mechanism in barrier opening and closure remains elusive. We studied the rapid changes in cerebrovascular permeability after hyperosmotic and hypothermic BBB opening in rats, and then demonstrated that the Na+/Ca++ exchange blocker (KB-R7943) prolongs opening. BBB opening was attained by using intra-arterial infusion of hyperosmotic mannitol (1.6 M) and 1.1 M mannitol (which is less hyperosmotic than commonly used mannitol) at 4 degrees in Sprague-Dawley (SD) rats. To measure the changes in cerebrovascular permeability, perfusate-containing [14C]-sucrose was infused intra-arterially at different time points following hyperosmotic and hypothermic stress. Cerebrovascular permeability was then measured with the in situ brain perfusion technique. 1.6 M Mannitol produced opening of the BBB but the duration of the opening was less than 30 minutes. Use of 1.1 M Mannitol at 4 degrees indicated the same results. We then investigated the effect of a Na/Ca ion exchange blocker (KB-R7943) in both hyperosmotic and hypothermic BBB opening. KB-R7943 extended BBB opening up to 30 min without affecting the peak level of BBB permeability at 5 minutes. Our findings represent important experimental information regarding pharmacological manipulation of BBB opening. The possibility of prolonging the transient opening of the BBB has major clinical implications.

Animals↗

Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.

Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.

Alternative Splicing↗

In vivo selective expansion of gene-modified hematopoietic cells in a nonhuman primate model.

A major problem limiting hematopoietic stem cell (HSC) gene therapy is the low efficiency of gene transfer into human HSCs using retroviral vectors. Strategies, which would allow in vivo expansion of gene-modified hematopoietic cells, could circumvent the problem. To this end, we developed a selective amplifier gene (SAG) consisting of a chimeric gene composed of the granulocyte colony-stimulating factor (G-CSF) receptor gene and the estrogen receptor gene hormone-binding domain. We have previously demonstrated that primary bone marrow progenitor cells transduced with the SAG could be expanded in response to estrogen in vitro. In the present study, we evaluated the efficacy of the SAG in the setting of a clinically applicable cynomolgus monkey transplantation protocol. Cynomolgus bone marrow CD34(+) cells were transduced with retroviral vectors encoding the SAG and reinfused into each myeloablated monkey. Three of the six monkeys that received SAG transduced HSCs showed an increase in the levels of circulating progeny containing the provirus in vivo following administration of estrogen or tamoxifen without any serious adverse effects. In one monkey examined in detail, transduced hematopoietic progenitor cells were increased by several-fold (from 5% to 30%). Retroviral integration site analysis revealed that this observed increase was polyclonal and no outgrowth of a dominant single clonal population was observed. These results demonstrate that the inclusion of our SAG in the retroviral construct allows selective in vivo expansion of genetically modified cells by a non-toxic hormone treatment.

Animals↗

Quantitative analysis of papaverine-mediated blood-brain barrier disruption in rats.

The blood-brain barrier (BBB) is a permeability barrier of interconnected brain capillary endothelial cells. Intraarterial infusion of papaverine relieves cerebral vasospasms by inhibiting smooth muscle contractions and it may simultaneously lead to a disruption of BBB permeability. To date, the mechanism underlying this phenomenon and the quantification of BBB disruption remains elusive. We first examined the changes in cerebrovascular permeability after an intracarotid infusion of papaverine (0.20%) in rats by an in situ brain perfusion technique. We then demonstrated that changes in cerebrovascular permeability depend on the concentration of papaverine. This is the first study in which the degree of BBB disruption was accurately quantified in terms of [(14)C]sucrose and it was demonstrated that papaverine has a prolonged effect on cerebrovascular permeability. This result suggests the importance of in vivo experiments for a precise evaluation of permeability for many other agents, particularly for the central nervous system.

Animals↗

SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein.

Genetic etiologies of at least 20% of autosomal dominant cerebellar ataxias (ADCAs) have yet to be clarified. We identified a novel spinocerebellar ataxia (SCA) form in four Japanese pedigrees which is caused by an abnormal CAG expansion in the TATA-binding protein (TBP) gene, a general transcription initiation factor. Consequently, it has been added to the group of polyglutamine diseases. This abnormal expansion of glutamine tracts in TBP bears 47--55 repeats, whereas the normal repeat number ranges from 29 to 42. Immunocytochemical examination of a postmortem brain which carried 48 CAG repeats detected neuronal intranuclear inclusion bodies that stained with anti-ubiquitin antibody, anti-TBP antibody and with the 1C2 antibody that recognizes specifically expanded pathological polyglutamine tracts. We therefore propose that this new disease be called SCA17 (TBP disease).

Adult↗

The effects of the Na(+)/Ca(++) exchange blocker on osmotic blood-brain barrier disruption.

Osmotic disruption of the blood-brain barrier (BBB) by mannitol is currently being used to enhance drug delivery in human brains. Despite clinical and experimental interest, to date the time course in the early phase of disruption has not been accurately identified. The mechanism in barrier closure also remains elusive. We first studied the rapid change in cerebrovascular permeability after BBB disruption in rats, and then demonstrated that the Na(+)/Ca(++) exchange blocker (KB-R7943) prolongs osmotic disruption. Osmotic BBB disruption was attained by using intra-arterial infusion of hypertonic mannitol in Sprague-Dawley (SD) rats. To measure the changes in cerebrovascular permeability, perfusate containing [14C]-sucrose was infused intra-arterially at different time points following osmotic stress. Cerebrovascular permeability was then measured with the in situ brain perfusion technique. This is the first in vivo study demonstrating that osmotic disruption is prolonged by the Na(+)/Ca(++) exchange blocker, which did not affect the peak level of BBB disruption. The exact time course of cerebrovascular reversibility was studied and the earliest BBB disruption was seen to occur 5 min after osmotic stress. Histopathological examination after osmotic disruption with the Na(+)/Ca(++) exchange blocker showed no neuronal damage in rat brains. Our findings represent important experimental information regarding pharmacological manipulation of BBB disruption. The possibility of prolonging the transient opening of the BBB has major clinical implications.

Animals↗

Surgical approaches and strategies for skull base chordomas.

OBJECT: The management of chordomas involving the skull base continues to present a number of treatment-related problems. Recently, both radical resection and charged-particle irradiation or stereotactic radiosurgery have reportedly been found effective for tumor control and for promoting a better quality of life in patients. In this article the authors analyzed the outcomes in 17 patients with skull base chordomas who were surgically treated at Kobe University Hospital between 1972 and 2000. METHODS: Preoperative radiological examinations included magnetic resonance imaging, computerized tomography, angiography, and balloon occlusion test of the internal carotid artery. Among the various surgical approaches used to remove the tumor were the frontoorbitozygomatic, transmaxillary, transcondylar, transsphenoidal, and the transbasal. Total removal was achieved in two (12%), near-total removal in three (18%), subtotal removal in nine (52%), and partial removal in three patients (18%). Since 1990, chordomas have been radically resected via various skull base approaches; the combined total or near-total removal rate has been 80% in this period. Radical removal of the tumors has not led to an increased risk. At the final follow-up review (mean 59.5 month), 75% of the patients were still alive, and 25% had died of chordoma recurrence. The overall recurrence-free survival rate was 82% at 3 years and 51% at 5 years. The 5-year recurrence-free survival rate in the five patients who underwent the operation during the past decade was 77% (mean follow up of 5.2 years). In two patients with recurrent tumors who underwent radiosurgery, no evidence of tumor regrowth was demonstrated at 3 years posttreatment. CONCLUSIONS: The authors suggest that for the treatment of skull base chordomas radical resection is a key factor for longer survival and improved quality of life. Patients with sufficiently small tumors, which show a favorable configuration and location, can be suitable candidates for stereotactic radiosurgery.

Adolescent↗

Drug-resistance gene expression and progression of astrocytic tumors.

To clarify the influence of biochemotherapy on the progression of astrocytic tumors, the expression of O6-methylguanine DNA-methyltransferase (MGMT) mRNA, as well as of other drug-resistance- and drug-sensitivity-related genes such as multidrug resistance gene 1, multidrug resistance-associated protein, glutathione S-transferase-pi, DNA topoisomerase II, and interferon receptor mRNA, and the interferon regulatory factor (IRF)-1 and -2 ratios in gliomas were investigated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). The mean MGMT/beta2-microglobulin (beta2-MG) ratio for 130 neuroepithelial tumors was 8.2 +/- 17.8. The mean ratio of 45 glioblastomas was significantly higher than that for the other 85 tumors. In contrast, the mean of 26 low-grade gliomas was significantly lower than that of other tumors. The mean IRF-1/IRF-2 ratio of 16 other brain tumors that mainly consisted of medulloblastomas was significantly greater than that of the other 114 tumors. Almost no significant differences were observed between primary and recurrent tumors in the expression of any gene, and before and after therapy with corresponding drugs. The mean MGMT/beta2-MG ratio in primary glioblastomas was significantly higher than that in secondary tumors. These findings suggest that native drug resistance is more important than acquired resistance when glioma therapy is considered.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Quantitative morphometric analysis of fine needle aspirates of breast carcinoma.

BACKGROUND: Reports of morphometric analysis using computerized digitized images of fine needle aspirates of breast cancer are rare. We aimed to evaluate whether quantitative morphometric estimations of cytological nuclear features could be used for preoperative prediction of the risk of recurrence as well as chemosensitivity. METHODS: Seventy consecutive breast cancer patients were treated with preoperative chemotherapy (Doxifluridine 800 mg/body/day, orally) for 4 weeks and subsequently they underwent surgery. Using Papanicolaou-stained cytological materials, computerized morphometric analyses were performed. Mean nuclear area (NA) was measured and the coefficient of variation of NA (NACV) was calculated as the quantitative parameter of nuclear atypism. NA and NACV were compared with prognostic factors (tumor size, histological grade, hormone receptor status, nodal status, and ploidy status), and with the response to the chemotherapy. RESULTS: NA and NACV were significantly associated with hormone receptor status and ploidy status (p<0.05). NACV correlated with histological grade (p<0.05). Neither NA nor NACV were associated with tumor size and nodal status. Patients with high NACV (>35%) had lower rates of disease-free survival (p<0.05) than those with low NACV (< or =35%). Responders to preoperative chemotherapy had statistically larger NA, higher NACV and higher S-phase fraction at the time of diagnosis compared with non-responders (p<0.001, p<0.0005, and p<0.05 respectively). CONCLUSIONS: Morphometric analysis of preoperative fine needle aspirates reflects important clinical information, such as the risk of recurrence, and particularly, chemosensitivity.

Biopsy, Needle↗

Two mutations of the Gsalpha gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia.

Pseudohypoparathyroidism Ia (PHP-Ia), is an inherited disease with clinical hypoparathyroidism caused by parathyroid hormone resistance (PTH), and shows the phenotype of Albright hereditary osteodystrophy (AHO), including short stature, obesity, round face, brachydactyly, and subcutaneous ossification. This disease is caused by mutation that inactivates the alpha-subunit of Gs, the stimulatory regulator of adenylyl cyclase. Here, a novel frameshift mutation (delG at codon 88) in exon 4, and a missense mutation (R231H) in exon 9 of the Gsalpha gene were identified in two Japanese patients with sporadic PHP-Ia. Deletion of a G in exon 4 at codon 88 in the first patient produced a premature stop codon, resulting in the truncated protein. The second patient had a previously reported R231H mutation. Because this amino acid is located in a region, switch 2, that is thought to interact with the betagamma subunit of Gsalpha protein, this mutation may impair Gs protein function. We report here one novel Gsalpha mutation, and note that mutations in Japanese patients with PHP-Ia are probably heterogeneous.

Adult↗