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Biomedical subjects

T Inui

Publications and source records attributed to T Inui.

At least 73 records · Page 4Linked to original sources

Genomic alterations in human meningiomas detected by restriction landmark genomic scanning and immunohistochemical studies.

Using restriction landmark genomic scanning (RLGS) methods, 21 samples of human meningioma were analyzed. We found 3 alterations in the genomic DNAs of tumor samples located on chromosomes 5, 14 and 17 which appear to be common to the meningothelial subtype. Two other separate genetic abnormalities located on chromosomes 9-12 and 20 are apparently associated with atypical meningiomas. In addition, the neurofibromatosis type 2 gene is apparently involved in more than half of the tumor samples. There appear to be both common and type-specific genetic mutations associated with the formation and progression of human meningiomas.

Adult↗

[Properties of distortion of the figures in visual short-term memory].

We investigated the distortion that occurs during the storage of representations in visual short-term memory by using smooth closed figures with varying stimulus complexity and similarity. In similarity judgments, the results suggested that the psychological similarity between two figures was based on averaging physical similarities of matched features. In a detection experiment, the results showed that the processing of detection was limited in its capacity for the precision of shape, and that it was more difficult to detect the precise shape in the case of complex figures. In a recognition experiment, the results showed that forgetting occurred during a one-second retention interval. These two results showed that internal noise distorts both detection and retention processes. These findings suggested that representations of the complex figures with many features were distorted to a larger degree because each feature was individually masked with internal noise. It is concluded that the psychological similarity between an input pattern and a distorted pattern stored in short-term memory is invariant with stimulus complexity.

Adult↗

[A visual mechanism in curve detection].

To investigate how a smooth curve is processed in the human visual system, we introduce a new grouping principle explaining perceptual organization. Five observers were presented with arrays of band-pass elements, and the detection performance of an undulating path among randomly oriented distractors was measured as a function of the number of path elements and the orientation differences between adjacent path elements. We found that the undulating path was better detected when the number of path elements was large or the orientation differences were small and constant. Based on these results, we propose a model that groups the path elements to be perceived as a contour; local orientation differences are detected by curvature channels, the outputs of these channels are globally pooled with lateral inhibition, and the signals are detected by contour detectors of a threshold device.

Form Perception↗

Chemical synthesis of the precursor molecule of the Aequorea green fluorescent protein, subsequent folding, and development of fluorescence.

The present paper describes the total chemical synthesis of the precursor molecule of the Aequorea green fluorescent protein (GFP). The molecule is made up of 238 amino acid residues in a single polypeptide chain and is nonfluorescent. To carry out the synthesis, a procedure, first described in 1981 for the synthesis of complex peptides, was used. The procedure is based on performing segment condensation reactions in solution while providing maximum protection to the segment. The effectiveness of the procedure has been demonstrated by the synthesis of various biologically active peptides and small proteins, such as human angiogenin, a 123-residue protein analogue of ribonuclease A, human midkine, a 121-residue protein, and pleiotrophin, a 136-residue protein analogue of midkine. The GFP precursor molecule was synthesized from 26 fully protected segments in solution, and the final 238-residue peptide was treated with anhydrous hydrogen fluoride to obtain the precursor molecule of GFP containing two Cys(acetamidomethyl) residues. After removal of the acetamidomethyl groups, the product was dissolved in 0.1 M Tris. HCl buffer (pH 8.0) in the presence of DTT. After several hours at room temperature, the solution began to emit a green fluorescence (lambdamax = 509 nm) under near-UV light. Both fluorescence excitation and fluorescence emission spectra were measured and were found to have the same shape and maxima as those reported for native GFP. The present results demonstrate the utility of the segment condensation procedure in synthesizing large protein molecules such as GFP. The result also provides evidence that the formation of the chromophore in GFP is not dependent on any external cofactor.

Amino Acid Sequence↗

A functional MRI analysis of comprehension processes of Japanese sentences.

We tried to identify the mechanisms directly related to syntactic processing in an fMRI experiment using strictly controlled sets of verbal stimuli. In two conditions, center-embedding and left-branching conditions, the same sets of words were used to construct stimulus sentences, while only the word order reflecting their syntactic structure was different. The subject's task was to understand the relationship among three characters mentioned in the sentences. A difference of activation in Broca's area (BA44 and 45) between the two conditions was found. This result suggests that these areas are involved in syntax-related processing. Furthermore, it was suggested that the posterior part of the frontal lobe (BA6/9) and the inferior parietal area (BA39/40) are involved in the understanding of the relationship among the three characters mentioned in each sentence.

Frontal Lobe↗

Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.

We report on the clinical, pathological, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7+/-3.1 years (mean+/-SD), and loss of ambulance occurred at 38.5+/-2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes. In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family. The former mutation results in a W360R substitution in the proteolytic site of calpain 3, and the latter in a deletion of the Ca2+-binding domain.

Age of Onset↗

Frequent alterations of cell-cycle regulators in astrocytic tumors as detected by molecular genetic and immunohistochemical analyses.

Alterations of CDKN2A, RB, and cyclin D1 genes and expression of their products in astrocytic tumors were studied using a combination of molecular genetic and immunohistochemical assays. In addition, the association of gene status with clinical outcome was evaluated. Alterations of CDKN2A and RB gene in 30 lesions were analyzed by single-strand conformation polymorphism of polymerase chain reaction (PCR-SSCP), direct sequencing, and Western blotting. Methylation of the CDKN2A promoter was detected by methylation-specific PCR. Immunohistochemistry was applied to determine the expression of gene products in tumors from 94 patients for whom clinical outcome was also evaluated. Analyses of the CDKN2A gene revealed 12 homozygous or hemizygous deletions, one mutation in exon 1, and three methylations in the promoter. Expression of p 16 protein was not detected in 18 of 30 cases. RB mutations leading to loss of expression of the pRb were found in four (13%) cases, and six were immunohistochemically negative for this protein. Overexpression of cyclin D1 was obtained in 51 (54%) of 94 cases. Patients with pRb-negative tumors had a significantly greater risk of earlier death than those with p16 and cyclin D1 alterations, Both p16 and pRb immunohistochemistry provides useful complementary information and may provide valuable predictive information in screening. The biological consequences of deregulating individual components along cell control pathways are unequal, perhaps reflecting their hierarchical roles in the G1 checkpoint.

Adolescent↗

Genetic variations in recurrent astrocytic tumors detected by restriction landmark genomic scanning.

The genetic mechanisms associated with recurrence of advanced astrocytic tumors are poorly understood. We therefore analyzed 24 biopsy specimens from 12 patients with a recurrent astrocytic tumor by a two-dimensional gel electrophoresis method, termed restriction landmark genomic scanning (RLGS). Four spot changes were commonly present in the primary astrocytomas, indicating that the corresponding gene alterations were early events in the development of this tumor type. Altered spots were more frequent and of different distribution in recurrent tumors than in the primary astrocytomas. In particular, specifically increased intensity for spots on chromosomes 9-12 and 18 were observed in the secondary tumors, suggesting a relation with recurrence. The same spot changes observed in primary tumors were also found in the respective secondary lesions but with strikingly different densities in some cases, suggesting increased genetic instability. The altered segments provide important candidate regions for the search for genes involved in events leading to progression and more malignant recurrent tumors.

Astrocytoma↗

Cerebral revascularization using omentum and muscle free flap for ischemic cerebrovascular disease.

BACKGROUND: Indirect cerebral revascularization has been generally accepted in the management of brain ischemia in moyamoya disease. We performed indirect cerebral revascularization by using omental flap and muscle flap techniques for the treatment of ischemic cerebrovascular disease. METHODS: Ten patients with ischemic cerebrovascular disease including three with adult moyamoya disease underwent this procedure (omental flap on eight sides and muscle flap on five sides). The muscle used for the flap was the serratus anterior muscle on two sides and shaved latissimus dorsi muscle on three sides. Angiography and cerebral blood flow studies were performed in all patients preoperatively and postoperatively. All patients demonstrated severely impaired cerebrovascular reserve capacity due to occlusive disease. RESULTS: There was one patient each with perioperative death and intracranial infection following omental flap loss, and two patients had perioperative strokes. The average follow-up period was 23.2 months. Of the nine surviving patients, all eight except for the one with flap loss had good outcome with complete resolution of neurologic episodes. CONCLUSIONS: It is concluded that this method seems to be effective in selected patients with ischemic cerebrovascular disease.

Adult↗

Genomic aberrations in renal cell carcinomas detected by restriction landmark genomic scanning.

In order to reveal and characterise genetic events occurring in renal tumorigenesis, samples of sporadic renal cell carcinomas (RCCs) were examined using restriction landmark genomic scanning (RLGS), an electrophoretic separation technique which detects gene amplification and deletion. We were able to find two fragments frequently amplified and 10 others commonly showing reduced signal intensity within the 16 tumour samples analysed. These altered spots were located on chromosomes 2, 3, 9-12, 16, 17 and 18 according to chromosomal assigned RLGS. A subset of reduced fragments appeared to be correlated to tumour type and were located within a new chromosomal region, suggesting genetic specificity within the process of renal carcinogenesis.

Aged↗

Hospital participation in community partnerships to improve health.

BACKGROUND: The core business of hospitals now requires, for both competitiveness and quality improvement reasons, that hospitals move beyond their physical and conceptual walls to form community partnerships. THE HOSPITAL'S ROLE AS A PARTNER IN COMMUNITY-BASED HEALTH IMPROVEMENT SYSTEMS: Hospitals, as organizations that are significant health care, social, and economic institutions in their communities, should play a leading role in mobilizing resources for such community-level health improvement efforts. MOVING OUTSIDE THE WALLS TO IMPROVE QUALITY: Three examples of extending hospital efforts into the community demonstrate that improvement of a problem involving hospital care can derive from a collaborative, community-based activity. In Boston, infection control--once a standard, strictly in-house procedure--has been forced by altered patterns of hospital use to become a largely community-based process. In Chicago, a variety of health care providers and community representatives have worked effectively to reduce mortality and morbidity in a single disease (asthma) model. In Akron, Ohio, Lifelink program hospitals, working together with community agencies and groups in a door-to-door neighborhood program, improved the effectiveness of prenatal care and the quality of birth outcomes. CONCLUSION: Efforts to work with community groups to improve health status should not be simply an optional do-good endeavor, as they have often been in the past, but rather an essential part of quality improvement and good business practice. Marketplace incentives will increasingly reward hospitals that are able to form successful community partnerships.

Boston↗

Genomic alterations in oral squamous cell carcinoma cell lines detected by two-dimensional gel analysis.

To initially analyze the genomic abnormalities in human oral squamous cell carcinoma, DNA extracted from each of four oral carcinoma cell lines (Ca9-22, HO-1-u-1, HSC-2, KB) was examined using restriction landmark genomic scanning (RLGS), a method especially conducive to detection of amplifications and rearrangements of genomic DNA. Isolated cell line and normal oral epithial DNAs were sequentially cleaved with specific restriction enzymes, radiolabelled and separated in two-dimensional gel electrophoreses. Thirteen distinct fragments were commonly amplified in the oral cancer cell lines, six of which were evident in all samples. These results suggest genetic alterations characteristic of oral squamous cell carcinogenesis.

Carcinoma, Squamous Cell↗

Late-onset unilateral renal dysfunction combined with non-insulin-dependent diabetes mellitus and bronchial asthma following allogeneic bone marrow transplantation for acute lymphoblastic leukemia in a child.

We report a child with T cell acute lymphoblastic leukemia who developed late-onset multiple complications after allogeneic bone marrow transplantation from an HLA-matched sibling. The preparative regimen consisted of total body irradiation (TBI, 12 Gy), splenic irradiation (6 Gy) and cytosine arabinoside (3 g/m2 x 10). Splenic irradiation was added because of persistent splenomegaly in spite of intensive chemotherapy. He developed bronchial asthma 1 1/2 years post transplant. He presented with microhematuria and proteinuria 4 1/2 years post-transplant, which were due to unilateral left renal dysfunction. He developed type II, non-insulin-dependent diabetes mellitus 8 years post-transplant. A biopsy from the left kidney was not compatible with diabetic nephropathy. All these complications appear to be independently related to BMT, particularly TBI and/or splenic irradiation.

Adolescent↗

Pharmacokinetic properties and oral bioavailabilities of difloxacin in pig and chicken.

1. Pharmacokinetic properties of difloxacin have been studied in pig and chicken after intravenous and oral administration. 2. The serum concentrations of difloxacin in pig and chicken after intravenous administration were best described by a two-compartment open model, giving distribution half-lives of 0.50 and 0.66 h and elimination half-lives of 7.92 and 4.10 h for pig and chicken respectively. The steady-state distribution volumes were 1.70 and 3.06 l/kg for pig and chicken respectively. 3. After oral administration of 5 mg/kg to pig and chicken, the serum concentrations reached maximal levels of 3.61 and 0.96 microg/ml respectively at 1.25 and 1.40 h. The elimination half-lives were 11.8 and 7.35 h for pig and chicken respectively. 4. The bioavailabilities of difloxacin were calculated as 93.7 (pig) and 86.9% (chicken).

Administration, Oral↗

Increase of thyroid stimulating activity in Graves' immunoglobulin-G by high polyethylene glycol concentrations using porcine thyroid cell assay.

Cyclic adenosine monophosphate (cAMP) production during a 5-hour incubation using porcine thyroid cells (PTC) was stimulated significantly more by polyethylene glycol (PEG) 22.5% precipitated fractions (ppt frs) than by PEG 12.5% ppt frs from almost all Graves' sera. However, the thyrotropin (TSH) binding inhibition (TBI) activities of the PEG 12.5% and 22.5% ppt frs using porcine thyroid membranes were similar, and did not change in the 5-hour incubation. When the PEG 12.5% ppt fr from Graves' serum and the PEG 22.5% ppt fr from normal human serum (NHS) were coincubated, cAMP production was also stimulated as much as by the PEG 22.5% ppt fr from Graves' serum. When purified thyroid stimulating antibody (TSAb)-immunoglobulin G (IgG) and the PEG 22.5% ppt fr from NHS were coincubated, increased cAMP production was also observed, whereas bovine thyrotropin (bTSH) did not produce this effect. When purified TSAb-IgG and PEG solutions were coincubated, maximum increases in cAMP production (approximately 10-fold) with 5% PEG were found, whereas no increase was observed using bTSH. The stimulatory effect of high PEG concentrations on thyroid stimulating activity was observed by TSAb-IgG in salt-free or salt-containing medium (<0.15 mol/L NaCl concentration) but not by either TSAb-IgG conjugated to protein A-sepharose 4B or the inactivated TSAb-IgG by the treatment of 70 degrees C for 10 minutes. No stimulatory action by PEG was found with the thyroid stimulating substances such as GTPgammaS, forskolin, or pituitary adenylate-cyclase activating polypeptide (PACAP). The increased thyroid stimulating activity of Graves (IgG) at high PEG concentrations suggests the existence of some factors influencing the ability of TSAb to stimulate thyroid cells, although the exact mechanism remains to be clarified.

Animals↗

Clusters of basic amino acids in midkine: roles in neurite-promoting activity and plasminogen activator-enhancing activity.

The removal of N-terminally located clusters of basic amino acids (N-tail) or C-terminally located clusters of basic amino acids (C-tail) from the midkine (MK) molecule severely reduced its neurite-promoting activity. However, experiments involving chemically synthesized MK derivatives revealed that the roles of the N-tail and C-tail were mostly indirect ones, i.e. they probably maintain the steric arrangements of the N-terminal and C-terminal halves. In particular, the C-domain, which is the C-terminal half devoid of the C-tail, retained considerable neurite-promoting activity when it was uniformly coated on a dish. The removal of the N-tail or C-tail also reduced the enhancing activity of plasminogen activator (PA) in aortic endothelial cells, although the effect was lower. There are two heparin-binding sites in the C-domain, Clusters I and II. A mutation in Cluster I [R78-->Q] affected the PA-enhancing activity only slightly, and a mutation in Cluster II [K83K84-->QQ] abolished the activity, while both mutations are known to reduce the neurite-promoting activity moderately. Therefore, the two heparin-binding sites in the C-domain play different roles in these two activities. Indeed, heparin exhibited different effects on these two activities. We also observed that intact MK was required for ordered neurite-promotion along the path of MK; one possible interpretation of this is that the N-terminal half is necessary for the stability of the molecule. Furthermore, K76 and K99 were found to be required for the secretion of MK; i.e. mutants in which one of these K residues was changed to Q were produced in the host cells, but not found in the medium.

Amino Acid Substitution↗

Chemical synthesis of dendrotoxin-I: revision of the reported structure.

Dendrotoxin I (DTX-I) is a 60-residue peptide from the venom of the black mamba snake Dendroaspis polylepis, which binds to neuronal K+ channels. The structure reported previously for DTX-I was synthesized for the first time by a solution procedure. The synthetic product was confirmed to have the correct primary and disulfide structure determined by peptide mapping, sequence analysis and mass measurements. Comparison of synthetic DTX-I with the natural one by high-performance liquid chromatography and capillary zone electrophoresis, as well as by sequence analysis, revealed that the Asn residue at position 12 in the synthetic peptide was Asp in the natural product. Synthesis of DTX-I with Asp at position 12 gave a peptide identical with the natural product in all aspects. NMR analysis of synthetic [Asn12]- and [Asp12]-DTX-I also supported our findings that the Asn residue at position 12 in the DTX-I molecule should be revised as Asp. [Asn12]- and [Asp12]-DTX-I had very similar binding affinities when tested against radiolabeled dendrotoxin binding to rat brain synaptosomal membranes.

Amino Acid Sequence↗