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Biomedical subjects

T Imamura

Publications and source records attributed to T Imamura.

At least 253 records · Page 14Linked to original sources

Detection of triazolam in skeletal remains buried for 4 years.

Analyses of the hypnotic triazolam from the remains of two human skeletons buried underground for 4 years were made for purposes of confirmation. The bone marrow and mummified muscle were digested with 2 M sodium hydroxide, efficiently extracted using a 3-step solvent extraction procedure, and selectively analyzed by gas chromatography/mass spectrometry with the negative ion chemical ionization mode. Estazolam was the internal standard used. Triazolam was detected in all the samples; the concentrations were 0.36 ng/g in the bone marrow of one victim, and 0.37 and 5.5 ng/g in the bone marrow and mummified muscle of the other victim. This method should prove useful for determination of triazolam in extensively decomposed bodies.

Bone Marrow↗

A quantitative method for evaluation of FGF family and FGF receptor family gene expression by RT-PCR.

The reverse transcription linked polymerase chain reaction (RT-PCR) is a powerful technique for detecting mRNAs of low abundance while enabling distinction between homologous mRNAs such as family members and between alternative splice variants. We utilized this technique for quantitative analysis of expression of nine fibroblast growth factor (FGF) and four FGF receptor (FGFR) family genes in mouse brain during development and adulthood. The primer sets and reaction conditions for each family member were optimized for efficient amplification, and the amplified products were detected by hybridization with specific probes to ensure specificity. To achieve quantitative measurement, serial concentrations of the cloned cDNAs were simultaneously amplified and the results were used to titrate the amount of mRNA in the samples. Since FGF family has been recently recognized to be important in various functions of central nervous system and the protocol described here is directly applicable for a variety of small tissue samples, this protocol is very helpful in understanding the involvement of FGF family in various physiological phenomena.

Animals↗

Expression and localization of bone morphogenetic proteins (BMPs) and BMP receptors in ossification of the ligamentum flavum.

To clarify the pathogenesis of ossification of the ligamentum flavum (OLF), we examined the expression and localization of bone morphogenetic proteins (BMPs) and their receptors (BMPRs) in the ligamentum flavum of the patients with OLF by immunohistochemical staining and compared them with staining patterns in control patients. The BMPRs appeared extensively in mature and immature chondrocytes around the calcified zone and in spindle-shaped cells and round cells in the remote part from ossified foci in examined tissue of OLF. The ligands for BMPRs, BMP-2/-4 and osteogenic protein-1 (OP-1)/BMP-7, colocalized in OLF patients. In the control cases, expression of BMPs and BMPRs was observed around the calcified zone at the insertion of the ligamentum flavum to the bone, and limited expression was found in the smaller range. Thus, the expression profile of BMPs and BMPRs in OLF patients was entirely different from the control patients, suggesting that BMPs may be involved in promoting endochondral ossification at ectopic ossification sites in OLF, and that ossification activity is continuous in these patients.

Activin Receptors↗

Examining the diagnostic utility of the Fuld cholinergic deficit profile on the Japanese WAIS-R.

The diagnostic utility of the Fuld cholinergic deficit profile (Fuld, 1984) to dementia of the Alzheimer type (DAT) was evaluated on the Japanese version of the WAIS-R. Profiles were calculated for groups of subjects with DAT(n = 236), vascular dementia (n = 29), frontotemporal dementia (n = 22), and hydrocephalic dementia (n = 10). The frequency of positive profile occurrence for the subject groups was as follows: 23/236 for DAT (9.7%), 2/29 (6.9%) for vascular dementia, 2/22 (9.1%) for frontotemporal dementia, and 2/10 (20%) for hydrocephalic dementia. No significant difference in the frequency of positive profile occurrence was revealed across four types of dementia. We conclude from these findings that the Fuld profile lacks the diagnostic utility on the Japanese WAIS-R.

Adult↗

Porphyromonas gingivalis proteinases as virulence factors in the development of periodontitis.

Porphyromonas gingivalis contains exceedingly high concentrations of cysteine proteinases with trypsin-like activity which have been implicated as virulence factors in adult-onset periodontitis. These enzymes, referred to as gingipains, cleave protein and peptide substrates after arginine (gingipain R) and lysine residues (gingipain K), and it has been found that neither is easily inhibited by host proteinase inhibitors. Examination of the properties of each proteinase clearly indicates a role(s) for both in the dysregulation of a number of normally tightly controlled pathways. The effects of such uncontrolled proteolysis are the development of edema (kallikrein/kinin pathway activation by gingipain R), neutrophil infiltration (complement pathway activation by gingipain R), and bleeding (degradation of fibrinogen by gingipain K). Since three of the major hallmarks of periodontitis involve increased crevicular flow, neutrophil accumulation at infected sites and bleeding on probing, it seems likely that both P. gingivalis-derived proteinases are important virulence factors in the development of periodontal disease.

Bacterial Adhesion↗

Clinical significance of serum p53 antigen in patients with pancreatic carcinomas.

BACKGROUND: Alterations in the p53 gene are often found in pancreatic cancer, and accumulation of the p53 protein has been noted in tumour cells. AIMS: To investigate whether serum p53 protein concentrations could be used as markers for p53 gene mutations in neoplasms of the pancreas. METHODS: Serum p53 protein concentrations were determined by an enzyme linked immunosorbent assay (ELISA) in 104 cases of pancreatic adenocarcinoma, and 61 matched formalin fixed tissue sections were also stained by an anti-p53 DO-7 monoclonal antibody. RESULTS: The mean serum concentration of p53 protein in the adenocarcinoma patients was 0.27 (SEM 0.02) ng/ml, and was significantly higher than in 35 healthy blood donors (0.15 (0.02) ng/ml, SD = 0.11) or in 15 cases of chronic pancreatitis (0.15 (0.02) ng/ml). Adopting an arbitrary cut off value for the serum p53 protein concentration of 0.37 ng/ml, which corresponded to a value 2 SD above the mean value from the healthy blood donors, positive serum p53 protein concentrations were found in 23 out of 104 (22.1%) patients with adenocarcinomas examined, 16 out of 47 (34.0%) patients with carcinomas with distant metastases, but only seven of 57 patients (12.3%) with carcinomas without metastases (p < 0.05). In 11 patients with pancreatic adenocarcinomas, the mean serum p53 protein concentration after tumour resection was 0.21 (0.05) ng/ml, and had decreased compared with the preoperative concentrations (0.25 (0.05) ng/ml) (P < 0.05). There were no significant associations between the serum concentrations of p53 protein and serum concentrations of markers such as CA19-9 or CEA; however, serum concentrations of p53 protein demonstrated a potential role as an additional tumour marker. Immunohistochemical studies disclosed that the p53 protein was expressed in 28 out of 61 pancreatic adenocarcinomas (45.9%). Serum p53 protein concentrations in the positively immunostained cases were significantly higher than in the negatively immunostained cases (0.35 (0.05) ng/ml v 0.15 (0.01) ng/ml; p < 0.005). Furthermore, positive immunostaining for p53 protein was found in eight out of 10 (80%) serum positive p53 protein cases with adenocarcinomas. CONCLUSION: An increase in serum p53 protein concentrations appears during the progression of pancreatic adenocarcinoma and correlates with the accumulation of p53 protein as a result of a mutation of the p53 gene. An analysis of p53 antigen concentrations can detect p53 gene alterations, which could be useful for the selection of treatment regimens.

Adenocarcinoma↗

Immunohistochemical studies of proliferating cell nuclear antigen and cathepsin D in transitional cell carcinoma of the urinary bladder.

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and cathepsin D was performed on 60 transitional cell carcinoma (TCC) specimens from 60 patients with bladder cancer. The percentage of PCNA-positive cells (PCNA-labelling index) was determined by counting 500 or 1,000 cells, and cathepsin D expression was graded according to the extent of immunoreactivity to anti-cathepsin D antibody. The PCNA-labelling index was significantly higher in high-grade and high-stage tumors compared to that in low-grade and low-stage tumors. Cathepsin D was highly positive in grade-1 tumors. In contrast, 82% of grade-3 tumors and 76% of advanced tumors showed negative or low reactivity to anti-cathepsin D. Groups of high PCNA-labelling index and negative cathepsin D had significantly poorer prognoses compared to those of the low PCNA group and cathepsin D highly positive group, respectively, in univariate analyses. However, neither of these two factors were independent prognostic factors in multivariate analyses. These results suggest that the PCNA-labelling index and cathepsin D expression may indicate the malignant potential of TCC and may be able to provide additional information for predicting survival when stratifying for grade of bladder cancer.

Adult↗

Premorbid brain size as a determinant of reserve capacity against intellectual decline in Alzheimer's disease.

OBJECTIVE: Both the magnitude of brain atrophy and premorbid brain size determine the volume of the brain affected by Alzheimer's disease. To examine the possibility that premorbid brain volume is a determinant of cognitive reserve in patients with Alzheimer's disease, the relation between diffuse brain atrophy and cognitive decline and the impact of premorbid brain size on cognitive decline were studied in patients with Alzheimer's disease. METHOD: By measuring whole brain volume and intracranial volume in 60 patients with probable Alzheimer's disease, mild to moderate in severity, with the use of high-resolution magnetic resonance imaging and image processing, the authors studied the impact of premorbid brain volume and magnitude of diffuse brain atrophy on cognitive functions. On the basis of the normative brain-calvarium relationship derived from data an 28 healthy adults and the total intracranial volume measure of each patient, the magnitude of brain atrophy and premorbid brain volume were estimated. RESULTS: After control for the effects of age, sex, and education as confounding factors, it was found that the Alzheimer's disease patients' intelligence was correlated both positively with premorbid brain volume and negatively with magnitude of brain atrophy, while impairments in language and memory were correlated with magnitude of brain atrophy but not with premorbid brain volume. CONCLUSIONS: These findings partially support the hypothesis that premorbid brain volume is a determinant of reserves against intellectual decline in Alzheimer's disease.

Adult↗

Evidence for functional roles of Crk-II in insulin and epidermal growth factor signaling in Rat-1 fibroblasts overexpressing insulin receptors.

We examined the potential role of Crk-II in insulin and epidermal growth factor (EGF) signaling in Rat-1 fibroblasts overexpressing insulin receptors. Crk is an SH2 and SH3 domain-containing adaptor protein that has been reported to associate with p130cas, paxillin, c-cbl, c-abl, Sos, and C3G in vitro. Insulin- and EGF-induced association of Crk-II with these molecules was assessed by immunoblotting of anti-Crk-II precipitates in Rat-1 fibroblasts overexpressing insulin receptors. Neither insulin nor EGF treatment induced Crk-II association with either Sos or C3G. Basal tyrosine phosphorylation of c-abl and its constitutive association with Crk-II were not further increased by insulin or EGF. p130cas and paxillin were heavily tyrosine phosphorylated in the basal state. Both insulin and EGF stimulated their dephosphorylation, followed by p130cas-Crk-II dissociation and paxillin-Crk-II association, although the magnitude of these effects was greater with insulin than with EGF. Interestingly, EGF, but not insulin, stimulated tyrosine phosphorylation of c-cbl and its association with Crk-II. To investigate the functional roles of Crk-II in mitogenesis and cytoskeletal rearrangement, we performed microinjection analysis. Cellular microinjection of anti-Crk-II antibody inhibited EGF-induced, but not insulin-induced, DNA synthesis. Insulin, but not EGF, stimulated cytoskeletal rearrangement in the cells, and microinjection of anti-Crk-II antibody effectively inhibited insulin-induced membrane ruffling, suggesting that Crk-II is involved in insulin-induced cytoskeletal rearrangement. These results indicate that Crk-II functions as a multifunctional adaptor molecule linking insulin and EGF receptors to their downstream signals. The presence of c-cbl-Crk-II association may partly determine the signal specificities initiated by insulin and EGF.

Animals↗

Gastrointestinal stromal tumor of the stomach.

We report a case of gastrointestinal stromal tumor (GIST) of the stomach. The patient was a 79-year-old woman with two gastric submucosal tumors detected by ultrasonography. Proximal gastrectomy was carried out and the tumors were diagnosed as GIST by histological and immunohistochemical investigations. Mesenchymal tumors of the gastrointestinal tract have been traditionally regarded as largely leiomyomatous lesions. However, GIST and other tumors have been distinguished recently on the basis of tumor cell differentiation shown by immunohistochemical studies. We discuss the concept and the immunohistochemical characteristics of GIST.

Actins↗

Elevated L-kynurenine level and its normalization by prednisolone in a patient with eosinophilia-myalgia syndrome.

We report a L-tryptophan-induced case of eosinophilia-myalgia syndrome in a Japanese woman and describe the time course of changes in tryptophan metabolism observed during steroid therapy. She had taken 1.0 g of the implicated L-tryptophan daily. When admitted due to painful swelling of her extremities, eosinophil count was 22.3 x 10(9)/L. Before prednisolone treatment, her serum L-kynurenine level was 10.2 mumol/L, a level about three-fold higher than the normal value, while serum tryptophan level was abnormally low (23.1 mumol/L). On the 14th day of prednisolone treatment (40 mg daily), L-kynurenine was declined to 8.1 mumol/L and, concomitantly, L-tryptophan level increased to the normal range (51.0 mumol/L). Subsequently, on the 42nd day of therapy, serum L-kynurenine was normalized. In contrast, serum serotonin level was unchanged throughout the course of this therapy. Prednisolone dramatically reduced the elevated serum L-kynurenine with a reciprocal increase in serum L-tryptophan indicates that abnormal tryptophan metabolism, may play a role in the pathogenesis of eosinophilia myalgia syndrome, and that the observed effect of steroid treatment was due to suppression of elevated activity of indoleamine 2, 3-dioxygenase, a first rate-limiting enzyme of the kynurenine pathway.

Anti-Inflammatory Agents↗

Usefulness of elastica-van Gieson stain for the pathomorphological diagnosis of a cutaneous electric mark--a fatal electrocution case during arc welding.

Identification of an electric mark on a body is required for a precise diagnosis of electrocution at the time of forensic autopsy. We applied Elastica-van Gieson (EVG) stain as a means of obtaining the pathomorphological diagnosis of a cutaneous electric mark in relation to a fatal electrocution case. Using EVG stain, the characteristic findings of electric marks, such as elongation of basal-cell nuclei and vacuolation of cells within the epidermis, were clearly observed, while in addition, disarrangement of elastic fibers in the connective tissues within the dermis was also demonstrated. EVG staining was considered to be useful in enabling pathomorphological observations of a cutaneous electric mark to be made.

Accidents, Occupational↗

Bone morphogenetic protein receptors and activin receptors are highly expressed in ossified ligament tissues of patients with ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) is a pathological ossification in the spinal ligament, with formation of ectopic bone mainly through endochondral ossification. Bone morphogenetic proteins (BMPs) and activins are multifunctional proteins that belong to the transforming growth factor-beta superfamily and that have been implicated in the formation of new bone and cartilage. BMPs and activins signal via type I and type II receptors for BMPs (BMPRs) and activins (ActRs), respectively. OP-1/BMP-7 binds to BMPR-II and ActR-II and forms complexes with BMPR-IA and -IB and ActR-I. We studied the expression of BMPR-IA, -IB, and -II, ActR-I, ActR-II, and OP-1/BMP-7 by immunohistochemistry in ossified ligament tissues of patients with OPLL and control ligament tissues from patients with cervical disc herniation. The expression of BMPRs and ActRs was elevated in OPLL compared with controls. Expressions of BMPR-IA, -IB, and -II were observed not only in chondrocytes at the fibrocartilage tissue around the calcified zone but also in fibroblast-like spindle cells at the nonossified ligament. ActR-I and -II were found co-localized in the hypertrophic chondrocytes near the calcified zone and in the ossified tissue. OP-1/BMP-7 was expressed in chondrocytes near the calcified zone. In the control cases, the BMPRs and ActRs were only weakly expressed in the fibrocartilage tissue at the site of ligament attachments to bone and OP-1/BMP-7 was not detected. Enhanced expression of BMPRs at the nonossified ligament in OPLL patients suggests that these cells have a greater potential to differentiate into osteogenic cells than ligament cells from non-OPLL patients. The high expression of BMPRs and ActRs in the ectopic ossified ligament suggests that BMPs and activin may be tightly involved in the pathological ossification process of OPLL.

Activin Receptors↗

Alteration of white matter MR signal intensity in frontotemporal dementia.

PURPOSE: To determine the diagnostic potential of MR imaging to show white matter involvement in frontotemporal dementia. METHODS: We evaluated MR signal intensity in cerebral white matter by visually inspecting and by quantitatively measuring signal intensity on MR images in 22 patients with frontotemporal dementia. The findings were compared with those in 22 age- and sex-matched patients who had had Alzheimer disease for the same length of time and with 16 age- and sex-matched healthy control subjects. RESULTS: Patients with frontotemporal dementia had a significant increase in white matter signal intensity in the frontal and/or temporal lobes on T2- and proton density-weighted images. Visual inspection of regular proton density-weighted images and measurements made on the T2- and proton density-weighted images were sensitive to changes in white matter signal. CONCLUSION: Increased MR signal intensity in the frontotemporal white matter on T2- and proton density-weighted MR images is a useful diagnostic sign of frontotemporal dementia and distinguishes this condition from Alzheimer disease.

Aged↗

[Japanese version of the Neuropsychiatric Inventory--a scoring system for neuropsychiatric disturbance in dementia patients].

BACKGROUND AND PURPOSE: Neuropsychiatric disturbances are common and burdensome symptoms of dementias. Assessment and measurement of neuropsychiatric disturbances are indispensable to the management of patients with dementia and for clinical research. No standardized instruments have been developed for these purposes in Japan. The Neuropsychiatric Inventory (NPI), developed by Cummings et al., is a standardized, validated, and reliable tool to assess a wide range of neuropsychiatric derangements in patients with dementia, and has been used in clinical studies in North America. In this study, we prepared a Japanese version of the NPI and tested its reliability and usefulness in dementia patients. SUBJECTS AND METHODS: The subjects were 174 patients with dementia, including Alzheimer's disease (140), frontotemporal dementia (12), vascular dementia (19), and normal pressure hydrocephalus (3), whose diagnosis was made on the basis of the results of extensive examinations including MRI and PET/SPECT of the brain and appropriate clinical diagnostic criteria for each disorder. The subjects consisted of 133 women and 41 men; their mean age was 72.6 +/- 7.7 years (S.D.; range: 49 to 88) years. An examiner (neurologist) used the NPI to interview a caregiver familiar with the patient's everyday behavior. In 24 randomly selected patients interview was repeated by another examiner (psychiatrist) one month later, and test-retest reliability was evaluated. The Clinical Dementia Rating (CDR), the Mini-Mental State Examination (MMSE), and the Alzheimer's Disease Assessment Scale (ADAS) were used to assess the severity of the dementia and cognitive impairment. RESULTS: The MMSE scores ranged from 5 to 29 (mean +/- SD = 19.0 +/- 4.8) and the ADAS scores ranged from 7 to 63 (24.3 +/- 10.9). The CDR score was 0.5 in 17 patients, 1 in 95 patients, 2 in 52 patients, and 3 in 10 patient. Test-retest reliability of each score was acceptably high, and the correlation coefficient for each score obtained by repeated assessments in this study was similar to the coefficient in the original report. Apathy was the most common behavior in the ten abnormal behavioral domains, and euphoria was the least common. The prevalence of abnormal findings was also comparable to the results in the original report. The total NPI scores and many of the NPI subscale scores were significantly correlated with both the severity of dementia and cognitive impairment. CONCLUSIONS: This Japanese version of NPI, whose reliability and competency are comparable to those of the original version, is a reliable and useful tool for measuring neuropsychiatric disturbances in dementia patients.

Aged↗

Detection of drugs and poisons in postmortem tissues--determination of paraquat in tissues of rabbits buried underground.

The possibility of detecting paraquat in tissues of rabbits buried underground over a 2-year period was examined. Paraquat (1.2 g) was given orally to rabbits, which were sacrificed 1 h after administration. The animals were buried underground, and the skeletal muscles and the bones were collected 3 and 6 months after death, and 3, 6, 12, and 24 months after death, respectively. Paraquat was present in all bone marrow samples, showing a slight decrease in concentration until 12 months. Paraquat was also detected in all skeletal muscle samples, showing almost no change in concentration until 6 months. These results indicate that intoxication with paraquat as well as the degree of poisoning can both be determined from the skeletal muscles and bone marrow of cadavers which have been buried underground for a long period of time even in human cases.

Animals↗