Dinucleotide repeat polymorphism in the neurotrophin-3 gene and hippocampal volume in psychoses.
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Adolescent↗
Biomedical subjects
K Fujii
Publications and source records attributed to K Fujii.
Chaos and spectral analyses of heart rate variability during head-up tilting in essential hypertension.
To investigate nonlinear and linear components of heart rate variability (HRV) in essential hypertension (EHT), we analyzed HRV by chaos and spectral analyses in patients with EHT (n = 18) and normotensives (n = 10) during head-up tilting. We used the correlation dimension (CD) and Lyapunov exponents as the parameters of chaos. The CD, an index of complexity, was lower at rest in EHT group than in normotensives, and did not change in EHT group in response to head-up tilting, but decreased in normotensives. Head-up tilting did not change the Lyapunov exponents, an index of sensitive dependence on initial condition, a hallmark of chaos, in both groups. In the spectral analysis, the normalized high-frequency component (%HF) was decreased in EHT group at rest, and head-up tilting increased the low- to high-frequency ratio (L/H) and reduced the %HF in both groups. The CD and Lyapunov exponents at rest were correlated with the %HF and L/H. These results suggest that chaos analysis can assess the different aspect of HRV from spectral analysis and that nonlinear components of HRV may be associated with hypertension through an impaired dynamic regulation of HRV.
Adult↗
Impact of the expression of cyclin-dependent kinase inhibitor p27Kip1 and apoptosis in tumor cells on the overall survival of patients with non-early stage gastric carcinoma.
BACKGROUND: The expression of p27Kip1 and apoptosis have been implicated in tumor aggressiveness and proved to be prognostic predictors for several human malignancies. In this study, the authors sought to investigate the expression of p27Kip1 and apoptosis and their potential significance in determining the prognosis of patients with non-early stage gastric carcinoma. METHODS: Primary gastric tumor specimens from 225 patients were investigated by immunohistochemistry with anti-p27Kip1 and anti-Ki-67 antibodies, and their apoptotic indices were determined with the use of an Apop-Tag in situ detection kit. RESULTS: The median p27Kip1 labeling index (LI) was 48.4%. There was a significant association between the p27 LIs and the apoptotic indices (Als). However, there was no association between the p27 LIs and the Ki-67 LIs. p27 LI was demonstrated to be one of the most significant and independent prognostic factors in multivariate analysis. Although AI was found to be prognostically significant in univariate analysis, it failed to retain an independent and significant value regarding overall survival in multivariate analysis. CONCLUSIONS: Decreased expression of p27Kip1 and reduction of apoptotic potential were two of the most important factors in predicting a poor prognosis for patients with non-early stage gastric carcinoma. These findings support the hypothesis that decreased p27Kip1 expression, which may reflect a decreased rate of apoptosis, is closely related to the aggressiveness of gastric carcinoma. Therefore, the assessment of p27Kip1 expression and apoptotic potential may prove valuable in identifying patients with gastric carcinoma who are at high risk for recurrence and would benefit from adjuvant therapy.
Adenocarcinoma↗
Cross-linking of CD44 on rheumatoid synovial cells up-regulates VCAM-1.
CD44 is a ubiquitous molecule also known as hyaluronic acid or homing receptor. However, the cellular functions and its role in inflammation, for example, rheumatoid synovitis, are currently unknown. In this study, we propose a novel function for CD44. Using synovial cells from rheumatoid arthritis (RA) patients, we demonstrated that CD44 cross-linking and binding to hyaluronan augmented VCAM-1 expression and subsequently VCAM-1-mediated cell adhesion. Briefly, we found that 1) rheumatoid synovial cells highly expressed CD44; 2) cross-linking of CD44 markedly but transiently augmented VCAM-1 expression and its mRNA transcription much more than did IL-1beta and TNF-alpha; 3) hyaluronan, especially when fragmented, also up-regulated VCAM-1; 4) CD44 activated the transcription factor AP-1; and 5) the integrin-dependent adhesive function of RA synovial cells to T cells was also amplified by CD44 cross-linking. These results indicate that the adhesion of RA synovial cells to matrices such as hyaluronic acid through CD44 could up-regulate VCAM-1 expression and VCAM-1-mediated adhesion to T cells, which might in turn cause activation of T cells and synovial cells in RA synovitis. We therefore propose that such cross-talking among distinct adhesion molecules may be involved in the pathogenesis of inflammation, including RA synovitis.
Adjuvants, Immunologic↗
Antecedent angina pectoris as a predictor of better functional and clinical outcomes in patients with an inferior wall acute myocardial infarction.
We examined whether angina pectoris (AP) occurring shortly before the onset of acute myocardial infarction (AMI) can render the right ventricle and the conducting tissue resistant to ischemia in 75 patients with an inferior wall AMI. Each patient had total occlusion in the proximal right coronary artery and underwent successful coronary angioplasty < or =24 hours from the onset. We divided patients into 2 groups based on presence or absence of antecedent AP < or =24 hours before the system onset: group 1 (absent) = 57 patients; group 2 (present) = 18 patients. Collateral circulation was more frequently observed in group 2 than in group 1 (group 1 vs 2, 28% vs 61%, p <0.01). Elevation in ST segment > or =1 mm in lead V4R, hemodynamic right ventricular dysfunction, and frequency of high-degree heart block were more frequent in group 1 than in group 2 (75% vs 44%, 79% vs 39%, 53% vs 11%, p <0.05, respectively). Multivariate analysis demonstrated that antecedent AP is the only factor related to these complications. Thus, episodes of AP occurring shortly before onset may restrain development of ischemic damage of the right ventricle and conducting tissue, and are associated with better clinical and functional outcomes among patients with an inferior wall AMI.
Acute Disease↗
Multiple acrosomal vesicles and their differentiation during spermiogenesis in Ascidia zara and Ascidia gemmata (Ascidiacea, tunicata).
A fully differentiated spermatozoon of both Ascidia zara and Ascidia gemmata is approximately 35 microM long. It contains a head and a tail lacking a midpiece. The head (approximately 4 microM long for A. zara and 5 microM long for A. gemmata) contains an elongated nucleus and a single mitochondrion that flanks the nucleus. Multiple acrosomal vesicles (three or four in number) are present at the apex of the sperm head in both species. Each vesicle is approximately 50 x 50 x 60 nm, and contains moderately electron-dense material. During spermiogenesis of A. zara, three or four vesicles appear in a blister of an early stage spermatid. These vesicles transform into multiple acrosomal vesicles without fusing with each other. Spermiogenesis and acrosome differentiation are similar in A. gemmata and A. zara. Three types of acrosome differentiation in ascidians are described.
Acrosome↗
Pelizaeus-Merzbacher disease: three novel mutations and implication for locus heterogeneity.
We report a mutational and polymorphic analysis of the proteolipid protein gene in members of 27 Japanese families with Pelizaeus-Merzbacher disease. We found causative mutations in 6 members of 27 families (22.2%); 5 of the 6 mutations, including two novel mutations, Leu45Arg and 231 + 2T --> G, resulted in the typically severe clinical symptoms. Paradoxically, the Cys219Tyr mutation, presumed to disrupt the tertiary structure of proteolipid protein by removing the disulfide bond between Cys200 and Cys219, was associated with a mild clinical presentation wherein the patient could walk with assistance and speak. It was inferred that the structural change prevented the toxicity associated with a gain of function mutation. Moreover, in one family 3 patients exhibited a intragenic polymorphism that did not segregate with the disease, suggesting a locus heterogeneity for Pelizaeus-Merzbacher disease.
Adult↗
Evaluation of treatment strategies for gastric cancer in the elderly according to the number of abnormal parameters on preoperative examination.
The treatment strategies in patients with gastric cancer aged 80 years or older have not yet been well defined. We examined the incidence of postoperative complications and hospital mortality regarding the preoperative condition of such patients. A preoperative examination included evaluations of the cardiac, pulmonary, renal, and hepatic functions, the presence or absence of anemia, nutritional status, and blood sugar content. The incidence of postoperative complications and hospital mortality were then studied in relation to the number of preoperative abnormal parameters. The incidence of postoperative complications was 37.0%. The rate of hospital mortality was 11.1%. Among the patients with abnormalities in five or more items, the incidence of complications was 76.9% and the rate of hospital mortality was 23.1%. In the patients with an operative time of 4 h or longer, the same incidence was 71.4%. Among the patients who underwent a curative resection, the 5-year survival rate was 92.3%. For elderly gastric cancer patients with abnormalities in five or more items during a preoperative examination and for those showing a poor level of daily life activity, a less invasive treatment modality should be planned. Patients with abnormalities of four or fewer items at a preoperative examination appear to be good candidates for curative resection.
Activities of Daily Living↗
Functional evaluation of myocardial viability by 99mTc tetrofosmin gated SPECT--a quantitative comparison with 18F fluorodeoxyglucose positron emission CT (18F FDG PET).
UNLABELLED: To validate functional analysis of gated SPECT in detecting myocardial viability, seventeen patients (male 15, female 2, mean age 58) with angiographically proven chronic ischemic heart disease (RCA 6, LAD 10, LCX 1) and eight normal volunteers (all male) were studied. All patients underwent 18F FDG PET and 99mTc tetrofosmin (TF) gated SPECT within a week. After being displayed in a polar map, myocardial perfusion was regionally determined by the mean count in 9 segments at end diastole (ED) and end systole (ES) in gated SPECT. Systolic function was determined by the count increase ratio from ED to ES (WTI: ES - ED/ED). Glucose metabolism was assessed by 18F FDG PET in the segments correspondent to those defined for SPECT. TF %uptake of < 60% was defined as hypoperfusion, and FDG %uptake of < 50% was defined as reduced glucose metabolism. RESULTS: The myocardial segments were classified into 3 categories: "normal" perfusion (n = 85), "mismatch" (reduced perfusion with reserved FDG uptake, n = 25) and "matched" reduced perfusion and metabolic reduction (n = 26). Mean WTI in "mismatch" segment was 0.38 +/- 0.21, and was significantly greater than that in "matched reduced" segments, 0.15 +/- 0.20 (p < 0.001). It was also greater than that in "normal" segments, 0.27 +/- 0.16. Regression analysis showed that association between WTI and FDG %uptake was significant (r = 0.57, p < 0.0005) for the ischemic segments ("mismatch" + "matched", n = 51), but the association was weak for the entire segments although it was statistically significant (r = 0.26, p = 0.02, n = 136). CONCLUSION: For the segments determined as infarct by perfusion image, systolic functional analysis by gated SPECT is helpful in differentiation of a viable myocardial region or artifact from a scar. Nevertheless, further clinical and technical assessment is required for ECG gating to eliminate overestimation of viability and to warrant clinical use.
Adult↗
Comparison of biochemical characteristics of cultured fibrochondrocytes isolated from the inner and outer regions of human meniscus.
In order to evaluate the ability of fibrochondrocytes to synthesize collagen and proteoglycan, human medial meniscal cells were cultured in a monolayer. Meniscal cells were prepared from the two regions (outer 1/3 and inner 2/3) in consideration of the difference in vascular supply, and articular chondrocytes were also obtained from the same knee joint. Regarding total collagen synthesis, regional differences were not found, but age-related differences were found in human medial meniscus. In contrast, proteoglycan synthesis revealed significant regional differences; meniscal cells from the inner 2/3 synthesized a greater amount of proteoglycan. After long-term monolayer culturing, proteoglycan synthesis by meniscal cells decreased in a time-dependent manner, and morphological changes to fibroblast-like cells were found. In the presence of transforming growth factor (TGF)-beta, proteoglycan synthesis increased in a dose-dependent manner. These findings suggest that the inner regions of the human meniscus contain cells with a chondrocytic phenotype.
Adolescent↗
The factors influencing haematoma volume due to arteriovenous malformations.
Haemorrhage due to cerebral arteriovenous malformations (AVMs) varies from massive, requiring urgent operations, to clinically silent. The present study was designated to identify factors influencing haematoma size, and the pathophysiological mechanisms of massive haemorrhage were studied. 55 patients with intracerebral haematomas due to supratentorial AVMs were included in this study. Angiographic and clinical findings were retrospectively evaluated in relation to haematoma size. Statistical analysis demonstrated that small size and the presence of only one draining vein were high risk factors for massive haemorrhage. The haematoma volume in small AVMs (30 +/- 4 cm3) was significantly larger than in other AVMs (7 +/- 3 cm3) (p = 0.0005). AVMs with only one draining vein were associated with massive haematoma volume as compared to AVMs with two or more draining veins (30 +/- 4 versus 11 +/- 3 cm3, p = 0.0023). Our previous study demonstrated that feeding artery pressure (FAP) was significantly higher in AVMs with haemorrhage than in those without, as was draining vein pressure (DVP), and FAP and DVP were inversely related to the number of draining veins and the size of the AVMs. Thus, in small AVMs and AVMs with only one draining vein, local increase in DVP may thus contribute to massive haemorrhage.
Arteriovenous Malformations↗
Cerebral germinoma with syncytiotrophoblastic giant cells: feasibility of predicting prognosis using the serum hCG level.
As the biological behaviour of germinoma with syncytiotrophoblastic giant cells (STGC) is not well established, the present study was undertaken to ascertain the prognostic significance of serum hCG level in affected patients. Of a total of 23 cases studied, 12 patients were regarded as pure germinomas and 11 were germinomas with STGC. All but one of the former demonstrated an excellent outcome. The exception developed subarachnoid metastases, but the tumour disappeared on radiation therapy and the patient is enjoying a normal social life 13 years after the initial treatment. With the germinoma complicated by STGC, 3 cases showed local recurrence which were followed by a poor outcome. Their pretreatment hCG levels were 15.0, 26.0 and 29.6 mIU/ml respectively. The study showed a tendency, in germinomas with STGC, for a positive association between serum hCG, and the likelihood of a poor outcome. Germinomas with STGC and serum hCG levels higher than 15 mIU/ml thus have a high recurrence rate, and more aggressive treatment is indicated for the affected patients.
Adolescent↗
Differences in cellular properties and responses to growth factors between human ACL and MCL cells.
The anterior cruciate ligament (ACL) has poor healing responses compared with those of the medial collateral ligament (MCL). It has been implied that this is partially due to the poor reparative capacity of ACL cells for ligament injury. The present study was designed to elucidate the reparative capacities of human ACL and MCL cells by investigating their cellular properties and their responses to growth factors. Human ACL and MCL were obtained from seven fresh human cadavers. The cells were isolated from each tissue, and primary cultures were used for the examination. The growth rates of all the human ACL cells were lower than those of the human MCL cells; consistent with this, the doubling time of the ACL cells was 30 +/- 7.4% longer than that of the MCL cells. The chemotactic migration of human ACL cells was 33 +/- 8.1% slower and the synthesis of DNA and collagen in human ACL cells was 29 +/- 6.3% and 31 +/- 9.7% lower, respectively, in comparison with those of MCL cells. Cellular responses, in terms of DNA synthesis, in human ACL cells to either basic-fibroblast growth factor (1.0 and 10.0 ng/ml) or transforming growth factor-beta (1.0 ng/ml) were lower than those of human MCL cells. However, no differences in the cellular responses in terms of collagen synthesis were found. Composite data show that human ACL cells have poorer cellular properties and lower responses to growth factors compared with those of human MCL cells, which suggests that the reparative capacity of human ACL cells may be poorer than that of human MCL cells.
Anterior Cruciate Ligament↗
Surgical management of congenital permanent dislocation of the patella in nail patella syndrome by Stanisavljevic procedure.
We report a patient with nail patella syndrome associated with congenital permanent dislocation of the patella successfully operated on using a modified Stanisavljevic method. The patient, a 26-year-old woman, complained of inability to completely extend her right knee joint. She had occasionally experienced the "giving way" phenomenon since childhood, but she had not received any treatment since birth. Physical examination showed that all fingernails were deformed, with longitudinal striations, while the lunules were of an abnormal triangular shape or were missing. Both patellae were palpably hypoplastic, with the right patella dislocated laterally, and the knee had an extension lag of 90 degrees. Thigh and leg muscle were slightly underdeveloped, but quadriceps muscle contraction was good. Several radiographs were taken and they showed bilateral iliac horns and hypoplasia of the bilateral humero-radial joints and of both patellae, and complete dislocation of the right patella. We employed the Stanisavljevic procedure for the reduction of the patella, with Z-lengthening of the rectus femoris and medial translocation of the tibial tuberosity. Four years after the operation, a 30-degree extension lag still exists in the right knee, but the treatment resulted in stable alignment of the quadriceps mechanism, and notably improved gait appearance.
Adult↗
Impact of tranilast on restenosis after coronary angioplasty: tranilast restenosis following angioplasty trial (TREAT).
BACKGROUND: Tranilast is an antiallergic drug that suppresses the release of cytokines such as platelet-derived growth factor, transforming growth factor-beta1, and interleukin-1beta and prevents keloid formation after skin injury. Treatment with this drug reduced the restenosis rate after percutaneous transluminal coronary angioplasty in a preliminary study. METHODS AND RESULTS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial. A total of 255 patients with 289 lesions were randomly assigned to treatment with the oral administration of 600 mg/d tranilast, 300 mg/d tranilast, or a placebo for 3 months after successful angioplasty. Angiographic follow-up was done at 3 months, and a clinical follow-up examination was performed at 12 months. Two hundred ten (72.7%) lesions of 188 (73.7%) of the patients met the criteria and were eligible for the assessment of restenosis. The restenosis rates defined as >/=50% loss of the initial gain were 14.7% in the 600 mg/d tranilast group, 35.2% in the 300 mg/d tranilast group, and 46.5% in the placebo group (P <. 0001 for 600 mg/d tranilast vs placebo). The restenosis rates defined as percent diameter stenosis of >/=50% at follow-up were 17. 6% in the 600 mg/d tranilast group, 38.6% in the 300 mg/d tranilast group, and 39.4% in the placebo group (P =.005 for 600 mg/d tranilast vs placebo). CONCLUSIONS: The oral administration of 600 mg/d of tranilast for 3 months markedly reduced the restenosis rate after percutaneous transluminal coronary angioplasty.
Administration, Oral↗
Increase in nucleoli after x-radiation of fibroblasts of patients with Gorlin syndrome.
Gorlin syndrome (GS) is an autosomal dominant disorder in which patients are abnormally susceptible to ionizing radiation with radiotherapeutic doses. Radiogenic basal cell carcinomas may develop with a short latent period in patients. The mechanisms underlying the abnormal radiosusceptibility of cells in patients with GS has not been well characterized. In this study we report an increase in the number of nucleoli in fibroblast cells from 3 patients with GS after x-radiation. In GS fibroblasts, the increase in nucleolus number concomitant with the increase of ribonucleoprotein immunoreactive aggregates within the nucleus was observed after x-radiation, whereas significant change was not found in normal fibroblasts derived from healthy donors. This increase disappeared when cells were cultured with the RNA synthesis inhibitor actinomycin D after x-radiation but not when they were cultured with cycloheximide or aphydicolin, which are protein and DNA synthesis inhibitors, respectively. Ultraviolet exposure did not induce remarkable changes in the GS nucleoli. Thus the increase in nucleoli was induced after x-radiation of GS fibroblasts, and this increase seemed to be related to RNA synthesis metabolism.
Basal Cell Nevus Syndrome↗
Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency.
Serum phenylalanine concentrations decreased in 4 patients with hyperphenylalaninemia after loading with tetrahydrobiopterin. There were no abnormalities in urinary pteridine excretion or in dihydropteridine reductase activity. However, mutations were detected in the phenylalanine hydroxylase gene, suggesting a novel subtype of phenylalanine hydroxylase deficiency that may respond to treatment with cofactor supplementation.
Administration, Oral↗
Cerebellar clear cell ependymoma mimicking hemangioblastoma: its clinical and pathological features.
BACKGROUND: As the clinical and pathological significance of cerebellar clear cell ependymoma (CCE) has not been recognized in the past, eight cases of cerebellar CCEs were studied. METHODS: Subjects were six men and two women, and their ages ranged from 23 to 64 years old. Their neuroradiological, operative, and pathological features were reviewed. RESULTS: The tumors frequently showed high vascularity on angiography and marked enhancement on computerized tomography. Grossly, six tumors exhibited a "cyst with mural nodule" and two were mostly solid containing small cysts. At operation, the tumor nodules were dark red in color and the cysts contained xanthochromic fluid. Microscopically, all tumors displayed mostly clear round cells and abundant blood vessels. Although they commonly lacked the characteristic features of ependymomas, immunostaining and electron microscopy confirmed their ependymal origin. CONCLUSIONS: The results indicate that cerebellar CCEs closely mimic hemangioblastoma both clinically and pathologically, which suggests CCE should be considered in the differential diagnosis of vascular tumors of the cerebellum. Some diagnostic clues to differentiate CCE from hemangioblastoma are discussed.
Adult↗