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Biomedical subjects

S Kitamura

Publications and source records attributed to S Kitamura.

At least 19 recordsLinked to original sources

Preclinical evidence of Alzheimer changes in progressive mild cognitive impairment: a qualitative and quantitative SPECT study.

OBJECTIVES: Baseline brain single-photon emission computed tomography (SPECT) can predict mild cognitive impairment (MCI) patients at risk for progressive MCI (PMCI). METHODS: Twenty-eight subjects [12 MCI, 6 with probable Alzheimer's Disease (AD), and 10 normal subjects] underwent baseline brain SPECT and were clinically followed for a mean period of 36 months. RESULTS: Of 12 MCI patients, 6 progressed to PMCI and 6 remained stable. Baseline SPECT identified asymmetric perfusion reduction in the parahippocampus (-5%), lateral parietal (-8%), and posterior cingulate (-11%) cortices--reductions consistent with that of mild AD--in five of the six PMCI patients. Significant perfusion reduction was observed particularly in the frontal cortices of probable AD when compared with PMCI (P < 0.05). CONCLUSION: Baseline SPECT can identify brain perfusion abnormalities among patients with MCI for progression to PMCI. This imaging modality may aid in MCI treatment stratification.

Aged↗

Heart-type fatty acid binding protein is a novel prognostic marker in patients with non-ischaemic dilated cardiomyopathy.

OBJECTIVE: To determine whether concentrations of heart-type fatty acid binding protein (H-FABP) measured before hospital discharge predict critical cardiac events in patients with idiopathic dilated cardiomyopathy (DCM). PATIENTS: 92 consecutive patients with DCM were enrolled and followed up for four years. MAIN OUTCOME MEASURES: Serum concentrations of H-FABP, brain natriuretic peptide (BNP), cardiac troponin T before hospital discharge and survival rate. RESULTS: 23 patients died of cardiac causes, received a left ventricular assist device or underwent heart transplantation during the four-year follow up. Univariate analyses showed that New York Heart Association functional class, heart rate, ejection fraction, serum H-FABP and plasma BNP were significant variables. According to multivariate analysis, serum H-FABP and plasma BNP concentrations were independent predictors of critical cardiac events. Cardiac troponin T before hospital discharge was not a predictor. The area under the receiver operating characteristic curve for death from critical cardiac events was similar between H-FABP and BNP. Patients with an H-FABP concentration at or above the median (> or = 5.4 ng/ml) had a significantly lower survival rate than those below the median, according to analysis by log rank test (p < 0.0001). When combined with BNP concentration at or above the median (> or = 138 pg/ml), H-FABP below the median predicted the worst prognosis among the combinations. CONCLUSIONS: The concentration of serum H-FABP before discharge from hospital may be an independent predictor for critical cardiac events in DCM.

Biomarkers↗

Cardiorespiratory responses during passive walking-like exercise in quadriplegics.

STUDY DESIGN: Cross-sectional and comparative investigation using quadriplegics (QP) and nondisabled subjects (ND). OBJECTIVE: To evaluate cardiorespiratory responses during passive walking-like exercise (PWE) in QP. SETTING: National Rehabilitation Center for Persons with Disabilities in Japan. METHOD: The subjects were seven male QP with complete lesion (age: 27.0 +/- 5.4, injured level: C6-C7) and six male ND (age: 26.3 +/- 4.5). Cardiorespiratory responses were measured until voluntary fatigue during PWE, the rhythmical activity of paralyzed lower limbs synchronized with arm movements. RESULTS: There were no significant differences in oxygen consumption (VO(2)), pulmonary ventilation (VE), heart rate (HR) and oxygen pulse (O(2) pulse) between QP and ND during PWE. ND showed increased ventilatory equivalent for oxygen (VE/VO(2) ratio) during exercise, while QP showed a significantly greater respiratory rate (RR) during exercise than ND (P < 0.05). CONCLUSION: PWE elicited an increase in VO(2) with workload increment in QP similar to ND. However, higher RR suggested the intrinsic dysfunction of RR control during submaximal exercise in QP. From these results, it was thought that respiratory response would be the restriction factor of efficient oxygen transportation during PWE in QP.

Adult↗

Function of sigma1 receptors in Parkinson's disease.

OBJECTIVE: The objective of this study was to investigate the mapping of sigma1 receptors in Parkinson's disease (PD) using [11C]SA4503 and positron emission tomography (PET), and to assess whether sigma1 receptors are involved in the damaged dopaminergic system in PD patients. MATERIALS AND METHODS: We studied seven normal volunteers and six PD patients. The low density of dopamine transporters and the normal or high density of dopamine receptors were confirmed in the putamen of all patients using [11C]CFT and [11C]RAC PET. A dynamic series of PET data acquisition was performed with arterial blood sampling. We computed the binding potential (BP) of [11C]SA4503. RESULTS: In PD patients, the BP was significantly lower on the more affected than the less affected side of the anterior putamen, although there was no significant difference with respect to the BP between patients and controls. CONCLUSIONS: Release of dopamine is reduced asymmetrically in the putamen of early PD. [11C]SA4503 PET is an indicator of presynaptic dopaminergic damage in PD.

Adult↗

Non-malignant consequences of decreasing asbestos exposure in the Brazil chrysotile mines and mills.

AIMS: To investigate the consequences of improvement in the workplace environment over six decades (1940-96) in asbestos miners and millers from a developing country (Brazil). METHODS: A total of 3634 Brazilian workers with at least one year of exposure completed a respiratory symptoms questionnaire, chest radiography, and a spirometric evaluation. The study population was separated into three groups whose working conditions improved over time: group I (1940-66, n = 180), group II (1967-76, n = 1317), and group III (1977-96, n = 2137). RESULTS: Respiratory symptoms were significantly related to spirometric abnormalities, smoking, and latency time. Breathlessness, in particular, was also associated with age, pleural abnormality and increased cumulative exposure to asbestos fibres. The odds ratios (OR) for parenchymal and/or non-malignant pleural disease were significantly lower in groups II and III compared to group I subjects (0.29 (0.12-0.69) and 0.19 (0.08-0.45), respectively), independent of age and smoking status. Similar results were found when groups were compared at equivalent latency times (groups I v II: 30-45 years; groups II v III: 20-25 years). Ageing, dyspnoea, past and current smoking, and radiographic abnormalities were associated with ventilatory impairment. Lower spirometric values were found in groups I and II compared to group III: lung function values were also lower in higher quartiles of latency and of cumulative exposure in these subjects. CONCLUSIONS: Progressive improvement in occupational hygiene in a developing country is likely to reduce the risk of non-malignant consequences of dust inhalation in asbestos miners and millers.

Adult↗

Redo aortic valve replacement with ''porcelain'' aorta in an aortitis patient. A case report.

We report a successful reoperation of aortic valve replacement with the severely calcified, ''porcelain'' aorta due to Takayasu's disease. The patient was a 46-year-old female diagnosed with aortic prosthetic valve failure. Takayasu's aortitis had been noted at 17 years old and the patient underwent aortic valve replacement for aortic regurgitation at age 32. Chest CT scan revealed severe circumferential calcification of the whole thoracic aorta. Echocardiography revealed 100 mmHg of pressure gradient across the aortic prosthetic valve with pannus formation. Replacement of the aortic prosthetic valve was performed using the selective cerebral perfusion method under deep hypothermia. The postoperative course was uneventful without any neurological disorder. Selective cerebral perfusion was a useful method to avoid cross clamping in severely calcified ascending aortic.

Angiography, Digital Subtraction↗

Expression of lectin-like oxidized low-density lipoprotein receptor-1 in allografted hearts.

The pathogenesis of posttransplant coronary artery disease, which is thought to be a major form of chronic rejection after cardiac transplantation, is not fully understood. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) on endothelial cells induces reduction of NO release and up-regulation of adhesion molecules, thereby contributing to the development of vascular atherosclerosis. Herein, we investigated the expression of LOX-1 mRNA in murine allografted hearts that develop diffuse coronary obstruction. Allogeneic (C57BL/6 to BALB/c) and syngeneic (C57BL/6 to C57BL/6) heterotopic cardiac transplants were removed the 10th posttransplant day. LOX-1 mRNA expression was measured by RT-PCR. The heartbeat of the allografts gradually weakened and was almost stopped on day 10, whereas syngeneic hearts continued to pulsate throughout the experiment. Histologically, allografts showed fibrous luminal narrowing of the coronary arteries with severe mononuclear cell infiltration. In contrast, the vascular architecture of syngeneic grafts was almost normal. Marked increase in LOX-1 mRNA expression was observed only in allografts. The results indicate that alloimmune responses induce up-regulation of LOX-1 mRNA in transplanted hearts. Increased LOX-1 may be involved in the progression of obstructive vascular changes.

Animals↗

Midbrain hypometabolism as early diagnostic sign for progressive supranuclear palsy.

OBJECTIVE: Progressive supranuclear palsy (PSP) is often misdiagnosed in early phase. The purpose of this study is to investigate the feature of [(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography images for the early diagnosis of PSP. METHODS: We studied 15 patients with PSP and 16 normal subjects. Using SPM99 and analysis of covariance to eliminate the effect of aging, the differences between PSP and normals were displayed as a statistical map. In the PSP, we also investigated the correlation with duration and with the subscores of Unified Parkinson's Disease Rating Scale. RESULTS: The glucose metabolism of midbrain was significantly lower in PSP than in normals. However, correlation was not found between the metabolism of midbrain and clinical deterioration. CONCLUSIONS: The statistical map clearly demonstrated the hypometabolism of midbrain in PSP, which is independent of the clinical deterioration. The hypometabolism of midbrain is one of the most promising sign for early diagnosis of PSP.

Adult↗

Mechanism of improvement in exercise capacity after the maze procedure combined with mitral valve surgery.

OBJECTIVE: To clarify the mechanism of improvement in exercise capacity after the maze procedure. DESIGN: Retrospective study. SETTING: Tertiary referral centre. PATIENTS: 26 patients (mean (SD) age 57 (9) years) with atrial fibrillation (AF) and mitral valve disease were studied with echocardiography and cardiopulmonary exercise testing before and after the maze procedure combined with mitral valve surgery. Of these, eight had persistent AF and 18 had restored sinus rhythm (SR) by the surgery. Six patients (mean (SD) age 59 (12) years) with AF undergoing mitral valve surgery without the maze procedure who had cardiopulmonary exercise testing before and after the surgery formed the control group. MAIN OUTCOME MEASURES: Echocardiographic parameters of atrial function were measured from transmitral flow recordings. Peak oxygen uptake (VO2) and the slope of the relation between VO2 and workload (ratio of DeltaVO2 to Delta work) were determined as indices of exercise capacity. RESULTS: The degree of improvements in peak VO2 and the ratio of DeltaVO2 to Delta work after the mitral valve surgery was comparable between the maze and control group. It was also comparable between patients with and those without successfully restored SR after the maze procedure. The degree of the increase in peak VO2 correlated with the change in left atrial diameter (r = -0.40, p = 0.047) but atrial contraction did not correlate with the increase. CONCLUSIONS: Improvement in exercise capacity may not be caused by restored SR and atrial contraction but may at least partly relate to the reduction of left atrial size and improvement of haemodynamic variables by the surgery.

Adult↗

Cavitation phenomenon in monoleaflet mechanical heart valves with electrohydraulic total artificial heart.

Recently, cavitation on the surface of mechanical heart valves has been studied as a cause of fractures occurring in implanted mechanical heart valves. In this study, to investigate the mechanism of cavitation bubbles associated with monoleaflet mitral valves in an electrohydraulic total artificial heart (EHTAH), and to select the best valves for our EHTAH system, we measured three parameters. First, an image was created of the cavitation bubbles using a high-speed camera. Second, pressure drop in the vicinity of the valve surface was measured using mini pressure sensor. Then, the closing of the valve was observed using a Laser displacement sensor. Most of the cavitation bubbles in the Medtronic Hall valve were observed at the edge of the valve stop. With the Omnicarbon valve, the cavitation bubbles were observed at the edge of the valve and on the inner side of the leaflet. On the other hand, cavitation bubbles were observed only on the inner side of the leaflet in Björk-Shiley valve. Cavitation bubbles concentrated on the edge of the valve stop; the major cause of these cavitation bubbles was determined to be the squeeze flow. The formation of cavitation bubbles depended on the valve closing velocity and the valve leaflet geometry. From a viewpoint of squeeze flow, a low closing velocity and a small size of the valve stop could minimize cavitation.

Blood Pressure↗

Activation of estrogen response element dependent transcription by thyroid hormone with increase in estrogen receptor levels in a rat pituitary cell line, GH3.

Interrelationships between thyroid hormone and estrogen actions have been documented with regard to a variety of physiological functions. Both hormones stimulate transcription of target genes by binding to their nuclear receptors that interact with specific responsive elements (estrogen and thyroid hormone response elements, i.e ERE and TRE, respectively) in the regulatory regions of the gene. In vitro studies have suggested that interplay between the two hormones might be due to cross-talk at hormone responsive elements, with the respective hormone receptors and ligands able to interact, although physiological relevance has yet to be proved. We have proposed a simpler mechanism for thyroid hormone effects on estrogen responses via increase in estrogen receptor alpha (ERalpha) with resultant increase in progesterone receptors, prolactin production and tumor growth. A pituitary cell line, GH3, has been widely used to investigate the function of mammo-somatotropic cells, especially regarding regulation of GH and prolactin production. In the present study, an ERE-luc reporter was transfected into GH3 cells and the responses to endogenous ERalpha were examined. We demonstrated that: (1)l -3,5,3'-triiodothyronine (T3) induces mRNA expression of ERalpha; (2) T3 alone is able to induce ERE-luc activity and this is inhibited by OH-tamoxifen; (3) T3 synergistically acts on estradiol (E2)-induced ERE responses; and (4) ERE-luc activity is enchanted by co-transfection of an ERalpha expression vector. These results support the hypothesis that estrogen responses are potentiated by T3 through up-regulation of ERalpha levels.

Animals↗

In-situ visualization and quantification of mineralization of cultured osteogenetic cells.

An osteoblastic cell line (HOS cells) produces a prominent osteoid matrix with mineralization. Fibroblasts, on the other hand, do not exhibit this mineralization. To evaluate the degree of mineralization, we added calcein to the culture medium and then observed the culture wells by using an image analyzer. The calcein uptake into the cell/matrix layer was detected in the HOS cells but not in the fibroblasts. The calcein uptake was also quantified in situ by using an image analyzer, which revealed high levels in the HOS cells, which correlated well with the calcium content of the mineralized matrix. Rat marrow cells were also cultured in media containing calcein, fetal bovine serum, beta-glycerophosphate, L-ascorbic acid 2-phosphate, and with or without dexamethasone. With the dexamethasone, the cells exhibited osteogenic differentiation that resulted in mineralized matrix formation after about 10 days. The matrix formation coincided with the appearance of calcein uptake into the cell/matrix layer, with the amount of calcein uptake increasing with time. By contrast, the culture without the dexamethasone did not exhibit matrix formation and the calcein uptake was negligible. In the case of both HOS cell and rat marrow cell cultures in vitro, calcein did not affect expressions of their alkaline phosphatase activity or osteocalcin production. Furthermore, histologic observation revealed that rat marrow cells subcultured with calcein could show osteogenic ability after in vivo implantation. These results suggest that the current method of detecting calcein uptake in a culture allows the monitoring of the osteogenic capacity of cultured cells, as well as the measurement of the amount of mineralization produced by the osteogenic cells. Given that osteogenic cultured cells/mineralized matrices are used in bone reconstruction surgery, the in situ monitoring method is invaluable in that it allows us to evaluate the osteogenic capacity of in vitro constructs.

Alkaline Phosphatase↗

Gastrin activates nuclear factor kappaB (NFkappaB) through a protein kinase C dependent pathway involving NFkappaB inducing kinase, inhibitor kappaB (IkappaB) kinase, and tumour necrosis factor receptor associated factor 6 (TRAF6) in MKN-28 cells transfected with gastrin receptor.

BACKGROUND: We previously reported that gastrin induces expression of CXC chemokines through activation of nuclear factor kappaB (NFkappaB) in gastric epithelial cells that express gastrin receptor. AIMS: To clarify gastrin receptor mediated signals leading to activation of NFkappaB. METHODS: MKGR26 cells were created by transfecting gastrin receptor cDNA into MKN-28 cells. Degradation of inhibitor kappaB (IkappaB) and phosphorylation of protein kinase C (PKC)-delta were both detected by western blot analysis. NFkappaB activation was determined by luciferase assay and electrophoretic mobility shift analysis. RESULTS: Gastrin induced degradation of IkappaB-alpha and activation of NFkappaB, which was abolished by the selective gastrin receptor antagonist L-740,093 and the general PKC inhibitor GF109203X. Gastrin induced phosphorylation of PKC-delta, and its inhibitor rottlerin partially suppressed NFkappaB activation. However, the mitogen activated protein kinase (MAPK) kinase inhibitor PD98059, p38 MAPK inhibitor SB203580, and tyrphostin AG1478 had no effect on NFkappaB activation. Introduction of the dominant negative mutant of IkappaB kinase, of NFkappaB inducing kinase, and of tumour necrosis factor receptor associated factor 6 (TRAF6), but not that of TRAF2, inhibited gastrin induced activation of NFkappaB. CONCLUSIONS: Gastrin activates NFkappaB via a PKC dependent pathway which involves IkappaB kinase, NFkappaB inducing kinase, and TRAF6.

Animals↗

Type II citrullinaemia (citrin deficiency) in a neonate with hypergalactosaemia detected by mass screening.

Type II citrullinaemia (CTLN2) is an adult- or late childhood-onset liver disease characterized by a liver-specific defect in argininosuccinate synthetase protein. The enzyme abnormality is caused by deficiency of the protein citrin, which is encoded by the SLC25A 13 gene. Until now, however, few cases with SLC25A13 mutations have been reported in children with liver disease. We describe an infant who presented with neonatal hepatitis in association with hypergalactosaemia detected by neonatal mass screening. DNA analysis of SLC25A13 revealed that the patient was homozygous for a IVS11+1G>A mutation. This case suggests that SLC25A13 mutant should be suspected in neonatal patients with hypergalactosaemia of unknown cause.

Citrullinemia↗

Metabolism of 2-nitrofluorene, an environmental pollutant, by liver preparations of sea bream, Pagrus major.

1. The in vitro metabolism of 2-nitrofluorene (NF), an environmental pollutant, was examined in fish, focusing on nitro-reduction followed by N-acylation and hydroxylation. 2. When NF was incubated with liver microsomes or cytosol of sea bream, Pagrus major, in the presence of NADPH or 2-hydroxypyrimidine, 2-aminofluorene (AF) was formed. 3. When AF was incubated with liver cytosol in the presence of acetyl-CoA or N-formyl-L-kynurenine, 2-acetylaminofluorene (AAF) or 2-formylaminofluorene (FAF) was formed, respectively. AAF and FAF thus formed were deacylated to the parent AF by the liver preparations. 4. AF, AAF and FAF were oxidized to 7-hydroxy or 5-hydroxy derivatives by the liver microsomes. 5. Nitro-reduction, N-acylation and ring-hydroxylation of NF and the metabolites were also observed in rat liver preparations. These activities in sea bream livers were lower than those of rat liver. However, the order of magnitude of these activities in fish was the same as in rat. 6. It is suggested that NF is effectively reduced to AF by the cytochrome P450 system or aldehyde oxidase, and the acylated metabolites, AAF and FAF, generated by arylamine acetyltransferase and formamidase were hydroxylated by the cytochrome P450 system in fish in the same way as in rat. Further, the acetylamino and formylamino derivatives were interconverted via amino derivatives in the fish.

Air Pollutants↗