A novel nonsense mutation in the antithrombin III gene (Ser365 to stop) causing deep and mesenteric venous thromboses.
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Biomedical subjects
Publications and source records attributed to T Fujimoto.
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BACKGROUND: To examine regional metabolic changes in the human brain induced by free running in upright posture. METHODS. EXPERIMENTAL DESIGN: Regional brain changes in glucose uptake induced by running were examined by comparing brain images obtained by positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG). SETTING: The study was conducted at a research institute and involved participation of healthy young volunteers. Data sampling and analysis required special imaging device and special computer hardware/software. PARTICIPANTS: Subjects were 17 healthy male volunteers. They were divided at random into two equal groups, those who ran 4-5 km and the others sat in the room. MEASURES: differences in regional cerebral glucose uptake between runners and control groups were assessed statistically. Plasma glucose level was also measured and global cerebral uptake was estimated. RESULTS: Running was associated with a relative increase of glucose uptake in the temporoparietal association cortex, occipital cortex, premotor cortex and the cerebellar vermis. The highest activity was noted in the temporoparietal association cortex. Activity of the primary sensorimotor cortex was higher in the superomedial part (leg motor area) than the lateral part (thorax and arm). CONCLUSIONS: Running augmented energy consumption in the parieto-occipital region relative to the motor area, probably due to the higher energy consumption necessary for integration of multimodal sensory information than for generation of motor output. Our results indicate that FDG PET is a useful tool for brain mapping under various physiological conditions.
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Clinical diagnosis using positron emission tomography (PET) requires high costs. Therefore, sociomedical evaluation is very important for spread of clinical PET. In this report, sociomedical situation in European and Asia-Oceanian countries, especially concerning transportation of 18F-FDG and reimbursement of medical costs for clinical PET indications, is reported. It seems that UK, Germany and Belgium are the most advanced in clinical PET in Europe. In these countries, many PET investigations are reimbursed though systems are different among the countries. In UK, both public and private insurance gives authorization for clinical PET to some extent. In Germany, private health insurance companies give authorization but public insurance has not. In Belgium, private health insurance does not exist and public insurance gives authorization for clinical PET. Other European countries seem to be in transitional stages. Transportation of 18F-FDG has been already started in almost every country in Europe and Asia-Oceania. In Japan, neither transportation of FDG nor full reimbursement of clinical PET has not started yet and this situation seems to be exceptional. To promote clinical PET in Japan, there is the need of at least establishing a list of clinical indications for PET investigations and establishing commercial-based 18F-FDG supplying system. They could be regarded as a kind of infrastructure for spread of clinical PET.
We studied the factors of the elevation of serum creatine phosphokinase (CK) using the data from the routine medical checkup of Kanemi Yusho patients during 1995 and 1999. We also studied rat muscle plasma membrane by the freeze fracture method, which were given the polychlorinated biphenyls (PCB) and controls. The patients with elevation of serum CK showed significant elevation of PCB in their blood but not in polychlorinated quanterphenyls (PCQ). The rat muscle plasma membrane showed a slight increase of orthognal array density but it was not statistically significant. The densities of caveolae and particles were not changed. Accordingly, PCB were thought to be a factor in the elevation of CK in the serum.
Acute renal failure without oliguria developed in a 25-year-old male and a 19-year-old male after exercise. Marked hypouricemia became apparent during improvement of their renal function. Increased excretion of uric acid into the urine, increased fractional excretion of uric acid(clearance ratio of uric acid against creatinine), and normal concentration of plasma xanthine and hypoxanthine were observed in both cases. Probenecid and pyrazinamide loading test suggesting decreased reabsorption of uric acid in the proximal convoluted tubules revealed that presecretory reabsorption defect of uric acid resulted in the hypouricemia in both cases. These two cases were diagnosed as having idiopathic renal hypouricemia.
In a previous communication, we reported a leaflet fracture in a Jellyfish valve that was incorporated into a blood pump, after a 312-day animal implant duration. Subsequent finite element analysis revealed that the fracture location was consistent with an area of maximum strain concentration. Therefore, the aim of this study was to improve the durability in the light of these findings. Based on the engineering analysis results, a new valve seat having a concentric ring of 0.5-mm width, located at a radius of 7.0 mm, was designed and fabricated. Accelerated fatigue tests, conducted under the conditions recommended by ISO 5840, demonstrated that the durability of this new prototype was extended by a factor of 10, as compared to the original valve. Moreover, further finite element analysis indicated that the maximum equivalent elastic strain of the proposed new valve was reduced by 52.3% as compared to the original valve. Accordingly, it has been confirmed that the modified Jellyfish valve is suitable for use in long-term artificial hearts.
A Phase I trial of irinotecan hydrochloride (CPT-11) was performed to determine the maximum tolerated dose (MTD), the dose-limiting toxicities, and the incidence and severity of other toxicities in children with advanced neuroblastoma. Three children received 11 courses of CPT-11 administered as a 90-min i.v. infusion, daily for 3 days every 21 days. Doses ranged from 100 mg/m2 to 220 mg/m2. Two peaks in the total number of instances of diarrhea was observed, 25 stools at 3 days and 32 stools at 10 days. Myelosuppression was well controlled and of brief duration. One child achieved a clinical complete response (CR) and 2 had a partial response (PR). The MTD of CPT-11 administration was 180 mg/m2 for 3 days. These results indicate the usefulness of CPT-11 for the treatment of advanced neuroblastoma. Further investigation is necessary to establish its role in combination chemotherapeutic regimens.
A total of 334 diarrheal fecal samples (from 210 males and 124 females) collected in Kathmandu, Nepal, were studied for various kinds of enteropathogens. Overall, 33% (111/334) fecal samples were positive for one or more enteropathogens. There was no difference in detection rates between males and females. Enteropathogen detection rates in summer, winter, spring, and autumn were 61% (40/66), 52% (45/87), 31% (25/81), and 25% (25/100), respectively. Altogether eight species of bacteria, three genera of viruses, and five species of protozoan parasites were detected with considerable seasonal variations. Among the bacterial isolates, enteropathogenic Escherichia coli topped the list followed by Vibrio sp. Only one sample had Shigella (S. sonnei). Rotavirus type A was the most frequently detected among the enteric viruses, followed by human enterovirus and human adenovirus, respectively. Among the enteric protozoan parasites, Giardia intestinalis was the most frequently detected followed by Cryptosporidium parvum. Detection of bacterial and protozoan pathogens showed a slightly high tendency in the summer season compared with that in the other seasons (p>0.05), whereas the detection of viruses was significantly high in the winter season (p<0.05). Of the total 57 water samples, 43 (75%) showed one or more bacterial species out of which 51% (22/43) were E. coli. Among the E. coli isolates, 68% were EPEC. Enterohemorrhagic E. coli (O157) was not detected.
Alpha-N-acetylgalactosaminidase (alpha-GalNAc-ase; EC 3.2.1.49) is an exoglycosidase specific for the hydrolysis of terminal alpha-linked N-acetylgalactosamine in various sugar chains. The cDNA, nagA, encoding alpha-GalNAc-ase from Acremonium sp. was cloned, sequenced, and expressed in yeast Saccharomyces cerevisiae. The nagA contains an open reading frame which encodes for 547 amino acid residues including 21 residues of a signal peptide in its N-terminal. The calculated molecular mass of mature protein from the deduced amino acid sequence of nagA is 57260 Da, which corresponds to the value obtained from SDS-PAGE of native and recombinant enzymes treated with endo-beta-N-acetylglucosaminidase H. The amino acid sequence of NagA showed significant similarity to those of eukaryotic alpha-GalNAc-ases and alpha-galactosidases (alpha-Gal-ases), particularly alpha-Gal-ase A (AglA) from Aspergillus niger. Phylogenetic analysis revealed that NagA does not belong to the cluster of vertebrate alpha-GalNAc-ase and alpha-Gal-ase but forms another cluster with AglA and yeast alpha-Gal-ases. Thus, the evolutionary origin of the fungal alpha-GalNAc-ase is suggested to be different from that of vertebrate alpha-GalNAc-ase. This is the first report of a microbial alpha-GalNAc-ase gene.
Bacteriophage lambda surface display was used to isolate cDNA clones encoding autoantigens recognized by sera from patients with Sjögren's syndrome (SS). We made cDNA libraries from human HeLa and HepG2 cells, using the expression vector lambdafoo. By repeating affinity selection of the libraries with the sera immobilized in microtiter wells, we isolated three clones that encode previously unknown antigens as well as four clones previously known as SS autoantigens. The newly identified autoantigens include TRK-fused gene product (TFG), survival motor neuron gene product (SMN) and pM5, which has a similarity to the metal-binding domain of human fibroblast collagenase. Thus, the bacteriophage lambda surface display is powerful for isolating cDNA clones by affinity screening.
BACKGROUND: To the authors' knowledge there are few available data regarding the influence of lymphovascular space invasion, which has been examined separately as two components (lymphatic vessel invasion [LVI] and blood vessel invasion [BVI]), in the metastasis of cervical carcinoma. METHODS: LVI and BVI, which include capillary vessel invasion, were reviewed retrospectively based on the histopathologic slides of 239 women with cervical carcinoma who were treated with radical hysterectomy. The correlation between lymph node and/or ovarian metastases and LVI, BVI, and other histopathologic factors was investigated by multiple logistic regression analysis. The influence of LVI and BVI on survival was examined by Cox regression analysis. RESULTS: The rate of incidence of LVI was higher than that of BVI in all stages of cervical carcinoma (P < 0.0001 for International Federation of Gynecology and Obstetrics Stage IB and Stage II disease and P < 0.05 for Stage III disease). The incidence rate of BVI increased as LVI became more prominent and there was a significant correlation between the two findings (P < 0.0001). BVI was more frequent in adenocarcinoma/adenosquamous carcinoma than in squamous cell carcinoma (P < 0.05). LVI (P < 0.0001) and parametrial invasion (P < 0.0001) were significantly related to lymph node metastasis on multivariate analysis. Conversely, BVI (P < 0.05) and parametrial invasion (P < 0.0025), as well as adenocarcinoma or adenosquamous carcinoma (P < 0.0005), were significantly related to ovarian metastasis on multivariate analysis. With regard to the prognostic significance of these components, it was found that BVI (hazards ratio [HR] = 2.0), ovarian metastasis (HR = 6.5), and lymph node metastasis (HR = 5.5) were significantly related to a poor prognosis in women with cervical carcinoma. CONCLUSIONS: Ovarian metastasis may occur via hematogenous spread of cervical carcinoma. The results of the current study suggest that BVI, including capillary vessels, that is diagnosed separately from LVI using hematoxylin and eosin stained sections may be an important prognostic factor for patients with cervical carcinoma.
STUDY DESIGN: Experimental biochemical, behavioral, and histologic investigations of spinal cord injury in rats. OBJECTIVE: To investigate the effects of melatonin, a pineal hormone, in compression ischemic-induced spinal cord injury. SUMMARY OF BACKGROUND DATA: The implication of activated neutrophils in the worsening of spinal cord injury has been shown. Melatonin was shown to play an important role in protecting animal cells from neutrophil-induced toxicity and damage by free radicals. There is no report on using melatonin for spinal cord injury. METHODS: Spinal cord injury was induced by placing 25 g of weight extradurally on the rat spinal cord at T12 for 20 minutes. The rats were randomly divided into three groups. Sham rats had only laminectomy. Melatonin rats were injected with melatonin (2.5 mg/kg) intraperitoneally (intraperitoneal) five times: at 5 minutes, then 1, 2, 3, and 4 hours after the injury. Correspondingly, the control rats were injected with saline. Measured levels of lipid peroxidation estimated thiobarbituric acid reactive substances (TBARS) and the accumulation of leukocytes at the site of trauma, which were evaluated by measuring tissue myeloperoxidase activity. The recovery was assessed by using three clinical scoring systems, and histologic changes of the damaged spinal cord were examined. RESULTS: The thiobarbituric acid reactive substances content in the spinal cord increased after the injury, with two peaks (at 1 and 4 hours), and nitrogen mustard-induced leukocytopenia significantly attenuated the thiobarbituric acid reactive substances content in four 4 after injury. Also in these 4 hours, myeloperoxidase activity increased and melatonin injection reduced thiobarbituric acid reactive substances content and myeloperoxidase activity, which attenuated the motor deficits as well. Histologic findings showed that the melatonin group had less cavity formation than the control group. CONCLUSION: Results showed that injection of melatonin reduced thiobarbituric acid reactive substances content and myeloperoxidase activity, facilitating recovery of the damaged spinal cord.
Caveolin-1 is a major component of caveolae. Recent studies have suggested a possible role of caveolin-1 in cell transformation and normal cell proliferation. To observe the behavior of caveolin-1 in living mitotic cells, we prepared cDNA constructs encoding the chimeric protein of alpha- or beta-caveolin-1 and green fluorescent protein (GFP) and transfected culture cells with them. Correct targeting of the chimera to the caveolae was confirmed by colocalization with the caveolar inositol 1,4,5-trisphosphate receptor-like protein. By time-lapse observation of mitotic MDCKII cells, the GFP-caveolin-1 chimeras were seen throughout the plasma membrane before cell division, but became markedly concentrated at the cleavage furrow during cytokinesis. Accumulation around the spindle poles was also observed at late telophase. The result showed that caveolin-1 undergoes a drastic distributional change during cell division and suggested that the protein may be involved in the cytokinetic process.
By searching the EST database with the known cDNA sequence encoding alpha-caveolin-1 (full-length: FL), we found a variant having a hitherto unknown sequence in place of the first exon (5'-end variant: 5'V). The expression level of 5'V mRNA was equivalent to that of FL mRNA. The entire sequences of FL and 5'V mRNA were determined by 3'- and 5'-RACE analysis; their sizes were 2484 bp and 2533 bp, respectively, and the sequences were identical except for the region of the first exon. By Northern blotting, FL and 5'V mRNAs showed the same tissue distribution, and were intensely expressed in the lung, heart, and skeletal muscle. Analyzing the protein production from these mRNAs using green fluorescent protein as a tag, we found FL mRNA to produce the alpha-isoform predominantly, but to form little beta-isoform. The production of the beta-isoform from 5'V mRNA was also demonstrated. By sequence analysis of the first intron of the caveolin-1 gene, a TATA box was found at 28 bp upstream of the transcription initiation site for 5'V mRNA. This is the first demonstration of caveolin-1 mRNA variants generated by alternative transcription initiation, and it indicates that the two isoforms of caveolin-1 are produced from two distinct mRNAs.
Little is known about the molecular composition of the ciliary rootlet. We raised monoclonal antibodies to a crude preparation of striated rootlets isolated from the human oviduct, and obtained a clone (R4109) that specifically labeled the ciliary rootlets. Rootlets associated with the solitary cilium in secretory cells and fibroblasts were also labeled. R4109 identified a 195-kDa protein by immunoblotting. Ciliogenic cells in the oviduct epithelium of young mice were labeled in the globular and/or granular pattern by R4109 by immunofluorescence microscopy. Immunoelectron microscopy showed that they corresponded to fibrogranular complex and dense granule, respectively. The result demonstrated that the 195-kDa protein is a component common to the striated rootlet and dense granule, and thus suggested that dense granules are involved in the rootlet formation.
The purpose of this study was to examine, by positron emission tomography (PET), the distribution of [18F]fluoro-deoxy-glucose ([18F]FDG) uptake by human muscles during 35 min of running. Thirteen healthy male subjects were studied, seven of whom participated in the exercise study. Running intensity was kept constant such that the subjects' heart rates were maintained at between 140 and 150 beats per minute. [18F]FDG [62.9 (14.8) MBq, mean (SD)] was injected after 15 min of running. PET imaging was started immediately after the running ended. The ratio of [18F]FDG uptake by muscles in runners to that in control subjects (r-c ratio) varied from three to six for the muscles of the foot and leg below the knee joint. The r-c ratio of the medial head of the gastrocnemius (MG) was higher than that of its lateral head (LG). The r-c ratio of the rectus femoris (RF) was lower than that of the other three muscles of the quadriceps femoris (QF). The r-c ratio of inactive muscles located above the waist was approximately 0.7. These results suggest that, during the moderate running of this study: (1) glucose uptake by muscles of the foot and leg below the knee joint clearly increases, (2) the r-c ratio differs significantly among the skeletal muscles, which act synergistically, and (3) glucose uptake by inactive skeletal muscles decreases.