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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 73 records · Page 4Linked to original sources
PubMed2001

Neurogenic bladder in Lambert-Eaton myasthenic syndrome and its response to 3,4-diaminopyridine.

Autonomic dysfunction, as well as neuromuscular involvement, is a common manifestation of Lambert-Eaton myasthenic syndrome (LEMS). Dry mouth and impotence have been described as typical features of autonomic dysfunction, but neurogenic bladder is infrequent or subclinical in LEMS. We report a patient with neurogenic bladder secondary to LEMS whose condition responded to 3,4-diaminopyridine (3,4-DAP). In this patient's serum, results of repeated measurement with P/Q-type VGCC antibodies proved positive, but not with N-type VGCC and synaptotagmin antibodies. A review of the literature turned up a few patients with voiding dysfunction related to LEMS, but no urodynamic studies were done on these patients. Ours is the first case in which 3,4-DAP was efficacious in treating LEMS and neurogenic bladder. Responses of 3,4-DAP in urodynamic studies suggest that in this LEMS patient neurogenic bladder was caused by defective neurotransmission both in the autonomic detrusor and skeletal abdominal muscles.

4-Aminopyridine↗
PubMed2001

Effects of nitric oxide on matrix metalloproteinase-2 production by rheumatoid synovial cells.

Nitric oxide (NO) is a multifunctional messenger molecule generated from L-arginine by a family of enzymes, including nitric oxide synthase (NOS). This study was performed to examine whether NO modulates the production of matrix metalloproteinases (MMPs), which degrade all components of extracellular matrix (ECM), in rheumatoid synovial cells. We investigated the effects of exogenously generated NO by a NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), on the MMPs production by rheumatoid synovial cells. Culture media conditioned by SNAP-treated synovial cells were examined by gelatin zymography and immunoblot analysis. Incubation of synovial cells with SNAP resulted in gelatinase A production in a dose-dependent fashion. Furthermore, RT-PCR analysis demonstrated that MMP-2 mRNA expression was induced in SNAP-treated synovial cells. In contrast, SNAP did not influence the production of TIMP-1 and TIMP-2, which preferentially inhibit MMP-2, by rheumatoid synovial cells. Our data indicate that NO could modulate MMP production by rheumatoid synovial cells and therefore contribute to ECM degradation of articular components in RA.

Arthritis, Rheumatoid↗
PubMed2001

Alterations of the double-strand break repair gene MRE11 in cancer.

MRE11 plays a role in DNA double-strand break repair. Hypomorphic mutations of MRE11 have been demonstrated in ataxia-telangiectasia (AT)-like disorder. ATM mutations play a causal role in AT and have been demonstrated in lymphoid malignancies in patients without AT histories. By analogy with the relationship of ATM to lymphoid malignancies, it is probable that alterations of MRE11 are associated with tumor formation. We performed a mutation analysis of MRE11 in 159 unselected primary tumors. Three missense mutations at conserved positions were found in breast and lymphoid tumors. Additionally, an aberrant transcript without genomic mutation was found in a breast tumor. These findings suggest an occasional role for MRE11 alterations in the development of primary tumors.

Alternative Splicing↗
PubMed2001

Regulation of GAP-43 protein and mRNA in nigrostriatal dopaminergic neurons after the partial destruction of dopaminergic terminals with intrastriatal 6-hydroxydopamine.

Changes in the level of GAP-43 and its mRNA in nigrostriatal dopaminergic neurons in an animal model of the presymptomatic period of Parkinson's disease were measured to find the characteristic features of GAP-43 in nigrostriatal dopaminergic neurons. Since the dopaminergic neurons possess a relatively large amount of GAP-43 protein and mRNA, the dopaminergic neurons must be endowed with specific functions related to those of GAP-43. In this study, dopaminergic axon terminals were partially destroyed by intrastriatal 6-hydroxydopamine (6-OHDA). Rats were decapitated 3, 14, and 56 days following treatment. Levels of GAP-43 and tyrosine hydroxylase (TH) in the striatum were detected by immunoblotting and quantified. The number of GAP-43 mRNA-positive neurons and that of TH mRNA-positive neurons in the substantia nigra pars compacta (SNc) were detected by in situ hybridization using alkaline phosphatase (ALP)-labeled probes. Levels of GAP-43 in the striatum showed no significant alteration during the period of the experiment, although levels of TH were gradually restored. The number of GAP-43 mRNA-positive neurons as well as that of TH mRNA-positive neurons in the SNc decreased. These results suggests that dopaminergic neurons restore their axon terminals with little change in GAP-43, and that transcription and/or stability of GAP-43 mRNA in the dopaminergic neurons are susceptible to the toxin, although the dopaminergic neurons can maintain the translational product in the terminals. This feature may be related with a degeneration of dopaminergic neurons in Parkinson's disease.

Animals↗
PubMed2001

High-speed separation system of randomly suspended single living cells by laser trap and dielectrophoresis.

We developed a new system for random separation of a single microorganism, such as a living cell and a microbe, in the microfluidic device under the microscope by integrating the laser-trapping force and dielectrophoretic (DEP) force. An arbitrarily selected single microbe could be isolated in a microchannel, despite the presence of a large number of microbes in solution. Once the target microbe is trapped at the focal point of the laser, we can easily realize exclusion of excess microbes around the target by controlling the electric field, while keeping the target trapped by the laser at the focal point. To realize an efficient separation system, we proposed a new separation cell and produced it by microfabrication. Flow speed in the microchannel is adjusted and balanced to realize high-speed and high-purity extraction of the target. Some preliminary experiments are conducted to show the effectiveness. The target is trapped by the laser, transported, and is taken out from the extraction port. Total separation time is less than 20 s. Our method is extremely useful in the pure cultivation of the cell and will be a promising method for biologists in screening useful microbes.

Cell Separation↗
PubMed2001

Aberrant synaptic transmission in the hippocampal CA3 region and cognitive deterioration in protein-repair enzyme-deficient mice.

L-aspartate is the amino-acid residue most susceptible to spontaneous isomerization. This denaturation causes an alteration in the biological activity of the protein and is regarded as an aging process of the protein. Protein L-isoaspartyl methyltransferase (PIMT) repairs this post-translational modification and thus is implicated in retarding the aging process of proteins. PIMT is highly expressed in the brain, and its deficiency results in progressive epilepsy after 4 weeks of age, with a fatal seizure in mice. Here we report the pathophysiological role of this repair system in the hippocampal slice of PIMT-deficient mice. The hippocampal mossy fiber-CA3 synapses of PIMT-deficient mice showed hyperexcitation that was repressed by a gamma-aminobutyric acid (GABA)A receptor agonist muscimol. In addition, the mossy fiber-CA3 synapses failed to show long-term potentiation or paired-pulse facilitation. No abnormality, however, was observed in Schaffer collateral-CA1 synapses or in perforant path-dentate gyrus synapses. Electron microscopic study revealed aberrant distribution of synaptic vesicles in the mossy fiber terminals and vacuolar degeneration at the axon hillock of dentate granule cells in PIMT-deficient mice. Furthermore, the PIMT-deficient mice showed impaired spatial memory in Morris water maze test and exhibited fewer anxiety-related behaviors in the elevated-plus test. These results suggest that the mossy fiber-CA3 system is vulnerable to aspartate isomerization and that the PIMT-mediated repair system is essential for maintenance of normal functions of the hippocampus.

Aging↗
PubMed2001

Phylogeny and biogeography of the genus Lycium (Solanaceae): inferences from chloroplast DNA sequences.

Lycium comprises approximately 70 species and is disjunctly distributed in temperate to subtropical regions in South America, North America, southern Africa, Eurasia, and Australia. Among them, only Lycium sandwicense A. Gray sporadically occurs widely on oceanic islands in the Pacific Ocean. To investigate phylogenetic and biogeographic relationships of the genus with emphasis on L. sandwicense, the coding region of matK, the two intergenic spacers trnT (UGU)-trnL (UAA) and trnL (UAA)-trnF (GAA), and the trnL (UAA) intron of chloroplast DNA (cpDNA) were sequenced. A strict consensus tree resulting from the phylogenetic analysis indicates the following: (1) New World species comprise a potentially paraphyletic assemblage; (2) southern African, Australian, and Eurasian species together are monophyletic; (3) southern African species are a paraphyletic assemblage; and (4) L. sandwicense is in a clade with certain New World species. The estimated biogeographic events based on the cpDNA analysis indicate that (1) Lycium originated in the New World, (2) all southern African, Australian, and Eurasian species have a common ancestor from the New World, (3) Australian and Eurasian species originated once from a southern African progenitor, and (4) L. sandwicense differentiated from the New World species.

DNA, Chloroplast↗
PubMed2001

Expression of vascular endothelial growth factor (VEGF) and its two receptors in diffusely infiltrating astrocytomas and relationship to proliferative activity of tumor cells.

We studied the relationships among vascular endothelial growth factor (VEGF), its receptors (Flt1 and Flk1), and MIB-1. Their expression in 47 diffusely infiltrating astrocytomas obtained at surgery or autopsy was investigated by the ABC method and analyzed quantitatively. The positive rate of VEGF in tumor cells was higher than that in endothelial cells, and Flk1 was lower in tumor cells (P < 0.01, 0.01), whereas Flt1 in both tumor cells and endothelial cells was found at similar levels (P > 0.05). In tumor cells, VEGF became high with increased histological grades (P < 0.01). whereas both Flt1 and Flk1 were higher in grade 4 than in grades 2 and 3 (P < 0.01, 0.05). VEGF, Flt1, and Flk1 in endothelial cells were also highly expressed in grade 4 (P < 0.01). The distribution of MIB-1-positive nuclei in grade 4 was similar to VEGF, and the percent of positivity from grade 2 to grade 4 also increased (P < 0.01). There was a linear positive correlation between VEGF and both Flt1 and Flk1 in both tumor cells and endothelial cells (P < 0.01). So was the percent of positivity with VEGF, Flt1, and Flk1 in tumor cells and endothelial cells (P < 0.01). The experiment suggests that VEGF may act as a growth factor for both endothelial cells and tumor cells. VEGF, Flt1, and Flk1 can be considered as indicators of the malignancy potential of diffusely infiltrating astrocytomas. The expression of VEGF and the two receptors may be affected by the proliferative activity of tumor cells.

Astrocytoma↗
PubMed2001

Gouty tophus of the patella evaluated by PET imaging.

We report a case of gouty tophus of the patella, a rare lesion, which was evaluated using positron emission tomography (PET). This modality, which uses a combination of an amino-acid analog emitter, L-[3-(18)F]-alpha-methyl tyrosine (FMT), which neglects malignancies, and a glucose analog emitter, (18)F-fluoro-2-deoxy-D-glucose (FDG), which neglects benign lesions, simulating the radiographic findings, may be useful for the preoperative evaluation of gouty tophus occurring in patella partita, including detection, differentiation from malignant tumors, and possible pathogenetic diagnosis.

Gout↗
PubMed2001

Bax-induced apoptosis not demonstrated in the congenital toxoplasmosis in mice.

A prominent neuropathological change observed in a murine model of congenital toxoplasmosis is cerebral cortical hypoplasia. In the early embryonic life of toxoplasmosis mice, the number of apoptotic cell observed in cerebral cortex is increased, indicating that increased number of apoptotic cells might relate to the pathogenetic mechanism of the cortical hypoplasia. Immunohistochemical expression of apoptosis-related factors, Bcl-2 and Bax has been studied in fetal murine brains infected with toxoplasma and in controls. Paraffin sections of the fetal brains on embryonic day (ED) 10, 12, 14, 16 and 18 were applied for the immunostains of Bcl-2 and Bax. Totally, 47 experimental animals (ED10: n=8, ED12: n=6, ED14: n=12, ED16: n=6, ED18: n=15) and 48 control animals (ED10: n=6, ED12: n=8, ED14: n=9, ED16: n=9, ED18: n=16) were examined. Bcl-2 positive cells were detected on ED10, whereas Bax positive cells appeared on ED14. No difference of Bcl-2 and Bax expression between toxoplasmosis and control groups was detected, suggesting that there is no clear relation between Bax-induced apoptosis and cortical dysplasia in congenital toxoplasmosis.

Animals↗
PubMed2001

Mutation analysis of the methyl-CpG-binding protein 2 gene (MECP2) in Rett patients with preserved speech.

Genomic DNAs from 35 Japanese sporadic patients with Rett syndrome (RTT) were screened for DNA mutations in the entire coding region and exon-intron boundaries of methyl-CpG-binding protein 2 (MECP2). We detected mutations in 30 (85.7%) of 35 patients. Among these 35 RTT patients, five patients (14%) had the preserved speech variant of this disease. Four respective mutations (R133C, R306C, R294X, 2 base pair (bp) deletion) were found in these five patients. Two patients had the same missense mutation, R133C. The patients with the R133C mutation and one with frameshift mutation presented the relatively mild clinical presentation, and the R133C mutation was not found in any other patient without preserved speech. We confirmed that the preserved speech variant is one of the clinical phenotypes of RTT and is also caused by MECP2 mutation. We speculated that the clinical phenotype of patients with the R133C missense mutation might be mild.

Adult↗
PubMed2001

Long-term results of balloon-occluded retrograde transvenous obliteration for the treatment of gastric varices and hepatic encephalopathy.

PURPOSE: To evaluate the long-term results of balloon-occluded retrograde transvenous obliteration (B-RTO) for the treatment of gastric varices (GV) and hepatic encephalopathy. MATERIALS AND METHODS: A total of 43 patients who had undergone B-RTO were evaluated, 32 with GV, two with hepatic encephalopathy, and nine with both. All but one had been consecutively followed up with gastrointestinal endoscopy for more than 1 year (3-60 months; mean, 30.44 months). Collateral veins of gastric varices were graded using balloon-occluded retrograde left adrenal venography. The relation of both worsening of esophageal varices (EV) and improved Child-Pugh score after B-RTO to the grades of collateral vein development was analyzed. The relapse-free survival and the prognostic factors for survival after B-RTO were also assessed. RESULTS: GV disappeared or decreased markedly in size, and hepatic encephalopathy was completely cured in all patients. Improvement in Child-Pugh score was observed in 21 patient (50.0%) 6 months after B-RTO, but in only 11 patients (25.6%) 1 year after B-RTO. Worsening of EV was seen in eight patients and was related to a worsened grade of collateral veins. Cumulative relapse-free survival rate was 90.8% at 1 year and 87.4% at 3 years after B-RTO. The most significant prognostic factor was Child-Pugh classification (relative risk: 4.16) CONCLUSION: B-RTO is a safe and effective treatment for patients with GV and hepatic encephalopathy. The most important prognostic factors are the extent of Child-Pugh classification.

Balloon Occlusion↗
PubMed2001

Novel exon 11 skipping mutation in a patient with glycogen storage disease type IIId.

We report the molecular genetic abnormalities of a patient with GSD IIId presenting with progressive myopathy and cardiopathy leading to a fatal outcome. We identified two independent deletions including a 4 bp deletion (117-1120) and a 98 bp deletion (1135-1232) in cDNA. Sequencing of the genomic DNA of the corresponding region revealed a 4 bp deletion in exon 10; however, the other 98 bp deletion corresponding to exon 11, which was deleted in cDNA, was present in genomic DNA. We therefore concluded that skipping of exon 11 occurred in the cDNA of the patient. Intron/exon boundary analysis of the skipped exon 11 revealed no mutation in the consensus splice-site sequence. If normal splicing had occurred, a stop codon would have appeared within exon II due to frameshift mutation. The mechanism of exon skipping observed in our patient is as yet unknown, and it is still not clear whether intraexonal mutation of the preceding exon can influence splice-site selection. It is possible that a unique exon skipping occurred, preventing the appearance of a stop codon in our patient.

Adult↗
PubMed2001

Effect of intravenous prostaglandin E1 on pial vessel diameters and intracranial pressure in rabbits.

BACKGROUND: The main advantages of prostaglandin E1 (PGE1) for induced hypotension during neurosurgery include a rapid onset of action, a quick recovery from hypotension, lack of toxicity, maintenance of adequate perfusion to vital organs, and maintenance of cerebral blood flow reactivity to carbon dioxide during hypotension. However, there is no report that shows the effect of PGE1 on cerebral microvessel diameter and only a few data are available that show the effect of PGE1 on intracranial pressure. The aim of this study was to measure cerebral arteriole and venule diameters and intracranial pressure (ICP) during PGE1-induced hypotension to evaluate whether PGE1 is suitable for neuroanesthesia. METHODS: We measured the effects of 0.1, 0.3, 1.0, 3.0, and 10.0 microg x kg(-1) x min(-1) of intravenous PGE1 on mean arterial pressure (MAP), cerebral arteriole and venule diameters and ICP in anesthetized rabbits. RESULTS: MAP decreased statistically significantly from baseline at the infusion rates of 1.0, 3.0, and 10.0 microg x kg(-1) x ml(-1). Arteriole diameter increased significantly from the baseline at the infusion rate of 10.0 microg x kg(-1) x ml(-1) (18% from control). Venule diameter did not change from baseline value at any infusion rate. ICP did not change from baseline value at any infusion rate. CONCLUSION: We conclude that PGE1 might be a suitable drug for induced hypotension in neurosurgery from the viewpoint of its small effect on the cerebral microvessels and ICP.

Alprostadil↗
PubMed2001

Chronic lymphocytic leukemia (CLL) is rare, but the proportion of T-CLL is high in Japan.

Chronic lymphocytic leukemia (CLL) is a rare disease in Japan. Recent advances in molecular biology, diagnostic criteria and classification of CLL have reinforced the concept of each category of CLL as a distinct entity. Since there have been no recent studies on the incidence and prevalence of CLL in Japan, the Kyushu Hematology Organization for Treatment (K-HOT) Study Group conducted two studies of CLL. One study is a prospective registration of newly diagnosed hematological disorders, which gave us some idea of the incidence of CLL in our region (Kyushu island) where adult T-cell leukemia is endemic. A total of 677 patients with hematological disorders were registered over a 6-month period and 11 patients were diagnosed as having CLL among 182 leukemia patients. This amounts to 6% of all leukemias, which is twice as frequent as previously reported in Japan. The other study is a retrospective analysis of CLL. Eleven institutions of the K-HOT Group analysed their diagnostic records of chronic lymphoid leukemia, and 145 patients with CLL were found over a period of 3-12 yr. After the data were reviewed 11 patients were excluded through having a different type of leukemia. The proportion of chronic B-cell lymphoid leukemia was 73% (98/134), while that of T-cell leukemia was 18% (24/134). The proportion of T-cell chronic leukemia was 5-6 times higher than that in Western countries. Two institutions had a complete database on hematological disorders. From this database, the annual incidence of CLL was estimated to be 0.48 per 100 000. Thus, the incidence of CLL in Japan is at least 4-5 times lower than that in Western countries, suggesting that chronic B-cell leukemia is really rare, but chronic leukemia of T-cell lineage develops in Japan as frequently as in Western societies. Further investigation is required to delineate why the incidence of B-CLL is so low in Japan.

Adult↗
PubMed2001

Multifocal micronodular pneumocyte hyperplasia and lymphangioleiomyomatosis in tuberous sclerosis with a TSC2 gene.

A 45-year-old woman with a long-standing diagnosis of tuberous sclerosis (TSC) is presented. She has multifocal micronodular pneumocyte hyperplasia (MMPH) and lymphangioleiomyomatosis (LAM) of the lung, together with the detection of TSC2 gene mutation. During surgery for spontaneous pneumothorax, an open-lung biopsy was performed. Micronodules were well defined, measuring approximately 4 mm in diameter. These MMPHs were histologically composed of papillary proliferation of Type II pneumocytes, with positive immunoreactivity of keratin and surfactant apoprotein. The cystlike spaces, with dilatation and destruction of air spaces, were diffusely formed, and the walls were composed of the spindle cells. Such LAM showed positive immunoreactivity for HMB-45 (a monoclonal antibody specific for human melanoma) and tuberin (the gene product of TSC2). On germline mutation analysis using leukocytes of the present patient, a TSC2 gene mutation was confirmed as a deletion of G (or g) on Exon 9 by polymerase chain reaction-single-strand conformational polymorphism. However, no mutation was detected in her son. With microdissection analysis using paraffin-embedding lung tissues, LOH of the TSC2 gene preliminarily was detected in a LAM lesion but not in MMPH. It is suggested that MMPH, in addition to LAM, could be another pulmonary lesion in TSC patients and that the detection of TSC2 and/or TSC1 gene could essentially be useful for the pathogenesis of MMPH and LAM in TSC patients.

Adult↗
PubMed2001

CYP2C9*3 influences the metabolism and the drug-interaction of candesartan in vitro.

Candesartan cilexetil is an angiotensin II receptor antagonist, and candesartan, its active metabolite, is metabolized by CYP2C9. However, the effect of CYP2C9*3 on candesartan metabolism is not established. We characterized the kinetics of candesartan by CYP2C9*1/*1 and CYP2C9*1/*3 in human liver microsomes. The difference between the two was not significant. Subsequently, CYP2C9*1 and CYP2C9*3 (Leu359) were expressed in yeast, and the kinetics of candesartan were determined. The wild-type showed the lower Km (345 vs 439 microM; 3/4) and higher Vmax/Km (1/3) than the Leu359 variant. Also, we investigated potential interaction between candesartan and warfarin with both the wild-type and the Leu359 variant. Candesartan had no effect on S-warfarin 7-hydroxylation. In contrast, S-warfarin inhibited candesartan metabolism by the wild-type (K = 17microM) greater than by the Leu359 variant (Ki = 36 microM). These findings suggest that CYP2C9*3 may change not only the metabolic activity but also the inhibitory susceptibility compared with CYP2C9*1.

Alleles↗