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Biomedical subjects

M Fukuda

Publications and source records attributed to M Fukuda.

At least 199 records · Page 11Linked to original sources
PubMed2000

Endoscopic ultrasonography of the esophagus.

Endoscopic ultrasonography (EUS) is a generally accepted technique for the preoperative staging of malignant tumors in the upper and lower gastrointestinal tracts. In particular, EUS has been considered the method of choice in diagnosing esophageal carcinoma due to the relative ease in performing the examination and the accuracy of staging based on high-resolution ultrasonic imaging from within the lumen of the esophagus. This comprehensive review covers currently available EUS instruments, image characteristics of esophageal carcinoma, and images by the recently introduced miniprobe scanner. The role of the method in diagnosing superficial esophageal carcinoma and the possible treatment by endoscopic mucosal resection of this particular disease entity are discussed.

Endosonography↗
PubMed2000

Report of a patient with aortic dissection evolving into binocular ischemic retinopathy.

BACKGROUND: Carotid artery disease is known to cause a variety of ischemic ocular syndromes. We report a patient with an aortic dissection that evolved into binocular ischemic retinopathy. METHODS: Case report. RESULTS: A 49-year-old male patient presented with stomach pains and with no ophthalmologic symptoms. After extensive examination, a diagnosis of aortic dissection was made to account for the acute abdominal pain. Sixteen days later, he noted binocular photopsia and ophthalmoscopy revealed ischemic retinopathy. Arterial stent implantation and right coronary reconstitution surgery were performed. Subsequently, the ischemic lesions in the retina disappeared and no abnormality was observed by retinal angiography 1 year later. CONCLUSION: Binocular ischemic retinopathy can be a sign of aortic or carotid dissection, and these observations suggest that aortic dissection should be included in the differential diagnosis whenever ischemic changes are detected in the retina.

Aortic Dissection↗
PubMed2000

Does anovulation induced by oral contraceptives favor pregnancy during the following two menstrual cycles?

OBJECTIVE: To compare IVF and pregnancy outcomes before and after anovulation induced by oral contraceptives. DESIGN: Observational clinical study. SETTING: Infertility clinic. PATIENT(S): Forty women with two intact ovaries (32 of 40 couples with male factor infertility and 8 with unknown causes of infertility) underwent 190 IVF treatment cycles (55 natural cycles and 135 clomiphene citrate-stimulated cycles). INTERVENTION(S): If the women failed to conceive after 2-4 IVF treatment cycles, oral contraceptives were used to induce anovulation for 1 month before IVF was performed in two consecutive cycles. MAIN OUTCOME MEASURE(S): Rates of oocyte retrieval, fertilization, cleavage, preembryo formation, pregnancy, and implantation were compared before and after a period of anovulation. RESULT(S): The pregnancy rate per cycle of the first and second cycle combined (23%) and that of the second cycle alone (30%) after a period of anovulation were significantly higher than that observed before a period of anovulation (9%). CONCLUSION(S): Anovulation induced by oral contraceptives, showing bilateral ovarian quiescence, enhances pregnancy rates in the following two menstrual cycles of IVF treatment.

Adult↗
PubMed2000

Bezafibrate reduces blood glucose in type 2 diabetes mellitus.

The clinical efficacy of bezafibrate was examined with special reference to glucose metabolism in patients with type 2 diabetes mellitus (DM2). In protocol 1, 342 patients with DM2 and hyperlipidemias were randomly divided into 2 groups, 16-week bezafibrate treatment (n = 174) and no bezafibrate treatment (n = 168). In protocol 2, 20 DM2 patients were randomly divided into 2 groups, 8-week bezafibrate treatment (n = 10) and no bezafibrate treatment (n = 10), and a meal tolerance test (MTT) was performed. In protocol 1, bezafibrate treatment significantly reduced the fasting levels of triglyceride (TG) by 50% +/- 1.6%, total cholesterol (TC) by 12% +/- 1.1%, plasma glucose (PG) from 151.3 +/- 3.5 to 128.6 +/- 3.4 mg/dL, and hemoglobin A1c (HbA1c) from 7.2% +/- 0.1% to 6.9% +/- 0.1%, and significantly increased high-density lipoprotein cholesterol (HDL-C) by 20% +/- 0.8%. In protocol 2, fasting TG, PG, and insulin levels were significantly reduced by bezafibrate treatment. Moreover, in the MTT, postprandial increments of TG were significantly blunted after bezafibrate treatment, whereas postprandial PG and insulin levels were not significantly changed. Leptin levels were significantly decreased, while tumor necrosis factor alpha (TNF-alpha) levels were not changed. In conclusion, both hyperglycemia and hyperlipidemia can be improved by bezafibrate treatment in DM2.

Bezafibrate↗
PubMed2000

Mercury and cadmium in common cormorants (Phalacrocorax carbo).

Mercury (Hg) and cadmium (Cd) in common cormorants (Phalacrocorax carbo) collected in Lake Biwa, Japan and Tokyo, Japan, were investigated to elucidate the biological behaviors of these elements, and to assess exposure to these pollutants of wild, fish-eating birds. Hg and Cd concentrations were highest in the liver and kidneys, respectively. The lowest levels of both elements were observed in chicks. Hg concentrations in all tissues except brain increased significantly with growth from chicks to juveniles (p<0.05, U-test). Cd concentrations in the kidneys and liver also increased significantly during growth from juvenile to adult (p<0.005, U-test). When comparing hepatic Hg and Cd in adult birds between 10 samples from Lake Biwa and nine samples from Tokyo, the Cd concentrations in the Lake Biwa samples (1.4+/-0.37 microg/g dry wt) (mean+/-SD) were significantly higher than those from Tokyo (0.32+/-0.16 microg/g dry wt) (p<0.005, U-test), while no statistically significant difference was found in the Hg concentrations. Possible causes of these differences were discussed in relation to their prey.

Journal Article↗
PubMed2000

Congenital neuropathy with the absence of large myelinated fibers.

Twelve patients with hereditary motor and sensory neuropathy with the absence of large myelinated fibers have been reported. All of these patients had central nervous system involvement. In this report, we describe the first patient with pure motor and sensory neuropathy with the absence of large myelinated fibers without central nervous system involvement. Morphometric analysis of the biopsied sural nerve specimen revealed extremely small myelinated fibers compared with previously reported patients. It is supposed that the cause of this disease might be the abnormal development of axons of the peripheral nerves.

Abnormalities, Multiple↗
PubMed2000

The ST3Gal-I sialyltransferase controls CD8+ T lymphocyte homeostasis by modulating O-glycan biosynthesis.

T lymphocyte activation evokes distinct changes in cell surface O-glycans. CD8+ T cells undergo an elimination of sialic acid on core 1 O-glycans and an induction of core 2 O-glycans until either apoptotic death or differentiation into memory cells. We find that the ST3Gal-I sialyltransferase is required for core 1 O-glycan sialylation and its deficiency induces core 2 O-glycan biosynthesis. Apoptosis ensues with the loss of peripheral CD8+ T cells in the absence of immune stimulation. Cell surface ligation of the ST3Gal-I substrate CD43 recapitulates this phenotype by a caspase 3-independent mechanism. Control of core 1 O-glycan sialylation in T lymphocytes by ST3Gal-I comprises a homeostatic mechanism that eliminates CD8+ T cells by apoptosis while facilitating the production of viable CD8+ memory T cells.

Animals↗
PubMed2000

Suppressive effect of antiulcer agents on granulocytes--a role for granulocytes in gastric ulcer formation.

Many clinicians have believed that H2-blockers and proton pump inhibitors ameliorate gastric ulcers via their antacid function. We examined the effects of these antacids on granulocytes. Gastric ulcer patients were administered an H2-blocker or proton pump inhibitor for a week and the number of granulocytes and the superoxide production were examined. To determine the trafficking of granulocytes, mice were exposed to restraint stress for 24 hr. The H2-blocker decreased the number of granulocytes, while the proton pump inhibitor suppressed their superoxide production in humans and mice. The major function of H2-blockers and proton pump inhibitors in curing gastric ulcers seems to be their suppressive effects on granulocytes. In this case, stress accelerates the trafficking of granulocytes from the bone marrow to the gastric mucosa. If we demonstrate a role for granulocytes in gastric ulcer formation, an gap in the acid-pepsin theory and the Helicobacter pylori theory is filled in.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Regulation of cellular functions by nucleoside diphosphate kinases in mammals.

The role of nucleoside diphosphate (NDP) kinases in cell growth, differentiation, and tumor metastasis in relation to signal transduction was investigated. The essential role of NDP kinase in cell growth was validated by coupling between reduced NDP kinase levels, induced by antisense oligonucleotides, and the suppression of proliferative activity of a cultured cell line. In addition, because NDP kinase levels are often enhanced with development and differentiation, as has been demonstrated in postmitotic cells and tissues, such as the heart and brain, we further examined this possibility using the bone tissue (osteoblasts) and a cultured cell line PC12D. The enhanced NDP kinase accumulation was demonstrated in the matured osteoblasts in vivo and in vitro by immunohistochemistry. In PC12D cells, neurite outgrowth took place in NDP kinase beta-transfected clones without differentiation inducers, which was accompanied by prolongation of doubling time. Neurite outgrowth, triggered by nerve growth factor and a cyclic AMP analog, was down-regulated upon forced expression of inactive mutant NDP kinase by virtue of a dominant negative effect. NDP kinase alpha-transfected rat mammary adenocarcinoma cells (MTLn3) and nm23-H2-transfected human oral squamous cell carcinoma cells (LMF4) manifested reduced metastatic potential and were associated with an altered sensitivity to environmental factors, such as motility and growth factors. NDP kinase alpha, compared to NDP kinase beta, was involved in a wide variety of the cellular phenomena examined. Taken together, NDP kinase isoforms appear to elicit both their own respective and common effects. They may have an ability to lead cells to both proliferative and differentiated states by modulating responsiveness to environmental factors, but their fate seems to depend on their surrounding milieu.

Amino Acid Sequence↗
PubMed2000

Expression of human Wiskott-Aldrich syndrome protein in patients' cells leads to partial correction of a phenotypic abnormality of cell surface glycoproteins.

The Wiskott-Aldrich syndrome (WAS) is an uncommon X-linked recessive disease characterized by thrombocytopenia, eczema and immunodeficiency. The biochemical defect of this disorder primarily affects cells derived from bone marrow. To understand better the molecular mechanisms underlying this disease and to evaluate the possibility of correcting the genetic defects in hematopoietic cells, a Moloney murine leukemia virus (MoMLV)- based retroviral vector carrying a functional Wiskott-Aldrich syndrome protein (WASp) cDNA driven by an SV40 promoter (LNS-WASp) was constructed. A packaging cell line containing this vector produced a stable level of WAS protein and maintained a high titer of viral output. Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (B-LCL) from WAS patients, which lack expression of the WAS protein, were transduced by the LNS-WASp retroviral vector and showed expression of WASp by Western blot. Analysis of the O-glycan pattern on cell surface glycoproteins from WAS patients' B-LCL showed an altered glycosylation pattern, due to increased activity of beta-1, 6-N-acetylglucosaminyltransferase (C2GnT). Transduction by the retroviral vector carrying the functional WASp cDNA partially restored the abnormal glycosylation pattern, and was accompanied by a decreasing C2GnT activity. These findings imply a functional linkage between the WAS protein and the expression of the glycosyltransferase involved in the O-glycosylation, and also suggest a potential gene therapy via transferring a functional WASp cDNA into hematopoietic cells for Wiskott-Aldrich syndrome. Gene Therapy (2000) 7, 314-320.

Cells, Cultured↗
PubMed2000

Dental rehabilitation using endosseous implants and orthognathic surgery in patients with cleft lip and palate: report of two cases.

We describe the use of endosseous implants in the autogenous particulate cancellous bone and marrow grafted alveoli after orthognathic surgery for dental rehabilitation of patients with cleft lip and palate. This procedure has been applied to two patients and produced good results functionally and aesthetically. The results are encouraging and indicate that implant placement after orthognathic surgery is useful for patients both with congenital missing teeth and retrognathic maxillae.

Adult↗
PubMed2000

alpha(1,2)-fucosylation prevents sialyl Lewis x expression and E-selectin-mediated adhesion of fucosyltransferase VII-transfected cells.

E-selectin is a cytokine-inducible, calcium-dependent endothelial cell adhesion molecule that plays a critical role in the leucocyte-endothelium interaction during inflammation and is thought to contribute to the metastatic dissemination of tumour cells. Like the other selectins, E-selectin binds to ligands carrying the tetrasaccharide sialyl-Lewis x (NeuAcalpha2,3Galbeta1,4[Fucalpha1, 3]GlcNAc)1 or its isomer sialyl-Lewis a (NeuAcalpha2, 3Galbeta1, 3[Fucalpha1,4]GlcNAc). We examined the effect of expressing the H-type alpha(1,2)-fucosyltransferase or the alpha(2, 6)-sialyltransferase on the synthesis of sialyl-Lewis x by alpha(1, 3)fucosyltransferase. We found that H-type alpha(1, 2)-fucosyltransferase but not alpha(2,6)-sialyltransferase, strongly inhibited sialyl-Lewis x expression and E-selectin adhesion. We assume that H-type alpha(1,2)-fucosyltransferase competes with the endogenous alpha(2,3)-sialyltransferase for the N-acetyllactosamine structures assigned to further serve as acceptors for alpha(1, 3)fucosyltransferase.

Amino Sugars↗
PubMed2000

Identification of a nuclear export signal in MKK6, an activator of the carp p38 mitogen-activated protein kinases.

Carp homologues of p38 mitogen-activated protein kinase (MAPK) and its activator MAPK kinase 6 (MAPKK6, referred to as MKK6) were identified. There exist at least two distinct carp p38s, cp38a and cp38b, both of which consist of 361 amino acids. The transcript of c38a was exclusively expressed in the ovary, whereas that of cp38b was ubiquitously expressed. Western blot analysis with anti-(phosphorylated MAPK) Ig specific to the active p38 or JNK has shown that p38 was activated in response to hypertonic stress (1 M sorbitol) in epithelioma papilosum cyprini carp epithelial cells (EPC) and that the activation of p38 proceeded faster to the maximal level than that of JNK. Carp homologue (cMKK6) of p38 activator MKK6 consists of 404 amino acids. It was expressed ubiquitously but was most abundant in the ovary. An in vitro kinase assay demonstrated that cMKK6 is an upstream activator of cp38 and cp38b in carp because it specifically phosphorylated and activated cp38a and cp38b. Interestingly, we found that cMKK6 has a nuclear export signal (NES) sequence in its N-terminal region although upstream activators of stress-activated MAPKs, p38 and JNK, do not in other animals. The NES sequence facilitated nuclear export of cMKK6 and ovalbumin. Leucine residues in the sequence were crucial for the NES activity, as the activity was lost on replacement of the leucines to alanines. The existence of an NES in cMKK6 implies the requisite of strict regulation of the p38 MAPK pathway in carp. The abundance of these components for the stress-activated pathway in the ovary might be related to ectogenetic early development.

Amino Acid Sequence↗
PubMed2000

Synaptotagmin I and IV define distinct populations of neuronal transport vesicles.

Mammalian synaptotagmins constitute a multigene family of at least 11 membrane proteins. We have characterized synaptotagmin IV using antibodies directed against the C2A domain of the protein. Antibodies reacted specifically with a protein band that migrated as a 41-44 kDa doublet. Synaptotagmin IV expression was regulated throughout development. A strong decrease in the amount detected by Western blotting occurred between postnatal day 5 and adulthood, in agreement with studies on the expression of synaptotagmin IV transcripts. In subcellular fractionation, synaptotagmin IV was not detected in the synaptic vesicle-enriched fraction. Immunofluorescence microscopy was concordant with this finding. In 6-day-old rat cerebellum and cultured hippocampal neurons the subcellular distribution of synaptotagmin IV was clearly different from that of synaptotagmin I. Synaptotagmin IV displayed a punctate non-polarized distribution on neuronal extensions, whereas synaptotagmin I staining was essentially synaptic. Synaptotagmin IV staining was also observed in the soma in strong perinuclear fluorescent puncta superimposed on that of Golgi/TGN markers. Furthermore, synaptotagmin IV was seen in the proximal part of the growth cone domain and not in the microfilament-rich region which includes filopodia. Co-localizations with the adhesion molecules vinculin and zyxin at the proximal part of growth cones were observed. Synaptotagmin IV may thus be involved in the regulation of specific membrane-trafficking pathways during brain development.

Animals↗
PubMed2000

Synaptotagmin IV is present at the Golgi and distal parts of neurites.

Synaptotagmin IV (SytIV) is an immediate early gene induced by membrane depolarization in PC12 cells and in rat brain. However, little is known about the function of SytIV or the functional relationship between SytIV and SytI, because SytIV has yet to be localized. Here we show that SytIV was localized at the Golgi and distal part of neurites in nerve growth factor-differentiated PC12 cells and cultured hippocampal neurons by immunocytochemistry using an isoform-specific antibody (anti-SytIV). These SytIV signals were not colocalized well with SytI signals. Upon membrane depolarization, SytIV signals were increased at both the Golgi and distal part of neurites within several hours in both types of cells. We further show that the increase of SytIV protein levels results from protein kinase A-dependent gene up-regulation. In hippocampal neurons, SytIV was developmentally regulated. These results suggest that SytIV may play a role at the Golgi and tips of neurites during development and synaptic plasticity.

Animals↗