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Biomedical subjects

A Imamura

Publications and source records attributed to A Imamura.

At least 19 recordsLinked to original sources

Expression of endothelial cell-associated molecules in AML cells.

Recently, it has been clarified that interaction between hematopoietic cells and endothelial cells is important in normal hematopoiesis and leukemogenesis. In this study, we examined the relationship between AML cells and endothelial cells by analyzing the expression profile of angiogenic factors, angiopoietin-1 (Ang-1), Ang-2, Tie-2 (a receptor for angiopoietins) and vascular endothelial growth factor (VEGF). Our results demonstrated that CD7(+)AML expressed Ang-2 mRNA frequently and integrin-family adhesion molecules (CD11c and CD18) intensively, suggesting the close correlation with endothelial cells. On the other hand, in t(8;21) AML cells, expression of Ang-2 was infrequent and expression of integrin-family adhesion molecules (CD11b, CD11c and CD18) was weak, suggesting the sparse association with endothelial cells. As for CD7(+)AML cells, despite the frequent and intense expression of endothelial cell-associated molecules (such as Ang-2, CD11c and CD18), intensity of Tie-2 expression was quite low (P < 0.05). Ang-2 expressed in CD7(+)AML cells is not considered to act in an autocrine fashion, but to work on endothelial cells to "feed" leukemic cells. Although Ang-2 is recognized as a natural antagonist for Tie-2, our data presented here suggested the alternative role of Ang-2 in the relationship between endothelial cells and leukemia cells, at least in a subset of leukemia such as CD7(+)AML. These results were supported by the study using AML cell lines, KG-1 (CD7 negative) and its subline KG-1a (CD7 positive); KG-1 had mRNA expression profile of Ang-1(+)Ang-2(-)Tie-2(+), while KG-1a showed Ang-1(+)Ang-2(+)Tie-2(-). These difference in the expression profile of angiogenic factors between CD7(+)AML and t(8;21)AML may explain the characteristic morphological features of these leukemias (CD7(+)AML as blastic type and t(8;21)AML as differentiative type).

Acute Disease↗

Phenotype-genotype relationships in peroxisome biogenesis disorders of PEX1-defective complementation group 1 are defined by Pex1p-Pex6p interaction.

The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS), neonatal adrenoleucodystrophy (NALD) and infantile Refsum disease (IRD), are fatal autosomal recessive diseases caused by impaired peroxisome biogenesis, of which 12 genotypes have been reported. ZS patients manifest the severest clinical and biochemical abnormalities, whereas those with NALD and IRD show less severity and the mildest features respectively. We have reported previously that temperature-sensitive peroxisome assembly is responsible for the mildness of the clinical features of IRD. PEX1 is the causative gene for PBDs of complementation group E (CG-E, CG1 in the U.S.A. and Europe), the PBDs of highest incidence, encoding the peroxin Pex1p of the AAA ATPase family. It has been also reported that Pex1p and Pex6p interact with each other. In the present study we investigated phenotype-genotype relationships of CG1 PBDs. Pex1p from IRD such as Pex1p with the most frequently identified mutation at G843D was largely degraded in vivo at 37 degrees C, whereas a normal level of Pex1p was detectable at the permissive temperature. In contrast, PEX1 proteins derived from ZS patients, including proteins with a mutation at L664P or the deletion of residues 634-690, were stably present at both temperatures. Pex1p-G843D interacted with Pex6p at approx. 50% of the level of normal Pex1p, whereas Pex1p from ZS patients mostly showing non-temperature-sensitive peroxisome biogenesis hardly bound to Pex6p. Taking these results together, we consider it most likely that the stability of Pex1p reflects temperature-sensitive peroxisome assembly in IRD fibroblasts. Failure in Pex1p-Pex6p interaction gives rise to more severe abnormalities, such as those manifested by patients with ZS.

ATPases Associated with Diverse Cellular Activitie↗

Laparoscopic splenectomy for a lymphangioma of the spleen: report of a case.

We present the first case report of a successful laparoscopic complete excision of a splenic lymphangioma. The splenic tumor was preoperatively diagnosed to be a lymphangioma by the combined modalities of ultrasonography, computed tomography, magnetic resonance imaging, and angiography. A laparoscopic splenectomy was subsequently performed and the pathological examination of the mass confirmed the diagnosis of a lymphangioma. Based on the above findings, a laparoscopic splenectomy is recommended when a splenic tumor is suspected to be either benign or borderline.

Aged↗

Ruptured dissecting aneurysm in bilateral iliac arteries caused by Ehlers-Danlos syndrome type IV: report of a case.

Ehlers-Danlos syndrome (EDS) is an inherited disorder of connective tissue characterized by hyperextensible skin, hypermobile joints, and abnormalities of the cardiovascular system. Ten types and several subtypes of EDS have so far been recognized based on genetic, clinical, and biochemical characteristics. The spectrum of the disorder varies from mild to life-threatening vascular complications. EDS type IV is a particularly dangerous form with a lethal spontaneous rupture of the major arteries and aneurysmal formation. We present herein a case of a ruptured dissecting aneurysm in the bilateral iliac arteries caused by EDS type IV. A previously healthy 33-year-old man without any physical features of this connective tissue disorder experienced a metachronous vascular rupture two times. Successful synthetic bypass grafting was performed with great difficulty. The diagnosis of EDS type IV was made afterwards based on an electrophoresis analysis of a skin biopsy specimen which revealed a lack of type III collagen. Surgical intervention in cases of arterial complications in EDS type IV patients have been reported to be both difficult and frequently unsuccessful. The early clinical recognition of this syndrome is therefore of great importance due to the hazards of such surgical therapies.

Adult↗

The clinical course of childhood and adolescent adrenoleukodystrophy before and after Lorenzo's oil.

The clinical course of Japanese patients with childhood and adolescent adrenoleukodystrophy (ALD) who were treated with Lorenzo's oil after the progression of early symptoms was investigated by Kaplan-Meier analyses. Many of the early symptoms, including visual, personality, hearing, mental and speech disturbances, had already appeared when the oil therapy was started. These early symptoms appeared significantly faster than bed-ridden state or dysphagia (P<0.01). Gait disturbance appeared faster than bed-ridden state and dysphagia (P<0.05), and tended to appear later than the early symptoms. These results would reflect the early natural course of childhood and adolescent ALD before treatment, and provide a basis for the evaluation of therapeutic trials for ALD.

Adolescent↗

Piggyback foldable intraocular lens implantation in patients with microphthalmos.

PURPOSE: To evaluate the clinical results of phacoemulsification and implantation of 2 foldable acrylic intraocular lenses (IOLs) in microphthalmic eyes. SETTING: University of Tokyo School of Medicine, Tokyo, Eguchi Eye Hospital, Hakodate, and Osaka Rosai Hospital, Osaka, Japan. METHODS: This study comprised 5 eyes of 3 patients whose manifest spherical equivalent was +10.5 to +18.0 diopters (D) and axial length was 15.79 to 16.82 mm. After phacoemulsification, 2 foldable acrylic IOLs with a mean power of +43.0 D +/- 9.5 (SD) (range +32.0 to +55.0 D) were implanted in the capsular bag. RESULTS: There were no significant intraoperative complications, and there was significant improvement in uncorrected and best corrected visual acuities after surgery. The spherical equivalent decreased significantly; however, the postoperative refraction was considerably more hyperopic than predicted in all eyes. Except for posterior synechias in 2 eyes and slight interlenticular opacification in 2 eyes, no major postoperative complications occurred during the mean follow-up of 14.8 months. CONCLUSIONS: Implanting 2 piggyback IOLs was beneficial in eyes with an extremely short axial length. However, the current system of lens power calculation markedly underestimates the required lens power, resulting in a hyperopic refractive error after surgery. The benefits of in-the-bag placement of 2 foldable lenses are questionable.

Acrylic Resins↗

Laparoscopic cholecystectomy and choledocholithotomy in patients with a previous gastrectomy.

BACKGROUND: An increased incidence of cholelithiasis has been widely reported after truncal vagotomy and after gastric resection. In the early phase of patient selection, previous gastrectomy has been considered a relative contraindication to laparoscopic cholecystectomy (LC). In this study, we examined the management of LC in patients with previous gastrectomy. STUDY DESIGN: LC was attempted on 1,260 consecutive patients. Of these patients, 29 had a previous gastrectomy. Surgical procedures that had been performed included Billroth I gastrectomies (15), Billroth II gastrectomies (10), and total gastrectomies (4). There were 23 cases of cholelithiasis, 4 chronic cholecystitis, 2 gallbladder polyps, I porcelain gallbladder, and I gallbladder cancer. Nine patients were diagnosed with stones in their common bile duct or common hepatic duct. RESULTS: Preoperatively, seven of nine patients with common bile duct stones were subjected to endoscopic sphincterotomy, and the stones were removed successfully from five of these patients. In the remaining two patients, common bile duct stones were removed by laparoscopic choledocholithotomy by choledochotomy. The LC was completed in 26 patients (90%) who had undergone previous gastrectomy. In 449 patients who had previous abdominal surgery without a gastrectomy, only 4 patients (0.9%) required open surgery. In contrast, three patients (10%) with previous gastrectomy required open surgery. No major complications were recorded in this study series, and no residual or retained stones were seen during a followup period of 3 months. CONCLUSIONS: Clear visualization of anatomic structures and landmarks, and scrupulous hemostasis are needed to perform a safe LC in these patients. We conclude that in our study patients, a previous gastrectomy is considered an indication for LC and laparoscopic choledochotomy.

Adult↗

Clinical, biochemical and genetic aspects and neuronal migration in peroxisome biogenesis disorders.

Peroxisome biogenesis disorders (PBDs) are severe autosomal recessive neurological diseases caused by a defect of peroxisomal assembly factors. Zellweger syndrome, the most severe phenotype, is characterized by hypotonia, psychomotor retardation and neuronal migration disorder. Neonatal adrenoleukodystrophy and infantile Refsum disease are milder phenotypes of this disease. Thirteen complementation groups have been established since the genetic heterogeneity of PBDs was elucidated in 1988. Eleven genes for PBDs have been identified either by a functional complementation cloning or by EST homology searches. In 1992, the first gene for PBDs, PEX2, was identified. It encodes peroxisomal integral membrane protein with a RING finger domain. PEX5 and PEX7 are the genes for peroxisomal targeting signal (PTS)-1 and -2 receptors, respectively. PEX3, PEX16 and PEX19 are considered to be required for the early stage of peroxisome biogenesis. PEX13 protein has an SH3 docking site that binds to the PTS-1 receptor. PEX1 and PEX6 encode ABC protein, and PEX10 and PEX12 also encode integral membrane protein, with RING finger. Temperature-sensitivity, whereby peroxisomal biogenesis and metabolic dysfunctions are restored at 30 degrees C in cells from mild phenotypes, is a useful event for predicting the clinical severity and for elucidation of peroxisome biogenesis. Investigations using knockout mice are expected to facilitate understanding of migration disorders.

Animals↗

Lack of association between the hKCa3 gene and Japanese schizophrenia patients.

Several researchers have suggested an association between large numbers of CAG repeats in the hKCa3 gene and schizophrenia. However, these reports remain inconclusive and require further investigation. We tried to replicate these results in 112 Japanese schizophrenia patients and 102 control subjects of highly matched age and sex by applying an allele dichotomization model. No association was found. The overall distributions of allele frequencies were not significantly different between schizophrenic patients and normal control subjects. In addition, we tested the association between the size of the CAG repeats and the scores on three dimensions (positive and negative symptoms, and disorganization), but no significant results were obtained. Our results do not support the involvement of the hKCa3 gene in schizophrenia, at least in the Japanese population.

Adult↗

[Two cases of typhoid fever with reduced susceptibility to fluoroquinolones].

Two separate febrile Indian patients who reside in Japan and had recently returned from their country were diagnosed as suffering from typhoid fever. Fluoroquinolone therapy was clinically ineffective and the addition of a third-generation cephalosporin was required in each case. Each strain of Salmonella Typhi was resistant to nalidixic acid in vitro and also showed higher minimal inhibitory concentration to other quinolones than usual susceptible strains. Similar cases of typhoid fever responding poorly to quinolone treatment have been observed in the Indian subcontinent, south-east Asia and central Asia since the early 1990s, and potential spread by travelers into Japan is of serious concern. Although quinolones still remain the drugs of choice for treatment of typhoid fever, physicians should be aware of the possibility and implications of clinical treatment failure.

Adult↗

Cellular localization of the signaling components of Arabidopsis His-to-Asp phosphorelay.

In the higher plant, Arabidopsis thaliana, histidine-to-aspartate (His-to-Asp) phosphorelay signal transduction systems play crucial roles in propagation of environmental stimuli, including plant hormones. This plant has 11 sensor His-kinases, 5 histidine-containing phosphotransfer (HPt) factors (AHPs), and 20 response regulators (ARRs). To gain new insight into the functions of these phosphorelay components, their intracellular localization was examined with use of GFP-fusion proteins, constructed for certain representatives of HPt factors (AHP2) and type-A and type-B ARRs (ARR6/ARR7 and ARR10, respectively). The results showed that AHP2 is mainly located in the cytoplasmic space, while both the types of ARRs have an ability to enter preferentially into the nuclei, if not exclusively. Together with the results from an in vitro phosphorelay assay with AHP2 and ARRs, these results are discussed, in terms of a geneal framework of the Arabidopsis His-to-Asp phosphorelay network.

Arabidopsis↗

Malignant lymphoma of the bone associated with systemic sarcoidosis.

A 57-year-old woman was hospitalized with malignant lymphoma of the right talus. After treatment, complete remission was obtained. Gallium-67 scintigraphy to confirm the remission demonstrated increased uptake in the whole body skeletal muscle, especially in her thighs. Biopsy of right gastrocnemius muscle showed epithelioid granuloma. Serum angiotensin-converting enzyme activity (ACE) and lysozyme had increased to several times the normal range. We diagnosed her disease as bone-associated sarcoidosis-lymphoma syndrome. Human herpes virus 8 (HHV-8) genome was examined in the bone marrow specimen, and the relationship between sarcoidosis-lymphoma syndrome and HHV-8 was discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Catalase-less peroxisomes. Implication in the milder forms of peroxisome biogenesis disorder.

We established a Chinese hamster ovary cell line having a temperature-sensitive phenotype in peroxisome biogenesis. This mutant (65TS) was produced by transforming a PEX2-defective mutant, Z65, with a mutant PEX2 gene, PEX2(E55K), derived from a patient with infantile Refsum disease, a milder form of peroxisome biogenesis disorder. In 65TS, catalase was found in the cytosol at a nonpermissive temperature (39 degrees C), but upon the shift to a permissive temperature (33 degrees C), catalase gradually localized to the structures containing a 70-kDa peroxisomal membrane protein, PMP70. In contrast to catalase, other matrix proteins containing typical peroxisome targeting signals, acyl-CoA oxidase and peroxisomal 3-ketoacyl-CoA thiolase, were co-localized with PMP70 in most cells, even at 39 degrees C. We found that these structures are partially functional peroxisomes and named them "catalase-less peroxisomes." Catalase-less peroxisomes were also observed in human fibroblasts from patients with milder forms of peroxisome biogenesis disorder, including the one from which the mutant PEX2 gene was derived. We suggest that these structures are the causes of the milder phenotypes of the patients. Temperature-dependent restoration of the peroxisomes in 65TS occurred even in the presence of cycloheximide, a protein synthesis inhibitor. Thus, we conclude that in 65TS, catalase-less peroxisomes are the direct precursors of peroxisomes.

ATP-Binding Cassette Transporters↗

The yabG gene of Bacillus subtilis encodes a sporulation specific protease which is involved in the processing of several spore coat proteins.

The synthesis and proteolysis of the spore coat proteins, SpoIVA and YrbA, of Bacillus subtilis were analyzed using antisera. Almost no intact full-length proteins of either type were extracted from wild-type spores, while yabG mutant spores contained intact SpoIVA and YrbA proteins. We purified recombinant YrbA and YabG proteins from Escherichia coli transformants and found that YrbA was cleaved to the smaller moiety in the presence of YabG in vitro. These observations indicate that YabG is a protease involved in the proteolysis and maturation of SpoIVA and YrbA proteins, conserved with the cortex and/or coat assembly by B. subtilis.

Bacillus subtilis↗

Identification of PEX3 as the gene mutated in a Zellweger syndrome patient lacking peroxisomal remnant structures.

Peroxisome biogenesis disorders, of which 13 complementation groups have been identified, are subdivided with regard to two major dysfunctions: peroxisomal matrix protein import and peroxisomal membrane synthesis. Detectable remnant membrane structures are evident only in the former. Molecular defects have been defined in 10 PEX genes, including eight related to protein import and two to membrane synthesis. We now have evidence that the human complete cDNA encoding Pex3p, a peroxisomal membrane protein (PMP) factor for the proper localization of PMPs, rescues the import of both PMP and the matrix protein in fibroblasts from a Zellweger syndrome patient of complementation group G. This patient was homozygous for a 1 base insertion in the codon for V182, which resulted in a change of codon (182-183) and introduced a termination codon (184), which inactivated PMP and matrix protein import by Pex3p. A PEX3-defective CHO mutant clone, ZPG208, was of the same complementation group as group G.

ATP-Binding Cassette Transporters↗

Platelet-derived microparticles in patients with arteriosclerosis obliterans: enhancement of high shear-induced microparticle generation by cytokines.

We evaluated the plasma concentrations of cytokines and platelet-derived microparticles in patients with arteriosclerosis obliterans and studied the effect of cytokines on platelet-derived microparticle generation under high shear stress. Interleukin-6 levels peaked at 48 hours after vascular surgery, while thrombopoietin started to increase at 24 to 48 hours postoperatively and peaked on the seventh day. Platelet activation markers were increased in the arteriosclerosis obliterans patients preoperatively. Levels of P-selectin and CD63 both increased further, peaking at 6 to 24 hours postoperatively. Platelet-derived microparticle levels were also increased preoperatively. At 6 hours postoperatively, the plasma level of platelet-derived microparticles was significantly increased. Plasma platelet-derived microparticle level was lower at 12 hours but only returned to the preoperative value at 7 days after grafting. There was a difference in the platelet-derived microparticle level at 7 days between patients with or without antiplatelet therapy (cilostazol). The effect of cytokines on platelet activation under high shear stress was also studied. Interleukin-6 and thrombopoietin enhanced both P-selectin expression and platelet-derived microparticle generation under high shear stress. These results suggest that platelet-derived microparticles are released by platelet activation after vascular grafting when certain cytokines increase under high shear stress and that antiplatelet therapy may reduce platelet-derived microparticle levels postoperatively.

Aged↗