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Biomedical subjects

A Imamura

Publications and source records attributed to A Imamura.

At least 73 records · Page 4Linked to original sources

Peroxisome biogenesis disorders: identification of a new complementation group distinct from peroxisome-deficient CHO mutants and not complemented by human PEX 13.

Ten complementation groups of generalized peroxisome biogenesis disorders (PBD), (excluding rhizomelic chondrodysplasia punctata) have been identified using complementation analysis. Four of the genes involved have been identified using two different methods of (1) genetic functional complementation of peroxisome deficient CHO cell mutants and (2) homology searches for human dbEST, based on yeast genes involved in peroxisome biogenesis (PEX genes). We report here the first identification of a new complementation group which is genetically different from peroxisome deficient CHO mutants. There were no complementations by the human PEX 13 gene. The nature of the related gene is being investigated.

Animals↗

Effect of ultrahigh-dose methylcobalamin on compound muscle action potentials in amyotrophic lateral sclerosis: a double-blind controlled study.

To develop a symptomatic treatment for amyotrophic lateral sclerosis, we compared the effects of ultrahigh-dose and low-dose (25 and 0.5 mg/day, intramuscularly, for 14 days) methylcobalamin on averaged compound muscle action potential amplitudes (CMAPs) in a double-blind trial. No significant changes in CMAP amplitude were found in 12 patients who had the low-dose treatment at either 2 or 4 weeks after start of treatment. By contrast, 12 patients assigned to the ultrahigh-dose group demonstrated a significant increase at 4 weeks. This method may provide a clinically useful measure to improve or retard muscle wasting, if a larger extended trial fulfills its promise.

Action Potentials↗

Influence of luteinizing hormone-releasing hormone analogues on serum levels of prostatic acid phosphatase and prostatic specific antigen in patients with metastatic carcinoma of the prostate.

Serum concentrations of luteinizing hormone (LH), testosterone, prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) were measured in 16 patients with advanced prostatic cancer before and after treatment with luteinizing hormone-releasing hormone (LHRH) analogue. An initial rise of serum LH and testosterone levels was observed on day 2 of the treatment. Subsequently, serum concentrations of PAP and PSA showed a transient increase on day 5 of the treatment. This indicates that LHRH analogues had better be given in combination with antiandrogens in patients with metastatic carcinoma of the prostate.

Acid Phosphatase↗

Seroma with fibrous capsule formation requiring a surgical resection after a modified radical mastectomy: report of a case.

Seroma formation is the most common complication of a modified radical mastectomy for breast cancer. Although various management or risk factors for seroma formation have been previously reported, little has been published concerning seromas with fibrous capsule formation which ultimately require a surgical resection. We herein present a case who developed a seroma with a fibrous capsule after a modified radical mastectomy for breast cancer, in spite of an uneventful intraoperative and postoperative course. The seroma was refractory to all conventional treatments, and thus finally required a surgical resection.

Axilla↗

Anticipation in Japanese families with schizophrenia.

The identification of anticipation in schizophrenia is a recent focus in the genetic epidemiology of schizophrenia, although it involves some controversial methodological issues. We explored the evidence of anticipation among 44 Japanese two-generation pairs with schizophrenia found by reviewing nine years of admission records (1986-1994) at the Department of Neuropsychiatry, Nagasaki University Hospital and Michino-o Hospital, Nagasaki. The 44 pairs consisted of 27 two-generation pairs of first-degree relatives group (FDRG) and 17 pairs of second-degree relatives group (SDRG). On pairwise comparison and a life table analysis, the age at onset (AO) was significantly earlier in the lower generation (G2) than in the upper generation (G1) in all of the pairs and in the two subgroups, FDRG and SDRG. Earlier AO was shown in G2 even after minimizing some statistical biases for the study of anticipation in schizophrenia. A significant earlier mean AO was found in G2 even when a cohort effect was controlled for. There was no marked difference in AO between paternal and maternal transmission. These results provide further evidence for epidemiological anticipation, suggesting biological anticipation such as the involvement of trinucleotide repeats expansion in G2. The limitations of the study are also discussed.

Adolescent↗

A monoarthritis model in rabbits induced by repeated intra-articular injections of lipopolysaccharide.

We attempted to develop a monoarthritis model using repeated intra-articular injections of high-dose Lipopolysaccharide (LPS). Furthermore, the effect of dexamethasone on this arthritis model by intra-articular administration was studied to examine whether the model can be used to screen anti-rheumatic drugs in a short time. Arthritis was induced by one, two or three intra-articular injections of LPS (5-50 micrograms/joint) at 4-day intervals into the knee joint. The rabbits were sacrificed at 7 days following the last injection of LPS. Three intra-articular injections of LPS at 50 micrograms/joint resulted in persistent joint swelling. Hyperplasia of synovium with some discolouration was macroscopically observed. Infiltration of mononuclear cells and lymphoid follicles were histologically observed as the synovial lesions. Concerning the articular bone/cartilage, trabecular destruction of gastrocnemius sesamoid bone and severe loss of safranin-O staining of articular cartilage were observed. Immunohistochemical analysis revealed that inflammatory cells and lymphoid follicles in the synovial lesions consisted predominantly of CD4+ T cells, with few CD8+ T cells. Treatment with dexamethasone markedly reduced the joint swelling and the articular destruction. The results suggest that this arthritis model in rabbits can be utilized to screen anti-rheumatic drugs as a model of rheumatoid arthritis.

Animals↗

Temperature-sensitive mutation in PEX1 moderates the phenotypes of peroxisome deficiency disorders.

The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), are autosomal recessive diseases caused by deficiency of peroxisome assembly as well as malfunction of peroxisomes, where >10 genotypes have been reported. ZS patients manifest the most severe clinical and biochemical abnormalities, while those with NALD and IRD show the least severity and the mildest features, respectively. PEX1 is the causative gene for PBDs of complementation group I (CG1), the highest incidence PBD, and encodes the peroxin, Pex1p, a member of the AAA ATPase family. In the present work, we found that peroxisomes were morphologically and biochemically formed at 30 but not 37 degrees C, in the fibroblasts from all CG1 IRD patients examined, whereas almost no peroxisomes were seen in ZS and NALD cells, even at 30 degrees C. A point missense mutation, G843D, was identified in the PEX1 allele of most CG1 IRD patients. The mutant PEX1, termed HsPEX1G843D, gave rise to the same temperature-sensitive phenotype on CG1 CHO cell mutants upon transfection. Collectively, these results demonstrate temperature-sensitive peroxisome assembly to be responsible for the mildness of the clinical features of PEX1 -defective IRD of CG1.

ATPases Associated with Diverse Cellular Activitie↗

Histidine-containing phosphotransfer (HPt) signal transducers implicated in His-to-Asp phosphorelay in Arabidopsis.

His to Asp phosphorelay signal transduction mechanisms involve three types of widespread signaling components: a sensor His-kinase, a response regulator, and a histidine-containing phosphotransfer (HPt) domain. In Arabidopsis, several sensor His-kinases have recently been discovered (e.g., ETR1 and CKI1) through extensive genetic studies. Furthermore, a recent search for response regulators in this higher plant revealed that it possesses a group of response regulators (ARR-series), each of which exhibits the phospho-accepting receiver function. However, no signal transducer containing the HPt domain has been reported. Here we identify three distinct Arabidopsis genes (AHP1 to AHP3), each encoding a signal transducer containing a HPt domain. Both in vivo and in vitro evidence that each AHP can function as a phospho-transmitting HPt domain with an active histidine site was obtained by employing both the Escherichia coli and yeast His-Asp phosphorelay systems. It was demonstrated that AHP1 exhibits in vivo ability to complement a mutational lesion of the yeast YPD1 gene, encoding a typical HPt domain involved in an osmosensing signal transduction. It was also demonstrated that AHPs can interact in vitro with ARRs through the His-Asp phosphotransfer reaction. It was thus suggested that the uncovered sensors-AHPs-ARRs lineups may play important roles in propagating environmental stimuli through the multistep His-Asp phosphorelay in Arabidopsis.

Amino Acid Sequence↗

Preoperative assessment for laparoscopic cholecystectomy: feasibility of using spiral computed tomography.

OBJECTIVE: The authors investigated the preoperative feasibility of using spiral computed tomography (SCT) after intravenous infusion cholangiography (IVC-SCT) for laparoscopic cholecystectomy. SUMMARY BACKGROUND DATA: In laparoscopic cholecystectomy, the aberrant or unusual anatomy of the bile duct and severe inflammation or adhesions around the gallbladder sometimes require a conversion to open surgery. METHODS: Laparoscopic cholecystectomies (LC's) were attempted on 440 patients, and preoperative IVC-SCT also was attempted in all of these patients. Using this spiral scanning technique, the bile ducts, cystic duct, and gallbladder were assessed for contour abnormalities, relative position, and filling defects. Forty-seven patients were diagnosed with having stones in their common bile duct or common hepatic duct. RESULTS: Three-hundred eighty-seven patients out of the 440 patients (88.0%) who were subjected to IVC-SCT had the length and course of their cystic duct successfully determined. Anomalous unions of the cystic duct were seen in 59 (15.2%) of 387 patients with respect to the operative findings, and 48 of 440 patients (10.9%) had severe adhesions to Calot's triangle and the surrounding tissues. In these 48 patients, 45 patients (94%) had a nonvisualized cystic duct on IVC-SCT. The preoperative assessment of the feasibility (dense adhesions obscuring Calot's triangle) of using IVC-SCT demonstrated that the sensitivity, specificity, and accuracy were 93%, 98%, and 94%, respectively. Five patients had to be converted to open surgery, and the overall morbidity rates for patients undergoing laparoscopic cholecystectomy was 0.9% (4 of 440). CONCLUSIONS: The most important factor in assessing the feasibility of using laparoscopic cholecystectomy is not the nonvisualized gallbladder, but the nonvisualized cystic duct on IVC-SCT. IVC-SCT may be of benefit to those patients scheduled to undergo laparoscopic cholecystectomy.

Adolescent↗

Genomic discordance between monozygotic twins discordant for schizophrenia.

OBJECTIVE: Genomic DNA of monozygotic twins discordant for schizophrenia was analyzed to determine whether their genomes were truly identical. METHOD: The subjects were monozygotic male twins, one of whom had DSM-III-R schizophrenia, undifferentiated type. Genomic DNA was extracted from leukocytes and was applied to restriction landmark genome scanning analysis, which was developed for a high-speed survey of restriction sites throughout a genome and measurement of their copy number in each locus. RESULTS: After comparisons of patterns with approximately 2,000 spots, the authors detected at least two spots with autoradiographic intensities that obviously differed in the two twins. CONCLUSIONS: The discrepancies likely were generated either by differences in the methylation status at NotI sites between the twins or by submicroscopic changes occurring at NotI-flanking sites in one twin after (or simultaneous with) twinning. In either case, the difference may influence the transcription level of one or more genes.

Adult↗

Clinical evaluation of closed suction drainage following hepatectomy.

A prospective randomized study on 186 patients was conducted to determine the influence of closed suction drainage (n = 102) versus open drainage (n = 84) on the incidence of postoperative complications after elective hepatic resection. The patients were randomly allocated between the two groups. A total of 60 complications occurred in 31 of the 84 patients (36.9%) given open drainage, while 24 complications occurred in 15 of the 102 patients (14.7%) given closed suction drainage. The incidence of pleural effusion, postoperative ascites, and infected subphrenic collections was significantly lower in the closed suction drainage group than in the open drainage group, at 31% vs 16% (P < 0.05), 19% vs 3% (P < 0.01), and 17% vs 5% (P < 0.05) respectively. However, both groups showed similar rates of subphrenic hematoma and bile collection. These findings indicate that closed suction drainage significantly reduces the incidence of postoperative complications after elective hepatic resection.

Adult↗

Progression of articular destruction and the production of tumour necrosis factor-alpha in antigen-induced arthritis in rabbits.

We examined the progression of articular destruction and the production of tumour necrosis factor-alpha (TNF-alpha) in antigen-induced arthritis (AIA) in rabbits, i.e. flare-ups of inflammation induced by repeated intra-articular injections (single, twice and three times) of antigen. A marked progression of articular destruction and an infiltration of inflammatory cells in the synovium were observed with the increase in the number of antigen injections. An immunohistochemical analysis of the synovial lesions following three injections of antigen revealed that the lymphoid follicles consisted mainly of CD4+ T cells and IgG/IgM+ B cells. There were marked infiltrations of IgG+ plasma cells around the lymphoid follicles. In contrast, the production of TNF-alpha in the synovial fluid and the erythrocyte sedimentation rate (ESR), which is a marker of systemic inflammatory activity in rheumatoid arthritis, peaked at 6 h 24 h, respectively, following the last injection of antigen. These values were also greater following the repeated injections of antigen compared with the single injection. The TNF-alpha was produced markedly in the joints at the onset of the flare-ups of arthritis following the repeated injections of antigen, and the elevation of the ESR and an acceleration of the inflammatory response in the synovium were observed with a concomitant progression of severe articular destruction, suggesting that the marked production of TNF-alpha at the time of flare-ups may be involved in the exacerbation of AIA in rabbits.

Animals↗

Two novel missense mutations in the ATP-binding domain of the adrenoleukodystrophy gene: immunoblotting and immunocytological study of two patients.

Two novel missense mutations, 1939G to A (R518Q) and 2017A to G (Q544R) were identified in Japanese patients with adrenoleukodystrophy (ALD). They are located in exon 6, which encodes part of the putative adenosine triphosphate binding domain of ALD protein. The ALD protein carrying the R518Q mutation was undetectable in fibroblasts, by immunoblot and immunofluorescence analysis, while the Q544R mutation had no apparent effect on the stability and localization of the ALD protein, but is expected to affect its function.

ATP Binding Cassette Transporter, Subfamily D, Mem↗

Peroxisomal disorders: clinical aspects.

Peroxisomal disorders are divided into two groups from a clinical point of view. Diseases in the first group, peroxisome-deficient disorders (PDD), Zellweger-like syndrome, and isolated deficiencies of peroxisomal beta-oxidation enzymes, are characterized by common clinical features including psychomotor retardation, hypotonia, hepatic dysfunction and visual disturbance. The second group includes diseases with a unique manifestation, such as X-linked adrenoleukodystrophy, hyperoxaluria type I and rhizomelic chondrodysplasia punctata. We investigated clinical aspects and the genetic basis of PDD, and the significance of peroxisomes in the development of human brain. Neuroradiological and neurophysiological studies revealed that thick cortex, colpocephaly and multifocal spikes were characteristic findings of PDD patients in the early infantile period. Cytogenetic studies elucidated the presence of eleven complementation groups among PDD, indicating the presence of eleven pathogenic genes for PDD. Molecular studies elucidated two of these genes, PAF-1 and PXR-1. Immunohistochemical studies clarified that the catalase-positive neurons appeared in the basal ganglia, thalamus, and cerebellum at 28 weeks of gestation, and in the cortex at 35 weeks. Immunopositive glial cells appeared from the deep to superficial white matter with increasing gestational age. These results suggest the important role of peroxisomes in neuronal maturation and myelinogenesis.

Brain↗