Biomedical subjects

M Akaike

Publications and source records attributed to M Akaike.

At least 19 recordsLinked to original sources

PubMed2002

Circulating corticosterone alters the rate of neuropathological and behavioral changes induced by trimethyltin in rats.

When trimethyltin (TMT) is administered to rats, the plasma corticosterone concentration rises transiently 3 to 4 days later. We examined whether plasma corticosterone plays a causative role in the TMT-induced impairment of the hippocampus as assessed by pathological and behavioral tests. TMT-administered rats were supplementally treated with either adrenalectomy or metyrapone (twice daily for the first 7 days after TMT) in order to permanently deplete or transiently suppress circulating corticosterone. Loss of pyramidal cells in the CA1 and CA3 fields, mossy fiber sprouting, and impairment of spatial memory were observed after TMT intoxication. Adrenalectomy apparently aggravated both the hippocampal damage and the spatial memory impairment induced by TMT treatment. The TMT+metyrapone treatment groups exhibited a significant reduction in pyramidal cells in both the CA1 and the CA3 regions. However, the neuronal damage in CA1 was significantly different between the TMT and the TMT+metyrapone groups. Metyrapone significantly reduced the TMT-induced damage to pyramidal cells in CA1, but not CA3, and it also abolished mossy fiber sprouting. TMT-induced learning impairment and hyperactivity were alleviated by metyrapone treatment. It is thus concluded that both the high levels of corticosterone induced by TMT and the pathologically low levels of corticosterone induced by adrenalectomy will worsen the consequences of TMT.

Adrenalectomy↗

PubMed2001

Successful combination therapy--flunarizine, pentoxifylline, and cholestyramine--for spur cell anemia.

Spur cell anemia, a hemolytic anemia observed in patients with alcoholic cirrhosis, is characterized by unusual erythrocyte morphology and an increased ratio of free cholesterol to phospholipid in the erythrocyte membrane. The prognosis of spur cell anemia is usually extremely poor, however, we describe here a patient with spur cell anemia who was successfully treated with combination therapy consisting of flunarizine, pentoxifylline, and cholestyramine. Initial therapy with flunarizine alone for 6 weeks did not significantly decrease the number of spur cells on peripheral blood smears. So pentoxifylline was added to the regimen. The patient recovered from the anemia, showed remarkable improvement with regard to the hyperbilirubinemia, and the changes were accompanied by a significant decrease in the number of spur cells in peripheral blood smears. To correct the hypercholesterolemia, cholestyramine was added to the regimen, which resulted in a reduction in the serum level of free cholesterol and an increase in the molar ratio of free cholesterol to phospholipid in erythrocyte membrane. However, 6 months later a skin eruption developed that was considered an adverse reaction to the drugs, so the flunarizine and pentoxifylline were discontinued. With cholestyramine therapy alone, the remission of spur cell anemia was maintained for more than 11 months. These observations suggest that non-invasive combination therapy with flunarizine, pentoxifylline, and cholestyramine is effective and valuable in the treatment of patients with spur cell anemia.

Adult↗

PubMed2001

Sugar-responsible elements in the promoter of a gene for beta-amylase of sweet potato.

Expression of genes coding for sporamin and beta-amylase, the two most abundant proteins in storage roots of sweet potato, is coordinately inducible in atypical vegetative tissues by sugars. A sweet potato gene for beta-amylase (beta-Amy) with introns as well as a beta-Amy::GUS fusion gene composed of the beta-Amy promoter and the GUS coding sequence, both showed sugar-inducible expression in leaves of transgenic tobacco which occurred via a hexokinase-independent pathway. Analyses using various 5'-terminal and internal deletions of the beta-Amy promoter indicated that truncated promoters of beta-Amy containing a sequence between -901 and -820, relative to the transcription start site, and the basic promoter region can confer sugar-inducible expression. This 82 bp region contained the TGGACGG sequence that plays an essential role in the sugar-inducible expression of the truncated promoter of the sporamin gene. Deletion or base substitutions of this element in the truncated beta-Amy promoter abolished the sugar-inducible expression, the results suggesting that the TGGACGG element plays an important role in the coordinate induction of expression of genes for beta-amylase and sporamin by sugars.

Amino Acid Sequence↗

PubMed2001

Plasma concentration of tissue inhibitor of matrix metalloproteinase 1 in patients with colorectal carcinoma.

BACKGROUND: The expression of tissue inhibitor of matrix metalloproteinase (TIMP) 1 in tumour tissue from patients with colorectal carcinoma has been reported to be related to disease progression. However, the clinical significance of plasma TIMP-1 has not been fully elucidated. METHODS: The plasma level of TIMP-1 protein was determined by enzyme-linked immunosorbent assay in samples from 54 patients who underwent resection of the primary tumour. RESULTS: Plasma TIMP-1 levels were associated significantly with depth of invasion and metastasis to lymph nodes and liver. Circulating TIMP-1 levels were significantly higher in patients with serosal invasion, liver metastases and Dukes' stage C tumours. Using a cut-off value of 160 ng/ml, serosal invasion and Dukes' C stage could be predicted with an accuracy of 68.5 per cent. With a cut-off value of 170 ng/ml, metastasis to the lymph node and liver could be predicted with an accuracy of 66.7 and 70.4 per cent respectively. These values were greater than those for carcinoembryonic antigen and CA19-9. CONCLUSION: These data suggest that the plasma concentration of TIMP-1 correlates with both invasion and metastasis in patients with colorectal carcinoma.

Adult↗

PubMed2001

Homozygous deletion mutation of the parkin gene in patients with atypical parkinsonism.

Autosomal recessive juvenile parkinsonism (AR-JP) is characterised by homogenous clinical features and selective degeneration of nigral neurons. Recent progress in molecular genetic analyses of AR-JP has led to the identification of a novel ubiquitin-like protein, parkin, whose precise function still remains to be elucidated. Two unrelated Japanese families had levodopa unresponsive parkinsonism complicated with cerebellar and pyramidal tract dysfunction. Genetic analysis of the parkin gene and mRNA in both families disclosed identical mutations with large deletions extending from exons 3 to 4. These results suggest that the parkin protein possesses an important function not only in the substantia nigra but also in extranigral neurons of the CNS and that the phenotype of multiple system dysfunction can also be a complication in patients with AR-JP due to variations in sites of or changes in functions by parkin mutation.

Blotting, Southern↗

PubMed2001

Molecular mechanism of type I congenital heparin cofactor (HC) II deficiency caused by a missense mutation at reactive P2 site: HC II Tokushima.

We found a 66-year-old Japanese patient with type I congenital heparin cofactor (HC) II deficiency manifesting multiple atherosclerotic lesions. To investigate the molecular pathogenesis of our patient, we performed sequencing analysis and expressed recombinant human wild-type and mutant HC II molecules in COS-1 and CHO-K1 cells. Sequencing analysis following amplification of each of all 5 exons and its flanking region showed a single C to T transition at nucleotide position 12,854 in exon 5, which changed a Pro443 codon (CCG) to Leu codon (CTG). Because this mutation generates a new Bhv I site, the Bbv I digestion pattern of the PCR-amplified exon 5 fragments from each family member was analyzed. In all cases, the patterns were consistent with the activities and antigen levels of plasma HC I1 in those members. Transient transfection, metabolic labeling and pulse-chase experiments followed by immunoprecipitation analysis showed that the recombinant mutant HC II molecules were secreted from COS-1 cells in reduced amounts compared with the wild-type, and that an enhanced intracellular association of the mutant molecules with a chaperone, GRP78/BiP, was observed in CHO-K1 cells. Northern blot analysis indicated that the mutant HC I1 mRNA was transcribed at a similar level as that of wild-type. Immunohistochemical staining of the transfected cells revealed that COS-1 cells expressing the mutant HC II molecules were stained mainly in the perinuclear area. We conclude that the impaired secretion of the mutant HC II molecules, due to intracellular degradation, is the molecular pathogenesis of type I congenital HC II deficiency caused by a Pro443 to Leu mutation at reactive P2 site.

Aged↗

PubMed2001

[Therapeutic strategy for hepatic metastasis of primary colon cancer].

PURPOSE: To analyze the clinical results of treatments for hepatic metastasis of primary colon cancer for an evaluation of treatment strategies. MATERIALS AND METHODS: Two hundred and twenty-five patients with only hepatic metastasis of primary colon cancer (synchronous tumors, 164 patients: metachronous tumors, 61 patients) between 1983 and 1999 were studied. Of these 225 patients, 68 patients (synchronous tumors, 39 patients: metachronous tumors, 29 patients) were treated with curative resection. These 225 patients were categorized into group A (chemotherapy only), group B (hepatic arterial infusion only), group C (curative resection + hepatic arterial infusion), and group D (curative resection only). The therapeutic results were compared. RESULTS: The five-year survival rate and five-year recurrence-free rate of 68 patients with curative resection were 40.6% and 31.0%. By therapeutic modality, the five-year survival rate and five-year recurrence-free rate of the 36 patients of group C were 40.7% and 29.5%, and those of the 32 patients of group D were 43.4% and 33.0%, respectively. No significant difference was found between these two groups. However, in the patients with synchronous tumors, the five-year survival rate and five-year recurrence-free rate of group C and group D were 65.7, 49.6% and 13.8, 15.9%, respectively. The results of group C were significantly better than those of group D. Recurrence was found in 36 patients (52.2%). Among these patients, 25 (36.8%) recurred within one year from the end of treatment(s). Twenty-one patients (32.4) had the recurrence in the residual liver, and 14 (17.6%) had metastasis to the lung. In group B, in which curative resection was impossible, the one-year and two-year survival rates in the patients with synchronous tumors were good in comparison with those of group A. Herein we report two cases in which hepatic arterial infusion was effective. CONCLUSION: It is important to set aggressive resection and hepatic infusion as a fundamental treatment policy, and to perform not only hepatic infusion but to combine other treatments with consideration of the next recurrence.

Aged↗

PubMed2000

Functional association between nicotinic acetylcholine receptor and sarcomeric proteins via actin and desmin filaments.

By affinity chromatography utilizing alpha-cobrotoxin from digitonin-solubilized fractions of rabbit skeletal muscle, we found that many proteins are associated with the nicotinic acetylcholine receptor (AChR). In addition to the proteins we previously reported to bind to AChR (including dystrophin-dystrophin-associated protein (DAP) complex, utrophin, rapsyn, and actin; Mitsui et al. [1996] Biochem. Biophys. Res. Commun.224:802-807), alpha-actinin, desmin, myosin, tropomyosin, troponin T, and titin are also identified to be associated with AChR. Alkaline treatment or Triton X-100 solubilization released dystrophin-DAP complex, utrophin, and rapsyn from the AChR fraction, while actin and desmin remained associated. These findings demonstrate that AChR is supported primarily by a submembranous organization of actin and desmin filaments, and is linked to sarcomeric proteins via these filaments. To further investigate whether the association has any functional role, we studied the effect of acetylcoline on ATPase activity of the AChR fraction. Acetylcholine (0.5-4 microM) significantly activated Mg(2+)-ATPase activity of digitonin-solubilized AChR fraction (P < 0.05). Furthermore, we found that desmin as well as actin activated myosin Mg(2+)-ATPase activity. From these findings, it is suggested that desmin and actin form a submembranous organization in the postsynaptic region, and function as mediators of excitation of AChR to the sarcomeric contraction system.

Acetylcholine↗

PubMed1999

Aspirin reduces apolipoprotein(a) (apo(a)) production in human hepatocytes by suppression of apo(a) gene transcription.

High serum lipoprotein(a) (Lp(a)) is a risk factor for vascular disorders. Our preliminary observations suggest that, in some patients with coronary heart disease with high serum Lp(a) levels, administration of aspirin reduced Lp(a) levels. Therefore, we aimed to analyze the effects of aspirin on the production of apo(a), the expression of apolipoprotein(a) (apo(a)) mRNA and the transcriptional activity of apo(a) gene promoter. Aspirin (5 mM) reduced the apo(a) levels in culture medium of human hepatocytes and suppressed apo(a) mRNA expression to 73% and 85% of the controls, respectively. Aspirin also reduced the transcriptional activity of apo(a) gene transfected into HepG2 hepatoma cells in a dose-dependent manner, with a maximal effect at 5 mM (44.3 +/- 1.5% of the control). Sodium salicylate (5 mM) also reduced apo(a) gene transcription, whereas indomethacin (10 microM) had no effect. Deletion analysis of apo(a) gene promoter showed that promoter region extending from -30 to +138 is critical for the effect of aspirin. Furthermore, enhanced production, mRNA expression, and gene transcription of apo(a) by interleukin-6 were also inhibited by aspirin. These results demonstrate that aspirin reduces apo(a) production from hepatocytes via reduction of the transcriptional activity of apo(a) gene with suppression of apo(a) mRNA expression. The suppression of apo(a) production by aspirin may at least in part play a role in the anti-atherogenic effect of aspirin in vascular disorders.

Apolipoproteins A↗

PubMed1999

[Intraoperative radiation therapy (IORT) for locally unresectable pancreatic cancer].

To evaluate the therapeutic effect of IORT for unresectable locally advanced pancreatic cancer, 11 patients treated with IORT and 15 patients treated with palliative therapy only were retrospectively examined. The mean age of the IORT group was 61.9 years, 5 cases were classified into surgical stage IVa, and 6 into stage IVb. The mean age of the palliative therapy group was 69.1 years; 5 cases were classified into surgical stage IVa and 10 into stage IVb. The tumor size was measured in 6 cases in the IORT group, before and after IORT. The tumor was enlarged in 1 case, not changed in 4 cases, and reduced in 1 case. The serum CA19-9 level was measured in 8 cases of the IORT group. Serum CA19-9 was increased in 3 cases, not changed in 4 cases, and decreased in 1 case after IORT. ECOG pain scores were obtained in 9 patients who had complained of pain before IORT, and the score decreased in 7 cases. The median survival was 7.6 months in the IORT group and 3.0 months in the palliative therapy group. IORT may improve patients' QOL by decreasing their pain. However, further studies are necessary to confirm the efficacy of IORT for survival of locally unresectable pancreatic cancer patients, because the patient profile in this study was different in the two groups.

Aged↗

PubMed1998

Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.

We report on the clinical, pathological, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7+/-3.1 years (mean+/-SD), and loss of ambulance occurred at 38.5+/-2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes. In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family. The former mutation results in a W360R substitution in the proteolytic site of calpain 3, and the latter in a deletion of the Ca2+-binding domain.

Age of Onset↗

PubMed1998

The first cooperative living-related donor liver transplantation performed by two separate institution teams: The Kanagawa Liver Transplantation Program.

With the cooperation of surgeons in two separate institutes, living-related donor liver transplantation was safely performed at the Kanagawa Children's Medical Center. The donor operations were carried out at Kanagawa Cancer Center by surgeons of the hepatobiliary division and the liver grafts were immediately transported to Kanagawa Children's Medical Center by ambulance, and transplanted orthotopically. Since January 1995, five children with biliary atresia have been given partial liver grafts obtained from their mothers. The liver grafts were transported within 20 min, and functioned immediately after transplantation. The development of a pediatric liver transplantation program requires a multidisciplinary approach that can be provided only in a large tertiary referral children's medical center. Preparation for the clinical program involves training of surgical and nursing team members, both in an animal laboratory and at an established liver transplantation center. Special support for the program by the institute is essential and involves medical, nursing, and administrative divisions as well as social services, operating room personnel, and intensive care unit facilities. After careful planning, and with the invaluable help of the donor operating team, the Kanagawa Liver Transplantation Program has been realized, and its first transplantations conducted safely and successfully.

Adolescent↗

PubMed1998

Psoriatic arthritis associated with dilated cardiomyopathy and Takayasu's arteritis.

A 40-year-old Japanese man with psoriatic arthritis (PA) involving the spine, sacroiliac and peripheral joints presented with dyspnoea and ankle oedema. Blood pressure was 180/110 and 114/80 mmHg in the right and left upper arms, respectively. Examinations showed left ventricular dilatation and diffuse hypokinesis of the left ventricle, with no involvement of the coronary arteries. Aortography detected total occlusion of the left subclavian artery and stenosis of the origin at the right renal artery. Dilated cardiomyopathy and Takayasu's arteritis associated with PA was diagnosed. A few cases of PA have been reported in association with cardiovascular diseases, but the association of these three diseases has not been documented in the literature to date. Dermatologists need to be aware of cardiovascular manifestations in patients with PA, because cardiovascular diseases are not rare in other seronegative spondyloarthropathies.

Adult↗

PubMed1997

Relationship between the recurrence of hepatocellular carcinoma (HCC) and serum alanine aminotransferase levels in hepatectomized patients with hepatitis C virus-associated cirrhosis and HCC.

BACKGROUND: The relationship between the recurrence of hepatocellular carcinoma (HCC) and the serum alanine aminotransferase (ALT) level was studied in hepatectomized patients with hepatitis C virus (HCV)-associated cirrhosis and HCC. METHODS: Twenty-six hepatectomized patients with HCV-associated cirrhosis and HCC whose resected specimens showed neither portal vein nor hepatic vein invasion by HCC histologically were divided into 2 groups: 15 patients who had no recurrence 3 years after surgery (Group A) and 11 patients whose disease recurred 1-3 years after surgery (Group B). The patients' serum ALT levels during this period were examined. RESULTS: In Group A, serum ALT generally showed sustained low levels < 80 international units (INU) in 12 patients (80%). In contrast, ALT levels in Group B showed several peaks or plateaus > 80 INU in all patients except 2. The recurrence rate of HCC in the hepatectomized patients with sustained low levels of ALT was 14.3% (2 of 14 patients) at 3 years, and was significantly lower (P < 0.01) than that in those patients whose ALT levels showed several peaks or plateaus > 80 INU (9 of 12 patients; 75.0%). The average level of mode of ALT in Group A (48.8 +/- 26.0 INU) was significantly smaller than that in Group B (101.1 +/- 47.3 INU) (P < 0.005). CONCLUSIONS: The importance of hepatocytic necrosis in the recurrence of HCC in hepatectomized patients with cirrhosis and HCC of HCV origin was demonstrated and the significance of subsiding hepatic necroinflammatory process in the prevention of HCC recurrence suggested.

Aged↗

PubMed1997

Cardiac dysfunction in patients with chronic progressive external ophthalmoplegia.

BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO), which includes Kearns-Sayre syndrome, is a mitochondrial disorder with large deletions of mitochondrial DNA. Recently, mtDNA deletions in cardiac muscle cells were thought to be a cause of dilated cardiomyopathy. However, the cardiac involvement in patients with CPEO is generally considered to be limited to the cardiac conduction system. HYPOTHESIS: The purpose of this study was to evaluate left ventricular function in patients with CPEO. METHODS: We evaluated the cardiac function of five patients with CPEO by means of carotid pulse recording and Doppler echocardiography. RESULTS: The ratio of the pre-ejection period to ejection time was increased to 0.67 in one patient and to 0.50 in another. Echocardiography showed left ventricular dilatation and diffuse hypokinetic wall motion in both cases. Left ventricular fractional shortening was decreased to 5 and 19%, respectively, and the mean rate of circumferential shortening was decreased to 0.12 and 0.63 circ/s, respectively. One of the two patient died of congestive heart failure 2 months after the study. The Doppler pattern of left ventricular filling in the three remaining patients showed a decrease in the ratio of peak flow velocity in early diastole to that in late diastole, with an increase in deceleration time. CONCLUSION: Although cardiac involvement in patients with CPEO is generally considered to be limited to the cardiac conduction system, left ventricular dysfunction may be present and should receive more attention in the management of patients with CPEO.

Adult↗

PubMed1997

The major carotenoid in all known species of heliobacteria is the C30 carotenoid 4,4'-diaponeurosporene, not neurosporene.

The carotenoids of five species of heliobacteria (Heliobacillus mobilis, Heliophilum fasciatum, Heliobacterium chlorum, Heliobacterium modesticaldum, and Heliobacterium gestii) were examined by spectroscopic methods, and the C30 carotene 4,4'-diaponeurosporene was found to be the dominant pigment; heliobacteria were previously thought to contain the C40 carotenoid neurosporene. In addition, trace amounts of the C30 diapocarotenes diapolycopene, diapo-zeta-carotene, diapophytofluene, and diapophytoene were also found. Up to now, diapocarotenes have been found in only three species of chemoorganotrophic bacteria, but not in phototropic organisms. Furthermore, the esterifying alcohol of bacteriochlorophyll g from all known species of heliobacteria was determined to be farnesol (C15) instead of the usual phytol (C20). Heliobacteria may be unable to produce geranylgeranyol (C20).

Bacteria↗

PubMed1997

Trimethyltin syndrome as a hippocampal degeneration model: temporal changes and neurochemical features of seizure susceptibility and learning impairment.

The effects of trimethyltin on the hippocampus were investigated in terms of changes in histology, depth electroencephalography, learning acquisition and memory retention, choline acetyltransferase and neuropeptides, and seizure-induced c-fos messenger RNA expression. The results were as follows. (1) Morphologically, trimethyltin produced a progressive loss of hippocampal CA3 and CA4 pyramidal cells, starting from four days after peroral treatment with trimethyltin hydroxide (9 mg/kg), as described previously. (2) Neurophysiologically, the increased seizure susceptibility to pentylenetetrazol treatment reached a maximum at four days post-trimethyltin and then declined after five days post-trimethyltin. The maximal seizure susceptibility at four days post-trimethyltin was confirmed by the immediate and long-lasting appearance of spike discharge in the hippocampus. However, this was not verified by the expression of c-fos messenger RNA in the hippocampus, which was comparable between trimethyltin-treated and control rats. (3) Behaviorally, the time-courses of aggression and learning impairment were similar to that of the seizure susceptibility. (4) Neurochemically, trimethyltin treatment caused changes of neurochemical markers, which were manifested by the elevation of neuropeptide Y content in the entorhinal cortex, and of choline acetyltransferase in the hippocampal CA3 subfield. Trimethyltin may offer potential as a tool for investigations on the relationship between neuronal death in the hippocampus and the development of seizure susceptibility and learning impairment. Alterations in glucocorticoids, glutamate and neuropeptides may all contribute to the manifestation of the trimethyltin syndrome.

Animals↗

PubMed1997

Mutants of Arabidopsis thaliana with pleiotropic effects on the expression of the gene for beta-amylase and on the accumulation of anthocyanin that are inducible by sugars.

We identified a mutant of Arabidopsis thaliana ectotype Col-O in which significantly reduced levels of expression of the gene for beta-amylase (AT beta-Amy) were detected in leaves in response to high concentrations of sucrose, glucose or fructose. Genetic studies, including a cross with transgenic plants that harbored the AT beta-Amy:GUS transgene with the promoter of AT beta-Amy, indicated that this phenotype was caused by a recessive mutation, Iba1, that affected expression of AT beta-Amy in trans. We also found a reduced level of sugar-induced expression of AT beta-Amy in the Landsberg erecta (Ler) ecotype compared with other ecotypes. This phenotype seemed to be due to a recessive trait, provisionally designated Iba2, that was linked to neither erecta nor Iba1. The Iba2 mutation also affected expression of AT beta-Amy:GUS transgene. Accumulation of starch and sugars after treatment of leaves with sucrose was not affected in the Iba1 mutant and Ler plants. However, both Iba1 mutant and Ler plants accumulated low levels of anthocyanin in response to sucrose, results that suggested the existence of some genetic linkage between regulation of the expression of AT beta-Amy and regulation of the accumulation of anthocyanin. Although the Iba1 and Iba2 mutations did not affect sugar-inducible gene expression in general, the expression of sugar-regulated genes other than the gene for beta-amylase was differentially affected in the Iba1 mutant and Ler plants. These results suggest that the sugar-regulated expression of many genes in plants might be mediated by multiple signal-transduction pathways.

Anthocyanins↗