Biomedical subjects

J Akai

Publications and source records attributed to J Akai.

At least 19 recordsLinked to original sources

PubMed2006

Mobilization of arsenic in groundwater of Bangladesh: evidence from an incubation study.

The extensive extraction of arsenic (As)-contaminated groundwaters for drinking, household and agricultural purposes represents a serious health concern in many districts of Bangladesh. This laboratory-based incubation study investigated the sources and mechanisms of As mobilization in these groundwaters. Several incubation studies were carried out using sediments collected from the Bangladesh aquifer that were supplemented, or not, with different nutrients, followed by an analysis of the sediment suspensions for pH, ORP (oxidation-reduction potential), EC (electrical conductivity) and As and Fe(II) concentrations. In the substrate-amended sediment suspensions incubated under anaerobic environment, there was a mobilization of As (maximum: 50-67 microg/l) and Fe(II) (maximum: 182 microg/l), while the ORP value decreased immediately and drastically (as much as -468 mV to -560 mV) within 5-6 days. In the sediment suspensions incubated under control and aerobic conditions, no significant As mobilization occurred. The simultaneous mobilization of As and Fe(II) from sediments is a strong indication that their mobilization resulted from the reduction of Fe oxyhydroxide by the enhanced activity of indigenous bacteria present in the sediments; this phenomenon also provides insights on the mobilization mechanism of As in groundwater. The concentrations of As in the sediments used in the incubation studies were strongly linked to the gradients of redox potential development that was stimulated by the quantity of organic nutrient (glucose) used. The penetration of surface-derived organic matter into the shallow aquifer may stimulate the activity of microbial communities, thereby leading to a reduction of iron oxyhydroxide and As release.

Arsenic↗

PubMed2002

Arsenic poisoning in groundwater: health risk and geochemical sources in Bangladesh.

Of the 2508 water samples analyzed in 10 districts of Bangladesh, 51%, on an average, contained arsenic levels of 0.05 to 2.50 mg/l. 95% of nail, 96% of hair, and 94% of urine samples contained arsenic above the normal level. Approximately 3.58 million people out of a total of 17.92 million who are drinking water containing arsenic levels >0.20 mg/l are potentially exposed to high risk of health hazard. Eight thousand and five hundred arsenic patients are identified; they are suffering from various skin lesions, gangrene in leg, skin, lung, bladder, liver, and renal cancer. A big portion of the total population is highly vulnerable to various internal cancers. Lowest arsenic concentration in drinking water producing dermatological disease is found to be 0.103 mg/l. However, the exposure time to develop arsenicosis varies from case to case reflecting its dependence on arsenic level in drinking water and food, nutritional status, genetic variant of human being, and compounding factors. This study has determined the high intensity of fluorescent humic substances in drinking water containing elevated concentrations of arsenic and very low concentrations of heavy metals. The synergistic/antagonistic effect of fluorescent compounds present in drinking water may aggravate the toxicity of arsenic. Geochemical study suggests that arsenic may be released from both reductive dissolution of Fe and Mn (oxy)hydroxide and microbial oxidation of organic matter.

Arsenic Poisoning↗

PubMed2001

Isolation of novel heart-specific genes using the BodyMap database.

Two novel heart-specific genes, C3orf3 (chromosome 3 open reading frame 3) and MMGL (myomegalin-like), were isolated using BodyMap, a gene expression database based on site-directed 3' expressed sequence tags (3'-ESTs) which were collected from nonbiased cDNA libraries of various tissues. The cDNA of C3orf3 was 1667 bp and was composed of 12 exons within a 10-kb-long genomic sequence. MMGL consisted of 8 exons within a genomic sequence of over 70 kb, leading to four alternatively spliced transcripts. Both genes were strongly expressed in heart and also in skeletal muscle. C3orf3 and MMGL were mapped to 3p22 and 1q1, respectively. Subcellular localizations of their putative proteins were determined as being in the cytoplasm for C3orf3 and in the cytoplasm and nucleus for MMGL. This study showed that BodyMap is a useful database for the isolation of tissue-specific genes.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Identification of MICA alleles with a long Leu-repeat in the transmembrane region and no cytoplasmic tail due to a frameshift-deletion in exon 4.

MHC class I chain-related gene A (MICA) is located close to HLA-B gene and expressed in epithelial cells. The MICA gene is reported to be highly polymorphic as are the classical class I genes. To further assess the polymorphism in the MICA gene, we analyzed a total of 60 HLA-homozygous cells for the sequences spanning exons 2-6. In the analysis, four new MICA alleles were identified and six variations were recognized in exon 6. MICA*017, which was identified in three HLA-B57 homozygous cells (DBB, DEM and WIN), differed from MICA*002 in exon 3 and had a guanine deletion at the 3' end of exon 4. MICA*015 identified in an HLA-B45 homozygous cell (OMW) also had the same deletion that causes a frameshift mutation resulting in complete change of the transmembrane region and premature termination in the cytoplasmic tail; these alleles have a long hydrophobic leucine-rich region instead of the alanine repeat in the transmembrane region and terminate at the second position in the cytoplasmic domain. The frameshift deletion was found only in HLA-B45- or -B57-positive panels tested, suggesting a strong linkage disequilibrium between the deletion and B45 or B57. MICA*048, which was different in exon 5 from MICA*008, was identified in an HLA-B61 homozygous cell (TA21), while MICA*00901 identified in HLA-B51 homozygous cells (LUY and KT2) was distinguished from MICA*009 by exon 6.

Base Sequence↗

PubMed2000

A novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome.

Mutations in the human cardiac Na+ channel alpha subunit gene (SCN5A) are responsible for Brugada syndrome, an idiopathic ventricular fibrillation (IVF) subgroup characterized by right bundle branch block and ST elevation on an electrocardiogram (ECG). However, the molecular basis of IVF in subgroups lacking these ECG findings has not been elucidated. We performed genetic screenings of Japanese IVF patients and found a novel SCN5A missense mutation (S1710L) in one symptomatic IVF patient that did not exhibit the typical Brugada ECG. Heterologously expressed S1710L channels showed marked acceleration in the current decay together with a large hyperpolarizing shift of steady-state inactivation and depolarizing shift of activation. These findings suggest that SCN5A is one of the responsible genes for IVF patients who do not show typical ECG manifestations of the Brugada syndrome.

Adult↗

PubMed2000

Association of functional microsatellites in the human type I collagen alpha2 chain (COL1A2) gene with systemic sclerosis.

Systemic sclerosis (SSc) or scleroderma is a generalized disorder of connective tissue. The etiology is poorly understood; however, both genetic and environmental factors have been implicated. To investigate the disease-susceptible gene for SSc, we examined the association of the disease with a gene (COL1A2) for type I collagen, which accumulates excessively in the affected organs. The COL1A2 gene containing a specific combination of the two dinucleotide repeats, repeat-haplotype, is involved in the regulation of gene expression. Homozygotes for a 5'-(CA)13CGCACA(CG)6(CA)8 -(GT)12 -3' were found with significantly higher frequency (P = 0.029, relative risk, RR > 6.93) in SSc patients than in controls, and association was prominent (P = 0.0042, RR > 32.0) in the male patients positive for SSc-specific antinuclear antibodies (ANAs). This repeat-haplotype showed the highest stimulative activity for the transcription of the COL1A2 promoter among the reporter gene constructs tested. The results indicate that a portion of the patients having a specific dinucleotide repeat-haplotype homozygously and expressing the ANAs have a significantly higher risk for SSc than those individuals with other combinations of the repeat-haplotypes.

Base Sequence↗

PubMed2000

Characterization of the human nebulette gene: a polymorphism in an actin-binding motif is associated with nonfamilial idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDC) is characterized by a thin-walled heart with systolic dysfunction of unknown etiology. Because abnormalities in genes for cytoskeletal proteins related to Z-disc function have recently been reported to cause IDC, genomic organization of the gene for nebulette, a novel actin-binding Z-disc protein, was determined and its sequence variations were searched for in Japanese patients with IDC and healthy controls. The nebulette gene consists of 28 exons, and four sequence variations leading to amino acid replacement (Gln187His, Met351Val, Asn654Lys, and Thr728Ala) were identified in the patients. These variations were also found in the healthy controls and hence they were polymorphisms and not disease-specific mutations. Frequencies of Gln187His, Met351Val, and Thr728Ala variants were similar in the patients and controls. However, the frequency of homozygotes for Lys at codon 654, a variant at a relatively conserved residue in an actinbinding motif, was significantly increased in nonfamilial IDC patients (n=106) as compared with healthy control subjects (n=331) (7.54% vs 1.21%, OR=6.25, P=0.002, 95% CI=1.92-20.29), while this association was not found in familial IDC patients (n=24). These observations suggest that the nebulette polymorphism in the actin-binding motif was a novel genetic marker of susceptibility to nonfamilial IDC.

Adolescent↗

PubMed2000

[Biomineralization at hot springs and mineral springs, and their significance in relation to the Earth's history].

Recently, there is strong interest on microbe-mineral interactions. This is related also to recent expanded knowledges on extremely severe environments in which microbes live. Interaction between microbes and minerals contains biomineralization processes. Varieties of biomineralization products are found not only in various geologic materials and processes in the earth's history but also in present surface environments. Some hot springs represent such environments similar to those of unique and extremely severe environments for life. In this short review, the author briefly shows some examples of biomineralizations at some hot springs and mineral springs, Japan. In such environments, iron ore was formed and some varieties of growing stromatolites were found. The varieties of stromatolite are siliceous, calcic and manganese types. Cyanobacteria and the other bacteria are related to form the stromatolite structure. In the Gunma iron ore, sedimentary iron ores were mineralogically described in order to evaluate the role of microorganisms and plants in ore formation. The iron ore is composed of nanocrystalline goethite. Algal fossils are clearly preserved in some ores. Various products of biomineralization are found in the present pH 2-3, Fe2(+)- and SO4(2-)-rich streams. Bacterial precipitation had variations from amorphous Fe-P-(S) precipitates near the outlet of mineral spring, to Fe-P-S precipitates and to Fe-S-(P) precipitates. Mosses and green algae are also collecting Fe precipitates in and around the living and dead cells. The Gunma Iron Ore can be said as Biologically Induced Iron Ore. At Onikobe and Akakura hot springs, growing stromatolites of siliceous and calcareous types, were found, respectively. At Onikobe, The stromatolites grow especially near the geyser. Cyanobacterial filaments in stromatolite were well preserved in the siliceous and calcic stromatolites. The filaments oriented in two directions which form the layered structures were found. At Yunokoya hot spring, black and brittle stromatolitic structures which were composed of amorphous Mn minerals are growing. The form of these structures are hemispherical. Many bacteria that were coated with amorphous Mn minerals were found on these structures. Furthermore, Precambrian (Proterozoic : Wittenoom-Chichester region, western Australia) manganese stromatolite was briefly shown in comparison. The black stromatolite has been clarified to be composed of todorokite. Small spotty and donuts-like shaped todorokite aggregates which are very similar to biologically induced Mn-precipitates were found in massive dolomite layers.

Australia↗

PubMed1999

Transcriptional regulation of the human type I collagen alpha2 (COL1A2) gene by the combination of two dinucleotide repeats.

Human type I collagen alpha2 (COL1A2) gene has two dinucleotide repeats: one in the 5'-flanking region of the gene is composed of poly(dC-dA) and poly(dC-dG), while the other in the first intron consists of poly(dG-dT). In this study, we show that transcription of the COL1A2 gene is regulated by these repeats. Luciferase reporter gene assay indicated that the transcriptional activity of the COL1A2 gene was enhanced by the co-presence of both repeats, but not by either repeat alone. Analysis of the polymorphism in the two repeat regions indicated that both sequences have a variation in their repetition number, thus showing that these dinucleotide repeats constitute microsatellites. A study using constructs containing various combinations of the repeat alleles showed differences in their transcriptional activities. The results, however, showed that the stimulation rate of luciferase activity was not linear with the repetitive number of the repeats either in the 5' flanking region or in the first intron of the gene and that the stimulation was provided by the combination of these polymorphic repetitive sequences. These observations indicated that the dinucleotide repeats have an enhancing activity on transcription of the COL1A2 gene and that the variation in the number of repetitions may partly be responsible for the difference in the transcriptional activity of the gene.

Alleles↗

PubMed1998

MICA gene polymorphism in Takayasu's arteritis and Buerger's disease.

To further clarify the HLA-linked genes susceptible to arterio-vasculitis of unknown etiology, Takayasu's arteritis and Buerger's disease, polymorphism in the MICA gene, a newly identified gene near the HLA-B gene and expressed in epithelial cell lineage, was investigated. Polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis and subsequent sequencing of the MICA gene have revealed that there are 5 MICA alleles which are different in the number of a GCT repeat in exon 5: MICA alleles MICA-1.1, -1.2, -1.3 and -1.4 have 9, 6, 5 and 4 GCT repeats, respectively, and MICA-1.5 has 5 GCT repeats with a 1 bp frameshift insertion in the repeat. MICA genotyping data in 81 Japanese patients with Takayasu's arteritis, 38 Japanese patients with Buerger's disease, and 160 healthy Japanese controls showed that MICA-1.2 and -1.4 were significantly associated with Takayasu's arteritis and Buerger's disease, respectively. Because MICA-1.2 and -1.4 were in strong linkage disequilibria with HLA-B52 and -B54 in the Japanese populations, respectively, we have compared the odds ratio (OR) of the risk to the diseases for individuals having both or each of the disease-associated MICA and HLA-B alleles. It was found that MICA-1.2 gave a significantly high OR of risk to Takayasu's arteritis in the absence of HLA-B52, suggesting that the HLA-linked gene susceptible to Takayasu's arteritis is mapped near the MICA gene. In contrast, MICA-1.4 gave a significantly high OR of risk to Buerger's disease only in the presence of HLA-B54, suggesting that the HLA-linked gene susceptible to Buerger's disease is linked to the HLA-B54-MICA-1.4 haplotype, and may be differently mapped from that to Takayasu's arteritis.

Amino Acid Sequence↗

PubMed1998

Cell position-dependent reciprocal feedback regulation of type I collagen gene expression in cultured human skin fibroblasts.

In order to investigate possible cell positional effects on the gene expression of human dermal fibroblasts, the authors cultured the cells on non-coated polystyrene culture dishes, type I collagen-coated dishes, or collagen gels formed by type I collagen, or suspended them in type I collagen gels and measured collagen synthesis by the cells. The production rate of type I collagen was similar whether cells were cultured on non-coated polystyrene or on type I collagen-coated dishes, but it was suppressed significantly when the cells were placed within the collagen gel matrix. Time-dependent expression of genes for alpha 1 (I) and alpha 2 (I) collagen chains was measured by Northern blot analysis. A significant increase in mRNA levels for these chains was observed when the cells were cultured for three days on type I collagen-coated dishes or on collagen gels. On the other hand, a significant decrease in the mRNA levels was observed after 2 days and later, when the cells were cultured within type I collagen gel matrix. These results indicate that human dermal fibroblasts recognize their position on or in type I collagen (extracellular matrix) and respond by changing their expression patterns of type I collagen chain genes. The results of the kinetics of gene expression also suggest that upregulation and downregulation of type I collagen genes are controlled by different mechanisms.

Blotting, Northern↗

PubMed1997

[Familial Creutzfeldt-Jakob disease with the heterozygous point mutation at codon 200 of the prion protein gene (Glu-->Lys)--report of CJD200 brothers of Yamanashi Prefecture origin].

We report two brothers with familial Creutzfeldt Jakob disease (CJD) having a heterozygous point mutation at codon 200 of the prion protein gene (Glu-->Lys): CJD200. The brothers were born in Kitakoma-gun, Yamanashi Prefecture. Patient 1, a 62-year-old man, developed CJD in 1995 and died nine months later. Patient 2, his brother, developed CJD200 at the age of 58 in 1982 and died 13 months later. They both exhibited rapidly progressive dementia with myoclonus and periodic synchronous discharges on electroencephalograms and became bedridden with three or four months. DNA analysis of peripheral blood cells of patient I showed a point mutation in the prion protein gene at codon 200: GAG-->AAG (Glu-->Lys). Five families with CJD200, 11 patients, have been reported in Japan to date, and nine of the patients from four families were born in Yamanashi Prefecture and vicinity. Our patients were born in the same area. We suspect that there is a cluster of CJD200 in Yamanashi Prefecture and vicinity. In Europe and America the phenotype of CJD200 has been reported to be heterogeneous, whereas the clinical features in Japanese cases are fairly homogeneous. We suspect that these patients have a common ancestor with a codon 200 mutation, and that that explains why the phenotypes are homogeneous.

Creutzfeldt-Jakob Syndrome↗

PubMed1996

Histopathologic study of coexistent pathologic states in pancreatic fibrosis in patients with chronic alcohol abuse: two distinct pathologic fibrosis entities with different mechanisms.

The distribution and clinicopathologic features of pancreatic fibrosis were studied histopathologically in 137 autopsy cases of chronic alcohol abuse. Fibrosis was observed in 90 of the cases and was classified as perilobular sclerosis (PS) and intralobular sclerosis (IS). Fibrosis of the PS type was irregular and sometimes patchy and extended into the intralobular area in advanced cases. In some advanced cases, complete replacement of the pancreatic tissue by extensive fibrosis was seen. Fibrosis of the IS type was uniformly distributed. The tissues in some cases showed prominently periacinar fibrosis. In these cases, the pancreatic parenchyma had not been completely replaced by extensive fibrosis. Clinicopathologic comparisons revealed the following results: accompanying liver cirrhosis was greater in the IS than in the PS of fibrosis. However, a higher frequency of protein plugs, pancreatic stones, extensive fibrosis replacement, peripancreatic fibrosis, splenic vein involvement, choledochus involvement, pseudocyst, and ductal hyperplasia was found in the PS type compared to the IS type. In conclusion, the findings on the perilobular and intralobular distribution of fibrosis and differences in various components or accompanying diseases in pancreatic fibrosis suggest that this entity shows two distinct pathologic patterns with differing mechanisms.

Adult↗

PubMed1994

Capillary zone electrophoretic determination of organic acids in cerebrospinal fluid from patients with central nervous system diseases.

Organic acids in cerebrospinal fluid (CSF) from patients with various central nervous system (CNS) diseases were determined by capillary zone electrophoresis (CZE). Under one of the two sets of conditions employed, several anionic components of CSF were separated into corresponding peaks on the electropherograms and determined. The other conditions employed were also useful in measurement of the lactate contents in CSF. The CSF levels of lactate and pyruvate and the ratios of lactate to pyruvate were elevated in patients with cerebral infarction and bacterial meningitis, whereas CSF ascorbate was reduced mainly in inflammatory disorders of the CNS. The results showed that CZE can become a powerful tool in the biochemical diagnosis of CNS diseases.

Brain Diseases↗

PubMed1994

Pancreatic fibrosis in patients with chronic alcohol abuse: correlation with alcoholic pancreatitis.

OBJECTIVES: To investigate the incidence and histological features of pancreatic fibrosis, including chronic alcoholic pancreatitis, in patients with a history of chronic alcohol abuse. METHODS: Forty-six autopsy cases of alcoholic dependence syndrome, 53 cases of chronic alcoholism, and 30 cases of chronic alcoholic pancreatitis were studied histopathologically. RESULTS: Fibrosis was seen in 33 of 46 cases of alcoholic dependence syndrome, 20 of 53 cases of chronic alcoholism, and all 30 cases of chronic alcoholic pancreatitis. Fibrosis was categorized into three types: intralobular, perilobular, and mixed intralobular and perilobular sclerosis. In chronic alcoholic pancreatitis, fibrosis was found mainly in perilobular, or interlobular, areas, and in some advanced cases extended into intralobular areas, so that the pancreatic tissue was completely replaced by fibrosis. Hence, interlobular fibrosis was found in all cases of chronic alcoholic pancreatitis. In contrast, in cases that had predominantly intralobular fibrosis, which were usually cases of alcoholic dependence syndrome, the pancreatic tissue had not completely disappeared, even at an advanced stage, and some parenchymal regeneration similar to that seen in hemochromatosis was observed. CONCLUSION: Interlobular and intralobular pancreatic fibrosis associated with alcohol abuse appears in distinct pathological patterns with differing mechanisms.

Alcoholism↗

PubMed1994

[Autosomal recessive hereditary cortical cerebellar atrophy with striatal degeneration--two siblings showing choreoathetoid movement, ataxia, dementia, and amenorrhea].

We present two siblings with hereditary cortical cerebellar atrophy (CCA), who showed peculiar clinical features. Their unaffected parents are cousins. The mode of inheritance in this family was autosomal recessive. Both patients developed involuntary movement and ataxia during the fourth decade. The proband (patient 1) was the elder sister. She developed choreoathetoid involuntary movement and cerebellar ataxia at the age of 32. At the age of 39, she showed mental deterioration and marked gait disturbance due to severe ataxia and amyotrophy. At the age of 40, she took medication for hypertension. At the age of 42, she was bedridden and had generalized convulsions and dysautonomia. Involuntary movement continued until her death at age 44. She had amenorrhea since the age of 25 years. Neuropathological findings. The brain weighed 1,010 g. We found marked degeneration in the cerebellar cortex including the molecular, Purkinje cells, and granular cell layers, and in the inferior olivary nuclei. In the basal ganglia, the putamen and caudate nuclei were moderately affected, but the substantia nigra and globus pallidus were spared. The cerebral cortex was spared, but the cerebral white matter showed diffuse myelin pallor without fibrillary gliosis. In the pons, the volume of the tegmentum was moderately decreased, but the base was spared. The spinal cord was normal. The findings of the patient differed from those of the case originally reported by Gordon Holmes in 1907. Holmes autopsied a case showing severe degeneration in both the cerebellar cortex including all three layers and the inferior olivary nucleus as in our patient. However, the striatum of his case spared and the patient did not develop involuntary movement as did other patients. The patients presented here should be distinguished from Holmes' original case clinicopathologically.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Pancreatic fibrosis in patients with alcoholic dependence syndrome.

Pancreatic fibrosis in patients with alcoholic dependence syndrome was studied histopathologically. In 30 of 41 autopsied patients with alcoholic dependence syndrome, fibrosis was observed despite the absence of clinical pancreatitis. The fibrosis was categorized into three types, according to Martin's classification: intralobular sclerosis in 15 cases, perilobular sclerosis in seven cases, and a mixed intralobular and perilobular sclerosis in the remaining eight cases. The type of the fibrosis was not related to the duration of alcohol abuse. Alcoholic liver cirrhosis was coexistent in 23 of the 30 cases of pancreatic fibrosis. These cases were also divided into categories according to the three types, as follows: intralobular sclerosis in 12 (80%) of 15 cases, perilobular sclerosis in four (57%) of seven cases, and mixed sclerosis in seven (88%) of eight cases. That is, intralobular and mixed sclerosis were frequently coexistent with alcoholic liver cirrhosis. When the pancreases from the 19 subjects with intralobular sclerosis and mixed sclerosis coexistent with liver cirrhosis in alcoholic dependence syndrome were compared with 20 pancreases from patients with nonalcoholic liver cirrhosis, periacinar (or intralobular) fibrosis was found in all cases of the former, but in none of the latter. Hence, it was concluded that periacinar fibrosis occurred as a result of alcohol abuse. Pancreatic fibrosis in patients with alcoholic dependence syndrome was distributed mainly in the intralobular areas and was frequently coexistent with alcoholic liver cirrhosis.

Adult↗

PubMed1992

[A case of chronic toluene intoxication with atrophy of cerebrum, cerebellum and brainstem on CT and MRI].

A 28-year-old man developed neurological disorders consisting of cerebellar symptoms and dementia over a period of 8 years of inhalation of toluene. He also developed bilateral optic atrophy. CT scan and MRI revealed atrophy of cerebrum, cerebellum and brainstem. The severity of neurological symptoms corresponded with the findings of CT and MRI. Furthermore, MRI (T2) showed reduced signal intensity in bilateral thalamus. This patient was also admitted to another hospital 2.5 years ago. Compared with the previous findings, present examinations showed significant progress of the atrophy of cerebrum and brainstem. It was suggested from the results of ABR that the disturbance of the brainstem was aggravated through this period.

Adult↗