PubMed Health⌕ Search

Biomedical subjects

K Mizushima

Publications and source records attributed to K Mizushima.

At least 19 recordsLinked to original sources
PubMed2001

Luminescent FeSi(2) crystal structures induced by heteroepitaxial stress on Si(111).

The crystal structures and the luminescent properties of FeSi(2) in the FeSi(2)/Si heteroepitaxial system have been investigated by first principles calculations. The results indicate that the heteroepitaxial beta-FeSi(2) facing Si(111) by the (110) plane will be deformed from an orthorhombic to a monoclinic P2(1)/c structure with a gamma angle of 95 degrees. The strained crystal has a direct gap band structure and a finite oscillator strength of 0.7 between the band edges at the Y point. Since an indirect type band structure is obtained for other heteroepitaxial relationships, as well as for the bulk beta-FeSi(2), we propose the strained FeSi(2)(110)/Si(111) structure to be the origin of the luminescence observed in the FeSi(2)/Si systems.

Journal Article↗
PubMed2000

A novel G-protein-coupled receptor gene expressed in striatum.

Differential display screening for region-specific transcripts in rat brain revealed a novel striatum-specific transcript encoding an orphan G-protein-coupled receptor (GPCR) designated Strg/Gpr88 for striatum-specific GPCR. We isolated its homologues from human (HGMW-approved symbol GPR88) and mouse and mapped them to chromosomes 1p21.3 and 3G1, respectively. These loci are syntenic to each other, thereby suggesting their orthology. The predicted primary sequences of Strg/Gpr88 proteins are highly conserved between human and rodents and show the highest level of homology to receptors for biogenic amines. However, Strg/Gpr88 lacks some residues conserved in all known biogenic amine receptors and hence may represent a novel subtype of GPCR. Northern blot and in situ hybridization analyses revealed that Strg/Gpr88 transcripts are expressed almost exclusively in striatum in both human and rodents. Remarkable conservation in primary structure and a unique expression pattern may indicate a role for Strg/Gpr88 in the fundamental functions of striatum such as the control of motor behavior.

Amino Acid Sequence↗
PubMed1999

Analysis of spinocerebellar ataxia type 2 gene and haplotype analysis: (CCG)1-2 polymorphism and contribution to founder effect.

Spinocerebellar ataxia type 2 is a familial spinocerebellar ataxia with autosomal dominant inheritance. The gene responsible was recently cloned and this disorder was found to be the result of a CAG expansion in its open reading frame. We analysed 13 SCA2 patients in seven unrelated families in Gunma Prefecture, Japan. In four of the seven families, we detected CCG or CCGCCG interruptions in only the expanded alleles. Cosegregation of these polymorphisms with SCA2 patients was established within each family. Together with the results of haplotype analyses, we considered that at least two founders were present in our area and that these (CCG)1-2 polymorphisms may make analysis of founder effects easier. By sequencing analysis we found that although the number of the long CAG repeat varied in each subclone of expanded alleles, these polymorphisms did not change their configuration. This finding suggests that CCG or CCGCCG sequences are stable when surrounded by the long CAG repeat and a single CAG. Moreover, the presence of these polymorphisms may lead to miscounting the repeat size by conventional estimation using a size marker such as an M13 sequencing ladder. Therefore we should consider these polymorphisms and accurately determine the repeat size by sequencing.

Alleles↗
PubMed1998

Molecular analysis of a de novo mutation for spinocerebellar ataxia type 6 and (CAG)n repeat units in normal elder controls.

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant spinocerebellar degenerative disease caused by CAG repeat expansions in the human alpha1A voltage-dependent calcium channel subunit gene (CACNL1A4). We analyzed 15 SCA6 patients in 14 unrelated Japanese families and 52 healthy Japanese aged over 74 years. Sequence analysis was performed to determine the correct number of CAG repeats. The expanded CAG repeat number was 23.6+/-2.1 (mean+/-S.D., n=15) with a range of 20-29, and the shortest expanded allele was 20 repeats. Moreover, the analysis of normal subjects revealed that the CAG repeat number of normal alleles was 12.3+/-1.9 (n=104) with a range of 7-18. We concluded that the normal range of CAG repeats in the CACNL1A4 gene is 18 or less, and that the disease range is 20 or more. Of 15 SCA6 patients, three sporadic cases were observed. In one male patient with 26 CAG repeats, the CAG repeat numbers of his parents were within normal range. His expanded allele was considered to be caused by an expansion of a normal allele from his mother (14 or 17 repeats). This is the first SCA6 case which was genetically proven to occur due to a de novo mechanism, suggesting that larger CAG repeats of normal alleles in the CACNL1A4 gene may be unstable and result in full expansion.

Aged↗
PubMed1998

Combination assay of CSF tau, A beta 1-40 and A beta 1-42(43) as a biochemical marker of Alzheimer's disease.

Cerebrospinal fluid samples from a total of 157 subjects consisting of 55 patients with sporadic Alzheimer's disease (AD), 34 normal controls, 23 patients with non-AD dementia, and 45 with other neurological diseases were examined by ELISA of tau, A beta 1-40, and A beta 1-42(43). The AD group had a significantly higher level of tau than the normal control group (P < 0.001), and the diagnostic sensitivity was 31% and specificity was 94%. CSF A beta 1-40 levels did not show any significant differences. Although the level of A beta 1-42(43) was decreased significantly in the AD group compared to the control group (P < 0.005), the overlap of A beta 1-42(43) levels among all groups meant that none of the AD samples exceeded the cut-off value, the mean 2SD of normal control subjects. Reduction of A beta 1-42(43) levels in AD resulted in a significant increase in the ratio of A beta 1-40 to A beta 1-42(43) (A beta ratio) as an improved marker. The diagnostic sensitivity and specificity of A beta ratio were 51% and 82% respectively. The three indexes, using the tau level and A beta ratio (tau or A beta ratio, deviation score and tau x A beta ratio), showed better sensitivity (58%, 67%, 69%) and specificity (82%, 86%, 88%) than previously reported methods. Combination assay for CSF tau, A beta 1-40 and A beta 1-42(43) in CSF is a biological marker of AD and may be useful to biochemically monitor subjects under treatment.

Adult↗
PubMed1998

Analysis of spinocerebellar ataxia type 2 in Gunma Prefecture in Japan: CAG trinucleotide expansion and clinical characteristics.

We analyzed 13 patients with spinocerebellar ataxia type 2 (SCA2) in seven unrelated families who live in Gunma Prefecture, Japan (population approx. 2,000,000), and documented the clinical and molecular properties correlated with the CAG repeat expansion. Twelve of the 13 patients and one presymptomatic female were genetically examined, and the CAG repeat number of the expanded and normal alleles was 40.8+/-4.8 (mean+/-S.D., n=13) and 22+/-0 (n=13), respectively. The repeat size of the expanded alleles was inversely correlated with the patients' age at onset. Paternal anticipation was observed, accompanied by an increase of the CAG repeat size. The patients presented here were clinically characterized by a relatively higher frequency of slow saccades, hyporeflexia, hypotonia, and tremor. A number of peaks in the expanded allele on polyacrylamide gel electrophoresis showed the presence of cell mosaicism in SCA2 as well. In Gunma Prefecture, SCA2, Machado-Joseph disease and spinocerebellar ataxia type 6 are almost equally present and at higher frequencies than spinocerebellar ataxia type 1 and hereditary dentatorubropallidoluysian atrophy, which are rare. Thus, the difference of frequency of autosomal dominant spinocerebellar ataxias may be present in Japan.

Adolescent↗
PubMed1998

Longitudinal study of cerebrospinal fluid levels of tau, A beta1-40, and A beta1-42(43) in Alzheimer's disease: a study in Japan.

To clarify the alterations of tau, amyloid beta protein (A beta) 1-40 and A beta1-42(43) in the cerebrospinal fluid (CSF) that accompany normal aging and the progression of Alzheimer's disease (AD), CSF samples of 93 AD patients, 32 longitudinal subjects among these 93 AD patients, 33 patients with non-AD dementia, 56 with other neurological diseases, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme-linked immunosorbent assays. Although the tau levels increased with aging, a significant elevation of tau and a correlation between the tau levels and the clinical progression were observed in the AD patients. A significant decrease of the A beta1-42(43) levels and a significant increase of the ratio of A beta1-40 to A beta1-42(43) were observed in the AD patients. The longitudinal AD study showed continuous low A beta1-42(43) levels and an increase of the ratio of A beta1-40 to A beta1-42(43) before the onset of AD. These findings suggest that CSF tau may increase with the clinical progression of dementia and that the alteration of the CSF level of A beta1-42(43) and the ratio of A beta1-40 to A beta1-42(43) may start at early stages in AD. The assays of CSF tau, A beta1-40, and A beta1-42(43) provided efficient diagnostic sensitivity (71%) and specificity (83%) by using the production of tau levels and the ratio of A beta1-40 to A beta1-42(43), and an improvement in sensitivity (to 91%) was obtained in the longitudinal evaluation.

Aged↗
PubMed1998

Familial spinocerebellar ataxia with cerebellar atrophy, peripheral neuropathy, and elevated level of serum creatine kinase, gamma-globulin, and alpha-fetoprotein.

Here, we report a familial spinocerebellar ataxia (FSCA), which has clinical features similar to Friedreich's ataxia, an ataxia with isolated vitamin E deficiency, and ataxia telangiectasia. However, the serum levels of creatine kinase, gamma-globulin, and alpha-fetoprotein were elevated, and biochemical and genetic analyses ruled out diagnosis of these three ataxias as well as other FSCAs. Thus, this family is thought to have a new type of FSCA.

Adult↗
PubMed1997

Analysis of the McLeod syndrome gene in three patients with neuroacanthocytosis.

McLeod syndrome is a rare X-linked disorder involving neurological defects and acanthocytosis. We examined the XK gene in three patients with neuroacanthocytosis, one of whom had cardiomyopathy, and his symptoms were very similar to those of McLeod syndrome. We found two new transversions (C to G at codon 204 and G to C at codon 205) in exon 3 in all those cases. However, the transversion at codon 205 was found in all 70 Japanese normal subjects and four non-Japanese (two Caucasian males, one Chinese female and one Micronesian female) and that at codon 204 was also detected in all 14 normal Japanese males and the four non-Japanese. These findings suggest that they are not the cause of McLeod syndrome, but normal polymorphisms which have not been reported. Moreover, there is a possibility that patients with neuroacanthocytosis similar to McLeod syndrome exist without the XK gene abnormalities.

Acanthocytes↗
PubMed1996

Mitotic and meiotic stability of the CAG repeat in the X-linked spinal and bulbar muscular atrophy gene.

X-linked spinal and bulbar muscular atrophy (SBMA) occurs due to an expansion of the trinucleotide repeat (CAG)n in the androgen receptor gene. Anticipation is relatively rare in SBMA in contrast to spinocerebellar ataxia type 1 (SCAl), and dentatorubral and pallidoluysian atrophy (DRPLA) which show obvious paternal anticipation. The differences in the CAG repeat number were compared among sperm, leukocytes and skeletal muscles of SBMA patients. In SBMA, the sperm of most patients and the skeletal muscle of all patients showed the same repeat number as their leukocytes, whereas the increase in the repeat number from leukocytes to sperm was evident in SCA1 and DRPLA patients. The higher mosaicism level in sperm compared with leukocytes was common in SBMA, SCA1 and DRPLA, and the level of sperm was lower in SBMA than in SCA1 and DRPLA. Thus, spermatogenesis was suggested to be strongly associated with paternal anticipation. The mosaicism level was smaller in SBMA than in other (CAG)n expanded disorders, and smallest in the SBMA carrier females. These findings demonstrate that the CAG repeat in SBMA is relatively stable in mitotic and meiotic, processes, and there is a possibility that the lower mosaicism level of the carrier females compared with the SBMA patients is associated with X-linked recessive inheritance.

Female↗
PubMed1995

[A case of pulmonary tumorlet with tuberculoma misdiagnosed as small cell lung carcinoma by transbronchial lung biopsy].

A 59-year-old woman was picked up by chest X-ray findings. Her CT scan film showed a tumor shadow in the upper lobe of the left lung, and by transbronchial lung biopsy, she was diagnosed as a small cell lung carcinoma. Lobectomy was performed, but the lesion was diagnosed as tuberculoma by frozen section. Furthermore, on postoperative histological examination, a minute lesion of tumorlet, which was histologically identical to that preoperatively detected by transbronchial lung biopsy was found in the adjacent tissues of the tuberculoma. Pulmonary tumorlet is clinically a rare lesion, but the diagnosis and treatment for small-sized tumor or tumor-like lesion may be carefully done, taking into account the existence or co-existence of tumorlet lesion.

Biopsy↗
PubMed1994

[Experimental and clinical studies on ischemic lesions of the large intestine].

To clarify the pathogenesis and endoscopic features of ischemic lesions of the colon, experimental ischemia was induced in dogs by arterial ligation, gelfoam injection, and clipping. In addition, clinical and endoscopic features of ischemic lesions in ischemic colitis cases in human were studied. In the experimental model, arterial ligation including marginal arteries frequently induced erosions in the large intestine, whereas ligation of the colic artery alone did not induce apparent mucosal lesions of the large intestine. Gelfoam injection to produce thrombi into caudal mesenteric artery or middle colic artery induced ulcers with a high rate of incidence and frequently accompanied by intestinal perforation. Temporal impairment of blood supply by arterial clipping produced erosion, but not ulcers. A high incidence of erosion was obtained in a group that underwent clipping for a prolonged period and a group of receiving Alosenn. Mucosal blood flow measured by the hydrogen gas clearance method was significantly decreased at 1 hr and 4 hr after gelfoam injection compared with those after arterial ligation. In human cases of ischemia following arterial surgery, endoscopic features were similar to those lesions of the experimental ischemia induced by gelfoam injection. These results suggest that thrombi in peripheral small arteries may play a major role in the pathogenesis of ischemic lesions of the large intestine.

Adult↗
PubMed1992

Resistance of the melibiose carrier to inhibition by the phosphotransferase system due to substitutions of amino acid residues in the carrier of Salmonella typhimurium.

The melibiose carrier of Salmonella typhimurium is under the control of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS). We isolated mutants of the melibiose carrier that showed resistance to inhibition via the PTS. Growth of the mutants on melibiose was not inhibited by 2-deoxyglucose, a non-metabolizable substrate of the PTS, although growth of the parent strain was inhibited. Transport activity of the melibiose carrier in the mutants was fairly resistant to inhibition by 2-deoxyglucose, although the activity in the parent was sensitive to inhibition. We cloned the mutated melB gene that encodes the melibiose carrier, determined the nucleotide sequences, and identified replaced nucleotides. The mutations resulted in substitutions of Asp-438 with Tyr, Arg-441 with Ser, or Ile-445 with Asn. All of these residues are in the COOH-terminal region of the carrier. The secondary structure of this region is predicted to be an alpha-helix, and the mutated residues were on the same side of the helix. This region showed sequence similarity to a region of the MalK protein, in which substitution of amino acid residues also resulted in PTS-resistant mutants. Thus the COOH-terminal portion of the melibiose carrier is important for the interaction of dephosphorylated IIIGlc, which is an entity causing reversible inactivation of the carrier.

Amino Acid Sequence↗
PubMed1992

Cloning and sequencing of the melB gene encoding the melibiose permease of Salmonella typhimurium LT2.

The nucleotide sequence of the melB gene coding for the Na+ (Li+)/melibiose symporter of Salmonella typhimurium LT2 was determined, and its amino acid sequence was deduced. It consists of 1428 bp, corresponding to a protein of 476 amino acid residues (calculated molecular weight 52,800). The amino acid sequence is homologous to that of the melibiose permease of Escherichia coli K12, with 85% identical residues. All, except one, of the amino acid residues that have been reported to be important for cation or substrate recognition in the melibiose permease of E. coli are conserved in the melibiose permease of S. typhimurium. In addition, part of the sequence resembles the lactose permease of Streptococcus thermophilus, the animal glucose transporter (GLUT1), the plasmid-coded raffinose permease (RafB), and the NADH-ubiquinone oxidoreductase chain 4 (Nuo4) of Aspergillus amstelodami.

Amino Acid Sequence↗