Biomedical subjects

T Hashimoto

Publications and source records attributed to T Hashimoto.

At least 19 recordsLinked to original sources

PubMed1992

[MR imaging evaluation of plica synoviallis mediopatellaris of the knee joint].

To evaluate the diagnostic ability of MR imaging for plica synoviallis mediopatellaris (PSM), we retrospectively reviewed the MR imaging findings of patellofemoral space in 20 knee joints of 11 patients. In all 20 knee joints, arthroscopy and MR imaging were available. MR imaging was performed with a 1.5 Tesla Magnetom (Siemens) using a round surface coil. Pulse sequences were SE (TR 600 ms/TE 26 ms), SE (TR 200 ms/TE 26, 70 ms) and FLASH (TR 450 ms/TE 15 ms/FA 90 degrees). In six of the 20 knees with PSM proved by arthroscopy, a low intensity band was shown above the medial condyle of the femur on both T1- and T2-weighted MR images, and on FLASH images this band was shown as intermediate intensity. In the other 14 knees with no PSM observed by arthroscopy, the low intensity band was not shown on MR imaging. In all 20 knees, a similar low intensity band was shown about 1 cm cranial to the medial condyle of the femur. This should not be diagnosed as PSM. The low intensity band seen on T1- and T2-weighted MR images and its anatomical relation to the medial condyle are important in diagnosing PSM.

Adolescent↗

PubMed1992

The prognostic value of cytogenetic analyses in patients with acute nonlymphocytic leukemia treated with the same intensive chemotherapy.

BACKGROUND: Some specific chromosome abnormalities for the leukemias have been proven to be associated with the prognosis of acute nonlymphocytic leukemia (ANLL). However, most of these reports included patients treated with different protocols. Therefore, some bias has been involved in the evaluation of the prognostic factors in such reports. METHODS: The authors studied the morphologic, cytogenetic, and clinical features of 136 patients (86 males and 50 females) with de novo ANLL treated with the same protocol of intensive induction chemotherapy using multivariate analyses. RESULTS: Chromosome abnormalities were detected in 62.5% of the patients. The overall complete remission (CR) rate of disease was 85.5% in these patients. More than 90% of the patients with t(8;21) and pseudodiploid abnormalities achieved experienced CR. However, CR rates in the patients with abnormalities of chromosome 5 or 7 were 50%. With multivariate analyses by the type of karyotypic abnormality, CR duration and survival time of the patients with t(8;21) were longer than those of patients with normal karyotype and abnormalities of chromosome 5 or 7. Abnormalities of chromosome 5 or 7 and hyperdiploid were associated with poor prognosis. Older age and lower platelet counts also were factors contributing to shorter survival times. With the analysis with French-American-British (FAB) classification, only hypoplastic leukemia was a poor prognostic factor. CONCLUSIONS: These data suggest that cytogenetic analyses plays an important role in estimating the prognosis of patients treated with intensive induction chemotherapy.

Adolescent↗

PubMed1992

Metabolic engineering of medicinal plants: transgenic Atropa belladonna with an improved alkaloid composition.

The tropane alkaloid scopolamine is a medicinally important anticholinergic drug present in several solanaceous plants. Hyoscyamine 6 beta-hydroxylase (EC 1.14.11.11) catalyzes the oxidative reactions in the biosynthetic pathway leading from hyoscyamine to scopolamine. We introduced the hydroxylase gene from Hyoscyamus niger under the control of the cauliflower mosaic virus 35S promoter into hyoscyamine-rich Atropa belladonna by the use of an Agrobacterium-mediated transformation system. A transgenic plant that constitutively and strongly expressed the transgene was selected, first by screening for kanamycin resistance and then by immunoscreening leaf samples with an antibody specific for the hydroxylase. In the primary transformant and its selfed progeny that inherited the transgene, the alkaloid contents of the leaf and stem were almost exclusively scopolamine. Such metabolically engineered plants should prove useful as breeding materials for obtaining improved medicinal components.

Atropa belladonna↗

PubMed1992

Stabilization of Escherichia coli ribonuclease HI by strategic replacement of amino acid residues with those from the thermophilic counterpart.

Thermus thermophilus ribonuclease H is exceptionally stable against thermal and guanidine hydrochloride denaturations as compared to Escherichia coli ribonuclease HI (Kanaya, S., and Itaya, M. (1992) J. Biol. Chem. 267, 10184-10192). The identity in the amino acid sequences of these enzymes is 52%. As an initial step to elucidate the stabilization mechanism of the thermophilic RNase H, we examined whether certain regions in its amino acid sequence confer the thermostability. A variety of mutant proteins of E. coli RNase HI were constructed and analyzed for protein stability. In these mutant proteins, amino acid sequences in loops or terminal regions were systematically replaced with the corresponding sequences from T. thermophilus RNase H. Of the nine regions examined, replacement of the amino acid sequence in each of four regions (R4-R7) resulted in an increase in protein stability. Simultaneous replacements of these amino acid sequences revealed that the effect of each replacement on protein stability is independent of each other and cumulative. Replacement of all four regions (R4-R7) gave the most stable mutant protein. The temperature of the midpoint of the transition in the thermal unfolding curve and the free energy change of unfolding in the absence of denaturant of this mutant protein were increased by 16.7 degrees C and 3.66 kcal/mol, respectively, as compared to those of E. coli RNase HI. These results suggest that individual local interactions contribute to the stability of thermophilic proteins in an independent manner, rather than in a cooperative manner.

Amino Acid Sequence↗

PubMed1992

[Intracranial MR imaging of achondroplasia].

Intracranial MR imaging was performed in five patients with achondroplasia. All patients had narrowing of the subarachnoid space at the level of the foramen magnum that was mainly due to protrusion of the posterior aspect. Three patients had compressive deformities of the brainstem and/or upper cervical spine. Among them, two patients had deformities of the pons. Relative upward displacement of the brainstem was seen in all patients. Hydrocephalus was seen in three patients.

Achondroplasia↗

PubMed1992

The distribution of epithelial membrane antigen in thymic epithelial neoplasms.

Thymic carcinomas arising within a thymoma have been reported, but the relationship between thymoma and thymic carcinoma is poorly understood. Epithelial membrane antigen (EMA) is known to be an effective marker for establishing the epithelial nature of neoplastic cells, and it is reported that staining of tumors is clearly related to the degree of tumor differentiation. Eighty-one thymomas (59 noninvasive, 22 invasive) and 14 thymic carcinomas were studied immunohistologically using antiepithelial membrane antigen (anti-EMA) monoclonal antibody. Thymic carcinomas tended to express much larger quantities of EMA than thymomas, and instances of EMA-positive thymoma were seen significantly more often in invasive thymomas than in noninvasive ones (P < 0.05). However, EMA positivity was also associated with gland-like structures, which were not necessarily associated with malignant disease. Nevertheless, in view of the concept that thymoma and thymic carcinoma show a similar cellular differentiation, EMA-positive epithelial cells in thymoma with no relation to gland-like configurations might represent a pool of cells having a latent potential for malignant disease and might be transformed into thymic carcinoma cells under certain conditions. Immunolabeling for EMA appears to be a useful tool for determining the degree of malignant disease among thymic epithelial neoplasms.

Adult↗

PubMed1992

Yeast ribosomal proteins: XIV. Complete nucleotide sequences of the two genes encoding Saccharomyces cerevisiae YL16.

We isolated and sequenced YL16A and YL16B encoding ribosomal protein YL16 of Saccharomyces cerevisiae. The two nucleotide sequences within coding regions retain 91.1% identity, and their predicted sequences of 176 amino acids show 93.8% identity. Out of the ribosomal protein sequences from various organisms currently available, no counterpart to YL16 could be found.

Amino Acid Sequence↗

PubMed1992

Identification and characterization of two enhancers of the human albumin gene.

A 12.5-kilobase pair (kb) segment upstream of the human albumin gene was analyzed for transcription enhancing activity using transient transfection analysis, gel mobility shift assays, DNase I footprinting, and site-specific mutagenesis. Two enhancer regions were identified, one 1.7 kb upstream of the transcription initiation site (E1.7) and the other 6 kb upstream (E6). In E1.7, a nuclear protein from HuH-7 hepatoma cells binds to an AT-rich sequence, GTTACTAATTGAC. Competition gel mobility shift assays suggested that this protein is HNF-1, which regulates the promoter of the albumin gene and several other liver-specific genes. A 60-base pair E1.7 fragment carrying the AT-rich sequence stimulates a heterologous (alpha-fetoprotein) promoter in a dose-dependent manner. In E6, a HuH-7 nuclear protein binds to a GT-rich sequence, TGTTTGGC.A 27-base pair E6 fragment carrying this sequence is able to stimulate the SV40 promoter in an orientation-independent manner. An alteration of this sequence by site-specific mutagenesis resulted in the loss of transcriptional activity as well as binding to the HuH-7 nuclear protein. Competition gel mobility shift assays showed that homologous elements exist in the albumin promoter. These results show that the promoter and enhancer of the human albumin gene are regulated by two common transcription factors through two shared cis-acting elements, one AT-rich and the other GT-rich.

Albumins↗

PubMed1992

[Dynamic 3DFT FISP MR imaging of hepatocellular carcinoma].

Dynamic 3 dimensional Fourier transformation (3DFT) FISP MR imaging was performed in 5 patients with hepatocellular carcinoma before partial hepatectomy. Immediately after 0.1 mmol/kg of Gd-DTPA was administered intravenously, 3DFT FISP images (TR/TE/flip angle/slice thickness, 20 msec/8 msec/30 degrees/2-4 mm) were obtained every 30 seconds until 150 sec. We correlated dynamic MR images of the 5 patients with gross and microscopic findings. Some regions in the tumor corresponding to viable cells showed high intensity enhancement and other regions corresponding to necrotic regions showed no enhancement on the early phase images. We concluded that dynamic 3DFT FISP MR imaging which had good spatial resolution was useful in evaluating the vascularity of the tumor.

Aged↗

PubMed1992

Carboxyl-terminal consensus Ser-Lys-Leu-related tripeptide of peroxisomal proteins functions in vitro as a minimal peroxisome-targeting signal.

The minimal sequence requirement for a peroxisome-targeting signal was investigated using an in vitro import system. Carboxyl-terminal sequences Ser-Lys-Leu (SKL) and Leu-Gln-Ser-Lys-Leu (LQSKL) of acyl-CoA oxidase (AOX) directed to peroxisomes the fused proteins with import-incompetent forms of AOX and catalase that had been truncated, implying that the SKL tripeptide functions as a targeting signal. Elimination of the entire SKL sequence or deletion of any 1 or 2 amino acids in the sequence abolished the import activity of AOX. Substitution of alanine for serine did not affect the import activity. Topogenic activity was retained when lysine was mutated to either arginine or histidine, whereas mutation to glutamic acid completely abolished the activity. A synthetic peptide comprising the carboxyl-terminal 10 amino acid residues of AOX inhibited the import of the authentic AOX polypeptide, whereas other peptides in which SKL was mutated, deleted, or internally located were not effective. The uptake of AOX was little affected by the peptide with an amidated alpha-carboxyl group. These results strongly suggest that the carboxyl-terminal SKL motif sequence (Ser/Ala)-(Lys/Arg/His)-Leu functions as a topogenic signal in translocation of proteins into peroxisomes, requiring the whole tripeptide sequence with a free alpha-COOH group at the carboxyl terminus.

Acyl-CoA Oxidase↗

PubMed1992

The loss of beta II-protein kinase C in the striatum from patients with Huntington's disease.

We have examined the levels of protein kinase C (PKC) in autopsied brains of patients with Huntington's disease (HD), using [3H]4-beta-phorbol-12,13-dibutyrate ([3H] PDBu) and antisera against the PKC subspecies. In the caudate nucleus and putamen from patients with HD, the specific binding for [3H]PDBu was significantly decreased by 74 and 68%, respectively, as compared to findings in controls. The beta II-PKC immunoreactivities were significantly reduced by 65%, whereas the alpha-PKC immunoreactivities increased by 146%, in the putamen. There were no differences in the beta I- or gamma-PKC immunoreactivities in the putamen between HD and controls. These results suggest the differential localization of four PKC subspecies in human striatum and the involvement of four subspecies in different aspects of HD pathophysiology.

Brain↗

PubMed1992

Molecular basis of 3-ketothiolase deficiency: identification of an AG to AC substitution at the splice acceptor site of intron 10 causing exon 11 skipping.

3-Ketothiolase deficiency (3KTD) is the result of a deficiency in mitochondrial acetoacetyl-CoA thiolase (T2). The molecular basis of 3KTD was analyzed in a patient (GK10) and his family at the protein, cDNA and gene levels. Protein analyses showed that GK10's T2 protein was undetectable in fibroblasts even with the pulse-protein labeling method and that his parents were carriers of 3KTD. Complementary DNA analyses with PCR showed that T2 cDNA in the patient lacked the normal exon 11 sequence and that his parents were obligatory carriers of the DNA sequence which canceled exon 11. When the PCR-amplified genomic fragments around exon 11 were sequenced, an AG to AC mutation at the 3' splice site of intron 10 was detected. This mutation is presumed to be responsible for exon 11 skipping.

Acetyl-CoA C-Acyltransferase↗

PubMed1992

[Differentiation between hepatoma and hemangioma by inversion recovery snapshot FLASH MR imaging with variable TIs].

To differentiate hepatoma from hemangioma, MR studies were performed for 18 patients with 21 untreated liver tumors (hepatoma 10, hemangioma 11). We obtained inversion recovery snapshot FLASH images of liver tumors with variable TIs (50, 100, 150, 200, 250, 300, 400, and 500 msec). 8 hemangiomas showed higher intensity than liver parenchyma on the images at 150 msec and less of TI, and lower intensity at 200 msec or more TI. In 7, signal intensity of hepatoma became low at 150 msec or less of TI or remained high with prolonged TI. Inversion recovery snapshot FLASH imaging with variable TIs will be useful for differentiating between hepatoma and hemangioma.

Adult↗

PubMed1992

An immunohistologic study of the epithelial components of 81 cases of thymoma.

Eighty-one cases of thymoma were studied immunohistologically with the use of three mouse monoclonal antibodies: one was specific for subcapsular-cortical, one for intra-cortical, and one for medullary epithelial cells. Twenty-eight (60.9%) of 46 polygonal cell thymomas were of the cortical type and 1 (2.2%) was of the medullary type. Ten (55.6%) of 18 spindle cell thymomas and 7 (41.2%) of 17 mixed cell thymomas were of the medullary type, and 1 (5.6%) of 18 spindle cell thymomas was of the cortical type. Fourteen (17.3%) of 81 thymomas were composed of epithelial cells that were triple positive immunologically; although these are unusual, they also may be present in the normal thymus. Based on these findings, triple-positive epithelium in the normal thymus consists of common stem cells that can differentiate into subcapsular-cortical, intra-cortical, and medullary epithelium; these cells may be the target cells for tumorigenesis. Epithelium in polygonal cell thymoma tends to differentiate into cortical epithelium, whereas epithelium in spindle and mixed cell thymomas differentiates into medullary epithelium.

Adult↗

PubMed1992

cDNA cloning of a neural visinin-like Ca(2+)-binding protein.

A 21,000-dalton Ca(2+)-binding protein (Walsh, M.P., Valentine, K.A., Ngai, P.K., Carruthers, C.A., and Hollengerg, M.D. (1984) Biochem. J. 224, 117-127) was purified from the rat brain and through the use of oligonucleotide probe based on partial amino acid sequence, cDNA clones were obtained from rat brain cDNA library. The complete amino acid sequence deduced from the cDNA contains 191 residues and has a calculated molecular mass of 22,142 daltons. There are three potential Ca(2+)-binding sites like the EF hands in the sequence. It displays striking sequence homology with visinin and recoverin, retina-specific Ca(2+)-binding proteins. Northern blot analysis revealed that the protein is highly and specifically expressed in the brain.

Amino Acid Sequence↗

PubMed1992

Yeast ribosomal proteins: XIII. Saccharomyces cerevisiae YL8A gene, interrupted with two introns, encodes a homolog of mammalian L7.

We isolated and sequenced a gene, YL8A, encoding ribosomal protein YL8 of Saccharomyces cerevisiae. It is one of the two duplicated genes encoding YL8 and is located on chromosome VII while the other is on chromosome XVI. The haploid strains carrying disrupted YL8A grew more slowly than the parent strain. The open reading frame is interrupted with two introns. The predicted amino acid sequence reveals that yeast YL8 is a homolog of mammalian ribosomal protein L7, E.coli L30 and others.

Amino Acid Sequence↗

PubMed1992

Synthesis and biological action of the aminotetrahydroisoquinocarbazoles and related compounds: a new class of compounds with antiarrhythmic activity.

A series of 12-aminotetrahydroisoquinocarbazoles and related compounds were synthesized using an intramolecular Diels-Alder reaction and screened for antiarrhythmic activity in chloroform-induced ventricular arrhythmias in mice. Several compounds showed more potent activity than disopyramide. There was some correlation between substituents on aromatic ring and angular position, and antiarrhythmic activity. An amino group or some functional groups containing an amino group on C-12 seemed to be essential to exhibit the activity. Ring size also influenced the activity. The compound (+)-10 (RS-2135) had the most favorable combination of antiarrhythmic activity and toxicity and was selected for further evaluation.

Action Potentials↗

PubMed1992

[Sensory ataxia in peripheral neuropathies--etiological and pathological analysis of four cases].

Among 85 neuropathy patients admitted and studied in the Department of Neurology, University of Occupational and Environmental Health, Japan, from 1979 to 1990, four patients suffering from sensory ataxia are reported with special reference to their etiological and pathological conditions. All of them were classified as having immune-mediated neuropathy. The first patient, a 56-year-old woman, was diagnosed as having chronic progressive ataxic sensory neuropathy. Her symptoms became progressively worse over a nine-year period after onset, but no evidence of cancer has been revealed. The positive rheumatoid factor was the only other feature noted. The second patient, a 63-year-old woman, after extensive laboratory studies, including the biopsy of the lymph node at the bifurcation of the bronchus in search of the cancer, was diagnosed as having subacute sensory neuropathy with small cell carcinoma of the lung. Chemotherapy was completed without subsequent obvious clinical benefits. The clinical diagnosis was confirmed on autopsy 29 months after the onset. The symptoms of the first patient were indistinguishable from those of the second patient, especially in the early clinical stage. In both patients, the proprioceptive sensations were severely affected and the disturbance of the proprioceptive sensations seemed to be almost parallel with the ataxia signs. The main site of the lesion seemed to be the neuron in the dorsal root ganglion in the first patient, as well as in the second patient who showed a marked loss of neurons in the dorsal root ganglion considered to be the primary lesion on autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Ataxia↗