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M Fujioka

Publications and source records attributed to M Fujioka.

At least 73 records · Page 4Linked to original sources
PubMed1999

Crystallization and preliminary x-ray diffraction studies of guanidinoacetate methyltransferase from rat liver.

Guanidinoacetate methyltransferase is the enzyme which catalyzes the last step of creatine biosynthesis. The enzyme is found ubiquitously and in abundance in the livers of all vertebrates. Recombinant rat-liver guanidinoacetate methyltransferase has been crystallized with guanidinoacetate and S-adenosylhomocysteine. The crystals belong to the monoclinic space group P2(1), with unit-cell parameters a = 54.8, b = 162.5, c = 56.1 A, beta = 96.8 (1) degrees at 93 K, and typically diffract beyond 2.8 A.

Animals↗
PubMed1999

Trithorax- and Polycomb-group response elements within an Ultrabithorax transcription maintenance unit consist of closely situated but separable sequences.

In Drosophila, two classes of genes, the trithorax group and the Polycomb group, are required in concert to maintain gene expression by regulating chromatin structure. We have identified Trithorax protein (TRX) binding elements within the bithorax complex and have found that within the bxd/pbx regulatory region these elements are functionally relevant for normal expression patterns in embryos and confer TRX binding in vivo. TRX was localized to three closely situated sites within a 3-kb chromatin maintenance unit with a modular structure. Results of an in vivo analysis showed that these DNA fragments (each approximately 400 bp) contain both TRX- and Polycomb-group response elements (TREs and PREs) and that in the context of the endogenous Ultrabithorax gene, all of these elements are essential for proper maintenance of expression in embryos. Dissection of one of these maintenance modules showed that TRX- and Polycomb-group responsiveness is conferred by neighboring but separable DNA sequences, suggesting that independent protein complexes are formed at their respective response elements. Furthermore, we have found that the activity of this TRE requires a sequence (approximately 90 bp) which maps to within several tens of base pairs from the closest neighboring PRE and that the PRE activity in one of the elements may require a binding site for PHO, the protein product of the Polycomb-group gene pleiohomeotic. Our results show that long-range maintenance of Ultrabithorax expression requires a complex element composed of cooperating modules, each capable of interacting with both positive and negative chromatin regulators.

Animals↗
PubMed1999

Delayed ischemic hyperintensity on T1-weighted MRI in the caudoputamen and cerebral cortex of humans after spectacular shrinking deficit.

BACKGROUND AND PURPOSE: Transient internal carotid artery (ICA)-middle cerebral artery (MCA) occlusion caused by cardiogenic embolus can lead to spectacular shrinking deficit (SSD): sudden hemispheric stroke syndrome followed by rapid improvement. The aim of this study was to investigate sequential neuroradiological changes in the brains of patients after SSD compared with those after brief cardiac arrest and hypoglycemia, which we previously studied with the same methods. METHODS: We serially studied CT scans and MR images obtained at 1.5 T in 4 patients with SSD. All 4 patients suffered from transient neurological deficits due to cardiogenic embolus in ICA-MCA. The symptoms began to disappear from 25 to 50 minutes after onset. RESULTS: Repeated CT scans demonstrated no abnormal findings in the affected cerebral hemisphere in 3 of the 4 patients and a small cortical infarct in the remaining 1. In each patient, repeated MRI between day 7 and month 23 after stroke showed basal ganglionic and cortical lesions. These lesions were hyperintense on T1-weighted and relatively hypointense on T2-weighted imaging. These ischemic lesions of hyperintensity on T1-weighted MRI subsided with time. CONCLUSIONS: Transient ICA-MCA occlusion leading to SSD produces a specific ischemic change with delayed onset in the basal ganglia and cerebral cortex in humans on MRI but not CT scans. We speculate that the lesions represent incomplete ischemic injury, including selective neuronal death, proliferation of glial cells, paramagnetic substance deposition, and/or lipid accumulation. Unlike brief cardiac arrest or hypoglycemia, the localized lesions on MRI of patients after SSD seem to be incomplete and to differ from infarction or hemorrhage.

Aged↗
PubMed1999

Novel brain ischemic change on MRI. Delayed ischemic hyperintensity on T1-weighted images and selective neuronal death in the caudoputamen of rats after brief focal ischemia.

BACKGROUND AND PURPOSE: Specific change of persistent hyperintensity/hypointensity on T1-weighted (T1W) and T2-weighted (T2W) MRI, respectively, has been reported to develop in the human basal ganglia after brief hemispheric ischemia. We investigated whether this ischemic change observed in humans could be reproduced experimentally in rats after brief middle cerebral artery (MCA) occlusion (MCAO), and if so, what the neuroradiological change represented histologically. METHODS: The origin of the right MCA of male Wistar rats (n=25) was occluded for 15 minutes by inserting a silicon-coated nylon thread from the external carotid artery into the internal carotid artery. After 15 minutes' MCAO, coronal MR images (T1W, T2W, and T1W with fat saturation pulse) were obtained once at 3-day reperfusion (n=5) and twice at 3- and 7-day reperfusion (n=20). Brain specimens were examined histologically immediately after the last MRI study in all rats. RESULTS: Neither T1W nor T2W MRI showed marked signal changes 3 days after reperfusion following 15-minute MCAO. However, the ischemic change of hyperintensity and hypointensity on T1W and T2W MRI, respectively, appeared in the striatum following 7-day reperfusion after 15-minute MCAO (n=19/20). Histological examination revealed that the specific lesion in the rat striatum on MRI corresponded to selective neuronal death and proliferation of reactive astrocytes and microglia without infarct, hemorrhage, lipid accumulation, or calcification. CONCLUSIONS: Brief MCAO with reperfusion induces the delayed ischemic changes of hyperintensity and hypointensity on T1W and T2W MRI, respectively, in the rat striatum with high reproducibility. This specific ischemic change on MRI histologically corresponded to selective neuronal death and gliosis with preservation of the macroscopic structure of the brain. A similar MRI pattern reported in patients who have sustained brief ischemia may represent similar histology. We speculate that the ischemic change reflects some biochemical changes affecting the magnetic field as the brain tissue undergoes subtle structural changes.

Animals↗
PubMed1999

Analysis of an even-skipped rescue transgene reveals both composite and discrete neuronal and early blastoderm enhancers, and multi-stripe positioning by gap gene repressor gradients.

The entire functional even-skipped locus of Drosophila melanogaster is contained within a 16 kilobase region. As a transgene, this region is capable of rescuing even-skipped mutant flies to fertile adulthood. Detailed analysis of the 7.7 kb of regulatory DNA 3' of the transcription unit revealed ten novel, independently regulated patterns. Most of these patterns are driven by non-overlapping regulatory elements, including ones for syncytial blastoderm stage stripes 1 and 5, while a single element specifies both stripes 4 and 6. Expression analysis in gap gene mutants showed that stripe 5 is restricted anteriorly by Krüppel and posteriorly by giant, the same repressors that regulate stripe 2. Consistent with the coregulation of stripes 4 and 6 by a single cis-element, both the anterior border of stripe 4 and the posterior border of stripe 6 are set by zygotic hunchback, and the region between the two stripes is 'carved out' by knirps. Thus the boundaries of stripes 4 and 6 are set through negative regulation by the same gap gene domains that regulate stripes 3 and 7 (Small, S., Blair, A. and Levine, M. (1996) Dev. Biol. 175, 314-24), but at different concentrations. The 3' region also contains a single element for neurogenic expression in ganglion mother cells 4-2a and 1-1a, and neurons derived from them (RP2, a/pCC), suggesting common regulators in these lineages. In contrast, separable elements were found for expression in EL neurons, U/CQ neurons and the mesoderm. The even-skipped 3' untranslated region is required to maintain late stage protein expression in RP2 and a/pCC neurons, and appears to affect protein levels rather than mRNA levels. Additionally, a strong pairing-sensitive repression element was localized to the 3' end of the locus, but was not found to contribute to efficient functional rescue.

3' Untranslated Regions↗
PubMed1999

The Drosophila homeobox genes zfh-1 and even-skipped are required for cardiac-specific differentiation of a numb-dependent lineage decision.

A series of inductive signals are necessary to subdivide the mesoderm in order to allow the formation of the progenitor cells of the heart. Mesoderm-endogenous transcription factors, such as those encoded by twist and tinman, seem to cooperate with these signals to confer correct context and competence for a cardiac cell fate. Additional factors are likely to be required for the appropriate specification of individual cell types within the forming heart. Similar to tinman, the zinc finger- and homeobox-containing gene, zfh-1, is expressed in the early mesoderm and later in the forming heart, suggesting a possible role in heart development. Here, we show that zfh-1 is specifically required for formation of the even-skipped (eve)-expressing subset of pericardial cells (EPCs), without affecting the formation of their siblings, the founders of a dorsal body wall muscle (DA1). In addition to zfh-1, mesodermal eve itself appears to be needed for correct EPC differentiation, possibly as a direct target of zfh-1. Epistasis experiments show that zfh-1 specifies EPC development independently of numb, the lineage gene that controls DA1 founder versus EPC cell fate. We discuss the combinatorial control mechanisms that specify the EPC cell fate in a spatially precise pattern within the embryo.

Animals↗
PubMed1999

Bilateral chronic subdural hematomas resulting in unilateral oculomotor nerve paresis and brain stem symptoms after operation--case report.

An 85-year-old male presented with bilateral chronic subdural hematomas (CSDHs) resulting in unilateral oculomotor nerve paresis and brainstem symptoms immediately after removal of both hematomas in a single operation. Initial computed tomography on admission demonstrated marked thick bilateral hematomas buckling the brain parenchyma with a minimal midline shift. Almost simultaneous removal of the hematomas was performed with the left side was decompressed first with a time difference of at most 2 minutes. However, the patient developed right oculomotor nerve paresis, left hemiparesis, and consciousness disturbance after the operation. The relatively marked increase in pressure on the right side may have caused transient unilateral brain stem compression and herniation of unilateral medial temporal lobe during the short time between the right and left procedures. Another factor was the vulnerability of the oculomotor nerve resulting from posterior replacement of the brain stem and stretching of the oculomotor nerves as seen on sagittal magnetic resonance (MR) images. Axial MR images obtained at the same time demonstrated medial deflection of the distal oculomotor nerve after crossing the posterior cerebral artery, which indicates previous transient compression of the nerve and the brain stem. Gradual and symmetrical decompression without time lag is recommended for the treatment of huge bilateral CSDHs.

Aged↗
PubMed1999

Surgical treatment of internal carotid artery anterior wall aneurysm with extravasation during angiography--case report.

A 54-year-old female presented subarachnoid hemorrhage from an aneurysm arising from the anterior (dorsal) wall of the internal carotid artery (ICA). During four-vessel angiography, an extravasated saccular pooling of contrast medium emerged in the suprasellar area unrelated to any arterial branch. The saccular pooling was visualized in the arterial phase and cleared in the venophase during every contrast medium injection. We suspected that the extravasated pooling was surrounded by hard clot but communicated with the artery. Direct surgery was performed but major premature bleeding occurred during the microsurgical procedure. After temporary clipping, an opening of the anterior (dorsal) wall of the ICA was found without apparent aneurysm wall. The vessel wall was sutured with nylon thread. The total occlusion time of the ICA was about 50 minutes. Follow-up angiography demonstrated good patency of the ICA. About 2 years after the operation, the patient was able to walk with a stick and to communicate freely through speech, although left hemiparesis and left homonymous hemianopsia persisted. The outcome suggests our treatment strategy was not optimal, but suture of the ICA wall is one of the therapeutic choices when premature rupture occurs in the operation.

Aneurysm, Ruptured↗
PubMed1999

Characterization of urinary metabolites of a new benzofuroquinoline derivative, 3,9-bis(N,N-dimethylcarbamoyloxy)-5 H-benzofuro[3,2-c]-quinoline-6-one (KCA-098), in dogs.

The metabolism of 3,9-bis(N,N-dimethylcarbamoyloxy)-5 H-benzofuro[3,2-c]-quinoline-6-one (KCA-098), a new inhibitor of bone resorption and stimulator of bone formation, was examined after oral administration to dogs. Nine metabolites and the unchanged KCA-098 were isolated by extraction and HPLC from dog urine. The structures of these metabolites were characterized by LC/MS or LC/MS/MS, and/or were confirmed by comparison with corresponding authentic standards. The presumed main metabolic pathways were hydrolysis, hydroxylation, and N-demethylation of the N,N-dimethyl-carbamate ester group.

Animals↗
PubMed1999

[A case with traumatic internal carotid artery dissection in which the extent of the pseudolumen was defined by MR angiography].

We report a 29-year-old male with traumatic internal carotid artery (ICA) dissection who presented with cerebral ischemia developed after removal of a left acute subdural hematoma and external decompression. CT scans 4 days after the operation showed infarctions of the distribution of the bilateral cerebral hemispheres. Cerebral angiography on the 11th hospital day demonstrated narrowing of the extracranial internal carotid artery at C1-C2 vertebral levels. Slight arterial dilatation and retention of the contrast medium were found just above the narrowing segment, which was suspected to be a pseudolumen. Three D time-of flight MRA showed an intramural hematoma corresponding to the narrowing on the angiography. Original axial MRA images showed that narrowing of the lumen was surrounded by a crescent hematoma and that two flow velocity areas were in the area distal to the narrowing. High flow seemed to be ordinary artery flow rate. The low flow area, including turbulent flow, led to the retention of contrast medium mimicking a pseudolumen. Precise MRA imaging will bring us an accurate diagnosis of extracranial carotid dissections.

Adult↗
PubMed1999

[Clinical trial of prophylactic hepatic arterial chemotherapy for liver metastases in patients with Dukes' C colorectal cancer].

Preliminary results of a prospective non-randomized trial of prophylactic hepatic arterial chemotherapy for liver metastases from colorectal cancer are presented. Twenty-two colorectal cancer patients (infusion group) in Dukes' C stage were given hepatic arterial infusion of 5-FU (500 mg/body for 1 hr per week, repeated 50 times) and peroral UFT-E (2.0 g/body, daily). Informed consent was obtained from all patients. Adverse effects and postoperative recurrence in the infusion group were compared with those of patients with UFT-E alone (control group). Complications related to hepatic arterial infusion in the infusion group were also demonstrated. There was no adverse effect in the control group, while diarrhea (grade 1) developed in one patient (5%) and pigmentation in five (24%) in the infusion group. Complications related to infusion were found in five patients (5%). Three patients in the infusion group presented with metachronous hepatic lesions, two of which were resected successfully. In the control group, one patient died of marked hepatic metastases, and one developed ovarian metastasis with lymph node involvement. Our regimen appears hematologically safe, however, the high frequency of pigmentation should be kept in mind. The oncological benefit of this chemotherapy would be clarified by a larger series of cases and longer follow-up.

Administration, Oral↗
PubMed1998

A new isoform of human myosin phosphatase targeting/regulatory subunit (MYPT2): cDNA cloning, tissue expression, and chromosomal mapping.

Myosin phosphatase target subunit 1 (MYPT1), a subunit of myosin phosphatase, plays a pivotal role in the regulation of myosin phosphatase activity. Here we have cloned a novel isoform of MYPT1, termed MYPT2, from a human brain cDNA library screened with a cDNA fragment of rat MYPT1. Overlapping clones indicated an open reading frame of 3763 nucleotides and a predicted polypeptide of mass 110,398. Ankyrin repeats and leucine zipper motifs were identified for the sequences 57-316 and 956-982, respectively. Overall, the deduced amino acid sequence of MYPT2 was 61% identical to MYPT1. MYPT2 gene is transcribed abundantly in heart and skeletal muscle, while Western blots using an antibody specific for MYPT2 showed exclusive expression of MYPT2 in heart and brain. A recombinant of the N-terminal two-thirds of MYPT2 bound to the catalytic subunit of type 1 phosphatase (delta isoform) and increased activity toward phosphorylated myosin light chain. In situ hybridization localized the human MYPT2 gene on chromosome 1q32.1, compared to the chromosomal location 12q15-q21-2 for MYPT1. It is suggested that the products of the two gene families of myosin phosphatase target subunit may be localized differently among various tissues.

Amino Acid Sequence↗
PubMed1998

Mouse spermatogenic cell-specific type 1 hexokinase (mHk1-s) transcripts are expressed by alternative splicing from the mHk1 gene and the HK1-S protein is localized mainly in the sperm tail.

Unique type 1 hexokinase (HK1) mRNAs are present in mouse spermatogenic cells (mHk1-s). They encode a spermatogenic cell-specific sequence region (SSR) but not the porin-binding domain (PBD) necessary for HK1 binding to porin on the outer mitochondrial membrane. This study determined the origin of the multiple Hk1-s transcripts in mouse spermatogenic cells and verified that they are translated in mouse spermatogenic cells. It also showed that a single mHk1 gene encodes the mHk1 transcripts of somatic cells and the mHk1-sa and mHk1-sb transcripts of spermatogenic cells, that alternative exons are used during mHk1 gene expression in mouse spermatogenic cells, and that mHK1-S is translated in mouse spermatogenic cells and is localized mainly with the fibrous sheath in the tail region, not with the mitochondria in the midpiece of mouse sperm.

Alternative Splicing↗
PubMed1998

Plasticity of Drosophila paired function.

The Drosophila Paired (Prd) transcription factor has homeodomain (HD) and paired domain (PD) DNA-binding activities required for in vivo function. Correspondingly, Prd activation of late even-skipped (eve) expression occurs through a conserved target sequence (PTE) with HD and PD half sites, both of which are required for activation. To investigate the relationship between the HD and PD, and their roles in conferring specificity to Prd function, we tested altered versions of the Prd protein and of the PTE target site using in vivo assays in embryos. We found that function through PTE was constrained by the targeting specifications of both the HD and PD as well as the spatial relationship between these two domains. PTE function was also constrained by the spacing between the target half sites for the PD and HD, although surprisingly, late eve activation was retained when PTE was replaced by in vitro optimized binding sites for either the PD alone or for an HD dimer. In contrast to late eve regulation, other Prd targets tolerated more changes in the Prd protein, suggesting that their target sequences may be qualitatively different from PTE.

Animals↗
PubMed1998

Drosophila homeobox gene eve enhances trol, an activator of neuroblast proliferation in the larval CNS.

The regulation of stem cell division by developmental cues is critical for the assembly and function of multicellular organisms. Stem cell division in the Drosophila brain is controlled by trol, which is required for activation of proliferation by quiescent neuroblasts at the appropriate stage of larval development. We show that the transcriptional regulator eve is part of the trol activation pathway by identifying eve as a dominant enhancer of a weak trol allele, trolb22. Known eve mutations are capable of enhancing the lethality of trolb22 and uncovering a defective neuroblast proliferation phenotype. Additionally, genetic and molecular analysis reveals that an independent mutation which acts as a dominant enhancer of trol is also an allele of eve. The enhancement of trolb22 lethality can be suppressed by the presence of an eve transgene. Interestingly, extra copies of eve supplied by the eve transgene also enhance trolb22 lethality, suggesting that the level of Eve protein may be critical for neuroblast activation. Finally, activation of neuroblast proliferation is normal in eve4 heterozygotes, suggesting that the proliferation defect observed in trolb22;eve/+ animals is due to a synergistic interaction.

Alleles↗
PubMed1998

[Primary cardiac synovial sarcoma--a case report].

We report a case of cardiac synovial sarcoma, a very rare primary tumor of the heart. The patient was a 29-year-old man with chief complaint of dyspnea. On echocardiography, a tumor 42 mm in diameter occupying the most space of the left atrium was found. The tumor was obstructed the opening of the mitral valve. He was diagnosed with heart failure due to disturbance of the pulmonary venous return and hemodynamic mitral valve stenosis, and underwent surgery. The tumor was a 5-cm sphere originating in the left atrial posterior wall, and was covered with a sheath and solid. The atrial posterior wall was covered with a peel that appeared to be tumor tissue, and this tissue expanded toward the openings of the pulmonary veins bilaterally and the posterior cusp of the mitral valve. The tumor was resected together with the posterior wall. On pathologic examination, the tumor was diagnosed as a synovial sarcoma. Since no other primary focus was found, this tumor was judged to be a primary sarcoma of the heart. The patient was discharged with elimination of symptoms. The sarcoma recurred after 4 months, and the patient underwent a second operation. The recurrent tumor began from the site of resection of the previous operation and expanded up to the inferior pulmonary veins bilaterally. A wide area of the left atrial wall including the tumor was resected, and he was discharged again. The sarcoma recurred again, and he died of progression of heart failure and aggravation of general conditions after 8 months from the first operation.

Adult↗