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Biomedical subjects

T Hirose

Publications and source records attributed to T Hirose.

At least 235 records · Page 13Linked to original sources

Cloning of a cDNA encoding the murine orphan receptor RZR/ROR gamma and characterization of its response element.

In this study, we describe the cloning of the mouse homologue of the orphan receptor, RZR/ROR gamma, a member of the nuclear receptor superfamily, from a mouse muscle cDNA library. The amino acid sequence of mouse ROR gamma (mROR gamma) is highly homologous to that of human ROR gamma, with an overall identity of 88%. Northern blot analysis using RNA from different tissues showed that mROR gamma was found to be highly expressed in skeletal muscle, liver and kidney. Analysis of the ROR gamma-response element using in vitro synthesized ROR gamma revealed that it binds as a monomer to response elements composed of a single core motif GGTCA preceded by a 6 bp AT-rich sequence. The ROR gamma-binding specificity was further defined by mutational analysis of the consensus RORE. ROR gamma was able to activate RORE-dependent transcription of the CAT reporter gene in mouse fibroblast D1 cells. ROR alpha 1 and ROR gamma inhibit the transactivation induced by GAL4(DBD)-ROR gamma in fibroblast D1 cells suggesting that these receptors compete for binding to the same coactivators.

Amino Acid Sequence↗

Chemonucleolytic effects of chondroitinase ABC on normal rabbit intervertebral discs. Course of action up to 10 days postinjection and minimum effective dose.

STUDY DESIGN: This study demonstrated the chemonucleolytic effects of chondroitinase ABC and its histologic and biochemical background. OBJECTIVES: To determine the course of chondroitinase ABC action on normal rabbit discs, and to find its minimum effective dosage. SUMMARY OF BACKGROUND DATA: No previous study has assessed the chemonucleolytic action of chondroitinase ABC in a time- and dose-dependent manner. This study also investigated the biochemical causes of radiologic and histologic changes in the discs. METHODS: Rabbits were injected with 4 U of pharmaceutical-grade chondroitinase ABC intradiscally. They were radiologically and histologically observed, and biochemical analyses of the discs were conducted on days 1, 3, 5, 7, and 10 postinjection in the time course study. Different doses of chondroitinase ABC were injected, and radiologic observations and water content of the discs were measured in the dose-finding study. RESULTS: The time course study revealed that the chondroitin sulfate content of discs significantly decreased from day 1 postinjection until the end of the experimental period. The weight and water content of the nucleus pulposus decreased on day 3, and disc space narrowing was observed from the day after injection. The dose-finding study showed that a dose of 0.0002 U/disc still induced disc space narrowing and a decrease in water content. CONCLUSIONS: Chondroitinase ABC is estimated to have a chemonucleolytic effect at least by day 3 postinjection at a dose level of 0.0002 U/disc or higher in rabbits.

Animals↗

Early response gene signalling in bryostatin-stimulated primary B chronic lymphocytic leukaemia cells in vitro.

The protein kinase C activator bryostatin induces differentiation and antagonizes the effects of tumour-promoting phorbol esters in a number of different cell types. We show here that bryostatin preferentially inhibits phorbol 12-myristate 13-acetate (PMA)-induced proliferation compared with differentiation in a number of different B chronic lymphocytic leukaemia (BCLL) cell populations examined. By using a panel of 11 early-response gene probes in Northern hybridization analysis, we found that the profile of genes induced in response to bryostatin and PMA was qualitatively similar and displayed comparable sensitivities to inhibition with the serine-threonine kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine hydrochloride (H7), consistent with common signalling through protein kinase C. However, the nuclear oncogene. c-myc, which was induced strongly in response to PMA treatment, was only marginally up-regulated by bryostatin. In addition, bryostatin selectively inhibited the magnitude of PMA-responsive induction of c-myc, to a degree commensurate with its antagonistic effects seen at the biological level. Finally, an anti-sense oligonucleotide blockade of c-myc inhibited PMA-induced proliferation but not the differentiation of BCLL cells, implicating this nuclear oncogene as an important determinant distinguishing PMA from bryostatin-coupled biological responses and also as a candidate third-messenger effector target for the anti-tumour effects of bryostatin.

Bryostatins↗

Creation of a novel protein-coding region at the RNA level in black pine chloroplasts: the pattern of RNA editing in the gymnosperm chloroplast is different from that in angiosperms.

The phenomenon of RNA editing has been found to occur in chloroplasts of several angiosperm plants. Comparative analysis of the entire nucleotide sequence of a gymnosperm [Pinus thunbergii (black pine)] chloroplast genome allowed us to predict several potential editing sites in its transcripts. Forty-nine such sites from 14 genes/ORFs were analyzed by sequencing both cDNAs from the transcripts and the corresponding chloroplast DNA regions, and 26 RNA editing sites were identified in the transcripts from 12 genes/ORFs, indicating that chloroplast RNA editing is not restricted to angiosperms but occurs in the gymnosperm, too. All the RNA editing events are C-to-U conversions; however, many new codon substitutions and creation of stop codons that have not so far been reported in angiosperm chloroplasts were observed. The most striking is that two editing events result in the creation of an initiation and a stop codon within a single transcript, leading to the formation of a new reading frame of 33 codons. The predicted product is highly homologous to that deduced from the ycf7 gene (ORF31), which is conserved in the chloroplast genomes of many other plant species.

Amino Acid Sequence↗

A ribosomal protein gene (rpl32) from tobacco chloroplast DNA is transcribed from alternative promoters: similarities in promoter region organization in plastid housekeeping genes.

Multiple transcriptional start sites have been identified in the tobacco plastid ribosomal protein gene rpl32 by RNA mapping and in vitro capping techniques. A promotor with a canonical -10 Pribnow Box (P1) produces a major transcript in leaf chloroplasts. Transcription is also driven from additional promoters in non-photosynthetic plastids from heterotrophically cultured cells (BY2 line). Among them, a second promoter located downstream (P2) generates the most prominent transcript in this type of cell. The absence of typical plastid promoter motifs upstream of this site and the higher steady-state level of the P2-derived transcript in BY2 cells suggest a distinct modulation of transcription. Mobility shift experiments also seem to indicate the existence of differences in protein-DNA binding between both kinds of plastids with respect to a DNA fragment including the sequence upstream from the P2 starting site. The structure of the rpl32 promoter region is discussed in relation to that of other plastid housekeeping genes encoding elements of the genetic machinery.

Base Sequence↗

Establishment and characterization of two cultured cell lines derived from malignant rhabdoid tumors of the kidney.

Malignant rhabdoid tumor of the kidney (RTK) is a rare renal sarcoma of childhood. Its histogenesis is unclear, and it is highly resistant to multimodality therapy. To elucidate the origin and the oncogenetic potential of RTK, we investigated the characteristics of 2 newly established RTK cell lines, SWT-1 and SWT-2. Both cell lines were verified to be RTK, since they did not exhibit contact inhibition and exhibited intermediate filaments, a specific marker for RTK. These cells possess the characteristics of mesenchymal cells based on their positive reactions with anti-vimentin and anti-laminin antibodies and their negative reactions with anti-keratin and anti-desmin antibodies. The karyotype of SWT-1 was 46,XX and that of SWT-2 was 46,XX,del(11)(pter-p13::p12-qter). Since 11p13 is the location of the WT-1 tumor-suppressor gene, and del(11p13) is associated with the aniridia-Wilms'-tumor syndrome, these findings link RTK with Wilms' tumor. While SWT-1 was negative for the tumor markers examined, SWT-2 released tissue polypeptide antigen into the culture supernatant. No rearrangement or amplification of the myc and ras oncogenes or of the p53 tumor-suppressor gene were detected. Wild-type RB protein and cyclin A were expressed in both cells. Our data suggest that these 2 cell lines may be useful in identifying the oncogenetic pattern of RTK.

Antineoplastic Agents↗

Cis-acting elements and trans-acting factors for accurate translation of chloroplast psbA mRNAs: development of an in vitro translation system from tobacco chloroplasts.

Translational regulation is an important step of gene expression in chloroplasts. To analyze biochemical mechanisms of translational regulation unique to higher plant chloroplasts, an in vitro translation system has been developed from tobacco chloroplasts. Conditions for chloroplast extraction and the in vitro translation reaction have been optimized with a tobacco psbA-lacZ fusion mRNA. The in vitro system supports accurate translation of a variety of chloroplasts mRNAs. Using a series of mutant psbA mRNAs, we showed that three elements within the 5'-untranslated region of the mRNA are required for translation. Two of them are complementary to the 3'-terminus of chloroplast 16S rRNA (termed RBS1 and RBS2) and the other is an AU-rich sequence (UAAAUAAA) located between RBS1 and RBS2 and is termed the AU box. mRNA competition experiments using the in vitro translation reaction and gel mobility shift assays revealed the existence of a trans-acting factor(s) for translation and its possible interaction with the AU box. We propose a model for the initiation of psbA translation whereby RBS1 and RBS2 bind cooperatively to the 3'-end of 16S rRNA resulting in looping out of the AU box, which facilitates the interaction of a trans-acting factor(s).

Base Sequence↗

Rhabdoid tumor of the kidney: a report of two cases with respective tumor markers and a specific chromosomal abnormality, del(11p13).

Malignant rhabdoid tumor is a rare, aggressive, invariably lethal tumor that is resistant to multimodal treatment. In this report, two patients with malignant rhabdoid tumor of the kidney (RTK) are described. The first patient is the first case of RKT with hyperreninemia, and the second case is also the first case with a specific chromosomal abnormality, del 11p13. The first patient presented with hematuria and a mass in the left kidney. Plasma renin, angiotensin, and aldosterone levels were elevated and paralleled the tumor progression. The karyotype of the tumor cells was normal (46,XX). In the second patient, who presented with a mass in the right kidney, the concentration of plasma tissue polypeptide antigen was elevated and paralleled the tumor progression. The karyotype of the tumor cells was 46,XX, del(11)(pter-p13::p12-qter). RTK with a cytogenetic abnormality of del(11p13), which is usually found in aniridia-Wilms' tumor syndrome, has not been known. Both patients died of metastatic disease within 7 months of diagnosis in spite of the multimodal therapy. The clinicopathology of RTK and the differences between Wilms' tumor and RTK raise compelling questions which should be the subject of future studies.

Biomarkers, Tumor↗

Long-duration xenogeneic extracorporeal pig liver perfusion with human blood.

Hepatic xenografts can tolerate hyperacute rejection owing to their lower susceptibility to humorally mediated injury. We investigated the possibility of long-duration xenoperfusion without immunologically controlling natural antibodies or complements. Pig livers were perfused for 9 h with human blood (Group 1) or pig blood (Group 2). Physiological conditioning and administration of prostaglandin E1 and insulin was characteristic of our system. The portal vein and hepatic artery pressure and bile production did not significantly differ between the two groups. Despite a gradual decrease throughout the perfusion, overall oxygen consumption was significantly higher in Group 1. Liver enzymes were released at higher levels in Group 1. Histological examination revealed intact hepatic architecture in Group 2, while in Group 1 interlobular morphology was severely damaged by endothelial disruption, although hepatic sinusoidal architecture was preserved. It is concluded that, despite biochemically and histologically confirmed tissue injury, graft viability was well-maintained in xenoperfusion even without immunological manipulations.

Alprostadil↗

Occurrence of silent RNA editing in chloroplasts: its species specificity and the influence of environmental and developmental conditions.

We have identified three new C-to-U RNA editing sites, one in atpF and two in atpA transcripts from tobacco chloroplasts. Two of them lead to amino acid substitutions to restore the conserved amino acid found in the corresponding genes of other plants. However, one editing site in the atpA transcript was found to take place partially at the third base of a serine codon (CUC_ to CUU_), thus not leading to an amino acid substitution. This is the first report of silent editing in chloroplasts. The extent of silent editing depends on plastid stage and light conditions, while editing as another site (found 4 nt upstream from the silent editing site) takes place constitutively even in non-photosynthetic cultured cells and bleached white seedlings grown in the presence of spectinomycin and streptomycin. In pea and spinach, despite a conservation in sequence, no editing at the site corresponding to the silent site in tobacco was found. This observation suggests that the silent editing detected in this study is species-specific.

Amino Acid Sequence↗

Spatial frequency sweep pattern reversal VER acuity vs Snellen visual acuity: effect of optical defocus.

The effect of artificially induced image defocusing on visual acuities (VAs) measured by spatial frequency sweep pattern reversal visual evoked response (SPVER) and Snellen measurement was studied in six normal subjects. The steady-state SPVER was recorded using vertical gratings of 10 different spatial frequencies ranging from 0.52 to 30.36 c/deg. The SPVER acuity was compared with Snellen acuity (SA) measured under the same conditions of optical defocus. With moderate defocusing [< + 1.0 diopter (D), VA > 20/40], the SPVER acuities were equal to or poorer than the SAs. With more defocus (> + 1.5 D, VA < 20/70), the SPVER acuities became better than the SAs. The discrepancies between the SA and SPVER acuities may be the result of the influence of the parafoveal area on the SPVER at lower visual acuity levels.

Adult↗

Solitary fibrous tumor of the meninges: a lesion distinct from fibrous meningioma. A clinicopathologic and immunohistochemical study.

Seven solitary fibrous tumors (SFTs) of the meninges are presented and their clinicopathologic features are compared with those of 64 fibrous meningiomas (FM). Patients with SFT included 5 females and 2 males age 47 to 73 years. The dura-based tumors involved the parasagittal region (1), tentorium (2), cerebellopontine angle (2), and spinal region (2). One each showed invasion of brain and of a spinal nerve root. Of four SFTs with at least 1-year follow-up, one subtotally resected example recurred. No tumors metastasized. All consisted of spindle cells disposed in fascicles between prominent, eosinophilic bands of collagen. Whorls and storiform cell arrangements were lacking. Mitoses ranged from 1 to 7/10 400 x fields. MIB-1 labeling indices ranged from 1% to 18% (mean 4%). All were PAS negative and showed strong immunoreactivity for vimentin and CD34. Of cases studied, half were estrogen and all were progesterone receptor immunopositive. The majority (72%) of FMs occurred in females and most (72%) were supratentorial. Recurrence was noted in 15%. Mitotic activity varied from 0 to 3 mitoses per 10 400 x fields (mean < 1). MIB-1 labeling indices ranged from 1% to 5% (mean 1.5%). Unlike SFT, FMs were glycogen-containing and variously exhibited a storiform pattern (13 of 20), psammoma body formation (9 of 20), and calcification of collagen (4 of 20). Immunoreactivities included vimentin (100%), focal to patchy EMA (80%), S-100 protein (80%), collagen IV (25%), and patchy, mild-to-moderate CD34 staining (60%). Of cases studied, nearly half were estrogen and all were progesterone receptor staining positive. Meningeal SFTs represent a distinct morphologic entity, the morphologic and immunohistochemical features of which differ from those of FM and suggest a histogenetic relationship to pleural SFT. Although a minority histologically appear to be low grade malignant, our limited experience suggests that they behave in a benign fashion. The classification of mesenchymal tumors affecting the central nervous system must be expanded to include SFT.

Adult↗

Solitary fibrous tumor of the soft tissue. An immunohistochemical and ultrastructural study.

Solitary fibrous tumor is a rare spindle cell neoplasm of adults that usually arises in the pleura, recently reported in other locations. The authors describe three cases of solitary fibrous tumors in adults that occurred as circumscribed masses in the somatic soft tissue, including the arm, back, and abdomen. Histologically, they were characterized by a proliferation of spindle cells separated by thick bands of collagen and prominent vascularity often showing a hemangiopericytoma-like pattern. The spindle cells, having low mitotic figures and little nuclear atypicality, exhibited a variety of growth patterns, including storiform, fascicular and herringbone, and nuclear palisading. Vimentin and CD34 immunoreactivities were observed in many spindle cells of all tumors. They had ultrastructural features of fibroblast and myofibroblast in two cases examined. Solitary fibrous tumors seem to represent distinct mesenchymal neoplasms that require us to identify their unusual location other than the pleura and be familiar with their histologic appearances for arriving at the correct diagnosis.

Aged↗

Perinatal complications and schizophrenia. Data from the Maternal and Child Health Handbook in Japan.

A number of studies have shown that schizophrenics have increased obstetric complications compared with controls, but conflicting negative results have also been reported. Similarly, some studies found that obstetric complications were more frequently observed among male or nonfamilial schizophrenics than their female or familial schizophrenic counterparts, but others reported negative or inverse results. Since 1948 in Japan, every pregnant woman has been assigned a Maternal and Child Health Handbook in which obstetricians have been obliged to fill in obstetric data. In the current study, perinatal complications assessed using the scale of Parnas et al. (1982), based on information from the maternal and child health handbook were compared between DSM-III-R-diagnosed schizophrenics (N = 59), their healthy siblings (N = 31), and controls (N = 108). We found that female schizophrenics had experienced significantly more perinatal complications than siblings and controls. We could not detect any significant association between perinatal complications and family history.

Comorbidity↗

Myofibroblastic tumor of soft tissue displaying desmin-positive and actin-negative immunophenotypes.

Myofibroblasts have ultrastructural and functional characteristics intermediate between fibroblasts and smooth muscle cells. Previous studies indicated that most myofibroblasts express actin and vimentin but not desmin immunophenotypes. Two benign intramuscular myofibroblastic tumors which displayed a desmin-positive and actin-negative immunophenotype are reported. The tumors occurred on the back of a 45 year old man who had neurofibromatosis 1 and the thigh of a 37 year old man without neurofibromatosis. Both tumors were encapsulated and composed of short intersecting bundles of spindle cells in a collagenous background. Although the tumors were cellular, nuclear pleomorphism was minimal and mitotic figures were rare. Characteristically, most tumor cells were immunoreactive strongly for desmin and vimentin but gave negative staining for muscle-specific actin, alpha-smooth muscle actin, alpha-sarcomeric actin, myosin, S-100 protein, cytokeratins, and CD34. On electron microscopy, the tumor cells were characterized by short spindle-indented nuclei, abundant cytoplasmic intermediate filaments, prominent plasmalemmal pinocytosis and frequent cell coverage by basal lamina. Aggregation of thin myofilaments with focal condensations was identified occasionally. Although the tumors showed distinct morphological and immunohistochemical features enabling delimitation from other soft tissue lesions, they may overlap histologically with myofibroblastoma of the breast, lymph node and soft tissue, low grade malignant nerve sheath tumor, leiomyosarcoma, cellular schwannoma, inflammatory fibrosarcoma and nodular fasciitis.

Actins↗

Spatial tuning loss of pattern reversal visual evoked response in optic nerve disease.

We compared the pattern reversal visual evoked response (PVER) amplitude-check size functions from 25 eyes (25 normal subjects; visual acuities > or = 20/20) with those from 32 eyes (22 patients; visual acuities 20/15 to 20/50; mean, 20/25.5) with mild optic nerve disease to determine if spatial tuning loss of the PVER occurs in the presence of optic nerve dysfunction. The steady-state PVER was recorded with five check sizes (range, 160 to 10 minutes of arc). To analyze the PVER amplitude-check size function, we calculated the difference between the maximum and minimum PVER amplitudes and then calculated the area of spatial tuning (the area under the function). Values were significantly smaller in patients than in normal subjects (1.81 +/- 1.27 microV versus 5.73 +/- 3.27 microV; F = 41.24, p = 0.0001; 3.87 +/- 2.70 area units versus 12.57 +/- 7.60 area units; F = 38.62, p = 0.0001). There was no shift in the distribution of peak check sizes. Results suggest that a spatial tuning loss occurs in optic nerve disease. The shape of the function, including the area of spatial tuning, appears to be a sensitive indicator of early or mild optic nerve dysfunction.

Adolescent↗