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Biomedical subjects

H Shimura

Publications and source records attributed to H Shimura.

At least 109 records · Page 6Linked to original sources

Tactile pattern recognition by graphic display: importance of 3-D information for haptic perception of familiar objects.

Haptic recognition of familiar objects by the early blind, the late blind, and the sighted was investigated with two-dimensional (2-D) and three-dimensional (3-D) stimuli produced by small tactor-pins. The 2-D stimulus was an outline of an object that was depicted by raising tactor-pins to 1.5 mm. The 3-D stimulus was a relief that was produced by raising the tactors up to 10 mm, corresponding to the height of the object. Mean recognition times for correct answers to the 3-D stimuli were faster than those for the 2-D stimuli, in all three subject groups. No statistically significant differences in percentage of correct responses between the 2-D and the 3-D stimuli were found for the late-blind and sighted groups, but the early-blind group demonstrated a significant difference. In addition, the haptic legibility for the quality of depiction of the object, without regard to whether or not the stimulus was understood, was measured. The haptic legibility of the 3-D stimuli was significantly higher than that of the 2-D stimuli for all the groups. These results suggest that 3-D presentation seems to promise a way to overcome the limitations of 2-D graphic display.

Adult↗

[Effect of recombinant human granulocyte colony stimulating factor in patients with transitional cell carcinoma of the urothelium receiving methotrexate, etoposide and cisplatinum combination chemotherapy].

We determined the effective method of administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with transitional cell carcinoma of the urothelium receiving methotrexate, etoposide and cisplatinum (MEC) therapy. Recombinant human G-CSF was administered at 2 micrograms/kg subcutaneously starting after the white blood cell count was less than 3,000/mm3 (short administration) or starting immediately after finishing MEC therapy (prophylactic administration). The median white blood cell nadir for the control group, short administration group and prophylactic administration group, was 275 +/- 77, 250 +/- 317 and 2,066 +/- 47/mm3, respectively. The number of days with a white blood count of less than 1,000/mm3 for the control group, short administration group and prophylactic administration group was 6.6 +/- 0.6, 4 +/- 2 and 0.9 +/- 0.5 days, respectively. The difference between the control group and prophylactic administration group was statistically significant (p < 0.01). These findings indicated that the prophylactic administration of rhG-CSF following MEC therapy was effective for preventing leukopenia. Other side effects of stomatitis, diarrhea and pneumonia were also decreased using rhG-CSF after MEC therapy.

Adult↗

[Ureteral stump metastasis from renal cell carcinoma: a case report].

A case of ureteral metastasis from renal cell carcinoma is reported. A 71-year-old man who had received radical nephrectomy for left renal cell carcinoma, G1 and about two years earlier presented with asymptomatic macrohematuria. He had received interferon therapy and surgical treatments for bone metastasis two times after the operation. Cystoscopic examination revealed bleeding from the left residual ureter but CT scan showed no abnormal findings. Left ureterectomy and partial cystectomy was performed and a small finger tip-sized tumor was found at 13.5 cm above the ureteral orifice. Pathological examination showed metastatic renal cell carcinoma, G1 > G2. Histologically and clinically, this tumor seemed to have metastasized by a hematological pathway. Seventeen cases of ureteral metastasis of renal cell carcinoma have been reported previously in the Japanese literature.

Aged↗

[A case report of markedly effective recombinant interferon therapy in residual tumor of renal cell carcinoma].

A 53-year-old man complaining of pain in his right upper abdomen was diagnosed as suffering from right renal cell carcinoma with tumor thrombus. Right nephrectomy was performed but curative operation was not possible because of the adhesion of the tumor to psoas muscle. The residual tumor spread to the second lumbar vertebra and the patient complained of lumbago. The tumor continued to grow and the patient suffered from paraplegia even after the administration of natural interferon for 32 weeks. The administration of 9 x 10(6) units of recombinant interferon alfa 2a three times a week, however, resulted in an 86.5% reduction of the tumor after 13 weeks and the patient between able to walk. The PR continued for 17 months.

Carcinoma, Renal Cell↗

Characteristics of alveolar macrophages in experimental septic lung.

We investigated the pathogenesis of lung injury in sepsis (septic adult respiratory distress syndrome) by focusing on the functional changes of alveolar macrophages (AMs). Sepsis was induced in male WK rats by cecal ligation and puncture. Histological examination of the lungs from this experimental model revealed edematous change at 24 h after the surgery. The protein and endotoxin concentrations in the bronchoalveolar lavage fluid (BALF) increased with time after the surgery. The time course studies of AM function after surgery indicated that AMs from septic rats were activated by endotoxins. Specifically, this was suggested by the finding that AM adherence to and spreading on a plastic dish had increased. On stimulation, these AMs enhanced generation of superoxide anions and increased release of lysosomal enzymes, such as beta-glucuronidase. On the other hand, AMs in sepsis generated much smaller amounts of arachidonate lipoxygenase metabolites, such as leukotriene B4 (LTB4) and 12- and 5-hydroxyeicosatetraenoic acids (HETEs), on stimulation than did AMs from sham rats or untreated rats. However, the concentrations of immunoreactive LTC4 in the BALF of septic rats seemed to be higher than in untreated rats. It is suggested that the AMs of septic rats released lipoxygenase metabolites in alveoli and that these AMs could not be stimulated in vitro. These functional changes in the AMs of septic rats progressed along with the sepsis. These results implicate AMs in the development and progression of septic lung injury by releasing superoxide anions, beta-glucuronidase, and arachidonate metabolites. Furthermore, we speculate that reduced production of LTB4 by septic AMs may increase host susceptibility to severe pulmonary infection during septic ARDS.

Animals↗

Suppression by interferon-gamma of tumor cell-induced increase in mesothelial permeability.

The effect of interferon-gamma (IFN-gamma) on the interaction between tumor cells and mesothelial cell layers was studied from the aspect of changes in mesothelial permeability. Mesothelial permeability was assessed as the percentage diffusion of radiolabeled albumin across the mesothelial cell sheets on Matrigel-coated filter cup assemblies. When lined gastric carcinoma cells (KATO-III) were seeded on the confluent mesothelial cell layers, the fine cobblestone appearance of the cell sheet was disrupted and mesothelial permeability significantly increased. The increase in permeability was suppressed by the addition of as little as 1 U/ml of IFN-gamma. The effect of IFN-gamma was observed when either the conditioned medium of tumor cells alone or the IFN-gamma-resistant tumor cells, K-562, was placed onto the mesothelium. The cobblestone appearance of the cell sheet was relatively well preserved in the presence of IFN-gamma. In contrast, IFN-alpha did not suppress tumor-induced mesothelial permeability. These results suggest that IFN-gamma has the potential to protect the human mesothelial cell layers against tumor cells.

Cell Communication↗

A useful cholesterol solvent for medical dissolution of gallstones.

Dissolution of cholesterol gallstones by direct instillation of an agent into the biliary tract has been considered an alternate to surgical procedures. We developed an excellent direct solubilizer by combining d-limonene and medium-chain monoglyceride. This mixture enhances the advantages of each individual solvent and minimizes the disadvantages. In vitro experiments were done to determine the viscosities and the cholesterol dissolving rates of various combinations, and in vivo experiments were conducted to study their irritation effects on tissues. The optimal combination was a 3:2 mixture of d-limonene and medium-chain monoglyceride. It could quickly dissolve cholesterol gallstones with minimal or no observable side effect.

Animals↗

Role of the cyclic adenosine 3',5'-monophosphate response element in efficient expression of the rat thyrotropin receptor promoter.

The "minimal" promoter region of the TSH receptor gene, -195 to -39 basepairs (bp), exhibits basal promoter activity, thyroid specificity, and negative regulation by TSH via its cAMP signal. In FRT thyroid cells and by comparison to pTRCAT5'-199, 5'-deletion mutants of chloramphenicol acetyltransferase (CAT) constructs from -199 to -150 bp of the minimal promoter decrease basal CAT activity by 50%, whereas continued deletion to -146 bp increases activity more than 4-fold. Continued deletion to -131 bp results in basal activity less than that of the -199 bp construct. An octameric cAMP response element (CRE)-like sequence, TGAGGTCA, is within -146 to -131 bp and starts at -139 bp. Its mutation to a consensus CRE (TGACGTCA) or AP1 (TGAGTCA) site or mutation of several residues flanking its 3'-terminus can improve promoter activity as much as 8-fold compared to pTRCAT5'-199. A nonpalindromic mutation to CGAGGACA decreases basal promoter activity to the level of the 199-bp minimal promoter. The CRE-like sequence between -139 and -132 bp is a constitutive enhancer of promoter activity in FRT thyroid cells, since, ligated to a simian virus-40-promoter-driven CAT gene, it increases CAT activity in the absence of forskolin in proportion to copy number and independent of direction or position. It can, however, function as a cAMP-responsive CRE, as evidenced by the fact that forskolin increases the activity of the same simian virus-40-promoter-driven CAT gene constructs in Buffalo rat liver (BRL) cells. DNAase-I footprinting shows that the CRE region is protected by a purified binding region peptide of the CRE-binding protein, activating transcription factor-2, and recombinant AP1 (human c-jun) as well as by BRL, FRT, and FRTL-5 rat thyroid cell nuclear extracts. Gel mobility shift analyses show that multiple CRE-binding proteins in the BRL, FRT, and FRTL-5 cell nuclear extracts form complexes with the CRE-like site, that one of these is CRE-binding protein, and that all form complexes with mutant sequences of the CRE-like site in a manner that exactly parallels their effects on constitutive enhancer function in FRT thyroid cells. We show, therefore, that the CRE-like site in the minimal TSH receptor promoter functions as a constitutive enhancer of promoter activity in FRT thyroid cells yet is a cAMP-responsive CRE.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Characterization of the 5'-flanking region of the rat thyrotropin receptor gene.

Genomic clones containing 1.7 kilobases of the 5'-flanking region of the rat TSH receptor (TSHR) plus coding sequence from the ATG initiation codon [1 basepair (bp)] to the start of the first intron (170 bp) have been isolated and characterized. RNAase protection, primer extension, and cDNA sequences cloned by the anchored polymerase chain reaction identified multiple transcriptional start sites, the major ones clustered between -89 to -68 bp. This portion of the 5'-flanking region has neither a TATA nor a CCAAT box, is GC rich but has no GC box motif, and has features of promoters seen in "housekeeping" genes. Chimeras containing 1.7 kilobases (-1707 to -2 bp) of the 5'-flanking region, or deletions thereof, and the bacterial chloramphenicol acetyltransferase (CAT) gene expressed significant CAT activity when transfected into rat thyroid cell lines, FRTL-5 and FRT, but not BRL rat liver or HeLa cells. TSH decreased CAT activity in the FRTL-5 thyroid cells that had been stably transfected with the TSHR-CAT chimeric constructs. Negative regulation of promoter activity by TSH was duplicated by 10 microM forskolin in FRT thyroid cells, which express no TSHR mRNA. Deletion analyses indicated that a "minimal" region, exhibiting promoter activity, tissue specificity, and negative regulation by TSH, is located between -195 and -39 bp; this region is highly conserved in rat and human TSHR genes. Differential digestion of genomic DNA by MspI and HpaII revealed that the TSHR promoter is methylated in FRT, but not FRTL-5, cells; methylation of the promoter may be associated with loss of endogenous TSHR gene expression in FRT cells.

Amino Acid Sequence↗

Induction of DNA synthesis by fibroblast growth factor in temperature-sensitive cell-cycle mutants of rat 3Y1 fibroblasts arrested at restrictive temperature.

Four temperature-sensitive cell-cycle mutants of rat 3Y1 clonal fibroblasts representing separate complementation groups (3Y1tsD123, 3Y1tsF121, 3Y1tsG125 and 3Y1tsH203) are arrested at restrictive temperature, primarily with a G1-phase DNA content (temperature arrest). We examined various factors affecting signal transduction for activity which induces DNA synthesis at the restrictive temperature when added to the temperature-arrested cultures of these mutants. The factors examined were theophylline, dibutyryl cyclic AMP, cholera toxin (CT), dibutyryl cyclic GMP, sodium nitroprusside, phorbol 12-myristate 13-acetate, 1-oleoyl 2-acetylglycerol, bombesin, vasopressin, basic fibroblast growth factor (FGF), platelet-derived growth factor, A23187, monensin, epidermal growth factor (EGF), insulin and fetal calf serum (FCS). None of these factors induced DNA synthesis in 3Y1tsH203. In one mutant (3Y1ts121), FGF, EGF and FCS individually induced DNA synthesis. In the other 2 mutants (3Y1tsD123 and 3Y1tsG125), FGF and CT individually induced DNA synthesis. The FGF-induced DNA synthesis was suppressed by islet-activating protein (IAP) in 3Y1tsD123 and 3Y1tsG125, but not in 3Y1tsF121. The CT-induced DNA synthesis was also suppressed by IAP, as previously shown. When temperature-arrested cultures were shifted to a permissive temperature, all 4 mutants initiated DNA synthesis in the presence of IAP. These results suggest that (1) a cell can prepare for the initiation of DNA synthesis by using several independent signal transduction pathways, and (2) in a given situation, the cell uses a particular pathway because of its availability, which depends on the culture conditions.

Animals↗

Molecular basis for the autoreactivity against thyroid stimulating hormone receptor.

The present report identifies an important immunogenic region of the TSH receptor and determinants on the TSH receptor for the two types of autoantibodies seen in hyperthyroid Graves' disease and hypothyroid idiopathic myxedema, TSAbs and TSBAbs, respectively. The immunogenic domain with no important functional determinants, is contained within residues 303-382 and involves residues 352-366 in particular. There are determinants flanking the immunogenic domain on the C-terminal portion of the receptor which are the TSBAb and high affinity TSH binding sites: residues 295-306, 387-395, and tyrosine 385. Determinants on the N-terminal portion of the external domain, centered on residues 38-45, are TSAb interactions linked to low affinity TSH binding important for signal generation: threonine 40 and residues 30-33, 34-37, 42-45, 52-56, and 58-61. These determinants are conserved in human and rat receptors, are not present in gonadotropin receptors, and are each related to separate actions of TSH: binding vs. signal generation. They can, therefore, account for organ specific autoimmunity and the different disease expression effected by TSBAbs vs TSAbs, i.e. hypo- vs. hyperthyroidism, respectively. It is proposed that, in the thyroid, hormonal (TSH, insulin, hydrocortisone, IGF-I) suppression of class I genes might be one means of preserving self-tolerance in the face of the hormone action to increase the expression of tissue specific genes such as thyroglobulin and thyroid peroxidase. Inappropriately high class I expression in the thyroid, i.e. if induced by interferon, viruses, or some as yet unknown agent, would contribute to the generation of autoimmune disease. Thus, it would result in increased antigen presentation to the immune system, particularly those autoantigens increased by TSH and its cAMP signal such as thyroglobulin or thyroid peroxidase, or whose turnover is increased by TSH and its cAMP signal, such as the TSH receptor. In the case of the latter, peptide 352-366, known to be near a protease sensitive site on the receptor [41,49], would now act as a potent self-antigen and induce the formation of receptor autoantibodies. It is further proposed that methimazole and high doses of iodide are therapeutically effective agents in thyroid autoimmune disease because they, in part, decrease MHC class I gene expression. Speculation is presented which suggests that elimination of negative regulation of MHC class I and the TSH receptor is an important factor in the development of autoimmune thyroid disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

[A surgical case of coronary sinus ASD].

A case of coronary sinus ASD in a 56-years-old woman is reported. This defect was detected during operation for the first time. In this case, a LSVC was absent and coronary sinus opened into the left atrium. The defect was closed using a pericardial patch.

Coronary Vessel Anomalies↗

[A case of intimal dissection of the aorta during transfemoral angiography].

A 54-year-old man underwent right transfemoral angiography because of left renal hematuria. During angiography, dissection of abdominal aorta and thoracic aorta was encountered. It was initiated by intramural catheter passage at the bifurcation of the internal and external iliac artery. Transaxillary aortography about one month after the first angiography showed occlusion of the dissecting space in the thoracic aorta and existence of dissecting space in the abdominal aorta. Communicating orifices between the true space and the false space existed not only at the bifurcation of internal iliac artery and external iliac artery, but also at the abdominal aorta near the left renal artery. CT 1.5 months after the first angiography did not demonstrate more improvement. Surgery was performed. It was impossible to sew up and close the orifices of the space because of the fragility of the intima. Surrounding abdominal aorta and common iliac artery were wrapped near orifices with a dacron graft. A follow-up CT obtained 3 months postoperatively showed that the dissecting space in the abdominal aorta had disappeared. Wrapping was very useful to promote organization of the dissecting space.

Aortic Dissection↗

[Total aortic arch replacement through a median approach].

Seven patients underwent total aortic arch replacement only through a median approach since March 1990, in our institute. The woven Dacron graft with three side arm branches were used. After the proximal anastomosis at the ascending aorta, open distal anastomosis at the descending aorta was performed in five cases, under circulatory arrest of the lower body using separate perfusion to the brain. In two cases with true aneurysms involving the aortic arch, occlusion balloon catheters were employed for distal anastomosis. The anastomosis of the arch vessels was performed after coronary reperfusion. There was no early operative death, and our results demonstrate that total arch replacement can be safely accomplished through a median approach with an acceptably low operative risk.

Aged↗

[Clinical and pathological study of 152 cases of prostatic cancer].

A total of 152 prostatic cancer patients who underwent mainly hormone therapy was conducted. Our histological grading system combined with structure atypsim--SAT and nuclear anaplasia--NAN allowed for more accurate prognosis of prostatic cancer patients. The prognosis of G3 patients was obviously poor. The over-all 5-year survival rate for prostatic cancer patients with G1, G2 and G3 was 80%, 57% and 17%, respectively. The 5-year reactivation rate for patients with G1, G2 and G3 was 14%, 32% and 87%, respectively. The period for reactivation after initial hormone therapy for prostatic cancer patients with G1, G2 and G3 was 11.4, 10.0 and 3.2 years, respectively. Further improvements in survival for the patients with G3 prostatic cancer will require the development of effective systemic chemotherapy and the re-consideration of appropriate use of hormone therapy.

Aged↗

Medical dissolution of gallstones. Clinical experience of d-limonene as a simple, safe, and effective solvent.

Retained gallstones in the bile ducts account for 60-70% of all the cases of postcholecystectomy syndromes. A solvent d-limonene preparation was injected directly to the biliary system of 200 patients to dissolve or disintegrate the retained gallstones. The outcomes were: retained stones completely disappeared in 96 cases (48%); partial dissolution in 29 (14.5%); chelating agent was also used with partial dissolution in 16 (8%); ineffective in 59 (24.5%). To make this method more effective, several guidelines should be observed including an in vitro trial dissolution test. Cautious observation for possible side effects and frequent hepatic and pancreatic function tests during the treatment with this preparation also should be performed.

Bile Duct Diseases↗

Thyrotropin stimulates glucose-regulated protein (GRP78) gene expression in rat functional thyroid epithelial cells, FRTL.

We cloned a 1.2-kilobase cDNA (C17-16) from a transformed FRTL thyroid cell library. Northern blot analysis revealed that the size of the corresponding mRNA was 2.0 kilobases. C17-16 mRNA was found in all tissues investigated, but interestingly, its expression was 5- to 10-fold higher in the thyroid glands than in other tissues. Addition of TSH to FRTL cells showed a time- and dose-dependent increase in the steady state level of C17-16 mRNA, and the effect was mimicked by (Bu)2cAMP. An in vitro nuclear run-off assay demonstrated that the stimulatory effect was due to an increase in the transcription rate of the C17-16 gene. TSH had no effect on the half-life of the C17-16 mRNA. Transcriptional induction of the C17-16 gene was inhibited when the cells were treated with cycloheximide. Nucleotide sequencing revealed that C17-16 was identical to the cDNA of rat glucose-regulated protein (GRP78), a member of the heat shock protein family. These results suggest that the expression of GRP78 in thyroid cells is regulated by TSH via cAMP, for which cycloheximide-sensitive protein synthesis might be required, and that more GRP78 might be needed to assist in the synthesis and transport of glycoprotein molecules in TSH-stimulated cells.

Animals↗