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Biomedical subjects

H Shimura

Publications and source records attributed to H Shimura.

At least 19 recordsLinked to original sources

FFT analysis of the X-ray tube voltage waveforms of high-frequency generators for radiographic systems.

PURPOSE: To present a novel method for analyzing the voltage waveform from high-frequency X-ray generators for radiographic systems. MATERIAL AND METHODS: The output signal of the actual voltage across the tube of a high-frequency generator was measured using the built-in voltage sense taps that are used for voltage regulation feedback in X-ray generators. The output signal was stored in an analyzing recorder, and the waveforms were analyzed using FFT analysis. The FFT analysis of high-frequency generators consisted of obtaining the power spectrum, comparing the major frequency components in the tube voltage waveforms, and examining the intensity of each frequency component. RESULTS: FFT analysis enables an objective comparison of the complex tube voltage waveforms in high-frequency X-ray generators. FFT analysis detected the change in the X-ray tube voltage waveform that occurred when there were problems with the high-frequency generator. CONCLUSION: High-frequency X-ray generators are becoming the universal choice for radiographic systems. The X-ray tube voltage and its waveform are important features of an X-ray generator, and quality assurance (QA) is important, too. As a tool for engineers involved in the design and development of X-ray generators, we can see that our methods (FFT analysis) might have some value as a means of describing generator performance under varying conditions. Furthermore, since the X-ray tube voltage waveform of a high-frequency generator is complex, FFT analysis may be useful for QA of the waveform.

Algorithms↗

High concentration of deoxycholic acid abrogates in vitro transformation of IEC6 intestinal cells by azoxymethane.

In this study, we designed an in vitro azoxymethane (AOM)-induced carcinogenesis model and analyzed the effect of deoxycholic acid (DCA) on growth, apoptosis, genotoxicity, and transformation of IEC6 intestinal cells. CYP2E1 production was confirmed in IEC6 cells. The growth of IEC6 cells was enhanced by DCA (100 microg/ml). However, IEC6 cells treated with DCA (200 microg/ml) were inhibited and disappeared at 48 hrs after treatment. Apoptotic cells increased 11.2 times by treatment with DCA (200 microg/ml) as compared to cells with no treatment. DNA injury detected by comet assay was found in cells treated with AOM, but not in cells treated with DCA (100 microg/ml) and AOM. The number of colony formation in soft agar increased by AOM treatment. However, the number of foci treated with DCA (100 microg/ml) plus AOM was 69% that of cells treated with AOM alone. Two out of the 6 mice subcutaneously injected with AOM-treated IEC6 cells showed tumorigenesis, whereas IEC6 cells treated with DCA (100 microg/ml) plus AOM or DCA (100 microg/ml) alone did not form any tumor. Reduced protein expression of MLH1, Bcl-2 was detected in IEC6 cells treated with DCA (100 microg/ml). Production of Bax, pJNK, TGF-beta, TGFBRI, TGFBRII, and beta-catenin were higher in IEC6 cells treated with DCA (100 microg/ml) than that in cells with no treatment. These results suggest that high-dose DCA induced apoptosis and inhibited AOM-induced in vitro transformation of IEC6 cells.

Animals↗

[Kinking of skeletonized internal thoracic artery graft].

A 66-year-old woman underwent coronary artery bypass grafting (CABG). Postoperative angiography on postoperative day (POD) 11 revealed that right internal thoracic artery (RITA) anastomosed to left anterior descending artery (LAD) had a kinking. The angiography performed 30 months after operation revealed no specific changes in the kinking of RITA and in the left ventricular function. Another case was a 74-year-old man with chronic renal failure under hemodialysis. He underwent CABG with left internal thoracic artery (LITA) to LAD. Post-operatively he had chest pain during hemodialysis. On POD 10, angiography revealed that LITA had a kinking with moderate stenosis and normal left ventricular function. The angiography performed 10 months after operation revealed no specific changes in the kinking of LITA. However, left ventriculography revealed akinesis in the antero-apical region. It suggested that the viability was lost due to the graft kinking of LITA and steal phenomenon on hemodialysis.

Aged↗

Protection of trocar sites from gallbladder cancer implantation by sodium hyaluronate carboxymethylcellulose-based bioresorbable membrane (Seprafilm) in a murine model [corrected].

BACKGROUND: The risk of port site metastasis in laparoscopic surgery for cancer patients is a problem that has yet to be resolved. We examined the protective effect of a sodium hyaluronate-based bioresorbable membrane (Seprafilm) on tumor cell implantation at laparoscopic trocar sites. METHODS: Four 2-mm trocar sites were created in nude mice, and the peritoneal wounds were covered with different-sized pieces of Seprafilm. The protective effect of Seprafilm on the implantation of GB-d1 (a human gallbladder cancer cell line) at the trocar sites was assessed after 7 days. In addition, the effects of sodium hyaluronate and Seprafilm on the growth and motility of GB-d1 were examined in vitro. RESULTS: Seprafilm significantly decreased the incidence of implantation compared with the control group. Histologically, Seprafilm was observed on days 1 and 3, as a sheet of gel that covered the injured peritoneum and muscle layer. In an invasion assay using Seprafilm, no cells were found to infiltrate through the gel sheet. CONCLUSION: Seprafilm protects peritoneal wounds by physically covering the injured peritoneum. Therefore, if Seprafilm were attached to the injured peritoneum after laparoscopic surgery for cancer patients, it might reduce port site metastasis.

Adenocarcinoma↗

[Is the quality of off-pump coronary artery bypass grafting equivalent to that of conventional coronary artery bypass grafting].

We analyzed 44 patients undergoing coronary artery bypass grafting (CABG) from November 2001 to March 2003. Of 44 patients, 40 patients (29 men and 11 women; mean age 68.1 +/- 9.2 years) underwent off-pump CABG (OPCAB) [90.9%]. The mean number of bypass grafts was 2.53 +/- 0.78. In-hospital mortality was none and major complications except for one case of reexploration for bleeding were not seen. The early patency rate of over-all grafts was 94.6%. The quality of OPCAB was considered to be equivalent to conventional CABG.

Aged↗

[Total arch replacement using prior selective cerebral perfusion].

Prior selective cerebral perfusion is the method whereby selective cerebral perfusion and systemic perfusion start almost simultaneously, and the arch vessels are clamped. Cerebral circulation is isolated from systemic circulation to avoid cerebral embolization owing to detachment of atherosclerotic material from the aorta, caused by the "sandblasting" effect of high-velocity jets of blood exiting the aortic canula. Twenty-seven consecutive patients underwent total arch replacement for degenerative aortic arch aneurysm using prior selective cerebral perfusion from 1992 to 2001. Surgical death (within 1 month after operation) was 2 cases (7.4%), in-hospital death was 5 cases (18.5%). Systemic circulatory arrest time is almost equal to the time which distal anastomosis takes. The time was 81.4 +/- 24.3 minutes. Selective cerebral perfusion time was 194.9 +/- 30.9 minutes. Extracorporeal circulation time was 280.6 +/- 55.3 minutes. The time for emergence from anesthesia was 6.0 +/- 2.7 hours. Permanent neurologic dysfunction which was thought to occurred within 48 hours after surgery was noted in 1 case (3.7%). Postoperative survival at 8 years was 73.3%. There was 1 arch aneurismal related accident. Prior selective cerebral perfusion may be useful for avoiding cerebral embolization.

Aged↗

Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive accumulation in selected neurons of protein inclusions containing alpha-synuclein and ubiquitin. Rare inherited forms of PD are caused by autosomal dominant mutations in alpha-synuclein or by autosomal recessive mutations in parkin, an E3 ubiquitin ligase. We hypothesized that these two gene products interact functionally, namely, that parkin ubiquitinates alpha-synuclein normally and that this process is altered in autosomal recessive PD. We have now identified a protein complex in normal human brain that includes parkin as the E3 ubiquitin ligase, UbcH7 as its associated E2 ubiquitin conjugating enzyme, and a new 22-kilodalton glycosylated form of alpha-synuclein (alphaSp22) as its substrate. In contrast to normal parkin, mutant parkin associated with autosomal recessive PD failed to bind alphaSp22. In an in vitro ubiquitination assay, alphaSp22 was modified by normal but not mutant parkin into polyubiquitinated, high molecular weight species. Accordingly, alphaSp22 accumulated in a non-ubiquitinated form in parkin-deficient PD brains. We conclude that alphaSp22 is a substrate for parkin's ubiquitin ligase activity in normal human brain and that loss of parkin function causes pathological alphaSp22 accumulation. These findings demonstrate a critical biochemical reaction between the two PD-linked gene products and suggest that this reaction underlies the accumulation of ubiquitinated alpha-synuclein in conventional PD.

Brain↗

Transcriptional activation of the thyroglobulin promoter directing suicide gene expression by thyroid transcription factor-1 in thyroid cancer cells.

Gene therapy with thyroglobulin (TG) promoter and a prodrug/suicide gene combination may prove useful as a treatment for thyroid carcinoma. However, most poorly differentiated and anaplastic thyroid carcinomas have lost the ability to express the TG gene expression accompanied by loss of transcription factors [thyroid transcription factor-1 (TTF-1), TTF-2, or Pax-8] interacting with the TG promoter. In anticipation of developing transcriptionally targeted gene therapy of TG-nonproducing thyroid carcinomas, we investigated the effect of TTF-1 gene transfer on TG promoter activity and the cytotoxic effect obtained by the TG promoter-driven HSV-TK gene along with ganciclovir in thyroid carcinoma and nonthyroidal cells. Using a chimeric construct containing the 5'-flanking region of the rat TG gene between -826 and +39 bp and the luciferase gene, TG promoter activity was detected in a normal rat thyroid cell line (FRTL-5), but not in a dedifferentiated line of thyroid cells (FRT) expressing Pax-8 but not TTF-1, TTF-2, or TG [TTF-1(-)/TTF-2(-)/Pax-8(+)/TG(-)], or in a human papillary thyroid carcinoma cell line [BHP15-3; TTF-1(-)/TTF-2(-)/Pax-8(-)/TG(-)], a human pulmonary cell line [H441; TTF-1(+)/TTF-2(-)/Pax-8(-)/TG(-)], or a dog kidney epithelial cell line [MDCK; TTF-1(-)/TTF-2(-)/Pax-8(+)/TG(-)]. Cotransfection of the TTF-1 expression vector stimulated TG promoter activity in FRT and BHP15-3 dedifferentiated thyroid cells, but not in H441 pulmonary cells. Only weak activation was observed in MDCK kidney cells. We then constructed recombinant adenovirus vectors, AdTTF-1 and ADTGTK: AdTTF-1 contained cytomegalovirus promoter and rat TTF-1 cDNA; AdTGTK carried the TG promoter-driven HSV-TK gene. Infection with AdTGTK and combined with GCV treatment induced a cytotoxic effect in FRTL-5 cells but not in dedifferentiated thyroid or nonthyroid cells. Cotransduction of AdTTF-1 and AdTGTK permitted 90% cytotoxicity for BHP15-3 and >95% cytotoxicity for FRT, as well as for BHP7-13 and BHP18-21v thyroid cancer cell lines [both/TTF1(-)/TTF-2(-)/Pax-8(+)/TG(-)]. In contrast, little cytotoxicity was seen for H441 and MDCK cell lines even with 300 microg/ml of ganciclovir. These results suggest that cotransduction of a TG promoter-controlled suicide gene and the TTF-1 gene by adenoviral vectors confers transcriptionally targeted gene-mediated cytotoxicity in poorly differentiated thyroid carcinoma cells unable to express the TG gene.

Adenoviridae↗

Parkin is linked to the ubiquitin pathway.

Autosomal recessive juvenile parkinsonism (AR-JP) is one of the most common forms of familial Parkinson's disease. AR-JP is characterized by selective and massive loss of dopaminergic neurons in the substantia nigra of the midbrain and absence of Lewy bodies, the pathological hallmark of idiopathic Parkinson's disease. Parkin, the causative gene of AR-JP, encodes a 52-kDa protein that is a RING-type ubiquitin (Ub) protein ligase (E3) collaborating with a Ub-conjugating enzyme (E2) belonging to a cognate class of UbcH7 or UbcH8. Analysis of parkin mutations in AP-JP patients reveals that the functional loss of parkin as an E3 enzyme is the molecular basis of AR-JP. Thus it is now clear that AR-JP is due to failure of proteolysis mediated by the Ub-proteasome system and accumulation of as yet unidentified protein(s) causes nigral neuronal death without formation of Lewy bodies. These findings should shed new light on the mechanisms underlying neurodegeneration in sporadic Parkinson's disease as well as AR-JP.

Animals↗

Surgical treatment for chronic pulmonary thromboembolism under cardiopulmonary bypass with selective cerebral perfusion.

The median sternotomy approach for the treatment of chronic pulmonary thromboembolism was recently improved by Daily, Jamieson, and coworkers who adopted it for use under cardiopulmonary bypass with intermittent circulatory arrest; however, we have sometimes found that the circulatory arrest time was too short to complete thromboendarterectomy. Therefore, we attempted to perform a selective cerebral perfusion technique to extend the endarterectomy time. Although we noted slight back-bleeding from the bronchial arteries, we were able to extend the endarterectomy time without causing any postoperative delirium. We conclude that the median sternotomy approach using cardiopulmonary bypass with selective cerebral perfusion may be the best option for extending the thromboendarterectomy time.

Aged↗

Is a proliferation index of cancer cells a reliable prognostic factor after hepatectomy in patients with colorectal liver metastases?

BACKGROUND: In spite of many reports focusing on prognostic factors after hepatectomy in patients with colorectal liver metastases, few studies have investigated pathological factors, eg, fibrous pseudocapsulation, growth pattern at the tumor margin, and proliferation activity of cancer cells, other than histological type and surgical margin. The aim of the present study was to investigate whether absence of pseudocapsulation, infiltrative growth pattern of metastases, and higher proliferation of cancer cells shown by Ki-67 immunohistochemical reactivity were associated with poorer survival after hepatectomy among patients with colorectal liver metastases. METHODS: Between 1988 and 1998, 221 patients underwent hepatic resection of colorectal metastases with curative intent in our institution. Pathology analyses were focused on pseudocapsulation of liver metastases, growth pattern at the tumor edge, and Ki-67 labelling index (Ki-67 LI) of cancer cell nuclei. Univariate analyses of survival and of disease-free survival were performed for several clinicopathological factors, and multivariate analyses of survival and disease-free survival were also performed. RESULTS: The univariate survival analyses showed that pseudocapsulation, growth pattern, and Ki-67 LI were significant prognostic factors, besides synchronous versus metachronous occurrence of metastases, carcinoembryonic antigen level before hepatectomy, and number of metastases. A multivariate analysis showed that Ki-67 labeling index was the most reliable prognostic factor of survival. In addition, Ki-67 LI and microscopic growth pattern were multivariately predictive factors of disease-free survival. CONCLUSIONS: This large single-institution study showed that investigation of cancer cell proliferation and pathologic characteristics of the tumor margin are major prognostic factors.

Analysis of Variance↗

Homogeneous epithelial gamma delta T cell repertoire of the skin is shaped through peripheral selection.

In contrast to the T cell receptor (TCR) diversity of major alpha beta T cells in lymphoid tissues, epithelial T cells of the murine skin, called dendritic epidermal T cells (DETC), express exclusively an invariant gamma delta TCR. Fetal thymic precursors of DETC immigrate to the skin before birth, and in adult mice T cells expressing the canonical gamma delta TCR identical to that of DETC are not found in other lymphoid or epithelial tissues. Here, we show that DETC precursors migrate to the gut as well as to the skin during fetal periods, but preferentially survive and expand in the skin after birth. We propose that similar to the thymic selection of the diverse alpha beta T cell repertoire, 'peripheral selection' of the homogeneous epithelial gamma delta T cell repertoire may be mediated by TCR signaling upon the recognition of the self-ligand, because the ligand for the DETC TCR was expressed only in the skin.

Animals↗

Parkin is associated with cellular vesicles.

We recently identified a novel gene, parkin, as a pathogenic gene for autosomal recessive juvenile parkinsonism. Parkin encodes a 52-kDa protein with a ubiquitin-like domain and two RING-finger motifs. To provide a insight into the function of parkin, we have examined its intracellular distribution in cultured cells. We found that parkin was localized in the trans-Golgi network and the secretory vesicles in U-373MG or SH-SY5Y cells by immunocytochemical analyses. In the subsequent subcellular fractionation studies of rat brain, we showed that parkin was copurified with the synaptic vesicles (SVs) when we used low ionic conditions throughout the procedure. An immunoelectromicroscopic analysis indicated that parkin was present on the SV membrane. Parkin was readily released from SVs into the soluble phase by increasing ionic strength at neutral pH, but not by a non-ionic detergent. To elucidate its responsible region for membrane association, we transfected with green fluorescent protein-tagged deletion mutants of parkin into COS-1 cells followed by subcellular fractionation. We demonstrated the ability of parkin to bind to the membranes through a broad region except for the ubiquitin-like domain. The significance of SV localization of parkin is discussed.

Animals↗

Familial Parkinson's disease. Alpha-synuclein and parkin.

We have reviewed recent progress in establishing the function of alpha-synuclein and parkin in relation to nigral degeneration in autosomal dominant and autosomal recessive PD. Mutations of alpha-synuclein (Ala53Thr and Ala30Pro) cause a form of autosomal dominant PD with early onset. Parkin is a novel protein expressed in the cytoplasm, including the terminal regions and Golgi apparatus. Mutations of parkin cause a form of autosomal recessive young-onset PD (ARJP). Both proteins appear to be associated with fast axonal transport. In addition, in sporadic PD, normal alpha-synuclein shows an increased tendency to self-aggregate. Thus, altered axonal transport of presynaptic proteins appears to play a crucial role in neurodegeneration in PD.

Humans↗

HGF/NK4, a four-kringle antagonist of hepatocyte growth factor, is an angiogenesis inhibitor that suppresses tumor growth and metastasis in mice.

We reported that NK4, composed of the N-terminal hairpin and subsequent four kringle domains of hepatocyte growth factor (HGF), acts as the competitive antagonist for HGF. We now provide the first evidence that NK4 inhibits tumor growth and metastasis as an angiogenesis inhibitor as well as an HGF antagonist. Administration of NK4 suppressed primary tumor growth and lung metastasis of Lewis lung carcinoma and Jyg-MC(A) mammary carcinoma s.c. implanted into mice, although neither HGF nor NK4 affected proliferation and survival of these tumor cells in vitro. NK4 treatment resulted in a remarkable decrease in microvessel density and an increase of apoptotic tumor cells in primary tumors, which suggests that the inhibition of primary tumor growth by NK4 may be achieved by suppression of tumor angiogenesis. In vivo, NK4 inhibited angiogenesis in chick chorioallantoic membranes and in rabbit corneal neovascularization induced by basic fibroblast growth factor (bFGF). In vitro, NK4 inhibited growth and migration of human microvascular endothelial cells induced by bFGF and vascular endothelial growth factor (VEGF) as well as by HGF. HGF and VEGF activated the Met/HGF receptor and the KDR/VEGF receptor, respectively, whereas NK4 inhibited HGF-induced Met tyrosine phosphorylation but not VEGF-induced KDR phosphorylation. NK4 inhibited HGF-induced ERK1/2 (p44/42 mitogen-activated protein kinase) activation, but allowed for bFGF- and VEGF-induced ERK1/2 activation. These results indicate that NK4 is an angiogenesis inhibitor as well as an HGF antagonist, and that the antiangiogenic action of NK4 is independent of its activity as HGF antagonist. The bifunctional properties of NK4 to act as an angiogenesis inhibitor and as an HGF antagonist raises the possibility that NK4 may prove therapeutic for cancer patients.

Allantois↗

Cervical vertigo after hair shampoo treatment at a hairdressing salon: a case report.

STUDY DESIGN: A case report of cervical vertigo that occurred after shampoo treatment in a hairdressing salon. Abnormalities were detected on magnetic resonance images and magnetic resonance angiography scans. OBJECTIVES: To describe the diagnosis of cervical vertigo caused by neck hyperextension. SUMMARY OF BACKGROUND DATA: Neck hyperextension may induce vertigo and dizziness; the pathophysiology remains unclear, however, because subjective findings are usually difficult to document. METHODS: The diagnosis, treatment, and outcome of a patient with cervical vertigo that occurred after hair shampoo treatment in a hair dressing salon were assessed. RESULTS: Magnetic resonance angiography demonstrated narrowing of the left vertebral artery, whereas magnetic resonance imaging showed cerebellar infarction. Treatment included rest and drugs that activate cerebral circulation and prevent platelet aggregation. Improvement was noted within few days. CONCLUSIONS: The authors suggest that the hyperextended neck position during hair shampoo treatment in a beauty parlor may be a risk factor for back lifting or cerebellum vascular insufficiency. Public education should lead to avoidance of this position during hair shampoo treatment at hair dressing salons.

Beauty↗