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Biomedical subjects

Hiroshi Matsuo

Publications and source records attributed to Hiroshi Matsuo.

At least 19 recordsLinked to original sources

Frequency doubling technology perimetry in open-angle glaucoma eyes with hemifield visual field damage: comparison of high-tension and normal-tension groups.

PURPOSE: To evaluate the performance of frequency doubling technology (FDT) perimetry in open-angle glaucoma eyes with hemifield visual field damage and to compare it between open-angle glaucoma with high pressure [high-tension glaucoma (HTG)] and those with normal pressure [normal-tension glaucoma (NTG)] groups. METHODS: FDT perimetry with the N-30 full threshold protocol and standard automated perimetry (SAP) using the Humphrey Field Analyzer with the 30-2 full threshold protocol were performed in 20 eyes of 20 HTG patients and 36 eyes of 36 NTG patients with visual field damage confirmed with SAP in only one hemifield. RESULTS: There was no significant difference in demographics, the Heidelberg Retina Tomography indices, and the Humphrey Field Analyzer indices between HTG and NTG groups. Regarding the FDT perimetry results, mean deviation in the global field (P=0.009) and mean sensitivity in the SAP-spared (P=0.001) and SAP-impaired (P=0.011) hemifields were lower; the numbers of FDT abnormal test points (probability of abnormality <5%) in the SAP-spared hemifield were significantly greater (P=0.005) in HTG than in NTG groups. Eyes in which FDT results of the SAP-spared hemifield were judged as abnormal was more frequent in HTG groups (P=0.007). CONCLUSIONS: The performance of FDT perimetry to detect early or preperimetric glaucomatous functional changes should be different between HTG and NTG eyes.

Cross-Sectional Studies↗

Apoptosis inhibition by the human DEK oncoprotein involves interference with p53 functions.

The DEK proto-oncogene has been associated with human carcinogenesis-either as a fusion with the CAN nucleoporin protein or when transcriptionally upregulated. Mechanisms of intracellular DEK functions, however, have remained relatively unexplored. We have recently demonstrated that DEK expression is induced by the high-risk human papillomavirus (HPV) E7 protein in a manner which is dependent upon retinoblastoma protein function and have implicated DEK in the inhibition of cellular senescence. Additionally, overexpression of DEK resulted in significant life span extension of primary human keratinocytes. In order to determine whether DEK expression is required for cellular proliferation and/or survival, we monitored cellular responses to the knockdown of DEK in cancer and primary cells. The results indicate that DEK expression protects both HPV-positive cancer and primary human cells from apoptotic cell death. Cell death in response to DEK depletion was accompanied by increased protein stability and transcriptional activity of the p53 tumor suppressor and consequent upregulation of known p53 target genes such as p21CIP and Bax. Consistent with a possible role for p53 in DEK-mediated cell death inhibition, the p53-negative human osteosarcoma cell line SAOS-2 was resistant to the knockdown of DEK. Finally, expression of a dominant negative p53 miniprotein inhibited DEK RNA interference-induced p53 transcriptional induction, as well as cell death, thus directly implicating p53 activation in the observed apoptotic phenotype. These findings suggest a novel role for DEK in cellular survival, involving the destabilization of p53 in a manner which is likely to contribute to human carcinogenesis.

Apoptosis↗

Development of a multi-Fourier-transform interferometer: fundamentals.

We describe the development of an instrument that uses a Martin-Puplett-type Fourier-transform spectrometer to apply an aperture synthesis technique to millimeter and submillimeter waves. We call this instrument a multi-Fourier-transform interferometer (MuFT). The MuFT performs wideband imaging, spectroscopy, and polarimetry, at millimeter and submillimeter wavelengths. We describe the fundamentals of the MuFT and give an example of one potential implementation. A full description of the observables with a MuFT is provided. A physical explanation of the observability of complex visibility by the MuFT is given. Fundamental restrictions on observations with the MuFT, e.g., limits on spectral and spatial resolution and on fields of view, are discussed. The advantages of the MuFT are summarized.

Journal Article↗

Determinants of rapid progression of aortic root dilatation and complications in Marfan syndrome.

BACKGROUND: Progressive aortic dilatation has prognostic significance in the Marfan syndrome. METHODS: To identify which patients were at high risk of rapid progression, we echocardiographically studied 43 patients (age 22 +/- 14 years) with the mean follow-up period of 5.2 +/- 3.2 years. Aortic diameters, left ventricular (LV) size, fractional shortening, and the severity of aortic and mitral regurgitation were assessed. Transmitral peak early and atrial flow velocities, their ratio and the deceleration time of peak early velocity were also obtained. RESULTS: Mean annual increases of aortic diameters were 0.4 +/- 0.3 mm at the annulus, 1.5 +/- 1.3 mm at the sinuses of Valsalva, 0.7 +/- 0.6 mm at the supraaortic ridge and 0.4 +/- 0.4 mm at the proximal ascending aorta. Patients were divided into 2 groups according to the aortic growth rate at the sinuses of Valsalva level: rapid (R, >3% per year, 15 patients) or slow (S, < or =3% per year, 28 patients) progression groups. Measured variables did not show significant differences between the 2 groups except older age, higher blood pressure and more severe aortic regurgitation in group R. Multiple regression analysis identified prolonged deceleration time as the most important variable predicting aortic complications. Aortic dissection occurred more frequently in group R (7 patients, 47%) than in group S (0%, P < 0.001). CONCLUSIONS: Marfan patients at older age, with higher blood pressure, and with significant aortic regurgitation were at high risk of progression of aortic dilatation, with the most remarkable increase at the sinuses of Valsalva. Prolonged deceleration time may relate to an increased risk for aortic complications.

Adolescent↗

Dancin' deaminase.

New biochemical experiments with the retroelement restriction protein APOBEC3G indicate that it processively deaminates single-stranded DNA cytosines by a unique jumping and sliding mechanism.

APOBEC-3G Deaminase↗

[Adverse reaction after use of latanoprost in Japanese glaucoma patients].

PURPOSE: Although latanoprost has proven to have a strong hypotensive effect, some patients show adverse reactions such as eyelid pigmentation, iridial pigmentation, or hypertrichosis. We prospectively investigated these adverse reactions. SUBJECTS AND METHODS: One hundred and one Japanese glaucoma or ocular hypertension patients were included. Iridial, eyelid, and eyelash photographs were taken before and at 6 months after latanoprost treatment. Increased eyelid pigmentation, iridial pigmentation, eyelash pigmentation, vellus hair of the lid, and hypertrichosis were assessed from these photographs. The correlation between the incidence of these adverse reactions and the time of instillation, type of glaucoma, sex, age, or concomitantly used eye drops, and the overlap of these were evaluated. RESULTS: Increased pigmentation of the eyelid was found in 6 cases(5.9%), of the iris in 32 cases (31.7%), of the eyelashes in 29 cases (28.7%), vellus hair of the lid in 38 cases(37.6%), and hypertrichosis in 51 cases(50.5%). Pigmentation of the eyelid was more frequently observed in patients who used latanoprost concomitantly (16.7%) than in those who did not use anti-glaucomatous eye drops before latanoprost treatment (1.6%), or in those treated with latanoprost who had switched from other anti-glaucomatous eye drops (6.3%) (p= 0.03). CONCLUSIONS: The incidence of adverse reactions caused by latanoprost was higher in the eyelashes and iris than in the eyelid.

Adolescent↗

The SAF-box domain of chromatin protein DEK.

DEK is an abundant chromatin protein in metazoans reaching copy numbers of several millions/nucleus. Previous work has shown that human DEK, a protein of 375 amino acids, has two functional DNA-binding domains, of which one resides in a central part of the molecule and contains sequences corresponding to the scaffold attachment factor-box (SAF-box) domain as found in a growing number of nuclear proteins. Isolated SAF-box peptides (amino acids 137-187) bind weakly to DNA in solution, but when many SAF-box peptides are brought into close proximity on the surface of Sephadex beads, cooperative effects lead to a high affinity to DNA. Furthermore, a peptide (amino acids 87-187) that includes a sequence on the N-terminal side of the SAF-box binds efficiently to DNA. This peptide prefers four-way junction DNA over straight DNA and induces supercoils in relaxed circular DNA just like the full-length DEK. Interestingly, however, the 87-187 amino acid peptide introduces negative supercoils in contrast to the full-length DEK, which is known to introduce positive supercoils. We found that two adjacent regions (amino acids 68-87 and 187-250) are necessary for the formation of positive supercoils. Our data contribute to the ongoing characterization of the abundant and ubiquitous DEK chromatin protein.

Amino Acid Sequence↗

Penetration of topically applied fluorescein into eyes with avascular filtering bleb after trabeculectomy.

PURPOSE: To evaluate intraocular penetration of topical fluorescein in eyes with avascular blebs after trabeculectomy. DESIGN: Case control study. METHODS: The study included 11 eyes with open-angle glaucoma and functioning avascular blebs, six of which were treated with topical anti-glaucomatous medications and had no history of surgery, 15 with open-angle glaucoma, and untreated eyes suspected of having open-angle glaucoma. The fluorescein concentration in the superior peripheral and central corneal stroma and anterior chamber was determined 30 and 60 minutes after fluorescein instillation. RESULTS: The fluorescein concentration in the superior cornea was significantly higher in eyes with blebs or those topically treated than in untreated eyes (P <.01); there was no significant difference in the central cornea. The fluorescein concentration in the anterior chamber was much higher in eyes with blebs than in those that were untreated or topically treated (P <.001). CONCLUSION: The presence of avascular filtering blebs greatly enhances intraocular penetration of topically instilled fluorescein.

Administration, Topical↗

Expression and isotopic labeling of structural domains of the human protein DEK.

The 375 amino acid human protein DEK has been expressed in two functional, structured domains. DEK is an abundant nuclear protein that associates with chromatin and alters its topology by introducing positive supercoiling in DNA, which results in lower replication efficiency. DEK has clinical importance as transfection of the cDNA of the C-terminal region of DEK can partially reverse the abnormal DNA-mutagen sensitivity in fibroblasts derived from ataxia-telangiectasia (A-T) patients, and elevated levels of DEK mRNA are observed in various forms of cancer. Because high-level expression of full-length DEK has proved elusive, we sought an alternative for structural studies that would provide insights on DEK's function. We have discovered that DEK contains two structured domains and have expressed these domains at a high level in Escherichia coli in M9 minimal media. The N-terminal domain (amino acids 68-226) includes the region responsible for introducing supercoils into DNA, and the C-terminal domain (amino acids 309-375) includes the region that can reverse the abnormal DNA-mutagen sensitivity of A-T cells. 1H-15N correlation nuclear magnetic resonance spectra of these two fragments reveal the characteristic signature of folded proteins.

Chromosomal Proteins, Non-Histone↗

Changes in ventilatory responses to hypercapnia and hypoxia after intermittent hypoxia in humans.

The purpose of this study was to clarify the changes in hypercapnic and hypoxic ventilatory responses (HCVR and HVR) after intermittent hypoxia and following the cessation of hypoxic exposure. Twenty-nine males were assigned to one of four groups, i.e., a hypoxic (EX1-H, n=7) or a control (EX1-C, n=7) group in Experiment 1, and a hypoxic (EX2-H, n=8) or a control (EX2-C, n=7) group in Experiment 2. In each experiment, the hypoxic tent system was utilized for intermittent hypoxia, and the oxygen levels in the tent were maintained at 12.3+/-0.2%. In Experiment 1, the EX1-H group spent 3 h/day in the hypoxic tent for 1 week. HCVR and HVR were determined before and after 1 week of intermittent hypoxia, and again 1 and 2 week after the cessation of hypoxic exposure. In Experiment 2, the subjects in the EX2-H group performed 3 h/day for 2 weeks in intermittent hypoxia. HCVR and HVR tests were carried out before and after intermittent hypoxia, and were repeated again after 2 weeks of the cessation of hypoxic exposure. The slope of the HCVR in the EX1-H group did not show a significant increase after 1 week of intermittent hypoxia, while HCVR in the EX2-H group increased significantly after 2 weeks of intermittent hypoxia. The HCVR intercept was unchanged following 1 or 2 weeks of intermittent hypoxia. There was a significant increase in the slope of the HVR after 1 and 2 weeks of intermittent hypoxia. The increased HCVR and HVR returned to pre-hypoxic levels after 2 weeks of the cessation of hypoxia. These results suggest that 3 h/day for 2 weeks of intermittent hypoxia leads to an increase in central hypercapnic ventilatory chemosensitivity, which is not accompanied by a re-setting of the central chemoreceptors, and that the increased hypercapnic and hypoxic chemosensitivities are restored within 2 weeks after the cessation of hypoxia.

Adaptation, Physiological↗

Solution NMR structure of the C-terminal domain of the human protein DEK.

The chromatin-associated protein DEK was first identified as a fusion protein in patients with a subtype of acute myelogenous leukemia. It has since become associated with diverse human ailments ranging from cancers to autoimmune diseases. Despite much research effort, the biochemical basis for these clinical connections has yet to be explained. We have identified a structural domain in the C-terminal region of DEK [DEK(309-375)]. DEK(309-375) implies clinical importance because it can reverse the characteristic abnormal DNA-mutagen sensitivity in fibroblasts from ataxia-telangiectasia (A-T) patients. We determined the solution structure of DEK(309-375) by nuclear magnetic resonance spectroscopy, and found it to be structurally homologous to the E2F/DP transcription factor family. On the basis of this homology, we tested whether DEK(309-375) could bind DNA and identified the DNA-interacting surface. DEK presents a hydrophobic surface on the side opposite the DNA-interacting surface. The structure of the C-terminal region of DEK provides insights into the protein function of DEK.

Ataxia Telangiectasia↗

Ventilatory and circulatory responses at the onset of voluntary exercise and passive movement in sprinters.

The purpose of this study was to clarify the characteristics of ventilatory and circulatory responses at the onset of voluntary exercise and passive movement in sprinters. Eleven male university sprinters and 11 male untrained subjects participated in the present study. Voluntary exercise consisted of leg extension-flexion movement for 20 s with weights corresponding to 5% of each subject's body mass attached to each ankle. Passive movement was achieved without weights by the experimenter alternately pulling ropes that were connected to the subject's ankles for the same period and frequency as during voluntary exercise. In the present study, the following results were found: (1) the magnitude of relative changes (gain) of minute ventilation at the onset of passive movement in the sprinters was significantly smaller than that in the untrained subjects [mean (SEM) 33.3 (2.9) vs 61.7 (6.4)%, P<0.05]; (2) the time for reaching one-half of the gain (response time) of heart rate at the onset of voluntary exercise and passive movement in the sprinters was significantly slower than that in the untrained subjects [2.5 (0.2) vs 1.7 (0.2) s in voluntary exercise and 3.4 (0.8) vs 1.5 (0.1) s in passive movement, P<0.05]; (3) the gain and response time of mean blood pressure at the onset of voluntary exercise and passive movement showed no significant differences between the two groups. It is concluded that sprinters show slowed heart rate response at the onset of voluntary exercise, and attenuated ventilatory and slowed heart rate responses at the onset of passive movement as compared with untrained subjects.

Adaptation, Physiological↗

Effect of intermittent hypoxia on oxygen uptake during submaximal exercise in endurance athletes.

The purpose of the present study was to clarify the following: (1) whether steady state oxygen uptake (VO(2)) during exercise decreases after short-term intermittent hypoxia during a resting state in trained athletes and (2) whether the change in VO(2) during submaximal exercise is correlated to the change in endurance performance after intermittent hypoxia. Fifteen trained male endurance runners volunteered to participate in this study. Each subject was assigned to either a hypoxic group (n=8) or a control group (n=7). The hypoxic group spent 3 h per day for 14 consecutive days in normobaric hypoxia [12.3 (0.2)% inspired oxygen]. The maximal and submaximal exercise tests, a 3,000-m time trial, and resting hematology assessments at sea level were conducted before and after intermittent normobaric hypoxia. The athletes in both groups continued their normal training in normoxia throughout the experiment. VO(2) during submaximal exercise in the hypoxic group decreased significantly (P<0.05) following intermittent hypoxia. In the hypoxic group, the 3,000-m running time tended to improve (P=0.06) after intermittent hypoxia, but not in the control group. Neither peak VO(2) nor resting hematological parameters were changed in either group. There were significant (P<0.05) relationships between the change in the 3,000-m running time and the change in VO(2) during submaximal exercise after intermittent hypoxia. The results from the present study suggest that the enhanced running economy resulting from intermittent hypoxia could, in part, contribute to improved endurance performance in trained athletes.

Adaptation, Physiological↗

Expression of costimulatory molecules (4-1BBL and Fas) and major histocompatibility class I chain-related A (MICA) in aortic tissue with Takayasu's arteritis.

To further investigate the immunological mechanisms involved, we analyzed the expression of costimulatory molecules in aortic tissue and their counterpart molecules on infiltrating cells of patients with Takayasu's arteritis. We also examined the expression of major histocompatibility complex (MHC) class I chain-related (MIC) A in aortic tissue, which is known to be induced by external stress, and its counterpart NKG2D receptors on infiltrating cells. Among these costimulatory molecules, strong expression of 4-1BBL and Fas was induced in the aortic tissue, and most of the infiltrating cells expressed 4-1BB and FasL, suggesting these pathways play critical roles in T-cell-mediated vascular injury. We also found that MICA was strongly induced in the aortic tissue and that at least part of the infiltrating cells expressed NKG2D receptors. Some infiltrating cells - but not vascular smooth muscle cells - seemed to have undergone apoptosis. Our findings strongly suggest that 4-1BB/4-1BBL and Fas/FasL pathways play important roles in vascular injury in Takayasu's arteritis. We assume that gammadelta T cells infiltrated aortic tissue recognizing MICA, resulting in the induction of MHC antigens and costimulatory molecules, and then alphabeta T-cells infiltrated recognizing some auto-antigens presented by MHC antigens, leading to chronic inflammation.

4-1BB Ligand↗

Primary peritonitis associated with streptococcal toxic shock-like syndrome: report of a case.

Several reports over the past 15 years describe severe group A streptococcal infections causing septic shock, soft-tissue necrosis, and multiple organ failure; a phenomenon known as streptococcal toxic shock-like syndrome (TSLS). However, primary peritonitis associated with TSLS is rare. We report the case of a 40-year-old man admitted with pain in both thighs, hypotension, and severe abdominal pain. His daughter had been diagnosed with streptococcal pharyngitis 3 days earlier. We performed an emergency laparotomy for peritonitis, and culture of the ascites was positive for group A beta -hemolytic streptococcus (GAS). Further serotyping of the isolated GAS strain revealed the T-type 22 and the pyrogenic exotoxin gene, spe-C. The criteria for TSLS were clearly met, including the isolation of GAS from ascites, hypotension, liver failure, renal failure, coagulopathy, myositis, and a generalized erythematous macular rash with desquamation.

Acute Disease↗

Association of manganese effluent with the application of fertilizer and manure on tea field.

Manganese (Mn) concentrations in the tea field effluent were 1.1-3.5 mg/l over a 2 year period from June 1997 to May 1998 (first water year) and June 1998 to May 1999 (second water year). The annual Mn loads were 38,000 g/ha in the first water year and 19,000 g/ha in the second. The highest Mn loads were observed, respectively, in July 1997 (10,000 g/ha) in the first water year and in June 1998 (4100 g/ha) in the second. The water-soluble Mn content of soil of the tea field increased abruptly with decreasing soil pH in the pH region below 4.5. The large Mn load from the tea field during the rainy season is likely due to application of excess fertilizer and manure before the rainy season, which may lead to acidification of the soil.

Agriculture↗