Loud harsh holosystolic murmur in a middle-aged man.
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Biomedical subjects
Publications and source records attributed to T Matsuo.
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Ischemic cerebrovascular diseases are commonly induced by atherosclerosis and cardiogenic embolization but rarely they occur in association with Takayasu's arteritis and aortic lesion such as aortic dissection and aneurysm. Here we experienced two cases of acute aortic disease complicated by ischemic cerebrovascular disease (CVD). Patient 1 was a 77-year-old male. He complained of dyspnea and left hemiparesis. He was brought to our hospital by ambulance. Left hemiparesis and dyspnea improved soon. The patient only complained of left lower extremity pain and physical examination revealed hypotension. Brain CT showed no abnormality but chest CT revealed aortic dissection. The resection of the intimal tear and replacement of ascending aorta and aortic arch with 28 mm Hemashield graft were performed under hypothermia and selective cerebral perfusion. The postoperative course was uneventful and he has been doing well. Patient 2 was a 67-year-old female. She was found lying unconscious and brought to our hospital by ambulance. Physical examination revealed right hemiparesis and hypotension. Brain CT demonstrated low density area in the left corona radiata and ruptured aortic aneurysm was seen in abdominal CT. Just after the examination, the patient suddenly complained of severe back pain and died despite cardiopulmonary resuscitation. Aortic lesions can manifest ischemic symptom involving multiple organs following their vascular disorder. Aortic dissection rarely occurs in association with ischemic CVD and in that case it is likely to be seen by neurologists. Aortic dissection and aneurysm deteriorate so suddenly that immediate diagnosis and proper treatment are needed.
Bow hunter's stroke results from vertebrobasilar insufficiency caused by mechanical occlusion or stenosis of the vertebral artery at the C 1-2 level on head rotation. Commonly it is seen in elder people with cervical spondylosis. Here we reports a case of bow hunter's stroke in a 25-year-old male who complained of visual disturbance and syncope on rotation of the head 90 degrees or more to the left. This problem was frequently seen on driving a car. A cervical x-ray and MRI of the head revealed no abnormal findings such as atlantoaxial dislocation. Angiograms demonstrated obstruction of the right vertebral artery at the C 1-2 level on left rotation of the head. The hemodynamics on the circle of Willis were evaluated and surgical treatment was planned. The posterior fusion involving C 1-2 has long been used to limit atlantoaxial rotational movements. However, it has the serious disadvantage because the range of head motion is severely reduced. Recently decompression of the atlantoaxial portion of the affected vertebral artery has been used, but recurrence of occlusion with head rotation can be seen postoperatively. Since the patient could predict the onset of attack, we managed him conservatively, and no traffic accident reported during this period of observation. Due to several surgical disadvantages, we propose that whenever possible, patients with bow hunter's stroke should be managed conservatively especially in young patients.
Seventeen patients with newly diagnosed acquired severe aplastic anemia were treated with a combination of immunosuppressive drugs consisting of anti-lymphocyte or anti-thymocyte globulin, cyclosporin A (CyA), methylprednisolone, and recombinant human granulocyte colony-stimulating factor (G-CSF). Fourteen (82%) of the 17 patients achieved good response (GR), and 3 (18%) had no response. Among the 14 GR patients, 5 (36%) later evolved clonal diseases, 1 developed myelodysplastic syndrome, and 4 developed paroxysmal nocturnal hemoglobinuria. The numbers of granulocyte-macrophage colony-forming units (CFU-GM) and erythrocyte burst-forming units were markedly low or absent in all cases before therapy. After therapy, those numbers in 13 patients among 14 responders recovered to the level of the normal control at the time of GR. However, the CFU-GM number substantially declined after that but gradually recovered again to reach a normal level over longer clinical courses. The positive rate for HLA-DRB1*1501 was 60% (3/5) among 5 CyA-dependent patients, which tended to be higher than the 20% (1/5) among 5 CyA-independent patients. Thus, immunosuppressive therapy combined with G-CSF provides a high rate of good hematological response accompanied by the apparent recovery of the hematopoietic progenitor compartments.
Hepatic lipid hydroperoxides, which are produced when reactive oxygen intermediates react with polyunsaturated lipids, were measured in patients with chronic hepatitis C. Eight patients with chronic persistent hepatitis (chronic persistent hepatitis group), 16 patients with chronic active hepatitis (chronic active hepatitis group), and 11 patients with cirrhosis (cirrhotic group) were included in the study. Measurements from ten patients without liver disease were used as controls. The lipid hydroperoxide levels in the chronic persistent hepatitis, chronic active hepatitis, and cirrhotic groups were significantly higher than that in the controls (p < 0.05, p < 0.005, and p < 0.005, respectively). Among the patients with chronic hepatitis C, the lipid hydroperoxide levels in the chronic active hepatitis and cirrhotic groups were significantly higher than that in the chronic persistent hepatitis group (p < 0.05 in both groups). The activity and progression of liver disease, represented by the Histology Activity Index, were significantly correlated with the hepatic lipid hydroperoxide level (r = 0.654, p < 0.01). Our findings suggest that an increased hepatic lipid hydroperoxide level is closely related to the activity and progression of chronic hepatitis C.
Pancreatitis can develop as a complication of systemic lupus erythematosus (SLE). Steroids are considered one of the possible causes of this complication, but the pathological mechanism is unclear. We describe an autopsy case of a 29-year-old woman with cytomegalovirus (CMV) associated pancreatitis that developed during steroid therapy for her SLE. Many parenchymal cells with cytomegalic inclusions were seen in the patient's pancreas, especially in lesions showing active inflammation, and transcripts of CMV major immediate-early and late genes, markers of active viral replication, were detected. These findings suggest that CMV played an etiological role in the pancreatic disorder.
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The aim of this study was to investigate whether increased hepatic oxidative stress could be visualised in living animals before the onset of obvious liver injury. Acute hepatic injury was induced in mice by priming with heat-killed Corynebacterium parvum followed by injection of a low dose of lipopolysaccharide (LPS). Low frequency band electron spin resonance-computed tomography (ESR-CT) with 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) was used to visualize hepatic oxidative stress. Biochemical and histological investigations performed 3 h after injection of LPS revealed no obvious injury to the liver. Conversely, significant hepatic oxidative stress could be detected at this time. Nitroxides such as carbamoyl-PROXYL are rapidly reduced to the corresponding hydroxylamine in vivo. resulting in the disappearance of their ESR signals. The kinetic clearance of carbamoyl-PROXYL after intravenous administration was delayed significantly in mice that had received LPS, due to impairment of the reduction system by hepatic oxidative stress. ESR-CT of the murine abdomen revealed a high intensity area of carbamoyl-PROXYL which consisted mainly of the liver and enlarged spleen. Time-course observations with ESR-CT using carbamoyl-PROXYL showed that the high intensity area in the liver disappeared rapidly due to reduction of carbamoyl-PROXYL. Three hours after LPS injection into the same mouse, ESR-CT images were obtained again by intravenous injection of carbamoyl-PROXYL. The ESR-CT images of the mouse with hepatic oxidative stress clearly showed that the high intensity area of carbamoyl-PROXYL in the liver persisted for a long period of time. This study is the first report to describe the use of in vivo ESR-CT for visualizing the state of increased oxidative stress in the liver before the onset of obvious hepatic injury.
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In order to properly evaluate the results of the occupational biomonitoring of chemicals it is necessary to establish reference values for the biomarkers of exposure. The aim of this study was to determine the reference values for methanol in urine of the general population non-occupationally exposed to the xenobiotic under study. Thus, urinary methanol was measured in 84 occupationally non-exposed subjects from the city of São Paulo, Brazil, by means of headspace gas chromatography with a flame ionization detector. The results revealed a mean of 2.26 +/- 1.26 mg methanol/l urine and a geometric mean of 2.10 mg/l for the studied population. The reference values varied within the range of 0.50-4.78 mg/l (mean +/- 2 S.D.). Methanol levels in urine did not differ statistically between male and female subjects. Urinary methanol in the total population was less than 4.80 mg/l in 95% of cases.
PURPOSE: The authors have examined treatment effects of linear accelerator based radiosurgery for brain metastases. Optimal doses and indications were determined in an attempt to improve the quality of life for terminal cancer patients. METHODS AND MATERIALS: Ninety-two patients with 162 lesions were treated with Linac radiosurgery for brain metastases between April 1993 and September 1998. To determine prognostic factors, risk factors for recurrence, and appearance of new lesions, univariate and multivariate analyses were performed. To compare the local control between the high-dose (minimum dose > or =25 Gy: prescribed to the 50-80% isodose line) and low-dose (minimum dose <25 Gy) irradiated groups, matched-pairs analysis was performed. RESULTS: Median survival time was 11 months. In univariate analysis, extracranial tumor activity (p<0.001) and Karnofsky Performance Status (KPS) (p = 0.036) were two significant predictors of survival. In multivariate analysis, the status of an extracranial tumor was the single significant predictor of survival (p = 0.005). Minimum dose was the single most significant predictor of local recurrence in univariate, multivariate, and matched-pairs analyses (p<0.05). As to the appearance of new lesions, activity of extracranial tumors was a significant predictor (p<0.05). Side effects due to radiosurgery were experienced in 4 of 92 cases (4.3%). CONCLUSIONS: We concluded that brain metastases patients should be irradiated with > or =25 Gy, when extracranial lesions are stable and longer survival is expected. Combined surgery and conventional radiation may have little advantage over radiosurgery alone when metastatic brain tumors are small and extracranial tumors are well controlled. When extracranial tumors are progressive, the rate of appearance of new lesions in other nonirradiated locations becomes higher. In such cases, careful follow-up is required and a combination with whole brain irradiation should be considered.
Structural analysis of mutant hemoglobins has been efficiently accomplished by a consecutive mass spectrometric strategy: molecular mass measurement of the protein to detect mutation and to determine the molecular mass change, and fragmentation analysis with collision-induced dissociation to determine the site and type of mutation. A flaw of this method is an inherent inability to detect a mutation associated with no or little change of the molecular mass. In the present study, the strategy was improved by incorporating genetic analysis prior to mass spectrometry, which confirms the resulting amino acid change and searches for possible post-translational modifications. The method was applied to an unknown mutant, and elucidated a substitution of glutamine for glutamic acid at position 43 of beta-globin subunit, the mutation of Hb Hoshida.
To understand molecular mechanisms underlying the response to pressure in human trabecular cells of the eye, genes induced by cyclic mechanical stretching were isolated by subtractive hybridization assisted by polymerase chain reaction. A novel gene containing an Alu repetitive element in the 5' untranslated region was identified, and its expression was confirmed by Northern blot analysis to be stretch-specific in trabecular cells. The gene was also expressed in the retina, but not in the other tissues, including the brain. The gene encoded a putative small protein with 44 amino acids, which showed homology with neuromedin K. The putative novel protein was named as "oculomedin," and would be used as a candidate gene for glaucoma.
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Fcgamma receptors (FcgammaR) of guinea pig neutrophils were ligated and anti-Cbl immunoprecipitates prepared therefrom were assayed for the associated protein tyrosine kinase activity, which increased upon ligation of FcgammaR. The increases were overcome upon activation of cellular protein kinase C by simultaneous addition of phorbol 12-myristate 13-acetate (PMA) to the ligated cells. Syk proved to be the most important tyrosine kinase bound to Cbl that served as the major substrate; essentially no tyrosine phosphorylation occurred in the anti-Cbl immunoprecipitates prepared from the cell lysate that had been depleted of Syk by prior immunoprecipitation with anti-Syk antibodies. Exposure of the (32)P-labeled cells to PMA resulted in phosphorylation of cellular Cbl on serine residues. Thus, protein kinase C-induced serine phosphorylation of Cbl suppressed its tyrosine phosphorylation by Syk as a result of tyrosine kinase inhibition by unknown mechanisms, leading to inhibition of Cbl-mediated signaling such as phosphatidylinositol 3-kinase activation.
Rhabdomeres of the Drosophila melanogaster canoemisl mutant ommatidia were twisted, branched, and often fused to each other. A considerable proportion of rhabdomeres were found to have fallen below the retinal basement membrane. Electron-microscopic observations of the mutant ommatidia revealed that microvilli, the subcellular structures composing the rhabdome, were normal. As was the case with partial loss-of-function mutations in the canoe locus, overexpression of the wild-type canoe transgene driven by the heat shock promoter or sevenless enhancer in the wild-type canoe background caused malformation of the rhabdomeres in the adult ommatidia. Immunolabeling of the Canoe protein in the pupal retinae showed that it was accumulated in adherens junctions in photoreceptor rhabdomeres at high concentrations, as well as in pigment cells, bristle cells, and the interjunctional region of photoreceptors at a lower level. In the canoe mutant ommatidia, the Canoe protein concentration was dramatically decreased in adherens junctions, while it was maintained at a level comparable with the wild-type flies in the interjunctional region. Since Canoe or its mammalian homolog AF-6 is known to bind to F-actin and Ras, we suggest the possibility that Canoe couples Ras signaling with cytoskeleton, thereby supporting the straight elongation of rhabdomeres required for development of a regular array of ommatidia.
PURPOSE: To report the visual outcome of surgical treatment of submacular hemorrhage associated with idiopathic polypoidal choroidal vasculopathy. METHODS: Eight eyes of eight consecutive patients with thick submacular hemorrhages associated with idiopathic polypoidal choroidal vasculopathy were treated with pars plana vitrectomy and tissue plasminogen activator-assisted removal of subretinal blood (December 1995 to September 1997) or intravitreal 100% sulfur hexafluoride gas injection without tissue plasminogen activator (October 1997 to March 1998). RESULTS: Postoperatively, laser treatment was performed for active polypoidal lesions outside the foveal avascular zone in four eyes. A retinal pigment epithelial tear was seen outside the foveal avascular zone in three eyes, and one eye developed a retinal detachment. The best-corrected visual acuity improved (by 3 or more lines) or stabilized in seven of the eight eyes. Four eyes had a final best-corrected visual acuity of 20/40 or better, and three eyes had a final best-corrected visual acuity of 20/50 to 20/200. In one eye, the visual acuity decreased from 20/100 to 20/500 because of the development of a subfoveal neovascular membrane. The membrane was excised, and histologic examination showed fibrovascular tissue between the retina and retinal pigment epithelium (type 2 pattern). CONCLUSIONS: Surgical intervention may be of benefit in eyes with submacular hemorrhage associated with idiopathic polypoidal choroidal vasculopathy.