Biomedical subjects
Publications and source records attributed to M Ando.
alpha-Fe(2)O(3) single crystals containing 2.2% and 95% (57)Fe isotopes were characterized by means of X-ray topography, the diffraction rocking curve and the integrated intensity. These crystals were revealed to be nearly perfect and suitable for a further nuclear-resonant Bragg-scattering study.
A two-dimensional clinical intravenous coronary angiography system, comprising a large-size view area produced by asymmetrical reflection from a silicon crystal using intense synchrotron radiation from a multipole wiggler and a two-dimensional detector with an image intensifier, has been completed. An advantage of the imaging system is that two-dimensional dynamic imaging of the cardiovascular system can be achieved due to its two-dimensional radiation field. This world-first two-dimensional system has been successfully adapted to clinical applications. Details of the imaging system are described in this paper.
A Wolter-type grazing-incidence mirror was used as an objective for an imaging X-ray fluorescence microscope. The microscope was constructed at the beamline 6C2 of the Photon Factory. The shortest wavelength used was approximately 0. 1 nm, which was limited by the grazing-incidence angle of the mirror. To demonstrate the possibility of recording X-ray fluorescence images, several fine grids were used as test specimens. Characteristic X-rays emitted from each specimen could be clearly imaged. Spatial resolution was estimated to be better than 10 micro m.
In Japan, various medical applications of synchrotron X-ray imaging, such as angiography, monochromatic X-ray computed tomography (CT), radiography and radiation therapy, are being developed. In particular, coronary arteriography (CAG) is quite an important clinical application of synchrotron radiation. Using a two-dimensional imaging method, the first human intravenous CAG was carried out at KEK in May 1996; however, further improvements of image quality are required in clinical practice. On the other hand, two-dimensional aortographic CAG revealed canine coronary arteries as clearly as those on selective CAG, and coronary arteries less than 0.2 mm in diameter. Among applications of synchrotron radiation to X-ray CT, phase-contrast X-ray CT and fluorescent X-ray CT are expected to be very interesting future applications of synchrotron radiation. For actual clinical applications of synchrotron radiation, a medical beamline and a laboratory are now being constructed at SPring-8 in Harima.
The calibration of a compact precision goniometer equipped with a 22-bit absolute rotary encoder is presented. The goniometer is a modified Huber 410 goniometer: the diffraction angles can be coarsely generated by a stepping-motor-driven worm gear and precisely interpolated by a piezoactuator-driven tangent arm. The angular accuracy of the precision rotary stage was evaluated with an autocollimator. It was shown that the deviation from circularity of the rolling bearing utilized in the precision rotary stage restricts the angular positioning accuracy of the goniometer, and results in an angular accuracy ten times larger than the angular resolution of 0.01 arcsec. The 22-bit encoder was calibrated by an incremental rotary encoder. It became evident that the accuracy of the absolute encoder is approximately 18 bit due to systematic errors.
The presence of lipid peroxidation product in amyloid deposits from seven patients with Alzheimer disease and nine with non-Alzheimer disease was examined immunohistochemically by means of an affinity purified anti-HNE antibody to hydroxynonenal (HNE), a marker of lipid peroxidation. A positive reaction was found in amyloid deposits in all the specimens examined: most of the perivascular areas (89%) where amyloid deposition was confirmed by Congo red staining, showed immunoreactivity with the antibody in the specimens of Alzheimer disease. Twenty-one percent of senile plaques which were also stained by Congo red staining reacted with this antibody. Several perivascular cells were also stained by anti-HNE antibody. In other neurons both in Alzheimer and non-Alzheimer disease patients, only a few percent reacted with this antibody and no statistical difference was observed between them. These results verify that lipid peroxidation via free radical injury occurs in amyloid deposits in Alzheimer amyloid. Since HNE has been identified as a cytotoxic metabolite of free radical injury, amyloid deposits in the tissue may exhibit a toxic effect during the generation process of HNE.
The first clinical examination using a two-dimensional imaging system of coronary angiography with monochromated synchrotron radiation was carried out at the National Laboratory for High Energy Physics in May 1996. A rotating X-ray shutter was developed to produce a pulsed X-ray beam with 2-6 ms of beam spill to suppress image blurring, at a frequency of 30 Hz. A performance test of the X-ray shutter using synchrotron radiation was carried out, and it was verified that the shutter had satisfactory specifications for clinical applications. With this X-ray shutter the monitored radiation dose in clinical examinations was consistent with theoretical expectations and kept within a reasonable level of radiation protection.
We analyzed protein fractions extracted from the spinal cord of the motor neuron degeneration (Mnd) mouse, a mutant that exhibits progressive degeneration of lower spinal motor neurons, by one- and two-dimensional polyacrylamide gel electrophoresis (PAGE) after solubilization of the tissue with medium containing sodium dodecyl sulfate (SDS)-urea during growth of the animal, in comparison with those of age-matched controls (C57BL/6). Several protein spots were detected around a region of pI 5.6-6.0 and molecular mass of 35-50 kDa in Mnd spinal cord tissue on the two-dimensional PAGE separation profile with Coomassie brilliant blue staining, while only a few spots around the same region were found in the control spinal cord. These spots were all immunoreactive with an antibody against glial fibrillary acidic protein (GFAP), a cytoskeleton filamentous protein specific to astroglial cells. The protein spot with molecular mass of 50 kDa showed immunoreactivity with anti-GFAP antibody, had a blocked amino-terminus, and is assumed to be intact GFAP. Several protein spots with slightly smaller molecular masses of 35 to 48 kDa lacked the head domain of the GFAP molecule as a result of cleavage at the 29th and 56th residues from the amino terminus. In Mnd spinal cord tissue, the densities of the immunoreactive GFAP bands with smaller molecular masses increased with development, and became dominant at the time of the appearance of behavioral paralytic gait around 6 to 7 months of age. These results suggest that the increased GFAPs devoid of head domains are related to the degenerative loss of motor neurons in the Mnd spinal cord. Histopathological and GFAP immunohistochemical examination of Mnd spinal cord preparation demonstrated progressive degenerative loss of motor neurons, and considerable increases in number of GFAP-stained astrocytes in the ventral horn at 7 to 9 months of age. These processes of degenerative loss of motor neurons and proliferation of reactive astrocytes with increased levels of fragmented GFAP in the Mnd spinal cord during development seem to be characteristic and preceded the deterioration of motor activities in this animal model of amyotrophic lateral sclerosis.
BACKGROUND: CD44 is a cell surface glycoprotein implicated in such diverse biologic processes as lymphocyte activation and homing, extracellular matrix adhesion, and cellular migration. Primary transcripts of the CD44 gene can be alternatively spliced to produce a variety of messenger RNA (mRNA) species. The standard form of CD44 mRNA contains sequences from at least 20 genomic exons; variant mRNAs contain sequences from one or more additional exons (v1-10). Predominant expression of a specific CD44 variant, i.e., CD44v8-10, in several human carcinomas has been described previously. In this study, we developed a novel molecular approach for detecting cancer cells that overexpress CD44v8-10 mRNA. METHODS: After finding that CD44v8-10 was predominantly expressed in non-small-cell lung and bladder carcinomas and that CD44v10 was predominantly expressed in leukocytes, we developed a competitive reverse transcription-polymerase chain reaction assay (CC-RT-PCR) that allows quantification of the relative expression of these two mRNA species in clinical specimens (i.e., determination of a v8-10/v10 ratio). CC-RT-PCR analysis was applied to pleural effusion specimens from patients with benign or malignant lung diseases as well as to spontaneously voided urine samples from patients with benign or malignant urologic diseases. RESULTS: Fifty two of 54 samples from patients with benign diseases expressed CD44v10 predominantly (v8-10/v10 ratio < or = 0.65), whereas 46 of 61 samples from patients with malignant diseases expressed CD44v8-10 predominantly (v8-10/v10 ratio > 1.00) (two-sided P < .001). CC-RT-PCR detected predominant expression of CD44v8-10 in cytologically negative samples from 11 patients who were later diagnosed with malignant disease. CONCLUSIONS: CC-RT-PCR analysis of CD44v8-10 expression could be an important adjunct to cytologic examination in cancer diagnosis, especially in detecting exfoliated cancer cells in pleural effusions and urine.
The syntheses of (-)-7betaH-eudesmane-4alpha,11-diol (2) and (+)-ent-7betaH-eudesmane-4alpha,11-diol (ent-2) were carried out starting from (-)- and (+)-dihydrocarvones. As a result, the structure, including absolute configuration, of the naturally occurring eudesmane-4,11-diol isolated from Pluchea arguta was determined to be (+)-ent-7betaH-eudesmane-4alpha,11-diol (ent-2).
Although changes in the blood flow of the cerebral vessels and the peripheral vessels in the extremities after changing body postures have been well examined in patients with orthostatic hypotension (OH), such changes in visceral vessels have not been well investigated. To elucidate the effect of autonomic dysfunctions on changes in the abdominal blood flow, the blood flow velocity of the portal vein was measured by Doppler ultrasonography in 11 patients with familial amyloidotic polyneuropathy (FAP) (Met30), 3 with pandysautonomia, 1 with Shy-Drager syndrome, and 10 healthy controls, in the supine and at the upright position. Among the 15 patients with the above-mentioned autonomic disorders, 5 of the patients showed a marked decrease in blood flow after standing, and one of these 5 patients exhibited transient hepatic and intestinal ischemia during intensive rehabilitation because of a severe decrease in visceral blood flow. Another 7 patients exhibited moderate decreases in the blood flow after standing. In contrast, no such change was observed in the 10 healthy controls. The FAP patients with L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) administration showed no significant correlation between the degree of OH and the decrease in the blood flow of the portal vein, and the patients without the drug exhibited a weak correlation. On the contrary, the pandysautonomia and Shy-Drager syndrome patients exhibited a linear positive correlation. These results suggest that FAP is a disease for which this kind of ultrasonographic examination should be applied, and that Doppler ultrasonography may be a helpful tool to evaluate visceral OH.
The Smad3 gene is a member of the Smad family, vertebrate homologues of Drosophila Mad, and its gene product is a cytoplasmic element in the TGF-beta signaling pathway. Smad2 and Smad4/DPC4, other members of the Smad family, are possibly tumor suppressor genes because alterations of these genes occurred in various carcinomas. We determined the genomic structure of human Smad3 which consists of nine exons. Then we examined whether or not Smad3 gene mutations exist in sporadic and hereditary non-polyposis colorectal cancers and found no mutations in the entire coding region in 50 cancers. Loss of heterozygosity of Smad3 was observed in two of the 17 (11.8%) informative cases using a polymorphism found in intron 2. These findings suggest that the Smad3 gene may not play an important role in the tumorigenesis of colorectal cancers.
The inv mouse was reported as a novel strain with situs inversus Yokoyama et al., '93), and a few cases with heterotaxy were found in homozygotes. The original report by Yokoyama et al. described the location of the heart and the stomach using the index of arrangement of body structure. We newly examined 40 homozygous offspring for phenotypes of visceroatrial situs and the incidence of cardiovascular anomalies making use of morphological details defined in each organ structure. According to the arrangement of each organ, which ranged from the almost complete form of situs inversus to left isomerism, visceroatrial situs was classified into four categories: Situs inversus (4 cases), "variation type" of situs (17 cases), "abdominal heterotaxy" (15 cases), and visceroatrial heterotaxy (4 cases). In offspring with situs inversus, only one had aortic stenosis (25%). Seven with the "variation type" of situs had cardiovascular anomalies, such as aortic stenosis, endocardial cushion defect, and posterior vena cava interruption (41%). All 15 offspring with "abdominal heterotaxy" had anomalies of the posterior vena cava, and three of them also had tetralogy of Fallot. The remaining four with visceroatrial heterotaxy had endocardial cushion defect, which was associated with outflow tract anomaly in two cases (i.e. tetralogy of Fallot in one case and transportation of the great arteries in the other). These results revealed that visceroatrial heterotaxy frequently occurred in the inv homozygotes, especially in the abdomen, and often showed a propensity to left isomerism with posterior vena cava interruption.
Among aortic dissections, three-channeled aortic dissection, in which two parallel false lumens are present, is relatively rare. We surgically treated 26 patients with this type of dissection, they accounted for 7.4% of all 349 patients with aortic dissection surgically treated between 1978 and May 1997. Their ages ranged from 24 to 77 years (mean 45 years). The male/female ratio was 1:1. Marfan's syndrome was present in 15 patients and Bentall's-type operation had been performed in 12 patients. Pain at different times was observed in 19 patients. For preoperative diagnosis, computed tomography (CT) and magnetic resonance imaging (MRI) were useful. The morphology of the 1st and 2nd false lumens was Stanford type A + type B in 11 patients, type B + type B in 12, type A + type A in 2, and localized abdominal dissection in 1. Reentry of the second false lumen was observed in only 3 patients. Descending aortic replacement was performed in 13 patients, thoracoabdominal aortic replacement in 6, ascending aortic replacement in 3, and others in 4. Seven patients died in the hospital. There were 4 late deaths during follow-up for 10-158 months (mean, 58 months). When pain recurred in patients with aortic dissection, three-channeled dissection should be suspected. The incidence of this dissection is high in patients with Marfan's syndrome.
Human amyotrophic lateral sclerosis (ALS), a typical motor neuron disease, is characterized pathologically by selective degenerative loss of motoneurons in the CNS. We have demonstrated significant reductions of neurotransmitter-related factors, such as acetylcholine-(ACh)-synthesizing enzyme activity and glutamate and aspartate contents in the ALS, compared to the non-ALS spinal cord obtained at autopsy. We have also shown considerable reductions in activities of cytochrome-c oxidase (CO), an enzyme contributing to aerobic energy production, and transglutaminase (TG), a Ca(2+)-dependent marker enzyme for tissue degeneration, in the ALS spinal cord. We found marked increases in fragmented glial fibrillary acidic protein (GFAP), a filamentous protein specifically associated with reactive astrocytes, in the ALS spinal cord relative to non-ALS tissue. These biochemical results corresponded well to pathomor-phological neuronal degenerative loss and reactive proliferation of astroglial components in the ALS spinal cord tissue. However, these results only indicate the final pathological and biochemical outcomes of ALS, and it is difficult to follow up cause and process in the ALS spinal cord during progression of the disease. Therefore, we used an animal model closely resembling human ALS, motor neuron degeneration (Mnd) mutant mice, a subline of C57BL/6 that shows late-onset progressive degeneration of lower motor neurons with paralytic gait beginning around 6.5 mo of age, to follow the biochemical and pathological alterations during postnatal development. We detected significant decreases in CO activity during early development and in activity of superoxide dismutase (SOD), an antioxidant enzyme, in later stages in Mnd mutant spinal cord tissue. TG activity in the Mnd spinal cord showed gradual increases during early development reaching a maximum at 5 mo, and then tending to decrease thereafter. Amounts of fragmented GFAPs increased continuously during postnatal development in Mnd spinal cord. These biochemical changes were observed prior to the appearance of clinical motor dysfunctions in the Mnd mutant mice. Such biochemical analyses using appropriate animal models will be useful for inferring the origin and progression of human ALS.
We surgically treated a 35-year-old male with acute 3-channeled aortic dissection in Marfan syndrome. He had acute type A aortic dissection, and underwent Bentall's type operation, simultaneous graft replacement of the ascending aorta and total aortic arch. Pain recurred 5 years and 9 months after the first operation. CT scan showed two adjacent false lumens in the descending aorta. The morphology of the first and second dissections was Stanford type A + B. The second dissection was acute. In the second false lumen, a re-entry formation was observed in the abdominal aorta. Because severe pain was persistent, we immediately replaced the descending aorta using a femoro-femoral partial cardiopulmonary bypass. The patient was doing well and was discharged. When pain recurs in a Marfan patient with an aortic dissection, a 3-channeled aortic dissection should be suspected, and we recommend emergency surgery.
Congenital bicuspid aortic valve is a relatively rare malformation. It is reported that the presence of this anomaly predisposes the patient to the development of dissecting aortic aneurysms. Between 1981 and October 1997, 7 patients with aortic dissection associated with congenital bicuspid aortic valve underwent surgical treatment at our institution. The patients consisted of six males and one female. The age of the patients ranged from 54 to 74 years (mean 61 years). The classification of dissecting aortic aneurysms was DeBakey type I dissection in 4 patients, type II dissection in 2 patients and type IIIb dissection in 1 patient. These 7 patients constituted 2.0% (7/356) of all cases of surgical operation for dissecting thoracic aneurysm. Aortic valve dysfunction was noted in 5 patients, 4 of whom had previously undergone aortic valve replacement. We performed graft replacement of the ascending aorta in 4 patients, graft replacement of the ascending aorta and aortic arch in 2 patients, and graft replacement of the descending aorta in 1 patient. There were no hospital deaths in any of the 7 patients. Pathological examination of surgical specimens of the aortic wall showed cystic medial necrosis in 2 patients and mucoid degeneration in 4 patients. In addition to complication by valve dysfunction, patients with congenital bicuspid aortic valve are at risk for the development of aortic dissection.
Pulmonary thromboendarterectomy was performed on two patients with chronic pulmonary thromboembolism showing thrombotic tendency. Patient 1 was a 25-year-old male with the disease complicated by congenital antithrombin III deficiency. Patient 2 was a 21-year-old male with the disease complicated by antiphospholipid syndrome. Both patients were admitted to the center upon showing dyspnea. Lung perfusion scintigraphy revealed multiple defects in the right and left lungs. Pulmonary arteriography showed occlusion and stenosis from lobar to segmental arteries. Cardiac catheterization showed marked pulmonary hypertension. Pulmonary angioscopy confirmed the presence of organized thrombi while an intravascular ultrasound revealed a thickening of the pulmonary arterial walls in both lungs. After the insertion of an inferior vena cava filter in each patient, surgery was performed. Following a median sternotomy, a cardiopulmonary bypass was utilized to induce deep hypothermia at a pharyngeal temperature of 16 degrees C, after which a thromboendarterectomy of the bilateral pulmonary arteries was performed under intermittent circulatory arrest. A large amount of organized thrombi was extracted from these arteries. After surgery, both patients showed good postoperative outcome with improved blood flow in both lungs, reduced pulmonary arterial pressure and increased cardiac output.