[Proliferation and differentiation of fat cells].
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Biomedical subjects
Publications and source records attributed to H Sugihara.
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UNLABELLED: To analyze ploidy alterations during progression of colorectal tumors, we mapped the ploidy constitutions by cytofluorometry using (measurements of metaphase cells in) tissue sections as well as cell suspensions isolated from the tissue sections. Clonality of the tumor with heterogeneous ploidy constitution was checked by mutation pattern of K-ras codon 12. To assess the significance of polyploidy detected in the diploid tumor component, the present materials were confined to 23 tumors that contained diploid tumor cells. RESULTS: 1) Eight diploid tumors without polyploidy that invaded the submucosa or deeper were greater than 2 cm in diameter. 2) Aneuploidy was detected in tissue sections from 9 out of 15 tumors that had diploid component with polyploidy, and was occasionally predominant in the extramucosal invasive parts. 3) Near-diploid aneuploidy was detected in the cells isolated from diploid (+ polyploid) regions of 2 tumors with aneuploidy. 4) Three of the 6 tumors with heterogeneous ploidy constituents had ras mutation with the mutation patterns common to diploid and aneuploid parts. These findings suggest that aneuploid cells evolve preferentially from the diploid tumor cell population with polyploidy, which often include near-diploid aneuploidy.
We applied Fluorescence In Situ Hybridization to DNA-diploid head and neck squamous cell carcinomas to detect numerical chromosomal aberrations. Using centromeric repetitive probes of chromosomes 1, 7, 11, 17, X, and Y, we detected numerical aberrations of chromosomes in 4 of the 7 tumors examined, the main line of one tumor showed trisomy 1, while the other 3 tumors had subpopulations that showed trisomy or monosomy of 1 or 2 chromosomes examined. We found polyploidy by cytofluorometry in all 4 tumors with numerical chromosomal aberrations. These results suggest that from DNA-diploid tumors with polyploidy, subpopulation that are aneuploid at the chromosome level may arise before the ploidy of the main line shifts to over DNA-aneuploidy.
The purpose of this study was to reconstruct a urinary bladder mucosa in three-dimensional collagen gel culture conditions that included fibroblasts. Transitional epithelial cells and fibroblasts, isolated respectively from the epithelial and lamina propria layers of porcine urinary bladder, were cultured in monolayer. These fibroblasts were embedded and cultured within a collagen gel matrix to reconstruct a lamina propria. The isolated transitional epithelial cells were then seeded in vitro on this reconstructed lamina propria on which the transitional epithelial cells formed a stratified urothelium composed of basal, intermediate and superficial layers. Urothelial differentiation was observed only on the fibroblast-containing collagen matrix. Differentiation did not occur on a cell-free collagen matrix through use of fibroblast conditioned medium. Thus, urothelial differentiation depended upon a fibroblast-extracellular matrix interaction. The differentiated transitional epithelial cell layer thus produced closely resembled a urothelium in vivo. This culture model may provide a useful system in which to study various diseases of the urinary bladder.
Myocardial sympathetic nerve function can be evaluated by 123I-metaiodobenzylguanidine (MIBG) scintigraphy. Congestive heart failure is closely related to myocardial sympathetic nerve function. This study evaluated the severity of congestive heart failure in 30 patients with valvular heart disease [aortic regurgitation (AR): n = 20, mean age = 70 +/- 13 years; mitral regurgitation (MR): n = 10, mean age = 61 +/- 18 years], who had chronic heart failure by MIBG myocardial scintigraphy. Single photon emission computed tomography (SPECT) and anterior planar myocardial images were obtained 15 minutes (initial images) and 4 hours (delayed images) after injection of MIBG (111MBq). Defect score was determined by the delayed SPECT images visually as a semi-quantitative index. Myocardial MIBG uptake was quantified by the heart to upper mediastinum uptake ratio on the delayed anterior planar images (H/M) and mean cardiac MIBG washout rate during 4 hours was calculated from the bull's eye display data (clearance). These indices were compared with the NYHA class and echocardiographic findings of the patients. MIBG regional defect in the delayed image was most frequently seen in the inferoposterior wall, and defect score and clearance were significantly higher and the H/M ratio was significantly lower in NYHA class III patients than in class II patients. In patients with AR, clearance significantly correlated with left ventricular end-systolic dimension. In patients with MR, both the H/M ratio and clearance significantly correlated with left atrial dimension. Defect score, H/M, and clearance were closely related to the severity of AR and MR. These results indicate that MIBG scan can be used to assess the severity of valvular heart disease.
To improve the quality of 24 hours delayed images (24 DL) of stress thallium-201 myocardial SPECT, reinjection was performed at 24 hours later (24 RI), and the results were compared with those of 24 DL. A total of 45 patients were studied, including 18 patients in 24 DL, 27 patients in 24 RI. All of them showed persistent defect or incomplete redistribution on the routine stress and 3 hours delayed SPECT scans. In 24 RI, 37 MBq of thallium-201 was reinjected at 24 hours later. Myocardial count of 24 DL was about 1/4 of stress image, while 24 RI was about 1/2. Quality of 24 RI image was nearly equal to 3 hours delayed image. Of regions without redistribution at 3 hours delayed image, 5 (36%) regions showed new redistribution at 24 RI. Of regions incomplete redistribution, 6 (25%) regions showed further redistribution. Compared with 24 DL, the frequency of redistribution tended to be higher in this protocol than that of the 24 DL (11%, 17% respectively). In conclusion, the reinjection at 24 hours delayed imaging was considered to be useful to evaluate viability of myocardium in patient with CAD.
The aim of this study was to elucidate the characteristic feature of myocardial imaging with 123I-labeled 15-(p-iodophenyl)-3R,S-methylpentadecanoic acid (BMIPP) in the patients with hypertrophic cardiomyopathy (HCM). In 26 patients with asymmetric septal hypertrophy (ASH), the imaging data were acquired for 15 minutes after the injection of 123I-BMIPP by the emission computed tomography (ECT). ECT image was divided into 17 segments to score the severity of the defect in each segment using a 5-point grading system from score 3 to score -1; score 3 = severely decreased tracer uptake, score 2 = moderately decreased tracer uptake, score 1 = mildly decreased tracer uptake, score 0 = normal and score -1 = increased tracer uptake. Reduced uptake (Defect Score > or = 2) was frequently observed in septal portion of anterior wall (65%), septal portion of posterior wall (62%) and apical wall (73%). Defect score was higher in septal portion of anterior wall (p < 0.001), septal portion of posterior wall (p < 0.01) and apical wall (p < 0.01) than in the ventricular septum. This result indicates that in hearts with ASH, 123I-BMIPP image reveals severely impaired fatty acid metabolism in these regions. With the reference of the previous report about histologic features in necropsy hearts with HCM, myocardial fatty acid metabolic disorder shown by reduced 123I-BMIPP uptake is closely related to the histological abnormalities in hearts with HCM.
Myocardial perfusion and fatty acid metabolism may be unpaired in the patients of vasospastic angina (VSA), because abnormal regional wall motion of left ventricle has been shown in some cases of VSA without apparent history of myocardial infarction. To study the clinical utility of 123I-BMIPP scintigraphy in diagnosis of myocardial ischemia in VSA, both 123I-BMIPP (rest) and 201T1 (exercise) SPECT were performed in the 20 patients of VSA diagnosed by coronary angiography. Defect scores were calculated visually from the 17 segments of myocardial images and were compared with patient's anginal history, period from last attack, numbers of attack, left ventricular (LV) ejection fraction and severity of regional LV wall motion abnormality. 123I-BMIPP SPECT images showed decreased tracer uptake in 14 cases of 20 (70%) VSA patients. Exercise 201T1 SPECT images showed decreased tracer uptake in 3 cases of 20 (15%) of patients. Severity of regional LV wall motion abnormality was correlated with defect score of BMIPP. Though total defect score of BMIPP did not correlate with patient's anginal history, number of symptoms and LV ejection fraction, correlated inversely with period from last attack. It was suggested that 123I-BMIPP myocardial SPECT images in VSA patients showed "memories" of myocardial ischemic damages induced by vasospasm. In summary, 123I-BMIPP myocardial SPECT images could be a useful test for diagnosis and evaluation of VSA.
A case of hypertensive hypertrophy is described in which both regression of hypertrophy and improvement of the abnormalities in iodine-123-metaiodobenzylguanidine (MIBG) myocardial imagings were seen after 7 months of antihypertensive therapy. A 58-year-old man was diagnosed as having essential hypertension and hypertensive hypertrophy. The patient was treated with antihypertensive drugs and showed regression of left ventricular hypertrophy on electrocardiograms and echocardiograms. MIBG observations made before and after antihypertensive therapy showed increased heart-to-mediastinum activity ratio and decreased cardiac washout ratio. Despite the many theories addressing the mechanisms of regression of left ventricular hypertrophy, the process is still unclear. In the present case, the improvement of cardiac sympathetic nervous dysfunction might have been related to the regression of left ventricular hypertrophy because the abnormality in MIBG images improved. MIBG, therefore, may be helpful in clarifying the mechanisms of the regression of hypertensive hypertrophy.
A 55-year-old man with pheochromocytoma was examined by 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy before and after resection of the tumor. MIBG images showed decreased uptake in infero-posterior wall before operation. The heart to upper mediastinum uptake ratio was low at the delayed anterior planar image, and mean MIBG clearance from the left ventricle was increased. These abnormal scintigraphic findings improved after resection of the tumor. We thought that these abnormal MIBG findings were not due to abnormal cardiac sympathetic nerve function, because ECG, chest X-ray, UCG and 201Tl myocardial scintigram did not reveal any abnormality. It may be presumed that these abnormal MIBG findings were caused by high plasma catecholamines concentration. The mechanism of abnormal MIBG findings of the heart remains uncertain in various heart diseases. MIBG findings in this case with pheochromocytoma before and after resection may contribute to interpretation of the kinetics of MIBG in heart.
Myocardial viability was examined in 20 patients with myocardial infarction 24 +/- 3 (mean +/- standard deviation) days after onset. Postextrasystolic potentiation (PESP) was measured by left ventriculography and thallium-201 (Tl) single photon emission computed tomography (SPECT) redistribution was assessed after stress loading and reinjection of Tl. The results were compared with the improvement of left ventricular segmental wall motion after coronary revascularization which was performed successfully in all patients. The uptake of Tl was impaired initially in 41 segments, classified into three groups: normal group, 13 segments with smooth reversion to normal; new fill-in group, 15 segments with a new fill-in after reinjection of Tl; no fill-in group, 13 segments with no fill-in after reinjection. When evaluated by the PESP before coronary revascularization, segmental wall motion was significantly augmented in all segments in the normal group and new fill-in group (p < 0.001), but not in the no fill-in group. After coronary revascularization, left ventriculography revealed that segmental wall motion was significantly improved in normal group and new fill-in group, but not in the no fill-in group except for mild improvement in five segments. The sensitivity and specificity of PESP (90% and 93%) and Tl SPECT (80% and 100%) for improvement of segmental wall motion after the coronary revascularization were very high, with the accuracy of either method attaining 87%. This result indicates that both Tl SPECT and PESP are useful for detecting viable myocardium in patients with recent myocardial infarction.
A total of 110 patients suspected with CAD who had symptoms or ECG abnormalities were enrolled in the stress-rest ECG gated SPECT one day protocol using 99mTc-MIBI. All the patients underwent symptom-limited exercise testing and 250 MBq of MIBI was injected at peak exercise. Exercise perfusion SPECT images were reviewed by two trained doctors to classify into three groups; normal, equivocal and abnormal. Patients with normal stress image (n = 53) did not receive the resting study. On the other hand, those with equivocal (n = 20) and abnormal (n = 37) stress images performed resting study, including gated SPECT. Of 20 equivocal cases, 16 patients showed unchanged resting perfusion. All of these had normal wall motion. The remaining 4 patients showed improved resting perfusion, indicating presence of myocardial ischemia. Of 37 abnormal cases, 12 patients showed improved resting perfusion, whereas 25 patients showed unchanged resting perfusion. Cardiac events were more often observed in abnormal cases, especially those associated with myocardial ischemia, while good prognosis was obtained in normal cases. Values of this protocol are (1) Patients with normal stress images need no resting study. (2) All the procedure can be completed in one day. (3) Both cardiac function and perfusion can be obtained with gated SPECT. These data indicates that this protocol is valuable for screening patients suspected with CAD.
This study was carried out on patients with chronic cerebral vascular disease (CVD) to determine to what extent the intracranial vascular morphology and intracranial hemodynamics can be estimated from the common carotid artery blood flow (CF) and middle cerebral artery blood flow velocity (MV) determined by the ultrasound Doppler method. TCCAD (transcranial Doppler with computer aided design) was obtained based on MV information and its clinical implications were assessed. CF was 4.88 +/- 0.96 ml/sec for the patients with complete occlusion of the internal carotid artery or middle cerebral artery. MV ranged form 40 to 100 cm/sec and CF was 6.5 ml/sec or more for the majority of patients whose cerebral angiographic findings were unremarkable. In patients with complete occlusion of the internal carotid artery, however, MV was increased, while CF was decreased. It is clear from these results that the MV measurement was taken of blood flow increasing contralaterally to the direction of blood flow. Based on TCCAD, the vascular course of the middle cerebral artery M1 portion was classified into basilar, straight, and dorsal types in CVD patients. The frequency of the dorsal type was 0 and the proportion of the basilar type was significantly increased in patients under 50 years of age. These findings suggest that cerebral arteriosclersis progresses fast in CVD patients under 50.
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The effect of a newly developed growth hormone (GH)-releasing hexapeptide (KP-102) on GH secretion was studied in urethan-anesthetized adult male rats. Although KP-102 alone exerted a small influence on GH secretion, it produced a large plasma GH response in the presence of exogenous GH-releasing factor (GRF). During the continuous infusion of GRF, the somatotropes became refractory to a large bolus dose of GRF, but KP-102 induced a marked increase of plasma GH. The GH response to KP-102 alone or KP-102 with GRF was significantly augmented when antiserum to somatostatin (ASS) was previously administered. Although KP-102 and GRF acted synergistically on GH secretion in control animals, they acted additively in ASS-administered rats. The KP-102 effect on plasma GH was significantly attenuated in control animals and ASS-administered rats by prior i.v. injection of antiserum to GRF. Taken together, KP-102 stimulates GH secretion dependent on GRF and appears to act synergistically with GRF by antagonizing the SS effect.
Absent semilunar valve was found in three fetal cases with cystic hygroma. Two cases which simultaneously showed absent aortic and pulmonary valves (AAV and APV, respectively) had double-outlet right ventricle. The third case, which lacked only the aortic valve, had atrioventricular septal defect and anomalous origin of the right subclavian artery. Two of the three cases had a markedly hypoplastic thymus. Fifteen AAV and 179 APV cases, including the above-mentioned cases and others reported elsewhere, were discussed with special reference to the pathogenesis of absent semilunar valve. Of the 15 AAV cases, hypoplasia of the left heart was observed in 11 cases (73.3%), double-outlet right ventricle in 5 (33.3%), and aortic arch malformations in 6 (40.0%). In the 179 APV cases, there were 111 tetralogy of Fallot (62.0%) and 44 right-sided aortic arch (24.6%). DiGeorge anomaly was found in one AAV and eight APV cases. These results indicate a pathogenesis that is possibly related to hemodynamic abnormalities or abnormal neural crest cells. Further investigation will be needed to elucidate a more definite pathogenesis of absent semilunar valve.
The antemortem diagnosis of cardiac sarcoidosis is extremely difficult. We present a patient with congestive heart failure and cardiomyopathy of unknown cause who exhibited an abnormal accumulation of 201Tl in both hilar lymph nodes in addition to a perfusion defect of the left ventricular myocardium. The findings ultimately led to a diagnosis of myocardial sarcoidosis, which was treated successfully with prednisolone. Although such uptake in the hilar nodes has rarely been reported previously, and the mechanism is not known, this was a remarkable finding in diagnosing cardiac sarcoidosis in this case. When the abnormal hilar lymph nodes uptake of 201Tl is combined with the defect in the left ventricular myocardium, we should take cardiac sarcoidosis into consideration as the cause of secondary cardiomyopathy.