[Effect of clarithromycin on adhesion and infiltration of cancer cells].
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Biomedical subjects
Publications and source records attributed to A Azuma.
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Case 1 involved a 62-year-old woman with complete atrioventricular block and case 2 involved a 70-year-old woman with sick sinus syndrome. In both cases, echocardiography, 123I-15-(p-iodophenyl)-3-R,S-methyl pentadecanoic acid (BMIPP) and 99mTc-tetrofosmin myocardial single photon emission computed tomographic (SPECT) findings were normal. Coronary arteriography and left ventriculography also revealed normal in both cases. After pacemaker implantation (DDD-type in case 1 and VVI-type in case 2), both patient's electrocardiograms revealed left bundle branch block-type conduction disturbance, and echocardiography showed asynchronous hypokinesia in the septal region. One year later, although both patient's ATP loading tetrofosmin SPECT were normal, BMIPP SPECT showed reduced uptake and increased washout in the septal region. These findings suggest that these changes of BMIPP SPECT might be caused by left bundle branch block-type conduction disturbance after pacemaker implantation.
This study was designed to evaluate the clinical usefulness of delayed exercise images in 99mTc-tetrofosmin (TF) myocardial SPECT in the diagnosis of vasospastic angina pectoris. We studied 30 patients with vasospastic angina, 10 of 30 patients (group A) had both effort and rest angina, 20 of 30 patients (group B) had rest angina. A 370 MBq of TF was intravenously injected at peak exercise, and initial (EX-I) and delayed exercise (EX-D) images were obtained at 30 min and 180 min after the injection. An additional 740 MBq of TF was intravenously reinjected after EX-D image acquisition, and rest images were obtained 30 min after the reinjection. The left ventricular wall was divided into 9 segments. Regional myocardial uptakes of TF were scored by 4-point defect score (0 = normal, 1 = mildly reduced, 2 = moderately reduced, and 3 = severely reduced). Total defect score (TDS) was calculated from the sum of defect scores in 9 segments. Reverse redistribution (RR) was defined as increase of more than 2 in TDS on EX-D images. In group A, 4 of 10 cases (40%) showed decreased uptake on EX-I images, 6 of 10 cases (60%) revealed RR on EX-D images, and none of the patients showed decreased uptake on rest images. In group B, no one showed decreased uptake on EX-I and rest images, 11 of 20 cases (55%) revealed RR on EX-D images. The mean +/- SD of TDS were 2.9 +/- 3.4, 5.1 +/- 4.5, 0.5 +/- 0.5 on EX-I, EX-D, rest images in group A, and serially 0.4 +/- 0.5, 3.3 +/- 3.6, 0.4 +/- 0.5 in group B. Regional wall motion abnormality was reduced in regions with RR. RR on EX-D images may reflect ischemic damaged but viable myocardium in vasospastic angina. The clinical usefulness of exercise-rest TF imaging in detection of organic coronary artery disease has been well established. Therefore, exercise-rest TF imaging with additional delayed exercise image could evaluate not only organic coronary artery disease but also coronary artery vasospasm.
A 67-year-old man who had worked as an aluminum grinder had been given a diagnosis of pneumoconiosis. Ten years later, he was admitted with fever, dyspnea on exertion, and numbness. Chest roentgenograms showed linear-reticular shadows in both lower lung fields. ELISA-based tests were positive for perinuclear anti-neutrophil cytoplasmic antibody (P-ANCA). Renal biopsy specimens disclosed crescentic glomerulonephritis and angiitis of small arteries. Our diagnosis was microscopic polyangiitis accompanying interstitial pneumonia with aluminum lung. The results of high-energy dispersion X-ray microanalysis indicated that the patient's lungs contained aluminum. His general condition improved with the administration of corticosteroid and immunosuppressive agents, and his chief symptoms disappeared.
This study was designed to evaluate the clinical usefulness of 123I-BMIPP myocardial SPECT for detecting cardiac involvement in patients with collagen disease. We studied 12 patients with systemic lupus erythematosus (SLE), 8 with progressive systemic sclerosis (PSS), 6 with polymyositis/dermatomyositis (PM/DM) and 3 with allergic granulomatosis and angiitis (AGA). A 111 MBq of 123I-BMIPP was intravenously injected at rest, and SPECT images were obtained at 15 min after the injection. Seven of 12 SLE, 6 of 8 PSS, 3 of 6 PM/DM and all 3 AGA patients showed an abnormal tracer uptake. The left ventricular ejection fraction was inversely correlated with a BMIPP abnormality. The regional wall motion abnormality was reduced in regions with reduced tracer uptake. These findings suggest that 123I-BMIPP imaging could be useful for assessment of cardiac involvement in patients with collagen disease.
A 64-year-old woman with dilated hypertrophic cardiomyopathy was treated by beta-blocker, because of recurrent episodes of congestive heart failure. Carvedilol administration was started with a dose of 2.5 mg/day, and gradually increased to the dose of 20 mg/day 3 months later. Her functional class recovered from New York Heart Association stage IV to stage II. Thallium-201 scintigraphy demonstrated advanced myocardial damage: defect/low perfusion in the anteroseptal, infero-posterior and apical regions. Iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid scintigraphy confirmed these findings. However, the scintigraphic abnormalities had reversed to near normal perfusion and metabolism similar to those of stunned myocardium after an ischemic episode. This case demonstrates the recovery of myocardial impairment during beta-blocker therapy in a patient with dilated hypertrophic cardiomyopathy.
BACKGROUND AND AIM OF THE WORK: The causes of sarcoidosis are unknown. Propionibacterium acnes has been isolated from sarcoid lesions, and many genomes of P. acnes or P. granulosum have been detected in all biopsy samples tested from Japanese patients with sarcoidosis. We searched for protein antigens from propionibacteria that caused immune responses in patients with sarcoidosis but not in subjects without sarcoidosis. METHODS: A lambda gt11 genomic DNA expression library of P. acnes was screened with sera from patients with sarcoidosis. Antibodies to a recombinant protein from the insert recovered by the screening were measured in serum and bronchoalveolar lavage (BAL) fluid from patients with or without sarcoidosis by an immunofluorescence-based method. Peripheral blood mononuclear cells from patients with and without sarcoidosis were used to examine the lymphoproliferative response to the protein. RESULTS: Of 180,000 plaques screened, two clones coded for an identical recombinant protein, termed RP35, were recognized by sera. RP35 was the C-terminal region of P. acnes trigger factor. RP35 caused sarcoidosis specific proliferation of the mononuclear cells from 9 (18%) of the 50 patients with sarcoidosis; in a similar way, purified protein derived from Mycobacterium tuberculosis evoked specific responses in 8 (38%) of 21 patients with tuberculosis. Serum levels of IgG and IgA antibodies to RP35 were high in patients with sarcoidosis and other lung diseases. In BAL fluid levels IgG or IgA antibodies were high in 7 (18%) and 15 (39%), respectively, of 38 patients with sarcoidosis, and in 2 (3%) and 2 (3%), respectively, of 63 patients with other lung diseases. CONCLUSIONS: The RP35 protein from P. acnes causes a cellular immune response in some patients with sarcoidosis but not in subjects without sarcoidosis.
A 74-year-old woman suffering from dyspnea on effort and chest pain (New York Heart Association functional class III) was admitted to our hospital. Echocardiography and left ventriculography showed severe hypertrophy of the left ventricular wall and a severe intraventricular pressure gradient of about 150 mmHg. The diagnosis was hypertrophic obstructive cardiomyopathy. The intraventricular pressure gradient was decreased from 157 to 68 mmHg by percutaneous transluminal septal myocardial ablation (PTSMA), but this reduction was not adequate. Thereafter, dual-chamber pacing was additionally performed. The intraventricular pressure gradient was decreased to 26 mmHg with no complication. PTSMA is a certain way to decrease pressure gradient, but has some complications. Permanent dual-chamber pacing also can show the same effect, but is inferior to PTSMA. Combination of these 2 methods succeeded in abolishing the intraventricular pressure gradient with no complication.
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CD36 is homologous with myocardial long-chain fatty acid (LCFA) binding protein and has been suggested to relate to myocardial fatty acid metabolism. Myocardial scintigraphy with iodine-123 15-(p-iodophenyl)-3-(R, S)-methylpentadecanoic acid (BMIPP) revealed an impairment in LCFA metabolism chiefly in the hypertrophic myocardium in hypertrophic cardiomyopathy (HCM). Recently, the incidence of CD36 deficiency has been reported to be high in HCM patients, and CD36 deficiency was proposed as an etiology of hereditary HCM. However, the pathophysiological effect of CD36 deficiency on HCM has not been fully investigated. We analysed the expression of CD36 antigens on both platelets and monocytes obtained from 82 patients with HCM using two-color flow cytometry. Among the study patients, seven patients (8.5%) demonstrated type II CD36 deficiency, whereas type I CD36 deficiency was not detected. Two of 23 patients (8.7%) with a family history of HCM and five of 59 patients (8.5%) without a family history of HCM showed type II CD36 deficiency respectively. Contrary to the previous report, three of 53 patients with asymmetric septal hypertrophy (ASH) (5.7%) and four of 29 patients without ASH (13.8%) showed CD36 deficiency. Moreover, clinical characteristics, scintigraphic findings, echocardiographic data, and hemodynamic findings disclosed no significant differences between the HCM patients showing normal CD36 expression and those with CD36 deficiency. The incidence of CD36 deficiency in HCM patients is not higher than in the general population. Therefore, CD36 deficiency is not a characteristic factor of HCM and has little influence on the pathyphysiology of HCM.
We examined reverse redistribution (RR) of Tc-99m-tetrofosmin after a single injection in patients with acute myocardial infarction (AMI). Tc-99m-tetrofosmin myocardial SPECT was performed in 28 patients with AMI 10-14 days after the onset. Myocardial images were obtained 30 min and 180 min after the injection of 740 MBq of Tc-99m-tetrofosmin. The left ventricular wall was divided into 9 segments. Regional myocardial uptakes of Tc-99m-tetrofosmin were scored by 4-point scoring (0 = normal, 1 = mildly reduced, 2 = moderately reduced, and 3 = defect). RR was defined as an increase of more than 1 in the regional score in images at 180 min. RR of Tc-99m-tetrofosmin was observed in 17 of 20 patients with direct PTCA and 3 of 8 patients without reperfused therapy. RR was observed in 61 of all 252 segments. Coronary angiography performed 1 month later revealed that the infarct-related artery was patent in 19 of 20 patients (95%) with RR and in 3 of 8 patients (37.5%) with persistent defects (PD) (p < 0.05). In segment-by-segment analysis, the incidence of regional wall motion abnormality I month later was reduced in regions with RR compared to those with PD (p < 0.0001). In conclusion, RR of Tc-99m-tetrofosmin was frequently observed in patients with successful direct PTCA. As the segments with RR showed signs of preserved function 1 month later, this phenomenon may reflect a salvaged myocardium in AMI.
Diffuse panbronchiolitis (DPB) is a distinctive chronic inflammatory lung disease predominantly found in Asian populations. Although its etiology is unknown, DPB is considered to be a multifactorial disease of whose susceptibility is determined by genetic predisposition unique to Asians. We and others have previously reported that the B*5401 allele of the human leukocyte antigen (HLA)-B gene or a closely linked gene in the HLA region on 6p21.3 is one of the major genetic factors in susceptibility to this disease. However, the association with B*5401 is not absolute and the contribution of other genetic or environmental factors should also be considered. Here, four candidate genes that are postulated to play a role in the pathophysiology of DPB, namely, RON-kinase, CYP3A4, motilin, and interleukin (IL)-8, were chosen, and association studies between microsatellite markers at these loci and DPB were conducted. We demonstrated the presence of a specific allele at the IL-8 locus was associated with the disease (c2 = 9.13; P = 0.0025; corrected P [Pc] < 0.05). Although further studies are needed to examine whether neutrophil accumulation in the airways of patients with DPB is controlled by a possible genetic variation of IL-8 or other chemokine genes located in the region 4q12-q13, our data suggest that genes other than those of the HLA system may also contribute to a genetic predisposition to DPB.
BACKGROUND: The septal perforators in hypertrophic cardiomyopathy (HCM) show systolic compression. The compression is thought to be related to the malpositioned septal perforators, but its relation to the development of myocardial ischemia remains controversial. METHODS: We examined echocardiographically the blood flow and course of the major septal perforator in 142 consecutive patients with HCM; of these, 94 underwent coronary angiography to assess systolic compression of the septal perforators and 110 had thallium-201 scintigraphy. We then analyzed the relation of the findings in comparison with the results in 15 patients with valvular aortic stenosis (AS). RESULTS: The major septal perforator was visualized in 82 patients with HCM and in 8 patients with AS. The visualization did not depend on the pressure gradient between the left ventricle and aorta in the HCM patients, but did in the AS patients. In AS the perforator always showed a normal course near to, and convexly toward, the right ventricle. In 71 of the 82 HCM patients, the perforator was distant from the right-sided endocardium of the ventricular septum and often convex toward the left. The greater the leftward deviation, the higher was the grade of compression. In 48 of the 82 patients with HCM and in all of the 8 patients with AS who showed the flow signal, the septal perforator showed systolic retrograde flow; in the patients with HCM there was a significant correlation (r = 0.54, P <.05) between the peak velocity and the degree of leftward deviation. Furthermore, higher degrees of the leftward deviation and higher degrees of the systolic compression of the major perforator were each associated with a higher incidence of exercise-induced defect of thallium-201. CONCLUSION: The echocardiographic, angiographic, and scintigraphic findings in HCM may be closely related to one another. We speculate that the series of abnormalities is initiated by a high intramural pressure and impedance on the septal perforators due to their deviation toward the left.
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Diffuse panbronchiolitis is a chronic obstructive pulmonary disease found in Asian populations. Although diffuse panbronchiolitis is considered to be a multifactorial disease of unknown etiology, the disease susceptibility appears to be determined by a genetic predisposition unique to Asians. An earlier study showed that human leukocyte antigen (HLA)-B54 predominantly found in East Asians was strongly associated with the disease. A possible interpretation of this association is that the class I molecule or class I antigen presenting system is directly involved in its pathogenesis. Recent observations in which impaired expression of class I molecules causes a syndrome resembling diffuse panbronchiolitis further prompted us to test this possibility. Genes of the molecules implicated in the class I pathway, TAP1, TAP2 and LMP2, which are located in the HLA region of the sixth chromosome were analyzed in 76 patients with diffuse panbronchiolitis and 120 normal controls. The combination of Ala-665 and Gln-687 in exon 11 of the TAP2 gene was associated with the disease (P=0.0028, Pc<0.05). Although this positive association might be partly explained by linkage disequilibrium with HLA-B*5401, this TAP2 variation was associated with the disease even in the B*5401-negative subgroup. On the other hand, the His-60 substitution within the LMP2 gene exhibited a negative association with the disease. This negative association, however, could be explained by a strong linkage disequilibrium with HLA-B44 which showed a negative association with the disease in the previous study. These results support the notion that diffuse panbronchiolitis is influenced by genetic factors in the HLA region. Besides the class I gene itself, genes relevant to the class I antigen presenting system might contribute to its genetic predisposition.
Previous study has shown that the anti-Hu antibody titre of serum samples from patients with paraneoplastic encephalomyelitis/paraneoplastic sensory neuronopathy (PEM/PSN) was significantly higher than that from patients with small cell lung cancer without neurological disturbances (non-PEM/PSN). The aims of this study were (1) to identify the fine epitopes on HuD recognised by the anti-Hu antibody, (2) to determine if the pattern of epitopic reactivity differed between antibodies from patients with and without PEM/PSN, and (3) to determine if the pattern of epitopic reactivity correlated with the clinical features. Recombinant full length HuD and nine deletion fragments were constructed and immunoreacted by western blot analysis with 14 anti-Hu serum samples from eight patients with PEM/PSN and six without PEM/IPSN. All anti-Hu serum samples reacted with the deletion fragments containing amino acids (aa) 90-101 or aa 171-206. Some anti-Hu samples reacted with the deletion fragments containing aa 223-234, aa 235-252, or aa 354-373. There was no difference in the pattern of epitopic reactivity between patients with and without PEM/PSN. There was no correlation between the pattern of epitopic reactivity and the clinical features. The anti-Hu antibody titre from patients with PEM/ PSN was significantly higher than from patients without PEM/PSN, but there was overlap of their titre concentrations. In conclusion, aa 90-101 and aa 171-206 are the major epitopes with which all anti-Hu serum samples react, and aa 223-234, aa 235-252, and aa 354-373 are the minor epitopes with which only some anti-Hu serum samples react. The analyses suggested that the pattern of epitopic reactivity of the anti-Hu antibody on HuD was not a critical factor for the development or clinical features of PEM/PSN.
To analyze the recent change in the long-term survival of patients with dilated cardiomyopathy (DCM), the present study comprised consecutive 111 patients with ejection fraction <50% and left ventricular end-diastolic diameter >58 mm. who were admitted to hospital from January 1983 to December 1994. The patients were divided into 2 groups: group A who were diagnosed before 1989 and group B diagnosed after 1990. Basic characteristics at diagnosis, including age, NYHA functional class, left ventricular end-diastolic diameter and ejection fraction, were similar between these 2 groups. Calculated survival rate at 5 years was 90.0% in group B in contrast to 62.3% in group A. Event-free survival also improved in group B. In group B, beta-blockers and angiotensin converting enzyme inhibitors were more frequently used than in group A (p<0.0001) whereas digitalis and other positive inotropic agents were significantly less used. Left ventricular ejection fraction was significantly improved during the follow-up period in patients treated with beta-blockers compared with those not treated with beta-blockers. These data indicate a significant improvement in the survival of patients with dilated cardiomyopathy after 1990, which may be explained by the change of medical treatment, especially the use of beta-blockers.