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Biomedical subjects

S Maeda

Publications and source records attributed to S Maeda.

At least 595 records · Page 33Linked to original sources

[A clinicopathologic study of atrial infarction complicating left ventricular posterior myocardial infarction].

Among a series of 400 consecutive autopsy cases we performed a clinicopathologic study of atrial infarction in 46 autopsy-proven cases, which had acute or old left ventricular (LV) myocardial infarction. We used blocks taken from both atrial appendages, the region of the sinus-node, the lateral wall of the right atrium, the posterior wall of the right atrium, and the posterolateral wall of the left atrium. Atrial infarction was identified in 13 (28%) of 46 cases with LV posterior infarction which was caused by lesions of the right coronary artery; 10 cases were right atrial infarction and 3 were both right and left atrial infarction. Among 13 cases in which the acute phase of ventricular infarction could be followed, 3 cases exhibited transient atrial fibrillation. Of these 3 cases, 2 had atrial infarction. The mean stenotic index of the proximal right coronary artery was 4.3/5 in the 13 cases of atrial infarction, 3.2/5 in 17 cases of acute necrosis or scar and 3.1/5 in 16 cases without ischemic atrial lesions. Most of the atrial infarction was found in the right atrium; 10 in the right atrial appendage, 8 in the right atrial lateral wall, 3 in the region of the sinus node and the left atrial posterolateral wall, 2 in the right atrial posterior wall, and one in the left atrial appendage. In conclusion, the incidence of atrial infarction was unexpectedly high (28%) in LV posterior infarction caused by lesions of the proximal right coronary artery, particularly in severe stenosis or obstruction.

Aged↗

Activation of cathepsin B involved in enkephalin production by bradykinin and its cleavage products in cultured fibroblasts of the rat dental pulp.

Mechanisms of cathepsin B activation involved in methionine-enkephalin (ME) production induced by bradykinin (BK), des-Arg9-BK or L-arginine (L-Arg) were studied using cultured fibroblasts of the rat dental pulp, especially from a viewpoint of intracellular signal transduction. BK, des-Arg9-BK, L-Arg or cysteine enhanced the release of ME-like peptides from the cells, and the release of ME-like peptides induced by des-Arg9-BK was inhibited by des-Arg9-[Leu8]-BK (BK B1-receptor antagonist) and E-64 (a specific inhibitor of cysteine proteinases). The activation of cathepsin B by BK or des-Arg9-BK was inhibited by des-Arg9-[Leu8]-BK or islet-activating protein (IAP), and the activation of cathepsin B by L-Arg was inhibited by Leu-Arg (kyotorphin-receptor antagonist) or Botulinum C3-enzyme. The activation of cathepsin B by those stimulants was dependent on calcium ion. These results suggest that the ME production by BK or des-Arg9-BK may be mediated by Ca(2+)-dependent cathepsin B activation through B1-receptors and IAP-sensitive G-proteins, whereas the production by L-Arg may be mediated by Ca(2+)-dependent cathepsin B activation through kyotorphin-receptor and Botulinum C3-enzyme-sensitive G-proteins. On the other hand, the activation of cathepsin B was inhibited by neomycin B (phospholipase C inhibitor) and various serine/threonine kinase inhibitors. These results indicate that phospholipase C and serine/threonine kinases are involved in the activation of cathepsin B by BK, des-Arg9-BK or L-Arg. Genistein inhibited the activation of cathepsin B by des-Arg9-BK or L-Arg in a different fashion, suggesting that tyrosine kinase(s) is also involved in the activation. Cathepsin B activation by BK or L-Arg but not des-Arg9-BK was inhibited by L-NMMA (inhibitor of NO synthesis), and the activation by L-Arg was enhanced by beta-glycerophosphate (beta-GP: inhibitor of phosphatases), while the activation by BK or des-Arg9-BK was inhibited by beta-GP. These results suggest that BK-induced cathepsin B activation in the fibroblasts may be due to a combined effect of des-Arg9-BK and L-Arg.

Animals↗

[A clinicopathologic study of morphologic tricuspid valve prolapse in the aged: comparison with color Doppler evaluation].

Similar morphologic abnormalities have often been observed in the leaflets of tricuspid valve in patients with mitral valve prolapse. In the present study, morphologic tricuspid valve prolapse was analyzed in 500 consecutive autopsies of the aged over 60 years (mean 78.5 yrs, 266 men, 234 women). Additionally, the sensitivity and specificity of the color Doppler technique applied before death were assessed in 61 autopsy cases. The results were as follows: 1. The incidence of morphologic tricuspid valve prolapse was 22.2% at autopsy in 500 cases of the aged, however, tricuspid regurgitation had not clinically been detected in any of them. 2. The prolapse of 2- or 3-leaflets was common (78.5%). Among the 3 leaflets, the prolapse was more frequently observed in the anterior or posterior leaflet than in the septal leaflet. Combined tricuspid and mitral valve prolapses were observed in 22 cases (19.8%). 3. Among 61 cases examined by color Doppler echocardiography, autopsy showed that 16 cases had tricuspid valve prolapse and 14 cases tricuspid regurgitant flow signals (87.5%). 4. Regurgitant flow signals were also detected in 4 of 12 morphologically normal cases (33.3%). 5. In autopsy cases of the aged, generally, the incidence of morphologic tricuspid valve prolapse and tricuspid regurgitant flow signal were high, however, hemodynamically significant regurgitation due to prolapse was very rare.

Aged↗

Multiple hormone secretion and gene expression in clones isolated from rat insulinoma cell lines.

Current evidence suggests that a multipotential endodermal cell may give rise to all islet cell phenotypes. Five (N1-N5) and twenty-one (m1-m21) pluripotent rat islet cell clones were isolated from two hormone-producing cell line (RIN-r, RINm5F) derived from a radiation-induced islet tumor. To investigate the characteristics of these clones, we analyzed the hormone expression and secretion by Northern blot, immunocytochemistry, and radioimmunoassay. Increased expression and secretion of insulin and glucagon were observed in these clones. The present examination might also be proof of the secretion of both insulin and glucagon in the single cell of the m21 clone isolated from RINm5F. These cell lines also overexpress the Ha-ras proto-oncogene. In order to determine whether or not the overexpression was caused by gene translocation, the insulin and Ha-ras gene loci in N3 isolated from RIN-r were assigned by in situ hybridization. Both of the genes were located on the long arm of chromosome 1, but no gene translocation was observed. These findings suggest that the expression of insulin and Ha-ras is not affected by chromosomal translocation, but it may be functionally linked in these clones. Overexpression of these three genes may indicate that these clones have the same characteristics as the embryonic immature islet cell.

Animals↗

[Nerve-sparing retroperitoneal lymph node dissection for stage IIA testicular embryonal carcinoma: a case report].

A 32-year-old man who had left testicular embryonal carcinoma with low volume left para-aortic lymph node swelling was treated initially with 3 courses of cisplatin-based combination chemotherapy. Pathological findings of the primary lesion revealed no yolk sac element and no elevation of serum alpha fetoprotein (alpha-FP) and beta-human chorionic gonadotropin (beta-HCG) levels even before the left orchiectomy. Therefore, the retroperitoneal lymph node dissection (RPLND) was performed despite marked shrinkage of the enlarged nodes. The L1-3 lumber splanchnic nerves from the right sympathetic truncus were detected in the intra-aortocaval region to prevent impairment of ejaculatory function and the lymph nodes in the area were removed one by one between the preserved neurofibers. On the other hand, the left para-aortic lymphatic tissue which included enlarged nodes was dissected in en bloc manner. The pre-aortic lymphatic tissue caudally to the inferior mesenteric artery was preserved not to be touched. The patient ejaculated normally 3 weeks after the RPLND. Treatment of stage IIA disease with chemotherapy first might be helpful in performing RPLND, if necessary, with keeping both ejaculatory function and radicality.

Adult↗

Cholangiocellular carcinoma in the caudate lobe with intraluminal growth in the extrahepatic bile duct.

A case of cholangiocellular carcinoma in the caudate lobe with intraluminal growth in the extrahepatic bile duct is reported. The main tumor in the caudate lobe was detected by computed tomography and angiography, and two intraluminal tumors at the hepatic hilus and at the root of the right posterior segmental duct were well demonstrated by cholangiography and percutaneous transhepatic cholangioscopy. Independent total caudate lobectomy with bile duct resection was performed. Cholangiocellular carcinoma of the liver with intraluminal growth in the extrahepatic bile duct is very rare and has not been reported in the literature. Independent caudate lobe resection requires a rather complicated technique. However, this method has the advantage of reducing to a minimum the hepatic volume to be resected, and is useful for poor-risk patients or for cases with localized carcinoma at the hepatic hilus.

Adenocarcinoma↗

Effect of serum amyloid P component level on transthyretin-derived amyloid deposition in a transgenic mouse model of familial amyloidotic polyneuropathy.

To elucidate the pathogenesis of amyloid deposition associated with familial amyloidotic polyneuropathy (FAP), we developed several transgenic mouse lines carrying the human mutant transthyretin (TTR) gene. We found that human TTR and mouse serum amyloid P component (SAP) are deposited as amyloid in tissues of these mouse lines. Because SAP is a major acute-phase reactant in mice, we asked whether repeated injections of Escherichia coli lipopolysaccharide (LPS) would enhance the amyloid deposition in one of these transgenic mouse lines. During the course of repeated LPS injections, serum levels of SAP in the transgenic mice remained between severalfold to about 50-fold higher than seen in the absence of stimulation. As no significant difference was detected in the onset, progression, and tissue distribution of TTR-derived amyloid (ATTR) deposition between the LPS-stimulated and unstimulated transgenic mice, the induction of SAP synthesis by acute inflammation probably does not affect the onset and extent of ATTR deposition.

Amyloid↗

[A case of true aneurysm of the mitral valve associated with torn chordae].

The patient was a 62 year old woman complaining of severe exertional dyspnea. Preoperative echocardiogram demonstrated the abnormal uniform echo of the anterior leaflet of the mitral valve which protruded toward the left atrium in systole as well as in diastole. Severe mitral regurgitation was also detected. The aneurysm of the anterior leaflet of the mitral valve was confirmed during the operation and mitral valve replacement was performed. The postoperative course was uneventful. Pathological examination of the resected aneurysm showed myxomatous degeneration. There were no signs of the inflammatory processes. The aneurysm formation in this case was considered to be due to the myxomatous degenerative changes of the anterior leaflet of the mitral valve. Fifteen cases of true aneurysm of the mitral valve reported in Japan were reviewed.

Chordae Tendineae↗

[Reconstructive surgery in 59-year-old patient with coarctation of aorta under the monitoring of somatosensory evoked potential and spinal cord perfusion pressure].

Postoperative paraplegia is a relatively rare complication in reconstructive surgery for coarctation of the aorta and the operative treatment is usually performed without any adjuncts. A 59-year-old male patient underwent replacement of descending thoracic aorta with vascular prosthesis under the monitoring of SEP and spinal cord perfusion pressure (SCPP) [pressure difference between mean distal aortic pressure (MDAP) and the cerebrospinal fluid pressure (CSFP)]. During cross-clamping of the aorta, MDAP decreased from 61 to 40 mmHg and CSFP increased from 6 to 15 mmHg, SCPP was 25 mmHg, and the amplitude of the SEP waves rapidly decreased. As the ischemic changes of spinal cord were suspected, the aortic cross-clamping was released. The amplitude of SEP recovered to the preoperative level immediately after de-clamping. In order to prevent spinal cord ischemia, the partial cardio-pulmonary bypass was employed, and SCPP was maintained above 60 mmHg, so that SEP did not show any ischemic changes during cross-clamping of the aorta. The patient did not develop any neurological deficit postoperatively. The monitoring of SEP and SCPP appears to be useful for prevention of postoperative paraplegia in the surgical treatment for coarctation of the aorta.

Aortic Coarctation↗

Synergistic effects of interleukin-1 beta and interleukin-3 on the expansion of human hematopoietic progenitor cells in liquid cultures.

In the present study, we show that recombinant human interleukin-1 beta (rhIL-1 beta), which has no effect on the proliferation of human progenitor cells, has synergistic effects on the expansion of human progenitor cells induced by rhIL-3 in liquid cultures. The synergistic effects of rhIL-1 beta with rhIL-3 were observed in liquid cultures using not only fresh bone marrow mononuclear cells, but also selected populations of nonadherent cells, non-T nonadherent cells, and CD34-positive cells. Anti-granulocyte-macrophage colony-stimulating factor (anti-GM-CSF) antibody partially blocked the synergistic effects of rhIL-1 beta on the proliferation of colony-forming unit (CFU)-GM burst-forming unit-erythroid (BFU-E), and CFU-Mix in liquid cultures in the presence of rhIL-1 beta plus rhIL-3, suggesting that the synergistic effects of rhIL-1 beta plus rhIL-3 are explained in part by the secondary production of GM-CSF. Limiting dilution assays and liquid culture assays using CD34-positive cells indicate that rhIL-1 beta directly increases the numbers of colony-forming cells in liquid cultures. These results suggest that rhIL-1 beta has unique direct and indirect effects on the expansion of hematopoietic progenitor cells in liquid cultures.

Antibodies↗

Inactivation of the retinoblastoma gene in human bladder and renal cell carcinomas.

The retinoblastoma (RB) gene was the first tumor suppressor gene isolated and its inactivation is associated with the pathogenesis of several types of human cancer. In this study, we investigated the involvement of the RB gene in bladder and renal cell carcinomas by determining the loss of heterozygosity (LOH) at the RB locus and by DNA, RNA, and protein analysis of the RB gene. Whenever possible, the latter included Western blotting and immunohistochemical staining of the RB protein. In bladder carcinoma, 2 of the 8 cell lines we studied had an inactivated RB gene; one cell line lacked RB expression without a gross RB deletion, whereas the other cell line expressed only the underphosphorylated form of the RB protein. None of 16 low-grade noninvasive bladder carcinomas showed an alteration in RB protein by direct Western blot analysis, whereas 2 of 14 high-grade, invasive tumors had no RB protein as measured by both Western blotting and immunohistochemical staining. This suggests that the loss of RB function may be more important in the progression of bladder cancer than in its initiation, although more extensive studies are required. LOH within the RB locus was observed in 5 of 27 informative cases of primary bladder, ureter, or renal pelvis carcinoma. However, none of the 5 cases with LOH at the RB locus had a functional loss of RB protein expression. In renal cell carcinoma, one of the 12 cell lines had a gross homozygous deletion of the RB gene, and 2 of 32 primary tumors were negative for RB protein expression. LOH at the RB locus also was found in only 2 of 30 informative cases, one of which lacked RB expression. These results are the first to demonstrate the involvement of RB inactivation in the development of advanced primary bladder carcinoma and suggest that RB loss could have a role in certain renal cell carcinomas. Our data, however, show no correlation between LOH at the RB locus in bladder cancer and actual inactivation of the RB gene at the protein level. This may suggest that there is a second tumor suppressor or recessive cancer gene on chromosome 13 in bladder cancer and/or that the mechanism of RB inactivation in bladder cancer frequently involves independent mutations of each RB allele.

Base Sequence↗

Expression of micF involved in porin synthesis in Escherichia coli: two distinct cis-acting elements respectively regulate micF expression positively and negatively.

micF RNA, whose sequence is highly complementary to a 5'-portion of ompF mRNA, has been implicated in the osmoregulation and thermoregulation of the ompF porin gene in Escherichia coli. To define and characterize cis-acting regulatory regions upstream of the micF promoter, a series of deletions of the micF promoter fused to the lacZ gene were constructed. Two distinct regions, which function differently, were identified as cis-acting regulatory elements, namely, one responsible for OmpR-dependent activation and the other for OmpR-independent repression of micF expression. The former contains the OmpR-binding site, which simultaneously regulates both the genes, micF and ompC, in response to the medium osmolarity. The latter may be involved in an unknown regulatory process of micF expression.

Bacterial Outer Membrane Proteins↗

Immunohistologic evaluation of parathyroid hormone-related protein in human lung cancer and normal tissue with newly developed monoclonal antibody.

With a newly developed monoclonal anti-PTHrP antibody, 4B3, the immunohistochemical localization of the parathyroid hormone-related protein (PTHrP) was studied on the formalin-fixed and paraffin-embedded sections of normal human tissues and various subtypes of lung cancer. Among normal epithelial tissues, keratinocytes in squamous epithelia, transitional and bronchial epithelia with squamous metaplasia, meningoepithelial cells, and mammary ductal cells with lactating changes showed positive immunoreactivity. Also, among endocrine tissues, cells in the parathyroid gland, pancreatic islets, adrenal cortex, pituitary gland, and testis were sporadically positive for PTHrP. These distribution patterns suggested that in a physiologic condition, PTHrP was closely related to keratinization and local secretion and/or the metabolism of calcium in specifically differentiated tissues. In lung cancer, however, PTHrP was detected in all cases of well-differentiated and moderately differentiated squamous cell carcinoma and in most cases of small cell carcinoma, irrespective of the patients' serum calcium level. However, PTHrP was not detected in two of five cases of poorly differentiated squamous cell carcinoma and in all cases of adenocarcinoma. Consequently, it was found that PTHrP was commonly produced by squamous cell carcinomas of the differentiated type, and that humoral hypercalcemia of malignancy could be induced when the PTHrP transgressed the homeostatic mechanisms.

Adenocarcinoma↗

Allelotype of renal cell carcinoma.

Several recent studies based on restriction fragment length polymorphism analysis have supported the concept that the accumulation of multiple genetic alterations converts a normal cell to a malignant cell. Activation of oncogenes and/or inactivation of tumor suppressor genes have been observed during tumor progression in colorectal cancer, lung cancer, and breast cancer. To investigate the possibility that multiple genes are altered during the progression of renal cell carcinoma, we have used restriction fragment length polymorphism markers throughout the genome to test for loss of heterozygosity in 38 renal cell carcinomas. Nearly 64% of the tumors had lost heterozygosity on the short arm of chromosome 3. We also observed loss of heterozygosity averaging about 30% at informative loci on six other chromosomal arms (chromosomes 5q, 6q, 10q, 11q, 17p, and 19p). These results lead us to suspect the existence of several tumor suppressor genes associated with carcinogenesis of renal cell carcinoma.

Carcinoma, Renal Cell↗