Biomedical subjects
Publications and source records attributed to K Shimada.
This paper reports a case of right ventricular dysplasia, in which the patient presented with atrioventricular block and was followed for more than 8 years under left ventricular epicardial pacing. Five years after first epicardial pacemaker implantation, loss of capture occurred. Replacement of the epicardial leads was performed.
Early hepatocellular carcinoma (HCC) has been defined as a well-differentiated cancer containing Glisson's triad, but it remains unknown whether this lesion is curable. We prospectively studied 70 patients (enrolled from 1,172 referrals between 1982 and 1991) who had a diagnosis of a single HCC 2 cm or less in diameter (Stage T1) and who underwent curative hepatectomy and long-term follow-up (range, 0.2 to 14.3 years). Patients were eligible for surgery if they had a tumor that met the diagnostic criteria for HCC and were in Child-Pugh class A (n = 59) or B (n = 11) status. Among the 70 patients, there was 1 operative death. Based on our typing system, the tumors were assigned as early HCC (n = 15), overt HCC (n = 52), and non-HCC tumor (n = 3). The rate of microscopic regional spread was lower in early HCCs than in overt HCCs (7% vs. 42%; P = .01). The early HCC group had a longer time to recurrence than did the overt HCC group (3.9 vs. 1.7 years; P < .001) and had no local recurrence. After a median follow-up of 6.3 years, both overall survival and recurrence-free survival in the early HCC group were significantly better than those in the overt HCC group (P = .01; P = .001). In these two groups, the 5-year rates of overall survival were 93% and 54% (P = .01), and those of recurrence-free survival were 47% and 16% (P = .05), respectively; a significant survival benefit persisted over a decade (57% vs. 21%; P = .05). The early HCC group was at a lower risk of recurrence (relative risk, 0.31; 95% CI, 0.15 to 0.65; P = .002) and death (relative risk, 0.26; 95% CI, 0.09 to 0.73; P = .01) than was the overt HCC group. Early HCC is a distinct clinical entity with a high rate of surgical cure, thereby justifying its definition. It can be a lesion that corresponds to "Stage 0" cancer in other organs.
The liver plays a major role in metabolism and elimination of leukotrienes (LT). It produces cysteinyl leukotrienes (cLT), and cLT have been implicated in hepatocellular toxicity in several models of lipopolysaccharide (LPS)-associated liver injury. However, the liver cell types responsible for cLT production are poorly defined, and the expression of the LT-synthesis enzymes, 5-lipoxygenase (5-LO) and LTC4 synthase (LTC4-S), in liver cells has never been demonstrated. The aim of the present study was to examine the ability of rat liver cells to produce cLT by determining whether hepatocytes, Kupffer cells, and sinusoidal endothelial cells express mRNA and enzyme activities of the LT-synthesis enzymes and whether expression is altered by LPS. 5-LO mRNA was expressed in whole liver, and expression was enhanced by LPS. Cell fractionation studies demonstrated that expression was present in Kupffer cells and sinusoidal endothelial cells, but not in hepatocytes. LTC4-S mRNA was detected in whole liver, hepatocytes, and sinusoidal endothelial cells, but not in Kupffer cells. Semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) showed that LPS increased LTC4-S expression in hepatocytes by a factor of 3 (n = 3; P < .03). LTC4-S enzyme activity in the microsomal fraction of hepatocytes was also increased from 0.52 +/- 0.13 to 1.90 +/- 0.66 nmol . mg protein-1 . 5 min-1 (n = 6; P < .015) after LPS treatment. These results indicate that hepatocytes do not possess the ability for de novo synthesis of cLT from arachidonic acid, but they may actively participate in cLT production by conjugation of LTA4 with glutathione to produce LTC4. LPS enhances LTC4-S expression in hepatocytes. This intrinsic cLT production may contribute to hepatocellular injury during inflammation.
Adeno-associated virus (AAV) vectors, derived from a non-pathogenic parvovirus, are considered to be an appropriate gene transfer vehicle for both dividing and non-dividing cells. In the present study, we investigated whether the rat heart could be efficiently transduced with AAV vectors. Rat cardiac myocytes (CM) were infected with AAV-lacZ vector containing beta-galactosidase (beta-gal) gene in vitro, and the expression of beta-gal in CM was evaluated by X-gal staining and beta-gal ELISA. With increasing multiplicities of infection (MOI), more than 60% of CM were stained positively with X-gal, and the beta-gal expression increased to 31.1 +/- 4.6 ng/mg protein in a MOI-dependent manner (MOI: 10(4) to 10(6) particles/cell). The beta-gal expression was also increased in an incubation period-dependent manner (1-24 h). beta-gal expression was maximal at day 3 and then gradually decreased with time. However, beta-gal expression at day 14 was almost the same level as that at day 1 (45.5 +/- 5.9 v 55.2 +/- 6.2 ng/mg protein). Excised rat right ventricular papillary muscles were also infected with AAV-lacZ ex vivo. When the beta-gal expression was evaluated by X-gal staining, more than 80% of CM in the papillary muscles were stained positively, indicating efficient gene transfer into CM using AAV vectors. These findings suggest that AAV vectors are promising for cardiac gene therapy.
A 17-year-old female who had, on two occasions, inserted a total of 7 needles into her heart and chest wall, resulting in autolesion on both occasions, was examined. On the first occasion, because the needle end was recognizably protruding from the right ventricle, we successfully removed the needle without using ECC. No complications arose prior to discharge, after which she regularly visited the psychiatric department for treatment. Two months after discharge, she again inserted needles into her chest wall and was admitted to hospital. At that time, five needles were evident in the chest wall. During preparation for removal of the needles under local anesthetic, she escaped from the room. When found in a ward several hours later, six needles were embedded in her chest wall, the sixth, most recently inserted needle was an injection needle. Due to the depth to which the needle had been inserted in the heart, neither the point nor end were visible, and thus the needle had to be removed using ECC and fluoroscopy.
We investigated the effects of the sulfhydryl-donor, N-acetylcysteine (NAC), on nitroglycerin (NTG)-induced relaxation of the vascular smooth muscle. Addition of histamine to isolated porcine coronary arteries induced an initial rapid contraction followed by a gradual decrease in tonic contraction. NTG applied to the coronary artery strips before histamine caused relaxation of the histamine-induced rapid (3 min) and tonic (48 min) contraction. The inhibition of the tonic contraction by NTG was less at 48 min than at 3 min. Application of NAC (NTG-NAC) enhanced the relaxing effects of NTG on the histamine-induced tonic contraction rather than the acute contraction. In phosphorylation studies, changes in the phosphorylation of an intermediate filament, desmin, were parallel with changes in contraction in NTG-treated and NTG-NAC samples at 48 min. These phosphorylation changes of desmin at 48 min, which might be responsible for tonic phase contraction, were more extensive than those of myosin light chain (MLC) phosphorylation at 3 min, which might be responsible for acute contraction. These results suggest that treatment with the sulfhydryl donor, NAC, inhibited the phosphorylation of desmin associated with the enhancement of NTG-induced relaxation, which might be related to the mechanisms of recovery from NTG tolerance by sulfhydryl groups.
Responsive areas for velopharyngeal closure were examined by recording diaphragmatic and superior pharyngeal constrictor activities of anesthetized rabbits. Pressure stimulation was applied with a cotton applicator to the mucosae of three pharyngeal areas: the anterior (palatal) and posterior walls of the nasopharynx and the posterior wall of the oropharynx. The intensity and duration of the stimulation were around 9.0 gf and 0.43 sec, respectively. Velopharyngeal closure was elicited more frequently from the posterior wall of the nasopharynx than the other two areas tested. The higher responsiveness of the posterior wall of the nasopharynx for velopharyngeal closure is suggested to be attributed to higher density and/or lower threshold of pressure receptors in this area than those in the other two areas tested. Possible physiological implications of the present results are discussed.
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BACKGROUND: Significant mitral regurgitation (MR) is protective against left atrial (LA) spontaneous echo contrast formation that is associated with an increased thromboembolic risk. However, the effects of MR on the risk of stroke in patients with nonrheumatic atrial fibrillation (AF) have been unknown. We studied whether or not MR was associated with a decreased risk of stroke in patients with nonrheumatic AF. METHODS: We performed an observational analysis of retrospectively collected data on 290 patients with nonrheumatic AF. Left atrial diameter (LAD) and the degree of MR were estimated by transthoracic echocardiography. Risk factors for stroke were assessed by univariate and multivariate analyses. The mean follow-up was 7.4 years. RESULTS: Among these patients, 68 had a stroke during the follow-up (rate of stroke per year of follow-up 3.2%). In 95 patients with LAD of > or =48 mm, the incidence of stroke (9%) in the severe MR group (moderate or severe, n=43) was significantly lower than that (25%) of the mild MR group (none, trivial, or mild; n=52) (chi-square=3.95, p=0.047). The relative risk of stroke for increase in MR from mild to severe groups, for every 10 mm increment in LA size, for sex, and for every increase of 10 years of age was 0.45 (95% CI, 0.20 to 0.97), 1.06 (95% CI, 0.75 to 1.49), 0.98 (95% CI, 0.55 to 1.72), and 1.33 (95% CI, 1.04 to 1.71), respectively. CONCLUSIONS: In patients with nonrheumatic AF, age was an independent predictor of an increased risk of stroke, and MR may be protective against stroke, especially in those patients with LA enlargement.
Although plasma levels of adrenomedullin are elevated in patients with heart failure, levels in patients with mitral stenosis are unknown. We determined plasma levels of adrenomedullin in specimens of blood obtained from the peripheral veins of 15 consecutively treated patients with mitral stenosis 1 week before and 1 week after percutaneous mitral valvuloplasty. We also measured adrenomedullin in blood obtained from the right and left atria of 13 of 15 patients immediately before valvuloplasty. Plasma adrenomedullin level in the peripheral vein was 27.3 +/- 3.2 pg/ml among healthy subjects (n = 15) and 59.8 +/- 2.7 pg/ml among patients with mitral stenosis (n = 15, p < 0.0001). Plasma adrenomedullin level in the peripheral veins of patients with mitral stenosis before valvuloplasty correlated significantly with mean pulmonary artery pressure, mean pulmonary arterial wedge pressure, and mean left atrial pressure. Plasma levels of adrenomedullin in the peripheral vein and the right atrium were significantly higher than those in the left atrium (59.5 +/- 3.0 and 55.8 +/- 2.4 versus 45.9 +/- 2.9 pg/ml, n = 13, p < 0.005). Percutaneous mitral valvuloplasty caused a significant decrease in plasma adrenomedullin levels in peripheral veins from 59.8 +/- 2.7 to 49.9 +/- 3.1 pg/ml (p < 0.02). Percentage decrease in plasma adrenomedullin levels in the peripheral vein correlated significantly with percentage decreases in mean pulmonary artery pressure and mean pulmonary arterial wedge pressure. This study demonstrated that plasma adrenomedullin levels of patients with mitral stenosis correlated positively with mean pulmonary artery pressure and pulmonary arterial wedge pressure. These findings suggested that adrenomedullin may play an important role in the pulmonary circulation of these patients.
A rare case of "complex" cardiac myxoma is reported. Complex cardiac myxoma manifests with more constitutional signs than the sporadic type. These constitutional signs are known to be associated with the overproduction of interleukin-6 by cardiac myxomas. In our study, immunohistochemical staining of the myxoma for interleukin-6 was strongly positive. The serum interleukin-6 level decreased after surgical removal of the tumor and has remained undetectable for the past 2 years.
OBJECTIVE: The purpose of this study was to investigate whether the synthesis of platelet-derived growth factor (PDGF), a major mitogen and chemoattractant for vascular smooth muscle cells, was induced by the direct cell-to-cell interaction between human monocytes and umbilical vein endothelial cells (ECs). METHODS: PDGF protein and mRNA expression were determined by cellular ELISA, immunohistochemical and Northern blot analyses. RESULTS: Coculture of monocytes and ECs secreted a large amount of PDGF into the supernatant, whereas culture of ECs or monocytes alone induced low levels of PDGF production. In Northern blot analysis, substantial amounts of PDGF-A and -B mRNA were induced by coculture of monocytes with ECs. Immunohistochemistry revealed that PDGF-B chain protein was detectable in both ECs and monocytes. PDGF production by ECs induced by conditioned medium of the coculture was significantly inhibited by Abs against interleukin-1 beta (IL-1 beta) and tumor necrosis factor- alpha (TNF alpha). CONCLUSIONS: These results indicate that the direct cell-to-cell interaction between human monocytes and ECs induces PDGF synthesis in both types of cells, suggesting that PDGF produced locally by monocyte-EC adhesive interaction plays an important role in the pathogenesis of atherosclerosis by promoting the migration and accumulation of vascular smooth muscle cells.
OBJECTIVE: The adhesive interaction of monocytes and vascular smooth muscle cells (VSMCs) has been suggested to be a regulatory signal in the cellular activation that is involved in the pathogenesis of atherosclerosis. We investigated the effects of monocyte-VSMC interaction on inducible nitric oxide (NO) synthase expression. METHODS: NO production by the cultured cells was determined by measuring the nitrite content of the culture media using the Griess reagent. The expression of inducible NO synthase protein was assayed by Western blotting. RESULTS: Interleukin-1 beta (IL-1 beta) induced nitrite production by VSMCs in a time-dependent manner. The addition of the mouse monocyte cell line J774 to IL-1 beta-stimulated VSMCs further increased nitrite production in a monocyte number-dependent manner. Enhanced nitrite production by coculture was accompanied by increased inducible NO synthase protein accumulation. Addition of tumor necrosis factor-alpha (TNF-alpha) also enhanced IL-1 beta-induced nitrite production by VSMCs, but TNF-alpha showed no effect in the presence of monocytes. Coculture of monocytes and VSMCs in the presence of IL-1 beta secreted substantial amounts of TNF-alpha. The production of nitrite by coculture was markedly inhibited by an anti-TNF-alpha antibody. CONCLUSIONS: The present study revealed that direct cell-to-cell interaction between monocytes and VSMCs enhances NO production, suggesting an important role for their interaction in the pathogenesis of atherosclerosis.
OBJECTIVE: The purpose of this study was to investigate the effects of vesnarinone on nitric oxide (NO) synthesis in cardiac myocytes. METHODS: We measured the accumulation of nitrite, a stable oxidation product of NO synthase (iNOS) protein in cultured neonatal rat cardiac myocytes. RESULTS: Incubation of the cultures with interleukin-1 beta (IL-1 beta; 10 ng/ml) and tumor necrosis factor alpha (TNF alpha; 10 ng/ml) caused a marked increase in nitrite production. Although vesnarinone by itself showed no effect on nitrite accumulation, it enhanced cytokine-induced nitrite production by cardiac myocytes in a dose-dependent manner. The effect of vesnarinone was completely abolished in the presence of NG-monomethyl-L-arginine or actinomycin D. The vesnarinone-induced nitrite production was accompanied by increased iNOS protein expression. In the presence of dibutyryl-cAMP, cytokine-induced nitrite accumulation was further increased, but the stimulatory effect on vesnarinone on nitrite accumulation was diminished. The effect of vesnarinone was also inhibited by Rp-8-Br-cAMPS, a competitive inhibitor of protein kinase A, in a dose-dependent manner. CONCLUSIONS: These findings indicate that vesnarinone increases NO synthesis in cytokine-stimulated cardiac myocytes, at least partially through a cAMP-dependent pathway.
Dopamine and two related catecholamines, L-3,4-dihydroxyphenylalanine (DOPA) and N-acetyl dopamine (NADA), were analyzed in whole body and tissue samples taken throughout late larval development of the drosophilid fly Chymomyza costata, which enters facultative diapause as a mature 3rd instar larva in response to short photophase. Wild-type (W) and mutant-nondiapause (M) strains reared under diapause inducing (d) and preventing (nd) photophases were compared. Developmental changes in the whole body of dopamine levels showed some general features irrespective of fly strain and rearing conditions: sharp major peaks during moult from second to third instar larva and during pupariation; lower minor peaks around the middle of both 2nd and 3rd instars. Significant differences between the strains and conditions were also found: dopamine levels were lower throughout the 2nd instar and during the 2nd to 3rd instar moult of mutant strain larvae (M/d) as compared to wild-type larvae (W/nd and W/d); while the late 2nd and late 3rd instar larvae destined to diapause (W/d) maintained relatively high dopamine concentrations, their counterparts destined to continuous development (W/nd and M/d) significantly decreased dopamine levels prior to the 2nd to 3rd instar moult or pupariation. Possible relationship between the dopamine levels and diapause induction/onset in C. costata larvae is discussed. Integument contained more than 90% of the dopamine found in the whole body. The gut and central nervous tissues showed relatively low pools of dopamine, only trace amounts were detected in haemolymph and no dopamine was found in fat body. DOPA levels were low and stable throughout larval development of both W and M strains and under both conditions. NADA levels peaked during second halves of 2nd and 3rd instars of both strains, then dropped to trace levels and were elevated again during 2nd to 3rd instar moult as well as in tanned prepupae. No elevation of NADA levels was recorded in 3rd instar W/d larvae which entered diapause.
PURPOSE: This retrospective study was conducted to determine the relationship between the computed tomographic findings for cervical lymph nodes (LN), histologic findings, and outcome in patients with squamous cell carcinoma of the oral cavity who underwent radical neck dissection. PATIENTS AND MATERIALS: Sixty-six patients were analyzed. Of these 66 operations, 43 were immediate therapeutic dissections in clinically N+ necks, and 23 were subsequent therapeutic dissections in patients whose necks were initially node free but progressed to positive nodes during observation. RESULTS: When the size criterion (area of the axial section) of nodal metastasis depicted on the scan of 45 mm2 was selected, almost 78% of LN were diagnosed consistent with the histologic diagnosis. As the size of the LN increased, the frequency of extranodal invasion also became higher, whereas patients with the higher histologic grades of malignancy often showed neck metastases with extranodal invasion in the early stage. Patients having LN smaller than 100 mm2, or without extranodal invasion, showed good outcome, whereas those having LN 100 mm2 or larger, with extranodal invasion, showed extremely poor outcome. CONCLUSIONS: These findings indicate that it is possible to delay neck dissection in node-free patients until neck disease is diagnosed with timely CT examination, although great caution is necessary, especially in those with a high histologic grade of malignancy.
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Vasoactive intestine polypeptide (VIP) and growth hormone releasing factor (GRF) stimulated an increase of cAMP accumulation with a concomitant release of PRL and GH, respectively. Release of PRL induced by VIP was partially suppressed by 5 and 25 microM of H-89, whereas VIP-induced gene expression of PRL was inhibited by all concentrations of H-89. Release and gene expression of GH induced by GRF was inhibited by H-89 in a dose-dependent manner and completely blocked by 25 microM of H-89. These results indicate that VIP-induced PRL release and gene expression may be mediated, at least in a part, by cAMP-dependent protein kinase pathway, whereas GRF-induced GH release and gene expression may be mediated predominantly by cAMP-dependent protein kinase.