Biomedical subjects

T Fukutomi

Publications and source records attributed to T Fukutomi.

At least 37 records · Page 2Linked to original sources

PubMed2001

Concordance in judgments among c-erbB-2 (HER2/neu) overexpression detected by two immunohistochemical tests and gene amplification detected by Southern blot hybridization in breast carcinoma.

We compared the c-erbB-2 protein overexpression status detected by the HercepTestTM (DAKO A/S, Grostrup, Denmark) with another conventional immunohistochemistry system using an anti-c-erbB-2 rabbit polyclonal antibody (Nichirei Co., Tokyo, Japan) and with the c-erbB-2 gene amplification status detected by Southern blot hybridization in 101 surgically resected breast carcinomas. According to the criteria for overexpression, recommended by the manufacturer, c-erbB-2 overexpression by HercepTestTM was detected in 24 cancers (24%), comprising six score-2 tumors and 18 score-3 tumors. The level of agreement in judgment of the HercepTestTM, among three independent observers, was excellent (kappa = 0.845). C-erbB-2 overexpression by Nichirei's antibody and c-erbB-2 gene amplification were detected in 21% and 16% of cases, respectively, and their concordance with HercepTestTM scores of 2-3 was 89% and 90%, respectively. In the score-3 cases by Hercep TestTM only, the concordance rates with overexpression by Nichirei's immunohistochemistry and with gene amplification were slightly higher, 94% and 93%, respectively. Score-2 cases by HercepTestTM were mostly judged as negative overexpression by Nichirei's antibody and as no amplification by Southern blot hybridization. The present results showed that HercepTestTM score-3 detected c-erbB-2 overexpression almost optimally as well as the conventional methods and the score-3 breast carcinomas had clinical and biological implications. Further examination would be necessary to decide the significance of breast cancers of HercepTestTM score 2.

Blotting, Southern↗

PubMed2001

Detection of numerical alterations of chromosome 1 in cytopathological specimens of breast tumors by chromogen in situ hybridization.

To investigate the effectiveness of chromogen in situ hybridization (CISH) in the diagnosis of breast tumors, numerical alterations of chromosome 1 were examined by CISH and fluorescence in situ hybridization (FISH) methods, and the presence of der(16)t(1;16) was also examined by FISH in imprinted cytology specimens from resected tissues of 14 carcinomas and five non-malignant lesions. The modal signal counts of chromosome 1 were compared between the specimens processed by CISH and FISH for each case. Aneusomies of the long arm of chromosome 1 were detected in 10 (71%) carcinomas as the major clones by both methods. In addition, one atypical papilloma demonstrated tetrasomy of 1q12 as a major clone by CISH, but such a clone was at first overlooked by FISH. Four other benign lesions showed disomic 1q12 signals as a major clone by both CISH and FISH. As additional information from FISH, eight cancers showed structural or numerical alterations of chromosome 16, and four showed der(16)t(1;16). In total, 10 carcinomas showed chromosome 16 alterations, and all of these overlapped with the carcinomas with 1q12 aneusomies. The CISH method provided almost the same results as the FISH method, and both methods were considered applicable in supportive diagnosis of cytological specimens of breast tumors. In addition, the CISH method was superior in the detection of numerical alterations in carcinoma cells by referring to the morphology of cells and in the detection of significant clones which might be missed under dark-field microscopy.

Breast Neoplasms↗

PubMed2001

Validation and problems of St-Gallen recommendations of adjuvant therapy for node-negative invasive breast cancer in Japanese patients.

BACKGROUND: The objectives of this study were to confirm the favorable outcome of invasive breast cancer in Japanese patients without lymph node metastasis who did not receive adjuvant therapies and to validate the St-Gallen recommendations in this population. METHODS: The subjects were a consecutive series of 920 node-negative invasive breast cancer patients who underwent surgery between 1987 and 1994 at our hospital. These patients did not receive adjuvant chemotherapy. Ten-year disease-free (DFS) and overall survival (OS) rates were analyzed by the St-Gallen risk categories (Minimal/Low, Intermediate, High). RESULTS: The median age of the patients at surgery was 52 years and the median follow-up period of patients was 10.2 years. At 10 years, the respective DFS and OS rates of all patients were 84.6 and 86.7%. The DFS and OS of patients in the Minimal/Low risk category (25 patients) both showed 100%. The DFS and OS of patients in the Intermediate risk category (356 patients) showed 92.0 and 93.1%, respectively. The DFS and OS of patients in the High risk category (539 patients) showed 79.4 and 82.2%, respectively, indicating a significant difference between those in the Minimal/Intermediate risk category (381 patients) (p < 0.001, p < 0.001, respectively). The DFS and OS of patients who had one pathological lymph node metastasis (775 patients) showed 72.7 and 75.2%, respectively, which indicated a non-significant difference between those in the High risk category (381 patients) (p = 0.10). These data support the validation of adjuvant therapy for high-risk node-negative breast cancers in Japanese patients. However, quality control is needed to define the histological grade included in the risk categories. CONCLUSION: Japanese patients with invasive breast cancer without lymph node metastasis showed a survival advantage compared with their Caucasian counterparts. However, patients in the High risk group as defined by St-Gallen recommendations should be indicated for adjuvant therapy.

Adult↗

PubMed2001

Association of breast cancer with meningioma: report of a case and review of the literature.

We report a case of meningioma subsequently developed in a patient with primary breast carcinoma. A 53-year-old woman received a left modified radical mastectomy because of stage IIA breast carcinoma. Histologically, the tumor was a predominantly intraductal carcinoma with negative lymph node metastasis. Estrogen receptor (ER) was negative but progesterone receptor (PR) of the left tumor was positive by immunohistochemistry. Four years later, cranial bone and/or brain metastasis was suspected from a routine follow-up bone scintigram. The patient showed no symptoms or signs at that time. Magnetic resonance imaging (MRI) and angiography revealed that the right parasagittal mass was suspicious of meningioma. A complete tumor removal was performed. On histological examination, this brain tumor was a transitional-type meningioma (meningotheliomatous and fibrous type) without malignant findings. ER was negative but PR was positive also in this tumor. She is currently well 6 years after the initial surgery. A review of the literature is presented with emphasis on the association between breast cancer and meningioma, which indicates a possible hormonal relationship. The knowledge of this association is important in the differential diagnosis of patients with breast cancer who develop central nervous manifestations.

Breast Neoplasms↗

PubMed2001

Effect of probucol in lecithin-cholesterol acyltransferase-deficient mice: inhibition of 2 independent cellular cholesterol-releasing pathways in vivo.

Cellular cholesterol release takes place by at least 2 distinct mechanisms: the lecithin-cholesterol acyltransferase (LCAT)-driven net efflux by cholesterol diffusion and the generation of high density lipoprotein (HDL) with cellular cholesterol and phospholipid on the cell-apolipoprotein interaction. Therefore, LCAT deficiency impairs the former pathway, and the latter can be inhibited by probucol, which interferes with the apolipoprotein-cell interaction. Hence, probucol was given to the LCAT-deficient mice in the attempt to suppress both of these pathways. The mice were fed low (0.2%) and high (1.2%) cholesterol diets containing 0.5% probucol for 2 weeks. LCAT deficiency and probucol markedly decreased plasma HDL, and the effects were synergistic. Tissue cholesterol content was lower in the adrenal glands and ovaries in the LCAT-deficient mice and in the probucol-treated mice, suggesting that HDL is a main cholesterol provider for these organs. It was also moderately decreased in the spleen of the low cholesterol-fed female mice and in the thyroid gland of the low cholesterol-fed male mice. On the other hand, the esterified cholesterol content in the liver was substantially increased by the probucol treatment with a high cholesterol diet in the LCAT-deficient mice but not in the wild-type mice. Among the groups, there was no significant difference in the tissue cholesterol levels in other organs, such as the liver, spleen, thymus, brain, erythrocytes, thyroid gland, testis, and aorta, resulting from either LCAT deficiency or probucol. Thus, the apolipoprotein-mediated mechanism plays a significant role in the export of cellular cholesterol in the liver, indicating that the liver is a major site of the HDL assembly. Otherwise, tissue cholesterol homeostasis can largely be maintained in mice even when the assembly of new HDL is inhibited by probucol in the absence of LCAT. Nonspecific diffusion of cholesterol perhaps adequately maintains the homeostasis in the experimental condition.

Animals↗

PubMed2001

Angiographic classification of coronary dissections after plain old balloon angioplasty for prediction of regression at follow-up.

Coronary dissection after plain old balloon angioplasty often shows regression during follow-up. This study sought to determine whether we can predict such phenomenon angiographically. We analyzed 64 patients with 71 type B-D coronary dissections determined by the National, Heart, Lung, and Blood Institute (NHLBI) criteria. Regression was considered present when minimal lumen diameter increased by more than 0.3 mm during follow-up. Dissections were divided into subgroups using the NHLBI criteria and our classification in which type a and b dissections were characterized by the width of a dissection lumen exceeding one quarter of the reference diameter with the outer edge of the dissection lumen within the boundary of reference in type a and beyond it in type b. In type c and type d dissections, the width of the dissection lumen was within one quarter of the reference with its outer edge within the boundary of reference in type c and beyond it in type d. Type e dissection had a protruding flap or spiral appearance. Regression was recognized in 23.9%. The distribution of dissection types was similar in the groups with and without regression by the NHLBI criteria, but type c dissection had regression more frequently than the other types of coronary dissections (p<0.001) using our classification.

Aged↗

PubMed2001

A new prognosis factor analysis based on nonhomogeneous Markov description.

To evaluate prognosis factors, Cox's proportional hazard model has been used. But it was found that the analytical ability was not sufficient. So we propose a new evaluation method combining Markov chain model and multiple logistic regression analysis to estimate the prognosis factors. Stage II breast cancer was chosen as the subject. The data was retrospective data gathered in National Cancer Center Central Hospital. As first step, a simple Markov chain model was constructed to describe the state transition of a breast cancer. Then the multiple property of each state transition was investigated in detail. And the patients who had gotten a recurrence for the first two and a half years were discriminated as the poor prognosis group by a nonparametric test (p < 0.05). And the result proved to corresponding with the clinical experience. As second step, three factors (n classification of pathological diagnosis, ductal spread, and estrogen receptor) were selected as the prognosis factors for the early death in Stage II breast cancer by a multiple logistic regression analysis. This new prognosis factor analysis could find out some scientific evidences. Especially, it was found to be remarkable efficient in proving clinically experienced observation.

Breast Neoplasms↗

PubMed2000

Combined measurement of the c-erbB-2 protein in breast carcinoma tissues and sera is useful as a sensitive tumor marker for monitoring tumor relapse.

c-erbB-2 protein levels in tissue extracts and sera were determined in a retrospective analysis of 158 patients who underwent surgical resection of breast carcinoma by means of a sandwich enzyme immunometric assay (EIA) using monoclonal antibodies (MAbs) directed to the extracellular domain of the c-erbB-2 oncogene protein (ErbB-2). In the analysis of tissue extracts, 48 samples (30.3%) showed ErbB-2 levels exceeding 18.0 ng/mg protein (group A), while in 110 samples these levels were below 18.0 ng/mg protein (group B). Immunohistochemical examination of resected tissues using anti-c-erbB-2 antibody revealed positive staining in 93.8% (45/48) in group A and 13.6% (15/110) in group B (p < 0.00001). The proportion of patients who preoperatively showed a serum ErbB-2 value above 5.4 ng/ml was 52.1% (25/48) in group A and 10.0% (11/110) in group B (p < 0.00001). Thus, the level of ErbB-2 in tissue extracts was significantly associated with immunohistochemistry and ErbB-2 levels in preoperative sera. During follow-up, 48 patients (30.3%) developed recurrent disease: 17 in group A (35.4%) and 31 in group B (28.2%). From an ROC analysis based on the postoperative serum ErbB-2 levels in patients either with or without relapse, the cutoff value of serum ErbB-2 for tumor relapse was determined to be 6.5 ng/ml. The sensitivity of serum ErbB-2 in patients with relapsed breast cancer was 58.3% (21/36) overall, 84.6% (11/13) in group A and 43.5% (10/23) in group B. In the analysis of serum samples taken before relapse, 90.9% (10/11) of the subjects in group A and 26.7% (4/15) of those in group B were shown to be positive for serum ErbB-2. Serum ErbB-2 in group A was a more sensitive marker than other tumor markers such as CEA, CA15-3, and NCC-ST-439. Thus, the determination of ErbB-2 in tissue extracts of breast carcinoma may be useful for assessing c-erbB-2 protein expression in the primary tissue and indicates that serum ErbB-2 may be a sensitive marker for monitoring tumor relapse.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed2000

A potent inhibitor of inducible nitric oxide synthase, ONO-1714, a cyclic amidine derivative.

(1S,5S,6R,7R)-7-Chloro-3-imino-5-methyl-2-azabicyclo[4.1.0]heptane hydrochloride (ONO-1714), a novel cyclic amidine analogue, inhibits human inducible nitric oxide (iNOS) with a K(i) of 1.88 nM and rodent iNOS with similar potency in vitro. ONO-1714 was found to be 10-fold selective for human iNOS over human endothelial NOS (ecNOS). When the inhibitory activity of ONO-1714 was compared for iNOS, it was found to be 451-fold and >20,000-fold more potent than L-NMMA and aminoguanidine (AG), respectively. In terms of human iNOS selectivity, ONO-1714 was approximately 34- and 2-fold more selective for iNOS than L-NMMA and AG, respectively. ONO-1714 inhibited the LPS-induced elevation of plasma nitrate/nitrite in mice with an ID(50) value of 0.010 mg/kg, s.c. The maximum tolerated dose of ONO-1714 was 30 mg/kg, i.v. Thus, ONO-1714 represents one of the most potent iNOS inhibitors in vitro and in vivo to date and has great potentials for use as an inhibitor for clarifying the pathophysiological roles of iNOS and for use as a therapeutic agent.

Amidines↗

PubMed2000

c-erbB-2 protein overexpression and p53 immunoreaction in primary and recurrent breast cancer tissues.

BACKGROUND AND OBJECTIVES: We investigated whether expression levels of c-erbB-2 and p53 proteins in breast cancer tissues differ in primary and metastatic lesions. METHODS: Immunohistochemical staining or sandwich enzyme immunoassay was used to determine expression levels of c-erbB-2 and p53 proteins in 42 breast cancer samples from 21 patients. Estrogen (ER) and progesterone receptors (PgR) were also measured by enzyme immunoassay in each case. All patients had undergone radical surgery for primary tumors and surgical resection of asynchronous metastatic lesions. Thirteen patients (62%) were premenopausal and 14 (67%) received postoperative adjuvant therapies. Median disease-free survival time was 26 months (range, 5-104). The resected metastatic lesions included 1 in the liver, 3 in the lung, and 3 in the supraclavicular lymph nodes. The remaining 14 were local skin lesions. RESULTS: There was no difference in the positivity rate of c-erbB-2 (38%: 8/21) and p53 (39%: 7/18) expression between the primary tumors and the recurrent lesions. In addition, no discordant c-erbB-2 or p53 expression was observed between the primary tumors and their respective metastatic lesions. Positivity rates for ER and PgR were 50% (10/20) and 60% (12/20) for the primary tumors, but only 25% (5/20) and 30% (6/20) for the recurrent lesions, respectively (P = 0. 19 for ER and P = 0.11 for PgR). CONCLUSIONS: c-erbB-2 and p53 expression levels in breast cancer cells were almost unchanged as the disease progressed and/or in response to adjuvant therapies, regardless of the hormone receptor status.

Adult↗

PubMed2000

Treatment of noninvasive carcinoma: fifteen-year results at the National Cancer Center Hospital in Tokyo.

The introduction of screening mammography (MMG) will lead to increased detection of preclinical early breast cancer in Japan. It has become more important to understand the nature of these lesions. We tried to elucidate the long term prognosis and clinical and pathological characteristics of noninvasive cancers. A total of 336 (5.4%) ductal carcinoma in situ (DCIS) and 32 (0.5%) lobular carcinoma in situ (LCIS) were diagnosed in 6 277 breast carcinomas at the National Cancer Center Hospital from 1962 to 1995. Most (80%) LCIS occurred in premenopausal women. LCIS has significantly higher bilaterality than that of DCIS. Local recurrence occurred in approximately 10% of patients after breast conserving surgery for DCIS and LCIS. Four patients died of breast carcinoma, which were initially diagnosed as noninfiltrating carcinoma. The 15-year cause specific survival rates of patients with DCIS and LCIS were 98.5 % and 100 %, respectively.

Breast Neoplasms↗

PubMed2000

Seven cases of breast cancer recurrence limited to the central nervous system without other visceral metastases.

We report 7 rare cases of recurrent breast cancers who presented with central nervous system (CNS) metastases as the initial relapse site without any other organ metastases. The average age of the patients at surgery was 42.6 years old of age (median 45:range 32-60), and 6 of the 7 cases (86%) were premenopausal. The mean disease-free period was 25.7 months (median 22, range 2-60 months). The primary tumors were all invasive ductal carcinomas. The estrogen receptor and progesterone receptor status of the 3 tumors available for study were all negative. The metastatic CNS lesions included the cerebrum (4 cases), cerebellum, cervical spinal cord, and meninges. In 6 out of these 7 cases (86%), the CNS metastasis was the initial recurrent lesion. Multidisciplinary treatments including surgery, radiotherapy and systemic or intrathecal chemotherapy were given. Although the mean survival time from clinical manifestations of the metastases of the 4 deceased patients was 20 months (median 20.5; range 6-33), one patient treated with surgery and radiotherapy is been still alive18 years later. These cases were also notable for the fact that the only metastatic site was in the CNS only during the entire clinical course, except for 2 cases, one with ocular adnexa metastasis, and the other with cervical lymph node metastasis. Premenopausal patients with negative hormone receptor status are more likely to develop this type of recurrence, regardless of the histological type. It is necessary to pay attention to neurological symptoms and signs during follow-up of breast cancer patients.

Adult↗

PubMed2000

Evaluation of histopathological criteria for identifying node-negative breast cancer with high risk of early recurrence in the NSAS-BC protocol study.

BACKGROUND: The histopathological criteria for high-risk node-negative primary breast cancer stated in the National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) protocol were used to grade a consecutive series of 488 cases at our hospital. METHODS: To validate the criteria retrospectively, we examined the histological features of node-negative primary breast cancers which showed early relapse within 2 years after surgical therapy. RESULTS: Early relapse occurred in 12 patients, distant metastases in 11, and local recurrence in one. Among 278 cases followed for up to 1.5 years or longer, early systemic relapse was detected in 10 (5.8%) of 172 higher-grade tumors (9 invasive ductal carcinomas of nuclear grade 3 and one invasive ductal carcinoma of nuclear grade 2) and one stromal cell sarcoma. Among the 115 low-risk tumors, only one case (0.9%) of invasive ductal carcinomas with nuclear grade 1 showed early local recurrence. Early relapse occurred in only one (1.5%) of 67 tumors with an invasive component of 1.0 cm but in 11 (5.2%) of 211 tumors with an invasive component of 1.1 cm. The recurrence rate increased to 9.3% (8/86) when tumor invasion was 2.1 cm. In 12 cancers showing recurrence, strand structure, large central acellular zones, and squamoid features were histologically observed in four, two, and three cases, respectively. The present results confirmed the reported tendency of correlation between strand pattern and bone metastasis, large central acellular zones and lung and brain metastasis, and squamoid features and lung metastasis. Synchronous bilateral and unilateral multiple cancers were characterized by lower nuclear grades. CONCLUSIONS: At our hospital, the criteria used in the NSAS-BC protocol were demonstrated to identify node-negative cancers with high risk of early recurrence at a hospital level. To further identify groups prone to recurrence, longer follow-up would be necessary. In addition, the histological criteria could be improved to correlate with patient outcome more accurately.

Adult↗

PubMed2000

Atypical medullary carcinoma of the breast with cartilaginous metaplasia in a patient with a BRCA1 germline mutation.

We examined a 34-year-old premenopausal woman who had noticed a left-breast lump a month previously. She had no past history of malignancies but had a family history of breast and ovarian cancers. Her mother had suffered from ovarian cancer when aged 47 years and had died of the disease at age 52. The younger two of the patient's four aunts had developed breast cancer when they were 37 and 48 years old. A physical examination showed an ill-defined mass, 1.5 cm in diameter, located in the upper outer quadrant of the patient's left breast. Mammography revealed diffuse microcalcification in both breasts but ultrasonography revealed an irregular tumorous lesion only in the left breast. Aspiration breast cytology revealed adenocarcinoma of the left breast. Modified radical mastectomy of the left breast and excision of a biopsy specimen from the right breast were carried out simultaneously. Histopathologically the left-breast tumor was an atypical medullary carcinoma with cartilaginous metaplasia, of histological grade 3, and the right-breast specimen showed fibrocystic changes with atypical ductal hyperplasia. Estrogen receptors were positive, but progesterone receptor was not detected on the tumor cells, which were immunopositive for nuclear p53 although c-erbB-2 overexpression was not observed. A nonsense germline mutation of the BRCA1 gene (exon5) was detected. The patient has been well since the operation (10 months). These findings may provide useful information about the carcinogenesis and biological behavior of BRCA1-associated breast cancers.

Adenocarcinoma↗

PubMed2000

Changes in findings of mammography, ultrasonography and contrast-enhanced computed tomography of three histological complete responders with primary breast cancer before and after neoadjuvant chemotherapy: case reports.

We report the changes in the findings of imaging examinations (mammography, ultrasonography and contrast-enhanced computed tomography) of three patients with primary breast cancer before and after neoadjuvant chemotherapy, who obtained histologically complete responses after the chemotherapy. The neoadjuvant chemotherapy consisted of four cycles of doxorubicin and docetaxel. All patients were clinically judged as partial responders, because of the remaining tumorous lesions in the imaging examinations. However, these tumorous lesions could be related to the chemotherapy-induced fibrosis and tumor necrosis or the remaining fibrocystic changes. In this study, it was considered very difficult to estimate the extent of residual tumors accurately in patients with primary breast cancer after neoadjuvant chemotherapy by any type of imaging examination.

Aged↗

PubMed2000

Large, central acellular zones indicating myoepithelial tumor differentiation in high-grade invasive ductal carcinomas as markers of predisposition to lung and brain metastases.

High-grade invasive ductal carcinomas (IDCs) of the breast with large, central acellular zones on their cut surfaces are usually associated with the myoepithelial immunophenotype of carcinoma cells, which includes the expression of S-100 protein, alpha-smooth muscle actin, and keratin 14. To clarify the clinical significance of these features of IDCs, the authors compared the incidence of the myoepithelial immunophenotype immunohistochemically, patient prognosis, and metastatic sites of the tumor between 20 high-grade IDCs with large, central acellular zones and 40 control high-grade IDCs without these zones. The myoepithelial immunophenotype was detected in 16 IDCs (80%) with large, central acellular zones but in only seven IDCs (18%) without. The risk ratio of metastasis, especially in the brain and lung, and death from cancer were significantly higher (p = 0.0096 and p = 0.030) for the 20 IDCs with large, central acellular zones than for those without by Cox's univariate analysis. Using Cox's multivariate analysis, large, central acellular zones in IDCs were an indicator of high risk of brain and lung metastases and of death by cancer independent of nodal status and tumor size. Examination of large, central acellular zones and myoepithelial immunophenotype in high-grade IDCs appears helpful in predicting patient prognosis and preferential metastatic sites of the tumors.

Actins↗

PubMed2000

Enhancement of the cAMP-induced apolipoprotein-mediated cellular lipid release by calmodulin inhibitors W7 and W5 from RAW 264 mouse macrophage cell line cells.

Apolipoprotein (apo) A-I generates high-density lipoprotein (HDL) by removing cellular cholesterol and phospholipid on the interaction with cells as a main source of plasma HDL. The reaction is induced by dibutylyl cyclic (dbc) adenosine monophosphate (AMP) in RAW 264, mouse macrophage cell line cells, and we investigated its pharmacologic modulation using this cell model. Release of cellular cholesterol and choline phospholipid by apoA-I was increased 9.9 and 4.2 times, respectively, by pretreatment of the cells with 300 microM dbcAMP for 24 h. Calmodulin inhibitors, W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide) and W5 (N(6-aminohexyl)-1-naphthalenesulfonamide), increased the apoA-I-mediated lipid release by 3 times from the dbcAMP-treated cells. The optimal drug concentrations (80 and 160 microM for W7 and W5, respectively) were not parallel with those reported for in vitro calmodulin inhibition (IC50, 28 and 240 microM for W7 and W5, respectively, toward phosphodiesterase activity), and in fact 40 microM W7 showed much stronger intracellular calmodulin inhibition than did 300 microM W5 using S7AAS2, a fluorescent peptide probe. Other calmodulin inhibitors such as amitriptyline, chlorpromazine, and trifluoperazine showed no effect on the apoA-I-mediated cholesterol release. In contrast to these results, neither dbcAMP nor W7 influenced the diffusion-mediated nonspecific cholesterol efflux to lipid microemulsion. We concluded that W7 and W5 increased the interaction of apoA-I with RAW 264 cells to generate more HDL. The effect did not seem directly correlated to their cal modulin inhibition or modulation of cAMP and protein kinase C.

Animals↗

PubMed2000

Effects of pimobendan and EGIS 9377, cardiotonic agents, and OG-VI, a nucleoside-nucleotide mixture, administered during reperfusion after ischemia on stunned myocardium in dogs.

BACKGROUND: Pimobendan is a so-called calcium sensitizer that exerts a positive inotropic action. EGIS 9377 is synthesized as a calcium sensitizer. OG-VI is a nucleoside-nucleotide mixture that ameliorates the myocardial dysfunction (myocardial stunning) after ischemia. OBJECTIVE: To determine whether administration of these agents after the onset of reperfusion after ischemia improves the condition of stunned myocardium. METHODS: Dogs anesthetized with pentobarbital were subjected to 20 min ligation of left anterior descending coronary artery and then 60 min reperfusion. The corresponding vehicle, 0.3 and 1 mg/kg pimobendan, or 1 and 3 mg/kg EGIS 9377 was injected intravenously 30 min after the onset of reperfusion. Saline solution or 1.2 mumol/kg per min OG-VI was infused for 30 min, starting 30 min after the reperfusion. Shortening of myocardial segment was measured by sonomicrometry. The tissue levels of energy and carbohydrate metabolites in the 60 min-reperfused hearts were determined. RESULTS: Shortening of myocardial segments significantly decreased during ischemia, and returned toward preischemic level after reperfusion for all groups, although the contractile dysfunction still remained. Injections and infusion of pimobendan, EGIS 9377, and OG-VI after the onset of reperfusion ameliorated the contractile dysfunction. Systemic vascular resistance was decreased by administrations of pimobendan and OG-VI. The levels of high-energy phosphates in 60 min-reperfused heart were not changed by either treatment. CONCLUSION: Administration of pimobendan, EGIS 9377, and OG-VI ameliorate the myocardial contractile dysfunction after ischemia even when these agents are administered after the onset of reperfusion. The increase in contractile function due to these agents did not worsen the myocardial energy balance.

Adenosine Triphosphate↗