Immunoreactive copper-zinc superoxide dismutase in damaged human myocardium.

The myocardium in 50 autopsy cases was studied using immunostaining for copper-zinc superoxide dismutase (CuZn-SOD) and standard histochemical procedures. Mucinous degeneration observed in 42 cases showed moderately enhanced expression of immunoreactive CuZn-SOD in lesions which were stained strongly by periodic acid-Schiff but negative with Heidenhain iron-hematoxylin (HIH), von Kossa and luxol fast blue (LFB) stains, whereas coagulation necrosis in 4 cases revealed almost identical immunostaining for CuZn-SOD and HIH to that of contraction band necrosis, i.e. strongly positive HIH staining but negative immunostaining. Basophilic alteration of the myocardial cells in sections fixed with 4% formalin in 2% calcium acetate was seen in 29 cases, being identified frequently in isolated cells as well as in several foci varying considerably in size. This type of alteration demonstrated significantly enhanced expression of immunoreactive CuZn-SOD and was strongly positive with von Kossa and LFB stains. The present study indicates that the myocardium can be affected by free radicals produced in any organ of the body, and that subsequently, insoluble phospholipids react with calcium ions in the fixative and accumulate in the basophilic sarcoplasm.     

‘Tissue’ transglutaminase release from apoptotic cells into extracellular matrix during human liver fibrogenesis

Enhanced apoptosis characterizes several pathologies affecting human liver. This study sought to determine whether apoptosis is involved in the formation of fibrotic lesions occurring in hepatic disease. The expression of Bcl-2 was analysed, and of ‘tissue’ transglutaminase (tTG), a cross-linking enzyme which recent evidence suggests plays a role in the formation of fibrotic lesions in experimental settings. Regardless of the degree of liver injury, tTG abnormally accumulated in the liver cells adjacent to fibrotic tissue. Many cells showing DNA fragmentation and morphological features of apoptosis were also observed near fibrotic lesions. Bcl-2 was detected predominantly in infiltrating lymphocytes within the liver tissue. Marked staining for both tTG protein and chromatin was also observed in the acellular fibrotic tissue, which suggested an active release of intracellular macromolecules from the dying cells into the extracellular matrix. This study indicates that fibrogenesis in the liver is associated with the release of tTG from dying cells. By cross-linking extracellular matrix proteins, this enzyme might play a role in the formation of fibrotic lesions. Copyright © 1999 John Wiley & Sons, Ltd.     

DNA fragmentation of human infarcted myocardial cells demonstrated by the nick end labeling method and DNA agarose gel electrophoresis.

Myocardial tissue taken from 19 autopsy cases of myocardial infarction were examined both by the nick and labeling method (NELM) and by DNA agarose gel electrophoresis in order to demonstrate the localization of cells with fragmented DNA and to confirm the internucleosomal cleavage of DNA biochemically. The nuclei corresponding to those with the histological features of acute myocardial infarction in hematoxylin and eosin (H&E)-stained sections were stained strongly positive with the nick end labeling method. Myocardial cells corresponding to those with nick end labeling method-stained nuclei, on the other hand, had mostly pyknotic and karyolytic nuclei and some unremarkable nuclei, even nuclear ghosts, and showed degenerated cytoplasm, including contraction band necrosis in H&E-stained preparations. The agarose gel electrophoresis of DNA extracted from the corresponding areas mentioned above showed the ladder pattern of internucleosomal cleavage characteristic of apoptosis. The present study revealed that infarcted myocardial cells with nuclear outlines, even nuclear ghosts, showed a distinct DNA fragmentation with the ladder pattern of internucleosomal cleavage. It is concluded from this study that the damaged myocardial cells of acute myocardial infarction represent a coagulation necrosis having the biochemical nature of apoptosis.     

The role of antitissue transglutaminase assay for the diagnosis and monitoring of coeliac disease: a French-Italian multicentre study

AIMS: Tissue transglutaminase (tTG) was recently identified as the major autoantigen in coeliac disease. The aim of this multicentre study was to evaluate the impact of a new immunoenzymatic assay for the detection of IgA anti-tGT antibodies. METHODS: Seventy four Italian and French clinical laboratories participated in this study; anti-tTG IgA with an enzyme linked immunosorbent assay (ELISA) method using guinea pig liver extract as the coating antigen, anti-endomysium IgA autoantibodies (EMA), and total serum IgA were determined in 7948 patients, 1162 of whom had coeliac disease (737 untreated cases and 425 on a gluten free diet). A proportion of the sera were then sent to a reference laboratory for anti-tTG retesting with an ELISA method using recombinant human tTG antigen. RESULTS: Seven thousand four hundred and fifty eight (93.8%) sera were EMA/antiguinea pig tTG concordant (positive or negative); 490 (6.2%) were non-concordant. The sensitivity of EMA and antiguinea pig tTG in the 737 untreated patients with coeliac disease was 92.1% and 94.8%, respectively, and the specificity was 99.8% and 99.2%, respectively. Retesting of the discordant sera showed that of the 162 sera classified as EMA negative/antiguinea pig tTG positive, only 49 were positive for human recombinant anti-tTG, and that 39 of these were also EMA positive. Furthermore, of the 36 sera classified as EMA positive/antiguinea pig tTG negative, only two were confirmed as EMA positive. CONCLUSIONS: The antiguinea pig tTG assay is more sensitive but less specific than EMA, whereas the antihuman recombinant tTG assay is far more specific and just as sensitive as antiguinea pig tTG. Testing for EMA presents considerable interpretative problems and is difficult to standardise.     

Down-regulation of tTG expression by RNAi inhibits HSC proliferation and attenuates liver fibrosis

Purpose: Expressed in hepatic stellate cell (HSC), tTG is involved in fibrotic diseases including human hepatic fibrosis by promoting the cross-linking of ECM and participating in the initiation and/or progression of liver fibrosis. The purpose of this study is to identify whether depletion of tTG could attenuate liver fibrosis. Methods: In this study, primary hepatic stellate cells were isolated, purified, and cultured from rat. Expression of tTG gene was downregulated by lentivirus-mediated RNAi, and the effects on the activation, proliferation and apoptosis of HSC were investigated both in vitro and in vivo. Results: Lentivirus-mediated RNAi successfully reduced the endogenous expression of tTG in cultured cells. The down-regulation of tTG markedly inhibited the proliferation of HSC and attenuated the synthesis of Collagen-1. The downregulation of tTG also markedly reduced the level of tTG and hydroxyproline induced by CCl₄ in rat livers at week 8 and week 12 after injection of CCl₄. Conclusions: In summary, tTG plays an important role in liver fibrosis. Lentivirus-mediated downregulation of tTG showed a potential anti-fibrosis effect in rats, providing new evidence that the involvement of tTG in HSC activation, also suggesting that RNAi-directed targeting of tTG may be used as a potent and specific therapeutic tool for the treatment of liver fibrosis, especially in inhibiting the activation of HSC.     

Presence of Tissue Transglutaminase in Granular Endoplasmic Reticulum is Characteristic of Melanized Neurons in Parkinson's Disease Brain

Parkinson's disease (PD) is characterized by the accumulation of α‐synuclein aggregates and degeneration of melanized neurons. The tissue transglutaminase (tTG) enzyme catalyzes molecular protein cross‐linking. In PD brain, tTG‐induced cross‐links have been identified in α‐synuclein monomers, oligomers and α‐synuclein aggregates. However, whether tTG and α‐synuclein occur together in PD affected neurons remains to be established. Interestingly, using immunohistochemistry, we observed a granular distribution pattern of tTG, characteristic of melanized neurons in PD brain. Apart from tTG, these granules were also positive for typical endoplasmic reticulum (ER)‐resident chaperones, that is, protein disulphide isomerase, ERp57 and calreticulin, suggesting a direct link to the ER. Additionally, we observed the presence of phosphorylated pancreatic ER kinase (pPERK), a classical ER stress marker, in tTG granule positive neurons in PD brain, although no subcellular colocalization of tTG and pPERK was found. Our data therefore suggest that tTG localization to granular ER compartments is specific for stressed melanized neurons in PD brain. Moreover, as also α‐synuclein aggregates were observed in tTG granule positive neurons, these results provide a clue to the cellular site of interaction between α‐synuclein and tTG.     

Expression of proliferation and apoptotic markers in human placenta during pregnancy

Trophoblast has unique properties in relation to its wide range of metabolic, endocrine and angiogenic functions. Trophoblastic cells invade endometrium and adjacent myometrium in a way that is imitated by malignant tumours. The aim of the present study was to analyse the expression of markers of proliferation and apoptosis in trophoblastic cells in normal human placenta during pregnancy. A total of 22 placentas, 12 of which were obtained from curettage and induced legal abortion and 10 placentas obtained from normal deliveries or caesarean sections were included in this study. Proliferation markers were strongly expressed in cytotrophoblast in early stages of gestation. In late term placentas, a distinct decrease in expression of these markers was observed. Syncytiotrophoblast was negative for proliferation markers in all placentas. Positive immunostaining for bcl-2, an anti-apoptotic marker, was observed only in syncytiotrophoblastic cells in first-trimester but also in third-trimester placentas. Cytotrophoblast and stromal mesenchymal cells of chorionic villi were negative for bcl-2. Expression of bcl-2 protein in syncytiotrophoblast may be one of the major factors preventing these structures from early cell death, which is indispensable for the maintenance of physiological pregnancy.     

DEVELOPMENTAL REGULATION OF TISSUE TRANSGLUTAMINASE DURING HUMAN PLACENTATION AND EXPRESSION IN NEOPLASTIC TROPHOBLAST

The expression of tissue transglutaminase (tTG) was studied during the formation of the normal human placenta and in molar pregnancies and choriocarcinoma, in order to correlate its expression with the functional characteristics of the recognized trophoblast cell types. tTG expression was found to be developmentally regulated. Before 6–7 weeks' gestation, only the chorionic villous cytotrophoblast expresses tTG. Thereafter the overlying syncytiotrophoblast becomes positive. tTG expression is gradually downregulated in the intermediate trophoblast cells emerging from the tips of the chorionic villi invading the uterine tissue. In the decidual wall, the intermediate trophoblast does not express tTG, whereas scattered syncytial cells, the placental bed giant cells, express tTG. Villi from complete hydatidiform mole (CHM) show tTG expression in both the cyto- and the syncytiotrophoblast. The intermediate trophoblast cells from CHM show heterogeneous tTG expression, with a majority of negative cells, whereas extravillous syncytia always express tTG. In choriocarcinoma, the tumour cells show heterogeneous tTG expression, with a majority of positive cells. Analysis of tTG protein and mRNA in placental extracts by Western and Northern blotting did not provide evidence for expression of the truncated form of tTG found in some cell types. The regulated expression of tTG in the normal placenta suggests that the enzyme is involved in important trophoblastic functions and may participate in the control of invasion. © 1997 by John Wiley & Sons, Ltd.     

CD146阳性亚群有作为软骨组织工程种子细胞的应用潜力

文题释义：CD146：也称为MUC18,MCAM,Mel-CAM或S-Endo1,是一种跨膜糖蛋白,同时属于免疫球蛋白超级家族的一员。在人体组织中,CD146阳性细胞被认为是微血管的壁细胞,其具有较强的增殖、迁移及自我更新能力。 组织工程种子细胞：组织工程包括3个关键要素——种子细胞、支架和活性因子,其中种子细胞应具有良好的细胞活性、增殖能力、分化及合成基质等生物功能。 背景：再生医学的发展、组织工程技术的出现为软骨缺损重建提供了新的解决思路。在组织工程中,间充质干细胞是应用广泛的种子细胞,然而干细胞作为一个异质性的细胞群体其不同亚群发挥着不同的功能。因此,应用间充质干细胞关键功能亚群进行软骨修复具有广泛应用前景。 目的：从人脂肪间充质干细胞中分离出CD146阳性亚群细胞,验证其生物学特性及其作为软骨组织工程种子细胞的潜力。 方法：人脂肪间充质干细胞由浙江金时代生物技术有限公司提供,通过流式细胞术对人脂肪间充质干细胞表面标志物进行鉴定,应用免疫磁珠分选方法从人脂肪间充质干细胞中分选出CD146阳性表达的细胞亚群。通过基因芯片检测技术及生物信息学分析技术揭示2种细胞的分子特性;体外诱导2种细胞成软骨分化并进行鉴定;冻存复苏前后检测2种细胞的细胞活性及凋亡情况。 结果与结论：①人脂肪间充质干细胞表达高水平干细胞相关标志物CD73、CD90,不表达造血干细胞相关标志物CD34、CD45、HLA-DR;②生物信息分析结果表明CD146阳性亚群细胞与脂肪间充质干细胞相比在炎症通路及骨骼肌肉系统疾病有不同功能;③CD146阳性亚群细胞能够成球软骨分化,并且其成软骨分化能力要优于人脂肪间充质干细胞;④CD146阳性亚群细胞复苏后凋亡情况和活性均要优于人脂肪间充质干细胞;⑤结果表明,CD146阳性亚群细胞具有良好的成软骨分化潜力,是一种具有前景的软骨组织工程种子细胞。 ORCID: 0000-0003-4210-4708(眭翔) 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

A new sensitive cardiac Troponin T rapid test (TROPT) for the detection of experimental acute myocardial damage in rats.

Cardiac Troponin T (cTnT) is a cardiac structural protein which is released in the circulation during myocardial cell damage. In this study we addressed the question of whether beta-sympathomimetic induced myocardial cell damage in rats can be detected in blood by the TROPT sensitive rapid test strip which is primarily manufactured for the detection of acute myocardial infarction in humans. Sixteen male rats and 16 female animals were treated once with orciprenalinesulphate s.c. to induce tachycardia. The control group which consisted of 16 rats of both sexes received vehicle (physiological saline). The heart rate of two groups of 10 rats (5 of each sex) was measured after orciprenaline or saline treatment. After 1-2 hours we could demonstrate an increased heart rate in the orciprenaline group. Furthermore in this group we could show elevated cTnT levels in peripheral blood measured with the enzyme-linked immunosorbent assay (ELISA) Enzymun-Test Troponin T for troponin T and a positive reaction of the TROPT sensitive test strip. When compared with the ELISA method, the test strip showed a positive reaction at cTnT levels of 0.64 ng/ml upwards. After 24 hours and 96 hours half of the animals were sacrificed for histological examination of the heart tissue. After 24 hours all orciprenaline treated and examined animals showed myofibrillar degeneration of the myocardial cells. The second half of the animals sacrificed 96 hours after treatment with the sympathomimetic drug showed reparative fibrosis of the myocardium. All animals with myocardial damage due to orciprenaline showed a positive test strip result 2 hours after injection. Twenty-four hours after injection only 8 of the 16 animals had a positive test strip result although histological cell damage was demonstrated. All animals treated with physiological saline had negative results of the test strip and showed no signs of myocardial cell damage. We conclude that the TROPT sensitive test strip is a rapid and reliable screening tool for detecting myocardial cell alteration in rats without the need of an expensive and time-consuming ELISA procedure if it is used in early phases of the experiment because all animals with myocardial damage were identified by the test 2 hours after induction of the damage. If the time range between the induction of the injury and the use of the test strip or the ELISA procedure is too wide, in our experiments 24 h, false negative results may occur.     

经bcl-2基因修饰的骨髓间充质干细胞移植对缺血性心功能不全兔心功能及血管新生的影响

目的:探讨经bcl-2基因修饰的骨髓间充质干细胞(BMSCs)移植对急性心肌梗死家兔心肌细胞凋亡、血管再生及心功能的影响。方法:体外分离、培养、纯化兔BMSCs,分别转染腺病毒及重组腺病毒-Bcl-2。结扎兔冠状动脉前降支制作心肌梗死(MI)模型,2周后于心梗边缘区分别注射等量的腺病毒-Bcl-2-BMSCs(MI+Bcl-2-BMSCs组)、腺病毒-BMSCs(MI+BMSCs组)及DMEM液(MI组)。细胞移植4周后经超声测定心功能;荧光显微镜观察BMSCs的存活及分布;TUNEL法检测心肌细胞凋亡;real-time PCR检测VEGF mRNA表达;免疫组化染色法检测CD31表达,计算新生毛细血管密度。以上数据分别与心功能进行相关性分析。结果:与MI组相比,MI+Bcl-2-BMSCs组和MI+BMSCs组的心功能改善、细胞凋亡率降低、VEGF mRNA表达增多、毛细血管密度增加,其中MI+Bcl-2-BMSCs组的变化更为显著(P0.05)。相关性分析显示左室射血分数与心肌细胞凋亡率呈负相关;与VEGF mRNA的表达量及毛细血管密度呈正相关(P0.01)。结论:经bcl-2基因修饰的BMSCs移植可显著减少缺血性心功能不全兔心肌细胞凋亡、促进血管再生、改善心功能。     

Detection of human immunodeficiency virus type 1 RNA by in situ hybridization in oral mucosa epithelial cells from anti-HIV-1 positive patients

Several in vitro studies have shown that HIV-1 can infect CD4 negative epithelial cells of different origin including normal human oral keratinocytes, but whether this infection of mucosal epithelial cells occurs in vivo is still unclear. In this report, the presence and cell types infected by HIV-1 in paraffin embedded oral mucosa biopsies from 17 anti-HIV-1 positive patients have been examined by in situ hybridization and immunohistochemistry. As controls, oral mucosa biopsies from eight patients without HIV-1 infection markers were also analyzed. The results showed that 8 out of the 17 anti-HIV-1 positive patients had HIV-1 RNA detectable in plasma. Positive hybridization signals were observed in the mucosa biopsies from 14 of the 17 anti-HIV-1 patients (82.3%). The mean percentage of cells showing HIV-1 RNA was 2.64% +/- 1.77% (range: 1% to 5.5%). No differences in the mean percentage of HIV-1 infected cells were found between patients with and without HIV-1 RNA in plasma (3.01% +/- 1.57% vs. 3.4% +/- 1.27% respectively), or between untreated patients and patients under antiretroviral therapy (2.83% +/- 1.63% vs. 3.42% +/- 1.29% respectively). Immunohistochemical detection of S-100 antigen, cytokeratin and CD4 showed that hybridization signals appeared in cytokeratin positive cells and CD4 positive cells but not in S-100 positive cells. In conclusion, this study has demonstrated that HIV-1 infects and replicates in oral mucosa epithelial cells in vivo and that these cells could represent a reservoir of the virus that may escape to the currently used antiretroviral therapy.     

APOPTOSIS OF EPITHELIAL CELLS IN VIVO INVOLVES TISSUE TRANSGLUTAMINASE UPREGULATION

Tissue transglutaminase (tTG) has been implicated in producing some of the cytoplasmic changes seen in apoptosis in vitro . The aim of this study was to investigate tTg protein and mRNA expression in three different epithelia induced experimentally in vivo to undergo apoptosis. They were castration-induced prostatic atrophy with subsequent testosterone-induced prostatic hyperplasia, apoptosis induced by mild ischaemia in the liver from ligation of the distal portal vein, and hydronephrosis due to ureteric ligation. tTG protein was consistently expressed with apoptosis in all three models, whereas the mRNA levels were different in each model. tTG mRNA was elevated in the later stages of hydronephrosis, when apoptosis was still occurring. In the prostate, the levels remained unchanged during the process of involution, but increased early in association with testosterone-induced proliferation. In the liver model, the mRNA levels remained unchanged. tTG protein expression may be a universal feature of apoptosis of epithelial tissues, whereas changes in tTG mRNA expression appear to be unique to each apoptosis-inducing agent.     

Atorvastatin inhibits myocardial cell apoptosis in a rat model with post-myocardial infarction heart failure by downregulating ER stress response

Objective: To determine the effect of atorvastatin on rat heart failure after myocardial infarction and to investigate the underlying mechanism of atorvastatin-mediated myocardium protection.Methods: Thirty-eight rats were randomly divided into three groups: a heart failure model group (model group), a heart failure plus atorvastatin treatment group (atorvastatin group) and a sham-surgery group (control group). The rat heart failure model was established by ligation of the left anterior descending of coronary arteries (LADs). Changes in hemodynamics parameters were recorded after the final drug administration. Plasma brain natriuretic peptide (BNP) concentration was determined by enzyme-linked immunosorbent assay (ELISA). Histological diagnosis was achieved by hematoxylin and eosin (H&E) and Masson''s trichrome staining. The expressions of 78kDa glucose-regulated protein 78 (GRP78), caspase-12 and C/EBP homologous protein (CHOP, also known as GADD153) in myocardial cells and cultured cardiac myocytes were examined by Western blot. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to evaluate myocardial cell apoptosis, and flow cytometry was performed to examine the cell apoptosis of cultured cardiac myocytes.Results: In the atorvastatin group, myocardial cells were lined up more orderly and myocardial fibrosis level was decreased compared to the model group. The expressions of GRP78, caspase-12 and CHOP in myocardial cells were decreased in atorvastatin group. Moreover, in the atorvastatin-treated group the cell apoptosis rate was reduced and the endoplasmic reticulum (ER) stress was activated in response to heart failure and angiotensin II(Ang II) stimulation.Conclusions: By down-regulating GRP78, caspase-12 and CHOP expressions in myocardial cells in rat heart failure after myocardial infarction, atorvastatin treatment decreased the apoptosis of myocardial cells, suggesting the possible mechanism by which atorvastatin functions in protecting against heart failure.     

CATECHOLAMINE-INDUCED CARDIOPATHY ACCOMPANIED WITH PHEOCHROMOCYTOMA

Catecholamine-induced cardiopathy accompanied with pheochromocytoma in a 28-year-old female including two other cases are reported and the relationship between pheochromocytoma and cardiac change was also discussed. In the first case, catecholamine in the tumor tissue showed extremely high values; 94.22 p g /g of adrenaline and 6,332.42 p g /g of noradrenaline. Histologically, myocardial degeneration and inflammatory cell infiltration between myocardial fibers were noted. In the second case, hypertrophied heart showed focal degeneration of myocardial fibers with a few inflammatory cells in the stroma. The third case showed increase of heart weight, but neither myocardial degeneration nor inflammatory infiltration was noted except for moderate myocardial hypertrophy. Although the cause of difference in degree of myocardial changes is not yet clear, it may be attributed to the blood cathecholamine level and/or duration of disease and/or area examined. A relative hypoxia theory is accepted for the mechanism of catecholamine-induced cardiopathy. This theory is supported by more severe lesions being noted near to the cardiac apex corresponding to peripheral coronary circulation.     

Secretory carcinoma coexistent with mucinous carcinoma in the breast. Report of a case

Secretory carcinoma and mucinous carcinoma were found to coexist in the breast of a 67-year-old post-menopausal woman, although the tumors were separated by a thin fibrous septum. Histochemically, intra- and extracellular secretory materials in both carcinomas were strongly positive for alcian blue, PAS and mucicarmine staining, but immunohistochemically negative for alpha-lactalbumin and CEA. Membrane-bound intracytoplasmic vacuoles showing emiocytosis were observed in both the secretory and mucinous carcinomas by electron microscopy. No differences were observed between the tumor cells of secretory carcinoma and those of mucinous carcinoma by histochemistry, immunohistochemistry and electron microscopy. However, there were definite statistically significant differences in the results of morphometry of tumor cell nuclei. Secretory carcinoma is considered to be an anaplastic variant type of mucinous carcinoma.     

Apoptosis in the pattern formation of the ventricular wall during mouse heart organogenesis.

Apoptosis is an important mechanism in organogenesis, but its role in heart development has been poorly characterized. We have here studied apoptosis in the developing ventricular wall of mouse embryonic heart. Developing mice hearts on days 11 to 16 of gestation were studied using in situ end-labeling of degraded DNA (TUNEL), immunocytochemistry of regulatory genes Bcl-2 and Bax, and light and electron microscopy. TUNEL end-labeled apoptotic cells were found in the ventricular wall on days 11 to 16 of gestation. The proportions of apoptotic cells of all cells in the ventricular wall differed between the trabecular and compact regions (P = 0.003) and between the days of gestation (P = 0.0001), the calculated apoptotic index was greater in the compact region at all ages except day 14. Ultrastructural analysis showed typical apoptotic shrinkage, chromatin degradation, and apoptotic bodies in several myoblastic and myocardial endothelial cells which were also positive by DNA end-labeling. Immunocytochemical reaction for the apoptosis checkpoint proteins in the ventricular wall showed clearly more Bcl-2 positive cells than Bax positive cells. The numerical densities of all cells in the compact and trabecular regions remained always higher in the compact region (P = 0.04) despite the fact that apoptosis was present in both areas at the same time. In conclusion, apoptosis takes place in the developing myocardial muscle as well as the myocardial endothelium during ventricular morphogenesis on days 11 through 16 and decreases clearly on day 16. We suggest that apoptosis and its regulatory factors are closely involved in the morphogenesis of the ventricular wall of the mammalian heart.     

Autoimmune markers are undetectable in end stage idiopathic dilated cardiomyopathy

BACKGROUND: Autoreactive humoral and cellular immune responses may be involved in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). Certain human leucocyte antigens (HLA) could also be linked to the development of IDC. AIM: To determine whether various markers of autoimmunity are present in the final phase of the disease, to substantiate the role of an autoimmune process in IDC. METHODS: 37 patients with end stage IDC were studied, together with 39 patients with end stage heart disease of known aetiology who were included for comparison. Multiple myocardial tissue samples from the explanted heart of each patient were evaluated (immuno)histologically. An indirect immunofluorescence assay was used to screen patient serum samples for the presence of heart specific autoantibodies. HLA class I and II frequencies were determined in each group and compared with HLA frequencies from healthy blood donors. RESULTS: Only scanty small mononuclear cell infiltrates were present in myocardial tissue of seven patients with IDC and of 11 patients with heart disease of known cause. The majority of these inflammatory cells were negative for T cell markers. All blood specimens were negative for heart specific autoantibodies and there was no apparent association of IDC with particular HLA phenotypes. CONCLUSIONS: These findings suggest that an active autoimmune process is not involved in the end stage of IDC.     

Secretory Carcinoma Coexistent with Mucinous Carcinoma in the Breast

Secretory carcinoma and mucinous carcinoma were found to coexist in the breast of a 67 year old post menopausal woman, although the tumors were separated by a thin fibrous septum. Histochemically, intra- and extracellular secretory materials in both carcinomas were strongly positive for alcian blue, PAS and mucicarmine staining, but immunohistochemically negative for α- lactalbumin and CEA. Membrane-bound intracytoplasmic vacuoles showing emiocytosis were observed in both the secretory and mucinous carcinomas by electron microscopy. No differences were observed between the tumor cells of secretory carcinoma and those of mucinous carcinoma by histochemistry, immunohistochemistry and electron microscopy. However, there were definite statistically significant differences in the results of morphometry of tumor cell nuclei. Secretory carcinoma is considered to be an anaplastic variant type of mucinous carcinoma. Acta Pathol Jpn 39: 593 598, 1989.