Phenotypic modulation in lipocytes in experimental liver fibrosis

The presence of a-smooth muscle actin (smA)-positive cells has recently been reported in the fibrotic liver. Lipocytes have been considered to play important roles in hepatic fibrosis. However, the relation of the a-smA-positive cells and lipocytes has not been determined. The biological implication of a-smA expression remains unknown. To study these questions, we carried out double immunofluorescent staining of a-smA and desmin (a marker for lipocytes), or a-smA and collagen, and double immunohistochemical staining of a-smA and 5-bromo-2'-deoxyuridine (BrdUrd) in carbon tetrachloride-induced fibrotic rat livers. In normal and control livers, a-smA-positive cells were not seen in the lobules, whereas scattered desmin-positive cells were present. With the development of hepatic fibrosis, a-smA was expressed only in a portion of desmin-positive cells located predominantly around collagen bundles. A number of a-smA-positive cells in the lobules were labelled with BrdUrd. These results suggest phenotypic modulation in lipocytes and differentiation of lipocytes towards myofibroblast-like cells, since a-smA is expressed with desmin in myofibroblasts in scar tissue. The expression of a-smA may be related to events of the fibrotic process, such as tissue contraction or fibrogenesis per se.     

Autoradiographic study of DNA synthesis in rats with experimental myocardial infarction

Tritium-labeled thymidine was injected into rats with an experimental myocardial infarct and the number of DNA-synthesizing nuclei was determined in various parts of the heart. Myocardial infarction activated DNA synthesis to some extent in the nuclei of monocytes lying at the periphery of the focus of injury. However, there was no doubt about the extremely low density of labeling in the muscle nucleus. Increasing the dose and giving three injections of thymidine-³H did not increase the number of labeled muscle cell nuclei. Activation of proliferation of the connective tissue cells was observed in all parts of the heart. The number of connective-tissue nuclei synthesizing DNA was increased after 24 h, reached a maximum on the second day, and remained above the control level until the end of the experiment.Central Pathological Anatomical Laboratory, Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 5, pp. 612–615, May, 1977.     

Cholesteryl Ester Transfer Protein (CETP) Genetic Variation and Early Onset of Non‐Fatal Myocardial Infarction

Although Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesteryl esters and triglycerides between lipoprotein particles and thus plays a crucial role in reverse cholesterol transport, the association of variations in the CETP gene with acute myocardial infarction (MI) remains unclear. In this study we examined whether common genetic variation in the CETP gene is related to early‐onset non‐fatal MI risk in a population‐based case‐control study from western Washington State. Genotyping for the CETP ?2708 G/A, ?971 A/G, ?629 A/C, Intron‐I TaqI G/A and exon‐14 A/G (I405V) SNPs was performed in 578 cases with first acute non‐fatal MI and in 666 demographically similar controls, free of clinical cardiovascular disease, identified randomly from the community. In‐person interviews and non‐fasting blood specimens provided data on coronary heart disease risk factors. In men, there was little evidence for an association between single SNPs and MI risk, but in women the age‐ and race‐adjusted OR was found to be significant in 4 out of the 5 CETP single variants. Haplotype analysis revealed two haplotypes associated with MI risk among men. As compared to men homozygous for the most common haplotype D (?2708 G, ?971 G, ?629 C, TaqI G and exon‐14 A), the fully‐adjusted multiplicative model identified haplotype G (?2708 G, ?971 A, ?629 A, TaqI G and exon‐14 G) was associated with a 4.0‐6.0‐fold increased risk of MI for each additional copy; [95%CI 2.4–14.8] and haplotype B (?2708 G, ?971 G, ?629 A, TaqI A and exon‐14 A) showed a significant decreased risk for early onset MI [OR = 0.18; 95%CI 0.04 – 0.75]. An evolutionary‐based haplotype analysis indicated that the two haplotypes associated with the MI risk are most evolutionarily divergent from the other haplotypes. Variation at the CETP gene locus is associated with the risk of early‐onset non‐fatal MI. This association was found to be independent of HDL‐C levels. These data and the sex‐specific findings require confirmation in other populations.     

Olfactory and taste sensitivity in children with cystic fibrosis.

Psychophysical experiments measured both olfactory sensitivity to 1-butanol and sodium chloride and taste sensitivity to sodium chloride in normal children and in children with cystic fibrosis. The sensitivity of the children with cystic fibrosis fell within the normal range. These results stand in contrast to those of Henkin and Powell, who found children with cystic fibrosis to be hypersensitive to both olfactory and taste stimuli. Apparent hypersensitivity to taste stimuli could have resulted from the adapting effects of the relatively high level of sodium in the saliva of children with cystic fibrosis. If the contaminating effects of saliva are removed, children with cystic fibrosis yield, on the average, a taste threshold identical to that of normal children. There appears to be no simple explanation for why Henkin and Powell found hypersensitivity to odorants. The present results indicate that, in fact, children with cystic fibrosis display a slight hyposensitivity to odorants.     

Pathological analysis of hypertrophic cardiomyopathy simulating dilated cardiomyopathy

The pathomorphologic features of hypertrophic cardiomyopathy simulating dilated cardiomyopathy in the late stage (HCM-DCM) were compared with those of ordinary hypertrophic cardiomyopathy (HCM). Seven autopsied hearts with HCM-DCM and 11 with HCM were assessed quantitatively using an image analyzer. Unlike HCM, significant left ventricular enlargement and wall thinning were observed in HCM-DCM, and the percentage areas of massive fibrosis and disarray were significantly greater. In HCM-DCM, the disarray was distributed diffusely, whereas massive fibrosis was distributed more intensively in the ventricular septum and anterior wall than in the lateral and posterior wall. Narrowing of intramyocardial small arteries was observed more frequently in HCM-DCM, especially in the ventricular septum and anterior wall, than in HCM. These results suggest that the enlargement and wall thinning of the left ventricle in HCM-DCM are attributable to non-uniform progression of massive fibrosis, which is closely related to small-arterial lesions.     

Effects of Cystic Fibrosis Serum and Fibroblast Culture Medium on Ion Distribution in Rat Submandibular Gland

The effects of cystic fibrosis (CF) serum and culture medium from CF fibroblasts on ion distribution in rat submandibular gland cells were investigated by X-ray microanalysis. These effects were compared to the effects of normal serum and culture medium from normal fibroblasts, of cholinergic and adrenergic agonists, and of the uncoupler 2,4-dinitrophenol.

Incubation of gland tissue with CF serum or normal serum caused a significant decrease in potassium and calcium concentrations and an increase in sodium in mucous acinar and serous granular duct cells. CF serum gave a significantly larger decrease of the potassium level than normal serum.

Culture medium from CF fibroblasts altered the cellular ion content in a way similar to CF serum. Exposure to medium from cultured normal fibroblasts did not affect the elemental composition of the gland cells significantly, compared to incubation with fresh medium or buffer. Hence, fibroblast culture medium is more suitable than serum to test specific effects of CF-associated factors.

The changes in elemental composition of gland eelIs caused by CF serum or CF fibroblast culture medium mimic some of the effects of the agonist car-bachol. They could, however, also in part result from nonspecific changes in membrane permeability.     

IgE antibody to Aspergillus fumigatus recombinant allergens in cystic fibrosis patients with allergic bronchopulmonary aspergillosis

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) is characterized by a heightened Th2 CD4+ T-cell response to Aspergillus fumigatus (Af) allergens and a hyper-immunoglobulin E (IgE) state compared with cystic fibrosis patients without ABPA. The IgE serologic differentiation of ABPA from atopic CF patients can be difficult. We propose as the reactivity with purified antigens varies qualitatively and quantitatively and that the antibody response is more specific than with crude Af antigen extract, the IgE responses to purified recombinant Af allergens may differentiate ABPA from atopic CF patients. METHODS: Serum IgE reactivity to seven recombinant purified allergens and to a crude extract of Af was measured in 15 ABPA, in 23 Af skin test positive (ST+), and in 19 Af skin test negative (ST-) CF patients. Four of the ABPA CF patients were studied before and after developing ABPA. Nine ABPA patients were studied during flares and remissions of ABPA. RESULTS: Allergic bronchopulmonary aspergillosis patients had significantly increased IgE reactivity to Asp f2, f3, f4, f6, and f16 compared with the Af ST+ and ST- non-ABPA CF patients. In the ABPA patients studied before and after developing ABPA, IgE reactivity also increased to Asp f2, f3, f4, and f6, and to the crude extract. In ABPA CF patients, IgE reactivity to Asp f1, f2, f3, and f6 significantly increased during periods of ABPA flares compared with periods of remission. Analysis of the receiver operating curve demonstrated that IgE reactivity to Asp f3 and f4 gave the best sensitivity and specificity and were better than IgE reactivity to a crude extract of Aspergillus. Furthermore, in ABPA patients studied during periods of remission the IgE reactivity to Asp f3 and f4 remained significantly elevated compared with Af ST+ non-ABPA patients. The IgE responses when considered either to be positive or negative to Asp f3 and f4 significantly differentiated ABPA from Af ST+ and ST- non-ABPA CF patients. In contrast, IgE reactivity was considered positive to the crude extract in 89% of ABPA, 61% of Af ST+, and 0% of Af ST- non-ABPA CF patients. CONCLUSIONS: Immunoglobulin E reactivity to a panel of purified Af allergens, especially to Asp f3 and f4, differentiates ABPA from atopic Af ST+ non-ABPA CF patients. Serial determinations of IgE reactivity to individual purified Aspergillus antigens, especially Asp f3, demonstrates that increases in IgE reactivity may provide improved distinction between stages of flares and remission compared with changes in IgE reactivity to a crude Aspergillus extract.     

肝毒清颗粒对大鼠实验性肝纤维化的防治作用

目的 :观察肝毒清颗粒的抗纤维化作用。方法 :将Wistar雄性大鼠随机分成 6组 ,即正常对照组、模型组、肝毒清大、中、小剂量组和乙肝宁阳性组 ,采用四氯化碳诱导肝纤维化模型。于造模第 2个月始给予治疗药物。实验持续 3月后将大鼠处死取血作肝功检查及取肝组织做病理检查。结果 :肝毒清能降低AST ,升高TP、ALB ,与模型组比较 (P <0 .0 5 ) ;减轻肝脂肪变性、减少纤维组织增生、促进肝细胞再生。结论 :肝毒清对大鼠肝纤维化有明显防治作用