A cytokeratin immunohistochemical study of alcoholic liver disease: evidence that hepatocytes can express ''bile duct-type'' cytokeratins

A cytokeratin immunohistochemical study was performed on 40 liver biopsies diagnosed as alcoholic liver disease to further investigate the cytoskeletal changes occurring in this disease. On paraffin sections of 29 cases, a variable number of hepatocytes were reactive with a polyclonal antiserum that normally stains only bile ducts. Using monoclonal antibodies specific for a single cytokeratin polypeptide on cryostat sections, a variable number of hepatocytes were immunoreactive for cytokeratin no. 7 in 23 cases and also for cytokeratin no. 19 in seven cases. Both these polypeptides are restricted to bile duct cells in the normal liver. The number of hepatocytes positive for bile duct-type cytokeratins increased and their location changed with the severity of the disease. Mallory bodies were reactive with monoclonal antibodies CAM 5.2 and anti-cytokeratin no. 18 but unreactive with anti-cytokeratin no. 8. except in one case. In two cases, Mallory bodies reactive with both monoclonal antibodies anti-cytokeratin no. 7 and anti-cytokeratin no. 19 were found. These results clearly indicate that hepatocytes in alcoholic liver disease can express immunoreactivity for bile duct-type cytokeratins. Our data also demonstrate heterogeneity in the composition of Mallory bodies. Whether hepatocytes expressing bile duct-type cytokeratins are the precursors of Mallory body-containing cells is not clear at present.     

Immunohistochemical profiles of Mallory body by a panel of anti-cytokeratin antibodies

Mallory bodies (MBs) are hyaline inclusions found in a variety of liver diseases. Because the major components of MBs are cytokeratins (CKs), CK profiles of MBs were examined immunohistochemically in 37 autopsied liver specimens (including a variety of nontumor pathological livers and hepatocellular carcinomas), using 13 antibodies against specific CKs: 34B4 (CK 1), OV-TL12/30 (CK 7), 34H11 (CK 8), LHP1 (CK 10), KS-1A3 (CK 13), LL002 (CK 14), LHK15 (CK 15), LL025 (CK 16), E3 (CK 17), DC10 (CK 18), b170 (CK 19), Ks20.8 (CK 20), and 34E12 (CKs 1, 5, 10, and 11). Positive staining rates of MBs in 37 cases were as follows: CK 8, 100% (37/37); CK 18, 100% (37/37); CK 19, 57% (21/37). CK 7, 49% (18/37); CK 20, 35% (13/37); CK 1, CK 5, CK 10, CK 11, CK 13, CK 14, CK 15, CK 16, and CK 17 were all negative in MBs. CK expression patterns in MBs found in tumor or non-tumor hepatocytes was basically similar. Thus, all present MBs were composed of similar material with common antigenic determinants, regardless of underlying disease; in particular, they consistently contained CK 8 and CK 18, and frequently contained CK 7, CK 19, and CK 20.     

胃贲门粘膜撕裂综合征内镜诊治的临床研究

目的　探讨有关胃贲门粘膜撕裂综合征(MWS)内镜诊断问题,比较内镜治疗与传统疗法的疗效。方法　将1993 年1 月～1998 年2 月收治的30 例有活动性出血的MWS病例随机分组,对比内镜微波治疗与内镜局部用药的效果。并将上述30 例与过去传统内科治疗的18 例做回顾性对照研究。结果　止血效果内镜治疗明显优于传统治疗。内镜治疗中微波治疗组一次止血率明显高于局部用药组,两者对裂伤粘膜愈合的影响差异无显著性意义。内镜治疗未见远期并发症。结论　内镜检查是确诊MWS的重要方法,内镜微波治疗效果肯定、方法简便,恰当使用能避免外科手术     

食管贲门粘膜撕裂症的内镜下诊断与治疗

目的探讨食管贲门粘膜撕裂症(MWS)的内镜下诊断及治疗。方法回顾性分析14例经内镜诊治的MWS的临床资料。结果MWS病变以右侧壁的贲门粘膜多见。7例患者内镜下止血效果显著。结论内镜是确诊MWS的首选方法。内镜止血效果肯定,方法简便。     

Enzyme-histochemical studies of griseofulvin-intoxicated mouse livers

ABSTRACT— Enzyme-histochemical studies were conducted on livers of mice chronically fed griseofulvin (GF) in order to produce Mallory bodies (MBs) in hepatocytes. The development of MBs is associated with derangement of the immunohistochemically detectable intermediate filament (IF) cytoskeleton of the cytokeratin (CK) type, although no strict correlation between appearance or involution of MBs and the cytoskeletal alterations exists. Since the function of the IF cytoskeleton and the relationship of its disturbance to cell injury is unknown, the aim of the present study was to correlate the activities of several key enzymes of cellular metabolic pathways with the disturbance of the cytoskeleton architecture. For that purpose enzyme-histochemistry in combination with immunohistochemical CK-IF stainings were performed on identical sections. In GF-intoxicated mouse livers the normal topography of enzyme activities was disturbed, but no strict colocalization of enzymatic and cytoskeletal changes was found. Glucose-6-phosphatase, a microsomal enzyme involved in glucose output and gluconeogenesis, showed elevated activity in MB-free hepatocytes with diminished immunostainable CK-IF cytoskeleton refuting the concept of a disability of those cells to export glucose. It could indeed indicate that those cells without MBs are in the state of recovery. However, these cells could also resemble “hyperactive foci“. Glycogen was decreased in MB-containing hepatocytes with disturbed cytoskeleton, and this feature favours the assumption of cell degeneration. On the other hand, the mitochondrial marker enzymes, i.e. succinate dehydrogenase, cytochrome-c-oxidase and 3-hydroxybutyrate dehydrogenase, remained unchanged in altered hepatocytes. Alkaline phosphatase activity at the canalicular pole of GF-intoxicated hepatocytes was elevated, indicating cholestatic features associated with this disorder. However, since altered hepatocytes did not show impairment of oxido-reductase activities, a severe impairment of bile secretion as a consequence of cell damage is unlikely. Unchanged or even increased ATPase activity of altered hepatocytes also indicated their sustained metabolic abilities. The results presented provide indirect evidence that hepatocytes with disturbed IF cytoskeleton do not significantly differ from normal cells with respect to oxidative metabolism, fatty acid synthesis and gluconeogenesis. This suggests that alterations of the IF cytoskeleton associated with GF intoxication and MB formation have no significant adverse influence on the metabolic functions of liver cells, as far as can be assessed by evaluation by enzyme-histochemical staining of several key enzymes.     

Airspace enlargement with fibrosis shows characteristic histology and immunohistology different from usual interstitial pneumonia,nonspecific interstitial pneumonia and centrilobular emphysema

The histologic characteristics of air space enlargement with fibrosis (AEF) are compared with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and centrilobular emphysema (CLE) to determine similarities and differences. Lung specimens from 39 patients were studied; 9 with AEF, 13 with UIP and 5 with CLE identified in lobectomy specimens for cancer and 12 NSIP cases identified on surgical lung biopsies. We determined the characteristics of cystic structures (i.e. abnormal airspace), degree of inflammation and severity of pneumocyte injury semi‐quantitatively. In AEF, the wall thickness of the cystic lesions (0.8 mm) was thinner than in UIP (2.1 mm) and thicker than in CLE (0.07 mm). The degree of inflammation and granulation tissue were milder in AEF than in UIP and NSIP and CLE showed milder inflammatory cells than AEF. As for pneumocyte injury, AEF had fewer erosions (0.1/case) and fewer ubiquitin‐positive pneumocytes than UIP (4.8 cells/slide) and NSIP (9.8 cells/slide). Our data suggested that the histological characteristics of AEF differed significantly from UIP, NSIP and CLE.     

奥曲肽治疗贲门粘膜撕裂综合征合并休克的效果研究

目的探讨奥曲肽治疗贲门粘膜撕裂综合征合并休克的临床效果。方法选择2006年1月—2012年12月收治的贲门粘膜撕裂综合征患者55例,随机分为观察组27例和对照组28例,所有患者入院后均由其家属签署知情同意书,对照组使用止血药物、输氧、镇静、补充血容量并维持酸碱电解质平衡等处理。观察组在对照组的基础上使用奥曲肽注射液首先0.1 mg静脉推注(5min),随后以0.6 mg溶于5%葡萄糖注射液500 ml中,通过输液泵以50μg/h的速度连续静脉滴注,12h 1次,连续治疗5d。比较两组总住院时间、血淀粉酶转阴时间及治疗效果。计量资料比较使用t检验,组间率的比较采用χ2检验,P<0.05差异有统计学意义。结果观察组总住院时间[(8.5±2.1)d]显著短于对照组[(11.6±3.4)d],血淀粉酶转阴时间[(14.6±2.5)h]快于对照组[(35.4±5.8)h],两组比较差异均有统计学意义(t=4.050、17.151,P<0.05)。观察组总有效率92.6%,对照组67.9%,两组比较差异有统计学意义(χ2=5.256,P<0.05)。结论对于失血性休克昏迷患者,使用奥曲肽能较理想的降低患者胃内pH值,促进凝血,提高临床治疗效果,值得临床推广。     

The pathology of diabetic hepatitis

Liver biopsies from nine patients with maturity-onset diabetes and fatty liver hepatitis were semiquantitatively assessed, and the findings compared with those in alcoholic hepatitis. Overall appearances were similar, but the lesion in some diabetics was periportal rather than perivenular in location, and nuclear vacuolation of hepatocyte nuclei was always present. The inflammatory infiltrate often included neutrophil leucocytes, as in the alcoholic. In three patients with multiple biopsies, progression appeared to be slow, but one patient developed cirrhosis.     

p62 is involved in the mechanism of Mallory body formation

p62 is a scaffolding protein that binds to polyubiquitin. It is involved in the degradation of proteins by the proteasome. To determine if p62 is critical in the development of Mallory bodies (MBs), primary culture hepatocytes from drug-primed mice were studied and the results were compared with normal hepatocytes. Gene-specific gripNA (gp62) was added to the medium of the primary cultures of the hepatocytes to inhibit the expression of p62. Overexpression of p62 was achieved by transfecting the hepatocytes with a plasmid containing green fluorescent protein (GFP) fused p62 (p62-GFP). Gp62 dramatically inhibited MB formation by 94% in drug-primed hepatocytes. The cells transfected with gp62 had decreased protein levels of p62, ubiquitin (Ub), and cytokeratin 8 (CK8). Overexpression of p62 accelerated and enhanced MB formation by 339% in drug-primed hepatocytes. Overexpression of p62 in normal mouse hepatocytes induced MB-like aggresomes that were stained by Ub but not by CK8. The results indicate that p62 is involved in the mechanism of MB formation.