1/167. Heteropolymerization of S, I, and Z alpha1-antitrypsin and liver cirrhosis.The association between Z alpha1-antitrypsin deficiency and juvenile cirrhosis is well-recognized, and there is now convincing evidence that the hepatic inclusions are the result of entangled polymers of mutant Z alpha1-antitrypsin. Four percent of the northern European Caucasian population are heterozygotes for the Z variant, but even more common is S alpha1-antitrypsin, which is found in up to 28% of southern Europeans. The S variant is known to have an increased susceptibility to polymerization, although this is marginal compared with the more conformationally unstable Z variant. There has been speculation that the two may interact to produce cirrhosis, but this has never been demonstrated experimentally. This hypothesis was raised again by the observation reported here of a mixed heterozygote for Z alpha1-antitrypsin and another conformationally unstable variant (I alpha1-antitrypsin; 39Arg-->Cys) identified in a 34-year-old man with cirrhosis related to alpha1-antitrypsin deficiency. The conformational stability of the I variant has been characterized, and we have used fluorescence resonance energy transfer to demonstrate the formation of heteropolymers between S and Z alpha1-antitrypsin. Taken together, these results indicate that not only may mixed variants form heteropolymers, but that this can causally lead to the development of cirrhosis.- - - - - - - - - - ranking = 1keywords = antitrypsin deficiency, antitrypsin, deficiency, alpha (Clic here for more details about this article) |
2/167. Immunohistochemical study on transforming growth factor-beta1 expression in liver fibrosis of Down's syndrome with transient abnormal myelopoiesis.A case of Down's syndrome associated with liver fibrosis is reported. The fibrosis was diffusely distributed along sinusoids, and an excess of megakaryocytes was also found in the liver. To determine the mechanism of liver fibrosis in Down's syndrome, we immunohistochemically stained the liver with markers of myofibroblast-like cells, antialpha smooth muscle actin antibodies and antidesmin antibodies. The myofibroblast-like cells were found along sinusoids, suggesting that liver fibrosis in Down's syndrome is caused by the myofibroblast-like cells derived from Ito cells/lipocytes. The expression of transforming growth factor (TGF)-betal, which is an important mediator of the activation of lipocytes, was immunohistochemically examined. The accumulation of TGF-betal was observed in cells in the sinusoidal spaces, which involve the intracellular expression of megakaryocytes. Together, these findings suggest that megakaryocyte-derived TGF-betal is one of the likely candidates in the lipocyte activation of liver fibrogenesis in Down's syndrome.- - - - - - - - - - ranking = 7.4070716657726E-5keywords = alpha (Clic here for more details about this article) |
3/167. Case report: rupture of a gastric varix in liver cirrhosis associated with glycogen storage disease type iii.glycogen storage disease type iii, or Cori's disease, is caused by a deficiency of amylo-1,6-glucosidase (debranching enzyme), which leads to the storage of an abnormal glycogen in the liver and in skeletal and heart muscle. glycogen storage disease type iii is usually characterized by hepatic symptoms, growth failure and myopathy. Even though liver cirrhosis is reported, portal hypertension is a rare complication of this disease. We describe the case of a glycogen storage disease type III patient who was diagnosed at 3 years of age and developed complications (liver cirrhosis and rupture of a gastric varix) at 31 years of age. We discuss the histological progression to cirrhosis of the liver and describe the liver enzyme profile at 3 and 31 years of age.- - - - - - - - - - ranking = 9.9313549564788E-5keywords = deficiency (Clic here for more details about this article) |
4/167. Septic shock due to helicobacter fennelliae in a non-human immunodeficiency virus-infected heterosexual patient.helicobacter fennelliae (formerly campylobacter fennelliae) has been reported to cause bacteremia in homosexual men with or without human immunodeficiency virus (hiv) infection. We report here a 48-year-old, non-hiv-infected, heterosexual man with diabetes mellitus and cirrhosis of the liver who developed bacteremia and septic shock due to H. fennelliae. The patient was treated successfully initially with intravenous ampicillin-sulbactam and ceftazidime, followed by ampicillin-sulbactam only. These agents were active in vitro against the isolate by E-test results. To our knowledge, this is the first documented case of septic shock due to H. fennelliae in a non-hiv-infected, heterosexual, immunocompromised patient.- - - - - - - - - - ranking = 0.00049656774782394keywords = deficiency (Clic here for more details about this article) |
5/167. Sarcomatoid hepatocellular-carcinoma showing rhabdomyoblastic differentiation in the adult cirrhotic liver.An unusual case of a massive liver tumour composed of rhabdomyosarcoma with a small focus of hepatocellular carcinoma in a 52-year-old man is presented. He had hepatitis b virus (HBV) surface antigen in his serum. Macroscopically, a large tumour with satellite nodules occupied the right lobe of the cirrhotic liver. Microscopically, the tumours were composed of small and short spindle-shaped undifferentiated cells, mixed with desmin-positive round rhabdomyoblasts and elongated striated muscle cells, strongly suggestive of rhabdomyosarcoma of the liver. Elevated levels of alpha-fetoprotein in the serum led us to examine the liver tumour closely in multiple sections, which disclosed a hepatocellular carcinoma component measuring 2 cm in diameter within the massive tumour. Immunohistochemically, the hepatocellular carcinoma cells were alpha-fetoprotein positive. There was neither a tumour capsule, nor distinct demarcation, and cytokeratin-positive clusters of undifferentiated cells were intermingled with the hepatocellular carcinoma and rhabdomyosarcoma at the border. The invading tumour outside the liver and metastatic tumours were pure rhabdomyosarcomas. It is suggested that the present case should be diagnosed as rhabdomyosarcoma transformed from hepatocellular carcinoma.- - - - - - - - - - ranking = 0.00014814143331545keywords = alpha (Clic here for more details about this article) |
6/167. High alpha-fetoprotein level in HCV-related nodular liver cell dysplasia.The diagnosis of hepatocellular carcinoma is generally made in patients with a mass lesion in the cirrhotic liver if the alpha-fetoprotein level is >1,000 ng/L. Other causes of elevation of alpha-fetoprotein to this extreme degree include nonseminomatous germ cell tumor and hepatic metastasis. However, it is extremely rare for benign hepatic lesions to cause alpha-fetoprotein of > 1,000 ng/ml. We report a Chinese patient with spontaneous normalization of alpha-fetoprotein with an initial value > 10,000 ng/ml due to nodular dysplasia complicating hepatitis c-related liver cirrhosis. The alpha-fetoprotein was secreted from the dysplastic liver cells.- - - - - - - - - - ranking = 0.00066663644991954keywords = alpha (Clic here for more details about this article) |
7/167. Right hepatic lobectomy for hepatocellular carcinoma which developed in primary biliary cirrhosis: report of a case.The case of a 74-year-old female patient who underwent a right hepatic lobectomy for hepatocellular carcinoma (HCC) which developed in primary biliary cirrhosis (PBC) is reported herein. During a follow-up examination for Parkinson's disease, an elevation of hepatobiliary tract-related enzymes and alpha-fetoprotein was uncovered. Diagnostic imagings showed a hypervascular, solitary, and encapsulated tumor measuring about 7 cm in diameter located mainly in the posterior segment. Positive antimitochondrial and antinuclear antibodies and a preoperative liver biopsy strongly suggested well differentiated HCC developed in PBC (Scheuer's classification stage II). Since the natural prognosis of PBC estimated by the Mayo risk score was fairly good and the liver function indicated sufficient tolerance for major hepatic resection, and preoperative computed tomography (CT) volumetry showed the atrophy of the right hepatic lobe, a right hepatic lobectomy was performed. A pathological examination revealed well encapsulated, moderately differentiated HCC with, in part, well-differentiated HCC in the tumor and stage II PBC in the noncancerous region. CT volumetry performed at postoperative day 14 showed a 146% enlargement of the remnant liver. An early detection of HCC and PBC by strict screening would prevent a limitation of surgical therapy due to a deteriorated liver function.- - - - - - - - - - ranking = 7.4070716657726E-5keywords = alpha (Clic here for more details about this article) |
8/167. listeria monocytogenes and recurrent mycobacterial infections in a child with complete interferon-gamma-receptor (IFNgammaR1) deficiency: mutational analysis and evaluation of therapeutic options.We describe the history of a girl with interferon-gamma-receptor (IFNgammaR1) deficiency and studies performed to identify the molecular and clinical characteristics of this recently discovered disorder. This is the first report of a child from Northern europe with IFNgammaR1 deficiency. The patient, now 7 years old, first presented with swelling and reddening at the Bacille Calmette-Guerin (BCG) vaccination site, swelling of lymph nodes, hepatomegaly, and an unusually severe varicella rash at the age of 4 months. At that time, she was diagnosed with BCG histiocytosis without typical granuloma formation and was treated with antituberculous agents. During the clinical course of her illness, several different types of atypical mycobacteria and (for the first time in an IFNgammaR1-deficient patient) listeria monocytogenes were detected. Flow cytometric analysis showed that the patient's monocytes could not bind a monoclonal antibody specific for the IFNgamma-receptor. Our analysis of mRNA derived from the alpha-chain (IFNgammaR1) gene of this receptor revealed deletions of 173 bp and 4 bp in cDNA sequences originating from individual alleles. The 173 bp deletion was located between nucleotide positions 200 and 372, exactly matching those of exon 3, and the 4 bp deletion was located between nucleotide positions 561 and 564 of the coding region of the cDNA. Analysis of genomic dna revealed the presence of a G to T transition at the 5'end of the splice consensus sequence of intron 3, which explains the absence of exon 3. The other allele carried the 4-base-pair deletion (ACTC) at nucleotide positions 15-18 of exon 5. Twelve months after an allogeneic bone marrow transplantation, the patient had clinically improved.- - - - - - - - - - ranking = 0.00066995201404645keywords = deficiency, alpha (Clic here for more details about this article) |
9/167. Correction of both prothrombin time and primary haemostasis by recombinant factor vii during therapeutic alcohol injection of hepatocellular cancer in liver cirrhosis.We evaluated the efficacy of recombinant factor vii to correct impaired haemostasis in a patient with liver cirrhosis requiring an invasive procedure. A test intravenous bolus of 80 microg/kg of recombinant factor vii was given to a Jehovah's Witness, with a solitary 4.4-cm hepatocellular carcinoma and underlying hepatitis c virus cirrhosis, in an attempt to correct his haemostatic disorders and safely inject the tumour with alcohol. An extensive portal block had precluded consideration of liver transplantation. Haemostasis was evaluated by clotting assays, bleeding time and thromboelastography 10 min before and 10 min and 1, 2, 4, 8 and 24 h after factor vii infusion. Parameters of both coagulation (prothrombin time) and platelet function (bleeding time and the alpha and ma parameters of thrombelastography) were improved 10 min after factor vii infusion; improvements lasted 4 to 8 h or more. platelet count did not change and there was no evidence of disseminated intravascular coagulation. The improvements in haemostatic parameters correlated significantly with the increases in factor vii plasma concentrations (p<0.04). factor vii clearance was 25.1 U/h/kg and its half-life was 5.8 h. The same dose of recombinant factor vii was given to the patient 1 week later, just before the alcohol injections. The patient had no subsequent bleeding or other complication, with no change in haemoglobin levels over 24 h. Thus, recombinant factor vii represents a therapeutic advance, as it can correct fully both coagulation and platelet function defects in cirrhosis and allow invasive procedures to be performed safely.- - - - - - - - - - ranking = 7.4070716657726E-5keywords = alpha (Clic here for more details about this article) |
10/167. liver transplantation in alpha(1)-antitrypsin deficiency.Only a minority of infants born with alpha(1)-antitrypsin deficiency will develop serious liver disease during childhood, mostly but not always after neonatal cholestasis. Early prognosis is difficult and all children have to be followed up carefully. The liver disease progresses with varying speed and it lacks specific features. At the time of liver transplantation the young patients have no pulmonary disease induced by the deficiency and in those with renal involvement, the kidney problems can mostly be dealt with by conservative therapy. The peri- and postoperative care of the patients who undergo liver transplantation does not differ from the usual routines.- - - - - - - - - - ranking = 1.6752223437118keywords = antitrypsin deficiency, antitrypsin, deficiency, alpha (Clic here for more details about this article) |
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