[Measurement of serum bile alcohol levels in liver dysfunction using isotope dilution-mass spectrometry].
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Activating transcription factor 3 (ATF3) is a member of the ATF/cAMP-response element-binding protein family of transcription factors. It is a transcriptional repressor, and the expression of its corresponding gene is induced by stress signals in a variety of tissues, including the liver. In this report, we demonstrate that ATF3 is induced in the pancreas by partial pancreatectomy, streptozotocin treatment, and ischemia coupled with reperfusion. Furthermore, ATF3 is induced in cultured islet cells by oxidative stress. Interestingly, transgenic mice expressing ATF3 in the liver and pancreas under the control of the transthyretin promoter have defects in glucose homeostasis and perinatal lethality. We present evidence that expression of ATF3 in the liver represses the expression of genes encoding gluconeogenic enzymes. Furthermore, expression of ATF3 in the pancreas leads to abnormal endocrine pancreas and reduced numbers of hormone-producing cells. Analyses of embryos indicated that the ATF3 transgene is expressed in the ductal epithelium in the developing pancreas, and the transgenic pancreas has fewer mitotic cells than the non-transgenic counterpart, providing a potential explanation for the reduction of endocrine cells. Because ATF3 is a stress-inducible gene, these mice may represent a model to investigate the molecular mechanisms for some stress-associated diseases.
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A 26-year old woman presented with acute hepato-renal dysfunction, coagulation abnormalities and diabetes insipidus associated with hypernatremia in the latter term of pregnancy (39 weeks). Such transient diabetes insipidus during pregnancy as in this case has been reported to be resistant to AVP, but to respond to DDAVP. Because of fetal compromise, an urgent cesarean section was performed. Spinal anesthesia was chosen because of the possible deleterious effects of general anesthesia on liver function. After delivery of twin babies, her symptoms recovered gradually. In conclusion, diabetes insipidus during pregnancy as in this case is transient and disappear after delivery. However, multiple organ dysfunction may become worse and cause fetal death, unless surgical procedure with appropriate anesthetic management is performed.
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BACKGROUND: Cyanamide, an aversive agent widely used in Japan, is known to induce various degrees of hepatic lesion with ground-glass inclusion bodies. When cyanamide-treated alcoholics relapse into drinking, more severe inflammation develops in the liver. However, it is controversial whether progressive hepatic lesions develop in complete abstainers as a result of long-term cyanamide treatment. CASE REPORTS: Case 1: A 53-year-old male alcoholic received cyanamide treatment for 4.5 months and completely abstained without cyanamide treatment for 6 years. A liver biopsy shortly after abstinence showed extensive pericellular fibrosis, but a biopsy after 6 years showed very mild fibrosis. Case 2: A 43-year-old male alcoholic remained completely abstinent with cyanamide treatment for 5 years and complained of general fatigue. His serum transaminases were slightly elevated and hepatic hyperechogenicity was observed on ultrasonography. Only mild pericellular fibrosis was present in the liver biopsy specimen obtained shortly after abstinence, but after 5 years the second liver biopsy showed that thin septum-like fibrosis that formed portal-to-portal and portal-to-central linkage had developed and ground-glass hepatocytes had emerged extensively. Case 3: A 29-year-old female alcoholic complained of general fatigue and a slight fever after 1.5 years of abstinence with cyanamide treatment. Slight elevation of serum transaminases and hepatic hyperechogenicity were observed. The liver biopsy showed extensive ground-glass hepatocytes and thin septum-like fibrosis that formed portal-to-portal linkage. Case 4: A 61-year-old male alcoholic who remained completely abstinent while taking cyanamide for 3 years showed slight elevation of serum transaminases. Liver biopsy showed extensive ground-glass hepatocytes and extension of thin septum-like fibers from portal tract to the lobule. Ultrasonography revealed hepatic hyperechogenicity. CONCLUSION: In some abstainers who take cyanamide for several years, thin septum-like liver fibrosis progresses along with the emergence of ground-glass hepatocytes. Hepatic hyperechogenicity on ultrasonography and slight elevation of serum transaminases might erroneously lead to a diagnosis of hepatic steatosis without liver histology.
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