Fatness and fat distribution in Mexican-American children and youths from the Hispanic health and nutrition examination survey

Mexican-American children are shorter but relatively heavier than non-Hispanic white children. The excess relative weight is probably due to increased fat rather than lean body mass and, more specifically, to increased fat deposition on the upper trunk sites. The objective of this paper is to describe the level of fatness and fat distribution in a large, representative sample of Mexican- American children and adolescents from the recently completed Hispanic Health and Nutrition Examination Survey (HHANES). As expected, Mexican-American children are generally fatter than white children measured in previous national surveys (National Health and Nutrition Examination Survey [NHANES] II, Health Examination Survey [HES]). Differences are particularly evident for trunk skinfold thicknesses and generally increase with age. Indices of fat distribution clearly show a centralized, upper body adiposity pattern among Mexican-Americans, a cause for concern since greater fat deposition on the trunk has been associated with increased risk of certain chronic disease.     

A serologic follow-up of the 1942 epidemic of post-vaccination hepatitis in the United States Army

An epidemic of icteric hepatitis in 1942 affected approximately 50,000 U.S. Army personnel. This outbreak was linked to specific lots of yellow-fever vaccine stabilized with human serum. To identify the responsible virus and the consequences of the epidemic, during 1985 we interviewed and serologically screened 597 veterans who had been in the army in 1942. These subjects were selected from three groups. Group I consisted of patients who had received the implicated vaccine and had jaundice; Group II had received the implicated vaccine but remained well; Group III had received a new, serum-free vaccine, with no subsequent jaundice. Ninety-seven percent of Group I, 76 percent of Group II, and 13 percent of Group III were positive for antibodies to hepatitis B virus. Only one subject had hepatitis B surface antigen, for a carrier rate of 0.26 percent among recipients of the implicated vaccine. The prevalence of hepatitis A antibody was similar in all three groups, and no subject had antibody to hepatitis delta virus. We conclude that hepatitis B caused the outbreak, that about 330,000 persons may have been infected, that the hepatitis B virus carrier state was a rare consequence, and that the outbreak induced hepatitis B antibodies that appear to persist for life.     

Protection from oxidant injury by sodium-dependent GSH uptake in retinal Müller cells.

Glutathione (GSH) is known to play an important role in regulating oxidative damage to cells. The present study was initiated to examine the effect of exogenous GSH on oxidative injury in a retinal Müller cell line and to characterize GSH transport in these cells. Rat Müller cells (rMC-1) were incubated with varying concentrations of t-butylhydroperoxide (t-BHP) to induce oxidative stress, and cell viability was measured after addition of GSH. In other studies, kinetics of GSH uptake and Na+-dependency were examined by incubating cells with35S-GSH in Na+-containing and Na+-free buffers. GSH uptake was studied with GSH at concentrations varying from 0. 05-10 m m in NaCl buffer. In the presence of sodium, extracellular GSH provided protection against t-BHP-induced oxidant injury to rMC-1 cells; in contrast, the amino acid precursors of GSH did not have any effect on cell viability. GSH was taken up by rMC-1 cells in a concentration- and sodium-dependent manner. Kinetic studies revealed both a high affinity (Km approximately 0.31 m m) and low affinity Km( approximately 4.2 m m) component. Furthermore, GSH depletion had no significant effect on the rate of GSH uptake. The results show that physiological concentrations of GSH can protect Müller cells from oxidative injury. Both Na+-dependent and Na+-independent transport systems for GSH exist in Müller cells, and the Na+-dependent GSH transporter may be involved in the protective role of GSH.     

Common bile duct stenosis from chronic pancreatitis: a clinical and pathologic spectrum

The chronic pancreatitis population of Wadsworth VA Hospital over the past five years was screened for two-fold or greater alkaline phosphatase elevation at any time during their course, as a marker for either distal common bile duct stenosis or other hepatobiliary disease. Forty-seven of 207 patients screened met this criterion and are reviewed in detail. Of the 16 patients with persistent alkaline phosphatase elevation (group B), 15 had proven common bile duct stenosis, demonstrating a clear pathophysiologic role of partial bile duct obstruction in their liver disease. Three had developed secondary biliary cirrhosis, marking this entity the commonest cause of secondary biliary cirrhosis at our hospital. Of the remaining 31 patients with transient alkaline phosphatase elevation (group A), only 4 had proven duct abnormalities which may resolve during recovery. Alcoholic liver disease was demonstrated with normal extrahepatic ducts in the remainder in group A adequately studies. Persistent greater than two-fold alkaline phosphatase elevation in pancreatitis thus represents a reliable marker of distal common bile duct stenosis, whose sequelae may include cholangitis and secondary biliary cirrhosis and which requires operative intervention in these cases. When a persistent alkaline phosphatase elevation greater than two-fold is encountered in a chronic pancreatitis patient, adequate cholangiography and liver histology are both necessary to confirm and grade this frequent and treatable complication.     

Immune-mediated drug-induced liver disease

Drug-induced immune-mediated hepatic injury is an adverse immune response against the liver that results in a disease with hepatitic, cholestatic, or mixed clinical features. Drugs such as halothane, tienilic acid, dihydralazine, and anticonvulsants trigger a hepatitic reaction, and drugs such as chlorpromazine, erythromycins, amoxicillin-calvulanic acid, sulfonamides and sulindac trigger a cholestatic or mixed reaction. Unstable metabolites derived from the metabolism of the drug may bind to cellular proteins or macromolecules, leading to a direct toxic effect on hepatocytes. Protein adducts formed in the metabolism of the drug may be recognized by the immune system as neoantigens. Immunocyte activation may then generate autoantibodies and cell-mediated immune responses, which in turn damage the hepatocytes. Cytochromes 450 are the major oxidative catalysts in drug metabolism, and they can form a neoantigen by covalently binding with the drug metabolite that they produce. Autoantibodies that develop are selectively directed against the particular cytochrome isoenzyme that metabolized the parent drug. The hapten hypothesis proposes that the drug metabolite can act as a hapten and can modify the self of the individual by covalently binding to proteins. The danger hypothesis proposes that the immune system only responds to a foreign antigen if the antigen is associated with a danger signal, such as cell stress or cell death. Most clinically overt adverse hepatic events associated with drugs are unpredictable, and they have intermediate (1 to 8 weeks) or long latency (up to 12 months) periods characteristic of hypersensitivity reactions. Immune-mediated drug-induced liver disease nearly always disappears or becomes quiescent when the drug is removed. Methyldopa, minocycline, and nitrofurantoin can produce a chronic hepatitis resembling AIH if the drug is continued.     

Correlation of rickettsial titers, circulating endotoxin, and clinical features in Rocky Mountain spotted fever

Blood rickettsial titers, skin biopsy results, and circulating endotoxin measurements were correlated with the clinical course of disease in patients with Rocky Mountain spotted fever (RMSF). Nine of 11 patients with documented RMSF had Rickettsia rickettsii isolated from plasma samples. Of the eight patients in whom rickettsial titers were measured, seven had 10(0.7) to 10(1.2) median tissue culture infective doses (TCID50) per milliliter; all seven had mild to moderately severe disease. One patient with fulminant, fatal untreated RMSF had 10(3) TCID50/mL of postmortem plasma. Two patients from whom rickettsiae were not isolated had positive direct immunofluorescent stains of skin biopsy material for R rickettsii. Circulating endotoxin was present in two patients, one with documented rickettsemia and one with a positive skin biopsy alone. Only low levels of circulating rickettsiae are present in patients with moderately severe disease. Measurement of plasma endotoxin is not useful in the early diagnosis of RMSF.     

Innate immune system plays a critical role in determining the progression and severity of acetaminophen hepatotoxicity

BACKGROUND & AIMS: Inflammatory mediators released by nonparenchymal inflammatory cells in the liver have been implicated in the progression of acetaminophen (APAP) hepatotoxicity. Among hepatic nonparenchymal inflammatory cells, we examined the role of the abundant natural killer (NK) cells and NK cells with T-cell receptors (NKT cells) in APAP-induced liver injury. METHODS: C57BL/6 mice were administered a toxic dose of APAP intraperitoneally to cause liver injury with or without depletion of NK and NKT cells by anti-NK1.1 monoclonal antibody (MAb). Serum alanine transaminase (ALT) levels, liver histology, hepatic leukocyte accumulation, and cytokine/chemokine expression were assessed. RESULTS: Compared with APAP-treated control mice, depletion of both NK and NKT cells by anti-NK1.1 significantly protected mice from APAP-induced liver injury, as evidenced by decreased serum ALT level, improved survival of mice, decreased hepatic necrosis, inhibition of messenger RNA (mRNA) expression for interferon-gamma (IFN-gamma), Fas ligand (FasL), and chemokines including KC (Keratinocyte-derived chemokine); MIP-1 alpha (macrophage inflammatory protein-1 alpha); MCP-1 (monocyte chemoattractant protein-1); IP-10 (interferon-inducible protein); Mig (monokine induced by IFN-gamma) and decreased neutrophil accumulation in the liver. Hepatic NK and NKT cells were identified as the major source of IFN-gamma by intracellular cytokine staining. APAP induced much less liver injury in Fas-deficient (lpr) and FasL-deficient (gld) mice compared with that in wild-type mice. CONCLUSIONS: NK and NKT cells play a critical role in the progression of APAP-induced liver injury by secreting IFN-gamma, modulating chemokine production and accumulation of neutrophils, and up-regulating FasL expression in the liver, all of which may promote the inflammatory response of liver innate immune system, thus contributing to the severity and progression of liver injury downstream of the metabolism of APAP and depletion of reduced glutathione (GSH) in hepatocytes.