Denitrification is a process that reduces nitrogen levels in headwaters and other streams. We compared
nirS and
nirK abundances with the absolute rate of denitrification, the longitudinal coefficient ...of denitrification (i.e.,
K
den
, which represents optimal denitrification rates at given environmental conditions), and water quality in seven prairie streams to determine if
nir-gene abundances explain denitrification activity. Previous work showed that absolute rates of denitrification correlate with nitrate levels; however, no correlation has been found for denitrification efficiency, which we hypothesise might be related to gene abundances. Water-column nitrate and soluble-reactive phosphorus levels significantly correlated with absolute rates of denitrification, but
nir-gene abundances did not. However,
nirS and
nirK abundances significantly correlated with
K
den
, as well as phosphorus, although no correlation was found between
K
den
and nitrate. These data confirm that absolute denitrification rates are controlled by nitrate load, but intrinsic denitrification efficiency is linked to
nirS and
nirK gene abundances.
Denitrification efficiency best correlated to
nirS and
nirK gene abundances.
Total annual nutrient loads are a function of both watershed characteristics and the magnitude of nutrient mobilizing events. We investigated linkages among land cover, discharge and total phosphorus ...(TP) concentrations, and loads in 25 Kansas streams. Stream monitoring locations were selected from the Kansas Department of Health and Environment stream chemistry long-term monitoring network sites at or near U.S. Geological Survey stream gauges. We linked each sample with concurrent discharge data to improve our ability to estimate TP concentrations and loads across the full range of possible flow conditions. Median TP concentration was strongly linked (R ² = 76%) to the presence of cropland in the riparian zones of the mostly perennial streams. At baseflow, discharge data did not improve prediction of TP, but at high flows discharge was strongly linked to concentration (a threshold response occurred). Our data suggest that on average 88% of the total load occurred during the 10% of the time with the greatest discharge. Modeled reductions in peak discharges, representing increased hydrologic retention, predicted greater decreases in total annual loads than reductions of ambient concentrations because high discharge and elevated phosphorus concentrations had multiplicative effects. No measure of land use provided significant predictive power for concentrations when discharge was elevated or for concentration rise rates under increasing discharge. These results suggest that reductions of baseflow concentrations of TP in streams without wastewater dischargers may be managed by reductions of cropland uses in the riparian corridor. Additional measures may be needed to manage TP annual loads, due to the large percentage of the TP load occurring during a few high-flow events each year.
Background/Aims: Non-alcoholic steatohepatitis (NASH) is increasingly recognized, and its pathogenesis is believed to involve increased oxidative stress. Elevated levels of serum ferritin and ...positive liver iron stains are often observed in patients with NASH, and the pathogenesis of liver injury due to iron is also thought to involve oxidative stress. The aim of this study was to determine whether there is an association of NASH and mutations in the HFE gene associated with hereditary hemochromatosis (HHC).
Methods: Clinical, laboratory, and histopathological data on all 57 subjects with a final diagnosis of NASH seen between August 1990 and August 1997 at our Liver Center were analyzed. Thirty-six Caucasian subjects (23 men) with NASH underwent mutational analyses of HFE gene mutations performed. The prevalence of HFE gene mutations was compared to that in 348 Caucasian normal controls. Data were analyzed by both parameteric and non-parametric methods with similar results.
Results: One subject (2.8%) with NASH was homozygous for the C282Y mutation and six (16.7%) were heterozygous, compared with 0% and 11.2%, respectively, of controls. Two (5.6%) subjects with NASH were homozygous for the H63D mutation and 16 (44.4%) were heterozygous, whereas 2.9% and 26.4%, respectively, of controls had these genotypes. The prevalence of heterozygosity (61.1%) for either mutation was significantly higher in subjects with NASH than in controls (38%) (
p=0.008), and the prevalence of homozygosity or heterozygosity combined in NASH subjects (69.4%) was significantly higher than for controls (40.5%,
p=0.001). Sex (63–67% male) and age at diagnosis of NASH did not differ between those with or without HFE mutations, but men with NASH were significantly more likely than women to have the H63D mutation (15/23
vs. 3/13,
p<0.05) Levels of serum ferritin, iron, transferrin saturation levels, and the degree of hepatic iron staining were significantly higher (
p<0.05) in subjects with NASH who carried an HFE mutation than in those without. Differences in hepatic iron concentrations or hepatic iron indices between NASH subjects with and without HFE mutations were not significant. Those with C282Y mutations had significantly more hepatic fibrosis than those without (
p<0.05). Those with HFE mutations had significantly higher levels of serum ALT (90±11 mean±SE) than those without (55±6;
p=0.02).
Conclusion: The prevalences of the HFE gene mutations associated with hereditary hemochromatosis are increased among North American subjects with NASH.
Iron and chronic viral hepatitis Bonkovsky, H L; Banner, B F; Rothman, A L
Hepatology (Baltimore, Md.),
March 1997, Letnik:
25, Številka:
3
Journal Article
Two patients (a 48-year-old woman and a 62-year-old man) developed clinical and laboratory signs of hepatotoxicity due to troglitazone (Rezulin), a thiazolidinedione used in treatment of diabetes ...mellitus. There was no clear clinical evidence of drug allergy, although the woman experienced colitis before the onset of recognized hepatotoxicity. Liver biopsies showed bridging necrosis and fibrosis in the woman and hepatitis with granuloma formation in the man. The abnormalities in liver chemistries resolved promptly upon cessation of the drug. Cases involving 46 patients reported to the United States Food and Drug Administration are also reviewed. Troglitazone is a useful new oral antihyperglycemic agent, but in about 1.9% of patients hepatotoxicity has occurred, which may be severe and even fatal. Frequent monitoring of serum liver chemistries in patients taking the drug is essential.
Patients with chronic hepatitis C and low serum and hepatic iron stores may have an improved response to interferon (IFN). We tested whether iron reduction before and during IFN therapy would lead to ...an improved sustained biochemical and virological response compared with IFN alone. Eighty‐two previously untreated patients with chronic hepatitis C were randomized to either: group A IFN‐α2b 3 MU 3 times per week for 6 months, or group B iron reduction before and during IFN‐α2b 3 MU 3 times per week for 6 months. Group B patients had lower mean serum alanine transaminase (ALT) levels than group A patients during treatment and follow‐up. Group B patients had significantly lower mean hepatitis C virus (HCV)‐RNA levels at treatment weeks 4 and 12 (P < .05). Serum HCV RNA was undetectable at the end of treatment in 15 group B patients compared with 7 group A patients (P = .03); 7 group B patients and 3 group A patients had persistently undetectable serum HCV RNA 24 weeks after the end of therapy (P = .20). Paired pre‐ and posttreatment liver biopsies in 18 group B patients demonstrated significant improvements in 2 of the 3 inflammation scores of the Knodell histological activity index (P < .05). No changes occurred in the paired biopsies from 15 group A patients. We conclude that iron reduction via therapeutic phlebotomy improves the end‐of‐treatment virological and histological response to short‐term IFN therapy. Additional studies are needed to determine if iron reduction in combination with higher doses or longer duration of IFN may be of benefit.
Expression of cytokeratins 7 (CK7) and 20 (CK20) may help distinguish the site of origin for metastatic carcinomas. Little is known regarding their expression in biliary tract and pancreatic ...carcinomas. Our aim was to study the expression of CK7 and CK20 in these tumors.
Fifty-three carcinomas of the extrahepatic bile ducts (n = 8), ampulla of Vater (n = 7), gallbladder (n = 11), and pancreas (n = 27), were retrieved from the surgical pathology files of the University of Massachusetts Medical Center. Formalin-fixed, paraffin-embedded sections were immunostained with mouse monoclonal antibodies to CK7 and CK20 using an avidin-biotin immunoperoxidase technique with microwave antigen retrieval. The percentage of cells positive for each antibody was assessed on a scale of 0 to 3 (0, <10%; 1+, 10% to 50%; 2+, 51% to 90%; 3+, >90%).
The majority of carcinomas in all groups were positive for CK7 (CK7+) and negative for CK20 (CK20-). Of the CK7+ tumors, the majority of tumors in each group were 3+ positive.
(1) Carcinomas of the extrahepatic biliary tract and pancreas are strongly positive for CK7 and negative for CK20 and can be included in the differential diagnosis of other carcinomas with this profile in metastatic sites. (2) The CK7/CK20 immunostaining profile will not identify the site of origin for tumors with extensive growth in the porta hepatis region.
Recent evidence suggests that patients with chronic hepatitis C virus (CHCV) who respond to interferon-alpha (IFN) therapy have a lower hepatic iron concentration than those who do not. The object of ...this study was to assess the concentration and distribution of iron in liver biopsies from 15 patients with CHCV seen at the authors' medical center between June 1992 and March 1993. Patients with complete response to IFN were compared to those with non-complete response with respect to quantitative hepatic iron concentration, serum iron indices, and a detailed analysis of histologic features of hematoxylin-and-eosin and iron-stained pre-IFN biopsies. Patients with non-complete response had significantly higher scores for stainable iron in sinusoidal cells (P = .02) and portal tracts (P = .05) than did patients with complete response. Total hepatic iron scores, mean quantitative hepatic iron, and mean serum ferritin were higher in patients with noncomplete response, but the differences were not significant. In conclusion, iron deposition in sinusoidal cells and portal tracts is significantly less frequent in patients with complete response to IFN than in those with poor or no response, and may be a useful, objective predictor of response to IFN therapy.
Ubiquitin (UB), an intracellular protein that binds to other proteins to target them for proteolysis, is associated with Mallory hyalin (MH), which supports a biopsy diagnosis of nonalcoholic ...steatohepatitis (NASH). We analyzed 54 liver biopsy specimens from 49 patients with a clinical diagnosis of NASH for immunoreactive UB and multiple features of necroinflammation, fibrosis, and Prussian blue-positive iron to determine whether the presence of immunoreactive UB increases detection of MH or correlates with other features of cell injury or mutations of the HFE gene. MH and UB were graded. Analysis for HFE gene mutations was performed in 48 patients. Biopsy diagnoses were distributed as follows: NASH, 42; steatosis, 10; and nonspecific changes, 2. UB was present in 20 specimens and MH in 23. Of 31 specimens with 0 MH, 6 had UB; of 14 with 1 + (questionable) MH, 7 had 1+ or 2+ UB. UB correlated positively and significantly with the diagnosis and grade of NASH, presence of MH, cell swelling, lobular inflammation, and fibrosis. Immunostaining for UB may enhance detection of MH in questionable cases, support the diagnosis of NASH, and indicate which patients may be at risk for progression of disease.
Recombinant human intercrine reduced in hepatomas (hIRH)/stromal cell‐derived factor 1 (SDF1‐α)/pre‐B‐cell growth‐stimulating factor (PBSF), a new chemokine, exhibits an in vitro chemotaxis to ...neutrophils and a mixed in vivo chemotactic activity to neutrophils, lymphocytes, and monocytes in a rat intradermal injection model. We have investigated the messenger RNA (mRNA) expression of interleukin‐8 (IL‐8) and hIRH, in chronic hepatitis C of differing severity. Levels of expression of IL‐8 and hIRH mRNA obtained from 37 human liver biopsy samples were measured by reverse‐transcription and semiquantitative polymerase chain reaction (RT‐PCR) amplification. We examined the correlation between mRNA expression and components of the histological activity index (HAI). Patients with HAI ≥ 8 had a significantly higher corrected IL‐8 mRNA expression ratio (0.24 ± 0.13 mean ± SD; n = 20) than those with HAI ≤ 7 (0.05 ± 0.03; n = 17; P< .0001). Additionally, IL‐8 mRNA expression was strongly associated with the severity of portal inflammation (PI) (high PI vs. low PI, 0.22 ± 0.14 vs. 0.05 ± 0.04; P < .0001) and with the presence of bile duct lesions (0.29 ± 0.15 vs. 0.11 ± 0.1; P < .01). In contrast, hIRH mRNA expression was not associated with the total HAI, any components of the HAI, or bile duct inflammation or injury. These results suggest that hIRH, although having the ‐CXC‐, alpha chemokine motif, and exhibiting in vivo and in vitro inflammatory activity as does IL‐8, plays a different role from IL‐8 in hepatic inflammation and injury. IL‐8 expression is directly associated with inflammation in patients with chronic hepatitis C, while hIRH expression does not correlate with histopathological severity of inflammation.
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