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At least 775 records · Page 43Linked to original sources
PubMed1999

Non-alcoholic fatty liver: another feature of the metabolic syndrome?

BACKGROUND AND AIMS: Hepatic steatosis and nonalcoholic steatohepatitis (NASH) have been associated with obesity, non insulin-dependent diabetes mellitus and hyperlipidemia. The present study was designed in order to evaluate whether patients with steatosis/NASH presented common features with the metabolic syndrome. METHODS: In 30 patients with nonalcoholic fatty liver the prevalence of hypertension and diabetes; the glucose/insulin profile, lipid profile, and serum leptin were evaluated and correlated with body composition and energy expenditure, assessed by bioimpedance spectroscopy and indirect calorimetry, respectively. Results were compared with a group of eight controls. RESULTS: Obesity was present in 80% of patients, hypertension in 50% and non insulin dependent diabetes in 33%. Glucose metabolism was altered in 69%, with elevated insulin in 14 patients. Serum leptin, higher in women, was increased in patients: 33.9 +/- 38.9 vs 9.6 +/- 6.9 ng/ml, P< 0.05. There was a correlation between insulin and leptin, both of which correlated with body mass index, fat mass and percentage of body fat. Dyslipidaemia was found in 80% of patients: 45% presented low high density lipoproteins cholesterol, 58% high low density lipoproteins and 38% elevated very low density lipoproteins. CONCLUSIONS: There is a strong association between nonalcoholic fatty liver and features of the metabolic syndrome, suggesting a simultaneous insulin resistance and decreased sensitivity to leptin.

Adult↗
PubMed2002

Many species partial adaptive dynamics.

A system of n asexual populations is considered in which both intra- and interspecific frequency-dependent matrix game conflicts with a lack of information are involved and the weak perturbation condition is satisfied (mutation is a very rare event and selection is quick). A new partial adaptive game dynamics is proposed that takes into account that the mutants interact not only with the residents but among themselves as well. It is also shown that if the Nash equilibrium (NE) is totally mixed and the interaction matrices are Replicator-Lyapunov stable (RL-stable), then the NE is an asymptotically stable point of these new dynamics.

Adaptation, Physiological↗
PubMed2000

Hydroperoxide specificity of plant and human tissue lipoxygenase: an in vitro evaluation using N-demethylation of phenothiazines.

Since hydroperoxide specificity of lipoxygenase (LO) is poorly understood at present, we investigated the ability of cumene hydroperoxide (CHP) and tert-butyl hydroperoxide (TBHP) to support cooxidase activity of the enzyme toward the selected xenobiotics. Considering the fact that in the past, studies of xenobiotic N-demethylation have focused on heme-proteins such as P450 and peroxidases, in this study, we investigated the ability of non-heme iron proteins, namely soybean LO (SLO) and human term placental LO (HTPLO) to mediate N-demethylation of phenothiazines. In addition to being dependent on peroxide concentration, the reaction was dependent on enzyme concentration, substrate concentration, incubation time, and pH of the medium. Using Nash reagent to estimate formaldehyde production, the specific activity under optimal assay conditions for the SLO mediated N-demethylation of chlorpromazine (CPZ), a prototypic phenothiazine, in the presence of TBHP, was determined to be 117+/-12 nmol HCHO/min/mg protein, while that of HTPLO was 3.9+/-0.40 nmol HCHO/min/mg protein. Similar experiments in the presence of CHP yielded specific activities of 106+/-11 nmol HCHO/min/mg SLO, and 3.2+/-0.35 nmol HCHO/min/mg HTPLO. As expected, nordihydroguaiaretic acid and gossypol, the classical inhibitors of LOs, as well as antioxidants and free radical reducing agents, caused a marked reduction in the rate of formaldehyde production from CPZ by SLO in the reaction media fortified with either CHP or TBHP. Besides chlorpromazine, both SLO and HTPLO also mediated the N-demethylation of other phenothiazines in the presence of these organic hydroperoxides.

Benzene Derivatives↗
PubMed1998

Spectrophotometric investigation of the formed chelate between timonacic and palladium(II) and its analytical applications.

A simple spectrophotometric method for the determination of timonacic is presented. The procedure is based on the chelate formation with palladium(II) chloride in buffered medium. The optimum conditions for the complex formation were ascertained and the method was developed for the determination of timonacic in the concentration range of 28-48 micrograms ml-1. The emperical formula of the formed complex was determined, by applying different spectrophotometric methods, at optimum pH of 4.8 and an ionic strength of mu = 0.5. The stoichiometric ratio was found to be 2:1 (timonacic/palladium) as calculated by the mole ratio, continuous variations and Asmus methods. The continuous variations and Nash methods were applied for the determination of the conditional stability constant of the formed yellow-water soluble complex and was found to be 3.27 x 10(7). The proposed methods was found to be suitable for the determination of timonacic in bulk and in its pharmaceutical tablets.

Antineoplastic Agents↗
PubMed2003

Does mammography hurt?

The documented incidence of pain associated with screening mammography varies from 1% to 62%. Some researchers suggest that pain may undermine compliance with screening mammography. As a part of a quality improvement project, we have surveyed women undergoing mammography in 2 centers in Jerusalem to identify the prevalence, severity, and duration of mammography-associated pain, demographic risk factors, and the degree that this may undermine compliance with breast cancer screening. A 23-item questionnaire was administered to 399 women (32% at the Shaare Zedek Medical Center [SZMC] and 68% at the Rachel Nash Comprehensive Breast Clinic [HALA]). Of the total, 77% of the women reported that the procedure was painful. Of those reporting pain, 60% described pain intensity as moderate or severe. In 67%, the pain resolved within 10 minutes. By univariate analysis, the only significant predictor for pain during mammography was cyclic breast pain (P = 0.053). No significant correlation was identified for age, breast size, pre-mammography counseling, and examination center (SZMC vs. HALA). The prevalence of pre-mammography counseling or explanation was low (51%). Despite that, 61% of the respondents expected that mammography would be painful. Indeed, most of those who anticipated pain reported that the actual severity was not greater than the anticipated severity. Even among women who reported pain of moderate or greater severity, less than 5% expressed preference to receive pre-emptive analgesia prior to their next mammogram. A substantial minority of women acknowledged that the experience of their mammography invoked reactions that may impend future compliance; 26% reported anxiety and 12% reported pain as factors that may interfere with ongoing compliance with regular mammographic screening. These data serve to emphasize the need for appropriate pre-test counseling and suggest a possible role for post-test debriefing to address those factors which may interfere with future test compliance.

Female↗
PubMed1994

Mechanism of catalysis by eukaryotic DNA topoisomerase I.

The elucidation of the chemistry of the topo I reaction has provided the first example of how a phosphodiester bond in DNA can be temporarily broken and the energy for reclosure stored in a covalent linkage between the end of the broken strand and the enzyme (Champoux, 1977a, 1981). This type of reaction offers several advantages to the cell. First, unnecessary exposure of DNA ends to nucleolytic attack is prevented. Second, breakage and reclosure of DNA strands can occur without an expenditure of ATP energy. Third, the combined breakage and rejoining reactions can be both spatially and temporally coordinated with other cellular activities by regulating the activity of a single protein molecule. This general mechanism has not only been extended to type II topoisomerases (see Chapters 3 and 5), but also to the specialized single-stranded phage replication proteins (e.g., phi X174 gene A protein) (Ikeda et al., 1976; Eisenberg et al., 1977) and to site-specific recombinases such as the bacteriophage lambda integrase (Craig and Nash, 1983), the delta gamma and Tn3 resolvases (Reed, 1981; Reed and Grindley, 1981; Krasnow and Cozzarelli, 1983; Hatfull and Grindley, 1986), and the yeast 2-microns circle FLP recombinase (Andrews et al., 1985; Gronostajski and Sadowski, 1985). Since the site-specific recombinases attach the broken strand to a different terminus rather than simply restoring the original phosphodiester bond as conventional topoisomerases do, they have been referred to as DNA strand transferases. It is conceivable that a similar mechanism applies to the rearrangement of immunoglobulin genes (Schatz et al., 1990) and to other specific genomic rearrangements that might occur during development (Matsuoka et al., 1991).

Animals↗
PubMed2003

Hepatic function and physiology in the newborn.

The liver develops from progenitor cells into a well-differentiated organ in which bile secretion can be observed by 12 weeks' gestation. Full maturity takes up to two years after birth to be achieved, and involves the normal expression of signalling pathways such as that responsible for the JAG1 genes (aberrations occur in Alagille's syndrome), amino acid transport and insulin growth factors. At birth, hepatocytes are already specialized and have two surfaces: the sinusoidal side receives and absorbs a mixture of oxygenated blood and nutrients from the portal vein; the other surface delivers bile and other products of conjugation and metabolism (including drugs) to the canalicular network which joins up to the bile ductules. There is a rapid induction of functions such as transamination, glutamyl transferase, synthesis of coagulation factors, bile production and transport as soon as the umbilical supply is interrupted. Anatomical specialization can be observed across the hepatic acinus which has three distinct zones. Zone 1 borders the portal tracts (also known as periportal hepatocytes) and is noted for hepatocyte regeneration, bile duct proliferation and gluconeogenesis. Zone 3 borders the central vein and is associated with detoxification (e.g. paracetamol), aerobic metabolism, glycolysis and hydrolysis and zone 2 is an area of mixed function between the two zones. Preterm infants are at special risk of hepatic decompensation because their immaturity results in a delay in achieving normal detoxifying and synthetic function. Hypoxia and sepsis are also frequent and serious causes of liver dysfunction in neonates. Stem cell research has produced many answers to the questions about liver development and regeneration, and genetic studies including studies of susceptibility genes may yield further insights. The possibility that fatty liver (increasingly recognized as non-alcoholic steatohepatitis or NASH) may have roots in the neonatal period is a concept which may have important long-term implications.

Fatty Liver↗
PubMed2001

Influence of TT virus on the histopathological features of nonalcoholic fatty liver disease.

The sera of 38 patients with nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH), were tested for TT virus (TTV) DNA by polymerase chain reaction (PCR) using three different primer pairs (UTR PCR, N22 PCR and genotype-1 PCR), and various histological features of the liver biopsy specimens were compared among those who were positive or negative for TTV infection. By UTR PCR which detects all TTV genotypes, TTV DNA was detected in 37 (97%) of the 38 patients. In contrast, N22 PCR which detects primarily TTV genotypes 1-4, detected TTV DNA in 18 patients (47%). In the liver biopsy specimens, moderate to many acidophilic bodies, moderate to marked focal/spotty necrosis of hepatocytes and marked stellate, pericellular or perivenular fibrosis were observed significantly more frequently among those who were positive for TTV DNA by N22 PCR, than among those who were negative by N22 PCR. Twelve patients (32%) were positive for TTV genotype 1. Moderate to marked vacuolation of nuclei, moderate to many acidophilic bodies, and moderate to marked focal/spotty necrosis as well as marked stellate, pericellular or perivenular fibrosis were found significantly more frequently in the TTV genotype 1-positive group than in the TTV genotype 1-negative group. These results suggest that certain TTV genotypes including genotype 1 influence the necrosis and inflammation of hepatocytes and liver fibrosis in NAFLD patients.

Journal Article↗
PubMed2003

T cell proliferative responses to malondialdehyde-acetaldehyde haptenated protein are scavenger receptor mediated.

Malondialdehyde-acetaldehyde (MAA) haptenated proteins have been described in disease processes related to prolonged oxidative stress (via malondialdehyde production), such as alcohol liver disease (ALD), non-alcoholic non-steatohepatitis (NASH) and atherosclerosis. Experimentally, high titer IgG1 antibody responses are seen after immunization without adjuvant; however, T cell proliferative responses and the role of scavenger receptors in this immunogenicity has not previously been described. In this study, T cell proliferative responses to the carrier protein, but not the MAA hapten itself, were identified in vitro. Moreover, these T proliferative responses were inhibited when MAA-hen egg lysozyme (HEL) was co-immunized with excess scavenger receptor ligand polyG (poly-guanylic acid), implicating the role of (a) scavenger receptor(s) in initiating the T helper cell response. Activated B cells were unable to process and present MAA-HEL preferentially to T cells, while thioglycollate-elicited (but not Con A-elicited) macrophages and dendritic cells (DC) did so with approximately 32-fold less MAA-HEL than native antigen necessary to initiate equal proliferative responses. While this preferential processing and presentation may be related to several factors, preferential binding of MAA haptenated proteins mediated by scavenger receptors may be one mechanism. IL-4 was absent from the supernatants of T proliferative assays despite a strong IgG1 response in vivo, although the TH2 cytokines IL-6 and IL-10 were expressed. Since the modification of proteins by the MAA have previously been shown to occur after ethanol consumption in vivo, the ability of MAA haptens to experimentally enhance immune responses, specifically humoral and T cell responses, may represent mechanisms by which autoimmune phenomena found in ALD occur.

Acetaldehyde↗
PubMed1993

Structure/function studies of HIV-1(1) reverse transcriptase: dimerization-defective mutant L289K.

Virion-derived HIV-1 reverse transcriptase (RT) has subunits of molecular mass 66 and 51 kDa (p66 and p51, respectively) in an approximately 1:1 ratio. Since enzyme activity appears to depend on dimerization of these subunits, identification of critical regions of primary sequence required for proper dimerization could lead to potential targets for antiviral therapy. A central region of primary sequence contains a leucine hepta-repeat motif from leucine 282 to leucine 310 that has been suggested to be involved in dimerization [Baillon, J. G., Nashed, N. T., Kumar, A., Wilson, S. H., & Jerina, D. M. (1991) New Biol. 3, 1015-1019]. A region including this hepta-repeat was recently shown to be involved in protein-protein interactions required for dimerization [Becerra, S. P., Kumar, A., Lewis, M. S., Widen, S. G., Abbotts, J., Karawya, E. M., Hughes, S. H., Shiloach, J., & Wilson, S. H. (1991) Biochemistry 30, 11708-11719]. To investigate the role of this repeat motif in dimerization, we performed site-directed mutagenesis of these leucine residues from position 282 to position 310. Mutations were introduced into p66 and p51 RT coding sequences, and the individually purified RT subunit polypeptides were compared with wild-type polypeptides for dimerization. Physical characterization of the purified mutant peptides was conducted by circular dichroism analysis. Binding between p66 and p51 was studied by gel filtration, ultracentrifugation, and CD analysis. L289K-p66 was unable to dimerize with itself and wild-type or L289K-p51. The leucine repeat motif in the p66 subunit appears to be critical in formation of the heterodimer.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1976

2' Derivatives of guanosine and inosine cyclic 3',5'-phosphates. Synthesis, enzymic activity, and the effect of 8-substituents.

A series of representative derivatives of guanosine cyclic 3',5'-phosphate (cGMP) and inosine cyclic 3',5'-phosphate (cIMP) which contained modifications in either the 2' position or the 8 and 2' positions were synthesized. Three types of derivatives were investigated: (1) derivatives in which the 2' position has been altered to produce a 2'-deoxynucleoside cyclic 3',5'-phosphate or a 9-beta-D-arabinofuranosylpurine cyclic 3',5'-phosphate; (2) 2'-omicron-acyl derivatives; and (3) doubly modified derivatives containing a 2' modification [as in (1) and (2)] and an 8-substitution. 2'-Deoxyinosine cyclic 3',5'-phosphate and 9-beta-D-arabinofuranosylhypoxanthine cyclic 3',5'-phosphate were obtained by HNO2 deamination of 2'-deoxyadenosine cyclic 3',5'-phosphate and 9-beta-D-arabinofuranosyladenine cyclic 3',5'-phosphate (ara-cAMP), respectively. Treatment of 8-bromo-2'-omicron-(p-toluenesulfonyl) adenosine cyclic 3',5'-phosphate with NaSH yielded the intermediate 8,2'-anhydro-9-beta-D-arabinofuranosyl-8-mercaptoadenine cyclic 3',5-phosphate, which was converted directly to 2'-deoxyadenosine cyclic 3',5'-phosphate (dcAMP) by treatment with Raney nickel. 8-Bromo-2'-omicron-(p-toluenesulfonyl) guanosine cyclic 3',5'-phosphate was converted to 8,2'-anhydro-9-beta-D-arabinofuranosyl-8-mercaptoguanine cyclic 3',5'-phosphate, and the latter was desulfurized with Raney nickel to give 2-deoxyguanosine cyclic 3',5'-phosphate. Ara-cAMP, 9-beta-D-arabinofuranosylguanine cyclic 3',5'-phosphate, and 9-beta-D-arabinofuranosyl-8-mercaptoguanine cyclic 3',5'-phosphate have been previously reported (Mian et al. (1974), J. Med. Chem. 17, 259). 8-Bromo-2'-omicron-acetylinosine cyclic 3',5'-phosphate and 8-[(p-chlorophenyl)thio]-2'-omicron-acetylinosine cyclic 3',5'-phosphate were produced by acylation of 8-bromoinosine cyclic 3',5'-phosphate and 8-[(p-chlorophenyl)thio]inosine cyclic 3',5'-phosphate, respectively; while 8-bromo-2'-omicron-butyrylguanosine cyclic 3',5'-phosphate was synthesized by bromination of 2'-omicron-butyrylguanosine cyclic 3',5'-phosphate.

Animals↗
PubMed2002

Iron carbonyl sulfides, formaldehyde, and amines condense to give the proposed azadithiolate cofactor of the Fe-only hydrogenases.

The azadithiolate (SCH2NHCH2S) cofactor proposed to occur in the Fe-only hydrogenases forms efficiently by the condensation of Fe2(SH)2(CO)6 (1), formaldehyde, and ammonia (as (NH4)2CO3). The resulting Fe2[(SCH2)2NH](CO)6 reacts with Et4NCN to give (Et4N)2[Fe2[(SCH2)2NH](CO)4(CN)2], for which crystallographic characterization confirmed an axial N-H and an elongated C-S bond of 1.858(3) A. Primary amines RNH2 (R = Ph, t-Bu) also participate in the condensation reaction, and Fe3S2(CO)9 can be employed in place of 1. Mechanistically, the Fe2[(SCH2)2NH] moiety is shown to arise via two pathways: (i) via the intermediacy of Fe2[(SCH2OH)2](CO)6, which was detected and shown to react with amines, and (ii) via the reaction of 1 with cyclic imines (CH2)3(NR)3 (R = Ph, Me). The reaction of 1 with (CH2)6N4 (hexamethylenetetramine) gives Fe2[(SCH2)2NH](CO)6. Trace amounts of Fe2[(SCH2)2N-t-Bu](CO)6 arise via the reaction of aqueous FeSO4, formaldehyde, NaSH, and t-BuNH2 under an atmosphere of CO.

Amines↗
PubMed2003

Electrochemical synthesis of alkyl nitroaromatic compounds.

Alkyl nitroaromatic compounds were readily prepared via nucleophilic aromatic substitution for hydrogen or a heteroatom by electrochemical oxidation of the sigma-complex. Butyllithium and butylmagnesium chloride were used as nucleophiles, and several nitrocompounds were tested to explore the possibilities of the NASH and NASX reactions promoted electrochemically.

Journal Article↗
PubMed2003

A beautiful mind.

It is often difficult to discern the line between creativity and madness. This presents a particular hazard for the analyst, whose failure to recognize real potential can result in undermining the individual's developmental strivings. This dilemma is explored through a case illustration of a woman whose creativity was undermined by a lack of recognition. To vivify the dilemma, the author invites the reader to look through her eyes into the lens offered by the film A Beautiful Mind, which portrays the struggles of Nobel Prize-winning mathematician John Nash to maintain his sanity while also testing the limits of his mind and imagination. These illustrations encourage us to consider the dilemma of the gifted individual when excessive tension arises between absorption in one's medium versus needs for recognition.

Cognition↗
PubMed2003

Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: prevalence and correlates.

Eighty-four consecutive subjects with nonalcoholic fatty liver disease (NAFLD) were tested for non-organ-specific autoantibodies (NOSA) by indirect immunoflorescence. Indices of insulin resistance and biochemical and anthropometric parameters were assessed. The overall prevalence of anti-nuclear-antibodies (ANA), smooth muscle antibodies (SMA) and anti-mitochondrial-antibodies (AMA) was 35.7% (30/84), 18 subjects (21.4%) being positive for ANA, 4 (4.7%) for SMA, 6 for ANA and SMA, and 2 for AMA. NOSA-positive subjects were older (P < 0.01) and mostly females (63.3%). No significant difference was found in the age-corrected parameters studied, except for copper and ceruloplasmin, which was more elevated in NOSA-positive patients. The subset of high titer (>1:100) ANA-positive patients had significantly (P < 0.05) greater insulin resistance than ANA-negative patients. In contrast, SMA-positive patients had higher gammaglobulin and significantly lower insulin resistance as compared to high-titer ANA-positive patients. In 3 NOSA-positive but not in NOSA-negative patients, liver biopsy disclosed features of overlapping NASH with autoimmune hepatitis, partially responding to diet combined with steroid treatment. In conclusion, NOSA positivity in NAFLD is more prevalent than in the general population. High-titre ANA but not SMA positivity is associated with insulin resistance.

Adult↗
PubMed2005

[Drug therapy in chronic liver disease].

Treatment of virally induced chronic hepatitis consists of interferons, nucleotide and nucleoside analogues. So far, combination therapies are not superior to a monotherapeutic regimen. If detected early, inherited metabolic diseases (e.g. hereditary hemochromatosis, M. Wilson) can be successefuly treated, leading to a normal life expectancy of the patients. In contrary treatment of cholestatic chronic liver disease, especially of PSC, is far from being satisfying, due to our very limited knowledge of the etiology of this diseases. The same holds true for the therapy of NASH. Weight reduction and treatment of the often underlying diabetes are therapeutic cornerstones in the moment. On the other hand, immuosuppression, some times life-long, remains a (highly successful) treatment option in cases of proven autoimmune-hepatitis.

Adenine↗
PubMed2003

Hepatic and systemic haemodynamic changes after MARS in patients with acute on chronic liver failure.

Hyperdynamic circulation and portal hypertension characterize acute on chronic liver failure (AoCLF), partially because of circulating mediators. Molecular Absorbents Recirculating System (MARS) may remove some of these substances. The objective of this study was to evaluate the effect of MARS on portal pressure, systemic haemodynamic and endogenous vasoactive systems. MARS treatment was performed in four patients with AoCLF (mean age 36.2 +/- 3.1 years; Child-Pugh C 11 +/- 1.8 points; three AAH and one NASH). Systemic and splanchnic haemodynamic measurements were performed before and after each session. Plasmatic renin activity (PRA) and NE were measured at baseline, at the end of the sessions and 10 days after MARS. All patients had severe portal hypertension (HVPG=23 +/- 7 mmHg) and pronounced hyperdynamic circulation (MAP 77.8 +/- 11.7 mmHg; CO 11.2 +/- 1.6 L/min; SVRI 478.5 +/- 105 dyne s/cm5). HVPG decreased at the end of the first session in all patients (23 +/- 7 mmHg vs 17.3 +/- 9.9 mmHg; P=0.05; mean decrease 32 +/- 24%) because of a decrease in WHVP (40.7 +/- 5.6 mmHg vs 34 +/- 9.6 mmHg; P=0.025; mean decrease 18 +/- 19%). MARS significantly attenuated hyperdynamic circulation as shown by a decrease in CO (11.2 +/- 1.6 L/min vs 9.4 +/- 2.1 L/min; mean decrease 12.3%), with an increase in MAP (77.8 +/- 11.7 mmHg vs 84.2 +/- 8 mmHg; mean increase 9.2%) and in SVRI (478.5 +/- 105 dyne s/cm5 vs 622 +/- 198 dyne s/cm5; mean increase 41%). PRA and NE decreased significantly (14.2 +/- 17.2 ng/mL/h vs 3.7 +/- 3.4 ng/mL/h; 1319 +/- 1002 pg/mL vs 617 +/- 260 pg/mL, respectively). The NE decrease was correlated to HVPG decrease (r=1, P=0.01). MARS decreases portal hypertension and ameliorates hyperdynamic circulation in patients with AoCLF, probably mediated by clearance of vasoactive substances. Further studies are necessary to confirm these results.

Adult↗