Biomedical subjects

G Y Minuk

Publications and source records attributed to G Y Minuk.

At least 19 recordsLinked to original sources

PubMed2006

The effects of colectomy on immediate-early proto-oncogene expression and hepatic regeneration in the rat.

The intact liver exists in a state of replicative quiescence. The factor(s) responsible for maintaining this state and their tissue sources have yet to be identified. Because the colon synthesizes and/or absorbs numerous agents that inhibit hepatocyte proliferation, the principle purpose of this study was to determine whether total colectomy would result in the conversion of quiescent livers to a state of replicative competence. Thus, adult, male Sprague-Dawley rats (250-300 g) were randomized to undergo either total colectomy with ileostomy or sham surgery. Thereafter, rats were sacrificed (N=3-6/group) at times 15 and 30 min and 1, 2, 6, and 24 hr and the livers analyzed by Northern blot analyses for mRNA of the following immediate-early proto-oncogenes (IEP genes): c-fos, c-jun, and c-myc. Rats sacrificed at 24 hr also had hepatic regenerative activity documented by [3H]thymidine incorporation into hepatic DNA. The results of the study revealed that within 15 min, c-fos and c-jun mRNA expression increased in colectomized rats, with peak expression occurring at 30 and 60 min, respectively. c-myc mRNA expression was more delayed, with peak expression occurring at 6 hr post-colectomy. IEP gene expression also increased somewhat in sham-colectomy controls but the increases were not as prompt and, in general, were of lower magnitude than those in the colectomy group. Despite the differences in IEP gene expression between the two groups, [3H]thymidine incorporation at 24 hr was similar (mean+/-SE: colectomy group, 17.2+/-2.6 dpm/microg DNA; sham-colectomy controls, 14.8+/-1.4 dpm/microg DNA). To determine whether the increases in IEP gene expression expedite or augment the hepatic regenerative response to partial hepatectomy (PHx), rats that had undergone colectomy or sham colectomy 1 hr earlier and rats with no previous abdominal surgery then underwent a 70% PHx and were sacrificed at 8, 16, and 24 hr thereafter. At each time interval, [3H]thymidine incorporation was documented and found to be similar in the three groups. In conclusion, the results of this study indicate that total colectomy, and to a lesser extent abdominal surgery, induces the conversion of an intact, quiescent liver to a state of replicative competence. The results also suggest that, in addition to colectomy, the presence of mitogens and/or co-mitogens is required for further progression of hepatocytes through the cell cycle. Finally, a "primed" liver does not respond more promptly or vigorously to a regenerative stimulus than a "resting" liver.

Animals↗

PubMed2005

Patient concerns regarding chronic hepatitis C infections.

Counselling of patients with chronic hepatitis C infections is often limited to discussions regarding how the virus is transmitted and what can be done to decrease the risk of transmission to others. The purpose of the present study was to document the principal concerns of newly diagnosed and follow-up patients with chronic hepatitis C, and thereby enhance counselling strategies and content. Seventy newly diagnosed and 115 follow-up patients with chronic hepatitis C virus (HCV) infection were initially asked in an open-ended manner (volunteered concerns) and then to prioritize from a prepared list of seven potential concerns (prioritized concerns), to identify those concerns that were of utmost importance to them. The most common volunteered concerns of newly diagnosed patients in decreasing order were: disease progression (27%), premature death (19%), infecting family members (13%), side-effects of treatment (11%) and miscellaneous others. In decreasing order, prioritized concerns included: infecting family members, development of liver cancer, infecting others, development of cirrhosis, social stigma of having liver disease, need for liver transplant and loss of employment. The principal volunteered and prioritized concerns of follow-up patients were similar to those of newly diagnosed patients. Volunteered and prioritized concerns were relatively consistent across the different genders, age groups, ethnic backgrounds, education level, marital status, employment, modes of viral acquisition and in the case of follow-up patients, duration of follow-up. These results indicate that health care providers who focus counselling efforts exclusively on viral transmission are unlikely to address other important concerns of newly diagnosed and follow-up patients with chronic HCV infection.

Adult↗

PubMed2004

Quantitative hepatic phosphorus-31 magnetic resonance spectroscopy in compensated and decompensated cirrhosis.

Few studies have examined the physiological/biochemical status of hepatocytes in patients with compensated and decompensated cirrhosis in situ. Phosphorus-31 magnetic resonance spectroscopy ((31)P MRS) is a noninvasive technique that permits direct assessments of tissue bioenergetics and phospholipid metabolism. Quantitative (31)P MRS was employed to document differences in the hepatic metabolite concentrations among patients with compensated and decompensated cirrhosis as well as healthy controls. All MRS examinations were performed on a 1.5-T General Electric Signa whole body scanner. The concentration of hepatic phosphorylated metabolites among patients with compensated cirrhosis (n = 7) was similar to that among healthy controls (n = 8). However, patients with decompensated cirrhosis (n = 6) had significantly lower levels of hepatic ATP compared with patients with compensated cirrhosis and healthy controls (P < 0.02 and P < 0.009, respectively) and a higher phosphomonoester/phosphodiester ratio than controls (P < 0.003). The results of this study indicate that metabolic disturbances in hepatic energy and phospholipid metabolism exist in patients with decompensated cirrhosis that are not present in patients with compensated cirrhosis or healthy controls. These findings provide new insights into the pathophysiology of hepatic decompensation.

Adenosine Triphosphate↗

PubMed2004

Transforming growth factor-beta (TGF-beta) protein levels are not elevated in the blood or bile of patients with primary sclerosing cholangitis: a pilot study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder of unknown etiology characterized by progressive fibrosis and stricturing of the biliary tract. Transforming growth factor-beta (TGF-beta) is a family of cytokines produced by biliary tract epithelial cells that promote fibrinogenesis. Our objective was to determine whether TGF-beta levels are increased in the blood and/or bile of PSC patients compared to patients with other causes of obstructed biliary tracts (controls). Serum and bile TGF-beta levels were documented by enzyme-linked immunoassay in 10 adult PSC and 10 control patients obtained at the time of endoscopic retrograde cholangiography. Serum and bile TGF-beta levels were similar in the two groups (PSC versus control sera, 33.4 +/- 4.3 versus 27.5 +/- 7.7 ng/ml, and bile, 367 +/- 275 versus 457 +/- 247 ng/mg, respectively). Serum and bile TGF-beta levels are not increased in patients with PSC. Hence, the results of this pilot study do not support the hypotheses that PSC is caused by dysregulated TGF-beta expression.

Alkaline Phosphatase↗

PubMed2004

Serum immunoglobulins predict the extent of hepatic fibrosis in patients with chronic hepatitis C virus infection.

Recently, we documented that immunoglobulins stimulate the proliferative activity of rat hepatic stellate cells in vitro. The aim of the present study was to determine whether there is any association between serum immunoglobulin levels and hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection. Charts from 116 patients with biochemical, serologic, virologic and histologic evidence of chronic hepatitis C infection and serum immunoglobulin levels (IgA, IgG, IgM and total) were reviewed. The mean (+/-SD) age of the study population was 46 +/- 11 years and 67 (58%) were male. There were significant correlations between serum IgA (r = 0.39, P = 0.00001), IgG (r = 0.49, P = 0.000002) and total (r = 0.51, P = 0.000003) immunoglobulin levels and the stage of hepatic fibrosis. When serum immunoglobulin levels were included into logistic regression analysis with variables known to be associated with advanced disease (male gender, age >40 years at onset of infection, duration of infection beyond 20 years and concurrent alcohol abuse) only IgA, IgG and total immunoglobulin levels (P < 0.05, <0.05 and <0.005, respectively) emerged as independent predictors of hepatic fibrosis. Our data indicate a strong association between serum immunoglobulin levels (IgA, IgG and total) and hepatic fibrosis in patients with HCV infection. This finding supports the need to further investigate whether immunoglobulins independently promote disease progression in patients with chronic HCV infection.

Adult↗

PubMed2003

Serial percutaneous liver biopsies in laboratory rats.

The percutaneous liver biopsy is an essential tool that provides histological assessment of the liver for diagnostic, therapeutic, and prognostic purposes. To date, this procedure has not been described in the laboratory setting for studies with small laboratory animals. The aim of the present study was to assess the feasibility and diagnostic value of performing serial percutaneous liver biopsies in a rat model of chronic liver disease. Adult male Sprague-Dawley rats (N = 27) were exposed to thioacetamide (TAA) for six months, throughout which serial liver biopsies were performed at baseline and two, four, and six months. An additional group of isocaloric-fed rats (N = 6) not exposed to TAA served as controls. Following the biopsies at each time point, a subset of rats was killed to determine whether the histologic findings seen in the biopsies were consistent with the histology of the entire organ. Seven rats (21%) died from complications of the procedure (one from anaesthetic overdose and six from postbiopsy bleeding). A total of 72 biopsies were performed, resulting in a procedural mortality of 8%. In the remaining rats, biopsies were well tolerated with no overt signs of pain or discomfort. Histologic activity and fibrosis in the biopsy specimens reflected the results observed in wedge sections of liver tissue at all stages of TAA-induced liver disease. The results of this study indicate that serial percutaneous liver biopsies can be successfully performed and reflect the extent of hepatic injury in a common model of chronic liver disease.

Animals↗

PubMed2003

Hepatic 31P MRS in rat models of chronic liver disease: assessing the extent and progression of disease.

BACKGROUND: Hepatic adenosine triphosphate (ATP) levels are an accurate reflection of functioning hepatic mass following surgical resections and acute liver injury. OBJECTIVE: To determine whether hepatic ATP levels can serve as a non-invasive means of documenting progression of chronic liver disease to cirrhosis. METHODS: In vivo phosphorus-31 magnetic resonance spectroscopy ((31)P MRS) was performed in three animal models of chronic liver disease. Sixty six adult Sprague- Dawley rats were subjected to either thioacetamide, carbon tetrachloride (CCl(4)), or common bile duct ligation (CBDL) to induce liver disease (n=35, 21, and 10, respectively). Serial MRS examinations, blood samples, and liver biopsies (when appropriate) were obtained throughout and/or on completion of the study. RESULTS: Over the course of the chronic liver disease, a progressive decrease in hepatic ATP levels was consistently observed in each model. The findings were most striking when end stage liver disease (cirrhosis) was established. The reduction in hepatic ATP levels correlated with significant changes in serum albumin concentrations (CCl(4) and CBDL models) and the extent of hepatocyte loss seen histologically (all models). CONCLUSION: The results of this study indicate that during progression of chronic liver disease to cirrhosis, there is a progressive reduction in hepatic ATP levels. In addition, changes in hepatic ATP levels correlate with changes in liver function and histology. Thus hepatic (31)P MRS provides a non-invasive means of documenting the severity and progression of parenchymal and cholestatic models of chronic liver disease in rats.

Adenosine Triphosphate↗

PubMed2003

Increasing cell membrane potential and GABAergic activity inhibits malignant hepatocyte growth.

Increasing hepatocyte membrane potentials by augmenting GABAergic activity inhibits nonmalignant hepatocyte proliferative activity. The objectives of this study were to document 1) potential differences (PDs) of four malignant hepatocyte cell lines, 2) GABAA receptor mRNA expression in the same cell lines, and 3) effects of restoring malignant hepatocyte PDs to levels approximating those of resting, nonmalignant hepatocytes. Hepatocyte PDs were documented in nonmalignant and malignant (Chang, HepG2, HuH-7, and PLC/PRF/5) hepatocytes with a fluorescent voltage-sensitive dye and GABAA receptor expression by RT-PCR and Western blot analyses. Compared with nonmalignant human hepatocytes, all four malignant cell lines were significantly depolarized (P < 0.0001, respectively). Only PLC/PRF/5 cells had detectable GABAA-beta3 receptor mRNA expression and all cell lines were negative for GABAA-beta3 receptor protein by Western blot analysis. Stable transfection of Chang cells with GABAA-beta3 receptor cDNA resulted in significant increases in PD and decreases in proliferative activity as manifest by decreased [3H]thymidine and bromodeoxyurieine incorporation rates, 4-[3-(4-lodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate activity, a lower mitotic index, prolongation of cell-doubling times, and attenuated growth patterns compared with cells transfected with vector alone. Colony formation in soft agar and the number of abnormal mitoses were also significantly decreased in GABAA-beta3 receptor transfected cells. The results of this study indicate 1) relative to healthy hepatocytes, malignant hepatocytes are significantly depolarized, 2) GABAA-beta3 receptor expression is absent in malignant hepatocyte cell lines, and 3) increasing the PD of malignant hepatocytes is associated with less proliferative activity and a loss of malignant features.

Carcinoma, Hepatocellular↗

PubMed2003

Hepatic regeneration: If it ain't broke, don't fix it.

The capacity for the liver to regenerate after injury or resection has long been recognized, as implied by the legend of Prometheus. Resections of up to 70% of the liver are followed by a sequence of events that generally result in complete restitution of hepatic mass and function. Hypertrophy of hepatocytes begins within hours, with accumulation of amino acids and triglycerides and activation of enzymes that are associated with proliferative activity. Increased DNA synthesis is associated initially with hyperplasia of hepatocytes, and then other cells, which begins in the periportal region and spreads in a wave-like fashion to the pericentral region of the lobule. Quiescent hepatocytes are primed to enter the cell cycle and then proceed through the G1/S and G2/M restriction points, under the influence of a variety of proteins, growth factors (especially hepatocyte growth factor) and cycle dependent kinases. At each stage there is interplay between growth promoters and inhibitors, including transforming growth factor-beta and GABA. Factors that initiate hepatic regeneration are unknown, and might include hepatic depolarization, increases in blood flow, destruction of liver matrix (with release of growth factors), and increased production or expression of growth promoters compared to inhibitors. Regenerative activity increases with the amount of resection to a point, and then relatively declines. Uncontrolled proliferation of liver tissue after resection or injury is not necessarily beneficial, because it could lead to a diversion of resources from the maintenance of hepatic function and to an increased risk of neoplasia. Therefore, it is unclear whether clinicians should attempt to enhance hepatocyte regeneration. Since both hepatic regeneration and metabolic function require energy from high-energy nucleotide triphosphates, especially adenosine triphosphate (ATP), a reasonable strategy might be to augment energy delivery and ATP production. Mortality rates after limited (fewer than 70%) resections and mild or moderate injuries of previously normal livers are low, and supportive care is often sufficient. The prognosis is unclear; however, in cases of more massive resection, resections in the setting of underlying liver disease or cirrhosis, and fulminant hepatic failure, and liver transplantation is still an important option.

Adenosine Triphosphatases↗

PubMed2003

Viral hepatitis in a Canadian First Nations community.

Serological markers for hepatitis A (HAV), B (HBV) and C (HCV) were documented in 315 inhabitants (27%) of a central Manitoba First Nations community. Serologic evidence of HAV infection (anti-HAV positive) was almost universal (92%) by the age of 20 years. HBV infection (antibody to hepatitis B core antigen positive) had occurred in only 2.3% of the study population and no chronic carriers were identified. Serological evidence of HCV infection (anti-HCV positive) was documented in 2.2% of the population but ongoing viremia (HCV-RNA positive by polymerase chain reaction) was absent. The results of this study highlight the importance of universal HAV vaccination; likely reflect the efficacy of existing prenatal screening and immunoprophylaxis programs for HBV; and raise the possibility that First Nations peoples have an enhanced ability to spontaneously clear HCV.

Adult↗

PubMed2002

A cyclin-dependent kinase inhibitor (p21(WAF1/CIP1)) affects thymidine incorporation in human liver cancer cells.

p21(WAF1/CIP1) is a universal cyclin-dependent kinase inhibitor. To investigate the role of p21(WAF1/CIP1) in proliferation of human liver cancer cells, we examined the expression of p53, p21(WAF1/CIP1), cdk2 and cdk4 expression in two human liver cancer cell lines (HepG2 and PLC/PRF/5 cells). The effects of p21(WAF1/CIP1) on [(3)H]thymidine incorporation and cdks were also examined in these cells. HepG2 cells expressed all these proteins with lower level of cdk4. PLC/PRF/5 cells expressed the other proteins except p21(WAF1/CIP1). Transfection of p21(WAF1/CIP1) gene inhibited [(3)H]thymidine incorporation of both cells with different extent. Although the transfection of p21(WAF1/CIP1) did not affect cdk2 and cdk4 expression, it did reduce cdk2 kinase activity by 20%. These results suggest that: (a) p21(WAF1/CIP1) involved in DNA synthesis of human liver cancer cells; (b) p21(WAF1/CIP1) could be a target gene for the treatment of human hepatocellular carcinoma.

Adenosine Triphosphate↗

PubMed2002

Liver development in a rat model of fetal alcohol syndrome.

The inhibitory effects of alcohol on hepatic growth in adults raises the possibility that the liver may be involved in fetal alcohol syndrome (FAS) in infants. To test this hypothesis, pregnant Sprague-Dawley rats were fed liquid diets containing either ethanol as 36% of the total calories, or were allowed ad libitum feeding of a control liquid diet (controls) throughout pregnancy. Other dams were exposed to the ethanol diet only during the first or last half of pregnancy. Pups delivered of dams exposed to the various diets (N = 40-45/group) were killed at 1, 3, 7, and 14 days of age. In addition to brain weights, crown-rump lengths, and facial features, the following parameters of liver development were documented; liver weight, liver/body weight ratio, liver histology, hepatic ornithine decarboxylase activity (ODC), hepatic protein content, and rate of hepatic DNA synthesis (as determined by [3H]thymidine incorporation). The results revealed that pups exposed to ethanol throughout pregnancy but not ad libitum control diet pups had brain weights, crown-rump lengths, and facial features in keeping with FAS. With respect to liver development, the livers in FAS pups were consistently smaller than in the control group. However, total body weights were decreased to a greater extent, such that when corrected for body weights, the smaller livers in FAS pups only became significant on day 14 of life. Liver histology was similar in the two groups with no signs of active inflammation or fibrosis. Hepatic ODC activity was also similar, indicating no impairment in polyamine synthesis. Hepatic DNA synthesis rates were decreased in FAS pups at all time intervals. Pups delivered of dams exposed to ethanol during either the first or last half of pregnancy had results comparable to those of controls. To identify the mechanism(s) responsible for these findings, a second series of experiments was performed wherein the hepatic expression of the following factors associated with liver development were documented by northern-blot analyses; growth hormone receptor (GHr), insulin-like growth factor-I (IGF-I) and -II (IGF-II) and IGF binding proteins (IGFBPs) 1, 2, 3, and 4 mRNA on gestational days 16 and 20 and postpartum days 1 and 7. In this series, a third group of pups derived from dams in whom caloric consumption was matched to that of the ethanol-fed dams (isocaloric controls) were also studied. The results revealed no consistent differences in GHr, IGF, or IGFBP mRNA expression in the three groups. In conclusion, liver development and hepatic DNA synthesis were significantly impaired in this animal model of FAS. That impairment, however, was not associated with decreases in either polyamine synthesis or disturbances in the hepatic component of the GH/IGF/IGFBP axis.

Animals↗

PubMed2002

Proliferative and nutritional dependent regulation of glyceraldehyde-3-phosphate dehydrogenase expression in the rat liver.

Glyceraldehyde-3-phosphate dehydrogenase is a multifunctional protein possessing numerous cytoplasmic and nuclear functions associated with cellular proliferation. Despite the emerging role of glyceraldehyde-3-phosphate dehydrogenase in regulating the proliferative process, there is a paucity of data regarding its expression and intracellular distribution in non-malignant proliferating hepatocytes. Thus the aim of the present study was to document the intracellular distribution of glyceraldehyde-3-phosphate dehydrogenase protein in proliferating hepatocytes derived from regenerating rat livers, and glyceraldehyde-3-phosphate dehydrogenase gene expression in fasted and re-fed rats following partial hepatectomy (PHx). Glyceraldehyde-3-phosphate dehydrogenase mRNA and protein expression were documented by Northern and Western blot analyses, respectively, at various times following 70% PHx in adult Sprague-Dawley rats. At 24 h post-surgery, glyceraldehyde-3-phosphate dehydrogenase mRNA expression was significantly increased in both PHx and sham operated rats (P < 0.001), respectively. Despite the increase in glyceraldehyde-3-phosphate dehydrogenase mRNA expression in both groups, only PHx rats had a significant increase in the nuclear fraction of glyceraldehyde-3-phosphate dehydrogenase protein (threefold increase compared to sham and baseline levels, P < 0.01), cytoplasmic levels of glyceraldehyde-3-phosphate dehydrogenase protein remained unaltered in both groups. In terms of the effects of feeding and fasting on rats there were no significant differences in glyceraldehyde-3-phosphate dehydrogenase mRNA levels, whether fasted or refed, in rats that had undergone PHx, 8 h earlier. On the other hand, glyceraldehyde-3-phosphate dehydrogenase mRNA levels were significantly increased in refed compared to fasted sham operated rats 8 h following surgery. Serum insulin concentrations were higher in the refed PHx and sham groups compared to their fasted counterparts. The results of this study indicate that although glyceraldehyde-3-phosphate dehydrogenase mRNA are altered to the same extent in PHx and sham-operated rats following surgery, increases in the nuclear fraction of glyceraldehyde-3-phosphate dehydrogenase protein only occur in PHx rats. The results also indicate that glyceraldehyde-3-phosphate dehydrogenase expression is affected by the nutritional status of animals undergoing abdominal sham surgery.

Animals↗

PubMed2002

Use of fluoroquinolones in patients with chronic hepatitis C virus-induced liver failure.

Fluroquinolone antibiotics have been reported to have antiviral properties against RNA viruses, including hepatitis C virus (HCV). In the present study, five patients with advanced liver disease secondary to chronic HCV received 500 mg daily of oral ciprofloxacin for 30 days. Serum HCV-RNA levels and liver enzyme abnormalities remained largely unchanged. Thus, the role of fluoroquinolones as antiviral agents for chronic HCV in patients with advanced liver disease appears to be limited.

Alanine Transaminase↗

PubMed2001

Shear stress-induced nitric oxide release triggers the liver regeneration cascade.

The trigger of the liver regeneration cascade is currently unknown and has been the subject of debate. We hypothesize that, following 2/3 partial hepatectomy (PHX), an increase in the blood flow-to-liver mass ratio results in shear stress-induced nitric oxide (NO) release, which triggers the liver regeneration cascade. Portal venous pressure (PVP), reflecting shear stress in the liver, increased to the same extent following PHX and selective portal vein branch ligation (PVL), a hemodynamic model of PHX, suggesting similar amounts of shear stress in both models. Two indices of the initiation of the liver regeneration cascade were used: proliferative factor (PF) activity in blood 4 h after PHX or PVL and hepatic c-fos mRNA expression 15 min. after PHX or PVL. PF activity and c-fos mRNA expression were increased to similar extents after PHX and PVL, suggesting a similar stimulus in both models. PF activity and c-fos mRNA expression were inhibited by administration of the nitric oxide synthase antagonist, l-NAME, and the NO donor, SIN-1, reversed the inhibition in both models. These results provide support for the hypothesis that a hemodynamic change results in increased shear stress in the liver causing generation of NO, which then triggers the liver regeneration cascade.

Animals↗

PubMed2001

Immediate-early protooncogene expression and liver function following various extents of partial hepatectomy in the rat.

Immediate-early protooncogenes (IEP) are thought to play an important role in hepatocyte replication. Whether the extent of their expression correlates with the strength of the proliferative stimulus and subsequent regenerative activity has yet to be documented in vivo. Data are also lacking with respect to the level at which liver disease is associated with biochemical evidence of hepatic dysfunction. Thus, the objectives of this study were to determine whether a correlation exists between IEP gene mRNA expression and varying extents of partial hepatectomy (PHx) and to document the extent of resection required to result in increases in serum bilirubin levels. Eighty-nine adult, male Sprague-Dawley rats underwent either sham surgery or 20%, 35%, 55%, 70% or 90% PHx. Postoperatively, rats were killed (N = 3-6/group) at 15 and 30 mins and 8 and 24 hrs for c-fos, c-jun, and c-myc mRNA expression by northern blot analyses. Rats killed at 24 hrs also had hepatic regenerative activity documented by [3H]thymidine incorporation into hepatic DNA and serum bilirubin determinations. While c-fos mRNA expression at 15 mins and c-myc mRNA expression at 8 hrs after PHx did not correlate with the extent of PHx (r2 = 0.478 and 0.018, respectively), a weak correlation existed between c-jun mRNA expression at 30 mins and the extent of PHx (r2 = 0.662, P < 0.05). In terms of IEP mRNA expression and hepatic regenerative activity, a strong correlation existed between c-fos mRNA expression and [3H]thymidine incorporation (r2 = 0.851, P < 0.01) but not c-jun or c-myc mRNA expression. Compared to sham operated controls, [3H]thymidine incorporation was 2.0x, 3.4x, 3.2x, 7.8x, and 2.2x increased following 20%, 35%, 55%, 70%, and 90% PHx, respectively. Serum bilirubin levels remained unchanged until 70% PHx, when they increased from baseline values of 0.54+/-0.05 mg/dl to 1.02+/-0.15 mg/dl (P < 0.05). A further increase occurred following 90% PHx (1.83+/-0.30 mg/dl, P < 0.01). In conclusion these findings indicate that c-fos mRNA expression 15 mins after PHx correlates with hepatic regenerative activity but not the strength of the regenerative stimulus and that hepatic parenchymal loss of 55-70% must occur prior to the detection of elevated serum bilirubin levels. The results also indicate that relative to a 70% PHx, 90% PHx is associated with decreased rather than increased hepatic regenerative activity.

Animals↗

PubMed2001

The impact of medical informatics on the confidence of rural physicians caring for patients with chronic hepatitis C viral infections.

OBJECTIVE: The purpose of the present study was to determine whether CD-based medical informatics enhances rural physicians' confidence in the management of patients with chronic hepatitis C viral infections. METHODS: A total of 385 Canadian rural physicians were mailed a CD-based medical software programme that outlines all aspects of HCV care including diagnosis, counselling, treatment and follow-up. Accompanying the CD was a brief questionnaire that addressed physicians' confidence in the following areas: (i) identifying HCV patients in their practice; (ii) laboratory use and interpretation; (iii) patient counselling; (iv) selection of candidates for treatment; (v) sharing treatment delivery; and (vi) providing follow-up. Three months thereafter, the same questionnaire was repeated. RESULTS: Of the 385 mailings, 59 (15%) physicians returned the initial questionnaire and 57 (15%) the follow-up questionnaire. Twenty-five (44%) respondents indicated they had used the CD. Baseline physician confidence was low in three of the six areas addressed. At follow-up, in addition to now being confident in all areas, CD users were significantly more confident than those who had not used the CD. Increases in physician confidence for CD users were approximately 150-300% in the six areas addressed. The value assigned the CD programme was 8/10. CONCLUSION: The results of this study indicate that: (i) rural physicians are uncomfortable in dealing with many aspects of HCV management; (ii) CD-ROM-based medical informatics can significantly enhance rural physicians' confidence in these areas; (iii) approximately 50% of physicians will employ CD-ROM-based medical informatics in their offices; and (iv) physician level of satisfaction with such programmes is high.

Attitude of Health Personnel↗

PubMed2001

Sequence and chromosomal assignment of a human novel cDNA: similarity to gamma-aminobutyric acid transporter.

Gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the mammalian brain. Although initially thought to be confined to the central nervous system, GABAergic activity has also been described in other tissues throughout the body. In the present study, we report the cloning and localization of human GABA transporter cDNA and document its expression in various human tissues. A human liver cDNA library was initially screened by a 32P-labeled murine brain GABA transporter 3 (GAT-3) cDNA probe, and full-length cDNA was cloned by employing Marathon-Ready human kidney cDNA. The human GABA transporter cDNA encoded a 569 amino acid hydrophobic protein with 12 transmembrane domains (TMs). Search of published sequences revealed high homology with rat GAT-2, murine GAT-3 cDNA, human solute carrier family 6 member 13 (SLC6A13), and a human peripheral betaine/GABA transporter. Northern blot analyses demonstrated that the human GABA transporter is expressed strongly in the kidney and to a lesser extent in the liver and brain. The sequence was well matched with human chromosome 12p13.3, suggesting the human GABA transporter contains 14 exons. The above findings confirm the existence of and further characterize a specific GABA transporter in human tissues.

Amino Acid Sequence↗