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Biomedical subjects

J Lake

Publications and source records attributed to J Lake.

At least 37 records · Page 2Linked to original sources
PubMed1995

Liver transplantation for sclerosing cholangitis.

The clinical course of 37 patients who underwent 46 liver transplantations for primary (n = 33) and secondary (n = 4) sclerosing cholangitis was reviewed. The median follow-up was 37 months. The patient and graft survivals for patients with primary sclerosing cholangitis at 1, 2, and 5 years were 96.9%, 91.6%, 87.9%, and 83.1%, 74.2%, 65.2%, respectively. In the patients with primary sclerosing cholangitis (PSC), prior surgery except for simple cholecystectomy was associated with significantly greater operative time and blood loss. No cholangiocarcinoma was identified at the time of transplantation. Human leukocyte antigen typing for PSC patients was heavily weighed toward B8 (58.8%) compared with control (11.8%). Sixty-two percent of patients with PSC also had inflammatory bowel disease. Moderate or severe rejection requiring OKT3, "rescue therapy" with FK506, or retransplantation was relatively higher in patients with inflammatory bowel disease (70%) versus patients without inflammatory bowel disease (36.4%) and a matched control group (37.5%). Progressive inflammatory bowel disease was seen in 6 of 19 patients, with 3 developing cancer and a dysplasia. Two patients in the entire group died of sepsis and 3 of colon cancer (2 recurrent and 1 primary). These data demonstrate that excellent survival results can be achieved in this group of patients. Rejection is frequent and often severe and steroid refractory. Colon cancer represents the most frequent cause of death in PSC patients after liver transplantation and demands constant attention.

Adenocarcinoma↗
PubMed1994

Localization of Saccharomyces cerevisiae ribosomal protein L16 on the surface of 60 S ribosomal subunits by immunoelectron microscopy.

Antibodies raised against a trpE-L16 fusion protein expressed in Escherichia coli were used to examine immunological relatedness between Saccharomyces cerevisiae ribosomal protein L16 and ribosomal proteins from eubacteria, halobacteria, methanogens, eocytes, and other eukaryotes. Homologues of L16 also were identified by searches of sequence data bases. Among the bacterial proteins that are immunologically related and similar in sequence to L16 are ribosomal proteins that bind 5 S rRNA. L16 protein fused near its carboxyl terminus to E. coli beta-galactosidase could assemble into functional yeast 60 S ribosomal subunits. The RPL16A-lacZ gene fusion partially complemented the slow growth or lethality of mutants containing null alleles of one or both RPL16 genes, respectively. L16-beta-galactosidase fusion protein cosedimented with ribosomes and polyribosomes, and remained associated with high salt-washed ribosomes. Monoclonal antibodies against beta-galactosidase were used to map the location of L16-beta-galactosidase on the surface of the 60 S subunit by immunoelectron microscopy. L16 was localized near the top surface of the central protuberance, where the 60 S subunit potentially contacts the 40 S subunit. This is similar to the location of the bacterial homologues of L16 in 50 S ribosomal subunits.

Amino Acid Sequence↗
PubMed1993

Immunogenicity of two recombinant hepatitis B vaccines in older individuals.

PURPOSE: Currently available hepatitis B vaccines are recombinant, yeast-derived preparations given in 10-micrograms or 20-micrograms doses. The optimum dose remains controversial. We sought to assess the relative immunogenicity of two hepatitis B vaccines, given in different doses, in older individuals. PATIENTS AND METHODS: In a multicenter, double-blind, randomized clinical trial, a total of 460 healthy subjects between 39 and 70 years of age were screened and immunized with either Engerix-B 20 micrograms or Recombivax HB 10 micrograms in standard, intramuscular, 3-dose regimens. Of these, 397 subjects were eligible to continue vaccination. Immunogenicity was measured by determination of antibody to hepatitis B surface antigen (anti-HBs). Seroconversion and seroprotection rates, and geometric mean titers of anti-HBs were calculated at 1, 3, 6, and 8 months after the initial dose of vaccine. RESULTS: Seroprotection rates for subjects receiving the 20-micrograms dose of vaccine were slightly, but not significantly, greater than for subjects receiving the 10-micrograms dose, at each time point. However, at 3 months, males receiving the higher dose had significantly higher seroprotection rates than males receiving the lower dose: 63% versus 37% (p < 0.001). At 8 months, geometric mean titers for the group receiving Engerix-B 20 micrograms were significantly greater than that for the group receiving Recombivax HB 10 micrograms: 840 mIU/mL versus 340 mIU/mL (p = 0.001). CONCLUSIONS: Immunization with the 20-micrograms dose of recombinant hepatitis B virus vaccine appeared to result in more rapid development of seroprotective anti-HBs titers in older men and in higher titers of anti-HBs at the completion of vaccination when compared to the 10-micrograms dose. The latter data suggest that the 20-micrograms dose may result in a longer duration of seroprotective anti-HBs titers.

Adult↗
PubMed1993

Hepatitis C--its prevalence in end-stage renal failure patients and clinical course after kidney transplantation.

There is a high incidence of chronic liver disease in end-stage renal failure patients on dialysis. Hepatitis C virus appears responsible for 80% of posttransfusion hepatitis, and up to 80% of sporadic hepatitis and cryptogenic cirrhosis. Anti-HCV antibodies correlate highly with the presence of active infection. The clinical implications of HCV infection in patients undergoing renal transplantation is unknown. Part I: We undertook a descriptive cross-sectional study of all renal failure patients admitted for kidney transplant between 1/84 and 12/88. Pretransplant sera were assayed for anti-HCV using an ELISA. Patients were divided into anti-HCV-positive (study group) and anti-HCV-negative (controls). Part II: A cohort study was performed with both groups followed from the time of transplantation to the present. Comparisons were made by t tests, chi-square analysis with Yates correction, Mann Whitney test for nonparametric results and multiple regression analysis. Part I: Anti-HCV was present in 76 of 716 sera assayed. There were no differences in sex, age, number of previous transplants, and underlying renal disease. Four variables predicted the presence of anti-HCV: number of blood transfusions; duration on dialysis; i.v. drug abuse, and nonwhite race. Part II: A group of 596 patients was further analyzed. The mean duration of follow-up was not different between the two groups. There were no differences in graft survival, overall mortality, or mortality secondary to liver disease or sepsis. Based on these results, the presence of anti-HCV should not be a contraindication for kidney transplantation.

Adolescent↗
PubMed1993

Evidence for a nonclassical pathway of graft rejection involving interleukin 5 and eosinophils.

The role of IL-5 and eosinophils in allograft rejection was studied in human liver allograft recipients. Liver allograft biopsies were analyzed for intragraft IL-5 gene expression, and the percentages of eosinophils and plasma cells within the portal infiltrate as well as peripheral eosinophil levels were determined. The majority of allografts with evidence of rejection had concomitant IL-5 mRNA and eosinophilia, while no resolving or nonrejecting allografts had simultaneous IL-5 mRNA and eosinophilia. In fact, rejecting liver allografts that contain IL-5 mRNA and eosinophils also contain infiltrating cells that produce the cytotoxic mediator major basic protein. In contrast, intragraft plasma cell and peripheral eosinophil levels did not correlate with the histopathologic status of the allograft. Cyclosporine and FK506 had similar effects on the frequency of IL-5 gene expression in rejecting and nonrejecting allografts. However, OKT3 appeared to profoundly modulate IL-5 gene expression, since 0 of 11 biopsies obtained during OKT3 treatment for rejection contained IL-5 transcripts. These observations raise the possibility of a cellular pathway of liver allograft rejection mediated by IL-5-activated eosinophils.

Base Sequence↗
PubMed1993

IL-2 and IL-5 gene expression in response to alloantigen in liver allograft recipients and in vitro.

IL-2 and IL-5 gene expression in response to alloantigen was studied in liver allograft recipients and in an in vitro system. Seventy-seven sequential liver allograft biopsies from 22 patients were analyzed for IL-2 and IL-5 mRNA by polymerase chain reaction and Southern blot hybridization. Message for IL-5 was present in 74% of allografts with rejection, 46% of allografts with resolving rejection, and 33% of allografts with no evidence of rejection. The frequency of IL-5 transcripts in rejecting allografts was significantly different than the frequency of IL-5 transcripts in grafts without evidence of rejection (P = 0.003). Message for IL-2 was detected in 29% of rejecting allografts, 18% of allografts without evidence of rejection, and 43% of allografts with resolving rejection. There was no significant association between IL-2 gene expression and the histopathological status of the allograft. Interestingly, 9 of 15 biopsies that contained IL-2 message in the no rejection and resolving rejection categories went on to display rejection shortly thereafter. IL-2 and IL-5 gene expression rarely occurred simultaneously within allografts. An in vitro system consisting of irradiated, allogeneic stimulator cells and normal peripheral blood mononuclear cells as responders was established to further investigate alloantigen-driven IL-2 and IL-5 production. Both IL-2 and IL-5 were produced in response to alloantigen as determined by specific bioassays. Maximal levels of IL-5 activity in culture supernatants generally followed maximal IL-2 levels by 24 hr, but both IL-2 and IL-5 production were dramatically inhibited by CsA. Analysis of cytokine gene expression revealed that IL-2 transcription peaked within the initial 24 hr of culture, whereas IL-5 transcription was maximal at 120 hr of culture. The expression of a CTL-specific serine esterase gene was similar to IL-5 in that it was maximal during the latter phases of the culture period. Thus, both human IL-2 and IL-5 are produced in response to alloantigen and are inhibitable by CsA. These data suggest that IL-2 and IL-5 may participate in cellular pathways of tissue damage within the rejecting allograft.

Base Sequence↗
PubMed1993

Molecular mimicry in primary biliary cirrhosis. Evidence for biliary epithelial expression of a molecule cross-reactive with pyruvate dehydrogenase complex-E2.

Sera from patients with primary biliary cirrhosis (PBC) react with enzymes of the 2-oxo dehydrogenase pathways, particularly PDC-E2. These enzymes are present in all nucleated cells, yet autoimmune damage is confined to biliary epithelial cells. Using a panel of eight mouse monoclonal antibodies and a human combinatorial antibody specific for PDC-E2, we examined by indirect immunofluorescence and confocal microscopy sections of liver from patients with PBC, progressive sclerosing cholangitis, and hepatocarcinoma. The monoclonal antibodies gave typical mitochondrial immunofluorescence on biliary epithelium and on hepatocytes from patients with either PBC, progressive sclerosing cholangitis, or hepatocarcinoma. However, one of eight mouse monoclonal antibodies (C355.1) and the human combinatorial antibody reacted with great intensity and specificity with the luminal region of biliary epithelial cells from patients with PBC. Simultaneous examination of these sections with an antiisotype reagent for human IgA revealed high IgA staining in the luminal region of biliary epithelial cells in patients with PBC. IgG and IgA antibodies to PDC-E2 were detected in the bile of patients with PBC but not normal controls. We believe that this data may be interpreted as indicating that a molecule cross-reactive with PDC-E2 is expressed at high levels in the luminal region of biliary epithelial cells in PBC.

Antibodies, Monoclonal↗
PubMed1993

Use of Prograf (FK 506) as rescue therapy for refractory rejection after liver transplantation. US Multicenter FK 506 Liver Study Group.

This report describes the clinical characteristics and demographics of patients enrolled into this rescue trial for patients experiencing refractory rejection after liver transplantation. Actuarial graft and patient survival at 12 months postconversion was 50% and 72%, respectively. Actual treatment success at 3 months postconversion was 70%. Karnofsky scores and liver function tests were significantly improved for patients continuing on therapy indicating clinical benefit in these patients. The safety profile of FK 506 is acceptable for such a high-risk group of patients. These preliminary clinical results support the conclusion that FK 506 can effectively control and reverse refractory rejection in a majority of liver transplantation patients.

Acute Disease↗
PubMed1992

Hepatitis B virus and apparent fulminant non-A, non-B hepatitis.

While there is evidence that hepatitis C virus (HCV) does not cause fulminant non-A, non-B hepatitis, the causal agent remains unknown. To evaluate the role of hepatitis B virus (HBV) in this disease, we used a two-step polymerase chain reaction (PCR) to amplify the surface and core regions of HBV DNA in serum and liver samples taken prospectively from twenty-six patients (mean age 36 years, range 1 to 64) with acute hepatic failure undergoing liver transplantation. HBV DNA was absent from the serum of all patients before transplantation. Seventeen patients were diagnosed as having non-A, non-B hepatitis because they lacked serological evidence of hepatitis A virus or HBV infection. Liver samples were taken from twelve of these patients, and six samples were positive for HBV DNA. By contrast HBV DNA was not detected in liver from three patients with acute liver failure caused by hepatitis A or toxins. HCV RNA was not found in pretransplant samples by PCR. Four of the six patients with detectable HBV DNA in liver and presumptive non-A, non-B hepatitis had detectable HBV DNA in serum after transplantation. One additional patient who did not donate pretransplant liver had HBV DNA in a post-transplant serum sample. Thus, HBV DNA was present before or after transplantation in seven of seventeen patients with apparent non-A, non-B hepatitis. Three of five patients with detectable post-transplant serum HBV DNA were serologically positive for HBV surface antigen. These findings indicate that HBV may be a common cause of fulminant hepatic failure in patients lacking serological evidence of HBV infection.

Acute Disease↗
PubMed1992

Hepatitis C viral infection in liver transplant recipients.

In this study we examined multiple serial liver biopsy specimens from liver transplant recipients to determine the pathological features of hepatitis C virus-induced hepatitis. Hepatitis C virus infections acquired after transplantation and previous infections that recurred in patients after transplantation were confirmed by the results of the polymerase chain reaction. Of 43 patients infected with the hepatitis C virus, 18 had a mild form of chronic hepatitis. Four patients had hepatitis that progressed to focal bridging fibrosis or cirrhosis. There were no significant clinical or pathological differences between infections acquired after transplantation and recurrent infections (as determined by polymerase chain reaction) except that acquired infections more often developed into hepatitis. Findings indicative of hepatitis C infection included portal and parenchymal mononuclear infiltrates of varying degrees, acidophilic necrosis and swollen hepatocytes. Other common findings included lymphoid aggregates, bile duct damage and fatty change. Atypical pathological conditions included extensive hepatocyte swelling or acidophilic necrosis with minimal inflammation mimicking ischemia and ductal or ductular damage and proliferation with mixed portal infiltrates mimicking rejection or obstruction. We conclude that in transplant recipients infection by the hepatitis C virus usually produces a mild disease state, but the diagnosis of hepatitis can be difficult to make because indicators of hepatitis may mimic those of rejection, ischemia, obstruction or other hepatic infections. Serial biopsy specimens with persistent pathology and polymerase chain reaction may be necessary to define the presence of a hepatitis C virus lesion.

Bile Ducts↗
PubMed1992

Incidence and diagnostic features of macroregenerative nodules vs. small hepatocellular carcinoma in cirrhotic livers.

In Japan, the presence of a large regenerative nodule within a cirrhotic liver, referred to as a macroregenerative nodule or adenomatous hyperplasia, is thought to play a role in the pathogenesis of hepatocellular carcinoma. These lesions, however, have received little attention outside of Japan. We examined 110 sequentially explanted cirrhotic livers for the presence of such nodules. By gross examination, 19 livers (17.3%) had 40 nodules (10 livers had more than one nodule) between 0.8 and 3.5 cm in diameter. By histological examination, 28 of these were macroregenerative nodules and 12 were hepatocellular carcinomas. Three of these hepatocellular carcinomas, however, appeared to have arisen in association with a macroregenerative nodule. We found that the architectural features of thickened cell plates, formation of trabeculae and loss of reticulin were usually very helpful in differentiating benign macroregenerative nodules from hepatocellular carcinoma. The incidence of macroregenerative nodules in our series was similar to that seen in the Japanese studies, and although we feel that they may play a role in the pathogenesis of carcinoma, we do not believe their presence is necessary for the development of hepatocellular carcinoma.

Adenoma↗
PubMed1992

Intragraft cytokine profile during human liver allograft rejection.

Forty-three human liver allograft biopsies and normal liver were directly analyzed for inflammatory and immunoregulatory cytokine gene expression by polymerase chain reaction (PCR). IL-5 gene expression was predominantly present in biopsies from liver allografts with histopathological evidence of acute rejection. IL-2 gene expression was rarely observed in rejecting allografts or allografts without evidence of rejection. In contrast, IL-4 message was readily detectable in the majority of liver allografts regardless of clinical status. The inflammatory mediators IL-1 beta, TNF-alpha, and IL-6 were detected with similar frequency in rejecting allografts and allografts without evidence of rejection. These findings suggest that inflammatory and immunoregulatory cytokines are produced within the allograft. Moreover, IL-5 may play a role in the local mechanisms of liver allograft rejection.

Base Sequence↗