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Biomedical subjects

N Bach

Publications and source records attributed to N Bach.

At least 19 recordsLinked to original sources

Assessment of hepatitis C virus RNA and genotype from 6807 patients with chronic hepatitis C in the United States.

Hepatitis C virus (HCV) RNA status and HCV genotype have become important tools in the diagnosis and monitoring of therapy in chronic HCV infection. To establish a database with respect to HCV genotype and serum HCV RNA concentrations in chronic hepatitis C patients in the United States, we analysed 6807 chronic hepatitis C patients who had HCV RNA and HCV genotype tests conducted at a central laboratory. The HCV RNA concentration cut-off for the lower 25th percentile of this population (low titre) was 0.9 x 106 copies ml-1. The median HCV RNA concentration was 3.5 x 106 copies ml-1 and the cut-off for the upper 25th percentile (high titre) was 5 x 106 copies ml-1. Male patients had a median HCV RNA concentration of 3.9 x 106 copies ml-1, which was significantly higher than the median HCV RNA level for females (2.75 x 106 copies ml-1; P < 0.001). HCV genotype 1 was detected in 73% of patients; genotype 2 in 14%; genotype 3 in 8%; mixed genotype in 4%; and genotypes 4, 5 and 6 with a frequency of < 1%. Patients from the Northeast, Southeast and Midwest had significantly (P < 0.001) more infections with genotype 1 than patients from the Western and Southern regions. African-American patients were more likely to be infected with genotype 1 when compared with Caucasian, Hispanic or Asian Pacific Islanders (P < 0.001). Patients infected with HCV genotype 1 and mixed HCV genotypes had significantly higher serum HCV RNA concentrations when compared with HCV genotypes 2 and 3 (P < 0.001 for all comparisons).

Black People↗

Amplification of tumor immunity by gene transfer of the co-stimulatory 4-1BB ligand: synergy with the CD28 co-stimulatory pathway.

We have explored the role of an activation-induced T cell molecule, 4-1BB (CDw137), in the amplification of tumor immunity by retrovirus-mediated transduction of the 4-1BB ligand (4-1BBL) into tumor cells. Mice inoculated with P815 tumor cells expressing 4-1BBL developed a strong cytotoxic T lymphocyte (CTL) response and long-term immunity against wild-type tumor. The optimal effect of 4-1BBL in CTL stimulation required B7-CD28 interaction since blockade of this interaction by antibodies down-regulated the expression of 4-1BB on T cells and decreased CTL activity. Furthermore, co-expression of 4-1BBL and B7-1 in the poorly immunogenic AG104A sarcoma enhanced the induction of effector CTL and the rejection of the wild-type tumor while neither 4-1BBL nor B7-1 single transfectants were effective, suggesting a synergistic effect between the 4-1BB and the CD28 co-stimulatory pathways. Our results underscore the importance of the 4-1BB T cell stimulation pathway in the amplification of an antitumor immune response.

Animals↗

The histologic effects of low-dose methotrexate therapy for primary biliary cirrhosis.

OBJECTIVE: Primary biliary cirrhosis is a progressive liver disease that is believed to be autoimmune in nature. Treatment, at best, may slow the progression of the disease, although no therapy has been able to halt its progression. Preliminary data suggest a beneficial effect of methotrexate in the treatment of primary biliary cirrhosis. We evaluated the histologic effect of 2 years of treatment with methotrexate. DESIGN: Liver biopsies were obtained before methotrexate was started and after 2 years of therapy. Ninety-six paired biopsies from 48 patients with primary biliary cirrhosis were reviewed by a pathologist who was blinded to all clinical history and sequence of the biopsies. Variables examined included stage of the disease, degree of portal fibrosis, portal inflammation and piecemeal necrosis, bile duct injury or loss, bile ductular proliferation, lobular inflammation and necrosis, steatosis, granulomas, cholestasis, and nuclear pleomorphism of hepatocytes. RESULTS: In most categories, pretreatment and posttreatment biopsies did not reflect a change over the 2-year period of treatment. There was a trend toward progression of the stage of the disease, portal fibrosis, bile duct loss, fat, and pleomorphism over the 2 years and toward regression in piecemeal necrosis, bile duct injury, ductular proliferation, granulomas, and lobular inflammation and necrosis. CONCLUSION: After 2 years of treatment with methotrexate, the stage of disease and fibrosis of primary biliary cirrhosis continue to progress, although overall, inflammation and bile duct injury decrease with methotrexate treatment.

Biopsy↗

Costimulation, tolerance and ignorance of cytolytic T lymphocytes in immune responses to tumor antigens.

Despite the fact that many tumors express MHC class I molecules presenting "foreign" peptide antigens, a vigorous tumor-destructing immune response is seldom detected. A possible explanation is that tumors cannot provide adequate costimulatory signals as provided by professional antigen presenting cells. CD28, upon interacting with B7, triggers costimulatory signals critical for the T-cell response. Transfection of tumor cells with B7 augments the immunogenicity of the tumor so that an anti-tumor immune response can be amplified. When B7-CD28 costimulation is provided CTL specific for otherwise silent epitopes can be activated. Therefore, unresponsiveness of T cells to many tumor antigens should be considered as ignorance rather than tolerance. Immunological ignorance may thus contribute to the failure of the immune system to respond against the tumor antigens.

Animals↗

[Enalapril treatment of a pre-eclamptic woman].

A case is reported describing severe pre-eclampsia, treated firstly with antihypertensive drugs and Caesarean section. Contrary to expectation blood pressure did not fall and proteinuria still remained. Blood pressure reducing drugs had no effect at all. The patient was then treated with Renitec (enalapril), an ACE-inhibitor, with good result--even when given in a small dosis. No influence on lactation was documented for five weeks. Teratogenicy has been reported using ACE-inhibitors, and only a little is known about their effect on lactation. We found Renitec to have a good effect on reducing blood pressure postpartum and no effect on lactation at all.

Adult↗

Familial primary biliary cirrhosis.

To estimate the prevalence of primary biliary cirrhosis in family members with this disease and determine if a family history of primary biliary cirrhosis predisposes to the development of this disease, we performed a retrospective review of charts and a prospective mail survey of patients with primary biliary cirrhosis. Prevalence of primary biliary cirrhosis in family members of 405 patients with disease was compared to known prevalence of disease in the general population. Twenty-six patients with primary biliary cirrhosis had at least one family member with primary biliary cirrhosis. The estimated prevalence per 100,000 was 6420 or 6.4%. Exclusion of family members with primary biliary cirrhosis who were patients in our practice, in order to avoid duplication, changed the prevalence to 4282 per 100,000 or 4.3%. Affected family members included mothers, daughters, sisters, brothers, aunts and cousins. Estimates of prevalence of primary biliary cirrhosis are between 0.7 and 7.5 cases per 100,000. Therefore, compared to estimates in the general population, the prevalence of primary biliary cirrhosis in family members of patients with this disease is markedly increased. A family history of primary biliary cirrhosis is therefore a predisposing factor for the development of this disease.

Causality↗

HLA-DR expression in bile duct damage in hepatitis C.

Several investigations have demonstrated aberrant expression of HLA-DR on damaged bile duct epithelium of patients with primary biliary cirrhosis, liver allograft rejection, graft versus host disease, and AIDS. Since bile duct damage is a prominent feature of chronic hepatitis C, it may also be associated with HLA-DR induction. Therefore, we examined the expression of HLA-DR antigen in formalin-fixed, paraffin-embedded liver biopsy sections of 30 patients with chronic hepatitis C by the avidin-biotin peroxidase complex method using a monoclonal antibody to HLA-DR. HLA-DR was not detected on bile duct epithelium in any of the cases, although bile duct damage of varying degree was observed in 90% of the cases. HLA-DR was expressed by Kupffer cells; inflammatory infiltrates in portal tracts, and in areas of piecemeal necrosis and lobular necrosis; dendritic cells in portal and periportal areas; and occasionally hepatocytes. These observations suggest that the mechanism of bile duct injury in chronic hepatitis C may be different from that of other conditions such as primary biliary cirrhosis, liver allograft rejection, and graft versus host disease.

Antibodies, Monoclonal↗

The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis.

Before the availability of serological markers for hepatitis C, the morphological features of this diagnosis, which represents most non-A, non-B hepatitis, could not be confirmed. We examined biopsy specimens from 50 patients with chronic hepatitis C and 21 patients with autoimmune chronic hepatitis. Each biopsy specimen was graded on 19 different histological features. The results indicated that at the time of biopsy, the average age of patients with chronic hepatitis C was 46 yr vs. 36 yr for autoimmune chronic hepatitis. Cirrhosis was seen more frequently in autoimmune chronic hepatitis (90%) than in hepatitis C (58%). Features more commonly observed in chronic hepatitis C were bile duct damage (91% vs. 40%), bile duct loss (91% vs. 20%), steatosis (72% vs. 19%) and lymphoid cell aggregation (follicles) within portal tracts (49% vs. 10%). Severe lobular necrosis and inflammation (76% vs. 38%), piecemeal necrosis (81% vs. 10%), multinucleated hepatocytes (29% vs. 6%) and broad areas of parenchymal collapse (76% vs. 6%) were seen more often in autoimmune chronic hepatitis. Exclusion of five patients with autoimmune chronic hepatitis who received immunosuppression before biopsy accentuated these differences. In conclusion, morphological criteria, in addition to serological data, may be useful for differentiating chronic hepatitis C from autoimmune chronic hepatitis, which histologically is a more aggressive disease.

Adult↗

Hepatic histopathology in the acquired immunodeficiency syndrome.

Involvement of the liver with the same opportunistic organisms and neoplasms affecting other organs has been recognized since the beginning of the AIDS epidemic. In this overview of hepatic histopathologic features in AIDS, we review the range of opportunistic infections and neoplasms accompanying HIV infection. Hepatic disease may result from viral, bacterial, protozoal, or fungal infection, or secondary to drugs and neoplasms. Liver involvement in AIDS usually reflects disseminated rather than primary disease. CMV and mycobacteria are the most common organisms in liver identified in biopsy and autopsy studies. A variety of nonspecific features, including steatosis, granulomas, and sinusoidal abnormalities may also be seen. HIV-1 itself was recently identified in the liver. Speculation regarding the significance of this finding has been discussed in this review. Hepatitis B, C, and D may also complicate the course of disease in patients with AIDS. Hepatitis B behaves differently in the population with AIDS than in immunocompetent patients. We concluded our review with a discussion of the present recommendations regarding the use of liver biopsies in these patients. This topic continues to be widely debated in the literature.

Acquired Immunodeficiency Syndrome↗

Hepatocellular carcinoma in a long-term survivor of intrahepatic biliary duct hypoplasia.

We describe the development of hepatocellular carcinoma (HCC) in a 46-yr-old woman with intrahepatic biliary duct hypoplasia. Her underlying liver disease was quiescent for many years until a dramatic rise in serum bilirubin was seen. Orthotopic liver transplantation was performed, and a large tumor was found during surgery. A bile-producing HCC was identified, infiltrating about 50% of an otherwise noncirrhotic liver which had a paucity of intrahepatic ducts. The findings of HCC in this long-term survivor of intrahepatic biliary duct hypoplasia indicates HCC may occur in patients with long-standing disease.

Bile Ducts, Intrahepatic↗

Foot growth in children age one to five years.

As part of the protocol on the Development of the Child's Arch, foot growth studies were monitored prospectively in 107 children from 1 year of age till 5 years of age. Under 15 months of age, growth necessitated a 1/2 size footwear change in less than 2 months; from 15 months to 2 years of age, 1/2 size increase occurred every 2 to 3 months; from 2 to 3 years of age, 1/2 size change every 3 to 4 months; and from 3 to 5 years of age, 1/2 size change every 4 months. Although foot growth in boys and girls is parallel, boys' feet tend to average one size longer and one size wider. Width growth remained proportional to length growth throughout the study.

Age Factors↗