BACKGROUND:Since the discovery of hepatitis C virus (HCV) as a major cause of non-A non-B hepatitis, advances have been made in our understanding of the molecular biology of HCV and its relatedness to the flaviviruses and pestiviruses. The use of molecular techniques to construct an antibody assay has enabled the accumulation of information concerning the natural history and pathogenesis of HCV infection.OBJECTIVES:The objective was to review the literature to March 1994 on the structure, function and genetics of HCV and to correlate these findings with approaches to diagnosis that have contributed to our understanding of HCV infections.STUDY DESIGN:We reviewed the virological and medical literature from 1988 to March of 1994 with a focus on the stated objectives.RESULTS:Although the structure of HCV has been well-defined, our knowledge of the function of all the genes of HCV is incomplete. Structural core and envelope proteins as well as enzymes have been described. The 5' end of the polypeptide is most conserved. Genotyping of isolates varies according to the part of the gene examined. Several genotypes exist and tend to predominate in global populations. Antibodies to the various proteins can be measured by EIA assays and positive specimens often require confirmatory testing. Uniquely sensitive nucleic acid detection systems for RNA amplified by PCR have enabled a better understanding of the natural history, epidemiology and responses to treatment.CONCLUSIONS:Well-designed studies for the detection of nucleic acid, antibodies and antigens using a variety of viral gene products will provide even more information about HCV infections and help lead to treatment and prevention.

In 1890 at the International Medical Congress in Berlin, Robert Koch discussed difficulties in research progress and reminded his colleagues: “As recently as 15 years ago we knew little more than the fact that in anthrax and relapsing fever, strange exotic structures were produced in the blood and that occasionally, so-called vibrios occurred in wound infections…. With the exception of a few researchers who were considered to be dreamers, such structures were viewed more as curiosities than pathogens”. One hundred years later the magnitude of achievements in medical microbiology, virology and immunology is unanimously recognised, especially in the field of immunization against infectious diseases. The contribution of active immunization has been decisive in the control of at least nine major infections — smallpox, diphtheria, tetanus, yellow fever, pertussis, poliomyelitis, measles, mumps and rubella. Vaccines and clean water have exerted a more profound influence on world health than any other public health measure or programme.

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic pulmonary conditions worldwide which often coexist. Patients with asthma COPD overlap (ACO) may have worse outcomes than those with either disease alone, for example, more respiratory symptoms and frequent exacerbations, and worse lung function. Additionally, there is a growing interest in factors that affect the disease including comorbid conditions. Indeed, recent studies have demonstrated higher rates of comorbid conditions in the ACO population, but the mechanisms behind these observations remain unclear. The objective of this review is to describe current knowledge and clinical implications of the overlapping features of asthma and COPD, and discuss the prevalence and impact of comorbidities, such as osteoporosis, cardiovascular disease, gastroesophageal reflux disease, and depression, in this subgroup of patients.

The study of the distribution of various markers of hepatitis B virus in carrier pregnant mothers in Saudi Arabia showed that 11 % of them were HBeAg-positive, compared to 82 % who were anti-HBeAg-positive and 6 % who were negative for both HBeAg and anti-HBe. All carrier mothers who were HBeAg-positive were also positive for HBV DNA.

This review article describes several applications of the widely used enzyme immunoassay (EIA) procedure. EIA methods have been adapted to solve problems in diagnostic virology where sensitivity, specificity, or practicability is required. Concurrent developments in hybridoma and conjugation methods have increased significantly the use of these assays. A general overview of EIA methods is given together with typical examples of their use in diagnostic medical virology; attention is drawn to possible pitfalls. Recent advances in recombinant DNA technology have made it possible to produce highly specific nucleic acid probes that have a sensitivity approximately 100 times greater than that of EIA. Some applications of these probes are described. Although the non-labelled nucleic acid probes for use in the field are not as refined as non-labelled immunoassays, their range of applications is expected to expand rapidly in the near future.

The antigens of herpes simplex virus types 1 and 2 are detected and localized in vitro in Hep-2 cells by indirect and direct immunoperoxidase. The direct procedure is applied successfully for the diagnosis of genital disease on cytosmears of cervical cells of patients with herpes simplex type 2 infection. With other procedures, as anti-complement immunoperoxidase (ACIP) and anti-IgG immunoperoxidase (AIIP) the Epstein-Barr Nuclear Antigen (EBNA) was detected precisely in EB3, Jijoye and Raji lymphocytes using anti-EBNA antibodies from patients with nasopharyngeal carcinoma or Burkitt lymphoma, in dilution 1:10-1:5120. The indirect immunoperoxidase localized intracytoplasmic early antigen (EA) in 5% of EA--positive Raji cells induced by superinfection of EBV. The viral capsid antigen (VCA) is detected by this method in 5%-10% of virus producing cell lines Jijoye and P3HR-1. The standardized kits of immunoperoxidase procedures for diagnosis of intracellular viral antigens using monoclonal antibodies are under investigation.

Detection of the Epstein-Barr (EBV) antigens, early antigen (EA), viral capsid antigen (VCA), and nuclear antigen (EBNA) by the indirect immunoperoxidase technique was highly sensitive. Antibody titers to EBNA, EA, and VCA were determined in more than 25 sera of patients with Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC), or normal persons. A good correlation between the titers of these antigens was obtained by the immunoperoxidase and immunofluorescence methods. The indirect (anti-IgG) immunoperoxidase technique for the detection of EBNA is, in contrast to the indirect immunofluorescence method, highly sensitive. EBNA was associated with the chromosomes in cells arrested in the metaphase with colchicine.

12. WOLFF E, GLASSER M, GORDON GG, et al: Virilizing luteoma of pregnancy. Report of a case with measurements of testosterone and testosterone binding in plasma. Am J Med 54: 229, 1973 13. KRAUSE DE, STEMBRIDGE VA: Luteomas of pregnancy. Am J Obstei Gynecol 95: 192, 1966 14. STERNBERG WH, BARCLAY DL: Luteoma of pregnancy. Ibid, p 165 15. NoRRIS HJ, TAYLOR HB: Nodular theca-lutein hyperplasia of pregnancy (so-called "pregnancy luteoma"). A clinical and pathologic study of 15 cases. Am J Clin Pathol 47: 557, 1967 16. RIcE BF, BARCLAY DL, STERNBERG WH: Luteoma of pregnancy: steroidogenic and morphologic considerations. Am J Obstet Gynecol 104: 871, 1969 17. LLOYD CW, LOBOTSKY J, SEGRE EJ, et al: Plasma testosterone and urinary 17-ketosteroids in women with hirsutism and polycystic ovaries. J Clin Endocrinol Metab 26: 314, 1966 18. KORENMAN SG, KIRSCHNER MA, Lip5ETT MB: Testosterone production in normal and virilized women and in women with the Stein-Leventhal syndrome or idiopathic hirsutism. J Clin Endocrinol Metab 25: 798, 1965