An investigation into the aetiology, diagnosis, and treatment of biliary atresia was carried out because the prognosis remains so poor.In an electron microscopical study no viral particles or viral inclusion bodies were seen, nor were any specific ultrastructural features observed. An animal experiment suggested that obstruction within the biliary tract of newborn rabbits could be produced by maternal intravenous injection of the bile acid lithocholic acid.A simple and atraumatic method of diagnosis was developed using(99) (m)Tc-labelled compounds which are excreted into bile. Two compounds, (99m)Tc-pyridoxylidene glutamate ((99m)Tc-PG) and (99m)Tc-dihydrothioctic acid ((99m)Tc-DHT) were first assessed in normal piglets and piglets with complete biliary obstruction. Intestinal imaging correlated with biliary tract patency, and the same correlation was found in jaundiced human adults, in whom the (99m)Tc-PG scan correctly determined biliary patency in 21 out of 24 cases. The (99m)Tc-PG scan compared well with liver biopsy and (131)I-Rose Bengal in the diagnosis of 11 infants with prolonged jaundice.A model of extrahepatic biliary atresia was developed in the newborn piglet so that different methods of bile drainage could be assessed. Priorities in biliary atresia lie in a better understanding of the aetiology and early diagnosis rather than in devising new bile drainage procedures. (+info)
From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future.
A progression from viral myocarditis to dilated cardiomyopathy has long been hypothesized, but the actual extent of this progression has been uncertain. However, a causal link between viral myocarditis and dilated cardiomyopathy has become more evident than before with the tremendous developments in the molecular analyses of autopsy and endomyocardial biopsy specimens, new techniques of viral gene amplification, and modern immunology. The persistence of viral RNA in the myocardium beyond 90 days after inoculation, confirmed by the method of polymerase chain reaction, has given us new insights into the pathogenesis of dilated cardiomyopathy. Moreover, new knowledge of T-cell-mediated immune responses in murine viral myocarditis has contributed a great deal to the understanding of the mechanisms of ongoing disease processes. Apoptotic cell death may provide the third concept to explain the pathogenesis of dilated cardiomyopathy, in addition to persistent viral RNA in the heart tissue and an immune system-mediated mechanism. Beneficial effects of alpha1-adrenergic blocking agents, carteolol, verapamil, and ACE inhibitors have been shown clinically and experimentally in the treatment of viral myocarditis and dilated cardiomyopathy. Antiviral agents should be more extensively investigated for clinical use. The rather discouraging results obtained to date with immunosuppressive agents in the treatment of viral myocarditis indicated the importance of sparing neutralizing antibody production, which may be controlled by B cells, and raised the possibility of promising developments in immunomodulating therapy. (+info)
Candidate viral diseases for elimination or eradication.
This article discusses the possibilities for elimination or eradication of four viral diseases--measles, hepatitis B, rubella and yellow fever. (+info)
Qualitative and quantitative requirements for CD4+ T cell-mediated antiviral protection.
CD4+ Th cells deliver the cognate and cytokine signals that promote the production of protective virus-neutralizing IgG by specific B cells and are also able to mediate direct antiviral effector functions. To quantitatively and qualitatively analyze the antiviral functions of CD4+ Th cells, we generated transgenic mice (tg7) expressing an MHC class II (I-Ab)-restricted TCR specific for a peptide derived from the glycoprotein (G) of vesicular stomatitis virus (VSV). The elevated precursor frequency of naive VSV-specific Th cells in tg7 mice led to a markedly accelerated and enhanced class switching to virus-neutralizing IgG after immunization with inactivated VSV. Furthermore, in contrast to nontransgenic controls, tg7 mice rapidly cleared a recombinant vaccinia virus expressing the VSV-G (Vacc-IND-G) from peripheral organs. By adoptive transfer of naive tg7 CD4+ T cells into T cell-deficient recipients, we found that 105 transferred CD4+ T cells were sufficient to induce isotype switching after challenge with a suboptimal dose of inactivated VSV. In contrast, naive transgenic CD4+ T cells were unable to adoptively confer protection against peripheral infection with Vacc-IND-G. However, tg7 CD4+ T cells that had been primed in vitro with VSV-G peptide were able to adoptively transfer protection against Vacc-IND-G. These results demonstrate that the antiviral properties of CD4+ T cells are governed by the differentiation status of the CD4+ T cell and by the type of effector response required for virus elimination. (+info)
Preventing zoonotic diseases in immunocompromised persons: the role of physicians and veterinarians.
We surveyed physicians and veterinarians in Wisconsin about the risk for and prevention of zoonotic diseases in immunocompromised persons. We found that physicians and veterinarians hold significantly different views about the risks posed by certain infectious agents and species of animals and communicate very little about zoonotic issues; moreover, physicians believe that veterinarians should be involved in many aspects of zoonotic disease prevention, including patient education. (+info)
Virulence evolution in a virus obeys a trade-off.
The evolution of virulence was studied in a virus subjected to alternating episodes of vertical and horizontal transmission. Bacteriophage f1 was used as the parasite because it establishes a debilitating but non-fatal infection that can be transmitted vertically (from a host to its progeny) as well as horizontally (infection of new hosts). Horizontal transmission was required of all phage at specific intervals, but was prevented otherwise. Each episode of horizontal transmission was followed by an interval of obligate vertical transmission, followed by an interval of obligate horizontal transmission etc. The duration of vertical transmission was eight times longer per episode in one treatment than in the other, thus varying the relative intensity of selection against virulence while maintaining selection for some level of virus production. Viral lines with the higher enforced rate of infectious transmission evolved higher virulence and higher rates of virus production. These results support the trade-off model for the evolution of virulence. (+info)
Seminal tract infections: impact on male fertility and treatment options.
Bacterial and viral infections of the genital tract may be important aetiological factors for male infertility. Infectious processes may lead to deterioration of spermatogenesis, impairment of sperm function and/or obstruction of the seminal tract. Detection of bacteria in semen does not necessarily signify infection since bacteriospermia may represent contamination, colonization or infection. Reported prevalence of Ureaplasma urealyticum in human semen varies from 10 to 40%. Enterobacteria can even be found in up to 90% of semen samples depending on the sensitivity of detection methods used. Chlamydia trachomatis is the most frequent sexually transmitted bacterial organism in industrialized countries. It is suggested that its main influence is due to sexual transmission resulting in tubal disease and subsequent infertility in the female partner rather than a direct influence on male reproductive functions. The effect of leukocytospermia on male fertility is controversial. This is probably due to different detection methods, different populations studied and to the fact that leukocyte subtypes in semen may have different functions. In addition to potentially negative effects, leukocytes may even have protective effects on spermatozoa. Only recently have amplification methods been established to detect viruses in semen with high sensitivity and specificity. It is unclear if these infections significantly contribute to male infertility. (+info)
NK cells and apoptosis.
Natural killer (NK) cells are a cell of the innate immune system that play an important role in the early response to viral infections and tumours. Natural killer cells are cytolytic, and secrete cytokines that influence the developing antigen-specific immune response. In the present article the NK cell surface molecules regulating effector function, the NK cell effector mechanisms involved in apoptosis, and the role of NK cell effector mechanisms in immune responses are reviewed. (+info)