The role of the microbiology laboratory in surveillance and control of nosocomial infections.

The microbiology laboratory's rapid and consistent identification of nosocomial pathogens is a keystone in the surveillance and control of hospital-acquired infections. In addition, the laboratory serves as a source of expert consultation for clinicians and infection control personnel and as an "early warning center" for infection problems. In making its contributions to infection control most effective, the laboratory must recognize its capabilities and limitations, must insure that the materials and methods it uses and the specimens it processes meet high standards, must provide retrievable records, and must have a good working knowledge of microbiologic technics used to evaluate both endemic and epidemic infections. Moreover, because laboratory workers come into contact daily with potentially infectious specimens and isolates, the laboratory's contributions to infection control should also include the prevention and surveillance of laboratory-acquired infections.     

Liver immunity and tumour surveillance

Adult liver has a complex defence system that is critical in protection against infectious challenge. Its role in tumour surveillance is poorly understood. Because of its location, function and complex blood supply, the liver will be exposed to metastatic cells generated anywhere else in the body. Moreover, the role of the liver in detoxification can result in the generation of products with carcinogenic properties. It should not be surprising, then, to discover that the liver has a specialized immune system tailored to protect against and respond to significant immunological challenge, particularly metastasis and malignancy. This tumour surveillant role is the focus of this review.     

The role of annexins in tumour development and progression

The annexins are a super-family of closely related calcium and membrane-binding proteins. They have a diverse range of cellular functions that include vesicle trafficking, cell division, apoptosis, calcium signalling and growth regulation. Many studies have shown the annexins to be among the genes whose expression are consistently differentially altered in neoplasia. Some annexins show increased expression in specific types of tumours, while others show loss of expression. Mechanistic studies relating the changes in annexin expression to tumour cell function, particularly tumour invasion and metastasis, angiogenesis and drug resistance, are now also emerging. Changes in the expression of individual annexins are associated with particular types of tumour and hence the annexins may also be useful biomarkers in the clinic.     

The role of mycoses in intrabdominal infections

In the last few years, there has been a continuous, marked increase in serious mycotic infections, with a high incidence of morbidity and mortality especially among patients undergoing surgery in Intensive Therapy Units. Many risk factors are associated with the development of mycotic infections, amongst which the following may be highlighted: immunosuppression, protracted antibiotic treatment, long NPT, serious trauma, central venous catheterization and, in critical patients, a high APACHE II score. Mycotic peritonitis, an increasingly rare complication found in patients undergoing peritoneal dialysis, seems to be linked to gastric or duodenal perforations treated late (> 24 h) or to secondary, chiefly post-operative peritonitis, in the case of anastomotic dehiscences or fistules, and more generally in surgical patients in unstable conditions, i.e. those with severe acute pancreatitis and cirrhotic imbalances. In the absence of clear clinical signs of mycotic infection, diagnosis is based on the positivity of the culture test carried out in all explorable sites (expectorate, urine, blood, drainage, ascites, intrabdominal sampling), while positivity of haemoculture alone is a real dilemma for the clinician as it may be the result of transitory fungemia or a widespread infection. As yet, there is no reliable diagnostic test, though histopathology, the general signs of sepsis and positive culture in normally sterile sites are used to provide clear indications. Until recently, most patients with intrabdominal infections were not treated with general antimycotics, both because of the relatively low probability of developing a systemic infection and the feared toxicity of amphotericine B. Nowadays, this wait-and-see approach has been discarded, such that high-risk patients are recommended early empirical antimycotic treatment or even prophylaxis. The choice of antimycotic agent, dosage and duration of therapy depends on the aetiologic agent isolated, on the source of infection, renal functionality and associated pathologies. In conclusion, while the incidence of serious mycotic infection has sharply increased, an appropriate therapeutic strategy has not yet been definitively identified, due both to the lack of numerically significant clinical studies and especially the extreme variability and complexity of patients to be treated.     

The role of infections in autoimmune disease

Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious pathogens) are thought to play a major role in the development of autoimmune diseases. In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity.     

Dichotomy of Notch signalling in regulating tumour immune surveillance

Notch signalling is an evolutionarily conserved multifaceted pathway that controls diverse cellular processes. Its role in regulating development and tissue homeostasis is well established. Aberrant activation of the Notch pathway has been implicated in the initiation and progression of many types of cancers. However, although in some cancers Notch signalling acts as a tumour‐promoter, in others it is reported to suppress tumour growth and progression. Accumulating evidence suggests the involvement of both the innate and adaptive immune system in the development of various tumours. Currently, extensive studies on investigating the effects of Notch signalling in tumour immune surveillance are being carried out. Interestingly, recent literature shows how the changing expression of Notch genes in different T cell subsets like CD4 and CD8 helps in controlling anti‐tumour immune responses. In this review, we discuss in depth the roles of Notch signalling molecules and different immune cells in the context of the tumour microenvironment. We also outline how current knowledge can be exploited to develop novel therapies in order to control the propagation of cancer stem cells.     

Epidemiological surveillance of nosocomial pyo-septic infections

The paper analyzes the parameters of epidemiological surveillance of nosocomial pyoseptic infections (NPSI) at surgical hospitals. It considers its basic concepts and presents the authors own findings. Particular emphasis is laid on guidelines for detecting NPSI cases and on epidemiological surveillance. A method of a follow-up is proposed to solve problems in the informational and analytical support of surveillance.     

The role of urokinase and urokinase inhibitor in tumour cell metastasis

In this paper we summarize experiments in which murine melanoma B16-F1 cells of low metastatic potential were transfected with the human gene for prep rourokinase. B16-F1 cells selected for their secretion of high amounts of the human urokinase gene product (3- to 4-fold higher plasminogen activator activity than control cells) formed between 4- and 16-fold greater numbers of lung tumours in C57BL mice after tail vein injection. In correlative results, highly malignant B16-F10 melanoma cells transfected with a urokinase antisense sequence showed a significant inhibition of endogenous urokinase expression and a corresponding significant decrease in the number of tumours formed after tail vein injection.The human urokinase gene product expressed by the transfected cells does not bind to murine cell surface urokinase receptors, and the results may provide direct evidence for a role of secreted (non-surface bound) urokinase in the extravasation steps of tumour cell metastasis. These human urokinase secreting cells also showed a greater ability to spontaneously metastasize from a primary footpad tumour to the mouse lung.Extending the study of urokinase to the role of its natural inhibitor, plasminogen activator inhibitor 2 (PAI-2), we determined the constitutive and phorbol ester inducibility of the mRNA for PAI-2 and urokinase in human A375 melanoma cell lines and human prostate PC3 carcinoma cell lines of different metastatic potentials. Analysis of the changes in PAI-2 and urokinase mRNA levels indicate that variation in the levels of PAI-2 may be more important than urokinase in explaining the different metastatic abilities of A375 and PC3 sublines. Urokinase activity may promote metastasis by its initiation of a specific proteolysis pathway leading to the activation of metalloproteinases. We have previously shown that the metalloproteinase inhibitor, recombinant tissue inhibitor of metalloproteinases (rTIMP), inhibits B16 melanoma cell lung colonization.     

The possible role of fungal infections in AIDS

The acquired immunodefficiency syndrome (AIDS) is characterized by a gross defect in the cell-mediated immune response. However, infection with human immunodeficiency virus (HIV), which is the generally accepted etiological factor of AIDS, cannot explain by itself the following problems: why do not some of the seropositive subjects develop AIDS or AIDS-related complex; why are some of the patients with AIDS seronegative for HIV and its corresponding antibodies; what is the reason why some of the healthy seronegative subjects from groups at a high risk for AIDS (homosexuals, hemophiliacs and drug abusers) have low T-helper to T-suppressor ratios. We suggest that some additional factor is necessary for the development of AIDS. We propose that the factor needed is a 'partial functional thymectomy'. We suspect that slow fungal infections, producing thymotoxic metabolites, may be a major cause for the latter.     

The distribution of perforin in normal tissues

We describe the production of monoclonal antibodies to murine and human forms of the lymphocyte pore-forming protein (perforin, PFP, or cytolysin), a major granule-localized cytolytic mediator of CTL and NK cells. Antibodies were raised against both murine perforin purified from a CTL line, and human perforin expressed in bacteria as a fusion protein with the Escherichia coli TrpE protein. Antibodies raised against either immunogen inhibited the hemolytic activity of murine perforin, and thus may enable us to identify the pore-forming or self-associative domain of perforin. One mAb, MP1, was used to study the distribution of perforin in murine tissues under physiological conditions. We found that perforin was expressed in the granular metrial gland (GMG) cells of the pregnant murine uterus, but not in other tissues examined. These results further support the view that perforin is induced only in activated cytolytic lymphocytes, and raise the question whether perforin-containing GMG cells represent an effector of a maternal immune response to the fetus.