Cryptococcosis as an opportunistic infection in immunodeficiency secondary to paracoccidioidomycosis

We describe the case reports of two patients with immunodeficiency secondary to paracoccidioidomycosis (PCM) and opportunistic Cryptococcus neoformans infections. Secondary immunodeficiency likely occurred as a consequence of the intestinal loss of proteins and lymphocytes associated with malabsorption syndrome due to obstructed lymphatic drainage. Both patients had had severe abdominal involvement during the acute PCM disease. Immunological evaluation showed cellular and humoral immunity impairment. Cryptococcosis manifested as relatively well circumscribed lesions: osteolytic lesions of the skull in one patient, and pulmonary nodules in the other. The latter was treated surgically and with amphotericin B, whereas the other was treated with the combination amphotericin-B and flucytosine. Both patients had a good response to treatment with complete regression of the lesions. They have now 2 and 4 years of follow-up with maintenance therapy and no indication of reactivation of the infection. PCM also did not reactivate. The clinical and immunological characteristics of these patients are discussed and compared to the opportunistic C. neoformans infections of AIDS and transplant patients.     

Gramnegative opportunistic microflora as etiological factor of secondary infection in patients with pulmonary tuberculosis]

The results of the laboratory diagnoses of respiratory tract secondary infections in patients with pulmonary tuberculosis within a period of 12 months in a tuberculosis clinic were generalized. The species composition of the causative agents of lower respiratory tract secondary infection and the frequency of their detection in various clinical speciments (sputum, bronchial washings) were determined. The data on resistance of the opportunistic gramnegative bacilli (enterobacteria, pseudomonads, Acinetobacter spp.) isolated from the patients with pulmonary tuberculosis to various groups of antibacterials are presented.     

Characteristics of nonspecific resistance in children with lung diseases due to opportunistic microflora

Acute destructive pneumonia in children was found to be complicated by acute pleural empyema (APE) on days 3-21 of the disease. The time of the development of this complication depended on the state of the nonspecific resistance of the body: the greater was the degree of deficiency as manifested by cell-mediated and humoral immunity indices, the earlier developed APE. Staphylococci and Pseudomonas aeruginosa infected the pleural cavity of children under the conditions of essentially decreased phagocytic activity, phagocytic index, C'H50 and one of the classes of immunoglobulin. The reaction of the body to staphylococci and P. aeruginosa took its course after the type of primary or secondary immune response, depending on the time of infection.     

Increased titers of antibodies to bifidobacteria as a marker of intestinal dysbacteriosis

The study showed that a high titer of antibodies to bifidobacteria can serve as a laboratory sign of intestinal dysbacteriosis.Translated from Fiziologiya Cheloveka, Vol. 31, No. 2, 2005, pp. 132–134.Original Russian Text Copyright © 2005 by Anikhovskaya, Vyshegurov, Likhoded, Yakovlev.     

4-hydroxynonenal as a bioactive marker of pathophysiological processes

The review is focused on the currently major aspect of 4-hydroxynonenal (HNE) research--studies that combine biological activities of the aldehyde together with the methods of its identification in cells and tissues. Because there were some excellent reviews on HNE published in recent years, starting in 1990 and 1991 with supreme reviews done by Hermann Esterbauer, who discovered the aldehyde, and colleagues from the Institute of Biochemistry in Graz, this article pays most of attention to the most recent articles, published in the last 15 months. Additionally, an overview on the relevance of HNE is given with respect to the research and publication trends in the period of 10 years (1993-2002) according to the data in the Current Contents and Medline data bases. It is obvious that HNE started in 1993 as a "toxic product of lipid peroxidation" and "second toxic messenger of free radicals", to become in 2002 a reliable marker of oxidative stress, a possible causative agent of several diseases (such as Alzheimer's disease), growth modulating factor and a signaling molecule. Novel analytical methods developed suitable pathways for HNE to become a clinically applicable marker of lipid peroxidation on one side and on the other a standardized parameter of food quality control. As it is also present physiologically in various cells and tissues, it is likely that HNE will soon become one of the most attractive factors for those who search for a small and reactive molecular link between genomics and proteomics.     

Role of some representatives of opportunistic microflora in development of secondary infection in patients with pulmonary tuberculosis]

The results of the laboratory diagnosis of secondary (mixed) infection of the respiratory tracts in patients with respiratory tract tuberculosis were summarized. The study was performed for 12 months in a Tuberculosis Clinic. The species of the pathogens and the frequency of their detection in various clinical specimens from pulmonary tuberculosis patients were determined. The data on resistance of the strains of Streptococcus viridans group isolated from the pulmonary tuberculosis patients to various antimicrobials including new fluoroquinolones are presented.     

Monoclonal antibodies to alpha DNA polymerase as a marker of cell proliferative activity

A hybridoma cell line (5F) secreting monoclonal antibodies directed to alpha DNA polymerase has been developed. Kinetic studies on peripheral blood lymphocytes stimulated with mitogen and human colon cancer cell lines established in vitro were made by the two autoradiographic techniques of Thymidine Labelling Index and Primer-dependent alpha DNA polymerase Labelling Index and the immunoperoxidase assay (PAP) with monoclonal antibody to alpha DNA polymerase. We demonstrated the exclusively intranuclear presence of alpha DNA polymerase in lymphocytes induced to proliferate and actively growing colon cancer cells in contrast with the cytoplasmic distribution of the enzyme in resting stage populations. The feasibility of using monoclonal antibodies to alpha DNA polymerase to determine cell growth fraction was evaluated.     

Lupus serum and normal human serum contain anti-DNA antibodies with the same idiotypic marker

We have previously shown that serum from patients with active SLE contain high levels of Id-16/6 and anti-DNA antibodies. In this study we investigated whether serum Id 16/6 is related to anti-DNA antibodies. Sera from 12 patients with active SLE were absorbed individually with poly(dT) cellulose (to purify anti-DNA antibodies) and rabbit (R) anti-Id-16/6 Sepharose (to purify Id 16/6 Ig). Removal of all anti-DNA activity removed most of the Id-16/6. Conversely, removal of all Id 16/6 removed most of the anti-DNA activity. Although there was no measurable anti-DNA antibody activity in normal serum, such antibodies were isolated by absorption with poly(dT) cellulose. The eluted immunoglobulins also had Id 16/6 activity. Similarly, Id 16/6 with anti-DNA activity were isolated from normal serum by absorption with R anti-Id 16/6 Sepharose. We conclude that a large fraction of anti-DNA antibodies in SLE serum are Id-16/6+, and that most Id 16/6 immunoglobulins in lupus serum have anti-DNA activity. Our observations suggest that lupus anti-DNA antibodies result from an overproduction of autoantibodies that are present in normal people.     

The Galectin-1 level in serum as a novel marker for stress

Galectin-1(Gal-1), a carbohydrate-binding protein with an affinity for β-galactoside, is widely expressed in various normal and pathological tissues and it also plays an important role in regulating immune cell homeostasis and tumorigenesis. This study investigated the effects of restraint stress on serum Gal-1 by Western blot analyses and enzyme-linked immunosorbent assays. The Gal-1 levels of the restraint-stress group were significantly higher than those of the control group. However, this increase by stress was not obvious in adolescent rats. The pattern of these changes was similar to that of corticosterone. Furthermore, this Gal-1 increase in the serum was prevented by pre-treatment with a neurotoxin 6-hydroxydopamine (6-OHDA), which destroys the noradrenergic nerve terminals. However, a bilateral adrenalectomy (ADX) had no effect on the Gal-1 increase. These results suggest that Gal-1 is a candidate stress marker protein and that the stress-induced increase of Gal-1 in serum is regulated by the sympathetic nervous system under stress conditions.     

Current based antibodies detection from human serum enhanced by secondary antibodies labelled with gold nanoparticles immobilized in a nanogap

We present the electrical detection of immunoglobulin G (IgGs) from human serum using a nanogap-based biosensor. The detection method is based on the capture of IgGs by a probe immobilized between gold nanoelectrodes of 30-90nm spacing. The captured IgGs are further reacted with secondary antibodies labelled with gold nanoparticles (GNPs). Insertion of GNPs into the nanogap resulted in increasing the conductance through the nanogap. The use of a chip with 90 nanogaps enabled the calculation of a quality factor for the detection which, coupled with a non-linear regression analysis of the data, easily discriminated specific and differential capture of human antibodies by arrayed probes. We obtained a 500-fold higher quality factor with protein A compared to goat anti-murine antibodies. This method can be applied, through these proof-of-concept experiments, to the detection of protein-protein interactions in biological samples.     

Interleukin-25 in sputum as a marker of airway inflammation in children asthma

<正>Dear Editor,Interleukin-25 (IL-25, also called IL-17E) is an important IL-17 family member that helps initialize and regulate type 2immunity, exerting an important influence on the pathogenesis of asthma (Corrigan et al., 2011; Barlow et al., 2012).Furthermore, it plays a vital role in initiating type 2 innate lymphoid cell activation and maintenance (Tong and Li,2018) and inducing Th2-type cytokine-mediated allergic airway eosinophilia (Morita et al., 2015). IL-25 expression     

Indigenous microflora and opportunistic pathogens of the freshwater zebra mussel, Dreissena polymorpha

Freshwater fouling invertebrate zebra mussels (Dreissena polymorpha) harbor a diverse population of microorganisms in the Great Lakes of North America. Among the indigenous microorganisms, selective species are opportunistic pathogens to zebra mussels. Pathogenicity to zebra mussels by opportunistic bacteria isolated from the mussels was investigated in this study. Among the more than 30 bacteria isolated from temperature-stressed mussels, Aeromonas media, A. veronii, A. salmonicida subsp. salmonicida, and Shewanella putrefaciens are virulent pathogens to juvenile zebra mussels. Inoculation of a bacterial concentration of A. media, A. salmonicida subsp. salmonicida and S. putrefaciens at 10⁷ cells per zebra mussel resulted in 100% mortality within 5 days, and only 64.9% for A. veronii. In contrast, mortality was less than 12.3% following inoculation of a sterile phosphate buffer solution as a control. In addition, mortality was dependent on the size of the pathogen population used in inoculation and the incubation temperature, indicating the close relationship between the bacterial population and subsequent death. On the mussel tissue, a dense microbial population was evident from the moribund mussels viewed with Scanning Electron Microscope (SEM). Opportunistic bacteria invaded and destroyed the D. polymorpha tissue after 7 days of incubation when the bacterial inoculation was larger than 10⁵ per zebra mussel. Our results suggest that mussels are reservoirs of opportunistic pathogenic microorganisms to aquatic organisms and humans and a better understanding of the microbial ecology of the mussels will provide insights to the possible health hazards from these microorganisms.     

Serum anti-p53 antibodies as a useful marker for prognosis of gastric carcinoma

Mutations in the TP53 gene are the most common genetic alterations in cancer. Accumulation of mutated protein may induce circulating anti-p53 antibodies (anti-p53Ab) in sera of cancer patients. The aim of our work was to evaluate the presence and prognostic value of anti-p53Ab in gastric cancer patients and to investigate whether their presence is related to p53 overexpression in tumor tissue. Anti-p53Ab were analyzed in sera from 111 patients with gastric carcinoma and from 64 healthy donors by ELISA. p53 expression was also quantified by ELISA in biopsies of 54 gastric cancers and 22 healthy gastric mucosas. Significant anti-p53Ab levels were found in 15.3% of patients, whereas none of the 64 donor sera were positive. High levels of p53 expression were detected only in tumor tissue, in 72.2% of cases. A significant correlation was observed between anti-p53Ab and high levels of mutated p53 in tissue (p<0.05). The survival time of serum-positive patients was significantly longer than that of patients with low/negative serum levels, with a survival rate of 41.2% and 14.9%, respectively, over 48 months (p<0.05). Thus, detection of serum anti-p53Ab in gastric cancer patients can be useful to identify a subset of patients with better prognosis.     

Evaluation of human LOX-12 as a serum marker for breast cancer

The high concentration of prostaglandins has been associated with chronic inflammatory diseases and several types of human cancers. This is due to the over expression of inflammatory enzymes like Cyclooxygenase (COX), Lipoxygenase (LOX) etc. The aim of this study was to quantify the LOX-12 with clinicopathological parameter of breast cancer patients and its response after chemotherapy to establish serum LOX-12 as a prognostic marker. This case-controlled study was performed on 86 biopsy proven breast cancer patients. Blood and tissue samples were collected from the patients. Serum LOX-12 of the study group was quantified by Surface Plasmon Resonance (SPR) and ELISA techniques by antibody–antigen interaction strategy. A significant increase in LOX-12 levels was observed in breast cancer patients (Mean ± SD = 40.54 ± 13.61 ng/ml) as compared to healthy controls (Mean ± SD = 13.42 ± 2.4 ng/ml) (p < 0.0001). Serum LOX-12 levels were significantly higher (p < 0.002) in patients with lymph node involvement. More than 75% patients had shown significant (p < 0.0001) reduction of LOX-12 levels after chemotherapy. This was also confirmed by ELISA. This study for the first time had co-related the quantity of serum LOX-12 with breast cancer and also with the effect of chemotherapy.     

Low fasting serum triglyceride level as a precocious marker of autoimmune disorders

The authors recently reported the occurrence of low fasting serum triglyceride (TG) and high free fatty acid (FFA) levels in idiopathic pulmonary fibrosis. TG estimation in diverse groups of patients with autoimmune disease or hyperactive immune response confirmed the occurrence of a similar decrease of TG. In some patients, serum FFA level was also evaluated. TG value in lean and obese patients was compared with that in lean (n = 108) and obese (n = 208) control subjects without autoimmune disease. In patients affected by autoimmune chronic thyroiditis with enhanced concentration of antithyroglobulin antibodies and without thyroidal failure (n = 24), lean and obese patients had reduced TG (-69/%, P < .01 and -52%, P < .0001, respectively). Both lean and obese patients affected by chronic active B or C hepatitis (n = 26), with autoantibodies and without signs of hepatic insufficiency or cirrhosis, presented reduced TG (-57%, P < .01 and -61%, P < .001, respectively). A marked TG decrease (-73%, P < .001) was observed in the lean patients affected by lupus-like syndrome (n = 7). The lean and obese patients with systemic lupus erythematosus or rheumatoid arthritis (n = 11) showed TG decrease (-66%, P < .01 and -55%, P < .05, respectively). In patients affected by anamnestic allergy or atopic dermatitis/asthma (n = 66), both lean and obese, TGs were reduced (-67%, P < .0001 and -62%, P < .001, respectively). In isolated cases of diverse autoimmune diseases (scleroderma, APECED [autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy], urticaria or urticarial vasculitis, Reiter or Sjogren syndromes, ulcerative colitis or Crohn's disease, multiple sclerosis or Guillain-Barré syndrome) (n = 14), decreased TG was also observed both in the lean and obese subjects (-59%, P < .01 and -57%, P < .01, respectively). Concerning FFA (n = 69), value in lean patients (n = 22) vs that in lean controls (n = 18) was increased (520 +/- 31 vs 299 +/- 30 mcEq/L, +74%, P < .001), whereas value in obese patients (n = 18) vs that in obese control subjects (n = 11) was decreased (542 +/- 34 vs 774 +/- 62, -30%, P < .01). This opposite behavior of FFA in lean and obese patients needs to be confirmed. Data in this study seem to indicate that low TG value may be a precocious marker of autoimmunity or immune system hyperreactivity.     

Comparative population study of the etiological role of causative agents of purulent inflammatory diseases and serum antibodies to antigens of opportunistic microorganisms

The comparative study of the relationship between the levels of serum antibodies to the antigens of opportunistic microorganisms of 5 genera (Pseudomonas, Proteus, Staphylococcus, Klebsiella, Escherichia) and the microbial status was carried out. A total of 854 patients from 10 profile departments of a surgical hospital were examined. Population analysis and statistical methods of processing the results of the examination of 353 practically healthy subjects and 268 blood and plasma donors permitted the norms for the levels of specific antimicrobial antibodies (decreased, normal, elevated levels) were established. The constancy coefficients of Pseudomonas, Staphylococcus, Klebsiella, Escherichia and the number of patients with elevated titers of specific serum antibodies were found to be positively correlated (r = +0.47-0.89, p < 0.01). The data thus obtained made it possible to substantiate the importance of population serological investigations for the evaluation of the epidemiological situation in the surgical hospital.     

Hsp27 as a marker of cell damage in children on chronic dialysis

Intracellular heat shock protein (Hsp) 27 is a potent anti-apoptotic factor that, among other activities, prevents the binding of membrane receptor Fas to its ligand FasL. However, the potential role of extracellular Hsp27 and possibilities to control it have not been clarified. Moreover, there are no data on relations between Hsp27, sFas/sFasL system, matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in patients with chronic kidney disease (CKD)—neither children nor adults. The aim of this study was to evaluate serum concentrations of Hsp27 and their potential regulators (sFas, sFasL, MMP-7, TIMP-1) in children with CKD and on chronic dialysis. Twenty-six CKD children stage 5 still on conservative treatment, 19 patients on hemodialysis (HD), 22 children on automated peritoneal dialysis (APD), and 30 controls were examined. Serum concentrations of Hsp27, sFas, sFasL, MMP-7, and TIMP-1 were assessed by ELISA. Median values of Hsp27 were significantly elevated in all dialyzed patients vs. those in pre-dialysis period and vs. controls, the highest values being observed in subjects on HD. Regression analysis revealed that MMP-7, TIMP-1, sFas, and sFasL were the best predictors of Hsp27 concentrations in dialyzed patients. Children with CKD are prone to Hsp27 dysfunction, aggravated by the dialysis commencement, and more pronounced in patients on hemodialysis. Correlations between Hsp27 and examined parameters suggest the potential role for Hsp27 as a marker of cell damage in the pediatric population on chronic dialysis.     

Autoimmunity, immunodeficiency and mucosal infections: Chronic intestinal inflammation as a sensitive indicator of immunoregulatory defects in response to normal luminal microflora

Despite the fact that target antigens and the genetic basis of several autoimmune diseases are now better understood, the initial events leading to a loss of tolerance towards self-components remain unknown. One of the most attractive explanations for autoimmune phenomena involves various infections as possible natural events capable of initiating the process in genetically predisposed individuals. The most accepted explanation of how infection causes autoimmunity is based on the concept of “molecular mimicry” (similarity between the epitopes of an autoantigen and the epitopes in the environmental antigen). Infectious stimuli may also participate in the development of autoimmunity by inducing an increased expression of stress proteins (hsp), chaperones and transplantation antigens, which leads to abnormal processing and presentation of self antigens. Superantigens are considered to be one of the most effective bacterial components to induce inflammatory reactions and to take part in the development and course of autoimmune mechanisms. It has long been known that defects in the host defense mechanism render the individual susceptible to infections caused by certain microorganisms. Impaired exclusion of microbial antigens can lead to chronic immunological activation which can affect the tolerance to self components. Defects in certain components of the immune system are associated with a higher risk of a development of autoimmune disease. The use of animal models for the studies of human diseases with immunological pathogenesis has provided new insights into the influence of immunoregulatory factors and the lymphocyte subsets involved in the development of disease. One of the most striking conclusion arising from work with, genetically engineered immunodeficient mouse models is the existence of a high level of redundancy of the components of the immune system. However, when genes encoding molecules involved in T cell immunoregulatory functions are deleted, spontaneous chronic inflammation of the gut mucosa (similar to human inflammatory bowel disease) develops. Surprisingly, when such immunocompromised animals were placed into germfree environment, intestinal inflammation did not develop. Impairment of the mucosal immune response to the normal bacterial flora has been proposed to play a crucial role in the pathogenesis of chronic intestinal inflammation. The use of immunodeficient models colonized with defined microflora for the analysis of immune reactivity will shed light on the mode of action of different immunologically important molecules responsible for the delicate balance between luminal commensals, nonspecific and specific components of the mucosal immune system.