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PubMed2024

A novel start-loss mutation of the SLC29A3 gene in a consanguineous family with H syndrome: clinical characteristics, in silico analysis and literature review.

BACKGROUND: The SLC29A3 gene, which encodes a nucleoside transporter protein, is primarily located in intracellular membranes. The mutations in this gene can give rise to various clinical manifestations, including H syndrome, dysosteosclerosis, Faisalabad histiocytosis, and pigmented hypertrichosis with insulin-dependent diabetes. The aim of this study is to present two Iranian patients with H syndrome and to describe a novel start-loss mutation in SLC29A3 gene. METHODS: In this study, we employed whole-exome sequencing (WES) as a method to identify genetic variations that contribute to the development of H syndrome in a 16-year-old girl and her 8-year-old brother. These siblings were part of an Iranian family with consanguineous parents. To confirmed the pathogenicity of the identified variant, we utilized in-silico tools and cross-referenced various databases to confirm its novelty. Additionally, we conducted a co-segregation study and verified the presence of the variant in the parents of the affected patients through Sanger sequencing. RESULTS: In our study, we identified a novel start-loss mutation (c.2T > A, p.Met1Lys) in the SLC29A3 gene, which was found in both of two patients. Co-segregation analysis using Sanger sequencing confirmed that this variant was inherited from the parents. To evaluate the potential pathogenicity and novelty of this mutation, we consulted various databases. Additionally, we employed bioinformatics tools to predict the three-dimensional structure of the mutant SLC29A3 protein. These analyses were conducted with the aim of providing valuable insights into the functional implications of the identified mutation on the structure and function of the SLC29A3 protein. CONCLUSION: Our study contributes to the expanding body of evidence supporting the association between mutations in the SLC29A3 gene and H syndrome. The molecular analysis of diseases related to SLC29A3 is crucial in understanding the range of variability and raising awareness of H syndrome, with the ultimate goal of facilitating early diagnosis and appropriate treatment. The discovery of this novel biallelic variant in the probands further underscores the significance of utilizing genetic testing approaches, such as WES, as dependable diagnostic tools for individuals with this particular condition.

Humans↗
PubMed1980

[Interest in gnotoxenic systems for the study of host-microbial flora of the digestive tract].

It is necessary to use experimental models in all studies of interactions between a host, its digestive tract microbial flora and the environment because these interactions are complex. The gnotoxenic animal, reared in an isolator as the axenic animal and harbouring a known microbial flora, constitutes either an analytic or mimetic experimental model. The gnotoxenic animal may be considered as an analytic model when used to determine which biotic or abiotic environmental factor of the host-animal plays a role in the intestinal ecosystem. The potential metabolic or immunologic role of a given bacterial strain in the intestinal ecosystem may be determined when the axenic animal is associated with this strain. The variation of the expression of the potential role of this strain in relation to the environment can be ascertained by diversifying the diet of the host or by introducing other bacterial strains into the intestinal ecosystem. The role of an association of strains in host physiology and host protection against potentially pathogenic target strains can also be studied using this analytic model. An analytic model is created by associating either isolated strains of the holoxenic or heated or diluted suspensions of holoxenic digestive tract flora. Axenic mice associated with these simplified flora are called meroxenic. The gnotoxenic animal is considered to be a mimetic model when it harbours a microbial flora isolated from an animal of a different species. The advantage of the mimetic model is that it provides an easy-to-use biological tool, i.e. gnotoxenic mice, to first determine the potential role of these microbial strains. The validity of the mimetic model is then tested by comparing gnotoxenic mice and gnotoxenic piglets or chickens. When all the gnotoxenic animals are given the same diet, this comparison permits an estimation of the animal-host role in the expression of the potential activities of microbial strains. The mimetic model, composed of gnotoxenic animals harbouring microbial strains of human origin, is the only experimental model which can be used to study the role of microorganisms in the intestinal ecosystem of man.

Animals↗
PubMed1989

Branhamella catarrhalis bronchopulmonary isolates in PICU patients.

Branhamella catarrhalis is commonly considered a respiratory commensal but has recently been implicated as a pathogen, particularly in adults. Over a 28 month period, B. catarrhalis was isolated from bronchopulmonary secretions of 14 PICU patients with acute respiratory infections. Twelve patients had pneumonia and two had tracheitis. The mean age was 3.5 years. Seven patients had chronic cardiopulmonary disease including two who were immunosuppressed. Three had an acute underlying condition and four had no complicating medical problem. Polymorphs and Gram-negative diplococci on Gram stain were found in respiratory secretions of all patients. Twelve of 14 isolates produced beta-lactamase, and six patients had a second potentially pathogenic bronchopulmonary isolate. All patients were treated for B. catarrhalis infection and none died. When isolated in pure culture from bronchopulmonary secretions in symptomatic patients, B. catarrhalis should be considered a pathogen. When isolated in mixed culture, its pathogenic role is uncertain. We conclude that B. catarrhalis can be a bronchopulmonary pathogen in critically ill children with otherwise normal cardiopulmonary function as well as in those with chronic cardiopulmonary dysfunction. When administering antibiotics the high frequency of beta-lactamase-producing strains must be taken into consideration.

Adolescent↗
PubMed1994

Expression of a maize proteinase inhibitor gene is induced in response to wounding and fungal infection: systemic wound-response of a monocot gene.

The isolation and characterization of cDNA and genomic clones encoding a proteinase inhibitor protein (MPI) in maize is reported. Accumulation of the MPI mRNA is induced in response to fungal infection in germinating maize embryos. The expression pattern of the MPI gene, in healthy and fungal infected maize tissues, was examined and compared with the expression pattern of a gene that codes for a pathogenesis-related protein (the PRms protein) from maize. These two genes are induced by fungal infection, however different signals trigger their activation. Accumulation of the proteinase inhibitor mRNA is more a consequence of the wound produced by the penetration and colonization of the host tissues by the pathogen, than the result of a direct molecular recognition of the pathogen by the plant, as is the case for the induction of the PRms gene. Wounding, or treatment with abscisic acid or methyl jasmonate, stimulate MPI mRNA accumulation, but not PRms mRNA accumulation. Local and systemic induction of the MPI gene expression in response to wounding occurs in maize plants. To the authors' knowledge, this is the first example of a gene from a monocotyledonous species that clearly shows a systemic wound response. The possible functional implications for the existence of different signal transduction pathways that simultaneously activate a battery of defense mechanisms against potential pathogens are discussed.

Abscisic Acid↗
PubMed2000

Recycling dead hens by enzyme or sodium hydroxide pretreatment and fermentation.

This study was conducted to evaluate the recycling of whole dead hens into feed ingredients by enzyme or sodium hydroxide pretreatment and fermentation. Evaluation criteria included nutrient preservation, pathogenic microorganism elimination, and assays of nutritional quality. The pH levels of enzyme- and NaOH-treated hen carcasses decreased from 6.01 and 7.66 to 4.18 and 4.24, respectively, during the 21-d fermentation. Hydrogen sulfide levels were not detected on Days 1 and 3 from the enzyme treatment; however, high levels (800 ppm) were measured from the NaOH treatments. By Day 21, H2S levels of both treatments had decreased to 78 ppm. The control, enzyme, and NaOH treatments before fermentation contained high levels of Escherichia coli and Staphylococcus aureus; however, after fermentation, these potential pathogens were eliminated in the enzyme and NaOH treatments. Levels of CP, EE, and ash of the control product were higher than either the enzyme or NaOH treatment. NaOH reduced pepsin digestibility by 11% compared to the enzyme treatment. In a bioassay, the chicks fed control autoclaved hen meal (CHM) had higher (P < 0.05) feed intake, weight gain, protein efficiency ratio (PER), and net protein ratio (NPR) than enzyme-treated, fermented, and autoclaved hen meal (EHM) or NaOH-treated, fermented, and autoclaved hen meal (NHM). However, the AMEn of the CHM and EHM were higher than the NHM (P < 0.05) when evaluated using mature cockerels. These results indicated that fermentation processing of dead hens reduced the concentration of some nutrients and depressed growth performance when hen meals were fed to young chicks.

Amino Acids↗
PubMed2004

Slime production by clinical isolates of Blastoschizomyces capitatus from patients with hematological malignancies and catheter-related fungemia.

In order to expand the present knowledge of the pathogenic potential of Blastoschizomyces capitatus in central venous catheter (CVC)-related bloodstream infections, six strains of the organism recovered from three leukemic patients with CVC-related fungemia in different years were investigated. Isolates and control strains were tested for their genetic relatedness and for their ability to produce slime in glucose-containing solutions. DNA restriction enzyme analysis revealed that all strains of B. capitatus were identical, whereas slime production assays and examination of ex vivo material showed that they were able to produce large amounts of slime. Slime production may therefore play a relevant pathogenic role in cases of CVC-related fungemia caused by B. capitatus.

Biofilms↗
PubMedDate not supplied

The acute phase response and innate immunity of fish.

Tissue trauma or invasion by pathogens or parasites induce changes in the quantities of several macromolecules in animal body fluids. These changes comprise one aspect of the acute phase response (APR), which in toto involves metabolic changes in several organ systems. One clear indication of the response is the increase in synthesis and secretion by the liver of several plasma proteins, with simultaneous decreases in others. These acute phase proteins (APP) function in a variety of defense-related activities such as limiting the dispersal of infectious agents, repair of tissue damage, inactivation of proteases, killing of microbes and other potential pathogens, and restoration of the healthy state. Some APP are directly harmful to microbes, while others modify targets thus marking them for cell responses. Some work alone while others contribute to cascades. Proteins that are APP in mammals, and that have been identified in both teleosts and elasmobranchs include C-reactive protein, serum amyloid P, and several components of the Complement system. Others reported in teleosts include transferrin and thrombin. Of these, only CRP has been reported to increase in acute phase plasma. In trout, a precerebellin-like protein is an APP with unknown functions. A cDNA library enriched in fragments of transcripts that were more abundant in livers from fish undergoing an APR recently yielded sequences resembling 12 additional known APP, and as many others either not known to be APP, or not similar to others yet in public databases. It appears that, as in mammals, hepatocytes are the prime source of APP in fish, and that pro-inflammatory cytokines induce transcription of their genes.

Acute-Phase Proteins↗
PubMed2005

Consequences of the electrogenic function of the phagocytic NADPH oxidase.

NADPH oxidase of phagocytic cells transfers a single electron from intracellular NADPH to extracellular O2, producing superoxide (O.-2), the precursor to several other reactive oxygen species. The finding that a genetic defect of the enzyme causes chronic granulomatous disease (CGD), characterized by recurrent severe bacterial infections, linked O.-2 generation to destruction of potentially pathogenic micro-organisms. In this review, we focus on the consequences of the electrogenic functioning of NADPH oxidase. We show that enzyme activity depends on the possibilities for compensating charge movements. In resting neutrophils K+ conductance dominates, but upon activation the plasma membrane rapidly depolarizes beyond the opening threshold of voltage-gated H+ channels and H+ efflux becomes the major charge compensating factor. K+ release is likely to contribute to the killing of certain bacteria but complete elimination only occurs if O.-2 production can proceed at full capacity. Finally, the reversed membrane potential of activated neutrophils inhibits Ca2+ entry, thereby preventing overloading the cells with Ca2+. Absence of this limiting mechanism in CGD cells may contribute to the pathogenesis of the disease.

Bacteria↗
PubMed2005

Mycoplasmas and ureaplasmas as neonatal pathogens.

The genital mycoplasmas represent a complex and unique group of microorganisms that have been associated with a wide array of infectious diseases in adults and infants. The lack of conclusive knowledge regarding the pathogenic potential of Mycoplasma and Ureaplasma spp. in many conditions is due to a general unfamiliarity of physicians and microbiology laboratories with their fastidious growth requirements, leading to difficulty in their detection; their high prevalence in healthy persons; the poor design of research studies attempting to base association with disease on the mere presence of the organisms in the lower urogenital tract; the failure to consider multifactorial aspects of diseases; and considering these genital mycoplasmas only as a last resort. The situation is now changing because of a greater appreciation of the genital mycoplasmas as perinatal pathogens and improvements in laboratory detection, particularly with regard to the development of powerful molecular nucleic acid amplification tests. This review summarizes the epidemiology of genital mycoplasmas as causes of neonatal infections and premature birth; evidence linking ureaplasmas with bronchopulmonary dysplasia; recent changes in the taxonomy of the genus Ureaplasma; the neonatal host response to mycoplasma and ureaplasma infections; advances in laboratory detection, including molecular methods; and therapeutic considerations for treatment of systemic diseases.

Adult↗
PubMed2025

Whole-exome sequencing uncovers the genetic basis of hereditary concomitant exotropia in ten Chinese pedigrees.

PURPOSE: To explore possible pathogenic genes for concomitant exotropia using whole-exome sequencing. METHODS: In this study, 47 individuals from 10 concomitant exotropia (including intermittent exotropia and constant exotropia) pedigrees were enrolled. Whole-exome sequencing was used to screen mutational profiles in 25 affected individuals and 10 unaffected individuals. Sanger sequencing and in silico analysis were performed for all participants. Two target genes were used to capture the sequences of 220 sporadic samples. RESULTS: All 10 concomitant exotropia pedigrees presented autosomal dominant inheritance with childhood onset (3.35&#x2009;&#xb1;&#x2009;1.51 years old). Eleven different missense variants were identified among seven potential pathogenic genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that cosegregated with pedigree members. All variants were predicted to be deleterious and had low frequencies in the general population. Distinct variants of COL4A2 were present in three pedigrees, and distinct variants of SYNE1 were present in two pedigrees. Fifteen variants in AUTS2 and four variants in GTDC2 were identified in 220 patients with sporadic concomitant exotropia using a target-capture sequencing approach. CONCLUSION: This is the first study to explore the genetic mechanism of concomitant exotropia and identify seven associated genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that may be candidate genes causing concomitant exotropia. More samples and in-depth studies are needed to verify these findings.

Adult↗
PubMed2005

Isolation of Salmonella serotypes in wastewater and effluent: Effect of treatment and potential risk.

The characteristics of strains of Salmonella isolated in wastewater were compared before and after treatment with activated sludge (conventional sewage treatment). Of the 21 strains studied, 11 came from raw wastewater and 10 from treated water. Our objective was to determine if the treatment affected all serotypes to the same extent, and whether it had an effect on the plasmidic composition and selection of resistances to antibiotics and disinfectants. The serotypes of all strains were identified, and we also determined the sensitivity to antibiotics, the minimal bactericidal concentration of three disinfectants (peracetic acid, glutaraldehyde, and sodium hypochlorite), and plasmidic content. Results showed no significant differences in the isolated strains before versus after treatment, thus indicating that the conventional treatment of sewage does not constitute a risk factor in the selection of Salmonella strains with a greater pathogenic potential.

Disinfectants↗
PubMed2006

Protection from autoimmunity: immunological indifference versus T-cell mediated suppression?

A long-held dogma was that immune tolerance could only be achieved through central deletion of potentially reactive cells at their site of origin, a concept supported by the direct demonstration of natural negative selection in bone marrow and thymus; however, it is now extensively documented that although deletion mechanisms ensure the elimination of most autoreactive cells, this purging is far from complete. There are major immune mechanisms that ensure tolerance in the periphery which are clearly non-deletional. A paper in this issue of the European Journal of Immunology demonstrates that T cell-mediated immunoregulation involving in particular the CTLA-4 signaling pathway plays a key role in controlling the pathogenic potential of fully differentiated autoreactive T cells.

Animals↗
PubMed2003

Acanthamoeba interactions with human brain microvascular endothelial cells.

Acanthamoeba are opportunistic protozoan parasites that can cause fatal granulomatous amoebic encephalitis, however, the pathogenic mechanisms associated with this disease remain unclear. One of the primary factors in Acanthamoeba encephalitis is the haematogenous spread, followed by invasion of the blood-brain barrier resulting in the transmigration of Acanthamoeba into the central nervous system. In this study, we have used human brain microvascular endothelial cells, which constitute the blood-brain barrier and studied their interactions with Acanthamoeba. Using in vitro cultures, we showed that Acanthamoeba isolates belonging to genotypes T3, T4 and T11, exhibited increased cytotoxicity on human brain microvascular endothelial cells as well as exhibited higher binding and were considered potential pathogens. In contrast, Acanthamoeba isolates belonging to genotypes T2 and T7 exhibited minimal cytotoxicity and significantly less binding to human brain microvascular endothelial cells (P< 0.01). Furthermore, exogenous alpha-mannose inhibited binding but increased cytotoxicity of human brain microvascular endothelial cells. This is the first demonstration of Acanthamoeba interactions with primary human brain microvascular endothelial cells.

Acanthamoeba↗
PubMed1991

Teratogenicity of the Palyam serogroup orbiviruses in the embryonated chicken egg model.

Embryonated chicken eggs were used as a model for assessing the teratogenic potential of several Palyam serogroup orbiviruses. Infection of 4-day-old embryonated chicken eggs via the yolk sac with eight of the viruses resulted in deaths or congenital deformities which included retarded development, arthrogryposis and reduced feathering. Statistical analysis showed that the viruses could be divided into three groups: those that caused death (Gweru virus isolates 866/77 and 1726/76; and Apies River virus), those that caused deaths only when large amounts of virus were inoculated (Gweru isolate AR11869 and Marondera virus) and those that caused death and deformities (Abadina, Kasba, Nyabira, Petevo and Vellore viruses). Differences in pathogenic potential were noted between isolates identified as the same serotype by serological tests.

Animals↗
PubMed2003

Highly polymorphic microsatellite for identification of Candida albicans strains.

The polymorphism of a new microsatellite locus (CAI) was investigated in a total of 114 Candida albicans strains, including 73 independent clinical isolates, multiple isolates from the same patient, isolates from several episodes of recurrent vulvovaginal infections, and two reference strains. PCR genotyping was performed automatically, using a fluorescence-labeled primer, and in the 73 independent isolates, 26 alleles and 44 different genotypes were identified, resulting in a discriminatory power of 0.97. CAI was revealed to be species specific and showed a low mutation rate, since no amplification product was obtained when testing other pathogenic Candida species and no genotype differences were observed when testing over 300 generations. When applying this microsatellite to the identification of strains isolated from recurrent vulvovaginal infections in eight patients, it was found that 13 out of 15 episodes were due to the same strain. When multiple isolates, obtained from the same patient and plated simultaneously, were typed for CAI, the same genotype was found in each case, confirming that the infecting population was clonal. Moreover, the same genotype appeared in isolates from the rectum and the vagina, revealing that the former could be a reservoir of potentially pathogenic strains. This new microsatellite proves to be a valuable tool to differentiate C. albicans strains. Furthermore, when compared to other molecular genotyping techniques, CAI proved to be very simple, highly efficient, and reproducible, being suitable for low-quantity and very-degraded samples and for application in large-scale epidemiological studies.

Candida albicans↗
PubMed2000

Molecular basis for recognition of an arthritic peptide and a foreign epitope on distinct MHC molecules by a single TCR.

KRN TCR transgenic T cells recognize two self-MHC molecules: a foreign peptide, bovine RNase 42-56, on I-Ak and an autoantigen, glucose-6-phosphate isomerase 282-294, on I-Ag7. Because the latter recognition event initiates a disease closely resembling human rheumatoid arthritis, we investigated the structural basis of this pathogenic TCR's dual specificity. While peptide recognition is altered to a minor degree between the MHC molecules, we show that the receptor's cross-reactivity critically depends upon a TCR contact residue completely conserved in the foreign and self peptides. Further, the altered recognition of peptide derives from discrete differences on the MHC recognition surfaces and not the disparate binding grooves. This work provides a detailed structural comparison of an autoreactive TCR's interactions with naturally occurring peptides on distinct MHC molecules. The capacity to interact with multiple self-MHCs in this manner increases the number of potentially pathogenic self-interactions available to a T cell.

Amino Acid Sequence↗
PubMed2000

Endotoxic activity of lipopolysaccharides isolated from emergent potential cystic fibrosis pathogens.

Improved antimicrobial therapies against the classical spectrum of pathogenic bacteria which colonise the lungs of cystic fibrosis (CF) patients has resulted in improved life expectancy and quality of life. Bacterial species that are resistant to a broad range of antibiotics including Stenotrophomonas maltophilia and Alcaligenes xylosoxidans have now emerged as potential new pathogens to fill the niche. At present, it is unclear from clinical data whether these microbes are commensal or pathogenic. In this study we have quantified the inflammatory potential of lipopolysaccharide (LPS) from eight species of Gram-negative organisms which have been cultured with increasing frequency from CF patients. Inflammatory responses induced by LPS from whole human blood and a human-derived monocyte cell line (THP-1) were assessed. Enzyme-linked immunosorbent assays were used to detect interleukin-6, interleukin-8, and tumour necrosis factor alpha (TNF). A bioassay was also used to assess TNF activity. With the exception of S. maltophilia, LPS extracted from all of the bacteria tested upregulated, by varying degrees, expression of each of the proinflammatory cytokines assayed. This study represents the first comprehensive report of the endotoxic potential of a new wave of microbes which are associated with CF.

Cell Line↗
PubMed1997

[Isolation and characterization of Yersinia enterocolitica from pigs and bovines in Chile].

The occurrence of Yersinia enterocolitica in tonsils and rectal swabs from 100 healthy pigs and the rectal swabs of 100 healthy cattle slaughtered at Santiago-Chile were analysed. Yersinia enterocolitica was isolated from 48 (48%) pigs but not from cattle. 98.2% of strains were of 4/O3 bioserogroup, considered to be pathogenic for humans. All of the strains were resistant to penicillin producing beta-lactamase. Most of them were resistant to neomicin and tetracycline. The pYV marker was used to demonstrate pathogenicity in all strains by four different assays: 65.5% of the strains were pYV positive by their plasmid profile; 73.3% by crystal violet binding; 84.5% by calcium dependency and 87.9% by hybridization with probe associated with cytotoxicity to Hep-2 cells in vitro. All of the Yersinia enterocolitica strains were pYV positive with at least one of the four tests analysed, 46/58 strains were positive by three tests simultaneously. The similarities between associated cytotoxic genes of porcine and human strains is discussed. The phenotypic and genotypic characteristics demonstrated by the isolates strains suggest that the pigs in Chile are reservoir of potential pathogenic Yersinia enterocolitica for humans.

Animals↗