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At least 325 records · Page 18Linked to original sources
PubMed1993

Bacterial adhesins and host factors: role in the development and outcome of Escherichia coli bacteremia.

To assess the contributions of bacterial virulence factors and defects in host defense to Escherichia coli bacteremia, we examined isolates and available medical records from 169 episodes at two hospitals. Adhesins and hemolysin virulence factors were documented in 84% of bacteremia-associated isolates originating from the urinary and respiratory tracts and in 50% of such isolates originating from other extraurinary foci. Of the evaluable episodes of bacteremia involving 35 adhesin-negative isolates, 21 (60%) were in patients who had mucocutaneous defects at the primary site of infection, and another 13 (37%) were in patients who had comorbid systemic diseases (i.e., chronic renal failure or alcoholism) associated with impaired leukocyte function. In contrast, of 93 evaluable episodes with adhesin-positive isolates, 22 (24%) were in patients who had none of these host conditions (P = .008). Overall, of evaluable episodes of bacteremia involving 128 isolates, 71 (55%) had both bacterial virulence-associated and host-related risk factors. Mortality was related to the severity of comorbid illnesses and was not affected by the presence of the bacterial virulence factors assessed.

Adhesins, Escherichia coli↗
PubMed1986

Purification and properties of the Escherichia coli host factor required for inversion of the G segment in bacteriophage Mu.

G inversion in bacteriophage Mu requires the product of the DNA invertase gene gin and an Escherichia coli host factor termed FIS (factor for inversion stimulation). A recombination substrate must contain two recombination sites, arranged as inverted repeats, and a recombinational enhancer sequence termed sis. FIS has been purified to homogeneity. The purified protein has a relative molecular weight of 12,000 when analyzed under denaturing conditions. The intact protein behaves as a dimer of relative molecular weight 25,000 in gel filtration analysis. The purified protein does not possess any recombinogenic activity when assayed in the absence of the DNA-invertase Gin. In the presence of purified Gin FIS is the only additional protein required for efficient inversion. By performing gel retention assays, we show that FIS is a DNA-binding protein, which specifically binds to DNA fragments containing the recombinational enhancer sis.

Chromatography↗
PubMed1994

Viral and host factors that contribute to efficacy of interferon-alpha 2a therapy in patients with chronic hepatitis C.

Using conventional statistical analysis and multiple regression analysis, we investigated the viral and host factors that influence the response to recombinant interferon-alpha 2a therapy in patients with chronic hepatitis C. A total of 36 patients was randomly assigned to three administration schedules, 12 patients in each. Response to treatment was set as the criterion variable. Four variables were statistically significant in the conventional method in predicting a good therapeutic outcome: HCV genotype III and IV, lower histology activity index (HAI) score for liver, higher total dose of interferon administration, and lower serum HCV RNA concentration. In multiple regression analysis, a combination of the above four variables resulted in a higher multiple correlation coefficient (R = 0.84, P < 0.0001) using a stepwise method. Of those four, HCV genotype had the highest absolute value of standard partial regression coefficient (0.51). The HCV RNA concentration was correlated with HCV genotype and HAI score, whereas HCV genotype and HAI score showed no correlation. Thus, HCV RNA concentration was not statistically significant in multiple regression analysis. These findings indicate that HCV genotype, HAI score, and schedule of administration can be important predictors of the response to interferon therapy.

Adult↗
PubMed1994

Identification by Tn10 transposon mutagenesis of host factors involved in the biosynthesis of K99 fimbriae of Escherichia coli: effect of LPS core mutations.

Tn10 transposon mutagenesis of Escherichia coli producing K99 fimbriae was carried out to identify host factors involved in regulation of biosynthesis of fimbriae. Two chromosomal mutants were obtained that showed a strongly reduced cell surface expression of K99 fimbriae upon colony blotting and ELISA. Analysis by inversed PCR and nucleotide sequencing showed that one mutant (EP14) contained the Tn10 transposon in rfaQ, affecting the expression of the rfaQGP gene cluster, whereas the other mutant (EP35) was affected in a, to date, unknown region of the genome. Immunoblotting analysis confirmed a Rd1 type of LPS of mutant strain EP14. These findings for the first time indicated an effect of LPS core biosynthesis on the biogenesis of fimbriae at the cell surface. Preliminary experiments indicated that K99 major subunits, in contrast to K88 subunits, strongly bind LPS molecules.

Antibodies, Monoclonal↗
PubMed1998

The barrier-to-autointegration protein is a host factor for HIV type 1 integration.

In vivo, retroviral integration is mediated by a large nucleoprotein complex, termed the preintegration complex (PIC). PICs isolated from infected cells display in vitro integration activity. Here, we analyze the roles of different host cell factors in the structure and function of HIV type 1 (HIV-1) PICs. PICs purified by size exclusion after treatment with high salt lost their integration activity, and adding back an extract from uninfected cells restored this activity. In parallel, the native protein-DNA intasome structure detected at the ends of HIV-1 by Mu-mediated PCR footprinting was abolished by high salt and restored by the crude cell extract. Various purified proteins previously implicated in retroviral PIC function then were analyzed for their effects on the structure and function of salt-treated HIV-1 PICs. Whereas relatively low amounts (5-20 nM) of human barrier-to-autointegration factor (BAF) protein restored integration activity, substantially more (5-10 microM) human host factor HMG I(Y) was required. Similarly high levels (3-8 microM) of bovine RNase A, a DNA-binding protein used as a nonspecific control, also restored activity. Mu-mediated PCR footprinting revealed that of these three purified proteins, only BAF restored the native structure of the HIV-1 protein-DNA intasome. We suggest that BAF is a natural host cofactor for HIV-1 integration.

Animals↗
PubMed2000

N-mediated transcription antitermination in lambdoid phage H-19B is characterized by alternative NUT RNA structures and a reduced requirement for host factors.

Gene expression in lambdoid phages in part is controlled by transcription antitermination. For most lambdoid phages, maximal expression of delayed early genes requires an RNA polymerase modified by the phage N and host Nus proteins at RNA NUT sites. The NUT sites (NUTL and NUTR) are made up of three elements: BOXA, BOXB and an intervening spacer sequence. We report on N antitermination in H-19B, a lambdoid phage carrying shiga toxin 1 genes. H-19B N requires NusA, but not two other host factors required by lambda N, NusB and ribosomal protein S10. The H-19B NUT site BOXA is not required, whereas the BOXB is required for N action. H-19B nut sites have dyad symmetries in the spacer regions that are not in other nut sites. Changes in one arm of the dyad symmetry inactivate the NUT RNA. Compensating changes increasing the number of mutant nucleotides but restoring dyad symmetry restore activity. Deletion of the sequences encoding the dyad symmetry has little effect. Thus, the specific nucleotides composing the dyad symmetry seem relatively unimportant. We propose that the RNA stem-loop structure, called the 'reducer', by sequestering nucleotides from the linear RNA brings into proximity sites on either side of the dyad symmetry that contribute to forming an active NUT site.

Bacteriophage lambda↗
PubMed1985

[Host factors in lung cancer patients--with reference to family and past histories].

An analysis of cigarette smoking habits and family and past histories of 494 lung cancer patients was undertaken to determine whether host factors in such patients could be related to cancer. In men, 35.8% of the patients with squamous cell carcinoma had family histories of cancer, which is significantly higher than the ratio in control subjects (P less than 0.05). In women, 58.3% of the patients with bronchoalveolar cell carcinoma had family histories of cancer, and, in six out of eight of them, their parents had had the disease. As for past histories, 7.7% of the women with lung cancer had undergone surgery ovarian tumor. These results suggest that familial (hereditary) factors and predisposition play a role in the etiology of lung cancer.

Adenocarcinoma↗
PubMed2002

Rheumatoid factors: host resistance or autoimmunity?

Rheumatoid factors (RFs), autoantibodies that bind to the Fc portion of IgG, are important in the immune response. RF-committed B-cells exist in the circulating lymphocyte pool in a high frequency (approximately 1-2 %) in normal individuals and in patients with pathological conditions associated with the sustained levels of circulating RF, such as rheumatoid arthritis (RA), Sjogren's syndrome (SS), and mixed cryoglobulinemia, associated with hepatitis C virus infection. RFs are induced by many infectious entities (viruses, bacteria, parasites) as a consequence of a secondary immune response to the pathogen, but usually the response is transient. It is likely that RFs play an important role in the host's defense against infection, both at the cellular level, where the RF B-cell can be an antigen presenting cell which can promote the antipathogen response, and at the humoral level, where RFs can contribute to the mopping up of the IgG antipathogen antibodies by contributing to immune complex formation and clearance. There has been much research on RFs in chronic pathological conditions, and the literature pertaining to their origin, structure, binding specificities, and possible roles in disease are discussed. The importance of the host defense, sometimes at the expense of an autoimmune response, is a balance that needs to be considered in light of a possible outcome of health or disease.

Animals↗
PubMedDate not supplied

Defence of mucous membranes by antibodies, receptor analogues and non-specific host factors.

Most infections reach man via the mucosal membranes, and more than half of the lymphoid system is found in connection with mucosae. The major antibodies found on mucous membranes are secretory IgA, which function primarily by binding microorganisms and thereby preventing their contact with the host tissues. The optimal mode of immunization to obtain a secretory IgA response is not well defined. Repeated mucosal exposure with antigen may result in oral tolerance, with decreasing circulating antibodies but a remaining secretory IgA response. The secretory IgA response is usually short-lived and can be difficult to boost. IgM as well as IgG antibodies may add to host defence at the mucosal level, but when engaged, they usually induce inflammation in host tissues. Analogues to bacterial receptors on mucosal epithelium may be present in exocrine secretions such as human milk. During an attack on the host, it is possible that such receptor analogues may aid in the prevention of attachment of bacteria to mucous membranes used as an initial site. A number of non-specific host factors support mucosal defence. One of them is lactoferrin. Lactoferrin deficiency seems to result in recurrent bacterial infections, suggesting its importance in normal host defence.

Administration, Oral↗
PubMed1985

Defence of mucous membranes by antibodies, receptor analogues and non-specific host factors.

Most infections reach man via the mucosal membranes, and more than half of the lymphoid system is found in connection with mucosae. The major antibodies found on mucous membranes are secretory IgA, which function primarily by binding microorganisms and thereby preventing their contact with the host tissues. The optimal mode of immunization to obtain a secretory IgA response is not well defined. Repeated mucosal exposure with antigen may result in oral tolerance, with decreasing circulating antibodies but a remaining secretory IgA response. The secretory IgA response is usually short-lived and can be difficult to boost. IgM as well as IgG antibodies may add to host defence at the mucosal level, but when engaged, they usually induce inflammation in host tissues. Analogues to bacterial receptors on mucosal epithelium may be present in exocrine secretions such as human milk. During an attack on the host, it is possible that such receptor analogues may aid in the prevention of attachment of bacteria to mucous membranes used as an initial site. A number of non-specific host factors support mucosal defence. One of them is lactoferrin. Lactoferrin deficiency seems to result in recurrent bacterial infections, suggesting its importance in normal host defence.

Antibody Formation↗
PubMed2025

Proximity interactome of alphavirus replicase component nsP3 includes proviral host factors eIF4G and AHNAK.

All positive-strand RNA viruses replicate their genomes in association with modified intracellular membranes, inducing either membrane invaginations termed spherules, or double-membrane vesicles. Alphaviruses encode four non-structural proteins nsP1-nsP4, all of which are essential for RNA replication and spherule formation. To understand the host factors associated with the replication complex, we fused the efficient biotin ligase miniTurbo with Semliki Forest virus (SFV) nsP3, which is located on the cytoplasmic surface of the spherules. We characterized the proximal proteome of nsP3 in three cell lines, including cells unable to form stress granules, and identified >300 host proteins constituting the microenvironment of nsP3. These included all the nsPs, as well as several previously characterized nsP3 binding proteins. However, the majority of the identified interactors had no previously identified roles in alphavirus replication, including 39 of the top 50 interacting proteins. The most prominent biological processes involving the proximal proteins were nucleic acid metabolism, translational regulation, cytoskeletal rearrangement and membrane remodeling. siRNA silencing confirmed six novel proviral factors, USP10, AHNAK, eIF4G1, SH3GL1, XAB2 and ANKRD17, which are associated with distinct cellular functions. All of these except SH3GL1 were also important for the replication of chikungunya virus. We discovered that the small molecule 4E1RCat, which inhibits the interaction between the canonical translation initiation factors eIF4G and eIF4E, exhibits antiviral activity against SFV. Since the same molecule was previously found to inhibit coronaviruses, this suggest the possibility that translation initiation factors could be considered as targets for broadly acting antivirals.

Viral Nonstructural Proteins↗
PubMed1997

Complement evasion by Echinococcus granulosus: sequestration of host factor H in the hydatid cyst wall.

Hydatid disease, which affects humans and various livestock species, is caused by the larval stages of the cestode parasite Echinococcus granulosus. The disease involves the growth of a fluid-filled cyst in the host's internal organs. The hydatid cyst wall is generally thought to preclude the access of host immune cells to the cyst, while allowing passage of macromolecules. Thus, evasion of humoral effector mechanisms, in particular the complement system, may be crucial to parasite survival. Evasion of complement might involve inhibition of the C3b deposition step, which can in principle be achieved through parasite-derived or host-derived and parasite-bound regulatory molecules. In this work, extracts from bovine hydatid cysts were analyzed for the presence of factor H-like function, namely the cofactor activity for the breakdown of amidated bovine C3 by bovine factor I. Both this activity and antigenically detectable bovine factor H were found in most extracts. The cofactor activity was retained by an anti-bovine factor H Ab column; as no factor H-cross-reactive parasite molecules were detected in the active extracts, the activity was indeed due to host factor H. The pattern of extraction of host factor H from the parasite tissue indicated that at least part of it was selectively bound to the cyst wall, and that a strong charge component was involved in the binding. Our results indicate that the selective concentration of host factor H from plasma/interstitial fluid may contribute to complement evasion by E. granulosus.

Animals↗
PubMed1982

[Host factors in human carcinogenesis].

In human cancers, the contribution of genetic determinants is often difficult to distinguish from environmental influences. However, some cancers are inherited in Mendelian pattern, and some have closely associated with the diseases with hereditary factors. This paper reviewed characteristics of hereditary cancers, the diseases with high incidence of cancers and familial aggregation of cancers, and discussed the role of host factors in the etiology of cancer clinico-epidemiologically.

Adolescent↗
PubMed1992

Host factors and breast cancer growth characteristics.

The rate of growth and spread of breast cancer varies considerably from patient to patient. An observational study was undertaken to identify possible associations between breast cancer growth characteristics and a wide variety of host factors, including demographic, anthropometric, hormonal and dietary variables in 91 patients with breast cancer. Increasing age was associated with favourable growth characteristics, while previous tonsillectomy was associated with adverse growth characteristics. There were no significant associations in anthropometric variables. For postmenopausal women, increasing bioavailability of oestradiol was associated with favourable growth characteristics, while increasing prolactin concentration was associated with adverse growth characteristics. Increasing consumption of sugar, fibre, fruit and vegetables and vitamins was associated with favourable growth characteristics. Consumption of fat (monounsaturated and saturated) was associated with adverse characteristics when adjustment was made for total energy intake. The host environment may play a role in the control of breast cancer growth. In particular, the associations with oestrogen and progesterone receptor status indicate that nutrients may be of value as biological response modifiers in patients having hormonal therapy. This requires further investigation to assess therapeutic potential.

Age Factors↗
PubMedDate not supplied

Bacteraemia with Escherichia coli in diabetic patients. Studies on bacterial virulence and host factors.

A total of 70 episodes of E. coli bacteraemia occurred in 10 patients with insulin-dependent, and 54 patients with non-insulin-dependent diabetes mellitus. The bacteraemic strains were tested for aerobactin mediated iron uptake, a property that is regarded as a virulence factor of E. coli. Aerobactin mediated iron uptake was present in 60% of the isolated strains from the diabetic patients. A similar prevalence, 54%, was noted in E. coli from a control group of non-diabetic patients with bacteraemia. The prevalence of aerobactin positive strains, isolated from both diabetic and non-diabetic patients, was significantly higher than in faecal E. coli strains (39%) obtained from healthy subjects. In E. coli from diabetic patients, another bacterial virulence factor, P-fimbriae, was present on 62% of the aerobactin positive strains but only on 33% of strains lacking aerobactin mediated iron uptake. No examined host factors in the diabetic patients, such as age, sex, duration of diabetes, serum creatinine and presence of proteinuria, influenced the prevalence of aerobactin mediated iron uptake. In conclusion, bacterial virulence mediated by the aerobactin system occurs as frequently in diabetic as in non-diabetic patients with E. coli bacteraemia, and furthermore seems to co-exist with P-fimbriation.

Diabetes Mellitus, Type 1↗
PubMed1992

The sialylation of gonococcal lipopolysaccharide by host factors: a major impact on pathogenicity.

The resistance of gonococci in most patients to complement mediated killing by human serum is due to sialylation of their lipopolysaccharide (LPS) which prevents bactericidal antibody from reacting with target sites. Two of the host factors responsible are: cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA), a well-known sialylating agent, and another factor which enhances the transfer of sialyl groups from CMP-NANA to LPS catalysed by a gonococcal sialyltransferase. The bacterial determinant of resistance is a conserved LPS component of about 4.5 kDa which is sialylated at a terminal Gal beta 1-4GlcNAc site on its side chain. The sialylated LPS forms a surface coat which is stainable by ruthenium red and connected with previously described 'capsules'. These observations sparked off an explosion of research. Recent publications show that sialylation of LPS by CMP-NANA affects additional important aspects of gonococcal pathogenicity, notably interactions with antibodies and phagocytes, and rendering the gonococcal surface more 'host-like'. Also, the observations have prompted an examination of LPS from some other pathogens for the presence of sialyl groups with positive results for Neisseria meningitidis and Haemophilus influenzae.

Antibodies, Bacterial↗
PubMed1997

Host factors in chronic viral hepatitis.

The clinical outcomes of both hepatitis B and C virus infection are immensely variable, ranging from subclinical, self-limiting infection to end-stage liver disease with hepatocellular carcinoma. Knowledge of the host factors that determine these outcomes is important for the understanding and management of these diseases and may in the future guide rational drug development. Epidemiologic studies have elucidated the role of age (at the time of infection) and sex on disease outcome and the complex role of HIV coinfection has become clearer with time. More recently, investigation of genetic susceptibility to the most adverse outcomes of infection has identified the importance of polymorphisms in the MHC class I and II loci, mannose-binding protein, and the TNF alpha promoter. However, relative to malaria, the study of genetic susceptibility in viral hepatitis is still in its infancy.

Adolescent↗