Effects Of Host Factors Research Articles

Estrogen-stimulated uropathogenic E. coli mediate enhanced neutrophil responses

Urinary tract infection (UTI) is one of the most common bacterial infections worldwide and the most common cause is uropathogenic Escherichia coli (UPEC). Current research is mostly focused on how UPEC affects host factors, whereas the effect of host factors on UPEC is less studied. Our previous studies have shown that estrogen alters UPEC virulence. However, the effect of this altered UPEC virulence on neutrophils is unknown. The aim of the present study was to investigate how the altered UPEC virulence mediated by estrogen modulates neutrophil responses. We found that estradiol-stimulated CFT073 increased neutrophil phagocytosis, NETs formation and intracellular ROS production. We observed that the total ROS production from neutrophils was reduced by estradiol-stimulated CFT073. We also found that estradiol-stimulated CFT073 induced less cytotoxicity in neutrophils. Additionally, we found that several cytokines and chemokines like IL-8, IL-1β, CXCL6, MCP-1 and MCP-4 were increased upon estradiol-stimulated CFT073 infection. In conclusion, this study demonstrates that the estrogen-mediated alterations to UPEC virulence modulates neutrophil responses, most likely in a host-beneficial manner.

Effect of host factors and COVID-19 infection on the humoral immune repertoire in treated HIV.

People with HIV (PWH) appear to be at higher risk for suboptimal pathogen responses and for worse COVID-19 outcomes, but the effects of host factors and COVID-19 on the humoral repertoire remain unclear. We assessed the antibody isotype/subclass and Fc-receptor binding Luminex arrays of non-SARS-CoV-2 and SARS-CoV-2 humoral responses among antiretroviral therapy-treated (ART-treated) PWH. Among the entire cohort, COVID-19 infection was associated with higher cytomegalovirus (CMV) responses (vs. the COVID- cohort ), potentially signifying increased susceptibility or a consequence of persistent inflammation. Among the COVID+ participants, (a) higher BMI was associated with a striking amplification of SARS-CoV-2 responses, suggesting exaggerated inflammatory responses, and (b) lower nadir CD4 was associated with higher SARS-CoV-2 IgM and FcγRIIB binding capacity, indicating poorly functioning extrafollicular and inhibitory responses. Among the COVID-19- participants, female sex, older age, and lower nadir CD4 were associated with unique repertoire shifts. In this first comprehensive assessment of the humoral repertoire in a global cohort of PWH, we identify distinct SARS-CoV-2-specific humoral immune profiles among PWH with obesity or lower nadir CD4+ T cell count, underlining plausible mechanisms associated with worse COVID-19-related outcomes in this setting. Host factors associated with the humoral repertoire in the COVID-19- cohort enhance our understanding of these important shifts among PWH.

INTERLEUKIN-1β LEVELS IN THE HUMAN GINGIVAL SULCUS: RATES AND FACTORS AFFECTING ITS LEVELS IN HEALTHY SUBJECTS

Background and objective: Gingival crevicular fluid (GCF) affords a exceptional window for investigation of periodontal condition as the levels of inflammatory mediators, which consequences owing to the increased local destruction of connective tissue structural elements. This study aimed to explore the interleukin 1β (IL-1β)) levels in the human gingival sulcus in healthy normal people; and the effect of host factors as age , gender, type of tooth used in pro-inflammatory biomarkers. Methods: Eighty seven patients, 54 (62.1%) female and 33 (37.9%) male (aged 12–34 years; mean 19.58±4.4 years), participated in this study. Each subject underwent a session on professional oral hygiene and received oral hygiene instructions. Gingival crevicular fluid (GCF) sampling was conducted (baseline). GCF was collected from the Central incisor, the Lateral incisor, the Canine, the First premolar and the second premolar in this study. Results: In total, the mean±SD of central incisor IL-1β was 32.16±4.83 pg/ml, with a mode equal to 28.01 pg/mL, the median was 32.71 pg/mL, and ranged from 20.98 to 41.25 pg/ml with the 75% interquartile range (IQR) equal to 35.94 pg/ml. For males the mean±SD of central incisor IL-1β was 31.6±5.51 pg/ml VS 32.5±4.4 pg/ml of females. For the lateral incisor, canine, first premolar, second premolar: Conclusion: This study provides the upper limit of normal values ​​for interleukin 1β (IL-1β) levels for subjects aged 12–34 years in the GCF. These upper limits of normal values ​​will guide dentists in Yemen when they consider the diagnosis of periodontal disease, as well as its role during orthodontic tooth movement where they play important role in osteocyte activities (e.g, osteoclasts and osteoblasts), and will provide useful baseline data for future studies of interventions against periodontal disease, and teeth movement by orthodontics appliances, in Yemen. Peer Review History: Received: 1 September 2022; Revised: 11 October; Accepted: 6 November, Available online: 15 November 2022 Academic Editor: Dr. Emmanuel O. Olorunsola, Department of Pharmaceutics & Pharmaceutical Technology, University of Uyo, Nigeria, olorunsolaeo@yahoo.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Rima Benatoui,Laboratory of Applied Neuroendocrinology, Department of Biology, Faculty of Science, Badji Mokhtar University Annaba, Algeria. benattouiryma@gmail.com Dr. Gulam Mohammed Husain,, National Research Institute of Unani Medicine for Skin Disorders, Hyderabad, India, gmhusain@gmail.com Similar Articles: THE EFFECT OF NANOSILVER AND CHLORHEXIDINE MOUTHWASH ON ANAEROBIC PERIODONTAL PATHOGENS COUNTS

Effect of Host Factors on the Prevalence of Gastrointestinal Parasites in Goats of Maharashtra

Effect of Host Factors on the Prevalence of Gastrointestinal Parasites in Goats of Maharashtra

Effects of host factors on the dynamics of fleas (Siphonaptera) in Sigmodontinae rodents (Cricetidae) from El Espinal Ecoregion, Argentina

We investigated the patterns of flea infestation in wild populations of eight Sigmodontinae rodent species: Akodon azarae, Calomys callidus, Calomys venustus, Holochilus chacarius, Necromys lasiurus, Oligoryzomys flavescens, Oligoryzomys nigripes and Oxymycterus rufus. Rodents were captured in systematic trapping sessions carried out along 2 years at two localities from El Espinal Ecoregion, Argentina. Mean flea intensity, occurrence (presence/absence) of flea infestation, richness and diversity were compared for different ages, body condition, sex and rodent tribes (Akodontini, Oryzomyini and Phyllotini). A total of 376 fleas of the following species and subspecies were collected: Craneopsylla minerva wolffhuegeli, Polygenis (Neopolygenis) pradoi, Polygenis (Polygenis) axius axius, and Polygenis (Polygenis) byturus. The most important factor driving flea infestation was the rodent tribe, with Phyllotini showing the highest values of occurrence, abundance and species richness. Only C. m. wolffhuegeli was affected by the sex of the host. Age and body condition of the hosts did not affect flea infestation. Our results contribute to knowledge of the ecology of fleas on rodent hosts in El Espinal Ecoregion. The relevance of host taxonomy as driver of flea dynamics highlight the importance of considering host community structures at the time of studying the ecology of parasites.

Influenza Pathogenesis: The Effect of Host Factors on Severity of Disease.

Influenza viruses continue to be a major global health threat. Severity and clinical outcome of influenza disease is determined by both viral and host factors. Viral factors have long been the subject of intense research and many molecular determinants have been identified. However, research into the host factors that protect or predispose to severe and fatal influenza A virus infections is lagging. The goal of this review is to highlight the recent insights into host determinants of influenza pathogenesis.

Impact of Cell Surface Molecules on Conjugative Transfer of the Integrative and Conjugative Element ICESt3 of Streptococcus thermophilus.

Integrative conjugative elements (ICEs) are chromosomal elements that are widely distributed in bacterial genomes, hence contributing to genome plasticity, adaptation, and evolution of bacteria. Conjugation requires a contact between both the donor and the recipient cells and thus likely depends on the composition of the cell surface envelope. In this work, we investigated the impact of different cell surface molecules, including cell surface proteins, wall teichoic acids, lipoteichoic acids, and exopolysaccharides, on the transfer and acquisition of ICESt3 from Streptococcus thermophilus The transfer of ICESt3 from wild-type (WT) donor cells to mutated recipient cells increased 5- to 400-fold when recipient cells were affected in lipoproteins, teichoic acids, or exopolysaccharides compared to when the recipient cells were WT. These mutants displayed an increased biofilm-forming ability compared to the WT, suggesting better cell interactions that could contribute to the increase of ICESt3 acquisition. Microscopic observations of S. thermophilus cell surface mutants showed different phenotypes (aggregation in particular) that can also have an impact on conjugation. In contrast, the same mutations did not have the same impact when the donor cells, instead of recipient cells, were mutated. In that case, the transfer frequency of ICESt3 decreased compared to that with the WT. The same observation was made when both donor and recipient cells were mutated. The dominant effect of mutations in donor cells suggests that modifications of the cell envelope could impair the establishment or activity of the conjugation machinery required for DNA transport.IMPORTANCE ICEs contribute to horizontal gene transfer of adaptive traits (for example, virulence, antibiotic resistance, or biofilm formation) and play a considerable role in bacterial genome evolution, thus underlining the need of a better understanding of their conjugative mechanism of transfer. While most studies focus on the different functions encoded by ICEs, little is known about the effect of host factors on their conjugative transfer. Using ICESt3 of S. thermophilus as a model, we demonstrated the impact of lipoproteins, teichoic acids, and exopolysaccharides on ICE transfer and acquisition. This opens up new avenues to control gene transfer mediated by ICEs.

Effect of host factors on neutrophil functions in response to Burkholderia pseudomallei in healthy Thai subjects.

Burkholderia pseudomallei is an intracellular pathogenic bacterium that causes melioidosis in humans. On infection, neutrophils eliminate the majority of intracellular B. pseudomallei. Previous reports on the risk factors for melioidosis have shown that host factors, particularly age and diabetes mellitus, increase susceptibility to B. pseudomallei; however, whether these factors influence neutrophil functions in response to infection remains unknown. In this study, whole blood samples were collected from healthy Thai blood donors and co-cultured with B. pseudomallei, and phagocytic and respiratory burst functions of neutrophils were then measured by flow cytometry. The results show reduced neutrophil functions in older donors or those with poor glycemic control. Furthermore, the levels of antibody against B. pseudomallei showed a positive correlation with neutrophil functions. This study therefore indicated the importance of age, glycemic control, and antibody levels in the activity of neutrophils in melioidosis.

Some mechanisms of FLIP expression in inhibition of HIV‐1 replication in Jurkat cells, CD4+ T cells and PBMCs

HIV-1 infection and replication are affected by host factors. Recent studies demonstrate that molecules from apoptotic pathways regulate HIV-1 replication. Therefore, studies on effects of host factors that maintain host cell survival and influence HIV-1 replication are critical to understanding the mechanisms of HIV-1 replicative cycle. Using the susceptible Jurkat cell line, CD4(+) T cells, and peripheral blood mononuclear cells (PBMCs), we studied the role of FLIP, an inhibitor of caspase-8, in HIV-1 production. Full length cellular FLIP (cFLIP) inhibited HIV-1 replication in these cells. cFLIP upregulated the expression of viral restriction factors, such as TRIM5, Apobec3G, and Bst2/tetherin, decreased nuclear factor 1C expression and inactivated ERK and p38 induced by HIV-1 in Jurkat cells. cFLIP blocked the trafficking of gp120 and Gag p24 capsid protein into lipid rafts with inhibition of Tsg101 and Alix in ESCRT signaling pathway. cFLIP also promoted Bst2/tetherin trafficking into lipid rafts. These results indicate that cFLIP may inhibit the HIV-1 replication cycle at multiple steps, including viral RNA release, transcription, traffic and assembly. We also found that cFLIP expression downregulated Fas expression and inactivated FADD in the Fas-mediated apoptotic pathway. The inactivated FADD also inhibited HIV-1 replication.

Optimization of an Agrobacterium-mediated Transient Assay for Gene Expression Studies in Anthurium andraeanum

Gene function studies in anthurium (Anthurium andraeanum) have been hindered by the low efficiency of stable transformation, the long regeneration time required as well as the genotype-dependent nature of Agrobacterium (Agrobacterium tumemaciens)-mediated transformation protocols. Agrobacterium-mediated transient expression assays can serve as an attractive alternative for investigating gene function once such assays are optimized. The effects of host factors (genotype, explant type, and developmental maturity of explants), Agrobacterium factors (strain, growth phase, and its concentration), media conditions (infiltration medium used, acetosyringone concentration, type of surfactant, and its concentration), and other experimental factors (infiltration time, cocultivation time, and vacuum infiltration) were investigated on the efficiency of Agrobacterium transient transformation, with replications, using transient expression of β-glucuronidase as an indicator. Although the efficiency of transient transformation was initially found to be highly host genotype-dependent, the genotypic differences in transient transformation efficiency diminished as the protocol was optimized. Agrobacterium strain GV3101 grown to an optical density at 600 nM (OD600) of 1.5 and resuspended to a final OD600 of 0.8 in infiltration medium [0.5% glucose, 10 mm 2-(N-morpholino) ethanesulfonic acid] supplemented with 100 μM acetosyringone and 0.05% of a non-ionic surfactant (S240), for an infiltration period of 16 hours and a cocultivation timeframe of 2 days yielded transient transformation efficiencies as high as 100%.

Bacterial interactions in the nasopharynx – Effects of host factors in children attending day-care centers

The nasopharynges of preschool children are often colonized by potentially pathogenic bacteria. The interactions between these common pathogens and certain host factors were investigated in healthy preschool children 1-6 years of age. Nasopharynx samples were collected from all 63 children attending a day-care center that experienced an outbreak of penicillin-resistant Streptococcus pneumoniae. The samples were analyzed for S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Group A Streptococci. A model for the risk of carrying these bacteria was established using logistic regression. S. pneumoniae and H. influenzae antagonize each other, whereas M. catarrhalis and S. pneumoniae have a positively association. The risk of carrying M. catarrhalis decreases with age. The time spent in day care each week was not shown to influence the rate of carriage of any of these pathogens. The negative effect of H. influenzae on S. pneumoniae is discussed in relation to the carriage of penicillin-resistant S. pneumoniae, and possible mechanisms involved in this interaction are presented.

Effect of host factors on the susceptibility of Rhododendron to Phytophthora ramorum

Phytophthora ramorum causes sudden oak death (SOD) in western coastal forests of the USA. In Europe, the pathogen is mainly present in the nursery industry, particularly on Rhododendron. Because of the primary role of Rhododendron as a host and potentially as a vector, the effect of Rhododendron host factors on P. ramorum susceptibility and sporulation was investigated. Inoculation methods using either wounded or non‐wounded detached leaves were applied to 59 Rhododendron cultivars and 22 botanical species, replicated in three separate years. All Rhododendron species and cultivars were susceptible when using wounded leaves, but not when using non‐wounded leaves, suggesting a resistance mechanism operating at the level of leaf penetration. Using a regression tree analysis, the cultivars and species were split into four susceptibility classes. Young leaves were more susceptible than mature leaves when wounded, but less susceptible when non‐wounded. This effect was not correlated with leaf hydrophobicity or the number of leaf hairs. The presence or the type of rootstock did not affect the cultivar susceptibility level. Sporangia and chlamydospore production in the leaf lesions varied widely among Rhododendron cultivars and was not correlated with the susceptibility level. The susceptibility to P. ramorum correlated well with the susceptibility to P. citricola and P. hedraiandra × cactorum, suggesting that the resistance mechanisms against these species are non‐specific. Susceptibility to P. kernoviae was low for most cultivars. These findings have implications for detection, spread and disease control, and are therefore important in pest risk assessment.

Host Genetic Determinants of Human Immunodeficiency Virus Infection and Disease Progression in Children

Increasing data support host genetic factors as an important determinants of human immunodeficiency virus type-1 (HIV-1) susceptibility, mother-to-child transmission (MTCT), and disease progression. Of these genetic mediators, those impacting innate and adaptive immune responses seem to play a critical role in viral infectivity and pathogenesis. During primary infection, CCR5 using virus is predominantly transmitted and polymorphisms that affect the expression of CCR5 alter the risk for MTCT and rate of disease. Chemokines that naturally bind to coreceptors alter infectivity and viral pathogenesis. Additional genes that affect innate immunity including those encoding for MBL2 and those modulating the adaptive immune response including CX3CR1 and human leukocyte antigen types can significantly modify susceptibility and response to HIV-1 infection. As young children develop, the dependence on certain arms of the immune system varies and can alter the effect of genetic variants. Additionally, host genetic factors may alter the response to antiretrovirals. Finally, because HIV-infected children progress more rapidly than adults and have fewer background cofactors, such as drug use and coinfections, the effects of host factors on HIV-1 disease may be more clearly identified. In this review, we summarize available data on the impact of host genetics on MTCT and disease progression of HIV-infected children.

An Evaluation of Pfmdr1 Mutations in Chloroquine Resistance: Effect of Host Factor

Background: Pfcrt and Pfmdr1 mutations have been reported to be associated with chloroquine resistance, but these reports have been inconsistent. Red cell factors, sickle cell trait, ABO blood group antigens and glucose-6-phosphate dehydrogenase (G6PD) deficiency are known to confer some degree of resistance against malaria parasite infection but their interplay with CQ resistance is yet unknown. This study therefore aims at evaluating the correlation of CQ resistance with Pfmdr1 mutation and certain host factors in humans. Methods: One hundred and twenty patients (1–15yrs) with acute uncomplicated falciparum malaria were enrolled into the study. They were administered standard doses of CQ and followed up for parasitological and clinical response for 14 days. Thick and thin blood films as well as filter paper blood samples were obtained from patients before enrolment and during follow up. Blood samples were collected in EDTA bottles for assessment of haematological parameters. DNA was extracted from filter paper using the methanol fixation method and used for Pfmdr1 and msp1 analyses by polymerase chain reaction. Results: Seventy patients were followed up to day 14.53% of the patients were cured, with a 47% failure rate to CQ. Although Pfmdr1Y86 was detected in majority of the patients (19/33) with clinical failure, this was not statistically significant (p > 0.05). 88% of the clinical failures was due to recrudescence and this was highly significant with treatment outcome (p = 0.000). No significant association was found between Pfmdr1 alleles and red cell factors. However, individuals with HbAA were found to be 2.3 times more likely to develop resistance to CQ treatment compared to those having HbAS. Conclusion: In conclusion, the prevalence of CQ resistance and Pfmdr1Y86 mutation was high in this malaria endemic setting. There was no clear influence of ABO, G6PD deficiency and Hb genotype on CQ resistance and Pfmdr1 mutation.

Effect of host factors and experimental conditions on the horizontal transmission of Enteromyxum leei (Myxozoa) to gilthead sea bream, Sparus aurata L., and European sea bass, Dicentrarchus labrax (L.)

Journal of Fish DiseasesVolume 30, Issue 4 p. 243-250 Effect of host factors and experimental conditions on the horizontal transmission of Enteromyxum leei (Myxozoa) to gilthead sea bream, Sparus aurata L., and European sea bass, Dicentrarchus labrax (L.) A Sitjà-Bobadilla, A Sitjà-Bobadilla Instituto de Acuicultura de Torre de la Sal, CSIC, Castellón, SpainSearch for more papers by this authorA Diamant, A Diamant NCM – Israel Oceanographic & Limnological Research, Eilat, IsraelSearch for more papers by this authorO Palenzuela, O Palenzuela Instituto de Acuicultura de Torre de la Sal, CSIC, Castellón, SpainSearch for more papers by this authorP Alvarez-Pellitero, P Alvarez-Pellitero Instituto de Acuicultura de Torre de la Sal, CSIC, Castellón, SpainSearch for more papers by this author A Sitjà-Bobadilla, A Sitjà-Bobadilla Instituto de Acuicultura de Torre de la Sal, CSIC, Castellón, SpainSearch for more papers by this authorA Diamant, A Diamant NCM – Israel Oceanographic & Limnological Research, Eilat, IsraelSearch for more papers by this authorO Palenzuela, O Palenzuela Instituto de Acuicultura de Torre de la Sal, CSIC, Castellón, SpainSearch for more papers by this authorP Alvarez-Pellitero, P Alvarez-Pellitero Instituto de Acuicultura de Torre de la Sal, CSIC, Castellón, SpainSearch for more papers by this author First published: 28 March 2007 https://doi.org/10.1111/j.1365-2761.2007.00804.xCitations: 37 A Sitjà-Bobadilla, Instituto de Acuicultura de Torre de la Sal, Consejo Superior de Investigaciones Científicas, Torre de la Sal s/n, 12595 Ribera de Cabanes, Castellón, Spain(e-mail: [email protected]) Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume30, Issue4April 2007Pages 243-250 RelatedInformation

Randomized double-blinded trial of rifampin with either novobiocin or trimethoprim-sulfamethoxazole against methicillin-resistant Staphylococcus aureus colonization: prevention of antimicrobial resistance and effect of host factors on outcome

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in hospitals. Current antimicrobial regimens for eradicating colonizing strains are not well defined and are often complicated by the emergence of resistance. The combination of novobiocin plus rifampin in vitro and in vivo was found to prevent the emergence of resistant populations of initially susceptible strains of MRSA, particularly resistance to rifampin. We therefore studied, in a randomized, double-blind, multicenter comparative trial, the combination of novobiocin plus rifampin versus trimethoprim-sulfamethoxazole (T/S) plus rifampin in order to determine the efficacy of each regimen in eradicating MRSA colonization and to further characterize the host factors involved in the response to this antimicrobial therapy. Among the 126 individuals enrolled in the study, 94 (80 patients; 14 hospital personnel) were evaluable. Among the 94 evaluable subjects, no significant demographic or medical differences existed between the two treatment groups. Successful clearance of the colonizing MRSA strains was achieved in 30 of 45 (67%) subjects receiving novobiocin plus rifampin, whereas successful clearance was achieved in 26 of 49 (53%) subjects treated with T/S plus rifampin (P = 0.18). The emergence of resistance to rifampin developed more frequently in 14% (7 of 49) of subjects treated with T/S plus rifampin than in 2% (1 of 45) of subjects treated with novobiocin plus rifampin (P = 0.04). Restriction endonuclease studies of large plasmid DNA demonstrated that the same strain was present at pretherapy and posttherapy in most refractory cases (24 of 29 [83%] subjects). Among the 56 successfully treated subjects, clearance of MRSA was age dependent: 29 of 36 (80%) subjects in the 18- to 49-year-old age group, 19 of 35 (54%) subjects in the 50- to 69-year-old age group, and 8 of 23 (35%) in the 70- to 94-year-old age group (P < 0.01). Clearance was also site dependent; culture-positive samples from wounds were related to a successful outcome in only 22 (48%) of 46 subjects, whereas culture-positive samples from sites other than wounds (e.g., nares, rectum, and sputum) were associated with a success rate of 34 of 48 (71%) subjects (P = 0.02). Foreign bodies in wounds did not prevent the eradication of MRSA by either regimen. T/S plus rifampin was less effective in clearing both pressure and other wounds, whereas novobiocin plus rifampin was equally effective in clearing both pressure and other wounds. There were no significant differences in toxicity between the two regimens. Thus, the combination of novobiocin plus rifampin, in comparison with T/S plus rifampin, was more effective in preventing the emergence of resistance to rifampin and demonstrated a trend toward greater activity in clearing the MRSA carrier state. The response to either combination depended on host factors, particularly age and the site of MRSA colonization.

Investigation of Tumor Angiogenesis in an Id Mouse Model: Role of Host-Tumor Interactions

The role of host-tumor interactions in tumor angiogenesis was studied in an id mouse model. Although many previous studies have described the effects of certain host factors (age, nutritional status, tumor location, etc.) on experimental tumor systems, the effects of these factors on tumor angiogenesis have not been reported. In preliminary studies we inoculated cloned tumor cells id into syngeneic mice and found positional differences in tumor growth that did not correlate with measured angiogenesis levels. In addition, while tumor growth was inhibited by radiation, tumor-induced (but not fibroblast-induced) angiogenesis was not. This id system may provide an assay not only for examining the effect of host factors on tumor angiogenesis, but also for elucidation of the mechanisms underlying neovascular induction and host response.

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In a study of 261 male melanoma patients and age-and sex-matched controls, a strong positive univariate association between socioeconomic status, as determined by usual occupation, and risk of melanoma was detected. This association, however, was substantially explained by host constitutional factors and occupational, recreational, and vacation sunlight exposure. The study demonstrated an increased risk of melanoma in draftsmen and surveyors and a reduced risk of melanoma in construction workers and individuals employed in the finance, insurance, and real estate industry even after control for the effect of host factors and sunlight exposure.

Estimation of radiation doses to the lungs of early uranium processing plant workers

Methods are described for the crude estimation of radiation doses to the lungs of workers in early uranium processing plants. Using data on selected plants, we estimated lung doses for groups of workers exposed to uranium dust alone, or in association with γ rays and radon gas derived from radium in uranium ores. Estimated 30-year lung doses for groups of chemical workers at a large uranium enrichment plant (in operation from 1943 to 1947) varied considerably, depending upon such factors as length of employment, types of uranium compounds, average air concentrations of uranium, and isotopic composition of the uranium. Some workers may have received lung doses as high as several hundred rem. The uncertainties in these crude dose estimates are described, along with the possible effects of host factors. Implications of these dose estimates for assessment of long-term health effects (i.e., lung cancer) are discussed, with reference to preliminary findings of mortality studies on workers at uranium processing plants.

Effect of host factors in the cure of gram-negative bacterial infections

It has been shown among patients with gram negative bacterial infections, either life-threatening bacteraemia or common urinary tract infections, that categorical host factors markedly impinge on the observed effects of treatment with antimicrobial drugs. These factors have statistical significance in predicting the results that will be obtained with any particular chemotherapeutic regimen. The mechanisms mediating the host effects are not known, but in bacteraemia some conditions such as those that cause a decrease in circulating phagocytes, deficient function of fixed macrophages, delayed bacterial clearance and a reduced tolerance to shock, can be assumed to be important. In others, such as urinary tract infections, the finality of the eradication of bacteria from infected tissues may be paramount. The host factors are independent of, but also influence and integrate the effect of specific bacterial and drug features of infection and treatment. Readily recognizable clinical conditions permit some grouping of patients by host categories in order to make comparable analysis of antimicrobial drugs and regimens. In the search for clinical measures of synergy, host effects may dominate and obscure differences observed in vitro or in experimental infections in animals. However, the treatment of infection in host comparable groups of patients provides the opportunity to examine critically the clinical applicability of in vitro synergy and to devise more meaningful tests and procedures to achieve synergy in the treatment of infection in persons with unfavourable host conditions.