| 1. |
- Bhuiyan, Taufiqur Rahman, 1974, et al.
(författare)
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Cholera caused by Vibrio cholerae O1 induces T-cell responses in the circulation.
- 2009
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Ingår i: Infection and immunity. - 1098-5522. ; 77:5, s. 1888-93
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Tidskriftsartikel (refereegranskat)abstract
- Considerable effort is being made to understand the acute and memory antibody responses in natural cholera infection, while rather less is known about the roles of cellular immune responses involving T and B lymphocytes. We studied responses in adult patients hospitalized with cholera caused by Vibrio cholerae O1. Peripheral blood mononuclear cells from patients (n = 15) were analyzed by flow cytometry after stimulation with V. cholerae O1 membrane protein (MP) or toxin-coregulated pilus antigen (TcpA). The gamma interferon (IFN-gamma) and interleukin-13 (IL-13) responses in stimulated-lymphocyte supernatants were studied. The responses were compared with those of healthy controls (n = 10). Patients responded with increased frequencies of gut-homing CD4(+) T cells (CD4(+) beta7(+)), gut-homing CD8(+) T cells (CD8(+) beta7(+)), and gut-homing B cells (CD19(+) beta7(+)) at the early and/or late convalescent stages compared to the acute stage. After stimulation with MP or TcpA, proliferation of CD4(+) and CD8(+) T cells was increased at the acute stage and/or early convalescent stage compared to healthy controls. Increased IL-13 and IFN-gamma responses were observed after antigenic stimulation at the acute and convalescent stages compared to healthy controls. Thus, increases in the levels of gut-homing T and B cells, as well as involvement of CD8 and CD4 Th1-mediated (IFN-gamma) and CD4 Th2-mediated (IL-13) cytokine responses, take place in acute dehydrating disease caused by V. cholerae O1. Further studies are needed to determine if such responses are also stimulated after immunization with oral cholera vaccines and if these responses play a role in protection following exposure to cholera.
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| 2. |
- Bhuiyan, Taufiqur Rahman, 1974, et al.
(författare)
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Comparison of mucosal B- and T-cell responses in Helicobacter pylori-infected subjects in a developing and a developed country.
- 2008
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Ingår i: FEMS immunology and medical microbiology. - 0928-8244. ; 54:1, s. 70-9
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori is highly endemic in developing countries, but comparatively little is known about mucosal immune responses to H. pylori in these settings. Therefore, we have compared B- and T-cell responses, with a focus on the gastrointestinal mucosa, in H. pylori-infected adults in a developing (Bangladesh) and a developed (Sweden) country. We found comparable numbers of CD19(+) B cells and CD4 (+)T cells and similar levels of H. pylori-specific IgA antibodies in gastric mucosa from Bangladeshi and Swedish volunteers. However, about threefold higher numbers of CD19(+) B cells and 12-fold increased levels of H. pylori-specific IgA antibodies were found in the duodenum of Bangladeshi subjects. The gastric and duodenal immune responses in Bangladeshi asymptomatic carriers and duodenal ulcer patients were comparable. Bangladeshi subjects had about twofold lower titers of H. pylori-specific IgA and IgG antibodies in the circulation compared with Swedish volunteers. In conclusion, our findings suggest that Bangladeshi individuals have comparable gastric immune responses, but lower systemic antibody responses to H. pylori, compared with Swedish volunteers. Increased inflammation is present in the duodenum of Bangladeshi volunteers, maybe as a result of frequent exposure to enteric infections in these individuals.
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| 3. |
- Bhuiyan, Taufiqur Rahman, 1974, et al.
(författare)
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Evaluation of immune responses to an oral typhoid vaccine, Ty21a, in children from 2 to 5 years of age in Bangladesh
- 2014
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 32:9, s. 1055-1060
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Tidskriftsartikel (refereegranskat)abstract
- Young children are very susceptible to typhoid fever, emphasizing the need for vaccination in under five age groups. The parenteral Vi polysaccharide vaccine is not immunogenic in children under 2 years and the oral Ty21a vaccine (Vivotif) available in capsular formulation is only recommended for those over 5 years. We studied immune responses to a liquid formulation of Ty21a in children 2-5 years of age. Since children in developing countries are in general hypo responsive to oral vaccines, the study was designed to determine if anti-helminthic treatment prior to vaccination, improves responses. In a pilot study in 20 children aged 4-5 years, the immune responses in plasma and in antibody in lymphocyte secretions (ALS) to the enteric coated capsule formulation of Ty21a was found to be comparable to a liquid formulation (P > 0.05). Based on this, children (n = 252) aged ≥2-<3 years and ≥3-<5 years were randomized to receive a liquid formulation of Ty21a with and without previous anti-helminthic treatment. The vaccine was well tolerated with only a few mild adverse events recorded in <1% of the children. De-worming did not improve immune responses and both age groups developed 32-71% IgA, IgG, and IgM responses in plasma and 63-86% IgA responses in ALS and stool specimens to a membrane preparation (MP) of Ty21a. An early MP specific proliferative T cell response was also seen. We recommend that safety and efficacy studies with a liquid formulation of the vaccine are carried out in children under five, including those less than two years of age to determine if Ty21a is protective in these age groups and applicable as a public health tool for controlling typhoid fever in high prevalence areas of typhoid fever including Bangladesh. © 2014 Elsevier Ltd. All rights reserved.
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| 4. |
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| 5. |
- Bhuiyan, Taufiqur Rahman, 1974, et al.
(författare)
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Th1 and Th17 responses to Helicobacter pylori in Bangladeshi infants, children and adults
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Both Th1 and Th17 cells are important components of the immune response to Helicobacter pylori (Hp) in adults, but less is known about T cell responses to Hp during early childhood, when the infection is often acquired. We investigated Th1 and Th17 type responses to Hp in adults, children and infants in Bangladesh, where Hp is highly endemic. IL-17 and IFN-γ mRNA levels in gastric biopsies from Hp-infected Bangladeshi adults were analyzed and compared to levels in infected and uninfected Swedish controls. Since biopsies could not be collected from infants and children, cytokine responses in Bangladeshi infants (6-12 months), children (3-5 years) and adults (>19 years) were instead compared by stimulating peripheral blood mononuclear cells (PBMCs) with a Hp membrane preparation (MP) and analyzing culture supernatants by ELISA and cytometric bead array. We found significantly higher expression of IL-17 and IFN-γ mRNA in gastric mucosa of Hpinfected Bangladeshi and Swedish adults compared to uninfected Swedish controls. PBMCs from all age groups produced IL-17 and IFN-γ after MP stimulation, but little Th2 cytokines. IL-17 and IFN-γ were primarily produced by CD4+ T cells, since CD4 + T cell depleted PBMCs produced reduced amounts of these cytokines. Infant cells produced significantly more IL-17, but similar levels of IFN-γ, compared to adult cells after MP stimulation. In contrast, polyclonal stimulation induced lower levels IL-17 and IFN-γ in infant compared to adult PBMCs and CD4+ T cells. The strong IL-17 production in infants after MP stimulation was paralleled by significantly higher production of the IL-17 promoting cytokine IL-1β from infant compared to adult PBMCs and monocytes. In conclusion, these results show that T cells can produce high levels of IL-17 and IFN-β in response to Hp from an early age and indicate a potential role for IL-1β in promoting Th17 responses to Hp during infancy. © 2014 Bhuiyan et al.
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| 6. |
- Janzon, Anders, 1978, et al.
(författare)
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Presence of high numbers of transcriptionally active Helicobacter pylori in vomitus from Bangladeshi patients suffering from acute gastroenteritis.
- 2009
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Ingår i: Helicobacter. - : Wiley. - 1523-5378 .- 1083-4389. ; 14:4, s. 237-47
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Helicobacter pylori is one of the most prevalent human bacterial pathogens; however, its transmission pathways remain unknown. New infections of H. pylori during outbreaks of gastroenteritis have been suggested previously, and to explore this transmission route further H. pylori was quantified in vomitus and diarrheal stool of patients suffering from acute gastroenteritis in Dhaka, Bangladesh. MATERIALS AND METHODS: Vomitus and stool samples from 28 patients seeking care at the International Centre for Diarrhoeal Disease Research hospital were analyzed for presence of H. pylori and other pathogens using quantitative culturing, real-time polymerase chain reaction (PCR), and H. pylori stool antigen test. Bacterial gene expression was analyzed using reverse transcriptase real-time PCR. RESULTS: The results of real-time PCR show that 23 (88%) of the 26 vomitus samples and 17 (74%) of the 23 stool samples were H. pylori positive, while stool antigen test show that 14 (67%) of the 21 stool samples were H. pylori positive. H. pylori could not be isolated by culture. Analysis using quantitative culture and real-time PCR to detect Vibrio cholerae showed strong correlation between these methods, and validating real-time PCR. Analysis of H. pylori virulence gene transcription in vomitus, diarrheal stool, antral and duodenal biopsy specimens, and in vitro cultures showed that cagA, flaA, and ureA were highly transcribed in vomitus, biopsy specimens, and cultures, whereas hpaA and vacA were expressed at lower levels. No H. pylori gene expression was detected in diarrheal stool. CONCLUSIONS: We conclude that high numbers of transcriptionally active H. pylori are shed in vomitus, which indicates that new infections may be disseminated through vomiting.
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| 7. |
- Lundgren, Anna, 1974, et al.
(författare)
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Characterization of Th17 responses to Streptococcus pneumoniae in humans: Comparisons between adults and children in a developed and a developing country
- 2012
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 30:26, s. 3897-3907
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Tidskriftsartikel (refereegranskat)abstract
- Intranasal exposure to Streptococcus pneumoniae as well as mucosal or parenteral immunization with a recently developed killed pneumococcal whole cell vaccine, confer Th17-mediated protection against subsequent S. pneumoniae colonization in mice. Given our interest in the function of Th17 cells and the ongoing efforts to develop this vaccine for use in infants and children in developing countries, we analyzed Th17 responses to the whole cell antigen (WCA) and individual pneumococcal antigens in healthy individuals and patients with pneumococcal disease and compared responses in children and adults from Sweden and Bangladesh. Peripheral blood mononuclear cells (PBMCs) isolated from Swedish adults produced IL-17A after stimulation with WCA, with the pneumolysoid PdT and with the protein required for cell separation in group B streptococci (PcsB). IL-22 and IFN-gamma responses were also detected, but these cytokines originated from separate CD4+T cell subsets. PBMCs from Swedish children produced lower levels of IL-17A in response to WCA compared to adults, whereas no such difference was noted from the samples from Bangladesh, where responses by children and adults were both significantly higher than those in Sweden. High IL-17A responses to stimulation with WCA were also observed in children with proven or probable pneumococcal pneumonia. Our results thus demonstrate the presence of Th17-type T cells that are specific for pneumococcus in both children and adults. The different levels of Th17 responses to pneumococci in children and adults in developing and developed countries, which may at least partly be due to differences in exposure to pneumococci, are important factors to consider in the evaluation of candidate pneumococcal protein-based vaccines in human trials. (C) 2012 Elsevier Ltd. All rights reserved.
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| 8. |
- Akhtar, Marjahan, et al.
(författare)
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T helper cell responses in adult diarrheal patients following natural infection with enterotoxigenic Escherichia coli are primarily of the Th17 type
- 2023
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Ingår i: FRONTIERS IN IMMUNOLOGY. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Infection with enterotoxigenic Escherichia coli (ETEC) gives rise to IgA antibodies against both the heat labile toxin (LT) and colonization factors (CFs), which are considered to synergistically protect against ETEC diarrhea. Since the development of ETEC-specific long lived plasma cells and memory B cells is likely to be dependent on T helper (Th) cells, we investigated if natural ETEC diarrhea elicits ETEC-specific Th cells and their relation to IgA responses.Methods: Th cell subsets were analyzed in adult Bangladeshi patients hospitalized due to ETEC diarrhea by flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) isolated from blood collected day 2, 7, 30 and 90 after hospitalization as well as in healthy controls. The LT- and CF-specific Th responses were determined by analysis of IL-17A and IFN-gamma in antigen stimulated PBMC cultures using ELISA. ETEC-specific IgA secreted by circulating antibody secreting cells (plasmablasts) were analyzed by using the antibodies in lymphocyte supernatants (ALS) ELISA-based method and plasma IgA was also measured by ELISA.Results: ETEC patients mounted significant ALS and plasma IgA responses against LTB and CFs on day 7 after hospitalization. ETEC patients had significantly elevated proportions of memory Th cells with a Th17 phenotype (CCR6+CXCR3-) in blood compared to controls, while frequencies of Th1 (CCR6-CXCR3+) or Th2 (CCR6-CXCR3-) cells were not increased. Antigen stimulation of PBMCs revealed IL-17A responses to LT, most clearly observed after stimulation with double mutant heat labile toxin (dmLT), but also with LT B subunit (LTB), and to CS6 in samples from patients with LT+ or CS6+ ETEC bacteria. Some individuals also mounted IFN-gamma responses to dmLT and LTB. Levels of LTB specific IgA antibodies in ALS, but not plasma samples correlated with both IL-17A (r=0.5, p=0.02) and IFN-gamma (r=0.6, p=0.01) responses to dmLT.Conclusions: Our results show that ETEC diarrhea induces T cell responses, which are predominantly of the Th17 type. The correlations between IL-17A and IFN-g and intestine-derived plasmablast responses support that Th responses may contribute to the development of protective IgA responses against ETEC infection. These observations provide important insights into T cell responses that need to be considered in the evaluation of advanced ETEC vaccine candidates.
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| 9. |
- Bhuiyan, Taufiqur Rahman, 1974
(författare)
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Humoral and cellular immune response to Helicobacter pylori in Bangladeshi children and adults that may be related to protection
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Helicobacter pylori (Hp) colonizes the human gastric and duodenal mucosa and the infection may cause peptic ulcers and gastric adenocarcinoma. Half of the world’s population is infected with Hp with the highest prevalence in developing countries. Hp infection is normally acquired during childhood, but comparatively little is known about immune responses to acute infection or potential differences in responses between individuals in Hp endemic and nonendemic countries. The overall aim of this thesis was to analyze humoral and cellular immune responses to Hp in children and adults living in a country with a high prevalence of Hp infections, i.e. Bangladesh. T- and B-cell responses to Hp were analyzed in Hp infected adults from Bangladesh and Sweden. Comparable numbers of CD19+ B cells and CD4+ T cells and similar levels of Hp-specific IgA antibodies were found in gastric mucosa from Bangladeshi and Swedish subjects. However, higher numbers of CD19+ B cells and higher levels of specific and total IgA antibodies were found in the duodenum of the Bangladeshis, possibly due to frequent enteric infections causing recruitment of Hp-specific and unspecific lymphocytes to this site. Furthermore, Bangladeshi subjects had about two-fold lower Hp-specific IgA and IgG serum antibody titers. To determine the incidence of Hp infection during early childhood in a high endemic area and possible associations between infection and different host and environmental factors, a birth cohort (BC) study was undertaken in Bangladeshi children from birth up to 24 months. Using diagnostic methods suitable for use in less well-equipped laboratories, i.e. stool antigen test and serology, 50-60% of the children were found to be positive for Hp at 24 months. Most children were initially infected with Hp during spring or autumn and blood group A children had increased susceptibility to the infection. Serum and stool samples collected every third month from the BC children were analyzed for development of systemic and mucosal antibody responses to acute Hp infection. Almost all children mounted specific, ≥4-fold serum IgA and stool IgA responses following infection. Serum IgG levels at birth were comparable to the maternal antibody levels and decreased during the initial 6 months, whereafter they increased in response to infection. An association between spontaneous eradication of Hp infection (in approximately 10% of the children) and increased serum antibody responses was found. Pre-existing maternal IgG and breast milk IgA antibody levels were associated with delayed onset of Hp infection. To analyze if certain T-cell responses (Th1 and Th17) may contribute to the immune responses against Hp, peripheral blood mononuclear cells were isolated and stimulated with Hp antigens. Cells from both Bangladeshi children and adults responded with production of both IL-17 and IFN-γ, with higher IL-17 responses in children. These results suggest that Th17 as well as Th1 type T-cell responses may be important for initial T-cell responses to Hp in young children. These studies give important information regarding acquisition of Hp during early childhood in a high endemic country and provide clues about immune responses that may be related to protection against Hp infection.
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| 10. |
- Bhuiyan, Taufiqur Rahman, 1974, et al.
(författare)
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Infection by Helicobacter pylori in Bangladeshi children from birth to two years: relation to blood group, nutritional status, and seasonality.
- 2009
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Ingår i: The Pediatric infectious disease journal. - 0891-3668. ; 28:2, s. 79-85
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A birth cohort of 238 children was followed in an urban slum in Dhaka, Bangladesh, to determine incidence, prevalence, and epidemiologic factors related to Helicobacter pylori infection. METHODS: H. pylori infection was determined by a specific stool antigen test as well as enzyme-linked immunosorbent assay for detecting specific IgA and IgG antibodies in sera in children who completed 2 years of follow-up. RESULTS: Using the stool antigen test and serology, 50% and 60% of infants respectively, were positive for H. pylori by 2 years; an increase in the infection rate was seen after 6 months of age. Determination of specific antibodies in sera and detection of H. pylori antigen in stool were comparable. A typical seasonality, peaking in spring and autumn, was observed for acquisition of initial H. pylori infection. Children with blood group "A" were more susceptible to H. pylori infection than those with other ABO blood groups. Malnutrition did not seem to promote colonization by H. pylori. However, H. pylori-infected children were more often infected by multiple enteropathogens, often isolated at different time points. CONCLUSIONS: This study shows that noninvasive diagnostic methods such as serology and the stool antigen test are suitable for the study of acquisition of H. pylori infections in infants and can be used in field settings as well as in laboratories and clinical setting having less well equipped facilities. The study also shows seasonality for initial H. pylori infection and a relationship between blood group "A" and infection.
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| 11. |
- Flach, Carl-Fredrik, 1977, et al.
(författare)
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Broad up-regulation of innate defense factors during acute cholera.
- 2007
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Ingår i: Infection and immunity. - 0019-9567. ; 75:5, s. 2343-50
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Tidskriftsartikel (refereegranskat)abstract
- We used a whole-genome microarray screening system (Affymetrix human GeneChips covering 47,000 different transcripts) to examine the gene expression in duodenal mucosa during acute cholera. Biopsies were taken from the duodenal mucosa of seven cholera patients 2 and 30 days after the onset of diarrhea, and the gene expression patterns in the acute- and convalescent-phase samples were compared pairwise. Of about 21,000 transcripts expressed in the intestinal epithelium, 29 were defined as transcripts that were up-regulated and 33 were defined as transcripts that were down-regulated during acute cholera. The majority of the up-regulated genes characterized were found to have an established or possible role in the innate defense against infections; these genes included the LPLUNC1, LF, VCC1, TCN1, CD55, SERPINA3, MMP1, MMP3, IL1B, LCN2, SOCS3, GDF15, SLPI, CXCL13, and MUC1 genes. The results of confirmative PCR correlated well with the microarray data. An immunohistochemical analysis revealed increased expression of lactoferrin in lamina propria cells and increased expression of CD55 in epithelial cells, whereas increased expression of the SERPINA3 protein (alpha1-antichymotrypsin) was detected in both lamina propria and epithelial cells during acute cholera. The expression pattern of CD55 and SERPINA3 in cholera toxin (CT)-stimulated Caco-2 cells was the same as the pattern found in the intestinal mucosa during acute cholera, indicating that the activation of the CD55 and SERPINA3 genes in intestinal epithelium was induced by CT. In conclusion, during acute cholera infection, innate defense mechanisms are switched on to an extent not described previously. Both direct effects of CT on the epithelial cells and changes in the lamina propria cells contribute to this up-regulation.
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| 12. |
- Flach, Carl-Fredrik, 1977, et al.
(författare)
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Differential expression of intestinal membrane transporters in cholera patients.
- 2007
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Ingår i: FEBS letters. - : Wiley. - 0014-5793. ; 581:17, s. 3183-8
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Tidskriftsartikel (refereegranskat)abstract
- Vibrio cholerae causes the cholera disease through secretion of cholera toxin (CT), resulting in severe diarrhoea by modulation of membrane transporters in the intestinal epithelium. Genes encoding membrane-spanning transporters identified as being differentially expressed during cholera disease in a microarray screening were studied by real-time PCR, immunohistochemistry and in a CaCo-2 cell model. Two amino acid transporters, SLC7A11 and SLC6A14, were upregulated in acute cholera patients compared to convalescence. Five other transporters were downregulated; aquaporin 10, SLC6A4, TRPM6, SLC23A1 and SLC30A4, which have specificity for water, serotonin (5-HT), magnesium, vitamin C and zinc, respectively. The majority of these changes appear to be attempts of the host to counteract the secretory response. Our results also support the concept that epithelial cells are involved in 5-HT signalling during acute cholera.
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| 13. |
- Qadri, Firdausi, et al.
(författare)
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Reduction in capsular content and enhanced bacterial susceptibility to serum killing of Vibrio cholerae O139 associated with the 2002 cholera epidemic in Bangladesh
- 2005
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Ingår i: Infect Immun. ; 73:10, s. 6577-6583
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Tidskriftsartikel (refereegranskat)abstract
- Vibrio cholerae O139 emerged in 1992 as a major cause of epidemic cholera. However, the incidence of disease due to this new serogroup subsequently decreased for almost a decade. In April 2002, there was a dramatic resurgence of V. cholerae O139 in Bangladesh. We compared the phenotypic properties of the bacterial isolates and the immunological responses in patients with disease due to V. cholerae O139 during the 2002 epidemic with those dating to the emergence of this disease in 1993 to 1995. Strains isolated from patients in the two time periods were compared with respect to capsular polysaccharide, their resistance to the bactericidal effect of serum, and their capacity to be used as target strains in complement-mediated vibriocidal assays. Phase-contrast microscopy showed that strains isolated in 2002 had less capsular material than those isolated from 1993 to 1995 (P = <0.001), a finding confirmed by electron microscopic studies. Strains isolated in 2002 were more susceptible to the bactericidal activity of serum compared to strains from 1993 to 1995 (P = 0.013). Compared to results using a standard O139 strain, a modified vibriocidal assay utilizing a 2002 strain, CIRS 134, as the target organism detected higher vibriocidal responses in both O139-infected cholera patients as well as O139 vaccine recipients. The vibriocidal assay utilizing the less encapsulated 2002 strain, CIRS 134, is a more sensitive indicator of adaptive immune responses to recent infection with V. cholerae O139. Consequently, this assay may be useful in studies of both O139-infected patients and recipients of O139 vaccines.
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| 14. |
- Qadria, Firdausi, et al.
(författare)
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Immune responses and protection in children in developing countries induced by oral vaccines.
- 2013
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 31:3, s. 452-460
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Tidskriftsartikel (refereegranskat)abstract
- Oral mucosal vaccines have great promise for generating protective immunity against intestinal infections for the benefit of large numbers of people especially young children. There however appears to be a caveat since these vaccines have to overcome the inbuilt resistance of mucosal surfaces and secretions to inhibit antigen stimulation and responses. Unfortunately, these vaccines are not equally immunogenic nor protective in different populations. When compared to industrialized countries, children living in developing countries appear to have lower responses, but the reasons for these lowered responses are not clearly defined. The most likely explanations relate to undernutrition, micronutrient deficiencies, microbial overload on mucosal surfaces, alteration of microbiome and microbolom and irreversible changes on the mucosa as well as maternal antibodies in serum or breast milk may alter the mucosal pathology and lower immune responses to interventions using oral vaccines. The detrimental effect of adverse environment and malnutrition may bring about irreversible changes in the mucosa of children especially in the first 1000 days of life from conception to after birth and up to two years of age. This review aims to summarize the information available on lowered immune responses to mucosal vaccines and on interventions that may help address the constraints of these vaccines when they are used for children living under the greatest stress and under harmful adverse circumstances.
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