Search PubMed⌕ Search

Biomedical subjects

S E Holm

Publications and source records attributed to S E Holm.

At least 37 records · Page 2Linked to original sources
PubMed1998

Estimation of type-specific anti-streptococcal M-protein antibodies with biotinylated peptides in human sera.

The design of a novel enzyme-linked immunosorbent assay for the estimation of antibodies directed against the N-terminus of the M-protein of Streptococcus pyogenes is described. The ELISA employs biotinylated peptide antigens of the types 1, 4, 12 and 19 immobilized by (strept-)avidin on the surface of polystyrene microtiter wells. In rabbit hyperimmune sera and in human serum samples, antibodies against the corresponding serotype could be detected with high sensitivity and specificity.

Adult↗
PubMed1998

Streptokinase as a mediator of acute post-streptococcal glomerulonephritis in an experimental mouse model.

Group A streptococcal infections are sometimes followed by the inflammatory kidney disease acute post-streptococcal glomerulonephritis (APSGN). To test the importance of streptokinase in the pathogenesis of this disease, isogenic strains of the nephritis isolate NZ131, differing only in the ability to produce streptokinase of the nephritis-associated ska1 genotype, were used for infection in a mouse tissue cage model for APSGN. Streptokinase production was found to be a prerequisite for the capacity of the strain to induce APSGN in mice. In addition, streptokinase was demonstrated in the kidneys of mice infected with the nephritogenic NZ131 and EF514 strains. After infection with the nonnephritogenic strain S84, neither streptokinase nor C3 deposition were observed. Deposition of streptokinase in the glomeruli was detected as soon as 4 days after infection. These findings provide support for the hypothesis that streptokinase initiates the nephritis process by glomerular deposition, which leads to local activation of the complement cascade. Detection of streptokinase in kidney tissue increased with the degree of glomerular hypercellularity. Thus, the severity of the pathological process may be a reflection of the degree of streptokinase deposition.

Animals↗
PubMed1997

Chloroform mode of action: implications for cancer risk assessment.

Risk assessment methodology, particularly pertaining to potential human carcinogenic risks from exposures to environmental chemicals, is undergoing intense scrutiny from scientists, regulators, and legislators. The current practice of estimating human cancer risk is based almost exclusively on extrapolating the results of chronic, high-dose studies in rodents to estimate potential risk in humans. However, many scientists are questioning whether the logic used in this current risk assessment methodology is the best way to safeguard public health. A major tool of human cancer risk assessment is the linearized multistage (LMS) model. The LMS model has been identified as an aspect of risk assessment that could be improved. One way to facilitate this improvement is by developing a way to incorporate a carefully derived, more biologically relevant mechanism of action data on carcinogenesis. Recent data on chloroform indicate that the dose-response relationship for chloroform-induced tumors in rats and mice is nonlinear, based upon events secondary to cell necrosis and subsequent regeneration as the likely mode of action for the carcinogenic effects of chloroform. In light of these data, there is a sound scientific basis for removing some of the uncertainty that accompanies current cancer risk assessments of chloroform. The following points summarize the critical data: (1) a substantial body of data demonstrates a lack of direct in vivo or in vitro genotoxicity of chloroform; (2) chloroform induces liver and kidney tumors in long-term rodent cancer bioassays only at doses that induce frank toxicity at these target sites; (3) the chloroform doses required to produce tumors in susceptible species exceed the MTD, often by a considerable margin; (4) cytotoxicity and compensatory cell proliferation are associated with the chloroform doses required to induce liver or kidney tumors in susceptible rodent species; (5) there are no instances of chloroform-induced tumors that are not preceded by this pattern of dose-dependent toxic responses; (6) it is biologically plausible that cytolethality leads to chronically stimulated cell proliferation and related events such as inflammation and growth stimulation which act to initiate and promote the carcinogenic process; and (7) the consistently linked cellular events of cytolethality and subsequent cell proliferation, for which doses of no adverse effect have been clearly shown to exist, are one of the biological prerequisites for chloroform-induced tumors in animals. Based on these data, it is inappropriate to extrapolate cancer risk from high doses that produce necrosis and regenerative cell proliferation to low doses that do not with a model that presumes genotoxicity and a linear dose-response relationship. The weight of the scientific evidence concerning chloroform-induced tumors in rodents is consistent with and supports a cancer risk assessment methodology based on mode of action as the basis for establishing regulatory standards for this compound.

Administration, Inhalation↗
PubMed1997

The role of household contacts in the transmission of group A streptococci.

The intrafamilial spread and recurrence of group A beta-haemolytic streptococci (GAS) infections was investigated. The evaluation was based on 114 patients and their families treated with penicillin for 5 days and followed for 1 month. GAS of the same T-type as that of the isolate from the index case were found in other family members in 33% of the families. Genetic finger-printing using RFLP was performed on 33 of the isolates. The mothers dominated among the index cases, 40 patients experienced recurrences, 27 of them were clinical 28 recurrences occurred within 10 days after the end of treatment. Of 20 T-typed patients with early clinical treatment failures, infected family members were detected in 16 families (p < 0.001). In 19% of the patients GAS could be isolated from the nose. These patients had more ill family members than did other patients. An extensive intrafamilial streptococcal spread was found. Most recurrences of GAS pharyngotonsillitis after penicillin treatment are probably due to "ping pong" infection from family members.

Adolescent↗
PubMed1997

The prevalence of beta-haemolytic streptococci in throat specimens from healthy children and adults. Implications for the clinical value of throat cultures.

OBJECTIVE: To examine the influence of age and season of the year on the carrier rate of beta-haemolytic streptococci (BHS) in healthy individuals and patients with throat pain. DESIGN: The prevalence of BHS in throat specimens from healthy individuals was compared with that from patients with throat pain of the same age in a defined geographical area, collected during the same mid-winter and late summer periods. RESULTS: The prevalence of BHS in healthy individuals was low before the age of 3 years (1.9-7.1%) and in adults > or = 16 years (2.4-3.7%) and highest in the age group 3-15 years (5.0-21.2%). The difference in prevalence of BHS between healthy individuals and patients with throat pain was small during the late summer season and large during the mid-winter season. CONCLUSION: Prevalence of BHS varies with age and season in healthy individuals and patients with throat pain. During the summer, it is much more difficult to interpret the result of a throat culture in individuals aged < 16 years.

Adolescent↗
PubMed1996

Erysipelas: clinical and bacteriologic spectrum and serological aspects.

The bacteriologic, serological, and clinical characteristics of 229 patients with erysipelas diagnosed during a 2-year period at a university hospital for infectious diseases in Sweden are presented. Beta-Hemolytic streptococci were detected in 34% of these patients. Group A was the dominant serogroup, but group G streptococci were found in about half as many cases. Bacteremia was present in 5%. A serological response with antistreptolysin O (ASO) and antideoxyribonuclease B (ADNase B) was seen primarily in patients harboring group A streptococci but also in those from whom no pathogen was isolated. ASO was also found in high titers in some patients with Group G streptococcal infection. The clinical course was usually benign, with few complications, but recurrences were common (occurring in 21% of the patients). No cases of streptococcal toxic shock were seen. Culture of skin biopsy specimens had low sensitivity; Beta-hemolytic were isolated from only two of 15 patients.

Adult↗
PubMed1996

Strong cytotoxicity to human gingival fibroblasts by Porphyromonas gingivalis ATCC 33277.

The aim of the present study was to analyze the cytotoxicity of some bacterial species associated with periodontal diseases. The specificity of cytotoxicity was estimated against cells of various origin and from different individuals. The reference bacteria were Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. These bacteria were cultured for 24 h in liquid media and the supernatants were used in cytotoxicity assays. The target cells used were human gingival fibroblasts (GF), dermal fibroblasts (K4), gingival epithelial cells (E) and HeLa-cells (HeLa). These cells were exposed at 4 h or 24 h, respectively, to various concentrations of culture supernatants from the selected bacteria. The influence on the viability and metabolism of the cells were estimated quantitatively as increase in neutral red uptake and lactic acid production. Growth medium supernatants of P. gingivalis 33277 were strongly cytotoxic to gingival fibroblasts after 24 h incubation, compared to supernatants of P. gingivalis 381 or W 50, A. actinomycetemcomitans or F. nucleatum cultures. The toxic effect of P. gingivalis 33277 decreased drastically after heat inactivation, which indicates effects of proteins. By adding anti-sera the cytotoxicity of P. gingivalis 33277 could be dose dependently neutralized, which was not the case when supernatants of A. actino-mycetemcomitans was tested. Target cells of epithelial origin did not show increased cytotoxicity to P. gingivalis 33277. The results of the present study strengthen the hypothesis that P. gingivalis remains as a suspect causative key component in periodontal diseases.

Aggregatibacter actinomycetemcomitans↗
PubMed1996

The interference of gingival cell cultures with growth of selected bacteria.

The aim of the present study was to analyze the interference of oral tissue cells or cell lines (effector cells) with growth of reference bacteria, and furthermore to investigate whether cells derived from different individuals differ in such activity. The reference bacteria were Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mitis, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Fusobacterium nucleatum. The effector cells used were gingival fibroblasts (GF) from 21 periodontally involved persons, gingival epithelial cells (E) from 2 such persons, HeLa cells (HeLa), and an amnion cell line (Amnion). The cells were cultivated and their supernatants tested for antibacterial activity in a Bioscreen robot analyzer (Labsystems, Finland). Results suggest that the antibacterial activity of each tested primary cell line of tissue had its own profile depending on cell type and donor, and that the composition of oral microbiota was influenced by oral cells, which might, in turn, contribute to the variations in the pathogenesis of periodontal diseases.

Aggregatibacter actinomycetemcomitans↗
PubMed1996

An experimental model for acute poststreptococcal glomerulonephritis in mice.

A number of factors have been implicated in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN). The lack of a reliable animal model has made it difficult to further examine the role of these factors in the pathogenetic process. In this report, we present a tissue cage model in mice for the study of APSGN. Morphological and immunohistological changes in the kidney, resembling those of APSGN in man, were induced at high frequency in the experimental model after infection with group A streptococcal nephritis isolates. Nephritis-associated strain induced hypercellularity, occlusion of capillaries, and C3 deposition at high frequencies compared to the changes induced in animals infected with a non-nephritis-associated strain and non-infected controls. In animals infected with a nephritis isolate, hematuria and proteinuria were also detected. If penicillin treatment was initiated on the third day of infection, the development of the nephritis process was prevented. Streptokinase, as well as preabsorbing antigen and streptococcal pyrogenic exotoxin B (SpeB), have been implicated in the pathogenesis of APSGN. These proteins, as well as SpeA and SpeF, were detected in the fluids of the infectious focus, regardless of the origin of the strains and whether or not glomerulonephritis was seen. Antibodies to streptokinase were evoked in the majority of the infected animals. This immune response did not correlate with the nephritic process since hypercellularity was also seen in animals which lacked detectable streptokinase antibodies. The results show that the mouse tissue cage model can be used to study APSGN and to evaluate factors involved in the pathogenesis of the disease.

Animals↗
PubMed1996

A new procedure for the purification of streptococcal pyrogenic exotoxin A from Streptococcus pyogenes supernatant.

An important role in the pathogenesis of invasive group A streptococcal disease has been ascribed to the production of streptococcal pyrogenic exotoxin A. We present a new technique for the purification of streptococcal pyrogenic exotoxin A from Streptococcus pyogenes NY-5 supernate, which is highly efficient with respect to yield (35%), purity (> or = 99%), and time.

Bacterial Proteins↗
PubMed1996

Recolonization with selected alpha-streptococci for prophylaxis of recurrent streptococcal pharyngotonsillitis--a randomized placebo-controlled multicentre study.

In a randomized, placebo-controlled, double-blind, multicentre study, 130 patients with recurrence of group A beta-hemolytic streptococci (GAS) and clinical signs of pharyngotonsillitis were enrolled. The patients received antibiotic treatment for 10 days, followed by 10 days of alpha-streptococci-inhibitory to GAS-or placebo spray treatment. Patients taking antibiotic treatment for at least 9 days and using the spray for at least 5 days were included in the efficacy analysis. In addition, recurrence within the first 5 days of spray treatment was classified as 'early treatment failure'. The clinical recurrences (bacteriologically verified) in the alpha- (n = 51) and placebo-treated (n = 61) patient groups were 2% (n = 1) and 23% (n = 14) respectively, in patients given spray for at least 5 days (p = 0.004). The inclusion of 'early treatment failures' reduces this difference (p = 0.064). Both treatments were equally well tolerated. Thus, alpha-streptococci given as a spray and used for at least 5 days significantly prevented recurrence of GAS pharyngotonsillitis.

Adolescent↗
PubMed1995

Congenital streptococcal toxic shock syndrome with absence of antibodies against streptococcal pyrogenic exotoxins.

Congenital infection with group A beta-hemolytic streptococcus was complicated by toxic shock syndrome in a neonate. We hypothesize that the severity of the clinical syndrome was related to the streptococcal pyrogenic exotoxin in the absence of corresponding antibodies. The outcome may have been favorably influenced by the antibodies to streptococcal pyrogenic exotoxin present in the immunoglobulins given as treatment.

Antibodies, Bacterial↗
PubMed1995

Antimicrobial screening of zinc in the absence or presence of oleoresins and various resin acids.

Zinc and oleoresins are the main components of several wound dressings, and are also frequently used in root canal treatment. The in vitro antibacterial effects of zinc, six highly purified resin acids and two commercial oleoresins alone or combined in varying proportions were analysed. Oleoresins are composed of approximately 90% resin acids and the most common acids were included in this study. The antibacterial activity of the various chemicals was estimated using a Bioscreen robot analyser, which allowed 24 h kinetic documentation of bacterial growth. The bacteria employed were reference species commonly occurring on human skin or of oral origin. Zinc as well as the oleoresins and the pure resin acids all showed antibacterial activity when present in growth media, but the sensitivity of the bacteria varied. The presence of resin acids and oleoresins increased the antibacterial effect of zinc to varying degrees depending on the combination and the bacterial species tested. The results of the present study indicate that zinc, resin acids, or oleoresins alone, as well as combined, show antibacterial activity against selected aerobic Gram-positive and anaerobic Gram-negative bacteria.

Abietanes↗
PubMed1995

Correlation between serum TNF alpha and IL6 levels and severity of group A streptococcal infections.

The multiorgan failure syndrome caused by group A streptococci (GAS) designated streptococcal toxic shock syndrome (STSS) is believed to be mediated by cytokines induced by superantigens. In order to study the relationship between superantigen production, cytokine levels in patient sera, and clinical GAS manifestation we examined acute-phase sera and strains from 25 patients with GAS bacteremia. The patients had various disease manifestations, including STSS (44%), erysipelas (28%), septicemia (24%), wound infections (16%), and pneumonia (12%). Serotype T1M1 dominated, representing 56% of the isolates, but also strains of other serotypes were identified. The strains were found to produce the streptococcal pyrogenic exotoxins (Spe) A, B, and F, as determined by immuno-blot analyses. There was no difference in amounts of toxin produced between strains isolated from patients with different manifestations of disease. Levels of TNF alpha, IL1 alpha, IL6, IL8, and IFN gamma in acute-phase sera were determined by use of ELISA and RIA assays. The analyses showed higher levels of IL6 in sera from patients with STSS than in sera from patients with bacteremia without shock. TNF alpha was elevated in sera from patients with STSS, as compared to sera from patients with uncomplicated pharyngotonsillitis. No increase in the levels of IL1 alpha, IL8, and IFN gamma could be found in the patient sera and there was no difference in the level of those cytokines between the various patient categories.

Adolescent↗