Roland Arnold - Academia.edu (original) (raw)

Papers by Roland Arnold

Research paper thumbnail of Critical Role of Apoptotic Speck Protein Containing a Caspase Recruitment Domain (ASC) and NLRP3 in Causing Necrosis and ASC Speck Formation Induced by <i>Porphyromonas gingivalis</i> in Human Cells

Journal of Immunology, Feb 15, 2009

Periodontal disease is a chronic inflammatory disorder that leads to the destruction of tooth-sup... more Periodontal disease is a chronic inflammatory disorder that leads to the destruction of tooth-supporting tissue and affects 10-20 million people in the U.S. alone. The oral pathogen Porphyromonas gingivalis causes inflammatory host response leading to periodontal and other secondary inflammatory diseases. To identify molecular components that control host response to P. gingivalis in humans, roles for the NLR (NBD-LRR) protein, NLRP3 (cryopyrin, NALP3), and its adaptor apoptotic speck protein containing a C-terminal caspase recruitment domain (ASC) were studied. P. gingivalis strain A7436 induces cell death in THP1 monocytic cells and in human primary peripheral blood macrophages. This process is ASC and NLRP3 dependent and can be replicated by P. gingivalis LPS and Escherichia coli. P. gingivalis-induced cell death is caspase and IL-1 independent and exhibits morphological features consistent with necrosis including loss of membrane integrity and release of cellular content. Intriguingly, P. gingivalis-induced cell death is accompanied by the formation of ASC aggregation specks, a process not previously described during microbial infection. ASC specks are observed in P. gingivalis-infected primary human mononuclear cells and are dependent on NLRP3. This work shows that P. gingivalis causes ASC-and NLRP3-dependent necrosis, accompanied by ASC speck formation.

Research paper thumbnail of Mechanisms and Consequences of Neutrophil Interaction with the Subgingival Microbiota

Research paper thumbnail of Interferon activated gene 204 protects against bone loss in experimental periodontitis

Journal of Periodontology

BackgroundPeriodontal destruction can be the result of different known and yet‐to‐be‐discovered b... more BackgroundPeriodontal destruction can be the result of different known and yet‐to‐be‐discovered biological pathways. Recent human genetic association studies have implicated interferon‐gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) with high periodontal interleukin (IL)‐1β levels and more destructive disease, but mechanistic evidence is lacking. Here, we sought to experimentally validate these observational associations and better understand IFI16 and AIM2's roles in periodontitis.MethodsPeriodontitis was induced in Ifi204–/– (IFI16 murine homolog) and Aim2–/– mice using the ligature model. Chimeric mice were created to identify the main source cells of Ifi204 in the periodontium. IFI16‐silenced human endothelial cells were treated with periodontal pathogens in vitro. Periodontal tissues from Ifi204–/– mice were evaluated for alveolar bone (micro‐CT), cell inflammatory infiltration (MPO+ staining), Il1b (qRT‐PCR), and osteoclast numbers (cathepsin K+ staining...

Research paper thumbnail of Cofactor Requirements for Expression of Lactoferrin Bactericidal Activity on Enteric Bacteria

Recent Advances in Mucosal Immunology, 1987

Lactoferrin (LF), is an iron-binding glycoprotein that is common to most mammalian excretions (1–... more Lactoferrin (LF), is an iron-binding glycoprotein that is common to most mammalian excretions (1–3) and is a prominent component of the specific granule of neutrophilic leukocytes (4,5). It shares its distribution on mucosal surfaces with that of secretory IgA. Its high affinity binding in coordination with suitable anion has been well characterized (6–9). This ability to bind iron has been associated with a bacteriostatic deprivation of this essential nutrient (10–12). A variety of other biological activities have also been attributed to LF, including a direct bactericidal effect on a variety of bacteria (13,14). This killing mechanism is temperature and pH dependent and requires direct interaction of the LF with the bacterial cell surface (15). There are a variety of bacteria that are resistant to the bactericidal effects of purified LF binding including selected Gramnegative enteric bacteria (14). The resistance of these bacteria appears related, in part, to the impermeability of their outer cellular structures (16).

Research paper thumbnail of Introduction to the Oral Cavity

How Fermented Foods Feed a Healthy Gut Microbiota, 2019

The oral cavity plays a critical role as the seeder and gatekeeper of the microbiome that populat... more The oral cavity plays a critical role as the seeder and gatekeeper of the microbiome that populates the continuum of mucosal surfaces of the gastrointestinal tract, as well as that of the respiratory tract. The mouth has a variety of discrete niches and environmental conditions (microhabitats) that select for and discriminate against a vast array of microorganisms that ultimately determine the microbiome. The oral microbiome is an important contributor to host health and refers specifically to the microorganisms that reside on or in the human oral cavity and its contiguous mucosal surfaces to the distal esophagus. The oral microbiome is composed of approximately 700 species of bacteria, and also includes viruses, fungi, protozoa and archaea associated with the varied microhabitats that define the oral microbial ecosystem. The normal microbiota of the mouth is responsible for maintaining homeostasis of the oral cavity, but is also responsible for two of the most common diseases of ba...

Research paper thumbnail of Role of interferon in resistance and immunity to protozoa

Research paper thumbnail of Bactericidal Activity of Different Forms of Lactoferrin

Advances in, Experimental Medicine and Biology, 1994

Mucosal surfaces provide the portal of entry for most pathogenic microorganisms. In protection th... more Mucosal surfaces provide the portal of entry for most pathogenic microorganisms. In protection the mammalian host has concentrated a number of defense factors in the exocrine secretions that bathe mucosal surfaces. Understanding how these factors operate to prevent pathologic consequences of microbial challenge and what mechanisms a pathogen uses to evade this host defense is essential to the development of interventive approaches. Lactoferrin (LF) and secretory IgA (slgA) are both secreted in significant quantities at most mucosal surfaces and in milk. Both of these factors are reported to have bacteriostatic activity (1–8) and interact with each other and other defense factors (including lysozyme, complement, and lactoperoxidase) to modify their effectiveness (9, 10). In addition purified iron-free LF has been shown to have microbicidal activity against a variety of bacteria and yeast via mechanisms that are not reversed by the addition of free iron (11–16). A factor present in many commercial LF-enriched preparations, which co-purifies with slgA, has been reported to result in syner-gistic bactericidal activity and these impure LF preparations are able to kill bacterial strains that are resistant to purified LF (17).

Research paper thumbnail of Equivalent Mortality in Normal and Athymic Mice Infected with Naegleria fowleri

The Journal of Parasitology, 1985

Naegleriafowleri, a normally free-living amoeba, is the causative agent of primary amoebic mening... more Naegleriafowleri, a normally free-living amoeba, is the causative agent of primary amoebic meningoencephalitis (PAM), and since its first description in 1965 over 100 cases have been reported worldwide (John, 1982, Annual Review of Microbiology 36: 101-123). A perplexing aspect of PAM is that pathogenic N. fowleri are often isolated from recreational waters, yet exposed individuals only rarely develop PAM and it occurs in apparently healthy humans. Although affected individuals might have some underlying immune dysfunction it is most likely PAM is the result of environmental or genetic factors that serve to enhance virulence of amoebae. Studies have been directed at elucidating the role of the immune system in resistance to PAM. In laboratory animals, immunization by a variety of routes with Naegleria antigen can heighten resistance to a subsequent lethal infection (John et al., 1977, Infection and Immunity 16: 817820; Thong et al., 1978, The American Journal of Tropical Medicine and Hygiene 27: 238-240). Investigations of cellular immune components showed that Naegleria antigen could elicit a delayed hypersensitivity reaction in guinea pigs (Diffley et al., 1976, Zeitschrift fur Parasitenkunde 49: 133-137) and macrophage inhibition by lymphokine macrophage inhibition factor (Cursons et al., 1980, Infection and Immunity 29: 408-410). Although Naegleria antigen can evoke an immunological response which may lessen susceptibility to a lethal infection, little is known about the role of the humoral and cellular immune systems in innate resistance to PAM. Congenitally athymic (nude [nu/nu]) mice are deficient in T-cell-dependent cell-mediated immunity and in the humoral response to Tcell-dependent antigens (Wortis, 1974, Contemporary Topics in Immunobiology 3: 243-263). Investigations on the pathogenicity of N. fowleri in nude mice would serve as an useful aid for delineating the role of T-cell-dependent activities in the innate resistance against development of PAM. Providing that the T-cell-dependent arm of the immune system is a significant factor in innate resistance, it would be expected nude mice would show increased susceptibility and the course of PAM would be more rapid compared to normal mice. The purpose of this study was to determine if the development of PAM and the course of the disease was more rapid in congenitally athymic mice than in phenotypically normal mice. Mice were also infected with trophozoites of Naegleria lovaniensis, an amoeba physiologically and morphologically similar to N. fowleri, but nonpathogenic in immunocompetent mice (Stevens et al., 1980, International Journal for Parasitology 10: 51-64). The Lee strain of N. fowleri and N. lovaniensis were cultivated in tubes containing Chang's medium (De Jockheere, 1977, Applied and Environmental Microbiology 33: 751-757). Amoebae in late exponential growth were enumerated by hemacytometer counts, centrifuged (1,000 g for 15 min), and adjusted to the desired density in Chang's medium so that 25 1l delivered the appropriate number of amoebae (Fig. 1). Mice were of Swiss Webster background and congenitally athymic mice were obtained by mating homozygous (nu/nu) males with heterozygous (+/nu) females. Mice were maintained under specific pathogen free conditions in an area separate from other laboratory animals. For infection, mice of either sex and approximately 12 wk old were anesthetized with ether and 25 Al of an amoebae suspension was delivered into the nares with a micropipet. Development of PAM was evident by typical symptoms of anorexia, excitability, and ruffling of neck hair, which were followed by convulsions and death. PAM was

Research paper thumbnail of Enhancement of Streptococcus mutans Colonization by Direct Bonded Orthodontic Appliances

Journal of Dental Research, 1983

Patients undergoing orthodontic therapy were evaluated for longitudinal changes in relative S. mu... more Patients undergoing orthodontic therapy were evaluated for longitudinal changes in relative S. mutans numbers in plaque at discrete sites on the tooth surface associated with direct bond appliances. There was a significant linear increase in the percentage of S. mutans in the total streptococci isolated from the last pre-bracket sample through the last bracket sample.

Research paper thumbnail of Effects of Natural Cross-Linkers on the Stability of Dentin Collagen and the Inhibition of Root Caries in vitro

Caries Research, 2008

Results: While all collagen was digested with collagenase in the control groups, only a small pro... more Results: While all collagen was digested with collagenase in the control groups, only a small proportion was solubilized in the GA-, PA-, and GE-treated groups. The root caries was significantly inhibited by treatment with PA or GA. Drops in pH in the cross-linker-treated groups were essentially the same as in the untreated group. Conclusion: Naturally occurring cross-linkers, especially PA, could be used to modify root dentin collagen to efficiently stabilize collagen and to increase its resistance against caries.

Research paper thumbnail of Effects of Escherichia coli and Porphyromonas gingivalis lipopolysaccharide on pregnancy outcome in the golden hamster

Infection and Immunity, Oct 1, 1994

This report describes the elfects of two gram-negative bacterial endotoxin (lipopolysaccharide [L... more This report describes the elfects of two gram-negative bacterial endotoxin (lipopolysaccharide [LPS]) preparations on hamster pregnancy outcome variables. Single intravenous challenges with Escherichia coli and Porphyromonas gingivalis LPS on day 8 of pregnancy produced dose-dependent effects on fetal weight malformation and fetal resorption with E. coli LPS having potent embryolethal effects. Premating maternal exposure to P. gingivalis produced embryolethal effects similar to those of E. coli. These data suggest that maternal exposure to P. gingivalis LPS prior to and during pregnancy can induce deleterious effects on the developing fetus.

Research paper thumbnail of Helper and Suppressor Functions of Thymus-Derived Lymphocytes in the Humoral Response to Heterologous Erythrocytes in Rabbits

This material was produced from a microfilm copy o f the original document. While the most advanc... more This material was produced from a microfilm copy o f the original document. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the original submitted. The following explanation o f techniques is provided to help you understand markings or patterns which may appear on this reproduction. 1 .T h e sign or "target" for pages apparently lacking from the document photographed is "Missing Page(s)". I f it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting thru an image and duplicating adjacent pages to insure you complete continuity. 2. When an image on the film is obliterated with a large round black mark, it is an indication that the photographer suspected that the copy may have moved during exposure and thus cause a blurred image. You will find a good image o f the page in the adjacent frame. 3. When a map, drawing or chart, etc., was part o f the material being photographed the photographer followed a definite method in "sectioning" the material. I t is customary to begin photoing at the upper left hand corner of a large sheet and to continue photoing from le ft to right in equal sections w ith a small overlap. If necessary, sectioning is continued again-beginning below the first row and continuing on until complete. 4. The majority of users indicate that the textual content is of greatest value, however, a somewhat higher quality reproduction could be made from "photographs" if essential to the understanding of the dissertation. Silver prints of "photographs" may be ordered at additional charge by writing the Order Department, giving the catalog number, title, author and specific pages you wish reproduced. 5. PLEASE NOTE: Some pages may have indistinct print. Filmed as received.

Research paper thumbnail of Dysbiosis of the Oral Microbiome

How Fermented Foods Feed a Healthy Gut Microbiota, 2019

The oral cavity is influenced by the dietary characteristics of each individual. It is in the ora... more The oral cavity is influenced by the dietary characteristics of each individual. It is in the oral cavity that food will cause the first impact within the human body and its microbiome, due to its composition and consistency. On the other hand, the oral microbiome will affect food processing and impact the human gut microbiome, since bacterial biofilm that is processed within saliva forms the food bolus, which will then be swallowed. The mouth is one of the most heavily colonized parts of our bodies and its microbiome consists of microorganisms that live in symbiosis with healthy individuals who have adequate dietary and oral hygiene habits. Nevertheless, perturbations in the microbiome due to certain stress factors, such as high carbohydrate intake and biofilm accumulation, can lead to dysbiosis and the development of oral diseases. The most prevalent diseases in the oral cavity are dental caries and periodontal diseases including gingivitis and periodontitis, but endodontic (pulp)...

Research paper thumbnail of Oral vaccination of rats with Streptococcus mutans: induction of secretory antibodies and reduced caries

Journal of Dental Research, 1976

Research paper thumbnail of Antimicrobial Activity of the Secretory Innate Defense Factors Lactoferrin, Lactoperoxidase and Lysozyme1

Research paper thumbnail of A clinical study of bacterial contamination of chlorhexidine-coated filaments of an interdental brush

The Journal of clinical dentistry, 1998

The purpose of this study was to assess the effectiveness of a chlorhexidine coating on the nylon... more The purpose of this study was to assess the effectiveness of a chlorhexidine coating on the nylon filaments of an interdental brush in reducing bacterial contamination from actual clinical usage. In addition, the residual antimicrobial capacity of the coating over time from clinical exposure was studied. The same type of interdental brush, one with chlorhexidine-coated nylon filaments (antibacterial) and one with uncoated (control) nylon filaments was used with 20 subjects who were participating in a periodontal maintenance program. All subjects had more than four interproximal spaces large enough to accommodate the interdental brush at the start of the study. The subjects served as their own controls in this cross-over design. They used their brushes daily for one and two weeks, respectively. After the last use, each brush was kept in a controlled environment (20-22 degrees C, 65% relative humidity) for 24 hours for air drying. It was found that antimicrobial activity was detected ...

Research paper thumbnail of Use of Mutants in the Elucidation of Virulence of Streptococcus Mutans

Advances in Experimental Medicine and Biology, 1978

In the presence of sucrose, Streptococcus mutans displays certain unique metabolic activities whi... more In the presence of sucrose, Streptococcus mutans displays certain unique metabolic activities which are believed to be important factors in determining its virulence. Of the various carbohydrates metabolized by S. mutans, only sucrose is utilized for the production of acid, fructans and glucans (1,2). The adhesive water-insoluble glucans have been shown to be most important for the attachment of cells of S. mutans to smooth surfaces (1,3,5); probably both the water-insoluble and water-soluble glucans are required for the cell to cell aggregation which results in plaque production (6,7). Several laboratories have employed bacterial mutants and model systems of cell adherence and aggregation to study the cariogenic nature of S. mutans (5,8–13). We present results of certain biochemical activities of mutants of S. mutans strain 6715 and attempt to relate these findings to the cariogenic and immunogenic nature of these organisms.

Research paper thumbnail of Hydrogen Peroxide Inhibits Glucose Metabolism and Collagen Synthesis in Bone

Journal of Periodontology, 1987

Effects of H2O2 on bone were evaluated in an organ culture system. Tibiae from chick embryos were... more Effects of H2O2 on bone were evaluated in an organ culture system. Tibiae from chick embryos were incubated for up to 3 days in culture medium containing 0.07 to 20 mM H2O2. Glucose metabolism was monitored by measuring lactate production and oxygen consumption, and collagen synthesis was determined by hydroxylation of proline. In addition to markedly inhibiting these parameters, H2O2 also decreased bone weight and alkaline Phosphatase activity. Multiple exposures to H2O2 were somewhat more effective than a single exposure. Since H2O2 inhibits bone at low concentrations in vitro, the results suggest that the potential for harmful effects of H2O2 in the oral cavity should be investigated.

Research paper thumbnail of Effects of Porphyromonas gingivalis infection on human gingival epithelial barrier function in vitro

European Journal of Oral Sciences, 2010

Groeger S, Doman E, Chakraborty T, Meyle J. Effects of Porphyromonas gingivalis infection on huma... more Groeger S, Doman E, Chakraborty T, Meyle J. Effects of Porphyromonas gingivalis infection on human gingival epithelial barrier function in vitro. Eur J Oral Sci 2010; 118: 582–589. © 2010 Eur J Oral Sci The gingival epithelium plays an important role in the protection of oral tissues from microbial challenge. Oral keratinocytes form various cellular contacts, including tight junctions, and thus are able to create an epithelial barrier. A measurable indicator of barrier function in vitro is the transepithelial electrical resistance (TER). Porphyromonas gingivalis is recognized as a major aetiologic agent of periodontal disease and exhibits a variety of virulence factors. The aim of the study was to investigate the effect, in vitro, of infection with P. gingivalis on gingival barriers composed of primary and immortalized human keratinocytes. Primary and immortalized human gingival keratinocytes were infected with different strains of P. gingivalis. The impact of the bacterial challeng...

Research paper thumbnail of Bactericidal activity of human lactoferrin: sensitivity of a variety of microorganisms

Infection and Immunity, 1980

Lactoferrin is an iron-binding protein that has been detected in secretions that bathe human muco... more Lactoferrin is an iron-binding protein that has been detected in secretions that bathe human mucosal tissues. Previous studies have shown that, when this protein is in the iron-free state, it is capable of a direct bactericidal effect on Streptococcus mutans and Vibrio cholerae. The present study demonstrates variable susceptibilities for a variety of different microorganisms. The list of susceptible organisms includes gram-positive and gram-negative microbes, rods and cocci, facultative anaerobes, and aerotolerant anaerobes. Similar morphological and physiological types are represented among the lalctoferrin-resistant bacteria. S. mutans was more resistant to lactoferrin when grown on a sucrose-contaning medium than when it was grown on brain heart infusion broth without added scurose. When a lactoferrin-sensitive, avirulent strain of Streptococcus pneumoniae was passed through mice, the resultant virulent culture became lactoferrin resistant. Since organisms of the same species an...

Research paper thumbnail of Critical Role of Apoptotic Speck Protein Containing a Caspase Recruitment Domain (ASC) and NLRP3 in Causing Necrosis and ASC Speck Formation Induced by <i>Porphyromonas gingivalis</i> in Human Cells

Journal of Immunology, Feb 15, 2009

Periodontal disease is a chronic inflammatory disorder that leads to the destruction of tooth-sup... more Periodontal disease is a chronic inflammatory disorder that leads to the destruction of tooth-supporting tissue and affects 10-20 million people in the U.S. alone. The oral pathogen Porphyromonas gingivalis causes inflammatory host response leading to periodontal and other secondary inflammatory diseases. To identify molecular components that control host response to P. gingivalis in humans, roles for the NLR (NBD-LRR) protein, NLRP3 (cryopyrin, NALP3), and its adaptor apoptotic speck protein containing a C-terminal caspase recruitment domain (ASC) were studied. P. gingivalis strain A7436 induces cell death in THP1 monocytic cells and in human primary peripheral blood macrophages. This process is ASC and NLRP3 dependent and can be replicated by P. gingivalis LPS and Escherichia coli. P. gingivalis-induced cell death is caspase and IL-1 independent and exhibits morphological features consistent with necrosis including loss of membrane integrity and release of cellular content. Intriguingly, P. gingivalis-induced cell death is accompanied by the formation of ASC aggregation specks, a process not previously described during microbial infection. ASC specks are observed in P. gingivalis-infected primary human mononuclear cells and are dependent on NLRP3. This work shows that P. gingivalis causes ASC-and NLRP3-dependent necrosis, accompanied by ASC speck formation.

Research paper thumbnail of Mechanisms and Consequences of Neutrophil Interaction with the Subgingival Microbiota

Research paper thumbnail of Interferon activated gene 204 protects against bone loss in experimental periodontitis

Journal of Periodontology

BackgroundPeriodontal destruction can be the result of different known and yet‐to‐be‐discovered b... more BackgroundPeriodontal destruction can be the result of different known and yet‐to‐be‐discovered biological pathways. Recent human genetic association studies have implicated interferon‐gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) with high periodontal interleukin (IL)‐1β levels and more destructive disease, but mechanistic evidence is lacking. Here, we sought to experimentally validate these observational associations and better understand IFI16 and AIM2's roles in periodontitis.MethodsPeriodontitis was induced in Ifi204–/– (IFI16 murine homolog) and Aim2–/– mice using the ligature model. Chimeric mice were created to identify the main source cells of Ifi204 in the periodontium. IFI16‐silenced human endothelial cells were treated with periodontal pathogens in vitro. Periodontal tissues from Ifi204–/– mice were evaluated for alveolar bone (micro‐CT), cell inflammatory infiltration (MPO+ staining), Il1b (qRT‐PCR), and osteoclast numbers (cathepsin K+ staining...

Research paper thumbnail of Cofactor Requirements for Expression of Lactoferrin Bactericidal Activity on Enteric Bacteria

Recent Advances in Mucosal Immunology, 1987

Lactoferrin (LF), is an iron-binding glycoprotein that is common to most mammalian excretions (1–... more Lactoferrin (LF), is an iron-binding glycoprotein that is common to most mammalian excretions (1–3) and is a prominent component of the specific granule of neutrophilic leukocytes (4,5). It shares its distribution on mucosal surfaces with that of secretory IgA. Its high affinity binding in coordination with suitable anion has been well characterized (6–9). This ability to bind iron has been associated with a bacteriostatic deprivation of this essential nutrient (10–12). A variety of other biological activities have also been attributed to LF, including a direct bactericidal effect on a variety of bacteria (13,14). This killing mechanism is temperature and pH dependent and requires direct interaction of the LF with the bacterial cell surface (15). There are a variety of bacteria that are resistant to the bactericidal effects of purified LF binding including selected Gramnegative enteric bacteria (14). The resistance of these bacteria appears related, in part, to the impermeability of their outer cellular structures (16).

Research paper thumbnail of Introduction to the Oral Cavity

How Fermented Foods Feed a Healthy Gut Microbiota, 2019

The oral cavity plays a critical role as the seeder and gatekeeper of the microbiome that populat... more The oral cavity plays a critical role as the seeder and gatekeeper of the microbiome that populates the continuum of mucosal surfaces of the gastrointestinal tract, as well as that of the respiratory tract. The mouth has a variety of discrete niches and environmental conditions (microhabitats) that select for and discriminate against a vast array of microorganisms that ultimately determine the microbiome. The oral microbiome is an important contributor to host health and refers specifically to the microorganisms that reside on or in the human oral cavity and its contiguous mucosal surfaces to the distal esophagus. The oral microbiome is composed of approximately 700 species of bacteria, and also includes viruses, fungi, protozoa and archaea associated with the varied microhabitats that define the oral microbial ecosystem. The normal microbiota of the mouth is responsible for maintaining homeostasis of the oral cavity, but is also responsible for two of the most common diseases of ba...

Research paper thumbnail of Role of interferon in resistance and immunity to protozoa

Research paper thumbnail of Bactericidal Activity of Different Forms of Lactoferrin

Advances in, Experimental Medicine and Biology, 1994

Mucosal surfaces provide the portal of entry for most pathogenic microorganisms. In protection th... more Mucosal surfaces provide the portal of entry for most pathogenic microorganisms. In protection the mammalian host has concentrated a number of defense factors in the exocrine secretions that bathe mucosal surfaces. Understanding how these factors operate to prevent pathologic consequences of microbial challenge and what mechanisms a pathogen uses to evade this host defense is essential to the development of interventive approaches. Lactoferrin (LF) and secretory IgA (slgA) are both secreted in significant quantities at most mucosal surfaces and in milk. Both of these factors are reported to have bacteriostatic activity (1–8) and interact with each other and other defense factors (including lysozyme, complement, and lactoperoxidase) to modify their effectiveness (9, 10). In addition purified iron-free LF has been shown to have microbicidal activity against a variety of bacteria and yeast via mechanisms that are not reversed by the addition of free iron (11–16). A factor present in many commercial LF-enriched preparations, which co-purifies with slgA, has been reported to result in syner-gistic bactericidal activity and these impure LF preparations are able to kill bacterial strains that are resistant to purified LF (17).

Research paper thumbnail of Equivalent Mortality in Normal and Athymic Mice Infected with Naegleria fowleri

The Journal of Parasitology, 1985

Naegleriafowleri, a normally free-living amoeba, is the causative agent of primary amoebic mening... more Naegleriafowleri, a normally free-living amoeba, is the causative agent of primary amoebic meningoencephalitis (PAM), and since its first description in 1965 over 100 cases have been reported worldwide (John, 1982, Annual Review of Microbiology 36: 101-123). A perplexing aspect of PAM is that pathogenic N. fowleri are often isolated from recreational waters, yet exposed individuals only rarely develop PAM and it occurs in apparently healthy humans. Although affected individuals might have some underlying immune dysfunction it is most likely PAM is the result of environmental or genetic factors that serve to enhance virulence of amoebae. Studies have been directed at elucidating the role of the immune system in resistance to PAM. In laboratory animals, immunization by a variety of routes with Naegleria antigen can heighten resistance to a subsequent lethal infection (John et al., 1977, Infection and Immunity 16: 817820; Thong et al., 1978, The American Journal of Tropical Medicine and Hygiene 27: 238-240). Investigations of cellular immune components showed that Naegleria antigen could elicit a delayed hypersensitivity reaction in guinea pigs (Diffley et al., 1976, Zeitschrift fur Parasitenkunde 49: 133-137) and macrophage inhibition by lymphokine macrophage inhibition factor (Cursons et al., 1980, Infection and Immunity 29: 408-410). Although Naegleria antigen can evoke an immunological response which may lessen susceptibility to a lethal infection, little is known about the role of the humoral and cellular immune systems in innate resistance to PAM. Congenitally athymic (nude [nu/nu]) mice are deficient in T-cell-dependent cell-mediated immunity and in the humoral response to Tcell-dependent antigens (Wortis, 1974, Contemporary Topics in Immunobiology 3: 243-263). Investigations on the pathogenicity of N. fowleri in nude mice would serve as an useful aid for delineating the role of T-cell-dependent activities in the innate resistance against development of PAM. Providing that the T-cell-dependent arm of the immune system is a significant factor in innate resistance, it would be expected nude mice would show increased susceptibility and the course of PAM would be more rapid compared to normal mice. The purpose of this study was to determine if the development of PAM and the course of the disease was more rapid in congenitally athymic mice than in phenotypically normal mice. Mice were also infected with trophozoites of Naegleria lovaniensis, an amoeba physiologically and morphologically similar to N. fowleri, but nonpathogenic in immunocompetent mice (Stevens et al., 1980, International Journal for Parasitology 10: 51-64). The Lee strain of N. fowleri and N. lovaniensis were cultivated in tubes containing Chang's medium (De Jockheere, 1977, Applied and Environmental Microbiology 33: 751-757). Amoebae in late exponential growth were enumerated by hemacytometer counts, centrifuged (1,000 g for 15 min), and adjusted to the desired density in Chang's medium so that 25 1l delivered the appropriate number of amoebae (Fig. 1). Mice were of Swiss Webster background and congenitally athymic mice were obtained by mating homozygous (nu/nu) males with heterozygous (+/nu) females. Mice were maintained under specific pathogen free conditions in an area separate from other laboratory animals. For infection, mice of either sex and approximately 12 wk old were anesthetized with ether and 25 Al of an amoebae suspension was delivered into the nares with a micropipet. Development of PAM was evident by typical symptoms of anorexia, excitability, and ruffling of neck hair, which were followed by convulsions and death. PAM was

Research paper thumbnail of Enhancement of Streptococcus mutans Colonization by Direct Bonded Orthodontic Appliances

Journal of Dental Research, 1983

Patients undergoing orthodontic therapy were evaluated for longitudinal changes in relative S. mu... more Patients undergoing orthodontic therapy were evaluated for longitudinal changes in relative S. mutans numbers in plaque at discrete sites on the tooth surface associated with direct bond appliances. There was a significant linear increase in the percentage of S. mutans in the total streptococci isolated from the last pre-bracket sample through the last bracket sample.

Research paper thumbnail of Effects of Natural Cross-Linkers on the Stability of Dentin Collagen and the Inhibition of Root Caries in vitro

Caries Research, 2008

Results: While all collagen was digested with collagenase in the control groups, only a small pro... more Results: While all collagen was digested with collagenase in the control groups, only a small proportion was solubilized in the GA-, PA-, and GE-treated groups. The root caries was significantly inhibited by treatment with PA or GA. Drops in pH in the cross-linker-treated groups were essentially the same as in the untreated group. Conclusion: Naturally occurring cross-linkers, especially PA, could be used to modify root dentin collagen to efficiently stabilize collagen and to increase its resistance against caries.

Research paper thumbnail of Effects of Escherichia coli and Porphyromonas gingivalis lipopolysaccharide on pregnancy outcome in the golden hamster

Infection and Immunity, Oct 1, 1994

This report describes the elfects of two gram-negative bacterial endotoxin (lipopolysaccharide [L... more This report describes the elfects of two gram-negative bacterial endotoxin (lipopolysaccharide [LPS]) preparations on hamster pregnancy outcome variables. Single intravenous challenges with Escherichia coli and Porphyromonas gingivalis LPS on day 8 of pregnancy produced dose-dependent effects on fetal weight malformation and fetal resorption with E. coli LPS having potent embryolethal effects. Premating maternal exposure to P. gingivalis produced embryolethal effects similar to those of E. coli. These data suggest that maternal exposure to P. gingivalis LPS prior to and during pregnancy can induce deleterious effects on the developing fetus.

Research paper thumbnail of Helper and Suppressor Functions of Thymus-Derived Lymphocytes in the Humoral Response to Heterologous Erythrocytes in Rabbits

This material was produced from a microfilm copy o f the original document. While the most advanc... more This material was produced from a microfilm copy o f the original document. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the original submitted. The following explanation o f techniques is provided to help you understand markings or patterns which may appear on this reproduction. 1 .T h e sign or "target" for pages apparently lacking from the document photographed is "Missing Page(s)". I f it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting thru an image and duplicating adjacent pages to insure you complete continuity. 2. When an image on the film is obliterated with a large round black mark, it is an indication that the photographer suspected that the copy may have moved during exposure and thus cause a blurred image. You will find a good image o f the page in the adjacent frame. 3. When a map, drawing or chart, etc., was part o f the material being photographed the photographer followed a definite method in "sectioning" the material. I t is customary to begin photoing at the upper left hand corner of a large sheet and to continue photoing from le ft to right in equal sections w ith a small overlap. If necessary, sectioning is continued again-beginning below the first row and continuing on until complete. 4. The majority of users indicate that the textual content is of greatest value, however, a somewhat higher quality reproduction could be made from "photographs" if essential to the understanding of the dissertation. Silver prints of "photographs" may be ordered at additional charge by writing the Order Department, giving the catalog number, title, author and specific pages you wish reproduced. 5. PLEASE NOTE: Some pages may have indistinct print. Filmed as received.

Research paper thumbnail of Dysbiosis of the Oral Microbiome

How Fermented Foods Feed a Healthy Gut Microbiota, 2019

The oral cavity is influenced by the dietary characteristics of each individual. It is in the ora... more The oral cavity is influenced by the dietary characteristics of each individual. It is in the oral cavity that food will cause the first impact within the human body and its microbiome, due to its composition and consistency. On the other hand, the oral microbiome will affect food processing and impact the human gut microbiome, since bacterial biofilm that is processed within saliva forms the food bolus, which will then be swallowed. The mouth is one of the most heavily colonized parts of our bodies and its microbiome consists of microorganisms that live in symbiosis with healthy individuals who have adequate dietary and oral hygiene habits. Nevertheless, perturbations in the microbiome due to certain stress factors, such as high carbohydrate intake and biofilm accumulation, can lead to dysbiosis and the development of oral diseases. The most prevalent diseases in the oral cavity are dental caries and periodontal diseases including gingivitis and periodontitis, but endodontic (pulp)...

Research paper thumbnail of Oral vaccination of rats with Streptococcus mutans: induction of secretory antibodies and reduced caries

Journal of Dental Research, 1976

Research paper thumbnail of Antimicrobial Activity of the Secretory Innate Defense Factors Lactoferrin, Lactoperoxidase and Lysozyme1

Research paper thumbnail of A clinical study of bacterial contamination of chlorhexidine-coated filaments of an interdental brush

The Journal of clinical dentistry, 1998

The purpose of this study was to assess the effectiveness of a chlorhexidine coating on the nylon... more The purpose of this study was to assess the effectiveness of a chlorhexidine coating on the nylon filaments of an interdental brush in reducing bacterial contamination from actual clinical usage. In addition, the residual antimicrobial capacity of the coating over time from clinical exposure was studied. The same type of interdental brush, one with chlorhexidine-coated nylon filaments (antibacterial) and one with uncoated (control) nylon filaments was used with 20 subjects who were participating in a periodontal maintenance program. All subjects had more than four interproximal spaces large enough to accommodate the interdental brush at the start of the study. The subjects served as their own controls in this cross-over design. They used their brushes daily for one and two weeks, respectively. After the last use, each brush was kept in a controlled environment (20-22 degrees C, 65% relative humidity) for 24 hours for air drying. It was found that antimicrobial activity was detected ...

Research paper thumbnail of Use of Mutants in the Elucidation of Virulence of Streptococcus Mutans

Advances in Experimental Medicine and Biology, 1978

In the presence of sucrose, Streptococcus mutans displays certain unique metabolic activities whi... more In the presence of sucrose, Streptococcus mutans displays certain unique metabolic activities which are believed to be important factors in determining its virulence. Of the various carbohydrates metabolized by S. mutans, only sucrose is utilized for the production of acid, fructans and glucans (1,2). The adhesive water-insoluble glucans have been shown to be most important for the attachment of cells of S. mutans to smooth surfaces (1,3,5); probably both the water-insoluble and water-soluble glucans are required for the cell to cell aggregation which results in plaque production (6,7). Several laboratories have employed bacterial mutants and model systems of cell adherence and aggregation to study the cariogenic nature of S. mutans (5,8–13). We present results of certain biochemical activities of mutants of S. mutans strain 6715 and attempt to relate these findings to the cariogenic and immunogenic nature of these organisms.

Research paper thumbnail of Hydrogen Peroxide Inhibits Glucose Metabolism and Collagen Synthesis in Bone

Journal of Periodontology, 1987

Effects of H2O2 on bone were evaluated in an organ culture system. Tibiae from chick embryos were... more Effects of H2O2 on bone were evaluated in an organ culture system. Tibiae from chick embryos were incubated for up to 3 days in culture medium containing 0.07 to 20 mM H2O2. Glucose metabolism was monitored by measuring lactate production and oxygen consumption, and collagen synthesis was determined by hydroxylation of proline. In addition to markedly inhibiting these parameters, H2O2 also decreased bone weight and alkaline Phosphatase activity. Multiple exposures to H2O2 were somewhat more effective than a single exposure. Since H2O2 inhibits bone at low concentrations in vitro, the results suggest that the potential for harmful effects of H2O2 in the oral cavity should be investigated.

Research paper thumbnail of Effects of Porphyromonas gingivalis infection on human gingival epithelial barrier function in vitro

European Journal of Oral Sciences, 2010

Groeger S, Doman E, Chakraborty T, Meyle J. Effects of Porphyromonas gingivalis infection on huma... more Groeger S, Doman E, Chakraborty T, Meyle J. Effects of Porphyromonas gingivalis infection on human gingival epithelial barrier function in vitro. Eur J Oral Sci 2010; 118: 582–589. © 2010 Eur J Oral Sci The gingival epithelium plays an important role in the protection of oral tissues from microbial challenge. Oral keratinocytes form various cellular contacts, including tight junctions, and thus are able to create an epithelial barrier. A measurable indicator of barrier function in vitro is the transepithelial electrical resistance (TER). Porphyromonas gingivalis is recognized as a major aetiologic agent of periodontal disease and exhibits a variety of virulence factors. The aim of the study was to investigate the effect, in vitro, of infection with P. gingivalis on gingival barriers composed of primary and immortalized human keratinocytes. Primary and immortalized human gingival keratinocytes were infected with different strains of P. gingivalis. The impact of the bacterial challeng...

Research paper thumbnail of Bactericidal activity of human lactoferrin: sensitivity of a variety of microorganisms

Infection and Immunity, 1980

Lactoferrin is an iron-binding protein that has been detected in secretions that bathe human muco... more Lactoferrin is an iron-binding protein that has been detected in secretions that bathe human mucosal tissues. Previous studies have shown that, when this protein is in the iron-free state, it is capable of a direct bactericidal effect on Streptococcus mutans and Vibrio cholerae. The present study demonstrates variable susceptibilities for a variety of different microorganisms. The list of susceptible organisms includes gram-positive and gram-negative microbes, rods and cocci, facultative anaerobes, and aerotolerant anaerobes. Similar morphological and physiological types are represented among the lalctoferrin-resistant bacteria. S. mutans was more resistant to lactoferrin when grown on a sucrose-contaning medium than when it was grown on brain heart infusion broth without added scurose. When a lactoferrin-sensitive, avirulent strain of Streptococcus pneumoniae was passed through mice, the resultant virulent culture became lactoferrin resistant. Since organisms of the same species an...