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PubMed1990

Prepubertal periodontitis: a review of diagnostic criteria, pathogenesis, and differential diagnosis.

This paper reviews the literature on prepubertal periodontitis (PP) according to the definition and the classification of PP by Page. The generalized form of PP (G-PP) defined by Page was identified as the oral manifestation of a systemic disease called leukocyte adhesion deficiency (LAD) and thus the pathogenesis is known at the molecular level. On the other hand, the localized form of PP (L-PP) is a disease defined by clinical criteria and its pathogenesis is not known at the molecular level. The reported prevalence of L-PP differs widely in reports, according to the methodology and population studied. However, it seems to be at least 0.84% or greater. Potential periodontal pathogens that have been associated with L-PP include the following bacteria: Actinobacillus actinomycetemcomitans (A.a.), Bacteroides intermedius, Bacteroides gingivalis, Capnocytophaga sputigena, and Eikenella corrodens. Suggested contributing factors have included PMN or monocyte chemotactic defects and cementum defects. There is no unique pattern of bone loss in L-PP; however, there may be a type of periodontitis that affects all deciduous teeth, in the absence of LAD. L-PP may lead to localized juvenile periodontitis (LJP) or generalized juvenile periodontitis (GJP). Histiocytosis X, hypophosphatasia and mild forms of blood dyscrasias may have minimal or no clinical signs and symptoms except for alveolar bone loss. Therefore diseases known to be associated with alveolar bone loss must be definitively excluded in prepubertal children until the pathogenesis of L-PP at the cellular and molecular levels is understood and L-PP can be definitively diagnosed either as a distinct disease entity or entities.

Adolescent↗
PubMed1999

Periodontitis-atherosclerosis syndrome: an expanded model of pathogenesis.

The early reports of a linkage between periodontitis and atherosclerosis have garnered further support by additional data generated by several investigative teams in many different countries. The evidence continues to suggest that periodontitis may be an important risk factor or risk indicator for cardiovascular pathology for some individuals. The term periodontitis-atherosclerosis syndrome (PAS) is proposed as a new diagnostic term to describe this condition in these individuals. Current evidence, albeit preliminary in nature, which describes a cluster of clinical signs and symptoms that are associated with this condition, is presented. It is clear that this syndrome will require considerable study and refinement before a definitive diagnosis and treatment plan can be formulated. Potential mechanisms by which systemic inflammation and infectious challenge of periodontal origin may serve as a potential modifier of cardiovascular disease are discussed in the context of a detailed working model of pathogenesis. This hypothetical model embraces many cellular and molecular components of atherogenesis and thromboembolic diseases from the perspective of periodontitis pathogenesis. Many aspects of the hypothetical model remain unproved; however, it is our opinion that only through the clarification of the mechanisms of pathogenesis can we ultimately construct a knowledge framework for accurate diagnoses and successful therapies. The concept of diagnosing and treating a periodontal patient to minimize the deleterious effects of this chronic infectious and inflammatory condition on the cardiovascular system represents an unprecedented challenge to our profession.

Arteriosclerosis↗
PubMed2000

Applications of differential-display reverse transcription-PCR to molecular pathogenesis and medical mycology.

The host-fungus interaction is characterized by changes in gene expression in both host and pathogen. Differential-display reverse transcription PCR (DDRT-PCR) is a PCR-based method that allows extensive analysis of gene expression among several cell populations. Several limitations and drawbacks to this procedure have now been addressed, including the large number of false-positive results and the difficulty in confirming differential expression. Modifications that simplify the reaction time, allow the use of minute quantities of RNA, or address unusual species- or gene-specific sequences have been reported. DDRT-PCR has been used to address biological questions in mammalian systems, including cell differentiation, cell activation, cell stress, and identification of drug targets. In microbial pathogenesis and plant pathogenesis, DDRT-PCR has allowed the identification of virulence factors, genes involved in cell death, and signaling genes. In Candida albicans, DDRT-PCR studies identified TIF-2, which may play a role in the upregulation of phospholipases, and the stress-related genes, CIP1 and CIP2. In Histoplasma capsulatum and C. albicans, genes involved in the host-pathogen interaction, including a member of the 100-kDa family in Histoplasma and an ALS and 14-3-3 gene in Candida, were potentially identified by DDRT-PCR. Although very few reports have been published in medical mycology, studies in mammalian, nonfungal microbial, and plant pathogen systems are easily applied to basic questions in fungal pathogenesis and antifungal therapeutics.

Animals↗
PubMed1981

Influence of the bursa of Fabricius on the pathogenesis of Marek's disease.

A series of experiments was conducted to study the influence of embryonal bursectomy (EBX) on the early and late pathogenesis of Marek's disease (MD). The early lytic infection in the lymphoid organs normally associated with oncogenic MD virus infection in intact chickens was not seen in EBX chickens. Therefore, the damage to the immune system was minimal. EBX chickens also had lower viremia levels, higher lymphocyte responses to mitogens, and a lower or delayed MD mortality when compared with intact chickens. Furthermore, it was shown that although vaccination with SB-1 by itself did not protect against a highly virulent MD transplantable tumor, the combination of EBX and vaccination gave significant protection. All these effects could be explained by an enhanced immune response in EBX birds. In contrast, the pathogenesis of nononcogenic MD virus was not influenced by EBX. The possible mechanism(s) involved in these observed effects of EBX on MD pathogenesis are discussed.

Animals↗
PubMed1994

Role of fimbriae expressed by nontypeable Haemophilus influenzae in pathogenesis of and protection against otitis media and relatedness of the fimbrin subunit to outer membrane protein A.

Nontypeable Haemophilus influenzae is a primary pathogen in both acute otitis media (OM) and chronic OM, yet the pathogenesis of this disease is not fully understood. Although fimbriae have been observed on all clinical OM isolates examined to date, their role in pathogenesis remains unclear. Therefore, the gene which codes for the fimbrial subunit protein (fimbrin) in nontypeable H. influenzae 1128 was isolated, cloned, and sequenced. The nucleotide sequence of the fimbrin gene was found to contain an open reading frame of 1,077 bp which would encode a mature fimbrin protein consisting of 338 amino acid with a calculated molecular mass of 36.4 kDa. The translated amino acid sequence was found to be homologous with various OmpA proteins of other gram-negative bacteria, and algorithmic analysis predicted that this protein is organized as a coiled coil. To directly test whether fimbriae are involved in pathogenesis, the fimbrin gene was disrupted, and the biological consequences of disruption were absence of both expression of the fimbrial appendage and the specific immunogold labeling thereof with antisera directed against isolated fimbrial protein, reduced adherence to human oropharyngeal cells in vitro, augmented clearance from the tympanum post-transbullar inoculation, and significantly reduced induction of OM post-intranasal inoculation in a chinchilla model compared with the fimbriated parent strain. We additionally find that either passive immunization or active immunization against isolated fimbrial protein confers partial protection against transbullar challenge. A Western blot (immunoblot) indicated a degree of serological relatedness among fimbrin proteins of 15 nontypeable and type b isolates. These data suggest that fimbrin could be useful as a component of a vaccine to protect against OM.

Amino Acid Sequence↗
PubMed1999

Characterization of the importance of polysaccharide intercellular adhesin/hemagglutinin of Staphylococcus epidermidis in the pathogenesis of biomaterial-based infection in a mouse foreign body infection model.

The production of biofilm is thought to be crucial in the pathogenesis of prosthetic-device infections caused by Staphylococcus epidermidis. An experimental animal model was used to assess the importance of biofilm production, which is mediated by polysaccharide intercellular adhesin/hemagglutinin (PIA/HA), in the pathogenesis of a biomaterial-based infection. Mice were inoculated along the length of a subcutaneously implanted intravenous catheter with either wild-type S. epidermidis 1457 or its isogenic PIA/HA-negative mutant. The wild-type strain was significantly more likely to cause a subcutaneous abscess than the mutant strain (P < 0.01) and was significantly less likely to be eradicated from the inoculation site by host defense (P < 0.05). In addition, the wild-type strain was found to adhere to the implanted catheters more abundantly than the PIA/HA-negative mutant (P < 0.05). The reliability of the adherence assay was assessed by scanning electron microscopy. To exclude contamination or spontaneous infection, bacterial strains recovered from the experimental animals were compared to inoculation strains by analysis of restriction fragment length polymorphism patterns by pulsed-field gel electrophoresis. In vitro binding of the wild-type strain and its isogenic mutant to a fibronectin-coated surface was similar. These results confirm the importance of biofilm production, mediated by PIA/HA, in the pathogenesis of S. epidermidis experimental foreign body infection.

Abscess↗
PubMed2002

Leishmania pifanoi pathogenesis: selective lack of a local cutaneous response in the absence of circulating antibody.

Recently, a role for B cells in the pathogenesis associated with infection by Leishmania (Leishmania mexicana complex and L. donovani) has been established. In the case of L. mexicana complex parasites (L. mexicana, L. pifanoi, and L. amazonensis), a critical role for immunoglobulin G-mediated mechanisms for the amastigote stage in the host is evident; however, the immunological mechanisms involved remain to be established. In vitro analysis of the kinetics of parasite uptake by macrophages failed to indicate a major effect of antibody opsonization. Given the importance of CD4(+) T cells in the development of disease caused by these parasites, the possibility that the lack of pathogenesis was due to the lack of development of an immune response at the local site (draining lymph node and/or cutaneous site) was explored. Interestingly, the level of CD4(+)-T-cell activation (proliferation and cytokine) in draining lymph nodes from mice lacking circulating antibody (resistant) was found to be comparable to that in nodes from wild-type mice (susceptible) at 2, 5, and 10 weeks postinfection. However, antibody-deficient animals had markedly reduced numbers of monocytes and lymphocytes recruited or retained at the site of cutaneous infection in comparison to wild-type mice, indicating a selective impairment in the local cutaneous immune response. In vitro antigen presentation studies employing tissue-derived (opsonized) amastigotes demonstrated that L. pifanoi-infected FcR(-/-) macrophages, in contrast to comparably infected wild-type cells, failed to activate Leishmania antigen-specific T lymphocytes. These data, taken together, suggest that one possible mechanism for the role of antibody in pathogenesis may be to mediate parasite uptake and regulate the immune response at the local cutaneous site of infection.

Animals↗
PubMed2002

Streptococcus-zebrafish model of bacterial pathogenesis.

Due to its small size, rapid generation time, powerful genetic systems, and genomic resources, the zebrafish has emerged as an important model of vertebrate development and human disease. Its well-developed adaptive and innate cellular immune systems make the zebrafish an ideal model for the study of infectious diseases. With a natural and important pathogen of fish, Streptococcus iniae, we have established a streptococcus- zebrafish model of bacterial pathogenesis. Following injection into the dorsal muscle, zebrafish developed a lethal infection, with a 50% lethal dose of 10(3) CFU, and died within 2 to 3 days. The pathogenesis of infection resembled that of S. iniae in farmed fish populations and that of several important human streptococcal diseases and was characterized by an initial focal necrotic lesion that rapidly progressed to invasion of the pathogen into all major organ systems, including the brain. Zebrafish were also susceptible to infection by the human pathogen Streptococcus pyogenes. However, disease was characterized by a marked absence of inflammation, large numbers of extracellular streptococci in the dorsal muscle, and extensive myonecrosis that occurred far in advance of any systemic invasion. The genetic systems available for streptococci, including a novel method of mutagenesis which targets genes whose products are exported, were used to identify several mutants attenuated for virulence in zebrafish. This combination of a genetically amenable pathogen with a well-defined vertebrate host makes the streptococcus-zebrafish model of bacterial pathogenesis a powerful model for analysis of infectious disease.

Animals↗
PubMed2006

Contribution of hemagglutinin/protease and motility to the pathogenesis of El Tor biotype cholera.

Vibrio cholerae is a highly motile organism that secretes a Zn-dependent metalloprotease, hemagglutinin/protease (HapA). HapA has been shown to have mucinase activity and contribute to the reactogenicity of live vaccine candidates, but its role in cholera pathogenesis is not yet clear. The contribution of motility to pathogenesis is not fully understood, since conflicting results have been obtained with different strains, mutants, and animal models. The objective of this work was to determine the contribution of HapA and motility to the pathogenesis of El Tor biotype cholera. To this end we constructed isogenic motility (motY) and mucinase (hapA) single and double mutants of an El Tor biotype V. cholerae strain. Mutants were characterized for the expression of major virulence factors in vitro and in vivo. The motility mutant showed a remarkable increase in cholera toxin (CT), toxin coregulated pilus major subunit (TcpA), and HapA production in vitro. Increased TcpA and CT production could be explained by increased transcription of tcpA, ctxA, and toxT. No effect was detected on the transcription of hapA in the motility mutant. The sodium ionophore monensin diminished production of HapA in the parent but not in the motility mutant. Phenamil, a specific inhibitor of the flagellar motor, diminished CT production in the wild-type and motY strains. The hapA mutant showed increased binding to mucin. In contrast, the motY mutation diminished adherence to biotic and abiotic surfaces including mucin. Lack of HapA did not affect colonization in the suckling mouse model. The motility and mucinase defects did not prevent induction of ctxA and tcpA in the mouse intestine as measured by recombinase-based in vivo expression technology. Analysis of mutants in the rabbit ileal loop model showed that both V. cholerae motility and HapA were necessary for full expression of enterotoxicity.

Animals↗
PubMed2006

Amelioration of influenza virus pathogenesis in chickens attributed to the enhanced interferon-inducing capacity of a virus with a truncated NS1 gene.

Avian influenza virus (AIV) A/turkey/Oregon/71-SEPRL (TK/OR/71-SEPRL) (H7N3) encodes a full-length NS1 protein and is a weak inducer of interferon (IFN). A variant, TK/OR/71-delNS1 (H7N3), produces a truncated NS1 protein and is a strong inducer of IFN. These otherwise genetically related variants differ 20-fold in their capacities to induce IFN in primary chicken embryo cells but are similar in their sensitivities to the action of IFN. Furthermore, the weak IFN-inducing strain actively suppresses IFN induction in cells that are otherwise programmed to produce it. These phenotypic differences are attributed to the enhanced IFN-inducing capacity that characterizes type A influenza virus strains that produce defective NS1 protein. The pathogenesis of these two variants was evaluated in 1-day-old and 4-week-old chickens. The cell tropisms of both viruses were similar. However, the lesions in chickens produced by the weak IFN inducer were more severe and differed somewhat in character from those observed for the strong IFN inducer. Differences in lesions included the nature of inflammation, the rate of resolution of the infection, and the extent of viral replication and/or virus dissemination. The amelioration of pathogenesis is attributed to the higher levels of IFN produced by the variant encoding the truncated NS1 protein and the antiviral state subsequently induced by that IFN. The high titer of virus observed in kidney tissue ( approximately 10(9) 50% embryo lethal doses/g) from 1-day-old chickens infected intravenously by the weak IFN-inducing strain is attributed to the capacity of chicken kidney cells to activate the hemagglutinin fusion peptide along with their unresponsiveness to inducers of IFN as measured in vitro. Thus, the IFN-inducing capacity of AIV appears to be a significant factor in regulating the pathogenesis, virulence, and viral transmission of AIV in chickens. This suggests that the IFN-inducing and IFN induction suppression phenotypes of AIV should be considered when characterizing strains of influenza virus.

Animals↗
PubMed2006

The role of CD4 T cells in the pathogenesis of murine AIDS.

LP-BM5, a retroviral isolate, induces a disease featuring retrovirus-induced immunodeficiency, designated murine AIDS (MAIDS). Many of the features of the LP-BM5-induced syndrome are shared with human immunodeficiency virus-induced disease. For example, CD4 T cells are critical to the development of MAIDS. In vivo depletion of CD4 T cells before LP-BM5 infection rendered genetically susceptible B6 mice MAIDS resistant. Similarly, MAIDS did not develop in B6.nude mice. However, if reconstituted with CD4 T cells, B6.nude mice develop full-blown MAIDS. Our laboratory has shown that the interaction of B and CD4 T cells that is central to MAIDS pathogenesis requires ligation of CD154 on CD4 T cells with CD40 on B cells. However, it is not clear which additional characteristics of the phenotypically and functionally heterogeneous CD4 T-cell compartment are required. Here, in vivo adoptive transfer experiments using B6.nude recipients are employed to compare the pathogenic abilities of CD4 T-cell subsets defined on the basis of cell surface phenotypic or functional differences. Th1 and Th2 CD4 T cells equally supported MAIDS induction. The rare Thy1.2(-) CD4 subset that expands upon LP-BM5 infection was not necessary for MAIDS. Interestingly, CD45RB(low) CD4 T cells supported significantly less disease than CD45RB(high) CD4 T cells. Because the decreased MAIDS pathogenesis could not be attributed to inhibition by CD45RB(low) CD25(+) natural T-regulatory cells, an intrinsic property of the CD45RB(low) cells appeared responsible. Similarly, there was no evidence that natural T-regulatory cells played a role in LP-BM5-induced pathogenesis in the context of the intact CD4 T-cell population.

Adoptive Transfer↗
PubMed1993

Herpes simplex virus pathogenesis in transgenic mice is altered by the homeodomain protein Hox 1.3.

The DNA sequence TAAT is the core binding motif for the mouse homeodomain protein Hox 1.3 (proposed new name, Hoxa-5). These sequences are present within the multiple TAATGARAT regulatory motifs in the promoters of the immediate-early genes which control herpes simplex virus type 1 replication. To investigate the role of this homeodomain protein in the regulation of herpes simplex virus gene expression and pathogenesis, transgenic mice containing a mouse Hox 1.3 cDNA under the control of the virus- and interferon-inducible Mx 1 promoter were generated. After infection of transgenic mice with herpes simplex virus, Hox 1.3 RNA and protein were expressed at the sites of virus replication. In these transgenic mice, herpes simplex virus replication, spread of virus through the host, and virus-induced mortality were markedly enhanced. Increased spread and replication of herpes simplex virus were also observed in cultured fibroblasts from transgenic mice. This finding suggests that in vivo, Hox 1.3 may increase viral spread by increasing viral replication at the level of the individual infected cells. These results demonstrate that expression of a transgene encoding a single host protein, Hox 1.3, alters the pathogenesis of experimental herpes simplex virus infection. We conclude that a protein that belongs to a class of DNA-binding proteins which are best known for their role in regulating embryonic development may also regulate herpesvirus pathogenesis.

Animals↗
PubMed1998

Role of individual T-cell epitopes of Theiler's virus in the pathogenesis of demyelination correlates with the ability to induce a Th1 response.

Intracerebral inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelination. Three major T-cell epitopes have previously been identified within the VP1 (VP1233-250), VP2 (VP274-86), and VP3 (VP324-37) capsid proteins in virus-infected SJL/J mice. These epitopes appear to account for the majority ( approximately 90%) of major histocompatibility complex class II-restricted T-cell responses to TMEV. Interestingly, the effect of immunization with synthetic peptides bearing the predominant T-cell epitopes on the course of TMEV-induced demyelination indicates that T cells reactive to the VP1 and VP2 epitopes, but not VP3, accelerate the pathogenesis of demyelination. The predominant pathogenic role of the T cells is verified by similar immunization with the fusion proteins containing the entire individual capsid proteins. The order of appearance and level of T cells specific for the individual epitopes during the course of demyelination are similar to each other. However, cytokine profiles of T cells from virus-infected mice indicate that T cells specific for the VP1 (and perhaps the VP2) epitope are Th1, whereas T cells reactive to VP3 are primarily Th2. These results suggest that Th1-type cells specific for VP1 and VP2 are involved in the pathogenesis of viral demyelination induced by TMEV. Thus, a predominance of Th1-inducing viral epitopes is likely critical for the pathogenesis of demyelination.

Animals↗
PubMed2005

Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus.

Coronaviruses are a family of enveloped, single-stranded, positive-strand RNA viruses classified within the Nidovirales order. This coronavirus family consists of pathogens of many animal species and of humans, including the recently isolated severe acute respiratory syndrome coronavirus (SARS-CoV). This review is divided into two main parts; the first concerns the animal coronaviruses and their pathogenesis, with an emphasis on the functions of individual viral genes, and the second discusses the newly described human emerging pathogen, SARS-CoV. The coronavirus part covers (i) a description of a group of coronaviruses and the diseases they cause, including the prototype coronavirus, murine hepatitis virus, which is one of the recognized animal models for multiple sclerosis, as well as viruses of veterinary importance that infect the pig, chicken, and cat and a summary of the human viruses; (ii) a short summary of the replication cycle of coronaviruses in cell culture; (iii) the development and application of reverse genetics systems; and (iv) the roles of individual coronavirus proteins in replication and pathogenesis. The SARS-CoV part covers the pathogenesis of SARS, the developing animal models for infection, and the progress in vaccine development and antiviral therapies. The data gathered on the animal coronaviruses continue to be helpful in understanding SARS-CoV.

Animals↗
PubMed2026

Lineage-associated differences in adenine methylation patterns of mammalian-associated Campylobacter fetus isolates: a possible role for epigenetic factors in host tropism and pathogenesis.

Mammalian Campylobacter fetus (CF) is divided into two subspecies, C. fetus fetus (CFF) and C. fetus venerealis (CFV), the latter being bovine-adapted and responsible for the notifiable disease bovine genital campylobacteriosis (BGC). Differentiation between CF subspecies has traditionally been undertaken by a few biochemical tests, but these are complicated by the existence of a biotype, C. fetus venerealis intermedius (CFVi), which shares attributes of both CFF and CFV. Molecular methods targeting specific genes have gained acceptance for more accurate subtype identification and align well with whole-genome analysis. However, limited genomic diversity between subtypes has confounded efforts to understand the genetic basis for differential host tropism and pathogenesis of these organisms. A previous study of a small cohort of C. fetus isolates suggested that dam gene coding variations might correlate with CF subtype. Accordingly, this study examines a cohort of 331 C. fetus genomes, representative of all seven phylogenetic groups for their complement of adenine methylases and the genomic motifs they target in representative isolates. All CF isolates retained a cfeM1 gene, the presence of which correlates with RAATTY methylation, while seven other adenine methylase genes exhibited distinct cladal distributions. Notably, a cjeM1 gene appears to target the CCAN7TAG/CTAN7TGG motif in CFV and CFVi isolates only. Given the increasing recognition of the impact of adenine methylation on bacterial-host interactions, further exploration of the role of adenine methylation in C. fetus pathogenesis could reveal mechanisms contributing to BGC and thus aid in its eradication.IMPORTANCECampylobacter fetus remains an important zoonotic pathogen, for which a better understanding of its host tropism and pathogenesis is sought. However, the limited genomic variation observed between subtypes has to date confounded efforts in this regard. This study suggests that an alternative approach that examines epigenetic differences between subtypes, specifically adenine methylation patterns, may reveal mechanisms critical to the pathologies of these organisms.

Animals↗
PubMed2004

Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis.

BACKGROUND AND AIMS: The incidence of irritable bowel syndrome (IBS) or functional bowel disorders (FBD) after bacillary dysentery (BD) has not been extensively evaluated, and little is known of the pathogenesis of post-infective (PI) IBS. Therefore, we investigated the incidence of IBS and FBD in a Chinese patient population who had recovered from BD. To further elucidate its pathogenesis, neuroimmunological changes, including interleukins (IL), mast cells, neuropeptides, and the relationship between mast cells and intestinal nerves, were investigated. METHODS: A cohort study of 295 patients who had recovered from BD (shigella identified from stool in 71.4%) and 243 control subjects consisting of patient siblings or spouses who had not been infected with BD were included in the study. All subjects were followed up using questionnaires for 1-2 years to explore the incidence of FBD and IBS, as defined by the Rome II criteria. In 56 cases of IBS (PI and non-PI) from another source, the number of mast cells in biopsy specimens from the intestinal mucosa were stained with antitryptase antibody and counted under light microscopy. Also, the relationship of mast cells to neurone specific enolase (NSE), substance P (SP), 5-hydroxytryptamine (5-HT), or calcitonin gene related peptide positive nerve fibres was observed using double staining with alcian blue and neuropeptide antibodies. In 30 cases of IBS (PI-IBS, n = 15) taken at random from the 56 cases, expression of interleukin (IL)-1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1ra) mRNAs in intestinal mucosa were identified using reverse transcription-polymerase chain reaction. The above results were compared with 12 non-IBS controls. RESULTS: In the BD infected cohort, the incidences of FBD and IBS were 22.4% and 8.1% (in total)-10.2% (among those in who shigella were identified) respectively, which were significantly higher (p<0.01) than the incidences of FBD (7.4%) and IBS (0.8%) in the control cohort. A longer duration of diarrhoea (>or=7 days) was associated with a higher risk of developing FBD (odds ratio 3.49 (95% confidence interval 1.71-7.13)). Expression of IL-1beta mRNA in terminal ileum and rectosigmoid mucosa was significantly higher in PI-IBS patients (p<0.01). The number of mast cells in the terminal ileum mucosa in PI-IBS (11.19 (2.83)) and non-PI-IBS patients (10.78 (1.23)) was significantly increased compared with that (6.05 (0.51)) in control subjects (p<0.01). Also, in the terminal ileum and rectosigmoid mucosa of IBS patients, the density of NSE, SP, and 5-HT positively stained nerve fibres increased (p<0.05) and appeared in clusters, surrounding an increased number of mast cells (p<0.01 compared with controls). CONCLUSIONS: BD is a causative factor in PI-IBS. The immune and nervous system may both play important roles in the pathogenesis of PI-IBS.

Adult↗
PubMed2001

Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia (UIP).

BACKGROUND/AIMS: The pathogenesis of idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), a chronic and incurable human respiratory disease, is not well established. This study was designed to investigate whether the apoptosis of type II pneumocytes could be the precipitating factor in the pathogenesis of IPF. METHODS: Nineteen specimens obtained by retrospective review of the medical and pathological records of 55 patients with IPF, four normal subjects, and 10 disease control lungs were analysed. The selected specimens had normal alveoli with intervening patchy scarring of the lung parenchyma, fulfilling the pathological criteria for UIP. To identify individual cells undergoing apoptosis in the normal alveoli, electron microscopy and in situ end labelling of fragmented DNA were performed on paraffin was embedded sections using digoxigenin-11-dUTP and the enzyme terminal deoxynucleotidyl transferase. RESULTS: Apoptosis was detected in the normal alveoli of 17 of the 19 patients with IPF/UIP and was absent in the controls. Electron microscopy demonstrated apoptotic changes in type II pneumocytes. These results indicate that apoptotic type II pneumocyte death occurs in normal alveoli of IPF/UIP and could be the principal cause of several events that account for the histological, clinical, and functional alterations seen in IPF/UIP. CONCLUSIONS: In conclusion, numerous type II pneumocytes from the normal alveoli of most patients with IPF/UIP actively undergo programmed cell death. This finding may shed new light on the pathogenesis of this disease, with implications mainly for the treatment of affected patients.

Aged↗
PubMed2005

Role of the renin-angiotensin system in the pathogenesis of preeclampsia.

Preeclampsia is a hypertensive disorder unique to pregnancy with consistent involvement of the kidney. The renin-angiotensin system (RAS) has been implicated in the pathogenesis of preeclampsia. In the gravid state, in addition to the RAS in the kidney, there is a tissue-based RAS in the uteroplacental unit. Increased renin expression observed both in human preeclampsia and in a transgenic mouse model with a human preeclampsia-like syndrome supports the concept that activation of the uteroplacental RAS, with angiotensin II entering the systemic circulation, may mediate the pathogenesis of preeclampsia. A novel disease paradigm of the two-kidney one-clip (2K-1C) Goldblatt model is presented for preeclampsia, wherein the gravid uterus is the clipped "kidney" and the two maternal kidneys represent the unclipped kidney. Validation of the 2K-1C Goldblatt model analogy requires evidence of elevated angiotensin II in the peripheral circulation before vascular maladaptation in preeclampsia. Convincing evidence of the elevation of angiotensin II in preeclampsia does not exist despite the fact that much of vascular pathogenesis appears to be due to angiotensin type I (AT(1)) receptor activation. Vascular maladaptation with increased vasomotor tone, endothelial dysfunction, and increased sensitivity to angiotensin II and norepinephrine in manifest preeclampsia may be explained on the basis of angiotensin II-mediated mechanisms. Recently, novel angiotensin II-related biomolecular mechanisms have been described in preeclampsia. These include AT(1) and bradykinin B(2) receptor heterodimerization and the production of an autoantibody against AT(1). Various organ systems with a predilection for involvement in preeclampsia are each a site of a tissue-based RAS. How angiotensin II-mediated mechanisms may explain the primary clinical-pathological features of preeclampsia is described. Future investigations are proposed to more precisely define the role of activation of the uteroplacental RAS in the mechanisms underlying preeclampsia.

Animals↗