Ocular adnexal marginal zone lymphoma: Clinical presentation, pathogenesis, diagnosis, prognosis, and treatment.

Ocular adnexal marginal zone lymphoma (OAML) represents 1-2% of all non Hodgkin lymphomas. In the last few years many advances in understanding the pathogenesis and the molecular basis involved in its development have been done. Many potential risk factors have been proposed; a dysregulation of immune response in association with a chronic antigenic stimulation, have been hypothesized as possible pathogenic mechanism. In particular, Chlamydia psittaci infection has been related to OAML arising, and eradicating antibiotic therapy has been addressed as a safe and cost-effective approach. Management of OAML is still heterogeneous and matter of debate. There is no consensus about the best upfront treatment and therapeutic decision should take into account several patient-, lymphoma- and treatment-related factors. Novel agents and chemotherapy-free strategies are being investigated to reduce side effects and improve tumor control. This review is focused in recent knowledge improvements in this lymphoma.

A novel transport mechanism for MOMP in Chlamydophila pneumoniae and its putative role in immune-therapy.

Major outer membrane proteins (MOMPs) of Gram negative bacteria are one of the most intensively studied membrane proteins. MOMPs are essential for maintaining the structural integrity of bacterial outer membranes and in adaptation of parasites to their hosts. There is evidence to suggest a role for purified MOMP from Chlamydophila pneumoniae and corresponding MOMP-derived peptides in immune-modulation, leading to a reduced atherosclerotic phenotype in apoE(-/-) mice via a characteristic dampening of MHC class II activity. The work reported herein tests this hypothesis by employing a combination of homology modelling and docking to examine the detailed molecular interactions that may be responsible. A three-dimensional homology model of the C. pneumoniae MOMP was constructed based on the 14 transmembrane ß-barrel crystal structure of the fatty acid transporter from Escherichia coli, which provides a plausible transport mechanism for MOMP. Ligand docking experiments were used to provide details of the possible molecular interactions driving the binding of MOMP-derived peptides to MHC class II alleles known to be strongly associated with inflammation. The docking experiments were corroborated by predictions from conventional immuno-informatic algorithms. This work supports further the use of MOMP in C. pneumoniae as a possible vaccine target and the role of MOMP-derived peptides as vaccine candidates for immune-therapy in chronic inflammation that can result in cardiovascular events.

Multiple sclerosis: a chronic infective cerebrospinal venulitis?

The aetiology proposed for the development of chronic cerebrospinal venous insufficiency (CCSVI) associated with multiple sclerosis (MS) has been the presence of congenital truncular venous malformations. However, this hypothesis is not consistent with the epidemiology or geographical incidence of MS and is not consistent with many of the ultrasonographic or radiographical findings of the venous disturbances found in MS patients. However, the probability of a venous aetiology of MS remains strong based on evidence accumulated from the time the disorder was first described. The method used in this review was to search PubMed for all past medical publications related to vascular, venous, haematological, epidemiological, biochemical, and genetic investigations and treatments of MS. Epidemiological and geographical findings of prevalence of MS indicate the involvement of an infective agent. This review of the venous pathology associated with MS describes a hypothesis that the pathogenesis of the venous disease could be initiated by a respiratory infective agent such as Chlamydophila pneumonia, which causes a specific chronic persistent venulitis affecting the cerebrospinal venous system. Secondary spread of the agent would initially be via the lymphatic system to specifically involve the azygos, internal jugular and vertebral veins. The hypothesis proposes mechanisms by which an infective venous vasculitis could result in the specific neural damage, metabolic, immunological and vascular effects observed in MS. The hypothesis described is consistent with many of the known facts of MS pathogenesis and therefore provides a framework for further research into a venous aetiology for the disease. If MS does result from a chronic infective venulitis rather than a syndrome involving congenital truncular venous malformations, then additional therapies to the currently used angioplasties will be required to optimize results.

[Contemporary risks of infections by Mycoplasma pneumoniae and Chlamydophila pneumoniae]. / Wspólczesne zagrozenia zakazeniami Mycoplasma pneumoniae i Chlamydophila pneumoniae.

Atypical microorganisms, like Mycoplasma pneumoniae and Chlamydophila pneumoniae are common subject of studies because of caused diseases. In the last years, attention is paid on serious complications, which persistent infection of this atypical pathogens can cause and on the immunological body answer for them.

Comparison of koala LPCoLN and human strains of Chlamydia pneumoniae highlights extended genetic diversity in the species.

BACKGROUND: Chlamydia pneumoniae is a widespread pathogen causing upper and lower respiratory tract infections in addition to a range of other diseases in humans and animals. Previous whole genome analyses have focused on four essentially clonal (> 99% identity) C. pneumoniae human genomes (AR39, CWL029, J138 and TW183), providing relatively little insight into strain diversity and evolution of this species. RESULTS: We performed individual gene-by-gene comparisons of the recently sequenced C. pneumoniae koala genome and four C. pneumoniae human genomes to identify species-specific genes, and more importantly, to gain an insight into the genetic diversity and evolution of the species. We selected genes dispersed throughout the chromosome, representing genes that were specific to C. pneumoniae, genes with a demonstrated role in chlamydial biology and/or pathogenicity (n = 49), genes encoding nucleotide salvage or amino acid biosynthesis proteins (n = 6), and extrachromosomal elements (9 plasmid and 2 bacteriophage genes). CONCLUSIONS: We have identified strain-specific differences and targets for detection of C. pneumoniae isolates from both human and animal origin. Such characterisation is necessary for an improved understanding of disease transmission and intervention.

Chlamydophila pneumoniae.

Chlamydophila pneumoniae is estimated to cause about 10% of community-acquired pneumonia (CAP) cases and 5% of bronchitis cases, although most patients with C pneumoniae infection are asymptomatic, and the course of respiratory illness is relatively mild. The incubation period of C pneumoniae infection is around 21 days, and such symptoms as cough and malaise show a gradual onset, yet may persist for several weeks or months despite appropriate antibiotic therapy. Diagnosis by nasopharyngeal specimen culture, serum antibody titers, or molecular techniques is usually delayed with respect to the onset of symptoms, antibiotic treatment, or disease resolution and there is no accurate, standardized, commercial US Food and Drug Administration-cleared diagnostic method available. Erythromycin, tetracycline, and doxycycline are used as first-line therapy, although some investigators report no clinical or survival benefits from treating CAP caused by atypical pathogens. Meanwhile, adequate prospective studies have met with ethical and logistic barriers. Despite these limitations, North American guidelines recommend the antimicrobial treatment of patients with acute C pneumoniae respiratory infection.

Severe late-onset nosocomial pneumonia caused by Chlamydophila pneumoniae.

We report two cases of severe late-onset nosocomial pneumonia caused by Chlamydophila pneumaniae. The clinical course of the disease in these patients suggests that nosocomial pneumonia caused by this agent can lead to profound respiratory insufficiency and acute respiratory distress syndrome, particularly in patients with significant comorbidities and during the postoperative period. Intravenous azithromycin treatment was used to cure pneumonia in both of our patients.

Infection and primary biliary cirrhosis.

Primary biliary cirrhosis is an autoimmune cholestatic liver disease characterized by humoral and cellular response directed at mitochondrial autoantigens, mainly the E2 component of the pyruvate dehydrogenase complex. The etiology of PBC, like most polygenic autoimmune diseases, belongs to the "complex" category, including genetic elements and environmental factors. Many environmental factors, such as xenobiotics, smoking, hormonal therapy, toxins, oxidative stress and recurrent urinary tract infections, are associated with PBC. Infectious agents can trigger autoimmunity via several mechanisms and are associated with various autoimmune diseases. A relationship between PBC and several infectious agents, and a possible role for Escherichia coli in the pathogenesis of PBC, have been suggested. The identification of a culprit agent that induces or exacerbates PBC might have diagnostic and therapeutic implications. This review evaluates the evidence for an infectious agent role in the pathogenesis of PBC.

Therapeutic Chlamydophila abortus and C. pecorum vaccination transiently reduces bovine mastitis associated with Chlamydophila infection.

Infections with Chlamydophila abortus and C. pecorum are highly prevalent in cattle and have been associated with bovine mastitis. A prospective cohort study was conducted with a herd of 140 Holstein dairy cows to investigate the influence of Chlamydophila infection on subclinical inflammation of the bovine mammary gland as characterized by somatic cell numbers in milk. PCR detection of C. abortus and low serum antibody levels against Chlamydophila spp. were significantly associated with subclinical mastitis. To examine the effect of the infection by response modification, immune perturbation was done by two subcutaneous administrations of an experimental vaccine preparation of inactivated C. abortus and C. pecorum elementary bodies. Vaccination against Chlamydophila highly significantly decreased milk somatic cell numbers, thus reducing bovine mastitis, and increased antibody levels against Chlamydophila but did not eliminate shedding of C. abortus in milk as detected by PCR. The protective effect peaked at 11 weeks after vaccination and lasted for a total of 14 weeks. Vaccination with the Chlamydophila vaccine, a mock vaccine, or a combination vaccine against bovine viral diseases highly significantly increased C. abortus shedding in milk for 1 week, presumably mediated by the vaccine adjuvant. In summary, this study shows an etiological involvement of the widespread Chlamydophila infections in bovine mastitis, a herd disease of critical importance for the dairy industry. Furthermore, this investigation shows the potential for temporary improvement of chlamydial disease by therapeutic vaccination. Chlamydophila vaccination of cattle might serve as a testing ground for vaccines against human chlamydial infections.

Infections and asthma.

A new paradigm is developing in regard to the interaction between infection and asthma. This paradigm comprises the acute exacerbations seen in asthma and also asthma chronicity. Viral infections have been commonly evaluated in acute exacerbations, but findings suggest viral-allergen and viral-bacterial interactions are important for chronicity. Most recently, studies are also invoking atypical bacterial infections, Mycoplasma pneumoniae and Chlamydia pneumoniae, as factors in both acute exacerbation and chronic asthma.

Feline chlamydiosis.

Chlamydiae are an important cause of acute and chronic conjunctivitis in cats. Until recently, only one organism was thought to infect cats, Chlamydophila felis (previously Chlamydia psittaci var. felis). Recently, other Chlamydia-like organisms belonging to the family Parachlamydiaceae, which comprises organisms that reside and proliferate within free-living amoeba, have been identified in cats with neutrophilic and eosinophilic conjunctivitis. The relative importance of these organisms and their amoebic hosts requires investigation. There is also weak evidence that chlamydiae may also be capable of causing reproductive tract disease and lameness in cats. Diagnosis of chlamydial conjunctivitis requires use of specialized culture techniques or the polymerase chain reaction. The antibiotic of choice to treat these infections is doxycycline; azithromycin is less effective. All cats in the household should be treated simultaneously. The zoonotic potential of these organisms appears low, but some precaution is warranted when handling affected cats.

[A case of severe Chlamydia pneumoniae pneumonia requiring mechanical ventilation and complicated with disseminated intravascular coagulation].

A previously healthy 48-year-old man presented to his primary care physician with high fever, dry cough and dyspnea. Pneumonia was diagnosed and intravenous administration of imipenem/cilastatin was begun, but his respiratory condition worsened and he was admitted to our hospital with severe hypoxia. A chest radiograph showed reticular opacity and consolidation in both lung fields. The case was complicated with disseminated intravascular coagulation. Analysis of the bronchoalveolar lavage fluid showed increases in the total cell counts and an elevated percentage of lymphocytes. Sputum, blood and bronchoalveolar lavage examinations failed to reveal etiology to explain his severe respiratory illness. Treatment consisted of mechanical ventilation and administration of steroid pulse-therapy and gabexate mesilate. On the basis of his clinical course, we suspected possible atypical pneumonia, and began therapy with intravenous minocyclin and oral erythromycin administration. On the third hospital day, the arterial blood gas data improved and the bilateral pulmonary infiltration on the chest radiographs disappeared. Using paired sera, we detected increases of 1.35 in ID for anti-Chlamydia pneumoniae IgG antibodies by ELISA, and arrived at a diagnosis of Chlamydia pneumoniae pneumonia.

Pneumonia due to Chlamydia pneumoniae in children: epidemiology, diagnosis, and treatment.

The term "atypical" pneumonia has been used to differentiate infections caused by Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella, and other related organisms from pneumonia caused by classic bacteria, the prototype being Streptococcus pneumoniae. However, recent studies demonstrated that the clinical presentation of pneumonia due to atypical pathogens cannot readily be differentiated from those caused by "typical" bacteria. This is further complicated by the observation that coinfections with atypical pathogens and other bacteria are frequent. Nonetheless, the term "atypical" can be useful, as these organisms share a number of characteristics that separate them from "typical" bacteria. They are either obligate or facultative intracellular parasites that cannot be isolated using routine microbiologic methods. The most commonly used method of diagnosis of these infections is serology, which has significant limitations. Although C. pneumoniae is now recognized worldwide as a common cause of respiratory infections in adults and children, major gaps remain in our knowledge of the biology of this organism and how it causes disease, in major part due to the lack of readily available, standardized diagnostic methods.

Chlamydia pneumoniae as a respiratory pathogen.

Chlamydia pneumoniae is a recently recognized human respiratory pathogen with a unique biphasic life cycle characterized by an obligate intracellular (replicative) and an extracellular (infectious) form of the organism. C. pneumoniae is widely distributed and, via the respiratory route, infects the majority of the world's population. The majority (70%) of acute human C. pneumoniae respiratory tract infections are asymptomatic or only mildly symptomatic but a minority (30%) cause more severe respiratory illnesses including community-acquired pneumonia, bronchitis and a variety of upper airway illnesses. After acute infection the C. pneumoniae intracellular life cycle is characterized by the development of metabolically inert (and thus antibiotic resistant) atypical "persistent" inclusions; this biologic behavior correlates with a clinical course following acute symptomatic illness that is characterized by persistence of symptoms that are difficult to treat with antibiotics. A role for C. pneumoniae in chronic respiratory illness is currently under investigation: "persistent" intracellular inclusions contain increased quantities of chlamydial heat shock protein 60 (hsp 60), a highly immunogenic protein that has been implicated in the pathogenesis of established chronic inflammatory chlamydial diseases (blinding trachoma, pelvic inflammatory disease and tubal infertility). An emerging body of evidence, including host immune response to chlamydial hsp 60, links C. pneumoniae infection with a spectrum of chronic inflammatory lung diseases of currently unknown etiology (asthma, chronic bronchitis and chronic obstructive pulmonary disease (COPD)). Further laboratory developments, including reliable and practical diagnostic methods and antibiotics effective against persistent infection, will be required to recognize and treat acute C. pneumoniae infection, and to advance our knowledge and understanding of the role of chronic infection in asthma, chronic bronchitis and COPD.

A case of splenic abscess due to Chlamydia pneumoniae.

In this report, a case of chlamydial disease with splenic abscess associated with Chlamydia pneumoniae antigen and antibody was described. On spleen biopsy of the patient, an antigen specific to C.pneumoniae was detected by immunofluorescence staining with a monoclonal antibody. Serologic studies revealed a high antibody titer to C.pneumoniae in sera collected from the patient and her husband. Treatment with the antibiotic minocycline improved her condition.