Archive for December, 2010

Link: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=21106783&retmode=ref&cmd=prlinks

Excerpt:

We genotyped 102 Borrelia burgdorferi sensu lato strains isolated from
ticks, animals, and patients in 11 provinces in China by PCR restriction
fragment length polymorphism (PCR-RFLP) amplification of 5S (rrf)-23S (rrl)
ribosomal DNA spacer amplicons and multilocus sequence analysis (MLSA). The
results showed that B. garinii was the main genotype in China (65/102), and
it was mainly distributed in northern China. B. afzelii was the second
(22/102), and it was distributed in both northern and southern China. All B.
valaisiana strains were isolated from Guizhou Province. Additionally, one B.
burgdorferi strain was isolated from Hunan Province. Our results show the
diversity and wide distribution of B. burgdorferi sensu lato in China.

Link: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=21099401&retmode=ref&cmd=prlinks

Excerpt:

PURPOSE:: To report a case of a cat-scratch uveitis caused by Bartonella
henselae, which was confirmed by histology, serology, and polymerase chain
reaction (PCR) methodology. 
METHODS:: An iris nodule was biopsied from a 4-year-old child who was
scratched by a kitten on the side of his face and developed redness of the
eye associated with cervical lymphadenopathy. Sections of the iridectomy
specimen were stained with hematoxylin-eosin, periodic acid-Schiff, and
Warthin-Starry technique for histopathologic evaluation.
Additionally, serologic tests and molecular diagnosis using B.
henselae-specific PCR were performed. 
RESULTS:: Histopathologically, sections of the iridectomy specimen showed a
zonal granulomatous inflammation with a central iris necrotic abscess
surrounded by a mantle of epithelioid histiocytes and more peripherally by
lymphocytes and plasma cells. The Warthin-Starry stain disclosed scattered
short bacilli within the necrotic abscess morphologically compatible with B.
henselae. Report of serologic tests for B. henselae disclosed a negative
immunoglobulin G antibody (negative: less than 12) and a positive
immunoglobulin M antibody of 18 (positive: greater than 15). Other serologic
studies including Toxocara, histoplasmin, blastomycin, coccidioidin,
aspergillin, and Chlamydia were all negative. PCR was positive for B.
henselae DNA. 
CONCLUSIONS:: Our case
showed a unilateral chronic granulomatous iritis with the histopathologic
features compatible with CSD caused by B. henselae bacillus as demonstrated
in the iris biopsy and confirmed by serology and PCR technique. This case is
an example of a relatively rare uveal manifestation of CSD.

Excerpt:

Overview

Two strong and rapidly growing disciplines, neuroscience and immunology, each have made substantial scientific achievements. Yet the two rarely find a common language and purpose necessary to support scientific breakthroughs. A growing number of reports in the past 10 years may finally change this status quo as the interplay between immunology and neuroscience comes into focus. Coming from the study of a variety of seemingly disparate diseases, elements that were previously considered to be domains of one discipline are now discovered in the other. Examples include synapses made by T cells, and cytokines as neuromodulators.

This symposium, Neuroscience and Immunology: Intersection Yields Clues for the Etiology of Psychiatric and Neurodegenerative Diseases, held at the New York Academy of Sciences on October 26, 2010, provided an introduction to the interdisciplinary field of neuroimmunology and presents a compelling case for the role of specific inflammatory cytokines in sickness behavior and in clinical depression. Additional topics included how cytokines mediate the stress response at molecular, cellular, and systems levels; the molecular mechanisms of cellular stress in Alzheimer’s disease; and pro-inflammatory signaling’s role in amyloid-beta peptide-mediated neuronal dysfunction and memory impairment. Research was presented that identified the neurotoxic mechanisms and transduction pathways that are associated with TNFα signaling. Presenters discussed modulating glial reactivity and inflammatory cytokines as a possible therapeutic strategy against neurodegenerative diseases, and they unveiled recent discoveries on specific receptors for fibrinogen that advance our understanding of its role as a clotting factor, a regulator of inflammation, and many functions in between.

Andrew Miller from Emory University School of Medicine provided an introduction to the interdisciplinary field of neuroimmunology and began with an overview of depression, which affects 9% of the population in the U.S. Of these, around one third, or around 9 million people, are resistant to or intolerant of conventional antidepressant therapies. He provided an outline of inflammation as a common mechanism of diseases, including neuropsychiatric disorders such as major depression, and he went on to present a compelling case for the role of specific inflammatory cytokines in this mechanism. Building on the description of cytokines’ myriad roles in normal and pathological cell functioning, Raz Yirmiya from Hebrew University then elaborated on how cytokines, such as interleukin 1 (IL-1) mediate the stress response at molecular, cellular, and systems levels. He discussed studies from the last two decades that demonstrate that inflammatory cytokines in the brain mediate the detrimental effects of chronic stress, infections, and autoimmune and neurodegenerative diseases on memory functioning and mood. Such harm mitigation occurs particularly through microglial activation and the production of pro-inflammatory cytokines such as IL-1, and works especially against damage to hippocampal-dependent memory that might ordinarily occur as a result of chronic stress or disease.

Shi Du Yan from Columbia University then discussed the molecular mechanisms of cellular stress in Alzheimer’s disease and considered how pro-inflammatory signaling plays a role in amyloid-beta peptide-mediated neuronal dysfunction and memory impairment. Great detail was provided concerning RAGE, a receptor for advanced glycation end-products. RAGE is an immunoglobulin-like cell surface receptor that is often described, in reference to the structural heterogeneity of its ligand, as a pattern recognition receptor. RAGE inhibitors hold great potential for significant therapeutic advances against Alzheimer’s disease in the near future. Malú Tansey from Emory University School of Medicine captivated the audience with a description of her research identifying the neurotoxic mechanisms and transduction pathways associated with tumor necrosis factor (TNF) signaling. She explained potential therapeutic strategies for neurodegenerative diseases, strategies that involve altering glial reactivity and adjusting inflammatory cytokines. Katerina Akassoglou from Gladstone Institute & UCSF discussed studies in animal models that have demonstrated that extravascular fibrinogen can contribute to inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, and myocardial infarction. She illustrated her presentation with some movies from animal model studies of multiple sclerosis. These studies have demonstrated that fibrinogen is not merely a marker of BBB (blood–brain barrier) disruption, but also a mediator of neuroinflammation, both of which have known links to neurological disease initiation.

Link: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=21083369&retmode=ref&cmd=prlinks

Excerpt:

Abstract In a countrywide investigation of the ecological factors that
contribute to Lyme borreliosis risk, a longitudinal study on population
dynamics of the sheep tick Ixodes ricinus and their infections with Borrelia
burgdorferi sensu lato (s.l.) was undertaken at 24 sites in The Netherlands
from July 2006 to December 2007. Study sites were mature forests, dune
vegetations, or new forests on land reclaimed from the sea. Ticks were
sampled monthly and nymphal ticks were investigated for the presence of
Borrelia spp. I. ricinus was the only tick species found. Ticks were found
in all sites, but with significant spatial and temporal variations in
density between sites. Peak densities were found in July and August, with
lowest tick numbers collected in December and January. In some sites,
questing activities of I. ricinus nymphs and adults were observed in the
winter months. 
Mean monthly Borrelia infections in nymphs varied from 0% to 29.0% (range:
0%-60%), and several sites had significantly higher mean nymphal Borrelia
infections than others. Four genospecies of Borrelia burgdorferi s.l. were
found, with B. afzelii being dominant at most sites.
Borrelia infection rates in nymphal ticks collected in July, September, and
November 2006 were significantly higher (23.7%, p < 0.01) than those in the
corresponding months of 2007 (9.9%). 
The diversity in Borrelia genospecies
between sites was significantly different (p < 0.001). Habitat structure
(tree
cover) was an effective discriminant parameter in the determination of
Borrelia infection risk, as measured by the proportion of nymphal ticks
infected with B.
burgdorferi s.l. Thickness of the litter layer and moss cover were
positively related to nymphal and adult tick densities. The study shows that
Borrelia-infected ticks are present in many forest and dune areas in The
Netherlands and suggests that in such biotopes, which are used for a wide
variety of recreational activities, the infection risk is high.

Excerpt:

Nod (nucleotide-binding oligomerization domain) 1 and Nod2 are intracellular PRMs (pattern-recognition molecules) of the NLR (Nod-like receptor) family. These proteins are implicated in the detection of bacterial peptidoglycan and regulate pro-inflammatory pathways in response to bacteria by inducing signalling pathways such as NF-kappaB (nuclear factor kappaB) and MAPKs (mitogen-activated protein kinases). The Nod proteins act independently of the TLR (Toll-like receptor) cascade, but potently synergize with the latter to trigger innate immune responses to microbes. Most importantly, mutations in Nod2 have been shown to confer susceptibility to several chronic inflammatory disorders, including Crohn’s disease, Blau syndrome and early-onset sarcoidosis, underscoring the role of Nod2 in inflammatory homoeostasis. This review summarizes the most recent findings in the field of Nod1 and Nod2 research.

Abstract

The innate immune system comprises several classes of pattern recognition receptors, including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-1-like receptors (RLRs). TLRs recognize microbes on the cell surface and in endosomes, whereas NLRs and RLRs detect microbial components in the cytosol. Here we discuss the recent understanding in NLRs. Two NLRs, NOD1 and NOD2, sense the cytosolic presence of the peptidoglycan fragments meso-DAP and muramyl dipeptide, respectively, and drive the activation of mitogen-activated protein kinase (MAPK) and the transcription factor NF-kappaB. A different set of NLRs induces caspase-1 activation through the assembly of large protein complexes named inflammasomes. Genetic variations in several NLR members are associated with the development of inflammatory disorders. Further understanding of NLRs should provide new insights into the mechanisms of host defense and the pathogenesis of inflammatory diseases.

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Curr Opin Immunol. 2008 Aug;20(4):377-82. Epub 2008 Jul 2.

NOD-like receptors (NLRs): bona fide intracellular microbial sensors.

Shaw MH, Reimer T, Kim YG, Nuñez G.

Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Abstract

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) (nucleotide-binding domain leucine-rich repeat containing) family of proteins has been demonstrated to function as regulators of innate immune response against microbial pathogens. Stimulation of NOD1 and NOD2, two prototypic NLRs, results in the activation of MAPK and NF-kappaB. On the other hand, a different set of NLRs induces caspase-1 activation through the assembly of an inflammasome. This review discusses recent findings regarding the signaling pathways utilized by NLR proteins in the control of caspase-1 and NF-kappaB activation, as well as the nonredundant role of NLRs in pathogen clearance. The review also covers advances regarding the cellular localization of these proteins and the implications this may have on pathogen sensing and signal transduction.

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Cell Host Microbe. 2008 Mar 13;3(3):146-57.

Caspase-12 modulates NOD signaling and regulates antimicrobial peptide production and mucosal immunity.

LeBlanc PM, Yeretssian G, Rutherford N, Doiron K, Nadiri A, Zhu L, Green DR,Gruenheid S, Saleh M.

Department of Medicine, Division of Critical Care, and Centre for Study of Host Resistance, McGill University, Montreal H3A 1A1, Canada.

Link: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=21162040&retmode=ref&cmd=prlinks

Excerpt:

Two children presented with a history of fever and rash. Lab values revealed
pancytopenia, elevated ferritin, coagulopathy, and elevated triglycerides.
Both children quickly developed respiratory distress and hypotension
requiring admission to the ICU. Bone marrow biopsies revealed
hemophagocytosis. Studies for Ehrlichia returned positive. The patients were
started on doxycycline and treated for hemophagocytic lymphohistiocytosis
(HLH). Each made a full recovery.
In both patients, testing for MUNC and perforin genes were found to have no
mutation. These two cases demonstrate the importance of considering
Ehrlichiosis as a possible trigger of HLH. Pediatr Blood Cancer (c) 2010
Wiley-Liss, Inc.

Martin Pall has made a major contribution to our understanding of many of the CHRONIC degenerative diseases we see today. I like the fact that this provides a molecular based explanation that leads to improved understanding of the need for a total nutritional support program in these diseases, which our colleagues all too often dismiss as psychosomatic.

Garry F. Gordon MD,DO,MD(H)
President, Gordon Research Institute
www.gordonresearch.com

Link: http://www.thetenthparadigm.org/

Excerpt:

Novel Disease Paradigm Produces Explanations for a Whole Group of Illnesses

A Common Causal (Etiologic) Mechanism for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, Multiple Chemical Sensitivity, Fibromyalgia and Post-Traumatic Stress Disorder

Martin L. Pall, Professor Emeritus of Biochemistry and Basic Medical Sciences,
Washington State University and Research Director, The Tenth Paradigm Research Group.

The Tenth Paradigm of Human Disease

The basic proposal that is developed here and is amplified further in my book and in my other web pages, is that the NO/ONOO- cycle explanatory model is the tenth major paradigm of human disease.  There are nine well-accepted paradigms listed below along with the NO/ONOO- cycle:

Major Disease Paradigms

1.   Infectious diseases.

2.   Genetic diseases.

3.   Nutritional deficiency diseases.

4.   Hormone dysfunction diseases.

5.   Allergies.

6.   Autoimmune diseases.

7.   Somatic mutation/selection (cancer).

8.   Ischemic cardiovascular diseases.

9.   Amyloid (including prion) diseases.

10.  NO/ONOO- cycle diseases

Link: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=21083370&retmode=ref&cmd=prlinks

Excerpt:

Abstract The presence of antibodies toOccurrence of Spotted Fever Rickettsiosessera of 129 forest
workers from northeastern and southern Poland was assayed by indirect
immunofluorescence. Previous environmental studies revealed presence of
spotted fever group (SFG) rickettsiae in ticks collected from these areas.
Additionally, the workers were examinated for the presence of antibodies
specific to other tick-borne bacteria: Anaplasma phagocytophilum, Bartonella
spp., and B.
burgdorferi. 
The results of the studies have shown the presence of specific SFG
rickettsiae antibodies in 14.7% of tested forest workers, among them 78.9%
had species-specific antibodies to R. massiliae. Contrary to previous
detection R.
helvetica and R. slovaca in ticks collected in the environment of the
examined area, no species-specific antibodies to these species were detected
in studied workers. Antibodies to B. burgdorferi (44%) were found in forest
workers more often than antibodies to other tested pathogens. B. burgdorferi
was also the main component of coinfections. The most frequent confirmed
serologically coinfections were simultaneous infections with B. burgdorferi
and Bartonella spp. found in 10% of tested individuals. So far, SFG
rickettsiae infections have not been diagnosed in Poland; however, the
presence of the bacteria in ticks and presence of specific antibodies in
humans exposed to arthropods show the need for monitoring the situation. The
list of tick-borne pathogens is increasing, but knowledge about the
possibility of humans acquiring multipathogens infections after tick bite
still needs evaluation.

Link: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=21079901&retmode=ref&cmd=prlinks

Excerpt:

The article outlines examples of a viral (varicella-zoster virus, VZV), a
bacterial (Lyme borreliosis) and a parasitic (scabies) infection in
pregnancy with their risk for the mother and/or child as well as their
management. VZV infections cause various clinical scenarios depending on the
maternal immune status and the time of infection. Herpes zoster usually
poses no risk to the pregnant woman and there is no need for antiviral
therapy. VZV infection of a seronegative mother, however, may lead to severe
varicella in the pregnant woman and to congenital malformations (congenital
varicella syndrome) in case of early infection or neonatal varicella in case
of perinatal infection. Prompt therapy with acyclovir or administration of
VZV immunoglobulin for prophylaxis is mandatory in those patients. 
In case of Lyme borreliosis of the mother, adequate antibiotic therapy with
amoxicillin prevents harm to the fetus. Doxycycline is contraindicated
during pregnancy. 
Scabies represents an important differential diagnosis of pruritic
dermatoses in pregnancy and should be treated with permethrin 5% cream.

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