[leish-l] RefScout 2005/03/02 newsletter 9/2005
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This is RefScout-Newsletter 9/2005.
REQUEST: [ leishmaniasis ]
(6 articles match this request)
PMID: 15728505
TITLE: Nonhealing Infection despite Th1 Polarization Produced by a Strain of
Leishmania major in C57BL/6 Mice.
AUTHORS: Charles F Anderson, Susana Mendez, David L Sacks
AFFILIATION: Laboratory of Parasitic Diseases, National Institute of Allergy
and
Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
REFERENCE: J Immunol 2005 Mar 174(5):2934-41
Experimental Leishmania major infection in mice has been of immense
interest because it was among the first models to demonstrate the
importance of the Th1/Th2 balance to infection outcome in vivo. However
, the Th2 polarization that promotes the development of nonhealing
cutaneous lesions in BALB/c mice has failed to adequately explain the
mechanisms underlying nonhealing forms of leishmaniasis in humans. We
have studied a L. major strain from a patient with nonhealing lesions
that also produces nonhealing lesions with ulcerations and high parasite
burden in conventionally resistant C57BL/6 mice. Surprisingly, these
mice develop a strong, polarized, and sustained Th1 response, as
evidenced by high levels of IFN-gamma produced by Leishmania-specific
cells in the draining lymph node and in the ear lesion, and an absence
of IL-4 or IL-13. The parasites fail to be effectively cleared despite
high level induction of inducible NO synthase in the lesion, and despite
their sensitivity to killing by IFN-gamma-activated macrophages in
vitro. Infection of IL-10(-/-) mice, blockade of the IL-10R, or
depletion of CD25(+) cells during the chronic phase promotes parasite
killing, indicating that IL-10 and regulatory T cells play a role in
rendering the Th1 responses ineffective at controlling infection in the
skin. Mice with nonhealing primary lesions are nonetheless resistant to
reinfection in the other ear. We suggest that nonhealing infections in
animal models that are explained not by aberrant Th2 development, but by
overactivation of homeostatic pathways designed to control inflammation
, provide better models to understand nonhealing or reactivation forms
of leishmaniasis in humans.
PMID: 15730396
TITLE: Mononuclear cells from patients recovered from cutaneous leishmaniasis
respond to Leishmania major amastigote class I nuclease with a predominant
Th1-like response.
AUTHORS: S Farajnia, F Mahboudi, S Ajdari, N E Reiner, A Kariminia, M H
Alimohammadian
AFFILIATION: Drug Applied Research Center, Tabriz University of Medical
Sciences, Tabriz, Iran.
REFERENCE: Clin Exp Immunol 2005 Mar 139(3):498-505
Summary The Leishmania major amastigote class I nuclease (LmaCIN) is a
developmentally regulated protein that is highly expressed in the
amastigote stage of L. major. This protein is homologous to the P4
nuclease of L. pifanoi, which has been shown to induce protective immune
response in a murine model. To evaluate LmaCIN as a potential human
vaccine candidate, cellular immune responses to recombinant LmaCIN were
examined in individuals recovered from Old World cutaneous leishmaniasis
. Peripheral blood mononuclear cells (PBMC) from patients recovered from
L. major infection were cultured either with recombinant LmaCIN or
autoclaved L. major (ALM) as control. rLmaCIN induced significant
proliferation of PBMC from 90% of recovered patients. Phenotypic
analysis of proliferating cells showed that CD8(+) cells were the
predominant cell type proliferating in response to rLmaC1N. Screening of
culture supernatants for cytokines showed that rLmaCIN induced high
levels of interferon (IFN)-gamma (mean +/- s.e.m.: 1398 +/- 179 pg/ml)
associated with little interleukin (IL)-10 and little or no IL-5
production. These findings show that LmaCIN is immunogenic in humans
during L. major infection and that it can elicit immunological responses
relevant to immunoprophylaxis of leishmaniasis.
PMID: 15730828
TITLE: Fine needle aspiration cytology versus histopathology in the diagnosis
of
cutaneous leishmaniasis in pakistan.
AUTHORS: Asher Ahmed Mashhood, Iqbal Muhammad Khan, Shagufta Nasir, Humayun
Agha, Muhammad Saleem, Arshi Imran
AFFILIATION: Department of Skin, Combined Military Hospital, Peshawar.
REFERENCE: J Coll Physicians Surg Pak 2005 Feb 15(2):71-3
Objective: To compare FNAC with histopathology as an alternate method of
diagnosing cutaneous leishmaniasis. Design: Comparative study. Place
and Duration of Study: The duration of the study was from August 2003 to
April 2004 at CMH, Peshawar. Materials and methods: A total of 40
patients were included in this study. They were referred from various
areas of North-West Frontier Province. FNAC and skin biopsy was
performed on every patient. Haematoxylin and eosin (H&E) stain was
used for both procedures. Results: The study group included 39 males and
one female, their age ranging from 8-60 years with a mean age of 31.97
years. Detection of LT bodies was considered as a single criterion of
the positive result. Histopathological examination was able to diagnose
14 out of 40 patients (positive yield of 35%), while FNAC picked up 11
out of 40 patients (positive yield of 27.5%). Conclusion: FNAC is easier
, less painful and more cost-effective than the conventional skin biopsy
. The high sensitivity and specificity eliminate the need for other time
-consuming and invasive procedures. However, if LT bodies are not
detected then any further comment cannot be made regarding the diagnosis
and it is necessary to perform skin biopsy.
PMID: 15610728
TITLE: Development of a time-resolved fluorometry based immunoassay for the
determination of canine haptoglobin in various body fluids.
AUTHORS: MarÃa Dolores Parra, Ville Väisänen, José JoaquÃn Cerón
AFFILIATION: Department of Animal Medicine and Surgery, Faculty of Veterinary
Medicine, University of Murcia, 30100 Espinardo Campus Murcia, Spain.
REFERENCE: Vet Res 2005 Jan-Feb 36(1):117-29
A time-resolved immunofluorometric assay (TR-IFMA) was developed for the
determination of haptoglobin (Hp) in canine serum. Haptoglobin was
purified from canine acute phase serum by ammonium sulphate
precipitation followed by gel filtration. This isolated dog Hp was used
as the standard to calibrate the assay. Intra- and inter-assay
coefficients of variation of the assay were, respectively, 5.7% and 16.6
% at 0.51 mg/mL, 2.4% and 10.6% at 2.1 mg/mL and 10.5% and 11.9% at 32.5
mg/mL. The dilution of serum samples with high Hp concentrations
resulted in linear regression equations with R2 of 0.99 and 0.97. A high
correlation was found in serum Hp measurements by TR-IFMA and a
commercial assay based on peroxidase activity of haemoglobin bound to
haptoglobin (R2 = 0.96). The limit of detection for the TR-IFMA method
was 0.002 microg/mL. The addition of fresh haemolysate to serum samples
did not affect the haptoglobin concentration (P = 0.694). Statistical
differences (P < 0.003) were found between healthy dogs and dogs with
different pathological processes. In whole blood, Hp concentrations
were much lower than in serum but closely related (R2 = 0.84) whereas
saliva Hp concentrations were poorly related with serum concentrations (
R2 = 0.53). However, the concentration of Hp in saliva was significantly
(P < 0.039) higher in dogs with pathological processes compared to
healthy dogs. The assay sensitivity was adequate to also be applied to
whole blood and saliva specimens.
PMID: 15728863
TITLE: Nexus of infection with human immunodeficiency virus, pulmonary
tuberculosis and visceral leishmaniasis: a case report from bihar, India.
AUTHORS: Krishna Pandey, Prabhat K Sinha, Vidya N Ravidas, Nawin Kumar, Neena
Verma, Chandra S Lal, Sanjeev Bimal, Dipika Sur, Sujit K Bhattacharya
AFFILIATION: Rajendra Memorial Research Institute of Medical Sciences, Patna,
Bihar, India; National Institute of Cholera and Enteric Diseases, Kolkata,
India.
REFERENCE: Am J Trop Med Hyg 2005 Jan 72(1):30-2
A 37-year-old man was diagnosed as being infected with human
immunodeficiency virus (HIV), tuberculosis (TB), tuberculoma of the
brain, and visceral leishmaniasis (VL) at the Rajendra Memorial
Institute of Medical Sciences in Bihar, India. He had taken anti-
tuberculosis therapy (ATT) for two and a half months and had episodes of
convulsions with loss of consciousness, tongue bites, and incontinence
of urine. The results of a neurologic examination were normal except for
a left plantar extensor. He was positive for both HIV-I (confirmed by
Western blot) and VL (confirmed by splenic aspirate). Treatment was
initiated with amphotericin B lipid complex, a four-drug regimen (
rifampicin, isoniazid, ethambutol, and pyrazinamide) of ATT, highly
active antiretroviral therapy, anti-convulsants, and other supportive
therapies. A repeat computed tomography scan of the brain showed the
disappearance of the lesion followed by gliosis. After six months, he
was also cured of VL. The triad of infections (HIV, VL, and TB) is a
real threat in Bihar as an emerging combination of diseases of public
health importance. Keeping these facts in mind, efforts to develop
simple and cost effective diagnostic techniques coupled with affordable
therapeutic facilities are urgently needed in developing countries.
PMID: 15720898
TITLE: Is hypertriglyceridaemia a new concept for visceral leishmaniasis?
AUTHORS: Omer Erdeve, Yildaz Dallar, Zeynep Siklar
REFERENCE: Ann Trop Paediatr 2004 Dec 24(4):369
REQUEST: [ leishmania ]
(6 articles match this request. 2 articles matching other requests removed)
PMID: 15734543
TITLE: Cellular immunophenotyping of exfoliative dermatitis in canine
leishmaniosis (Leishmania infantum).
AUTHORS: E I Papadogiannakis, A F Koutinas, M N Saridomichelakis, J Vlemmas, S
Lekkas, A Karameris, A Fytianou
AFFILIATION: Clinic of Companion Animal Medicine, School of Veterinary
Medicine,
Aristotles University of Thessaloniki, 11 Stavrou Voutyra, GR-54627
Thessaloniki, Greece.
REFERENCE: Vet Immunol Immunopathol 2005 Apr 104(3-4):227-37
Lymphocyte subsets, major histocompatibility complex (MHC)-II expressing
cells and number of amastigotes in the epidermis and dermis were
investigated immunohistochemically in 48 dogs with patent leishmaniosis
, with or without exfoliative dermatitis (ED) to study the
immunopathogenesis of this common cutaneous form of the disease. Skin
biopsies were obtained and compared for ED sites (group A, n=26), normal
-appearing skin from the same animals (group B, n=24), and leishmanial
dogs not exhibiting ED (group C, n=22), and normal controls (group D, n=
22). The CD3+, CD45RA+, CD4+, CD8+ (CD8a+), CD21+, and MHC-II+ cells and
leishmania amastigotes were identified immunohistochemically and
counted with the aid of an image analysis system. Pyogranulomatous to
granulomatous dermatitis, expressed in various histopathological
patterns, was noticed in all groups A and B and in half of group C dogs
. In the epidermis, the low number of T-cells and their subsets did not
differ significantly between groups A and B, but CD8+ outnumbered CD4+
lymphocytes in both groups. MHC-II+ expression on epidermal
keratinocytes was intense in the skin with and without lesions from dogs
with ED but not in group C dogs. CD3+, CD8+ and MHC-II+ cells were
fewer in group C compared to group A and B dogs. In the dermis, CD3+
cells in group A animals were mainly represented by the CD8+. CD45RA+
and CD21+ cells were also seen in high numbers. MHC-II expression,
potentially in lymphocytes, fibroblasts, dendritic cells, and
macrophages was intense. The numbers of all cellular subpopulations in
the dermis were significantly different between the groups, being
highest in group A and lowest in group D. In sebaceous adenitis sites,
CD4+ outnumbered CD8+ cells in contrast to the neighbouring dermis and
the epidermis. The number of CD21+ and CD45RA+ cells was much lower in
the inflamed sebaceous glands compared to the dermis. Finally, the
number of amastigotes in the normal-appearing skin was significantly
higher in the ED dogs (group B) than in those not exhibiting this
cutaneous form of the disease (group C).
PMID: 15730289
TITLE: Synthesis of Proteophosphoglycans of Leishmania major and Leishmania
mexicana.
AUTHORS: Debatosh Majumdar, Galal A Elsayed, Therese Buskas, Geert-Jan Boons
AFFILIATION: Complex Carbohydrate Research Center, The University of Georgia,
315 Riverbend Road, Athens, Georgia 30602.
REFERENCE: J Org Chem 2005 Mar 70(5):1691-7
A novel approach for the synthesis of various fragments of
proteophosphoglycans from Leishmania major and Leishmania mexicana
proteophosphoglycans has been developed. These compounds have been
obtained by coupling alpha-mannosyl and alpha-N-acetyl-glucosamine
phosphoramidite derivatives with the serine hydroxyl of various amino
acids and peptides to give, after oxidation with tert-BuOOH,
phosphotriesters exclusively as alpha-anomers in good yield. The
resulting compounds could be deblocked using conventional methods.
Glycophosphorylation of preassembled and properly protected peptides was
found to be more efficient for the preparation of proteophosphoglycan
fragments than a building block approach strategy using a
phosphoglycosylserine derivative.
PMID: 15601666
TITLE: Slc11a1-mediated resistance to Salmonella enterica serovar Typhimurium
and Leishmania donovani infections does not require functional inducible nitric
oxide synthase or phagocyte oxidase activity.
AUTHORS: Jacqueline K White, Pietro Mastroeni, Jean-François Popoff, Carlton A
W Evans, Jenefer M Blackwell
AFFILIATION: Wellcome Trust/MRC Building, University of Cambridge School of
Clinical Medicine, Addenbrookes Hospital, Hills Road, Cambridge CB2 2XY, UK.
jennie.blackwell at cimr.cam.ac.uk.
REFERENCE: J Leukoc Biol 2005 Mar 77(3):311-20
Solute carrier family 11a member 1 (Slc11a1; formerly natural resistance
-associated macrophage protein 1) encodes a late endosomal/lysosomal
protein/divalent cation transporter, which regulates iron homeostasis in
macrophages. During macrophage activation, Slc11a1 exerts pleiotropic
effects on gene regulation and function, including generation of nitric
oxide (NO) via inducible NO synthase (iNOS; encoded by Nos2A) and of
reactive oxygen intermediates (ROI) via the phagocyte oxidase complex.
As NO and ROI have potent antimicrobial activity in macrophages, it was
assumed that their activities would contribute to Slc11a1-regulated
innate resistance to Salmonella enterica serovar Typhimurium and
Leishmania donovani. By intercrossing mice with gene disruptions at
Nos2A and Cybb (encoding gp91phox, the heavy chain subunit of cytochrome
b-245 and an essential component of phagocyte NADPH oxidase) onto
equivalent Slc11a1 wild-type and mutant genetic backgrounds, we
demonstrate that neither iNOS nor gp91phox activity is required for
Slc11a1-mediated innate resistance to either infection. Functional
gp91phox and iNOS are required to control S. enterica serovar
Typhimurium in non-Slc11a1-regulated phases of infection. For L.
donovani, an organ-specific requirement for iNOS to clear parasites from
the spleen was observed at 50 days post-infection, but neither iNOS nor
gp91phox influenced late-phase infection in the liver. This contrasted
with Leishmania major infection, which caused rapid lesion growth and
death in iNOS knockout mice and some exacerbation of disease with
gp91phox deficiency. This highlights the adaptive differences in tissue
and cellular tropisms between L. donovani and L. major and the different
genes and mechanisms that regulate visceral versus cutaneous forms of
the disease.
PMID: 15730255
TITLE: Bisnortriterpenes from Salacia madagascariensis.
AUTHORS: Deborah A Thiem, Albert T Sneden, Shabana I Khan, Babu L Tekwani
AFFILIATION: Department of Chemistry, Virginia Commonwealth University, P.O.
Box
842006, Richmond, Virginia 23284-2006, and National Center for Natural Products
Research, School of Pharmacy, The University of Mississippi, University,
Mississippi 38677.
REFERENCE: J Nat Prod 2005 Feb 68(2):251-4
A new bisnortriterpene quinone methide, 20-epi-isoiguesterinol (2), and
a new 6-oxophenolic triterpene, 6-oxoisoiguesterin (5), as well as two
known compounds, isoiguesterin (1) and isoiguesterinol (4), were
isolated from the petroleum ether extract of the roots of Salacia
madagascariensis. Isoiguesterin (1) and 20-epi-isoiguesterinol (2)
showed potent activity against Leishmania.
REQUEST: [ sand fly ]
(1 article matches this request)
PMID: 15728873
TITLE: INFLAMMATORY CELL INFILTRATION AND HIGH ANTIBODY PRODUCTION IN BALB/c
MICE CAUSED BY NATURAL EXPOSURE TO LUTZOMYIA LONGIPALPIS BITES.
AUTHORS: Francinaldo Silva, Regis Gomes, Deboraci Prates, José C Miranda,
Bruno
Andrade, Manoel Barral-Netto, Aldina Barral
AFFILIATION: Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Salvador, Bahia,
Brazil; Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Bahia,
Brazil.
REFERENCE: Am J Trop Med Hyg 2005 Jan 72(1):94-8
Sand flies inject saliva into the mammalian host when probing for a
blood meal. Understanding the initial vertebrate reactions against sand
fly saliva is important for possible interventions because these insects
transmit diseases to humans and other animals. Little is known of these
reactions to New World sand flies. Repeated exposure of BALB/c mice to
Lutzomyia longipalpis bites leads to local inflammatory cell
infiltration comprised of neutrophils, macrophages, and eosinophils.
Total IgG and IgG1 antibodies react predominantly with three major
protein bands (45, 44, and 16 kD) of the insect saliva by Western blot.
The injection of immune serum previously incubated with salivary gland
homogenate induced an early infiltration with neutrophils and
macrophages, suggesting the participation of immune complexes in
triggering inflammation.
REQUEST: [ sandfly ]
(0 articles match this request)
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