bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency of PowerCore in core set development using amplified fragment length polymorphic markers in mungbean
Authors: Moe Kyaw Thu , Gwag Jae‐Gyun , Park Yong‐Jin
Published: September 2011

With 2 figures and 5 tables

The mungbean [Vigna radiata (L.) Wilczek] is a member of the Fabaceae, consists of around 20 000 species. With the rapid increase in the number of germplasm collections, many gene banks face problems of redundant resources. To cope with this problem, the development of an allele‐mining set is especially important. Our present study supports the efficiency of PowerCore in the development of core set from 705 collected accessions using AFLP markers. The result demonstrated the higher allele (fragment) capturing efficiency of PowerCore than other strategies (distance‐based, stratified random and random) tested at any level of sample size (5%, 10%, 15%, 20% of total accessions) selected. Highly significant correlation (r = 0.96) was observed between allele frequency distribution of entire collections and that of core set developed by PowerCore. The resulted core set was confirmed with 15 SSR data. The result will be useful, especially for reducing the redundant resources in the gene bank and allele mining from a large germplasm collection.
Comparison of Alcoholism Subtypes as Moderators of the Response to Sertraline Treatment
Authors: Kranzler Henry R. , Feinn Richard , Armeli Stephen , Tennen Howard
Published: September 2011

Background:  A variety of typologies have been used to categorize alcoholism’s diverse manifestations. Although the most widely studied typologies are dichotomous ones based on genetic epidemiologic findings or using cluster analytic methods, recent efforts have utilized a single item or the onset of a diagnosis of alcohol dependence to subtype individuals based on the age of alcoholism onset. We compared 3 different methods to subtype alcoholics.

Methods:  This secondary analysis used data from 134 alcohol‐dependent participants in a placebo‐controlled trial of sertraline (Kranzler et al., 2011). We compared cluster analysis to distinguish 2 risk/severity subtypes (Babor et al., 1992) with 2 age‐of‐onset subtypes (i.e., based on the age of onset of problem drinking or the age at which alcohol dependence criteria were first met).

Results:  Each method yielded subgroups that differed significantly from one another on demographic and clinical measures. Although concordance was high between the 2 age‐of‐onset methods, it was poor between the age‐of‐onset methods and the cluster analysis–derived approach. All 3 subtyping approaches significantly moderated the effects of sertraline or placebo, but only in the L’L’ genotype group, as originally reported (Kranzler et al., 2011). In all cases, sertraline treatment was superior to placebo in later‐onset individuals and inferior to placebo in the earlier‐onset groups.

Conclusions:  Because age‐of‐onset subtypes can be defined retrospectively on an individual basis, they may be more clinically useful than cluster‐derived subtypes, which require group data. Because the 2 age‐of‐onset measures we examined appear to have comparable validity, a single item is easier to use as a measure of the age of onset of problem drinking.
An Optimized Method for the Measurement of Acetaldehyde by High‐Performance Liquid Chromatography
Authors: Guan Xiangying , Rubin Emanuel , Anni Helen
Published: September 2011

Background:  Acetaldehyde is produced during ethanol metabolism predominantly in the liver by alcohol dehydrogenase and rapidly eliminated by oxidation to acetate via aldehyde dehydrogenase. Assessment of circulating acetaldehyde levels in biological matrices is performed by headspace gas chromatography and reverse phase high‐performance liquid chromatography (RP‐HPLC).

Methods:  We have developed an optimized method for the measurement of acetaldehyde by RP‐HPLC in hepatoma cell culture medium, blood, and plasma. After sample deproteinization, acetaldehyde was derivatized with 2,4‐dinitrophenylhydrazine (DNPH). The reaction was optimized for pH, amount of derivatization reagent, time, and temperature. Extraction methods of the acetaldehyde‐hydrazone (AcH‐DNP) stable derivative and product stability studies were carried out. Acetaldehyde was identified by its retention time in comparison with AcH‐DNP standard, using a new chromatography gradient program, and quantitated based on external reference standards and standard addition calibration curves in the presence and absence of ethanol.

Results:  Derivatization of acetaldehyde was performed at pH 4.0 with an 80‐fold molar excess of DNPH. The reaction was completed in 40 minutes at ambient temperature, and the product was stable for 2 days. A clear separation of AcH‐DNP from DNPH was obtained with a new 11‐minute chromatography program. Acetaldehyde detection was linear up to 80 μM. The recovery of acetaldehyde was >88% in culture media and >78% in plasma. We quantitatively determined the ethanol‐derived acetaldehyde in hepatoma cells, rat blood and plasma with a detection limit around 3 μM. The accuracy of the method was <9% for intraday and <15% for interday measurements, in small volume (70 μl) plasma sampling.

Conclusions:  An optimized method for the quantitative determination of acetaldehyde in biological systems was developed using derivatization with DNPH, followed by a short RP‐HPLC separation of AcH‐DNP. The method has an extended linear range, is reproducible and applicable to small‐volume sampling of culture media and biological fluids.
Acamprosate for Alcohol Dependence: A Sex‐Specific Meta‐Analysis Based on Individual Patient Data
Authors: Mason Barbara J , Lehert Philippe
Published: September 2011

Background:  It is unknown whether women derive comparable benefits and have a similar safety and tolerability profile as men from acamprosate, a widely prescribed drug for the maintenance of abstinence in alcohol dependence. The objective of this study was to assess sex‐specific differences in the efficacy, safety, and tolerability of acamprosate in the treatment of women and men with alcohol dependence.

Methods:  A sex‐specific meta‐analysis was conducted based on individual patient data (IPD). Data were obtained from double‐blind, randomized controlled trials with quantitative drinking measures in patients with alcohol dependence receiving oral acamprosate or placebo. Sources included PubMed, PsychInfo, and Cochrane electronic databases; reference lists from retrieved articles and presentations at professional meetings; and direct access to authors and companies who provided IPD.

Results:  Individual records were obtained from 1,317 women and 4,794 men who participated in 22 eligible studies conducted in 18 countries. IPD meta‐analyses found a significant beneficial effect of acamprosate relative to placebo across all 4 efficacy end points: an incremental gain of 10.4% (95% CI 7.1 to 13.7, p < 0.001) in percentage of abstinent days, an incremental gain of 11.0% (7.4 to 14.6, p < 0.001) in percentage of no heavy drinking days, an odds ratio of 1.9 (1.6 to 2.2, p < 0.001) for rate of complete abstinence, and an odds ratio of 1.9 (1.6 to 2.3, p < 0.001) for rate of no heavy drinking, over the study duration. Acamprosate was also associated with significantly higher rates of treatment completion (p = 0.004) and medication compliance (p < 0.001) than placebo. Men and women did not differ on any measure of acamprosate efficacy, safety, or tolerability.

Conclusions:  This sex‐specific IPD meta‐analysis provides evidence that acamprosate has a significant effect compared with placebo in improving rates of abstinence and no heavy drinking in both women and men with alcohol dependence. Further, acamprosate was associated with significantly higher rates of treatment completion and medication compliance than placebo among both women and men and had a comparable safety and tolerability profile.
Henry George and the Intellectual Foundations of the Open Source Movement
Authors: NIMAN NEIL B.
Published: September 2011

Abstract

The emergence of a common development platform (either in the form of open source projects or proprietary products) and the corresponding economic communities that emerge to support those platforms is similar in scale and scope to the concept of the city found in Henry George's economics of time and place. A modern counterpart to the 19th‐century focus on land can be found in the 20th‐century concern with the establishment of intellectual property rights that fence off a portion of the creative commons in order to construct temporary monopolies. Captured in the open source movement where licenses that specify property rights are adopted in order to provide a great deal of flexibility in terms of how ideas are used and shared, a strong connection can be drawn between this modern movement and the work of Henry George. Building a connection between the two provides greater clarity in terms of understanding how in a modern technology‐based economy, progress can be achieved without poverty.
Spontaneous renal lymphosarcoma in a juvenile cynomolgus monkey (Macaca fascicularis)
Authors: Anderson Wayne I. , Inhelder James L. , King Norval W.
Published: September 2011

Spontaneous lymphosarcoma, likely of renal origin, was diagnosed in a naive, juvenile, male cynomolgus monkey (Macaca fascicularis). Histologically, renal architecture was effaced by dense infiltrating sheets of plump cells with indistinct borders and scant amphophilic cytoplasm. Mitoses were uncommon. Similar neoplastic infiltrates were also present in the right renal cortex, one adrenal medulla, the prostate, seminal vesicles, myocardium, and the pulmonary interstitium. Serological tests were negative for infection with Simian Immunodeficiency Virus (SIV), Simian T‐Lymphotropic Virus‐1 (STLV‐1), and Simian Retrovirus‐5.
Comparison of the efficacy of AZT and PMEA treatment against acute SIVmne infection in macaques
Authors: Tsai Che‐Chung , Follis Kathryn E. , Grant Richard , Sabo Alexander , Nolte Randolph , Bartz Curtis , Bischofberger Norbert , Benveniste Raoul
Published: September 2011

The antiretroviral drugs azidothymidine (AZT) and 9‐(‐2‐phosphonylmethoxyethyl) adenine (PMEA) were individually tested for prevention of simian immunodeficiency virus (SIVmne) infection in macaques (Macaca fascicularis). Macaques were pretreated with either drug before inoculation with SIVmne, and drug treatment was continued for four weeks. The virus, antibody, and clinical status of the macaques was monitored for up to 36 weeks following inoculation. While AZT prophylaxis resulted in reduced virus load in some macaques, PMEA prophylaxis was highly efficacious in preventing acute SIVmne infection.
Genetic estimates for plasma lipids and lipoproteins in cynomolgus monkeys under assortative mating
Authors: Spray Beverly J. , Morgan Timothy M. , Clarkson Thomas B.
Published: September 2011

Data obtained from cynomolgus monkeys selected for total plasma cholesterol (TPC) response to dietary cholesterol and nonselected controls were used to estimate heritability of TPC and lipoprotein concentrations. A total of 345 observations were collected on 57 progeny from 18 sires. Heritability estimates obtained by a paternal half‐sib analysis and by regression of offspring on mid‐parent values were 0.45 ± 0.24 and 0.69 ± 0.18 for TPC, 0.63 ± 0.30 and 0.64 ± 0.17 for LDLC, and 0.80 ± 0.36 and 0.59 ± 0.14 for HDLC, respectively. These results suggest that TPC and lipoprotein concentrations are influenced by additive genetic effects in cynomolgus monkeys, establishing their importance as an animal model for studying the genetics of lipoproteins.
Histochemical and immunohistochemical similarities between hepatic tumors in two chimpanzees and man
Authors: Tabor Edward , Hsia Chu Chieh , Muchmore Elizabeth
Published: September 2011

A well‐differentiated trabecular hepatocellular carcinoma (HCC) and a well‐differentiated tumor resembling HCC from each of two chimpanzees were found to have histochemical and immunohistochemical staining characteristics similar to those in human HCCs. Transforming growth factor α was overexpressed in both tumors. Oval cells, thought to be liver stem cell progeny with a possible role in hepatocarcinogenesis, were observed among nontumorous hepatocytes, particularly near the tumors. Hepatic tumors are rare in chimpanzees but their similarities to human HCC provides a useful research model.
A baboon (Papio hamadryas) model of insulin‐dependent diabetes
Authors: Heffernan Scott , Phippard Andrew , Sinclair Alan , McLennan Susan , Hennessy Annemarie , Gillin Adrian , Horvath John , Tiller David , Yue Dennis , Turtle John
Published: September 2011

Over a period of four years, streptozocin has been used to induce diabetes in 10 baboons, all of whom are insulin dependent. We describe our experience with their husbandry, induction of diabetes, insulin therapy, metabolic control and growth rate. Streptozocin dosage of 60 mg/kg readily induces hyperglycemia with minimal hepatic or renal toxicity. Using a once daily injection of mixed short and intermediate acting insulins at a dosage of 2–4 U/kg, it is possible to maintain a degree of metabolic control similar to that attained in patients.
Neutralising epitopes of simian immunodeficiency virus envelope glycoprotein
Authors: Kent Karen A.
Published: September 2011

Abstract: Monoclonal and polyclonal antibodies with weak SIV neutralising activity bind to the V2 and V4 regions of gp120 or bind to the amino acids DWNND in gp41. Antibodies with the most potent neutralising activity recognise conformation‐dependent epitopes involving the V3 and V4 regions of gp120. Monoclonal antibodies that map to the V3 region of SIVmac failed to neutralise. However, one antibody to SIV AGM neutralised but only in the presence of soluble CD4.
Simian varicella virus antibody response in experimental infection of African green monkeys
Authors: Gray Wayne L. , Gusick Nanette J. , Fletcher Thomas M. , Solke Kenneth F.
Published: September 2011

Abstract: The humoral immune response to simian varicella virus (SVV) was investigated following primary and secondary experimental infection of African green monkeys. Neutralization and immunoprecipitation assays were used to determine antibody titers to SVV throughout the course of infection. The immune response to specific viral polypeptides was analyzed by immunoprecipitation analysis. The results demonstrate that the simian varicella model offers a useful approach to investigate immune mechanisms in human varicella zoster virus (VZV) infections.
Enumeration of lymphokine‐secreting cells as a quantitative measure for cellular immune responses in rhesus macaques
Authors: van der Melde Peter H. , Groenestein Reno J. , de Labie Miranda C. D. C. , Heeney Jonathan , Pala Pletro , Slaoui Moncef
Published: September 2011

Abstract: We investigated whether enumeration of lymphokine‐secreting T cells can be used as a quantitative measure to determine the immunogenicity of foreign proteins in rhesus monkeys. In addition, it was assessed whether this approach can supplement and/or substitute for the well‐established lymphoproliferation assay. Two candidate vaccine proteins (e.g., HIV‐1 gp120 and HSV‐2gD) were used as model antigens for immunization. PBMCs from immunized animals were antigenically stimulated and evaluated on their proliferative capacity and lymphokine release at the single cell level. The experiments showed a close quantitative correlation between antigen‐triggered proliferative responses and the antigen‐induced generation of Il‐2 and IFN‐gamma producing cells (pc). Il‐4pc were found to appear relatively late after the initiation of antigen exposure. The data indicate that ELISPOT assays provide valuable tools for the assessment of the antigenicity of foreign proteins in vivo.
Fetal ultrasonography: Normal biometric ranges in the baboon (Papio hamadryas)
Authors: Devonald Katherine J. , Harewood Winthrop J. , Ellwood David A. , Phippard Andrew F.
Published: September 2011

Normal biometric ranges for fetal growth in a captive breeding baboon (Papio hamadryas) colony are described. Measurements include crown‐rump length, biparietal diameter, binocular distance, head circumference, abdominal circumference, femur length and amniotic fluid index. The pattern of fetal growth is compared with other baboon subspecies and man. The uses and limitations of such data for breeding colony management and optimum utilisation of experimentally derived data are discussed.
Endocrine neoplasia in New World primates
Authors: Dias Josélc , Montali Richard J. , Strandberg John D. , Johnson Linda K. , Wolff Michael J.
Published: September 2011

Abstract: Of 1,106 New World primates necropsied from the National Zoological Park (Washington, D.C.) and the Department of Comparative Pathology, Johns Hopkins University School of Medicine (Baltimore, Maryland) 22 (1.9%) animals were identified with 27 neoplasms. Of this group, nine animals (two females, seven males) had a total of 13 endocrine neoplasms. All animals were adults, with an age range of 2.7–25 years (average, 12.1 years). Seven were Callitrichidae and two were Cebidae. The adrenal gland was the most affected organ, with seven (53.8%) neoplasms, followed by the pituitary and thyroid gland with two (15.4%) cases each, and the pancreas and parathyroid gland with one tumor (7.7%) each. All neoplastic disorders were benign. Immunocytochemistry assays for growth hormone, adrenocorticotropic hormone, prolactin, follicle‐stimulating hormone, luteinizing hormone, thyroid‐stimulating hormone, and chromogranin A were performed on two pituitary neoplasms. Pheochromocytoma was the most frequent neoplasm, representing 5 (38.4%) of the 13 neoplasms. The remaining were thyroid cystadenoma (two, 15.4%), corticotrophic cell pituitary adenoma (two, 15.4%), adrenal ganglioneuroma (one, 7.7%), adrenal cortical adenoma (one, 7.7%), parathyroid chief‐cell adenoma (one, 7.7%), and pancreatic islet‐cell adenoma (one, 7.7%).
Reproductive efficiency in the common marmoset (Callithrix jacchus): A longitudinal study from ovulation to birth monitored by ultrasonography
Authors: Nubbemeyer R. , Heistermann M. , Oerke A.‐K. , Hodges J.K.
Published: September 2011

Abstract: This study examines reproductive efficiency in the common marmoset monkey, Callithrix jacchus, using sequential ultrasound examinations to establish ovulation number, implantation rate, and incidence of prenatal loss. Ultrasound was carried out with a 10 or 7.5 mHz probe in nonsedated animals, daily during the late follicular phase, approximately twice a week until day 20 after ovulation, and at days 35, 56, and 85 of pregnancy to enable visualization of gestation sacs, heartbeats, and fetal heads, respectively. Ovulatory follicles could be seen 3–4 days before ovulation and by day –2, 98% of ovulating follicles were >2mm diameter, although almost 10% of follicles of this size disappeared without ovulating. Total number of ovulating follicles for 15 females was 45 (mean ovulation rate ? 3.0, range 2–4). In the 14 animals that conceived, 41 corpora lutea were identified (mean ovulation rate = 2.9) within 10 days of ovulation. All pregnancies went to term (no abortion occurred) resulting in the birth of 37 neonates (9 triplets, 5 twins) and an average litter size of 2.64. All four losses were confined to the embryonic period (< day 85), two occurring before day 35, one between days 35 and 56, and one between days 56 and 85. In demonstrating that 90% of ovulatory follicles gave rise to live offspring, the results of this study indicate an extremely high reproductive efficiency in the marmoset monkey (when maintained under favorable captive conditions) and a rate of prenatal loss much lower than that reported for other primate species.
Proteinuric hypertension in a pregnant baboon: Was this pre‐eclampsia?
Authors: Ramsay M.M. , Tame J.D. , Winter J.A. , Carbone L.G. , Schlafer O.H. , Nathanielsz P.W.
Published: September 2011

Abstract: We report the results of investigating a pregnant baboon that developed hypertension, proteinuria, and oedema in late gestation. Although the clinical presentation suggested a diagnosis of preeclampsia, the evolution of her clinical signs and results of a renal biopsy performed 3 weeks after delivery suggested that glomerulonephritis was the underlying disease.
Ultrasonographic and hormonal monitoring of pregnancy in the saddle back tamarin, Saguinus fuscicollis
Authors: Kuederling Irmgard , Heistermann Michael
Published: September 2011

Ultrasonography was used in six saddle back tamarin females (Saguinus fuscicollis) to diagnose pregnancy, monitor the patterns of uterine growth and embryonic/foetal development and examine the incidence loss of single embryos/foetuses. Pregnancy was reliably diagnosed 17 days after conception, 10 days earlier than by plasma progesterone measurement. The patterns of uterine and embryonic/foetal growth paralleled those reported for the common marmoset, including a delay in embryonic development. The results support the hypothesis of retardation of organogenesis in most callitrichid species. Individual embryos could be reliably identified from day 50 of pregnancy; a loss of single embryos/foetuses after this stage did not occur. All pregnancies were carried to term, resulting in five times twins and one singleton. The smaller litter size compared to the common marmoset may be due to loss of single embryos at earlier stages of pregnancy or to a lower ovulation rate.
Risk of occupational exposure to potentially infectious nonhuman primate materials and to simian immunodeficiency virus
Authors: Sotir Mark , Switzer William , Schable Charles , Schmitt James , Vitek Charles , Khabbaz Rima F.
Published: September 2011

Abstract: Five hundred fifty persons who worked with nonhuman primates (NHP) or with NHP material in 13 North American research institutions were surveyed for potential occupational exposures and tested for antibodies to simian immunodeficiency virus (SIV). Needlesticks and mucocutaneous exposures were reported more frequently among persons who handled SIV‐negative or SIV‐status‐unknown (SIV‐N/U) animals (36% and 35%) or who worked with SIV‐N/U material in the laboratory (18% and 17%) than among persons who handled SIV‐positive NHP (SIV‐P) (9% and 4%) or worked with SIV‐P material (6% and 8%). The risk for needlesticks when working with both SIV‐N/U and SIV‐P animals and the risk for mucocutaneous exposures from SIV‐N/U animals increased with the number of years working with NHP. Persons who performed invasive tasks (e.g., obtaining blood samples, performing surgery/autopsies) were more likely than others to sustain needlesticks (adjusted OR = 3.55, 95%CI = 1.40–9.02). Two (0.4%) of 550 persons had antibodies to SIV. One appears to be infected with SIV, as previously reported. These data suggest that persons who work with NHP or with NHP material are at risk for occupational exposure to potentially infectious materials including SIV. Prevention strategies are needed to reduce the risk for needlesticks and mucocutaneous exposures around all NHP, and safety guidelines should emphasize prevention options for invasive tasks performed with animals.
Immune and hematopoietic parameters in HIV‐1‐infected chimpanzees during clinical progression toward AIDS
Authors: Villinger Francois , Brar Sukhdev S. , Brice Gary T. , Chikkala Nathaniel F. , Novembre Francis J. , Mayne Ann E. , Bucur Silvana , Hillyer Christopher D. , Ansari Aftab A.
Published: September 2011

Abstract: Until recently, chimpanzees were considered susceptible to human immunodeficiency virus type 1 (HIV‐1) infection, but refractory to disease induction based on the asymptomatic status of all experimentally infected chimpanzees after over 10 years postinfection (PI). However, a decline in peripheral CD4+ T cells was noted in one chimpanzee (C499) of the Yerkes cohort of HIV‐1 infected apes, after 11 years PI concurrent with increasing plasma viral load. These clinical signs were followed by the occurrence of opportunistic infections, thrombocytopenia, and progressive anemia leading to euthanasia. A second chimpanzee (C455) was transfused with blood from C499 collected during the symptomatic stage. Shortly thereafter, this second animal showed a rapid decline in peripheral CD4+ T‐cell levels and sustained high viral load. Hematological analyses showed a 50% decrease in CFU‐GM for both apes during the symptomatic phase and a reduction of 40% and 73% of the total CFU despite normal levels of CD34+ cells in the bone marrow. Cryopreserved sequential PBMC samples from these two chimpanzees were analyzed for constitutive and PHA‐P induced levels of cytokines and chemokines. Data show that whereas there were no detectable constitutive levels of mRNA coding for IL‐2, 4, and 10, there appears to be a transient increase in IFN‐γ message level coincident with increased viremia and this IFN‐γ synthesis decreased with disease progression. PHA‐induced cytokine mRNA analysis showed low or undetectable levels of IL‐4 and IL‐10 mRNA in all samples and a marked decrease in the levels of IL‐2 shortly after HIV infection. In addition, there was also a gradual decrease in IFN‐y mRNA with progression of disease. Of interest were the findings of high to normal levels of PHA‐induced synthesis of the chemokines MIP‐1γ, MIP‐1β, and RANTES in samples during the asymptomatic and early symptomatic period, which also dramatically decreased at late stages of the disease. These data suggest important roles for IL‐2, IFN‐γ, and the chemokines in the regulation of immune responses in HIV‐1‐infected chimpanzees.
Reproductive exocrine and endocrine profiles and their seasonality in male langur monkeys (Presbytis entellus entellus)
Authors: Lohiya N.K. , Sharma R.S. , Manivannan B. , Kumar T.C. Anand
Published: September 2011

The reproductive exocrine and endocrine profiles in male langurs are reported with an emphasis on seasonality. The animals showed positive response to electroejaculation throughout the year. The sperm concentration varied between 10–383 × 106/ejaculation with wide fluctuations all through the year. No appreciable changes in the motility and percent live sperm were observed throughout the year. The levels of seminal fructose and magnesium remained unchanged throughout the year, while acid phosphatase showed wide fluctuations. Citric acid showed elevation during February and March and LDH showed elevated levels during April and May. The annual range of serum testosterone was 6–34 nMol/l with a peak during July. Cortisol ranged between 575–1587 nMol/l and prolactin ranged between 107–900 mU/l. Wide fluctuations were observed in hormonal levels. No seasonality was exhibited in the seminiferous tubule diameter, nuclear diameter of Sertoli cells and Leydig cells, and the cholesterol, glycogen, and sialic acid contents of testis. None of the parameters studied have shown any correlation with season. The results suggest that the male langurs lack seasonality in their reproductive exocrine and endocrine profiles and thus could be used as model for research in human reproduction.
Peptide immunization restimulates the memory CD4 T cell response but fails to induce cytotoxic T lymphocytes in cynomolgus monkeys
Authors: Mavoungou Elie , Toure Fousseyni S. , Yaba Philippe , Délicat André , Poaty‐Mavoungou Virginie
Published: September 2011

A potential strategy to induce peptide specific CTL in vivo was investigated. A synthetic vaccine consisting of an SIV‐derived, HLA‐A2.1‐binding CTL epitope and a tetanus toxin‐derived T helper epitope was evaluated for its capacity to induce peptide‐specific CTL in monkeys. Thirteen animals were immunized and boosted twice with 150 μg of CTL plus 250 μg of the T helper peptide (p30). Peripheral blood mononuclear cells (PBMC) were regularly analysed for cytotoxic and proliferative responses before, between, and after the immunizations, and the serum was tested for anti‐peptide antibodies. No unequivocal induction of SIV peptide‐specific CTL in any of the monkeys was observed. However, a wide pattern of mild and transient side reactions were observed, ranging from local redness at the injection site to generalized exanthema, myalgias, arthralgias, and fever. The side‐effects were related to the T helper epitope, as they were similar to the side‐effects experienced after tetanus immunization, correlated to the magnitude of the p30‐specific in vitro proliferative response, and occurred only if p30 was co‐injected. No antibody against the SIV‐derived peptides nor against p30 was detectable in the serum after repeated immunizations. The data suggest that the CTL peptide, at the concentration used in this study, failed to induce a cytotoxic immune response in vivo, although the T helper peptide seems to be capable of restimulating the specific memory T cells.
Sequence diversity of SIVMne Nef in vivo and in vitro
Authors: Heidecker G. , Muñoz H. , Lloyd P.A. , Hodge D.R. , Pei G.‐K. , Rick S.W. , Brehm K. , Ruscetti F.W. , Kuller L. , Polacino R. , Hu S.‐L. , Morton W.R. , Benveniste R.E.
Published: September 2011

Abstract: We have compared nef gene sequences isolated by PCR from peripheral blood lymphocyte DNA of macaques which had been inoculated with either biologically or molecularly cloned SIVMne. Two samples from each animal obtained either early after infection (week 2–8) or after significant CD4+ depletion (week 21–137) were analyzed. Three substitutions in the predicted Nef amino acid sequence were seen in all animals at the late time point, and two more in all but one. Two of the common exchanges are located about 40 residues apart in the Nef core sequence, but are in proximity on the tertiary structure as judged by computer modelling using the structure of the HIV Nef core protein as a guide. Most recurring in vivo changes replaced a residue found in the cloned Nef sequence with one present in a consensus derived by aligning the Nef sequences of the SIVsm/HIV‐2 groups. Animals inoculated with virus already containing the “late version” nef gene developed a more aggressive disease. The macaque adapted (MA)nef conferred a threefold higher infectivity to the cloned virus, but had no effects on CD4 downregulation. Propagation of virus with MAnef in tissue culture resulted in the rapid emergence of variants with newly attenuated nef. These findings suggest that the selective presssure on nef in vivo and in vitro are different.
Intracellular cytokine expression in the CD4+ and CD8+ T cells from intestinal mucosa of simian immunodeficiency virus infected macaques
Authors: Smit‐McBride Zeljka , Mattapallil Joseph J. , Villinger Francois , Ansari Aftab A. , Dandekar Satya
Published: September 2011

Abstract: Isolated intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) from jejunum of SIV infected animals were examined for alterations in basal cytokine expression by RT‐PCR. Remarkable changes in IFNγ and IL‐10 RNA levels were observed in IEL and LPL in SIV infection while IL‐4 and IL‐2 RNA levels remained unaltered. In addition, the CD4+ and CD8+ LPL were examined for intracellular cytokine production following mitogenic activation by flowcytometry. Both CD4+ and CD8+ T lymphocytes in intestinal mucosa retained the potential to produce IFNγ in response to mitogenic stimulation in vitro, without a remarkable change in IL‐4 production. The dominant IFNγ cytokine response could be one of the major contributing factors in SIV associated enteropathy.
Motor skill impairment in SIV‐infected rhesus macaques with rapidly and slowly progressing disease
Authors: Marcario Joanne K. , Raymond Leigh A.M. , McKiernan Brian J. , Foresman Larry L. , Joag Sanjay V. , Raghavan Ravi , Narayan Opendra , Cheney Paul D.
Published: September 2011

Abstract: A number of studies have shown that simian immunodeficiency virus (SIV) infection in rhesus macaques parallels many aspects of HIV disease in humans. The purpose of this study was to further characterize the rhesus macaque infected with neurovirulent SIV as a model of neuroAIDS. Using a motor skill task, our objective was to detect SIV‐related movement impairments in behaviorally trained macaques. The motor skill task required retrieval of a food pellet from a cup in a rotating turntable across a range of speeds. Nine monkeys were infected with neurovirulent strains of SIVmac (R71/17E); four monkeys served initially as controls pre‐inoculation. Seven monkeys developed simian AIDS within 4 months of inoculation (rapid progressors), and two survived more than 18 months post‐inoculation (slow progressors). Of the rapid progressors, five exhibited significant deficits in this task, most showing a gradual decline in performance terminating in a sharp drop to severely impaired levels of performance. One slow progressor (AQ15) showed no performance declines. The other slow progressor (AQ94) showed a significant decrease in maximum speed that was concurrent with the onset of clinical signs. For AQ94, the role of sickness behavior related to late stage simian AIDS could not be ruled out. These results demonstrate that motor system impairment can be detected early in the course of SIV infection in rhesus macaques, further establishing the SIVmac‐infected macaque monkey as a viable model of neuroAIDS.
8‐Methoxypsoralen photoadduct formation in complementary oligonucleotides containing a cross‐linkable site
Authors: Park J. , Amici L. , Gasparro F. P.
Published: September 2011

The complete profile of 8‐methoxypsoralen photoadduct formation in complementary oligonucleotides (5′‐GAGTATGAG and 5′‐CATAC) has been determined. Equimolar solutions of the oligonucleotides were irradiated at 4°C in order to stabilize the mini‐double helix. Photomodified oligonucleotides were separated by reversed phase chromatography on a Vydac C4 column. Photoadduct formation favored the 5′TAT site in the 9mer over the 5′ATA site in the 5mer by a factor of two. Split‐dose studies showed that the monoadducts formed on GAGTATGAG were preferencially converted to cross‐links by an additional UVA exposure.
Immunomodulation at the initiation of phototherapy and photochemotherapy
Authors: Guckian M. , Jones C. D. , Vestey J. P. , Cooper E. J. , Dawe R. , Gibbs N. K. , Norval M.
Published: September 2011

The numbers and function of circulating lymphocyte subsets are within normal ranges in patients with psoriasis and are not affected by 4 weeks of ultraviolet (UV) therapy, except for a suppression in natural killer (NK) cell activity. However, it is possible that immunomodulation might occur at the initation of phototherapy with a return to control values on more prolonged UV exposure. Thus, in this study the responses of 15 patients with chronic plaque psoriasis undergoing broad‐band UVB therapy, 10 narrow‐band (311–313 nm) UVB therapy and 10 PUVA therapy were compared. In each case, samples were taken immediately before starting treatment and 1 week later. Broad‐band UVB and PUVA therapy had no effect on NK activity, but a significant reduction was found in the group receiving narrow‐band UVB. In vitro lymphoproliferative responses to mitogens and to herpes simplex virus antigens did not alter with therapy, except there was a significant increase in mitogen responses (at optimal mitogen concentrations only) in the narrow‐band UVB group. Generally no alterations in overall percentages of circulating mononuclear cells were found in any group. Samples were taken from the epidermis of the forearm and back of the patients receiving narrow‐band UVB for the quantification of urocanic acid (UCA) isomers. The total UCA concentration remained unchanged after 1 week of therapy, while the percentage of cis‐UCA increased significantly at both sites in the majority of patients. However, this rise did not correlate with the decrease in NK cell activity and the two parameters may not be related causally.
Skin response to ultraviolet B light in patients infected with human immunodeficiency virus
Authors: Kaporis A. , Lim H. W. , Moy J. , Soter N. A. , Sanchez M.
Published: September 2011

Photosensitivity disorders have been reported in human immunodeficiency virus (HIV)‐infected patients, often as the initial manifestation of the disease. The objective of this study was to evaluate whether the HIV‐infected population demonstrates increased sensitivity to ultraviolet B (UVB) radiation. Minimal erythema dose values to UVB (MED‐B) of 57 consecutive HIV‐infected patients were compared to those of a control group of 57 consecutive patients with skin diseases, who were otherwise healthy and had no risk factors for HIV infection. MED‐B determinations were performed in all individuals prior to the initiation of phototherapy for treatment of skin disease. None of the patients had a history of photosensitivity. Furthermore, the mean levels of the highest UVB doses received by each group during the treatment courses were compared. The mean age of the HIV‐infected cohort was 43 years (range 26–61 years). The mean MED‐B for this group was 82.8±3.8 (SEM) mJ/cm2. The mean age of the control group was 45 years (range 24–77 years), and their mean MED‐B was 81.0±3.8 (SEM) mJ/cm2. After 12 weeks of treatment, one HIV‐infected patient developed photosensitivity associated with a decreased MED‐B value. The mean level of the highest UVB doses received by the HIV‐infected group [427.5±67.2 (SEM) mJ/cm2] was lower than that received by the control group [640.8±65.9 (SEM) mJ/cm2], since HIV‐infected patients received fewer treatments (mean: 34.7 treatments per patient) than the patients in the control group (mean: 65.6 treatments per patient). These data indicate that the HIV‐infected patient population, without history of photosensitivity, does not show increased sensitivity to UVB light as determined by MED‐B values.
Comparison of changes in endothelial adhesion molecule expression following UVB irradiation of skin and a human dermal microvascular cell line (HMEC‐1)
Authors: Rhodes L. E. , Joyce M. , West D. C. , Strickland I. , Friedmann P. S.
Published: September 2011

We have assessed the pattern of dermal endothelial adhesion molecule expression following broadband UVB irradiation in vivo and in vitro. Skin biopsies were taken from 4 human volunteers at baseline and at 4, 8 and 24 h post‐irradiation with 2.5 minimal erythema doses of UVB. Sections were stained immunohistochemically for E‐selectin, intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), CD31 and neutrophil elastase. The effect of direct UVB irradiation on E‐selectin, ICAM‐1 and VCAM‐1 was examined in a human dermal microvascular endothelial cell line, HMEC‐1. Cultured HMEC‐1 were irradiated with 2.5–40 mJ/cm2 of UVB, and assessed for adhesion molecule expression by immunofluorescence microscopy and fluorescence‐activated cell sorter analysis. In vivo, E‐selectin was minimally expressed on EC at baseline and was induced by 4 h following irradiation, P<0.01. ICAM‐1 was moderately expressed at baseline and appeared mildly induced at 24 h, although this did not reach statistical significance. VCAM‐1 was weakly expressed in unirradiated skin while CD31 was moderately expressed, but neither was induced by UVB irradiation. A significant neutrophilic infiltrate appeared by 8 h and was maximal at 24 h, P<0.05. Neutrophil infiltration correlated with E‐selectin expression, r=0.96. In HMEC‐1, ICAM‐1 was upregulated at 24 h post‐irradiation, with an increase in mean channel fluorescence from 100% at baseline to 145 (SD12)%> at 24 h, P<0.05. No change was seen in expression of E‐selectin, VCAM‐1 or CD31. These studies support the involvement of endothelial adhesion molecules E‐selectin and ICAM‐1 in UVB‐induced inflammation. Whereas ICAM‐1 is upregulated by direct irradiation of endothelial cells, E‐selectin stimulation appears to be an indirect effect.
Porphyria cutanea tarda and chronic lymphoid leukemia
Authors: Remenyik É. , Ujj G. , Kiss A. , Kószó F. , Horkay I.
Published: September 2011

A case of a familial porphyria cutanea tarda (PCT‐II) is reported in which the clinically overt form of PCT was provoked by factors relating to chronic lymphoid leukemia (CLL). Typical lesions of PCT developed on a 55‐year‐old woman after several blood transfusions and chlorambucil treatment. Besides these provoking factors, cytomegalovirus (CMV) infection was diagnosed. Erythrocyte uroporphyrinogen decarboxylase activity was about 50% of normal in the patient and in her two children. This case supports the suggestion that development of PCT in patients with hematological disorders is more than coincidental but may in fact be provoked by exogenous factors relating to the treatment of leukemia.
In vitro photoinhibition by psoralen and ultraviolet A radiation of human hematopoietic progenitors
Authors: Procaccini E.M. , Selleri C. , Monfrecola G. , Camera A. , Villa M. R. , Notaro R. , di Grazia C. , Posteraro G. , Rotoli B.
Published: September 2011

The in vitro sensitivity of human hematopoietic progenitors to PUVA, 8‐MOP and UVA alone was investigated. 8‐MOP alone at final concentrations of 150, 200, 600 and 1000 ng/ml did not modify colony growth of circulating and bone marrow erythroid (BFU‐E), myeloid (CFU‐GM) and immature (CFU‐GEMM) hematopoietic progenitors obtained from normal controls. The exposure of the same progenitors to increasing doses of UVA, up to 12 J/cm2, progressively decreased hematopoietic colony growth (with estimated 50% inhibition occurring at about 5 J/cm2). In vitro PUVA treatment (8‐MOP 200 ng/ml followed by UVA 5 J/cm2) caused 90% growth inhibition of circulating and bone marrow hematopoietic progenitors. In addition, the treatment completely inhibited the formation of spontaneous erythroid colonies, obtained from 5 polycythemic patients, that are considered to be a marker of this neoplastic disease. PUVA cytotoxicity was assessed by the colorimetric MTT assay. The percentage of cell death after PUVA exposure was 29 ± 10% for both peripheral and bone marrow mononuclear cells. Our findings indicate that 8‐MOP alone is not toxic to hematopoietic progenitors whereas UVA treatment determines in vitro a dose‐dependent inhibition of the clonogenic capacity of normal hematopoietic cells. PUVA treatment enhances this effect, causing a quite complete inhibition of hematopoietic progenitors colony formation from normal donors and spontaneous BFU‐E colony formation from polycythemic patients.
Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen‐induced phototoxic reactions as well as depletion of Langerhans cells in human skin
Authors: González S. , Pathak M. A. , Cuevas J. , Villarrubia V. G. , Fitzpatrick T. B.
Published: September 2011

Sunburn, immune suppression, photoaging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photoprotection, are helpful and can be achieved by topical sunscreening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo inmunomodulating properties. Its beneficial photoprotective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photoprotective property of natural extract of PL after topical application or oral ingestion. Twenty‐one healthy volunteers [either untreated or treated with oral psoralens (8‐MOP or 5‐MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD la‐expressing epidermal cells were also performed. PL was found to be photoprotective after topical application as well as oral administration. PL increased UV dose required for IPD (P<0.01), MED (P<0.001) and MPD (P<0.001). After oral administration of PL, MED increased 2.8±0.59 times and MPD increased 2.75±0.5 and 6.8±1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photoprotection of Langherhans cells by oral as well as topical PL. The observed photoprotective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photoprotection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such phototherapies.
Factors influencing the photo‐reproduction of hydroa vacciniforme lesions
Authors: Leroy D. , Dompmartin A. , Michel M. , Tack B. , Bravard P. , Louvet S.
Published: September 2011

Hydroa vacciniforme vesicles can be reproduced experimentaly with repetitive UVA irradiations, but this photo‐reproduction is not constant. The aim of this study was to search for the factors that influence photo‐reproduction. To reproduce hydroa vacciniforme lesions six patients underwent repetitive UVA and polychromatic irradiations on the back. In four patients out of six, UVA irradiation with high doses induced papulo‐vesicular lesions. Photo‐induced lesions were very close to those induced by sunlight. Photo‐reproduction failed when phototesting was done after or shortly before remission. Therefore, the absence of photo‐reproduction appears to be a good prognostic factor.
Human Pregnancy Serum Suppresses the Proliferative Response of Lymphocytes to Autologous PHA‐Activated T Lymphoblasts
Authors: Wolf‐Levin Ronit , Aoki Koji , Azuma Takachika , Yagami Yoshiaki , Okada Hidechika
Published: September 2011

PROBLEM: We have previously demonstrated that human serum can suppress the proliferative response in autologous mixed lymphocyte reaction (AMLR) in which phytohemagglutinin (PHA)‐activated T lymphoblasts act as stimulators (T‐TPHAAMLR). The aim of the present work was to determine whether pregnancy serum (PS) possesses an inhibitory capacity similar or different in magnitude.

METHODS: Sixteen PS were added to T‐TPHAAMLR cultures and the proliferative response was compared with that in the presence of human serum. The effect of PS on the IL‐2 dependent proliferation of PHA‐activated T Lymphoblasts was examined as well.

RESULTS: PS induced a significantly more pronounced suppression of T‐TPHAAMLR than human serum (P< 0.05). One PS tested was not inhibitory but rather stimulatory. This PS was obtained from a woman who subsequently had IUGR. The inhibition is related to the existence of a serum inhibitory factor and not to the lack of a serum supporting factor. PS inhibited not only T‐TPHAAMLR of the same woman but also T‐TPHAAMLR of other individuals as well, implying that the inhibitor is a non‐MHC restricted factor. IL‐2 dependent cell proliferation was not inhibited by PS, implying that the inhibitor detected in T‐TPHAAMLR is not a general cell proliferation inhibitor.

CONCLUSIONS: These results suggest that a non‐MHC restricted inhibitory factor present in PS may play an important biological role in regulating local immune responses in the fetal‐placental unit mediated by autoreactive T cells restricted to autologous activated T lymphocytes.