bluuebunny/crossref_metadata_2025 huggingface dataset:
A method for creating reversible ureteric obstruction in the primate
Authors: Evans J.P. , Candy G.P. , Veller M.G. , Esser J.D.
Published: September 2011

A technique has been developed for the establishment of a state of reversible, ureteric obstruction in the primate. Ten adult males had baseline 99mTc‐DTPA renogram studies. A randomly selected ureter was totally occluded and obstruction confirmed on renogram. The occlusion was reversed and subsequent renograms confirmed recovery of activity in the obstructed kidneys of the eight animals who survived the reversal procedure. Seven were alive on conclusion of the study. Prevention of ureteric strictures was achieved with an intra‐ureteric silastic tube. Autopsies demonstrated patency of every previously occluded ureter. This is the first study to be reported in primates, and the second overall, in which complete ureteric obstruction and its successful reversal has been confirmed on renogram using this surgical method. The technique is suitable for the study of the effect of reversible ureteric obstruction on renal function.
Experimental simian varicella virus infection of St. Kitts vervet monkeys
Authors: Gray Wayne L. , Williams Rhonda J. , Chang Ruixin , Soike Kenneth F.
Published: September 2011

Experimental simian varicella virus (SVV) infection of St. Kitts vervet monkeys was evaluated as an animal model to investigate human varicella‐zoster virus (VZV) infections. During the incubation period, viremia disseminated infectious virus throughout the body via infected peripheral blood lymphocytes (PBLs). A vesicular skin rash in the inguinal area, and on the abdomen, extremities, and face appeared on day 7–10 postinfection. Necrosis and hemorrhage in lung and liver tissues from acutely infected monkeys were evident upon histologic analysis. Recovery from simian varicella was accompanied by a rise in the serum neutralizing antibody response to the virus. SVV latency was established in trigeminal ganglia of monkeys which resolved the acute infection. This study indicates that experimental SVV infection of St. Kitts vervets is a useful animal model to investigate SVV and VZV pathogenesis and to evaluate potential antiviral agents and vaccines.
SIVMAC vaccine studies using whole inactivated virus antigen sequentially depleted of viral proteins
Authors: Norley Stephen , Beer Brigitte , König Herbert , Jensen Fred , Kurth Reinhard
Published: September 2011

Groups of four rhesus monkeys were immunised at 0, 1, 2, and 13 months with whole inactivated SIVmac32H, SIVmac depleted of the outer envelope glycoprotein gp130, virus cores depleted of the lipid membrane (and hence transmembrane glycoproteins), or purified gag protein. These macaques plus controls were challenged with either the homologous SIVmac251–32H. grown in human cells or the same virus passed once through monkey cells. None of those challenged with monkey‐grown virus were protected, whereas all in the whole and gp130‐depleted virus groups, and one in the core group resisted challenge with human‐grown virus. As the only difference between the challenge viruses was a single in vitro passage in monkey cells it can be concluded that protection was solely due to human cell components. Finally, passive transfer of high titer IgG from monkeys infected with the homologous challenge virus failed to protect monkeys from infection despite the presence of circulating neutralising antibodies.
To the Editor: Analysis on reactivity of human lymphocyte and monocyte‐specific antibodies with peripheral blood mononuclear cells from squirrel monkeys (Saimiri sciureus)
Authors: Garraud Olivier , Contamin Hugues , Perraut Ronald , Behr Charlotte , Gysin Jürg
Published: September 2011

A comment on the paper entitled: Flow cytometric analysis on reactivity of human T lymphocyte‐specific and cytokine‐receptor‐specific antibodies with peripheral blood mononuclear cells of chimpanzee (Pan troglodytes), rhesus macaque (Macaca mulatto), and squirrel monkey (Saimiri sciureus). Ozwara et al., J Med Primatol 26:164–167, 1997.
Spontaneous hyperthyroidism in an aged male and femaleMacaca mulatta
Authors: Brammer David W. , Juneau Paul L. , Chrisp Clarence E. , O'Rourke Christine M. , Altrogge Doug M. , Peter Gregory K. , Hofing Gary L.
Published: September 2011

Abstract:A 31‐year‐old male and a 31‐year‐old female rhesus monkey developed clinical signs consistent with hyperthryoidism. These included a ravenous appetite, hyperactivity, and accentuated ratchet movement and hand tremors while performing fine motor tasks. Bilaterally enlarged thyroid glands were palpated in both monkeys. A unique clinical finding of the female as the hypertrophic cardiomyopathy. The T3 and T4 levels in the male rhesus were 3.79 ng/ml and 28.20 μg/dl, respectively. T3 and T4 levels in the female were 4.33 ng/ml and 22.2 μg/dl, respectively. A biopsy of the enlarged thyroids demonstrated a typical multinodular goiter with cystic hyperplasia. The female rhesus was successfully treated with methimazole, but the hypertrophic cardiomyopathy did not resolve. The relationship between erythrocytosis and T4 levels common to humans and cats is also evident in the rhesus monkey.
Study of prenatal growth in the capuchin monkey (Cebus apella) by ultrasound
Authors: Corradini P. , Recabarren M. , Serón‐Ferré M. , Parraguez V.H.
Published: September 2011

Abstract: Capuchin monkey (Cebus apella) is a new world primate that in recent years has become important in biomedical research. The purpose of this study was to establish and correlate normal fetal growth parameters with gestational age in capuchin monkeys. In seven pregnant animals serial ultrasonic assessment of gestational sac (GS), embryo/fetal greatest length (GL), biparietal diameter (BPD), thorax height (TH), and femur length (FL) were performed. Identification of the GS was possible on day 23 ± 2.8 (X ± SE). The embryo and its heartbeat was detected on day 32.7 ± 2.8, the GL being measurable thereafter. By day 45.4 ± 1.4 BPD and TH were measurable. FL could only be measured from day 70.6 ± 2.1. Predictive regression equations of gestational age (GA) were modeled with data obtained. In addition, preliminary data of fetal heart rate showed a decrease in frequency with advancing gestation.
Review of exertional rhabdomyolysis and a case in a rhesus monkey (Macaca mulatta)
Authors: Reuter Jon D. , Dysko Robert C. , Chrisp Clarence E.
Published: September 2011

Abstract:This is the first confirmed report of exertional rhabdomyolysis in a non‐human primate. The monkey was singly housed and presented with anorexia and reluctance to move. There was no external evidence of trauma. Clinicopathologic findings included mild azotemia, marked elevation in serum creatine phosphokinase (CPK), alanine aminotransferase, aspartate aminotransferase, and myoglobinuria. Two days post‐incident, the peripheral skeletal muscle had marked multifocal myonecrosis and fibrillar disruption without an inflammatory reaction. Treatment included diuresis and pain relief, and urinary output was monitored. The monkey recovered over the next two weeks. The major significance of skeletal muscle damage is the potential of released myoglobin to cause acute renal failure in the presence of other co‐factors such as hypovolemia, acidosis, or ischemia. CPK levels can be highly variable and are inconsistent with the degree of muscle damage; however, CPK is thought to be the most sensitive enzyme marker for muscle necrosis. Because of the potential life‐threatening sequelae, exertional rhabdomyolysis should be included as a differential diagnosis when similar clinical and pathological signs are observed.
Presence of circulating CTL induced by infection with wild‐type or attenuated SIV and their correlation with protection from pathogenic SHIV challenge
Authors: Vogel Thorsten U. , Fournier Jocelyn , Sherring Alice , Ko Doreen , Parenteau Monique , Bogdanovic Dragica , Mihowich Jennifer , Rud Erling W.
Published: September 2011

Abstract: The aim of this study was to evaluate the role of CTLs in the protection from challenge with pathogenic SHIV in macaques vaccinated with attenuated virus. More specifically, we have analyzed the CTL response in cynomolgus macaques vaccinated/infected with the attenuated SIVmacC8 or the wild‐type SIVmacJ5 and correlated these responses to the protection from SHIV89.6P challenge. SIVmacC8‐vaccinated monkeys demonstrated a broader CTL response than the SIVmacJ5‐infected animals. Nevertheless, CTL against some proteins in SIVmacC8‐vaccinated monkeys became progressively more difficult to detect through the day of challenge. In regards to protection from superinfection with SHIV89.6P, neither the presence of circulating CTL nor the CTL precursor frequency against any of the tested proteins correlated with the outcome of the challenge when SIVmacJ5‐ and SIVmacC8‐infected animals were analyzed together. By analyzing the SIVmacC8‐vaccinated animals separately, only the protected animal had detectable CTL precursors with moderate frequencies against all three tested proteins at the day of challenge.
In vitro HIV‐1 infection in Macaca nemestrina PBMCs is blocked at a step beyond reverse transcription
Authors: Kimball Louise E. , Bosch Marnix L.
Published: September 2011

Abstract: Various stages in the lifecycle of HIV‐1 were investigated in Macaca nemestrina and humans in vitro. Early events were analyzed by end point dilution DNA PCR with HIV‐1 and SHIV infected PBMCs, while p24 and p27 ELISA assays were used to analyze core antigen production from infected cells. The results demonstrate that a step in the virus life cycle, beyond reverse transcription is blocked for HIV‐1 infection in macaque cells.
Down‐modulation of the ZAP‐70 protein tyrosine kinase in macaque T lymphocytes infected with SIVsmmPBj14
Authors: Thai To‐Ha , Fultz Patricia N.
Published: September 2011

Abstract: The simian immunodeficiency virus SIV‐PBj14 is the most virulent primate lentivirus identified to date. Other SIV strains, including the parental SIVsmm9, require mitogen‐activated peripheral blood mononuclear cells (PBMC) for replication in vitro; however, SIV‐PBj14 replicates in quiescent pig‐tailed macaque PBMC and induces cellular proliferation, consistent with its in vivo pathogenesis. To identify mechanisms involved in SIV‐PBj14‐induced T‐cell proliferation, kinases important in early T‐cell receptor‐mediated activation pathways were studied. Immunoblot analyses showed that ZAP‐70 protein, a tyrosine kinase, was downregulated, primarily in CD8+ T cells, as early as 30 minutes after in vitro infection of quiescent macaque PBMC with SIV‐PBj14. Furthermore, this downregulation required the presence of either CD4+ T cells or adherent cells or both cell populations. In agreement with the in vitro results, ZAP‐70 expression was downregulated in macaque PBMC, spleen, and rectal lymph node cells as early as 2 days after rectal inoculation of pig‐tailed macaques with SIV‐PBj14. This phenomenon, however, was not observed in cells obtained from distal lymph nodes to which the virus had not disseminated, implying that the presence of SIV‐PBj14 is necessary to induce downregulation of ZAP‐70.
The absence of a triphasic renovascular response by the multicalyceal kidney of the primate in reaction to acute, complete, unilateral, ureteric obstruction
Authors: Evans J.R , Rogers G.G.
Published: September 2011

The early renovascular response by the ipsilateral kidney to acute, total, unilateral, ureteric obstruction was investigated in the adult male chacma baboon (Papio ursinus). Complete occlusion was effected by ligating the ureter at the brim of the bony pelvis (“N” = 10). Sham studies were enacted using the same method but the ureter was not obstructed (“N” = 11). Haemodynamic reactions were monitored for 12 hours. Compared with the sham‐occluded set, the renal pelvic pressures in the obstructed group were significantly increased (P < 0.05) from the second hour of the inquiry. However, there were no significant differences in renal blood flow, either between or within the respective cohorts.

In this study, the renovascular response to acute ureteric occlusion was similar to that displayed by the multicalyceal kidney of other species under identical conditions. This reaction was fundamentally different to that exhibited by the unicalyceal kidney under similar circumstances.
Telomere dynamics in monkeys: Increased cell turnover in macaques infected with chimeric simian‐human immunodeficiency viruses
Authors: Shibata Riri , Feng Yan‐Ru , Gee Dennis , Norwood David , Xiao Xiaodong , Zeichner Steven L. , Martin Malcolm A. , Dimitrov Dimiter S.
Published: September 2011

Abstract: To address the question of how cell turnover is affected by retroviral infections, we used the telomeric terminal restriction fragments (TRFs) as markers of cell replicative history and measured their length in macaques infected with chimeric simian‐human immunodeficiency viruses (SHIVs). The TRF lengths of mononuclear cells in 104 samples, including longitudinal samples from nine cynomolgus and ten pig‐tailed macaques infected with SHIV, and in samples from 26 uninfected macaques, were quantitated by an improved method, based on two‐dimensional calibration of DNA sizes, pulsed field electrophoresis, and high‐resolution Southern blot images. The average TRF lengths of peripheral blood mononuclear cells (PBMCs) from uninfected pig‐tailed (14.9 ± 1.6 kbp) and cynomolgus (14.1 ± 1.8 kbp) macaques were about 3 and 5 kbp longer than those of human infants and 30‐year‐old adults, respectively. The rate of TRF length shortening in infected pig‐tailed macaques was significantly (P = 0.035) higher (2.2‐fold) than in uninfected monkeys. The TRFs in SHIV‐infected cynomolgus monkeys, which, in general, had lower viral loads than pig‐tailed macaques, shortened on average more rapidly (1.6‐fold) than in uninfected animals, but the difference was not statistically significant. The TRFs of mononuclear cells from the lymph nodes of two rapidly progressing SHIV‐infected macaques that developed AIDS and died also shortened in parallel but somewhat more rapidly than in the PBMCs. These results suggest that the rate of PBMC turnover in macaques could be increased several‐fold during infections by immunodeficiency viruses, likely due to immune activation by SHIV antigens.
Presence of platelet‐activating factor in rhesus (Macaca mulatta) spermatozoa
Authors: Diaz Eneida , Szeto Ada C. , Roudebush William E.
Published: September 2011

Abstract: Platelet‐activating factor [1‐O‐alkyl‐2‐acetyl‐sn‐glycero‐phosphocholine; PAF] is a unique signaling phospholipid which has been implicated in a number of biological activities (e.g., reproduction). PAF has been detected in the spermatozoa from a number of laboratory and domestic species, including, but not limited to, rabbit, bovine, and the mouse. The concentration of PAF is inversely related to human (Homo sapien) spermatozoal quality. Additionally, PAF levels are significantly higher in Bolivian squirrel monkey (Saimiri sciureus) spermatozoa obtained during the breeding season than spermatozoa obtained during the nonbreeding season. There are no reports on the presence of PAF in rhesus (Macaca mulatta) spermatozoa. Therefore, the primary objective of this study was to detect the presence of PAF in rhesus spermatozoa. A second objective was to determine if PAF spermatozoa levels differ between animals housed individually (single‐caged) versus free‐ranging (open corrals). Semen were collected from mature rhesus via electro‐ejaculation. Spermatozoa were washed free of ejaculatory plug and quick frozen in PBS. Endogenous lipids were extracted from thawed spermatozoa and ejaculatory plugs then assayed for the presence of PAF by [125I]‐radioimmunoassay. PAF was not detected in any ejaculatory plugs. PAF levels were significantly higher (P < 0.01) in spermatozoa obtained from free‐ranging males (mean: 1.16 pmol/106 spermatozoa) than males housed individually in single cage units (mean: 0.53 pmol/106 spermatozoa). PAF was present in rhesus spermatozoa. Additionally, PAF levels were higher in spermatozoa obtained from corral‐housed animals. Additional studies are warranted to elucidate the role of PAF in spermatozoa function.
Spontaneous pericardial mesothelioma in a rhesus monkey
Authors: Chandra Manik , Mansfield Keith G.
Published: September 2011

Abstract: Spontaneous tumors in nonhuman primates are of great importance. A spontaneous pericardial mesothelioma was observed in an 18‐year‐old female rhesus monkey. Grossly, the visceral pericardium was multifocally irregular and thickened with tan discoloration and was soft in consistency. Histologically, the pericardium contained highly infolded branching fronds lined by a single layer of cuboidal cells. Tumor invaded into approximately half of the thickness of the atrial and ventricular muscles. Tumor penetration was not observed into the atrial or ventricular cavity. Within the myocardium, neoplastic cells formed glandular structures which were lined by cuboidal to columnar cells. Neoplastic cells were weakly positive with PAS and strongly positive for colloid iron and alcian blue. Immunohistochemically, neoplastic cells were positive for both vimentin and cytokeratin and negative with CEA and Leu‐M1, indicating mesothelial origin. To the best of the authors' knowledge, this is the first report of a spontaneous pericardial mesothelioma in a rhesus monkey.
Antigen‐specific cytokine responses in vaccinated Macaca nemestrina
Authors: Mulvania Thera , Lynch John B. , Robertson Michael N. , Greenberg Philip D. , Morton William R. , Mullins James I.
Published: September 2011

Abstract: We describe a new surrogate assay for CD8 + T lymphocyte activity that has the capability of discriminating between cytotoxic T lymphocyte (CTL) activity and cytokine‐mediated suppressive activity. We applied this approach to two groups of Macaca nemestrina vaccinated with a minimally pathogenic strain of human immunodeficiency virus type 2 [HIV‐2 (HIV‐2KR)] as a model of an attenuated virus vaccine. Group 1 was then inoculated with a non‐infectious stock of a pathogenic strain, HIV‐2287. Both groups 1 and 2 were subsequently challenged with an infectious stock of HIV‐2287. Five out of six group 1 animals were protected against CD4 decline, whereas three out of six animals in group 2 were protected. Analysis of CTL responses demonstrated strong activity against HIV‐2KR‐Gag in group 1. It was determined that strong CTL responses correlate with antigen‐specific T‐helper (Th) type 1 responses. This antigen‐specific cytokine assay has the potential to better elucidate the functional mechanisms of CD8 + T‐cell‐mediated protection than traditional methods to date.
Immunization against SIVmne in macaques using multigenic DNA vaccines
Authors: Mossman Sally P. , Pierce Christopher C. , Robertson Michael N. , Watson Andrew J. , Montefiori David C. , Rabin Michael , Kuller LaRene , Thompson Jannelle , Lynch John B. , Morton William R. , Benveniste Raoul E. , Munn Robert , Hu Shiu‐Lok , Greenberg Philip , Haigwood Nancy L.
Published: September 2011

Abstract: All structural and regulatory genes of SIVmne were cloned into mammalian expression vectors to optimize expression in vitro and immunogenicity in mice. Macaca fascicularis were immunized four times with plasmid DNA (n = 4), or two DNA priming inoculations followed by two boosts of recombinant gp160 plus Gag‐Pol particles (n = 4). Following intrarectal challenge with SIVmne, all macaques became infected. Three monkeys immunized with DNA alone maintained low plasma virus loads by 1 year post‐challenge; the fourth exhibited high virus loads and significant CD4 + cell decline. Two of the DNA plus boost and three control macaques had high virus loads and associated CD4 + cell decline. Both vaccine protocols elicited antibodies and comparable helper T‐cell proliferative responses to gp160. Cytokine mRNA levels in activated peripheral blood mononuclear cells (PBMC) taken at time of challenge suggested a dominant T helper (Th) 1 state in three DNA‐immunized and one protein‐boosted macaque, which correlated with low virus loads and high CD4 + cell counts post‐challenge.
Detection of simian immunodeficiency virus (SIV)‐specific T‐cell‐mediated cytotoxicity in the peripheral blood from infected cynomolgus monkeys
Authors: Mavoungou Elie , Touré Fousseyni S. , Yaba Philippe , Sall Aïcha , Délicat André , Poaty‐Mavoungou Virginie
Published: September 2011

Abstract: We have previously demonstrated that peptide immunization restimulates the memory CD4 T‐cell response, but fails to induce cytotoxic T lymphocyte (CTL) in cynomolgus macaques. To examine the nature of protective immunity to simian immunodeficiency virus (SIV) in this study, freshly isolated peripheral blood mononuclear cells (PBMC) from four infected juvenile cynomolgus macaques and from three uninfected control macaques were assessed for CTL activity monthly for 9 consecutive months, beginning 1 month after detection of infection. Target cells consisted of major histocompatibility (MHC) haploidentical parental PBMC which were stimulated with mitogen and then pulsed with heat‐killed SIVcyn. CTL activity was demonstrated in PBMCs from all four infected animals. The effector cells are T cells which mediate cytotoxicity against SIVcyn‐pulsed target cells in an MHC‐restricted manner. Furthermore, the cytotoxicity is virus specific and predominantly, if not exclusively, mediated by CD8 + T cells; it is also MHC class I restricted. Incubation of target cells with pepstatin A during antigen pulsing prior to the cytotoxic assay inhibited target cell generation, suggesting that viral antigens are processed via an endocytic pathway.
Morphologic and immunophenotypic characteristics of malignant lymphomas in SIV‐infected rhesus macaques
Authors: Mätz‐Rensing K. , Pingel S. , Hannig H. , Bodemer W. , Hunsmann G. , Kuhn E.‐M. , Tiemann M. , Kaup F.‐J.
Published: September 2011

Abstract: Eight cases of extranodal non‐Hodgkin's lymphoma in simian immunodeficiency virus (SIV)‐infected rhesus macaques, aged 4–9 years, were phenotypically and immunologically characterized, using the updated Kiel classification, in order to determine both the differences and the similarities between these types of lymphoma in immunodeficient rhesus macaques (Macaca mulatta) and man. The high‐grade malignant tumors were of B‐cell origin, with a predilection for extranodal growth in viscera and periorbital tissues. Immunophenotypical characterization showed that the monkey lymphomas were similar in many aspects to human immunodeficiency virus‐associated lymphomas. The number of Ki67 positive cells varied from case to case and ranged from 50 to 90%. A serological screening for the simian equivalent of the Epstein–Barr virus (sEBV) by immunofluorescence assay revealed a prevalence of 92% of the sEBV antibodies in our cohort. The presence of Ebstein–Barr virus nuclear antigen (EBNA‐2) could be demonstrated by immunohistochemistry in four out of eight cases. In situ hybridization revealed the presence of small EBV‐encoded RNAs (EBER‐1, EBER‐2) in six of the eight cases. Further studies should define the precise role of herpesvirus infection for lymphomagenesis in SIV‐induced immunodeficiency.
The effect of dietary protein on the mineral status of vervet monkeys with special reference to the impact of milk solids on calcium excretion
Authors: Johnson Q. , Veith W.J. , Aalbers J.
Published: September 2011

Abstract: This study assessed the impact of Westernised and traditional African diets on mineral metabolism in general and calcium status in particular in vervet monkeys. Twelve adult male vervet monkeys (Cercopithecus aethiops), with an average weight of 5 ± 0.58 kg each, were divided into two groups of six individuals each and fed traditional diets containing largely maize + legumes (17.4%) or Westernised diets containing milk solids (17.2%) as the source of high crude protein for 8 weeks. Blood was taken at 2‐week intervals, the animals were weighed, while urine and stool samples were collected over 24 hours. The monkeys on the milk solids diet had diarrhoea for 6 weeks post‐dietary intervention, and produced significantly greater quantities (P < 0.02) of stool. These animals also produced significantly more urine (P < 0.02). There was no difference in the degree of calciuresis of the two groups, but the monkeys on maize + legume proteins absorbed significantly more calcium during weeks two and six (P < 0.04). Furthermore, both groups of monkeys showed a significant decline in plasma calcium levels over the experimental period (P < 0.001). The diets had no effect on phosphate levels in the plasma or urine. However, both groups of animals absorbed less phosphate (P < 0.09). There was an increasing loss of urinary magnesium (P = 0.03) in both groups, with the milk solids group showing lower plasma levels of this element (P = 0.09). However, the milk solids group lost less magnesium through the stool (P < 0.03). In addition, the animals on milk solids showed significant natriuresis (P < 0.05), while plasma sodium levels in both groups declined over time (P < 0.03). Both diets induced a state of urinary potassium loss (P = 0.0003) and decrease in plasma potassium (P < 0.0002). Urinary pH and plasma urea were unaffected by the diets, but the monkeys on maize + legumes excreted significantly less (P < 0.001) urinary urea. This study indicates that the milk solids diet compromised mineral homeostasis by interfering with gut and renal functioning, while the traditional African diet did not induce these effects.
In vivo estimation of pigmentation in ultraviolet‐exposed hairless mice
Authors: Hansen A. B. , Bech‐Thomsen N. , Wulf H. C.
Published: September 2011

A new in vivo method of visual scoring of pigmentation in hairless hr/hr mice with a C3H/Tif background is described. The mice were placed under a bank of 6 Philips TL08 fluorescent ultraviolet A (UVA) tubes in a dark room, and the pigmentation of the skin was compared with a Kodak Gray Scale with 20 different shades from white to black. The radiation from the tubes changed both the color of the back of the mouse and the gray scale into purple hues. The purple color of the back of each mouse could then be classified as one of 20 shades on the gray scale. An experiment was conducted exposing 3 groups of 20 mice to different doses of UV radiation from Philips TL01 tubes. One group of 20 mice was not irradiated and served as control. The pigmentation of each mouse was scored by one investigator every 2–3 weeks. After a few weeks of exposure a clear distinction between the groups was seen. To evaluate the inter‐ and intrapersonal variation of the method, 30 mice with various degrees of pigmentation were scored independently and blindly by two investigators. This was done twice during the study with a few days' interval. No interpersonal difference was found, but one investigator scored differently the first and second time by only 0.5 points. The described method provides a reproducible in vivo method, with very good discrimination, for estimation of pigmentation in hairless mice.
Recurrent recall of sunburn by methotrexate
Authors: Guzzo C. , Kaidby K.
Published: September 2011

An unusual recall reaction of sunburn with methotrexate use has been previously reported. Heretofore, all reports have documented a single occurrence of this reaction in each patient. We report, for the first time, a patient who developed recurrent facial sunburn recalls while receiving methotrexate for psoriasis. This reaction is distinct from true photosensitivity. Photosensitivity is listed in the drug brochure for methotrexate. However, a review of the literature does not support true photosensitivity associated with methotrexate.
Two cases of mequitazine‐induced photosensitivity reactions
Authors: Kim T. H. , Kang J. S. , Lee H. S. , Youn J. I.
Published: September 2011

Mequitazine is a phenothiazine derivative antihistamine. We experienced 2 cases of mequitazine‐induced photosensitivity reaction in patients who took mequitazine for their dermatologic problems. Case no. 1 showed features of photoallergy such as 1‐month incubation period, decreased MED to UVA, strong positive photopatch test result, cross reaction to chlorpromazine, and angry back phenomenon found in allergic contact dermatitis. In addition, an immediate erythematous macule was observed on the photopatch test site of mequitazine directly after UV exposure which was similar to the immediate erythema noted in chlorpromazine photoallergy. During the follow‐up period of two months, there was transiently decreased MED to UVB, which became normalized after 1 month treatment with cyclophosphamide. In case no. 2, the pathogenic mechanism seemed to be persistent light reaction preceded by systemic photoallergy, as he had taken mequitazine for 6 months, and there were strong positive photopatch test results with immediate erythema reaction, cross‐reaction to promethazine, decreased MED to both UVA and UVB, and persistence of the photosensitivity over a 3‐year follow‐up period after discontinuation of the mequitazine. Photopatch tests to 1% mequitazine with 5 J/cm2 of UVA in 30 normal subjects were all negative, which means that 1% concentration may be appropriate for the photopatch test. Mequitazine seemed to play a part similar to chlorpromazine, and absence of mequitazine‐induced photosensitivity may be due to a relatively low dosage of the drug. However, dermatologists should be cautious about a photosensitivity reaction induced by mequitazine or other phenothiazine‐derivative drugs.
Photoprotection due to pigmentation and epidermal thickness after repeated exposure to ultraviolet light and psoralen plus ultraviolet A therapy
Authors: Bech‐Thomsen N. , Wulf H. C.
Published: September 2011

Tanning and thickening of the epidermis are cardinal defensive responses of human skin to ultraviolet (UV) radiation that lead to increased photoprotection. Earlier studies have shown that skin pigmentation can be used to predict minimal erythema dose and minimal phototoxic dose. In this study it was calculated how much of the increase in photoprotection after 4 weeks of repeated exposure to suberythemogenic doses of either UVA or UVB radiation sources or psoralen plus UVA (PUVA) therapy that was attributable to melanogenesis. The backs of 12 volunteers were exposed to 6 different UVA and UVB radiation sources 9 times during 4 weeks. Skin pigmentation was assessed by skin reflectance measuring. Photoprotection was determined from the minimal erythema dose. Melanogenesis accounted for 63–95% of the increase in photoprotection after 4 weeks of exposure to UVA radiation. Exposure to two UVB sources induced a significant increase in photoprotection but not in pigmentation. Melanogenesis accounted only for 6–11% of the increase in photoprotection after 4 weeks of UVB exposure. The pigmentary and photoprotective responses to PUVA therapy were followed in 14 patients. After 2 weeks of exposure, the increase in photoprotection was significantly higher than predicted from the increase in skin pigmentation. After 4 weeks, melanogenesis accounted for only 36% of the increase in photoprotection. This study shows that melanogenesis accounts for the increased photoprotection after 2 weeks of exposure to UVA radiation, but after 4 weeks other protective mechanisms occur. During suberythemal UVB exposure and during PUVA therapy the importance of skin pigmentation in the overall photoprotection gradually decreases during a 4‐week irradiation period.
Photodegradation products of sulphonamide‐derived oral antidiabetics and diuretics are not phototoxic in vitro
Authors: Selvaag E. , Thune P.
Published: September 2011

The oral antidiabetics glibenclamide and glipizide, and the diuretics bendroflumethiazide and furosemide, all sulphonamide derived drugs, were investigated in vitro for phototoxic properties. Irradiation with broad‐band UV induced phototoxic inhibition of colony forming ability in cell cultures. During irradiation, the substances lost one absorption maximum in the UVA region, demonstrated by UV spectroscpoy. These findings correlate well with the UV applied, the action spectrum being in the UVA region. Photoproducts detected during and after irradiation showed a decomposition of the substances due to ionization and fragmentation. Incubation of these preirradiated drugs with the cell cultures revealed no phototoxic effects.
Ultraviolet radiation B induces differentiation and protein kinase C in normal human epidermal keratinocytes
Authors: Matsui M. S. , Wang N. , DeLeo V. A.
Published: September 2011

Mid‐wave ultraviolet radiation (UVB, 280–320 nm) is highly efficient at inducing erythema, pyrimidine dimers in DNA, oncogene expression and initiation of cutaneous tumors. These UVB‐induced responses of epidermal cells have been correlated with the direct effects of UVB on DNA. However, UVB has also been shown to have biologic effects at the cellular level that appear to mimic some of the membrane‐associated effects produced by phorbol ester tumor promoters such as 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA). For example, we have previously shown that both UVB irradiation and TPA treatment are followed by release of arachidonic acid and a rapid, dose‐dependent inhibition of epidermal growth factor (EGF) binding. TPA generates cellular responses through activation of a phospholipid‐dependent, calcium‐sensitive protein kinase, protein kinase C (PKC). The primary goal of the studies described here was to compare the cellular effects of TPA with those of UVB with special regard to PKC and keratinocyte growth control, using normal human epidermal keratinocytes. The results obtained showed that both TPA and UVB radiation induced differentiation in normal human keratinocytes. UVB radiation, however, increased both cytosolic and membrane‐associated levels of PKC, in contrast to TPA, which increased PKC primarily in the membrane fraction. PKC is probably not the initial chromophore or target molecule of UVB, but because activation of PKC has been shown to be essential for keratinocyte differentiation, differentiation induced by UVB may be caused by activation of PKC by UVB‐induced release of diacylglycerol or arachidonic acid.
Interaction of ultraviolet‐B‐rich and ultraviolet‐A‐rich radiation in ketoprofen‐induced photohemolysis
Authors: Eberlein‐König B. , Rueff F. , Przybilla B.
Published: September 2011

Interactions between different wavelengths can cause inhibition or enhancement of various biological reactions. We evaluated in vitro the effect of UVB‐rich irradiation on UVA‐induced phototoxicity. Suspensions of human erythrocytes were incubated with ketoprofen, a phototoxic nonsteroidal anti‐inflammatory drug. These samples were exposed to 0, 20, 40, 80, 160 or 320 mJ/cm2 UVB followed by irradiation with 0 or 6 J/cm2 UVA. Photo‐induced hemolysis was calculated as a percentage of complete hemolysis. Ketoprofen‐dependent hemolysis due to UVA alone was 63% (median). UVB did not induce ketoprofen‐dependent photohemolysis at doses <80 mJ/cm2. Exposure to UVB at all doses enhanced significantly (P<0.01) UVA‐induced ketoprofen‐dependent hemolysis in samples from 9 of 15 donors. However, with erythrocytes from the other 6 donors, 20 or 40 mJ/cm2 UVB reduced the median of UVA‐induced photohemolysis by 69% (P<0.05) or 47% (not significant), respectively. Co‐incubation of samples with ascorbic acid resulted in a profound inhibition of ketoprofen‐dependent photohemolysis. These results indicate that the effect of low UVB doses on UVA‐induced phototoxicity depends on individual, yet unknown characteristics of the target cells.
Skin temperature and phototest evaluation
Authors: Gniadecka M. , Lock‐Andersen J. , de Olivarius F. Fine , Wulf H. C.
Published: September 2011

The degree of erythema following UV irradiation is known to depend upon skin temperature at the time of UV exposure. We investigated whether changes in skin temperature at the time of erythema assessment influenced the level of erythema. Twenty‐two healthy people (mean age 26 years) were irradiated with solar simulated radiation on previously UV un‐exposed buttock skin. The erythematous reactions were evaluated 20–24 h after irradiation by visual scoring and by measurements of skin reflectance and laser Doppler flowmetry. The readings were done at the baseline level at 21°C room temperature where skin temperature was 30.0±1.7°C and subsequently after skin warming to 37.2±2.5°C and after cooling to 22.8±2.6°C. After skin warming, a clinically evaluated erythema grade [0, (+), +, + +, +++] was scored higher for at least one reaction in 10 of 22 individuals (45%). In the same proportion of subjects, changes to lower erythema grades were detected upon cooling. Skin warming caused an increase in laser Doppler blood flux, but skin cooling did not have a significant effect on cutaneous perfusion. Skin redness measured by skin reflectance was relatively stable during the cooling phase, but a significant increase in skin redness was noted for 0 reaction upon skin warming. For + + and + + + reactions a small but significant decrease in reflectance was noted. Our results indicate that alterations in skin temperature, especially a temperature increase, modulates the degree of UV‐induced erythema moderately. The temperature‐dependent changes as an assessment of the (+) reaction are of practical significance, since this reaction is used for the assessment of cutaneous photosensitivity.
The effect of L‐cysteine and N‐acetylcysteine on porphyrin/heme biosynthetic pathway in cells treated with 5‐aminolevulinic acid and exposed to radiation
Authors: He D. , Behar S. , Roberts J. E. , Lim H. W.
Published: September 2011

The effects of L‐cysteine (LC) and N‐acetylcysteine (NAC) on porphyrin accumulation in a human dermal microvascular endothelial cell line (HMEC‐1) and a human epidermoid carcinoma cell line (A431) loaded with 5‐aminolevulinic acid (ALA) and exposed to ultraviolet A (UVA) and blue light radiation were determined. Porphyrin accumulation was decreased in the presence of 0.1–7.5 mM LC (24.8%‐31.4% suppression in HMEC‐1 cell; 35.8%‐48.9% suppression in A431 cells), and in the presence of 0.1–10.0 mM NAC (30.9%‐58.0% suppression in HMEC‐1 cells; 8.5%‐45.3% in A431 cells). The suppression occurred in a LC or NAC dose‐dependent fashion. The above was associated with partial reversal of suppression of ferrochelatase (FeC) activity in HMEC‐1 cells and in A431 cells. As compared to FeC activity in cells treated with ALA and irradiation, enzyme activity was higher (by 31.9%‐62.1%) in the presence of LC (1.0 mM or 5.0 mM) and in the presence of NAC (1.0 mM or 5.0 mM). These data indicate that LC and NAC have protective effects on porphyrin‐ and irradiation‐induced diminution of FeC activity in HMEC‐1 cells and A431 cells in vitro.
Inhibition of thiazide photohemolysis in vitro by antioxidants and a nitrogen atmosphere
Authors: Selvaag E.
Published: September 2011

The diuretics acetazolamide, bemetizide, bendroflumethiazide, benzthiazide, benzylhydrochlorothiazide, bumetanide, butizide, chlorazanile, chlorothiazide, chlortalidone, clopamide, cyclopenthiazide, cyclothiazide, diazoxide, etozoline, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, mefruside, metolazone, piretanide, polythiazide, trichlormethiazide, and xipamide were screened in vitro for phototoxic effects by means of a photohemolysis test. In all, 19 out of the 25 test substances revealed phototoxic hemolytic properties after irradiation with either solar simulating irradiation, UVA and/or visible light. Addition of the antioxidants ascorbic acid, alpha‐tocopherole or superoxide dismutase significantly inhibited the phototoxic hemolysis, as well as did investigations carried out in a nitrogen rich atmosphere, findings which indicate the involvement of reactive oxygen species in the phototoxic process.
Photodermatitis from ketoprofen with cross‐reactivity to fenofibrate and benzophenones
Authors: Leroy D. , Dompmartin A. , Szczurko C. , Michel M. , Louvet S.
Published: September 2011

The aim of this study was to evaluate the possibility of cross‐reactivity between ketoprofen, fenofibrate and benzophenones because of their structural similarities. Seven patients presenting Photodermatitis from ketoprofen underwent patch and photopatch tests. Ketoprofen, fenofibrate, benzophenone 3, benzophenone 10, benzophenone 4, personal medications and topical creams were tested. All patients had positive patch or photopatch tests to ketoprofen and fenofibrate, four patients had positive UVA photopatch tests to benzophenone 3, and two to benzophenone 10. Patients presenting photosensitization to ketoprofen may also have cross‐reactivity to fenofibrate and some benzophenones.
Diagnosis of photosensitivity to flupenthixol by photoprick testing
Authors: Bourrain J. L. , Paillet C. , Woodward C. , Beani J. C. , Amblard P.
Published: September 2011

We report the case of a 38‐year‐old patient with an erythematous eruption, initially confined to photo‐exposed areas and then becoming more generalized, which was attributable to flupenthixol, a thioxanthene derivative used for its neuroleptic properties. The compound has the same polycyclic aromatic hydrocarbons as phenothiazines, but without any cross‐reaction in our patient. A photoallergic cause for the eruption was verified on clinical, histological and photobiologic grounds. Photopatch tests were negative, but photoprick testing was positive after UV irradiation of the test site. Photopatch test methods using better skin penetration have been already reported for testing drug photosensitivity. Photoprick testing combines better penetration with greater ease of use.
Total body heliotherapy
Authors: Alora M. B. T. , Fitzpatrick T. B. , Taylor C. R.
Published: September 2011

Sunlight has long been known to be beneficial for a variety of skin diseases. Patients with psoriasis and eczema frequently employ ambient heliotherapy to control their conditions. However, social norms do not permit a person to expose the entire body in public, thus placing severe restrictions on the utility of this modality for the treatment of generalized psoriasis, for example. Tan‐ThruTM bathing suits, designed to attract those who wish to tan without an accentuated “tan line”, are reported to absorb ultraviolet (UV) rays up to a maximum equivalent of a sun protection factor (SPF) 10 sunblock, thus offering approximately 89% protection while in use, according to their manufacturer. If so, this bathing suit may allow patients with UV‐responsive skin dermatoses to achieve full body exposure in a socially acceptable manner. The objective of this study was to verify the SPF and to determine the actual transmittance to skin covered by a Tan‐ThruTM bathing suit. Ten healthy adult subjects were recruited for this investigation. UVB minimal erythema dose (MED) was determined on unaffected gluteal or lower back skin, once with and once without the swimsuit on. Our results showed that the mean SPF afforded by the bathing suit was in fact 4.9 (range 4.5‐5.6). In conclusion, theoretically, the Tan‐ThruTM bathing suits could allow enough UVB penetration under ambient conditions to be beneficial for patients with UVB responsive conditions.
Laboratory testing of UV transmission through fabrics may underestimate protection
Authors: Ravishankar J. , Diffey B.
Published: September 2011

Laboratory testing of the ultraviolet protection factor (UPF) provided by fabrics normally utilizes a collimated source of UV radiation and either a broadband sensor or spectroradiometer to detect the radiation, both unattenuated and after passing through the fabric sample held in a flat tensionless state. We report the results of an in vivo study of UV transmission through various T‐shirts at several sites on the trunk and arms of a life‐size mannequin irradiated with diffuse radiation and using UV sensitive polymer films as the sensor. We found a variation in UPF by a factor of two or more at different anatomical sites for a given T‐shirt, with lower UPFs seen at sites where the fabric is stretched; and found that at every site and for each T‐shirt this in vivo UPF was higher than the conventional in vitro UPF determined using collimated radiation.
Lymphocytes—Their Possible Endocrine Role in the Regulation of Fertility
Authors: Shahani D. Savitri K. , Gupta Sadhana M. , Meherji Pervin K.
Published: September 2011

PROBLEM: Peptide secretion by peripheral lymphocytes obtained from fertile and infertile women.

METHOD: LH, FSH, and prolactin were estimated in the serum and culture supernatants obtained from Con‐A stimulated human lymphocytes by RIA.

RESULTS: The levels of LH, FSH and prolactin were low in the culture supernatants obtained from lymphocytes of infertile women, when compared with proven fertile women.

CONCLUSION: The results indicated impairment in endocrine functions of lymphocytes obtained from infertile women. This impairment in lymphocyte function could be one of the causes of infertility in these women.
Mixed Maternal‐Paternal Lymphocyte Cultures Before and After Immunotherapy for Recurrent Spontaneous Abortions
Authors: Komlos L. , Vardimon D. , Notmann J. , Ben‐Rafael Z. , Hart J. , Klein T. , Levinsky H. , Halbrecht I.
Published: September 2011

PROBLEM: The increased reactivity of maternal lymphocytes in reciprocal mixed‐maternal‐paternal lymphocyte cultures (MMPLC), observed in the presence of control serum after immunotherapy, suggests that immunization with paternal lymphocytes may induce a highly significant cell mediated immune response in specifically alloactivated maternal lymphocytes.

METHOD: Reciprocal one‐way MMPLC were set up with responding maternal or paternal lymphocytes and mitomycin C‐treated stimulating lymphocytes. Cultures were set up for 6 days in the presence of 15% maternal or control serum. The degree of lymphocyte stimulation was measured by tritiated thymidine uptake.

RESULTS: In maternal serum, after immunotherapy, a highly significant blocking effect on MMPLC was observed in both directions. The extent of the blocking effect in maternal serum and the stimulation in control serum was much higher, after immunotherapy, in two cases of abortions, as compared to cases with normal pregnancy outcome.

CONCLUSIONS: Although the number of cases is very small, it may be that in abortions, in the presence of maternal serum, disturbances in the balance of cytokines or/and specific antibodies could have cytotoxic effects on MMPLC and down regulate, or “block” the specific response. For a possibly better utilization of the MMPLC test in the prediction of pregnancy outcome after immunotherapy, it may be important to examine specific antibodies in maternal serum, to investigate specifically induced cytokines in MMPLC and to evaluate T cell subsets in MMPLC in the presence of maternal and control serum.
Maternal HLA Class II Alleles Predispose to Pregnancy Losses in Danish Women With Recurrent Spontaneous Abortions and Their Female Relatives
Authors: Christiansen Ole B. , Pedersen Bjørn , Mathiesen Ole , Husth Merete , Grunnet Niels
Published: September 2011

PROBLEM: If damage to the trophoblast mediated through autoimmune mechanisms is responsible for recurrent spontaneous abortions (RSA), maternal class II HLA antigens might be expected to be involved. We wanted to evaluate the impact of these antigens on pregnancy outcome in RSA women and their relatives.

METHOD: HLA‐DR and ‐DQ typing using RFLP and PCR‐SSP methods was carried out in 234 Danish women with unexplained RSA and 360 controls. The HLA‐DR types were correlated to outcome of the next pregnancy in 94 patients. Sisters, brothers, and wives of brothers of 146 consecutive patients were HLA typed and their pregnancy outcomes were correlated to the HLA‐DR types.

RESULTS: HLA‐DR1/Br and ‐DR3 were each significantly increased in women with at least four previous pregnancy losses (both P‐values < 0.05 after correction for multiple comparisons). In the prospective study, 62% of the HLA‐DR1/Br and/or ‐DR3 positive patients miscarried the next pregnancy compared with only 29% of those negative for both allogenotypes (P ? 0.025). The family studies indicated that female relatives of RSA patients had a greater risk (odds ratio ? 5.0, 95% CI = 2.0–11.0) of pregnancy losses when positive for HLA‐DR1/Br and/or ‐DR3 than those negative for the allogenotypes.

CONCLUSIONS: Maternal HLA‐DR allogenotypes DR1/Br and ‐DR3 or closely linked genes seem to predispose to pregnancy losses in RSA patients and their first degree relatives.