bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproduction of the owl monkey (Aotus spp.) in captivity
Authors: Málaga Carlos A. , Weller Richard E. , Buschbom Raymond L. , Baer Janet F. , Kimsey Barbara B.
Published: September 2011

Abstract: The reproduction performance of captive owl monkeys, a breed used extensively in biomedical research, was observed at the Battelle Primate Facility (BPF). The colony grew through captive breeding, imports from the Peruvian Primatological Project, and others to a peak size of 730. It included seven karyotypes of Aotus sp. Results showed that owl monkeys can breed successfully in a laboratory in numbers sufficient to sustain modest research programs. Reproductive success increases when pairs are compatible, of the same karyotype, and stabilized; however, mated pairs of different karyotype are also productive. Under conditions of controlled lighting and heating, owl monkeys at BPF showed no birth peak nor birth season.
A malignant astrocytoma containing simian virus 40 DNA in a macaque infected with simian immunodeficiency virus
Authors: Hurley John P. , Ilyinskii Petr O. , Horvath Christopher J. , Simon Meredith A.
Published: September 2011

Abstract: Polyomaviruses have proven oncogenicity in nonhost experimental animals; however, studies concerning the association between human brain tumors and simian and human polyomaviruses have yielded inconclusive results. We examined the relationship of SV40 to a malignant astrocytoma found in the right frontal lobe of a pigtail macaque (Macaca nemestrina) infected with simian immunodeficiency virus (SIV). Consistent with the histologic diagnosis, the tumor was immunoreactive with antibodies to S‐100 protein, vimentin, and glial fibrillary acidic protein, but negative for neurofilament protein, synaptophysin, neuron‐specific enolase, and chromogranin A. At the time of SIV inoculation, the animal was seropositive for SV40. Polymerase chain reaction assay of tumor DNA, but not normal brain DNA, yielded a 300 base‐pair fragment corresponding to the carboxy‐terminal coding region (C‐terminus) of the large T antigen gene of SV40, suggesting an association with the tumor.
Immune stimulation may contribute to enhanced progression of SIV induced disease in rhesus macaques
Authors: Folks Thomas , Rowe Thomas , Villinger Francois , Parekh Bharat , Mayne Ann , Anderson Daniel , McClure Harold , Ansari Aftab A.
Published: September 2011

Abstract: A number of rhesus macaques experimentally infected with SIV isolates such as SIVmac251, fail to seroconvert, develop high plasma viremia and die rapidly (within 6–7 months p.i.). We hypothesized that such rapid progression is a result of a state of hyperimmune activation and concomitant immune suppression of these animals at the time of virus challenge. In efforts to test the hypothesis that immune activation leads to rapid progression of lentivirus‐induced disease, adult rhesus macaques were infected with SIVmac251 and received an alternate monthly schedule of repeated immunization with allogeneic cells, keyhole limpet hemocyanin and tetanus toxoid (group I). For purposes of controls, a group of monkeys was infected with the same pool and dose of virus but were not immunized (group II) and a group was immunized with the same schedule of multiple antigens as group I but were not infected with SIV (group III). All the animals in group I (n ? 3) either failed to seroconvert or developed very low levels of SIV antibodies, had high plasma p27 defined antigenemia, and died within 8 months (2/3 died within 4 months). Of the animals in group II (n = 8), two patterns emerged as we had noted before. One subgroup (3 animals), displayed the same profile as group I (failure to fully seroconvert, high p27 levels and death by 8 months), whereas the other subgroup (5 animals) seroconverted, had low plasma p27 levels, and survived past 11 months (2/5 still alive past 22 months). All 3 animals in group III remained healthy. The data provided herein suggest that either experimental or natural (due to factors not clear at present) immune stimulation may lead to accelerated lentivirus induced disease progression most likely due to immune suppression and has implications for the understanding of the mechanisms for the rate of disease progression in human HIV‐1 infection.
The effect of diet on the Vervet monkey endocrine pancreas
Authors: Louw J. , Woodroof C. , Seier J. , Wolfe‐Coote S.A.
Published: September 2011

Vervet monkeys (Cercopithecus aethiops) used for pancreatic endocrine cell distribution studies were found to have been maintained on different diets. Although the effect of dietary changes on the exocrine pancreas has been described in several animals, little, apart from the effect of malnutrition, has been reported for the endocrine pancreas. Reported here are pancreatic endocrine cell distributions in monkeys on a standard diet (n ? 3) compared with monkeys on an atherogenic diet (n = 3).

Quantitation of immunolabelled pancreatic endocrine cell types revealed a significant 80% increase in A (glucagon) cell volume in monkeys on an atherogenic diet concomitant with a significant reduction in B (insulin) cell volume to approximately 60% of normal. This reflects a pattern of events that occurs in non‐insulin dependent diabetes. An accompanying reduction in PP (pancreatic polypeptide) cell volumes supports our hypothesis that altering A and PP cell volumes could reflect differential gene expression in those cells in the adult in which glucagon and PP are co‐localized.
Growth retardation in premenarchial female rhesus monkeys during chronic administration of a GnRH agonist (leuprolide acetate)
Authors: Golub Mari S. , Styne Dennis M. , Wheeler Mark D. , Keen Carl L. , Hendrickx Andrew G. , Moran Fernando , Gershwin M. Eric
Published: September 2011

Abstract: Leuprolide acetate in depot form (0.75 mg/kg body weight/month, im) was administered to four female rhesus monkeys from 18–30 months of age, a period that includes the premenarchial growth spurt. They were compared to eight age matched controls. As anticipated, sexual maturation was blocked in the Leuprolide group and menarche did not occur. Growth was also severely retarded; no weight gain occurred during the study in the Leuprolide group as compared to a 25% weight gain (P = .004) in the control group. The Leuprolide group also lost muscle mass. Food intake normalized for body weight was not affected. Linear growth averaged 35% less in the Leuprolide group. Serum IGF‐1 concentrations increased from 486±84 to 965±47 ng/mL (P = .0025) in the Leuprolide group and from 838±139 to 3,006±545 ng/mL (P = .0016) in the control group. These data suggest that premenarchial pituitary/gonadal suppression results in a distinctive pattern of growth retardation in monkeys.
Immunization of Macaca mulatta with aroA attenuated Salmonella typhimurium expressing the SIVp27 antigen
Authors: Steger Krista K. , Pauza C. David
Published: September 2011

Abstract: Attenuated bacteria expressing foreign antigens stimulate both systemic and mucosal immune responses to the recombinant protein. We studied the infection of rhesus macaques with an attenuated Salmonella typhimurium expressing the simian immunodeficiency virus p27 capsid protein. Juvenile rhesus macaques were inoculated by intragastric intubation with doses ranging from 3 to 9 × 109 viable aroA attenuated S. typhimurium. The bacterial infection was self‐limiting with no overt clinical signs. Salmonella were shed in the feces of macaques for approximately five days. Salmonella were isolated from fecal material to examine the in vivo stability of both the attenuating mutation and the integrated SIVp27 expression cassette. All Salmonella isolates retained both the attenuating mutation and the recombinant expression construct. In vitro analysis showed that a minimum of 7.2 μg of p27 was delivered by a single oral dose with attenuated, recombinant S. typhimurium.
A model for the maturation of protective antibody responses to SIV envelope proteins in experimentally immunized monkeys
Authors: Cole Kelly Stefano , Rowles Jennifer L. , Murphey‐Corb Michael , Clements Janice E. , Robinson James , Montelaro Ronald C.
Published: September 2011

Abstract: Studies using live attenuated virus vaccines in the simian immunodeficiency virus (SIV) rhesus macaque model have demonstrated broad protection against experimental challenge. Protection in these studies was found to be critically dependent on the length of time postvaccination, suggesting that protective immunity involves a necessary maturation of immune responses. The current study characterizes the evolution of protective envelope‐specific antibody responses from monkeys inoculated with the highly attenuated SIV/17E‐C1 virus vaccine. For comparison, the same antibody assays were used to characterize the properties of SIV envelope‐specific antibodies elicited by inactivated whole virus and envelope subunit vaccines that failed to provide protection from experimental virus challenge. Results of these studies identify a continuous and complex maturation of envelope‐specific antibody responses during the first six to eight months postinfection. Furthermore, the time required for maturation of SIV envelope‐specific antibodies parallels the time required for the development of protective immunity against experimental challenge with heterologous strains of SIV. While no single immune correlate of protection has been identified, we suggest that a combination of antibody parameters may serve as prognostic indicators in the development of candidate AIDS vaccines.
Immunohistochemical localization of retroviral‐related antigens expressed in normal baboon placental villous tissue
Authors: Langat Daudi K. , Johnson Peter M. , Rote Neal S. , Wango Emmanuel O. , Owiti George O. , Mwenda Jason M.
Published: September 2011

Abstract: Endogenous retroviral particles (ERVs) have been detected in the genome of all eukaryotes. They are generally non‐pathogenic except in mice where they have been found to induce tumors and immunological disorders. The ERVs have morphological features consistent with type‐C retroviral particles and are commonly expressed in normal placental villous tissues. ERVs may have a role in the regulation of placental gene expression, syncytiotrophoblast formation, or pregnancy‐related immunosuppression. In this study, well‐characterized antibodies (monoclonal and polyclonal antibodies) raised against retroviral proteins (anti‐HIV and anti‐SIV) and endogenous retroviral (ERV) particles were assessed for their cross‐reactivity (by using immunohistochemistry) with normal baboon placental and other adult tissues. The monoclonal antibodies to exogenous retroviral proteins (anti‐HIV‐2 gp120, anti‐HIV‐1 gp41, anti‐SIVmac p27, anti‐HIV‐1 RT, and anti‐HIV‐2 core protein) showed specific immunohistochemical reactivity with the syncytiotrophoblast. Antibodies to endogenous retroviral gene products (anti‐ERV3 env, anti‐HERV‐K RT, and anti‐HERV‐K env) also reacted in a similar manner and did not cross‐react with other adult tissues. These studies have shown that retroviral‐cross‐reactive proteins are expressed in baboon placental syncytiotrophoblast and may have a role to play at the feto‐maternal interface.
SIVrcm infection of macaques
Authors: Smith Stephen M. , Makuwa Maria , Lee Fred , Gettie Agegnehu , Russo Christine , Marx Preston A.
Published: September 2011

Abstract: In a prior report, we described the isolation and characterization of SIVrcm, a distinct primate lentivirus found in a household pet Red‐Capped Mangabey (RCM) in Gabon. SIVrcm is divergent from HIV‐1 and HIV‐2/SIV families of primate lentiviruses. In this report, additional in vitro replication studies and the results of SIVrcm infection in macaques are presented. SIVrcm causes little cytopathic effedct in Molt 4 Clone 8 cells and in rhesus and human PBMCs. In vivo, SIVrcm is non‐pathogenic after 200 days in rhesus macaques and after one year in cynomolgous macaques, but does cause a chronic infection in both macaques.
Telomere dynamics in HIV‐1 infected and uninfected chimpanzees measured by an improved method based on high‐resolution two‐dimensional calibration of DNA sizes
Authors: Feng Yan‐Ru , Norwood D. , Shibata Riri , Gee Dennis , Xiao X. , Martin M. , Zeichner Steven L. , Dimitrov Dimiter S.
Published: September 2011

We developed an improved method for accurately measuring telomere lengths based on two‐dimensional calibration of DNA sizes combined with pulsed field electrophoresis and quantitative analysis of high‐resolution gel images. This method was used to quantify the length of telomeres in longitudinal samples of peripheral blood mononuclear cells (PBMCs) from five chimpanzees infected with human immunodeficiency virus type 1 (HIV‐1) and three uninfected animals, 14 to 27 years of age. The average length of the telomere restriction fragments (TRF) of infected and uninfected chimpanzees were 11.7 ± 0.25 kbp, and 11.6 ± 0.61 kbp, respectively, and were about 1 kbp and 3 kbp longer than those of human infants and 30 year old adults, respectively. There was a trend of a slight decrease (30–60 bp per year) in the TRF of two HIV infected chimpanzees over 30–35 months, while the TRF of one naive chimpanzee slightly increased over 20 months. Although the number of chimpanzees in this study is small and no statistically significant linear dependencies on time were observed, it appears that in chimpanzees, rates of shortening of the TRF are comparable or smaller than in adult humans and are not significantly affected by HIV‐1 infection, which may be related to the inability of HIV‐1 to cause disease in these animals.
Determination of fetal biparietal diameter without the use of ultrasound in squirrel monkeys
Authors: Brady Alan G. , Williams Lawrence E. , Hoff Charles J. , Parks Virginia L. , Abee Christian R.
Published: September 2011

This study evaluated manual caliper measurement of fetal BPD in Saimiri through the abdomen of the dam (TBPD) for correlation with paired ultrasound measurements, prediction of delivery date, subspecies variation, prediction of pregnancy outcome, and correlation between postpartum BPD and TBPD. Regression analysis revealed a close relationship between TBPD measurements and those obtained by ultrasound (P < 0.001). TBPD for Saimiri boliviensis boliviensis increased from a mean of 14.8 ± 0.3 mm for 11 weeks prepartum to a delivery week measurement of 33.2 ± 0.2mm. Delivery‐week TBPD of Saimiri boliviensis peruviensis were significantly smaller than Saimiri sciureus sciureus (P < .05). Delivery week TBPD had a correlation coefficient of 0.64 with paired post‐patrum measurements. No complications were associated with the technique. Delivery date could be predicted within two weeks. TBPD is an inexpensive, safe, rapid method of approximating fetal growth during the last half of pregnancy in Saimiri.
Efficacy and effects of short‐ and medium‐term contraception in the common marmoset (Callithrix jacchus) using melengestrol acetate implants
Authors: Möhle U. , Heistermann M. , Einspanier A. , Hodges J.K.
Published: September 2011

Abstract: This study examines the effect of melengestrol acetate (MGA) implants on reproductive function and various biochemical parameters, ovarian activity, and uterine morphology in ten female common marmosets implanted for either 6–8 or 19–21 months. Measures of body weight, concentrations of urinary glucose and blood liver enzymes were taken. Ovarian activity was assessed by analysis of urinary progestin levels and ultrasound examinations of the ovaries. Ultrasonography was also used to evaluate uterine morphology. MGA was highly effective in preventing pregnancies in the study animals. No changes in biochemical parameters were found; however, seven females developed a substantial weight gain during the study. Follicular development was not suppressed, as indicated by the presence of antral follicles, luteinized structures, and elevated urinary progestin levels. The uteri of the MGA‐treated subjects were moderately enlarged with a thickened endometrium that showed a marked change in structural appearance indicative of hypertrophy and decidualization. After implant removal these changes quickly disappeared and all females ovulated within 3 weeks and conceived within 4 months post‐treatment. MGA appears to be an acceptable contraceptive in the marmoset, although non‐steroidal methods should be evaluated as possible potential alternatives.
Towards an AIDS vaccine: The role of nonhuman primates
Authors: Nathanson Neal , Mathieson Bonnie J.
Published: September 2011

Abstract: Over the last 10 years, about 20 human immunodeficiency virus (HIV) vaccine candidates have been tried in humans, with disappointing results as gauged by limited immune responses or protection against infection. These difficulties suggest that a new strategy is needed to test systematically new vaccine candidates. That opportunity is now afforded by nonhuman primate models with SIV, which have been shown to provide an excellent mirror of HIV infection in humans. The recent introduction of SHIVs, chimeric viruses that carry the HIV envelope and are able to infect and cause AIDS in monkeys, also has added an important additional research tool. These models can be used to address a series of questions, including the following: (1) Can protection be provided by partial immunity or is sterilizing immunity required? (2) What are the immune parameters that best predict protection against a potentially pathogenic challenge? (3) What role does mucosal immunity play and can it be induced by practical modes of immunization? (4) Can an attenuated virus be selected that is both protective and safe? An orderly strategy for the evaluation of vaccine candidates could be adopted that would involve several phases: (a) the selection of a limited set of challenge models, ranging from very severe to mild and requiring consideration of primate species, age, route of infection, and challenge viruses; (b) the assessment of candidate vaccines using comparable virus challenges; and (c) accelerated testing in humans of any candidate vaccines that have met a ‘proof of efficacy’ in primates.
Progress and challenges in therapies for AIDS in nonhuman primate models
Authors: Haigwood Nancy L.
Published: September 2011

Abstract: Efforts to develop animal models for human immunodeficiency virus type‐1 (HIV‐1) vaccine testing have focused on lentivirus infection of nonhuman primates. A long‐term goal of this primate research is to utilize the models to understand the mechanisms of pathogenesis leading to AIDS. Because the time to disease is compressed relative to HIV infection in humans, therapeutic strategies and compounds can be tested in nonhuman primate models in a shorter time frame and under more controlled conditions than are possible in many clinical studies. Recent interventive studies in primates using antiviral drugs or passive immune globulin (IgG) have demonstrated that multiple log reductions in plasma virus can be achieved and sustained, with accompanying health benefits. Information gained about timing and dosage may be of utility in designing clinical studies. The development of reliable and predictable animal models for effective therapies and vaccines against AIDS remains a critical priority for primate research.
Recombinant human CD40 ligand inhibits simian immunodeficiency virus replication: A role for interleukin‐16
Authors: Lee Mark E. , Bucur Silvana Z. , Gillespie Theresa W. , Adams Jonathan W. , Barker Andrew T. , Thomas Elaine K. , Roback John D. , Hillyer Christopher D.
Published: September 2011

Abstract: CD40 ligand (CD40L), expressed on activated T cells, binds its receptor, CD40, on dendritic cells, B cells, and monocytes/macrophages. Human immunodeficiency virus (HIV)‐infected individuals exhibit normal B‐cell CD40 expression but diminished expression of CD40L on CD4 + T cells. Thus, we studied recombinant human CD40L (huCD40L) in an in vitro rhesus macaque model of acquired immunodeficiency syndrome (AIDS). huCD40L induced peripheral blood mononuclear cell (PBMC) proliferation independent of mitogenic cytokines and led to a 70% reduction in p27 production by simian immunodeficiency virus (SIV) mac239 infected PBMCs (P < 0.05). Reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis showed reduced expression of SIV gag and increased expression of interleukin (IL)‐16 mRNA. Supernatants from huCD40L‐stimulated PBMC and control cultures contained similar amounts of IL‐16, suggesting an intracellular antiviral effect by IL‐16. Phytohemagglutinin (PHA)‐stimulated PBMCs similarly cultured with huCD40L showed only slight increases in chemokine production (P > 0.05). These results suggest that huCD40L inhibits replication (antigen and mRNA production) of SIVmac239. This response involves huCD40L induction of IL‐16 mRNA expression and appears to be independent of β‐chemokines.
Characterization of SIV‐specific CD4 + T‐helper proliferative responses in macaques immunized with live‐attenuated SIV
Authors: Gauduin Marie‐Claire , Glickman Rhona L. , Ahmad Shabbir , Yilma Tilahun , Johnson R. Paul
Published: September 2011

Abstract: Analysis of immune responses generated by live‐attenuated simian immunodeficiency virus (SIV) strains may provide clues to the mechanisms of protective immunity induced by this approach. We examined SIV‐specific T‐helper responses in macaques immunized with the live‐attenuated SIV strains SIVmac239Δnef and SIVmac239Δ3. Optimization of the concentration and duration of antigenic stimulation resulted in the detection of relatively strong SIV‐specific proliferative responses, with peak stimulation indices of up to 84. SIV‐specific proliferative responses were mediated by CD4 + T cells and were major histocompatibility (MHC) class II restricted. Limiting dilution analysis revealed SIV‐specific T‐helper precursor frequencies of up to 96 per 106 peripheral blood mononuclear cells (PBMC). Intracellular flow‐cytometric analysis demonstrated the production of interleukin (IL)‐2, interferon (IFN)‐γ, RANTES and macrophage inhibitory protein‐1α (MIP‐1α) by T lymphocytes from SIVmac239Δnef‐vaccinated animals following SIV p55 stimulation. Induction of strong SIV‐specific T‐helper responses by live‐attenuated SIV vaccines may play a role in their ability to induce protective immunity.
Protective immunity of gene‐deleted SHIVs having an HIV‐1 Env against challenge infection with a gene‐intact SHIV
Authors: Ui M. , Kuwata T. , Igarashi T. , Miyazaki Y. , Tamaru K. , Shimada T. , Nakamura M. , Uesaka H. , Yamamoto H. , Hayami M.
Published: September 2011

Abstract: We constructed three simian–human immunodeficiency viruses (SHIVs) lacking regulatory gene(s) and analyzed their induction of protective immunity against challenge infection with gene‐intact SHIV in rhesus macaques. Inoculation of SHIV‐dn lacking nef and SHIV‐drn lacking nef and vpr induced transient viremia, while that of SHIV‐dxrn lacking nef, vpr, and vpx induced no viremia. The SHIVs with fewer deletions were more effective in inducing neutralizing antibodies and cytotoxic T lymphocyte responses. When these macaques were challenged with parental gene‐intact SHIV‐NM‐3rN, all the SHIV‐dn‐vaccinated macaques and two of the four SHIV‐drn‐vaccinated macaques showed complete resistance. The other two SHIV‐drn‐vaccinated macaques and all SHIV‐dxrn‐vaccinated macaques did not show complete resistance, but they did show suppression of replication of the challenge virus. These results suggested that as more genes were deleted, protective immunity was decreased.
Clinical outcome of a protocol to produce immunosuppression in rhesus monkeys (Macaca mulatta): application to infectious disease and gene therapy studies
Authors: Jr Rudolf P. Bohm , Dennis Vida , Blanchard James L. , Philipp Mario T. , Gerber Micheal A.
Published: September 2011

Abstract: Induced immunosuppression is required for a number of studies using rhesus monkeys (Macaca mulatta). This report describes the clinical outcome and safety of a dose‐finding experiment that determined doses of cyclophosphamide and prednisone that could be used to induce a state of immunosuppression in rhesus monkeys. After determining the optimum dose of immunosuppressive agents, the protocol was then used on animals participating in infectious disease and gene therapy studies. Splenectomy was performed in some animals to increase the severity of immunosuppression. The onset, duration, and severity of lymphopenia and leukopenia were consistent in all animals. In most animals, physical examination findings and clinical serum chemistry profiles demonstrated only transient abnormalities. With proper clinical monitoring, combination treatment with cyclophosphamide and prednisone is an effective and safe method for inducing immunosuppression in rhesus monkeys.
Seed survival on experimental dishes in a central European old‐growth mixed‐species forest – effects of predator guilds, tree masting and small mammal population dynamics
Authors: Nopp‐Mayr Ursula , Kempter Iris , Muralt Gerald , Gratzer Georg
Published: September 2011

Predation of tree seeds can be a major factor structuring plant communities. We present a three year study on tree seed survival on experimental dishes in an old‐growth forest in central Europe in Austria. We addressed species specific, spatial and temporal aspects of post‐dispersal seed predation. Seeds of Norway spruce Picea abies, European beech Fagus sylvatica, and silver fir Abies alba were exposed on dishes in different types of exclosures which allowed access only to specific guilds of seed predators. Removal experiments were carried out in two old‐growth forests and a managed forest (macro‐sites), including micro‐sites with and without cover of ground vegetation. We conducted the experiment in three consecutive years with a mast year of beech and spruce before the first year of the study. The seed removal experiments were combined with live trapping of small mammals being potential seed predators. Our experiments showed a distinctly different impact of different predator guilds on seed survival on the dishes with highest removal rates of seeds from dishes accessible for small mammals. We observed differing preferences of small mammals for the different tree species. Seed survival in different macro‐ and micro‐habitats were highly variable with lower seed survival in old growth forests. In contrast to our assumption, and in contrast to the satiation hypothesis which assumes higher seed survival in and directly after mast years, seed survival was lower in the year following the mast year of beech when a population peak of small mammals occurred and higher in intermast periods when subsequently small mammal population crashed. This suggests a higher importance of sporadic masting shortly after mast years in intermast periods for establishment of forest trees provided that pollination efficiency is high enough in such years. Combined with the high seed mortality observed after the mast year, this corroborates the important role of seed predation for forest dynamics. An altered synchrony or asynchrony of masting of different tree species and changed masting frequencies through climate change may thus lead to strong and non‐linear effects on forest dynamics.
Reduction of ultraviolet‐induced skin cancer in mice by topical application of DNA excision repair enzymes
Authors: Bito T. , Ueda M. , Nagano T. , Fujii S. , Ichihashi M.
Published: September 2011

Ultraviolet (UV) irradiation produces two major photoproducts, cyclobutane pyrimidine dimers (CPD) and (6–4) photoproducts. T4 endonuclease V (T4N5), which specifically repairs CPD, is encapsulated in liposomes. A previous study has shown that UV‐induced carcinogenesis in mice was suppressed by the application of T4N5 liposomes. To confirm the suppressive effect, we applied T4N5 liposomes with repeated UVB exposure to hairless mice. At the end of the experiment, mice treated with T4N5 liposomes had 3.5 ± 1.3 tumors per mouse, and control mice had 6.3 ± 2.8 tumors per mouse. In addition, the incidence of tumors was reduced in T4N5 liposome‐treated mice compared with controls. The pathological diagnosis of the tumors was not significantly different between two groups. Immunohistochemical analysis of p53 protein in UV‐induced tumors showed that nearly half of the tumors in both groups were positive. When the biopsied normal‐looking skin taken during the experiment was stained with p53 antibody, there was no significant difference of the timing of p53 protein expression between the control mice and T4N5 liposome‐treated mice. These results confirmed that CPD plays a pivotal role in UV carcinogenesis, although the molecular mechanisms of the suppression by T4N5 liposomes should be further clarified.
Oxidative defense in cultured human skin fibroblasts and keratinocytes from sun‐exposed and non‐exposed skin
Authors: Applegate L. A. , Frenk E.
Published: September 2011

Skin fibroblasts and keratinocytes cultivated from chronically light‐exposed skin sites have higher levels of the protective protein ferritin than cells derived from unexposed areas of the body, suggesting an adaptive response of cells exposed to chronic external insults. In the same line, ferritin levels were always found to be 2‐to 7‐fold higher in epidermal keratinocytes than in the underlying dermal fibroblasts of the same person thus providing the keratinocyte with continuous protection by the higher cellular ferritin content. The activation of ferritin by oxidative stress including UVA radiation could represent an important cellular defense mechanism that operates in human skin. Following low fluences of UVA radiation (2–4×105 J/m2), ferritin levels increased by 20–30% in normal adult skin fibroblasts and showed a subsequent decrease at higher UVA fluences. In contrast, skin keratinocytes were not perturbed by UVA radiation exposure except for very high fluences (1.25× 106 J/m2) where slight decreases in cellular ferritin were noted in 7 of the 12 cell lines. Fibroblasts derived from light‐exposed skin sites that possessed higher levels of cellular ferritin were highly protected against UVA‐induced membrane damage as measured by lactate dehydrogenase release compared with fibroblasts from nonexposed body sites with lower levels of ferritin. It is clear from our results that ferritin plays an important role in protection at the cellular level in human skin cells, but the role of this putative protective protein in vivo remains to be defined.
In vitro mechanism(s) of ultraviolet‐induced tumor necrosis factor‐α release in a human keratinocyte cell line
Authors: Corsini E. , Bruccoleri A. , Marinovich M. , Galli C. L.
Published: September 2011

It has been demonstrated that ultraviolet (UV) irradiation is able to induce both in vivo and in vitro, tumor necrosis factor‐α (TNF) release. The purpose of the present study was to evaluate, using a human keratinocyte cell line NCTC 2544, the mechanism(s) of UV‐induced TNF release and the ability of commonly used sunscreens to modulate UV‐induced TNF release. TNF release can be partially prevented both by adding an anti‐human IL‐1α antibody after irradiation, suggesting an autocrine effect of IL‐1α in inducing TNF release, and by adding antioxidants indicating also a role of oxidant species. TPCK, a Iκ‐Bα protease inhibitor, was able to virtually abolish UV‐induced TNF release, indicating that UV‐induced TNF release requires NF‐κB activation. Anti‐human IL‐1β antibody was ineffective as expected, considering that keratinocytes are unable to process pre‐IL‐1β to its active form. To evaluate the sunscreen's modulation on UV‐induced TNF release, confluent cells were irradiated, in the presence or absence of the tested sunscreens (Uvinul MS40, Uvinul P25 and Uvinul DS49). Different IC50 values could be calculated, which may be related to different UV absorption spectrums: Uvinul MS40 offers great protection by virtue of its broader absorption spectrum, closely followed by Uvinul P25 and finally by Uvinul DS49.
A comparison of human‐ and headform‐based measurements of solar ultraviolet B dose
Authors: Airey D. K. , Wong J. C. F. , Fleming R. A.
Published: September 2011

New data on the distribution of solar ultraviolet B (UVB) radiation on the face are presented. Measurements made on human subjects and on rotating headform models are compared, and the effect of altering the orientation of the headform is considered. For a range of postures (standing, sitting, bending, kneeling) a corresponding headform angle (20°, 30°, 40°, 60° respectively) is determined that gives improved agreement with human‐based measurements. This suggests that a more realistic simulation of human exposure is achieved by appropriately tilting the model.
Photosensitivity reaction to intravenously administered fluorescein
Authors: Lentner A. , Böhler U.
Published: September 2011

Sodium fluorescein is an organic dye widely used as a diagnostic aid. This article reports a case of a photosensitivity reaction associated with intravenous administration in a healthy volunteer. To our knowledge, this is the 1st case of a photosensitivity reaction of the immediate type due to fluorescein reported in the literature, which probably indicates its very low incidence. The literature on photosensitization to fluorescein is reviewed.
Effects of ultraviolet A and antioxidant defense in cultured fibroblasts and keratinocytes
Authors: Moysan A. , Clément‐Lacroix P. , Michel L. , Dubertret L. , Morlière P.
Published: September 2011

Lipid peroxidation, measured by the thiobarbituric acid‐reactive substances assay, was evaluated for cultured human skin fibroblasts and keratinocytes exposed to ultraviolet A radiation (320–400 nm, UVA). Peroxidation increases with increasing UVA doses and is much lower for keratinocytes than for fibroblasts. Immediate UVA‐induced cytotoxicity, monitored by the trypan blue exclusion assay, is also lower for keratinocytes. Thus, cultured human skin keratinocytes are less sensitive than fibroblasts to the immediate deleterious effects of UVA with respect to membrane damage and lipid peroxidation. As a first attempt to understand this lower sensitivity of keratinocytes, basal levels of antioxidant defenses including total glutathione, superoxide dismutase, glutathione peroxidase and catalase were evaluated in both keratinocytes and fibroblasts from the same donors. We failed to correlate this lower susceptibility of keratinocyte to UVA‐induced lipid peroxidation and cytotocixity with a higher antioxidant status.
Contact allergy to 3‐(4‘ methylbenzylidene) camphor and contact and photocontact allergy to 4‐isopropyl dibenzoylmethane
Authors: Marguery M. C. , Rakotondrazafy J. , Sayed F. El , Bayle‐Lebey P. , Journe F. , Bazex J.
Published: September 2011

We report a clinical case of a 15‐year‐old boy who presented a photodistributed eruption after having used a sunscreen cream for 8 days. Photobiological testing showed a contact allergy to 3‐(4′ methylbenzylidene) camphor (Eusolex 6300) included in his sunscreen cream associated with a contact and photocontact allergy to 4‐isopropyl‐dibenzoylmethane (Eusolex 8020) not included.
Upregulation of nitric oxide synthase in cultured human keratinocytes after ultraviolet B and bradykinin
Authors: Kang‐Rotondo C. H. , Major S. , Chiang T. M. , Myers L. K. , Kang E. S.
Published: September 2011

Kang‐Rotondo CH, Major S, Chiang TM, Myers LK, Kang ES. Upregulation of nitric oxide synthase in cultured human keratinocytes after ultraviolet B and bradykinin. Photodermatol Photoimmunol Photomed 1996: 12: 57–65. © Munksgaard, 1996.

Ultraviolet B (UVB) irradiation of the skin has been reported to upregulate nitric oxide synthase (NOS) activity with enhancement of nitric oxide (NO) formation. Bradykinin, a known stimulator of NO production, is produced in the skin within minutes of UVB irradiation. The combined effect of UVB and bradykinin on NOS was therefore examined in a cultured human keratinocyte (KC) line. Activity was determined in KC homogenates by the recovery of [3H]l‐citrulline using labeled l‐arginine as the substrate in the presence of mM NADPH. Monoclonal antibodies to specific isoforms of NOS that cross‐react with their human counterparts were used to determine the isoform(s) in control, UVB, bradykin treated and UVB and bradykinin treated KC. Human KC express NOS activity which is lowest at confluence and highest during proliferation. UVB increased NOS activity when a set dose of irradiation was administered from 32.2–48.3 mJ/cm2 but was inhibitory after 64.4 and 80.5 mJ/cm2. Thirty min after 10−6 M bradykinin, NOS activity nearly doubled followed by return of activity to control levels at 60 min. Activity after UVB and bradykinin was only slightly higher than that observed with bradykinin alone. Immunochemically, an isoform of Mr 155 kDa was detected in control cells with the antibody for the constitutive brain enzyme, bNOS. Recovery of this isoform increased after UVB treatment as well as after bradykinin which was time dependent. When both stimulants were used, the recovery of the 155 kDa enzyme was markedly enhanced, unlike the enzyme activity findings. These data indicate that the expression of NOS activity under unstimulated conditions in human KC in culture is due to the constitutive NOS found in neuronal tissue, bNOS. The recovery of bNOS increased after UVB and after bradykinin while the combination of both resulted in the synergistic increase in bNOS protein with only a marginal further increase in NOS activity.
Development of cutaneous tolerance to ultraviolet B during ultraviolet B phototherapy for psoriasis
Authors: Gonzalez S. , Hegyi V. , Baqer A. , Sadiq I. , Kollias N.
Published: September 2011

During a schedule of multiple exposures to ultraviolet B radiation (UVB, 280–320 nm), skin develops a reduced sensitivity, variously called tolerance, photoadaptation, accomodation or acclimatization. In this study we have investigated the development of tolerance in the normal skin of a group of psoriatic patients during the course of UVB therapy Tolerance was assessed by phototests carried out on non‐lesional skin as frequently as possible throughout the treatment. Maximum tolerance was developed by the group of individuals most sensitive to UVB, which was twice that of the least sensitive group. The minimal perceptible erythema dose (MPE) increased rapidly in the first 2 weeks (220% per week) and reached a plateau by the eighth week of 800% above the baseline MPE dose. For the more sensitive patients there was a further increase in sensitivity (decrease in MPE dose) after the ninth week of continuous treatment. Tolerance to UVB also involves pigmentation in the first few weeks, but in these patients there was no evidence of hyperpigmentation by the end of treatment. While epidermal hyperplasia is most likely to play a leading role in the development of tolerance to UV, there is no reason to expect this protection to decrease under conditions of continuous exposure. Thus, accommodation to ultraviolet radiation (UVR) is not a monotonically increasing process but appears to alter the accepted reactions of human skin to UVR.
Annual reduction of solar UV exposure to the facial area of outdoor workers in Southeast Queensland by wearing a hat
Authors: Wong J. C. F. , Airey D. K. , Fleming R. A.
Published: September 2011

The total annual exposure to erythemally effective UVR was estimated for average work situations in a high exposure environment, viz, farm workers in Southeast Queensland (27.5° S), and the effect of hat usage was examined. If no sun protection is used, the annual erythema exposures for this group of workers at three facial sites: forehead, nose and cheek are 40, 57 and 34 J ṁ cm−2 respectively. If a hat is worn throughout the year, the exposures are reduced to 6, 19 and 20 J ṁ cm−2, respectively. The mean ratio of exposure without the hat to that with the hat (mean protection factor, MPF) was found to be 6 for the forehead, 3 for the nose and 2 for the cheek. The risk of non‐melanoma skin cancers without the protection of the hat is estimated to increase by up to 100 times for basal cell carcinomas and 13 times for squamous cell carcinomas for a whole year of exposure.
Threshold level for measurement of UV sensitivity: reproducibility of phototest
Authors: Lock‐Andersen J. , Wulf H. C.
Published: September 2011

The ultraviolet (UV) sensitivity is determined by a phototest where the skin is exposed to well‐defined doses of UV radiation and the resulting erythema is graded by visual scoring after 20–24 h. In this study we wanted to estimate the reproducibility of erythema assessment in phototesting. Twenty‐one healthy Caucasians with skin types I to IV were phototested on UV un‐exposed buttock skin using a xenon lamp solar simulator. Twenty‐four hours after UV exposure eight physicians independently graded the erythema reactions two times. Data were analysed using inter‐and intra‐observer agreement and kappa statistics, which adjusts for agreement that could be caused by chance alone. Observed agreement and kappa statistics were found to decrease with increasing intensity of erythema and to be lower for skin types III and IV compared to skin types I and II. Intra‐observer agreement was uniformly better than inter‐observer agreement. The difference between observers assessment could be as much as three clinical erythema grades. Physicians's previous experience with phototesting only had a minor influence on agreement. In conclusion, phototesting is based on subjective assessment of erythema and is not as precise and reproducible as expected. Agreement was better for barely perceptible erythema than for erythema with a well‐defined border and we therefore recommend that the barely perceptible erythema reaction should be used for measurement of the minimal erythema dose.
Sun‐protection behaviour and self‐assessed burning tendency among sunbathers
Authors: Stender I.‐M. , Lock‐Andersen J. , Wulf H. C.
Published: September 2011

A total of 805 sunbathing Caucasians were interviewed about sunprotection behaviour and self‐assessed burning tendency. Sixty‐seven percent of the interviewed sunbathers used one or more sunscreen factors. Sunscreen‐users and nonusers were exposed to the sun 206 min and 197 min (P=0.186), respectively. The sunscreen users were exposed to a marginally higher UV dose than non‐sunscreen users, 4.8 SED versus 4.5 SED (P=0.0348). The rate of sunscreen users was significantly higher among subjects who stated that they always were sunburnt in the spring when not using a sunscreen than subjects who stated that they never were sunburnt in the spring when not using a sunscreen (P=0.0001). However, when comparing subjects that always burn in the spring and subjects that never burn in the spring, we found no significant difference between level of the sun‐protection factor (P=0.11) nor the duration of sun exposure (P=0.967), nor to which UV doses the subjects were exposed (P=0,562). Furthermore we found that the interviewed sunbathers interpreted to “be sunburnt” as more severe than “to turn red”. Public campaigns recommend the use of sun protection cream when sunbathing without using other sun protective strategies; however, the use of sun protection cream is inadequate among sunbathers. More education is required to persuade those with more sun‐sensitive skin to use a higher protection‐factor, to reduce sun exposure at times when UV radiation is most intense, and to reduce the duration of exposure.
A new method for measurement of erythemal irradiance
Authors: Parisi A. V. , Wong J. C. F.
Published: September 2011

A composite system of four dosimeter materials, nalidixic acid (NDA), polysulphone, 8‐methoxypsoralen (8‐MOP) and phenothiazine, is presented for the passive measurement of the UV spectrum. The properties of the materials were investigated and found to be suitable to allow the materials to be applied in a system to evaluate the UV spectrum. The evaluation of the spectrum reduces by 70% the errors arising when only polysulphone dosimeters are employed to measure the exposure due to a source spectrum that differs from the spectrum they have been calibrated against. Knowledge of the spectrum provides an advantage over the Robertson‐Berger meter and polysulphone dosimeters, as the biologically effective exposure for any biological process may be calculated with better than 20% accuracy. The composite system was miniaturised to a size of 3 cm × 3 cm to eliminate errors due to spatial variation of the spectrum and to allow the application at any site on objects with complicated topography in a similar way as polysulphone dosimeters. Unlike the polysulphone dosimeters, the composite system does not require calibration against a specific source of UV in order to maintain a high degree of accuracy in the collected data.
Erythema and melanogenesis action spectra in heavily pigmented individuals as compared to fair‐skinned Caucasians
Authors: Kollias N. , Malallah Y. H. , Al‐Ajmi H. , Baqer A. , Johnson B. E. , González S.
Published: September 2011

The protective role of epidermal melanin pigmentation against chronic exposure to ultraviolet radiation is widely accepted, although its photoprotective effect against acute exposure is less certain. In this study, the action spectra of erythema and melanogenesis in heavily pigmented individuals (skin type V) were determined at 295, 305, 315, and 365 nm, and compared with those of skin types I and II. When the erythema and melanogenesis action spectra for skin type V were normalized to 295 nm, they were identical to the corresponding action spectra for fair‐skinned individuals, indicating that the photoprotection of epidermal melanin pigmentation is essentially independent of wavelength. The ratio of values for the minimum erythema dose (MED) between skin type V and skin types I and II was 2.29, which is close to the ratio of pigment in these skin types, as measured by diffuse reflectance spectroscopy in the visible range. The minimum immediate pigment darkening dose (IPD) and the minimum melanogenic dose (MMD) at 365 nm, and the MED and MMD at 315 nm were the same for all skin types, while the variation of MED for every skin type was maximum at 305 and 365 nm. The results provide circumstantial evidence that erythema and melanogenesis have the same mechanism at short‐wavelength UVB (295 and 305 nm), and different mechanisms in UVA (365 nm). Furthermore, the 24 h MED at 305 nm appears to be a sensitive indicator of skin type.
Flutamide photosensitivity
Authors: Leroy D. , Dompmartin A. , Szczurko C.
Published: September 2011

Flutamide is a non‐steroid antiandrogen used in advanced prostate cancer. This drug induces liver toxicity. Other side effects have been reported, especially four cases of photosensitivity. Our patient presented a sun‐exposed eruption that disappeared when flutamide was discontinued and relapsed when it was rechallenged. Photopatch tests were negative. UVA MED was much lower during the treatment and the rechallenge of flutamide. The action spectrum of the drug seems to be in the UVA range. According to the literature, this photosensitivity is probably due to a photoallergic mechanism.
Photoaugmentation effects demonstrated in vitro
Authors: Selvaag E.
Published: September 2011

A number of sulphonamide‐derived oral antidiabetics and diuretics were investigated for phototoxic properties, using different sources of light, by means of a photohemolysis test. Photohemolysis was obtained after irradiation with UVA, visible light and solar simulating irradiation. No phototoxic properties were seen when the test samples were exposed to UVB alone. The most prominent hemolysis was induced by solar simulating irradiation. When exposing the the test samples to UVB prior to the subsequently applied UVA, visible light or solar simulating irradiation, a significantly higher hemolysis was detected compared with the previous tests, suggesting photoaugmentation effects in this model.