bluuebunny/crossref_metadata_2025 huggingface dataset:
Can ultraviolet erythema be used to identify the basal cell carcinoma phenotype?
Authors: Ljunggren B. , Johnsson A. , Möller H.
Published: September 2011

Since a prolonged duration of a strong UBV erythema has been suggested as a marker for propensity to develop skin cancer, we objectively followed the duration and intensity of erythemas induced by UVB and UVA radiation for 28 days in 18 patients with basal cell carcinoma (BCC), and in 15 healthy controls using reflectance spectrophotometry. The erythema index, defined as the difference in redness between UV‐exposed skin and normal, adjacent skin on the lower abdomen, did not differ significantly between the two groups at 24 h, when the reaction was maximal, following a dose of 6 MED of UVB. Erythema values after 7 and 14 days were slightly higher in the BCC group, but this difference did not reach statistical significance. At day 7 some patients in the BCC group showed very strong erythemas. At days 21 and 28 the two groups had almost identical erythemal reactions. Following a standard dose of UVA of 100 J/cm2, patients with BCC and healthy controls both showed weak erythemal reactions, which declined somewhat over the study period. No significant differences in pigmentary response were noted between the BCC and the control group, neither following UVB nor UVA. Although individual patients with BCC deviate from the normal erythemal curve for UVB, the UVB response is not a suitable predictive instrument in screening patients with the basal cell carcinoma phenotype.
Topical W‐7 inhibits ultraviolet radiation‐induced melanogenesis in Skh:HR2 pigmented hairless mice
Authors: Dowdy J. C. , Anthony F. A. , Costlow M. E.
Published: September 2011

We studied the effect of N‐(6‐aminohexyl)‐5‐chloro‐1‐napthalenesulfonamide (W‐7) on ultraviolet radiation (UVR)‐induced melanogenesis (tanning) in Skh:HR2 pigmented hairless mice. Topically pretreated mice were exposed to subminimal edematogenic as well as edematogenic UVR doses to establish whether W‐7‐UVR‐induced edema prophylaxis allows increased melanogenesis while preventing edema. Ultraviolet light‐irradiated vehicle control animals developed visible tans; however, both W‐7‐treated groups failed to tan. Topical W‐7 before UVR exposure inhibited UVR induction of dopa oxidase activity in melanocytes by 49% (P=0.029) and inhibited UVR‐induced deposition of melanin in the epidermis by 88% (P=0.006). Topical W‐7 blocked 23% of the UVR but this blockage could not account for the inhibition of dopa oxidase and melanization. We conclude that, in addition to preventing edema, W‐7 inhibits UVR‐induced melanogenesis, possibly by affecting Ca2+‐calmodulin and/or protein kinase C‐dependent processes.
Ultraviolet‐induced suppression of the primary allergic reaction
Authors: Whitmore S. E. , Morison W. L.
Published: September 2011

The effect of localized irradiation with 4 times the minimal erythema dose (MED) of ultraviolet B (UVB) 24 h prior to sensitization with di‐nitrochlorobenzene (DNCB) was examined. In a placebo‐controlled design, 9 of 19 subjects were locally irradiated on the right buttock; 24 h later, DNCB (1000 μg) was applied to the right buttock in all 19 subjects, and subjects were examined 7 and 14 days later for the development of a primary allergic response (PAR). In those not developing a PAR, a challenge dose of DNCB (50 μg) was applied to the volar forearm and examined 2 days later for an elicitation response. A statistically significant difference was seen in the number of subjects developing a PAR, comparing the group irradiated with UVB versus the group not irradiated (33% vs 80%). There was no statistically significant difference seen in elicitation responses between the 2 groups. We have shown that intense localized UVB irradiation as early as 24 h prior to sensitization with a potent allergen at this site may inhibit the PAR but does not appear to affect the elicitation response at a distant site.
Bullous pemphigoid possibly induced by psoralen plus ultraviolet A therapy
Authors: George P. M.
Published: September 2011

An elderly white man with a long history of psoriasis, previously treated with topical steroids and ultraviolet B (UVB), developed bullous pemphigoid shortly after starting psoralen plus UVA (PUVA) therapy. The eruption spread from the forearms to the arms and neck after phototherapy was discontinued. The clinical features of the 12 reported cases of PUVA‐induced bullous pemphigoid are reviewed.
Relationship between skin color and cutaneous response to ultraviolet radiation in Thai
Authors: Leenutaphong V.
Published: September 2011

Predictors of sensitivity to ultraviolet (UV) light, including Fitzpatrick's sun reactive skin types, constitutive skin color and facultative skin color were assessed in 43 healthy Thai volunteers. These predictors were compared with one another and with responses of the skin to UV irradiation, as determined by a minimal erythema dose (MED) of UVB, a minimal immediate pigment darkening dose (MIPDD) of UVA, and a minimal delayed tanning dose (MDTD) of UVA, and by dose‐response curves for erythema and pigmentation, as measured objectively with the use of a narrow‐band spectrophotometer. The skin type did not correspond well to the constitutive and facultative skin color. There was no correlation between skin type and MED and no relation between skin type and the slope of the dose‐response curves for erythema and pigmentation. Constitutional skin color was also not a good predictor of the measured MED, MIPDD and MDTD values but did appear to correlate with the steepness of the dose‐response curves for erythema but not for pigmentation. The facultative skin color, however, did not correlate with the dose‐response angle of erythema or pigmentation. We have thus found that the skin type is not a good predictor of UV responses in Thai. The constitutive skin color is a better predictor of UV responses of the skin than skin type and that steepness of dose‐response curves for erythema is a better measure of the response of the skin to UV irradiation than is a MED measurement.
The effects of body size and orientation on ultraviolet radiation exposure
Authors: Parisi A. V. , Kimlin M. G. , Wong J. C. F. , Fleming R. A.
Published: September 2011

A method has been developed for determining the UV and erythemal exposures to the entire body. The difference between the ambient erythemal exposure and that to the body compared to the ambient exposure may be as high as 76%. The height, orientation, and overall height had a minimal effect on the exposure to the body with size, time of day and time of year having a significant effect. The diffuse component of UV to a side of the body ranged from 20% to 41% between different times of the year with different levels of cloud cover. The ratio of the body to the ambient erythemal exposures varied from 0.24 to 0.61, with the time of day and time of year with the smaller value for periods of high solar altitude.
Phototherapy of eczema
Authors: Larkö O.
Published: September 2011

Several studies have shown a beneficial effect of ultraviolet radiation on eczema, especially atopic dermatitis. The action spectrum lies at higher wavelenghts compared with psoriasis. UVAB seems to be superior to UVB and best suited for mild to moderate cases. From a carcinogenic point of view, the therapy seems safe and the doses are low compared with UVB treatment of psoriasis. UVA‐1 therapy seems to be a promising new alternative, especially for more severe cases. High‐dose regimens work well but the hazards are not yet fully elucidated. The very high dosage regimens should be reserved for very resistant cases where lower doses have been tried but proven inadequate. PUVA is also very effective, but due to the long‐term hazards it should be reserved for the most severe cases of atopic dermatitis.
The sunscreening effect of urocanic acid
Authors: de Olivarius F. Fine , Wulf H. C. , Crosby J. , Norval M.
Published: September 2011

Urocanic acid (UCA), present in the stratum corneum, is a major absorber of ultraviolet (UV) radiation and, on UV exposure, is induced to isomerize from the naturally occurring trans‐isomer to the cis‐isomer. Cis‐UCA has been shown to have immunosuppressive properties, while trans‐UCA may act as a natural sunscreen due to its UV‐absorbing properties. The photoprotective capacity of UCA was investigated in this study. Minimal erythema dose (MED) was determined on normal buttock skin in 36 healthy subjects and the concentration of UCA isomers was measured on the skin adjacent to the test site. On the contralateral buttock, MED was determined 20 min after application of trans‐UCA 5% in a cream base. The UCA cream gave a sun protection factor of 1.58. The amount of UCA applied was, however, 20–200 times higher than the amount of UCA found in normal skin, making a sunscreening effect of naturally occurring UCA very low This was further supported by a lack of correlation between naturally occurring UCA and the UV sensitivity of each subject determined by the MED.
Phototesting in bath‐PUVA: marked reduction of 8‐methoxypsoralen (8‐MOP) activity within one hour after an 8‐MOP bath
Authors: Schempp C. M. , Schöpf E. , Simon J. C.
Published: September 2011

It is not known how long after 8‐MOP bath‐PUVA administration erythema can be induced. Therefore, after determination of dose‐dependence and kinetics of bath‐PUVA erythema, we investigated the development of erythema using an erythematogenic UVA‐dose (3 J/cm2) in time course experiments. Our results show that there is a loss of biological 8‐MOP activity already 1 h after 8‐MOP bath. This has important consequences for clinical practice with bath‐PUVA, concerning the optimum time interval between the 8‐MOP bath and irradiation as well as the persistence of photosensitivity in normal skin after bath‐PUVA.
Effects of phototherapy on the production of cytokines by peripheral blood mononuclear cells and on systemic antibody responses in patients with psoriasis
Authors: Jones C. D. , Guckian M. , El‐Ghorr A. A. , Gibbs N. K. , Norval M.
Published: September 2011

Exposure to ultraviolet B (UVB) radiation results in the suppression of many cell‐mediated immune responses, and recent studies using mice and murine cells in vitro suggest a shift from a T‐helper 1 (Th1) to a Th2 type of response on irradiation. Active psoriasis is considered to be a Th1‐type disorder, chiefly on the basis of the cytokines produced by inflammatory cells in psoriatic lesions. We investigated the effect of phototherapy in patients with psoriasis on the cytokine profile of mitogen‐stimulated mononuclear cells from peripheral blood and the concentration of IgG subclasses and IgE in the plasma. Eight patients were irradiated with a broad‐band UV source (Sylvania UV6; 280–400 nm) three times a week and another eight with a narrow‐band UVB source (Philips TL‐01; 311–313 nm). Peripheral blood was collected before therapy started and after 1–4 weeks of therapy. Peripheral blood mononuclear cells were stimulated in vitro with phytohemagglutinin; proliferation was measured by incorporation of tritiated thymidine and culture supernatants assayed for interleukin (IL)−2, −4 and −10 and γ‐interferon (IFN) by enzyme‐linked immunosorbent assays. Lymphoproliferation was not consistently affected by 4 weeks of UV6 therapy, and there was also no consistent change in the production of IL‐2, IL‐10 or γ‐IFN. In contrast, 4 weeks of TL‐01 therapy significantly suppressed lymphoproliferative responses. In addition the production of IL‐2, IL‐10 and γ‐IFN was lowered after 1 week of TL‐01 therapy, and this was even more apparent after the treatment had been extended to 4 weeks. IL‐4 concentrations were below detectable levels in all the samples throughout the study. The amounts of IgG1, −2, −3 and −4 and IgE in the plasma of the patients did not vary with either of the two phototherapies. Thus, although no evidence was obtained to indicate that UV6 exposure affected T‐helper subsets in psoriasis, TL‐01 inhibited the activity of both Th1 and Th2 subsets while not altering plasma antibody concentrations.
Higher cyclobutane pyrimidine dimer and (6‐4) photoproduct yields in epidermis of normal humans with increased sensitivity to ultraviolet B radiation
Authors: Ueda M. , Matsunaga T. , Bito T. , Nikaido O. , Ichihashi M.
Published: September 2011

Cyclobutane pyrimidine dimer (CPD) and (6‐4) photoproduct induced in the epidermis of five Japanese volunteers exposed to ultraviolet (UVB) radiation were measured with monoclonal antibodies specific for each photoproduct. The volunteers comprised two individuals who are sensitive to solar irradiation (low minimal erythema dose [MED]) and three who are less sensitive. The yields of CPD and (6‐4) photoproduct were within similar ranges after 1 MED or 3 MED doses. The yields of both photoproducts after the same dose of irradiation (120 mJ/cm2) were higher in UV‐sensitive individuals than in less sensitive individuals. By 24 h after irradiation, an average of 60% of CPD had been removed after the 1 MED dose, 27% after the 3 MED dose and 34% after 120 mJ/cm2. The (6‐4) photoproduct was removed within 24 h, independently of the dose of UVB tested. These data suggest that DNA photoproducts participate in initiating UVB‐induced erythema, and partially explain why individuals with higher sensitivity to UVB have a higher risk of UV‐induced skin cancer.
Controlled drug trials in photodermatoses
Authors: Taylor C. R. , Hawk J. L. M.
Published: September 2011

While clinical drug trials in photodermatoses may be complex because of the fickleness of these disorders in their reproducibility following ultraviolet exposure, such investigations require the same general principles of careful design as those in any other disciplines. The ideal clinical trial in photodermatology is both randomized and double‐blind. Precise diagnostic terminology and monitoring of sun exposure must be employed. Polysulphone film badges are the most suitable personal dosimeters to date for these studies. Assessment of itching and discomfort may be reliably performed by the use of a visual analogue scale. Symptoms may also be assessed, but less precisely, by means of a diary record. Only by the use of controlled trials, however, will anecdotal dogma be prevented from inappropriately entering the therapeutic armamentarium of the dermatologist who manages such light sensitive conditions.
Microfluorometry using fluorescein diacetate reflects the integrity of the plasma membrane in UVA‐irradiated cultured skin fibroblasts
Authors: Skoog Marja‐Leena , Öllinger Karin , Skogh Marcus
Published: September 2011

The damaging effect of long‐wave ultraviolet radiation (UVA) on the plasma membranes of cultured human skin fibroblasts was evaluated by cytofluorometry performed after vital staining with fluorescein diacetate. The damage was associated with lipid peroxidation, as shown by accumulation of malondialdehyde and 4‐hydroxyalkenals; such accumulation was induced by a UVA dose of only 8 J/cm2. Pretreatment with the effective membrane peroxidation inhibitor α‐tocopherol (added in the form of α‐tocopherol succinate) or the singlet oxygen quencher β‐carotene protected the cells from membrane damage. Further, depletion of intracellular glutathione by exposure of the cells to buthionine sulfoximine, an inhibitor of γ‐glutamylcysteine synthetase aggravated the membrane‐damaging effects. The results confirm the photodynamic effects of UVA, which presupposes the excitation of endogenous photosensitizer(s) and the production of reactive oxygen species. The present results indicate that this method of detection of alterations in plasma membrane stability may be highly suitable for studying various photobiological phenomena and for use as a model for testing substances that could protect skin from UVA damage. The trypan blue exclusion test proved to be too insensitive to detect these changes.
GM‐CSF production by epithelial cell line: Upregulation by ultraviolet A
Authors: Park K. C. , Jung H. C. , Hwang J. H. , Youn S. W. , Ahn J. S. , Park S. B. , Kim K. H. , Chung J. H. , Youn J. I.
Published: September 2011

It was demonstrated that UVB increases synthesis and expression of IL‐1α and GM‐CSF by keratinocytes. Upregulation of GM‐CSF by UVB is reported to be mediated by IL‐1α. However, regulation of IL‐1α and GM‐CSF by UVA is not well‐known. The purpose of the present study was to evaluate the effects of UVA on IL‐1α and GM‐CSF production. Here we used a competitive RT‐PCR for measuring cytokine gene expression in an epidermal cell line after UVA irradiation. IL‐1α and GM‐CSF mRNA did not show any change at 1 h and 6 h following exposure to UVA. After UVA irradiation, however, IL‐1α mRNA decreased and GM‐CSF mRNA increased at 24 h and the level of GM‐CSF in culture supernatant increased at 24 h and 48 h. Addition of antihuman IL‐1α neutralizing antibody to UVA irradiated cells did not prevent the increase of GM‐CSF mRNA expression. These results suggest that UVA radiation may induce GM‐CSF production through an IL‐1α independent pathway.
Epidermal thickness, skin pigmentation and constitutive photosensitivity
Authors: Lock‐Andersen J. , Therkildsen P. , de Olivarius F. Fine , Gniadecka M. , Dahlstrem K. , Poulsen T. , Wulf H.‐C.
Published: September 2011

The important factors for UV sensitivity in humans are considered to be the skin pigmentation and the epidermal thickness. In this study on 73 Caucasians (age 20–85 years), we investigated in UV unexposed buttock skin the relationship between the UV sensitivity and constitutive skin pigmentation and thickness of the stratum corneum and the cellular part of the epidermis, in 34 normal people and in 39 skin cancer patients (20 patients with cutaneous malignant melanoma and 19 patients with basal cell carcinoma of the skin). Skin pigmentation was measured by skin reflectance spectroscopy, and UV sensitivity by phototest with a solar simulator. Thicknesses of the stratum corneum and the cellular part of the epidermis were determined by light microscopic evaluation of skin biopsies from the phototest areas. We found that epidermal thickness was independent of skin type and was not correlated to constitutive skin pigmentation. Thickness of the stratum corneum was statistically not different in normal persons and in skin cancer patients (P=0.4l) and was independent of gender (P=0.61) and age (P=0.56), while thickness of the cellular epidermis decreased with age (P<0.01). Stratum corneum thickness was found to be of minor importance for the constitutive UV sensitivity (accounting for on average 11% of the total photoprotection), which was mainly determined by the constitutive skin pigmentation (goodness‐of‐fit for correlation r=0.83). A theoretical model for the relationship of UV dose to induction of clinical erythema grade and skin pigmentation and thickness of the stratum corneum was developed. Objective measurements of skin pigmentation in UV unexposed skin by skin reflectance spectroscopy in Caucasians, normal people and people with cutaneous malignant melanoma and basal cell carcinoma of the skin predicts the constitutive UV sensitivity with a high degree of precision.
Physiologic doses of urocanic acid do not alter the allostimulatory function or the development of murine dendritic cells in vitro
Authors: Lappin M. B. , Weiss J. M. , Schöpf E. , Nerval M. , Simon J. C.
Published: September 2011

Exposure to UVB results in the isomerization of trans‐urocanic acid (UCA), localized in the stratum corneum, to cis‐UCA. Cis‐UCA can mediate at least some of the immunosuppressive effects of UVB, though the mechanism of cis‐UCA action remains incompletely defined. Alterations in Langerhans cells, and other dendritic antigen presenting cell populations in the skin, may contribute to the loss of skin immune function following UVB exposure. Hence, this study was designed to investigate whether cis‐UCA directly can induce changes in the immunostimulatory capacity of dendritic cells (DC) and the development of DC from precursor cells. Murine DC were generated from C57BL/6 bone marrow (BM) using granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and were used as stimulator cells in mixed lymphocyte reactions (MLR) using BALB/c lymph node cells (LNC) as responders. The addition of cis‐ and trans‐UCA at concentrations ranging from 0.1–500 μg/ml to the MLR did not affect proliferative responses. Cis‐ or trans‐UCA (100 μg/ml) was added to GM‐CSF stimulated mouse BM cells on day 0, day 3 or day 5 of culture, and the phenotype and allo‐stimulatory function of the DC were analysed on day 7. Treatment with cis‐ or trans‐UCA did not affect the numbers or the viability of cells in the BM cultures. In addition, the expression on DC of Iab, CD11c or the costimulatory molecules ICAM‐1, B7‐1, B7‐2 and CD40 was not altered by the addition of cis‐UCA to BM cultures. The inability of cis‐UCA to alter the development of DC in vitro was confirmed by analysing the functional capacity of DC in MLR. DC generated in the presence of cis‐UCA were equally efficient in the induction of allo‐stimulation, when compared with control DC. These results suggest that cis‐UCA does not exert its immunosuppressive activity through direct effects on DC. Such activity may be independent of DC, or alternatively, cis‐UCA may influence DC function indirectly, through the induction of secondary mediators.
Cosmetic efficacy evaluation of an anti‐acne cream using the 3D image analysis system
Authors: Choi Kyung Min , Kim So Jeong , Baek Ji Hwoon , Kang Seung‐Joo , Boo Yong Chool , Koh Jae Sook
Published: September 2011

Background/purpose

Acne is a skin disease which accompanies pathological and morphological changes. Although acne severity is scored by clinicians based on pathological status, aesthetic aspect of acne symptom is also concerned by patients. This study was conducted to examine the usefulness of a 3D image analysis method for the cosmetic efficacy evaluation of an anti‐acne cream.

Methods

Twenty‐one healthy volunteers with acne lesions were recruited for the study and treated with an ‘anti‐acne cream’ for 4 weeks. Acne symptoms on the facial skin were graded by the visual evaluation of photographs taken before and after the treatment. Skin color of acne lesions was and measured by a spectrophotometer. In addition, a 3D image analysis system was used to quantify skin surface roughness and acne volumes.

Results

Both visual and spectrophotometric assessments of acne lesions provided similar results indicating that the cream treatment improved acne symptoms significantly. The 3D image analysis of acne lesions confirmed that the cream treatment decreased skin surface roughness and acne volumes.

Conclusion

The current study demonstrated that the 3D image‐based analysis of the skin may be useful for the quantification of acne symptoms of cosmetic relevance.
Determination of the protection efficacy and homogeneity of the distribution of sunscreens applied onto skin pre‐treated with cosmetic products
Authors: Weigmann Hans‐Jürgen , de Sainte Claire Maude Suisse , Schanzer Sabine , Patzelt Alexa , Meinke Martina , Antoniou Christina , Sterry Wolfram , Lademann Jürgen
Published: September 2011

Background

The efficacy of sunscreens depends decisively on the homogeneity of its distribution on the skin surface, which is sensitively reflected by two spectroscopic data – the factor of inhomogeneity and the sum transmission – measured after tape stripping. The aim of this study was to investigate the influence of a skin pre‐treatment with body lotion on the layout of the formulations.

Methods

Six healthy volunteers were pre‐treated using the body lotion, Nivea Body (Beiersdorf AG, Hamburg, Germany). The sunscreen was an oil/water (o/w) emulsion, Roc SPF 8 (RoC SA, Paris, France). The tape stripped tesa films were measured with a modified UV/VIS spectrometer Lambda 5 (PerkinElmer, Frankfurt/Main, Germany), the data of which were used to calculate both measurands.

Results

The obtained results made clear that the original spectroscopic data must be corrected taking into account the changed amounts of horny layer particles removed with the individual tape strips after pre‐treatment. As a consequence of the correction, the factors of inhomogeneity as well as the sum transmissions confirm a more homogeneous distribution of the applied sunscreen.

Conclusion

The findings confirm that the applied method is well suited to obtain information on the distribution of topically applied substances, and furthermore that the influence of the pre‐treatment of the skin with the body lotion enhances the homogeneity of distribution and thus the sunscreen efficacy.
Quantitative method for measuring therapeutic efficacy of the 308 nm excimer laser for vitiligo
Authors: Oh Tae Seok , Lee Onseok , Kim Jeong Eun , Son Sang Wook , Oh Chil Hwan
Published: September 2011

Background

There are several available treatments for vitiligo, but measurement of their therapeutic efficacy is not standardized and is somewhat arbitrary based largely on the global impression of the overall response. The purpose of this study was to develop a quantitative method for evaluating the treatment response of vitiligo measuring changes in area using digital image analysis. We applied this parametric model to the evaluation of efficacy of the 308 nm excimer laser.

Methods

This study was a retrospective study, designed as a before and after trial with a single arm. A total of 18 patients were enrolled who had been treated with a 308 nm excimer laser as monotherapy twice a week for 20 sessions. The repigmentation percentage was calculated by measuring changes in area before and after treatment using digital image analysis and graded on a five‐point ordinal scale [global assessment scale (GAS)]. GAS was also measured by physician and patient for comparison with our estimates. Additional GASs were also measured by four different evaluators for inter‐rater variability.

Results

The mean repigmentation percentage after treatment was 45.3% (range, 0.7–100%). The changes in area after treatment were statistically significant (P < 0.05). A substantial agreement of outcomes was observed between physicians and digital image analysis (κw = 0.78), but lower agreement was observed between patients and digital image analysis (κw = 0.49). The inter‐rater variability for GAS was substantially low (Krippendorff's α = 79.3%).

Conclusion

Measurement of changes in area using digital image analysis could be used as a quantitative method in evaluating efficacy of treatment for vitiligo. Because vitiligo lesions can occur in any location with various shapes and sizes, digital image analysis would be a more objective method for measuring treatment response than a GAS.
Lymphocyte Subsets and Mitogen Stimulation of Blood Lymphocytes in Normal Pregnancy
Authors: Matthiesen Leif , Berg Göran , Ernerudh Jan , Håkansson Leif
Published: September 2011

PROBLEM: In normal pregnancy the maternal immune system should be directed towards tolerance or suppression in order not to reject the partly foreign feto‐placental unit. The aim of this investigation was to find hallmarks of systemic immunosuppression during normal pregnancy.

METHODS: Five healthy primigravidae were examined during pregnancy and postpartum with flow cytometric analysis to define T and B lymphocyte subsets in peripheral blood. In addition, we studied the proliferative response of lymphocytes to mitogens or interleu‐kin‐2 (IL‐2) alone or in combination with immunomodulating drugs or interleukin‐4 (IL‐4). The results were compared to healthy, non‐pregnant women.

RESULTS: During pregnancy and early puerperium we noted an immune balance in favour of suppression, as measured by increased numbers of T “helper/suppressor” (CD4+ CD45RA+) and “suppressor”/effector T cells (CD8+S6F1‐), and decreased numbers of T “helper/inducer” (CD4+CD29+), T “helper/memory” (CD4+CD45RO+), killer/effector T cells (CD8+S6F1+), and Natural Killer cells (CD56+), as well as decreased numbers of activated lymphocytes expressing IL‐2 receptor (CD25+) and T cells expressing HLA‐DR (HLA‐DR+CD3+). During pregnancy, lymphocyte proliferation was impaired in autologous serum with concanavalin A (ConA), phytohemagglutinin (PHA), or IL‐2. A difference in proliferative response to PHA or IL‐2 between cultures with AB serum and autologous serum is suggestive of an immunosuppressor factor in serum during pregnancy. Indomethacin significantly increased lymphocyte proliferation in autologous serum with ConA, indicating PGE2 mediated suppressor activity during pregnancy. Chlorambucil and cimetidine modulated the proliferative response to ConA, indicating an alkylating agent sensitive and a histamine dependent suppressor activity during pregnancy.

CONCLUSIONS: During normal pregnancy, a state of systemic suppression of the maternal immune system seems to be present.
Sequential Measurements of Human Decidua‐Associated Protein (hDP) 200 in the Uterine Fluid During the Menstrual Cycle
Authors: Halperin Reuvit , Herman Arie , Golan Abraham , Hadas Eran , Schneider David , Bukovsky Ian , Ron‐El Raphael
Published: September 2011

PROBLEM: To examine the relationship between the concentration of uterine fluid human decidua‐associated protein (hDP) 200, identified as a monoclonal rheumatoid factor, and different phases of the menstrual cycle.

METHODS: Sequential measurements of hDP 200 concentration in uterine fluid were performed in 11 normal ovulatory women, aged 22–36 years. The samples were collected in early proliferative phase, late proliferative phase, periovulatory period, early secretory phase, and late secretory phase.

RESULTS: Consistent fluctuations of hDP 200 levels in uterine fluid were found throughout the menstrual cycle. High levels were found during early proliferative phase and periovulatory period related to significantly lower levels during late proliferative and early luteal phases.

CONCLUSION: There is menstrual phase dependent variation in the uterine fluid levels of hDP 200.
Progress in the Development of Human Chorionic Gonadotropin Antifertility Vaccines
Authors: Stevens Vernon C.
Published: September 2011

Prototype human chorionic gonadotropin (hCG) vaccines have demonstrated the feasibility of effectively eliciting antibodies in women and inhibiting fertility in both humans and nonhuman primates. Also, no serious side‐effects due to immunization against self antigens have been revealed to date. However, the formulations so far tested in clinical trials are not suitable for widespread applications due to problems associated with complexities in production, burdensome application procedures, the need for frequent booster immunizations or cost of manufacture. Current research efforts involve the development of delivery systems to permit annual or biannual intervals between immunizations for protection from pregnancy, procedures for mucosal immunizations, methods to reduce hypersensitivity and local reactions, and procedures for reducing the cost of production. Recent progress in understanding the crystalline structure of the hCG molecule has stimulated further studies to define immunological epitope sequences that might constitute immunogens in future vaccines.

The incorporation of vaccine components into biodegradable microspheres has resulted in formulations that elicit elevated antibody levels in rabbits for more than one year. Preclinical and clinical studies with such formulations are planned. Studies using totally synthetic peptide immunogens constituting hCG B‐cell epitopes and “promiscuous” T‐cell epitopes from bacterial or viral proteins have been shown to be equally immunogenic as conjugates of hCG peptides with macromolecular carriers. Still other peptide immunogens have been developed that can elicit antibody production without detectable proliferation of helper T cells. Some of these peptides can induce systemic immunity from oral immunization or systemic injections. Alternative vehicles for administering vaccine components with reduced local reactivity show promise for new vaccine formulations.
Update on the Center for Recombinant Gamete Contraceptive Vaccinogens
Authors: Herr John C.
Published: September 2011

The overall goal of the Center for Recombinant Gamete Contraceptive Vaccinogens is to develop a contraceptive vaccine which will induce antibodies in the female reproductive tract at sufficient levels to block fertilization. It is envisioned that antibodies developed by this vaccine will act to agglutinate, immobilize or coat either the egg or the sperm in the oviduct, uterus, cervix or vagina. Thus, the vaccine will exert its effects before the fertilization event, as a “prefertilization contraceptive.”

The Center has focused its activities over the past 4 years on four areas: 1) sperm antigens: the identification and characterization of novel sperm surface molecules which are attractive candidates for inclusion in a vaccine; 2) zona antigens: the identification of synthetic peptides derived from the zona pellucida which possess contraceptive potential without adverse pathology; 3) oral vaccine delivery: the development of live Salmonella vectors which deliver vaccine antigens through the oral route and which will stimulate secretory immunity in the female reproductive tract; and 4) animal testing: the testing of vaccine formulations in in vitro fertilization models, in small animals, in monkeys and in baboons. In addition, preparations for human testing are underway through preparation of an Investigational New Drug Application to begin Phase I human trials of a LDH‐C4 peptide vaccine.
Decidua as a Site of Extrathymic VγI T‐cell Differentiation
Authors: Hayakawa Satoshi , Shiraishi Hisami , Saitoh Shigeru , Satoh Kazuo
Published: September 2011

PROBLEM: Decidual tissue is an interface between the host and fetus, which is regarded as a natural allograft. We have reported the possible presence of extrathymic T cells in human decidua through the expression of recombinase‐activating genes in the decidual CD16− CD56bright large granular lymphocytes.

METHODS: In this study we analyzed expression of TCR Vγδ gene segments in peripheral lymphocytes and decidual and nonpregnant endometrial samples using RT‐PCR and oligonucleotide hybridization.

RESULTS: Interestingly, a limited repertoire of Vγ gene segments were discovered in decidual lymphocytes of normal pregnancy when compared with peripheral lymphocytes, whereas usage of Vδ gene segments were ubiquitous in peripheral and decidual lymphocytes. Strong expression of VγI gene segment, often exceeding 50% of total Vγ, were noted in all (13/13) pregnant decidual tissues obtained at different gestational stages. Interestingly, this predominance of VγI gene is also noted in nonpregnant endometrial samples and the decidua of patients with ectopic pregnancies.

CONCLUSIONS: Our results suggest the nature of decidual VγI T cells as possible suppressors of rejective maternal cytotoxic T cells during the maintenance of normal pregnancies.
Platelet Activating Factor and Conception
Authors: Minhas B.S. , Ripps B.A. , Zhu Y.P. , Kim H.N. , Burwinkel T.H. , Gleicher N.
Published: September 2011

PURPOSE: This review provides evidence for the involvement of platelet activating factor (PAF) in the several facets of pregnancy establishment.

METHODS: A comprehensive literature review and new data.

RESULTS: PAF has a role in spermatozoal function, fertilization, embryo development, and implantation.

CONCLUSIONS: PAF is intimately involved in conception.
Progesterone Induced Blocking Factor Seen in Pregnancy Lymphocytes Soon After Implantation
Authors: H. Check Jerome , Szekeres‐Bartho Julia , O'Shaughnessy Althea
Published: September 2011

PROBLEM: The immunomodulatory effect of progesterone (P) in pregnancy manifested via a protein named the P‐induced blocking factor (PIBF) was previously reported. The goal of this study was to measure and compare the PIBF expression on lymphocytes between pregnant and non‐pregnant women especially in early pregnancy.

METHODS: PIBF expression was determined by immunocytochemistry using a PIBF‐specific polyclonal antibody. Levels were assessed during the mid‐cycle, luteal phase, and first trimester of pregnancy.

RESULTS: PIBF expression was found in 24.9% of mid‐cycle sera, 49% of luteal phase sera of women who failed to conceive, and 75% of luteal phase sera of women who conceived.

CONCLUSIONS: These data indicate that the percentage of PIBF expressing lymphocytes increases as a result of pregnancy and that the stimulus for PIBF induction occurs soon after implantation. These data support the concept that PIBF may play an important role in early implantation possibly by inhibiting the destructive function of natural killer lymphocytes.
The Suppression of Peritoneal Cellular Immunity in Women With Endometriosis Could Be Restored After Gonadotropin Releasing Hormone Agonist Treatment
Authors: Wu Ming‐Yih , Chao Kuang‐Han , Chen Shee‐Uan , Chen Hsin‐Fu , Yang Yu‐Shih , Huang Su‐Cheng , Ho Hong‐Nerng
Published: September 2011

PROBLEM: Our previous study reported that peritoneal natural killer (NK) cytotoxicity and CD3+CD25+ lymphocyte subpopulation were suppressed in women with advanced endometriosis. Whether these phenomena are general for all stages of endometriosis and whether these alterations could be restored by long‐term use of gonadotropin releasing hormone agonist (GnRHa) are further tested in this study.

METHOD: Lymphocyte subpopulations (B cells, NK cells, T cells, and T‐cell activation markers such as CD69, HLA‐DR, and CD25) and NK cell cytotoxicity of peripheral blood and peritoneal fluid by dual‐color flow cytometry and 5lCr release assay in 30 cases of endometriosis were compared with those in 26 controls. We also compared these changes before and after 6‐month treatment with GnRHa for advanced endometriosis.

RESULTS: Compared with the controls, only those women with advanced endometriosis showed lower NK cytotoxicity in peritoneal fluid mononuclear cells (PFMC). The CD3+CD69+ lymphocyte subpopulation decreased in peripheral blood mononuclear cells (PBMC) of advanced endometriosis, while the CD3+CD25+ lymphocyte subpopulation decreased in both PBMC and PFMC of mild and advanced endometriosis. After GnRHa treatment, the CD3+CD69+ lymphocyte subpopulation increased in both PBMC and PFMC and the CD3+CD25+ lymphocyte subpopulation increased in PFMC, but not in PBMC.

CONCLUSION: Impaired local immunological function in the PF of endometriosis was confirmed by this study and the impairments could be restored after long‐term GnRHa therapy.
Effects of Tumor Necrosis Factor‐Alpha on Human Trophoblast Cell Adhesion and Motility
Authors: Todt Jill C. , Yang Yan , Lei Jun , Lauria Michele R. , Sorokin Yoram , Cotton David B. , Yelian Frank D.
Published: September 2011

PROBLEM: Adhesive interaction between trophoblast cells and uterine endometrial basement membrane is one of the critical processes in embryo implantation. This interaction is directly or indirectly regulated by hormones, growth factors, and cytokines. Since tumor necrosis factor‐alpha (TNF‐α) is synthesized by both decidual and trophoblast cells, we hypothesized that TNF‐α may play a regulatory role in trophoblast cell invasion. To test this hypothesis, we have used in vitro models to determine the effect of TNF‐α on human trophoblast cell adhesion and motility, two major steps in trophoblast invasion.

METHODS: The effect of TNF‐α on the motility of extended‐lifespan first trimester trophoblasts (HTR) and JEG‐3 choriocarcinoma cells was tested using the phagokinetic track motility assay. An in vitro adhesion assay was used to determine the effect of TNF‐α on the adhesion of HTR and JEG‐3 cells to laminin, a major basement membrane component. In addition, the effect of TNF‐α on the surface expression of the laminin receptor β1 integrin subunit was examined using flow cytometry.

RESULTS: HTR or JEG‐3 cells were strongly adherent to laminin which was not significantly altered by TNF‐α treatment. We also measured the effect of TNF‐α on the surface expression of β1 integrin on HTR and JEG‐3 cells; no difference was observed between control and treatment groups. Interestingly, the motility of both HTR and choriocarcinoma JEG‐3 cells was significantly inhibited by TNF‐α.

CONCLUSIONS: The role of TNF‐α in human embryo implantation is currently unknown. Our data demonstrate that TNF‐α does not alter trophoblast cell adhesion to laminin, but significantly inhibits trophoblast cell motility in vitro, suggesting that TNF‐α may play a regulatory role in trophoblast cell invasion.
Immunosuppressive Properties of Monoclonal Antibodies and Human Polyclonal Alloantibodies to the R80K Protein of Trophoblast
Authors: Jalali G.R. , Arck P. , Surridge S. , Markert U. , Chaouat G. , Clark D.A. , Underwood J.L. , Mowbray J.F.
Published: September 2011

PROBLEM: The R80K protein on human trophoblast is antigenically polymorphic, and in all placentae of successful pregnancies, the protein is covered by maternal alloantibody. Alloantibody eluted from human placenta has been shown to inhibit killing by human NK cells. Do those antibodies to R80K that inhibit NK killing also affect the murine abortion models?

METHODS: We made three murine monoclonal antibodies to conserved epitopes on human R80K, all of which also reacted with the homologous murine molecule. One antibody only, BA11, suppressed NK cytotoxicity to K562 and of mouse spleen NK cells to murine trophoblast. All three were tested in mouse models of abortion: the CBA × DBA/2 model with a high resorption rate of F1 embryos compared with the parental strains, an endotoxin induced abortion/resorption model and a third model in which the pregnant mouse is subject to sonic stress.

CONCLUSION: Those IgG antibodies eluted from microvesicles which bound to K562, and one of the three monoclonals, BA11, inhibited NK killing. The antibodies react with the murine molecule, and BA11 inhibited abortion in all three mouse abortion models. This reinforces the thesis that interference with NK killing can influence abortion/resorption in mice, and the BA11 antibody may effect similar results in analogous human situations.
Effects of Products of Activated Immune Cells and Recombinant Cytokines on Spontaneous and Ionophore‐Induced Acrosome Reaction
Authors: Dimitrov Dimitar G. , Petrovská Marianna
Published: September 2011

PROBLEM: The purpose of this study was to examine whether the products of activated immune cells influence spontaneous and ionophore‐induced sperm acrosome reaction.

METHOD: The spontaneous and ionophore‐induced acrosome reaction were evaluated by staining with fluorescein isothiocyanate (FITC) Pisum sativam agglutinin after incubation in capacitating media supplemented with either supernatants from Con‐A activated leukocyte cultures or human recombinant (r) IL‐Iβ, TNF‐α, and INF‐γ.

RESULTS: The supernatants from Con A‐activated peripheral blood leukocyte cultures at 1:1 and 1:10 dilution significantly increased the rate of spontaneous acrosome reaction (P < 0.001 and P < 0.01). Along with displayed abnormally elevated levels of spontaneous acrosome loss, sperm cells showed an insufficient ability to undergo acrosome reaction in response to the ionophore treatment. Recombinant IL‐Iβ at increasing concentrations from 30 to 3 × 104 U/ml did not have an effect on spontaneous and ionophore‐induced acrosome reaction. In contrast, spermatozoa that underwent capacitation in media with 7 × 103, 7 × 104, and 7 × 105 U/ml of rINF‐γ showed a significant increase in spontaneous and induced acrosome reaction compared to the control (P < 0.001). Recombinant TNF‐α at concentrations of 3.5 × 103 U/ml and 3.5 × 104 U/ml significantly inhibited ionophore‐induced acrosome reaction (P <0.001). Both rINF‐γ and rTNF‐α together revealed an effect on the acrosome reaction similar to Con‐A generated supernatants (1:1 and 1:10 dilution) only at the highest concentrations.

CONCLUSIONS: Some cases of infertility may result from a defective acrosome reaction (premature acrosome loss or insufficient acrosome response to the stimulants) caused by products of activated lymphocytes and macrophages that are released into the male and female reproductive tracts.
Does In Vitro Fertilization (IVF) Influence the Levels of Sperm and Zona Pellucida (ZP) Antibodies in Infertile Women?
Authors: Ulčová‐Gallová Zdenka , Mardešic Tonko
Published: September 2011

The levels of sperm and zona pellucida antibodies in 250 women divided into four groups according to number of recurrent IVF failures (1–4) were analysed and compared with results of a control group of 211 unexplained infertile women never treated by IVF. Sperm antibodies in serum and in ovulatory cervical mucus were determined by mixed antiglobulin reaction (MAR) test, serum zona pellucida antibodies were detected using passive haemagglutination and ELISA.

These tests showed increased occurrence of zona pellucida antibodies in women after repeated IVF. Zona pellucida antibodies were found in 20% after one unsuccessful IVF (similarly to 27% in the control group), but in 64% after two, in 91% after three and in 4 of 5 cases after four IVF failures.

Sperm IgG, A, M and E antibodies in serum and in ovulatory cervical mucus do not seem to be influenced by IVF procedure.

The results show evolution of autoimmune process due to repeated ovarial intervention during oocyte collections. Presence of zona pellucida antibodies, on the other hand, may become a cause of IVF failure.
Estrogen Regulation of Lactoferrin Expression in Human Endometrium
Authors: Kelver Mae Ellen , Kaul Anil , Nowicki Bogdan , Findley William E. , Hutchens T. William , Nagamani Manubai
Published: September 2011

PROBLEM: Lactoferrin is an iron‐binding glycoprotein that has been shown to be overexpressed in human endometrial carcinomas. The purpose of our present study is to investigate the possible role of estradiol in the expression of lactoferrin.

METHOD OF STUDY: We investigated 1) serum levels of lactoferrin in five women during normal ovulatory cycles, 2) serum levels of lactoferrin during ten human menopausal gonadotropin induced cycles when estradiol levels are high, and 3) lactoferrin expression in five proliferative and five secretory phase endometrium by immunohistochemical studies. The serum concentrations of lactoferrin were measured by a peroxidase‐based enzyme‐linked immunosorbent assay.

RESULTS: In normal ovulatory cycles, the mean serum lactoferrin concentration during the proliferative phase (0.4013 ± 0.0242 μg/mL) was significantly higher (P<0.02) than in the secretory phase (0.3468 ± 0.0209 μg/mL). In induced cycles, there was gradual increase in lactoferrin levels with increasing estradiol concentrations. Peak lactoferrin levels in induced cycles (0.7495 ± 0.1148 μg/mL) were significantly higher (P<0.003) than the midcycle levels (0.423 ± 0.0424 μg/mL) in normal cycles. Immunohistochemical analysis of the endometrium revealed greater expression of lactoferrin in proliferative endometrium (50.7 ± 13%, range 28–72%) than in secretory endometrium (19.2 ± 4%, range 7–31%).

CONCLUSION: These results indicate that estradiol may play a role in the regulation of lactoferrin expression in human endometrium.
Induction and Postranslational Expression of G‐CSF and RANTES in a First Trimester Trophoblast Cell Line by Lipopolysaccharide
Authors: Svinarich David M. , Bitonti Ornella M. , Araneda Hereberto , Romero Roberto , Gonik Bernard
Published: September 2011

PROBLEM: Comparatively little is known about the capacity of first trimester trophoblasts to respond to an infection and coordinate an immune response. This study characterizes the LPS induction of G‐CSF and RANTES in a first trimester trophoblast cell line.

METHODS: HTR‐8/SVneo cells were exposed to LPS (1 μg/ml) for 0, 2, 4, 6, 8, and 24 hours in DMEM‐Ham's F‐12 media supplemented with 10% fetal bovine serum. Cytokine levels in culture supernatants were measured by ELISA. Northern analysis of total RNA was conducted using antisense cytokine probes.

RESULTS: Levels of immunoreactive G‐CSF and RANTES from LPS induced cultures at 24 hours were 10‐fold and 8.5‐fold greater than cytokine levels from non‐induced cells at 24 hours, respectively (P<0.01). Under LPS induction, maximal rates of G‐CSF and RANTES transcription occurred at 24 hours and 8 hours, respectively.

CONCLUSION: The LPS induction of proinflammatory cytokines in a first trimester trophoblast cell line supports the contention that first trimester trophoblasts participate in cytokine based immune signaling in response to infection.