bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of near‐infrared radiation on the epidermal proliferation and cutaneous immune function in mice
Authors: Danno K. , Sugie N.
Published: September 2011

While ultraviolet radiation alters various cutaneous cell functions, little is known about the photobiological effects of infrared radiation (IR) on the skin except its local thermal effect. This study demonstrated that single exposure of mouse skin to near IR (0.7‐1.3 μm) reversibly suppressed the proliferating activity of the epidermis, the density of Langerhans cells, and the ability of skin to induce contact hypersensitivity reaction. During the exposure, the ear surface temperature was elevated from a mean of 27 to 31.2°C. The results suggest that near IR can modulate the epidermal proliferation and part of the skin immune system, with a mild thermal effect.
Clinical drug photosensitivity. A retrospective analysis of reports to the Norwegian Adverse Drug Reactions Committee from the years 1970–1994
Authors: Selvaag E.
Published: September 2011

Adverse drug reactions reported to the Norwegian Medicine Control Authority from 1970 to 1994 were analyzed, especially with regard to cutaneous reactions and photosensitization. In the time period, almost 13,000 unwanted side effects were reported. Of these, 799 reports involved the skin and appendages, of which 64 reports (8%) were classified as photosensitivity reactions. Tetracyclines, diuretics, antihypertensive agents, and urologicals were the drugs that most often caused photosensitivity reactions. In addition, a number of uncommon photosensitizing drugs were reported. The risk for photosensitization is discussed on the basis of experimental data and the prescription rates of these substances.
Measurement of suberythema UVA radiation effects on skin by 31P magnetic resonance spectroscopy
Authors: Zemtsov A.
Published: September 2011

31P magnetic resonance spectroscopy (MRS) scans were obtained from the same anatomical location in four healthy Caucasian individuals before and after 1/2 MED UVA radiation. Suberythema UVA radiation induced in skin production of phosphomonoesters, phosphodiesters, and also depleted phosphocreatine and adenosine triphosphate (ATP). This data seems to indicate that 31P MRS is a sensitive enough technique to detect UVA induced changes in skin phosphometabolites. Furthermore, this data also appears to indicate that suberythema UVA radiation and dexamethasone induce in skin nearly identical pharmacodynamic effects.
Epidermal stratification reduces the effects of UVB (but not UVA) on keratinocyte cytokine production and cytotoxicity
Authors: Corsini E. , Sangha N. , Feldman S. R.
Published: September 2011

Ultraviolet (UV) radiation induces cytokine release from cultured keratinocytes as well as from epidermis in vivo. The purpose of this study was to determine whether differentiation of cultured keratinocytes into stratified epithelium decreases the effects of UVA and UVB radiation on cytokine release. Interleukin‐1 (IL‐1)α, IL‐1β and tumor necrosis factor (TNF)‐α release from human keratinocytes and reconstituted human epidermis was measured after exposure to UVA or UVB radiation. Release of IL‐1α, IL‐1β, and TNF‐α was induced by both UVA and UVB radiation from both keratinocytes and reconstituted epidermis. Release of these cytokines was correlated with cytotoxicity. Keratinocyte cultures were far more sensitive to UVB radiation than reconstituted epidermis, in terms of both cytotoxicity and cytokine release. In contrast, epidermal stratification/differentiation had much less effect on the sensitivity to UVA radiation. We conclude that epidermal stratification and the formation of a stratum corneum provide protection against UVB radiation but have limited barrier effect against UVA radiation.
Assessment of skin types, skin colours and cutaneous responses to ultraviolet radiation in an Asian population
Authors: Wee L. K. S. , Chong T. K. , Quee D. Koh Soo
Published: September 2011

Ninety normal individuals were included in this study on skin types, skin colours and cutaneous responses to ultraviolet radiation. Skin types were recorded using Fitzpatrick's classification, skin colours were measured using the Minolta Chromameter CR‐300, and cutaneous responses to UV radiation were measured in terms of minimal erythema dose (MED) to UVA, UVB and the immediate pigment darkening dose to UVA (IPDDA). Skin colour measurements were taken from the right cheek to represent facultative skin colours, and from the buttock to represent constitutive skin colours. The colours measured were expressed by the L*a*b colour space. Skin types and some colour parameters (L and b from covered parts of body) correlated fairly well with the minimal erythema doses (MED) to UVA and UVB. Skin colour measurements are more objective than skin type assessment and could be better markers of photosensitivity. However, there is still considerable overlap in MEDs for persons with different skin colours, and further studies of these parameters are warranted. Our MEDs are higher than other reports on similar skin types and skin colours. This could be due to differences in methodology, genetic make‐up or acclimatization from chronic sun exposure. This illustrates the importance of local controls for each institution dealing with photosensitive disorders.
Phototoxic lysis of erythrocytes from humans is reduced after oral intake of ascorbic acid and d‐α‐tocopherol
Authors: Eberlein‐König B. , Placzek M. , Przybilla B.
Published: September 2011

Ultraviolet (UV) radiation causes hemolysis of human erythrocytes in the presence of photosensitizers. This can be used as an in vitro model for evaluating photosensitizing properties of substances. Antioxidants such as ascorbic acid (vitamin C) and d‐α‐tocopherol (vitamin E) have been found to be photoprotective in such test systems. We assessed the effect of combined systemic intake of both ascorbic acid and d‐α‐tocopherol by human volunteers on phototoxic in vitro lysis of their erythrocytes. In a double‐blind placebo‐controlled study, 10 subjects took daily 2 g ascorbic acid combined with 1000 IU d‐α‐tocopherol, and 10 took a placebo. Blood was taken before and after 7 days of treatment, erythrocytes were prepared and then incubated with 10‐3 mol/1 fenofibrate, a photosensitizer acting in the UVA and UVB region. The suspensions were exposed to radiation rich in UVA (up to 40 J/cm2 UVA) or to radiation rich in UVB (up to 1.6 J/cm2). Photohemolysis of the samples was calculated as a percentage of complete hemolysis. At the end of the treatment phase, in the placebo group photohemolysis was not significantly reduced compared with the initial values at all irradiation doses except for 1.6 J/cm2 UVB (96% vs 79%; P < 0.01). In the group taking vitamins, photohemolysis was significantly reduced at nearly all UV doses, most impressively after moderate UVA irradiation (20 J/cm2 UVA: 86.5% vs 14.5%; P < 0.01). It is concluded that the results of the photohemolysis test are influenced by the antioxidative status of the cell donor and that ascorbic acid and d‐a‐tocopherol also may protect against phototoxic damage in vivo.
Green light is effective and less painful than red light in photodynamic therapy of facial solar keratoses
Authors: Fritsch C. , Stege H. , Saalmann G. , Goerz G. , Ruzicka T. , Krutmann J.
Published: September 2011

Photodynamic therapy (PDT) with topically applied δ‐aminolevulinic acid (ALA) is increasingly employed to treat patients with multiple solar keratoses and superficial skin tumors. For these indications, ALA‐PDT has been shown to be highly efficient. Treatment of multiple or extended lesions, however, is substantially hampered by the fact that ALA‐PDT is associated with burning pain during the irradiation procedure. The standard irradiation devices commonly used for ALA‐PDT emit red light around 630 nm. In the present half‐side comparison study we have observed that ALA‐PDT employing a green light irradiation device (543–548 nm) is equally effective, as compared with standard red light ALA‐PDT. In contrast to red light ALA‐PDT, however, green light ALA‐PDT caused only little tingling and burning but no pain. These observations indicate that green light ALA‐PDT is superior to standard ALA‐PDT, because it is associated with less unwanted side effects.
How well are sunscreen users protected?
Authors: Stokes R. , Diffey B.
Published: September 2011

Previous studies have shown that people often apply less sunscreen than the recommended amount of 2 mg/cm2. Our purpose in this study was to determine objectively how photoprotection varies with application thickness. The protection provided by differing quantities of sunscreens containing varying amounts of titanium dioxide was measured in vitro using excised human epidermis as the substrate. It was found that application thickness had a significant effect on the sun protection factor (SPF), with most users probably achieving a mean SPF of between 20–50% of that expected from the product label. Underprotection due to inadequate application, coupled with overexposure to the sun, might partially explain why sunscreen use has been reported to be a risk factor in melanoma.
Clearance of UVB‐induced erythema in patients with non‐melanoma skin cancer
Authors: Holmes S. C. , Aitchison T. C. , MacKie R. M.
Published: September 2011

We have examined the clearance of UVB‐induced erythema in 10 non‐melanoma skin cancer (NMSC) patients, comparing their responses to a control group. All participants were followed to resolution of erythema, as measured by a chromameter. The resultant response pattern was modelled in three phases, with comparison of the rates of decay in erythema carried out. Analysis of the rapid decay phase demonstrated a significantly slower rate of resolution of erythema in the NMSC group, compared with the controls. Further elucidation of the molecular and genetic mechanisms controlling this response may improve our understanding of UV‐induced carcinogenesis.
The antimicrobial effect of narrow‐band UVB (313 nm) and UVA1 (345–440 nm) radiation in vitro
Authors: Fluhr J. W. , Gloor M.
Published: September 2011

Two new UV lamps were investigated with respect to their antibacterial effectiveness in vitro. Propioni (n=20 strains) and Micrococcaceae (n=16 strains) bacteria extracted from acne patients were applied to RCM and sheep blood agar plates and irradiated with a narrow‐band UVB lamp (TL 100W/10R) at a wavelength of 313 nm and a UVA1 lamp (TL 01) at a wavelength of 345–440 nm. The precisely defined energy levels were, in the case of narrow‐band UVB, 0.00, 0.30, 0.50, 1.00, 2.00 and 3.00 J/cm2 and, in the case of UVA1, 0.00, 2.50, 5.00, 7.50, 10.00 and 20.00 J/cm2. UVA1 inhibited neither the growth of Propioni nor Micrococcaceae bacteria. In contrast, the growth of Micrococcaceae was inhibited already at a dosage of 0.30 J/cm2 of narrow‐band UVB (P<0.05), highly significant from 0.50 J/cm2 (P<0.01) and to a maximum of 2.2 powers of 10 at 3.00 J/cm2 compared with non‐radiated control plates. Propioni bacteria were significantly inhibited at the minimum dosage of 0.30 J/cm2 of narrow‐band UVB (P<0.01) and to a maximum of 2.8 powers of 10 at 3.00 J/cm2.
Identification of the Complement Regulatory Protein CD59 in Human Colostrum and Milk
Authors: Børge Line , Jensen Tone Skeie , Kristoffersen Einar Klæboe , Ulstein Magnar , Matre Roald
Published: September 2011

PROBLEM: Complement lytic activity has been demonstrated, and a potential for its activation is present in human colostrum and milk. This necessitates the presence of regulatory mechanisms protecting epithelial cells in the oropharynx and the gastrointestinal tract of the infant, the milk cellular elements, and bacteria colonizing the oropharynx and the gastrointestinal tract. Lactoferrin and C1 inhibitor have been attributed such a role. However, it is likely that additional protection against the cytolytic activity of the membrane attack complex is required. This has lead us to investigate the presence of the complement regulatory protein CD59 in human colostrum and milk, and to further characterize the source of secretion.

METHOD: Samples of human colostrum and milk were obtained from volunteers at different stages of lactation, and separated into fat, skim milk, and milk cellular elements by centrifugation. Normal human mammary gland tissues were obtained from patients undergoing biopsy for benign conditions. SDS‐PAGE and Western blotting, and an immuno dot‐blot assay were used to identify CD59 in human milk. Immunohistochemistry was performed on all tissue samples and cytospins of the milk cellular elements, using monoclonal antibodies to CD59.

RESULTS: CD59 was present in cell‐free colostrum and milk as a 19–25 kDa glycoprotein. No variation in CD59 levels was detected between colostrum and milk. CD59 was present in great amounts in the cytoplasm and was highly expressed on the surface membrane on mammary gland acinar and ductal epithelial cells, while the milk cellular elements contained CD59 mainly in their cytoplasm.

CONCLUSION: The complement regulatory protein CD59 present in cell‐free human colostrum and milk may exert its effects both in the mammary gland and in the oropharynx and gastrointestinal tract of the infant. The lobuloalveolar epithelial cells in the mammary gland are the likely source of secretion.
Termination of Pregnancy in Rodents by Oral Administration of Praneem, a Purified Neem Seed Extract
Authors: Mukherjee Sutapa , Talwar G.P.
Published: September 2011

PROBLEM: Development of an orally administered abortifacient.

METHODS: Subjects were female Wistar rats, weighting 150 to 200 g at the time of experiments. Praneem (a purified extract of neem Azadirachta indica) at a dose of 0.6 ml was given orally from day 8 to 10 after confirming presence and number of implants surgically on day 7 of pregnancy. The animals were examined again under anesthesia on day 15 of pregnancy to check the number of developing embryos. Controls received an equivalent regime of peanut oil. The number and size of implants were counted five days after treatment.

RESULTS: Complete resorption of embryos was observed on day 15 of pregnancy in every animal treated with Praneem in contrast to normally developing embryos in rats given peanut oil. In repeat batch experiments, it was established that the effect of the treatment was reversible and animals regained fertility in cycles subsequent to treatment with Praneem. Cytokines of TH1 type, i.e., gamma interferon and TNF, were raised on administration of Praneem, which may be the probable cause of pregnancy termination.

CONCLUSIONS: Praneem on oral adminstration can cause termination of pregnancy in rodents, and the action is probably mediated by TH1 cytokines.
Steroid Sex Hormones and Macrophage Function: Regulation of Chemiluminescence and Phagocytosis
Authors: Chao Tzu‐chieh , Phuangsab Anan , Van Alten Pierson J. , Walter Robert J.
Published: September 2011

PROBLEM: Female sex hormones modulate a variety of humoral and cell‐mediated immunologic functions. In this study, the effects of estrogen, progesterone, and testosterone on the chemiluminescence (CL) response and phagocytic ability of male rat peritoneal macrophages (Mφ) were examined.

METHOD: In Mφ pretreated with 10−2ng/ml of 17β‐estradiol (E2) for 20 hours, the CL generated in response to phorbol myristate acetate (PMA), 1,2‐dioctanoyl‐rac‐glycerol (C8:0), or opsonized zymosan (OZ) was significantly increased by 135%, 140%, and 136% of control values, respectively. In addition, Mφ treated with 10−5ng/ml or 10 ng/ml of E2exhibited a significantly greater PMA‐or OZ‐stimulated CL response than did untreated controls.

RESULTS: At 10−2ng/ml, progesterone enhanced and testosterone reduced the CL response, but these changes were not statistically significant. In time course studies, the PMA‐stimulated CL response of Mφ treated with 10−2ng/ml of E2or progesterone for 5 h was significantly less than that of the untreated group. In the presence of endotoxin (12 pg/ml), the CL response in Mφ treated with E2or testosterone was significantly depressed as compared to untreated controls. Phagocytosis of opsonized sheep erythrocytes also was significantly enhanced (140% to 190% of control) when Mφ were pretreated with 10−12M to 10−8M of either E2or progesterone.

CONCLUSIONS: These findings suggest that, at physiological concentrations, E2is capable of modulating both CL generation and phagocytic uptake by Mφ in a manner not shared by other steroid hormones.
Detection of Antiendometrial Antibodies in Patients With Endometriosis by Cell ELISA
Authors: Hatayama Hiroshi , Imai Kimitoshi , Kanzaki Hideharu , Higuchi Toshihiro , Fujimoto Mariko , Mori Takahide
Published: September 2011

PROBLEM: To determine whether infertile patients with endometriosis have serum antiendometrial antibodies.

METHODS: Sera from 40 infertile patients with or without endometriosis were tested by cell enzyme‐linked immunosorbent assay (ELISA), in which endometrial cancer cells were used as endometrial antigens, and uterine cervix cancer cells as control antigens. As a negative control, eight healthy adult males were included. The level greater than the mean + 2 standard deviations (SD) of the male control group was judged positive.

RESULTS: The mean value of antiendometrial antibody level was significantly higher in patients with endometriosis than in those without endometriosis (ANOVA, P < 0.01). The frequency of antiendometrial antibody‐positive patients was also higher in the former than in the latter (χ2 test, P < 0.05). However, when uterine cervix cancer cells were used as antigens, no difference was observed in the mean antibody levels or in the positive rates between the two groups.

CONCLUSIONS: Endometriosis seems to be associated with autoantibody production against the endometrium‐related antigen(s).
Structural Analysis of the Carboxyl Terminal Peptide From Human Chorionic Gonadotropin β‐Subunit by Two‐Dimensional Nuclear Magnetic Resonance Spectroscopy
Authors: Rock Edwin P. , Czaplicki Jerzy , Milon Alain
Published: September 2011

PROBLEM: Vaccines that target human chorionic gonadotropin (hCG) might be made more effective through greater understanding of the solution three‐dimensional structure and behavior of the hormone.

METHOD: A 37‐amino acid carboxyl terminal peptide of the hCG beta subunit was synthesized, purified, and analyzed by two‐dimensional nuclear magnetic resonance spectroscopy. RESULTS: Double‐quantum filtered correlated spectroscopy data on the peptide in water at 4°C reveals 27 multiplets in the peptide fingerprint region, as expected. A nuclear Overhauser effect spectroscopy spectrum shows several intraresidual peaks in the amide region but lacks clearly assignable interresidual signals.

CONCLUSION: By itself in water the carboxyl terminal peptide of hCG lacks defined secondary structure elements and is thus likely a random coil. The presence of beta turns appears possible although neither their existence nor their localization can be confirmed.
The Potential of the Zona Pellucida as a Target for Immunocontraception
Authors: Aitken R.J. , Paterson M. , Duin M. van
Published: September 2011

PROBLEM: To investigate the contraceptive potential of the zona pellucida. METHOD: Generation of antibodies against native and recombinant zona glycoproteins which have then been assessed for their capacity to disrupt sperm‐zona interaction in vivo and in vitro. The animal model selected for these studies was the common marmoset and the end points examined were antibody titre, ovarian cyclicity and fertility.

RESULTS: The fact that antibodies against the major zona glycoprotein, ZP3, block both the primary and secondary phases of sperm‐zona interaction suggests that this molecule might have potential for contraceptive vaccine development. Active immunization of marmoset monkeys with native porcine ZP3 or recombinant human ZP3 produced long term infertility but also precipitated a premature decline in the primordial follicle population.

CONCLUSIONS: Future studies will have to determine whether a safe, effective vaccine can be engineered by coupling unique B‐cell epitopes from ZP3 to foreign T‐cell antigens.
Luminal and Glandular Endometrial Epithelium Express Integrins Differentially Throughout the Menstrual Cycle: Implications for Implantation, Contraception, and Infertility
Authors: Lessey Bruce A. , Ilesanmi Abiodun O. , Lessey Meredith A. , Riben Michael , Harris Jocelyn E. , Chwalisz Kristof
Published: September 2011

PROBLEM: Integrins belong to a family of cell adhesion molecules that are present on virtually all cells. The temporal and spatial expression of these important proteins on the human endometrium suggests that certain integrins may participate in the cascade of molecular events leading to successful implantation.

METHODS: Using immunohistochemistry, we studied the expression of 12 different integrins in up to 600 samples of human endometrium throughout the menstrual cycle. Intensity and distribution of staining was determined using the semiquantitative HSCORE, with specific focus on the differences between glandular and luminal expression.

RESULTS: We noted that the glandular and luminal epithelium undergo independent alterations in integrin expression throughout the menstrual cycle. Specifically, glandular epithelium express certain integrins only during the window of implantation, while luminal epithelium down‐regulate certain integrins during this time. The expression of one integrin (the αvβ3 vitronectin receptor) on both luminal and glandular epithelium coincides with the time of embryo attachment; aberrant expression of this integrin is associated with infertility.

CONCLUSION: It appears that the endometrium is a unique tissue with regard to the number of integrins that undergo temporal and spatial changes during the menstrual cycle. These data may offer new directions for the development of a novel contraceptive approach targeted to the endometrium as well as a better understanding of occult causes of infertility in women.
Anomalous Inheritance of a Paternally Derived Trophoblast Antigen
Authors: Rezai A. , Underwood J.L. , Jalali G.R. , Mathias S. , Allen W.R. , Mowbray J.F.
Published: September 2011

PROBLEM: Recurrent spontaneous abortion occurs in 1 in 500 random matings and usually results in abortion of all pregnancies. If absence of antibody to a paternally derived antigen caused abortion, the woman would be expected to make antibody to the other paternal antigen and abort only half her pregnancies.

METHODS: Microvesicles were prepared from equine placentae. Acid‐eluted IgG antibody was eluted from the polymorphic R80K antigen and used to type the residual R80K antigen on vesicles or on peripheral blood leucocytes.

RESULTS: In several equine sibships all the half‐sibs had the same paternal R80K alloantigen. In the extended horse family descended from the stallion Nearco, three allotypes were found. The allele present was usually the grandpaternal one, but exceptions are seen. Whichever allele is transmitted all the progeny have the same alloantigen (probability of this occurring by chance = 2‐45).

CONCLUSION: Because only one paternal allotype is present in all progeny, lack of antibody to the R80K antigen would result in loss of all pregnancies, not one half.
Modulation of the Humoral Immune Response by Placental Secretory Factors
Authors: Borel Ileana Malan , Miranda Silvia , Freire Songeli Menezes , Canellada Andrea , Bueno Marta Eslava , Binaghi Ruben , Margni Ricardo A.
Published: September 2011

PROBLEM: To investigate how the factors secreted by human placenta modify the quality and the quantity of the antibody produced by the hybridoma as well as its cellular proliferation.

METHOD: Supernatants of cultures of human placenta (PS) were added to a mouse IgG1 hybridoma culture producing anti‐DNP antibodies. The quantity of monoclonal antibody produced, the nature of these antibodies and the proliferation of the hybridoma cells were studied.

RESULT: It was found that PS augmented by 40–50% the quantity of total antibody produced, increased the proportion of asymmetric (blocking) antibodies from 15% to 30%, and diminished the cellular proliferation, as measured by 3H‐thymidine incorporation.

CONCLUSION: These results, together with other similar observations already described in human, rat and mouse pregnancies, suggest that secretory factors produced by the placenta do modify the immune response of the mother against paternal antigens and participate in the mechanisms that make possible the survival of the allogenic fetus.
Expression of γδT Cells and Adhesion Molecules in Endometriotic Tissue in Patients With Endometriosis and Adenomyosis
Authors: OTA HIROTAKA , IGARASHI SHINICHI , TANAKA TOSHINOBU
Published: September 2011

PROBLEM: Are T cell subsets, including γδT cells, HLA antigens or adhesion molecules, expressed in eutopic and ectopic endometria in patients with endometriosis and adenomyosis?

METHODS: Subjects consisted of 23 patients with adenomyosis and 21 patients with endometriosis. Controls consisted of 15 patients with adenomyoma and 42 infertile women without habitual abortion and autoimmune diseases. Staining of the glandular cells in eutopic and ectopic endometria or T lymphocyte subsets or macrophages in the stroma were analyzed immunohistochemically to localize the expression of the antigens.

RESULTS: Immunohistochemical analysis revealed significantly increased expression of the antigens, particularly of the number of γδT cells in the stroma and adhesion molecules and HLA antigens on the glandular cells in eutopic and ectopic endometria, compared with materials from patients with adenomyoma and infertile patients.

CONCLUSION: It is likely that three distinct pathways of cell‐cell interactions are activated in patients with endometriosis or adenomyosis.
Effects of Gonadotropin‐Releasing Hormone Agonist (GnRHa) and Ovariectomy on Leukocyte Subpopulations in Rats With Autotransplanted Endometrium
Authors: Matsubayashi Hidehiko , Iwasaki Ken‐Ichi , Maruyama Tetsuo , Ozawa Nobuaki , Nemoto Taiko , Iwasaki Shinya , Sun Wen‐Shu , Nakazawa Kazumi , Nozawa Shiro , Makino Tsunehisa
Published: September 2011

PROBLEM: To determine the effect of estrogen deficiency on populations of immune cells in rats with autotransplanted endometrium.

METHOD OF STUDY: Autologous endometrial segments were implanted in the peritoneum of rats. Leukocyte subsets in the peripheral blood (PB) and peritoneal fluid (PF) of autotransplanted rats treated with gonadotropin‐releasing hormone agonist (GnRHa) or ovariectomy were analyzed by flow cytometry.

RESULTS: Endometrial growth was suppressed in association with increases in natural killer (NK) cells and macrophages in rats treated surgically or medically after endometrial implantation compared with autotransplanted‐only rats. Normal rats treated with GnRHa showed no significant alterations in PB and PF leukocyte subsets, even in NK cells and macrophages, compared with untreated normal rats.

CONCLUSIONS: Data suggest that GnRHa itself did not have an immunomodulating effect when rats were treated for 3 weeks, but that a hypoestrogenic state reduced the size of the ectopic endometrium in association with increases in NK cells and macrophages. Our findings support the hypothesis that ectopic endometrial cells may release immunosuppressive factors.
Matrix Metalloproteinase Expression During Mouse Peri‐implantation Development
Authors: Sharkey Mark E. , Adler Richard R. , Nieder Gary L. , Brenner Carol A.
Published: September 2011

PROBLEM: The purpose of this study was to define the temporal expression and to quantitate the mRNA levels of collagenase, 72 kDa, 92 kDa, and membrane‐type matrix metallo‐proteinases during the peri‐implantation period of pregnancy in the mouse uterus. Embryonic expression of 72 kDa and 92 kDa matrix metalloproteinases, as well as interleukin 1α, was also investigated.

METHODS: Uterine matrix metalloproteinases were detected using gelatin substrate gel electrophoresis (zymography) and reverse‐transcription polymerase chain reaction methodology was used to detect and quantitate different mRNA species in the mouse uterus and blastocyst.

RESULTS: Collagenase, 72 kDa, and 92 kDa matrix metalloproteinases are developmentally regulated during the peri‐implantation period of pregnancy, but membrane‐type matrix metalloproteinase appears to be expressed constitutively. Matrix metalloproteinase mRNA levels have been quantitated and confirm the observed developmental expression patterns. Prominent expression of both 92 kDa matrix metalloproteinase and interleukin 1α was observed in blastocysts during outgrowth while weak expression of the 72 kDa matrix metalloproteinase was detected.

CONCLUSIONS: The data provide evidence of matrix metalloproteinase expression in vivo and substantiate their potential role in tissue remodeling prior to and during blastocyst implantation. Expression of interleukin 1α, 92 kDa, and 72 kDa matrix metalloproteinases suggests that these proteins are important for trophoblast invasion associated with implantation of the early embryo.
Human Sperm Coating Antigen From Seminal Plasma Origin
Authors: Iborra A. , Morte C. , Fuentes P. , García‐Framis V. , Andolz P. , Martinez P.
Published: September 2011

Sperm surface glycoproteins may be involved in sperm‐zona pellucida recognition. Some of these coating proteins are of seminal plasma origin and their expression may change in the process of capacitation and acrosome reaction. Sperm specific monoclonal antibodies (mAb) define the presence and role of sperm membrane associated proteins. We have isolated a monoclonal antibody (SEM‐12) specific for human sperm that shows, by indirect immunofluorescence, a discontinuous distribution of the antigen on the head and tail surfaces of non capacitated sperm. This antigen is also present in human seminal plasma as detected by ELISA. The antigen is detectable in sperm of goat, ram, and mouse. Two proteins in the range of 80–84 kDa have been isolated by affinity chromatography with SEM‐12 mAb. The same result is obtained by immunoprecipitation. This antibody inhibits sperm motility and acrosome reaction (spontaneous and A23187 ionophore induced).
Quantitative Changes in Macrophage Distribution in Normal Mouse Ovary Over the Course of the Estrous Cycle Examined With an Image Analysis System
Authors: Petrovská Marianna , Dimitrov Dimitar G. , Michael Sandra D.
Published: September 2011

PROBLEM: The current study considered the distribution of macrophages within the major ovarian structures throughout the estrous cycle.

METHODS: Immunohistochemical analyses were carried out using an avidin‐biotin‐peroxidase staining method and the rat anti‐mouse macrophage monoclonal antibody anti‐Mac‐1 was applied to stain macrophages. A computer‐assisted image analysis system was used to quantify and compare the distribution of macrophages within individual ovarian structures during the estrous cycle. The following morphological structures were analyzed: primordial, preantral, antral, pre‐Graafian, and atretic follicles; first‐, second‐, and third‐generation corpora lutea; and the interstitium. The analysis included follicular and corpus luteum substructures: theca, granulosa cells, and interstitium. The system allows the estimation of macrophage distribution as a macrophage density per μm2 of the defined area.

RESULTS: Primordial and preantral follicles did not contain macrophages during all stages of the estrous cycle. In antral, pre‐graafian, and graafian follicles, macrophages were located and quantified only in the theca and were not detected in the granulosa cell layer. In contrast, atretic follicles showed macrophage localization in both thecal and granulosa cell layers. Macrophages were present in small numbers in the granulosa luteal cell layer and in high numbers in the thecal layer of newly developing corpora lutea. In the second generation of corpus luteum, macrophages followed the same pattern of distribution, while old corpora lutea contained significantly higher numbers of macrophages in both thecal and luteal cell layers. Surprisingly, significant quantitative changes in the macrophages distribution were detected over the course of the estrous cycle. Macrophage density was significantly higher in proestrus and metestrus when compared with the density in diestrus and estrus in most of the studied substructures with the exception of atretic follicles. Atretic follicles showed high macrophage density throughout the cycle with a two‐fold higher density at metestrus.

CONCLUSION: Macrophages were present in the mouse ovary over the course of the estrous cycle. The greatest numbers of macrophages appearing in corpora lutea and in atretic follicles suggest a role for macrophages in corpus luteum differentiation and follicular atresia. Their patterns of distribution at proestrus and metestrus within microenvironmental compartments suggests a functional correlation with the events of ovarian development.
Amniotic Fluid Endothelin‐1 Levels Are Increased in Pregnancy‐Induced Hypertension and Intrauterine Growth Retardation
Authors: Iorio Romolo Di , Marinoni Emanuela , Anceschi Maurizio M. , Emiliani Serena , Letizia Claudio , Cosmi Ermelando V.
Published: September 2011

Endothelin‐1 (ET‐1) is a potent vasoconstrictor released by vascular endothelium. Because endothelial cell damage is considered determinant in the pathophysiology of pregnancy‐induced hypertension (PIH), this study was conducted to evaluate the role of ET‐1 produced by feto‐placental tissues in PIH.

Amniotic fluid samples obtained by amniocentesis from patients with PIH (N=33), intrauterine growth retardation (IUGR) (N=16), and PIH associated with IUGR (N=12) were evaluated for ET‐1 and compared to 42 normotensive pregnancies using a specific radioimmunoassay.

ET‐1 levels were significantly increased in PIH (35.6 ± 1.9 pg/ml) and IUGR groups (33.8 ± 4.6 pg/ml) compared to controls (20.8 ± 1.4 pg/ml) (P <0.01). In patients with PIH associated with IUGR, ET‐1 concentrations were higher (P <0.05) with no correlation with the severity of IUGR.

Our data indicate that in PIH and IUGR ET‐1 production and/or secretion is enhanced in the amniotic compartment, suggesting that the peptide may contribute to the pathophysiologic modifications observed in these conditions.
Human Endometrial Expression of Granulocyte Colony‐Stimulating Factor (G‐CSF) and Its Receptor, Stimulation of Endometrial G‐CSF Production by Interleukin‐1β, and G‐CSF Inhibition of Choriocarcinoma Cell Proliferation
Authors: Vandermolen David T. , Gu Yang
Published: September 2011

PROBLEM: To investigate the expression, regulation thereof, and actions of human endometrial granulocyte colony‐stimulating factor (G‐CSF).

METHODS: Endometrial expression of messenger ribonucleic acids for G‐CSF and its receptor were studied using reverse transcriptase‐polymerase chain reaction. In tissue culture, endometrial G‐CSF protein production, baseline and in response to interleukin‐1β, was determined by enzyme‐linked immunosorbant assay of the conditioned media. G‐CSF effects on proliferation of three choriocarcinoma cell lines were determined.

RESULTS: In vivo, human endometrium expressed messenger ribonucleic acids for G‐CSF and its receptor throughout the menstrual cycle, and endometrium expressed G‐CSF protein in vitro. Interleukin‐1β stimulated endometrial G‐CSF protein production in time and dose dependent manners. G‐CSF inhibited proliferation of two choriocarcinoma cell lines.

CONCLUSIONS: These results suggest that 1) G‐CSF may have physiologic roles in the endometrium throughout the menstrual cycle; 2) endometrial G‐CSF protein production is stimulated by interleukin‐1β; and 3) that G‐CSF may, in part, mediate local actions of interleukin‐1β and modulate trophoblast proliferation.
Cytokine Expression by Models of Human Trophoblast as Assessed by a Semiquantitative Reverse Transcription‐Polymerase Chain Reaction Technique
Authors: Bennett William A. , Lagoo‐Deenadayalan Sandhya , Brackin Martha N. , Hale Enatra , Cowan Bryan D.
Published: September 2011

PROBLEM: Cytokines form an important communication network between the mother and fetus. Defining the significance of these factors requires an understanding of their constitutive expression by maternal and fetal tissues. This study examines cytokine expression by human trophoblast.

METHODS: A reverse transcription polymerase chain reaction (RT‐PCR) technique was used to assess cytokine expression by choriocarcinoma cells (BeWo, JEG‐3, and JAR) and term trophoblast. Placental digests were enriched for trophoblast by immunoaffinity (CD‐9) columns.

RESULTS: Interleukin (IL)‐1, tumor necrosis factor (TNF)‐α and interferon (IFN)‐γ were weakly expressed or absent in the choriocarcinoma cells. In contrast, these cytokines were expressed by term trophoblast. IL‐6, IL‐10, IFN‐α, IFN‐β, and granulocyte macrophage‐colony stimulating factor (GM‐CSF) mRNA were detected in all trophoblast cells, except for a paucity of IL‐10 expression by JEG‐3 cells.

CONCLUSIONS: Human choriocarcinoma cells and term trophoblast express cytokines that may regulate critical reproductive events. Expression of inflammatory cytokines such as IL‐1, TNF‐α, and IFN‐γ by term trophoblast could trigger labor or be a consequence of labor‐associated events.
Functional Characteristics of Human Trophoblast Interferons
Authors: Aboagye‐Mathiesen George , Tóth Ferenc D. , Zdravkovic Milan , Ebbesen Peter
Published: September 2011

Human trophoblast populations from first‐ and third‐trimester placentas produce interferons (IFNs) in the presence of growth factors (CSF and PDGF) or when infected with virus. The highly invasive extravillous trophoblast population produced a higher level of IFNs (three‐ to eightfold, P < 0.05) than the noninvasive villous trophoblast population when stimulated with growth factors and/or virus. The level of IFN produced was dependent on the type of trophoblast population, the type of inducer and the stage of differentiation of the trophoblasts. Tandem immunoaffinity chromatography of the virus‐induced trophoblast IFNs resulted in the isolation of trophoblast IFN‐α and ‐β types. The purified trophoblast IFNs have antiviral, antiproliferative and immunoregulatory properties. Furthermore, the trophoblast IFNs inhibited the expression of proto‐oncogenes such as EGF‐R, c‐erbB2 and c‐fms reported to be involved in normal trophoblast growth and differentiation. These data suggest essential roles of interferons in normal human development during pregnancy.
Control of Cell Proliferation by Embryonal‐Origin Factors
Authors: Barnea Eytan R. , Barnea Jean‐David , Pines Mark
Published: September 2011

Embryogenesis can be paralleled and contrasted with cancerous cell proliferation; both embryogenesis and cancer are associated with extremely rapid cell proliferation. However, unlike cancer, embryogenesis is characterized by a delicate balance of proliferative and anti‐proliferative processes. We have found two chromatographically separated fractions derived from human embryonal neural tissue extracts that significantly suppress the proliferation of human breast cancer cells. The reduction in cell number was time dependent, with maximal inhibition (70%) observed after 4 days of incubation while maintaining cell viability. The anti‐proliferative effect was also evidenced by decreased [3H]‐thymidine incorporation. Significant inhibition of proliferation of osteosarcoma, fibrosarcoma, and Balb/c 3T3 cell lines was also obtained with a low concentration of the active fractions. Embryonal factors inhibited mouse and rat cell lines, indicating cross‐species effectiveness. The SDS‐PAGE of the biologically active ˜ 10.7 kDa region revealed several protein bands, while the biologically active ˜ 4.5 kDa fraction contained only weakly stainable bands.

Thus, the embryo contains factors that control the proliferation of malignant cells. These potent and possibly novel compounds should be investigated for their potential therapeutic role in cancer and other proliferative disorders.
Embryotoxicity as a Marker for Recurrent Pregnancy Loss
Authors: Sargent Ian L. , Dokras Anuja
Published: September 2011

Some cases of unexplained recurrent pregnancy loss may be due to embryotoxic factors present in the mother's serum. In vitro assays have been devised to study the effect of these factors on pre‐implantation, peri‐implantation, and somite stage rodent embryos. Embryotoxic activity has been found in a high percentage of recurrent aborters but is also present in women with endometriosis and unexplained infertility, suggesting that there may be a range of factors acting at different stages of development. Embryotoxic activity may be predictive of pregnancy outcome and has been shown to be decreased after hormone and immunotherapy. However, its true value can only be assessed when the nature of the toxic factors is understood. Preliminary characterisation studies suggest that toxic activity may due to both immunological (antibodies or cytokines) and nutritional factors.
Neuroimmunological Aspects of Fetus and Newborn Brain Damage in Complicated Pregnancy
Authors: Borodin Yuriy , Chekhonin Vladimir
Published: September 2011

PROBLEM: The role of neuroautoimmune mechanisms in pathogenesis of perinatal damage of fetus and neonate brain during complicated pregnancy is considered to be important.

METHOD: To determine neurospecific antigens (NSA) and their antibodies, ELISA and two‐site column enzyme immunoassay were used.

RESULTS: The contents of NSA and anti‐brain antibodies, associated with fetal brain congenital development defects, account for the development of neuroautoimmune shifts in the mother‐fetus system. The time of NSA appearance in serum from pregnant women, the dynamics of their level during pregnancy, and the appearance of anti‐brain antibodies were determined, not by the nosology of extragenital pathology, but by the degree of fetus suffering, i.e., by the state of its central nervous system, connected with the decompensation of metabolic processes and homeostatic disorder in a mother‐fetus system.

CONCLUSIONS: Approved immunodiagnostic test systems should be recommended as markers for determination of pregnancy risk group, prognosticating perinatal pathology of neonatal and childhood CNS disorders.
The Interleukin‐1 System and Human Implantation
Authors: Simón Carlos , Mercader Amparo , Gimeno Maria José , Pellicer Antonio
Published: September 2011

PROBLEM: Cytokines and growth factors are increasingly implicated in embryonic implantation. In the present study, we focus on the interleukin‐1 system as an example of local regulator in human implantation.

METHOD: Three different approaches are considered. First, we present evidence demonstrating its presence, regulation, and relevance on the human endometrium. Second, we demonstrate the presence of the IL‐1 system in the human embryo and the selective IL‐1 release only when embryos were co‐cultured with human endometrial epithelial cells (EEC) or EEC‐conditioned media, indicating an obligate role of the endometrium in the regulation of the embryonic IL‐1 system. Finally, we show data regarding the presence, hormonal regulation, and endometrial origin of IL‐1α, IL‐1β, and IL‐1ra levels in the endometrial fluid inside the endometrial cavity. Specifically, we present the IL‐1 intracavitary microenvironment surrounding the human embryo at the apposition phase.

RESULTS: This work suggests that the IL‐1 system seems to be relevant for human endometrial and embryonic physiology. Furthermore, this family of molecules must be considered as a relevant paracrine language displayed by both partners that may be important to endometrial and embryonic crosstalk during embryonic implantation.
Phospholipid Binding Plasma Proteins Required for Antiphospholipid Antibody Detection—An Overview
Authors: McIntyre John A. , Wagenknecht Dawn R. , Sugi Toshitaka
Published: September 2011

PROBLEM: Antibodies to phospholipid antigens (aPA) are associated with thrombosis thrombocytopenia and recurrent pregnancy loss. Contemporary data show many aPA target phospholipid‐binding plasma proteins and not phospholipids. The purpose of this overview is to describe several phospholipid‐binding proteins and provide data to demonstrate how the interaction between phospholipids and phospholipid binding proteins results in expression of neo‐autoantigenic epitopes.

METHOD: Review of existing data.

RESULTS: Illustrations of how certain plasma proteins β2 glycoprotein I, prothrombin, high and low molecular weight kininogens interact with the anionic phospholipids, cardiolipin and phosphatidylserine and the zwitterionic phospholipid, phosphatidylethanolamine are shown and discussed. A model of aPA mediated thrombosis is presented.

CONCLUSIONS: Some aPA recognize phospholipids directly, however, the majority and many which correlate with pathology target phospholipid binding proteins. Published data indicate that aPA represent a constellation of antibodies with multiple specificities. Insight into mechanisms responsible for aPA‐associated thrombosis should provide a basis for treatment.
Immune Responses of Chemically Modified Homologous LDH‐C4 and Their Effect on Fertility Regulation in Mice
Authors: Gupta G.S. , Syal N.
Published: September 2011

PROBLEM: Lactate dehydrogenase‐C4 (LDH‐C4) is an iso‐, allo‐ and auto‐antigen of mammalian sperm. In spite of being cell specific, LDH‐C4 does not induce infertility in females of homologous species after immunization. The present study examines the application of homologous LDH‐C4 after chemical modifications in the immunological infertility of female mice.

METHODS: LDH‐C4 from testes of LACA mice was chemically modified by interacting it with gossypol (gossy‐LDH‐C4) and glucosylation with lactose (Glu‐LDH‐C4) in vitro and evaluated for immune responses and induced immunological infertility in allogeneic Balb/c mice after inoculation through intrarectal route using Al(OH)3 as adjuvant.

RESULTS: Native LDH‐C4, which elicited high antibody response after immunization with a primary (50 μg) and three secondary doses (30 μg each) at an interval of 15 days each, did not reduce fertility significantly in mice. In contrast, study provides evidence that chemically modified LDH‐C4 induces high infertility, since 85–100% of mice failed to conceive in two independent sets of experiments. Mice inoculated with modified LDH‐C4 were associated with 2–3‐fold anti‐LDH‐C4 antibody titre compared to antibody response elicited by native LDH‐C4. Splenocytes from immunized non‐pregnant mice were evaluated for polyclonal activation using Con A as mitogen. It was found that splenocytes primed with native LDH‐C4 were significantly more stimulated than the non‐immune control cultures. However cells primed with gossy‐LDH‐C4 were non‐reactive to Con A and cells primed with glu‐LDH‐C4 were suppressed for ConA proliferation.

CONCLUSIONS: It is concluded that LDH‐C4‐gossypol adduct offers a potential application in the induction of infertility of homologous species in marked contrast to native LDH‐C4. Application of Al(OH)3 as adjuvant in the induction of immune response through intra‐rectal route has been suggested.