Management of vulvar melanoma and review of the literature.

BACKGROUND: Vulvar melanoma represents a rare group of malignancies and is the second most common vulvar malignancy. Treatment options range from local excision of the tumor and sentinel lymph node dissection to radical resection involving en bloc vulvectomy and inguinofemoral lymphanedectomy. Vulvar melanomas have an overall poor prognosis, and there is lack of consensus in the published literature regarding treatment options. OBJECTIVE: To discuss the management of vulvar melanomas through review of the actual literature. METHODS: Identification of studies through computerized searches (January 2006) was conducted using MEDLINE (1966 to present), the Cochrane Central Register of Controlled Trials, the National Research Register and the Medical Research Council's Clinical Trials Register. The medical subject headings and text words used were: vulvar melanoma, malignant, management, case report, and therapy. The literature review was done over the past 36 years. RESULT: Results of these primary retrospective series have shown no improvement in the overall recovery or disease survival rates. CONCLUSION: Patients with malignant melanoma are often diagnosed at 70 years of age with multiple comorbidities. Less radical surgery presents a more realistic option for many patients without decreasing their survival rates. Surgery is still the gold standard of treatment and offers the best available treatment for controlling and potential curing of malignant melanomas. However, the whole concept of therapy should be tailored to meet the specific needs of individual patients.

Ovine placental eluate immunoglobulins recognise isologous and third party acid-treated trophoblast microvesicle antigens in vitro.

Placental microvesicles were prepared from ovine placentae and immunoglobulins eluted with 0.5 M glycine buffer pH 2.5. The ability of eluate immunoglobulins to re-associate with isologous (self) and third party acidified microvesicles was tested by ELISA. Ovine placental immunoglobulins re-associated with isologous and third party acidified microvesicles suggesting that at least 2 types of antigenic epitopes I and II maybe expressed on the ovine placentae. Type I antigens may be present on placentae of all ovines while type II epitopes may be paternally derived, hence unique to each pregnancy. Analysis by SDS PAGE revealed the heavy and light chains of IgG at 57 and 27 kDa, respectively, together giving a relative molecular weight of 158 kDa. Results suggest that immunoglobulins produced to placental microvesicle antigens may be directed to some but not all antigenic epitopes expressed on the trophoblast, possibly defining a mechanism by which the foetus evades maternal immunological rejection.

Human placental immunoglobulins show unique re-association patterns with isologous and third party acid treated trophoblast microvesicles in vitro.

OBJECTIVE: To study re-association pattern of human placental eluate immunoglobulins with acid treated isologous and third party trophoblast derived placental microvesicles. DESIGN: Laboratory based experimentation. SETTING: Biological Sciences Department and Discipline for Reproductive Medicine University of Newcastle, Australia and the Department of Biochemistry, University of Nairobi, Kenya. RESULTS: Placental eluate immunoglobulins re-associated with isologous and third party acidified microvesicles in three distinct patterns. I: eluate immunoglobulins re-associated more strongly with isologous and third party acid treated placental microvesicles, II: eluate immunoglobulins re-associated strongly with isologous but weakly with third party acid treated placental microvesicles, III: eluate immunoglobulins did not show preferential re-association with isologous and third party acid treated placental microvesicles. CONCLUSION: Two types of antigenic epitopes I and II may be expressed on the human placentae. Type I antigens may be present on all human placentae while type II epitopes may be paternally derived hence unique to each pregnancy. Also, immunoglobulins produced to placental microvesicle antigens may be directed to some but not all antigenic epitopes expressed on the human placental trophoblast.

Immunoglobulin G bound to ovine placenta is eluted by surgical cannulation and acid perfusion in situ.

OBJECTIVE: To elute placental bound immunoglobulin G (IgG) in situ. DESIGN: Laboratory based experimentation. SETTING: Biological Sciences Department, The University of Newcastle Australia and the Department of Biochemistry, University of Nairobi, Kenya. SUBJECTS: Twelve pregnant ewes 10 to 15 days before the onset of natural parturition. RESULTS: Placental eluates were rich in IgG, and IgG2. The relative molecular weight of placental IgG was estimated at 158kDa by gel filtration chromatography. Analysis of eluate by SDS PAGE revealed the heavy and light chains of IgG at 57 and 27kDa respectively together giving a relative molecular weight of 168kDa. CONCLUSION: Placental bound IgG may be crucial in immunology of pregnancy and together with the cognate antigen thereof may be useful as models for the study of maternal-fetal interaction in human pregnancy and in the development of experimental immunotherapy to immunologically compromised pregnancies in humans and livestock.

Cellular and molecular interactions in HIV infections: a review.

OBJECTIVE: To review the cellular and molecular interactions between HIV and the host immune system that lead to full-blown AIDS. DATA SOURCES: Published reports on HIV/host interaction during a fifteen year period beginning from 1987. STUDY SELECTION: Only those studies involving humans and non-human primates were selected. The studies included original articles and state-of-the-art reviews covering in vivo and in vitro findings. DATA EXTRACTION AND SYNTHESIS: This article presents a critical review of the cellular and molecular mechanisms of HIV infection and their relationship to the onset of AIDS. CONCLUSION: HIV has elaborated diverse and somewhat complicated mechanisms for the subversion and evasion of the host immune defence strategies. These include escape through mutation, prolonged latency of the infection, masking of the viral envelope proteins, down-regulation of MHC-I and up-regulation of the Fas-ligand on infected cell surfaces. This review enhances our understanding of HIV/AIDS disease and presents a basis on which management strategies could be developed.

Possible immunological basis for recurrent spontaneous abortions: a review.

BACKGROUND: In normal pregnancy, the pregnant mother paradoxically tolerates the semi-allogeneic foetus until term. Experimental and clinical data to explain such tolerance in man reflects the involvement of multiple mechanisms. OBJECTIVE: To review the data pertaining to the experimental and clinical efforts to explain why the mother immunologically tolerates a semi-allogeneic pregnancy to term. DESIGN, SETTING AND METHODS: A review of the literature on state of the art thinking among researchers and clinicians on recurrent spontaneous abortions is summarised. RESULTS: A large body of recently published data strongly suggest that a breakdown in immunological maternal-foetal interactions may lead to occasional or recurrent foetal loss. Immunoregulatory activities involving blocking antibodies, regulatory factors, immunological cells, hormones, structural proteins and cytokines constitute the pregnancy-sustaining network. CONCLUSION: The majority of the evidence reviewed points to the involvement of immunological factors in successful pregnancies. However, the underlying mechanisms are inadequately explained, are largely speculative and require more focused investigation. A complete understanding of the mechanisms involved would enhance our capacity to develop rational ways of addressing recurrent pregnancy losses.

Immunological Role of the Placenta, Blocking Factors and NK Cells in Post-implantation Pregnancy.

The unexpected failure of the mother to immunologically reject the foetus is partly thought to result from immunological properties of the placenta. The placental trophoblast produces immunosuppressive factors including progesterone and blocking antibodies which together down-regulate maternal immune responses to the foetoplacental unit. This article reviews the post implantation immunology of pregnancy emphasizing the roles of placenta, blocking factors and natural killer (NK) cells.

Ovine and Human Placental IgG inhibit Human Natural Killer Cell Cytotoxicity in vitro.

To determine the effect of ovine and human placental IgG on human Natural Killer (NK) cell cytotoxicity in vitro placental IgG was eluted at acidic pH and purified by ion exchange and subsequently by affinity chromatography on protein G and protein A sepharose columns. These antibodies were analysed for presense of IgG by immuno-electrophoresis and relative purity determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE). The effect of these antibodies on human NK cell cytotoxicity was investigated by slChromium Release Assay using human K562 cells as targets and human peripheral blood lymphocytes as effector cells. Both ovine and human placental IgG inhibited human NK cell cytotoxicity in a dose dependent manner. Placental IgG may down-regulate the cytotoxic effects of NK cells in vivo by competitively excluding the binding of NK cells to their respective targets on the trophoblast. Alternatively, these antibodies may themselves be toxic to NK cells. Either way, the presence of these antibodies on the placental trophoblast may prevent the binding of NK cells and subsequent immunological rejection of the fetal allograft. Also, ovine placental IgG may be functionally similar to its human counterpart and may therefore be suitable as a model for the study of maternal fetal interaction during pregnancy in humans.

Recurrent pregnancy losses and the role of immunotherapy.

Post implantation pregnancy losses are psychologically and economically stressful to the childbearing population. The etiology in the vast majority of cases is unknown but is partly thought to result from a break-down of the maternal tolerance to the fetoplacental unit. Immunologically based therapy remains controversial but no alternative therapy is available at the moment. This article reviews the conceived immunological basis of recurrent pregnancy losses, discussing the controversies arising, and recommending the use of intravenous immunoglobulin, IVIg, in well controlled experiments for further clinical trials.

Elution and partial characterization of immunoglobulins bound to ovine placenta.

Immunoglobulins were eluted from ovine placentae and characterized by immunoprecipitation, electrophoresis, western blotting and ELISA. IgG was shown to comprise the bulk of placental-bound immunoglobulins while smaller amounts of IgM and only trace amounts of IgA were demonstrated. Results suggest that ovine placental IgG eluted by surgical cannulation of the uterine blood vessels in situ is similar to that eluted from postpartum placentae in vitro, implying that there may be some transfer of antibodies across the maternal side of the placental barrier to the trophoblast. These antibodies are rich in IgG1 and IgG2, have a relative molecular weight of 158 kDa, and bind to an 80 kDa peptide prepared from pre-acidified ovine placental cotyledons. We propose that the binding of placental IgG to the 80 kDa antigen may prevent immunological rejection of the foetus by competitively excluding cytotoxic cells of maternal origin such as NK cells. Also, given that a similar antigen (80 kDa) has been reported in humans and equines, and shown to be saturated with IgG in term placentae, we propose that this antigen may be conserved in several mammalian species for reproductive purpose. Consequently, we suggest that the ovine placental IgG and the 80 kDa antigen may be suitable as models for the study of maternal-foetal interactions in mammalian pregnancies.

Defects in resting metabolic rates and mitochondrial respiration in Kwashiorkor and dietary obese rats.

Resting metabolic rates have been measured and compared with hepatic mitochondrial respiration in Kwashiorkor and diet-induced obese weaned rats. In Kwashiorkor, resting metabolic rate was 21% lower than the value of controls, while that of the obese rats was 14% higher than in control animals. The resting metabolic rate for Kwashiorkor animals was 50% of the predicted basal metabolic rate (BMR), whereas that of the obese rats was 23% higher than the predicted BMR. The mitochondrial oxygen consumption patterns, using malate plus glutamate or succinate as respiratory substrates, revealed that the resting respiration (state 4) was 23.9% higher in Kwashiorkor and 29.1% higher in obese animals, while the active (state 3) respiration was 34.8% lower in Kwashiorkor and 43.3% lower in obese rats compared to controls. The respiratory control ratios (RCR) were 51.1% and 43.8% in Kwashiorkor and obese rats, respectively, relative to the values in control rats. It is concluded from these studies that Kwashiorkor disease and diet-induced obesity appear to interfere with oxygen utilization at the level of state 3 mitochondrial respiration, which is markedly decreased when compared to the values for control animals.