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PubMed1990

[Lowering effect of estrogen replacement treatment on immunoglobulins in menopausal women].

Similarly to the results reported in pregnancy and during oral contraceptive use, estrogen replacement therapy (ERT) had a lowering effect on serum immunoglobulins (IgG, IgA, IgM) of 20 postmenopausal women with a mean age of 52.2 years, in parallel with an increase in the blood values of estradiol (E2). The clinical implications of this phenomenon warrant the study on a bigger series and during a longer period of time. It is recommended to use with precaution the ERT in women with known defects in the immunologic system. A study on the effect of the new transdermal therapeutic system (Estraderm, TTS, Ciba) on the immunoglobulins is in course.

Adult↗
PubMed1988

[Pregnancy determination by the detection of early pregnancy associated protein].

First results of the immunoelectrophoretic detection of an early pregnancy associated protein (EPAP) are reported. For this a rabbit antiserum was produced against a serum fraction, which had early pregnancy factor activity, and used for rocket immunoelectrophoresis. By this method 95.3 per cent of 64 sera from patients with intact pregnancies were classified to be pregnant. There was found a positive correlation (r = 0.05; p less than 0.01) between the concentration of EPAP and the period of gestation (4th to 14th gestational week). However, the EPAP antiserum also reacted with serum proteins from probands using hormonal contraception. Further characterization and purification of the EPAP will help to produce an antiserum with higher specificity and therefore it will be possible to make a more reproducible early pregnancy test.

Animals↗
PubMed1979

A solid-phase enzyme-linked immunosorbent assay for the quantitation of human plasma alpha 1-acid glycoprotein.

We describe a solid-phase enzyme-linked immunosorbent assay for alpha 1-acid glycoprotein in human plasma. Plasma samples are incubated with alkaline phosphatase-linked, purified alpha 1-acid glycoprotein in alpha 1-acid glycoprotein-specific antibody-coated polystyrene tubes. The alkaline phosphatase that becomes attached to the tube via an immunological reaction between the alpha 1-acid glycoprotein and the specific antibody is measured spectrophotometrically. This assay is accurate reproducible, simple, and economical. As little as 4 microgram of alpha 1-acid glycoprotein per liter can be detected. The normal range for alpha 1-acid glycoprotein in the plasma of healthy adults, as measured by this method, is 0.48-1.27 g/L; the range is significantly different, 0.29-0.73 g/L, for women who are taking oral contraceptive pills.

Adult↗
PubMed1985

Ectopic pregnancy.

The diagnosis of ectopic pregnancy has become precise and reliable. Consequently, the management of ectopic pregnancy has progressed to the point where the physician is often able to preserve fertility. Therefore, conservative surgery is indicated if the patient desires future fertility and conditions are appropriate. The combination of ultrasound, beta-hCG pregnancy testing, and laparoscopy has led to a rising incidence of diagnosed ectopic pregnancy prior to rupture. This has greatly facilitated the use of the conservative approach to the management of tubal pregnancy. Although ectopic pregnancy can be diagnosed early and managed conservatively, it is, and will remain a potentially life-threatening disease and must be approached as such. Table 3 summarizes our proposed surgical management of tubal pregnancy. Table 4 summarizes the results of conservative surgery for tubal pregnancy.

Chorionic Gonadotropin↗
PubMed1997

Review: immunobiology of preeclampsia.

Preeclampsia has been recognized clinically since the time of Hippocrates: however its etiology and pathophysiology remain enigmatic. This pregnancy-specific syndrome typically presents in late pregnancy as hypertension, edema, and proteinuria. Investigations over the past 15 years have revealed that preeclampsia is associated with abnormal placentation, reduced placental perfusion, endothelial cell dysfunction, and systemic vasospasm. Since it occurs more commonly in primigravidae and in women with underlying collagen-vascular diseases, an immunological component has long been suspected. Increased prevalence in high-order and molar pregnancies and those associated with increased placental mass suggests that trophoblastic volume and fetal antigen load are correlated with the syndrome. Epidemiological reports indicate that the prevalence of preeclampsia is decreased in women who received heterologous blood transfusions, practiced oral sex, or when a long period of cohabitation preceded an established pregnancy. Conversely, the use of condoms as a primary mode of contraception is associated with a higher risk of preeclampsia. These studies suggest that prior exposure to foreign or paternal antigens imparts a protection against the likelihood of developing preeclampsia. Clinical evidence of cellular and humoral immune dysfunction is associated with the syndrome. Fibrin and complement deposition and "foam" cells in atherosis lesions resemble the histopathology of renal allograft rejection. Relative T-cell, natural killer cell, and neutrophil activation have been reported in preeclampsia and circulating cytokines and antiphospholipid antibodies are more prevalent in preeclampsia than in normal pregnant women. These abnormalities are consistent with the systemic endothelial cell dysfunction that has been postulated as a pathophysiological feature of preeclampsia. While such associations do not prove causality, they suggest testable hypotheses for continued basic and clinical investigation of this major complication of human pregnancy.

Female↗
PubMed1990

Immunosuppression by seminal plasma and its possible biological significance.

The data support the role of seminal plasma facilitating the transmission of virus and establishment of infection when all depositions of semen occur, but systemic absorption would also be possible by vaginal intercourse if lesions or abrasions caused for example by other s.t.d's, were present. The severity and rapid increase in the population of certain sexually transmitted agents make it imperative that epidemiological studies are initiated to study any correlation with changes in sexual behaviour and contraceptive practices. Finally, further isolation and characterization of seminal plasma components should lead to a clear understanding of their action as both regulatory molecules and in their possible contribution to disease.

Humans↗
PubMed2002

Highly immunogenic and totally synthetic lipopeptides as self-adjuvanting immunocontraceptive vaccines.

In this study, we describe the synthesis of various lipopeptides based on the sequence of luteinizing hormone-releasing hormone (LHRH) and report on their abilities to induce Abs against this "self" hormone when inoculated into mice in the absence of additional adjuvant. The peptides consisted of a colinear CD4(+) T helper cell epitope from the L chain of influenza virus hemagglutinin and LHRH, which has B cell epitopes but no T cell epitopes present in its sequence. Lipids were attached either at the N terminus or between the T cell epitope and LHRH, in the approximate center of the peptide. The lipopeptide constructs displayed different solubilities and immunological properties that depended not only on the lipid content but also on the position of attachment of the lipids. Some of these constructs were highly immunogenic, inducing high titers of Ab, which were capable of efficiently sterilizing female mice when administered in saline by s.c. or intranasal routes. The most effective vaccines were highly soluble, contained the dipalmitoyl-S-glyceryl cysteine moiety, and had this lipid attached at the center of the molecule. The relative ability of the lipopeptides to induce an Ab response in the absence of external adjuvant was reflected by their ability to up-regulate the surface expression of MHC class II molecules on immature dendritic cells. These results demonstrate that the composition and position within peptide vaccines of self-adjuvanting lipid groups can influence the ability to induce the maturation of dendritic cells and, in turn, the magnitude of the resulting Ab response.

Adjuvants, Immunologic↗
PubMed1986

Male fertility regulation: recent advances.

Acceptable antifertility drugs for men are proving difficult to produce. Such drugs must aim to achieve complete azoospermia over a long period. This requirement may be relaxed only if it can be shown that the residual sperm produced by men whose spermatogenesis has been suppressed by antifertility drugs to oligospermia are incapable of fertilizing ova. Hormonal methods involving suppression of the secretion of gonadotrophin hormones by the pituitary gland invariably require androgen supplementation, and the use of steroids either alone or in combination requires careful monitoring for their side-effects. A chemical (non-hormonal) approach involving the incapacitation of sperm in the epididymis has been shown to be feasible in animal studies using alpha-chlorohydrin and 6-chloro-6-deoxy sugars, although such compounds cannot be developed for human use because of their toxicity. Immunological approaches have the inherent problem of delivery of the antibody to the target. While the search for new and safer chemical and hormonal approaches goes on, the recent evidence that vasectomy offers a safe surgical option leaves responsible men with some choice to add to the condom.

Androgens↗
PubMed2006

Premature ageing prevention: limitations and perspectives of pharmacological interventions.

A significant increase of the elderly in populations of developed countries is followed by increase morbidity and mortality from main age-related diseases--cardiovascular and neuro-degenerative, cancer, diabetes mellitus, declining in a resistance to infections. Obviously, the development of means of the prevention of the premature ageing and these diseases in humans are crucial at present. However, data on such type means rather scarce, contradictory and often not reliable from the points of view of the adequacy of the experiments to current scientific requirements, as well as the interpretation of the results and safety. Available data on the life span extension and adverse effects of chemical compounds and drugs suggested as geroprotectors are critically analyzed: antidiabetic drugs, growth and thyroid hormones, glucocorticoids, DHEA, sex steroids and contraceptives, melatonin and peptide preparations modulating the pineal gland, antioxidants, chelate agents and lathyrogens, adaptogens and herbs, neurotropic drugs, inhibitors of monoamine oxidase, immunomodulators and some other. Most of the results could not convincingly evidence the life span extension and safety of the suggested geroprotectors. We believe that it is necessary to establish an international program for the expert evaluation of the life span extension potential of pharmacological interventions for humans. The scope of the program should be to evaluate chemical, immunological, dietary and behavioural interventions that may lead to life span extension or retard premature ageing and the objective--preparation of critical reviews and evaluations on evidence of the life span extending properties of a wide range of potential geroprotectors and strategies by international groups of working experts. The program may assist national and international authorities in devising programs of health promotion and premature ageing prevention.

Aging↗
PubMed1990

Pregnancy and the risk of developing rheumatoid arthritis.

There have been conflicting reports on, and no plausible biologic explanation for, a protective effect of oral contraceptive (OC) use on the development of rheumatoid arthritis (RA). Therefore, we investigated aspects of behavior related to OC use that could explain the preventive effect of OC on the onset of RA. In the present case-control study, past pregnancy, age at first pregnancy, and pregnancies with adverse outcome were studied as possible risk factors for RA. Interview information on reproductive variables was obtained from 135 young adult women with confirmed definite or classic RA of recent onset, and from 378 control patients with soft tissue rheumatic disorders or osteoarthritis. All patients had at least 2 years of followup to confirm the consistency of the diagnosis. We found a decreased risk of RA in women who had been pregnant. The risk of RA in women who had ever been pregnant compared with women who had never been pregnant was 0.49 (95% confidence interval 0.27-0.91). The earlier the first pregnancy, the lower the risk of RA. Pregnancy with adverse outcome (i.e., gestation less than 25 weeks) did not substantially change the risk of RA (relative risk 0.73, 95% confidence interval 0.50-1.07). The protective effect of pregnancy was independent of OC use, the presence of HLA-DR4, or a family history of RA. Immune modulation by female hormonal influences could be an explanation for the results of the present study.

Adult↗
PubMed1995

Thalidomide: rationale for renewed use in immunological disorders.

Despite its inherent teratogenic risk, thalidomide has over the years proven to be of clinical use in a small number of mainly immunological diseases (e.g. erythema nodosum leprosum, Behçet's syndrome and rheumatoid arthritis). The mode of action of thalidomide is still poorly understood. Recent research has shown a decrease in tumour necrosis factor-alpha (TNF alpha) during thalidomide treatment in several settings. Others have found altered expression of adhesion molecules. Currently, the most interesting new fields of application are the prevention and treatment of graft-versus-host disease in allogeneic bone marrow transplantation and the treatment of aphthous ulceration in HIV-positive patients. Contraceptive measures must be instituted in women receiving thalidomide, and careful monitoring for neurological adverse effects is required in all patients.

Bone Marrow Transplantation↗
PubMed2006

Designing a new generation of anti-hCG vaccines for cancer therapy.

The heterodimeric 'pregnancy-specific' hormone human chorionic gonadotropin (hCG) has been used as the basis for a contraceptive vaccine. More recently, the observation that hCG, particularly in the form of the beta-chain expressed in the absence of alpha-chain, is aberrantly expressed in a number of different tumors has opened up a second potential application for such vaccines. Drawbacks of the currently available vaccines are that they are either relatively weakly immunogenic or that they induce antibodies that cross-react with human leuteinizing hormone (hLH). We have explored the possibility of creating mutated versions of the hCG beta-chain with improved immunologic properties.

Animals↗
PubMed1996

Kallistatin, a novel human tissue kallikrein inhibitor: levels in body fluids, blood cells, and tissues in health and disease.

Kallistatin, a human serine proteinase inhibitor, is a newly identified tissue kallikrein inhibitor. It binds strongly to tissue kallikrein but weakly to other serine proteinases such as chymotrypsin and elastase. The tissue distribution and changes in kallistatin levels in human diseases were characterized by using specific monoclonal and polyclonal antibodies against kallistatin. Kallistatin antigen levels in blood cells, fluids, and tissues measured with a specific enzyme-linked immunosorbent assay showed displacement curves that were parallel with those in purified kallistatin, indicating their immunologic identity. Expression of kallistatin mRNA in platelets, neutrophils, lymphocytes, monocytes, endothelial cells, hepatocytes, and colon and prostate carcinoma cells was identified by reverse transcription-polymerase chain reaction followed by Southern blot analysis. Plasma kallistatin concentration was 22.1 +/- 3.5 micrograms/ml in 30 normal subjects and 21.1 +/- 3.8 micrograms/ml in 5 patients with C1 inhibitor deficiency. A significantly reduced kallistatin level (7.2 +/- 2.5 micrograms/ml, p < 0.001) was seen in plasma samples from 9 patients with liver disease and 10 patients with sepsis (7.7 +/- 3.5 micrograms/ml, p < 0 .001). Further, kallistatin levels in 10 women taking oral contraceptives (19.8 +/- 3.8 micrograms/ml) and 21 pregnant women (14.9 +/- 3.3 microg/ml) were significantly lower than those seen in healthy individuals. These data suggest that kallistatin is found in plasma, is produced mostly in the liver, and can be consumed during sepsis. Its consumption in sepsis may indicate a protective role to prevent blood pressure lowering.

Antibodies, Monoclonal↗
PubMed2001

Reproductive factors and risk of intermediate- or high-grade B-Cell non-Hodgkin's lymphoma in women.

PURPOSE: The incidence rates of non-Hodgkin's lymphoma (NHL) unrelated to human immunodeficiency virus infection are lower for women than for men; yet, few factors have been identified that may account for this difference in risk. NHL is difficult to study epidemiologically because this disorder represents a group of malignancies that differ in terms of morphologic presentation, immunologic features, genetic characteristics, prognosis, and etiology. PATIENTS AND METHODS: We conducted a population-based case-control study in women to determine whether reproductive factors or hormonal exposures might be related to the risk of high- or intermediate-grade B-cell NHL. We interviewed 177 female residents of Los Angeles County who were diagnosed with high- or intermediate-grade B-cell NHL between 1989 and 1992; each case patient was individually matched on age and race to a control subject who lived in her neighborhood. RESULTS: Women who had used oral contraceptives had significantly lower risk of intermediate- or high-grade NHL (multivariate odds ratio [OR] = 0.47; 95% confidence interval [CI], 0.26 to 0.86) than women who had never used these compounds. Among parous women, those who had used lactation suppressants (which contain high levels of estrogen) had significantly lower risk of NHL (multivariate OR = 0.50; 95% CI, 0.29 to 0.85) than unexposed women. Postmenopausal women had a somewhat greater risk of NHL than premenopausal women, whereas those postmenopausal women who had used hormone replacement therapy (HRT) (primarily estrogen) had somewhat lower risk than those who had not used HRT. CONCLUSION: Exogenous estrogens seem to have a protective effect on the risk of high- and intermediate-grade B-cell NHL. Although the mechanisms for such protection are not known, alterations in immune reactivity, cytokine expression, or B-cell modulation may play a role.

Adult↗
PubMed1988

Prevention of sexually transmitted diseases in women.

The frequency and severity of sexually transmitted diseases (STDs) and their sequelae, including sterility, numerous perinatal infections, genital tract neoplasia and possibly death (from ectopic pregnancy, ruptured tuboovarian abscess, human immunodeficiency virus-1 and hepatitis B virus infection), should be acknowledged by all sexually active individuals. Aspects of sexuality that place individuals at risk of STDs must be reexamined. Health care providers must effectively inform patients and the public of these often-ill-appreciated risks in a straightforward fashion, free of judgmental and punitive attitudes. New, more-effective means of prevention, diagnosis and treatment are being sought using research techniques in microbiology, immunology and behavioral science. In the meantime, medical screening, treatment and contact tracing should be carried out for patients and their sexual partners. Sexually active individuals must be empowered with knowledge and emboldened to protect themselves and their established or potential families from these common infections. Existing means of screening and treating must be utilized fully.

Contraception↗
PubMed1979

Food allergies and migraine.

60 migraine patients completed elimination diets after a 5-day period of withdrawal from their normal diet. 52 (87%) of these patients had been using oral contraceptive steroids, tobacco, and/or ergotamine for an average of 3 years, 22 years, and 7.4 years respectively. The commonest foods causing reactions were wheat (78%), orange (65%), eggs (45%), tea and coffee (40% each), chocolate and milk (37%) each), beef (35%), and corn, cane sugar, and yeast (33% each). When an average of ten common foods were avoided there was a dramatic fall in the number of headaches per month, 85% of patients becoming headache-free. The 25% of patients with hypertension became normotensive. Chemicals in the home environment can make this testing difficult for outpatients. Both immunological and non-immunological mechanisms may play a part in the pathogenesis of migraine caused by food intolerance.

Adolescent↗