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The immune response to vasectomy and its relation to the HLA system.

We examined 188 men who had undergone vasectomy up to 6 years previously and, for comparative purposes, 100 men who were about to undergo the operation. Blood specimens were available from a total of 283 men. Sperm antibody assays using immunofluorescence, microagglutination, and microimmobilization confirmed that the prevalance of several types of antibody is higher after vasectomy. Immobilizing and agglutinating antibodies appeared to be the most important. Trends in antibody prevalence according to the time after the operation were analyzed. Screening against lymphocytes and lymphoid lines showed that the anti-sperm activity of era was not related to anti-HLA or anti-Ia activity. Associations were examined between different types of sperm antibody, and between these antibodies and autoantibodies to other antigens. When antibody prevalence was studied in relation to HLA types, the HLA antigen A28 was found to be strongly associated with production of head agglutinating antibody (and immobilizing and immunofluorescent equatorial antibodies) after vasectomy. This is one of the first clear-cut examples of antibody production associated with the HLA system.

Acrosome↗

Translation of the mRNA for rabbit uteroglobin in cell-free systems. Evidence for a precursor protein.

Uteroglobin, an hormonally induced protein composed of two similar subunits, represents around 50% of the proteins synthesized and secreted into the uterine lumen of rabbits treated sequentially with estradiol and progesterone. The endometrium of these animals was used as a source for the isolation of the mRNA for uteroglobin. Poly(A)-rich RNA, extracted from purified polysomes with phenol chloroform and isolated on oligo(dT)-cellulose columns, contains one fourth of the total protein coding activity of the endometrium. Between 20--25% of the polypeptides synthesized by this RNA in cell-free systems derived from Krebs II ascites cells or wheat germs react with a monospecific antiserum prepared in guinea pigs against uteroglobin. The material bound to the antibody was identified as a precursor of uteroglobin according to the following criteria. 1. The product synthesized in vitro can be displaced from the complex with the specific immunoglobulin by purified uteroglobin. 2. Analysis of the immunoprecipitate on polyacrylamide gels containing urea and dodecylsulfate demonstrate the existence of a single labelled polypeptide with an apparent molecular weight larger than the uteroglobin subunits. 3. The tryptic digest of this polypeptide, labelled in vitro with [3H]lysine, shares seven peptides with mature uteroglobin labelled with the same amino acid in perfused uteri, and exhibits and additional peptide not present in uteroglobin. 4. Injection of the same mRNA preparation into Xenopus oocytes results in the production of uteroglobin. The endometrium of intact animals treated with estradiol alone also contains the same mRNA bound to polysomes but in a smaller proportion, indicating that the progesterone-induced synthesis of uteroglobin is accompanied by an accumulation of the specific mRNA in the polysomes.

Animals↗

Determination of sperm-antibodies in sera of sterile women by affinity-chromatography (affinity-chromatography of sperm-antibodies).

The total amount of humoral sperm antibody protein is determined following its isolation by affinity-chromatography on spermatozoa. Serum proteins are eluted by Sorensen phosphate buffer. Antibodies attached to spermatozoa suspended in Sephadex G 75 columns resist elution by Sorensen buffer. They can be quantitatively washed out by 8 ml Tris HCl-buffer pH 8,9 and be determined as proteins by the Folin-Ciocalteu method.

Adsorption↗

Experimental findings with spermantibodies: condom therapy (a case report).

A couple with no demonstrable cause for their infertility, except for a pronounced antisperm activity in the blood serum of the female partner, were instructed to use a condom while our laboratory monitored the wifes antibody titer. The antibody activity declined sufficiently and an artificial husband insemination were performed after seven months of therapy. A precise report of the spermantibody activity over an eleven month period are given by the authors.

Antibodies↗

Comparison of antibody reactivity to human immunodeficiency virus type 1 (HIV-1) gp160 epitopes in sera from HIV-1-infected individuals from Tanzania and from the United States.

In this study, we compared sera from 159 human immunodeficiency virus type 1 (HIV-1)-infected individuals from Tanzania and 103 infected individuals from the United States for antibodies reactive with 10 HIV-1 gp160 epitopes defined by synthetic peptides. Our data indicate that the anti-gp160 antibody fine specificity differs between infected individuals from these two geographically diverse populations. For example, 50% of the Tanzanian sera contained antibodies reactive with an immunodominant HIV-1 gp41 epitope defined by peptide 600-611, whereas 91% of the sera from the United States were reactive. Differences in serologic reactivity between HIV-1-infected individuals from Tanzania and the United States were also observed with gp160 epitopes defined by peptides 503-528 and 846-860. Included among the peptides examined were four which corresponded to the V3 region of gp120. The majority of sera from either country contained antibodies reactive with peptide RP142, whose V3 sequence is based upon that of HIV-1 isolate MN. Further characterization of serologic reactivity suggested that sera from Tanzania were more likely to neutralize HIV-1 isolate IIIB or MN in vitro than were sera from the United States. These differences in antibody fine specificity between HIV-1-infected individuals from Tanzania and the United States suggest that regional isolates of HIV-1 may exist.

Acquired Immunodeficiency Syndrome↗

Examination of sera from human immunodeficiency virus type 1 (HIV-1)-infected individuals for antibodies reactive with peptides corresponding to the principal neutralizing determinant of HIV-1 gp120 and for in vitro neutralizing activity.

Sera from human immunodeficiency virus type 1 (HIV-1)-infected individuals from the United States and Tanzania were examined for antibody reactivity to four synthetic peptides which corresponded to the principal neutralizing determinant from the V3 region of HIV-1 gp120. We observed that the majority of sera from both countries contained antibodies reactive with a V3 peptide whose sequence is based on that of the HIV-1 MN isolate. We were unable to establish a relationship between the presence of V3-reactive antibodies, as measured by enzyme-linked immunosorbent assay and neutralization of homologous HIV-1 isolates, in sera from either the United States or Tanzania. We observed that some sera which contained high antibody titers to the V3 peptides failed to neutralize HIV-1, while others with no antibody reactivity to the panel of V3 peptides exhibited in vitro neutralizing activity. These results suggest that neutralizing epitopes exist outside the V3 loop and that the presence of V3-reactive antibodies in sera does not imply in vitro neutralization of the homologous HIV-1 isolate. In addition, it appears that the V3 loop may consist of both neutralizing and nonneutralizing epitopes. The identification of neutralizing as well as nonneutralizing epitopes will be important for the design of potential HIV-1 vaccines.

Amino Acid Sequence↗

Risk of HIV infection from transfusion with blood negative for HIV antibody in a west African city.

OBJECTIVE: To estimate the risk of infection with HIV (HIV 1 or HIV 2, or both) from transfusion of a screened unit of blood in a high prevalence area in west Africa. DESIGN: Retrospective cohort study for January-July 1991. SETTING: National Blood Transfusion Centre, Abidjan, Côte d'Ivoire. SUBJECTS: Repeat donors (5831 units of blood) and first time donors (5076 units) in the first five months of 1991. MAIN OUTCOME MEASURES: Prevalence and estimated incidence of HIV infection in repeat and first time donors; estimated rate of potentially infected, HIV antibody negative units; and rate of (false negative) potentially infected units assuming a laboratory test sensitivity of 99%. RESULTS: Overall HIV prevalence was 11.0% in first time donors and 2.1% in repeat donors. In the first seven months of 1991, 29 HIV antibody positive (27 HIV 1, 1 HIV 2, 1 dually reactive) donors with a seronegative unit of blood earlier in the year were identified; 26 had donated blood eight weeks or less before their estimated dates of seroconversion and may have been infectious (minimum rate 26/5831 (4.5/1000 potentially infected units)). Estimated incidence of infection in repeat donors was 1.2-2.5%. Laboratory test insensitivity would result in an estimated 1.1/1000 false negative units from first time donors and 0.2/1000 units from regular donors. The overall rate of potentially infected units (all donors, seroconversions, and errors) was estimated at 5.4-10.6/1000. CONCLUSIONS: The risk of HIV infection from a single unit of blood remains substantial (5.4-10.6/1000 units). To prevent infection from blood transfusion in areas of high incidence and prevalence of HIV all but absolutely essential transfusions should be avoided, and donors with low incidence of HIV infection should be selected.

Blood Donors↗

Sex hormones and the immune response. II. Perturbation of antibody production by estradiol 17beta.

The administration of 75 microgram/kg of estradiol 17beta at successively later stages in the immune response of female guinea pigs to penicilloyl-coupled cavian globulins showed that this steroid reduces the rate of attainment of the maximum titer, the magnitude of the titer achieved, and the rate of titer decay. Control titers maximized at the third experimental week and diminished to one third the peak value by the 6th week. When steroid treatment was begun coincidentally with inoculation (week 0), the peak titer was delayed by 3 weeks, and by 2 weeks when hormone priming was begun at week 1 or 2. The highest antibody titers achieved in the presence of estrogen were 25-30% lower than those of sesame oil controls. The greatest immunosuppressive effect was observed when estradiol was given at the peak of the immune response, the titer dropping by 50% and remaining at that level for the next 4 weeks in spite of continued antigen inoculation and steroid treatment. Titer decay after the end of the inoculation course was prevented by estradiol but not by progesterone, CHP, or these same oil vehicle.

Animals↗

IgM-antibodies against T. pallidum detected in sera from mothers of stillborn babies in Mozambique by the solid-phase haemadsorption assay (SPHA).

Serum samples taken at the delivery from 27 syphilitic mothers in Mozambique, 16 with stillborn babies and 11 with healthy babies were tested upon presence of IgM antibodies against T. pallidum by the solid-phase haemadsorption assay (SPHA). Fourteen out of the 16 serum samples from mothers with stillborn babies but only one out of the 11 samples from mothers with healthy babies were found positive by the SPHA test. Clinical signs indicative of syphilis are difficult to find in the Maputo area as there were more than 40,000 annual births and only five obstetricians when the study was carried out. It is believed that the findings may indicate those mothers who were serologically positive with the SPHA test had clinically active syphilis and that syphilis might be the cause or a contributory cause of death in 14 of the stillborn babies. The SPHA test was easy to perform and we recommend its adoption by laboratories with facilities to perform the TPHA test.

Antibodies, Bacterial↗

Examination of the role of FSH in periovulatory events in the hamster.

The need for endogenous FSH in the periovulatory events such as oocyte maturation, ovulation, luteinization, maintenance of luteal function and follicular maturation was examined in the cyclic hamster. A specific antiserum to ovine FSH, shown to be free of antibodies to LH and to cross-react with FSH of the hamster, was used to neutralize endogenous FHS at various times. Administration of this antiserum during pro-oestrus did not affect oocyte maturation and ovulation, as judged by the normality of the ova to undergo fertilization and normal implantation. It also had no effect on the process of luteinization or on the maintenance of luteal function as indicated by the normal levels of plasma and luteal progesterone during pro-oestrus and oestrus during the cycle and in pregnancy. All these processes were, however, disrupted by administration of an antiserum to ovine LH, thereby demonstrating their dependence on endogenous LH. Although FSH antiserum given at pro-oestrus did not prevent the imminent ovulation, it blocked the ovulation occurring at oestrus of the next cycle. This antiserum was effective in preventing the ensuing ovulation when given at any other time of the cycle until the morning of pro-oestrus. It is concluded that, in the hamster, high levels of FSH during pro-oestrus and oestrus are required for initiating maturation of a new set of follicles which are dependent on the trophic support of FSH throughout the cycle until the morning of pro-oestrus. Such follicles then appear to need only LH for subsequent ovulatory and associated processes.

Animals↗

Antibodies to spermatozoa. VII humoral and cellular aspects of sperm inmunity and infertility.

The occurrence of sperm antibody in serum and cervical mucus of women from intertile couples in the serum of their male partners, as well as cellular immunity to sperm, has been studied by agglutination and immobilization techniques. For a total of about 260 couples, the tests on serum showed that 18% of the women and 8% of the men were positive by the Kibrick technique and that 15% of the women and 4% of the men were positive by the F-D technique. The women who were positive in their cervical mucus were 8% of the group by the K-agg (Kibrick agglutination) technique, 2% by the MIS-agg. (Microscale agglutination) technique, and 40% by the MIS-imm. (Microscale immobilization) tecnique. In considering all three techniques. 42% of a group of 132 women were positive. Cellular immunity to sperm, by the Migration Inhibition method, was positive in 18% and zero per cent of infertile and fertile women, respectively.

Antibody Formation↗

Attempt at "immunological castration" as an approach to the problem of the involvement of testosterone in control of expression of certain mouse antigens.

Adult male mice of the strain B10.A were immunized with a testosterone-protein conjugate, testosterone 3-(O-CARBOXYMETHYL)-oxime-bovine serum albumin which contained 27-75 steroid residues/mol BSA. Two different immunization doses of the conjugate were used, respectively, 2 x 40 mug and 2 x 200 mug in complete Freund's adjuvant or in alum adjuvant. There were two groups of control males, non-immunized and immunized with BSA in adjuvant. In the pooled immune sera, antibodies to testosterone were determined by radioimmunoassay; their titre ranged between 7 and 10. On histological sections of testes, inhibition of spermatogenesis (manifested by a sower frequency or even absence of tubules producing mature sperm, reduced frequency of tubular cells and their degenerative changes) was observed in almost all males immunized with the higher dose of the conjugate. In such animals, increased frequency of interstitial cells (except vascular elements) and enlarged nuclei of Leydig cells were found. In spite of these signs of a hyperproduction of testosterone by the Leydig cells, the product seemed to have lacked its normal biological activity as suggested not only by the low activity of spermatogenesis, but also by a significantly subnormal level of the androgen-dependent serum protein Ss.

Animals↗

Sperm autoantibodies as a consequence of vasectomy. II. Long-term follow-up studies.

Thirty-four out of fifty-two vasectomized men studied previously were studied again about 5 years after vasectomy for sperm-agglutinating and sperm-immoblizing antibodies, and for antibodies to human protamine. Only one man lost his already weak antibody activity, whilst one out of eight men, negative at 1 year, appeared to be positive at 5 years. Slightly higher titres in one of the three sperm antibody tests were found in the sera of about 30% of the men. Only in three (9%) was there a rise of two or more steps in more than one technique. Agglutinins and immobilizins were shown to be strongly correlated, as was the case with antibodies to human protamine and head-to-head agglutinins. Seminal plasma sperm agglutinins were detected in the samples of only four (out of thirty) men, in low titres. Circulating immune complexes tested with various techniques were only found in a few sera and not consistently. This prolonged study shows that sperm autoantibodies formed within 1 year after vasectomy are persistent. Their role in remaining infertility after reanastomosis requires further study.

Antigen-Antibody Complex↗

Ultrasound as a new method of male contraception.

Twenty male cats were treated once or twice with 1 watt/sq cm of ultrasound for 10 minutes. Each of 24 male dogs received one to three treatments with 1 watt/sq cm for 10 minutes. Another six dogs were treated with 2 watts/sq cm for 15 minutes. Four Cebus apella monkeys were treated with the same dosage as that used for the cats and dogs. A dosage of 1 watt/sq cm for 10 minutes was also applied to four human patients without the use of anesthetics, and no pain or side effects were noted. In all treated animals as well as in human patients the results indicate that ultrasound significantly suppresses spermatogenesis according to the dosage and frequency of treatment, without any effect on Leydig cells or blood testosterone levels.

Animals↗

The transient HLA antigenic loss dependent on hormonal state of organism in a healthy woman.

In a healthy 44-year-old female blood donor with HLA phenotype HLA-A 2, A 10/B 7, BW 15 repeatedly the transient loss of HLA antigens was proved during the menstrual period and supposed ovulation. Within the interval between menstruation and ovulation the antigens could reliably be proved. The results support the view that in women hormonal effects may influence the HLA antigenic expressivity. The significance of this observation for reliable typing of HLA antigens in women is discussed.

Adult↗

The heterocytotoxicity of human serum. III. Studies of the serum levels and distribution of activity in human populations.

A metabolic inhibition assay has been employed to investigate the distribution of serum heterocytotoxicity mediated by natural antibody activating the classical complement pathway and by antibody-independent activation of the alternative complement pathway in human serum samples derived from various groups of individuals. Levels in female cancer patients and in women taking oral contraceptives were significantly elevated over normal controls. Newborn infants exhibited approximately half of the average adult levels. Levels were maximally elevated in patients with visceral cancer, particularly in individuals with adenocarcinomas, while patients with sarcomas exhibited reduced levels. These and other data derived from the literature suggest that the metabolic inhibition assay may provide a useful measure of natural antibody and activation of the alternate complement pathway representative of mechanisms of natural immunity vs tumours.

Adult↗