Induction of sensitization and tolerance in contact sensitivity with haptenated epidermal cells in the guinea-pig.

Haptenated murine Langerhans' cells (LCs) have been reported to induce contact sensitivity when injected via the subcutaneous, intraperitoneal and, in some instances, the intravenous route. Similar studies were undertaken to elucidate the role of the LC in the induction of contact sensitivity in the guinea-pig. The subcutaneous injection of dinitrophenylated epidermal cells induced hapten-specific contact sensitivity in a dose-dependent fashion. This contrasts with the tolerance that was induced by the intravenous or intraperitoneal injection of similarly haptenated cells. Contact sensitivity by haptenated epidermal cells could be induced in syngeneic and allogeneic recipients and did not require the transfer of viable cells. Using the monoclonal antibody MSgp2, which detects LCs, LC-enriched and LC-depleted populations were prepared by an 'indirect antibody' panning technique. It was found that a haptenated LC-depleted epidermal cell population (0.1% LC) induced the same degree of contact sensitivity or tolerance, depending on the route of immunization, as a haptenated 'freshly isolated' epidermal cell population (1% LC). Whereas, a purified population of haptenated LC (85-90%) induced no significant degree of contact sensitivity or tolerance. These results confirm our previous conclusions based the in vivo depletions of Langerhans' cells, and suggest that the epidermal Langerhans' cell is not essential for the induction of contact sensitivity in the guinea-pig. However, this does not exclude the possibility that the LC is involved in the elicitation of contact sensitivity in a sensitized animal.     

Absence of need for amniocentesis in patients with elevated levels of maternal serum alpha-fetoprotein and normal ultrasonographic examinations.

BACKGROUND. Recent improvements in the accuracy of sonographic diagnosis of neural-tube and ventral-wall defects have raised a question about the wisdom of routinely offering amniocentesis to women who have elevated levels of maternal serum alpha-fetoprotein with a structurally normal fetus as determined by ultrasonography. METHODS. We reviewed the ultrasound findings in 51 consecutive fetuses with spina bifida, encephalocele, gastroschisis, or omphalocele that were delivered or aborted at a single hospital, to estimate the sensitivity of ultrasonography for these diagnoses. In all cases, the mothers had undergone prenatal sonography at one facility between 16 and 24 weeks after the last menstrual period. We used these data to calculate the probability of an affected fetus in a women with a given level of maternal serum alpha-fetoprotein and a normal sonogram. RESULTS. These four types of anomalies were correctly identified in all 51 cases, yielding a sensitivity of 100 percent (95 percent confidence interval, 94 to 100 percent). Using the lower limit of this confidence interval, we calculated that the probability of an affected fetus ranges from 0.01 to 0.15 percent for maternal serum alpha-fetoprotein levels ranging from 2.0 to 3.5 times the median, respectively. CONCLUSIONS. This level of risk is less than the reported risk of abortion due to amniocentesis and may lead some women with elevated levels of alpha-fetoprotein to decide not to proceed with amniocentesis.     

Role of self-carriers in the immune response and tolerance. II. Parameters of tolerance induced by haptenated lymphoid cells.

The induction of tolerance to the 2,4,6-trinitrophenyl (TNP) hapten has been studied in a system utilizing haptenated syngeneic lymphoid cells. Specific depression of the direct and indirect plaque-forming cell (PFC) responses to TNP-protein conjugates was regularly achieved by pretreatment of Lewis rats with 1 X 10(7) trinitrophenylated spleen cells or TNP lymph node cells. Very low numbers of haptenated lymphocytes were active since tolerance could be induced in vivo with as few as 10(5)-10(6) TNP spleen cells (SC). SC exposed to as little as 10-100 mug of the reactive hapten, trinitrobenzene sulfonic acid, were effective tolerogens in this system. Tolerance induced with 10(7) haptenated spleen cells persisted for at least 4 weeks. Viable intact cells did not seem to be required in this system since the cell-free supernatants from TNP-SC cultured for 24 h were also active. In addition, significant depression of an ongoing immune response could also be imposed by haptenated isologous lymphoid cells. Moderate suppression of the "hapten-specific" delayed hypersensitivity response (measured by the accumulation of 51Cr-labeled bone marrow cells) was also achieved with TNP-SC. These results suggest that haptenated isologous lymphoid cells are potent tolerogenic conjugates capable of inducing tolerance affecting antibody formation and delayed hypersensitivity. However, since we and others have shown that TNP-SC do not adversely affect the generation of hapten-specific cytotoxic T cells, it is postulated that there is a differential recognition of, or response to, hapten-modified self-carriers by functionally distinct lymphocyte subpopulations.     

Psychopathic and nonpsychopathic inmates differ from normal controls in tolerance levels of electrical stimulation

With a Tursky electrode applied to the ventral surface of the forearm two samples of inmates (28 psychopaths and 28 nonpsychopaths) were compared to 29 normal controls. No differences were found among the three groups in lower detection thresholds. While there was no difference between the inmate groups in terms of pain tolerance, both inmate groups had a higher tolerance for pain than did the controls. Results do not support previous findings or theories/hypotheses about pain thresholds in psychopathic and nonpsychopathic inmates. Differential learninng and experience of pain among inmates, as well as the association among testosterone, dominance, extraversion, and criminality, are suggested to account for the results.     

Low material serum alpha-fetoprotein levels and congenital diaphragmatic defects

We report on 2 cases of fetal congenital diaphragmatic defects with normal chromosomes among 105 patients referred for evaluation for low maternal serum alpha-fetoprotein (MSAFP) levels. The mechanism for this striking association is not clear. The association of low MSAFP levels and congenital diaphragmatic defects may have importance for MSAFP screening programs.     

Low maternal serum alpha-fetoprotein levels and congenital diaphragmatic defects

We report on 2 cases of fetal congenital diaphragmatic defects with normal chromosomes among 105 patients referred for evaluation for low maternal serum alpha-fetoprotein (MSAFP) levels. The mechanism for this striking association is not clear. The association of low MSAFP levels and congenital diaphragmatic defects may have importance for MSAFP screening programs.     

Radioimmunologic assay of alpha-fetoprotein in various normal and pathological conditions]

AFP can be measured by radioimmunoassay in 52 hours using an incubation at 18 degrees C for 48 hours and the double antibody solid phase method to separate the free labelled AFP from the labelled AFP bound to the antibodies. In these conditions, the sensitivity and precision of the assay are very satisfactory and the results are directly in correlation with the results obtained using the classical double antibody method. In the serum of normal people, except pregnant women, the concentration of AFP is not detectable or is less than 20 ng/ml. In the serum of pregnant women, AFP increases from the 8th. week of gestation to the 32nd., then stabilises or gradually decreases.     

Antibody deficiency syndrome: a case with normal immunoglobulin levels

A girl is reported in whom abnormal susceptibility to infections in many sites, involving many types of bacteria and leading to fatal bronchopneumonia, was associated with normal levels of all immunoglobulins, but complete absence of isohaemagglutinins, and failure of antibody response to some bacterial antigens (Salmonella typhi O, Salmonella paratyphi B, O and H, and pertussis), possible delay in developing antibodies to streptococcal infection, but normal antibody production to other Salmonellae (O and H), staphylococci, diphtheria and tetanus toxoid. Histology of lymphoid tissues, and delayed type hypersensitivity and in vitro lymphocyte transformation were normal.

This suggestive evidence of partial antibody deficiency syndrome, with normal concentration of all immunoglobulins, is compared with Aldrich's syndrome, and discussed as a possible instance of partial defect of the final stages of antibody synthesis or release.

     

Cardiac mechanisms underlying normal exercise tolerance: gender impact

The aim of this study is to test our hypothesis that normal exercise tolerance differs according to gender and to identify potential functional cardiac relationships, which could explain those differences. A total of 44 healthy individuals with mean age of 49 ± 12 years (28–74 years, 22 males) constituted the study cohort. All individuals underwent resting and exercise Doppler echocardiogram simultaneously with peak oxygen uptake analysis (pVO₂). At equal pVO₂, males achieved higher peak exercise workload (p < 0.001) and females higher heart rate (p < 0.001) but the two groups maintained similar indexed left ventricular (LV) stroke volume (SV) and cardiac output. Indexed LV end-diastolic (LVDVI) and end-systolic volumes (LVSVI) were smaller in females (p < 0.001 and p < 0.01, respectively), but filling time (FT) was shorter (p < 0.001) and they had higher early diastolic (E) velocity (p = 0.004), E/E _m (myocardial E velocity) (p < 0.001) and global longitudinal strain rate atrial velocity (GLSRa′) (p = 0.02), compared to males. In males, workload (p < 0.01), LVDVI (p < 0.01), LVSVI (p < 0.05), SVI (p < 0.001) directly but LV myocardial isovolumic relaxation time (IVRTm) (p < 0.01) inversely correlated with pVO₂. In females, mitral E velocity (p < 0.01), GLSRs′ (p < 0.05) positively and LVFT negatively (p < 0.05) correlated with pVO₂. In a multivariable analysis SVI in males (p < 0.01) and GLSRs′ in females (p < 0.01) were the strongest predictors for pVO₂. Thus, normal exercise capacity as determined by pVO₂ is related to the indexed stroke volume in males and left atrial pressure in females. These native normal differences between genders may explain the known vulnerability of women to endurance exercise compared to men.     

Rabbit antiserum to human thymocyte membranes: specificity for normal and malignant T-lymphocytes.

An antiserum was obtained by immunization of rabbits with human thymocyte membrane fractions. After appropriate absorptions, the antiserum was shown to detect specifically a population of T-cells. When tested by complement-mediated cytotoxicity the antiserum lysed 95% of thymocytes, 65% of normal PBL and 45% of tonsillar lymphocytes. It was also cytotoxic for three different T-cell lines (MOLT-4, CCRF-CEM and CCRF-HSB-2). When peripheral or tonsillar lymphocytes were separated into populations enriched in B- and T-cells, the percentage of cells lysed by the antiserum correlated well with the proportion of E-rosetting cells. Treatment of PBL with the antiserum and complement resulted in an increase of SmIg-positive B-cells in the residual cell fraction, which could no longer form E-rosettes. Treatment of PBL with the antiserum alone completely inhibited the E-rosette formation. The cytotoxic index on PBL from patients with various lymphoid disorders always correlated with the proportion of T-cells as assessed by E-rosette formation. Finally, the absorptive capacity of thymocytes for the antiserum was ten times higher as compared to that of PBL or tonsil cells.     

Maternal serum hCG and alpha-fetoprotein levels in pregnancies conceived after IVF or ICSI with fresh and frozen-thawed embryos

BACKGROUND: Studies have shown that levels of serum markers of Down's syndrome were altered in pregnancies conceived after IVF, though the reason for this remains unknown. METHODS: Second-trimester maternal serum levels of hCG and alpha-fetoprotein (AFP) in pregnancies conceived with fresh and frozen-thawed embryos after assisted reproduction were compared with those conceived spontaneously. RESULTS: There were 203 pregnancies with fresh embryo transfers (130 IVF cases, 73 ICSI cases) and 98 pregnancies with frozen-thawed embryo transfers (61 IVF cases, 37 ICSI cases). The controls consisted of 17 145 spontaneous pregnancies. The median hCG multiples of the median (MoM) was significantly increased to 1.24 in 98 pregnancies conceived after frozen embryo transfer. This elevation was observed only in the IVF-frozen embryo transfer subgroup (P < 0.001), but not in the ICSI-frozen embryo transfer subgroup. The median AFP MoM for 203 pregnancies after fresh embryo transfer was 0.90. Among the subgroups, the median AFP MoM was significantly reduced to 0.90 and 0.86 in IVF-embryo transfer (P = 0.04) and ICSI-embryo transfer (P = 0.001) pregnancies respectively, and significantly raised to 1.20 in the IVF-frozen embryo transfer subgroup. CONCLUSIONS: The degree of alterations in maternal serum hCG and AFP levels varied between fresh and frozen-thawed embryos, and also between the mode of fertilization. Pregnancies resulting from ICSI or frozen embryo transfer should be regarded as distinct entities from those of IVF-embryo transfer.     

Complement and cell-mediated lysis of haptenated erythrocytes sensitized with oligomers of rabbit igg antibody

Trinitrophenylated (TNP)‡ chicken erythrocytes were coated with various amounts of radiolabeled, affinity cross-linked oligomers of rabbit anti-TNP IgG. These cells were used as targets for lysis by complement or by several types of effector cells, normal splenocytes, cells of a macrophage line (P388D₁) or cells of two lymphoma lines (PL-1 and ABLS-5).With complement as mediator, lysis increased with the number and size of target-bound molecules. In contrast, antibody-dependent, cell-mediated cytolysis (ADCC) depended only on the number of sub-units bound, and was independent of oligomer size. Moreover, complement-mediated lysis required a threshold level of bound antibody before lysis occurred, whereas at low levels of sensitization ADCC increased linearly with increasing antibody. These results suggest that IgG clusters on the target cell are required for complement-mediated lysis but not for cell-mediated lysis. Furthermore, the data suggest that the crosslinking of neighboring Fc receptors on the surface of effector cells is not required for initiating ADCC.Non-immune IgM and small oligomers of non-immune IgG were used to block lysis mediated by each type of effector. ADCC was readily inhibited by small oligomers but not by IgM, while complement was inhibited by only larger IgG oligomers and by IgM. These results suggest that ADCC is not blocked by IgM, but is much more susceptible to inhibition by small IgG immune complexes than complement-mediated lysis.