Outcome of primary lethal and nonlethal Plasmodium yoelii malaria infection in BALB/c and IFN-γ receptor-deficient mice following chloroquine treatment

IFN-γ receptor-deficient (IFN-γR^?/?) mice and control wild-type (WT) mice, with or without chloroquine (CQ) treatment, were infected intraperitoneally with Plasmodium yoelii 17XL (lethal) and P. yoelii 17XNL (nonlethal), and then mouse survival, parasitemia, and antibody production were investigated during the course of infection. Without CQ treatment, both IFN-γR^?/? and WT mice were susceptible to infection showing 100 % mortality after infection with 1?×?10⁵ P. yoelii 17XL-parasitized erythrocytes. The P. yoelii 17XL-infected WT mice could survive by CQ treatment at a dose of 20 mg/kg for 3 days from day 3 postinfection (pi). Malaria parasites in their bloodstream could not be detected in the surviving mice after day 13 pi. CQ treatment, however, could not rescue IFN-γR^?/? mice infected with P. yoelii 17XL. Next, we examined the production of the parasite-specific antibodies in P. yoelii 17XL-infected, CQ-treated mice. Although the production of malaria-specific IgG1, IgG2a, IgG2b, and IgG3 antibodies was observed on days 14 and 28 pi in WT mouse sera, only IgG1 was detected on day 28 pi in IFN-γR^?/? mouse sera. On the other hand, in the nonlethal P. yoelii 17XNL infection, WT mice could control a primary infection with 1?×?10⁵ parasitized erythrocytes. Although IFN-γR^?/? mice could not control and died with increasing parasitemia, the mice could survive by CQ treatment. Both WT and IFN-γR^?/? mice with and without medication, which survived from P. yoelii 17XNL infection, showed the variable levels of malaria-specific IgG1, IgG2a, IgG2b, and IgG3 antibodies during the course of infection. The present data indicate that the IFN-γ receptors are needed to control the infection and parasite-specific IgG2a antibody plays an essential role in recovery from the infection of erythrocytic stages of P. yoelii 17XL or P. yoelii 17XNL parasite.     

Efficacy of chloroquine in treatment of non-complicated malaria with Plasmodium falciparum in children at the San Pedro dispensary in Côte d'Ivoire

A survey has been carried out in south-west of C?te d'Ivoire in order to study chloroquine resistance in treatment of malaria according to 14 days protocol of WHO (World Health Organisation) (1996) for evaluation of antimalarial drugs activity; 63 children, aged from 6 months to 15 years and suffering from noncomplicated malaria due to Plasmodium falciparum, received by oral way 25 mg/kg of chloroquine over three days (10-10-5). During the survey, they were subjected to a clinic and parasitologic (thick and thin blood film) follow up. We obtained, for 51 children (81%), a satisfactory clinical answer, for 8 children (13%) an early therapeutic failure and for the other 4 (6%) a late therapeutic failure. Moreover, we obtained 40% of failure in children of less than 24 months old, 25% between 24 months and 59 months and 7% beyond 6 years old.     

Temporal evolution of human autoantibody response to cytoplasmic rods and rings structure during anti-HCV therapy with ribavirin and interferon-α

Autoantibodies to inosine monophosphate dehydrogenase-2 (IMPDH2), an enzyme involved in de novo biosynthesis of guanine nucleotides, are observed in a subset of hepatitis C virus (HCV) patients receiving interferon alpha (IFN-α) plus ribavirin. Anti-IMPDH2 antibodies display a peculiar cytoplasmic “rod/ring” (RR) pattern in IIF-HEp-2. We examined the dynamics of anti-RR autoimmune response with respect to immunoglobulin isotypes, titer, avidity, and protein targets in 80 sequential samples from 15 HCV patients (plus 12 randomly selected anti-RR-positive, totalizing 92 samples) collected over an 18-month period, including samples collected before, during, and after IFN-α + ribavirin treatment. Immunoprecipitation showed reactivity with the 55 kDa IMPDH2 protein in 12/15 patients (80 %) and 11/15 (73 %) reacted with IMPDH2 in a sandwich ELISA. During treatment, anti-IMPDH2 autoantibodies hit their highest levels after 6–12 months of treatment and decreased post-treatment, while anti-HCV antibodies levels were stable over time. Anti-IMPDH2 IgM levels increased up until the sixth month of treatment and remained stable thereafter, while IgG levels increased steadily up to the twelfth month. Both IgG and IgM decreased during the post-treatment period. IgG avidity increased steadily up to the twelfth month of treatment. In conclusion, this study showed that the temporal kinetics of IFN-α + ribavirin-induced humoral autoimmune response to IMPDH2 exhibited a considerably delayed pace of increase in antibody levels and avidity as well as in isotype class switch in comparison with a conventional humoral response to infectious agents. These unique findings uncover intriguing differences between the autoimmune response and the immune response to exogenous agents in humans.     

Endotoxin exacerbates immunologically induced liver injury in cooperation with interferon-γ

OBJECTIVE AND DESIGN: To investigate the role of endotoxin in the development of immunologically induced liver injury. MATERIALS AND METHODS: A new model of liver injury induced in BALB/c mice by delayed-type hypersensitivity to picryl chloride and its in vitro assay for the interaction between liver nonparenchymal and parenchymal cells were used. RESULTS: Plasma endotoxin in the injured liver correlated well with serum alanine transaminase (ALT) activity (r = 0.601). Tolerance to lipopolysaccharide led to a significant inhibition of serum ALT elevation. However, lipopolysaccharide in vitro increased the ALT release from hepatocytes caused by nonparenchymal cells only in the presence of IFN-gamma. When nonparenchymal cells were separated into Kupffer and non-Kupffer cell populations, the synergistic hepatotoxicity of lipopolysaccharide and IFN-gamma was still observed in the former but not in the latter cell type. Lipopolysaccharide with IFN-gamma also enhanced TNF-alpha levels. Anti-TNF-alpha almost completely inhibited the ALT release. Combined use of TNF-alpha and IFN-gamma caused marked hepatocyte damage, while these cytokines alone did not. CONCLUSIONS: We suggest that elevated endotoxin levels accompanying the development of liver injury may activate Kupffer cells to release TNF-alpha leading to exacerbation of hepatocyte damage in cooperation with IFN-gamma produced during liver injury.     

Hepatitis C virus and interferon type III (interferon-λ3/interleukin-28B and interferon-λ4): genetic basis of susceptibility to infection and response to antiviral treatment

There has been a significant increase in our understanding of the host genetic determinants of susceptibility to viral infections in recent years. Recently, two single-nucleotide polymorphisms (SNPs), rs12979860 T/C and rs8099917 T/G, upstream of the interleukin (IL)-28B/interferon (IFN)-λ3 gene have been clearly associated with spontaneous and treatment-induced viral clearance in hepatitis C virus (HCV) infection. Because of their power in predicting the response to IFN/ribavirin therapy, the above SNPs have been used as a diagnostic tool, even though their relevance in the management of HCV infection will be blunt in the era of IFN-free regimens. The recent discovery of a new genetic variant, ss469415590 TT/ΔG, upstream of the IL-28B gene, which generates the novel IFN-λ4 protein, has opened up a new and alternative scenario to understand the functional architecture of type III IFN genomic regions and to improve our knowledge of the pathogenetic mechanism of HCV infection. A role of ss469415590 in predicting responsiveness to antiviral therapy has also been observed in HCV-infected patients receiving direct antiviral agents. The underlying biological mechanism that links the above IL-28B polymorphisms (in both IFN-λ3 and IFN-λ4) to spontaneous and treatment-induced clearance of HCV infection remains to be discovered. Despite this, shedding some light on this issue, which is the main aim of this review, may provide new insights into the general topic of ‘host genetics and viral infections’.     

Evaluation of the therapeutic efficacy of amodiaquine versus chloroquine in the treatment of uncomplicated malaria in Abie, Côte-d'Ivoire

The WHO 14-days' test and an in vitro survey were carried out to study the efficacy of amodiaquine versus chloroquine in Abie, a hyperendemic village in the southern forest area of C?te-d'Ivoire. One hundred and nineteen children less than 15 years old suffering from uncomplicated malaria were randomised. Among these, 62 were given amodiaquine treatment and 57 chloroquine treatment. both 4-aminoquinoleines were administered at the same dose of 30 mg/kg spread over three days by 10 mg/kg/day. Before the drug was administered, parasites were taken from some patients of each group and were evaluated in vitro to both drugs. In vivo, the amodiaquine treatment shows 95% of clinical success, 2% of early clinical failures and 3% of late clinical failures. For the chloroquine treatment, the rates are respectively. 79%, 7% and 14%. However, some patients still had a level of parasitaemia for both treatments but were asymptomatic. These parasites were found to be resistant in vitro. The authors recommend that the treatment to be used in Abie must be firstly amodiaquine followed by sulfadoxine-pyrimethamine in cases where there is persistent asymptomatic parasitemia.     

Regulatory T cell frequency in patients with melanoma with different disease stage and course, and modulating effects of high-dose interferon-α 2b treatment

Background

Cytokine-induced killer (CIK) cells are typically differentiated in vitro with interferon (IFN)-γ and αCD3 monoclonal antibodies (mAb), followed by the repeated provision of interleukin (IL)-2. It is presently unknown whether thymoglobulin (TG), a preparation of polyclonal rabbit γ immunoglobulins directed against human thymocytes, can improve the generation efficiency of CIK cells compared with αCD3 mAb in a clinical-grade culture protocol.

Methods

Peripheral blood mononuclear cells (PBMC) from 10 healthy donors and 4 patients with solid cancer were primed with IFN-γ on day 0 and low (50 ng/ml), intermediate (250 ng/ml) and high (500 ng/ml) concentrations of either αCD3 mAb or TG on day 1, and were fed with IL-2 every 3 days for 21 days. Aliquots of cells were harvested weekly to monitor the expression of representative members of the killer-like immunoglobulin receptor (KIR), NK inhibitory receptor, NK activating receptor and NK triggering receptor families. We also quantified the frequency of bona fide regulatory T cells (Treg), a T-cell subset implicated in the down-regulation of anti-tumor immunity, and tested the in vitro cytotoxic activity of CIK cells against NK-sensitive, chronic myeloid leukaemia K562 cells.

Results

CIK cells expanded more vigorously in cultures supplemented with intermediate and high concentrations of TG compared with 50 ng/ml αCD3 mAb. TG-driven CIK cells expressed a constellation of NK activating/inhibitory receptors, such as CD158a and CD158b, NKp46, NKG2D and NKG2A/CD94, released high quantities of IL-12p40 and efficiently lysed K562 target cells. Of interest, the frequency of Treg cells was lower at any time-point compared with PBMC cultures nurtured with αCD3 mAb. Cancer patient-derived CIK cells were also expanded after priming with TG, but they expressed lower levels of the NKp46 triggering receptor and NKG2D activating receptor, thus manifesting a reduced ability to lyse K562 cells.

Conclusions

TG fosters the generation of functional CIK cells with no concomitant expansion of tumor-suppressive Treg cells. The culture conditions described herein should be applicable to cancer-bearing individuals, although the differentiation of fully functional CIK cells may be hindered in patients with advanced malignancies.     

Evolution of the pfcrt T76 and pfmdr1 Y86 markers and chloroquine susceptibility 8 years after cessation of chloroquine use in Pikine, Senegal

The goal of the present study was to assess the evolution of the in vitro chloroquine resistance and also the prevalence of pfcrt T76 and pfmdr1 Y86 mutations in Pikine from 2000 while chloroquine (CQ) was the first-line treatment of malaria to 2009 when artemisinin-based combination therapies (ACTs) are in use. We genotyped pfcrt K76T and pfmdr1 N86Y polymorphisms by PCR-RFLP and assessed in vitro CQ susceptibility by double-site enzyme-linked pLDH immunodetection (DELI) assay in Plasmodium falciparum isolates collected in Pikine, Senegal. The proportions of the pfcrt T76 allele in the light of the three different treatment policies were 72.4?% before CQ withdrawal (2000 to 2003), 47.2?% while amodiaquine plus Fansidar was the first-line treatment (2004 to 2005), and 59.5?% since the ACT use was implemented (2006 to 2009). The prevalence of pfcrt T76 decreased significantly after CQ was stopped [X (2)?=?6.54, P?=?0.01 (2000-2003 versus 2004-2005)] and then slightly since ACTs have been implemented [X (2)?=?1.12, P?=?0.28 (2000-2003 versus 2006-2009)]. There were no significant differences on the prevalence of pfmdr1 Y86 throughout the three treatment policies. The DELI assay was carried out episodically in 2000 (n?=?36), 2001 (n?=?47), and 2009 (n?=?37). The mean IC(50)s of the isolates to CQ in 2000 versus 2009 and 2001 versus 2009 are significantly different (P?相似文献   

Effects of adalimumab therapy on disease activity and interferon-γ-mediated biochemical pathways in patients with rheumatoid arthritis

In patients with rheumatoid arthritis (RA), overwhelming inflammatory activity and immune activation are indicated by elevated concentrations of immune activation markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and neopterin. Furthermore, accelerated tryptophan (Trp) degradation by the enzyme indoleamine 2,3-dioxygenase (IDO) is detectable in blood samples of patients by an increased kynurenine (Kyn) to Trp ratio (Kyn/Trp). This study comprises 22 patients (20 women, 2 men) with long-standing, moderate to severe RA, who were treated with a monoclonal tumor necrosis factor (TNF)-antibody (Adalimumab 40 mg subcutaneously every other week) in addition to their concomitant, but inadequate anti-rheumatic therapies. Blood samples were collected before therapy and at week 12. ESR and CRP concentrations were measured within routine diagnostic. Serum concentrations of neopterin, Trp, and Kyn were determined by commercially available ELISA and by high performance liquid chromatography. Before therapy, disease activity as reflected by disease activity score 28 (DAS28) was significantly associated with concentrations of inflammation markers such as ESR (rs = 0.601, p < 0.01) and CRP (rs = 0.433, p < 0.05), but not with neopterin concentrations or Trp metabolic changes. Upon treatment, DAS28 improved significantly (median before therapy: 5.7 and after therapy: 3.1; p < 0.0001). During adalimumab treatment, only CRP decreased significantly (p < 0.05), while all other parameters investigated did not change significantly. Our results indicate that anti-TNF therapy does not influence neopterin concentrations or IDO activity in patients with RA, despite a highly significant improvement of patients' disease activity.     

Ventilatory response to moderate incremental exercise performed 24 h after resistance exercise with concentric and eccentric contractions

In order to test our hypothesis that muscle condition has an effect on the cognition of self-motion and consequently on the ventilatory response during exercise, six healthy subjects performed a moderate incremental exercise test (IET) on a cycle ergometer under two conditions [resistance exercise condition (REC) and control condition (CC)]. In the REC, resistance exercise (30 incline leg presses) was conducted during two sessions scheduled at 48 and then 24 h prior to the IET. For the CC, the subjects were instructed to refrain from participating in strenuous exercise for a period of 2 days prior to the IET. In the IET, the workload was increased from 78 to 118 watts in steps of 8 watts every 3 min. Although the ventilatory response during the IET was significantly higher in the REC than in the CC, there were no significant differences in cognitive indexes (RPE and awareness of change in workload) between the two conditions. In addition, the magnitude of muscle soreness was significantly higher in the REC than in the CC. However, the level of soreness in the REC was very low, and there were no significant differences in blood lactate concentration and integrated EMG between the two conditions. These results suggest that a change in peripheral neural reflex is the primary cause of increased ventilatory response to moderate exercise after resistance exercise, although the role of a cognitive element cannot be absolutely excluded.     

Impairment of the hematological response and interleukin-1β production in protein-energy malnourished mice after endotoxemia with lipopolysaccharide

The objectives of this study were to determine if protein-energy malnutrition (PEM) could affect the hematologic response to lipopolysaccharide (LPS), the interleukin-1β (IL-1β) production, leukocyte migration, and blood leukocyte expression of CD11a/CD18. Two-month-old male Swiss mice were submitted to PEM (N = 30) with a low-protein diet (14 days) containing 4% protein, compared to 20% protein in the control group (N = 30). The total cellularity of blood, bone marrow, spleen, and bronchoalveolar lavage evaluated after the LPS stimulus indicated reduced number of total cells in all compartments studied and different kinetics of migration in malnourished animals. The in vitro migration assay showed reduced capacity of migration after the LPS stimulus in malnourished animals (45.7 ± 17.2 × 10⁴ cells/mL) compared to control (69.6 ± 7.1 × 10⁴ cells/mL, P ≤ 0.05), but there was no difference in CD11a/CD18 expression on the surface of blood leukocytes. In addition, the production of IL-1β in vivo after the LPS stimulus (180.7 pg·h⁻¹·mL⁻¹), and in vitro by bone marrow and spleen cells (41.6 ± 15.0 and 8.3 ± 4.0 pg/mL) was significantly lower in malnourished animals compared to control (591.1 pg·h⁻¹·mL⁻¹, 67.0 ± 23.0 and 17.5 ± 8.0 pg/mL, respectively, P ≤ 0.05). The reduced expression of IL-1β, together with the lower number of leukocytes in the central and peripheral compartments, different leukocyte kinetics, and reduced leukocyte migration capacity are factors that interfere with the capacity to mount an adequate immune response, being partly responsible for the immunodeficiency observed in PEM.     

Pain-sensitive temperament: does it predict procedural distress and response to psychological treatment among children with cancer?

OBJECTIVE: To evaluate the relationship between pain sensitivity and children's distress during lumbar punctures (LPs), and whether pain sensitivity functions as a moderator of children's responses to a psychological intervention aimed at reducing LP distress. METHOD: Fifty-five children with acute lymphoblastic leukemia (ages 3 to 18) and their parents completed a questionnaire measure of pain sensitivity. Self-report, physiological, and observed measures of distress were collected during the study baseline LP. Children were then randomized into a psychological intervention or an attention control group. Postintervention and follow-up LPs were observed. RESULTS: Higher levels of pain sensitivity were associated with greater anxiety and pain, both prior to and during the LP. Preliminary analyses indicated that pain sensitivity moderated the effects of intervention on distress. Children who were more pain-sensitive and who received no intervention showed greater increases in LP distress over time. In contrast, children who were more pain-sensitive and who received intervention showed greater decreases in LP distress over time. CONCLUSIONS: A measurement of pain sensitivity may be useful in pediatric oncology settings for effectively targeting pain-vulnerable children for psychological intervention. Preliminary analyses indicate that an empirically-supported intervention for procedural distress is efficacious for those children who are most pain-sensitive.     

DNA polymeraseη protein expression predicts treatment response and survival of metastatic gastric adenocarcinoma patients treated with oxaliplatin-based chemotherapy

Background  

DNA polymerase η (pol η) is capable of bypassing DNA adducts produced by cisplatin or oxaliplatin and is associated with cellular tolerance to platinum. Previous studies showed that defective pol η resulted in enhanced cisplatin or oxaliplatin sensitivity in some cell lines. The purpose of the present study was to investigate the role of pol η protein expression in metastatic gastric adenocarcinoma.     

Viral load and humoral immune response in association with disease severity in Puumala hantavirus-infected patients—implications for treatment

Hantaviruses are the causative agents of haemorrhagic fever with renal syndrome (HFRS) in Eurasia and of hantavirus cardiopulmonary syndrome (HCPS) in the Americas. The case fatality rate varies between different hantaviruses and can be up to 40%. At present, there is no specific treatment available. The hantavirus pathogenesis is not well understood, but most likely, both virus-mediated and host-mediated mechanisms are involved. The aim of the present study was to investigate the association among Puumala hantavirus (PUUV) viral RNA load, humoral immune response and disease severity in patients with HFRS. We performed a study of 105 PUUV-infected patients that were followed during the acute phase of disease and for up to 1–3 months later. Fifteen of the 105 patients (14%) were classified as having moderate/severe disease. A low PUUV-specific IgG response (p <0.05) and also a higher white blood cell count (p <0.001) were significantly associated with more severe disease. The PUUV RNA was detected in a majority of patient plasma samples up to 9 days after disease onset; however, PUUV RNA load or longevity of viraemia were not significantly associated with disease severity. We conclude that a low specific IgG response was associated with disease severity in patients with HFRS, whereas PUUV RNA load did not seem to affect the severity of HFRS. Our results raise the possibility of passive immunotherapy as a useful treatment for hantavirus-infected patients.     

Decreased interferon-α production in response to CpG DNA dysregulates cytokine responses in patients with multiple sclerosis

Type I interferons (IFNs), represented by IFN-α and β, activate immune effector cells belonging to the innate and adaptive immune systems. Plasmacytoid dendritic cells (pDCs) produce IFN-α in response to CpG DNA. We aimed to examine the impact of pDC-produced IFN-α on the adaptive immune system in Multiple Sclerosis (MS). Our results demonstrated that CpG DNA-induced IFN-α production was significantly decreased in PBMCs from MS patients. Decreased levels of IL-12 p70, IFN-γ, and IL-17 and increased level of IL-10 were found in CpG DNA-treated PBMCs of healthy subjects unlike in those from MS patients. In samples pre-treated with IFN-α and IFN-β, decreased levels of IL-12 p70, IFN-γ, and IL-17 and increased level of IL-10 were detected in PBMCs from MS patients. These results suggest that CpG DNA-induced decreased IFN-α production causes pro-inflammatory cytokine secretion, and either IFN-α or IFN-β induces anti-inflammatory cytokine secretion in the adaptive immune system in MS.     

Does genotype predict response to treatment in children infected with hepatitis B perinatally?

HBV genotype may correlate with outcome and treatment response. Genotype has been compared with treatment response in children infected perinatally with hepatitis B following treatment with oral antiviral drugs (lamivudine or adefovir) or interferon (IFN) alone and with prednisolone priming (Pred/IFN). All children who took part in clinical trials in this unit since 1990 were included. Hepatitis B genotypes were determined by direct sequencing or using a commercial line probe assay (InnoLipa). Sixty‐five children were included; 20 were treated with IFN; 19 with Pred/IFN; 22 with lamivudine and 7 with adefovir, some took part in more than one treatment study. 63 out of 65 children were clearly typed into single genotypes; 16, 7, 3, and 37 typing as A, B, C, and D respectively. The majority of South‐Asian children had genotype D and European and Afro‐Caribbean children were more likely to have genotype A. Treatment response (seroconversion from HBeAg to Anti‐HBe) was better in children with genotypes A [n = 16] and D [n = 37] (55.5% and 48.7%), compared to those with B [n = 7] and C [n = 3] (12.5% and 0%) for all treatments. The response to interferon alone was better in children with genotype A compared to D (50% and 36%), but prednisolone priming improved the response so that there was no difference between genotypes A and D (66.7% and 70%). Assessment of genotype in children pre‐treatment may provide a guide to potential response. The response to treatment by genotype should be evaluated in future clinical trials in children. J. Med. Virol. 84:1535–1540, 2012. © 2012 Wiley Periodicals, Inc.     

Behavior of soluble HLA-A, -B, -C and HLA-G molecules in patients with chronic hepatitis C virus infection undergoing pegylated interferon-α and ribavirin treatment: potential role as markers of response to antiviral therapy

The serum levels of soluble HLA class I antigens (sHLA-A, -B, -C and sHLA-G) were determined in 40 HCV genotype 1-infected patients before (T ₀), after 3, 6, and 12 months (T ₃, T ₆, and T ₁₂) of pegylated-IFN-α plus ribavirin therapy and 6 months (T ₁₈) after the end of treatment. Twenty patients were sustained virological responders (SVR), and 20 were non-responders (NR). sHLA-A, -B, -C levels at T ₀ were significantly higher in both SVR (mean 10.48 μg/ml) and NR (mean 11.87 μg/ml) patients as compared to healthy controls (mean 0.34 μg/ml, p < 0.0001) and HIV-infected subjects (mean 1.22 μg/ml, p < 0.0001). sHLA-G levels at T ₀ were significantly higher in SVR (mean 24.78 ng/ml) and NR (mean 24.93 ng/ml) patients as compared to healthy controls (mean 10.34 ng/ml, p = 0.015 and p = 0.014, respectively) but were lower as compared to HIV-infected subjects (mean 48.00 ng/ml, p < 0.0001). The levels of sHLA-A, -B, -C and sHLA-G significantly decreased in SVR from T ₀ to T ₁₈ (mean 1.64 and 1.43 ng/ml, respectively, p < 0.0001) and correlated with HCV-RNA, AST, ALT, γGT, and ALP levels. The determination of soluble HLA class I levels could be proposed as a surrogate marker to discriminate SVR and NR HCV-infected patients during PEG-IFN-α plus ribavirin therapy.     

Antibody response against three epitopic domains on human chorionic gonadotropin (hCG) in women and rodents immunized with a βhCG-based immunocontraceptive vaccine

The antibody repertoire generated against human chorionic gonadotropin (hCG), following immunization with an immunocontraceptive vaccine based on the beta subunit of the hormone, in humans was compared with that generated in rats. Three epitopic domains represented by the hCG loop peptide 38–57, the carboxy-terminal peptide (CTP) 109–145, and a region defined by monoclonal antibody (MAb) 206 were probed. In both species, the titer of antibodies against the MAb 206-defined epitopic domain had a good correlation with the total anti-hCG antibody titers. However, the antibody response against the hCG loop peptide (38-57) was not observed in human subjects and there was a weak response against this peptide in rats. Despite the good anti-hCG antibody titers in all animals (n=8), only two had antibodies against this domain. A good antibody response was observed against CTP in rats, whereas in humans this region was weakly immunogenic. Antibodies against CTP were detected in random samples in only 57% of the subjects and this response had no correlation with the total anti-hCG antibody titers. The high antibody response against CTP in rodents compared to humans may be due to its recognition as a foreign determinant. Our results demonstrate that contraception can be achieved in women despite a poor antibody response against the CTP (109-145) and a receptor binding domain (38–57) of hCG.     

Are childhood psychiatric histories of bipolar adolescents associated with family history, psychosis, and response to lithium treatment?

OBJECTIVE: To examine if childhood psychiatric diagnoses are associated with family history, psychosis, age, and lithium response. METHOD: Associations among variables, and their contributions to explaining lithium response were examined in 48 bipolar adolescents enrolled in a study of lithium. RESULTS: Presence of a childhood diagnosis was not associated with family psychiatric history or lithium response. Subjects with psychotic features, however, were less likely to have a childhood psychiatric diagnosis, were older, and had a poorer response rate to lithium than subjects without psychosis. DISCUSSION: Heterogeneity within bipolar adolescents may be based on clinical features such as psychosis rather than childhood or family history alone.