A combination of iron metabolism indexes and tuberculosis-specific antigen/phytohemagglutinin ratio for distinguishing active tuberculosis from latent tuberculosis infection.

BACKGROUND: Discriminating active tuberculosis (ATB) from latent tuberculosis infection (LTBI) remains challenging. This study aimed to investigate a diagnostic model based on a combination of iron metabolism and the TB-specific antigen/phytohemagglutinin ratio (TBAg/PHA ratio) in T-SPOT.TB assay for differentiation between ATB and LTBI. METHODS: A total of 345 participants with ATB (n=191) and LTBI (n=154) were recruited based on positive T-SPOT.TB results at Tongji hospital between January 2017 and January 2020. Iron metabolism analysis was performed simultaneously. A diagnostic model for distinguishing ATB from LTBI was established according to multivariate logistic regression. RESULTS: The TBAg/PHA ratio showed 64.00% sensitivity and 90.10% specificity in distinguishing ATB from LTBI when a threshold of 0.22 was used. All iron metabolism biomarkers in the ATB group were significantly different from those in the LTBI group. Specifically, serum ferritin and soluble transferrin receptor in ATB were significantly higher than LTBI. On the contrary, serum iron, transferrin, total iron binding capacity, and unsaturated iron binding capacity in ATB were significantly lower than LTBI. The combination of iron metabolism indicators accurately predicted 60.00% of ATB cases and 91.09% of LTBI subjects, respectively. Moreover, the combination of iron metabolism indexes and TBAg/PHA ratio resulted in a sensitivity of 88.80% and specificity of 90.10%. Furthermore, the performance of models established in the Qiaokou cohort was confirmed in the Caidian cohort. CONCLUSIONS: The data suggest that the combination of iron metabolism indexes and TBAg/PHA ratio could serve as a biomarker to distinguish ATB from LTBI in T-SPOT-positive individuals.

Prenatal high-dose vitamin D3 supplementation has balanced effects on cord blood Th1 and Th2 responses.

BACKGROUND: Antenatal vitamin D3 (vitD3) supplementation significantly increases maternal and neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentration, yet the effect of an improvement in maternal-fetal vitamin D status on the neonatal immune response is unclear. METHOD: To assess the effect of prenatal vitD3 supplementation on cord blood T cell function, healthy pregnant Bangladeshi women (n = 160) were randomized to receive either oral 35,000 IU/week vitD3 or placebo from 26 to 29 weeks of gestation to delivery. In a subset of participants (n = 80), cord blood mononuclear cells (CBMC) were cultured, non-adherent lymphocytes were isolated to assess T cell cytokine responses to phytohemagglutinin (PHA) and anti-CD3/anti-CD28 (iCD3/iCD28), measured by multiplex assay. In 12 participants, lymphocyte gene expression profiles were analyzed by PCR array. RESULT: In supplemented group, increased concentrations of IL-10 (P < 0.000) and TNF-α (P = 0.05) with iCD3/iCD28 stimulation and IFN-γ (p = 0.05) with PHA stimulation were obtained compared to placebo group. No differences in the gene expression profile were noted between the two groups. However, PHA stimulation significantly induced the expression of genes encoding Th1 and Th2 cytokines and down-regulated a number of genes involved in T-cell development, proliferation and differentiation of B cells, signal transduction pathway, transcriptional regulation and pattern recognition receptors (PRRs) in the vitamin D group (vitD group). CONCLUSION: Third-trimester high-dose vitD3 supplementation in healthy pregnant women had balanced effects on biomarkers of cord blood Th1 and Th2 responses. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01126528 ).

Immune status of free-ranging green turtles with fibropapillomatosis from Hawaii.

Cell-mediated and humoral immune status of free-ranging green turtles (Chelonia mydas) in Hawaii (USA) with and without fibropapillornatosis (FP) were assessed. Tumored and non-tumored turtles from Kaneohe Bay (KB) on the island of Oahu and from FP-free areas on the west (Kona/Kohala) coast of the island of Hawaii were sampled from April 1998 through February 1999. Turtles on Oahu were grouped (0-3) for severity of tumors with 0 for absence of tumors, 1 for light, 2 for moderate, and 3 for most severe. Turtles were weighed, straight carapace length measured and the regression slope of weight to straight carapace length compared between groups (KB0, KB1, KB2, KB3, Kona). Blood was assayed for differential white blood cell count, hematocrit, in vitro peripheral blood mononuclear cell (PBMC) proliferation in the presence of concanavalin A (ConA) and phytohaemagglutinin (PHA), and protein electrophoresis. On Oahu, heterophil/lymphocyte ratio increased while eosinophil/monocyte ratio decreased with increasing tumors score. Peripheral blood mononuclear cell proliferation indices for ConA and PHA were significantly lower for turtles with tumor scores 2 and 3. Tumor score 3 turtles (KB3) had significantly lower hematocrit, total protein, alpha 1, alpha 2, and gamma globulins than the other four groups. No significant differences in immune status were seen between non-tumored (or KB1) turtles from Oahu and Hawaii. There was no significant difference between groups in regression slopes of body condition to carapace length. We conclude that turtles with severe FP are imunosuppressed. Furthermore, the lack of significant difference in immune status between non-tumored (and KB1) turtles from Oahu and Kona/Kohala indicates that immunosuppression may not be a prerequisite for development of FP.

New SCM (structuredness of the cytoplasmatic matrix)-based approach in breast cancer detection.

AIMS AND BACKGROUND: We evaluate the possibility to use a combination of techniques such as lymphocyte stimulation and the Cell Scan Instrument for early detection of breast cancer. This method can detect differences in lymphocytes activation in the presence of absence of cancer. METHODS: The Cell Scan is a static cytometer system able to examine cellular membrane polarization. We screened 88 women with benign breast lesions, 207 women with mammary carcinoma and 325 healthy blood donors. After lymphocytes separation, each blood sample was incubated with encephalitogenic factor (EF), phytohaemagglutinin (PHA) and Breast Antigen (-BrAg) then SCM test was performed. RESULTS: Positivity was 50% among breast cancer patients, 34% among women affected by benign disease and 27% and 22% respectively among healthy female and male controls with an increase of the specific predictivity of the test during the period of ovulation. A significant difference (P < 0.0001) was observed between healthy donors and breast cancer patients. CONCLUSIONS: This results suggest that the Cell Scan test could be useful to investigate patient's immunogenicity to molecules known to be involved in tumor development and progression, such as oncogene or suppressor gene products, which could be appropriate targets for immune-derived therapeutic approaches.

Long-term effect of radical gastrectomy on nutrition and immunity.

The long-term effects of gastrectomy on the nutritional and immunologic status were prospectively studied in 79 gastric cancer patients who underwent curative gastrectomy and were followed by us after operation for an average of 5 years and 3 months. The percent of actual weight to pre-illness normal weight was lower than 95% in 80% of all study patients. Retinol binding protein, prealbumin, and albumin were lower than normal in 17%, 26%, and 26% of the patients, respectively. The mean values of the percent normal weight, retinol binding protein, and prealbumin were significantly lower in the totally gastrectomized patients than in the subtotally gastrectomized ones (P < 0.01). The procedures of reconstruction did not affect the nutritional status except for the prealbumin level which was significantly decreased in Roux-en-Y cases than in interposed cases of totally gastrectomized patients. Cell-mediated immunological alterations after gastrectomy were observed in 31%, 37%, and 71% of all patients for OKT3 subpopulation, OKT4/OKT8 ratio, and blastogenesis by phytohemagglutinin, respectively. A multivariate analysis revealed that the long-term immunity of the gastrectomized patients after operation was not affected by the levels of albumin and rapid turnover proteins but by the splenectomy and weight loss they underwent.

3'-Azido-3'-deoxythymidine prevents induction of murine acquired immunodeficiency syndrome in C57BL/10 mice infected with LP-BM5 murine leukemia viruses, a possible animal model for antiretroviral drug screening.

Adult C57BL/10 mice (H-2b Fv-1b) inoculated with LP-BM5 murine leukemia virus develop a disease which has many features in common with human acquired immunodeficiency syndrome (AIDS), in particular abnormal lymphoproliferation and severe immunodeficiency. In the present study, we examined the possibility that this murine AIDS (MAIDS) model would be useful for evaluating antiretrovirus drugs in vivo through the use of a well-defined antiretrovirus drug, the reverse transcriptase (RT) inhibitor (H. Mitsuya, K.J. Weinhold, P.A. Furman, M.H. St. Claire, S. Nusinoff-Lehrman, R.C. Gallo, D. Bolognesi, D.W. Barry, and S. Broder, Proc. Natl. Acad. Sci. USA 82:7096-7100, 1985) 3'-azido-3'-deoxythymidine (AZT). We evaluated the effect of AZT treatment on de novo virus infection as well as on the induction of immunodeficiency by various parameters, including RT activity in serum, splenomegaly, proliferative responses against alloantigens and mitogens, soluble-antigen-presenting cell activity, and immunoglobulin G levels in serum. Our results demonstrated that AZT treatment of C57BL/10 mice infected with LP-BM5 murine leukemia virus efficiently prevented the induction of immunodeficiency if started at the time of virus inoculation. Starting AZT treatment 1 week later provided only a partial protective effect. Starting AZT treatment 2 weeks later was associated with suppression of RT activity in serum but no prevention of immunosuppression. This MAIDS model may allow rapid and cost-effective screening for antiretrovirus drugs targeted against retroviral functions shared between human AIDS and MAIDS, such as those encoded by gag, pol, or env.

[Characteristics of the carbohydrate structure of alpha 2-macroglobulin in stomach cancer]. / Osobennosti uglevodnoi struktury al'fa-2-makroglobulina pri rake zheludka.

A comparative study was made for alpha 2M preparations obtained from plasma of patients with gastric carcinoma and healthy individuals. No significant differences were found in trypsin-binding activity of alpha 2M, in isoelectric focusing microheterogeneity and in binding with lectins of Limulus polyphemus hemolymph. The study of alpha 2M-phytohemagglutinin (PHA) binding in sera of patients with gastrointestinal carcinoma and healthy people revealed highly significant differences. The alpha 2M preparations from the gastric carcinoma patients had less affinity for PHA. The data suggest the existence of an abnormal carbohydrate structure of alpha 2M in gastric carcinoma patients.

Clinical studies on cell-mediated immunity in gestational trophoblastic disease: nonspecific cellular immunocompetence in patients with hydatid mole and trophoblastic neoplasia.

The nonspecific cell-mediated immunocompetence of 51 patients with gestational trophoblastic disease (GTD), including 16 patients with hydatid mole (HM), 24 with nonmetastatic trophoblastic neoplasia (NTN) and 15 with metastatic TN (MTN), was studied with the use of both in vitro and in vivo parameters of cell-mediated immunity (CMI) such as lymphocyte blastogenic response to phytohemagglutinin (PHA), subpopulation constitution, and delayed cutaneous hypersensitivity responses to 2,4-dinitrochlorobenzene (DNCB) and to purified protein derivative of tuberculin (PPD). The pretreatment cell-mediated immune status of patients with HM developing no malignant sequelae was shown to be essentially similar, in terms of both in vitro PHA and in vivo DNCB reactivities, to that of normal women and of patients with benign gynecological diseases. In patients with TN, however, there was a significant depression in the blastogenic lymphocyte response to PHA before evacuation of the mole, which was persistently demonstrated after uterine evacuation and more marked throughout the course of disease in patients with MTN, than in those with NTN, with a tendency to return to normal in remission. Moreover, patients with TN had a significant depletion of T lymphocytes as determined by rosette-forming cell procedures before treatment, which was most evident in patients with MTN. Plasma from the MTN patients was also shown to have an inhibitory effect on PHA responsiveness of lymphocytes from normal women. There was an increased incidence of impaired reactivity to DNCB in patients with TN (higher in MTN than in NTN), compared with HM and benign diseases, while no such difference in incidence was observed in response to PPD. On the basis of these findings, a preliminary characterization of altered immunocompetence in patients with TN and its mechanism are discussed.