Time-series blood cytokine profiles correlate with treatment responses in triple-negative breast cancer patients.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype. Partly due to its heterogeneity, it is currently challenging to stratify TNBC patients and predict treatment outcomes. METHODS: In this study, we examined blood cytokine profiles of TNBC patients throughout treatments (pre-treatment, during chemotherapy, pre-surgery, and 1 year after the surgery in a total of 294 samples). We analyzed the obtained cytokine datasets using weighted correlation network analyses, protein-protein interaction analyses, and logistic regression analyses. RESULTS: We identified five cytokines that correlate with good clinical outcomes: interleukin (IL)-1α, TNF-related apoptosis-inducing ligand (TRAIL), Stem Cell Factor (SCF), Chemokine ligand 5 (CCL5 also known as RANTES), and IL-16. The expression of these cytokines was decreased during chemotherapy and then restored after the treatment. Importantly, patients with good clinical outcomes had constitutively high expression of these cytokines during treatments. Protein-protein interaction analyses implicated that these five cytokines promote an immune response. Logistic regression analyses revealed that IL-1α and TRAIL expression levels at pre-treatment could predict treatment outcomes in our cohort. CONCLUSION: We concluded that time-series cytokine profiles in breast cancer patients may be useful for understanding immune cell activity during treatment and for predicting treatment outcomes, supporting precision medicine. TRIAL REGISTRATION: The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index-j.htm ) with the unique trial number UMIN000023162. The association Japan Breast Cancer Research Group trial number is JBCRG-22. The clinical outcome of the JBCRG-22 study was published in Breast Cancer Research and Treatment on 25 March 2021. https://doi.org/10.1007/s10549-021-06184-w .

Serum antibodies to human leucocyte antigen (HLA)-E, HLA-F and HLA-G in patients with systemic lupus erythematosus (SLE) during disease flares: Clinical relevance of HLA-F autoantibodies.

T lymphocyte hyperactivity and progressive inflammation in systemic lupus erythematosus (SLE) patients results in over-expression of human leucocyte antigen (HLA)-Ib on the surface of lymphocytes. These are shed into the circulation upon inflammation, and may augment production of antibodies promoting pathogenicity of the disease. The objective was to evaluate the association of HLA-Ib (HLA-E, HLA-F and HLA-G) antibodies to the disease activity of SLE. The immunoglobulin (Ig)G/IgM reactivity to HLA-Ib and ß2m in the sera of 69 German, 29 Mexican female SLE patients and 17 German female controls was measured by multiplex Luminex(®)-based flow cytometry. The values were expressed as mean flourescence intensity (MFI). Only the German SLE cohort was analysed in relation to the clinical disease activity. In the controls, anti-HLA-G IgG predominated over other HLA-Ib antibodies, whereas SLE patients had a preponderance of anti-HLA-F IgG over the other HLA-Ib antibodies. The disease activity index, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000, was reflected only in the levels of anti-HLA-F IgG. Anti-HLA-F IgG with MFI level of 500-1999 was associated with active SLE, whereas inactive SLE revealed higher MFI (>2000). When anti-HLA-F IgG were cross-reactive with other HLA-Ib alleles, their reactivity was reflected in the levels of anti-HLA-E and -G IgG. The prevalence of HLA-F-monospecific antibodies in SLE patients was also associated with the clinical disease activity. Anti-HLA-F IgG is possibly involved in the clearance of HLA-F shed from lymphocytes and inflamed tissues to lessen the disease's severity, and thus emerges as a beneficial immune biomarker. Therefore, anti-HLA-Ib IgG should be considered as a biomarker in standard SLE diagnostics.

Trends in nutritional status and nutrient intakes and correlates of overweight/obesity among rural adult women (≥18-60 years) in India: National Nutrition Monitoring Bureau (NNMB) national surveys.

OBJECTIVE: To assess trends in nutrient intakes and nutritional status of rural adult women (≥18-60 years) and the association of sociodemographic characteristics with overweight/obesity. DESIGN: Community-based cross-sectional studies carried out during 1975-79 to 2011-12 by the National Nutrition Monitoring Bureau (NNMB) were used. Anthropometric measurements such as height, weight and waist circumference, carried out during the surveys, were used. Association and logistic regression analyses between sociodemographic characteristics and overweight/obesity and abdominal obesity were conducted using a complex samples procedure. SETTING: Ten NNMB states of India. SUBJECTS: Non-pregnant and non-lactating rural women aged ≥18-60 years covered during the above periods from ten states in India. RESULTS: The prevalence of chronic energy deficiency has declined from 52 % during 1975-79 to 34 % during 2011-12, while that of overweight/obesity has increased from 7 % to 24 % during the same period. Median intakes of most of the nutrients have increased over the same period, although they were below recommended levels. The chance of overweight/obesity and abdominal obesity was significantly (P<0·01) higher among women aged 40-60 years, those belonging to Christian religion and other backward communities, women living in pucca houses, literate women, women engaged in service and business, and those having higher per capita income. CONCLUSIONS: Prevalence of chronic energy deficiency has declined significantly; however, overweight/obesity has increased during the same period. This increase in overweight/obesity may be attributed to increased consumption of fatty foods, sedentary lifestyle and improved socio-economic status. There is a need to educate the community about regular physical exercise, low intakes of fats and oils, and a balanced diet.

Socio-economic & demographic determinants of hypertension & knowledge, practices & risk behaviour of tribals in India.

BACKGROUND & OBJECTIVES: An increase in prevalence of hypertension has been observed in all ethnic groups in India. The objective of the present study was to estimate prevalence and determinants of hypertension among tribals and their awareness, treatment practices and risk behaviours in nine States of India. METHODS: A community based cross-sectional study adopting multistage random sampling procedure was carried out. About 120 Integrated Tribal Development Authority villages were selected randomly from each State. From each village, 40 households were covered randomly. All men and women ≥ 20 yr of age in the selected households were included for various investigations. RESULTS: A total of 21141 men and 26260 women participated in the study. The prevalence of hypertension after age adjustment was 27.1 and 26.4 per cent among men and women, respectively. It was higher in the s0 tates of Odisha (50-54.4%) and Kerala (36.7-45%) and lowest in Gujarat (7-11.5%). The risk of hypertension was 6-8 times higher in elderly people and 2-3 times in 35-59 yr compared with 20-34 yr. Only <10 per cent of men and women were known hypertensives and more than half on treatment (55-68%). Men with general and abdominal obesity were at 1.69 (CI: 1.43-2.01) and 2.42 (CI: 2.01-2.91) times higher risk of hypertension, respectively, while it was 2.03 (CI=1.77-2.33) and 2.35 (CI 2.12-2.60) times higher in women. Those using tobacco and consuming alcohol were at a higher risk of hypertension compared with the non users. INTERPRETATION & CONCLUSIONS: The study revealed high prevalence of hypertension among tribals in India. Age, literacy, physical activity, consumption of tobacco, alcohol and obesity were significantly associated with hypertension. Awareness and knowledge about hypertension and health seeking behaviour were low. Appropriate intervention strategies need to be adopted to increase awareness and treatment practices of hypertension among tribals.

Immunoglobulin (Ig)G purified from human sera mirrors intravenous Ig human leucocyte antigen (HLA) reactivity and recognizes one's own HLA types, but may be masked by Fab complementarity-determining region peptide in the native sera.

Intravenous immunoglobulin (IVIg) reacted with a wide array of human leucocyte antigen (HLA) alleles, in contrast to normal sera, due possibly to the purification of IgG from the pooled plasma. The reactivity of IgG purified from normal sera was compared with that of native sera to determine whether any serum factors mask the HLA reactivity of anti-HLA IgG and whether IgG purified from sera can recognize the HLA types of the corresponding donors. The purified IgG, unlike native sera, mirrored IVIg reactivity to a wide array of HLA-I/-II alleles, indicating that anti-HLA IgG may be masked in normal sera - either by peptides derived from soluble HLA or by those from antibodies. A < 3 kDa peptide from the complementarity-determining region (CDR) of the Fab region of IgG (but not the HLA peptides) masked HLA recognition by the purified IgG. Most importantly, some of the anti-HLA IgG purified from normal sera - and serum IgG from a few donors - indeed recognized the HLA types of the corresponding donors, confirming the presence of auto-HLA antibodies. Comparison of HLA types with the profile of HLA antibodies showed auto-HLA IgG to the donors' HLA antigens in this order of frequency: DPA (80%), DQA (71%), DRB345 (67%), DQB (57%), Cw (50%), DBP (43%), DRB1 (21%), A (14%) and B (7%). The auto-HLA antibodies, when unmasked in vivo, may perform immunoregulatory functions similar to those of therapeutic preparations of IVIg.

Suppression of blastogenesis and proliferation of activated CD4(+) T cells: intravenous immunoglobulin (IVIg) versus novel anti-human leucocyte antigen (HLA)-E monoclonal antibodies mimicking HLA-I reactivity of IVIg.

Activated CD4(+) T cells undergo blastogenesis and proliferation and they express several surface receptors, including ß2-microglobulin-free human leucocyte antigen (HLA) heavy chains (open conformers). Intravenous immunoglobulin (IVIg) suppresses activated T cells, but the mechanism is unclear. IVIg reacts with HLA-Ia/Ib antigens but its reactivity is lost when the anti-HLA-E Ab is adsorbed out. Anti-HLA-E antibodies may bind to the peptides shared by HLA-E and the HLA-I alleles. These shared peptides are cryptic in intact HLA, but exposed in open conformers. The hypothesis that anti-HLA-E monoclonal antibodies (mAbs) that mimic HLA-I reactivity of IVIg may suppress activated T cells by binding to the shared peptides of the open conformers on the T cell surface was tested by examining the relative binding affinity of those mAbs for open conformers coated on regular beads and for intact HLA coated on iBeads, and by comparing the effects on the suppression of phytohaemagglutinin (PHA)-activated T cells of three entities: IVIg, anti-HLA-E mAbs that mimic IVIg [Terasaki Foundation Laboratory (TFL)-006 and (TFL)-007]; and anti-HLA-E antibodies that do not mimic IVIg (TFL-033 and TFL-037). Suppression of blastogenesis and proliferation of those T cells by both IVIg and the anti-HLA-E mAbs was dose-dependent, the dose required with mAbs 50-150-fold lower than with IVIg. TFL-006 and TFL-007 significantly suppressed blastogenesis and proliferation of activated CD4(+) T cells, but neither the non-IVIg-mimicking mAbs nor control antibodies did so. The suppression may be mediated by Fab-binding of TFL-006/TFL-007 to the exposed shared peptides. The mAb binding to the open conformer may signal T cell deactivation because the open conformers have an elongated cytoplasmic tail with phosphorylation sites (tryosine(320)/serine(335)).

Suppression of allo-human leucocyte antigen (HLA) antibodies secreted by B memory cells in vitro: intravenous immunoglobulin (IVIg)†versus a monoclonal anti-HLA-E IgG that mimics HLA-I reactivities of IVIg.

B memory cells remain in circulation and secrete alloantibodies without antigen exposure > 20 years after alloimmunization postpartum or by transplantation. These long-lived B cells are resistant to cytostatic drugs. Therapeutically, intravenous immunoglobulin (IVIg) is administered to reduce allo-human leucocyte antigen (HLA) antibodies pre- and post-transplantation, but the mechanism of reduction remains unclear. Recently, we reported that IVIg reacts with several HLA-I alleles and the HLA reactivity of IVIg is lost after its HLA-E reactivity is adsorbed out. Therefore, we have generated an anti-HLA-E monoclonal antibody that mimics the HLA-reactivity of IVIg to investigate whether this antibody suppresses IgG secretion, as does IVIg. B cells were purified from the blood of a woman in whose blood the B memory cells remained without antigen exposure > 20 years after postpartum alloimmunization. The B cells were stimulated with cytokines using a well-defined culture system. The anti-HLA-E monoclonal antibody (mAb) significantly suppressed the allo-HLA class-II IgG produced by the B cells, and that this suppression was far superior to that by IVIg. These findings were confirmed with HLA-I antibody secreted by the immortalized B cell line, developed from the blood of another alloimmunized woman. The binding affinity of the anti-HLA-E mAb for peptide sequences shared (i.e. shared epitopes) between HLA-E and other ß2-microglobulin-free HLA heavy chains (open conformers) on the cell surface of B cells may act as a ligand and signal suppression of IgG production of activated B memory cells. We propose that anti-HLA-E monoclonal antibody may also be useful to suppress allo-HLA IgG production in vivo.

Prevalence and determinants of undernutrition and its trends among pre-school tribal children of Maharashtra State, India.

A community-based cross-sectional study carried out in tribal areas of Maharashtra covering 1751 pre-school children to assess nutritional status. Nutritional status was assessed using new WHO Growth Standards. Household wealth index was constructed using principle component analysis. The prevalence of underweight, stunting and wasting was 64, 61 and 29%, respectively. There was a significant (p < 0.05) reduction in the prevalence of underweight and stunting over two time periods (1999 and 2008). Logistic regression showed that the risk of underweight was 1.7 times higher among children of illiterate mothers and those suffering from morbidities, while stunting was 1.4 times higher among children belonging to lowest and middle household's wealth indexes. Undernutrition is a public health problem and is associated with literacy of mother, household wealth index and morbidities. Therefore, improving socio-economic condition along with literacy of mothers and preventing infections through personal hygiene might help in improving the nutritional status of children.

Prevalence of under-nutrition and its correlates among under 3 year-old children in rural areas of Andhra Pradesh, India.

BACKGROUND: Under-nutrition continues to be a major public health problem, especially among young children in India. The present study was undertaken to assess the nutritional status of under-3 year-old children and factors associated with under-nutrition. METHOD: A community-based cross-sectional survey was carried out in 40 Anganwadi centre villages of Medak district of Andhra Pradesh, India. A total of 805 children were selected for nutritional assessment in terms of under-weight, stunting and wasting using the new WHO growth standards. Wealth index was calculated using principal components analysis. A conceptual hierarchical framework was used as a basis for controlling for the explanatory factors in multivariate analysis. RESULTS: Prevalence of under-weight, stunting and wasting was ~39%, 30% and 22%, respectively. The risk of under-weight and stunting was 1.80- and 3.02-times higher among 12-23 months and 3.13- and 5.50-times higher among 24-36 months children as compared to children under 12 months, respectively. The risk of under-weight was 2.74- and 1.73-times higher among children belonging to the lowest and middle household wealth index, respectively. CONCLUSIONS: Under-nutrition is a significant public health problem among under 3 year-old children. The prevalence of under-nutrition was significantly higher among boys and those belonging to the lowest and middle wealth index. Thus, implementation of appropriate nutritional intervention strategies and improvement in household socio-economic condition may help in improving nutritional status.

Micronutrient deficiency disorders among the rural children of West Bengal, India.

BACKGROUND: Multiple micronutrient deficiencies continue to be a major nutritional problem of public health significance in India. AIM: To assess the prevalence of micronutrient deficiencies among rural children of West Bengal, India. SUBJECTS AND METHODS: A community-based cross-sectional study was carried out on 9228 and 437 pre-school children, respectively, for assessment of vitamin A deficiency (VAD) and anaemia. Iodine deficiency disorders (IDD) were assessed in 3490 children of 6-12 years. RESULTS: The prevalence of Bitot's spots, an objective sign of clinical VAD, was 0.6% and was significantly (p < 0.01) higher among children of 3-5 years. Prevalence of blood vitamin A deficiency ( < 20 µg/dL) was 61% and ∼81% of children were anaemic. About 25% children had both sub-clinical VAD and anaemia. The children of Scheduled Caste and Scheduled Tribe (OR = 2.3: 95% CI = 1.3-3.9) were at higher risk of anaemia, whereas children of Scheduled Tribe (OR = 4.5; 95% CI = 2.1-10.5) and 3-5 years (OR = 1.4; 95% CI = 1.0-2.0) were at risk for VAD. The prevalence of goitre was 9%. CONCLUSIONS: Micronutrient deficiencies were found to be of public health significance among rural children of West Bengal. Therefore, there is a need to initiate sustainable long-term interventions for prevention and control of micronutrient deficiencies in children.

Prevalence of chronic energy deficiency in rural-dwelling older Indian adults during a period of severe drought.

The prevalence of chronic energy deficiency (CED = BMI < 18.5) among older adults (≥60 years) was assessed utilizing a large data set from a community-based cross-sectional study carried out in severely drought-affected rural areas of India. Anthropometric measurements (height, weight) were recorded for a total of 3,147 individuals, and a family diet survey (one day 24-hour recall) was carried out in 1,900 households (HHs) from 190 villages. As per the Body Mass Index (BMI), the prevalence of CED was 51.1% and 48.5% among older males and females, respectively. It was higher (p < 0.001) in the 70 years and older age group compared with those aged 60-69 years. In general, the prevalence of CED was higher (p < 0.001) for those belonging to the Scheduled Caste and Scheduled Tribes, for HHs of agricultural and non-agricultural labor, and for marginal or small farmers. The prevalence of CED was relatively lower (p > 0.05) among older adults during the drought period compared with the non-drought period. This could be attributed to intervention programs initiated by the government of India during the drought. These findings illustrate the value of intervention programs in drought-afflicted and drought-prone areas and underscore the importance of monitoring the nutritional status of older adults so that appropriate programs can be initiated as needed.

Diet and nutritional status of rural preschool children in Punjab.

OBJECTIVE: To assess diet and nutritional profile of rural preschool children of Punjab. STUDY DESIGN: Multistage random sampling method was adopted by following probability proportion to population size (PPS). SUBJECT: Four hundred households (HH) were covered in each district of Punjab for socio-economic and demographic information. All the available individuals from these HHs were included for anthropometry and clinical examination. Every fourth household was covered for 24-hour recall method of diet survey (individual dietary intake). RESULTS: At the state level, the intake of macro and micronutrient rich foods such as cereals, pulses and green leafy vegetables, milk and milk products and fats and oils were lower than the RDI among preschool children. Except for protein, calcium and thiamine, the mean intake of all the nutrients was lower than the recommended level. About a half of the preschool children (50.3%) were undernourished (> 2SD weight for age); 60% were stunted (> 2SD height for age) and 12% were wasted (> 2SD weight for height). The extent of undernutrition and stunting was lower than that reported for the country. There was significant variation in the prevalence of severe stunting between the districts (p < 0.001), with the highest being observed in the Rupnagar (55%) and the lowest in Hoshiarpur and Sangrur (30% each). CONCLUSION: Despite, the reported high rates of economic growth and food production in the state, a higher proportion of preschool children were consuming diets, which are inadequate with respect to energy, fat, iron, riboflavin, vitamin A and vitamin C. The prevalence of undernutrition was high as was found in other states.

Interleukin-2 binds to ganglioside GD(1b).

We have developed a solid matrix immunoassay to determine the binding of interleukin-2 (IL-2) to specific gangliosides. The assay establishes that recombinant human IL-2 binds to ganglioside GD(1b) but not to any other gangliosides (GM(1), GM(2), GM(3), GD(1a), GD(2), GD(3), and GT(1b)). The binding varies with the ratio of GD1b and IL-2. This assay enables distinguishing the nature of the sugar moiety of the ganglioside recognized by IL-2 and establishes the dosimetry of the ganglioside-IL-2 interaction. Since rIL-2 is administered systematically into stage IV melanoma patients, we have examined 45 tumor biopsies for GD(1b) content. The incidence of GD(1b) in tumor biopsies is 51%. We postulate that GD(1b) associated on the tumor or in the circulation of cancer patients may bind to rIL-2 and prevent the availability of rIL-2 to augment antitumor-immune response.

Does human melanoma express carcinoembryonic antigen?

BACKGROUND: Several investigators have proposed that carcinoembryonic antigen (CEA), an immunogenic antigen expressed by colon carcinoma, may also be expressed by human melanoma. Because sialyl Lewisx (sLex), the carbohydrate moiety of CEA, has been identified in melanoma, we compared CEA and sLex levels in colon carcinoma cells and melanoma cells. METHODS: CEA levels were assessed for expression on the cell surface and in cell lysates of cutaneous melanoma cell lines by two different kinds of ELISA, and by Western blot analysis of immunoprecipitated CEA using monoclonal antibodies (Mabs) T84-66 and COL-1, which have defined specificities for CEA. Colon carcinoma cells and purified CEA were positive controls. RESULTS: Both Mabs reacted strongly with cell surface and cell lysates of colon cancer. Mab T84-66 reacted well with cell surface but not cell lysates of melanoma. COL-1 reacted poorly with cell surface but its binding increased with the density of melanoma cell lysates. Both Mabs intensely stained the blots of purified CEA and colon carcinoma lysates immunoprecipitated with the respective Mabs, but failed to stain the immunoprecipitates of melanoma cell lysates. Both Mabs bound to lysates immunoprecipitated with anti-sLex Mab in colon carcinoma, but not in melanoma. Cell-surface expression of CEA and sLex was significantly correlated (r2: 0.88) in colon cancer cells but not in melanoma. CONCLUSION: Our results confirm the presence of CEA in colon carcinoma but not in human cutaneous melanoma cell lines.

Gangliosides as targets for immunotherapy for pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma cells express gangliosides and sialyl Lewis (sLe) antigens. It is not known whether these carbohydrate antigens can be targeted by immunotherapy. The authors measured the expression of GM(2) and sLe antigens on the surface of pancreatic carcinoma cells and the serum levels of total gangliosides, GM(2), and antiganglioside antibodies in patients with pancreatic carcinoma. METHODS: Cell surface GM(2) and sLe antigens were measured by cell suspension enzyme linked immunoadsorbent assay (ELISA) in four pancreatic carcinoma cell lines. Sera from 20 pancreatic carcinoma patients and 20 age- and gender-matched healthy volunteers were analyzed for antiganglioside and anti-sLe immunoglobulin (Ig) M titers by ELISA. Serum levels of total gangliosides and GM(2) also were measured. RESULTS: All cell lines expressed GM(2) and sLe antigens. When compared with age- and gender-matched volunteers, patients had significantly higher serum levels of total gangliosides (25.6 +/- 9.0 mg/dL vs. 15.6 +/- 2.7 mg/dL; P < 0.001), GM(2) (0.278 +/- 0.415 mg/dL vs. 0.013 +/- 0.018 mg/dL; P = 0.02), ELISA units of anti-GM(2) IgM antibody (368 +/- 95 vs. 155 +/- 25; P = 0.04) and anti-GD(1b) IgM antibody (351 +/- 91 vs. 138 +/- 26; P = 0.03), but not anti-sLe(x) IgM (1389 +/- 345 vs. 1081 +/- 224; P = 0.46) or anti-sLe(a) IgM antibody (1097 +/- 253 vs. 1200 +/- 315; P = 0.80). Patients with unresectable tumors had higher serum levels of total gangliosides compared with patients with resectable tumors, and a serum level > 25 mg/dL was found to correlate significantly with poor overall survival (P < 0.02). CONCLUSIONS: Increased serum levels of total gangliosides and GM(2) may reflect shedding or release of gangliosides from the surface of tumor cells. Production of IgM antibody against GM(2) and GD(1b) indicates that these gangliosides are immunogenic antigens that may be potential targets for effective active immunotherapy.

Immunology of gangliosides.

This review discusses the immunology of gangliosides from the perspective of tumor, neuronal and general immunology. Antiganglioside antibodies in human sera are invariably IgM and are found in healthy individuals. Their titers decline with age. Persistent high titer of IgM is associated with several diseases, particularly neuropathies. Membrane-bound gangliosides are important tumor-associated antigens and targets for immune attack. Cells enriched with gangliosides can be used as cancer vaccines. Efficacy of these vaccines depends on the viability of whole cells, integrity of the cell membranes, adjuvants and topography of the tumor-associated antigens. The role of antiganglioside IgM is to eliminate the immunosuppressive gangliosides shed from tissues during ageing, degeneration of neural and extraneural tissues, and tumor growth and necrosis. In addition, in vitro observations with human and murine monoclonal antibodies suggest that they are capable of complement dependent cytotoxicity and apoptosis.

Impact of mid day meal program on educational and nutritional status of school children in Karnataka.

OBJECTIVE: To assess the effect of the Mid Day Meal (MDM) Program on enrollment, attendance, dropout rate and retention rate in the schools and its impact on nutritional status as well as on school performance. DESIGN: Comparison by multistage random sampling. SUBJECTS: Primary school children, who are attending the school in the MDM and non-MDM areas. RESULTS: A total of 2,694 children (MDM: 1361; Non-MDM : 1333) from 60 schools were covered in the study. Results of the study indicated better enrollment (p<0.05) and attendance (p<0.001), higher retention rate with reduced dropout rate (p<0.001) a marginally higher scholastic performance and marginally higher growth performance of MDM children. CONCLUSION: MDM program is associated with a better educational and nutritional status of school children in Karnataka.

Ratio of IgG:IgM antibodies to sialyl Lewis(x) and GM3 correlates with tumor growth after immunization with melanoma-cell vaccine with different adjuvants in mice.

Human melanoma cells (from biopsies and culture) express sialyl-Lewis(x) and sialyl Lewis(a), the ligands for ECAM. These ligands may facilitate tumor progression and metastasis in human cancers. To test whether the antibodies to these ligands inhibit tumor progression, IgG and IgM responses to sLe(x) and sLe(a) were induced in C57BL/6j mice (n = 76) by immunization with human melanoma cells, with or without adjuvants (BCG, MPL, KLH). Control mice were treated with saline or BCG. Tumor growth and antigen expression were monitored after challenge with B16 mouse melanoma cells expressing sLe(x), sLe(a) and the ganglioside GM3. Tumor growth was reduced in mice immunized with BCG alone or cells with BCG or MPL, while tumors in mice receiving cells without adjuvants grew larger than in the control. Augmentation of IgM titers to sLe(x) and GM3 after immunization with BCG, or with cells with BCG or MPL correlated with retarded tumor growth, while increased IgG titers to sLe(x) significantly correlated with aggressive tumor growth in mice immunized with cells without adjuvants. SLe(x), sLe(a) and GM3 were expressed in tumors from mice treated with saline or BCG. SLe(x) expression, in particular, was lost in tumors growing in mice immunized with cells with or without adjuvants. Anti-sLe(x) antibodies may promote or prevent tumor growth by antigenic modulation or by cytotoxic killing of tumor cells. Since early anti-sLe(x) IgM correlated with tumor regression, in contrast to anti-sLe(x) IgG, it may serve as a potential early endpoint for the effectiveness of melanoma vaccines expressing the antigens.