Effects of Maharishi Amrit Kalash 5 as an Ayurvedic herbal food supplement on immune functions in aged mice

Background  

Maharishi Amrit Kalash (MAK) 5, one of the Ayurvedic food supplements, belongs to a group of substances known as Rasayana. MAK5 and other Rasayanas are believed to enhance the body's resistance to infections and disease, and enhance longevity. In this study, we determined the effects of administration of MAK5, one of the Ayurvedic food supplements on immune functions in young and old mice.     

Analysis of genomic downsizing on the basis of region-of-difference polymorphism profiling of Mycobacterium tuberculosis patient isolates reveals geographic partitioning

Mycobacterium tuberculosis, the etiological agent of tuberculosis, has lost many coding and noncoding regions in its genome during the course of evolution. We performed region-of-difference (RD) analysis using PCR-based genotyping of 131 M. tuberculosis clinical isolates obtained from four different countries, namely, India, Peru, Libya, and Angola. Our studies revealed that RD patterns are often distinct for strains circulating in specific geographical regions and can be used to trace the descent and spread of an isolate from its original reservoir. We describe our findings, which show that no single isolate from the four countries (n = 131) had all the 15 RDs either deleted or retained. Tuberculosis-specific deletion 1 (TbD1) was found to be conserved in 23% of the Indian isolates, indicating their possible ancient origin. RD9 was the most conserved region, RD11 was predominantly deleted, and RD6 was the most variable among the isolates in our collection irrespective of their geographic region. In contrast to earlier reports, our results demonstrate that the deletion of RD1 does not correlate with a decrease in the virulence potential of M. tuberculosis, as Indian isolates (n = 30) examined by us were from diseased individuals and yet had lost the RD1 region. Our results further illustrated that the intactness of the RD5 region may be associated with increased virulence of the organism. This study highlights that the RDs in M. tuberculosis genomes are geographically distributed and specific and may possibly be associated with virulence spectrum.     

Antibody- and complement-mediated lysis of HIV-infected cells and inhibition of viral replication

HIV-1-positive antisera were tested for their ability to lyse HIV-1-infected cells in the presence of active complement. Cytolytic effects caused by sera derived from infected humans were slower than those observed with sera from immunised chimpanzees. Lytic but also negative sera were found among HIV-1-infected asymptomatic men as well as among clinical AIDS cases. Human antisera that lysed infected cells reacted similarly irrespective of whether the complement was heterologous or autologous. Analysis of complement-mediated lysis using defined antisera against recombinant HIV-1 env or core antigens suggested that gp160/gp120 and p24 can act as target antigens for an antibody- and complement-mediated cytolysis of infected cells. Complement alone reduced the spread of HIV-1 infection in CD4+ cells and the ability of HIV-1 and HIV-2 to form plaques in CD4-transfected HeLa cells. Co-operative effects of specific antibodies and complement were the most effective in inhibiting HIV infections.     

Genetic susceptibility and anti-human platelet antigen 5b alloimmunization role of HLA class II and TAP genes

Platelet alloimmunization may result in post-transfusion purpura, and during pregnancy may cause neonatal alloimmune thrombocytopenia (NAIT), with a frequency estimated at 1.3 per 1000 live births. The risk of morbidity is significant: 20% of affected infants have neurologic sequelae and the death rate is about 10%. A better understanding of the immune response to platelet alloantigens would allow for a better definition, and thus better management of pregnant women at high risk. Limited data are available on the immune response against HPA-5b, the second most frequent antigen, after HPA-la, implicated in NAIT. We studied HLA class II and TAP gene polymorphism in 50 women immunized against HPA-5 system antigens. Our results suggest a strong association of alloimmunization with a cluster of HLA DR molecules sharing a particular polymorphic amino acid sequence at position 69–70 (Glu-Asp encoded by GAA-GAC nucleotide sequence) of the DRβl chain (RR = 2.95, RR = 5.70 when patients were homozygous for this sequence), and a negative association with the DRB1^*0301 allele (2.1% vs. 28%; RR = 0.08). Furthermore, increased frequency of a TAP2 dimorphism at position 379 was observed in immunized women against the HPA-5 antigens (RR = 4.7).     

Are HLA-DR or TAP Genes Genetic Markers of Severity in Ulcerative Colitis?

The pathogeny of ulcerative colitis (UC) is not yet elucidated, but some arguments suggest the implication of genetic factors. Among the candidate genes, those encoding for HLA class II genotypes have been extensively studied in UC; however, discordant data may be imputable to heterogeneity, characterized by immunological markers such as atypical ANCA (p-ANCA), or to inclusion of more or less intractable UC. The aim of our study is to evaluate the interest of HLA class II and TAP genetic markers to identify different clinical forms of UC, according to p-ANCA status. Unrelated patients with a history of UC (n=91) and healthy control subjects with no personal or family history of inflammatory bowel diseases (IBD) (n=200) were included. HLA-DRB103 was less frequent in UC patients than in healthy controls (8% vs 28%,PC<0.03). No association was found with any TAP genotypes. Moreover, there was no association with the HLA-DR2 specificity, either in the entire group of UC patients (38% vs 28%) or in the p-ANCA-positive subgroup of patients (30%). The most consistent finding in the present study is that some genetic markers may characterize intractability in UC patients. HLA-DR2 was associated with poor prognosis, regardless of p-ANCA status. In HLA-DR2 and non-HLA-DR2 groups, colectomy was done in 55% and 27% of patients, respectively (PC<0.05). Furthermore, in non-HLA-DR2 patients, p-ANCA could be of interest to characterize those with more severe prognosis. Our results confirm the interest of genetic studies to define UC genetic susceptibility, taking into account intractability of the disease. They do not support the hypothesis that p-ANCA is a subclinical marker of genetic susceptibility to UC.     

Chromosomal anomalies in two coexistent myeloproliferative disorders

A 58-year-old male presented with fatigue, tiredness, and pruritus after hot showers and an elevated white blood cell count (20000/mm(3)). A diagnosis of polycythemia vera (PV) was made after investigation revealed a low erythropoietin and elevated leukocyte alkaline phosphatase (LAP) score; he was treated with repeated phlebotomies. Two years later he developed elevated white counts again and investigation revealed Philadelphia chromosome positive (19/20 cells) chronic myelocytic leukemia (CML). The karyotype also revealed trisomy 9 in 1 of 20 cells. He was treated with imatinib mesylate and went into clinical, hematologic, cytogenetic, and molecular remission. Repeat chromosomal analysis revealed absence of Philadelphia chromosome and BCR/ABL translocation but presence of trisomy 9. To our knowledge, this is the first reported case of coexisting PV and CML both associated with separate chromosomal abnormalities. This also raises an interesting therapeutic consideration of using concomitant imatinib mesylate and hydroxyurea.     

Analysis of cytogenetic aberrations in esthesioneuroblastomas by comparative genomic hybridization

Esthesioneuroblastoma (ENB) are rare tumors originating from the olfactory epithelium of the superior nasal cavity. This lesion is morphologically closely related to Ewing sarcoma and other peripheral primitive neuroectodermal tumors (pPNET). The affiliation of ENB to the pPNET family is still under discussion. Only very limited and contradictory cytogenetic data are available on ENB and only one patient has been analyzed by comparative genomic hybridization (CGH), so far. In the present study, genomic imbalances of three ENB were analyzed by CGH to evaluate (1) a recurrent pattern of imbalances, and (2) its relation to the pPNET family. The CGH analysis of three ENB revealed multiple recurrent aberrations including DNA overrepresentations of chromosomal material of the entire chromosome 19, partial gains of the long arms of chromosomes 8, 15, and 22, and deletions of the entire long arm of chromosome 4. Beside these common aberrations, several single gains and losses occurred, that is, gains on 6p, 10q, 1p, 9q, and 13q. We confirmed the former observation of amplified genetic material on chromosome 8 and found several new, currently not described recurrent genetic aberrations distinct from those described for pPNET. Our findings give evidence that ENB is not part of the pPNET family. We suggest that the combined gain of genetic material on 15q, 22q, and chromosome 8 might be indicative for ENB. To verify our findings and to define prognosis-related aberrations, a larger number of cases needs to be studied.