Antibody responses in vivo in chromosome instability syndromes with immunodeficiency.

The primary IgG, IgM and IgA antibody responses to Helix pommatia haemocyanin (HPH) were defective in patients with ataxia telangiectasia (AT) and Nijmegen breakage syndrome (NBS). The results in patients with Bloom's syndrome (BS) were heterogeneous, but all showed abnormal kinetics of the IgG response. The secondary response to diphtheria, tetanus and polio vaccine was normal in patients with AT and BS, but disturbed in the patients with NBS. The abnormalities of antibody response of AT and NBS are similar, although more profound in NBS; BS is different.     

How to use Chlamydia antibody testing in subfertility patients

Screening for tubal factor subfertility by means of Chlamydia antibody testing (CAT) was introduced into the initial work-up of subfertile couples several years ago. The results reported, however, are heterogeneous, and no uniformity exists in cut-off levels of titres, or in definitions of tubal factor subfertility. We performed a prospective cohort study to evaluate the implications of varying the definitions of tubal pathology and of modifying the cut-off levels on the clinical impact of CAT in predicting tubal factor subfertility. In 227 consecutive patients who attended our fertility clinic, the Chlamydia IgG antibody titre was determined and related to tuboperitoneal abnormalities at laparoscopy as a reference standard. According to received operating characteristic (ROC) curve analysis, a titre of 16 is the optimum cut-off level. Increasing the cut-off level improves specificity and positive likelihood ratio (LR+), at the expense of sensitivity and negative LR (LR-). Changing the definition of tubal factor subfertility from unspecified tuboperitoneal abnormalities into extensive adhesions and/or bilateral distal tubal occlusion improves LR+, LR- and kappa significantly. We conclude that CAT is more accurate in predicting severe distal tubal pathology than unspecified tuboperitoneal abnormalities. Although from a statistical point of view a titre of 16 is the optimum cut-off level, from a clinical point of view 32 or 64 may be preferable, depending on the aim of screening and the inception cohort.      

Novel Hendra Virus Variant Circulating in Black Flying Foxes and Grey-Headed Flying Foxes,Australia

A novel Hendra virus variant, genotype 2, was recently discovered in a horse that died after acute illness and in Pteropus flying fox tissues in Australia. We detected the variant in flying fox urine, the pathway relevant for spillover, supporting an expanded geographic range of Hendra virus risk to horses and humans.     

ABCG2 expression, function, and promoter methylation in human multiple myeloma

We investigated the role of the breast cancer resistance protein (BCRP/ABCG2) in drug resistance in multiple myeloma (MM). Human MM cell lines, and MM patient plasma cells isolated from bone marrow, were evaluated for ABCG2 mRNA expression by quantitative polymerase chain reaction (PCR) and ABCG2 protein, by Western blot analysis, immunofluorescence microscopy, and flow cytometry. ABCG2 function was determined by measuring topotecan and doxorubicin efflux using flow cytometry, in the presence and absence of the specific ABCG2 inhibitor, tryprostatin A. The methylation of the ABCG2 promoter was determined using bisulfite sequencing. We found that ABCG2 expression in myeloma cell lines increased after exposure to topotecan and doxorubicin, and was greater in logphase cells when compared with quiescent cells. Myeloma patients treated with topotecan had an increase in ABCG2 mRNA and protein expression after treatment with topotecan, and at relapse. Expression of ABCG2 is regulated, at least in part, by promoter methylation both in cell lines and in patient plasma cells. Demethylation of the promoter increased ABCG2 mRNA and protein expression. These findings suggest that ABCG2 is expressed and functional in human myeloma cells, regulated by promoter methylation, affected by cell density, up-regulated in response to chemotherapy, and may contribute to intrinsic drug resistance.     

Spinal cord infarction as a severe complication of meningococcal meningitis

Spinal cord infarction is a rare complication of bacterial meningitis and is, therefore, generally unknown. We describe a patient who developed a flaccid paraparesis 2 weeks after being diagnosed with meningococcal meningitis. The etiology of spinal cord infarction is multifactorial, but vascular mechanisms and coagulation abnormalities play an important role. Epidural hemorrhage and spinal abscess should be considered in the differential diagnosis.     

The genetics of deliria

Delirium not induced by alcohol or other psychoactive substance and alcohol withdrawal delirium (or delirium tremens) are both cerebral syndromes with similar presentations and are associated with various adverse outcomes. Recently, interest in identifying genetic predisposing factors that influence the occurrence or the outcome of delirium has become a prominent point of delirium research. We systematically searched published articles concerning genetic associations and the occurrence and outcome of delirium. Of 33 identified articles, six investigated non-alcohol withdrawal delirium, and from those six, five evaluated an association with apolipoprotein E (APOE). One association of APOE genotype with the emergence of delirium and two associations of APOE genotype with the duration of delirium were reported. The remaining 27 identified articles investigated genetic associations with alcohol withdrawal delirium and were mainly related to dopamine. Two studies reported a significant association of alcohol withdrawal delirium with the dopamine transporter gene (SLC6A3) and the dopamine receptor 3 (DRD3). Results are inconclusive, and no hard evidence exists due primarily to insufficiently powered studies and other methodological issues. Prospective studies incorporating systematic and rigorous diagnostic criteria and involving long term follow up are needed to advance understanding of this field.     

Interactions of ACTH and TGFβ on monocyte proliferation: Implications for trauma and burn patients

The purpose of this study was to try to elucidate a possible biobehavioral mechanism associated with decreased immune function in trauma patients by determining whether there is an interaction between the effects of ACTH, a stress hormone, and TGFβ, a cytokine, on peripheral blood lymphocyte proliferation. Peripheral mononuclear lymphocytes (PMLs) from healthy donors were preincubated with varying concentrations of ACTH for 24 hr, stimulated with Conconavalin A and increasing concentrations of TGFβ, and incubated for 72 hr. Proliferation was assayed by tritiated thymidine incorporation. A parallel aliquot of PMLs were incubated in the presence of ACTH to determine the direct effect of ACTH on mononuclear cell TGFβ production. While harvested supernatant from cells incubated in the presence of ACTH did not contain any detectable TGFβ, ACTH as well as TGFβ were found to significantly decrease cellular proliferation independent of one another. An even greater decrease in cellular proliferation was found when both ACTH and TGFβ were used, compared to either ACTH or TGFβ alone. These results suggest a biobehavioral interaction between ACTH and TGFβ at the cellular level and that interactions to relieve stress may assist in improving function and recovery from trauma. © 1996 John Wiley & Sons, Inc.     

OraSure InteliSwab™ Rapid Antigen Test Performance with the SARS-CoV-2 Variants of Concern—Alpha,Beta, Gamma,Delta, and Omicron

The emergence of SARS-CoV-2 in the human population and the resulting COVID-19 pandemic have led to the development of various diagnostic tests. The OraSure InteliSwab^™ COVID-19 Rapid Test is a recently developed and FDA emergency use-authorized rapid antigen-detecting test that functions as a lateral flow device targeting the nucleocapsid protein. Due to SARS-CoV-2 evolution, there is a need to evaluate the sensitivity of rapid antigen-detecting tests for new variants, especially variants of concern such as Omicron. In this study, the sensitivity of the OraSure InteliSwab^™ Test was investigated using cultured strains of the known variants of concern (VOCs, Alpha, Beta, Gamma, Delta, and Omicron) and the ancestral lineage (lineage A). Based on dilution series in cell culture medium, an approximate limit of detection for each variant was determined. The OraSure InteliSwab^™ Test showed an overall comparable performance using recombinant nucleocapsid protein and different cultured variants, with recorded limits of detection ranging between 3.77 × 10⁵ and 9.13 × 10⁵ RNA copies/mL. Finally, the sensitivity was evaluated using oropharyngeal swabs from Syrian golden hamsters inoculated with the six VOCs. Ultimately, the OraSure InteliSwab^™ COVID-19 Rapid Test showed no decrease in sensitivity between the ancestral SARS-CoV-2 strain and any VOCs including Omicron.     

Indian Systems of Medicine: A Brief Profile

Medicinal plants based traditional systems of medicines are playing important role in providing health care to large section of population, especially in developing countries. Interest in them and utilization of herbal products produced based on them is increasing in developed countries also. To obtain optimum benefit and to understand the way these systems function, it is necessary to have minimum basic level information on their different aspects. Indian Systems of Medicine are among the well known global traditional systems of medicine. In this review, an attempt has been made to provide general information pertaining to different aspects of these systems. This is being done to enable the readers to appreciate the importance of the conceptual basis of these system in evolving the material medica. The aspects covered include information about historical background, conceptual basis, different disciplines studied in the systems, Research and Development aspects, Drug manufacturing aspects and impact of globalization on Ayurveda. In addition, basic information on Siddha and Unani systems has also been provided.