The promising role of monoclonal antibodies for immunotherapy of the HIV-associated cancer,non-Hodgkin lymphoma

Association between HIV/AIDS and some of the cancers such as lymphomais is well known. Relative risk for developing non-Hodgkin lymphoma (NHL) increases 60–200 folds in HIV-infected individuals. Diffuse large B cell lymphoma (DLBCL), primary effusion lymphoma (PEL), Burkitt's lymphoma (BL) and Plasmablastic Lymphoma (PBL) are among the most frequent subtypes. During the last century, scientists found that the immune system could potentially detect and destroy cancer cells. Therefore, they started a new field of study, which is named immunotherapy. There are different immunotherapeutic methods, among which therapeutic antibodies, such as Brentuximabvedotin (Adcetris), Ibritumomabtiuxetan (Zevalin) and rituximab (Rituxan), used for treatment of NHLs showed promising results. In this article, we will review the immunotherapeutic option, monoclonal antibodies, for treatment of HIV-associated NHLs as well as their recent clinical status. We will also discuss the selective monoclonal antibody for each subtype of NHLs.     

Cephalometric risk factors of obstructive sleep apnea

Introduction: Previous studies on risk factors of obstructive sleep apnea (OSA) are highly controversial and mostly identifying a few cephalometric risk factors.

Methods: OSA diagnosis was made according to the patients’ apnea-hypopnea index (AHI). Included were 74 OSA patients (AHI > 10) and 52 control subjects (AHI ≤ 10 + free of other OSA symptoms). In both groups, 18 cephalometric parameters were traced (SNA, SNB, ANB, the soft palate’s length (PNS-P), inferior airway space, the distance from the mandibular plane to the hyoid (MP-H), lengths of mandible (Go-Gn) and maxilla (PNS-ANS), vertical height of airway (VAL), vertical height of the posterior maxilla (S-PNS), superior posterior airway space (SPAS), middle airway space, distances from hyoid to third cervical vertebra and retrognathion (HH1), C3 (C3H), and RGN (HRGN), the maximum thickness of soft palate (MPT), tongue length (TGL), and the maximum height of tongue). These parameters were compared using t-test.

Results: Significant variables were SPAS (p = 0.027), MPT, TGL, HH1, C3H, HRGN, PNS-P, S-PNS, MP-H, VAL, and Go-Gn (all p values ≤ 0.006).

Conclusion: OSA patients exhibited thicker and longer soft palates, hyoid bones more distant from the vertebrae, retrognathion, and mandibular plane, higher posterior maxillae, longer mandibles, and smaller superior-posterior airways.     

Inherited disorders of gamma‐aminobutyric acid metabolism and advances in ALDH5A1 mutation identification

Inherited disorders of gamma‐aminobutyric acid (GABA) metabolism include succinic semialdehyde dehydrogenase (SSADH) and gamma‐aminobutyric acid transaminase (GABA‐T) deficiencies. The clinical features, pathophysiology, diagnosis, and management of both, and an updated list of mutations in the ALDH5A1 gene, which cause SSADH deficiency, are discussed. A database of 112 individuals (71 children and adolescents, and 41 adults) indicates that developmental delay and hypotonia are the most common symptoms arising from SSADH deficiency. Furthermore, epilepsy is present in two‐thirds of SSADH‐deficient individuals by adulthood. Research with murine genetic models and human participants, using [¹¹C] flumazenil positron emission tomography (FMZ‐PET) and transcranial magnetic stimulation, have led to therapeutic trials, and the identification of additional disruptions to GABA metabolism. Suggestions for new therapies have arisen from findings of GABAergic effects on autophagy, with enhanced activation of the mammalian target of rapamycin (mTOR) pathway. Details of known pathogenic mutations in the ALDH5A1 gene, three of which have not previously been reported, are summarized here. Investigations into disorders of GABA metabolism provide fundamental insights into the mechanisms underlying epilepsy, and support the importance of developing biomarkers and clinical trials. Comprehensive definition of phenotypes arising as a result of deficiencies in both SSADH and GABA‐T may increase our understanding of the neurophysiological consequences of a hyper‐GABAergic state.     

Epistatic interactions between HLA-DRB1 and interleukin 4, but not interferon-gamma, increase susceptibility to giant cell arteritis

OBJECTIVE: To assess the roles of the interleukin 4 (IL-4) and interferon-g (IFN-g) gene polymorphisms in a series of patients with biopsy-proven giant cell arteritis (GCA). METHODS: Eighty-two patients with biopsy-proven GCA and 102 ethnically matched controls from the Lugo region (Northwest Spain) were studied. The following single nucleotide polymorphisms (SNP) were assessed: IL-4 (SNP1: rs2070874, SNP2: rs2227284, SNP3: rs2227282, SNP4: rs2243266, and SNP5: rs2243267) and IFN-g (SNP1: rs1861494, SNP2: rs1861493, and SNP3: rs2069718). RESULTS: Significant differences in allele and genotype frequencies were observed for the IL-4 SNP between HLA-DRB1*04 negative patients and controls. Epistatic interaction between SNP2 (rs2227284) with HLA-DRB1 showed a significant interaction (p = 0.001) and carriage of the SNP2*T allele in the absence of HLA-DRB1*04 resulted in a 4-fold risk of developing GCA (OR 4.2, 95% CI 1.1-15.6). Also, a significant increase in the frequency of the T-T-C-A-C IL-4 haplotype was observed in HLA-DRB1*04 negative GCA patients compared to the controls (p = 0.02; OR 2.0, 95% CI 1.0-3.9). Similar distributions of allele and genotype frequencies were observed for the IFN-g polymorphisms in both GCA patients and controls. CONCLUSION: Our results suggest an association with IL-4 gene polymorphism that is dependent on HLA-DRB1 genotype in GCA susceptible individuals. These data indicate an interaction between HLA-DRB1 and IL-4 that contributes to pronounced disease susceptibility.     

Risks of nonchromosomal birth defects,small-for-gestational age birthweight,and prematurity with in vitro fertilization: effect of number of embryos transferred and plurality at conception versus at birth

Journal of Assisted Reproduction and Genetics - Excess embryos transferred (ET) (> plurality at birth) and fetal heartbeats (FHB) at 6 weeks’ gestation are associated with reductions...     

Pandemic 2009 influenza A (H1N1) infection among 2009 Hajj Pilgrims from Southern Iran: a real‐time RT‐PCR‐based study

Please cite this paper as: Ziyaeyan et al. (2012) Pandemic 2009 influenza A H1N1 infection among 2009 Hajj Pilgrims from Southern Iran: a real‐time RT‐PCR‐based study. Influenza and Other Respiratory Viruses 6(601), e80–e84. Background Hajj is a mass gathering undertaken annually in Mecca, Saudi Arabia. The 2009 Hajj coincided with both the pandemic influenza A/H1N1 2009 (A(H1N1)pdm09) and seasonal types of influenza A viruses. The interaction between pandemic influenza and Hajj could cause both a high level of mortality among the pilgrims and the spread of infection in their respective countries upon their return home. Objective The present study attempted to determine the point prevalence of A(H1N1)pdm09 among returning Iranian pilgrims, most of whom had been vaccinated for seasonal influenza but not A(H1N1)pdm09. Methods Pharyngeal swabs were collected from 305 pilgrims arriving at the airport in Shiraz, Iran. RNA was extracted from the samples and A(H1N1)pdm09 and other seasonal influenza A viruses were detected using TaqMan real‐time PCR. For A(H1N1)pdm09‐positive samples, the sensitivity to oseltamivir was also evaluated. Results Subjects included 132 (43·3%) men and 173 (56·7%) women, ranging in age from 24 to 65 years. The A(H1N1)pdm09 virus was detected in five (1·6%) pilgrims and other influenza A viruses in eight (2·6%). All the A(H1N1)pdm09 were sensitive to oseltamivir. Conclusions Only five cases were found to be positive for A(H1N1)pdm09, and it seems unlikely that the arrival of infected pilgrims to their homelands would cause an outbreak of a new wave of infection there. Thus, the low morbidity and mortality rates among the pilgrims could be attributed to the characteristics of A(H1N1)pdm09, which causes morbidity and mortality in a way similar to the seasonal influenza infections, absence of high‐risk individuals among the Iranian pilgrims, and the instructions given to them about contact and hand hygiene, and respiratory etiquette.