Efficacy of standard treatment protocol in recently diagnosed Lupus Nephritis at our tertiary care teaching hospital

Introduction: Lupus Nephritis occurred in approximately 50% of Systemic Lupus Erythematosus patients at some point during their illness and is associated with a poor prognosis. Material and Method: A prospective observational study of 50 newly diagnosed LN cases was conducted to investigate the response of standard treatment protocol (Cyclophosphamide -NIH protocol and Mycophenolate Mofetil-MMF). Results: Of the 50 newly diagnosed cases of LN, 94 % (n=47) were females, and 6 % (n=3) were males, with class IV LN accounting for the majority of patients 69.39 % (n=34). At six months, 36.7 % (n=11) of patients in the cyclophosphamide (CYP) group had a complete response. Only 27.3 % of patients in the MMF group had a complete response; however, this difference was not statistically significant. At the end of one year, only 56.7 % of the CYP group and 81.8 % of the MMF group had a complete response; however, this difference was not statistically significant (p=0.282). Although the initial response with CYP was better and later in the MMF group, these differences were not significant statistically. Tuberculosis or its reactivation was the most common complication during treatment, either with MMF or CYP. One patient died due to latent tuberculosis reactivation, another as a result of severe disease activity at presentation (proteinuria was 20 gm/24 hours in that patient), and the third as a result of pneumonia with septicemia. Conclusion: Treatment with either CYP or MMF is equally effective, but underlying infection, particularly tuberculosis, should be ruled out before initiating therapy

Enhanced Dopamine D1 and BDNF Signaling in the Adult Dorsal Striatum but not Nucleus Accumbens of Prenatal Cocaine Treated Mice

Previous work from our group and others utilizing animal models have demonstrated long-lasting structural and functional alterations in the meso-cortico-striatal dopamine pathway following prenatal cocaine (PCOC) treatment. We have shown that PCOC treatment results in augmented D1-induced cyclic AMP (cAMP) and cocaine-induced immediate-early gene expression in the striatum of adult mice. In this study we further examined basal as well as cocaine or D1-induced activation of a set of molecules known to be mediators of neuronal plasticity following psychostimulant treatment, with emphasis in the dorsal striatum (Str) and nucleus accumbens (NAc) of adult mice exposed to cocaine in utero. Basally, in the Str of PCOC treated mice there were significantly higher levels of (1) CREB and Ser133 P-CREB (2) Thr34 P-DARPP-32 and (3) GluA1 and Ser 845 P-GluA1 when compared to prenatal saline (PSAL) treated mice. In the NAc there were significantly higher basal levels of (1) CREB and Ser133 P-CREB, (2) Thr202/Tyr204 P-ERK2, and (3) Ser845 P-GluA1. Following acute administration of cocaine (15 mg/kg, i.p.) or D1 agonist (SKF 82958; 1 mg/kg, i.p.) there were significantly higher levels of Ser133 P-CREB, Thr34 P-DARPP-32, and Thr202/Tyr204 P-ERK2 in the Str that were evident in all animals tested. However, these cocaine-induced increases in phosphorylation were significantly augmented in PCOC mice compared to PSAL mice. In sharp contrast to the observations in the Str, in the NAc, acute administration of cocaine or D1 agonist significantly increased P-CREB and P-ERK2 in PSAL mice, a response that was not evident in PCOC mice. Examination of Ser 845 P-GluA1 revealed that cocaine or D1 agonist significantly increased levels in PSAL mice, but significantly decreased levels in the PCOC mice in both the Str and NAc. We also examined changes in brain-derived neurotrophic factor (BDNF). Our studies revealed significantly higher levels of the BDNF precursor, pro-BDNF, and one of its receptors, TrkB in the Str of PCOC mice compared to PSAL mice. These results suggest a persistent up-regulation of molecules critical to D1 and BDNF signaling in the Str of adult mice exposed to cocaine in utero. These molecular adaptations may underlie components of the behavioral deficits evident in exposed animals and a subset of exposed humans, and may represent a therapeutic target for ameliorating aspects of the PCOC-induced phenotype

Virus host interactions as studied in HIV-1 and SV40 model systems

An understanding of the nuclear processes taking place in eukaryotic cells has been achieved using HIV-1 and SV40 viruses. Their simple genomes provide excellent model systems. HIV-1, a retrovirus has been used to study the interaction of regulatory proteins with the negative regulatory element (NRE) within the long terminal repeat (LTR) of HIV-1. Three cDNA clones have been isolated by screening a HeLa expression library. One of the clones encodes NF-IL6, a transcription factor previously identified as an activator of Interleukin-6 (IL-6) gene expression in response to Interleukin-1 (IL-I) induction. NF-IL6 binds to multiple sites within the HIV-1 LTR and may play an important role in activating HIV-1 expression in response to IL-1 and IL-6 signal transduction. The second clone has been analyzed and examination of its amino acid sequence strongly suggests that it represents a DNA binding protein. SV40 has been used as a model system to study eukaryotic chromatin structure, since the viral genome forms a minichromosome similar to that of higher organisms. Location of nucleosomes assembled in vivo on the strain wt776 has been determined using micrococcal nuclease digestion of SV40 chromatin combined with M13 cloning and DNA sequencing. Several nucleosomes have been identified at and near the replication origin, the enhancer sequence, the early and late transcription initiation sites, the termination region and regions containing bent DNA. A complex pattern of overlapping nucleosomal clones has been observed. The results indicate that the nucleosomes do not occupy unique positions. However, the distribution of nucleosomes does not appear to be random. A stable nucleoprotein complex, obtained during the isolation of SV40 virions has been analyzed and considered to be an intermediate of virus assembly. The proteins topoisomerase I, topoisomerase II and T antigen along with SV40 chromatin have been identified as components of the complex. Topoisomerase II and T antigen have been identified previously as components of the nuclear scaffold and hence the results suggest that SV40 chromatin is associated with the nuclear scaffold during DNA replication and virus assembly

Study of Clinical profile of newly diagnosed lupus nephritis in case of systemic lupus erythematosus

Introduction:Lupus Nephritis (LN) affects 25-60% of people with Systemic Lupus Erythematosus (SLE) within the first 5 years of disease onset. We conducted a prospective observational study to look into the demographic and clinical characteristics of newly diagnosed LN patients. Material and Methods: Our study included 50 newly diagnosed cases of LN. Results:The female-male ratio was 15.67:1. The majority of patients had LN of class IV (69.39 percent ). The most common symptoms were alopecia, oral ulcers, and arthritis. All 50 patients were ANA positive, with 54 percent having anti-ds- DNA positivity. Conclusion:The most common type of LN in our study was IV. Although extrarenal manifestations, primarily mucocutaneous and musculoskeletal, were present, urine examination should be performed more frequently at the time of LN diagnosis for early diagnosis and treatment

Application of a Simple In-House PCR-SSP Technique for HLA-B* 27 Typing in Spondyloarthritis Patients

Background. Microlymphocytotoxicity (MLCT) and flowcytometry (FC) are the conventional serological methods to detect HLA-B* 27. Due to some disadvantages in these methods, most of the HLA laboratories have now switched over to molecular methods. Molecular techniques based on commercial kits are expensive; as such many laboratories with limited funds in developing countries cannot afford these techniques. Aims. Our main aim was to standardize a simple inexpensive in-house PCR-SSP technique for HLA-B* 27 typing. Materials and Methods. Sequence Specific primers were designed to amplify all the subtypes of B* 27 using IMGT-HLA sequence database. Accuracy was checked by retyping of 90 PCR-SSOP typed controls. Results. The presence of 149 bp specific band with control band on 2% agarose gel showed B* 27 positivity. No discrepancies were found when compared with PCR-SSOP results. The frequency of HLA-B* 27 was found to be significantly increased (68.75% versus 4.40%, O.R 46.909: P value 6.62E-32) among 700 SpA patients as compared to controls. Clinically, 54% of patients had polyarticular arthritis with SI joints involvement (68%) and restricted spine flexion (60%). Conclusion. In-house PCR-SSP technique is very simple and inexpensive technique to detect B* 27 allele, which was strongly associated with SpA patients from Western India

Cav1.2 channels mediate persistent chronic stress-induced behavioral deficits that are associated with prefrontal cortex activation of the p25/Cdk5-glucocorticoid receptor pathway

Chronic stress is known to precipitate and exacerbate neuropsychiatric symptoms, and exposure to stress is particularly pathological in individuals with certain genetic predispositions. Recent genome wide association studies have identified single nucleotide polymorphisms (SNPs) in the gene CACNA1C, which codes for the Cav1.2 subunit of the L-type calcium channel (LTCC), as a common risk variant for multiple neuropsychiatric conditions. Cav1.2 channels mediate experience-dependent changes in gene expression and long-term synaptic plasticity through activation of downstream calcium signaling pathways. Previous studies have found an association between stress and altered Cav1.2 expression in the brain, however the contribution of Cav1.2 channels to chronic stress-induced behaviors, and the precise Cav1.2 signaling mechanisms activated are currently unknown. Here we report that chronic stress leads to a delayed increase in Cav1.2 expression selectively within the prefrontal cortex (PFC), but not in other stress-sensitive brain regions such as the hippocampus or amygdala. Further, we demonstrate that while Cav1.2 heterozygous (Cav1.2+/â) mice show chronic stress-induced depressive-like behavior, anxiety-like behavior, and deficits in working memory 1â2 days following stress, they are resilient to the effects of chronic stress when tested 5â7 days later. Lastly, molecular studies find a delayed upregulation of the p25/Cdk5-glucocorticoid receptor (GR) pathway in the PFC when examined 8 days post-stress that is absent in Cav1.2+/â mice. Our findings reveal a novel Cav1.2-mediated molecular mechanism associated with the persistent behavioral effects of chronic stress and provide new insight into potential Cav1.2 channel mechanisms that may contribute to CACNA1C-linked neuropsychiatric phenotypes

Assignment of AR1, transcription factor 20 (TCF20), to human chromosome 22q13.3 with somatic cell hybrids and in situ hybridization.

Journal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.info:eu-repo/semantics/publishe

Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β) on Clinical Manifestations in Indian SLE Patients

Systemic lupus erythematosus (SLE) is an inflammatory rheumatic disease characterized by production of autoantibodies and organ damage. Elevated levels of cytokines have been reported in SLE patients. In this study we have investigated the effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) on clinical manifestations in 145 Indian SLE patients. One hundred and forty-five healthy controls of the same ethnicity served as a control group. Clinical disease activity was scored according to SLEDAI score. Accordingly, 110 patients had active disease and 35 patients had inactive disease. Mean levels of IL-6, TNF-α, and IL-1β were found to be significantly higher in SLE patients than healthy controls (P<0.001). Mean level of IL-6 for patients with active disease (70.45±68.32 pg/mL) was significantly higher (P=0.0430) than those of inactive disease patients (43.85±63.36 pg/mL). Mean level of TNF-α was 44.76±68.32 pg/mL for patients with active disease while it was 25.97±22.03 pg/mL for those with inactive disease and this difference was statistically significant (P=0.0161). Similar results were obtained for IL-1β (P=0.0002). Correlation between IL-6, TNF-α, and IL-1β serum levels and SLEDAI score was observed (r=0.20, r=0.27, and r=0.38, resp.). This study supports the role of these proinflammatory cytokines as inflammatory mediators in active stage of disease