Dr. Antik Bose
- Seattle WA
- [email protected]
Dr. Antik Bose's Publications:
Endovascular treatment of intracranial aneurysms with parent vessel reconstruction using balloon and self expandable stents.
Authors: Dr. Antik Bose, I Szikora, Z Berentei, Z Kulcsar, K Barath, A Berez, I Nyary
BACKGROUND AND PURPOSE: To assess the feasibility and results of parent vessel stent reconstruction with balloon expandable and self-expandable stents in the treatment of intracranial aneurysms. METHODS: In a total of 18 aneurysms balloon expandable (group A) and self expandable (group B) stents were used in 9 cases each. Stent implantation alone was used in 3 cases, and additional coil packing in the other 15. RESULTS: Stents were successfully deployed in 8 out of 9 in group A and in 9 out of 9 cases in group B. Nearly complete occlusion was achieved in all but one case. At 3 or 6 months stable occlusion was found in 4 group A and 2 group B patients, progressive thrombosis in 3 cases in both groups, and recanalisation in 1 case in group B. Late follow up at 1-4 years demonstrated one progressive thrombosis one recanalisation and 1 stable occlusion in 3 group A, and 2 stable occlusions in 2 group B. patients. Complications included one aneurysm perforation in group A, one in-stent thrombosis and a distal arterial perforation in group B and one groin hematoma in both groups. CONCLUSION: Stent reconstruction of intracranial arteries harbouring aneurysms is feasible and may result in aneurysm thrombosis without coil packing in some cases. Self expanding stents seem to provide a higher rate of success. Aggressive antiplatelet treatment increases the risk of hemorrhagic complications. less
Tomatoes versus lycopene in oxidative stress and carcinogenesis: conclusions from clinical trials.
European Journal of Clinical Nutrition/ Nature Publishing Group
Authors: Dr. Antik Bose, Victorine Imrhan
OBJECTIVE: To review the effects of tomato product supplementation, containing lycopene, on biomarkers of oxidative stress and carcinogenesis in human clinical trials. RESULTS: Supplementation of tomato products, containing lycopene, has been shown to lower biomarkers of oxidative stress and carcinogenesis in healthy and type II diabetic patients, and prostate cancer patients, respectively. Processed tomato products like tomato juice, tomato paste, tomato puree, tomato ketchup and tomato oleoresin have been shown to provide bioavailable sources of lycopene, with consequent increases in plasma lycopene levels versus baseline. Dietary fats enhance this process and should be consumed together with food sources of lycopene. The mechanisms of action involve protection of plasma lipoproteins, lymphocyte DNA and serum proteins against oxidative damage, and anticarcinogenic effects, including reduction of prostate-specific antigen, upregulation of connexin expression and overall decrease in prostate tumor aggressiveness. There is limited in vivo data on the health benefits of lycopene alone. Most of the clinical trials with tomato products suggest a synergistic action of lycopene with other nutrients, in lowering biomarkers of oxidative stress and carcinogenesis. CONCLUSIONS: Consumption of processed tomato products, containing lycopene, is of significant health benefit and can be attributed to a combination of naturally occurring nutrients in tomatoes. Lycopene, the main tomato carotenoid, contributes to this effect, but its role per se remains to be investigated. less
Chronic Allograft Nephropathy Score Before Sirolimus Rescue Predicts Allograft Function in Renal Transplant Patients
Authors: Dr. Antik Bose, J L Falcone, H P Tan, D Hassan, I Dvorchik, K Bahri, N Thai, P Randhawa, A Marcos, T E Starlz, R Shapiro
Chronic allograft nephropathy (CAN) is a major indication for initiation of sirolimus (SRL) in renal transplantation (TX) to prevent deterioration of renal function. We evaluated whether the CAN score at time of sirolimus rescue (SRL-R) predicts renal allograft function. CAN score is the sum of the following 4 categories: glomerulopathy (cg, 0–3), interstitial fibrosis (ci, 0–3), tubular atrophy (ct, 0–3), and vasculopathy (cv, 0–3). This is a retrospective cohort study of renal transplant recipients from July 2001 to March 2004. Immunosuppression consisted of preconditioning with rabbit anti-thymocyte globulin or alemtuzumab and maintenance with tacrolimus (TAC) monotherapy with spaced weaning, if applicable, SRL-R was achieved by conversion from TAC, or by addition to reduced doses of TAC. Ninety patients received SRL. Thirty-three of these patients met the inclusion criteria of the following: (1) receipt of SRL for >6 months, and (2) follow-up of ≥6 months. There were 16 patients in the low-CAN (0–4) group and 17 patients in the high-CAN (>4) group. Cockcroft-Gault (C-G) glomerular filtration rate (GFR) was calculated at SRL-R and at 1, 3, 6, and 12 months. The GFR was significantly better in the low-CAN group at 1, 3, and 6 months. A trend toward an improved GFR was present at 12 months in the low-CAN group (P = .16). CAN scoring at the time of SRL-R predicts recovery of renal allograft function (as measured using GFR), and should be used in preference to biochemical markers (Cr and C-G GFR), which may not be reliable predictors. less
Alemtuzumab pre-conditioning with tacrolimus monotherapy in pediatric renal transplantation.
American Journal of Transplantation
Authors: Dr. Antik Bose, R Shapiro, D Ellis, H P Tan, M L Moritz, A N Vats, K L Kayler, E Erkan, C G McFeaters, G James, M J Grosso
We employed antibody pre-conditioning with alemtuzumab and posttransplant immunosuppression with low-dose tacrolimus monotherapy in 26 consecutive pediatric kidney transplant recipients between January 2004 and December 2005. Mean recipient age was 10.7 +/- 5.8 years, 7.7% were undergoing retransplantation, and 3.8% were sensitized, with a PRA >20%. Mean donor age was 32.8 +/- 9.2 years. Living donors were utilized in 65% of the transplants. Mean cold ischemia time was 27.6 +/- 6.4 h. The mean number of HLA mismatches was 3.3 +/- 1.3. Mean follow-up was 25 +/- 8 months. One and 2 year patient survival was 100% and 96%. One and 2 year graft survival was 96% and 88%. Mean serum creatinine was 1.1 +/- 0.6 mg/dL, and calculated creatinine clearance was 82.3 +/- 29.4 mL/min/1.73 m(2). The incidence of pre-weaning acute rejection was 11.5%; the incidence of delayed graft function was 7.7%. Eighteen (69%) of the children were tapered to spaced tacrolimus monotherapy, 10.5 +/- 2.2 months after transplantation. The incidence of CMV, PTLD and BK virus was 0%; the incidence of posttransplant diabetes was 7.7%. Although more follow-up is clearly needed, antibody pre-conditioning with alemtuzumab and tacrolimus monotherapy may be a safe and effective regimen in pediatric renal transplantation. less
Transplantation of en bloc kidneys from very small pediatric donors.
American Journal of Transplantation
Authors: Dr. Antik Bose, A Martin, L K Kayler, R Shapiro
To the Editor:
We read with interest the article by Pelletier and colleagues entitled ‘Recovery and utilization of deceased donor kid-neys from small pediatric donors’ (1). The authors docu-mented that in the United States, between 1993 and 2002, recovery rates of kidneys from donors weighing <10 kg was very low compared to donors weighing from 10 to 21 kg (42.9% vs. 90.8%, respectively). Further compound-ing low recovery, discard rates of kidneys from donors weighing 10 kg was higher than the 10–20 kg subgroup (40.3% vs. 10.5%). Whereas this report found that donor weight independently predicted a higher risk of graft loss, there was no significant difference in long-term graft sur-vival between kidneys from donors weighing 10 kg trans-planted en bloc compared to solitary kidney transplants from donors weighing 15–21 kg. These data suggest that acceptable outcomes can be obtained with very small pe-diatric donors (≤10 kg).
Over the past year, we have adopted a more aggressive ap-proach to the utilization of anatomically challenged kidneys. At the University of Pittsburgh Medical Center, 8 recipients received en bloc kidneys from donors between 21 days of age and 13 months with weights between 4 and 10 kg. Seven of the 8 recipients achieved immediate graft func-tion and demonstrate mean creatinine levels of 1.2 mg/dL (range 0.9–1.8 mg/dL) at 5 months follow-up (range 3– 9 months). One pair failed (3 months old, 8.1 kg) because of poor reperfusion characteristics and subsequent primary nonfunction.
Two hundred living donor kidney transplantations under alemtuzumab induction and tacrolimus monotherapy: 3-year follow-up.
American Journal of Transplantation
Authors: Dr. Antik Bose, H P Tan, J Donaldson, M Unruh, P Randhawa, V Sharma, C Morgan, J McCauley, C Wu, N Shah, A Zeevi
Alemtuzumab has been used in off-label studies of solid organ transplantation. We extend our report of the first 200 consecutive living donor solitary kidney transplantations under alemtuzumab pretreatment with tacrolimus monotherapy and subsequent spaced weaning to 3 years of follow-up. We focused especially on the causes of recipient death and graft loss, and the characteristics of rejection. The actuarial 1-, 2- and 3-year patient and graft survivals were 99.0% and 98.0%, 96.4% and 90.8% and 93.3% and 86.3%, respectively. The cumulative incidence of acute cellular rejection (ACR) at the following months was 2%</=6, 9.0%</=12, 16.5%</=18, 19.5%</=24, 23.5%</=30, 24.0%</=36 and 25%</=42. The mean serum creatinine (mg/dL) and glomerular filtration rate (mL/min/1.73 m(2)) at 1 and 3 years were 1.4 +/- 0.6 and 58.7 +/- 21.6 and 1.5 +/- 0.7 and 54.9 +/- 20.9, respectively. Fifty (25%) recipients had a total of 89 episodes of ACR. About 88.7% of ACR episodes were Banff 1, and of those, 82% were steroid-sensitive. Nine (4.5%) recipients had antibody-mediated rejection (AMR). About 76.5% were weaned but only 46% are currently on spaced dose (qod or less) tacrolimus monotherapy, and 94.4% remained steroid-free from the time of transplantation. Infectious complications were uncommon. This experience suggests the 3-year efficacy of this approach.less
Anti-neutrophil cytoplasmic antibody associated crescentic IgA nephropathy in hematopoietic stem cell transplantation
Authors: Dr. Antik Bose, S D Navaneethan, J Taylor, B Goldman
Membranous glomerulonephritis and minimal change disease are the most common forms of glomerular diseases noted in patients with graft versus host disease after hematopoietic stem cell transplantation. Herein, we report a patient who developed anti-neutrophil cytoplasmic antibody associated crescentic IgA nephropathy within 3 months after autologous hematopoietic stem cell transplantation. He was treated with intravenous pulse steroids and monthly intravenous cyclophosphamide for 6 months followed by cyclophosphamide every 3 months and tapering dose of steroids. His proteinuria resolved and renal function remained stable. Two cases of crescentic IgA nephropathy have been reported in patients who underwent allogenic hematopoietic stem cell transplantation. The etiology of IgA nephropathy developing after hematopoietic stem cell transplantation is unclear and larger registry-based studies are needed to further explore this condition. less
Impact of Genomic Sequence Variability on Quantitative PCR Assays for Diagnosis of Polyomavirus BK Infection
Journal of Clinical Microbiology
Authors: Dr. Antik Bose, P Randhawa, J Kant, R Shapiro, H Tan, C Luo
Knowledge of polyomavirus BK (BKV) genomic diversity has greatly expanded. The implications of BKV DNA sequence variation for the performance of molecular diagnostic assays is not well studied. We analyzed 184 publically available VP-1 sequences encompassing the BKV genomic region targeted by an in-house quantitative hydrolysis probe-based PCR assay. A perfect match with the PCR primers and probe was seen in 81 sequences. One Dun and 13 variant prototype oligonucleotides were synthesized as artificial targets to determine how they affected the performance of PCR. The sensitivity of detection of BKV in the PCR assay was a function of the viral genotype. Prototype 1 (BKV Dun) could be reliably detected at concentrations as low as 10 copies/μl. However, consistent detection of all BKV variants was possible only at concentrations of 10,000 copies/μl or higher. For BKV prototypes with 2 or more mismatches (representing genotype IV, genotype II, and genotype 1c strains), the calculated viral loads were 0.57 to 3.26% of the expected values. In conclusion, variant BKV strains lower the sensitivity of detection and may have a substantial effect on quantitation of the viral load. Physicians need to be cognizant of these effects when interpreting the results of quantitative PCR testing in transplant recipients, particularly if there is a discrepancy between the clinical impression and the measured viral load. less
Inhibitory feedback promotes stability in an oscillatory network.
Journal of Neural Engineering
Authors: Dr. Antik Bose, F Nadim, S Zhao, L Zhou
Reliability and variability of neuronal activity are both thought to be important for the proper function of neuronal networks. The crustacean pyloric rhythm (∼1 Hz) is driven by a group of pacemaker neurons (AB/PD) that inhibit and burst out of phase with all follower pyloric neurons. The only known chemical synaptic feedback to the pacemakers is an inhibitory synapse from the follower lateral pyloric (LP) neuron. Although this synapse has been studied extensively, its role in the generation and coordination of the pyloric rhythm is unknown. We examine the hypothesis that this synapse acts to stabilize the oscillation by reducing the variability in cycle period on a cycle-by-cycle basis. Our experimental data show that functionally removing the LP-pyloric dilator (PD) synapse by hyperpolarizing the LP neuron increases the pyloric period variability. The increase in pyloric rhythm stability in the presence of the LP-PD synapse is demonstrated by a decrease in the amplitude of the phase response curve of the PD neuron. These experimental results are explained by a reduced mathematical model. Phase plane analysis of this model demonstrates that the effect of the periodic inhibition is to produce asymptotic stability in the oscillation phase, which leads to a reduction in variability of the oscillation cycle period. less
Efficacy of commonly used anthelmintics: First report of multiple drug resistance in gastrointestinal nematodes of sheep in Trinidad
Authors: Dr. Antik Bose, N George, K Persad, R Sagam, V N Offiah, A A Adesiyun, W Harewood, N Lambie
In Trinidad, small ruminant farms are semi-intensively managed under tropical conditions which support the development and survival of the infective stages of the helminths. Local farmers use anthelmintics to control gastrointestinal nematodes frequently. Frequent use of anthelmintics has the potential to select for populations of nematodes resistance to those chemicals. Hence, an attempt was made to study the efficacy of commonly used drugs on gastrointestinal nematodes of sheep. Three farms situated in different counties in Trinidad were selected. Sheep aged 6–15 months and not treated with anthelmintics for a minimum of six months previous and with faecal egg count (FEC) > 150 eggs per gram were selected for study. They were allocated into 5 groups, each consisting 10 animals. The Group TA animals were treated once with albendazole (5 mg/kg. b.wt.), group TF with fenbendazole (5 mg/kg.b.wt.), group TI animals with ivermectin (200 μg/kg b.wt.), group TL with levamisol (7.5 mg/kg b.wt.). The group NTC animals were not given any drug and served as control. The number of nematode eggs per gram of faeces from each animal was determined before treatment and at 14 days after treatment. The anthelmintic susceptibility to different drugs was detected by FECRT (in vivo) with EPG recorded at 14 day post-treatment. The data analysis using FECRT revealed that efficacy of albendazole (46–62%), fenbendazole (44–61%) and levamisol (53–81%) were reduced compared to ivermectin (95–97%). An attempt has also been made to find a suitable method for calculation of FECR (%). less
P-010 A Study of the novel 054 Penumbra aspiration device in the ICA and MCA
Journal of Interventional Surgery
January 9, 2011
Authors: Dr. Antik Bose, D Frei, R Bellon, D Huddle, G Dooley, J Gerber, A Turk, D Heck
Purpose The 054 reperfusion catheter is a newly introduced component of the Penumbra System specifically designed to enhance aspiration efficiency by increasing the catheter diameter. The goal of this study was to compare its safety and effectiveness in reducing clot burden in the internal carotid artery (ICA) and the middle cerebral artery (MCA).
Methods and Materials This study was a retrospective case review of 74 consecutive patients at 11 international centers with ICA or MCA occlusion who were treated with the Penumbra System. All patients reviewed presented to the hospital within 8 h of symptom onset with a treatable large vessel occlusion (TIMI 0 or 1). The primary endpoint was the rate of successful recanalization as defined by TIMI scores of 2–3.
Results Mean baseline values at enrollment were age 65 years, median NIHSS score 18 (range 2–38), 61% were females, and the median time from symptom onset to arterial puncture was 5 h. After use of the Penumbra System, 91.8% of the treated vessels were revascularized to TIMI 2 or 3. Median time of aspiration was 18 min. Four procedural/device related SAEs were reported in three patients (5.4%). There were a total of 8 (10.8%) symptomatic ICHs reported at 24 h. At 90 days, all cause mortality was 23.0%. Of the 54 patients who either died or reached the 90 days follow-up, 20 (37.0%) had mRS scores of <2. Below are comparisons of the results in the ICA and MCA:
Conclusions These results suggest that in acute stroke patients with large vessel occlusion, the 054 reperfusion catheter is equi-effective in the reduction of clot burden in the ICA and MCA. less
Simultaneous determination of 14N and 15N isotopes in opium by proton induced γ-ray emission technique
Journal of Radioanalytical and Nuclear Chemistry
Authors: Dr. Antik Bose, P Rao, J L N Reddy, V Kumar, J V Ramana, N Chattopadhyay, S Srivastava, R K Sarin, V S Raju, S K Kumar
The paper describes the simultaneous determination of 14N and 15N isotopes in opium by proton induced γ-ray emission (PIGE) technique. The isotopic ratio of 14N and 15N is a useful parameter for assigning provenance of (seized) illicit drugs. The measurement, non-destructive in nature, is performed on pellets made up of opium powders and is based on the prompt detection of 2.313 and 4.4 MeV γ-rays emanating from 14N(p,p′γ)14N and 15N(p,αγ)12C nuclear reactions respectively, induced simultaneously by 3.6–3.8 MeV proton beam. Positive as well as negative deviations from the natural isotopic abundance (99.63:0.37) were observed in the samples. The precision of the measurements is about 4%. The methodology provides an easy and rapid approach to determine the isotopic ratio of 14N and 15N and has been used for the first time in the analysis of opium less
Anti-Hepatitis C Virus Activity and Toxicity of Type III Phosphatidylinositol-4-Kinase Beta Inhibitors
Antimicrobial Agents and Chemotherapy
Authors: Dr. Antik Bose, M J LaMarche, J Borawski, C Capacci-Daniel, R Colvin, M Dennehy, J Ding, M Dobler, J Drumm, L A Gaither, J GaoX Jing
Type III phosphatidylinositol-4-kinase beta (PI4KIIIβ) was previously implicated in hepatitis C virus (HCV) replication by small interfering RNA (siRNA) depletion and was therefore proposed as a novel cellular target for the treatment of hepatitis C. Medicinal chemistry efforts identified highly selective PI4KIIIβ inhibitors that potently inhibited the replication of genotype 1a and 1b HCV replicons and genotype 2a virus in vitro. Replicon cells required more than 5 weeks to reach low levels of 3- to 5-fold resistance, suggesting a high resistance barrier to these cellular targets. Extensive in vitro profiling of the compounds revealed a role of PI4KIIIβ in lymphocyte proliferation. Previously proposed functions of PI4KIIIβ in insulin secretion and the regulation of several ion channels were not perturbed with these inhibitors. Moreover, PI4KIIIβ inhibitors were not generally cytotoxic as demonstrated across hundreds of cell lines and primary cells. However, an unexpected antiproliferative effect in lymphocytes precluded their further development for the treatment of hepatitis C. less
O-001 Pre-treatment CTA ASPECTS as a predictor of clinical outcome in endovascular stroke therapy (EVT): results from the penumbra START trial
Journal of NeuroInterventional Surgery
Authors: Dr. Antik Bose, D Frei, A Yoo, D Heck, F Hellinger, V McCollom, D Fiorella, A Turk
Introduction/purpose There is no standard imaging approach for EVT patient selection. CT remains the most widely used modality for stroke evaluation. Ischemic change on non-contrast CT (NCCT) quantified using ASPECTS has been demonstrated to predict clinical response to EVT. To date, definitive studies evaluating the impact of CTA source image (CTA-SI) pre-treatment ASPECTS (pre- ASPECTS) on outcomes following EVT are lacking. START was a prospective, multicenter study to evaluate the influence of pretreatment core infarct size in patients undergoing endovascular stroke therapy using the Penumbra System. Materials and Methods The imaging method was at each center's discretion and included NCCT, CTA-SI, CT perfusion, or MRI diffusion imaging. This study focused on the preliminary CTA-SI results. Results are reported from an interim analysis of the START trial data as adjudicated by a central Core Laboratory. Graded in a blinded fashion, ASPECTS was analyzed according to the a priori classification (0-4, 5-7, 8-10), as well as using the entire scale. Clinical outcomes were dichotomized as 90-day modified Rankin Scale scores of 0-2 (good) vs 3-6. Univariate and multivariate analyses were performed to determine predictors of outcome. Results Of the 147 patients enrolled, 77 met study criteria for this interim analysis. The mean age was 66.0614.1 years; median NIHSS was 19 (14-24). Target vessel occlusions were in the ICA (22.1%), MCA (75.3%), and other (2.6%). The median pre-ASPECTS on CTA-SI was 6 (4-7). There were 20 (26%) patients with scores of 0-4, 43 (55.8%) with 5-7, 14 (18.2%) with 8-10. The rate of TIMI 2-3 revascularization was 85.3% (64/75). The median time from groin puncture to aspiration discontinuation was 71.5 (40-108) min. 37 (48.1%) patients achieved a good 90-day outcome. 22 (28.6%) died. less
Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes.
An International Journal of Obstetrics and Gynaecology
Authors: Dr. Antik Bose, Y Yu, K F Hanssen, V kalyanaraman, A Chirindel, A J Jenkins, A J Nankervis, P A Torjensen, H Scholz, T Henriksen, B Loretzen
OBJECTIVE: Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE. DESIGN: Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset. SETTING: Antenatal clinics. POPULATION: Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21). METHODS: Maternal serum levels of sRAGE (total circulating pool), N(ε)-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays. Main outcome measures: Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE-). RESULTS: In DM PE+ versus DM PE-, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P < 0.05). Further, reflecting the net sRAGE scavenger capacity, sRAGE:hydroimidazolone was significantly lower in the second trimester (P < 0.05) and sRAGE:AGE and sRAGE:CML tended to be lower in the first trimester (P < 0.1) in women with T1DM who subsequently developed PE versus those who did not. These conclusions persisted after adjusting for prandial status, glycated haemoglobin (HbA1c), duration of diabetes, parity and mean arterial pressure as covariates. CONCLUSIONS: In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM. less
Pulmonary coccidiomycosis in New Delhi, India
Authors: Dr. Antik Bose, J K Oberoi, C Wattal, P K Aggarwal, S Khanna, K Verma
Coccidioidomycosis is an endemic disease of the western hemisphere. In cases occurring in non-endemic areas, eliciting a history of exposure as well as a high index of suspicion is imperative for timely and accurate diagnosis. In this case, a 65-year-old male presented to our hospital with fever, dry cough and malaise, and on X-ray chest, was found to have a lower lobe consolidation left lung with nodular lesions in both lungs and necrotic mediastinal lymphadenopathy. He lived in Arizona, USA, for 6 months before admission. Pulmonary coccidioidomycosis was confirmed by the isolation of Coccidioides spp. in pure culture from both broncho-alveolar lavage and lung biopsy specimens. The identity of the isolate was confirmed as C. posadasii by gene sequencing. The patient improved after being treated with fluconazole less
Purification, peptide sequencing and modelling of ostreolysin from Pleurotus ostreatus strain Plo5: Formation of Modified Ostreolysin with cytolytic effect only on cancer cell lines
Nature Reviews Cancer
Authors: Dr. Antik Bose
A 16 kDa ostreolysin ,a cytolytic protein has been purified from the fruiting body of Pleurotus ostreatus strain PLo5 using Q-sepharose, Superdex TM -75 gel filtration, Vydac C-18 reverse phase HPLC and SDS-PAGE. The complete peptide sequencing of the 50 amino acids ostreolysin was done and deposited in public protein database; UniPort B. Modeling of the 4 domains of ostreolysin and quaternary structure
of the native ostreolysin was elucidated. A modified ostreolysin was prepared on converting an antiparallel ß strand in domain 4 of the protein and changing its cholesterol binding site. Modified ostreolysin could kill cancer lines at nanomolar concentrations because of their higher membrane cholesterol levels ,and it has no effect on normal cell lines. Stability of Modified ostreolysin was shown by Ramachandran Plot. Modeling of Modified ostreolysin was also done. less
Adjuvant effect and TLR4 mediated activation of macrophages by polysaccharide from Polyporus albicans
Nature Reviews Immunology
Authors: Dr. Antik Bose
A water soluble polysaccharide from mycelium of Polyporus albicans has been identified for its potency in stimulating cellular and humoral immune response. The adjuvant potential of this polysaccharide was identified and found to be higher than conventional adjuvants. The 37 KDa polysaccharide was purified using different macroporous absorption resins and Reverse phase HPLC. Structural determination was done by sugar and methylation analysis, 13C NMR, FTIR, MALDI-TOF,ESI-IT, MALDI-PSD TOF spectroscopy. The molecular size of the polysaccharide was determined by Zetasier nanosystem. It showed TLR4 dependent NO, IL-1β and TNF-α production. less
Purification and Characterization of Alkaline Phosphatase from Pleurotus sajor-caju
The EMBO Journal
Authors: Dr. Antik Bose
Biochemical properties of alkaline phosphatase obtained from fruiting body extract of Pleurotus sajor-caju were described. The enzyme was purified 27117.64 fold with 9.6% recovery by DEAE-cellulose and Sephadex G-200 Chromatography. The molar mass estimated by Sephadex G-200 was 130KD and 6% SDS-PAGE, two subunits of molecular mass 89.8KD and 42.5KD were obtained indicating a C and pH 8.5 respectively. The enzyme was moderately glycosylated ( 44% saccharide content ). The activity was enhanced by Mg2+ (7-96.8%), Mn2+ (17-48%), Na+ (2.46-14.28%). 4-nitrophenyl phosphate was hydrolysed with KM and Vmax of 25mM-1 and 0.285μM of PNPP consumed/min respectively. Amino acids at the active site have been identified using Diisopropylphosphofloridate (DIPF), Diethylpyrocarbonate (DEPC), Diazomethane and 1-ethyl-3( 3-dimethyl) aminopropyl carbodiimide (EDAC) to be serine, histidine and aspartic acid respectively.
Purification of Urease from Pleurotus sajor-caju. Characterisation of GTPase Activity of UreG and Biochemical Properties of the enzyme
Canadian Journal of Microbiology
Authors: Dr. Antik Bose
Biochemical properties of urease obtained from fruiting body extract of Pleurotus sajor-caju have been described. The enzyme was purified 3176.623 fold by CM-cellulose, DEAE-cellulose and Sephadex G-200 column chromatography. The molar mass estimated by Sephadex G-200 was 510KD and saccharide content was 4%. 6% SDS-PAGE of purified urease showed subunits UreA/B homodimer (28.8 KD ), UreC (150 KD), UreD (104 KD), UreE (21.5 KD), UreF (102 KD) and UreG (103KD). GTPase activity of UreG was characterized with KM, Vmax & Kcat to be 2.6mM, 1.1μ mol GTP hydrolyzed/ min and 0.27 min-1. The enzyme hydrolyzed urea with KM and Vmax to be 1.85mM and 64.51 μ mol NH3 C and 7.4 respectively. The enzyme activity was enhanced by Ca2+ (2.94%), 5-10 mM, Mn2+ ( 2.67-52.406%), 20-50mM Ni2+ (2.6-6.93% ) and 5-10mM Mncl2 ( 0.58- 8.02% ). The enzyme showed product inhibition by NH4+. Competitive inhibition by thiourea and uncompetitive inhibition by NaF were also studied. Amino acids at the active site have been identified to be Histidine and Aspartic acid using DEPC and Diazomethane with EDAC less
Purification , Peptide Sequencing ,Characterisation and Study of Antiproliferative activity of Cicer arietinum L. Protein Phosphatase 2A on Chronic Myelogenous Leukemia K562 Cell line
CA: A Cancer Journal for Clinicians
Authors: Dr. Antik Bose
Protein Phosphatase 2A has been purified from 72 hrs germinating seeds of Cicer arietinum L. by Toyopearl DEAE -650 anion exchanger, Phenyl-sepharose CL-4B ,Microcystin –aminoethanethiol- sepharose chromatography ,PD-10 desalting column and Vydac C-18 Reverse phase HPLC chromatography with 4186.67 folds of purification ,3% recovery and final specific activity of 209.334 U/ g protein /min .The molar masses of catalytic subunit (38 KD) and regulatory subunits (65 and 75 KD) were determined by 6% SDS-PAGE .38 KD catalytic subunit was identified by Western Blotting with anti IgG2 monoclonal Ab against human PP2A catalytic subunit.Number of SH groups was found to be 11 in PP2A/c and its full peptide sequencing gave a 306 aa protein which was deposited in Protein Public database Uniprot with Acc no. Q07098 .Human PP2A was found to be inhibited in human CML cell line K562 due to Bcr:abl induced formation of binary complex between human PP2A/c and hnRNP A2 and ternary complex between human PP2A holoenzyme,hn RNP A2 and SET protein .In K562 mutant OA200 cell line lacking human PP2A ; chick pea PP2A was found to induce apoptosis of CML cells as it is not inhibited by hn RNP A2 or SET proteins in vivo or in vitro.Chick pea PP2A further induced nuclear localization of
SET-NUP214 complex and degradation of bcr:abl fusion proteins .RNA binding domains of hn RNP A2 was sufficient to inhibit human PP2A . Chick pea PP2A associated with human PR72 and induced dephosphorylation of SV 40 T antigen. pH and temperature optima of chick pea PP2A were 8.0 and 25 c respectively and Km and V max were 87.713 mM , 166.67 U/min for holoenzyme and 64.10 mM and 208.33 U/min for PP2A respectively. less
Purification, Peptide Sequencing and Study of Antiproliferative Activity of Laccase against Liver cancer cell line Hep G2 and human breast cancer cell line MCF 7
Authors: Dr. Antik Bose
Three isozymes of laccase LCC 1, LCC 2 and LCC 3 have been purified from Pleurotus ostreatus strain V-184 using Toyopearl DEAE-650 Isoelectric focusing, ConA-sepharose 4B chromatography, Superdex-75 gel filtration, PD10 desalting column and Vydac C-18 Reverse phase HPLC chromatography with 950, 1220 and 935 folds of purification for LCC 1, 2 and 3 respectively. The native molar mass of LCC 1 and 2 heterodimer was calculated to be 130Kda by gel filtration and by 6% SDS-PAGE bands of 65, 60 and 80Kda were obtained for LCC 1, 2 and 3 respectively. Number of SH groups in LCC 1 was calculated to be 4.68 and its full peptide sequencing gave a 533aa protein which was deposited in Protein public database Uniprot with Acc. no. Q12739. IC50 of LCC 1 on Hepatocellular Carcinoma human (Hep G2) and human brest cancer cell lines (MCF 7) were found to be 2.8 and 3.3 μM respectively. 1 to 5μM Menadione with 4.6μM LCC 1 was found to kill Hep G2 cells by production of hydroxyl radical from semiquinone produced by laccase catalysed Quinone-redox cycle. For elucidation of mode of action of laccase on killing Hep G2 cells; a patent has been registered with application no. 3299/DELP/2011 A at CGPDTM, West Bengal. The temperature and pH optima for all isozymes were found to be 30˚C and 5.0 respectively. Spectral analysis showed presence of Type 3 and Type 1 Cu (II) in LCC 1 and reduction of Type 1 during catalysis of Guaiacol. KM and Vmax for 3 isozymes with Guaiacol was found to be 84.034μM, 714.25 U/min; 74.074μM, 204.0816 U/min; 158.73μM, 714.3U/min respectively for LCC 1, 2 and 3. less
Purification and Characterisation of Alkaline Phosphatase from Fruticose Lichen Usnea.sp
Authors: Dr. Antik Bose
Biochemical properties of alkaline phosphatase obtained from fruticose lichen Usnea.sp have been described. The enzyme was purified 38439.26 fold with 7.32% recovery by DEAE-cellulose and Sephadex G-200 Chromatography. The molar mass was estimated by Sephadex G-200 was 132.7KD and by 6% SDS-PAGE, a single band of 66 KD was obtained indicating a homodimer. Temperature and pH optima were 35 C and pH 8.5 respectively. The enzyme was moderately glycosylated (42% saccharide content). The activity was enhanced by Mg2+ (6.07-128.3%), Mn2+ (18.66-85.1%), Na+ (6.07%-64.47%), Al3+ ( 4.5-52.58% ), Ba2+ (2.95-25.2%). 4-nitrophenylphosphate was hydrolysed with KM and Vmax of 6.67mM-1 and 22.22μM of PNPP consumed/min respectively at pH 8.5. Amino acids at the active site have been identified using Diisopropylphosphofloridate ( DIPF) , Diethylpyrocarbonate ( DEPC ), Diazomethane and 1-ethyl-3( 3-dimethyl) aminopropylcarbodiimide ( EDAC) to be serine, histidine and aspartic acid respectively. less
Purification & Characterisation of isozyme-1 and 2 of Acid Phosphatase from Cicer arietinum
Authors: Dr. Antik Bose
Biochemical properties of acid phosphatase isoforms obtained from germinating seeds of Cicer arietinum have been described. The isoforms were purified 3604.88 and 2390 fold with 1.4% recovery by CM-Cellulose, DEAE- Cellulose, (L)-tartarate-AH-Sepharose-4B affinity chromatography and Isoelectric focusing. The molar mass of both isoforms was estimated by Sephadex G-200 to be 100KD and by 6% SDS-PAGE a band of 55KD was obtained suggesting a homodimer. Temperature optima for both isoforms is 32 C and pH optima are 4.5 and 5.5 for isoforms 1 and 2. The isoforms were moderately glycosylated , 40% and 35% saccharide content for isoforms 1 and 2. Isoform-1 dephosphorylated Phosphotyrosine, PNPP, o-phospho-L- serine, Phosphoenolpyruvate, PPi and ATP. Both isoforms showed product inhibition by phosphate. The activity was enhanced by Mg2+ ( 2.2% for isoform-1 and 4.9% for isoform-2 ). 4-nitrophenyl phosphate was hydrolysed with KM and Vmax 2,27 mM and 238.095 μM PNPP consumed/min for isoform-2. Vanadium tetrachloride showed uncompetitive inhibition on isoform-1 and competitive inhibition on isoform-2. less
Could a herpesvirus be the cause of Kawasaki disease?
The Lancet Infectious Disease
Authors: D Shingadia, R Booy, Dr. Antik Bose
Kawasaki disease (KD) is an acute vasculitis of early childhood, the cause of which remains unknown. Many lines of evidence suggest an infectious aetiology, which may-in association with host genetic factors-lead to the characteristic clinical presentation of this disease. Accumulating data including animal models and epidemiological and immunological studies, suggest that viruses have an important role in human vasculitic disease. Whereas many infectious agents including viruses have been postulated as possible causes of KD, no single agent has been shown definitely to be associated with this disease and the causative agent remains elusive. We hypothesise that a ubiquitous virus of the γ herpesvirus family is the likely aetiological agent for KD in genetically susceptible individuals. less
Purification, peptide sequencing, modelling and characterization of extracellular laccase secreted by Pleurotus sajor-caju MTCC 141
Authors: Dr. Antik Bose
The extracellular laccase which is secreted by Pleurotus sajorcaju has been purified using Ammonium sulphate precipitation, DEAE-cellulose, Sephadex G-100, ConA-Sepharose 4B and HP1090A HPLC fitted with Vydac C-18 Reverse- Phase chromatography with 722.2 fold of purification and yield of 1.64%. 12% SDS-PAGE showed a monomer of 90KD. Western Blotting was done with monoclonal Lcc Cbr2 rabbit antibody raised against copper binding region II of laccase from Agaricus bisporus. Peptide sequencing of the purified laccase showed 529 amino acids long peptide with a 23 amino acids long signal peptide. Three Plastocyanin like domains were observed ( 25-159, 170-312 and 380-499). Residues 57, 239, 282 and 465 of the extracellular laccase showed N- linked N-acetyl D-glucoseamine residues. The enzyme showed KM of 36μM, 216pM, 380pM, 370pM and 260pM with 2,6 dimethoxyphenol, Catechol, m-cresol, pyrogallol and syringaldazine respectively. CuSo4, BaCl2, MgCl2, FeCL3, ZnCl3, Urea, PCMB, DTT, β-mercaptoethanol had no effect on enzyme activity while HgCl2 and MnCl2 were weak inhibitors and SDS, Sodium azide were strong inhibitors. Crystallization data, collection, synchrotron radiation and
processing have been carried out.Orthorhombic crystals of space group P2 12 121 w A, b= 85.0 A, c= 91.5 A 3/Da, assuming one molecule per asymmetric unit. Diffraction data was collected using Beamline BW7B of Synchroton Deutoches Elektonen Synchroton (DESY) at room temperature. Data was processed and scaled with programs DENZO and SCALEPACK of Hkl suit. For 1.9-20 A resolution shell, the data were 99.7% complete and scale with an overall Rsym of 0.063 and Rsym of 0.38 for data in highest resolution - - A resolution data, an Rcryst of 0.434 was obtained. A 2F 0Fe electron density map revealed clearly all four copper sites . less
Acanthosis Nigricansin PCOS Patients and Its Relation with Type 2 Diabetes Mellitus and Body Mass at a Tertiary Care Hospital in Southern India
Journal of Clinical and Diagnostic Research
February 1, 2013
Authors: Dr. Antik Bose, G Shivaprakash, A Kamath, P Shivapraksh, P Adhikari, U P Ratnakar, H N Gopalkrishna, J R Padubirdi
Background: Acanthosis nigricansis was viewed recently as a possible marker of an increased risk for diabetes. Acanthosis Nigricans (AN) can help in identifying the patients with an increased risk for Type 2 Diabetes Mellitus (T2DM) among Polycystic Ovary Syndrome (PCOS) cases. Hence, this study was carried to know the prevalence of AN in PCOS and its correlation with diabetes mellitus and the body mass. Methods: A prospective, longitudinal study in the patients with PCOS, who attended the Department of Medicine, Kasturba Medical College [KMC] Hospital, Attavar, Mangalore, Karnatka, India between December 2008 to April 2010, was carried out. A total of 119 patients with PCOS were included in the study. A complete history, along with the demographic data of the patients who were aged between 15-35 years, were considered for the analysis. Results: AN was observed in 56% of the PCOS patients. The Body Mass Index (BMI) and the waist circumference were significantly higher in the PCOS patients with AN, as compared to those without AN. Among the 119 PCOS patients,77% were found to have BMI values which were above the normal. Among the obese PCOS patients, 58% had BMI values of more than 30kg/m(2) as compared to 19% of the patients who did not have AN. Type 2 DM was observed in 77% of the PCOS patients with AN, while none of the PCOS patients were found to be diabetic among those without AN. A family history of DM in the first degree relatives was present in all the patients with AN. The results were analyzed by the Mann Whitney U test for the continuous data and by the Chi square test for the categorical data. Conclusion: The PCOS patients who had a family history of diabetes and obesity with a body mass index of more than 30 kg/m(2) and a waist circumference of ≥ 90 cm were more likely to develop AN, which is a marker of hyperinsulinaemia and insulin resistance. less
O-001 Pre-Treatment Imaging is Critical in Identifying Stroke Patients with Small and Medium Infarcts Who are Likely to Benefit from IA Therapy
Journal of NeuroInterventional Surgery
Authors: Dr. Antik Bose, D Frei, A Yoo, D Heck, F Hellinger, V McCollom, D Fiorella, A Turk, T Malisch, O Zeidat, M AlexanderZ Chaudhry
Introduction/Purpose The Penumbra START Trial is a multicentre, prospective, single-arm trial with a primary aim of determining whether core infarct size on pre-treatment neuroimaging predicts clinical response to intra-arterial acute stroke therapy.
Materials and Methods For this study, major inclusion criteria include presence of proximal artery occlusion in the anterior circulation, baseline NIHSS score of 10 or greater, evaluable pre-treatment neuroimaging [noncontrast CT (NCCT), CTA source imaging, CT perfusion or MRI DWI], and treatment with the Penumbra System within 8 hours. Core infarct size was evaluated by a blinded imaging Core Laboratory. As pre-specified, infarcts were trichotomised into small [ASPECTS 8–10 (NCCT, CTA-SI) or lesion volume <50 cc (CTP or DWI)], medium (ASPECTS 5-7 or volume 50–100 cc), or large (ASPECTS 0–4 or volume >100 cc). In total, 146 patients were enrolled at 27 centres, including 104 patients with Core Lab review and evaluation at 90 days. Good clinical outcome is defined as mRS 0–2 at 90 days. Case review is still ongoing, and statistical analysis is from the 104 patients with complete information. We will update results at the time of the meeting.
yO-007 Natural History of Acute Ischaemic Stroke from Large Vessel Occlusion Demonstrates Efficacy of Mechanical Thrombectomy: Preliminary Results of the Penumbra FIRST Study
Journal of NeuroInterventional Surgery
Authors: Dr. Antik Bose, V Janardhan, L Carlson, R Gianatasio, S Chen, P Bhuva, M Murray, M Vijayappa, P Hansen, R Cheung
Introduction/Purpose Current literature has only limited information on the natural history of the stroke cohort eligible for mechanical thrombectomy. This has contributed to the uncertainties over the benefits of mechanical thrombectomy devices since they were approved either by single arm trials or with another device as active control. The aim of FIRST is to gather real world control data to reference results from mechanical thrombectomy trials in the proper context.
Materials and Methods The FIRST Trial is a prospective, multicentre, single arm natural history study of a stroke cohort eligible for but untreated by endovascular therapy presenting within 8 hours of symptom onset from a large vessel occlusion and a NIHSS score ≥10. Patients should be ineligible or refractory to lytic therapy. The primary endpoint is 90-day functional outcome as defined by a mRS 0–2.
Results For this interim analysis, 61 enrolled patients met study criteria. The mean age was 67.7 ± 15.7 years; median NIHSS score was 18 (IQR14–22). Target vessel occlusions were located in the ICA (28%), MCA (67%), and other (5%). At admission, the TIMI 0–1 rate was 98% (59/60), and the TICI 0–1 rate was 98% (58/59). Of these, only 10% (4/41) and 12% (5/41) showed spontaneous recanalisation (TIMI 2–3 or TICI 2a-3). Twelve of 54 (22%) patients achieved a good 90-day outcome, and 25 of 61 (41%) died. The serious adverse event rate within 24 hours of stroke onset was 54% (33/61), including cerebral oedema (8 cases) and respiratory failure (4 cases). Eleven (18%) patients suffered intracerebral haemorrhage. 33 (56%) were refractory to IV rtPA. Compared with PROACT II placebo patients, the stroke cohort eligible for mechanical thrombectomy who were untreated have different baseline characteristics, a lower recanalisation rate, and worse outcome. The graph shows a comparison of 90-day good outcome in the FIRST vs Penumbra System Trials, trichotomised by pre-ASPECTS scores.