J Singh

North Dakota State University, Fargo, North Dakota, United States

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Publications (46)109.87 Total impact

  • K. S. Bhatia, J. Singh
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    ABSTRACT: Abstract The effect of penetration enhancer (PE) on the in vitro permeability of luteinizing hormone-releasing hormone (LHRH) through porcine epidermis was investigated. The permeability coefficient of LHRH significantly increased (p < 0.05) through PE-(e.g., n-methyl 2-pyrrolidone [NMP], and isopropyl myristate [IPM]) treated epidermis in comparison to the control (without PE-pretreated epidermis). The higher permeability coefficient was observed with NMP followed by IPM. This shows that PE such as NMP and IPM can enhance the percutaneous absorption of peptides such as LHRH.
    10/2008; 23(11):1111-1114.
  • H M Dani, J Singh, S Singh
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    ABSTRACT: The signal recognition particle (SRP) is a unique moiety in living cells, which has been conserved during evolution for protein targeting and translocation across membranes in collaboration with its receptor (SR). The structural and functional features of its components, (six polypeptides and RNA) are being rapidly elucidated. We have endeavored in this review to epitomize most recent advances in this field. Its two domains (S and Alu) play important roles in signal recognition, elongation arrest and protein targeting of the polypeptide being synthesized in the cytoplasm. SRP14 and SRP9 help in the elongation arrest by interacting with signal peptide. GTPase activity of SRP54 releases SRP from SR. In addition, alpha and beta subunits of SR also possess GTPase activities and the three GTPases help in docking of nascent peptide chain-ribosome complex to the translocation site. Further strides in proteomics employing mass spectrometry and X-ray crystallography are expected to throw more light on the molecular events occurring during protein targeting and translocation.
    Journal of biological regulators and homeostatic agents 01/2003; 17(4):303-7. · 5.18 Impact Factor
  • K Zhao, S Singh, J Singh
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    ABSTRACT: The effect of penetration enhancer (i.e., 1, 2, 3 and 5% menthone in combination with 50% ethanol (EtOH)) was investigated on the in vitro percutaneous absorption of tamoxifen, and post-recovery epidermal permeability after removal of the above enhancer. The flux of tamoxifen with menthone in combination with 50% EtOH was significantly greater (P<0.05) than the control (50% EtOH). The flux of tamoxifen increased with increasing concentrations of menthone. The post-recovery flux through enhancer exposed epidermis was significantly decreased (P<0.05) as compared to pre-recovery. However, post-recovery flux of tamoxifen through the enhancer-exposed epidermis did not completely recover to the baseline (i.e., post-recovery flux through phosphate buffered saline, pH 7.4 treated epidermis).
    International Journal of Pharmaceutics 06/2001; 219(1-2):177-81. · 3.99 Impact Factor
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    ABSTRACT: Transdermal iontophoresis would be a promising method for the systemic delivery of water soluble and ionic drugs of relatively high molecular size, including peptides. In the present study, the effect of biological parameters such as age of the animal and species variation (rat, rabbit, mouse, guinea pig and human) on the transdermal iontophoretic transport was studied using timolol maleate (TM) as a model drug. The iontophoretic transport of TM across the skins obtained from the rats of different age groups was found to be similar. The results of the present study suggest that the age of the animal (Wistar rats: 1-8 months) did not appear to influence the transdermal iontophoretic transport of TM significantly. The amount of TM transported during iontophoresis (2 h) was significantly different among the different skin species. But the total amount of TM transported up to 24 h (2 h iontophoresis+22 h post-iontophoretic passive diffusion) was not significantly different among the different species studied. The present study provides further evidence that iontophoresis technique reduces the interspecies differences in the transdermal permeation of drugs, which is normally observed in passive diffusion of drugs. However, it must be noted that excised skins have been used in the present study to investigate the role of age and species variation on the iontophoretic transport of TM. The influence of these parameters under in vivo conditions might be different considering the physiological differences in different species and in the animals of different age groups.
    Journal of Controlled Release 04/2001; 71(1):99-105. · 7.63 Impact Factor
  • K Zhao, J Singh
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    ABSTRACT: The effects of enhancers (5% terpenes; i.e., eugenol, limonene, and menthone) in combination with 50% propylene glycol in water (50% PG) on the in vitro percutaneous absorption of tamoxifen through the porcine epidermis, on biophysical changes in the stratum corneum (SC) lipids, on macroscopic barrier properties, and on binding of the drug to the SC were investigated. These enhancers in combination with 50% PG significantly increased (p<0.05) the permeability coefficient of tamoxifen in comparison with that of the control (50% PG in water). Fourier transform infrared spectroscopy (FT-IR) was employed to investigate the biophysical changes in the SC lipids. The FT-IR results showed that treatment of the SC with 5% terpenes/50% PG did not shift the asymmetric and symmetric C-H stretching absorbances peak positions to higher wavenumbers but resulted in a decrease in the peak heights and areas in comparison with the untreated SC. Treatment with menthone and limonene in combination with 50% PG significantly increased (p<0.05) the partition coefficient of tamoxifen in comparison with treatment with 50% PG alone. Also, exposure of the SC to 5% terpenes in combination with 50% PG significantly increased (p < 0.05) the in vitro transepidermal water loss (TEWL) in comparison with 50% PG alone. Thus, an enhancement by menthone, eugenol, and limonene in the permeability of the SC to tamoxifen is due to lipid extraction and macroscopic barrier perturbation. Moreover, the effective diffusion coefficient of tamoxifen through the epidermis was enhanced following the treatment with either 5% eugenol/50%PG or 5% limonene/50%PG compared with 50%PG alone.
    Journal of Pharmaceutical Sciences 06/2000; 89(6):771-80. · 3.13 Impact Factor
  • M Bi, J Singh
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    ABSTRACT: The stability of [Arg(8)]-vasopressin (AVP) as a function of buffer pH, buffer concentration, salt concentration, temperature, and skin with and without enzyme inhibitors was investigated. AVP was analyzed by reverse-phase high-performance liquid chromatography. The results indicated that the buffer's pH affected the degradation rate of AVP. Buffer ions (H(2)PO(4)(-) and HPO(4)(2-)) and salt concentrations had no effect on the degradation of AVP. Maximum stability was achieved at pH 3.35 among pH values tested. The activation energy for the overall reaction was 21.5 kcal mol(-1) at pH 3.35. From the Arrhenius equation, the shelf-life of AVP at 25 degrees C and pH 3.35 was calculated to be 1.38 years. The degradation rate of AVP in the skin (area: 9 cm(2), thickness: 0.5 mm) was 0.22 h(-1). Bestatin (an aminopeptidase inhibitor) had the best stabilizing effect on the degradation of AVP by skin among the three enzyme inhibitors (i.e. aprotinin, bestatin, and leupeptin) studied. The degradation rate of AVP in the skin was reduced to 0. 059 h(-1) in the presence of bestatin in comparison with no inhibitor (0.22 h(-1)).
    International Journal of Pharmaceutics 04/2000; 197(1-2):87-93. · 3.99 Impact Factor
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    ABSTRACT: The use of transdermal iontophoresis is a promising technique for the systemic delivery of water soluble and ionic drugs of relatively large molecular size. The present study investigates the skin pre-treatment with Azone (laurocapram) and iontophoresis on the pharmacodynamic effect of timolol maleate (TM) in vivo in albino rabbits. The pharmacodynamic effect of TM was evaluated by transdermal delivery and compared with an intravenous (i.v.) administration. Iontophoresis of TM (0.1 mg/ml) produced a significant inhibition in the isoprenaline (ISP)-induced tachycardia. Iontophoresis with higher concentration of TM (1 mg/ml) produced a 100% inhibition of the ISP induced tachycardia. Pre-treatment of skin with Azone (3% v/v emulsion) eliminated the lag time and prolonged the duration of action of iontophoresis from 4 to 6 h. The AUC of Azone treated group was significantly higher than that of the untreated group (P<0.05). Further, the AUC with iontophoretic delivery and pre-treatment of Azone was comparable to that of intravenous TM (30 microg/kg). In conclusion, iontophoresis in combination with Azone can increase the transdermal delivery of TM, whereby the required transport rate can be achieved with a lower drug concentration.
    International Journal of Pharmaceutics 03/2000; 197(1-2):69-76. · 3.99 Impact Factor
  • M Bi, J Singh
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    ABSTRACT: The purpose of this investigation was to determine the stability of luteinizing hormone releasing hormone (LHRH) as a function of solution pH, temperature, and pig skin with and without enzyme inhibitors. LHRH, incubated with a 0.1 M phosphate buffer (pH 2.5-8.1), pig skin, and pig skin with enzyme inhibitors, was analyzed using reversed-phase high performance liquid chromatography. The solution's pH affected the rate constants of LHRH, following apparent first-order kinetics. Maximum stability was achieved at pH 6.05. Therefore, the effect of various temperatures (i.e., 65, 75, 80, and 90 degrees C) was studied on the stability of LHRH at pH 6.05. The activation energy for the overall reaction was 23.4 kcal/mol at pH 6.05. The shelf-life of LHRH at 25 degrees C and pH 6.05, calculated using the Arrhenius equation, was approximately 4 years. The rate constant of LHRH in the skin (area: 9 cm2; thickness: 0.5 mm) was 0.167 hr-1. Out of three inhibitors (i.e., aprotinin, bestatin, and leupeptin), bestatin had the best stabilizing effect on the degradation of LHRH by the skin. The rate constant of LHRH in the presence of bestatin was 0.082 hr-1. Sixty percent of LHRH was found to be degraded in the skin within 5 hr in the absence of enzyme inhibitors, whereas only 33% of LHRH was degraded in the presence of bestatin (an aminopeptidase inhibitor).
    Pharmaceutical Development and Technology 02/2000; 5(3):417-22. · 1.33 Impact Factor
  • Kaidi Zhao, Jagdish Singh
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    ABSTRACT: The purpose of this study was to investigate the mechanism(s) of percutaneous absorption enhancement of propranolol hydrochloride (PHCL) across porcine epidermis by terpenes (e.g. menthone and limonene) in combination with ethanol. The in vitro percutaneous absorption experiments were performed using Franz diffusion cells. The solubility of PHCL in control and enhancer solutions was determined through high-performance liquid chromatography. Partitioning of PHCL to powdered SC from control or enhancer solutions was also determined in order to investigate the binding of PHCL to the SC from the SC/enhancer system. Fourier transform infrared spectroscopy (FT-IR) was employed to study the biophysical changes in stratum corneum (SC) lipids. The in vitro macroscopic barrier properties were investigated by measuring transepidermal water loss (TEWL) using Tewameter. Five percent menthone or limonene in combination with ethanol (EtOH) (menthone/EtOH or limonene/EtOH) significantly increased (P<0.05) the flux of PHCL through porcine epidermis in comparison to the control (EtOH). The partitioning of PHCL to the SC from the SC/enhancer system was also significantly greater than the SC/control system. The above enhancers showed a decrease in the peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison with the untreated SC, indicating the SC lipids extraction. Menthone/EtOH and limonene/EtOH enhanced (P<0.05) the in vitro TEWL through the epidermis in comparison to the control. Thus, an enhancement in the flux of PHCL by menthone/EtOH and limonene/EtOH is due to SC lipid extraction, macroscopic barrier perturbation, and improvement in the partitioning of the drug to the SC.
    Journal of Controlled Release 12/1999; 62(3):359-66. · 7.63 Impact Factor
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    ABSTRACT: The present study was undertaken to explore the possibility of delivering bovine insulin in streptozocin (STZ)-induced diabetic rats by iontophoresis. Further, the effect of iontophoresis of monomeric human insulin analogue (r-DNA origin) on the plasma glucose level (PGL) of diabetic rats was studied. Iontophoresis of bovine insulin (10-200 IU/ml) was not effective in decreasing the PGL in untreated diabetic rats. Pretreatment of skin with oleic acid or menthol for 3 h followed by iontophoresis of bovine insulin also failed to produce a fall in PGL. Application of a depilatory cream for hair removal (24 h before the experiment), followed by iontophoresis of bovine insulin (10, 30 and 100 IU/ml) produced a concentration-dependent fall in PGL. Further, application of depilatory cream immediately before the experiment produced a substantial fall in PGL both by passive diffusion and iontophoresis. Depilatory cream might have drastically reduced the barrier function of skin such that conventional bovine insulin (dimer and hexamer) penetrates through the intact skin by iontophoresis and even by passive diffusion. Depilatory cream or the active components of depilatory cream may be useful as penetration enhancers for transdermal delivery of drugs especially macromolecules such as insulin. Iontophoresis of monomeric human insulin analogue (B9 Asp, B27 Glu) through intact skin (untreated) produced a significant fall in PGL in diabetic rats. Monomeric human insulin analogues which have low tendency to self aggregation may be promising candidates for the transdermal iontophoretic delivery of insulin.
    Journal of Controlled Release 06/1999; 59(1):99-105. · 7.63 Impact Factor
  • K S Bhatia, J Singh
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    ABSTRACT: The effect of enhancer(s) (e.g. ethanol (EtOH), 5% linolenic acid/EtOH, and 5% limonene/EtOH) and iontophoresis was investigated on the in vitro percutaneous absorption of luteinizing hormone releasing hormone (LHRH) and ultrastructure of human epidermis by transmission electron microscopy (TEM). 5% linolenic acid/EtOH or 5% limonene/EtOH significantly enhanced (P<0.05) the passive flux of LHRH through human epidermis in comparison to the control (no enhancer treated epidermis). Iontophoresis further increased the flux of LHRH through enhancer(s) treated epidermis. Iontophoretic flux of LHRH through 5% linolenic acid/EtOH and 5% limonene/EtOH treated epidermis was significantly (P<0.05) enhanced in comparison to iontophoretic flux through the control epidermis. TEM is the most efficient way to visualize the ultrastructure of the stratum corneum (SC). TEM results reveal that iontophoresis in combination with enhancers (e.g. linolenic acid/EtOH or and limonene/EtOH) transformed the highly compact cells of the SC into a looser network of filaments, disrupted the keratin pattern, and resulted in swelling of SC cell layers of human epidermis. Thus, linolenic acid/EtOH or limonene/EtOH in combination with iontophoresis increased the flux of LHRH through human epidermis by disrupting keratin pattern as well as loosening and swelling of SC cell layers.
    International Journal of Pharmaceutics 04/1999; 180(2):235-50. · 3.99 Impact Factor
  • A K Levang, K Zhao, J Singh
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    ABSTRACT: The effect of the solvent systems ethanol (EtOH), propylene glycol (PG) and combinations thereof was examined on the in vitro percutaneous absorption of the antithrombotic, aspirin, through porcine epidermis. Biophysical changes in the stratum corneum lipids were studied through the use of Fourier transform infrared (FTIR) spectroscopy. Macroscopic barrier properties of the epidermis were examined through the use of in vitro transepidermal water loss (TEWL). The flux of aspirin increased with increasing concentrations of EtOH in the solvent systems. The maximum flux of aspirin was achieved by 80% EtOH in combination with 20% PG beyond which (i.e. 100% EtOH) there was no increase in the flux. FTIR spectroscopic study was enacted in order to determine the biophysical properties of the stratum corneum when the solvents were applied. The FTIR spectra of the stratum corneum treated with 80% EtOH/20% PG showed a maximum decrease in absorbance for the asymmetric and symmetric C&z. sbnd;H peaks, which suggests a greater loss of the lipids in the stratum corneum layers. In vitro TEWL studies allowed an investigation into the macroscopic barrier integrity properties of the stratum corneum. The TEWL results indicated that each of the solvent systems significantly enhanced (P<0.05) in vitro TEWL in comparison to the control. In conclusion, 80% EtOH/20% PG enhanced the percutaneous absorption of aspirin by perturbing the macroscopic barrier integrity of the stratum corneum and through a loss of stratum corneum lipids.
    International Journal of Pharmaceutics 04/1999; 181(2):255-63. · 3.99 Impact Factor
  • K S Bhatia, J Singh
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    ABSTRACT: The purpose of this study was to investigate the effect of 5% terpenes (i.e., limonene, carvone, thymol, and cineole)/ethanol (EtOH) and iontophoresis on the in vitro permeability of luteinizing hormone releasing hormone (LHRH) through the porcine epidermis and biophysical changes in the stratum comeum (SC) lipids by fourier transform infrared (FT-IR) spectroscopy. Methods. The porcine epidermis was pretreated with enhancer for 2 h. The permeability measurement system included Franz diffusion cells, Ag/AgCl electrodes, and SCEPTOR iontophoretic power source. FT-IR spectroscopy was performed to assess the possible contribution of lipid extraction to the transport enhancement of LHRH. Terpenes in combination with EtOH significantly (p < 0.05) increased the flux of LHRH in comparison with the control (epidermis which was not enhancer treated). Iontophoresis further enhanced (p < 0.05) the flux of LHRH through terpenes/EtOH treated epidermis in comparison with their passive permeability. Reversibility studies showed that the post-recovery passive flux of LHRH through 5% limonene in EtOH/iontophoresis treated epidermis was significantly (p < 0.05) decreased but did not significantly recover to the baseline flux (i.e., flux through control epidermis). The SC treated with terpenes/ EtOH showed a decrease in peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison to untreated SC. A greater percent decrease in peak heights and areas was obtained by limonene/EtOH. However, treatment of the SC with terpenes/EtOH followed by iontophoresis did not further decrease the percentage of peak height and area over and above terpene/EtOH suggesting that iontophoresis alone does not cause SC lipid extraction. Terpenes/EtOH increased LHRH permeability by enhancing the extraction of the SC lipids. Iontophoresis synergistically enhanced the permeability of LHRH through terpenes/EtOH treated epidermis. Thus, terpenes can be used as chemical enhancers in combination with iontophoresis to enhance the transdermal delivery of peptides such as LHRH.
    Pharmaceutical Research 12/1998; 15(12):1857-62. · 4.74 Impact Factor
  • K Zhao, J Singh
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    ABSTRACT: The effect of chemical penetration enhancers (e.g., eugenol, d-limonene and menthone in combination with 50% ethanol) on the in vitro percutaneous absorption of tamoxifen through porcine epidermis has been investigated. The above enhancers significantly increased (p<0.05) the permeability coefficient of tamoxifen in comparison with the control (50% ethanol). Fourier transform infrared spectroscopy (FT-IR) was employed to investigate the biophysical changes in the stratum corneum (SC) lipids by the enhancer(s). FT-IR results showed that the treatment of the SC with enhancers did not produce a blue shift in the asymmetric and symmetric C-H stretching peak positions. However, all of the above enhancers showed a decrease in peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison with the untreated SC. A decrease in peak heights and areas is a measure of lipid extraction. Partitioning of tamoxifen to powdered SC from control and enhancer solutions was also determined. FT-IR and partitioning studies reveal that the enhancement in the permeability coefficient of tamoxifen by eugenol and d-limonene is due to lipid extraction and improvement in the partitioning of the drug to the SC. However, menthone enhanced the permeability of tamoxifen by increasing extraction of the SC lipids and not by improving the partitioning of the drug to the SC.
    Journal of Controlled Release 12/1998; 55(2-3):253-60. · 7.63 Impact Factor
  • H M Dani, J Singh
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    ABSTRACT: Cytochrome b5 is unmasked on the removal of ribosomes by chemical degranulation of rat liver microsomes. Reattachment of ribosomes to stripped membranes remasks this enzyme on the membrane surface. This haemoprotein may be involved either in the attachment of ribosomes to reticular membranes or in protein biosynthesis by membrane-bound ribosomes.
    Cell Biochemistry and Function 07/1998; 16(2):149-51. · 1.85 Impact Factor
  • S Puri, H M Dani, J Singh
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    ABSTRACT: Carcinogenicity of salivarty extracts of different types of tobaccos smoked and chewed in India and Pan Parag were tested using microsomal degranulation technique. Results obtained on the basis of RNA/protein ratios (Indices to confirm the detachment of ribosomes from microsomes) showed that tobaccos used for cigarette, bidi, hukah and chewing tobacco with lime as well as Pan Parag were positively carcinogenic. Two fractions out of 7 isolated chromatographically from salivary extract of chewing tobacco plus lime were found to be carcinogenic. Elemental and spectral analyses indicated that the fractions are possibly an aromatic compound with an aliphatic side chain and N-(buty1 nitrosamine)-1-(3-pyridyl)-4-hydroxy-1-butanone.
    Indian journal of experimental biology 06/1998; 36(5):483-7. · 1.20 Impact Factor
  • M. Bi, K. S. Bhatia, J. Singh
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    ABSTRACT: An isocratic technique was developed for the analysis of luteinizing hormone releasing hormone (LHRH) by high performance liquid chromatography (HPLC) using 210 nm UV detection, ZORBAX ODS column (4.6 mm × 15 cm), mobile phase (86% triethylamine phosphate buffer: 14% acetonitrile), and 1.5 mL/min flow rate. The coefficient of variation (C.V.) for precision and proportionality assays was lower than 5% for all concentrations studied. The detection limit of LHRH was 1 ng/mL.
    Journal of Liquid Chromatography & Related Technologies - J LIQ CHROMATOGR RELAT TECHNO. 01/1998; 21(10):1503-1509.
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    ABSTRACT: Benzyl alcohol (BA), a non-electrolyte, was selected as a probe permeant to investigate its iontophoretic transport through human epidermis. The flux of BA and [3H]water were greater during anodal than cathodal iontophoresis. Increases in current density enhanced the permeability coefficient of BA during iontophoresis. The greater permeability of BA during anodal iontophoresis than cathodal may be due to permselective nature of human epidermis at physiological pH 7.4 for positively charged buffer ions and hence, associated [3H]water and BA. Thus, it is possible to enhance and control the transdermal transport of non-electrolyte by iontophoresis. Scanning electron microscopy of the human epidermis treated with iontophoresis showed greater loosening of epidermal cells and distention in intercellular space with increasing current densities.
    International Journal of Pharmaceutics 01/1998; · 3.99 Impact Factor
  • S. Ganga, P. Ramarao, J. Singh
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    ABSTRACT: This study was attempted to investigate the effect of Azone on the transdermal iontophoretic transport of metoprolol tartrate (MPL) through human epidermis in vitro. Investigations were done to probe the mechanism of action of this enhancer, and to see whether there is any synergistic effect of this enhancer in conjunction with iontophoresis. Along with comparison of iontophoretic and passive transport of the drug in presence of the enhancer, parameters like steady state flux (Jss), permeability coefficient (Kp) and enhancement factors (E) were evaluated. It was found that both during passive diffusion and iontophoresis, Azone caused increased transport of the drug through human epidermis and the transport was increased 130-fold during iontophoresis compared to passive flux. These results were supported by scanning electron microscopy studies of the epidermis after experimentation.
    Journal of Controlled Release 10/1996; 42(1):57-64. · 7.63 Impact Factor
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    ABSTRACT: Two lectins purified from the tubers of Arisaema consanguineum Schott (ACA) and A. curvatum Kunth (ACmA) belonging to the monocot family Araceae were mitogenic for human peripheral blood mononuclear cells (PBMC) in the [3H]-thymidine uptake assay. ACA and ACmA had an optimum stimulatory concentration of 10-25 micrograms/ml and 50-100 micrograms/ml, respectively, as observed in PBMC from five different individuals. The mitogenic response of PBMC was inhibitable in a dose-dependent manner by asialofetuin. The lectins were T-cell specific, and stimulation kinetic studies using ACA and ACmA showed that they induce maximum thymidine uptake in PBMC at day 4 and 3, respectively.
    Immunological investigations 08/1996; 25(4):273-8. · 1.73 Impact Factor

Publication Stats

479 Citations
109.87 Total Impact Points

Institutions

  • 1996–2008
    • North Dakota State University
      Fargo, North Dakota, United States
  • 1998–2003
    • Panjab University
      • Department of Biochemistry
      Chandīgarh, Union Territory of Chandigarh, India
  • 1989–1999
    • Banaras Hindu University
      • Department of Pharmacology
      Benares, Uttar Pradesh, India
  • 1988–1996
    • Guru Nanak Dev University
      • • Department of Molecular Bio. & Bio-Chemistry
      • • Department of Physics
      Amritsar, State of Punjab, India
  • 1995
    • University of California, San Francisco
      • Department of Dermatology
      San Francisco, CA, United States