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Biomedical subjects

R P Gupta

Publications and source records attributed to R P Gupta.

At least 19 recordsLinked to original sources
PubMed2006

The changing spectrum of severe falciparum malaria: a clinical study from Bikaner (northwest India).

BACKGROUND & OBJECTIVES: Recently there were reports from all over India about changing spectrum of clinical presentation of severe malaria. The present study was planned to study the same in the northwest India. METHODS: This prospective study was conducted on patients of severe malaria admitted in a classified malaria ward of a tertiary care hospital in Bikaner, Rajasthan (northwest India) during 1994 and 2001. It included adult patients of both sexes belonging to all age groups. The diagnosis of Plasmodium falciparum was confirmed by demonstrating asexual form of parasites in peripheral blood smear. All patients were treated with i.v./oral quinine. The specific complications were treated by standard WHO protocol. The data for individual complications for both the years were analysed by applying chi-square test. RESULTS: In a prospective study in 1994 the spectrum of complication was dominated by cerebral malaria (25.75%) followed by jaundice (11.47%), bleeding tendencies (9.59%), severe anaemia (5.83%), shock (5.26%), Acute respiratory distress syndrome-ARDS (3.01%), renal failure (2.07%) and hypoglycemia (2.07%) whereas in 2001 it was dominated by jaundice (58.85%) followed by severe anaemia (26.04%), bleeding tendencies (25.52%), shock (10.94%), cerebral malaria (10.94%), renal failure (6.25%), ARDS (2.08%) and hypoglycemia (1.56%). The sharp difference for presence of jaundice and severe anaemia in 2001 and cerebral malaria in 1994 was statistically significant. Similarly, the important cause of mortality in 2001 was multiple organ dysfunction syndrome (71.10%) with predominant presentation of jaundice and renal failure, whereas in 1994, it was cerebral malaria (77.96%). INTERPRETATION & CONCLUSION: The observation of changing spectrum of severe malaria in this study and a significant increase in presentation with jaundice as an important manifestation is highly essential for primary, secondary and tertiary level health care providers for proper diagnosis and management.

Acute Disease↗
PubMed2003

Clinico-haematological and mineral studies on experimental maduramicin toxicity in chickens.

Clinico-haematological and mineral studies were carried out in experimental chickens given maduramicin medicated feed at 5 and 10 ppm for 21 days. Maduramicin medication in both medicated groups caused growth retardation. Clinical signs namely watery diarrhoea, depression, dullness and ruffled feathers were noticed in chickens from second week of the medication at 10 ppm but this effect was seen from third week in the birds given maduramicin at 5 ppm. Maduramicin medication caused significant reduction in haemoglobin in both the medicated group from day 14 and total erythrocyte count and packed cell volume in 10 ppm group on day 21. There was an increase in MCV in 10 ppm group on day 21 indicating macrocytic anaemia and decrease in mean corpuscular haemoglobin concentration (MCHC) in both the medicated groups indicating hypochromic anaemia. The leucopenia due to lymphopenia was observed in 10 ppm group on day 21. Maduramicin medication caused significant increase in serum Zn in 10 ppm group and decrease in Cu concentration in both the medicated groups from day 14. It is concluded that maduramicin caused toxic effects from day 14 in both the medicated groups.

Anemia, Hypochromic↗
PubMed2001

Alteration in cytoskeletal protein levels in sciatic nerve on post-treatment of diisopropyl phosphorofluoridate (DFP)-treated hen with phenylmethylsulfonyl fluoride.

Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, and a single dose (1.7 mg/kg, sc.) of this compound produces mild ataxia in hens in 7-14 days and a severe ataxia or paralysis (OPIDN) in three weeks. OPIDN is associated with axonal swelling and their degeneration. We have previously observed alteration in neurofilament (NF) protein levels in the spinal cord of DFP-treated hens. The main objective of this investigation was to study NF protein levels in the sciatic nerves (SN) of hens, in which OPIDN has been potentiated by phenylmethylsulfonyl fluoride (PMSF) post-treatment. PMSF is known to protect DFP-treated (1.7 mg/kg) hens from developing OPIDN if injected before, and potentiate OPIDN if injected after the administration of DFP (0.5 mg/kg). The potentiation of OPIDN was accompanied by earlier elevation of NF proteins in the SN particulate fraction. In contrast, SN supernatant fraction showed a transient fall in NF protein levels in potentiation OPIDN. Out of the two other cytoskeletal proteins (i.e., tubulin, tau) studied in this investigation, tubulin also showed earlier elevation in its level in the particulate fraction in potentiated OPIDN. The earlier elevation of NF protein levels in SN particulate fraction in potentiated OPIDN suggested the possible involvement of NFs in delayed neurotoxicity.

Animals↗
PubMed2001

Enhanced activity and level of protein kinase A in the spinal cord supernatant of diisopropyl phosphorofluoridate (DFP)-treated hens. Distribution of protein kinases and phosphatases in spinal cord subcellular fractions.

Diisopropyl phosphorofluoridate (DFP) is a type I organophosphorus compound and produces delayed neurotoxicity (OPIDN) in adult hens. A single dose of DFP (1.7 mg/kg, s.c.) produces mild ataxia in hens in 7-14 days, which develops into severe ataxia or paralysis as the disease progresses. We have previously shown altered expression of several proteins (e.g. Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) alpha-subunit, tau, tubulin, neurofilament protein (NF), vimentin, GFAP) and an immediate early gene (e.g. c-fos) in DFP-treated hens. Here we show an increase in protein kinase A (PKA) protein level and activity in the spinal cord at 1-day and 5-days time periods after DFP administration. We also determined the protein levels of protein kinase C (PKC), CaM kinase II and several phosphatases (i.e. phosphatase 1 (PP1), phosphatase 2A (PP2A), phosphatase 2B (PP2B) in the spinal cord of DFP-treated hens after 1, 5, 10, and 20 days). There was increase in CaM kinase II alpha subunit level after 10 and 20 days of treatment, and decrease in PKC level at 1-day and 20-days time periods in spinal cord mitochondria. In contrast, the cerebrum, which is resistant to DFP-induced axonal degeneration, did not show change in PKA and CaM Kinase II levels at any time period DFP post-administration. No alteration was found in the protein levels of PP1, PP2A, and PP2B at any time period. An early induction in PKA, which is an important protein kinase in signal transduction, followed by that of CaM kinase might be contributing towards the development of OPIDN in DFP-treated hens.

Animals↗
PubMed2001

Effect of prevention and potentiation of diisopropyl phosphorofluoridate (DFP)-induced delayed neurotoxicity on the mRNA expression of neurofilament subunits in hen central nervous system.

Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, which produces mild ataxia in 7-14 days and severe ataxia or paralysis in about 20 days (OPIDN) in hens. Previous studies in this laboratory have shown enhanced temporal expression of neurofilament (NF) subunit mRNAs in the spinal cord (SC) of DFP-treated hens. The main objective of this investigation was to study the effect of DFP administration on NF subunit mRNAs expression, when OPIDN is protected or potentiated by pre-treatment or post-treatment, respectively, with phenylmethylsulfonyl fluoride (PMSF). The hens were sacrificed 1, 5, 10, and 20 days after the last treatment. In contrast with enhanced mRNA expression of NF subunits reported in OPIDN, there was no alteration in the expression of NF subunits in the SC of PMSF-protected hens that did not develop OPIDN. PMSF post-treatment of DFP-treated hens, which enhanced delayed neurotoxicity produced by a low dose of DFP, exhibited decrease in the mRNA expression of NF subunits in SC at all time periods (1-20 days) of observation. The expression of NF subunits was also studied in the degeneration-resistant tissue cerebrum of treated hens. The results from protected hens suggested that temporal enhanced expression of NF subunit mRNAs in DFP-treated hens might be contributing to the development of OPIDN in hens. By contrast, PMSF post-treatment seemed to potentiate OPIDN by a mechanism different from that followed by DFP alone to produce OPIDN.

Animals↗
PubMed2000

Altered expression of neurofilament subunits in diisopropyl phosphorofluoridate-treated hen spinal cord and their presence in axonal aggregations.

Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, which produces organophosphorus ester-induced delayed neuropathy (OPIDN) in hen and other sensitive species. A single dose of DFP (1.7 mg/kg, sc.) produces mild ataxia in 7-14 days in hens, which develops into severe ataxia or paralysis with the progression of disease. OPIDN is associated with axonal swellings and degeneration of axons. This study was carried out to investigate the expression of neurofilament (NF) subunits in the spinal cord of DFP-treated hens. Hens were treated with a single dose of DFP and sacrificed 1, 5, 10, and 20 days post-treatment. Western blot analysis showed increased expression of middle molecular weight neurofilament protein (NF-M), and decreased expression of high molecular weight (NF-H) and low molecular weight (NF-L) neurofilament proteins in the 2 M urea extracts of spinal cord particulate fraction. These changes were observed within 24 h of DFP administration and persisted for 10-20 days. Thus, there was increase in the stoichiometry of NF-M:NF-L in the spinal cord of DFP-treated hens. Immunoprecipitation, cross-linking, and two-dimensional polyacrylamide gel electrophoresis showed the presence of heterodimers, but not heterotetramers, in the hen spinal cord extract. Immunohistochemical staining revealed the presence of all three NF subunits in the cytoskeletal inclusions in DFP-treated hen spinal cord cross-sections. The results suggested that each NF subunit might be accumulated by a different mechanism in the axonal aggregations of DFP-treated hen.

Animals↗
PubMed2000

Neurofilament-L is a protein phosphatase-1-binding protein associated with neuronal plasma membrane and post-synaptic density.

Far Westerns with digoxigenin-conjugated protein phosphatase-1 (PP1) catalytic subunit identified PP1-binding proteins in extracts from bovine, rat, and human brain. A major 70-kDa PP1-binding protein was purified from bovine brain cortex plasma membranes, using affinity chromatography on the immobilized phosphatase inhibitor, microcystin-LR. Mixed peptide sequencing following cyanogen bromide digestion identified the 70-kDa membrane-bound PP1-binding protein as bovine neurofilament-L (NF-L). NF-L was the major PP1-binding protein in purified preparations of bovine spinal cord neurofilaments and the cytoskeletal compartment known as post-synaptic density, purified from rat brain cortex. Bovine neurofilaments, at nanomolar concentrations, inhibited the phosphorylase phosphatase activity of rabbit skeletal muscle PP1 catalytic subunit but not the activity of PP2A, another major serine/threonine phosphatase. PP1 binding to bovine NF-L was mapped to the head region. This was confirmed by both binding and inhibition of PP1 by recombinant human NF-L fragments. Together, these studies indicate that NF-L fulfills many of the biochemical criteria established for a PP1-targeting subunit and suggest that NF-L may target the functions of PP1 in membranes and cytoskeleton of mammalian neurons.

Amino Acid Sequence↗
PubMed2000

C-fos mRNA induction in the central and peripheral nervous systems of diisopropyl phosphorofluoridate (DFP)-treated hens.

A single dose of diisopropyl phosphorofluoridate (DFP), an organophosphorus ester, produces delayed neurotoxicity (OPIDN) in hen. DFP produces mild ataxia in hens in 7-14 days, which develops into severe ataxia or paralysis as the disease progresses. Since, OPIDN is associated with alteration in the expression of several proteins (e.g., Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) alpha-subunit, tau, tubulin, neurofilament (NF) protein, vimentin, GFAP) as well as their mRNAs (e.g., NF, CaM kinase II alpha-subunit), we determined the effect of a single dose of DFP on the expression of one of the best known immediate-early gene (IEG), c-fos. C-fos expression was measured by Northern hybridization in cerebrum, cerebellum, brainstem, midbrain, spinal cord, and the sciatic nerves of hens at 0.5 hr, 1 hr, 2 hr, 1 day, 5 days, 10 days, and 20 days after a single 1.7 mg/kg, sc. injection of DFP. All the tissues (cerebrum, 52%; cerebellum, 55%; brainstem, 49%; midbrain, 23%; spinal cord, 80%; sciatic nerve, 157%) showed significant increase in c-fos expression in 30 min and this elevated level persisted at least up to 2 hr. Expressions of beta-actin mRNA and 18S RNA were used as internal controls. The significant increase in c-fos expression in DFP-treated hens suggests that c-fos may be one of the IEGs involved in the development of OPIDN.

Animals↗
PubMed2000

Effect of experimental zinc deficiency on immunological responses in Salmonella-infected guinea-pigs.

Cellular and humoral immune responses to Salmonella dublin infection were studied in guinea-pigs given zinc-deficient (ZnD) or zinc-adequate (ZnA) diet, containing 1.03 or 52.4 mg Zn/kg, respectively. On day 30, each animal of each dietary group was inoculated intraperitoneally with 10(6)viable cells of S. dublin strain 493. On the 15th day after infection, the immune responses were assessed by skin hypersensitivity (SH) tests and enzyme-linked immunosorbent assay (ELISA) for serum antibody with Salmonella -extract antigen. ZnD animals had significantly decreased ability to produce Salmonella -specific immediate and delayed type SH responses. These results were further substantiated by histological examination of skin sections. The ELISA indicated significantly lower Salmonella -specific serum antibody titres in ZnD animals than in ZnA animals. Mean viable counts of S. dublin in the liver and spleen of ZnD animals were significantly higher than those in ZnA animals.

Animals↗
PubMed2000

Free oxygen radicals and immune profile in newborns with lung diseases.

Respiratory difficulties constitute the commonest cause of morbidity in new born infants and pulmonary pathology is the most frequent autopsy finding. Various components, such as free oxygen radicals, immunoglobulins, and compliment systems, play an important role in immunopathology and immune defence. The aim of the present study was to assess free oxygen radical markers in neonatal lung diseases, studying their relationship with immune profile and ascertaining their relevance as predictors of clinical outcome. Full term newborns with respiratory distress and X-ray proven lung disease formed the study group. Blood samples were assessed for lipid peroxide (LPO), superoxide dismutase (SOD), glutathione peroxidase (GPx), immunoglobulins IgM and G, CD4 and CD8 subpopulations of T-lymphocytes. Levels of free radical markers were significantly higher in the study group. The humoral immune response was seen in terms of raised IgM levels in the study group which were still within the normal range. The cellular immune response was demonstrated by a raised percentage of CD4 T-lymphocytes which in turn accentuated the CD4:CD8 ratio. Higher levels of reactive oxygen species (ROS) were associated with a prolonged duration of respiratory distress and oxygen dependence. Since the free radicals have emerged as the major final common pathway of tissue injury, free radical ablation offers substantial potential for treatment; but whether antioxidants, scavengers and other modalities would have a significant impact on clinical outcome, remains to be investigated.

Biomarkers↗
PubMed1999

Enhanced mRNA expression of neurofilament subunits in the brain and spinal cord of diisopropyl phosphorofluoridate-treated hens.

Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, and a single injection of this compound (1.7 mg/kg, s.c.) produces delayed neurotoxicity (OPIDN) in hens in 7-14 days. Clinically, the disease is marked by hindlimb ataxia followed by paralysis after some time. A characteristic feature of this neuropathy is axonal swelling in the initial stages and comparative dissolution of the accumulated material and degeneration of distal axons with disease progression. Axonal swelling consists of aggregated neurofilaments, microtubules, and proliferated smooth endoplasmic reticulum. We studied expression of neurofilament (NF) mRNAs in brain regions and spinal cord to elucidate their role in OPIDN. There was a 50-200% increase in NF transcripts in 24 hr after DFP administration. The NF-L mRNA level started falling after 1-5 days and came down to control level in susceptible brain regions (i.e. cerebellum and brainstem) and spinal cord, but not in cerebral cortex, which does not show degeneration of axons in OPIDN. Cerebral cortex exhibited elevated levels of both NF-L and NF-M transcripts in DFP-treated hens throughout the period of observation. The induction of NF messages is consistent with the previously reported effect on extension of neurites of human neuroblastoma cells in culture. The transient increase in NF messages in susceptible tissues either may be responsible for the delayed degeneration of axons in OPIDN or is the result of interruption of regulatory signal due to progressive degeneration of axons.

Animals↗
PubMed1999

Tau phosphorylation by diisopropyl phosphorofluoridate (DFP)-treated hen brain supernatant inhibits its binding with microtubules: role of Ca2+/Calmodulin-dependent protein kinase II in tau phosphorylation.

Diisopropyl phosphorofluoridate (DFP) produces organophosphorus ester-induced delayed neurotoxicity (OPIDN) in hen, human, and other sensitive species. This is characterized by mild ataxia, which progresses to severe ataxia or paralysis in a few days. Ultrastructurally, OPIDN is associated with the degeneration of axons in central and peripheral nervous systems. Bacterially expressed longest human tau protein (htau40) phosphorylated by DFP-treated hen brain supernatant showed a decrease in microtubule binding in a shorter time than that phosphorylated by control hen brain supernatant. The decrease in htau40-microtubule binding observed on htau40 phosphorylation by the recombinant Ca2+/calmodulin (CaM)-dependent protein kinase II (CaM kinase II) alpha-subunit showed that CaM kinase II present in brain supernatant could participate in tau phosphorylation even in the absence of Ca2+/CaM and decrease tau-microtubule binding. In addition, use of htau40 mutants, htau40m1 (Ala416) and htau40m6 (Asp416), suggested that replacement of Ser416 by neutral or acidic amino acid produced some change in htau40 conformation that caused diminished binding with microtubules phosphorylated by brain supernatant in the presence of ethylene glycol bis(beta-aminoethyl ether) N, N'tetraacetic acid (EGTA). The change in conformation produced by Ser416 phosphorylation, however, was different from that produced by mutants since only nonmutated htau40 showed a significant decrease in binding with microtubules on phosphorylation by recombinant CaM kinase II in the presence of Ca2+/CaM compared to that obtained by phosphorylation in the presence of EGTA. This study showed that enhanced Ca2+/CaM-dependent protein kinase activity in DFP-treated hen brain supernatant may cause decreased tau-microtubule binding and destabilization of microtubules and may be involved in axonal degeneration in OPIDN.

Amino Acid Substitution↗
PubMed1999

Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis.

We describe 4 patients with acute disseminated encephalomyelitis (ADEM) who were treated with intravenous immunoglobulins (IVIg) after getting no immediate response from a 3-5 day course of high dose intravenous methylprednisolone. All had clinical features to suggest poor prognosis and MRI findings to indicate extensive white matter changes in the brain. Two patients who had spinal cord involvement as well, required ventilatory support during acute phase of the illness. All the 4 patients recovered dramatically. Recovery pattern suggested that IVIg might be useful in fulminant ADEM. Further trials are needed to look for the efficacy of IVIg alone and in combination with methylprednisolone in the treatment of ADEM.

Adolescent↗
PubMed1999

Experimental salmonellosis in guinea-pigs: haematological and biochemical studies.

Some haematological and biochemical parameters were studied in guinea-pigs infected intraperitoneally with Salmonella dublin 493 at 1 x 10(6) viable cells per animal. The infected animals showed a rise in temperature within 24 h, followed by depression and loss of body weight. On the 15th day post infection, haematological studies revealed a significant increase in the total leukocyte count due to both lymphocytosis and neutrophilia, and a decrease in the total erythrocyte count and haemoglobin concentration. There was also a significantly higher mean corpuscular volume and lower mean corpuscular haemoglobin concentration, indicating a macrocytic hypochromic anaemia. The infection caused a significant increase in alanine aminotransferase activity and creatinine, blood urea nitrogen and globulin concentrations, and a decrease in albumin and triiodothyronine. There was no significant effect on serum total protein or on thyroxine, or in the activity of aspartate aminotransferase in the serum.

Alanine Transaminase↗
PubMed1998

Tau proteins-enhanced Ca2+/calmodulin (CaM)-dependent phosphorylation by the brain supernatant of diisopropyl phosphorofluoridate (DFP)-treated hen: tau mutants indicate phosphorylation of more amino acids in tau by CaM kinase II.

Diisopropyl phosphorofluoridate (DFP) produces organophosphorus ester-induced delayed neurotoxicity (OPIDN) in hen, human, and other sensitive species. A single dose of DFP (1.7 mg/kg, s.c.) produces mild ataxia in 7-14 days in hens, followed by progression to severe ataxia or paralysis. We studied the effect of DFP administration on Ca2+/calmodulin-dependent phosphorylation of tau proteins by the brain supernatants of control and DFP-treated hens. Brain supernatants from DFP-treated hens showed enhanced in vitro phosphorylation of htau40 and its various mutants, but no change in the two-dimensional phosphopeptide pattern, when compared to control hen brain supernatants. Analysis of tau mutants phosphorylated by brain supernatant and recombinant CaM kinase II alpha-subunit showed that (1) brain supernatant CaM kinase II is mainly responsible for the phosphorylation of Ser416, (2) Ser356, but probably not Ser262, is phosphorylated by CaM kinase II, (3) no amino acid between Lys395-Ala437 except Ser416 is phosphorylated by CaM kinase II, (4) a number of amino acids in the tau molecule, which are phosphorylated by the brain supernatant in the absence of Ca2+/calmodulin are also mildly phosphorylated by CaM kinase II. The enhanced Ca2+/calmodulin-dependent phosphorylation of tau proteins by brain supernatant of DFP-treated hens that includes phosphorylation of a number of amino acids is likely to alter the functional properties of tau proteins in OPIDN. The hyperphosphorylated tau may destabilize microtubules, alter axonal transport, and result in degeneration of axons in OPIDN.

Amino Acid Substitution↗
PubMed1998

cDNA cloning and sequencing of Ca2+/calmodulin-dependent protein kinase IIalpha subunit and its mRNA expression in diisopropyl phosphorofluoridate (DFP)-treated hen central nervous system.

Diisopropyl phosphorofluoridate (DFP) produces delayed neurotoxicity, known as organophosphorus ester-induced delayed neurotoxicity (OPIDN), in hen, human, and other sensitive species. A single dose of DFP (1.7 mg/kg, se.) produces first mild ataxia followed by paralysis in 7-14 days in hens. DFP treatment also increases in vitro autophosphorylation of Ca2+ calmodulin-dependent protein kinase II (CaM kinase II) and the phosphorylation of several cytoskeletal proteins in the hen brain. To investigate whether increase in CaM kinase II activity is associated with increased expression of its mRNA, we cloned and sequenced CaM kinase II alpha subunit cDNA, and used it to study CaM kinase II expression in brain regions and spinal cord. Hen CaM kinase II alpha subunit differs in 7 amino acids from that of rat CaM kinase II. Its mRNA occurs predominantly as a 6.7 kb message, which is very close to that of human CaM kinase II alpha subunit. Northern blot analysis showed a transient increase in CaM kinase II alpha subunit mRNA in the cerebellum and spinal cord of DFP-treated chickens. The increase in CaM kinase II mRNA expression is consistent with the previously reported increase in its activity in brain and spinal cord, and its increased expression only in cerebellum and spinal cord, which are sensitive to the Wallerian-type degeneration characteristic of OPIDN, suggests the probable role of this enzyme in delayed neurotoxicity.

Amino Acid Sequence↗