Biomedical subjects

P Sharma

Publications and source records attributed to P Sharma.

At least 91 records · Page 5Linked to original sources

PubMed2001

Aluminum bioavailability from drinking water is very low and is not appreciably influenced by stomach contents or water hardness.

The objectives were to estimate aluminum (Al) oral bioavailability under conditions that model its consumption in drinking water, and to test the hypotheses that stomach contents and co-administration of the major components of hard water affect Al absorption. Rats received intragastric 26Al in the absence and presence of food in the stomach and with or without concomitant calcium (Ca) and magnesium (Mg) at concentrations found in hard drinking water. The use of 26Al enables the study of Al pharmacokinetics at physiological Al concentrations without interference from 27Al in the environment or the subject. 27Al was intravenously administered throughout the study. Repeated blood withdrawal enabled determination of oral 26Al bioavailability from the area under its serum concentrationxtime curve compared to serum 27Al concentration in relation to its infusion rate. Oral Al bioavailability averaged 0.28%. The presence of food in the stomach and Ca and Mg in the water that contained the orally dosed 26Al appeared to delay but not significantly alter the extent of 26Al absorption. The present and published results suggest oral bioavailability of Al from drinking water is very low, about 0.3%. The present results suggest it is independent of stomach contents and water hardness.

Administration, Oral↗

PubMed2001

Alterations in signal transduction cascade in young and adult rat brain and lymphocytes.

Signal transduction cascade, phosphoinositide metabolism, and protein kinases were studied from discrete areas of rat brain like cerebral hemispheres, cerebellum, brainstem, and diencephalon as well as lymphocytes isolated from three different age groups of rats; young (1 month), young adult (3-4 months), and adult (12 months) rats. The activities of protein kinase A, protein kinase C, phospholipase A(2) and phospholipase C and inositol 1, 4, 5-triphosphate, diacylglycerol, cyclic adenosine monophosphate contents were assayed from different brain areas and lymphocytes from these three age group rats. An upregulatory effect on the signal transduction system was observed from 1 month to 3-4-month age group, whereas, the brain tissue and lymphocytes of adult rats showed lower contents and activities of signal transduction components as compared to young adults. In view of the established 'cross talk' between signal transduction system, the present results suggests that molecular/cellular changes in brain and immune cells signal transduction pathway along with neuronal cell loss may contribute to age-related decline in nervous as well as immune system functions.

Aging↗

PubMed2001

In vitro hemolysis of human erythrocytes -- by plant extracts with antiplasmodial activity.

Human erythrocytes were exposed in a dose dependent manner to various ethanolic plant extracts, and fractions obtained from plant parts of Calotropis procera (Ait.) R. Br. and the gum--oleo resin of Commiphora wightii (Arnott.) Bhand. These have been screened for in vitro schizontocidal activity and graded with respect to their 50% inhibitory concentration (IC(50)) derived from the twofold serial dilution of the dose range 0.0625--2 mg/ml. An attempt had been made to relate their antiplasmodial activity with their cytotoxicity as represented by the in vitro rate of hemolysis. Intact erythrocytes were found to respond with a dose--time-integral and fitted to models of pseudo first-order reaction, Michaelis--Menten equation and Hill equation with k(1), k(2) and k(3) as their rate constants, respectively. Hemolysis isotherms of flower and root of C. procera and gum--oleo resin of C. wightii extracts were representative. Erythrocytic membrane instability is possibly a major factor as has been earlier reported with ethanol and chloroquine for the cytotoxicity of these plant extracts.

Erythrocytes↗

PubMed2001

Direct activation of cloned K(atp) channels by intracellular acidosis.

ATP-sensitive K(+) (K(ATP)) channels may be regulated by protons in addition to ATP, phospholipids, and other nucleotides. Such regulation allows a control of cellular excitability in conditions when pH is low but ATP concentration is normal. However, whether the K(ATP) changes its activity with pH alterations remains uncertain. In this study we showed that the reconstituted K(ATP) was strongly activated during hypercapnia and intracellular acidosis using whole-cell recordings. Further characterizations in excised patches indicated that channel activity increased with a moderate drop in intracellular pH and decreased with strong acidification. The channel activation was produced by a direct action of protons on the Kir6 subunit and relied on a histidine residue that is conserved in all K(ATP). The inhibition appeared to be a result of channel rundown and was not seen in whole-cell recordings. The biphasic response may explain the contradictory pH sensitivity observed in cell-endogenous K(ATP) in excised patches. Site-specific mutations of two residues showed that pH and ATP sensitivities were independent of each other. Thus, these results demonstrate that the proton is a potent activator of the K(ATP). The pH-dependent activation may enable the K(ATP) to control vascular tones, insulin secretion, and neuronal excitability in several pathophysiologic conditions.

ATP-Binding Cassette Transporters↗

PubMed2001

Fifteen cases of t(1;19)(q23;p13.3) identified in an Australian series of 122 children and 80 adults with acute lymphoblastic leukemia.

The t(1;19)(q23;p13) has been reported in up to 6% of cytogenetically abnormal cases of acute lymphoblastic leukaemia (ALL), associated with a pre-B-ALL phenotype. In the 5-year period 1995-1999, we detected t(1;19) in 13 children and 2 adults with newly diagnosed ALL. This represented 10% of pediatric and 2.5% of adult diagnostic ALL samples successfully cultured in one center during this time. There were 9 males and 6 females. The mean age at diagnosis for the 13 children was 6.5 years (range 1.5 to 14 years) and the 2 adults were aged 42 and 45 years. The unbalanced t(1;19) occurred in 7 of 13 children (54%), contrary to the reported excess of unbalanced translocations at 75%; both adults had the unbalanced translocation. At diagnosis, the t(1;19) was the sole abnormality in 4 patients (26%), and in the remainder (74%) was part of a complex karyotype, which included i(7q) (2 patients), hyperdiploidy (2 patients) and del(6q) (2 patients). Correlation of karyotype with white cell, blast and platelet counts, cell surface markers, initial response to chemotherapy and short-term outcome showed no difference between the balanced and unbalanced forms of the translocation in children or whether t(1;19) was present as the sole abnormality or part of a complex karyotype.

Adolescent↗

PubMed2001

A review of plant species assessed in vitro for antiamoebic activity or both antiamoebic and antiplasmodial properties.

The resurgence of the protozoal diseases amoebiasis and malaria has been known to occur, from time to time, in endemic and epidemic proportions all over the world. Furthermore, the import of these individual pathogens to other areas from tropical regions encourages these protozoal diseases to occur on a global scale with considerable associated mortality and morbidity. From time immemorial, the cure of these diseases has been attempted with the use of traditional plant products, derived from such species as are available within local habitats and ecosystems, and dependent on their host community for their conservation. Scientific validation and in vitro investigation, continues to be an important requirement for drug development, particularly with the emergence of resistance and cross resistance to some standard drugs used in such protozoal diseases. This paper provides a comparative compilation of the various studies reported between 1982 and 1999, on plants with antiamoebic activities and those which possess both antiamoebic and antiplasmodial activities. The results suggest that it is advisable to increase efforts towards the conservation of such plants, in order to retain their economic and therapeutic significance.

Amebicides↗

PubMed2001

A minisatellite sequence in the upstream region of the DURA3 gene from the halotolerant yeast Debaryomyces hansenii.

The URA3 gene of Debaryomyces hansenii, encoding orotidine 5'-phosphate decarboxylase enzyme, was isolated by complementation in the yeast Saccharomyces cerevisiae. The deduced amino acid sequence is highly similar to Ura3 proteins from other yeast and fungal species. Analysis of the region upstream of the coding sequence revealed the presence of AG-rich minisatellite DNA sequences. In addition, upstream of the DURA3 sequence, we have found the 3'-terminal of a gene encoding a GEA2-like protein.

Amino Acid Sequence↗

PubMed2001

Nitric oxide- and oxygen-derived free radical generation from control and lipopolysaccharide-treated rat polymorphonuclear leukocyte.

Previous studies from this lab have shown NO-mediated modulation of free radical generation from polymorphonuclear leukocytes (PMNs), following hypoxic-reoxygenation as well as in the normoxic cells. The present study is an attempt to investigate further the regulation of NO and free radical generation in the lipopolysaccharide (LPS)-treated PMNs. PMNs were isolated from the rat blood and peritoneal cavity, 4 h after LPS (1 mg/kg, i.p.) treatment. Nitric oxide synthase (NOS) activity and nitrite content were increased in the peripheral and peritoneal PMNs following LPS treatment. An increase in the apparent V(max) for l-arginine uptake was also observed in the LPS-treated peripheral PMNs, while peritoneal PMNs exhibited increase in both apparent V(max) and affinity for l-arginine. Synthesis of nitrite did not augment after increasing the availability of substrate to control PMNs, however, peripheral and peritoneal PMNs from LPS-treated rats utilized l-arginine more efficiently for nitrite synthesis. NOS activity, l-arginine uptake, and its utilization were maximal in the peritoneal PMNs. Arachidonic acid (AA, 1 x 10(-6) M)-induced free radical generation from PMNs was also enhanced significantly after LPS treatment. Preincubation of PMNs with nitrite elevated the free radical generation and myeloperoxidase (MPO) release. MPO and antioxidant enzyme activity in the PMNs was significantly augmented after LPS treatment. NOS inhibitors, aminoguanidine and 7-nitroindazole, inhibited arachidonic acid-induced free radical generation from LPS treated PMNs. The results obtained thus indicate that augmentation of free radical generation from rat PMNs following LPS treatment appears to be regulated by NO and MPO.

Animals↗

PubMed2001

Current status of ablative therapies in esophageal disorders.

Endoscopic ablative therapies for esophageal diseases have been used for palliation of inoperable esophageal cancer, but their use in eradication of early esophageal cancer and Barrett's esophagus (with and without dysplasia) has been reported in recent publications. Pharmacologic and surgical treatment of reflux symptoms in patients with Barrett's esophagus has not consistently reversed the metaplastic epithelium. This has led investigators to try different modalities of local injury to the columnar mucosa in an acid-reduced environment. Endoscopic reversal of Barrett's esophagus (visual replacement of columnar mucosa by squamous mucosa) is more readily achievable than complete histologic reversal. Preliminary data show that endoscopic reversal of Barrett's esophagus can be achieved, but intestinal metaplasia underlying the new squamous mucosa is reported in almost all series. Incidence of adenocarcinoma in patients with Barrett's without dysplasia is probably so low that endoscopic ablation as a therapy cannot be advocated outside of study protocols. Endoscopic therapy as a definitive treatment for patients with high-grade dysplasia (HGD) and/or early adenocarcinoma holds promise, especially in older patients with comorbid illnesses. Future long-term randomized studies are needed to determine whether ablative therapies can provide an alternative approach for patients with HGD and early cancer. Advanced cancers that are not resectable for cure can be effectively treated by endoscopic therapy for palliation of dysphagia.

Adenocarcinoma↗

PubMed2001

Complex variant t(4;11) characterized by fluorescence in situ hybridization in infant acute lymphoblastic leukemia.

A 6-month-old girl was diagnosed with acute lymphoblastic leukemia (ALL). Chromosome analysis of bone marrow aspirate showed 46,XX,t(4;11)(q21;q23) with an atypical appearance of the 11p on the der(11) chromosome. FISH studies to fully characterize the translocation utilised 8 probes: whole chromosome painting probes for chromosome 11 and chromosome 4; separate chromosome 11 short arm and long arm paints; specific subtelomere probes from 11p, 11q, and 4q; MLL gene probe. Taken together, the results indicated a two-step abnormality: an initial standard t(4;11)(q21;q23), followed by another t(4;11)--this time, between the two derivative chromosomes. The MLL gene was split by the first translocation and its position altered by the second.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Routine fluorescence in situ hybridization with the MLL probe does not reliably detect two separate signals on one chromosome 11 in patients with trisomy 11.

Trisomy 11 is considered to be a rare cytogenetic abnormality in myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). Duplication of the MLL gene (localized to 11q23) has been found on one chromosome 11 in patients with trisomy 11, detected by DNA techniques. We investigated copy number of MLL in seven patients with trisomy 11 to see if duplication could be assessed by the detection of two separate signals on fluorescence in situ hybridization (FISH). If so, FISH could provide a quick easy screen of MLL status in routine referrals. The diagnostic bone marrow aspirate showed trisomy 11 in five adult patients with MDS/AML as part of a complex karyotype and in two children with acute lymphoblastic leukemia (ALL) as part of a hyperdiploid karyotype. Fluorescence in situ hybridization utilized the suspensions remaining after the cytogenetic harvest. Two FISH probes were used on the adult patients (MLL - Oncor and Vysis), and one (Vysis) for the two children with ALL. Analysis showed that the proximity of the two putative hybridization signals made it very difficult to unambiguously see two separate signals. The hybridisations (Oncor probe) were convincing of MLL duplication (namely two distinct signals) in only one patient, but this was not borne out with the other MLL probe (Vysis). We conclude that conventional FISH with MLL probe is not suited to act as a screen for MLL duplication in patients with trisomy 11.

Adult↗

PubMed2001

Acute transient bilateral diabetic posterior subcapsular cataracts(1).

A 62-year-old man in whom diabetes was recently detected presented with visually significant, bilateral posterior subcapsular cataracts within days of initiating antihyperglycemic therapy. With efficient control and a stable serum glucose level, the cataracts started regressing. Except for a few scattered opacities, the patient was left with essentially clear lenses. Visual acuity of counting fingers at 2 ft in the right eye and 20/63 in the left eye improved to 20/20 in both eyes within 5 weeks.

Acute Disease↗

PubMed2001

Ascorbate reduces superoxide production and improves mitochondrial respiratory chain function in human fibroblasts with electron transport chain deficiencies.

The present paper attempts to ascertain the role of ascorbate on the generation of superoxide radicals in skin fibroblasts of patients with deficiency of mitochondrial respiratory chain enzymes. Fibroblast cell lines were grown with or without ascorbate for the last 48 h of their growth period. The amount of superoxide radical production in cells was measured by the reduction of nitroblue tetrazolium and the activities of respiratory chain enzymes were examined in isolated fibroblast mitochondria. The results indicated a significant inverse correlation between the amount of superoxide radicals and the specific activities of complexes I-III and II-III of the respiratory chain. The ascorbate treatment of fibroblasts from control subjects did not show any effect on either superoxide radical production or respiratory chain enzymes' activities. While in patient's fibroblasts, this vitamin significantly decreased the superoxide radicals and increased the specific activities of I-III and II-III complexes but not complex IV. These observations indicate that superoxide radicals are increased in patients with deficient respiratory chain enzymes in their fibroblasts and ascorbate can prevent the loss of these enzymes by acting on the selected sites in the respiratory chain, which are related to the production of free radicals.

Journal Article↗

PubMed2001

Isolation of the first putative peroxidase cDNA from a conifer and the local and systemic accumulation of related proteins upon pathogen infection.

Peroxidases are associated with the active defence reactions in higher plants in response to foreign organisms. They are involved in the oxidation of phenolic compounds in cell walls, polymerization of lignin and suberin, and in several other oxidation processes but the exact function of individual peroxidases is not known. We have isolated a cDNA encoding the putative defence-related and basic plant peroxidase SPI2 (spruce pathogen-induced 2), with an estimated molecular mass of 34 kDa, from roots of Norway spruce (Picea abies) seedlings. This is the first description of the isolation of a complete cDNA encoding a putative peroxidase from a gymnosperm. The transcript was present in the roots of healthy seedlings, and during infection with the pathogen Pythium dimorphum there was a rapid initial increase followed by a dramatic reduction of the transcript. The 34 kDa mature SPI2 protein was detected in both the developing root and shoot of healthy seedlings and increased amounts of SPI2 and increased accumulation of highly basic peroxidase isoforms was observed in roots after infection. In addition, two SPI2-related proteins with apparent molecular masses of 38 and 39 kDa, were also detected. Both these proteins accumulated in roots only after infection, and the 39 kDa protein was in addition detected in shoots of root-infected seedlings. Thus, both SPI2 and the SPI2-related proteins accumulate as a local response, in roots, and as a systemic response to infection the 39 kDa protein accumulates in the shoot.

Amino Acid Sequence↗

PubMed2001

Small incision trabeculectomy: experiences with this new procedure for glaucoma surgery in Indian eyes.

PURPOSE: The purpose of this study was to evaluate the potential advantages and disadvantages, success rate and complications of this new procedure for glaucoma surgery, which includes the formation of a filtration fistula without any dissection of the Tenon's capsule; as an alternative to trabeculectomy with or without pharmacological wound modulation. METHODS: Small Incision Trabeculectomy avoiding Tenon's capsule was performed in 40 glaucomatous eyes through a 2.5 mm limbal incision and intraocular pressure was monitored serially over a period of 12 months. RESULTS: The mean postoperative intraocular pressure (16.60+/-5.93 mmHg) at 12 months follow-up was significantly lower than the mean preoperative IOP (30.20+/-10.70 mmHg). Thirty-six eyes (90%) had IOP less than 22 mmHg without antiglaucoma medications at the end of the 12-month follow-up. Blebs were pale and diffusely elevated. No serious complications were encountered. CONCLUSION: This new technique is a low-cost and safe alternative to conventional trabeculectomy that effectively reduces intraocular pressure. The use of a small 2.5 mm incision which obviates the dissection of the Tenon's capsule and subsequent subconjunctival fibrosis, the absence of requirement of any sophisticated instruments, and the absence of any major complications which are encountered with the use of anti-metabolites entails that this procedure be performed more often in glaucomatous eyes needing filtration surgery.

Adult↗

PubMed2001

Characterization of the phosphorylation sites of the squid (Loligo pealei) high-molecular-weight neurofilament protein from giant axon axoplasm.

Axonal caliber in vertebrates is attributed, in part, to the extensive phosphorylation of NFM and NFH C-terminal tail domain KSP repeats by proline-directed kinases. The squid giant axon, primarily involved in rapid impulse conduction during jet propulsion motility, is enriched in squid-specific neurofilaments, particularly the highly phosphorylated NF-220. Of the 228 serine-threonine candidate phosphate acceptor sites in the NF-220 tail domain (residues 401-1220), 82 are found in numerous repeats of three different motifs SAR/K, SEK/R, K/RSP, with 62 of these tightly clustered in the C-terminal repeat segment (residues 840-1160). Characterization of the in vivo NF-220 phosphorylated sites should provide clues as to the relevant kinases. To characterize these sites, proteolytic digests of NF-220 were analyzed by a combination of HPLC, electrospray tandem mass spectrometry and database searching. A total of 53 phosphorylation sites were characterized, with 47 clustered in the C-terminal repeat segment (residues 840-1160), representing 76% (47/62) of the total acceptor sites in the region. As in mammalian NFH, approximately 64% of the K/RSP sites (14/22) in this region were found to be phosphorylated implicating proline-directed kinases. Significantly, 78% of serines (31/40) in the KAES*EK and EKS*ARSP motifs were also phosphorylated suggesting that non proline-directed kinases such as CKI may also be involved. This is consistent with previous studies showing that CKI is the principal kinase associated with axoplasmic NF preparations. It also suggests that phosphorylation of large macromolecules with multiple phospho-sites requires sequential phosphorylation by several kinases.

Amino Acid Sequence↗

PubMed2001

Methylene blue chromoendoscopy for detection of short-segment Barrett's esophagus.

BACKGROUND: The yield of intestinal metaplasia (IM) with randomly obtained biopsy specimens in patients with short lengths of columnar-appearing mucosa in the distal esophagus is low (30%-50%). Vital staining would be beneficial if it identified more patients with short-segment Barrett's esophagus (SSBE). Our aim was to compare the confirmation of IM in patients with suspected SSBE (columnar-appearing mucosa <3 cm in length) by using methylene blue (MB)-directed versus random biopsies. METHODS: Consecutive patients undergoing EGD in whom columnar-appearing mucosa less than 3 cm in length was visualized underwent MB staining. Stained areas within suspected SSBE segments were targeted for biopsies. All biopsy specimens were stained with H & E with alcian blue at pH 2.5 and evaluated by a single pathologist. A historical control group (different from patients undergoing MB staining) consisted of patients with less than 3 cm of columnar-appearing mucosa in whom biopsy specimens were obtained randomly without MB staining. RESULTS: The MB group included 75 patients (mean age 63.8 +/- 10.9 years) with a mean length of columnar-appearing mucosa of 1.2 cm (range 0.5-2.5 cm). The control group included 83 patients (mean age 60.5 +/- 12.9 years) with a mean length of columnar-appearing mucosa of 1.16 cm (range 0.5-2.5 cm). IM (i.e., confirmed SSBE) was detected in 61% of the MB group versus 42% of the control group (p = 0.0237). Patients in the MB group required significantly fewer biopsies (4.3 +/- 1.5 vs. 5.1 +/- 12.3, p = 0.0162). Confirmation of IM by length was as follows: less than 1 cm (irregular Z line), MB 17.4% versus control 25% (p = 0.73); 1 to less than 2 cm, MB 77% versus control 45% (p = 0.03); 2 to less than 3 cm, MB 90% versus control 58% (p = 0.02). CONCLUSIONS: MB chromoendoscopy significantly increases the detection of IM and requires fewer biopsies in patients with suspected SSBE with greater than 1 cm of columnar-appearing mucosa. It does not appear to be beneficial in patients with irregular Z lines (<1 cm).

Barrett Esophagus↗

PubMed2001

Entry, half-life, and desferrioxamine-accelerated clearance of brain aluminum after a single (26)Al exposure.

The objectives of our study were to estimate the percentage of aluminum (Al) that enters the brain, the half-life of brain Al, and the ability of an Al chelator to reduce brain Al. Rats received an iv infusion of Al transferrin, the primary Al species in plasma, or Al citrate, the predominant small molecular weight Al species in plasma. The infusion contained approximately 0.2-0.3 nCi (0.4-0.6 nmol) (26)Al, enabling the study of Al distribution into and retention by the brain at physiological Al concentrations. Some Al transferrin-infused rats received ip injections of the Al chelator desferrioxamine (DFO), 0.15 mmol/kg, three times weekly. The others received saline injections. The rats were euthanized from 4 hr to 4 days (Al citrate) or 256 days (Al transferrin) later. Brain (26)Al was determined by accelerator mass spectrometry. Peak brain (26)Al concentration was approximately 0.005% of the (26)Al dose in each gram of brain, irrespective of Al species administered. In the absence of DFO treatments, brain (26)Al concentration decreased with a half-life of approximately 150 days. The brain Al half-life in the DFO-treated rats was approximately 55 days. The results show a small fraction of Al in blood enters the brain, where it persists for a long time. The ability of repeated DFO treatments to modestly accelerate the reduction of brain Al is consistent with the necessity of prolonged DFO therapy to significantly reduce Al-induced dialysis encephalopathy.

Aluminum↗