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Biomedical subjects

D Sen

Publications and source records attributed to D Sen.

At least 37 records · Page 2Linked to original sources

[Gastrointestinal hemorrhage due to traumatic superior mesenteric artery aneurysm (case report)].

We report the case of a 21-year-old male patient with superior mesenteric artery aneurysm due to missed arterial injuries, its complications of enteric fistula and results of surgical treatment. The aneurysm was excised, enteric fistula was closed and aorta-mesenteric bypass using saphenous vein graft was performed. The hemorrhage became masked because of the tamponade in the mesentery during penetrating abdominal injury and initial surgery, and the late complication of false aneurysm came on the scene in follow up. Aorta-mesenteric bypass by a transmesenteric approach provides successful result in surgical treatment of superior mesenteric artery aneurysm.

Adult↗

Non-diabetic renal disease in patients with type 2 diabetes mellitus.

OBJECTIVES: A wide spectrum of non-diabetic renal diseases (NDRD) are reported to occur in patients with type 2 diabetes mellitus. However, the prevalence and nature of NDRD in type 2 diabetics is not widely documented in our country. Therefore, the objectives of this study were to analyse prevalence and spectrum of non-diabetic renal disease in type 2 diabetic patients. METHODS: Two hundred sixty type 2 diabetic with clinical renal diseases were screened for evidence of NDRD, between April 1997 to March 1999. Renal disease other than diabetic nephropathy was found in 32 (12.3%) patients. Their (male 23; female 9) age ranged between 35-72 (mean 54.15+/-10.3) years. The duration of diabetes was < 5 years in 14 (43.7%), between 5-9 years in 8 (25%) and > 10 years in 10 (31.2%) patients. RESULTS: The presenting clinical syndromes were : chronic renal failure 15 (47%), acute nephritic syndrome 6 (18.7%), nephrotic syndrome 5 (15.6%), acute renal failure 4 (12.5%) and rapidly progressive glomerulonephritis (RPGN) in 2 (6.2%) cases. Overall, incidence of glomerular (46.8%) and tubulo-interstitial lesions (53.2%) were almost equal in type 2 diabetes patients. The spectrum of non-diabetic renal diseases includes : primary isolated glomerulopathy 12 (37.5%); mesangioproliferative GN superimposed on diabetic glomerulosclerosis (DGS) in 3 (9.3%); acute tubulo-interstitial nephropathy (TIN) 4 (12.5%); chronic TIN 10 (31.25%) and three patients had chronic pyelonephritis. Diabetic retinopathy was absent in 22 (69%) cases where 10 (31%) patients had background diabetic retinopathy. None of the patients with non-diabetic glomerular disease had diabetic retinopathy, except two who had DGS in addition to mesangioproliferative GN on renal biopsy. The background diabetic retinopathy was seen in 47% of patients with TIN without clinical evidence of diabetic nephropathy. The recovery of renal function or clinical improvement was observed in 47% of patients with NDRD with institution of appropriate treatment. CONCLUSION: The prevalence of NDRD was 12.3% in our type 2 diabetic patients. Both non-diabetic glomerulopathy (47%) and tubulo-interstitial nephropathy (53%) can occur with nearly equal frequency in such patients. It is also gratifying to diagnose and treat NDRD in type 2 diabetics in selected cases.

Adult↗

Use of intrinsic binding energy for catalysis by a cofactor-independent DNA enzyme.

The concept of the Circe effect, according to which an enzyme's substrate-binding energy is utilized to destabilize the substrate towards the reaction transition state, has been shown to be a relevant catalytic strategy for naturally occurring protein enzymes and for two ribozymes that use nucleotide-based substrates and metal ion cofactors. We wished to investigate whether such a catalytic strategy extends even to divergent and unevolved catalysts constructed from biopolymers. We examined the properties of a small, in vitro selected, and cofactor-independent DNA enzyme, PS5.M, which catalyzes porphyrin metallation. The metallation reaction is unique, in that the energies for binding and for metallation of both the substrate and of a transition-state analogue (TSA) can be measured. We report that PS5.M, originally selected for binding to the TSA, displays the Circe effect in channeling a significant component of entropy-rich "intrinsic" binding energy to distort and to alter the basicity of the bound substrate. The study demonstrates that nucleic acids are, by themselves, capable of creating active sites for the catalysis of chemical reactions involving non-nucleotide substrates. Furthermore, the study of the metallation of the TSA provides a quantitative estimate of the effectiveness of such a compound in mimicking the true transition state for porphyrin metallation.

Binding Sites↗

Shear bond strength of resin luting cement to glass-infiltrated porous aluminum oxide cores.

STATEMENT OF PROBLEM: Resin bonding surface treatment methods for conventional silica-based dental ceramics are not reliable for glass infiltrated high alumina content In-Ceram ceramics. PURPOSE: This study developed an alternative surface treatment to improve resin bonding of glass-infiltrated aluminum oxide ceramic blasting with diamond particles and then observed the efficiency of this treatment. Material and methods. In-Ceram test specimens were prepared and divided into 2 groups. All specimens were sandblasted with Al(2)O(3), and blasted with diamond particles and 2 adhesive resins were applied. After bonding and storage in humid conditions, shear bond strength values were measured with a universal testing machine. Surface roughness and fracture interfaces were determined with a perthometer and a SEM. RESULTS: The highest bond strength was obtained on the samples blasted with diamond particles (group II). The differences between the 2 groups and the 2 adhesive resin cements were both statistically significant. CONCLUSION: Panavia-Ex cement exhibited higher bond strength than Super-Bond cement. This higher bond strength was attributed to ceramic oxide and ester bond and the mechanical properties of Panavia-Ex cement.

Aluminum Oxide↗

Comparison of the tensile bond strength of high-noble, noble, and base metal alloys bonded to enamel.

STATEMENT OF PROBLEM: Although the bond strengths of various resin composite luting materials have been reported in the literature, the evaluation of these systems with various cast alloys of different compositions has not been completely clarified. PURPOSE: To evaluate the tensile bond strength of sandblasted high-noble, noble, and base metal alloys bonded to etched enamel by 2 different bonding agents of different chemical composition: Panavia-Ex (BIS-GMA) and Super-Bond (4-META acrylic). MATERIAL AND METHODS: Flat enamel surfaces were prepared on buccal surfaces of 60 extracted noncarious human incisors. Teeth were divided into 3 groups of 20 each. Twenty circular disks of 5 mm diameter were prepared for casting for each group. Group I was cast with a high-noble, group II with a noble, and group III with a base metal alloy. The surfaces of the disks were sandblasted with 250 microm Al(2)O(3). Ten disks of each group were bonded to exposed enamel surfaces with Super-Bond and 10 disks with Panavia-Ex as recommended by the manufacturer. The tensile bond strength was measured with an Instron universal testing machine with a crosshead speed of 0.5 mm/min until failure occurred. RESULTS: Two-way ANOVA was used to evaluate the results. The differences in bond strengths of Super-Bond and Panavia-Ex with different alloys were not significant. The highest bond strengths were obtained in base metal alloys, followed by noble and high-noble alloys. These results were significant. CONCLUSION: Panavia-Ex and Super-Bond exhibited comparable tensile bond strengths. For both luting agents, the highest bond strengths were achieved with base metal alloys and the lowest with high-noble alloys.

Analysis of Variance↗

Nutrition in dialysis patients.

Malnutrition is a common clinical problem in dialysis patients, which is multifactorial in origin. It is most often found in a patient of chronic renal failure (CRF) during the period when the glomerular filtration rate (GFR) falls below 10 ml/min, but dialysis is yet to be started. The loss of proteins, aminoacids and other essential nutrients during the procedure of dialysis may further aggravate the malnutrition. Poor nutrition in dialysis patients is associated with increased morbidity and mortality in the form of delayed wound healing, malaise, fatigue, increased susceptibility to infection and poor rehabilitation. In view of the above consequences, all patients on dialysis must undergo nutritional assessment. It is very vital to maintain good nutritional status in-patients on dialysis by adequate protein and calories intake, appropriate supplementation of iron, calcium, minerals and water-soluble vitamins and, of course, the supplementation should be individualised. Nutritional needs are enhanced in presence of stresses like infection or surgery to limit excessive tissue catabolism and therefore, these are the situations, which demand intensive nutrition therapy. Total parenteral nutrition (TPN) may be required for patients on dialysis in intensive care unit, using a central venous catheter. However, enteral route is always preferred to parenteral ones, whenever possible. Even after adequate dialysis has been given, dietary counselling is often required for both hemodialysis and peritoneal dialysis patients to ensure that they ingest the recommended amount of protein, calories and essential micronutrients.

Feeding Methods↗

Left-isomerism sequence and maternal type-1 diabetes.

Defects of lateralisation have previously been recognised in the offspring of women with type-1 diabetes. In a 3-year period, three of the six cases of left isomerism sequence notified to the Northern Region Congenital Abnormality Survey were the infants of diabetic mothers. This finding suggests a specific association between bilateral left-sidedness and maternal type-1 diabetes.

Abnormalities, Multiple↗

A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites.

BACKGROUND: An 18-nucleotide DNA oligomer, PS2.M, derived using an in vitro selection method was previously reported to bind hemin (Fe(III)-protoporphyrinIX) with submicromolar affinity. The DNA-hemin complex exhibited DNA-enhanced peroxidative activity. PS2. M is guanine-rich and requires potassium ions to fold to its active conformation, consistent with its forming a guanine-quaduplex. In investigating the specific catalytic features of PS2.M we tested the peroxidative properties of its RNA version (rPS2.M) as well as that of an unrelated DNA guanine-quadruplex, OXY4. RESULTS: The hemin-binding affinity of rPS2.M was found to be 30-fold weaker than that of PS2.M. The UV-visible spectra and kinetics of enzymatic peroxidation of the RNA-hemin complex, however, were nearly identical to those of its DNA counterpart. Both displayed peroxidase activity substantially greater than those of heme proteins such as catalase and Fe(III)-myoglobin. Kinetic analysis suggested that PS2. M and rPS2.M catalyzed the breakdown of the hemin-hydrogen peroxide covalent complex to products. The hemin complex of folded OXY4 (which bound hemin as strongly as did rPS2.M) had a distinct absorption spectrum and only a minor peroxidase activity above the background level. CONCLUSIONS: The results indicated that it is possible for RNA and DNA of the same sequence to fold to form comparable cofactor-binding sites, and to show comparable catalytic behavior. The results further suggest that only a subset of cofactor-binding sites formed within folded nucleic acids might be able to function as active sites, by providing the appropriate chemical environments for catalysis.

Base Sequence↗

Cation-regulated self-association of "synapsable" DNA duplexes.

The simple innovation of introducing a block of G.G mismatches into a Watson-Crick DNA duplex permits two such duplexes, under conditions of physiological temperature and salt, to "synapse" with one another at their G.G mismatch sites via guanine-quartet formation. The short quadruplex formed at the "synapsed" site necessarily has its strands in an antiparallel, or partially antiparallel orientation. We wished to test whether a different, and more stable, synapsis might be achieved if one of the two strands in the synapsable duplex had its domain of guanine residues in a reverse orientation to the rest of the strand, via 5'-5' and 3'-3' linkages. Such modified duplexes might synapse via the formation of the thermodynamically preferred parallel quadruplex. Our results indicate that such "parallel" and "antiparallel" synaptic events have dramatically different requirements for cations. We use chemical probing experiments to provide evidence for a kinetic model for this discrepancy. It may be possible to exploit the distinct properties of the above two kinds of synapsable duplexes for a variety of in vivo and in vitro applications.

Base Sequence↗

Lanthanide probes for a phosphodiester-cleaving, lead-dependent, DNAzyme.

Lanthanides are useful probes for studying metal ion interactions in biological systems. The trivalent cations of the lanthanide metals are unique in that their ionic radii and the first pKa values of bound water molecules vary monotonically along the period. In addition, the europium and terbium cations have the useful property that their luminescence is enhanced when bound to nucleic acids. We have found that lanthanide ions can function as effective co-factors for a lead-dependent, phosphodiester-cleaving catalytic DNA (DNAzyme). We used the unique properties of the lanthanide co-factors to study the metal binding site as well as the catalytic mechanism of the DNAzyme. The catalyzed lanthanide-mediated cleavage occurred at neutral pH and at room temperature, with multiple turnovers of substrate. A range of lanthanide ions could act as co-factors, but differentially, with the smaller lanthanides (Tb, Tm, Lu) being the most effective. The rate of cleavage of the phosphodiester did not vary linearly with either the ionic radius or the first pKa of lanthanide-coordinated water molecules. The DNAzyme appeared to use only a single bound lanthanide ion as co-factor. Luminescence spectroscopy with terbium revealed the importance of the 2' hydroxyl group at the cleavage site in lanthanide ion binding, and the substrate molecule alone appeared to generate substantially the catalytically relevant metal-binding site. This model system demonstrated further the utility of complexing lanthanide ions directly to DNA molecules for catalytic purposes. The use of lanthanide ions also provides a means for investigating the metal ion binding sites of nucleic acid enzymes in general.

Binding Sites↗

DNA-enhanced peroxidase activity of a DNA-aptamer-hemin complex.

BACKGROUND: In vitro selection (SELEX) previously identified short single-stranded DNAs that specifically bound N-methylmesoporphyrin IX (NMM), a stable transition-state analogue for porphyrin-metallation reactions. Interestingly, iron(III)-protoporphyrin (hemin) was a good competitive inhibitor for the DNA-catalyzed metallation reaction, and appeared to bind strongly to the NMM-binding DNA aptamers. We investigated the peroxidase activity of the aptamer-hemin complexes to see if the DNA component of the complex, like the apoenzymes in protein peroxidases, could enhance the low intrinsic peroxidatic activity of hemin. RESULTS: Two porphyrin-binding DNA aptamers bound hemin with submicromolar affinity. The aptamer-hemin complexes had significantly higher peroxidase activity than hemin alone, under physiological conditions. The Vobs of the PS2.M-hemin complex was 250 times greater than that of hemin alone, and significantly superior to a previously reported hemin-catalytic-antibody complex. Preliminary spectroscopic evidence suggests the coordination of the hemin iron in the complex changes, such that the complex more closely resembles horseradish peroxidase and other heme proteins rather than hemin. CONCLUSIONS: A new class of catalytic activity for nucleic acids is reported. The aptamer-hemin complexes described are novel DNA enzymes and their study will help elucidate the structural and functional requirements of peroxidase enzymes in general and the ways that a nucleic acid 'apoenzyme' might work to enhance the intrinsic peroxidatic ability of hemin. These aptamer-hemin complexes could be regarded as prototypes for redox-catalyzing ribozymes in a primordial 'RNA world'.

Catalysis↗

The modus operandi of a DNA enzyme: enhancement of substrate basicity.

BACKGROUND: We wished to investigate the mode of catalytic action of a small DNA enzyme (DNAzyme), PS5.M, that, when folded into an appropriate tertiary structure, catalyzes the insertion of copper and zinc ions into porphyrins such as mesoporphyrin IX (MPIX). PS5.M, originally derived from SELEX experiments for specific DNA binders of the distorted porphyrin N-methylmesoporphyrin (NMM), had enzymatic parameters (kcat/K(m) = 39,700 M-1 min-1; kcat/kuncat = 3,700) that rivalled those of an antibody that catalyzed the same reaction. RESULTS: We used ultraviolet-visible absorption and fluorescence spectroscopy to study the mode of action of PS5.M and related catalytic DNA molecules. We found that the MPIX-DNAzyme complexes had absorption spectra more closely resembling those of the DNAzymes complexed to NMM than to the spectra of MPIX itself, whether MPIX was in its monomeric or aggregated form. pH titration experiments revealed that the DNAzyme raised the protonation pK for MPIX by 3-4 pH units. CONCLUSIONS: Our results reveal that PS5.M works by enhancing the basicity (and hence the ease of metallation) of the bound porphyrin substrate. Large changes in the porphyrin's basicity may be brought about through distortion of the planar porphinato- core of MPIX to resemble that of the naturally deformed porphyrin NMM or through stabilization by a DNA phosphate of the growing positive charge in the transition state for porphyrin protonation/metallation or through a combination of the two. The catalytic strategy of enhancing substrate basicity may also hold true for porphyrin metallation by the recently described catalytic RNA and catalytic antibody for this reaction.

Hydrogen-Ion Concentration↗

DNA enzymes.

The past year has seen a coming-of-age in DNA enzyme research. Far from being laboratory curiosities, the activities of new DNA enzymes have broadened the known catalytic repertoire of nucleic acid enzymes, provided valuable insights into different mechanistic possibilities open to nucleic acid catalysts, and explored the importance for catalysis of native functionalities within DNA and RNA, as well as of a diversity of extrinsic cofactors. Thus, the first amino acid cofactor-utilizing DNA enzyme has been described, as well as DNA enzymes that cleave RNA without the assistance of any external cofactor. On the practical side, the most efficient RNA-cleaving nucleic acid enzyme described to date is a DNA enzyme.

DNA↗

Occupational asthma in fruit salad processing.

BACKGROUND: Three subjects employed in the preparation of fruit for fruit salads reported work-related respiratory symptoms. Their work entailed removing the peel from citrus fruits, primarily oranges, following soaking of the fruits in a bath of enzymes including fungal derived pectinase and glucanase. Objectives To investigate the respiratory symptoms reported by these workers and determine their causes. METHODS: The three workers were investigated by a respiratory physician, including spirometry and serial peak flow measurements. Blood was taken for the measurement of IgE and IgG antibody responses against the enzyme solution. RESULTS: Predominant symptoms in these workers were shortness of breath, chest tightness and wheezing which were all alleviated at weekends and holidays only to occur when returning to work. Serial peak flow measurements showed a clear work-related pattern. All three had strong IgE responses to the enzyme solution used at the workplace and showed distinct patterns of binding in immunoblots. All three improved immensely following withdrawal from the workplace environment. CONCLUSION: Enzymes appear to be widely used in the preparation of fruit and although they are used in liquid form, exposure can occur to induce immunological sensitization and asthma.

Adult↗

Hepatitis E virus infection in eastern India.

Most cases of enterically transmitted non-A, non-B hepatitis in India have so far been attributed to hepatitis E virus (HEV) infection. Most of the documented studies of hepatitis have focused on the incidence of this disease in northern, western, and south central India. A small seroprevalence study was conducted in the eastern Indian city of Patna to assess the degree of HEV infection among acute sporadic hepatitis cases. Forty-two percent (24 of 57) of the cases of acute sporadic hepatitis were positive for anti-HEV antibodies. Absence of any serologic markers of hepatitis A, B, or E in 58% (33 of 57) of the cases with symptoms of acute hepatitis suggest that there may be as yet unidentified enterically transmitted viruses in this area.

Adult↗

Prospective population based survey of outcome of pregnancy in diabetic women: results of the Northern Diabetic Pregnancy Audit, 1994.

OBJECTIVE: To determine whether the St Vincent declaration (1989) target of diabetic pregnancy outcome approximating non-diabetic pregnancy outcome in near to being achieved. DESIGN: Prospective collection of population based information on pregnancies in women with diabetes from all participating hospitals. SETTING: District general and teaching hospitals of the former Northern region. SUBJECTS: 111 diabetic women booking with pregnancy during 1 January to 31 December 1994. MAIN OUTCOME MEASURES: Diabetic control, perinatal mortality rate, fetal abnormality rate. RESULTS: The perinatal mortality rate was 48/1000 for diabetic pregnancies compared with 8.9/1000 for the background population (odds ratio 5.38; 95% confidence interval 2.27 to 12.70) and the neonatal mortality rate was 59/1000 compared with 3.9/1000 (15.0; 6.77 to 33.10). Two late neonatal deaths were due to congenital heart defects. Six per cent of all fetal losses (6/109 cases) were due to major malformations. The congenital malformation rate was 83/1000 compared with 21.3/1000 (3.76; 2.00 to 7.06) in the background population. CONCLUSIONS: Diabetic pregnancy remains a high risk state with perinatal mortality and fetal malformation rates much higher than in the background population.

Congenital Abnormalities↗

Toward an efficient DNAzyme.

A 33-nucleotide, guanine-rich DNA oligomer, PS5.ST1, has been reported to catalyze the metallation of mesoporphyrin IX (MPIX) by copper and zinc ions. In this paper we report a thorough investigation of the properties of this DNAzyme. We have established that a 24-nucleotide sequence (PS5.M), from within PS5.ST1, is both the minimal and most optimal catalytic unit. We have found that three related porphyrins are acceptable as substrates by this DNAzyme, of which protoporphyrin IX is preferred as a substrate over the expected substrate, MPIX. We have determined that it is unlikely that a strong, catalytically relevant binding site for copper ions exists in the DNAzyme and that high concentrations of copper destroy the active DNAzyme. This enzyme, whose folded structure likely contains guanine quartets, requires potassium ions for activity; we have shown that as little as 1 mM potassium is sufficient for its catalytic robustness, whereas as much as 0.5 M sodium still will not support catalysis. In determining the pH, temperature, and salt optima for the catalyzed reaction, we have found an unexpected stabilizing role for Tris buffer in both the catalyzed and background metallation reactions. As a consequence of various steps of optimization, we now have a vastly improved DNAzyme, one whose enzymatic parameters compare well both with those of natural ferrochelatases, as well as with those of artificially derived chelatases, composed of protein (a catalytic antibody) and RNA. The existence of this array of biocatalysts for porphyrin metallations allows one-to-one comparisons of the ways in which different biopolymers solve a given catalytic problem.

Binding Sites↗

Studies on some trace and minor elements in blood. A survey of the Kalpakkam (India) population. Part II: Reference values for plasma and red cell, and correlation with coronary risk index.

Since data on the trace element levels in Indian population are lacking, we chose to conduct a survey of the Kalpakkam township population. People in the age group 40-55 were included in this study. Reference values for trace and minor elements of the blood of the Kalpakkam population were arrived at by carrying out the analysis of plasma and red cells of healthy subjects of the Kalpakkam population. Although the "reference values" for many elements were found to be normal and comparable to values available in the literature, slight deficiency with respect to Se was noticed. Subjects with high coronary risk index were also included in the study to assess the possible correlation of elemental and lipid profile. A study of box plots showed that the elements Se, Mg, Na, K, and Fe show significant differences between "high risk" coronary risk index (CRI > 5) and "no risk" (CRI < 4.5). In the plasma, the levels of Mg, Na, and K were found to be less in the high-risk group. In red cells, the amount of Se, Fe, and K were found to be significantly less in the "high-risk" group as compared to the "no-risk" group.

Adult↗