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M K Ghosh

Publications and source records attributed to M K Ghosh.

At least 19 recordsLinked to original sources
PubMed1992

Measurement of femoral torsion with ultrasound: evaluation of a new technique using reference lines on the posterior surface of the femur.

A technique of measuring femoral torsion employing reference lines on the posterior surface of the femur has been described. This technique was evaluated on 27 dry adult femora and then on 40 adult patients. The technique was found to be reliable and reproducible. The values of femoral torsion obtained by this technique is lower than that obtained when anterior reference lines are used.

Adult↗
PubMed1992

Enhanced delivery of 5-iodo-2'-deoxyuridine to the brain parenchyma.

5'-Ester derivatives of 5-iodo-2'-deoxyuridine (IDU) with varying degrees of lipophilicity were examined to evaluate the effectiveness of lipophilic ester prodrugs for enhanced and sustained delivery of IDU to the brain parenchyma. Approximately 1.0% (1.0 +/- 0.19; n = 4) of the total radioactivity was found in the brain at 30 min following intravenous administration of the lipophilic benzoyl-5'-ester of 125I-labeled IDU, whereas IDU per se yielded only 0.01% (0.01 +/- 0.06; n = 4). Since the IDU 5'-esters generated significantly higher levels of IDU in the brain, an HPLC analysis of IDU in the presence of 5'-esters and the metabolite 5-iodouracil was developed to characterize IDU uptake in the brain. The drug was detected at levels of 6.6 and 9.5 micrograms/g of brain tissue at 3 hr following intravenous administration of valeryl and benzoyl IDU, respectively, at a dose level of 40 mg/kg IDU equivalent each. IDU, on the other hand, when injected at a similar dose level, produced concentration levels below 0.01 micrograms/g of brain tissue, which was too low to be detected accurately by the HPLC assay. These results suggest that the 5'-ester derivatives cross the blood-brain barrier effectively and generate significantly higher brain levels of the parent drug in the brain parenchyma. The regenerated hydrophilic drug because of its polarity is "locked in" the brain and is subsequently metabolized by pyrimidine phosphorylase to 5-iodouracil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Brain parenchymal metabolism of 5-iodo-2'-deoxyuridine and 5'-ester prodrugs.

In an attempt to generate derivatives of 5-iodo-2'-deoxyuridine (IDU) with enhanced blood-brain barrier (BBB) permeability, a series of 5' ester prodrugs of IDU was synthesized and their metabolism studied in rat brain homogenate and its different subcellular fractions. The rate of hydrolysis was dependent on the steric and polar nature of the ester substituent. Ester hydrolyzing activities were associated primarily with the cytosolic fraction and were due mainly to the presence of cholinesterases as confirmed by inhibition experiments performed with different esterase inhibitors. The metabolism of IDU to 5-iodouracil (5-IU) by the cytosolic fraction, in the presence and absence of specific pyrimidine nucleoside phosphorylase inhibitors, also suggests that there are two specific enzyme systems catalyzing two different metabolic processes. IDU 5'-esters competitively inhibit the metabolism of IDU and the inhibitory effect depends on the affinity of a particular ester toward the enzyme and also on the rate by which the ester itself undergoes hydrolysis. In the absence of any 5'-ester, 95% IDU was metabolized within 6 hr. However, in the presence of an eightfold molar excess of butyryl-IDU, the hydrolysis of IDU was completely inhibited over a 6-hr time period.

Animals↗
PubMed1992

Translation inhibition by phosphorothioate oligodeoxynucleotides in cell-free systems.

A detailed comparison was made of the concentration dependence of translation inhibition by phosphorothioate and phosphodiester oligodeoxynucleotides of the same anti-beta-globin sequence in cell-free systems using beta-globin mRNA and unrelated mRNAs as controls. The results confirm that at low concentrations the phosphorothioate oligomer is more potent as an antisense compound, while at higher concentration (greater than 4 microM) it exhibits more nonspecific inhibition than the phosphodiester oligomer for RNase H-mediated translation inhibition.

Base Sequence↗
PubMed1991

Effects of 5'-ester modification on the physicochemical properties and plasma protein binding of 5-iodo-2'-deoxyuridine.

A series of 5'-(O-acyl and O-benzoyl) derivatives of 5-iodo-2'-deoxyuridine (IDU) was synthesized by direct acylation of the parent nucleoside in a pyridine-N,N'-dimethylformamide mixture (1:1). Aqueous solubilities in phosphate buffer (pH 7.4), partition coefficients in 1-octanol/phosphate buffer (pH 7.4), plasma protein binding properties, and plasma reversion kinetics of these potential prodrugs were evaluated. The esters showed an expected increase in lipophilicity with a corresponding decrease in aqueous solubility relative to the parent compound. The association constants (Ka) with albumin also exhibited a good linear correlation with the lipophilicity of the compounds. However, the reversion rate constants in plasma varied with the steric and polar nature of the acyl or benzoyl substituent.

Animals↗
PubMed1991

Hamartoma--a benign intraluminal tumor of the oesophagus (a case report).

Benign tumours of the oesophagus are rare, representing less than 1% of all oesophageal neoplasms. Most of them are intramural leiomyomas while the other benign tumours are encountered only infrequently; among these pedunculated intraluminal hamartomas form a particularly rare group. We present here one such case.

Adult↗
PubMed1990

Purification and properties of acyl/alkyl dihydroxyacetone-phosphate reductase from guinea pig liver peroxisomes.

The peroxisomal acyl/alkyl dihydroxyacetone-phosphate reductase (EC 1.1.1.101) was solubilized and purified 5500-fold from guinea pig liver. The enzyme could be solubilized by detergents only at high ionic strengths in presence of the cosubstrate NADPH. Peroxisomes, isolated from liver by a Nycodenz step density gradient centrifugation, were first treated with 0.2% Triton X-100 to remove the soluble and a large fraction of the membrane-bound proteins. The enzyme was solubilized from the resulting residue by 0.05% Triton X-100, 1 M KCl, 0.3 mM NADPH, and 2 mM dithiothreitol in Tris-HCl buffer (10 mM) at pH 7.5. The enzyme was further purified after precipitating it by dialyzing out the KCl and then resolubilized with 0.8% octyl glucoside in 1 M KCl (plus NADPH and dithiothreitol). The second solubilized enzyme was purified to homogeneity (370-fold from peroxisomes) by gel filtration in a Sepharose CL-6B column followed by affinity chromatography on an NADPH-agarose gel matrix. NADPH-agarose was prepared by reacting periodate-oxidized NADP+ to adipic acid dihydrazide-agarose and then reducing the immobilized NADP+ with NaBH4. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified enzyme showed a single homogeneous band with an apparent molecular weight of 60,000. The molecular weight of the native enzyme was estimated to be 75,000 by size exclusion chromatography. Amino acid analysis of the purified protein showed that hydrophobic amino acid comprised 27% of the molecule. The Km value of the purified enzyme for hexadecyldihydroxyacetone phosphate (DHAP) was 21 microM, and the Vmax value in the presence of 0.07 mM NADPH was 67 mumol/min/mg. The turnover number (Kcat), after correcting for the isotope effect of the cosubstrate NADP3H, was calculated to be 6,000 mol/min/mol of enzyme, assuming the enzyme has a molecular weight of 60,000. The purified enzyme also used palmitoyldihydroxyactone phosphate as a substrate (Km = 15.4 microM, and Vmax = 75 mumol/min/mg). Palmitoyl-DHAP competitively inhibited the reduction of hexadecyl-DHAP, indicating that the same enzyme catalyzes the reduction of both acyl-DHAP and alkyl-DHAP. NADH can substitute for NADPH, but the Km of the enzyme for NADH (1.7 mM) is much higher than that for NADPH (20 microM). The purified enzyme is competitively (against NADPH) inhibited by NADP+ and palmitoyl-CoA. The enzyme is stable on storage at 4 degrees C in the presence of NADPH and dithiothreitol.

Amino Acids↗
PubMed1990

Carboxylic ester hydrolase activity in hairless and athymic nude mouse skin.

The carboxylic ester hydrolase activity was compared in athymic nude mouse skin and hairless mouse skin with respect to hydrolytic ability, heat inactivation, pH optima, and substrate specificity. Five aliphatic 5'-esters of 5-iodo-2'-deoxyuridine (IDU) were incubated with skin homogenate preparations, and the effect of linear chain length and branching of the ester substituent on hydrolysis rate was evaluated. The ester hydrolase activity was three times higher in athymic mouse skin relative to hairless variety. In both mice skin preparations maximum hydrolysis rates were obtained with the valeryl ester followed by butryl, isobutyryl, propionyl and pivaloyl derivatives. Kinetic studies, however, revealed that higher ester hydrolase activity (Vmax) in athymic mouse skin is also associated with higher Km values, while the carboxylic ester hydrolases from these two different strains of mice have similar biochemical properties with respect to heat inactivation and pH optima. Athymic mouse skin resembled hairless mice skin in terms of cholinesterase content. A significant fraction (70-80%) of ester hydrolyzing activities in both strains of mice skin resulted from cholinesterases (true and/or pseudo). The remaining activity was attributed to different ester cleaving enzymes in the two strains of mice. Carbonic anhydrases and arylesterases contributed to the ester hydrolyzing activity of the athymic and normal hairless mice skins, respectively. Product inhibition by the regenerated hydrolytic product, free IDU, was also noticed which resulted in incomplete conversion of rapidly hydrolyzable 5'-esters such as the valeryl and butyryl derivatives.

Animals↗
PubMed1990

Cherubism.

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Adolescent↗
PubMed1990

Calcified hypernephroma. A case report.

Pattern of classification in an renal neoplasm is variable. If calcium is located nonperipherally (within the mass) it is more likely to be a renal cell carcinoma. But peripheral calcification does not rule out malignancy.

Adult↗