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Biomedical subjects

T Joseph

Publications and source records attributed to T Joseph.

At least 91 records · Page 5Linked to original sources
PubMed1993

Facial neurorrhaphy with autologous sural nerve graft using the CO2 laser in a primate model.

Cranial nerves, being of fine caliber and having a poorly defined epineurium, pose problems in intracranial sutural anastomosis. The CO2 laser is a comparatively new prospect that is being evaluated for sutureless neural anastomosis. Because there are no reports on the laser anastomosis of a peripheral spinal nerve to a cranial nerve, we designed this study to explore the possibility of performing a laser anastomosis of the facial nerve, using an autologous sural nerve graft in a primate model. Six monkeys underwent resection of the right facial nerve in the parotid fossa. In five of them, the CO2 laser was used to anastomose sural nerve interposition grafts by the use of microsurgical techniques. In one control animal, the sural nerve graft was interposed between the cut ends of the facial nerve and no anastomosis was performed. Compound muscle action potentials were recorded preoperatively and 2, 4, and 6 weeks postoperatively. At the end of 6 weeks, the wound was again explored and the grafts were examined. The neurophysiological results showed that in the five laser-welded nerves, at 4 weeks and 6 weeks postoperatively, the proximal latencies showed an improving trend with each successive recording. It was concluded that the CO2 laser can be used for the anastomosis of interposition grafts to the facial nerve.

Anastomosis, Surgical↗
PubMed1993

Nondiagnostic CT-guided stereotactic biopsies in a series of 407 cases: influence of CT morphology and operator experience.

Nondiagnostic biopsies were analyzed in a consecutive series of 407 patients undergoing computerized tomography (CT)-guided stereotactic biopsies. These were categorized as either negative biopsies, when normal tissue or nonspecific pathology was found, or inconclusive, when a definitive diagnosis could not be made although representative tissue was obtained. Nineteen biopsies (4.7%) were negative and 10 (2.4%) were inconclusive, giving an overall nondiagnostic biopsy rate of 7.1% (29 of the 407 cases). Suspected neoplastic masses (390 cases) were classified on the basis of their CT morphology into four groups: Group 1 included purely hypodense nonenhancing masses; Group 2 included isodense nonenhancing masses; Group 3 included ring-enhancing masses; and Group 4 included mixed-density enhancing masses. Although a higher proportion of hypodense nonenhancing masses (six of 56, or 10.7%) yielded a negative result, there was no statistically significant difference in the negative biopsy rates for the different CT categories (p = 0.06). The negative biopsy rates for the 6 years of the study, 1987 to 1992 (1987 being an incomplete year) were as follows: 13.3%, 6%, 3.2%, 3%, 5.8%, and 2.7%. There was no significant decrease in the negative biopsy rate as experience with this procedure increased (p = 0.20). A total of eight surgeons independently performed the biopsies. There was no significant difference (p = 0.24) in the negative biopsy rate of the surgeon with the most experience (124 biopsies, 2.4% negative biopsy rate) compared with that of the seven other surgeons combined (283 biopsies; 5.7% negative biopsy rate). These findings suggest that the yield in a stereotactic biopsy is independent of the CT appearance of the mass. Adherence to certain basic principles in patient and target selection will ensure a reasonable percentage of positive yield with stereotactic biopsy procedures even if the surgeon is relatively inexperienced. There does not appear to be a learning curve in the performance of CT-guided stereotactic biopsies. The management of patients with nondiagnostic biopsies is discussed.

Biopsy↗
PubMed1993

Langerhans' cell histiocytosis--a case report.

A three and half year old boy with Langerhans' cell histiocytosis (LCH) formerly called as eosinophilic granuloma has been presented along with the desired treatment plan.

Child, Preschool↗
PubMed1993

Effects of ECT-dothiepin combination on learning in rats.

Electroconvulsive therapy (ECT) and antidepressant drugs are each known to impair learning and memory. No information is available on their effects on cognition when used concurrently in the treatment of depression, as is frequent in India. In the present study, therefore, the effects of electro-convulsive shocks (ECS) and dothiepin, separately and in combination, were studied in an animal model employing a complex maze operant learning paradigm. ECS were given on alternate days (3/week) for 2 weeks. Dothiepin (10 mg/kg, ip) was administered once daily for 2 weeks. Learning was assessed on days 2-10 post-treatment ECS produced greater initial impairment in learning while dothiepin produced a more sustained impairment. While impairment was maximum in the combined treatment group, the statistical significances that emerged to proscribed the combination were but weak.

Animals↗
PubMed1993

Improved colorimetric method for cholinesterase activity.

A modified colorimetric method for the estimation of cholinesterase activity has been worked out using two different substrates, acetylthiocholine iodide for total cholinesterase and a specific substrate, butyrylthiocholine iodide for pseudocholinesterase in the same sample. This is a modification of the method described by Voss and Sachsse (1970) wherein acetylthiocholine iodide was used for both total and pseudo cholinesterase activities. The pseudocholinesterase obtained with acetylthiocholine iodide was significantly higher (P < 0.0001) than that with butyrylthiocholine iodide either in whole blood or serum samples. Acetylthiocholine iodide while reacting with pseudocholinesterase in serum or plasma samples might also be interacting with the small quantities of acetylcholinesterase present. It is therefore suggested that butyrylthiocholine iodide and acetylthiocholine iodide may be used to determine pseudocholinesterase and total cholinesterase activities respectively. The use of two substrates with a few more alterations in the experimental conditions increased the validity of this simple and rapid colorimetric method.

Acetylthiocholine↗
PubMed1992

A 1H-NMR study of the DNA binding characteristics of thioformyldistamycin, an amide isosteric lexitropsin.

The interaction of thioformyldistamycin, an amide isostere of the naturally occurring antibiotic distamycin A, with a self-complementary decadeoxynucleotide duplex, d(CGCAATTGCG)2, has been examined using a variety of high-field 1H-NMR techniques. The ligand exhibits two forms in solution arising from geometric isomerism due to restricted rotation around the thioformamide bond. Only the thermodynamically more stable Z-form is shown to bind to the oligonucleotide along its minor groove at the central 5'-AATT segment with the end groups of the ligand extending into the flanking GC regions but without any close contact at the amidinium terminus. Cross-peaks involving characteristic intra- and interresidue proton connectivities in the 2D experiments (COSY and NOESY) were employed to assign individual resonances of both strands in the asymmetric DNA-drug complex. The solution structure of the complex was constructed by molecular mechanics calculations based upon initial estimates of drug-DNA NOE contacts and further refined through energy minimization. These results complement previous structural studies on distamycin and other lexitropsins with oligonucleotides. The exchange of the ligand between two equivalent binding sites on the DNA sequence was estimated to occur at 40 s-1 with a free energy of activation of 16.5 kcal.mol-1 at 321-326 K. There was no evidence of formation of a 2:1 drug-oligomer complex, in contrast to the case of the natural product, which is attributed to steric demands of the larger sulfur atom.

Base Sequence↗
PubMed1992

The balloon posterior tracheal split: a technique for managing tracheal stenosis in the premature infant.

Congenital tracheal stenosis (CTS) in the premature infant almost invariably leads to death for lack of effective reconstructive techniques. We hypothesized that the complete or near complete cartilaginous rings of CTS have a weak point in the posterior portion. Aggressive balloon dilation would result in a posterior longitudinal disruption of the trachea, and an expanded tracheal wall would be created after an appropriate period of endotracheal stenting. Three premature infants with multiple anomalies and CTS were treated with endoscopic posterior tracheal splitting, dividing the trachea as predicted. Although two died of complications of congenital heart disease 2 weeks after the procedure, the third child is alive and well at 9 months of age without airway symptoms. The posterior tracheal wall also split when we performed the procedure in a fresh cadaveric CTS patient. We believe that balloon dilation may prove to be a valuable technique in the treatment of premature infants with congenital or acquired tracheal stenosis and/or in children with such complex diseases that major surgery is precluded.

Cadaver↗
PubMed1992

Structure and dynamics of ligand-template interactions of topoisomerase inhibitory analogs of Hoechst 33258: high field 1H-NMR and restrained molecular mechanics studies.

The binding characteristics of Hoechst 33258 (1), a synthetic bis-benzimidazole, and its structural analog 2, with one of the benzimidazoles replaced by a pyridoimidazole, to the self-complementary decadeoxyribonucleotide sequences d(CGCAATTGCG)2 (A) and d-(CATGGCCATG)2 (B) respectively, were examined using high field 1H-NMR techniques. Selective complexation induced chemical shift changes, the presence of exchange signals and intermolecular NOE contacts between the ligands and the minor groove protons of the oligonucleotides suggest the preferred binding sites as the centrally located AATT segment for complex A1, and the CCAT segment for complex B2. The B-type conformations of the two DNA duplexes are preserved upon complexation, as confirmed by the 2D-NOESY based sequential connectivities involving DNA base and sugar protons. Close intermolecular NOE based contacts between the ligands and their respective DNA sequences were further refined to model the ligand-DNA complexes starting from the computer generated B-type structures for the oligonucleotides. Force field calculations of ligand-DNA interaction energies indicate a more favorable contribution from the van der Waals energy component in the case of complex A1 consistent with its stronger net binding compared with the complex B2. Overall, the incorporation of a pyridinic nitrogen in Hoechst 33258 structure alters its selectivity for base pair recognition from A.T to G.C, resulting largely from the formation of a hydrogen bond between the new basic center and the 2-NH2 group of a guanosine moiety. The rates for the exchange of ligands between the two equivalent binding sites (AATT for 1, and CCAT for 2) of the self-complementary DNA sequences, are estimated from analyses of coalescence of NMR signals to be 189s-1 at 301 K for A1 and 79s-1 at 297 K for B2; which correspond to delta G++ of 13.8 and 18.6 kcal.mol-1 respectively.

Base Sequence↗
PubMed1992

Effect of chemically different calcium antagonists on lipid profile in rats fed on a high fat diet.

Different classes of calcium antagonists, viz. verapamil (diphenylalkylamine), diltiazem (benzothiazepine), nifedipine, felodipine and nimodipine (dihydropyridines), were examined for their effects on lipid profile in rats. Clofibrate was the reference standard. Clofibrate significantly prevented the rise of serum triglycerides and total cholesterol produced by high fat diet and raised antiatherogenic index to 1.6 times than that of high fat diet controls. Of the calcium antagonists studied, felodipine was most effective in preventing the rise of serum triglycerides and total cholesterol in high fat diet fed rats. Felodipine's antiatherogenic index was very high (886%)--much more than that of clofibrate (303%). Diltiazem and nimodipine which also significantly prevented the rise in triglycerides and total cholesterol produced by high fat diet had a moderately beneficial antiatherogenic index similar to that of clofibrate. Though verapamil and nifedipine slightly increased the triglyceride levels, total cholesterol levels were reduced only by verapamil and not by nifedipine. Despite this both these drugs moderately raised antiatherogenic index similar to clofibrate.

Animals↗
PubMed1992

Delayed effects of acute oral and chronic inhalational exposure to methylparathion on learning and memory in rats.

Impairment of acquisition phase of the learning process was observed in rats even at 3 weeks after single oral exposure to the near-lethal dose of commercial grade methylparathion (MP) followed by atropine resuscitation. Though there was a trend towards memory impairment in this group of animals, memory retention was not significantly affected. Chronic inhalational exposure to MP (one exposure/day for 3 weeks) did not significantly alter learning or memory. No significant alteration in red blood cell or brain acetylcholinesterase levels were observed in either of the two groups. It appears that behavioural effects can persist even 3 weeks after exposure to acute near-lethal doses of the pesticide, as occurs in the clinical situation of suicidal attempts; while repeated exposure to no-observed-effect-level doses as occurs in farm and factory workers, may not be associated with behavioural changes.

Acetylcholinesterase↗
PubMed1992

Antiepileptic drugs delay the onset of seizures induced by aminophylline in conscious rats.

Aminophylline, 285.7 +/- 2.19 mg/kg infused intravenously in unanaesthetized rats produced onset of seizures within 3.2 +/- 0.99 minutes. Seizures were repetitive and death occurred in 10.5 +/- 1.75 minutes. Pretreatment of rats with carbamazepine, sodium valproate and diazepam at doses that prevented electroshock induced seizures were effective in significantly postponing seizures and death, but did not reduce mortality. Concomitant EEG studies in aminophylline infused rats showed that cortical excitability evidenced by initial cortical spiking occurred at 42 secs and polyspiking at 165 seconds. Following diazepam, the initial cortical spike was delayed 50 fold, appearing after 36 minutes. Antiepileptic drugs and EEG monitoring may prove useful in patients with status asthmaticus receiving intravenous aminophylline.

Aminophylline↗
PubMed1991

Photoprotection of Bacillus thuringiensis kurstaki from ultraviolet irradiation.

Irradiation of Bacillus thuringiensis var. kurstaki HD1 at 300-350 nm for up to 12 hr using a photochemical reactor results in a rapid loss of its toxicity to larvae of Heliothis armigera. Photoprotection of the toxic component was obtained by adsorption of cationic chromophores such as acriflavin (AF), methyl green, and rhodamine B to B. thuringiensis. AF gave the best photoprotection and a level of 0.42 mmol/g dye absorbed per gram of B. thuringiensis was highly toxic even after 12 hr of ultraviolet (uv) irradiation as compared to the control (77.5 and 5% of insect mortality, respectively). Ultraviolet and Fourier-transform infrared spectroscopic studies indicate molecular interactions between B. thuringiensis and AF. The nature of these interactions and energy or charge transfer as possible mechanisms of photoprotection are discussed. It is speculated that tryptophan residues are essential for the toxic effect of B. thuringiensis. It is suggested that photoprotection is attained as energy is transferred from the excited tryptophan moieties to the chromophore molecules.

Bacillus thuringiensis↗
PubMed1991

Structural and dynamic aspects of non-intercalative (1:1) binding of a thiazole-lexitropsin to the decadeoxyribonucleotide d-[CGCAATTGCG]2: An 1H-NMR and molecular modeling study.

The location, orientation and dynamics of a thiazole-containing analogue of distamycin 1 bound to the decadeoxyribonucleotide d-[CGCAATTGCG]2 have been studied by non-exchangable and imino proton NMR resonances of the 1:1 complex. Using NOE difference, COSY and NOESY experiments, lexitropsin (1) was located in the minor groove of DNA at 5'-CAAT sequence. This was concluded by an intermolecular NOE between the ligand and a minor groove A4H2 proton. The NOE cross-correlations in the NOESY map confirmed that the DNA decamer duplex in the 1:1 complex remains in a right-handed B-conformation similar to that in the free decamer. Experiments on non-exchangeable and exchangeable proton NMR resonances placed the N-formylamino terminus of drug 1 on the 5'-C3 nucleotide, while the rest of the molecule extends onto the 5'-AAT sequence. The structural evidence for sequence preferential binding at 5'CAAT rather than 5'AATT suggests this reflects an attempt on the part of the sterically demanding inward directed sulfur of the thiazole to minimize compression by moving part of the molecule to the somewhat wider CG base site. The lack of evidence for a 2:1 drug:DNA complex, in contrast to distamycin, is in accord with this interpretation. The lexitropsin 1 was found to be in an exchange between the equivalent 5'-CAAT sites at a rate of approximately 35S-1 with a delta G degree of 65 +/- 5 kJ mol-1 at 303 K. The experimental data suggests a slide-swing mechanism for this exchange process.

Base Sequence↗
PubMed1991

Amide isosteres of lexitropsins: synthesis, DNA binding characteristics and sequence selectivity of thioformyldistamycin.

The synthesis and properties of an amide isostere of the antibiotic distamycin, thioformyldistamycin 3 is described. Compound 3 exists predominantly in the E conformation of the thioamide group in freshly prepared DMSO solution but is converted into the Z form, predicted by molecular mechanics to be more stable, on standing for 24 h. The coalescence temperature in DMSO is 110 degrees C by 1H-NMR. The thioformyl moiety of 3 is resistant to both peptidase action and acid treatment. Complementary strand MPE footprinting on a EcoRI/Hind III restriction fragment of pBR322 DNA demonstrated that either E or Z forms of 3 give a single set of footprints very similar to that of the parent antibiotic with strongest protection at TAAG and TATTAT with moderately strong protection at ATTT and AAAA. The strength of binding of 3 and distamycin from delta Tm measurements to either poly.d(AT) or calf thymus DNA is comparable. Molecular modeling predicted a preferred conformation for 3 wherein the C = S bond has a torsional angle of 110 degrees with the pyrrole ring. The energy difference between this conformation and the E form is less than 1 kcal/mole. In contrast the E-form has an energy 17.3 kcal/mole greater than the Z and a value of 26.3 kcal/mole was calculated for the energy barrier between the two isomers.

Base Sequence↗
PubMed1991

Single small enhancing CT lesions in Indian patients with epilepsy: clinical, radiological and pathological considerations.

Thirty consecutive Indian patients with focal or generalised seizures and single, small (less than 10 mm), enhancing lesions on CT scans (SSECTL) were studied. Five patients (Group A) were treated with anticonvulsants alone and did not have a biopsy. In ten patients (Group B) a CT guided stereotaxic biopsy of the lesion was carried out and in the remainder (15-Group C) and excision biopsy of the lesion was carried out following CT guided stereotaxic localisation. In all patients in Group B the lesion were reported as "chronic nonspecific inflammation". In seven of 15 patients in Group C the lesions showed a cysticercus with a granuloma and in a further five the pathology was that of a "parasitic granuloma" but the parasite could not be identified. Biopsy did not reveal a tuberculoma or neoplasm in any of the patients. The lesions studied are the same as "disappearing" CT lesions reported in Indian patients, as in 12 of 15 patients in Groups A and B, who could be followed up for more than three months, the lesions had spontaneously disappeared or left calcific residues. It is concluded that in Indian epileptic patients with SSECTL cysticercosis is the commonest aetiology. A treatment protocol for these patients is suggested on the basis of the findings.

Biopsy↗