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Biomedical subjects

M Gopal

Publications and source records attributed to M Gopal.

At least 19 recordsLinked to original sources

Neuro-fuzzy decision trees.

Fuzzy decision trees are powerful, top-down, hierarchical search methodology to extract human interpretable classification rules. However, they are often criticized to result in poor learning accuracy. In this paper, we propose Neuro-Fuzzy Decision Trees (N-FDTs); a fuzzy decision tree structure with neural like parameter adaptation strategy. In the forward cycle, we construct fuzzy decision trees using any of the standard induction algorithms like fuzzy ID3. In the feedback cycle, parameters of fuzzy decision trees have been adapted using stochastic gradient descent algorithm by traversing back from leaf to root nodes. With this strategy, during the parameter adaptation stage, we keep the hierarchical structure of fuzzy decision trees intact. The proposed approach of applying backpropagation algorithm directly on the structure of fuzzy decision trees improves its learning accuracy without compromising the comprehensibility (interpretability). The proposed methodology has been validated using computational experiments on real-world datasets.

Decision Making, Computer-Assisted↗

4-Anilinopyrimido[4',5':4,5]selenolo(2,3-b)quinoline and 4-piperazino pyrimido[4',5':4,5]selenolo(2,3-b)quinoline: new DNA intercalating chromophores with antiproliferative activity.

We have used circular dichroism, hydrodynamic methods, absorbance, and fluorescence titration to study the interaction of 4-anilinopyrimido[4',5':4,5] selenolo (2,3-b)quinoline (APSQ) and 4-piperazinopyrimido[4',5':4,5] selenolo(2,3-b)quinoline (PPSQ) with DNA. The association constants of APSQ and PPSQ were of the order of 10(4)M(-1). The fluorescence properties at ionic strength 0.01M are best fit by the neighbor exclusion model, with K=0.58-9.2 x 10(4)M(-1) and an exclusion parameter of 0.9-6.4 bp. Binding to the GC-rich DNA of Micrococcus lysodeikticus was stronger than the binding to calf thymus DNA, suggest that drug binds preferentially to G+C pairs at low r. CD spectra indicate that stacking of these compounds with DNA induces a strong helicity in the usually disordered structure of this double strand. Viscosity experiments show with sonicated calf thymus DNA with PPSQ an twice increase in slope (m) as that with APSQ. PPSQ increases the T(m) for calf thymus DNA melting by approximately 10 degrees C as binding approaches saturation, with biphasic melting. The cytotoxicities of these compounds on leukemia HL-60, K-562, B16F10 melanoma and Colo-205 are quite similar and inhibition (IC(50)) was in the range of 0.39-9.80 microM. The anticancer efficacy against B16F10 melanoma has provided evidence of major anticancer activity for PPSQ. Single or multiple intraperitonial (i.p.) doses of drug proved high level activity against the subcutaneous (s.c.) grafted B16 melanoma, significantly increase in life span (ILS 139% and 170%). The aim of this study was to analyze the physiochemical properties of these compounds in an attempt to understand its superior biological activity.

Animals↗

Synthesis and biological evaluation of novel angularly fused polycyclic coumarins.

In a three-step sequence, an array of angularly fused polycyclic heterocycles with coumarin, benzofuran and pyridine rings were synthesized from 4-bromomethylcoumarins and salicylonitrile. All the final compounds were fully characterized and screened for anti-microbial, anti-inflammatory and analgesic activities. Several compounds exhibited promising inflammation inhibiting and anti-microbial properties.

Analgesics↗

The genotoxicity of DNA intercalating drug 8-methoxy pyrimido [4',5':4,5]thieno(2,3-b)quinoline-4(3H)-one.

8-methoxypyrimido[4',5':4,5]thieno(2,3-b)quinoline-4(3H)-one (MPTQ) is known to have antitumor and cytotoxic activities on various types of tumors. This compound showed a strong clastogenic effect on bone marrow cells of Swiss albino mice treated in vivo (17.5-35 mg/kg body weight). MPTQ induced micronuclei formation (MN) at doses of 17.5, 23.3, and 35 mg/kg. Dose and time-yield effect of MPTQ was studied in the case of chromosome aberration assay. MPTQ induced a statistically significant increase in the frequency of chromosome aberrations and micronuclei induction. The drug induced significant abnormal sperms even in the sperm shape abnormality assay. Based on the data reported in the literature, we have tried to establish the relationship between the clastogenic effect observed and process of MPTQ intercalation into DNA and the formation of protein-associated DNA-strand breaks probably promoted by topoisomerase enzymes.

Animals↗

Comparative evaluation of TRI-DOT Rapid HIV test with fourth-generation ELISA for the detection of human immunodeficiency virus.

This study evaluated the TRI-DOT Rapid HIV test for the early detection of human immunodeficiency virus (HIV) infection in comparison with a fourth-generation ELISA (Vironostika HIV Uniform II). Of 23,609 sera, seven (0.03%) gave discordant results. Six of these were reactive only by the fourth-generation assay and were p24 antigen-positive by VIDAS DUO, Western blot and qualitative RT-PCR tests. The remaining discordant serum was considered to be false-positive by the TRI-DOT assay, as it was negative by repeat ELISA and Western blot tests. The sensitivity and specificity of the TRI-DOT test were 99.48% and 99.99%, respectively, compared with the fourth-generation ELISA.

AIDS Serodiagnosis↗

On the structure and initial parameter identification of Gaussian RBF networks.

We consider the efficient initialization of structure and parameters of generalized Gaussian radial basis function (RBF) networks using fuzzy decision trees generated by fuzzy ID3 like induction algorithms. The initialization scheme is based on the proposed functional equivalence property of fuzzy decision trees and generalized Gaussian RBF networks. The resulting RBF network is compact, easy to induce, comprehensible, and has acceptable classification accuracy with stochastic gradient descent learning algorithm.

Algorithms↗

Biological properties of 8-methoxypyrimido[4(1),5(1):4,5]thieno(2,3-b)quinoline-4(3H)-one, a new class of DNA intercalating drugs.

BACKGROUND & OBJECTIVES: The compounds containing novel tetracyclic condensed quinoline ring system is of interest because of its close relationship with anticancer drug ellipticine. 8-Methoxypyrimido[4(1),5(1):4,5]thieno(2,3-b)quinoline-4(3H)-one (MPTQ) was investigated to study its effect on in vitro growth inhibition and clonogenic cell survival assay on three tumour cell lines, human promyelocytic leukemia HL-60, melanoma B16F10 and neuro 2a. A systematic study was carried out to evaluate its antitumour efficacy against B16 murine melanoma. Antiinflammatory and analgesic activities of MPTQ were also studied. METHODS: The cytotoxicity of MPTQ on HL-60, B16F10 and neuro 2a cells was estimated by trypan blue exclusion test. The antitumour activity was evaluated using single dose, multiple/daily injections (days 3-6) or intermittent treatments over two weeks against s.c. implanted B16melanoma, both in terms of increased life span and tumour growth inhibition. Antiinflammatory activity was seen on carrageenan induced hind paw oedema. Counting the number of abdominal constrictions after the injection of acetic acid assessed the analgesic response. RESULTS: MPTQ is cytotoxic to all the cell lines tested and ID50 being in the range of 0.08-1.0 microM. MPTQ was studied for anticancer activity in the clonogenic assay. Drug was applied over a wide dose range by 24 h exposure, yielding clear dose-response effects. In vivo antitumour efficacy against B16 melanoma showed evidence of major antitumour activity for MPTQ. Single and multiple i.p. doses of drug proved high level activity against the s.c. grafted B16melanoma, significantly increasing survival (P<0.001) and inhibiting tumour growth (T/C of 3.0%). A reduction (76.48%) in paw volume was noted in 40 mg/kg dose of which was comparable to antiinflammatory activity of 150 mg/kg i.p. of phenylbutazone. Analgesic activity was found to be of peripheral type as there was reduction of 74 per cent in writhing response by MPTQ in dose of 40 mg/kg in mice. INTERPRETATION & CONCLUSION: The results suggested that the compounds containing pyrimidothienoquinoline system particularly 8-methoxy derivative might be potentially useful antitumour agent. We conclude that the correlation of physicochemical properties of the new series of pyrimidothienoquinolines with their pharmacological properties, might help in trying to understand the mechanism of pyrimidothienoquinolines series.

Analgesics↗

Antitumor activity of 4-amino and 8-methyl-4-(3diethylamino propylamino)pyrimido[4',5':4,5]thieno (2,3-b) quinolines.

The interaction of 4-aminopyrimido [4',5':4,5] thieno (2,3-b) quinoline and 8-methyl-4-(3-diethylaminopropylamino) pyrimido [4',5':4,5] thieno (2,3-b) quinoline with DNA was studied by UV-Vis and fluorescence spectrophotometry as well as by hydrodynamic methods. On binding to DNA, the absorption spectra underwent bathochromic and hypochromic shifts and the fluorescence was quenched. These compounds are able to bind to DNA with an affinity of about 10(6) M(-1) for calf thymus DNA at ionic strength 0.01 M and their intercalating characteristic (lengthening of the DNA) depends upon the length of the chain. Binding to the GC-rich DNA of Micrococcus lysodeikticus was stronger than the binding to calf thymus DNA at ionic strength 0.01 M. The cytotoxicities of these compounds on leukemia HL-60, melanoma B16F10 and neuro 2a cells are quite similar and inhibition (IC50) is in the range of 0.992-3.968 microM. The anticancer efficacy against B16 melanoma, has provided evidence of major antitumor activity for 8-methyl-4-(3diethylaminopropylamino) pyrimido [4',5':4,5] thieno(2,3-b)quinoline. Single or multiple intraperitonial (i.p) doses of drug proved high level activity against the subcutaneous (s.c) grafted B16 melanoma, significantly increasing survival (p<0.001) and inhibiting tumor growth (T/C of 4%). This study offers a new intercalation functional group to DNA-targeted drug design.

Animals↗

Successful in vitro fertilization pregnancy after conservative management of endometrial cancer.

OBJECTIVE: To report a successful IVF pregnancy in an infertile couple after conservative treatment of endometrial cancer. DESIGN: Case report and literature review. SETTING: University teaching hospital. PATIENT(S): A 29-year-old infertile white woman. MAIN OUTCOME MEASURE(S): Successful pregnancy after conservative management of endometrial cancer. INTERVENTION(S): Grade 1 endometrial adenocarcinoma diagnosed at hysteroscopy, followed by dilatation and curettage (D&C). On follow-up D&C, pathologic examination was normal after high-dose progesterone therapy. The patient subsequently underwent an IVF cycle with transfer of three blastocysts. RESULT(S): The patient delivered triplets by cesarean section. Laparoscopic-assisted vaginal hysterectomy and bilateral salpingo-oophorectomy was then done. No residual endometrial cancer was evident in the hysterectomy specimen, but a 1.1-cm cystic mixed endometrioid and clear cell-type adenocarcinoma was discovered in the left ovary. The patient is doing well after 3 cycles of chemotherapy; her CA-125 level is normal. The triplets are also doing well. CONCLUSION(S): In carefully chosen situations, deferring surgery in infertile patients with endometrial cancer may be a viable option permitting subsequent successful pregnancy.

Adenocarcinoma↗

Sonographic fetal weight estimation in a south-east Asian population.

OBJECTIVES: To determine the optimal sonographic fetal weight estimation formula for a mixed south-east Asian population near term. METHODS: Seventy-eight uncomplicated pregnancies were monitored between January 1996 and January 1997. Biparietal diameter, head circumference, abdominal circumference and femur length were measured and the following formulae were tested: Campbell, Shepherds and Hadlock. The estimated fetal weight was calculated by 12 different methods. The weight estimate was then projected forward to the time of delivery using the gestation-adjusted forward projection method. The weight estimation error was derived from the difference between the projected fetal weight and birth weight, and expressed as a percentage of birth weight. RESULTS: The mean time interval from the time of ultrasound fetal weight estimation to delivery was 4.4 days. The birth weight ranged between 2,330 to 4,215 g. The best performing formula was Hadlock's formula using the head circumference, abdominal circumference and femur, with the perimeters calculated using the ellipse function. The standard deviation of error for this formula was 8.66%. CONCLUSION: Even though the Hadlock formula was originally derived from an American population, it was equally useful in south-east Asian population.

Adult↗