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Biomedical subjects

U Mukherjee

Publications and source records attributed to U Mukherjee.

17 recordsLinked to original sources

Uterine choriocarcinoma in a postmenopausal woman.

Uterine choriocarcinoma developing in patients beyond reproductive age is a rare occurrence. We report a case of choriocarcinoma of uterine corpus in a 54-yr-old woman after 7 yr of menopause and 25 yr after last child birth. She presented with pain in the abdomen, and on radiological investigation a left uterine adnexal mass of 3.4 x 2.8 cm size was detected. Her serum CA125 level was 40 mIU/mL (normal up to 35 mIU/mL). Hysterectomy revealed an intramural growth in left uterine cornu measuring 3.5 x 3.0 x 2.5 cm. Histological features of the tumor were consistent with choriocarcinoma, and immunohistochemistry detected strong reactivity for beta-hCG in the tumor cells. Serum beta-hCG level 4 wk after surgery was 1345 mIU/mL. The patient was put on combination chemotherapy (EMACO). She achieved serological remission but showed a rise in serum beta-hCG level 4 wk after completion of chemotherapy. We conclude that a high level of suspicion may help in preoperative diagnosis of uterine choriocarcinoma in the postmenopausal age group. However, the response to chemotherapy in these cases may not be as encouraging as in choriocarcinoma of reproductive age.

Antineoplastic Combined Chemotherapy Protocols↗

Pericardial synovial sarcoma.

A 29-year-old young man presented with acute breathlessness. After investigative work-up he was found to have a massive pericardial tumour. Thoracotomy and near total surgical excision of the pericardial tumour was carried out. Histopathology and immunohistochemical markers study revealed it to be a synovial sarcoma arising from the left lateral pericardial surface. Postoperatively, he received external radiation and chemotherapy. Thirteen months after surgery he developed local recurrence which was unresectable.

Adult↗

Molecular architecture of the thylakoid membrane: lipid diffusion space for plastoquinone.

We have determined the stoichiometric composition of membrane components (lipids and proteins) in spinach thylakoids and have derived the molecular area occupied by these components. From this analysis, the lipid phase diffusion space, the fraction of lipids located in the first protein solvation shell (boundary lipids), and the plastoquinone (PQ) concentration are derived. On the basis of these stoichiometric data, we have analyzed the motion of PQ between photosystem (PS) II and cytochrome (cyt.) bf complexes in this highly protein obstructed membrane (protein area about 70%) using percolation theory. This analysis reveals an inefficient diffusion process. We propose that distinct structural features of the thylakoid membrane (grana formation, microdomains) could help to minimize these inefficiencies and ensure a non-rate limiting PQ diffusion process. A large amount of published evidence supports the idea that higher protein associations exist, especially in grana thylakoids. From the quantification of the boundary lipid fraction (about 60%), we conclude that protein complexes involved in these associations should be spaced by lipids. Lipid-spaced protein aggregations in thylakoids are qualitatively different to previously characterized associations (multisubunit complexes, supercomplexes). We derive a hierarchy of protein and lipid interactions in the thylakoid membrane.

Adenosine Triphosphatases↗

Elevated serum cancer antigen 125 levels in advanced abdominal tuberculosis.

A 48-yr-old female presented with a 1-yr history of pain in the hypochondrium and epigastrium. All routine investigations and computed tomography (CT) of the abdomen were done. CT findings revealed a well-defined cystic mass in the right ovary, and ascitis with features suggestive of secondaries over the omentum and peritoneal surface. The serum CA125 was 1255 U/mL (normal range 0-35 U/mL), which was indicative of ovarian malignancy. An exploratory laparotomy was performed. Histopathological examination of organs revealed the presence of granuloma. The patient was advised to undergo antitubercular treatment (ATT) and follow-up every month. After 1 mo of ATT, the CA125 level came down to 42 U/mL, which was near normal. As tuberculosis requires only a conservative management, we suggest that in cases of abdominopelvic mass with or without ascitis, high serum CA125 should always raise a suspicion of tuberculosis and a laparoscopy combined with peritoneal biopsy should be performed to confirm the diagnosis. This will prevent unnecessary laparotomies. Moreover, serum CA125 can be used to monitor the response of disease to antitubercular treatment.

Adnexal Diseases↗

Oxidative damage of DNA and benzoate by chelated and non-chelated copper in presence of hydrogen peroxide.

Benzoate hydroxylation test revealed that Cu(II) reacting with H2O2 produced OH degree radicals, which nicked or damaged DNA or hydroxylated benzoate, the extent of damage or hydroxylation depending on the period of incubation. The production of OH degree free radicals was also supported by the scavenger studies. Neither Cu(II) nor H2O2 alone could damage DNA or hydroxylate benzoate. EDTA-chelated Cu(II) plus H2O2 could damage DNA or hydroxylate benzoate only in presence of the biological reductant, L-cysteine, the damage increased with the increasing molar ratio of L-cysteine to Cu-EDTA. The biological relevance of the EDTA chelated Cu(II) and H2O2 system is discussed.

Benzoates↗

Effects of nitrofurantoin on viability, DNA synthesis and morphology of Vibrio cholerae cells.

Nitrofurantoin caused a dose dependent inhibition of growth and decrease in viability of V. cholerae cells, the 10% (D10) and 37% (D37) survival doses being 50 and 19 micrograms/ml respectively. The drug at a concentration of 60 micrograms/ml caused 86% inhibition of DNA synthesis. Both light and electron microscopic observations revealed that treatment with nitrofurantoin (60 micrograms/ml for 1 hr at 37 degrees C) led to a significant filamentation of the V. cholerae cells, ultrastructure of the cell cytoplasm, plasma membrane and cell wall however remaining unaltered from those of untreated cells. The results are discussed in relation to DNA lesions produced by and the carcinogenic potential of the drug.

Cell Division↗

Adaptive response of Vibrio cholerae and Escherichia coli to nitrofurantoin.

Pretreatment with sublethal doses of nitrofurantoin induced adaptive response in both Vibrio cholerae and Escherichia coli cells as indicated by their greater resistance to the subsequent challenging doses of the same drug. Adaptive response was maximum corresponding to pretreatment drug concentrations of 0.40 microgram/ml and 0.015 microgram/ml respectively for V. cholerae OGAWA 154 (wild type) and E. coli K-12 AB 2463 (recA-) cells. Adaptive response was inhibited by chloramphenicol (100 micrograms/ml) indicating the need of concomitant protein synthesis. Induction of adaptive response in recA deficient E. coli cells indicated that it was different from the conventional "SOS" response. Melting temperature of DNA of V. cholerae cells subjected to adaptive (0.4 microgram/ml for 1 hr) and challenging (120 micrograms/ml for 1 hr) doses of nitrofurantoin (76 degrees C) was closer to that of native DNA (75 degrees C) vis-a-vis DNA isolated from nonadapted and drug treated cells (77.5 degrees C). Also, DNA isolated from V. cholerae cells subjected to adaptive and challenging doses of the drug revealed the presence of fewer interstrand cross-links (16% reversible DNA) vis-a-vis DNA from nonadapted but drug treated cells (55% reversible DNA). Photomicrographic studies revealed that V. cholerae cells that were nonadapted but drug treated grew into long filamentous forms (4.25 +/- 2.97 micron) whereas those subjected to both adaptive and challenge doses of the drug exhibited much less filamentation (2.08 +/- 0.84 micron) vis-a-vis native cells (1.42 +/- 0.5 micron). Similar results on DNA melting temperature, cross-links in DNA, and filamentation of cells were obtained for E. coli AB 2463 (recA-) cells subjected to adaptive and challenging treatments with nitrofurantoin. Almost equal degree of resistance against nitrofurantoin could be induced in both V. cholerae OGAWA 154 (wild type) and E. coli strain PJ3 (AB 1157 ada-) when these cells were pretreated with nontoxic doses of hydrogen peroxide or nitrofurantoin. Evidence obtained in this work on the nature of the nitrofuratoin induced adaptive response with particular references to the oxidative and/or alkylating DNA damages were discussed. Nitrofuratoin induced adaptive response appeared similar to that elicited by furazolidone in V. cholerae cells and appeared to be directed towards oxidative and not alkylating adaptive repair pathway.

Adaptation, Physiological↗

In-vitro interaction between nitrofurantoin and Vibrio cholerae DNA.

In-vitro interaction of nitrofurantoin with V. cholerae DNA resulted in a quenching and red spectral shift of the drug absorption pattern. Scatchard analysis revealed that the drug binding involved more than one processes and that the strongest mode of binding was characterised by an association constant (k) of 5.04 x 10(6) M-1 and the number of binding sites per nucleotide (n) of 0.015. Based on viscosity measurements, the mode of drug binding to DNA appeared to be through intercalation, the helix unwinding angle of supercoiled plasmid pBR322 DNA being 10 degrees. Nitrofurantoin binding to DNA resulted in an elevation of the thermal melting temperature (Tm) of DNA by 6 degrees C and inhibition of the action of DNase on DNA.

Binding Sites↗

DNA damage and prophage induction and toxicity of nitrofurantoin in Escherichia coli and Vibrio cholerae cells.

Repair-deficient and repair-proficient strains of E. coli K12 were sensitive to nitrofurantoin treatment to varying degrees with the double mutant strain (uvrA 6, recA 13) being most sensitive. Ultraviolet absorption data and thermal chromatography through a hydroxyapatite column revealed that nitrofurantoin treatment of V. cholerae strain OGAWA 154 produced a maximal amount of 55% reversibly bihelical DNA at a nitrofurantoin dose of 120 micrograms/ml/h, which indicated the formation of inter-strand cross-links in DNA. Nitrofurantoin also produced prophage-lambda induction in E. coli K12 strain GY 5027: envA, uvrB, ampA 1, strA (lambda), in a dose-dependent manner, the maximum induction being highly significant (P less than 0.001). Previously published mutation data coupled with the prophage induction data presented here suggest that the genotoxic properties of nitrofurantoin are mediated through the SOS pathway.

Bacteriophage lambda↗

DNA damage and cell killing by nitrofurantoin in relation to its carcinogenic potential.

Nitrofurantoin inhibited growth and produced loss of viability of Vibrio cholerae cells in a dose-dependent manner, the 10% (D10) and 37% (D37) survival doses being 18.0 and 5.5 micrograms/ml x hr. respectively. The drug also caused filamentation of the cells in a very significant manner. Ultraviolet absorption data and thermal chromatography through hydroxyapatite column revealed that nitrofurantoin treatment of Vibrio cholerae cells produced a maximum amount of 55% of DNA reversibly bihelical due to the formation of inter-strand cross-links. Helix-coil transition studies carried out by viscometric and also, spectrophotometric methods revealed that the nitrofurantoin-induced cross-links in Vibrio cholerae DNA, imparted to this DNA greater thermal stability than that of native DNA. The quantitative aspect and also the mode of nitrofurantoin action on DNA of Vibrio cholerae and Escherichia coli cells vis-à-vis the carcinogenic potential of the drug were discussed.

Carcinogens↗

Cytological analysis of radiation-induced DNA amplification in C57BL/6 mice.

Inbred mouse strain C57BL/6 pre-treated with or without the drug with suspected anticancer activity, DADH (N, N'-Diacetyl-1, 6-Diaminohexane) by daily feeding for five consecutive days to a total dose of 1 mmol of the drug in aqueous solution, were exposed to an acute dose of 1 Gy gamma radiation. Appropriate controls without radiation were maintained both for water and DADH-fed groups of animals. At 18 and 36 h post-irradiation the animals from all four groups (designated as A to D with each group having six animals) were sacrificed and their bone marrows were cultured for chromosomal analysis. Special emphasis was put on the estimation of the frequency of occurrence of extra chromosomal elements, such as minutes, single or double (DMS) as a possible assay for radiation-induced DNA amplification (presumably representing the proliferation specified genes(?) causing initiation of a very early tumourigenesis event). Gamma irradiation alone yielded the highest frequency of such minute chromosomal structures concerned (DMS), which was significantly reduced by DADH pre-treatment. The preliminary cytological data are discussed in the light of current information on DNA amplification pertaining to carcinogenic induction.

Acetamides↗

Fructose 2,6-bisphosphate, carbohydrate partitioning, and crassulacean Acid metabolism.

Fructose 2,6-bisphosphate (F 2,6-P(2)) was detected in the CAM species, Ananas comosus and Bryophyllum tubiflorum, and in C(3)- and CAM-Mesembryanthemum crystallinum. In both Mesembryanthemum tissues, F 2,6-P(2) was located outside the chloroplast. The levels of F 2,6-P(2), malate, starch, or soluble sugars were measured during various periods during the day-night cycle in the leaves of Ananas, a species which stores carbohydrate in an extrachloroplastic compartment, and in Bryophyllum, a species which stores carbon as starch in the chloroplast. In both species, the levels of F 2,6-P(2) were correlated with the stages of the day-night CAM cycle. Immediately following the dark-light transition the F 2,6-P(2) levels exhibited a rapid transient increase followed by a decrease. F 2,6-P(2) reached a daily minimum soon after the onset of deacidification and remained low until the malic acid pools approached their daily minima; the levels of F 2,6-P(2) then began a slow increase which accelerated during the period of afternoon CO(2) uptake. Immediately following the light-dark transition F 2,6-P(2) levels fluctuated. The levels were usually low after the fluctuations had ceased. The pools then increased as the rate of malate synthesis increased, remained at relatively constant high levels when the rates of malate synthesis were constant, and decreased as malate synthesis decreased towards the end of the dark period. The absolute levels of F 2,6-P(2) were always higher in Ananas than in Bryophyllum. The ratios of the activity of pyrophosphate fructose-6-phosphate l-phosphotransferase to cytoplasmic fructose 1,6-bisphosphatase and to phosphofructokinase were also far higher in Ananas than in Bryophyllum or in C(3)- or CAM-Mesembryanthemum.

Journal Article↗

Induction of sister-chromatid exchanges by restriction endonucleases.

Restriction endonucleases Cfo 1, Pvu II, Sma I, Hpa II, Taq I and Hae III were tested for their ability to induce SCEs in CHO cells. The results indicate that the DNA double-strand breaks induced during S-phase by these enzymes lead to an increase in the frequencies of SCEs.

Animals↗

Evaluation of radiation-induced chromosomal aberrations in human peripheral blood lymphocytes in vitro: result of an IAEA-coordinated programme.

The results of an IAEA coordinated programme on radiation induced chromosomal aberrations in human peripheral blood lymphocytes in vitro are presented. In a master experiment, a whole blood sample from one donor was irradiated with 200 R of X-rays. Different fixation times from 46 to 82 h were used. The progression of cells into mitosis was monitored by BrdUrd incorporation. 14 investigators took part in the scoring of chromosomal aberrations. The main conclusions of this study are: (1) The mean frequencies of aberrations changed with fixation time. (2) The number of cells scored as aberrant by different laboratories was very similar, but there was variability in the number of aberrations scored per aberrant cell. (3) The differences in the frequencies of aberrations between laboratories were minimal when the scoring was restricted to the first major peak of mitotic activity and sufficient cells were scored. It is concluded that using controlled experimentals conditions, human peripheral blood lymphocytes can effectively be used as a reliable biological dosimeter for absorbed radiation dose.

Argentina↗

Visual communication with non-literates: a review of current knowledge including research in northern India.

In this article previous research on the perception of visual aids by non-literates in Kenya, Zambia, Ghana, Papua New Guinea, Mexico, as well as among immigrant groups in London and Paris, in Nepal and, by the authors in northern India, is reviewed. Recognition of pictures is affected by the particular culture of each group. In Africa, photos are better understood and liked: in the Indian subcontinent, line drawings are well recognized and appreciated. Recognition can be reduced by inaccurate detail, stylization and perspective. The authors found that overall size could be kept small if the pictures were simple. Complicated pictures, or a group of interrelated pictures, are not usually well recognized. Familiarity, realism and simplicity seem the most important components for a successful picture. Ways of attaching value ("good" or "bad", for example) have not in the past been very successful, but the authors found that a "vocabulary" of fourteen signs were, once explained, well understood. The values of colours in the culture must be understood and utilized. To be successful, visual materials for non-literates must start from the local culture and not come untested from behind a desk in the capital city.

Audiovisual Aids↗

Effect of low-dose acute X-irradiation on the frequencies of chromosomal aberrations in human peripheral lymphocytes in vitro.

In a coordinated research programme sponsored by the International Atomic Energy Agency, the frequencies of chromosomal aberrations induced in peripheral blood lymphocytes (in vitro) by 250 kV X-rays at low doses (0.4, 1, 2, 3, 5, 10 and 30 rad) were determined. Blood from 2 donors was used to conduct one master experiment at these dose levels. The culture time used was 48 h and all samples including the controls were processed according to a standard protocol. The coded slides were scored by investigators from 10 participating laboratories. The main results are the following: (1) the frequencies of all types of chromosome aberrations at 0.4 rad are significantly lower than the control values; (2) there is no increase in the frequencies of dicentrics up to 2 rad and in those of terminal deletions up to 5 rad; (3) the mean frequencies of all aberrations considered together are not significantly different from one another at 1, 2 and 3 rad (P = 0.05); and (4) over the entire dose range the dose-effect relationship is clearly non-linear. A fit of these data to a linear quadratic model (E(D) = c + alpha D + beta D2) showed that the observed total aberration frequencies at doses 1, 2, 3 and 5 rad are below the curve defined by the model. The deviations can be explained by an altered kinetics of aberration production at very low doses probably due to DNA repair mechanisms operating these cells.

Adult↗

Utility of free/total prostate specific antigen (f/t PSA) ratio in diagnosis of prostate carcinoma.

The discovery that PSA exists in serum in both free and complexed forms led to development of immunoassays specific for different PSA forms. This helped in measuring free PSA in the presence of PSA-ACT (PSA-alpha antichymotrypsin), hence it was possible to calculate the percent free PSA or free to total PSA ratio, measurement of which was helpful in reducing the number of unnecessary biopsies significantly, while maintaining a high clinical sensitivity for detection of cancer. The study was performed on 103 consecutive male patients (mean age 68 +/- 10.8 years SD) comprising of 90 patients with benign disease (87%) and 13 prostate carcinoma patients (13%), who had histologically proven prostate cancer. Patients with total PSA between 2-25 ng/ml were included in the study. 30 normal healthy males with age 58 +/- 10 years, served as control. Serum total PSA and free PSA were analyzed using streptavidin biotin EIA method (M/s Roche Diagnostics, Germany). The mean total PSA in normal healthy control subjects was 1.86 +/- 1.07 ng/ml. It was increased significantly in diseased condition. Its mean concentration in carcinoma patients was 12.6 +/- 5.3 ng/ml and in benign patients it was 6.3 +/- 4.6 ng/ml. The free to total PSA ratio in all the three groups was significantly different (p < 0.004) from each other. In carcinoma patients, mean f/t PSA ratio was 0.12 +/- 0.06 as compared to 0.21 +/- 0.11 and 0.28 +/- 0.17 in benign patients and in control respectively. The sensitivity and specificity of the test was calculated at different f/t PSA ratio cutoff. At 0.1 cutoff value, sensitivity of the test was 54% and specificity was 83%. The positive predictive value (ppv) was 32% and negative predictive value (npv) was 92%. From cutoff value of 0.12 to 0.16, sensitivity was increased from 54% to 85% but specificity was reduced from 78% to 67%. The ppv did not show much change and npv was increased from 92% to 97%. Increasing the cut off value thereafter showed no change in sensitivity but specificity was further reduced to 40%, therefore in this patient series, f/t PSA ratio cutoff of 0.16 was found to be the appropriate cutoff value. Combination of this ratio cutoff with other parameters like serum total PSA, DRE and TRUS helped in increasing the sensitivity of the test and this also helped in reducing the number of unnecessary biopsies. In 103 men who were biopsied, 13 (12.6%) prostatic carcinoma were identified. Among these 13 cancer patients, 9 patients had abnormal findings in DRE.7 individuals out of these 9, also had free to total PSA ratio lower than 0.16 and would have been biopsied and diagnosed anyway. If we use only f/t PSA ratio less than 0.16, to decide whom to biopsy, we would have biopsied and diagnosed 11/13 cases i.e. sensitivity of 85% but If we decide to biopsy those patients who had abnormal DRE and those who had low f/t PSA ratio, we could identify 13/13 carcinoma i.e. 100% sensitivity. Combining the f/t PSA ratio with total PSA, DRE and TRUS findings could help in reducing the number of unnecessary biopsies. 37 patients who were negative for malignancy having total PSA in the range of 5-20 ng/ml, normal DRE and TRUS findings, have been biopsied but with combination of total PSA in the range of 5-20 ng/ml, normal findings in digital rectal examination and TRUS and f/t PSA ratio more than 0.16 (cutoff), we could have avoided 16 biopsies which were unnecessary that means there was 43% reduction in unnecessary biopsies.

Aged↗