PubMed Health⌕ Search

Biomedical subjects

R Seshadri

Publications and source records attributed to R Seshadri.

At least 127 records · Page 7Linked to original sources
PubMed1985

Calmodulin inhibitor trifluoperazine selectively enhances cytotoxic effects of strong vs weak DNA binding antitumor drugs in doxorubicin-resistant P388 mouse leukemia cells.

Doxorubicin-resistant P388 mouse leukemia cells are cross-resistant to anthracycline and non-anthracycline DNA intercalators as well as to natural and semisynthetic anthracyclines which bind weakly or not at all to DNA. In the presence of a non-lethal concentration of 5 microM trifluoperazine cytotoxic effects of the strong DNA binding drugs actinomycin-D, mitoxantrone and m-AMSA were enhanced less than 2 fold in doxorubicin-sensitive cells and up to 50 fold in doxorubicin-resistant cells. Additionally, trifluoperazine induced a greater than 2-fold enhancement in the cytotoxic effects (but not accumulation and retention) of the strong DNA binder N,N-dimethyladriamycin-14-valerate only in doxorubicin resistant cells. In contrast, cell kill, drug accumulation and retention in P388/S and P388/DOX cells treated with the weak DNA binders N-benzyl-adriamycin-14-valerate and 7(R)-O-methylnogarol, and DNA-nonbinding N,N-dibenzyldaunorubicin was similar with or without trifluoperazine treatment. The study demonstrates that the calmodulin inhibitor trifluoperazine induces a specific and marked enhancement in the cytotoxic effects of strong vs weak DNA binding antitumor drugs in doxorubicin-resistant cells.

Aminoacridines↗
PubMed1985

A morphometric classification of acute lymphoblastic leukemia in children.

In order to reduce the subjective errors in subtyping leukemic lymphoblasts using the French-American-British (FAB) classification, computer-assisted morphometry was used. Bone marrow smears obtained at diagnosis from 99 children with acute lymphoblastic leukemia (ALL) were analysed by this method and compared with the subjective FAB classification. The results confirm that lymphoblast morphology, as a single variable, is a very significant predictor of survival in ALL. This computer-assisted morphometric analysis would be of great value in large-scale clinical trials in ALL.

Bone Marrow↗
PubMed1985

FMC-HU-1-B: a lymphoma B-cell line with unusual characteristics.

A cell line (FMC-Hu-1-B) was established from a biopsy of an abdominal mass of a child with non-Burkitt's lymphoma. The establishment of the cell line initially required the presence of normal bone marrow stromal cells and phytohaemagglutinin stimulated leucocyte conditioned medium. The cell line lacked Epstein-Barr virus nuclear antigen and exhibited numerous chromosomal abnormalities. Cell-surface marker analysis using a panel of monoclonal antibodies revealed only markers of the B lineage. Within the B-cell lineage FMC-Hu-1-B seemed to occupy a level of maturation equivalent to normal mature B-cells (surface membrane IgM, secretion of immunoglobulin and FMC-1 positive). However, the cells also weakly expressed the common acute lymphoblastic leukaemia antigen, normally found on early precursors of B-cells. The cells appear to secrete auto-stimulatory growth factor(s).

B-Lymphocytes↗
PubMed1985

Adriamycin analogues. rationale, synthesis, and preliminary antitumor evaluation of highly active DNA-nonbinding N-(trifluoroacetyl)adriamycin 14-O-hemiester derivatives.

N-(Trifluoroacetyl)adriamycin 14-valerate (AD 32), a novel DNA nonbinding analogue of adriamycin with superior experimental antitumor activity, has undergone extensive clinical trial, with documentation of antitumor activity and low toxicity in human subjects. However, poor water solubility necessitates that the drug be administered to patients by continuous intravenous infusion at high dilution in a surfactant-containing formulation, with steroid prophylaxis to protect against a chest pain syndrome associated with the vehicle. On the basis of pharmacologic considerations, the title compounds have been prepared as second-generation analogues of N-(trifluoroacetyl)adriamycin 14-valerate with improved aqueous solubility; use is made of the available carboxylic acid function to solubilize the products in dilute aqueous alkaline medium. Target compounds were made by treating N-(trifluoroacetyl)-14-halodaunorubicin (bromo or iodo) with monosodium salts of dibasic acids (malonic, succinic, glutaric, adipic, pimelic, azelaic, sebacic) in aqueous acetone. All of the products showed significant in vivo antitumor activity against the murine P388 leukemia (ip tumor, ip treatment once daily on days 1, 2, 3, and 4); most compounds were superior to the +181% increase in life span afforded by adriamycin (optimal dose 3.0 mg/kg per day), one of two drugs used as positive controls for the assays. Several of the test compounds showed highly curative activity in this system, similar to N-(trifluoroacetyl)adriamycin 14-valerate, the other positive control agent. The hemiadipate product exhibited the most desirable properties of high antitumor efficacy (86% cure rate all P388 tumor-bearing animals through four levels of a 40-70 mg/kg dose-response range), aqueous solubility (60 mg/mL in pH 7.4 phosphate buffer), and solution stability (no decomposition at 4 degrees C, 0.5% hydrolysis at 27 degrees C, over 24 h at pH 7.4).

Animals↗
PubMed1985

Relationship between peroxidase activity and steroid receptors in human mammary tumors.

The interrelationships between levels of estradiol receptors (ER) and estrogen-dependent proteins, peroxidase and progesterone receptors (PgR) were examined in 54 histologically proven primary breast tumors in Indian women. ER and PgR were determined by the agar gel electrophoresis and dextran coated charcoal methods, respectively. Peroxidase activity (PA) was estimated by the guaiacol method. Our results showed a lack of correlation between ER and PA as well as between concentrations of PgR and PA in the tumors. It was concluded from this preliminary investigation that, in addition to ER and PgR, estimation of PA does not contribute significantly to more accurate assessment of hormone dependence of human breast tumors.

Breast Neoplasms↗
PubMed1985

Effects of new N-alkyl analogues of adriamycin on in vitro survival and cell cycle progression of L1210 cells.

The effects of N-benzyladriamycin-14-valerate (AD198) and N,N-dimethyladriamycin-14-valerate (AD199), two novel lipophilic N-alkyl derivatives of Adriamycin (ADR), on cell growth and cell cycle distribution were investigated in L1210 cells grown in suspension. Following a 1-h exposure to the drug levels selected, growth inhibition was noticeable in all cultures for most or all of the observation period of 96 h. With flow cytometry, an asynchronous cell population was measured with respect to cellular DNA, RNA, and light scatter (size) properties following a 1-h incubation with the various ADR analogues. In addition, flow cytometric techniques were utilized to determine whether drug treatment altered the sensitivity of DNA in situ to acid-induced denaturation or to binding by small DNA-intercalating dyes. Unlike the parent compound ADR or its DNA-nonbinding derivative N-trifluoroacetyladriamycin-14-O-hemiadipate (AD143), the N-alkyl derivatives AD198 and AD199 only slightly affected L1210 cell cycle traverse over the first 5 h posttreatment. However, by 24 h, AD199 (0.62 micrograms/ml) caused an S- and G2 + M-phase accumulation which became more dramatic at 48 and 72 h. AD198 (3.27 micrograms/ml) also caused an accumulation of cells predominantly in G2 + M phase at longer culture times (48 to 96 h). The two half-substituted congeners N-benzyladriamycin (AD288) and N,N-dimethyladriamycin (AD280) affected L1210 cell cycle traverse over a similar time scale at concentrations of 12.3 and 4.17 micrograms/ml, respectively. AD280 blocked cells in G1 and G2 + M whereas AD288 caused predominantly a G2 + M accumulation. While neither ADR nor AD143 interfered appreciably with binding and fluorescence of the intercalating dye acridine orange, all of the N-alkyl analogues tested reduced the fluorescence signal of acridine orange-stained L1210 cells by 26 to 60%. This effect lasted, with decreasing intensity, for at least 48 h following a 1-h exposure to the drugs. In addition, while ADR appeared to stabilize DNA in situ against acid-induced denaturation, all N-alkyl derivatives, to varying degrees, tended to increase DNA denaturability. Thus alkylation at the glycoside amine combined with the lipophilic 14-valerate side chain function accounts for several new biochemical and biological properties of AD198 and AD199, relative to ADR.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Sensitivity of lymphocytes from patients with cancer to x- and ultraviolet radiation.

It has been suggested that radiation sensitivity may be increased in certain patients with cancer. Using a high-efficiency limiting dilution cloning technique, the sensitivity to x- and ultraviolet (UV)-radiation of lymphocytes from untreated patients with cancer to that of age-matched controls was compared. Sensitivity to x-radiation in 19 patients with carcinoma and 10 with lymphoma, and sensitivity to UV-radiation in 8 patients with carcinoma and 4 with lymphoma were studied. The proportion of unirradiated lymphocytes forming clones was significantly lower in patients with cancer, particularly lymphoma, but there was no suggestion of increased sensitivity to either x- or UV-radiation in any of the patients studied.

Adult↗
PubMed1984

The effect of bone marrow stromal cells on the cloning of human leukemia/lymphoma cell lines.

The cloning of established human leukemia and lymphoma cell lines at limiting dilutions in microwells and soft agar is described. Growth of most cell lines was improved by the addition of human AB serum and irradiated human bone marrow stromal cells. In general, the cloning efficiency in microwells was greater than in soft agar. The effect of bone marrow stromal cells appeared to be caused by a diffusable factor(s), but close cellular interaction could not be excluded since cloning in microwells produced consistent and optimal cell growth compared to growth in soft agar. It was concluded that cloning of leukemia and lymphoma cell lines in microwells was the preferred method and that similar techniques could improve the cloning of fresh leukemia and lymphoma cells.

Bone Marrow Cells↗
PubMed1984

T-cell growth factor production by adult, but not childhood. Acute lymphoblastic leukaemic cells.

The production of T-cell growth factor (TCGF) by acute lymphoblastic leukaemia (ALL) cells was determined in seven children and in three adults. A significant production of TCGF by adult, but not childhood, ALL cells was observed. The adult ALL cells were classified as "non-T-non-B" by surface marker analysis. It is suggested that TCGF production may not be confined to the cells of T-lineage.

Acute Disease↗
PubMed1984

Mutation frequency in human lymphocytes increases with age.

Several theories of ageing predict that somatic mutations should increase with age. This prediction was tested for human lymphocytes using a recently developed clonal technique for enumeration of mutations, and an increase of 1.6% per year in mutations with age was detected.

Adolescent↗
PubMed1984

Decreased cloning of lymphocytes from elderly individuals.

Limiting-dilution cloning of human lymphocytes was used to study cloning and proliferation of lymphocytes in 10 young and 10 elderly individuals. The cloning efficiency for elderly individuals, 3.5%, was significantly lower than that for young individuals, 19.8%. Mixing experiments showed that this decrease was due to both a decrease in the frequency of the clone-forming cells and a decrease in the interacting ability of the lymphocytes. Lymphocytes from elderly individuals which did form clones, however, proliferated at the same rate as did those from young individuals.

Adult↗
PubMed1984

Mutation frequency in nurses and pharmacists working with cytotoxic drugs.

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.

Adult↗
PubMed1983

Peroxidase activity (PA) and progesterone receptors (PgR) in normal rat mammary glands.

PA and PgR appear to be reliable markers of estradiol action in normal female rat mammary glands, as seen by simultaneous expression of both proteins between the ages of 61 and 131 days. However, expression of PA at certain periods, when PgR was undetectable suggests, that the extent of availability of both estradiol and progesterone at target sites may act as controlling factors in synthesis of one protein over another.

Aging↗
PubMed1983

Adriamycin analogues. Preparation and biological evaluation of some novel 14-thiaadriamycins.

Condensation of 14-bromodaunorubicin with thiols in methanol, in the presence of potassium carbonate, resulted in the formation of 14-thia analogues of the antitumor antibiotic adriamycin. However, similar condensation of N-(trifluoroacetyl)-14-iododaunorubicin with thiols invariably led to a redox reaction, with the formation of N-(trifluoroacetyl)daunorubicin and disulfides. Accordingly, N-(trifluoroacetyl)-14-bromodaunorubicin was used for reaction with thiols to yield thia analogues of the clinically active but non-DNA-binding adriamycin analogue N-(trifluoroacetyl)adriamycin 14-valerate (AD 32). Reaction of 14-bromoadunorubicin with alpha, omega-alkanedithiols gave bis(thiaadriamycin) analogues as potential difunctional intercalating agents. The aforementioned products, plus two related phenylselena derivatives, were examined for in vitro growth inhibition, in vivo antitumor activity, and, where appropriate, DNA binding. A number of agents, most notably 14-(carbethoxymethyl)-14-thiaadriamycin and N-(trifluoroacetyl)-14-phenyl-14-selenaadriamycin, were active against murine L1210 leukemia in vivo. Several of the amino glycoside unsubstituted 14-thiaadriamycin analogues exhibited DNA-binding properties equivalent to those of adriamycin.

Animals↗
PubMed1983

Fine needle aspiration cytology in the management of lymphoma.

The use of fine needle aspiration (FNA) cytology in the management of patients with lymphadenopathy was investigated. The cases of non-Hodgkin's lymphoma were classified using the Kiel classification, which is based strictly on cytological criteria. Of the 59 cases of biopsy confirmed lymphoma, FNA of nodes showed lymphoma in 53 (90%), no definite diagnosis in five (8%), and false negative diagnosis in one (2%). During the follow-up of patients FNA was positive in seven of the eight cases with a suspected recurrence which was later confirmed by lymph node biopsy. Results suggest that FNA is useful on the initial presentation of a patient with lymphadenopathy. If the diagnosis is unequivocal it helps in planning staging procedures and in selecting involved nodes for biopsy. In some cases with intra-abdominal disease it may obviate laparotomy. However, because false negative diagnoses do occur and because cytological classification of lymphoma is not always accurate FNA should not replace lymph node biopsy at initial presentation, but it can be used as the only investigation to confirm suspected recurrence.

Adolescent↗
PubMed1983

Infantile pyknocytosis: a cause of intrauterine haemolysis in 2 siblings.

Infantile pyknocytosis, a rare cause of intrauterine haemolysis and potential perinatal death, is described and the relevant literature reviewed. Treatment consists of preterm delivery with exchange transfusion as necessary to control the haemolytic process and hyperbilirubinaemia.

Amniocentesis↗