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Biomedical subjects

G Kaur

Publications and source records attributed to G Kaur.

At least 19 recordsLinked to original sources

Growth inhibition with reversible cell cycle arrest of carcinoma cells by flavone L86-8275.

BACKGROUND: Previous studies have shown that polyhydroxylated flavonoids such as quercetin and genistein can inhibit tumor cell growth in vitro, and preliminary in vivo studies of the flavone L86-8275 have shown growth inhibition of LX529 and A549 lung carcinomas. L86-8275 [(-)cis-5,7-dihydroxy-2-(2-chlorophenyl)-8[4-(3-hydroxy-1-methyl)- piperidinyl]-4H-1-benzopyran-4-one] is a flavone of novel structure. PURPOSE: The purpose of this study was to determine in vitro whether L86-8275 is a more potent inhibitor of growth in breast carcinoma and lung carcinoma cells than quercetin or genistein. METHODS: We studied the effects of L86-8275 on cell growth in seven breast carcinoma cell lines and five lung carcinoma cell lines. MDA468 breast carcinoma was then selected for further study. Cell proliferation was measured by a colorimetric dye reduction assay; synthesis of DNA, RNA, and protein by incorporation of the radioactive metabolic precursors thymidine, uridine, or leucine, respectively; adenosine triphosphate (ATP) content by a luciferase-mediated bioluminescence reaction; and cell cycle progression by the use of cell-synchronizing drugs (aphidicolin and nocodazole) and flow cytometry. RESULTS: L86-8275 was not cytotoxic to stationary-phase cells but reversibly inhibited the growth of cells in exponential growth phase. At concentrations of 25-160 nM, L86-8275 inhibited growth of human breast and lung carcinoma cell lines by 50%. MDA468 breast carcinoma cells were 60-fold and 400-fold more sensitive to L86-8275 than to quercetin and genistein, respectively. By 24 hours after addition of L86-8275, DNA synthesis in MDA468 cells was inhibited by greater than 95%, protein synthesis by 80%, and RNA synthesis by 40%-60%, under conditions that preserved cellular ATP levels at approximately 80%-90% of control values. When MDA468 cells released from aphidicolin-induced cell cycle arrest were exposed to 200 nM L86-8275, they completed the S phase but arrested in G2. When cells released from nocodazole-induced cell cycle arrest were exposed to 200 nM L86-8275, they completed mitosis but arrested in G1. CONCLUSIONS: L86-8275 is a potent, yet reversible, growth-inhibitory flavone that can selectively block cell cycle progression in vitro at more than one point in the cell cycle. IMPLICATIONS: These findings suggest that L86-8275 is a candidate for further preclinical development, as well as a model for the synthesis of other flavonoids that might potently delay cell cycle progression to achieve inhibition of tumor growth. Future studies need to address optimal schedules for antiproliferative activity in vivo and inhibition of clonogenic activity.

Adenosine Triphosphate

Acute starvation decreases acetylcholinesterase activity in different regions of rat brain.

The activity of acetylcholinesterase (AChE) was assayed spectrophotometrically in four brain regions of rats that had been deprived of food for 96 h. A significant decrease in the total AChE activity (by 4-45%) as well as in its specific activity (by 14-28%) was observed in the supernatant and total particulate fractions from cerebral hemispheres, cerebellum, brainstem and diencephalon + basal ganglia. Similarly, blood glucose, body weight and protein content of subcellular fractions from most brain regions showed decreases after starvation.

Acetylcholinesterase

Growth inhibition by cholera toxin of human lung carcinoma cell lines: correlation with GM1 ganglioside expression.

The effect of cholera toxin (CT) on the growth of 12 small cell lung carcinoma (SCLC) and 15 non-small cell lung carcinoma (NSCLC) cell lines is presented. CT inhibited the growth of nine SCLC cell lines (concentration for 50% inhibition of growth, 27-700 ng/ml), all of which had abundant expression of GM1 ganglioside, the surface receptor for CT. CT-resistant SCLC all had greatly decreased GM1 expression. In contrast, CT inhibited the growth of only four of 15 NSCLC cell lines. Seven of the 11 CT-resistant NSCLC had levels of GM1 comparable to CT-sensitive NSCLC or SCLC. In a limited panel of cell lines, cyclic AMP (cAMP) agonists including forskolin, 8Br[cAMP], and dibutyryl[cAMP] did not consistently reproduce CT-mediated inhibition of cell growth, nor did these compounds overcome resistance of cells to the growth inhibitory effects of CT. Expression of the RI and RII regulatory subunits of cAMP-dependent protein kinase was similar in CT-resistant and CT-sensitive SCLC or NSCLC cell lines. In the presence of isobutylmethylxanthine, intracellular cAMP levels induced by CT in a CT-resistant, GM1(+) NSCLC cell line were comparable to those achieved in a CT-sensitive NSCLC cell line. We conclude that inhibition of lung carcinoma cell growth by CT in all cases requires expression of GM1, and in the case of SCLC cell lines the presence of GM1 is sufficient. In NSCLC cell lines, expression of GM1 is not sufficient for growth inhibition by CT. These findings imply refractoriness to growth inhibition by cAMP in GM1(+), CT-resistant NSCLC cell lines and the possibility of non-cAMP-related mechanisms for growth inhibition in CT-sensitive cell lines.

1-Methyl-3-isobutylxanthine

Effect of dietary amino acids on in vitro rumen bacterial protein synthesis in buffaloes.

The effect of different ratios of urea to amino acid N at a fixed concentration of soluble sugars as energy source and varying levels of soluble sugars at optimum urea cell suspension was obtained from the rumen fluid of buffalo (Bubalus bubalis) calves fed on a growth ration. Under glucose fermentation, the bacterial protein content of the incubation mixture (I. M.) was increased to 3.91, 6.31 and 5.08 times the control value (urea alone) when 25, 50 and 75% of urea-N was replaced with amino acid N, respectively. With cellobiose, the corresponding increase was 4.06, 5.29 and 5.63 times. At 50% urea-N replacement with amino acid N (a ratio for maximum protein synthesis), the bacterial content was maximum when 1 g glucose or cellobiose per 100 ml of I. M. was added. Per cent incorporation of radioactivity from amino acids into bacterial protein was maximum at 25% amino acid N level with both the soluble sugar sources. The total amino acids incorporated into bacterial protein were, however, more at 50% than at 25% amino acid N level.

Amino Acids

A clinical, immunological, and histological study of neuritic leprosy patients.

An assessment has been made of 108 neuritic leprosy patients to find out if the number of affected nerves and the clinical presentations of these patients give any indication of the underlying severity (classification) of the disease. Detailed clinical recordings, skin smears, lepromin testing with Dharmendra antigen, and a leukocyte migration inhibition test (LMIT) using sonicated Mycobacterium leprae antigens were done in these patients. Nerve biopsies of available affected nerves were taken in 39 patients. The results show that neuritic leprosy patients also have a spectrum. However, none of the clinical parameters, including the number and distribution of affected nerves, the immune response and the nerve histology, were found to be inter-related. Further, even though all of the patients were skin-smear negative, a significant proportion showed lepromatous histology and nearly two thirds had a moderate-to-heavy bacterial load within the nerves.

Adolescent

Effect of acute starvation on monoamine oxidase and Na+,K(+)-ATPase activity in rat brain.

The activities of monoamine oxidase (MAO), responsible for oxidative deamination of many biogenic amines, and Na+, K(+)-ATPase, which plays a crucial role in the release mechanism of neurotransmitters, were determined in rat brain after acute starvation. They were assayed biochemically from four different regions of the brain in two subcellular fractions. Acute starvation decreased the activity of MAO, whereas the Na+,K(+)-ATPase activity was increased. An effect of starvation was also seen on the blood glucose level, body wt, and the protein content of different brain regions. Starvation or normal dietary fluctuations of certain nutrients that exert precursor influence over neurotransmitter synthesis are important to the brain, and contribute to its regulation of both neuroendocrine response and behavior. A rise in the substrate level, i.e., ATP, as a result of increased utilization of ketone bodies and low level of monoamines in the brain after acute starvation, may be the underlying factor for increasing the activity of Na+,K(+)-ATPase in rat brain. These results suggest that, probably, certain adaptive mechanisms become operative in the brain under disturbed physiological conditions.

Acute Disease

Effect of training on weight and certain physiological parameters of Indian female hockey players with respect to their field positions.

The present study was conducted on 18 female players of the Punjabi University hockey team during their camp held at Punjabi University from 4.10.1988 to 24.10.1988; before participating in the Inter-varsity competition held at Ranchi. Weight, heart rate and blood pressure of each subject was taken before doing the exercise on the treadmill. The players were asked to run on the treadmill for four minutes at the speed of 10 km/hr. Recovery heart rate and blood pressure were also taken. All these tests were taken twice on each player, i.e. initially at the commencement of the training and finally at the completion of the training camp. It has been observed that there is a reduction of body weight in all the categories of players, the maximum being in halves (2.5 kg). There is an improvement in the percentage recovery in the heart rates of all the categories of players except the halves where the recovery is much less at the end of the training camp as compared to the values in the beginning of the camp.

Adolescent

Morphine-induced inhibition of ovulation in normally cycling rats: neural site of action.

Intracerebral injection of morphine (3 micrograms/0.2 microliter of solvent) on the day of proestrus at 1200 hr bilaterally in the medial preoptic area (mPOA) and median eminence-arcuate (ME-ARC) region inhibited ovulation in the cycling female rats. The morphine antagonist, lethidrone (2 micrograms/0.2 microliter of solvent) when injected in the mPOA and ME-ARC region followed by intraperitoneal morphine (3 mg/100 g body weight) administration, was found to reverse the ovulation blocking action of this opiate. Implantation site at which morphine was effective in blocking ovulation were restricted to a narrow medial band encompassing the mPOA and ME-ARC region. Our data are consistent with the view that the endogenous opioid peptides in mPOA and ME-ARC region of the hypothalamus may be involved in the physiological regulation of the central neural events which lead to ovulation in the rat.

Animals

Studies on Streptococcus faecalis enterotoxin.

Streptococcus faecalis has been reported to cause food poisoning. Six strains of S. faecalis were tested for Sherman's criteria. These strains were non-hemolytic, DNase+ and Ent+. The enterotoxin was purified on Sephadex G-200 column and maximum activity was observed at 37 C and pH 7.0. Enterotoxin treated with trypsin and papain elicited very poor response to fluid accumulation. The sensitivity of all the strains against different antibiotics was determined. Strain 53 M was treated with acridine orange and ethidium bromide and a total of 44 Amps Strr and 3 Amps Strs mutants were tested for toxin production. Out of these only 4 were toxin negative, amongst which 3 were also DNase negative and 1 showed partial DNase activity.

Acridine Orange

Changes in hexokinase isoenzymes in regions of rat brain during thyroid deficiency.

In this work, activities of hexokinase isoenzymes Type I and Type II were measured in the soluble and particulate fractions from the brain regions (cerebral hemispheres (cerebrum), cerebellum and brain stem) of the thyroidectomized adult rats as well as of the thyroidectomized rats administered with triiodothyronine. Thyroidectomy generally decreased the hexokinase activity associated with particulate and soluble fractions. Hexokinase Type II isoenzyme was more affected than the Type I isoenzyme. Administration of triiodothyronine to the hypothyroid rats abolished the effect of thyroidectomy. Adult brain enzymes have been generally considered not be affected by thyroid hormones. The data obtained in this work are suggestive of an effect of thyroid hormones on hexokinase in the adult brain. Since the effects of thyroidectomy on the energy metabolism of the heart tissue are well known, the heart tissue was also studied for comparison.

Animals

Metabolic activity of lysosomes in tin-intoxicated regenerating rat liver.

The metabolic activity of lysosomes was monitored by assaying the lysosomal enzymes. DNase, RNase, acid phosphatase and cathepsin in rat liver regenerating after partial hepatectomy at various intervals after the operation. Results of the present study demonstrate that the activities of lysosomal enzymes are increased significantly during the process of rapid regeneration, especially at 24 h and 48 h. A small rise in enzymatic activities was noticed at 36 and 72 h of regeneration, leading towards normalisation at 168 h. Administration of tin(II) tartrate (25 mu mol Sn2+/100 gm body wt.) significantly increased the DNAse and RNAse activity at 24 h of the regeneration, while a decrease was noticed in acid phosphatase activity. An increase was also found in the catheptic activity of tin-treated hepatectomized rats. It can thus be concluded that an increased metabolic activity of lysosomes is reflected by the increased activity of its hydrolytic enzymes during the regeneration, and tin at low concentrations is helpful to this process. Further work is in progress to gain insight into the other metabolic activity of the lysosomes during the process of regeneration.

Acid Phosphatase