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Biomedical subjects

J Kaur

Publications and source records attributed to J Kaur.

At least 37 records · Page 2Linked to original sources

Dietary fat effects on brush border membrane composition and enzyme activities in rat intestine.

The effect of dietary fats on the chemical composition and enzyme activities has been studied in intestinal brush border membranes (BBM) or rats. Animals were given commercial rat pellet diet (RP) or semisynthetic diet rich in either saturated [coconut oil (CCO))] or polyunsaturated [n-6, corn oil (CO) or n-3, fish oil (FO)] fat at the 10% level for 5 weeks. The membrane cholesterol/phospholipid ratio was augmented in CO- or RP-fed rats. There was an increase in level of saturated fatty acids in BBM from CCO- or FO-fed animals. n-3 polyunsaturated fatty acid content was raised in FO-fed rats, while the proportion of linoleic acid and arachidonic acid was enhanced in animals given a CO diet. Membrane fluidity was in the order of CCO < RP = CO < FO. The membrane hexose content was high (p < 0.05) in the CCO group. Hexosamines were elevated (p < 0.05) in CCO- or FO-fed rat brush borders. Membrane fucose was unaltered, while sialic acid content was elevated in CO- (p < 0.05) and FO- (p < 0.01) fed vs. CCO-fed rats. Lectin binding to brush borders corroborated these findings. The activities of alkaline phosphatase, sucrase and lactase were augmented (p < 0.001) in CCO-fed animals. Leucine-aminopeptidase and sucrase activities were depressed by FO feeding. The activities of PNP-beta-glycosidases were the highest in FO-fed rats. These results indicate that dietary fat quality markedly affects microvillus membrane lipid composition, glycosylation and enzyme functions in rat intestine.

Alkaline Phosphatase

Novel Taxol formulation: polyvinylpyrrolidone nanoparticle-encapsulated Taxol for drug delivery in cancer therapy.

Taxol is a novel antitumor alkaloid that has shown clinical activity against several tumors. However, due to its low aqueous solubility, Cremophor EL (polyoxyethylated castor oil) and ethanol are used as excipients in the pharmaceutical drug formulations. These agents are implicated in hypersensitivity reactions. Hence the goal of this work was to design a novel Taxol formulation using polymeric nanoparticles to eliminate the Cremophor EL vehicle for drug delivery. Polyvinylpyrrolidone nanoparticles containing Taxol were prepared by a reverse microemulsion method. The size of the nanoparticles as determined by quasielastic light scattering was found to be between 50 and 60 nm. The antitumor effect of Taxol encapsulated nanoparticles was evaluated in B16F10 murine melanoma transplanted in C57B1/6 mice. The in vivo efficacy of Taxol-containing nanoparticles as measured by reduction in tumor volume and increased survival time was significantly greater than that of an equivalent concentration of free Taxol. These results suggest that encapsulation of Taxol in polymeric nanoparticles could be useful in improving its therapeutic efficacy in treatment of solid tumors.

Animals

Changes in tubular membrane glycosylation in diabetic, insulin and thyroxin treated rat kidneys.

The effect of insulin, thyroxine and alloxan induced diabetes has been studied on brush border membrane glycosylation in rat kidneys. Expressed on dry weight basis, the membrane protein was elevated in insulin, thyroxine and diabetic membranes compared to the control group. Sialic acid content of the membranes was significantly reduced in insulin and thyroxine injected animals whereas fucose level was unaffected under these conditions. Brush border fucose content was significantly reduced in diabetic animals but sialic acid content was unaffected. Membrane hexose and hexosamines levels were unaltered by hormone treatments, but in diabetic rats hexosamine level was significantly reduced. The binding of radiolabelled UEA, WGA, PNA to purified brush borders corroborated changes in membrane saccharides. These findings suggest the role of hormones in membrane glycosylation of rat kidney tubules.

Animals

Differential expression of 70-kDa heat shock-protein in human oral tumorigenesis.

To understand the biological events underlying the multistep process of oral tumorigenesis we have studied the expression of 70-kDa heat-shock protein, HSP70, in human normal, pre-malignant and malignant oral tissues. Expression of HSP70 was assessed in oral-tissue specimens using a mouse monoclonal antibody against HSP70 by immunostaining and immunoblotting analysis. Strong nuclear and cytoplasmic HSP70 immunostaining was observed in oral squamous-cell carcinomas (30/38). Mild to moderate HSP70 expression was observed in oral dysplastic lesions (19/30) and basal low level of HSP70 was observed in normal oral tissues. The results were corroborated by immunoblotting analysis. The wide variation in HSP70 expression in normal, pre-malignant and malignant oral lesions suggests that it is differentially expressed during oral carcinogenesis and may be implicated in tumor development.

Adult

Heat stress stimulates high affinity GTPase in cervical carcinoma cells.

A primary cellular site involved in heat shock response of eukaryotic cells is located in plasma membranes. The mechanism by which heat shock is sensed and the signals that trigger heat shock response remain an enigma. We aim to determine the role of guanine-nucleotide binding proteins (G)-proteins in mediating heat shock response in eukaryotic cells. The effect of heat shock on high affinity GTPase activity in presence or absence of modulators of G-proteins, such as pertussis toxin was studied by measuring GTPase catalyzed release of 32[Pi] from gamma-32[P]GTP. The effect of pertussis toxin on induction of heat shock proteins in cells subjected to thermal stress was studied by SDS-PAGE analysis of 35[S]-methionine labelled cellular proteins. Exposure of cultured human malignant cells to thermal stress (43 degrees C) resulted in a significant increase in activity of high affinity GTPase in the membranes (P < 0.001). This response to heat shock was inhibited by prior exposure of the cells to nanogram concentrations of pertussis toxin, suggesting the involvement of G-proteins in mediating heat shock response. To characterize this G-protein dependence further, we assayed thermal stress stimulated high affinity GTPase activity in cells pretreated with antisera (AS/7) raised against a synthetic peptide corresponding to the last 10 amino acids of alpha-subunit of inhibitory G-protein (Gi). A partial reduction in heat shock induced stimulation of GTPase activity was observed in the presence of this antisera. The pertussis toxin treated cells did not show induction of heat shock proteins in response to thermal stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies

Effect of chronic ethanol administration and dietary protein regimens on intestinal absorption of macromolecules in rats.

The effect of feeding ethanol daily for 40 days has been studied on intestinal absorption of bovine serum albumin (BSA) and gamma-globulin (IgG) in rats fed a low (8%) protein (LP) or a high (30%) protein (HP) diet. Feeding the LP diet enhanced the tissue uptake of BSA (p < 0.05) and absorption of BSA and IgG into serum (p < 0.001) as compared with controls. Feeding the HP diet also augmented the uptake of IgG (p < 0.001) by the intestinal tissue and significantly enhanced serum levels of BSA and IgG. Ethanol feeding to rats for 40 days enhanced the uptake of BSA and IgG (24-84%) and their absorption into serum (p < 0.001) as compared with the controls. Ethanol administration to rats fed LP or HP diets did not alter the uptake of these proteins as compared with their respective controls. Luminal degradation of BSA and IgG was higher in ethanol-administered (48-50% and 36-39%, respectively) and LP-fed rats (50 and 38%, respectively). It was reduced by 17-21% in HP-fed rats as compared with the control group. This indicated that the observed increase in protein absorption is not related to the luminal degradation of the proteins under these conditions. These findings suggest that the absorption of macromolecules from intestine in response to ethanol feeding is influenced by the dietary status of the animals.

Animals

Organomercury (II) complexes with anti-carcinogenic agents. I. Synthesis and characterization.

A few organomercury (II) complexes involving anti-carcinogenic ligands have been synthesized. The compounds are of the type p-MeOC6H4HgL1 (I), p-NO2C6H4HgL2 (II), p-MeOC4H4HgL3 (III) and p-MeC6H4HgL4 (IV) (HL1-6-mercaptopurine, HL2-6-thioguanine, HL3-5-fluorouracil, L4-phenyldithiocarbazate). Their composition has been determined from elemental analysis. Thin layer chromatography (TLC) studies demonstrate that the compounds are pure. Conductance measurement reveal that these derivatives are non-electrolytes. From IR and UV spectral studies the bonding modes of the ligands to the mercury (II) ion have been elucidated. The stoichiometry of the compounds has been confirmed on the basis of 1H and 13C NMR spectra. Some preliminary results of anti-neoplastic activity are reported.

Antineoplastic Agents

Organomercury (II) complexes with anti-carcinogenic agents. II. Anti-neoplastic activity.

Organomercury(II) complexes of the type, p-MeOC6H4HgL1 (I), p-NO2C6H4HgL2 (II), p-MeOC6H4HgL3 (III) and p-MeC6H4HgL4 (IV) (HL1-6-mercaptopurine, HL2-6-thioguanine, HL3-5-fluorouracil, L4-phenyldithiocarbazate) have been screened against the following cell panels: leukemia, non-small cell lung cancer, small cell lung cancer, brain cancer, melanoma, ovarian cancer and renal cancer. The variation in anti-neoplastic activity has been correlated with the structural parameters of the complexes.

Antineoplastic Agents

Safety of intrauterine administration of purified neem seed oil (Praneem Vilci) in women & effect of its co-administration with the heterospecies dimer birth control vaccine on antibody response to human chorionic gonadotropin.

Praneem Vilci (PV), purified neem oil was reported to exercise a reversible antifertility effect after a single intrauterine instillation in rodents and primates without any adverse effects. After toxicology, drug regulatory and ethical clearances, a phase I clinical trial was conducted on PV. Eighteen healthy tubectomised women were enrolled to evaluate the safety of a single intrauterine instillation of PV and to determine the effect of its co-administration on anti-hCG response to the heterospecies dimer (HSD) hCG vaccine. Eight women received PV alone and ten women were given the HSD-hCG vaccine in addition. Base-line and post-treatment haematological and biochemical profiles were determined as also the mid-luteal serum progesterone. Endometrial biopsies were examined to assess ovulatory status and the effect of intrauterine treatment with PV on the endometrium. Anti-hCG antibody titres were estimated in women who were concurrently immunized with the HSD vaccine. No untoward reaction was observed in any woman. Menstrual pattern and ovulatory status remained unaltered. Endometrial biopsy after PV instillation in one woman showed non-specific endometritis but she remained asymptomatic. Mild eosinophilia was seen in two women and this reverted to normal on its own. All women receiving PV and the HSD vaccine generated antibodies against hCG. Our data show that intrauterine administration of PV is safe and does not prevent the antibody response to HSD-hCG vaccine.

Adult

Elevation in diacylglycerol level and activation of protein kinase C in liver of mice administered with carcinogenic dose of 1,2-dimethylhydrazine.

Five weeks treatment of male mice with 1,2-dimethylhydrazine leads to elevation in the level of diacylglycerol in liver. Increase in diacylglycerol content is accompanied by an increase in particulate activity of protein kinase C with a fall in its activity in cytosolic fraction. Quantitative analysis of neutral lipids of different subcellular fractions from liver reveals that diacylglycerol levels increases highly significantly in liver microsomal membranes of carcinogen treated mice. Separation of neutral lipids by thin layer chromatography indicates that also there is an increase in cholesterol esters in nuclei, mitochondria and microsomes of mice liver whereas monoacylglycerol almost disappeared in mitochondria and microsomes after DMH administration in comparison to their respective controls.

1,2-Dimethylhydrazine

Differential expression of Mr 70,000 heat shock protein in normal, premalignant, and malignant human uterine cervix.

Transformed cells differ from normal cells in their pattern of heat shock protein expression. Here, we report differential expression of a Mr 70,000 heat shock protein (HSP70) in squamous cell carcinomas of the uterine cervix compared to normal or premalignant uterine cervix. Expression of HSP70 was measured using a mouse mAb against HSP70 by an ELISA. A significant increase in the level of expression of HSP70 was observed in fresh tumor cells as compared to normal or dysplastic ones (P < 0.001). The induction of HSP70 in tumor cells subjected to hyperthermia was less than that in normal or premalignant cells. Strong cytoplasmic and nuclear immunostaining was observed in cancerous tissues using anti-HSP70 mAb, biotinylated rabbit antimouse immunoglobulins, avidin combined in vitro with biotinylated horseradish peroxidase, and diaminobenzidine tetrachloride. HSP70 immunostaining was not detected in normal or dysplastic tissue sections. The results were confirmed by immunoprecipitation using anti-HSP70 mAb. These results are the first demonstration of overexpression of HSP70 in squamous cell carcinomas of the uterine cervix as compared to that in dysplastic or normal uterine cervix cells. We conclude that tumor cells differ from normal cells in their pattern of HSP70 expression, and increased levels of HSP70 correlate with an increase in tumor size.

Adult

A vaccine that prevents pregnancy in women.

We report here results of clinical trials on a birth control vaccine, consisting of a heterospecies dimer of the beta subunit of human chorionic gonadotropin (hCG) associated noncovalently with the alpha subunit of ovine luteinizing hormone and conjugated to tetanus and diphtheria toxoids as carriers, that induces antibodies of high avidity (K(a) approximately 10(10) M-1) against hCG. Fertile women exposed to conception over 1224 cycles recorded only one pregnancy at antibody titers of > 50 ng/ml (hCG bioneutralization capacity). The antibody response declines with time; fertility was regained when titers fell to < 35 ng/ml. This study presents evidence of the feasibility of a vaccine for control of human fertility.

Adult

Overexpression of p53 protein in betel- and tobacco-related human oral dysplasia and squamous-cell carcinoma in India.

The aetiological factors for oral cancer are not the same in India and in Western countries. Epidemiological studies have shown a correlation between high incidence of oral cancer and heavy consumption of betel and/or tobacco in the Indian population, while this study indicates an association with a genetic change. The p53 tumour-suppressor gene is the most commonly identified mutated gene in human malignancies. Expression of p53 protein was examined in premalignant and malignant oral lesions from Indian patients who were consumers of betel, areca nut and/or tobacco, using anti-p53 monoclonal antibodies PAb 1801 and PAb 421. Cryosections from normal, premalignant or malignant oral mucosa were used for immunostaining and the observations were confirmed by immunoprecipitation. p53 protein was detected in 55% (15/27) premalignant oral lesions (leukoplakia). Strong p53-positive staining was detected in 75% (24/32) of oral squamous-cell carcinomas. Normal oral mucosa did not show positive p53 staining (0/24). The detection of p53 protein in premalignant oral lesions suggests that p53 aberrations are an early event in the development of oral cancer in India. The high incidence of p53 positivity in leukoplakia may be due to differences in aetiological factors. p53 overexpression in premalignant oral lesions is important in view of the significantly earlier onset of leukoplakia in the Indian population compared to the development of oral malignancy, and may be helpful in identifying lesions that are more likely to progress to malignancy. The frequency of p53 protein overexpression was high in premalignant and malignant oral lesions of patients who were heavy consumers of betel, areca nut and tobacco.

Adult

Organomercury(II) complexes of kojic acid and maltol: synthesis, characterization, and biological studies.

A number of organomercury(II) complexes of kojic acid (HL1, I) and maltol (HL2, II) of the type p-XC6H4HgL1 (III) and p-XC6H4HgL2 (IV) [X = Me, MeO, NO2] have been synthesized and characterized. [formula: see text] Conductance measurements indicate the nonelectrolyte behavior of the complexes. From IR and UV studies, the bonding modes of the ligands to the organomercury(II) moieties have been elucidated. The 1H and 13C NMR spectra support the stoichiometry of the complexes. The fragmentation pattern has been analyzed on the basis of mass spectra. From thermal studies (TG and DTA), various kinetic and thermodynamic parameters for thermal degradation have been enumerated. The complexes have been screened against some pathogenic bacterial strains. The bactericidal activity has been correlated with the thermal data.

Anti-Bacterial Agents

Expression of brush border enzymes in ethanol fed rat intestine.

The effect of feeding ethanol daily for 40 days was studied on various brush border enzymes in rat intestine. Brush border alkaline phosphatase (AP), lactase, gamma-glutamyltranspeptidase (gamma-GTP), p-nitrophenyl (PNP)-beta-D-galactosidase (P < 0.01) and sucrase (P < 0.001) were significantly enhanced while leucine aminopeptidase and PNP-beta-D-glucosidase activities were unaltered in ethanol fed rats compared to the controls. Kinetic studies revealed that an increase in Vmax together with a decrease in affinity in case of gamma-GTP and an increase in Vmax for AP and sucrase were responsible for the observed stimulation of enzyme activities in ethanol administered rats. Significant changes in enzyme activities were observed in different populations of enterocytes along the crypt-villus unit in the ethanol fed animals. These observations suggest that ethanol feeding modifies the brush border enzymes in rat intestine but the underlying mechanisms seem to be distinct in differentiating enterocytes.

Alkaline Phosphatase

Phacolytic glaucoma--its treatment by planned extracapsular cataract extraction with posterior chamber intraocular lens implantation.

Phacolytic glaucoma has traditionally been treated with intracapsular lens extraction to avoid any anaphylaxis. Various mechanisms have been described for the rise of intraocular pressure in these cases. The present study was undertaken to evaluate the response of extracapsular cataract extraction (ECCE) with posterior chamber intraocular lens implantation (PC IOL) in five cases of phacolytic glaucoma that occurred between March 1989 and August 1990. A planned extracapsular cataract extraction with can-opener capsulectomy was done in all the cases with placement of a sulcus-fixated modified J-loop Sinskey design intraocular lens. With a mean follow-up period of two years, all patients (100%) maintained a normal postoperative intraocular pressure of less than 20 mm Hg without any additional medical therapy. The final best-corrected visual acuity in 4 cases (80%) was 6/12 or better, while in one case it was 6/24 due to a senile maculopathy. These results show that ECCE with PC IOL implantation is a safe and efficacious method of visual rehabilitation in cases of phacolytic glaucoma.

Aged

Effect of feeding high fat, high fiber diet on brush border enzymes in mice intestine.

The effect of dietary fat content on brush border enzymes has been studied in mice intestine. The results obtained from 26 per cent fat (high fat; HF)-fed mice were compared with those fed 10 per cent fat (pair-fed; PF and ad libitum-fed). Brush border alkaline phosphatase (AP), leucineaminopeptidase (LAP) and gamma-glutamyltranspeptidase (gamma-GTP) activities were significantly enhanced while sucrase activity was reduced (P < 0.001) in HF group compared to the controls. Activities of lactase, p-nitrophenyl (PNP)-beta-D-glucosidase and PNP-beta-D-galactosidase were unaltered under these conditions. Kinetic studies with AP, sucrase and LAP revealed that changes in enzyme levels in response to HF diet were due to change in Vmax. Significant changes in enzyme activities as a consequence of HF intake were observed in enterocytes all along the crypt-villus unit as compared to the control group. These results indicated that feeding a fat-rich diet produced selective changes in brush border enzyme activities in mice intestine.

Animals