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Biomedical subjects

J Kaur

Publications and source records attributed to J Kaur.

At least 19 recordsLinked to original sources
PubMed1996

Role of N-terminal domain of streptokinase in protein transport.

Streptokinase (SK), an extracellular protein of several haemolytic strains of Streptococcus, is utilized as a potent thrombolytic agent for the treatment of various myocardial disorders. Functional properties of SK remain unchanged when the first 13 N-terminal amino acid (aa) residues are removed. At present, role of this segment in protein structure function is unclear. skc gene encoding for the mature SK and its deletion variant, lacking its first 13 aa residues, were cloned and expressed in E. coli. Full length SK, deprived of any leader sequences, was able to translocate slowly, across the cyto-plasmic and outer membranes of E.coli. Whereas, SK derivative, devoid of its first 13 N-terminal aa residues, could not do so. Cell fractionation studies as well as genetic evidences utilizing alkaline phosphatase fusion, point towards the existence of additional information for protein transport, within the N-terminal domain of SK. To further investigate the role of this region in protein secretion, genetic fusions were created in between full length and 13 aa deleted SK with OmpA leader peptide. Studies on kinetics of SK export from E.coli, revealed that translocation of protein is 3-4 times faster when the first 13 N-terminal residues of SK are intact. On the basis of results obtained, it has been proposed that the N-terminus of mature SK maintains the export competent status of protein and, thus, confer speed and efficiency upon the translocation process of streptokinase.

Biological Transport↗
PubMed1996

p53-HSP70 complexes in oral dysplasia and cancer: potential prognostic implications.

We have previously shown overexpression of p53 and 70 kDa heat shock protein (HSP70) in potentially malignant, as well as malignant, oral lesions in an Indian population, suggesting that alterations of p53 and HSP70 expression may occur in the early stages of oral tumorigenesis. Herein we report immunological evidence for the specific association between p53 and HSP70 in potentially malignant and malignant oral lesions. This association was indicated by coimmunoprecipitation of p53 and HSP72/73 proteins observed with either an anti-p53 monoclonal antibody or an anti-HSP72/73 antibody. Furthermore, reciprocal blotting analysis showed that HSP72/73 proteins did not share an epitope with p53, confirming that the coimmunoprecipitation of p53 and HSP72/73 is a physical association of the proteins in potentially malignant lesions (dysplasia) and oral squamous cell carcinomas (SCCs). p53-HSP70 complex formation was observed in 19/52 cases of oral SCCs and 10/53 cases of potentially malignant lesions (leucoplakia). Normal oral mucosa did not show the presence of p53-HSP70 complexes (0/20 cases). p53-HSP70 complex formation may be one of the mechanisms of stabilisation of p53 protein resulting in its increased levels in potentially malignant and malignant oral lesions and may be implicated in oral carcinogenesis.

Adult↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

Intraoperative mitomycin C in complicated glaucomas.

Filtering surgery has been found to be less successful in certain types of glaucoma. These include young patients, those with pigmentary glaucoma, secondary glaucoma, angle recession glaucoma, aphakic or pseudophakic glaucoma, and patients requiring reoperation. This study describes the authors' attempt to evaluate the effectiveness of conventional trabeculectomy with intraoperative application of mitomycin C in such patients. Ten eyes of 8 patients were evaluated in this study. Of these cases 4 eyes (2 bilateral cases) were from the primary juvenile open angle group; 2 eyes each had pseudophakic glaucoma and previous anti-glaucoma surgery which had failed; one eye had aphakic glaucoma and the last suffered from angle recession glaucoma. The intraocular pressure was successfully controlled in all the ten eyes. The preoperative IOP ranged from 28 to 50 mm Hg and the postoperative IOP ranged from 7 to 16 mm Hg. The postoperative complications were minimal.

Adult↗
PubMed1992

Effect of cyproterone acetate on structure and function of rhesus monkey reproductive organs.

A low dose of Cyproterone acetate (CPA; 1 mg/kg body weight/day for 70 days) was administered to adult male rhesus monkeys to assess its effects on testicular and epididymal structure and function in a nonhuman primate species. CPA caused extensive degenerative changes in morphology of seminiferous, efferent duct, and epididymal epithelia, including decrease in diameter of seminiferous and epididymal tubules and their lumen, height of epididymal epithelium, and an increase in intertubular connective tissue. The protein profile of spermatozoa showed alterations during their epididymal transit in control and CPA-treated monkeys. In CPA-treated animals, 19 polypeptides were acquired and nine were eliminated during epididymal transit in contrast to acquisition of 12 and loss of 14 polypeptides in control animals. Treatment with CPA also resulted in the appearance of 14 new polypeptides in epididymal cytosol and luminal fluid, probably of lysosomal origin. The protein pattern of caput and cauda epididymal tubule cytosol, maintained in organ culture and exposed to 100 microM CPA for 3 days, showed absence of eight polypeptides. These results indicate that even at the low dose used in this study, CPA has caused spermatogenic arrest, degenerative changes in the epididymal structure, and alterations in epididymal and sperm protein profile. Suppression of serum testosterone levels indicates the need for androgen supplementation if CPA is to be used for male contraception.

Androgen Antagonists↗