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Biomedical subjects

P Kaur

Publications and source records attributed to P Kaur.

At least 55 records · Page 3Linked to original sources
PubMed1997

Identification of a cell surface protein with a role in stimulating human keratinocyte proliferation, expressed during development and carcinogenesis.

In an attempt to define cell surface molecules with an important role in the development of squamous cell carcinomas (SCCs), we generated monoclonal antibodies (MoAbs) to a human keratinocyte cell line (FEP18-11-T1) capable of giving rise to SCCs in nude mice. MoAb 10G7 was selected for further study because it bound to a cell surface component preferentially expressed by this cell line as compared with normal human foreskin keratinocytes. This MoAb recognizes a cell surface protein (10G7 antigen) that is not detectable on normal keratinocytes in the foreskin in vivo, but whose expression is induced when the keratinocytes are dissociated from this tissue and placed in culture. Interestingly, the 10G7 antigen is downregulated upon keratinocyte differentiation in vitro. Consistent with its expression in hyper-proliferative epithelia in vitro, 10G7 antigen exhibited a classic oncofetal pattern of expression in vivo. Thus, although no reactivity was obtained with MoAb 10G7 in the epithelia of normal foreskin or cervical tissue, strong reactivity was detected in epithelia from genital lesions ranging from benign warts to invasive SCCs. Epidermis from developing fetal tissue also exhibited strong reactivity with MoAb 10G7. We have been able to demonstrate that this MoAb is capable of stimulating FEP18-11-T1 keratinocyte proliferation in vitro in a concentration-dependent manner in the absence of growth factors, suggesting that the 10G7 antigen may play an important role in regulating cellular proliferation during development and in carcinogenesis in epithelial tissues.

Animals↗
PubMed1997

Expression and characterization of DrrA and DrrB proteins of Streptomyces peucetius in Escherichia coli: DrrA is an ATP binding protein.

Streptomyces peucetius, a microorganism that produces the anticancer drugs doxorubicin and daunorubicin, is itself resistant to the action of these drugs. The genes conferring resistance to doxorubicin and daunorubicin in S. peucetius have been sequenced (P. G. Guilfoile and R. Hutchinson, Proc. Natl. Acad. Sci. USA 88:8553-8557, 1991). Two open reading frames, drrA and drrB, were proposed to encode for an ABC (ATP-binding cassette) type of permease that carries out export of the antibiotics in an ATP-dependent manner. This article reports subcloning of the drrA and drrB genes into Escherichia coli expression vectors and characterization of their gene products. Upon induction from the lac promoter, a 36-kDa DrrA protein could be identified on Coomassie blue-stained gels. The DrrB protein was identified by use of a polyclonal antiserum generated against a synthetic peptide corresponding to a portion of the DrrB protein. Together, the DrrA and DrrB proteins conferred resistance to doxorubicin in E. coli. The DrrB protein was localized to the cell membrane. The DrrA protein bound ATP or GTP in a Mg2+-dependent fashion. ATP binding was enhanced on addition of doxorubicin or daunorubicin.

ATP-Binding Cassette Transporters↗
PubMed1997

Multilaboratory comparison of in vitro tests for chromosome aberrations in CHO and CHL cells tested under the same protocols.

Different test results have been reported for the same chemicals in two in vitro chromosome aberration test systems, CHL cells tested by a Japanese protocol and CHO cells tested by the US National Toxicology Program [Sofuni et al., Mutat Res 241:173-213,1990]. Here, laboratories in Japan, the US and the UK tested 9 such chemicals in CHL and CHO cells using the same protocols and found all 9 positive in both cell types; differences in earlier conclusions with these chemicals were due mainly to test protocol, not to different sensitivities of the cells. The most important protocol difference is sampling time. Chemicals that were negative in the NTP series using a sampling time of 10 to 13 hours often produced positive results when retested here with a 20- to 24-hour sampling time. While positive results were obtained in both cell types, CHL cells sometimes had higher aberration levels and survived at higher doses than CHO cells would tolerate. This may reflect some intrinsic difference in sensitivity but may also be affected by factors such as cell cycle length and culture media (e.g., oxygen scavenging capacity). The collaboration reported here also contributed to a better understanding of scoring aberrations, especially "gaps"; there was good agreement on what types of aberrations should be included in the totals when scoring criteria were clearly defined, for example, many changes classified as "gaps" by the Japanese system were classified as "breaks" in the scoring systems used in the United States and the United Kingdom, and were appropriately included in total aberration counts.

Animals↗
PubMed1996

Purification, crystallization and preliminary crystallographic analysis of mare lactoferrin.

Lactoferrin is an iron-binding glycoprotein with a molecular weight of 80 kDa. The protein has two iron binding sites. It has two structural lobes, each housing one Fe(3+) and the synergistic CO(3)(2-) ion. The protein was isolated from the colostrum/milk of mares maintained at National Research Centre on Equines, Hisar, India. The purified samples of the protein were crystallized using a microdialysis method. The protein was dialysed against low ionic strength buffer solution. Several crystal forms were obtained, out of which three were characterized which have cell dimensions as follows. Form I a = 79.8, b = 103.5, c = 112.0 A, space group P2(1)2(1)2(1), with one protein molecule per asymmetric unit and a solvent content of 57%. Form II a = 84.9, b = 99.7, c = 103.5 A, space group P2(1)2(1)2(1) with one molecule per asymmetric unit and a solvent content of 55%. Form III a = 151.0, b = 151.0, c = 240.6 A, space group P4(1)2(1)2 with three molecules in the asymmetric unit and a solvent content of 57%. The intensity data up to 3.8 A resolution for form I, 2.9 A resolution data for form II and 6 A resolution data for form III have been collected. Further calculations are in progress.

Journal Article↗
PubMed1996

Backbone--side-chain interactions in serine. Synthesis, crystal structure and solution conformation of a linear model peptide N-Boc-L-Ser-L-Phe-OCH3.

The peptide Boc-Ser-Phe-OCH3 was synthesised by a solution-phase method using the usual workup procedure. The peptide was crystallized from a 70:30 (v/v) methanol-water mixture. The crystals are monoclinic, space group P21 with a = 5.128(2), b = 17.873(2), c = 11.386(2) A, and beta = 98.03(3) degrees. The structure was determined by direct methods and refined by structure factor least-squares procedure. The final R-value for 1499 observed reflections was 0.041. The structure contains one peptide and one solvent water molecule. The peptide adopts a beta-strand-like conformation with phi 1 = -100.3(5), psi 1 = 99.9(5), phi 2 = -122.2(5), psi T2 = -172.5(6) degrees. The Ser side-chain assumes an extended conformation with chi 11 = -177.0(4) degrees. The O gamma H group of serine acts as a proton donor in an intramolecular weak hydrogen bond with (Ser) O'1 [O gamma 1 - H gamma 1 ... O'1 = 3.253(6) A]. The Phe side-chain adopts a staggered conformation with chi 1(2) = -70.9(6), chi 2,1 (2) = 88.4(7) degrees, chi 2,2(2) = -89.2(6) degrees. The water molecule generates a loop through two hydrogen bonds with O gamma 1 [OW ... O gamma 1 = 2.893(5) A] and O'2 [OW ... O'2 = 2.962(7) A] atoms. The unit-translated peptide molecules along the a-axis are held by hydrogen bonds: N1 - H1 ... O2 (chi - 1, y, z) = 2.954(4) A and N2 - H2 ... O'1 (chi + 1, y, z) = 2.897(6) A in a manner similar to those observed in parallel beta-pleated sheet structures. There is an additional interaction involving O gamma 1 and the water molecule [OW ... O gamma 1 (chi + 1, y, z) = 2.789 (4) A]. The strong NOE peak of Ci(H) ... Ni + 1 (H) and a simultaneous weak NOE peak of Ni(H) ... Ni + 1 (H) in the ROESY spectra of two-dimensional NMR in dimethyl sulfoxide indicate a beta-strand-like conformation for the peptide in solution.

Models, Molecular↗
PubMed1996

Effect of noise stress on some cardiovascular parameters and audiovisual reaction time.

A study of the effect of noise stress on some of the physiological parameters was carried out on healthy male workers of thermal power station (exposed to sound level 90-113 dBA) and compared with age and sex matched healthy controls (exposed to sound level 48-66 dBA). The parameters recorded were heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), galvanic skin resistance (GSR), auditory and visual reaction time (ART and VRT) and audiogram. Significant impairment in audiogram at 3000 Hz and 4000 Hz, increase in HR, SBP, DBP and decrease in GSR, ART and VRT were recorded in workers who were exposed to noise stress. Also a higher prevalence of hypertension was observed in them and that they were at a higher risk of developing hypertension than the control group. It was also observed that these modifications are related to duration of exposure to noise stress. It is presumed that all the above extra auditory effects are due to activation of autonomic nervous system and hypothalamo-hypophyseal adrenal axis, and the resultant release of catecholamines from adrenal medulla due to noise stress.

Acoustic Stimulation↗
PubMed1995

Plant growth hormone kinetin delays ageing, prolongs the lifespan and slows down development of the fruitfly Zaprionus paravittiger.

A cytokinin plant growth hormone kinetin (Kn) retards senescence in plants and delays ageing in human cells in culture. We have now observed that Kn also slows down ageing and prolongs the lifespan of the fruitfly Zaprionus paravittiger when these insects are fed with 25-125 ppm Kn added in their diet medium. In addition, 25 ppm Kn also slows down the larval and the pupal stages of the developing insects. However, the anti-ageing effects of Kn are not merely due to the slowing-down of development, but are mainly due to a reduction in the age-specific death rates throughout the adult lifespan.

Adenine↗
PubMed1995

Primary structures of seven metallothioneins from rabbit tissue.

Metallothionein from tissues of rabbits exposed to cadmium chloride was separated into seven distinct isoforms by reverse-phase liquid chromatography and their complete amino acid sequences were determined. Five of the seven isometallothioneins showed structural features so far not identified in other mammalian metallothioneins. Thus, two isoproteins contain a polypeptide with a chain length of 62 rather than 61 amino acid residues. Two isoforms are characterized by an additional positive charge and one by the presence of an isopeptide bond between aspartic acid and serine in the N-terminal half of the protein. The isoproteins characterized were identified from different sources: rabbit liver and kidney and a rabbit kidney cell-line (RK-13). In all three, the structural characteristics of the individual isoforms are retained, indicating that in the different tissues the same mechanisms control the synthesis and the stability of the different cadmium-induced isoMTs.

Amino Acid Sequence↗
PubMed1995

Phenolphthalein: induction of micronucleated erythrocytes in mice.

Phenolphthalein was tested for the induction of micronucleated erythrocytes in mice. Results of an initial investigation revealed significant, dose-related increases in micronucleated polychromatic erythrocytes (MN-PCE) and normochromatic erythrocytes (MN-NCE) in peripheral blood samples of male and female mice exposed to 0.6% to 5% phenolphthalein (approximately 1100 to 10,000 mg/kg/day) in feed for 90 days (Dietz et al., 1992). Results from a second long-term feed study with Swiss CD-1 mice confirmed this effect. However, administration of comparable doses of phenolphthalein by corn oil gavage on two consecutive days gave negative results in a mouse bone marrow micronucleus test. Subsequent tests were performed to clarify the conflicting results seen in the chronic exposure, dosed-feed, peripheral blood studies and the acute, corn oil gavage, bone marrow studies. Phenolphthalein was administered to male B6C3F1 mice in feed (3%) for 14 days. Peripheral blood samples taken at 4, 7, and 14 days all showed significant increases in micronucleated PCE; bone marrow samples taken on days 7 and 14 also were clearly positive for micronucleus induction. Therefore, comparable results were obtainable from both bone marrow and peripheral blood analyses. Because of the negative results in the two-exposure gavage test, additional tests were then designed to investigate the effects of bolus vs continuous dosing, feeding vs gavage administration, and corn oil vs feed as a carrier for phenolphthalein. Results of these tests indicated that the rate of exposure to phenolphthalein affects the frequency of induced MN-PCE and that micronucleated erythrocytes can be induced by phenolphthalein either by feeding or by corn oil gavage administration. In all the acute exposure studies, relatively high doses of phenolphthalein (2000-6000 mg/kg/day for at least 2 days) were required to induce micronuclei. The positive results obtained with phenolphthalein in vivo were consistent with the results of an in vitro chromosomal aberration test in Chinese hamster ovary cells, where dose-related increases in aberrations were noted only in cells treated in the presence of induced rat liver S9.

Animals↗
PubMed1995

Japanese encephalitis virus is an important cause of encephalitis among children in Penang.

This study was carried out to determine if Japanese encephalitis virus is an important causative agent of viral encephalitis among pediatric admissions in Penang, Malaysia. 195 children with CNS symptoms and 482 children with non-specific febrile illness admitted into the Pediatric Ward of Penang Hospital during a 16 month period were entered into the study. The presence in serum of cerebrospinal fluid (csf) of Japanese encephalitis virus (JEV) specific IgM was determined by an IgM capture ELISA and cytomegalovirus (CMV) specific IgM was determined using a commercially available kit (Behringwerke AG). It was determined that 5 of 13 children with a discharge diagnosis of viral encephalitis had JEV specific IgM in csf, indicating that 38.5% of the viral encephalitis cases was due to JEV. One of the non-JEV cases was found to have mumps virus specific IgM in csf, while no etiology was determined for the other cases. It was also determined that 4 of the 195 (2.1%) cases with CNS symptoms had IgM to CMV, suggesting CMV may be an agent of encephalopathy in children in Penang. Other viruses found to be associated with CNS symptoms in children admitted into our study were measles and herpes simplex virus. A viral etiology was confirmed for 13 or the 195 cases (6.7%). We also screened 482 non-specific febrile cases for IgM to JEV and to dengue viruses and found that 2 (0.4%) had IgM specific for JEV and 9 (1.9%) had IgM specific for dengue virus.

Antibodies, Viral↗
PubMed1994

Identification of the site of [alpha-32P]ATP adduct formation in the ArsA protein.

The ArsA protein, the catalytic subunit of the oxyanion-translocating ATPase encoded by the bacterial plasmid-encoded ars operon, and truncated derivatives were labeled with alpha-[32P]ATP. The labeled polypeptides were cleaved with cyanogen bromide. From gas-phase microsequencing the site of labeling was deduced to lie within residues 283-323 of the ArsA protein, a region postulated to be in a flexible linker connecting the two homologous halves of the ArsA protein.

Adenosine Triphosphatases↗
PubMed1994

In vitro assembly of an anion-stimulated ATPase from peptide fragments.

The oxyanion-translocating ATPase encoded by the ars operon of plasmid R 773 confers resistance to antimonials and arsenicals in Escherichia coli by extrusion of the oxyanions from the cells. The catalytic subunit, the ArsA protein, is an oxyanion-stimulated ATPase with two nucleotide binding consensus sequences, one in the N-terminal half and one in the C-terminal half of the protein. In this report subclones of the arsA gene were constructed to produce polypeptide fragments of the ArsA protein. By themselves none of the fragments exhibited anion-stimulated ATPase activity. Denaturation and renaturation of mixtures of N- and C-terminal polypeptides that between them comprised an entire ArsA protein resulted in active ATPase complexes.

Adenosine Triphosphatases↗
PubMed1994

Cytogenetic studies of sodium fluoride in mice.

The cytogenetic effects of sodium fluoride (NaF) were measured in mice following administration in the drinking water for 6 weeks. Bone fluoride levels were determined and showed a dose-related incorporation of fluoride. Micronuclei were measured in peripheral blood erythrocytes following 1 and 6 weeks of NaF administration. Bone marrow cell preparations were examined for the presence of chromosome aberrations following 6 weeks of treatment; metaphase and anaphase cells were examined. Anaphase cells were scored in three independent laboratories, two of which also scored metaphase cells from the same slides. No increases in micronuclei were seen in peripheral erythrocytes at either time point, and no increases in chromosome aberrations were seen in bone marrow cells when metaphase or anaphase cells were examined. A concurrent positive control, cyclophosphamide, produced significant increases in peripheral blood cell micronuclei and in chromosome aberrations in bone marrow cells in metaphase. No increases in aberrations were seen in the same cyclophosphamide-treated mice when anaphase cells were examined.

Anaphase↗
PubMed1994

Hemothorax due to hemorrhagic disease of the newborn.

A three day old male, term infant with hemothorax due to hemorrhagic disease of the newborn was treated successfully with vitamin K and thoracocentesis. Exclusive breast feeding and absence of vitamin K prophylaxis were important diagnostic clues, although hemothorax as a sole manifestation of hemorrhagic disease of the newborn is rare. This case highlighted the good prognosis of an uncommon complication when prompt diagnosis and appropriate treatment are instituted. The importance of vitamin K prophylaxis to all newborns is emphasized.

Drainage↗