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Biomedical subjects

S Paul

Publications and source records attributed to S Paul.

At least 55 records · Page 3Linked to original sources
PubMed2001

Comparative analysis of a BAC contig of the porcine RN region and the human transcript map: implications for the cloning of trait loci.

The poorly developed transcript maps and the limited resources for genome analysis hamper positional cloning of trait loci in farm animals. This study demonstrates that this will now be easier by the combined use of BAC contigs and the import of the near complete human transcript map. The conclusion was obtained by a comparative analysis of a 2.4-Mb BAC contig of the RN region in pigs. The contig was constructed as part of a successful positional cloning project, which identified PRKAG3 as the causative gene for the RN phenotype. A comparative map including the corresponding regions on human chromosome 2q35 and mouse chromosome 1 (region 36-44 cM) is reported. Sixteen coding sequences were mapped on the BAC contig. The majority of these were identified by BLAST searches of BAC end sequences and BAC shotgun sequences generated during the positional cloning project. Map data for the orthologues in humans were available for 12 of the 16 coding sequences, and all 12 have been assigned to 2q35. Furthermore, no evidence for any rearrangement in gene order was obtained. The extensive linkage conservation indicates that the near complete human transcript map will be an invaluable resource for positional cloning projects in pigs and other domestic animals.

Animals↗
PubMed2001

Molecular cloning, expression and purification of truncated midkine and its growth stimulatory activity on Wilms' tumor (G401) cells.

Midkine (MK) is a heparin binding growth factor identified as a product of a retinoic acid-responsive gene; it is frequently expressed at high levels in many human carcinomas. Although the expression of the mRNA encoding truncated MK (tMK) in unique human cancer cells has been reported, the tMK polypeptide itself has not yet been identified. In order to clarify the biological role of tMK, recombinant tMK was expressed in Escherichia coli and purified. Recombinant tMK was purified as a single band in SDS-PAGE under reducing conditions showing an apparent molecular mass of 10 kDa. Purified recombinant tMK showed the same extent of proliferative activity towards Wilms' tumor (G401) cells as full length human MK. These results suggest that the structure of this recombinant tMK is same as the native polypeptide.

Amino Acid Sequence↗
PubMed2001

Detection of truncated midkine in Wilms' tumor by a monoclonal antibody against human recombinant truncated midkine.

Although the expression of a truncated midkine (tMK) mRNA has been detected in many cancer cells, the tMK protein itself has not yet been identified. The expression, purification and characterization of human recombinant tMK were described in the former report. A mouse hybridoma cell line producing an IgG2b monoclonal antibody (mab) against purified recombinant tMK was established. This anti-tMK mab did not cross react with synthetic full length (or c-half) human midkine. A putative native tMK was identified in G401 cells using this mab, and showed the same apparent Mw as the recombinant tMK in SDS-PAGE. This mab was also used in an immunohistochemical study to evaluate the expression of tMK in Wilms' tumor cell line, G401 cells, as well as in Wilms' tumor patient specimens. G401 cells and all Wilms' tumor patient specimens immunoreacted with this anti-tMK mab. We conclude that Wilms' tumor cells express tMK and that this mab is useful for the detection of tMK in the Wilms' tumor.

Antibodies, Monoclonal↗
PubMed2001

Integration of telomere sequences with the draft human genome sequence.

Telomeres are the ends of linear eukaryotic chromosomes. To ensure that no large stretches of uncharacterized DNA remain between the ends of the human working draft sequence and the ends of each chromosome, we would need to connect the sequences of the telomeres to the working draft sequence. But telomeres have an unusual DNA sequence composition and organization that makes them particularly difficult to isolate and analyse. Here we use specialized linear yeast artificial chromosome clones, each carrying a large telomere-terminal fragment of human DNA, to integrate most human telomeres with the working draft sequence. Subtelomeric sequence structure appears to vary widely, mainly as a result of large differences in subtelomeric repeat sequence abundance and organization at individual telomeres. Many subtelomeric regions appear to be gene-rich, matching both known and unknown expressed genes. This indicates that human subtelomeric regions are not simply buffers of nonfunctional 'junk DNA' next to the molecular telomere, but are instead functional parts of the expressed genome.

Chromosomes, Artificial, Bacterial↗
PubMed2001

High injection pressure during intralesional injection of corticosteroids into capillary hemangiomas.

BACKGROUND: Intralesional injection of corticosteroids is an effective treatment for tumors of the head and neck. Complications are rare but include permanent loss of vision. We designed a study to investigate the mechanism for this complication. METHODS: Three fellowship-trained pediatric ophthalmologists participated in the study in a nonmasked fashion. Four patients received 5 separate treatment sessions of an intralesional injection of a 50-50 mixture of triamcinolone diacetate (40 mg/mL) and betamethasone sodium phosphate and betamethasone acetate (6 mg/mL) into capillary hemangiomas. Injection pressure was obtained in real time using a cannula designed for this purpose. Maximum pressure, mean pressure, and volume of corticosteroid were measured from each injection. RESULTS: A total of 71 injections (range, 8-33 injections per patient) was performed. The total volume of corticosteroid ranged from 0.9 to 2.1 mL. In 63 of 71 injections, the maximum pressure exceeded 100 mm Hg (range, 18.65-842.18 mm Hg). Each surgeon produced injection pressures greater than the systemic arterial pressures of each patient. CONCLUSIONS: Injection pressures exceeding the systemic arterial pressures routinely occur during intralesional injections of corticosteroids into capillary hemangiomas. Experienced surgeons participating in a nonmasked protocol were unable to prevent high injection pressures of corticosteroid. A sufficient volume of corticosteroid injected at high injection pressure would account for the embolization of corticosteroid particles into the ocular circulation from retrograde arterial flow. We recommend limiting the volume of corticosteroid and performing indirect ophthalmoscopy on all patients receiving injections of long-acting corticosteroids into the orbit and periorbital soft tissue.

Betamethasone↗
PubMed2001

Regulation of nitric oxide production by murine peritoneal macrophages treated in vitro with chemokine monocyte chemoattractant protein 1.

Monocyte chemoattractant protein 1 (MCP-1) is an important mediator of monocyte/macrophage recruitment and activation at the sites of chronic inflammation and neoplasia. In the current study, the role of nitrogen monoxide (NO) in the activation of murine peritoneal macrophages to the tumoricidal state in response to in vitro MCP-1 treatment and the regulatory mechanisms involved therein were investigated. Murine peritoneal macrophages upon activation with MCP-1 showed a dose- and time-dependent production of NO together with increased tumoricidal activity against P815 mastocytoma cells. N-monomethyl-l-arginine (L-NMMA), a specific inhibitor of the l-arginine pathway, inhibited the MCP-1-induced NO secretion and generation of macrophage-mediated tumoricidal activity against P815 (NO-sensitive, TNF-resistant) cells but not the L929 (TNF-sensitive, NO-resistant) cells. These results indicated l-arginine-dependent production of NO to be one of the effector mechanisms contributing to the tumoricidal activity of MCP-1-treated macrophages. Supporting this fact, expression of iNOS mRNA was also detected in the murine peritoneal macrophages upon treatment with MCP-1. Investigating the signal transduction pathway responsible for the NO production by the MCP-1-activated murine peritoneal macrophages, it was observed that the pharmacological inhibitors wortmannin, H-7 (1-(5-isoquinoline sulfonyl)-2-methyl piperazine dihydrochloride), and PD98059 blocked the MCP-1-induced NO production, suggesting the probable involvement of phosphoinositol-3-kinase, protein kinase C, and p42/44 MAPkinases in the above process. Various modulators of calcium and calmodulin (CaM) such as EGTA, nifedipine, TMB-8 (3,4,5-trimethoxybenzoic acid-8-(diethylamino)octyl ester), A23187, and W-7 (N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide) were also found to modulate the in vitro macrophage NO release in response to MCP-1. This observation indicated the regulatory role of calcium/CaM in the process of MCP-1-induced macrophage NO production. Similarly, the role of serine/threonine and protein tyrosine phosphatases in the above pathway was suggested using the specific inhibitors of these phosphatases, okadaic acid and sodium orthovanadate.

Animals↗
PubMed2001

Radiological evaluation of the urinary tract in children with urinary infection.

OBJECTIVE: This article in to study the association of structural abnormalities of the urinary tract in children with urinary tract infection (UTI) using ultrasound examination. METHODS: 262 children with culture proven urinary tract infection were studied. Antibiotics were given as per sensitivity pattern. All children had an ultrasound of the abdomen done within 3 weeks. A micturating cystourethrogram (MCU) was done in those with abnormalities of the lower urinary tract detected on ultrasound, as well as in those who had recurrence of infection, after a normal ultrasound. IVU and renal isotope scans were done in selected cases. RESULT: All children were followed up until one year after the study period. Fifty-four patients had an underlying urinary tract anomaly; 42 were picked up by ultrasound and 12 by MCU. 22.9% of males and 15.9% of females had anomaly of the urinary tract. Children less than 2 years had the highest incidence of anomalies. CONCLUSION: Pelviureteric junction obstruction with hydronephrosis, vesicoureteric reflux and non-refluxing megaureter are the major anomalies picked up. 20% of children with urinary tract infections have an underlying structural abnormality of the urinary tract, three-fourth of which are picked up on ultrasound. An ultrasound abdomen is recommended in all children after the first UTI. In addition, an MCU is also indicated in all boys below 2 years with UTI, since one-third of anomalies will be missed if only ultrasound is done.

Age Distribution↗
PubMed2001

A mammary gland EST showing linkage disequilibrium to a milk production QTL on bovine Chromosome 14.

As part of a genome scan, ESTs derived from mammary gland tissue of a lactating cow were used as candidate genes for quantitative trait loci (QTL), affecting milk production traits. Resource families were genotyped with 247 microsatellite markers and 4 polymorphic ESTs. It was shown by linkage analysis that one of these ESTs, KIEL_E8, mapped to the centromeric region of bovine Chromosome (Chr) 14. Regression analysis revealed the presence of a QTL, with significant effect on milk production, in this chromosome region, and analysis of variance showed no significant interaction of marker genotype and family. The estimated significant differences between homozygous marker genotypes were 140 kg milk, -5.02 kg fat yield, and 2.58 kg protein yield for the first 100 days of lactation. Thus, there was strong evidence for a complete or nearly complete linkage disequilibrium between KIEL_E8 and the QTL. To identify the biological function of KIEL_E8, we extended the sequence for 869 bp by 5'-RACE. A 560-bp fragment of this shows a 90.9% similarity to a gene encoding a cysteine- and histidine-rich cytoplasmic protein in mouse. Although such a protein may have a regulatory function for lactation and a linkage disequilibrium between the EST marker and the QTL has been observed, it remains to be elucidated whether they are identical or not. Nevertheless, KIEL_E8 will be an efficient marker to perform marker-assisted selection in the Holstein-Friesian population.

Alleles↗
PubMed2001

A comparison of the affective state and quality of life of chemotherapy patients who do and do not develop chemotherapy-induced oral mucositis.

The purpose of this longitudinal study was to compare the quality of life and affective state of patients receiving chemotherapy who developed oral mucositis to patients who did not. Outpatients had their mouths assessed at the beginning of their chemotherapy, completed the Multidimensional Quality of Life scale, Cancer version (MQOLS-CA) and the Profile of Mood States (POMS). Patients again completed the MQOLS-CA and POMS if they developed mucositis during their three cycles (monthly), or if they did not and were exiting the study. Seventy-seven outpatients completed the study; 28 patients developed mucositis and 49 did not. The MQOLS-CA total scores for the entire sample decreased significantly over time (F(1,75) = 25.44, P < 0.001), but there was no group by time interaction, i.e., the change in MQOLS-CA total scores did not depend on mucositis status. While the POMS Total Mood Disturbance scores for the entire sample increased significantly over time (F(1,75) = 19.55, P < 0.001), there was a significant group by time interaction (F(1,75)= 4.85, P = 0.03). Patients who developed mucositis had a significant increase in mood disturbance compared to patients who did not. Further, the POMS subscales of depression and anger showed the same pattern of significant increases. In conclusion, the development of mucositis adversely affected the outpatients' affective states, but not their QOL.

Adult↗
PubMed2001

Adenovirus-mediated delivery of antiangiogenic genes as an antitumor approach.

Based on the observation that the growth of solid tumors is dependent on the formation of new blood vessels, therapeutic strategies aimed at inhibiting angiogenesis have been proposed. A number of proteins with angiostatic activity have been described, but their development as therapeutic agents has been hampered by difficulties in their production and their poor pharmacokinetics. These limitations may be resolved using a gene therapy approach whereby the genes are delivered and expressed in vivo. Here we compared adenoviral delivery of endostatin, proliferin-related protein (PRP), and interferon-inducible protein 10 (IP10) genes. Recombinant adenoviruses carrying the three angiostatic genes express biologically active gene products as determined in vitro in endothelial cell proliferation and migration assays, and in vivo by inhibition of neoangiogenesis in rat chambers. Eradication of established tumors in vivo, in the murine B16F10 melanoma model in immunocompetent mice, was not achieved by intratumoral injection of the different vectors. However, the combination of intravenous plus intratumoral injections allowed rejection of tumors. Ad-PRP or Ad-IP10 were significantly more efficient than Ad-endostatin, leading to complete tumor rejection and prolonged survival in a high proportion of treated animals. These data support the use of in vivo gene delivery approaches to produce high-circulating and local levels of antiangiogenic agents for the therapy of local and metastatic human tumors.

Adenoviridae↗
PubMed2001

Suppression of the vertical vestibulo-ocular reflex in older persons at risk of falling.

A case-control design was used to assess eye-head-trunk coordination for community-dwelling elders performing a stand-walk task. Eighteen elders with a high risk of falling were matched to 18 subjects with low risk on the basis of age, living status (living alone or with someone) and category of residence (independent living or assisted living facility). Standard electro-oculography was used in conjunction with an electromagnetic tracking device to measure eye and head-trunk motion, respectively. For the low-risk group, the mean slope of gaze-head and gaze-trunk relationships was significantly greater than zero (0.91 and 0.64, respectively), whereas high-risk elders did not demonstrate slope magnitudes significantly different from zero (0.52 and 0.16, respectively) due to large inter-subject variations. While the majority of subjects showed some counter-rotation of the eyes with head pitch, a greater percentage of subjects in the high-risk group did not suppress this response and consequently gaze and gaze velocity overcompensated for head pitch. These findings suggest that the vertical vestibulo-ocular reflex is not adequately suppressed during the stand-walk task in elders who are at a high risk of falling. Possible mechanisms contributing to these findings are discussed.

Accidental Falls↗
PubMed2001

Evaluating eye-body coordination during unrestrained functional activity in older persons.

BACKGROUND: Traditional paradigms for the study of ocular-motor control restrain subject motion and have not adequately quantified the sensorimotor strategies used by older persons to control gaze while performing activities of daily living. The purpose of our study was to describe eye-head-trunk coordination during a functional activity in freely moving community-dwelling older persons. METHODS: Thirty-five community-dwelling older persons (age range 71-92 years) participated in this study. Surface electro-oculography was used with an electromagnetic tracking device to measure vertical eye movement and linear and angular head position while each subject performed a stand-from-chair task. RESULTS: Standing from a chair involved low-frequency head motion (median z = 0.25 Hz; median pitch = 0.32 Hz). The distribution of phase for eyes versus vertical body motion were skewed toward head-trunk leading, suggesting that eye motion follows vertical body motion. Vertical gaze, however, was in phase with and moved in the same direction as head pitch. CONCLUSIONS: Gaze (eye position in space) was an active, integrated component of the standing motion. The results imply that both the oculomotor system and the head motor system in older persons are coordinated to direct gaze and, when necessary, work to suppress the vestibuloocular reflex. The interaction of eye-head-trunk motion provides a basis for understanding how a breakdown in the gaze control mechanisms in older persons might contribute to the risk of falling and fall-related injuries.

Aged↗
PubMed2001

Wideband reflectance tympanometry in chinchillas and human.

Wideband reflectance tympanometry was performed on twelve chinchillas ears. The complex input impedance of the middle ear, multifrequency admittance tympanograms, reflectance patterns (reflectance versus frequency), and reflectance tympanograms (reflectance versus ear-canal air pressure) were analyzed and compared to human data. The complex impedance of the chinchilla ear has a lower stiffness reactance at low frequencies, a higher mass reactance at high frequencies, and a lower resistance compared to the human. Multifrequency admittance tympanograms from chinchillas follow the same sequence of patterns as humans for low frequencies (<2 kHz). At higher frequencies tympanograms from both species are poorly organized and do not follow a consistent sequence of patterns. Reflectance patterns of chinchillas and humans are different. However, both species show high reflectance at low frequencies, regions of lower reflectance in mid-frequencies (2-6 kHz), and high reflectance at high frequencies (>8 kHz). Reflectance tympanograms for the two species show a single, centrally located minimum at low frequencies (<2 kHz) and are substantially different at higher frequencies. Results are shown for two animals that underwent eustachian tube obstruction. Reflectance patterns obtained with different ear-canal air pressures are substantially different. Reflectance results at any single ear-canal pressure (including ambient pressure) do not completely characterize the effects of middle-ear pathology.

Acoustic Impedance Tests↗
PubMed2001

Two ResD-controlled promoters regulate ctaA expression in Bacillus subtilis.

The Bacillus subtilis ResDE two-component system plays a positive role in global regulation of genes involved in aerobic and anaerobic respiration. ctaA is one of the several genes involved in aerobic respiration that requires ResD for in vivo expression. The ctaAB-divergent promoter regulatory region has three ResD binding sites; A1, A2, and A3. The A2 site is essential for in vivo promoter activity, while binding sites A2 and A3 are required for full ctaA promoter activity. In this study, we demonstrate the role of ResD~P in the activation of the ctaA promoter using an in vitro transcription system. The results indicate that the ctaA promoter (binding sites A2 and A3) has two transcriptional start sites. Binding site A2 was sufficient for weak transcription of the upstream promoter (Pv) by Esigma(A), transcription which was enhanced approximately 1.5-fold by ResD and 5-fold by ResD~P. The downstream promoter (Ps) required both binding sites A2 and A3 and was not transcribed by Esigma(A) with or without ResD~P. RNA polymerase (RNAP) isolated from B. subtilis when cells were at the end of exponential growth (T(0)) or 3, 4, or 5 h into the stationary phase (T(3), T(4), or T( 5), respectively) was used in in vitro transcription assays. Maximal transcription from Ps required T(4) RNAP plus ResD~P. RNAP isolated from a spo0A or a sigE mutant strain was not capable of Ps transcription. Comparison of the Ps promoter sequence with the SigE binding consensus suggests that the ctaA Ps promoter may be a SigE promoter. The collective data from ResD footprinting, in vivo promoter deletion analysis, and in vitro transcription assays suggest that ctaA is transcribed during late exponential to early stationary phases of growth from the Pv promoter, which requires ResD binding site A2, Esigma(A), and ResD~P, and during later stationary phase from Ps, which requires binding sites A2 and A3, ResD~P, and Esigma(E) or a sigma factor whose transcription is dependent on SigE.

Aerobiosis↗
PubMed2001

Understanding advanced concepts in atrioventricular block.

Not all atrioventricular blocks occur in the atrioventricular node. Understanding the physiological concept behind the various blocks makes recognizing the relevant ECG indications easier. Furthermore, the implications to patients are clear when healthcare providers understand the level of the block and the dangers the block may impose. Until a more accurately descriptive classification system of conduction blocks becomes universally accepted, the current labels will continue to be used. It is imperative that nurses, particularly those caring for cardiac patients, recognize and understand the ECG indications of various degrees of block.

Electrocardiography↗
PubMed2000

Enzyme mimicry by the antiidiotypic antibody approach.

The concept of "internal image" of antiidiotypic antibodies has provided the basis for eliciting catalytic antibodies. A monoclonal IgM 9A8 that was obtained as an antiidiotype to AE-2 mAb, a known inhibitor of acetylcholinesterase, displayed esterolytic activity. Study of recombinant Fab fragments and separate light and heavy chains of 9A8 confirmed that the antibody variable domain encodes the catalytic function, whereas neither part of the primary sequence of the Fab exhibited homology with the enzyme. The specific modification of the 9A8 variable domain by an active site-directed covalent inhibitor revealed the presence of an active site Ser residue. A three-dimensional modeling suggests the existence of a functional catalytic dyad Ser-His. Comparison of active sites of 9A8 and 17E8 esterolytic abzyme raised against transition-state analog revealed structural similarity although both antibodies were elicited by two different approaches.

Amino Acid Sequence↗