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Biomedical subjects

G Paul

Publications and source records attributed to G Paul.

At least 55 records · Page 3Linked to original sources
PubMed2000

Modifying a motor go-kart to accommodate children with disabilities.

As an educational exercise with real-world application, a standard motor go-kart was altered so that a person with disabilities could control it with one hand via a joystick. The first step was to establish the exact design requirements. Then the power systems to operate the steering, throttle, and brakes were selected and the analog control circuits and amplifiers to drive and control the power systems were built. Finally, the mechanisms to connect the power systems to the various functions on the go-kart were designed and built. The complete system was then tested with a group of children with disabilities, and problems with the system were identified.

Child↗
PubMed2000

Idiopathic pulmonary haemosiderosis.

Idiopathic pulmonary haemosiderosis (IPH) is a rare disorder characterized by recurrent bouts of haemoptysis, iron deficiency anaemia, and pulmonary infiltrates on chest radiograph. We present such a case and believe that it is the first report from the Middle East.

Child, Preschool↗
PubMed2000

Further delineation of the DOOR syndrome.

Two related sibships from an extended family have been observed with the features of the DOOR syndrome. These features included deafness, onychodystrophy, osteodystrophy, microcephaly, and global developmental retardation with progressive blindness. Seizures, which were associated with hypsarrhythmia, were frequent and difficult to control and ultimately were the cause of death in two patients. An MRI brain scan of case 1 showed a number of abnormalities including markedly reduced myelination. The urine organic acid analysis showed a ten-fold increase of 2-oxoglutarate. In one patient the placenta was noted to have multiple fluid filled cysts, which is a feature reported in other metabolic diseases. It is suggested that there may be genetic heterogeneity in the syndrome, and the presence of increased 2-oxoglutarate is associated with a more severe phenotype which is frequently lethal.

Abnormalities, Multiple↗
PubMed2000

Dependence of conductance on percolation backbone mass

We study , the average conductance of the backbone, defined by two points separated by Euclidean distance r, of mass M(B) on two-dimensional percolation clusters at the percolation threshold. We find that with increasing M(B) and for fixed r, asymptotically decreases to a constant, in contrast with the behavior of homogeneous systems and nonrandom fractals (such as the Sierpinski gasket) in which conductance increases with increasing M(B). We explain this behavior by studying the distribution of shortest paths between the two points on clusters with a given M(B). We also study the dependence of conductance on M(B) above the percolation threshold and find that (i) slightly above p(c), the conductance first decreases and then increases with increasing M(B) and (ii) further above p(c), the conductance increases monotonically for all values of M(B), as is the case for homogeneous systems.

Journal Article↗
PubMed2000

Flow between two sites on a percolation cluster

We study the flow of fluid in porous media in dimensions d=2 and 3. The medium is modeled by bond percolation on a lattice of L(d) sites, while the flow front is modeled by tracer particles driven by a pressure difference between two fixed sites ("wells") separated by Euclidean distance r. We investigate the distribution function of the shortest path connecting the two sites, and propose a scaling ansatz that accounts for the dependence of this distribution (i) on the size of the system L and (ii) on the bond occupancy probability p. We confirm by extensive simulations that the ansatz holds for d=2 and 3. Further, we study two dynamical quantities: (i) the minimal traveling time of a tracer particle between the wells when the total flux is constant and (ii) the minimal traveling time when the pressure difference is constant. A scaling ansatz for these dynamical quantities also includes the effect of finite system size L and off-critical bond occupation probability p. We find that the scaling form for the distribution functions for these dynamical quantities for d=2 and 3 is similar to that for the shortest path, but with different critical exponents. Our results include estimates for all parameters that characterize the scaling form for the shortest path and the minimal traveling time in two and three dimensions; these parameters are the fractal dimension, the power law exponent, and the constants and exponents that characterize the exponential cutoff functions.

Journal Article↗
PubMed2000

Nucleotide sequence of the bla(RTG-2) (CARB-5) gene and phylogeny of a new group of carbenicillinases.

We determined the nucleotide sequence of the bla gene for the Acinetobacter calcoaceticus beta-lactamase previously described as CARB-5. Alignment of the deduced amino acid sequence with those of known beta-lactamases revealed that CARB-5 possesses an RTG triad in box VII, as described for the Proteus mirabilis GN79 enzyme, instead of the RSG consensus characteristic of the other carbenicillinases. Phylogenetic studies showed that these RTG enzymes constitute a new, separate group, possibly ancestors of the carbenicillinase family.

Amino Acid Sequence↗
PubMed1999

Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia.

BACKGROUND: Between February and April, 1999, an outbreak of viral encephalitis occurred among pig-farmers in Malaysia. We report findings for the first three patients who died. METHODS: Samples of tissue were taken at necropsy. Blood and cerebrospinal-fluid (CSF) samples taken before death were cultured for viruses, and tested for antibodies to viruses. FINDINGS: The three pig-farmers presented with fever, headache, and altered level of consciousness. Myoclonus was present in two patients. There were signs of brainstem dysfunction with hypertension and tachycardia. Rapid deterioration led to irreversible hypotension and death. A virus causing syncytial formation of vero cells was cultured from the CSF of two patients after 5 days; the virus stained positively with antibodies against Hendra virus by indirect immunofluorescence. IgM capture ELISA showed that all three patients had IgM antibodies in CSF against Hendra viral antigens. Necropsy showed widespread microinfarction in the central nervous system and other organs resulting from vasculitis-induced thrombosis. There was no clinical evidence of pulmonary involvement. Inclusion bodies likely to be of viral origin were noted in neurons near vasculitic blood vessels. INTERPRETATION: The causative agent was a previously undescribed paramyxovirus related to the Hendra virus. Close contact with infected pigs may be the source of the viral transmission. Clinically and epidemiologically the infection is distinct from infection by the Hendra virus. We propose that this Hendra-like virus was the cause of the outbreak of encephalitis in Malaysia.

Adult↗
PubMed1999

Extension of the polyanionic cosalane pharmacophore as a strategy for increasing anti-HIV potency.

The anti-HIV agent cosalane inhibits both the binding of gp120 to CD4 as well as an undefined postattachment event prior to reverse transcription. Several cosalane analogues having an extended polyanionic "pharmacophore" were designed based on a hypothetical model of the binding of cosalane to CD4. The analogues were synthesized, and a number of them displayed anti-HIV activity. One of the new analogues was found to possess enhanced potency as an anti-HIV agent relative to cosalane itself. Although the new analogues inhibited both HIV-1 and HIV-2, they were more potent as inhibitors of HIV-1 than HIV-2. Mechanism of action studies indicated that the most potent of the new analogues inhibited fusion of the viral envelope with the cell membrane at lower concentrations than it inhibited attachment, suggesting inhibition of fusion as the primary mechanism of action.

Animals↗
PubMed1999

Inhibitor-resistant TEM beta-lactamases: phenotypic, genetic and biochemical characteristics.

Beta-lactamases represent the main mechanism of bacterial resistance to beta-lactam antibiotics. The recent emergence of bacterial strains producing inhibitor-resistant TEM (IRT) enzymes could be related to the frequent use of beta-lactamase inhibitors such as clavulanic acid, sulbactam and tazobactam in hospitals and in general practice. The IRT beta-lactamases differ from the parental enzymes TEM-1 or TEM-2 by one, two or three amino acid substitutions at different locations. This paper reviews the phenotypic, genetic and biochemical characteristics of IRT beta-lactamases in an attempt to shed light on the pressures that have contributed to their emergence.

Anti-Bacterial Agents↗
PubMed1999

Coefficient scaling.

We prove a remarkably simple but powerful recursion relation for the coefficients of iterated polynomials. We also prove that the recursion relation holds for the coefficients of certain functions of the iterated polynomial. Using the recursion relations, we obtain a closed-form expression for the average number of closed-loop self-avoiding walks per site on a family of fractal lattices. We describe numerical results, which exhibit log-periodic oscillations, and find good agreement between these results and the theory developed here, which predicts the existence of the log-periodic oscillations and their amplitudes. Finally, we discuss insights gained into the mathematical origins of critical phenomena.

Journal Article↗
PubMed1999

Traveling time and traveling length in critical percolation clusters.

We study traveling time and traveling length for tracer dispersion in two-dimensional bond percolation, modeling flow by tracer particles driven by a pressure difference between two points separated by Euclidean distance r. We find that the minimal traveling time t(min) scales as t(min) approximately r(1.33), which is different from the scaling of the most probable traveling time, t* approximately r(1.64). We also calculate the length of the path corresponding to the minimal traveling time and find l(min) approximately r(1.13) and that the most probable traveling length scales as l* approximately r(1.21). We present the relevant distribution functions and scaling relations.

Journal Article↗
PubMed1999

Characterization and nucleotide sequence of CARB-6, a new carbenicillin-hydrolyzing beta-lactamase from Vibrio cholerae.

A clinical strain of Vibrio cholerae non-O1 non-O139 isolated in France produced a new beta-lactamase with a pI of 5.35. The purified enzyme, with a molecular mass of 33,000 Da, was characterized. Its kinetic constants show it to be a carbenicillin-hydrolyzing enzyme comparable to the five previously reported CARB beta-lactamases and to SAR-1, another carbenicillin-hydrolyzing beta-lactamase that has a pI of 4.9 and that is produced by a V. cholerae strain from Tanzania. This beta-lactamase is designated CARB-6, and the gene for CARB-6 could not be transferred to Escherichia coli K-12 by conjugation. The nucleotide sequence of the structural gene was determined by direct sequencing of PCR-generated fragments from plasmid DNA with four pairs of primers covering the whole sequence of the reference CARB-3 gene. The gene encodes a 288-amino-acid protein that shares 94% homology with the CARB-1, CARB-2, and CARB-3 enzymes, 93% homology with the Proteus mirabilis N29 enzyme, and 86.5% homology with the CARB-4 enzyme. The sequence of CARB-6 differs from those of CARB-3, CARB-2, CARB-1, N29, and CARB-4 at 15, 16, 17, 19, and 37 amino acid positions, respectively. All these mutations are located in the C-terminal region of the sequence and at the surface of the molecule, according to the crystal structure of the Staphylococcus aureus PC-1 beta-lactamase.

Amino Acid Sequence↗
PubMed1998

Fatal enterovirus 71 encephalomyelitis.

During an outbreak of hand-foot-mouth disease caused by enterovirus 71 (EV-71) in 1997, 4 children presented with sudden cardiopulmonary collapse and minimal neurologic features. All children received cardiopulmonary resuscitation but died within a few hours of admission. Postmortem studies showed infection by EV-71 with extensive damage to the medulla and pons. We postulate an etiologic link between EV-71 and brainstem encephalomyelitis as the cause of pulmonary edema and death.

Child, Preschool↗
PubMed1998

Phenotypic study of resistance of beta-lactamase-inhibitor-resistant TEM enzymes which differ by naturally occurring variations and by site-directed substitution at Asp276.

At this time an amino acid substitution at position 276 in the TEM-1 enzyme is associated with an additional substitution at position 69 in natural beta-lactamase-inhibitor-resistant (IRT) beta-lactamases. The effect of the Asn276-->Asp substitution on resistance was assessed with the Asn276Asp variant, generated by site-directed mutagenesis. The mutant was resistant to beta-lactamase inhibitors, but the MICs of amoxicillin combined with clavulanic acid or tazobactam were strikingly different for E. coli strains producing the Asn276Asp variant and those producing naturally occurring IRTs with single or double substitutions. The inhibitory effects of clavulanic acid and tazobactam were the same in IRTs with substitutions at position 69 (IRT-5 and IRT-6). The effect of clavulanic acid on the MICs of amoxicillin for the Asn276Asp variant was greater than that of tazobactam. In IRTs with double substitutions, at positions 69 plus 276 (IRT-4, IRT-7, and IRT-8) or 69 plus 275 (IRT-14), tazobactam was a more potent inhibitor than clavulanic acid. The effect of the Asn276-->Asp substitution on the values of the kinetic constants and the concentration required to inhibit by 50% the hydrolysis of benzylpenicillin confirms that this single mutation is responsible for resistance to beta-lactamase inhibitors. Molecular modeling of the Asn276Asp mutant shows that Asp276 can form two salt bonds with Arg244 close to the penicillin-binding cavity. The addition of the Asp276 mutation to that preexisting at position 69 confers a higher selective advantage to bacteria, as shown by the reduction in beta-lactamase inhibitor efficiencies of the double variants. Therefore, the emergence of multiple mutations in TEM beta-lactamases by virtue of the use of beta-lactamase inhibitors increases selection pressure resulting in the convergent evolution of resistant strains.

Amoxicillin↗
PubMed1997

Machine milking of Ostfriesian and Lacaune dairy sheep: udder anatomy, milk ejection and milking characteristics.

Mammary cistern anatomy derived from ultrasound measurement, milk ejection in response to exogenous oxytocin and oxytocin release and milking characteristics with and without manual prestimulation in early (months 2-4) and late (months 5-8) lactation were investigated in Lacaune and Ostfriesian dairy ewes. Vertical ultrasound cisternal cross sections of the cisternal cavities did not differ in the two breeds, whereas the cisternal area fraction located lower than the exit into the teat channel was larger in Ostfriesian than in Lacaune sheep. The cisternal area enlarged within 1 min in response to i.v. oxytocin injection, indicating milk ejection. During milking, oxytocin concentrations in Lacaune generally increased dramatically within 0.5 min from the start of prestimulation or milking, whereas only slight or no oxytocin release was detected during milking without prestimulation in Ostfriesian ewes. Prestimulation induced oxytocin release in Ostfriesian sheep within 1-2 min after the start of milking, indicating delayed response to stimulation. Two peaked milk flow curves were observed when oxytocin release and milk ejection occurred only after removal of cisternal milk. This type of milk flow was more frequent in Ostfriesian than in Lacaune ewes and was reduced in both breeds by prestimulation, while the frequency of one peaked milk flow curves increased. During the course of lactation, milk yield, main milk fraction and milk flow rates decreased, while stripping yield was almost unchanged. Although milk yield was similar in both breeds, milk flow was lower and stripping yield was higher in Ostfriesian than in Lacaune ewes. We conclude that milk ejection in ewes occurred in response to elevated oxytocin concentrations. In Ostfriesian ewes reduced and delayed oxytocin response to teat stimulation resulted in milk ejection only during stripping. Therefore, and probably because a larger volume of the cistern was located below the teat exit in the Ostfriesian breed, stripping yield was higher in Ostfriesian than in Lacaune sheep.

Animals↗
PubMed1997

Properties of IRT-14 (TEM-45), a newly characterized mutant of TEM-type beta-lactamases.

IRT-14 (TEM-45) is a new mutant TEM-type beta-lactamase that was isolated from clinical Escherichia coli P37 and that confers resistance to broad-spectrum penicillins with reduced sensitivity to beta-lactamase inhibitors. The MICs of amoxicillin alone and of amoxicillin combined with 2 micrograms of clavulanic acid or 2 micrograms of tazobactam per ml were 4,096, 2,048, and 1,024 micrograms/ml, respectively. The strain was susceptible to cephalosporins, aztreonam, moxalactam, and imipenem. The enzyme was purified to homogeneity, and values of the kinetic parameters Kcat, Km, and Kcat/Km were determined for different substrates. This enzyme, with a pI of 5.2, was found to have reduced affinity for broad-spectrum penicillins and cephalosporins. The values of 50% inhibitory concentrations of clavulanic acid, sulbactam, tazobactam, and brobactam are correlated with the higher KmS for substrates. The resistance of E. coli P37 to mechanism-based inactivators results from a higher level of production of the TEM-derived enzyme due to the G-to-T substitution at position 162 (G-162-->T) in the promoter region of blaTEM and from the structural modifications resulting from the Met-69-->Leu and Arg-275-->Gln substitutions that characterize IRT-14 beta-lactamase.

Anti-Bacterial Agents↗
PubMed1997

Response of catecholamines to manual teat stimulation or machine-milking of Lacaune and Friesen dairy ewes.

Increased sympathetic activity, including peripheral release of catecholamines, has been hypothesized to inhibit the milk ejection reflex by blocking the release of oxytocin, by blocking the effect of oxytocin at the mammary gland, or both. We attempted to relate differences in milking characteristics of Lacaune and East Friesen ewes to the degree of sympathetic arousal, responses of catecholamines and oxytocin to machine-milking and to manual teat stimulation followed by milking. Peripheral concentrations of epinephrine, 67 +/- 6 pg/ml for Lacaunes and 57 +/- 5 pg/ml for Friesens, were essentially constant. Peripheral concentrations of norepinephrine averaged 682 +/- 68 pg/ml for Lacaunes and 250 +/- 54 pg/ml for Friesens. Elevated norepinephrine concentrations during the pretreatment period were associated with the inhibition of oxytocin responses. When norepinephrine concentrations during the pretreatment period exceeded 300 pg/ml for Friescens, or were rising and exceeded 700 pg/ml at initiation of the experimental period for Lacaunes, oxytocin release was inhibited. Results from this study clearly showed that basal concentrations of norepinephrine vary with breed of ewes and provided the first direct evidence that increased sympathetic activity can result in central inhibition of the milk ejection reflex.

Animals↗