PubMed Health⌕ Search

Biomedical subjects

R Roy

Publications and source records attributed to R Roy.

At least 37 records · Page 2Linked to original sources
PubMed2001

Hidradenitis suppurativa and acne conglobata associated with spondyloarthropathy.

Hidradenitis suppurativa and acne conglobata are well-described chronic dermatologic diseases. Although the exact incidence of these disorders is unknown, both are relatively uncommon conditions. The incidence of spondyloarthropathy is less than 1% in the general population. Therefore, a triad of hidradenitis suppurativa, acne conglobata and spondyloarthropathy is a rare syndrome described only in a few case reports in the literature. We report a case of hidradenitis suppurativa and acne conglobata associated with spondyloarthropathy.

Acne Vulgaris↗
PubMed2001

CYP1A2 activity as measured by a caffeine test predicts clozapine and active metabolite steady-state concentrationin patients with schizophrenia.

Clozapine is an atypical antipsychotic drug and displays efficacy in 30% to 60% of patients with schizophrenia who do not respond to traditional antipsychotics. A clozapine concentration greater than 1,150 nmol/L increases the probability of antipsychotic efficacy. However, plasma clozapine concentration can vary more than 45-fold during long-term treatment. The aim of this study was to assess the contribution of CYP1A2 to variability in steady-state concentration of clozapine and its active metabolite norclozapine. Patients with schizophrenia or schizoaffective disorder were prospectively monitored during clozapine treatment (N = 18). The in vivo CYP1A2 activity was measured using the caffeine metabolic ratio (CMR) in overnight urine. Trough plasma samples were drawn after at least 5 days of treatment with a constant regimen of clozapine. A significant negative association was found between the CMR and the dose-corrected clozapine (r(s) = -0.87,p < 0.01) and norclozapine (r(s) = -0.76,p < 0.01) concentrations. Nonsmokers displayed a higher clozapine (3.2-fold) and norclozapine (2.3-fold) concentration than smokers (p < 0.05). Furthermore, there was marked person-to-person variation in CYP1A2 activity during multiple-dose clozapine treatment (coefficient of variation = 60%). Age, weight, serum creatinine, and grapefruit juice consumption did not significantly contribute to variability in clozapine and norclozapine concentration (p > 0.05). In conclusion, CYP1A2 is one of the important contributors to disposition of clozapine during multiple-dose treatment. Although further in vitro experiments are necessary, the precise metabolic pathways catalyzed by CYP1A2 seem to be subsequent to the formation of norclozapine, hitherto less recognized quantitatively important alternate disposition routes, or both. From a clinical perspective, an environmentally induced or constitutively high CYP1A2 expression can lead to a decrease in steady-state concentration of clozapine as well as its active metabolite norclozapine. Thus, interindividual variability in CYP1A2 activity may potentially explain treatment resistance to clozapine in some patients. CYP1A2 phenotyping with a simple caffeine test may contribute to individualization of clozapine dosage and differentiate between treat ment noncompliance and high CYP1A2 activity.

Adult↗
PubMed2001

Treatment-resistance to clozapine in association with ultrarapid CYP1A2 activity and the C-->A polymorphism in intron 1 of the CYP1A2 gene: effect of grapefruit juice and low-dose fluvoxamine.

Antipsychotic response to clozapine varies markedly among patients with schizophrenia. The disposition of clozapine is dependent, in part, on the cytochrome P-450 (CYP) 1A2 enzyme in vivo. In theory, a very high CYP1A2 activity may lead to subtherapeutic concentrations and treatment resistance to clozapine. This prospective case study evaluates the clinical significance of ultrarapid CYP1A2 activity and a recently discovered single nucleotide (C --> A) polymorphism in intron 1 of the CYP1A2 gene (CYP1A2*F) for treatment resistance to clozapine. In addition, we describe the effect of grapefruit juice or low-dose fluvoxamine (25-50 mg/d) coadministration on clozapine and active metabolite norclozapine steady-state plasma concentration and antipsychotic response.

Adult↗
PubMed2001

Selection of specific endophytic bacterial genotypes by plants in response to soil contamination.

Plant-bacterial combinations can increase contaminant degradation in the rhizosphere, but the role played by indigenous root-associated bacteria during plant growth in contaminated soils is unclear. The purpose of this study was to determine if plants had the ability to selectively enhance the prevalence of endophytes containing pollutant catabolic genes in unrelated environments contaminated with different pollutants. At petroleum hydrocarbon contaminated sites, two genes encoding hydrocarbon degradation, alkane monooxygenase (alkB) and naphthalene dioxygenase (ndoB), were two and four times more prevalent in bacteria extracted from the root interior (endophytic) than from the bulk soil and sediment, respectively. In field sites contaminated with nitroaromatics, two genes encoding nitrotoluene degradation, 2-nitrotoluene reductase (ntdAa) and nitrotoluene monooxygenase (ntnM), were 7 to 14 times more prevalent in endophytic bacteria. The addition of petroleum to sediment doubled the prevalence of ndoB-positive endophytes in Scirpus pungens, indicating that the numbers of endophytes containing catabolic genotypes were dependent on the presence and concentration of contaminants. Similarly, the numbers of alkB- or ndoB-positive endophytes in Festuca arundinacea were correlated with the concentration of creosote in the soil but not with the numbers of alkB- or ndoB-positive bacteria in the bulk soil. Our results indicate that the enrichment of catabolic genotypes in the root interior is both plant and contaminant dependent.

Bacteria↗
PubMed2001

Key role for sulfur in peptide metabolism and in regulation of three hydrogenases in the hyperthermophilic archaeon Pyrococcus furiosus.

The hyperthermophilic archaeon Pyrococcus furiosus grows optimally at 100 degrees C by the fermentation of peptides and carbohydrates. Growth of the organism was examined in media containing either maltose, peptides (hydrolyzed casein), or both as the carbon source(s), each with and without elemental sulfur (S(0)). Growth rates were highest on media containing peptides and S(0), with or without maltose. Growth did not occur on the peptide medium without S(0). S(0) had no effect on growth rates in the maltose medium in the absence of peptides. Phenylacetate production rates (from phenylalanine fermentation) from cells grown in the peptide medium containing S(0) with or without maltose were the same, suggesting that S(0) is required for peptide utilization. The activities of 14 of 21 enzymes involved in or related to the fermentation pathways of P. furiosus were shown to be regulated under the five different growth conditions studied. The presence of S(0) in the growth media resulted in decreases in specific activities of two cytoplasmic hydrogenases (I and II) and of a membrane-bound hydrogenase, each by an order of magnitude. The primary S(0)-reducing enzyme in this organism and the mechanism of the S(0) dependence of peptide metabolism are not known. This study provides the first evidence for a highly regulated fermentation-based metabolism in P. furiosus and a significant regulatory role for elemental sulfur or its metabolites.

Culture Media↗
PubMed2001

Role of single-stranded DNA binding activity of T antigen in simian virus 40 DNA replication.

We have previously mapped the single-stranded DNA binding domain of large T antigen to amino acid residues 259 to 627. By using internal deletion mutants, we show that this domain most likely begins after residue 301 and that the region between residues 501 and 550 is not required. To study the function of this binding activity, a series of single-point substitutions were introduced in this domain, and the mutants were tested for their ability to support simian virus 40 (SV40) replication and to bind to single-stranded DNA. Two replication-defective mutants (429DA and 460EA) were grossly impaired in single-stranded DNA binding. These two mutants were further tested for other biochemical activities needed for viral DNA replication. They bound to origin DNA and formed double hexamers in the presence of ATP. Their ability to unwind origin DNA and a helicase substrate was severely reduced, although they still had ATPase activity. These results suggest that the single-stranded DNA binding activity is involved in DNA unwinding. The two mutants were also very defective in structural distortion of origin DNA, making it likely that single-stranded DNA binding is also required for this process. These data show that single-stranded DNA binding is needed for at least two steps during SV40 DNA replication.

Adenosine Triphosphatases↗
PubMed2001

Salmonella Give infection in 2 dairy herds.

Salmonella Give infection was investigated in 2 adjacent dairy herds because of the impact of milk contamination on public health. Once the status of the infection in a herd was established by fecal analyses, consecutive fecal testings, in conjunction with preventive measures, appeared to be consistent and cost-effective tools for the monitoring and control of salmonellosis in dairy herds.

Animals↗
PubMed2001

Differentiation of tuberculous from pyogenic brain abscesses with in vivo proton MR spectroscopy and magnetization transfer MR imaging.

BACKGROUND AND PURPOSE: MR imaging features are nonspecific with respect to the causative organism for patients with brain abscesses. On the basis of the hypothesis that the biochemical environment depends on the infecting organism and might be different in tuberculous compared with pyogenic brain abscesses, this study attempted to determine whether pyogenic brain abscesses can be differentiated from tuberculous brain abscesses by use of magnetization transfer (MT) MR imaging and in vivo proton MR spectroscopy. METHODS: Twenty-seven patients with a total of 33 pyogenic brain abscesses and three patients with a total of 12 tuberculous abscesses were evaluated with in vivo MR spectroscopy and MT MR imaging. The diagnosis in all cases was based on the culture of the causative organisms and histopathology whenever done as a part of clinical management. RESULTS: All 27 patients with pyogenic brain abscesses had lipid and lactate levels of 1.3 ppm and amino acid levels of 0.9 ppm with or without the presence of succinate, acetate, alanine, and glycine, while the three patients with tuberculous abscesses showed only such lipid and lactate levels. The MT ratio from the wall of the pyogenic abscesses was significantly higher (P <.001) than that from the tuberculous abscess wall. CONCLUSION: It might be possible to differentiate tuberculous abscesses from pyogenic abscesses by using MT MR imaging and in vivo MR spectroscopy, which could be of value in influencing the management of such cases.

Adolescent↗
PubMed2001

Leprosy bacillus--possibly the first chemoautotrophic human pathogen cultivated in vitro and characterised.

Leprosy bacillus (LB) and leprosy derived in vitro culture forms, the chemoautotrophic nocardioform (CAN) bacteria, showed an extremely close homology and identity with each other as regards a chemoautotrophic nutritional pattern, a nocardioform morphology, a weak acid-fastness coupled with Gram and Gomori's stain positivity, an exclusive mycolate and lipid profile, a phenolic glycolipid (PGL-I) and a highly sequestrated DNA characteristic, namely, a unique small size, a low G+C % mole, an exceptionally high gamma and UV radiation resistance, and a high thermal resistance. LB/CAN bacteria (CANb) gave positive signals for 36 kDa protein PCR, as well as, for 65 kDa epitope, and hybridisation with two or more probes and also by RFLP-analysis. Both LB/and CAN bacteria exhibited bacillary multiplication in the mouse footpads (MFP), nerve infiltration and evidences for local pathogenicity associated with pronounced systemic invasion. A highly reproducible mutilation model could be established which enabled a successful application of the postulates of Koch. The proof of their total identity was their anergic reactions in LL cases counterpoised against Mitsuda type strong nodular responses, mirroring the reactions of leprosy bacilli in TT cases, in accordance with the dictum of XIth International Leprosy Congress (1978). Thus, the chemoautotrophic nutritional requirements of LB, entirely unsuspected for a medically important pathogenic bacterium, having dimorphic (both bacillary and mycelial) characters with spores, mycelia and granules and unique pathogenicity of multilation manifested through the virulence factor, the enzyme collagenase, made LB or M leprae the highly enigmatic bacterium for so long.

Animals↗
PubMed2000

Synthesis of persialylated beta-cyclodextrins.

The synthesis of homogeneous hepta-antennated C-6 branched sialosyl cyclomaltoheptose derivatives (persialylated beta-cyclodextrins) has been performed in good to excellent yields, and the compounds have been fully characterized. The thioacetate N-acetylneuraminic acid derivative 6 was selectively de-S-acetylated and coupled by nucleophilic displacement in a one-pot reaction to the heptakis(chloroacetamido) beta-CDs 2 and 5, yielding multivalent sialosides 8 and 9, respectively. The thiourea-linked sialyl-CD 10 was obtained by reaction of the 4-isothiocyanatophenyl N-acetylneuraminic acid derivative 7 with the per-tert-butoxycarbonylamino beta-CD derivative 2 after suitable deprotection of the amino function.

Carbohydrate Conformation↗
PubMed2000

Cytokine and cytotoxic molecule gene expression determined in peripheral blood mononuclear cells in the diagnosis of acute renal rejection.

BACKGROUND: Prevention of acute rejection is the most prevalent measure used to reduce the long-term risk of chronic allograft rejection. Until now, biopsy was the only useful diagnostic tool for monitoring allograft acute rejection, but invasiveness of this procedure limits its use. The aim of this study was to investigate the implication of peripheral blood immune markers as a predictive diagnostic tool preceding biopsy in acute renal allograft rejection determination. METHODS: Of the 61 patients studied, 13 had no rejection episodes, 8 had a proven acute rejection, and 40 were excluded for graft dysfunction causes. Mitogen-induced peripheral blood mononuclear cells were tested for interleukin- (IL) 2, IL-4, IL-5, IL-6, IL-10, IL-15, Interferon-gamma, Perforin, Granzyme B, and Fas L using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). An up-regulated mRNA expression value was calculated in which a patient's sample was deemed positive if its differential expression value was equal or higher than the mean differential expression value calculated from the nonrejecting patients. RESULTS: IL-4, IL-5, IL-6, Interferon-gamma, Perforin, and Granzyme B mRNA levels were associated with acute rejection. When at least two of these cytokine markers were up-regulated in a given patient, 75% of the rejecting recipients were identified against 15% of the nonrejecting patients. CONCLUSIONS: We have shown that acute rejection episodes in renal transplant recipients were associated with an increase in mRNA expression of cytokines in mitogen-induced peripheral blood mononuclear cells. The evaluation of pro-inflammatory cytokines and cytotoxic molecules prove useful in the clinical identification of acutely rejecting transplant recipients and in the justification of concomitant antirejection therapy before histological diagnosis confirmation.

Biomarkers↗
PubMed2000

Decreased LH pulsatility during initiation of gonadotropin superovulation treatment in the cow: evidence for negative feedback other than estradiol and progesterone.

LH pulse secretion is suppressed during superovulation of cattle. The objective of this study was to determine how soon after initiation of superovulation treatments this suppressive effect occurs, and to test the hypothesis that decreased LH pulsatility is not related to changes in circulating estradiol or progesterone. Heifers (n = 7/group) were injected with eCG (FOLLIGON: a single injection of 2,500 IU) or twice daily injections of decreasing doses of FOLLTROPIN-V (total equivalent of 280 mg of NIH-FSH-P1) or F.S.H.-P (total equivalent of 28 mg of Armour standard) or saline (time controls), starting on Day 10 (Day 0 = estrus). Blood samples were taken every 10 min for 12 h intervals on the day prior to first injection, at 8 to 20 h and 32 to 44 h after initiation of gonadotropin treatment, and also during prostaglandin (PG)-induced luteolysis. A simple method based on robust statistics and on graphical representations of time series was developed to characterize LH pulses. There was a significant interaction between time and treatment for mean LH, estradiol and progesterone when control and treated groups were analyzed together, and no interaction when only the gonadotropin groups were analyzed together. When compared to pretreatment values, pulse frequency of LH was significantly reduced (P<0.05) in each treatment group, 8 to 20 h and 32 to 44 h following initiation of gonadotropin treatment. Mean LH concentrations were also reduced 32 to 44 h following initiation of treatments (P<0.05). Mean estradiol concentrations increased two to threefold at 8 to 20 h following initiation of superovulation treatments (P<0.05). Progesterone concentrations also increased by 20 or 44 h. There was no significant correlation between estradiol or progesterone and LH pulse frequency, amplitude and mean concentrations at any time in control or superovulated animals. This study demonstrates that superovulation treatment in the cow causes a rapid decrease in pulsatile release of LH and suggests that this effect is not mediated through the negative feedback actions of estradiol and progesterone.

Animals↗
PubMed2000

Dynamics of activated escape and its observation in a semiconductor laser

We report a direct experimental observation and provide a theory of the distribution of trajectories along which a fluctuating system moves over a potential barrier in escape from a metastable state. The experimental results are obtained for a semiconductor laser with optical feedback. The distribution of paths displays a distinct peak, which shows how the escaping system is most likely to move. We argue that the specific features of this distribution may give an insight into the nature of dropout events in lasers.

Journal Article↗
PubMed2000

Synthesis of "sugar-rods" with phytohemagglutinin cross-linking properties by using the palladium-catalyzed Sonogashira reaction

A palladium-catalyzed Sonogashira reaction has been applied for the syntheses of divalent "sugar-rods" which exhibited excellent lectin cross-linking properties. The procedure, which involves a tetrakis(triphenylphosphine)palladium-catalyzed cross-coupling reaction between an alkyne and a halogen-bearing sp2-carbon in DMF at 60 degrees C, is very efficient and the dimeric or heterobifunctional "sugar-rods" (8-13, 15-17) were isolated in 65-100% yields. Dimers 8a and 15a were both shown to form insoluble cross-linked lattices when mixed with the tetrameric plant lectin from Canavalia ensiformis (Concavalin A, Con A). Moreover, the relative inhibitory properties of the synthetic dimannosides were determined by means of the hemagglutination of rabbit erythrocytes, whereby dimer 15a was shown to be 20-fold more potent than monomeric methyl alpha-D-mannopyranoside.

Journal Article↗
PubMed2000

Binding of multivalent carbohydrates to concanavalin A and Dioclea grandiflora lectin. Thermodynamic analysis of the "multivalency effect".

Binding of a series of synthetic multivalent carbohydrate analogs to the Man/Glc-specific lectins concanavalin A and Dioclea grandiflora lectin was investigated by isothermal titration microcalorimetry. Dimeric analogs possessing terminal alpha-D-mannopyranoside residues, and di-, tri-, and tetrameric analogs possessing terminal 3, 6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside residues, which is the core trimannoside of asparagine-linked carbohydrates, were selected in order to compare the effects of low and high affinity analogs, respectively. Experimental conditions were found that prevented precipitation of the carbohydrate-lectin cross-linked complexes during the isothermal titration microcalorimetry experiments. The results show that the value of n, the number of binding sites on each monomer of the lectins, is inversely proportional to the number of binding epitopes (valency) of each carbohydrate. Hence, n values close to 1.0, 0.50, and 0.25 were observed for the binding of mono-, di-, and tetravalent sugars, respectively, to the two lectins. Importantly, differences in the functional valency of a triantennary analog for concanavalin A and D. grandiflora lectin are observed. The enthalpy of binding, DeltaH, is observed to be directly proportional to the number of binding epitopes in the higher affinity analogs. For example, DeltaH of a tetravalent trimannoside analog is nearly four times greater than that of the corresponding monovalent analog. Increases in K(a) values of the multivalent carbohydrates relative to monovalent analogs, known as the "multivalency effect," are shown to be due to more positive entropy (TDeltaS) contributions to binding of the former sugars. A general thermodynamic model for distinguishing binding of multivalent ligands to a single receptor with multiple, equal subsites versus binding to separate receptor molecules is given.

Calorimetry↗
PubMed2000

Hexadecane mineralization and denitrification in two diesel fuel-contaminated soils.

The effect of nitrate, ammonium and urea on the mineralization of [(14)C]hexadecane (C(16)H(34)) and on denitrification was evaluated in two soils contaminated with diesel fuel. In soil A, addition of N fertilizers did not stimulate or inhibit background hexadecane mineralization (4.3 mg C(16)H(34) kg(-1) day(-1)). In soil B, only NaNO(3) stimulated hexadecane mineralization (0.91 mg C(16)H(34) kg(-1) day(-1)) compared to soil not supplemented with any nitrogen nutrient (0.17 mg C(16)H(34) kg(-1) day(-1)). Hexadecane mineralization was not stimulated in this soil by NH(4)NO(3) (0.13 mg C(16)H(34) kg(-1) day(-1)), but the addition of NH(4)Cl or urea suppressed hexadecane mineralization (0.015 mg C(16)H(34) kg(-1) day(-1)). Addition of 2 kPa C(2)H(2) did not inhibit the mineralization process in either soil. Denitrification occurred in both soils studied when supplemented with NaNO(3) and NH(4)NO(3), but was not detected with other N sources. Denitrification started after a longer lag in soil A (10 days) than in soil B (4 days). In soil A microcosms supplemented with NaNO(3) or NH(4)NO(3), rates of denitrification were 20.6 and 13.6 mg NO(3)(-) kg(-1) day(-1), respectively, and in soil B, they were 18.5 and 12.5 mg NO(3)(-) kg(-1) day(-1), respectively. We conclude that denitrification may lead to a substantial loss of nitrate, making it unavailable to the mineralizing bacterial population. Nitrous oxide was an important end-product accounting for 30-100% of total denitrification. These results indicate the need for preliminary treatability studies before implementing full-scale treatment processes incorporating commercial fertilizers.

Journal Article↗