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Biomedical subjects

A Pappas

Publications and source records attributed to A Pappas.

At least 19 recordsLinked to original sources
PubMed2000

Relative frequencies of DRB1*11 alleles and their DRB3 associations in five major population groups in a United States bone marrow registry.

One hundred sixty-one individuals from each of five US population groups, Caucasians (CAU), African Americans (AFA), Asians/Pacific Islanders (API), Hispanics (HIS), and Native Americans (NAT), were randomly selected from a volunteer bone marrow registry database consisting of 14,452 HLA-DRB1*11 positive individuals. This sampling provided at least an 80% probability of detecting a rare allele that occurred at 1% in the DRB1*11 positive population. Samples were typed for DRB1*11 alleles by polymerase chain reaction-sequence specific oligonucleotide probe typing (PCR-SSOP). A total of 10 DRB1*11 alleles out of 27 possible alleles were detected. The distribution and diversity of DRB1*11 alleles varied among populations although DRB1*1101 was the predominant DRB1*11 allele in all populations. Caucasians were the least diversified; only four common alleles (DRB1*1101-*1104) were observed. As well as the four common alleles, other groups also carried one or two other less frequent alleles including DRB1*1105 (API), *1106 (API), *1110 (AFA), *1114 (HIS), *1115 (NAT), and *1117 (AFA). A subset (418) of these individuals were also typed for DRB3 alleles. Most (97.6%) showed a strong association of DRB1*11 with DRB3*0202.

Black or African American↗
PubMed2000

Dynamic pedobarography (DPB) in operative management of cavovarus foot deformity.

Dynamic pedobarography (DPB) was performed in 21 patients, 9 male and 12 female with cavovarus foot deformity mostly of Charcot-Marie-Tooth origin. Age ranged from 14 to 52 years (mean 30 y). Twenty-six feet were examined pre- and postoperatively clinically, radiologically and by dynamic pedobarography with a follow-up time from 9 to 49 months (mean 22.5 mo). The EMED SF system was used for data collection during walking. Gait line, contact areas (CA), peak pressures (PP) and pressure time integral (PTI) were determined. According to the contact pattern the examined feet could be divided into three groups with antegrade, retrograde and inversion contact pattern. Data analysis showed postoperatively considerable increase in CA and decrease in PP and PTI. Clinical results such as plantar callosities and "roll over avoidance gait" did not always correlate with pedobarographic data. DPB adds a dynamic component in the diagnosis and management of cavovarus feet but certain limitations exist.

Adolescent↗
PubMed1999

Characterization of a novel dUTP-dependent activity of CTP synthetase from Saccharomyces cerevisiae.

CTP synthetase [EC 6.3.4.2, UTP:ammonia ligase (ADP-forming)] from the yeast Saccharomyces cerevisiae catalyzes the ATP-dependent transfer of the amide nitrogen from glutamine to the C-4 position of UTP to form CTP. In this work, we demonstrated that CTP synthetase utilized dUTP as a substrate to synthesize dCTP. The dUTP-dependent activity was linear with time and with enzyme concentration. Maximum dUTP-dependent activity was dependent on MgCl(2) (4 mM) and GTP (K(a) = 14 microM) at a pH optimum of 8.0. The apparent K(m) values for dUTP, ATP, and glutamine were 0.18, 0.25, and 0.41 mM, respectively. dUTP promoted the tetramerization of CTP synthetase, and the extent of enzyme tetramerization correlated with dUTP-dependent activity. dCTP was a poor inhibitor of dUTP-dependent activity, whereas CTP was a potent inhibitor of this activity. The enzyme catalyzed the synthesis of dCTP and CTP when dUTP and UTP were used as substrates together. CTP was the major product synthesized when dUTP and UTP were present at saturating concentrations. When dUTP and UTP were present at concentrations near their K(m) values, the synthesis of dCTP increased relative to that of CTP. The synthesis of dCTP was favored over the synthesis of CTP when UTP was present at a concentration near its K(m) value and dUTP was varied from subsaturating to saturating concentrations. These data suggested that the dUTP-dependent synthesis of dCTP by CTP synthetase activity may be physiologically relevant.

Carbon-Nitrogen Ligases↗
PubMed1999

Identification of Ser424 as the protein kinase A phosphorylation site in CTP synthetase from Saccharomyces cerevisiae.

The URA7-encoded CTP synthetase [EC 6.3.4.2, UTP:ammonia ligase (ADP-forming)] in the yeast Saccharomyces cerevisiae is phosphorylated on a serine residue and stimulated by cAMP-dependent protein kinase (protein kinase A) in vitro. In vivo, the phosphorylation of CTP synthetase is mediated by the RAS/cAMP pathway. In this work, we examined the hypothesis that amino acid residue Ser424 contained in a protein kinase A sequence motif in the URA7-encoded CTP synthetase is the target site for protein kinase A. A CTP synthetase synthetic peptide (SLGRKDSHSA) containing the protein kinase A motif was a substrate (Km = 30 microM) for protein kinase A. This peptide also inhibited (IC50 = 45 microM) the phosphorylation of purified wild-type CTP synthetase by protein kinase A. CTP synthetase with a Ser424 --> Ala (S424A) mutation was constructed by site-directed mutagenesis. The mutated enzyme was not phosphorylated in response to the activation of protein kinase A activity in vivo. Purified S424A mutant CTP synthetase was not phosphorylated and stimulated by protein kinase A. The S424A mutant CTP synthetase had reduced Vmax and elevated Km values for ATP and UTP when compared with the protein kinase A-phosphorylated wild-type enzyme. The specificity constants for ATP and UTP for the S424A mutant CTP synthetase were 4.2- and 2.9-fold lower, respectively, when compared with that of the phosphorylated enzyme. In addition, the S424A mutant enzyme was 2.7-fold more sensitive to CTP product inhibition when compared with the phosphorylated wild-type enzyme. These data indicated that the protein kinase A target site in CTP synthetase was Ser424 and that the phosphorylation of this site played a role in the regulation of CTP synthetase activity.

Alanine↗
PubMed1998

Nucleotide-dependent tetramerization of CTP synthetase from Saccharomyces cerevisiae.

The nucleotide-dependent tetramerization of purified native URA7-encoded CTP synthetase (EC 6.3.4.2, UTP: ammonia ligase (ADP-forming)) from the yeast Saccharomyces cerevisiae was characterized. CTP synthetase existed as a dimer in the absence of ATP and UTP. In the presence of saturating concentrations of ATP and UTP, the CTP synthetase protein existed as a tetramer. Increasing concentrations of ATP and UTP caused a dose-dependent conversion of the dimeric species to a tetramer. The kinetics of enzyme tetramerization correlates with the kinetics of enzyme activity. The tetramerization of CTP synthetase was dependent on UTP and Mg2+ ions. ATP facilitated the UTP-dependent tetramerization of CTP synthetase by a mechanism that involved the ATP-dependent phosphorylation of UTP catalyzed by the enzyme. The glutaminase reaction that is catalyzed by the enzyme was not required for enzyme tetramerization. CTP, a potent inhibitor of CTP synthetase activity, did not inhibit the ATP/UTP-dependent tetramerization of the enzyme. Phosphorylation of the purified native CTP synthetase with protein kinase A and protein kinase C facilitated the nucleotide-dependent tetramerization. Dephosphorylation of native CTP synthetase with alkaline phosphatase prevented the nucleotide-dependent tetramerization of the enzyme. This correlated with the inactivation of CTP synthetase activity. Rephosphorylation of the dephosphorylated enzyme with protein kinase A and protein kinase C resulted in a partial restoration of the nucleotide-dependent tetramerization of the enzyme. This tetramerization correlated with the partial restoration of CTP synthetase activity. Taken together, these results indicated that enzyme tetramerization was required for CTP synthetase activity and that enzyme phosphorylation played an important role in the tetramerization and regulation of the enzyme.

Adenylyl Imidodiphosphate↗
PubMed1998

Generic noun phrases in mother-child conversations.

Generic noun phrases (e.g. Tigers are fierce) are of interest for their semantic properties: they capture 'essential' properties, are timeless, and are context-free. The present study examines use of generic noun phrases by preschool children and their mothers. Mother-child pairs were videotaped while looking through a book of animal pictures. Each page depicted either a single instance of a particular category (e.g. one crab) or multiple instances of a particular category (e.g. many crabs). The results indicated a striking difference in how generics vs. non-generics were distributed, both in the speech of mothers and in the speech of preschool children. Whereas the form of non-generic noun phrases was closely linked to the structure of the page (i.e. singular noun phrases were used more often when a single instance was presented; plural noun phrases were used more often when multiple instances were presented), the form of generic noun phrases was independent of the information depicted (e.g. plural noun phrases were as frequent when only one instance was presented as when multiple instances were presented). We interpret the data as providing evidence that generic noun phrases differ in their semantics and conceptual organization from non-generic noun phrases, both in the input to young children and in children's own speech. Thus, this simple linguistic device may provide input to, and a reflection of, children's early developing notion of 'kinds'.

Adult↗
PubMed1998

Genetic uncoupling of the dsRNA-binding and RNA cleavage activities of the Escherichia coli endoribonuclease RNase III--the effect of dsRNA binding on gene expression.

RNase III, a double-stranded RNA-specific endonuclease, is proposed to be one of Escherichia coli's global regulators because of its ability to affect the expression of a large number of unrelated genes by influencing post-transcriptional control of mRNA stability or mRNA translational efficiency. Here, we describe the phenotypes of bacteria carrying point mutations in rnc, the gene encoding RNase III. The substrate recognition and RNA-processing properties of mutant proteins were analysed in vivo by measuring expression from known RNase III-modulated genes and in vitro from the proteins' binding and cleavage activities on known double-stranded RNA substrates. Our results show that although the point mutation rnc70 exhibited all the usual rnc null-like phenotypes, unlike other mutations, it was dominant over the wild-type allele. Multicopy expression of rnc70 could suppress a lethal phenotype of the wild-type rnc allele in a certain genetic background; it could also inhibit the RNase III-mediated activation of lambdaN gene translation by competing for the RNA-binding site of the wild-type endonuclease. The mutant protein failed to cleave the standard RNase III substrates in vitro but exhibited an affinity for double-stranded RNA when passed through poly(rI):poly(rC) columns. Filter binding and gel-shift assays with purified Rnc70 showed that the mutant protein binds to known RNase III mRNA substrates in a site-specific manner. In vitro processing reactions with purified enzyme and labelled RNA showed that the in vivo dominant effect of the mutant enzyme over the wild-type was not necessarily caused by formation of mixed dimers. Thus, the rnc70 mutation generates a mutant RNase III with impaired endonucleolytic activity but without blocking its ability to recognize and bind double-stranded RNA substrates.

Alleles↗
PubMed1998

Beyond labeling: the role of maternal input in the acquisition of richly structured categories.

Recent research shows that preschool children are skilled classifiers, using categories both to organize information efficiently and to extend knowledge beyond what is already known. Moreover, by 2 1/2 years of age, children are sensitive to nonobvious properties of categories and assume that category members share underlying similarities. Why do children expect categories to have this rich structure, and how do children appropriately limit this expectation to certain domains (i.e., animals vs. artifacts)? The present studies explore the role of maternal input, providing one of the first detailed looks at how mothers convey information about category structure during naturalistic interactions. Forty-six mothers and their 20- or 35-month-old children read picture books together. Sessions were videotaped, and the resulting transcripts were coded for explicit and implicit discussion of animal and artifact categories. Sequences of gestures toward pictures were also examined in order to reveal the focus of attention and implicit links. drawn between items. Results indicate that mothers provided a rich array of information beyond simple labeling routines. Taxonomic categories were stressed in subtle and indirect ways, in both speech and gesture, especially for animals. Statements and gestures that linked two pictures were more frequent for taxonomically related animal pictures than for other picture pairs. Mothers also generalized category information using generic noun phrases, again more for animals than for artifacts. However, mothers provided little explicit discussion of nonobvious similarities, underlying properties, or inductive potential among category members. These data suggest possible mechanisms by which a notion of kind is conveyed in the absence of detailed information about category essences.

Child Development↗
PubMed1997

An erbium:YAG laser to obtain capillary blood samples without a needle for point-of-care laboratory testing.

BACKGROUND: Needlestick injury poses an occupational hazard to health care workers that will increase with the increasing availability of point-of-care testing using capillary blood obtained with a lancet. OBJECTIVES: To demonstrate the safety and efficacy of a portable pulsed erbium:yttrium-aluminum-garnet (Er:YAG) laser in obtaining a blood sample from patients in a clinical setting and to determine whether the laser radiant energy alters the level of various components of blood, resulting in misleading laboratory results. DESIGN: Comparison of laboratory values of blood samples obtained with the laser and conventional lancet and comparison of patient and user preferences by questionnaire. PATIENTS AND METHODS: One hundred patients with diabetes mellitus attending a diabetes clinic were randomized to have capillary blood sampling from the fingertip performed either by the laser or a conventional lancet first, then with the other device. MAIN OUTCOME MEASURES: A comparison of pain, healing, hematocrit, and glycosylated hemoglobin (HbAlc), blood urea nitrogen, sodium, potassium, bicarbonate, and glucose levels. RESULTS: Adequate blood was obtained with both devices 97% of the time. Blood flow was greater with the laser perforation, resulting in higher operator preference. Although patients felt greater pain and experienced slower healing with the laser, these were not serious problems. Modification of the laser energy output led to a reduction in pain. Possibly owing to hemolysis, the potassium level in the blood obtained with the laser was significantly elevated and unsuitable for clinical decision making in many cases. None of the other measurements were similarly affected. CONCLUSIONS: We conclude that the laser device has the potential to obtain a blood sample for routine tests without a needle. This needle-free method will decrease the risk of bloodborne infections caused by needlestick injuries and thus lead to considerable cost savings and public health advantages. Further work is needed to alter the laser energy so that hemolysis can be decreased, thus enabling a more reliable potassium estimation.

Bicarbonates↗
PubMed1994

Circulating gonadotrophin surge-attenuating factor from superovulated women suppresses in vitro gonadotrophin-releasing hormone self-priming.

A perifusion system based on ovine pituitary tissue explants was used to investigate the effects of follicular fluid (hFF) and serum from superovulated women on pituitary responsiveness to gonadotrophin-releasing hormone (GnRH). The specific aims of the study were to determine both if gonadotrophin surge-attenuating factor (GnSAF) bioactivity is present in the peripheral circulation as well as in the follicles of superovulated women and if GnSAF suppresses GnRH self-priming in vitro. Two pulses of GnRH, 1 h apart, produced marked peaks in LH secreted from control chambers, with GnRH self-priming evident in the significant difference between the first (134.4 +/- 1.7 - 232.1 +/- 24.0% of basal secretion) and second (183.9 +/- 15.8 - 313.9 +/- 14.0% of basal secretion) LH peaks. Both follicular fluid and serum pooled from two different groups of women produced marked suppression of the first (unprimed) and second (primed) LH peaks. The hFF reduced the first LH peak to 69.6 +/- 7.8 and 60.2 +/- 9.7% and the second LH peak to 57.4 +/- 6.7 and 42.6 +/- 6.5% of control LH secretion. Overall, the serum reduced the first and second LH peaks to 76.8 +/- 4.2 and 62.9 +/- 3.6% of control respectively. These results demonstrated that GnSAF bioactivity suppresses GnRH self-priming, and is present in both the peripheral circulation and hFF. The same material administered to dispersed ovine pituitary monolayers produced similar marked suppression of GnRH-induced LH secretion, with approximately 50-fold less GnSAF bioactivity in serum compared with hFF. Combined doses of oestradiol and progesterone, or hFF from large follicles containing little GnSAF, produced stimulation of GnRH-induced LH secretion and GnRH self-priming (second peaks 78.1 +/- 38.9 and 27.4 +/- 15.7% respectively higher than first peaks). Thus, in conclusion, GnSAF in hFF and serum markedly attenuated both unprimed and primed pituitary response to GnRH, virtually abolishing the GnRH self-priming effect.

Animals↗
PubMed1991

Nuclear magnetic resonance in pathology: I. Principles and general aspects.

Nuclear magnetic resonance (NMR) has become established as a powerful diagnostic imaging technique in medicine. The power of NMR as a tool for characterizing molecular structure and for quantitative analysis of complex mixtures in the clinical laboratory or even in vivo is beginning to be exploited. In the clinical laboratory, NMR can analyze the complex mixtures of bodily fluids, intact cells, tissues, and their extracts. Phosphorus-31 or 1H NMR spectroscopy in vivo can provide a noninvasive probe of high-energy compounds, amino acids, and compounds of phospholipid metabolism. The basic principles of NMR spectroscopy are presented here, with emphasis on the various NMR parameters and the information they provide. A companion article presents a survey of applications in pathology.

Magnetic Resonance Imaging↗
PubMed1991

Separation of pseudohypoparathyroidism into types I and II using only basal nephrogenous cAMP determinations.

The separation of pseudohypoparathyroidism (PHP) into Type I (non responders, usually with signs of Allright's hereditary osteodystrophy--AHO--and resistance to other hormones secretion) and Type II (responders) is classically done with the parathyroid hormone (PTH) infusion test using as criterion of cellular response total urinary cAMP determinations. But since total urinary cAMP is not an accurate index of intracellular cAMP production from the renal tubular cells--as is nephrogenous cAMP (NcAMP)--it was considered worthwhile to examine the diagnostic value of NcAMP in this case. A total of 12 PHP patients were studied along with 19 controls of corresponding age and sex. All 31 persons underwent--inter alia--to a 2 hrs I.V. PTH infusion test with 500 I.U. of human 1-34 PTH. Using as criterion total urinary cAMP, the PHP patients were separated into Type I (7 patients, of whom 5 with AHO) and Type II (5 patients). The same results were obtained when the NcAMP stimulation values were used instead, although in PHP Type II patients the mean increase of NcAMP at the end of PTH infusion was 2 fold than the corresponding increase of total urinary cAMP. But the most impressing finding was that the separation of PHP patients to the Types I or II was possible by using the basal NcAMP values only (NcAMP basal values ranged from 0.35 to 0.56 nmols/100 ml GFR in Type I and from 0.93 to 1.75 in Type II PHP). These results render possible the use of NcAMP basal values as a screening test for the separation of PHP patients into Types I and II.

Cyclic AMP↗
PubMed1987

The acute urethral syndrome in routine practice.

Midstream samples of urine from 185 acutely dysuric women and 89 symptom-free controls were screened according to the modified criteria of Kass by both conventional and microaerophilic culture. Among the 185 symptomatic women, coliform bacilli were isolated from 125 (67.5%) and in 45 (36%) of the latter the concentration of these organisms in the urine was less than 10(8)/l. Fastidious organisms were isolated in pure and mixed cultures from 25 (13.4%) of the 185 patients and from 4 (4.5%) of 89 controls. Staphylococcus species were isolated from 10.8% (9.7% S. saprophyticus; 1.1% S. epidermidis) and Ureaplasma urealyticum from 2.7%. All patients infected with conventional organisms but only 30.4% of those yielding fastidious organisms had pyuria. The isolation rate of fastidious organisms tended to be higher (P = 0.055) in symptomatic women that in symptom-free controls.

Acute Disease↗
PubMed1981

Comparison of ftorafur with 5-fluorouracil in combination chemotherapy of advanced gastrointestinal carcinoma.

The aim of the study was to compare the combination 5-FU-carmustine with ftorafur-carmustine in the treatment of advanced gastrointestinal cancer. To this end, a prospective, multicenter, randomized trial was initiated. Part I of this trial showed that similar response rates can be obtained with 5-FU-carmustine and ftorafur-carmustine in 109 patients (32.7% versus 26.3%). However, median survival was better in patients treated with 5-FU-carmustine (307 days versus 163 days). Part II of the trial revealed that neither a higher dosage of ftorafur (2 g/m2/day X 5 days) nor the addition of vincristine to both regimens changed the previously obtained results significantly. Again, median survival was found to be better in patients treated with 5-FU combination chemotherapy (304 days versus 144 days). Both the 5-FU and the ftorafur combination were tolerated reasonably well. The results suggest that combination chemotherapy including 5-FU is superior to ftorafur at the applied dosages in terms of survival.

Adult↗