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PubMed2003

Body modification and substance use in adolescents: is there a link?

PURPOSE: To describe the characteristics of body modification among adolescents and to determine whether adolescents who engage in body modification are more likely to screen positive for alcohol and other drug problems than those who do not. METHODS: Adolescents aged 14 to 18 years presenting to an urban adolescent clinic for routine health care completed a questionnaire about body modification and a substance use assessment battery that included the 17-item Problem Oriented Screening Instrument for Teenagers Alcohol/Drug Use and Abuse Scale (POSIT-ADS). Body modification was defined as piercings (other than one pair of bilateral earlobe piercings in females), tattoos, scarification, and branding. Problem substance use was defined as a POSIT-ADS score > or =1. Data were analyzed using logistic regression to determine whether the presence of body modification was an independent predictor of problem substance use. RESULTS: The 210 participants had a mean (+/- SD) age of 16.0 (+/- 1.4) years and 63% were female. One hundred adolescents (48%) reported at least one body modification; girls were more likely than boys to have body modification (59% vs. 28%, p < or = .0005). Ninety (42%) reported piercings, 22 (10%) tattoos, 9 (4%) scarification, and 1 (< 1%) branding; 21 (10%) had more than one type of body modification. These were in a variety of locations, most commonly the ear and the nose (piercings) or the extremities (tattoos). One-third of the sample (33%) screened positive for problem substance use on the POSIT-ADS questionnaire. Controlling for age, adolescents with body modification had 3.1 times greater odds of problem substance use than those without body modification (95% CI 1.7, 5.8). CONCLUSIONS: Body modification was associated with self-reported problem alcohol and other drug use among middle adolescents presenting for primary care. More research is needed to determine the clinical and sociocultural significance of body modification and its relationship to substance use in this population.

Adolescent↗
PubMed1995

Preferred sites of glycosylphosphatidylinositol modification in folate receptors and constraints in the primary structure of the hydrophobic portion of the signal.

The divergent carboxyl-terminal signal peptides for glycosylphosphatidylinositol (GPI) membrane anchor attachment in folate receptor (FR) types alpha and beta were characterized. All of the candidate amino acid residues for GPI modification were identified and tested by substituting individually and in combination with amino acids that cannot be modified by GPI. Thus the GPI modification in FR-alpha was decreased to 22% by mutation of Ser234 to Thr but unaltered by changing the other candidate, Gly235, to Met. However, the double mutant FR-alpha Ser234-Thr,Gly235-Met showed half of the GPI modification seen in FR-alpha Ser234-Thr. This result suggests that Ser234 is the preferred GPI modification site, while Gly235 is a minor, alternate GPI modification site. Similarly, in FR-beta, mutation of Asn230 to Gln decreased GPI modification to 32%, while mutation of the other candidate site, Gly237, to Met had no effect. However, mutation at both sites further reduced the GPI modification by a half. A five amino acid carboxyl-terminal deletion (FR-beta delta 5) caused no decrease in the extent of GPI modification. However, the same deletion in FR beta Asn230-Gln decreased the residual GPI modification by 66%. These results suggest that Asn230 is the preferred GPI modification site in FR-beta, while Gly235 offers a minor alternate modification site; consistent with this conclusion is the fact that modification at the downstream site is hindered by its proximity to the carboxyl terminus in FR-beta delta 5. Further, the suggestion that the hydrophobic portion of the GPI signal is a random sequence of neutral amino acids with overall moderate hydrophobicity was tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed2001

Is sinus node modification appropriate for inappropriate sinus tachycardia with features of postural orthostatic tachycardia syndrome?

Inappropriate sinus tachycardia and postural orthostatic tachycardia are ill-defined syndromes with overlapping features. Although sinus node modification has been reported to effectively slow the sinus rate, long-term clinical response has not been adequately assessed. Furthermore, whether patients with postural orthostatic tachycardia would benefit from sinus node modification is unknown. The study prospectively assessed the short- and long-term clinical outcomes of seven consecutive female patients with postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia who were treated with sinus node modification. The study was conducted in a tertiary care center. The electrophysiological and clinical responses were prospectively assessed as defined by autonomic function testing, including Valsalva maneuver, deep breathing, tilt table testing, and quantitative sudomotor axonal reflex testing. Among the study population (mean age was 41+/-6 years), 5 (71%) patients had successful sinus node modification. At baseline, heart rates were 101+/-12 beats/min before modification and 77+/-9 beats/min after modification (P = 0.001). With isoproterenol, heart rates were 136+/-9 and 105+/-12 beats/min (P = 0.002) before and after modification, respectively. The mean heart rate during 24-hour Holter monitoring was also significantly reduced: 96+/-9 and 72+/-6 beats/min (P = 0.005) before and after modification, respectively. Despite the significant reduction in heart rate, autonomic symptom score index (based on ten categories of clinical symptoms) was unchanged before (15.6+/-4.1) and after (14.6+/-3.6) sinus node modification (P = 0.38). Sinus rate can be effectively slowed by sinus node modification. Clinical symptoms are not significantly improved after sinus node modification in patients with inappropriate sinus tachycardia and postural orthostatic tachycardia. A primary subtle autonomic disregulation is frequently present in this population. Sinus node modification is not recommended in this patient population.

Adult↗
PubMed1991

Chemical modification and NMR studies on a mushroom lectin Ischnoderma resinosum agglutinin (IRA).

Chemical modification and NMR studies on a beta-galactosyl-specific lectin which was isolated from the fruiting bodies of a mushroom, Ischnoderma resinosum, has been carried out in order to investigate the amino acid residues involved in its sugar-binding sites. Modification of amino groups with succinic anhydride greatly affected the hemagglutinating activity. Inhibitory sugar lactulose could prevent the loss of the activity. Modification of carboxyl groups with glycine ethyl ester led to a 75% loss of the activity, the presence of inhibitory sugar being protective against the modification. Treatment with cyclohexane-1,2-dione for modification of arginine residues was accompanied by a complete loss of the activity. The arginine residues modification could also be protected by the inhibitory sugar. N-Bromosuccinimide treatment for modification of tryptophan residues caused a loss of the activity, although the inhibitory sugar exhibited no protective effect against this treatment. Modification of thiol groups with 5,5'-dithiobis(2-nitrobenzoic acid) resulted in a 50% loss of the activity. Modification of histidine residues with ethoxyformic anhydride led to a complete loss of the activity. The loss of the activity could be protected by the inhibitory sugar. Treatment with N-acetylimidazole for modification of tyrosine residues was accompanied by a loss of the activity. This modification was completely prevented in the presence of the inhibitory sugar. The activity of the tyrosine-modified lectin was recovered by the treatment with hydroxylamine. Furthermore, in the NOESY spectrum of the mixture of IRA and its inhibitory sugar, methyl beta-galactoside, an NOE cross peak between H-3 and/or 5 of the p-hydroxyphenyl group of a tyrosine in the lectin, and H-5 of the galactoside could be observed. These results indicate that a tyrosine residue is involved in the carbohydrate-binding site of the lectin. In addition, line broadening and down-field shifts of the galactoside-protons were observed in the presence of the lectin.

Agglutinins↗
PubMed2001

Nature, frequency and determinants of prescription modifications in Dutch community pharmacies.

AIMS: To examine the nature, frequency and determinants of prescription modifications in Dutch community pharmacies. METHODS: A prospective case-control study comparing modified prescriptions with nonmodified prescriptions was carried out in 141 Dutch community pharmacies. 2014 modified prescriptions (cases), collected in the selected pharmacies on a predetermined day in a specific period (25th February until 12th March 1999) and 2581 nonmodified prescriptions (controls) randomly selected on the same day were studied. The nature and frequency of prescription modifications and patient, drug and prescriber related determinants for a modified prescription were assessed. RESULTS: The overall incidence of prescription modifications was 4.3%, with a mean of 14.3 modifications per pharmacy per day. For prescription only medicines (POM) the incidence was 4.9%. The majority of POM modifications concerned a clarification (71.8%). In 22.2% a prescription could potentially have had clinical consequences when not altered; in more than half of the latter it concerned a dose error (13.7% of all cases). POM prescriptions of patients of 40-65 years had a significantly lower chance of modification compared with those of younger people (OR = 0.74 [0.64-0.86]). With respect to medication-class, we found a higher chance of POM modifications in the respiratory domain (OR = 1.48 [1.23-1.79]) and a decreased chance for nervous system POMs (OR = 0.71 [0.61-0.83]). With regard to prescriber-related determinants modifications were found three times more often in non printed prescriptions than in printed ones (OR = 3.30 [2.90-3.75]). Compared with prescriptions by the patient's own GP, prescriptions of specialists (OR = 1.82 [1.57-2.11]), other GP's (OR = 1.49 [1.02-2.17]) and other prescribers such as dentists and midwives (OR = 1.95 [1.06-3.57]) gave a higher probability of prescription modifications. When a GP had no on-line access to the computer of the pharmacy the chance of a modification was also higher (OR = 1.61 [1.33-1.94]). Multivariate analysis revealed that a nonprinted prescription was the strongest independent determinant of prescription modifications (OR = 3.32 [2.87-3.84]), remaining so after adjustment for GP computer link to the pharmacy and for type of prescriber. CONCLUSIONS: At least 30% of Dutch community pharmacies corrected 2.8 POM prescriptions per pharmacy per working day, which could potentially have had clinical consequences if not altered. If the study sample is representative for The Netherlands, Dutch community pharmacies correct a total of approximately 4400 of these prescriptions per working day. Using computerized systems to generate prescriptions is an important strategy to reduce the incidence of prescription errors.

Adult↗
PubMed2025

Prediction of gene expression using histone modification patterns extracted by Particle Swarm Optimization.

MOTIVATION: Histone modifications play an important role in transcription regulation. Although the general importance of some histone modifications for transcription regulation has been previously established, the relevance of others and their interaction is subject to ongoing research. By training Machine Learning models to predict a gene's expression and explaining their decision making process, we can get hints on how histone modifications affect transcription. In previous studies, trained models were either hardly explainable or the models were trained solely on the abundance of histone modifications. Based on other studies, which used histone modification patterns, rather than their abundance, to identify potential regulatory elements, we hypothesize the histone modification pattern in a gene's promoter to be more predictive for gene expression. We used an optimization algorithm to extract predictive histone modification profiles. RESULTS: Our algorithm called PatternChrome achieved an average area under curve (AUC) score of 0.9029 over 56 samples for binary classification, outperforming all previous algorithms for the same task. We explained the models decisions to deduce the effect of specific features, certain histone modifications or promoter positions on transcription regulation. Although the predictive histone modification patterns were extracted for each sample separately, they can be used to predict gene expression in other samples, implying that the created patterns are largely generalizable. Interestingly, the impact of histone modifications on gene regulation appears predominantly indifferent to cellular specificity. Through explanation of the classifier's decisions, we substantiate established literature knowledge while concurrently revealing novel insights into the intricate landscape of transcriptional regulation via histone modification. AVAILABILITY AND IMPLEMENTATION: The code for the PatternChrome algorithm, the scripts for the analyses and the required data can be found at (https://gitlab.gwdg.de/MedBioinf/generegulation/patternchrome).

Humans↗
PubMed1977

Sequential chemical modification of a histidyl and a cysteinyl residue in bacterial luciferase.

Sequential modification of two amino acid residues (a histidyl and a cysteinyl residue), both essential for the enzymatic function of bacterial luciferase from Beneckea harveyi, has been conducted to determine if the inactivation arising from the chemical modification of either of these residues is due to a conformational change. This experimental approach has shown that modification of the histidyl or cysteinyl residue did not affect the reactivity of the remaining 'essential' residue, suggesting that chemical modification had not caused a change in conformation. Furthermore, since substrates protect luciferase against inactivation due to modification of either of these residues, it was possible to determine if the initial modification of the histidyl or cysteinyl residue prevented substrate binding by conducting the modification of the remaining residue (i.e., the cysteinyl or histidyl residue, respectively) in the presence of substrates. The results have shown that after modification of the histidyl residue substrates no longer protected the cysteinyl residue against modification, whereas after modification of the cysteinyl residue substrates still protected the histidyl residue against modification. These results have provided evidence that the histidyl residue and not the cysteinyl residue of luciferase is essential for the binding of substrates in the bacterial bioluminescent reaction.

Bacteria↗