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Biomedical subjects

S French

Publications and source records attributed to S French.

At least 55 records · Page 3Linked to original sources

Patterns of health-compromising behaviors among Minnesota adolescents: sociodemographic variations.

OBJECTIVES: This study compared prevalence rates of health-compromising behaviors among boys and girls from different ethnic backgrounds in early, middle, and late adolescence and compared co-occurrences of such behaviors across gender and ethnic groups. METHODS: The study population included 123 132 adolescents in grades 6, 9, and 12. Adolescents completed a classroom-administered statewide survey focusing on high-risk behaviors, including unhealthy weight loss, substance abuse, suicide risk, delinquency, and sexual activity. RESULTS: Prevalence rates of most health-compromising behaviors differed by gender, increased with age, and tended to be highest among American Indian youth and lowest among Asian Americans. Strong associations were found between substance abuse and delinquency across all ethnic groups. Substance abuse and delinquency were associated with suicide risk across most ethnic groups. Covariations with sexual activity and unhealthy weight loss behaviors showed more ethnic variation. CONCLUSIONS: Prevention interventions should take into account the tendency for health-compromising behaviors to co-occur and should be sensitive to demographic and socioeconomic differences in behavior patterns.

Adolescent↗

A phase II clinical trial of echinomycin in metastatic soft tissue sarcoma. An Illinois Cancer Center Study.

Echinomycin, a cyclic peptide in the family of quinoxaline antibiotics, was evaluated in patient with metastatic, soft tissue sarcoma not previously treated for metastatic disease. The starting dose of echinomycin was 1,200 mcg/m2 administered intravenously, once weekly x 4, followed by a two-week break. The protocol design called for dose escalation on subsequent cycles of therapy, but because of significant toxicity, dose escalation occurred in only 5 of 25 treatment cycles. Severe nausea and vomiting was the most common toxicity. No clinical responses were observed in the 12 evaluable patients. Echinomycin at this dose and schedule is inactive in metastatic soft tissue sarcoma.

Adult↗

Phase II study of amonafide in the treatment of patients with advanced squamous cell carcinoma of the head and the neck. An Illinois Cancer Center study.

Amonafide (nafidimide), a synthetic organic compound with an inhibitory effect on cellular replication, was used in a phase II study conducted by the Illinois Cancer Center in order to assess its efficacy and toxicity in advanced or recurrent squamous cell cancer of the head and neck. Eligible patients had received no more than one prior adjuvant or neoadjuvant chemotherapy, had normal bone marrow, renal and hepatic function, ECOG performance status of 0-2, and bidimensionally measurable disease. Eligible patients were administered amonafide at a starting dose of 300 mg/m2 for five consecutive days every 3 weeks with dose escalation or de-escalation according to established hematologic criteria in the absence of disease progression. Nineteen of 22 entered patients were evaluable for response and all patients were evaluable for toxicity. Eleven of 19 patients achieved stable disease. Median time to progression after start of treatment was 57 days, for the 18 patients for whom the date of progression is known. There were no partial or complete responses. Hematologic toxicity was dose limiting with grade 3-4 neutropenia in 50 percent of patients and 4 deaths associated with neutropenic sepsis. Non-hematologic toxicity was mild to moderate with nausea and vomiting predominating. In this study, amonafide was a myelotoxic, inactive treatment in advanced/recurrent head and neck cancer. Further use in head and neck cancer appears unwarranted.

Adenine↗

Identification of novel peptide antagonists for von Willebrand factor binding to the platelet glycoprotein Ib receptor from a phage epitope library.

We have constructed a fusion phage epitope library in the filamentous bacteriophage fuse5. The library was made by inserting a degenerate oligonucleotide which encodes 15 variable amino acids into the NH2-terminal region of the phage gene III protein. This library, containing over 10(7) different epitope bearing phage, has been used in an attempt to identify inhibitors of the von Willebrand factor (vWF)-platelet Glycoprotein Ib interaction. The library was screened with a monoclonal antibody (RG46) that recognizes the GPIb binding domain of vWF (amino acids 445-733). A total of 30 clones falling into 8 classes have been identified that react with the RG46 antibody. Isolates from all 8 classes are positive by immunoblot analysis. The amino acid sequence of the gene III fusion protein from positive clones showed a strong homology to the known RG46 epitope. Peptides identified from the screen were synthesized and used to demonstrate that some of the synthetic peptides exhibited inhibitory activity towards ristocetin induced binding of vWF to the GPIb receptor. Thus, we have demonstrated that screening a fusion phage epitope library with a monoclonal antibody that inhibits vWF binding to the GPIb receptor can be a useful tool not only for mapping antibody recognizing determinants, but also can serve as a source for identifying novel peptides that are antagonists for vWF binding to the platelet GPIb receptor.

Amino Acid Sequence↗

Identification of a Src SH3 domain binding motif by screening a random phage display library.

A phage display library was constructed in the filamentous bacteriophage fuse5. The library was made by inserting a degenerate oligonucleotide which encodes 15 variable amino acids into the NH2-terminal region of the phage gene III protein. This library, containing over 10(7) different phage, was screened with a glutathione S-transferase (GST) fusion protein containing the Src homology 3 (Src SH3) domain and a protein kinase A phosphorylation site (GST/PKA/Src SH3). A family of proline-rich sequences was isolated following four cycles of enrichment and amplification. Phage containing these sequences were shown to specifically bind to the GST/PKA/Src SH3 protein but not to GST/PKA only. A comparison of the inferred amino acid sequence of the different phage clones revealed a consensus sequence, RPLPXXP, which conforms to a Src SH3 domain binding motif identified independently during an affinity screen of a lambda-lox mouse embryo cDNA library using a 32P-labeled Src SH3 protein fragment as the probe (Y. Ivashchenko, manuscript in preparation). Peptides based upon the 7-amino acid SH3 binding domain core motif displayed strong binding to both the Src and to the Fyn SH3 domains, but failed to bind to the SH3 domain of p21 Ras-GTPase-activating protein (Ras-GAP) and other proteins. We anticipate that further screening of the phage display library will be a useful tool for the rapid identification of additional SH3 domain binding sequences and will also help to establish the essential core motifs that define the specificity of interactions among the diverse proteins containing SH3 domains and those containing SH3 binding motifs.

Amino Acid Sequence↗

High-dose aminothiadiazole in advanced colorectal cancer. An Illinois Cancer Center phase II trial.

Thirty-three patients with advanced colorectal carcinoma were entered on a phase II trial of weekly IV aminothiadiazole (175 mg/m2 escalated to 200 mg/m2) with concomitant allopurinol and non-steroidal anti-inflammatory agents (NSAID's). Toxicity was predominantly GI, cutaneous, and chest pain/dyspnea. Twenty-five percent of patients had grade 3 or 4 toxicity. There were no responses in 27 evaluable patients. Median survival was 12 months. Aminothiadiazole, at higher doses than used in previous reports, when given with NSAID's, had no significant activity against large bowel cancer.

Adenocarcinoma↗

Protective effect of epidermal growth factor in an experimental model of colitis in rats.

BACKGROUND/AIMS: The role of epidermal growth factor (EGF) in the maintenance of mucosal integrity in the lower gastrointestinal tract is unknown. The aim of this study was to determine the effect of EGF in experimental colitis. METHODS: Colitis was induced with 2,4,6-trinitrobenzenesulfonic acid/ethanol enemas. Rats were pretreated with intraperitoneal administration of recombinant human EGF (600 micrograms/kg) or vehicle 1 hour before induction of colitis and daily thereafter until killed at 8 hours, 48 hours, and 1 week. A separate group received an identical dosage and administration of EGF or vehicle for 1 week with treatment initiated 24 hours after the induction of colitis. Colonic tissue was evaluated macroscopically, histologically, and for myeloperoxidase activity. RESULTS: Pretreatment with EGF reduced microscopic erosions at 8 and 48 hours by 74% and 54%, respectively (P < 0.05). At 1 week, microscopic ulcerations and myeloperoxidase activity were reduced by 65% in the EGF-pretreated group (P < 0.05). No significant difference in macroscopic injury, histological damage, or myeloperoxidase activity was noted when EGF treatment was initiated after the induction of colitis. CONCLUSIONS: Systemic EGF administration reduces mucosal damage and inflammation in a trinitrobenzenesulfonic acid/ethanol model of colitis in rats through a mechanism involving mucosal protection.

Animals↗

Comparison of a low-fat, ad libitum complex-carbohydrate diet with a low-energy diet in moderately obese women.

This study compared the effect of a low-fat, ad libitum, complex-carbohydrate (LFAL) diet with a low-energy (LE) diet on weight loss over 6 mo in moderately obese women. Weight loss was 4.4 kg in the LFAL (n = 47) and 3.8 kg in the LE (n = 42) participants. The difference was not statistically significant. The LFAL participants decreased percent energy from fat by 13%, increased percent energy from carbohydrate by 11.4%, and reduced energy intake by 1654 kJ. The corresponding values in the LE group were 3.8%, 3.5%, and 1991 kJ, respectively. Changes in fat and carbohydrate energy were significantly different by treatment (P < 0.0001). Palatability, satiety, and quality of life (QOL) improved in the LFAL group but diminished in the LE group. Palatability and QOL changes were significantly different by treatment (P < 0.029 and P < 0.048, respectively). It is concluded that an LFAL diet can result in substantial weight loss and is associated with improved palatability and QOL compared with an LE diet.

Adult↗

The role of the gut in regulating food intake in man.

In addition to various psychosocial and metabolic factors, food intake is also influenced by gastrointestinal mechanisms that trigger both the initiation and termination of eating behaviors. Although gastric distension is one of the most obvious signs of "fullness" and clearly plays a role in controlling food intake, its effects are only temporary and are distinct from the feelings of satiety generally associated with a meal. Such postprandial sensations appear to be related to the activation of intestinal chemoreceptors. Other evidence indicates that the release of cholecystokinin and perhaps other transmitters as well may contribute to satiety. Although the stomach probably does not expand or shrink in response to different levels of food intake, nutrient receptors in the small intestine probably do adapt to changes in food intake. Intestinal adaptation also occurs in response to thyroid hormone, insulin, and cortisol as well as to obesity, pregnancy, and illness, which all may have an important bearing on changes in eating behavior in these situations.

Cholecystokinin↗

Depletion of functional ribosomal RNA operons in Escherichia coli causes increased expression of the remaining intact copies.

The synthesis of ribosomal RNA is a complex and highly regulated process. To study this process, we have used deletion-insertions to disrupt sequentially from one to four of the seven rRNA (rrn) operons on the Escherichia coli genome. Inactivation of four rrn operons caused a 2.3-fold increase in the expression of a chloramphenicol acetyl transferase reporter gene fused to the tandem promoters of rrnA and a similar increase in the expression of the trp tRNA gene at the end of rrnC. This reflected enhanced expression of the remaining operons to compensate for having only three intact copies. The elevated expression was caused by an increase in both transcription initiation and RNA polymerase elongation rates specifically on rrn operons and occurred in the absence of changes in the intracellular concentration of ppGpp, suggesting that ppGpp is not involved in the regulation of this phenomenon. We discuss these results in relation to the ribosome feedback inhibition model described by Nomura and coworkers.

Base Sequence↗

Consequences of replication fork movement through transcription units in vivo.

To examine the basis for the evolutionary selection for codirectionality of replication and transcription in Escherichia coli, electron microscopy was used to visualize replication from an inducible ColE1 replication origin inserted into the Escherichia coli chromosome upstream (5') or downstream (3') of rrnB, a ribosomal RNA operon. Active rrnB operons were replicated either in the same direction in which they were transcribed or in the opposite direction. In either direction, RNA polymerases were dislodged during replication. When replication and transcription were codirectional, the rate of replication fork movement was similar to that observed in nontranscribed regions. When replication and transcription occurred in opposite directions, replication fork movement was reduced.

DNA Replication↗

Phase II trial of fludarabine phosphate for adenocarcinoma of the pancreas. An Illinois Cancer Center study.

We have conducted a phase II trial of fludarabine phosphate for advanced measurable adenocarcinoma of the pancreas. The drug was administered every 4 weeks by a daily-times-5 bolus schedule beginning at 20 mg/m2/day. No responses were observed in 20 evaluable patients, 18 of whom were previously untreated. Dose-limiting toxicity was leukopenia, and gastroenterologic side effects were frequent. Life-threatening or fatal renal dysfunction occurred in 3 patients. In this schedule fludarabine phosphate is ineffective against adenocarcinoma of the pancreas and appears to have unpredictable severe renal toxicity.

Adenocarcinoma↗

Definition of an advanced nursing practice role in the NICU: the clinical nurse specialist/neonatal practitioner.

We surveyed 655 health professionals affiliated with tertiary level neonatal intensive care units in Canada and the United States to define an expanded role for nurses in neonatology and to determine the educational requirements for the role. The role, comprising advanced clinical practice, educational, research, and administrative responsibilities, is a blend of nurse practitioner and clinical nurse specialist activities. Based on survey findings, a neonatal stream within the existing Master of Health Sciences program at McMaster University was developed. To date, 15 clinical nurse specialists/neonatal practitioners (CNS/NPs) are employed in five neonatal intensive care units in Ontario and other related institutions. A randomized trial to evaluate these individuals is in progress.

Humans↗

Conventional and right precordial ECGs, creatine kinase, and radionuclide angiography in post-traumatic ventricular dysfunction.

Right ventricular infarction due to ischemic heart disease can be diagnosed by a right precordial electrogram or by first-pass radionuclide angiography (FPRNA). Prior FPRNA studies have shown that cardiac dysfunction after blunt chest trauma (myocardial contusion) is most often due to right ventricular dysfunction. We hypothesized that right ventricular dysfunction due to ischemic heart disease and myocardial contusion should produce similar ECG changes due to myocyte disruption. The purpose of our study was to evaluate the diagnostic value of the right precordial electrogram in suspected cardiac contusion. Thirty-five patients with suspected myocardial contusion based on mechanism of injury/clinical findings and no history of clinical heart disease were enrolled prospectively. All patients had conventional ECG, right precordial electrogram, and FPRNA studies. Twenty patients had normal cardiac scans (group 1); percentage of myocardial creatine kinase (CK-MB) was measured in 12 of these patients and was less than 5% in 11. Fifteen patients had abnormal cardiac scans (wall motion abnormality and/or decreased right ventricular ejection fraction) (mean, 34% +/- 7% [SD]; normal, greater than 40%) (group 2); percentage of CK-MB was measured in 13 of 15 patients and was less than 5% in all 13. Conventional ECGs and right precordial electrograms in all patients were analyzed for differences in heart rate, PR interval, QRS duration, corrected QT interval, and the axis of the frontal and horizontal plane QRS complex and ST segment. There were no significant differences between group 1 and group 2 patients. No patient with myocardial contusion diagnosed by FPRNA had elevated ST segments in V4R through V6R or a percentage CK-MB of more than 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗