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Biomedical subjects

K Smith

Publications and source records attributed to K Smith.

At least 361 records · Page 20Linked to original sources

Lives in a balance: perceived family functioning and the psychosocial adjustment of adolescent cancer survivors.

Childhood cancer patients have a greater likelihood of long-term survival than ever before. This study examined both the perceived family functioning of adolescents who had successfully completed treatment for pediatric cancer and the relationship between family functioning and post-treatment adjustment. Eighty-eight adolescent survivors of hematologic malignancies were assessed regarding their family functioning, mental health, self-esteem, global competence, and problem behaviors. Contrary to expectations about the influence of cancer on these families, adolescent cancer survivors reported lower levels of family cohesion than the normative sample of healthy adolescents and their families. While current age, gender, age at diagnosis, and time since treatment completion were generally not associated with adolescents' adjustment, perceived family cohesion and adaptability were strongly related to post-treatment psychological adjustment.

Adaptation, Psychological↗

A randomized trial of one versus three doses of Augmentin as wound prophylaxis in at-risk abdominal surgery.

In a randomized prospective trial of prophylactic antibiotics in at-risk abdominal surgery, one dose of intravenous Augmentin (amoxycillin 250 mg and clavulanic acid 125 mg) on induction has been compared with three 8 hourly doses in 900 patients. Wound infection rates which included minor and delayed infections were very similar in those given one dose: 48/449 (10.7%) compared with those given three doses: 49/451 (10.9%) 95% confidence limits - 4.25% + 3.9%. There were more septic and sepsis-related deaths in those patients given one dose (14 deaths) than in those given three doses (7 deaths) P > 0.1 95% CL - 0.4% + 3.0%. However, there were more very elderly patients in the one dose group: 64% of the deaths were aged over 80 and all but one had an emergency operation. There was no difference in the other outcome measures studied which included non-fatal deep sepsis, length of postoperative hospital stay, duration of postoperative fever or the use of antibiotics for postoperative infection. One dose of a suitable intravenous antibiotic gives prophylaxis against wound infection in at-risk abdominal surgery which is at least as effective as multiple doses. However, there may be a risk of overwhelming systemic sepsis in very elderly patients having emergency surgery.

Abdomen↗

Effect of growth hormone and resistance exercise on muscle growth in young men.

The purpose of this study was to determine whether growth hormone (GH) administration enhances the muscle anabolism associated with heavy-resistance exercise. Sixteen men (21-34 yr) were assigned randomly to a resistance training plus GH group (n = 7) or to a resistance training plus placebo group (n = 9). For 12 wk, both groups trained all major muscle groups in an identical fashion while receiving 40 micrograms recombinant human GH.kg-1.day-1 or placebo. Fat-free mass (FFM) and total body water increased (P less than 0.05) in both groups but more (P less than 0.01) in the GH recipients. Whole body protein synthesis rate increased more (P less than 0.03), and whole body protein balance was greater (P = 0.01) in the GH-treated group, but quadriceps muscle protein synthesis rate, torso and limb circumferences, and muscle strength did not increase more in the GH-treated group. In the young men studied, resistance exercise with or without GH resulted in similar increments in muscle size, strength, and muscle protein synthesis, indicating that 1) the larger increase in FFM with GH treatment was probably due to an increase in lean tissue other than skeletal muscle and 2) resistance training supplemented with GH did not further enhance muscle anabolism and function.

Adipose Tissue↗

Flooding with L-[1-13C]leucine stimulates human muscle protein incorporation of continuously infused L-[1-13C]valine.

To investigate why flooding methods give higher rates than constant-infusion methods for muscle protein synthesis, we studied seven healthy postabsorptive male volunteers (20-42 yr; 67-74 kg) during a 7.5-h primed constant infusion of L-[1-13C]valine (99 atoms %, 1.5 mg/kg prime, 1.5 mg.kg-1.h-1); at 6.5 h they were given a flood of L-[1-13C]leucine (20 atoms %, 0.05 g/kg). Musculus tibialis anterior biopsies were taken at 0.5, 6, and 7.5 h, and blood was sampled as appropriate. The enrichment of valine and leucine in muscle protein (isotope ratio mass spectrometry of protein amino acid-derived 13CO2) was compared with the average enrichment of various amino acid pools (gas chromatography-mass spectrometry). During infusion of [13C] valine the rate of muscle protein synthesis measured using alpha-ketoisovalerate (alpha-KIV) as precursor surrogate was 0.043 +/- 0.002%/h (SE). After flooding with leucine, the incorporation rate of [13C]valine increased by 70% (P less than 0.05), i.e., apparent muscle protein synthetic rate (based on alpha-[13C]KIV) increased to 0.065 +/- 0.009%/h (P less than 0.05); the rate calculated from the [13C]leucine flood was 0.060 +/- 0.005%/h (P less than 0.01). The synthetic rates calculated using the constant-infusion method were higher after flooding, irrespective of the precursor chosen, raising serious concern about the validity of the flooding-dose method.

Adult↗

Changes in human muscle protein synthesis after resistance exercise.

The purpose of this study was to investigate the magnitude and time course for changes in muscle protein synthesis (MPS) after a single bout of resistance exercise. Two groups of six male subjects performed heavy resistance exercise with the elbow flexors of one arm while the opposite arm served as a control. MPS from exercised (ex) and control (con) biceps brachii was assessed 4 (group A) and 24 h (group B) postexercise by the increment in L-[1-13C]leucine incorporation into muscle biopsy samples. In addition, RNA capacity and RNA activity were determined to assess whether transcriptional and/or translational processes affected MPS. MPS was significantly elevated in biceps of the ex compared with the con arms of both groups (group A, ex 0.1007 +/- 0.0330 vs. con 0.067 +/- 0.0204%/h; group B ex 0.0944 +/- 0.0363 vs. con 0.0452 +/- 0.0126%/h). RNA capacity was unchanged in the ex biceps of both groups relative to the con biceps, whereas RNA activity was significantly elevated in the ex biceps of both groups (group A, ex 0.19 +/- 0.10 vs. con 0.12 +/- 0.05 micrograms protein.h-1.microgram-1 total RNA; group B, ex 0.18 +/- 0.06 vs. con 0.08 +/- 0.02 micrograms protein.h-1.microgram-1 total RNA). The results indicate that a single bout of heavy resistance exercise can increase biceps MPS for up to 24 h postexercise. In addition, these increases appear to be due to changes in posttranscriptional events.

Adult↗

Respiratory muscle training in chronic airflow limitation: a meta-analysis.

The purpose of this study was to determine the effect of respiratory muscle training on muscle strength and endurance, exercise capacity, and functional status in patients with chronic airflow limitation. Computerized bibliographic data bases (MEDLINE AND SCISEARCH) were searched for published clinical trails, and an independent review of 73 articles by two of the investigators identified 17 relevant randomized trials for inclusion. Study quality was assessed and descriptive information concerning the study populations, interventions, and outcome measurements was extracted. We combined effect sizes across studies (the difference between treatment and control groups divided by the pooled standard deviation of the outcome measure). Across all studies, the effect sizes and associated p-values were as follows: maximal inspiratory pressure 0.12, p = 0.38; maximal voluntary ventilation 0.43, p = 0.02; respiratory muscle endurance 0.21, p = 0.14; laboratory exercise capacity -0.01, p = 0.43; functional exercise capacity 0.20, p = 0.15; functional status 0.06, p = 0.72. Secondary analyses suggested that endurance and function may be improved if resistance training with control of breathing pattern is undertaken. Overall, there is little evidence of clinically important benefit of respiratory muscle training in patients with with chronic airflow limitation. The possibility that benefit may result if resistance training is conducted in a fashion that ensures generation of adequate mouth pressures may be worthy of further study.

Breathing Exercises↗

Bovine papillomavirus E5 oncoprotein binds to the 16K component of vacuolar H(+)-ATPases.

The major transforming protein of bovine papillomavirus type 1, E5, is mainly associated with endomembranes, specifically binding to a cellular protein of relative molecular mass 16,000 (16K). At the same time as transformation, E5 causes the phosphorylation of tyrosine residues in epidermal and platelet-derived growth factor receptors. We show here that the 16K protein associated with E5 is the 16K component of vacuolar ATPases. This protein is known to be an integral membrane protein in endosomes, bovine chromaffin granules, synaptic vesicles, fungal and plant vacuoles and clathrin-coated vesicles, as well as a component of gap-junction-like membrane complexes. Because proton pumps are critical for the function of cellular compartments that process growth-factor receptors, the interaction of E5 with the 16K protein could explain the pleiomorphic features of cells transformed by E5.

Adenosine Triphosphatases↗

Phosphorylated thiosugars: synthesis, properties, and reactivity in enzymatic reactions.

A number of phosphorylated thiosugars have been prepared and tested as substrates for metabolic reactions. 6-Thioglucose-6-P is readily synthesized by reaction of 6-tosylglucose with trisodium thiophosphate at pH 10 in aqueous solution; the product has only sulfur between carbon and phosphorus. When ethyl glycerate is tosylated and treated similarly with thiophosphate, a 5:1 mixture of 3-thioglycerate-3-P and the 2-isomer is formed. 6-Thioglucose-6-P is converted by glycolytic enzymes to triose phosphates, 3-thioglycerol-3-P and 3-thioglycerate-3-P, and is oxidized by enzymes of the hexose monophosphate shunt to 5-thioribulose-5-P, which can be converted via phosphoribulokinase and ribulose-bis-P carboxylase into 3-P-glycerate and 3-thioglycerate-3-P. For most of the non-phosphoryl-transferring enzymes there are only moderate effects on Vmax and Km. Phosphoglucoisomerase, however, is very sensitive to the sulfur for oxygen change, with Vmax decreasing 60-fold and Km increasing 15-fold. Surprisingly, phosphoribulokinase has a V/K value for 5-thioribulose-5-P that is over 3 orders of magnitude less than for ribulose-5-P. 6-Thio-glucose-6-P was found to be a substrate for several enzymes that transfer the phosphoryl group. It is as good a substrate for alkaline phosphatase as glucose-6-P, and with phosphoglucomutase it is converted to 6-thioglucose-1-P with a rate that is 11% of the rate of reaction of glucose-1-P, with a Keq value of 45.6. The free energy of hydrolysis of the phosphorylated thiol is thus -7.2 kcal/mol at pH 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

The three-dimensional structure of canine parvovirus and its functional implications.

The three-dimensional atomic structure of a single-stranded DNA virus has been determined. Infectious virions of canine parvovirus contain 60 protein subunits that are predominantly VP-2. The central structural motif of VP-2 has the same topology (an eight-stranded antiparallel beta barrel) as has been found in many other icosahedral viruses but represents only about one-third of the capsid protein. There is a 22 angstrom (A) long protrusion on the threefold axes, a 15 A deep canyon circulating about each of the five cylindrical structures at the fivefold axes, and a 15 A deep depression at the twofold axes. By analogy with rhinoviruses, the canyon may be the site of receptor attachment. Residues related to the antigenic properties of the virus are found on the threefold protrusions. Some of the amino termini of VP-2 run to the exterior in full but not empty virions, which is consistent with the observation that some VP-2 polypeptides in full particles can be cleaved by trypsin. Eleven nucleotides are seen in each of 60 symmetry-related pockets on the interior surface of the capsid and together account for 13 percent of the genome.

Amino Acid Sequence↗

Low serum interleukin-2 receptor levels correlate with a good prognosis in patients with Hodgkin's lymphoma.

In order to evaluate the clinical significance of soluble interleukin-2 receptor (sIL-2R) levels in the serum of patients with Hodgkin's disease (HD), we tested the pretreatment sera of 82 patients. The HD patients had significantly higher sIL-2R levels than normal controls (4787 U/ml versus 290 U/ml; P less than 0.001). In patients presenting with B-symptoms, the median sIL-2R levels were significantly higher than in patients without B-symptoms (7978 versus 2128 U/ml; P less than 0.01). Patients in stage IVB had the highest sIL-2R levels (10,450 U/ml). Of 77 patients evaluable for response, all patients with sIL-2R levels less than 1000 U/ml achieved complete remission and no relapses occurred in this group after a median of 20 months. The fact that sIL-2R levels dropped after therapy, even in patients who suffered from progressive disease, suggests that Hodgkin and Reed-Sternberg cells are only a minor source of sIL-2R in HD. Therefore sIL-2R levels are of limited value as a marker of disease activity. However, pretreatment sIL-2R levels less than 1000 U/ml define a subgroup of adult HD patients with an excellent prognosis, and this fact might be helpful for the design of more custom-tailored therapy programs.

Adolescent↗

The acute and chronic toxicity of ten chlorinated organic compounds to the American flagfish (Jordanella floridae).

The acute toxicity (96-hr median lethal concentrations (LC50s) of ten chlorinated isomers of benzene, phenol, ethane, and ethylene to the American flagfish (Jordanella floridae) were determined in both static and flow-through systems. Chronic toxicity to embryo-larval fish was also estimated from hatching success and post-hatch survival as well as fry growth rates and survival. Maximum acceptable toxicant concentrations (MATC) were estimated where possible. In general, for both acute and chronic toxicity tests, the order of increasing relative toxicity based on the water-borne exposure concentrations was: chloroethanes, chloroethylenes, chlorobenzenes, and chlorophenols. Within groups, more highly chlorinated isomers were usually more toxic. The presence of suspended or colloidal 1,2,4,5-tetrachlorobenzene was observed in acute toxicity testing and affected toxicity estimates.

Animals↗

Synthesis of N-benzyloxycarbonyl-L-cysteinylglycine 3-dimethylaminopropylamide disulfide: a cheap and convenient new assay for trypanothione reductase.

Trypanothione disulfide [N1,N8-bis(glutathionyl)-spermidine], the physiological substrate for the chemotherapeutic target enzyme trypanothione reductase, is difficult to isolate, expensive to buy, and awkward to synthesize. Here we describe the straightforward synthesis of N,N'-bis(benzyloxycarbonyl)-L-cysteinylglycyl-3-dimethylaminopropylam ide disulfide, which is shown to be a good alternative substrate for the trypanothione reductases from Crithidia fasciculata and Trypanosoma cruzi.

Animals↗