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Biomedical subjects

L Green

Publications and source records attributed to L Green.

At least 253 records · Page 14Linked to original sources

Transposable element IS50 improves growth rate of E. coli cells without transposition.

Insertion sequence IS50R, which encodes the transposase and an inhibitor of transposition of the kanamycin-resistance transposon Tn5, increases the growth rate of E. coli K12 cells relative to that of their otherwise isogenic counterparts during competition in continuous culture. Most clones isolated from chemostats in which selection had occurred retain their original number of copies of IS50R at their original genomic locations, implying that the increased growth rate is not mediated by transposition. The selective advantage due to a single IS50R element averages about 5% per hour. When the number of copies of IS50R is small, the growth-rate advantage is approximately proportional to the number of copies of IS50R. These results imply that IS50R has effects on cells that are independent of both position and transposition and may be important in the initial selection leading to the appearance of such elements in bacterial populations.

Chromosomes, Bacterial↗

Degradation of proline peptides in peptidase-deficient strains of Salmonella typhimurium.

A mutant strain of Salmonella typhimurium that lacks two proline-specific peptidases (peptidases P and Q) could not complete the degradation of proline peptides formed as intermediates in starvation-induced protein breakdown. The wild-type strain produced free proline as the product of degradation of proline-labeled proteins. The pepP pepQ mutant, however, produced a mixture of small proline peptides. In the absence of peptidase Q only, peptidase P could complete the degradation of most of the proline peptide intermediates formed. In the absence of peptidase P only, about 50% of the proline-labeled, acid-soluble products were proline peptides. These results are consistent with in vitro specificity data indicating that peptidase Q hydrolyzes X-Pro dipeptides only, whereas peptidase P attacks both X-Pro dipeptides and longer peptides with X-Pro at their N-termini. A mutant strain lacking four broad-specificity peptidases (peptidases N, A, B, and D), but containing peptidases P and Q, also produced proline peptides as products of protein breakdown. This observation suggests that broad-specificity peptidases are required to generate the X-Pro substrates of peptidases P and Q. A strain lacking six peptidases (N, A, B, D, P, and Q) was constructed and produced less free proline from protein breakdown than either the pepP pepQ strain or the pepN pepA pepB pepD strain. These observations suggest that the degradation of peptide intermediates involves the sequential removal of N-terminal amino acids and requires both broad-specificity aminopeptidases (peptidases N, A, and B) and the X-Pro-specific aminopeptidase, peptidase P.

Aminopeptidases↗

Oligopeptidase-deficient mutants of Salmonella typhimurium.

An oligopeptidase that hydrolyzes N-acetyl-L-alanyl-L-alanyl-L-alanyl-L-alanine (AcAla4) has been identified in extracts of Salmonella typhimurium. Mutants lacking this activity have been isolated in dcp mutant strains by screening extracts of mutagenized clones for failure to hydrolyze AcAla4 or by screening colonies for inability to use AcAla4 as a nitrogen source. Double mutants (dcp optA) lacking both oligopeptidase A and dipeptidyl carboxypeptidase cannot use AcAla4 as a nitrogen source, although dcp+ optA and dcp optA+ strains grow on this peptide. The mutations responsible for the loss of activity map at a locus (optA) between asd (75 map units) and xylA (78 map units). Oligopeptidase A hydrolyzes certain N-blocked tetrapeptides, unblocked pentapeptides, and unblocked hexapeptides, usually but not always liberating the C-terminal tripeptide. These two activities seem to be responsible for the production of a large fraction of the dipeptides that accumulate during protein breakdown in a pepN pepA pepB pepD strain.

Alanine↗

Matching and maximizing with concurrent ratio-interval schedules.

Animals exposed to standard concurrent variable-ratio variable-interval schedules could maximize overall reinforcement rate if, in responding, they showed a strong response bias toward the variable-ratio schedule. Tests with the standard schedules have failed to find such a bias and have been widely cited as evidence against maximization as an explanation of animal choice behavior. However, those experiments were confounded in that the value of leisure (behavior other than the instrumental response) partially offsets the value of reinforcement. The present experiment provides another such test using a concurrent procedure in which the confounding effects of leisure were mostly eliminated while the critical aspects of the concurrent variable-ratio variable-interval contingency were maintained: Responding in one component advanced only its ratio schedule while responding in the other component advanced both ratio schedules. The bias toward the latter component predicted by maximization theory was found.

Animals↗

Market-based planning for a successful PPO.

The preferred provider organization (PPO) is rapidly evolving as an innovative, cost-reducing alternative to traditional provider modalities. Literature to date, however, has devoted little attention to opportunities and risks associated with PPO development. The authors address PPO development strategy, recommending a market-based planning approach which matches hospital resources with market demand and other environmental forces.

Feasibility Studies↗

Colonic inhibition of pancreatic and biliary secretion.

The purpose of this study was to determine whether or not nutrients in the colon influence pancreatic and biliary secretion in humans. In six healthy subjects, similar caloric loads (117 cals) of oleic acid, essential amino acids, and glucose in isomolar (280 mosmol/L), similar pH (7.4) solutions were infused into the right colon at 10 ml/min through a colonic tube passed by mouth. A background of submaximal pancreatic and biliary secretion was maintained by continuous intravenous infusion of the octapeptide of cholecystokinin. Biliary and pancreatic secretions were quantitated using the gastroduodenal intubation perfusion technique. Among the three nutrients tested, only oleic acid in the colon decreased pancreatic enzymes and bicarbonate outputs. The mean trypsin output decreased from 26.3 +/- 2.6 kU/h to 12.3 +/- 1.9 kU/h (46% +/- 6% of control), while the lipase output decreased from 62 +/- 6.6 kU/h to 36 +/- 5.6 kU/h (58% +/- 6% of control). Similarly, the output of bicarbonate in the duodenal aspirate decreased from 31 +/- 7.2 mEq/h to 16.3 +/- 3.1 mEq/h (61% +/- 5% of control). Intracolonic perfusion of essential amino acids or glucose had no effect on pancreatic enzymes and bicarbonate secretion. In contrast, all three nutrients in the colon inhibited biliary secretion. The mean output of bilirubin decreased from 56 +/- 6 mg/h to 19 +/- 2 mg/h (35% +/- 5% of control) during intracolonic perfusion of oleic acid. Essential amino acids lowered the output of bilirubin from 54 +/- 12 mg/h to 31 +/- 8.6 mg/h (65% +/- 6% of control), whereas glucose lowered it from 53 +/- 12 mg/h to 22 +/- 4 mg/h (45% +/- 5% of control). This differing response of pancreatic and biliary output to intracolonic perfusion of nutrients suggests differential sensitivity of the pancreas and gallbladder to these inhibitory influences. In malabsorption states, unabsorbed nutrients in the colon may inhibit pancreatic and biliary secretion, further contributing to the loss of nutrients from the gastrointestinal tract.

Adolescent↗

Salmonella typhimurium mutations affecting utilization of L-leucine beta-naphthylamide.

L-leucine-beta-naphthylamide (LNA) will support growth of a leucine auxotroph of Salmonella typhimurium. Utilization of this compound depends on the presence in the cells of active peptidase N. Selection for improved growth on a suboptimal concentration of LNA yields mutants some of which contain elevated levels of peptidase N. The properties of these strains indicate that they carry tandem genetic duplication of the pepN locus: they show rec-dependent genetic instability; they contain an approximately doubled level of the pepN gene product; neighboring chromosomal loci are also duplicated; and, the mutants occur with a greatly diminished frequency in rec- strains. When selection for improved growth on LNA is applied to a rec- strain, the mutants obtained do not contain duplications. These strains appear to contain lesions in the pepN gene that lead to the production of a peptidase N with altered substrate specificity.

Aminopeptidases↗

Acquisition and extended retention of a conditioned taste aversion in preweanling rats.

The time course of memory decay for infant rats may shed light on the processes responsible for infantile amnesia. A taste aversion conditioning procedure appropriate for both neonatal and adult rats was employed in four experiments to investigate the ontogeny of extended retention. In Experiment 1, rats trained at 1, 10, 20, or 60 days of age were tested for retention of the taste aversion 25 days later. At testing, only those rats conditioned when 20 or 60 days old demonstrated significant taste aversions. Experiments 2 and 3 established that rats 14-15 days old and older were able to retain significant taste aversions following a 25-day retention interval. Younger rats did, however, acquire and retain the aversion for several days and showed a gradual retention loss over progressively longer retention intervals (Experiment 4). These findings suggest that preweanling rats demonstrate initial consolidation, storage, and retrieval of conditioned taste aversions. It is only after this initial period that retention deficits become evident.

Aging↗

Hemodialysis clearance of theophylline.

The serum hemodialysis clearance of theophylline was determined in 4 patients compared to systemic serum clearance off dialysis in 3 patients. The serum extraction ratio values obtained were compared to those of urea. Hemodialysis clearance of theophylline averaged 84.3 +/- 11.6 ml/min (mean +/- SD), and extraction ratios obtained were found to be a fairly consistent fraction of the urea extraction ratio (0.72 +/- 0.08). Hemodialysis clearance increased total body clearance (ClTB) off dialysis by 130%, 387%, and 176% in the patients who had their theophylline serum clearance estimated off dialysis. Difference in reported hemodialysis clearance are probably related to the type of dialyser used. Studies utilizing hollow fiber systems (the present study) consistently yielded higher theophylline dialysis clearance values than those using coil systems (84.3% to 88.1 ml/min versus 32 to 39.4 ml/min). Patients receiving theophylline on hemodialysis should be closely monitored for bronchospasm during and after the hemodialysis procedure. Measurement of serum concentrations should be employed to facilitate dosage increases during hemodialysis.

Aged↗

A note on the "paradoxical" effect of stimulants on hyperactivity with reference to the rate-dependency effect of drugs.

The administration of stimulant drugs to hyperactive children often leads to a decrease in their excessive motor activity. This "paradoxical" effect is discussed in terms of the rate-dependency hypothesis which states that the effect of a given drug is determined by the baseline rate of behavior emitted by the subject. Amphetamines decrease response output under schedules maintaining high response rates, but increase response output under schedules maintaining low response rates. In hyperactive children, when baseline motor activity is high, the stimulant drug should, therefore, produce a reduction in such behavior. We also suggest that greater emphasis be placed on reporting individual data and that more detailed specification be made of the target responses.

Amphetamines↗

Degradation of abnormal proteins in peptidase-deficient mutants of Salmonella typhimurium.

The degradation of abnormal proteins produced as a result of incorporation of the arginine analog L-canavanine or generated by exposure to puromycin was studied in wild-type and multiply peptidase-deficient strains of Salmonella typhimurium. Both types of abnormal protein were rapidly degraded during growth of Pep+ strains of this organism. Peptidase--deficient mutants (lacking peptidases N, A, B, and D) could also degrade these abnormal proteins, although the rate of production of trichloroacetic acid-soluble degradation products was slower in the mutant strain than in a strain carrying a normal complement of peptidases. Analysis of these trichloroacetic acid-soluble degradation products of ion-exchange chromatography showed that free amino acid was the major breakdown product produced by the wild-type strain. The acid-soluble degradation product produced by the mutant strain, however, was a complex mixture that contained a variety of small peptides as well as free amino acids. These results indicate that the same group of peptidases shown previously to function in the degradation of exogenously supplied peptides and in protein turnover during carbon starvation also lie on the pathway by which abnormal proteins are degraded.

Bacterial Proteins↗

Arthritis in psoriasis.

A group of 61 unselected patients with psoriasis attending a dermatology clinic were studied to determine the prevalence of psoriatic arthritis. On defined criteria arthritis was present in 41.6%. Peripheral arthritis was present in 15.5%, and sacroiliitis in 43%. A strong association of distal interphalangeal arthritis with psoriasis and nail dystrophy was confirmed. Tissue typing showed a strong association of B23, 17, in Caucasoid psoriatics, while the haplotype A1/B8 was increased in mixed Caucasoid--Negroid psoriatics.

Adolescent↗

Prevention of nifedipine of abnormal coronary vasoconstriction in patients with coronary artery disease.

The hemodynamic and myocardial metabolic responses to the cold pressor test were studied in 15 patients with coronary artery disease and stable exertional angina. Every patient had abnormal coronary vasoconstriction during a control cold pressor test, even though 14 were receiving propranolol and 12 were receiving long acting nitrates. Mean coronary vascular resistance for the group increased 18 +/- 6% (SD) (from 0.80 +/- 0.12 to 0.94 +/- 0.20 mm Hg/ml/min, p less than 0.05); coronary sinus blood was unchanged, and the arterial-coronary sinus oxygen difference widened significantly (from 11.5 +/- 1.2 to 12.3 +/- 1.2 ml/100 ml, p less than 0.05). Four patients developed angina, accompanied in each instance by a negative arterial-coronary sinus lactate difference. After the administration of nifedipine (10 mg buccally) in 10 patients, the coronary vascular responses to a repeat cold pressor test were normal in each patient. Mean coronary sinus blood flow increased 27 +/- 12% (from 122 +/- 32 to 153 +/- 35 ml/min, p less than 0.05), coronary vascular resistance decreased 10 +/- 6% (from 0.85 +/- 0.16 to 0.76 +/- 0.16 mm Hg/ml/min, p less than 0.05), and the arterial-coronary sinus oxygen difference was unchanged. No patient experienced angina. The hemodynamic and coronary vascular responses to a repeat cold pressor test in five patients given placebo were unaltered from control responses. The protective effects of nifedipine were unaccompanied by any change in mean arterial pressure, left ventricular filling pressure or myocardial oxygen consumption either at rest or in response to the cold pressor test. Nifedipine appears to exert a selective antivasoconstrictor effect on the coronary vasculature.

Adult↗