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G Eng

Publications and source records attributed to G Eng.

15 recordsLinked to original sources

Synthesis and biophysical analysis of transmembrane domains of a Saccharomyces cerevisiae G protein-coupled receptor.

The Ste2p receptor for alpha-factor, a tridecapeptide mating pheromone of the yeast Saccharomyces cerevisiae, belongs to the G protein-coupled family of receptors. In this paper we report on the synthesis of peptides corresponding to five of the seven transmembrane domains (M1-M5) and two homologues of the sixth transmembrane domain corresponding to the wild-type sequence and a mutant sequence found in a constitutively active receptor. The secondary structures of all new transmembrane peptides and previously synthesized peptides corresponding to domains 6 and 7 were assessed using a detailed CD analysis in trifluoroethanol, trifluoroethanol-water mixtures, sodium dodecyl sulfate micelles, and dimyristoyl phosphatidyl choline bilayers. Tryptophan fluorescence quenching experiments were used to assess the penetration of the membrane peptides into lipid bilayers. All peptides were predominantly (40-80%) helical in trifluoroethanol and most trifluoroethanol-water mixtures. In contrast, two of the peptides M3-35 (KKKNIIQVLLVASIETSLVFQIKVIFTGDNFKKKG) and M6-31 (KQFDSFHILLINleSAQSLLVPSIIFILAYSLK) formed stable beta-sheet structures in both sodium dodecyl sulfate micelles and DMPC bilayers. Polyacrylamide gel electrophoresis showed that these two peptides formed high molecular aggregates in the presence of SDS whereas all other peptides moved as monomeric species. The peptide (KKKFDSFHILLIMSAQSLLVLSIIFILAYSLKKKS) corresponding to the sequence in the constitutive mutant was predominantly helical under a variety of conditions, whereas the homologous wild-type sequence (KKKFDSFHILLIMSAQSLLVPSIIFILAYSLKKKS) retained a tendency to form beta-structures. These results demonstrate a connection between a conformational shift in secondary structure, as detected by biophysical techniques, and receptor function. The aggregation of particular transmembrane domains may also reflect a tendency for intermolecular interactions that occur in the membrane environment facilitating formation of receptor dimers or multimers.

Amino Acid Sequence↗

Chemical specificity of the PDR5 multidrug resistance gene product of Saccharomyces cerevisiae based on studies with tri-n-alkyltin chlorides.

To understand the chemical basis of action for the PDR5-encoded multidrug resistance transporter of Saccharomyces cerevisiae, we compared the relative hypersensitivities of the wild-type (RW2802) and null mutant strains toward a series of tri-n-alkyltin compounds. These compounds differ from each other in a systematic fashion-either by hydrocarbon chain length or by anion composition. Using zone-of-inhibition and fixed-concentration assays, we found that the ethyl, propyl, and butyl compounds are strong PDR5 substrates, whereas the methyl and pentyl compounds are weak. We conclude that hydrophobicity and anion makeup are relatively unimportant factors in determining whether a tri-n-alkyltin compound is a good PDR5 substrate but that the dissociation of the compound and the molecular size are significant.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Disturbances of brain maturation and neurodevelopment during chronic renal failure in infancy.

Fifteen infants with moderate to severe congenital renal disease were prospectively studied by serial renal, neurodevelopmental, neurophysiologic, and anthropometric assessments. The observation period ranged from 3 to 25 months (mean = 10.9). Eight patients maintained a Mental Development Index (MDI) above the 16th percentile (greater than -1 SD) and comprised group 1. Of the remaining seven patients (group 2), three had an MDI less than 16th percentile when first studied and four had serial decreases of the MDI to less than 16th percentile. Although motor development was more delayed in group 2 at study entry, there were no significant changes of motor performance levels for either group during the study period. Group 2 patients had smaller length (p less than 0.05) and head circumference (p less than 0.05) standard deviation scores in comparison with group 1, and they had higher serum creatinine values (mean = 3.8 vs 1.3 mg/dl, respectively; p less than 0.01). By spectral electroencephalography, the expected progressive increase of the frequency of cerebral cortical background activity with age was demonstrated in group 1 but was not seen in group 2 (multivariate analysis of variance p less than 0.03). This increase of faster-frequency activity was primarily manifested in the left cerebral hemisphere of group 1 patients (p less than 0.01), a finding that was also absent in group 2. The frequent occurrence of neurodevelopmental abnormalities in infants with renal failure is possibly a consequence of impaired dominant hemispheric maturation in the first several years of life, which is clinically manifested as deterioration of cognitive function.

Cephalometry↗

The prune belly syndrome: a comprehensive approach to management.

Our approach to management of the prune belly syndrome entails a program of comprehensive early reconstruction, including abdominoplasty, bilateral orchiopexy, reduction cystoplasty, and selective ureteral tailoring and reimplantation. Of 20 patients with the prune belly syndrome treated at our institution during the last 18 years 15 underwent comprehensive reconstruction. Abdominoplasty was performed in 16 patients. Results were evaluated as to cosmetic appearance, functional performance, and preoperative and postoperative electromyography. Immediate good results were obtained in 9 patients. Of 16 patients 6 required more than 1 abdominal wall tailoring and 3 had minor complications that did not compromise the ultimate result. Transabdominal orchiopexy was performed on 32 testes; 28 (88 per cent) are in the scrotum and growing. Of the 4 failures 3 occurred in patients greater than 2 years old at repair. Selective urinary tract reconstruction has been performed; 13 patients underwent tapering and reimplantation of 1 or both ureters. Reduction cystoplasty was done in all 15 patients. Functional assessment of the upper urinary tract by improved radiological techniques and the necessity for long-term antibiotic prophylaxis have led to a more conservative approach in 5 recent patients. Renal function as measured by serum creatinine and/or glomerular filtration rate has remained stable in 12 of 15 patients (92 per cent) undergoing comprehensive reconstruction. Aggressive surgical management of patients with the prune belly syndrome provides improved abdominal wall function and appearance, and offers excellent testicular salvage. Surgical reconstruction of deformed ureters should be selective and decided on longitudinal studies of renal function.

Abdomen↗

Hemophiliac knee: rehabilitation techniques.

Hemophilia is an inherited bleeding disorder which produces its greatest morbidity in the musculoskeletal system. This article reviews current rehabilitation techniques for the hemophiliac knee--including restrictions of physical activity, external support, and corrective orthotic devices--reports our experience using aggressive strengthening techniques in 2 children, and compares the effectiveness of the 2 methods. It is the impression of the authors that strengthening, rather than immobilization, can bring about increased range of motion, increased strength, and decreased bleeding frequency.

Adolescent↗

Abdominal wall reconstruction in the prune belly syndrome.

In our institution, 12 patients have been encountered with prune belly syndrome. Eight children have undergone evaluation of their abdominal musculature by electromyography. Results of their studies show that major functioning or recoverable muscle exists in the lateral and upper sector of the abdomen, but that little or no muscle exists in the lower central abdomen. Based in part on these findings, an operation has been devised which spares all potentially functioning musculature and corresponding motor nerves, and disposes of nonfunctioning and nonrecoverable muscle. In terms of cosmetic appearance and gross motor testing, these growing boys show significant improvement.

Abdominal Muscles↗

Surgical correction and rehabilitation for children with "Prune-belly" syndrome.

Until the recent past, patients born with congenital absence of the abdominal musculature, and associated deformity of the urinary collecting system, have often had an unhappy life and an early death. Twelve years ago, a treatment protocol was devised in our institution which included the following major steps: 1) bilateral tubeless pyelostomy immediately after birth; 2) serial evaluation of renal status during the first year of life; 3) laparotomy at one year of age with orchiopexy, reconstruction of the urinary collecting system and reconstruction of the abdominal wall; 4) serial electromyographic evaluation of the growth and development of the lateral abdominal musculature; 5) serial studies of renal function; 6) secondary revision of the abdominal wall and of the urinary drainage system as needed. Nine patients so treated have been followed from the third through the twelfth years of life. All are alive and growing well. Four patients had chronic urinary infection treated with long-term antibiotics; three of these have required a second surgical correction of some aspect of the urinary drainage system. Three patients have required additional surgery on the abdominal wall, but have recaptured enough function so that corsets and other devices have not been necessary. Electromyographic studies show good growth and development of some aspects of the lateral abdominal musculature which has been used in the repair. The outcome in these patients is highly encouraging for this constellation of anomalies. The cause remains controversial.

Abdominal Muscles↗

Computerized tomography in cerebral-palsied children.

Of a total of 160 patients with cerebral palsy, 80 were studied by computerized tomography. In the congenital group, abnormal studies were found in two of the 12 patients with diplegia, 16 of 18 with hemiplegia, 14 of the 18 with quadriplegia and five of the seven with atonic diplegia. 18 of 21 patients with acquired disease had abnormal CT scans. Computerized tomography is a useful tool for demonstrating the anatomical lesion responsible for cerebral-palsied patients' clinical findings. It is also useful in making a prognosis of functional outcome, and in defining lesions which are correctable by neurosurgery.

Adolescent↗

Long-term hemodialysis and nerve conduction in children.

Initial observations in adults revealed that peripheral neuropathy, as documented by reduced conduction velocity is common in chronic renal failure. Critical analysis of this problem in children on long-term dialysis is scarce, consisting of a simgle report which demonstrated that the motor nerve conduction velocities were decreased early and frequently with more severe depression in peroneal nerve velocities. This is in distinct contrast to data from adults, in whom uniform rates of deterioration are encountered. In addition, a direct correlation of the degree of nerve conduction defect with the severity of the renal failure is found in adult patients. The present study showed a relative lack of nerve conduction defects in 11 children on long-term hemodialysis. With rare exceptions, the conduction velocities were normal. To date, no clinical symptoms of neuropathy were evident in our patients. It would seem that, with the short-dialysis schedule of 12--14 h/wk over a period of up to 5 yr, there is no progressive neuropathy as quantitated by nerve conduction measurements.

Adolescent↗