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Biomedical subjects

E Mueller

Publications and source records attributed to E Mueller.

At least 73 records · Page 4Linked to original sources

Formylglycinamide ribonucleotide synthetase from Escherichia coli: cloning, sequencing, overproduction, isolation, and characterization.

The purL gene of Escherichia coli encoding the enzyme formylglycinamidine ribonucleotide (FGAM) synthetase which catalyzes the conversion of formylglycinamide ribonucleotide (FGAR), glutamine, and MgATP to FGAM, glutamate, ADP, and Pi has been cloned and sequenced. The mature protein, as deduced by the structural gene sequence, contains 1628 amino acids and has a calculated Mr of 141,418. Comparison of the purL control region to other pur loci control regions reveals a common region of dyad symmetry which may be the binding site for the "putative" repressor protein. Construction of an overproducing strain permitted purification of the protein to homogeneity. N-Terminal sequence analysis and comparison of glutamine binding domain sequences (Ebbole & Zalkin, 1987) confirm the amino acid sequence deduced from the gene sequence. The purified protein exhibits glutaminase activity of 0.02% the normal turnover, and NH3 can replace glutamine as a nitrogen donor with a Km = 1 M and a turnover of 3 min-1 (2% glutamine turnover). The enzyme forms an isolable (1:1) complex with glutamine: t1/2 is 22 min at 4 degrees C. This isolated complex is not chemically competent to complete turnover when FGAR and ATP are added, demonstrating that ammonia and glutamine are not covalently bound as a thiohemiaminal available to complete the chemical conversion to FGAM. hydroxylamine trapping experiments indicate that glutamine is bound covalently to the enzyme as a thiol ester. Initial velocity and dead-end inhibition kinetic studies on FGAM synthetase are most consistent with a sequential mechanism in which glutamine binds followed by rapid equilibrium binding of MgATP and then FGAR. Incubation of [18O]FGAR with enzyme, ATP, and glutamine results in quantitative transfer of the 18O to Pi.

Amino Acid Sequence↗

Changes in accommodation with age: static and dynamic.

Accommodative amplitude decreases with age, not with aging. The decrease is largely completed by age 40 years; only minor residual accommodation is present in most subjects after the mid-40s. Dynamical measurements show the accommodative response of subjects over 30 years of age to be significantly slowed (time constants of accommodation increases). Accommodation amplitude is less than 3 D by 30 years of age. Thus prepresbyopia is a sign of continual development, not of deterioration of the accommodative mechanism. Accommodation, or the change of clear vision with change in lens power, has been studied by many distinguished scientists including Descartes and Thomas Young. Helmholtz's "Theory of Accommodation" is a dual, indirect, active theory. There are both lenticular, including lens and capsule, and also extralenticular mechanisms, comprised of the zonule of Zinn or suspensory ciliary ligament and the ciliary muscle itself. The ciliary muscle does not act directly on the lens but indirectly through its action on the zonule of Zinn. Active contraction of the ciliary muscle, a unified muscle, produces accommodation; relaxation of the ciliary muscle permits relaxation of accommodation.

Accommodation, Ocular↗

MR imaging of the normal shoulder.

Magnetic resonance (MR) images of the shoulders of a healthy volunteer were obtained in axial, sagittal, and coronal orientations using a 0.5-T imaging system. Multiple high-resolution spin-echo images were generated using an off-center zoom technique and a specially designed surface coil. Several anatomic structures, including the rotator cuff, long biceps tendon, articular capsule, muscles, and bones, were visualized. The coronal and sagittal views were the most useful for demonstrating the rotator cuff. MR imaging has potential as a new non-invasive tool for the evaluation of the shoulder region.

Adult↗

Description of flow phenomena in magnetic resonance imaging.

The magnetic resonance (MR) signal from the hydrogen nuclei of blood is not only determined by the MR parameters T1, T2 and proton density, but is strongly dependent on the movement of the protons. Magnetic resonance imaging (MRI) offers therefore the possibility to visualize the distribution of moving spins, especially blood flow, noninvasively and without contrast agents; moreover, the velocity of the moving spins can be quantified. Flow phenomena in MRI are a pretentious field because the complicated hydrodynamics of the living system is coded in the MR signal; therefore, an understanding of the underlying physical principle of the MR signal is required to interpret and extract flow information from the image. However, rather simple theoretical and experimental models of fluid transport in vessels allow to explain the main features of various effects observed in images.

Blood Circulation↗

The nonlaboring transverse lie. A management dilemma.

During a one-year period, 29 patients at 37 weeks' gestation or later were referred to the breech version clinic at Los Angeles County/University of Southern California Medical Center and found to have sonographic evidence of a transverse lie. Because of the relative instability of the lie and the high probability of spontaneous conversion, the patients were not considered candidates for version and were returned to their referral agencies for subsequent prenatal care. The subsequent outcomes in these patients were reviewed. Twenty-four (83%) spontaneously converted to a longitudinal lie and presented in labor with either a vertex (15 [52%]) or breech (9 [31%]) presentation. The five (17%) remaining patients presented in labor with a persistent transverse lie. Overall, the cesarean section rate was 13 of 29, or 45%. The indications for cesarean section were breech presentation, eight (62%), and transverse lie, five (38%). Major complications included two prolapsed cords, one spontaneous uterine rupture and one neonatal death. Based on a review of our experience, it appears reasonable to consider external version in any patient with a persistent transverse lie around 39 weeks. The high rate of subsequent cesarean section and major morbidity associated with expectant management of these patients suggests that if version is unsuccessful, strong consideration should be given to elective cesarean section.

Adolescent↗

The effect of dietary manipulation on hepatic lipid accumulation in rats undergoing small intestinal bypass.

Small intestinal bypass performed for morbid obesity produces hepatic fat infiltration which persists in some patients for more than 5 years. In an attempt to define causative and preventative factors of hepatic steatosis following small intestinal bypass, a rat model was developed. In this study, nutritionally obese rats underwent sham operations or bypass of 90 per cent of their small intestine and postoperatively were fed various diets to determine the effects of dietary manipulations on hepatic lipid content. After 30 days the rats were killed and their hepatic lipid content and lipogenic enzyme activity determined. In rats that underwent intestinal bypass neither a high fat, a high carbohydrate nor a high protein diet increased hepatic lipid content over that present in sham operated animals. A low (4.5 per cent) protein diet increased total hepatic lipid and hepatic triglyceride content. The increased triglyceride levels were not associated with significant changes in lipogenic enzyme activity and were associated with decreased serum triglycerides suggesting impaired triglyceride transport from the liver secondary to decreased lipoprotein formation as a possible etiologic mechanism. A significant inverse relationship was found between hepatic triglyceride content and hepatic protein content. These results support previous reports from human studies of hypoproteinemia associated with hepatic steatosis following small intestinal bypass.

Acetyl-CoA Carboxylase↗

Observations of fetal heart rate characteristics related to external cephalic version and tocolysis.

External cephalic version performed in conjunction with tocolysis in the term breech presentation has been found to decrease the number of breech presentations at delivery and thus reduce the number of cesarean sections for breech presentation. However, information regarding the fetal heart rate (FHR) patterns associated with version is limited. In an attempt to broaden our understanding of the FHR changes that occur in association with version, the FHR tracings of 141 patients who had undergone version were analyzed. Approximately 39% of the fetuses exhibited changes in FHR characteristics during and/or after attempted version. These FHR changes were primarily manifested as bradycardias and/or decelerations. However, some of the fetuses (less than 5%) demonstrated a tachycardia or sine wave pattern. All of these FHR changes were transient and bore no apparent relationship to the subsequent outcome of the fetus. In addition to these FHR alterations, the incidence of diminished FHR variability (less than or equal to 5 bpm) was significantly higher after version than before version (p less than 0.01). The decline in FHR variability lasted 15 +/- 12 minutes. While this decline in variability appeared to be related to the success or failure of the version, the decreased variability observed after version was found to be unrelated to the tocolytic agent used and to the subsequent fetal outcome. In summary, alterations in FHR activity were frequent during the version process. All were transient and most responded to cessation of manipulation. Subsequent fetal outcome was apparently unrelated to the observed FHR alterations. Nonetheless, continuous fetal monitoring during and after the version is recommended.

Breech Presentation↗

Effect of antepartum glucocorticoid administration upon neonatal respiratory distress syndrome and perinatal infection.

A double-blind, randomized study comparing the antepartum use of betamethasone (12 mg), methylprednisolone (125 mg), and hydrocortisone (250 mg) was performed to evaluate effect on neonatal respiratory distress syndrome and perinatal infection. Of 144 mothers and 149 infants entered, 92 mothers and 97 infants were available for analysis. The betamethasone-treated group had a significantly reduced incidence of severe respiratory distress syndrome (4%) compared with the control group (26%; p = 0.038); this effect was confined to patients who received at least two doses. No similar effect was found in the methylprednisolone or hydrocortisone groups. Neonatal infection and neonatal mortality rate were not affected by glucocorticoid use. Maternal infection was significantly increased in hydrocortisone-treated patients who were delivered vaginally compared with control patients (all patients: 50% versus 9.5%, p less than 0.05; with ruptured membranes: 63% versus 15%, p = 0.04). No similar increase in maternal infection was found with betamethasone or methylprednisolone use.

Apgar Score↗

Phenylethylamine excretion in depression.

Urinary phenylethylamine (PEA) excretion was evaluated in two populations of depressed hospitalized patients. Seven of 53 patients had PEA values exceeding three times the highest value found in 16 normal controls. The patients with high PEA excretion were all females. They were not, however, otherwise clinically distinguishable from depressed patients with low PEA. In a subsample of 31 patients and 10 controls, PEA excretion was not correlated with phenylacetic acid (PAA) excretion. These results suggest that depression is not associated with a generalized PEA deficit and that PAA reductions, previously reported in a depressed patient population, may not reflect a PEA abnormality.

Adolescent↗

Long-term effects of small intestinal bypass on hepatic lipid content in congenitally obese rats.

This study compares the early (30-d) with the late (14-month) effects of small intestinal bypass on hepatic lipid accumulation in congenitally obese Zucker rats. Heterozygote, lean and homozygote, obese Zucker rats underwent sham operations and homozygote obese rats underwent bypass of 90 percent of their small intestine. Evaluation of hepatic lipid content at 30 d following the operation demonstrated increased hepatic triglyceride content in homozygote obese rats compared to heterozygote lean rats; however, the homozygote rats with small intestinal bypass did not have significantly different hepatic triglyceride content from that present in the homozygote obese sham operated rats. Fourteen months following the operations hepatic lipid content increased from 63 +/- 14 mg/g liver in homozygote, obese sham operated rats to 132 +/- 55 mg/g in homozygote, obese rats with small intestinal bypass. The increased lipid was secondary to increased hepatic triglyceride content. Histologic evaluations of liver specimens demonstrated no increased inflammation, granuloma formation or fibrosis when sham operated rat liver tissue was compared to liver tissue from rats with intestinal bypass. These data indicate that at a late stage following small intestinal bypass, the obese Zucker rat develops hepatic steatosis, as do humans, and can serve as an experimental model for evaluation of methods to decrease the triglyceride accumulation.

Animals↗

Fetal hiccups: an associated fetal heart rate pattern.

Fetal hiccups are commonly diagnosed during the antepartum period, and they have a tendency to recur. The reflex of hiccuping is similar to that of gasping, except hiccuping efforts are made against a closed airway. An episode of intrapartum hiccups was confirmed via real-time ultrasound scanning during monitoring with a direct fetal scalp electrode. A neonatal heart rate pattern during hiccuping is also included. Distinctive fetal and neonatal heart rate patterns were observed during the hiccuping episode. It is speculated that the fetal heart rate pattern seen with hiccups may resemble that of fetal gasping.

Female↗

Maternal and fetal response to alphaprodine during labor. A preliminary study.

Alphaprodine is a synthetic narcotic, structurally similar to meperidine. Respiratory depression has been reported as a not-infrequent side effect when larger doses of alphaprodine were used, particularly intravenously. In this study, the maternal respiratory rate and tissue pO2 and pCO2 were determined in patients receiving alphaprodine, 0.4 mg/kg of prepregnancy weight, for first-stage analgesia. Statistically significant falls in maternal tcpO2 and increases in tcpCO2 were observed. The baseline fetal heart rate decreased significantly 20 minutes after the injection (139 to 132 bpm). There was no increase in abnormal fetal heart rate patterns. The variability of the baseline fetal heart rate was unchanged until 25 minutes following alphaprodine administration, when a significant reduction occurred. The changes seen in the parameters monitored in this study were not associated with any clinically adverse effects on the mother or fetus.

Alphaprodine↗

Quantitation of uterine activity: clinical evaluation of a new method of data presentation.

An on-line, automated system, voltage-controlled oscillator (VCO), with digital print-out of uterine activity units (UAU) at designated intervals, has been used in clinical studies and appears reliable. A comparison was made between the VCO system and a microprocessor-controlled digital integrator system (MCDI), which displays UAUs as a bar graph every 10 minutes on the uterine activity channel of the clinical fetal monitor.

Data Display↗

Role of intracellular Ca2+ sequestration in beta-adrenergic relaxation of a smooth muscle.

Various mechanisms have been proposed for beta-adrenergically mediated relaxation of smooth muscle. All theories suggest the involvement of cyclic AMP as a second messenger: beta-agonists stimulate adenylate cyclase which converts ATP to cyclic AMP and protein kinase, activated by cyclic AMP, is then thought to catalyse a protein phosphorylation that leads to a reduction in free Ca2+, thus effecting relaxation. How this last step is accomplished is much debated, but the following possibilities are currently considered as the mechanisms responsible for cyclic AMP-induced reduction of cytoplasmic Ca2+: activation of a Ca2+-ATPase in the plasma and/or sarcoplasmic reticulum membranes which lowers cytoplasmic [Ca2+] in a direct manner or stimulation of (Na+-K+)ATPase in the cell membrane which may indirectly effect Ca2+ extrusion. Among the hypotheses suggested, those of Ca2+ sequestration by the sarcoplasmic reticulum and of Ca2+ extrusion across the cell membrane are consistent with each other if it is assumed that both processes are effected by a cyclic AMP-sensitive Ca2+-ATPase. However, quite a different mechanism is implied by involving the Na+-K+ pump and Na+-Ca2+ exchange carrier. In this report, we present evidence that suggests intracellular Ca2+ sequestration is the mechanism involved.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

Guinea pig histocompatibility antigens. I. Serological and genetic characterization of GPLA antigens.

Lymphocytotoxic alloantisera were obtained by cross immunization among outbred guinea pigs from a closed colony. Groups of antisera recognizing the same specificities were established by panel analysis, cross immunization among appropriate phenotypes, and absorption studies. Three antigens designated B1, B2, and B3 (perviously B, C, and D) were detected in our outbred colony and also found to be present in a wide variety of guinea pig strains. These antigens were shown by population and breeding studies to be allelic gene products of a first guinea pig locus (GPLA) (designated locus B). Four new guinea pig families homozygous for their B locus antigens are now in the seventh generation of inbreeding. NIH guinea pig strains 2 and 13, which share the B1 antigen, differ by a number of other antigens which have been designated I1, I2, I3 (previously A), and I4. These antigens differ from the B locus gene products in their molecular size and tissue distribution and it is, therefore, postulated that they represent an equivalent of the Ia antigens in mice (designated I region). Cross immunizations among inbred or outbred guinea pigs identical for currently known B locus and I region antigens yield further antisera, possibly recognizing additional Ia specificities and/or a second GPLA locus designated locus S. Whereas the conventional eosin lymphocytoxicity technique easily permits the detection of the widely distributed antigens (such as the B locus antigens), a more sensitive 51Cr release technique is required to demonstrate the "Ia equivalent" antigens of the guinea pig, possibly due to their restricted presence on the membrane of only some lymphoid cell populations.

Absorption↗