Input-output analysis of nonlinear dissipative quantum systems in the Fokker-Planck approximation.
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Journal Article↗
Biomedical subjects
T Langer
Publications and source records attributed to T Langer.
Chaperonin-mediated protein folding: GroES binds to one end of the GroEL cylinder, which accommodates the protein substrate within its central cavity.
The mechanism of GroEL (chaperonin)-mediated protein folding is only partially understood. We have analysed structural and functional properties of the interaction between GroEL and the co-chaperonin GroES. The stoichiometry of the GroEL 14mer and the GroES 7mer in the functional holo-chaperonin is 1:1. GroES protects half of the GroEL subunits from proteolytic truncation of the approximately 50 C-terminal residues. Removal of this region results in an inhibition of the GroEL ATPase, mimicking the effect of GroES on full-length GroEL. Image analysis of electron micrographs revealed that GroES binding triggers conspicuous conformational changes both in the GroES adjacent end and at the opposite end of the GroEL cylinder. This apparently prohibits the association of a second GroES oligomer. Addition of denatured polypeptide leads to the appearance of irregularly shaped, stain-excluding masses within the GroEL double-ring, which are larger with bound alcohol oxidase (75 kDa) than with rhodanese (35 kDa). We conclude that the functional complex of GroEL and GroES is characterized by asymmetrical binding of GroES to one end of the GroEL cylinder and suggest that binding of the substrate protein occurs within the central cavity of GroEL.
Bacterial Proteins↗
[Gait pattern of patients with hip arthritis].
Automatic recording of the kinematic and kinetic gait pattern has so far not been commonly used in the diagnosis of problems affecting the human loco motor apparatus. In recent decades gait analysis has increasingly been applied in the development of endoprostheses and sports shoes and in rehabilitation, especially of patients with neurological diseases. When a gait laboratory is set up, this demands interdisciplinary cooperation, biomechanical knowledge in physicians and (physio-)therapists, and elaboration of treatment plans allowing direct therapeutic exploitation of the gait data. There are determinant factors in gait pattern, which does not vary qualitatively in the sagittal plane (flexion/extension) with sex and age until the age of 70 years. Quantitatively there is a great deal of individual variation, and the diagnosis of a pathologic function in a particular patient can be difficult. A normal reference population was used to determine the gait pattern characteristic for 32 patients with osteoarthritis of the hip on one or on both sides, and the possible significance of the results for physical and surgical therapy is discussed. The main characteristic of this gait pattern ist the limitation of hip extension before toe-off in the late stance phase. One-third of the patients answer compensate with this increased hip flexion at heel strike, which in turn leads to an increased load on the (more severely) affected side. In consequence, the increased load might lead to progression of the osteoarthritis. In the development of endoprostheses it should be borne in mind that the design may influence the gait pattern, producing overloading of the extremity and perhaps reducing the life of the prosthesis.
Adult↗
Chaperonin-mediated protein folding at the surface of groEL through a 'molten globule'-like intermediate.
Folding of two monomeric enzymes mediated by groE has been reconstituted in vitro. The groEL protein stabilizes the polypeptides in a conformation resembling the 'molten globule' state. Mg-ATP and groES then promote the acquisition of ordered tertiary structure at the surface of groEL. Folding requires the hydrolysis of about 100 ATP molecules per protein monomer. This active process of surface-mediated chain folding might represent a general mechanism for the formation of protein structure in vivo.
Adenosine Triphosphate↗
Heat shock proteins hsp60 and hsp70: their roles in folding, assembly and membrane translocation of proteins.
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Animals↗
Lactate dehydrogenase from the extreme halophilic archaebacterium Halobacterium marismortui.
D-Lactate dehydrogenase from the extreme halophilic archaebacterium Halobacterium marismortui has been partially purified by ammonium-sulfate fractionation, hydrophobic and ion exchange chromatography. Catalytic activity of the enzyme requires salt concentrations beyond 1M NaCl: optimum conditions are 4M NaCl or KCl, pH 6-8, 50 degrees C. Michaelis constants for NADH and pyruvate under optimum conditions of enzymatic activity are 0.070 and 4.5mM, respectively. As for other bacterial D-specific lactate dehydrogenases, fructose 1,6-bisphosphate and divalent cations (Mg2+, Mn2+) do not affect the catalytic activity of the enzyme. As shown by gel-filtration and ultracentrifugal analysis, the enzyme under the conditions of the enzyme assay is a dimer with a subunit molecular mass close to 36 kDa. At low salt concentrations (less than 1M), as well as high concentrations of chaotropic solvent components and low pH, the enzyme undergoes reversible deactivation, dissociation and denaturation. The temperature dependence of the enzymatic activity shows non-linear Arrhenius behavior with activation energies of the order of 90 and 25 kJ/mol at temperatures below and beyond ca. 30 degrees C. In the presence of high salt, the enzyme exhibits exceptional thermal stability; denaturation only occurs at temperatures beyond 55 degrees C. The half-time of deactivation at 70 and 75 degrees C is 300 and 15 min, respectively. Maximum stability is observed at pH 7.5-9.0.
Archaea↗
[Comparative urine protein analysis using SDS electrophoresis and isoelectric focusing].
Urinary specimens of 156 patients were examined simultaneously by SDS electrophoresis and isoelectric focusing (IEF). Simultaneous separated protein test mixtures may help to a rapid orientation on the isoelectric points and molecular weights of the urinary proteins. The SDS electrophoresis as well as the IEF make possible a safe proteinuria typing, whereby both methods have specific advantages.
Adolescent↗
[Gallbladder agenesis: a diagnostic problem?].
A rare case of an agenesis of the gallbladder in combination with cardiac malformation (anomalous pulmonary venous return with associated atrial septal defect) is reported. Despite modern diagnostic methods this agenesis which is often combined with a variety of malformations is first realized during operation or postmortem. Combinations of atypical clinical signs and sonografical or radiological absence of the gallbladder ("vésicule exclue") should point at agenesia of the gallbladder and to look for further malformations.
Gallbladder↗
The reliability of auditory thresholds in the 8- to 20-kHz range using a prototype audiometer.
This study was designed to evaluate both intra- and intertester reliability of auditory thresholds in the 8- to 20-kHz range using a recently developed high-frequency audiometer [Stevens et al., J. Acoust. Soc. Am. 81, 470-484 (1987)]. With this device, signals from a high-frequency transducer are introduced into the ear canal via a plastic tube. A calibration function is calculated for each ear and used to estimate the sound-pressure level (SPL) at the tympanic membrane. Twenty normal-hearing listeners were tested four times, twice by each of two examiners. In the higher frequencies, accurate calibration functions could not be obtained for many subjects; in these cases, values extrapolated from lower frequencies were used to estimate SPL. Findings reveal that the standard error of measurement for both intra- and intertester measures increases as a function of frequency. Intertester variability was only slightly higher than intratester variability. In most cases, variability of threshold estimates in dB SPL was higher than that observed for the uncorrected attenuator settings. Exclusion of extrapolated values improved reliability substantially.
Adult↗
Kinetics of chylomicron remnant clearance in normal and in hyperlipoproteinemic subjects.
The kinetics of chylomicron metabolism have been studied by measuring retinyl palmitate in chylomicrons and their remnants for 10-12 hr following oral administration of vitamin A and Lipomul in three groups of adult male subjects: A) normal plasma triglyceride levels (n = 7); B) endogenous hypertriglyceridemia (n = 12); C) apolipoprotein E (apoE) phenotype E2/2, with Type 3 hyperlipoproteinemia (n = 4) or normal plasma lipids (n = 1). A multicompartmental model was developed using SAAM 27 to characterize the appearance, intravascular metabolism, and clearance from the plasma of retinyl palmitate-labeled dietary lipoproteins. The half-times for retinyl palmitate clearance from the chylomicron remnant fraction (T1/2 REMNANT) were 14.1 +/- 9.7 min in Group A; they were prolonged in Group B (50.7 +/- 20.8 min) and were extremely prolonged for Type 3 subjects in Group C (611.9 +/- 419.9 min). One subject with the apoE 2/2 phenotype and normal plasma triglycerides had a T1/2 REMNANT of 66.8 min. T1/2 REMNANT was highly correlated with fasting plasma triglycerides in Group A and B (r = 0.77, slope = 0.15), and in Group C (r = 0.97, slope = 0.85). These results support the interpretation that delayed chylomicron remnant clearance in subjects with endogenous hypertriglyceridemia may be largely secondary to overproduction of VLDL particles, whose remnants compete with chylomicron remnants for removal by the liver via apoE receptor-mediated endocytosis. The subjects with apoE 2/2 have an additional defect in the removal of chylomicron remnants presumably due to the structural abnormality in their apoE.
Adult↗
Afferents to the abducens nucleus in the monkey and cat.
The abducens nucleus is a central coordinating element in the generation of conjugate horizontal eye movements. As such, it should receive and combine information relevant to visual fixation, saccadic eye movements, and smooth eye movements evoked by vestibular and visual stimuli. To reveal possible sources of these signals, we retrogradely labeled the afferents to the abducens nucleus by electrophoretically injecting horseradish peroxidase into an abducens nucleus in four monkeys and two cats. The histologic material was processed by the tetramethyl benzidine (TMB) method of Mesulam. In both species the largest source of afferents to the abducens nucleus was bilateral projections from the ventrolateral vestibular nucleus and the rostral pole of the medial vestibular nucleus. Scattered neurons were also labeled in the middle and caudal levels of the medial vestibular nucleus. Large numbers of neurons were labeled in the ventral margin of the nucleus prepositus hypoglossi in the cat and in the common margin of the nucleus prepositus and the medial vestibular nucleus in the monkey, a region we call the marginal zone. Substantial numbers of retrogradely labeled neurons were found in the dorsomedial pontine reticular formation both caudal and rostral to the abducens nuclei. In the monkey, large numbers of labeled neurons were present in the contralateral medial rectus subdivision of the oculomotor complex, while smaller numbers occurred in the ipsilateral medial rectus subdivision and elsewhere in the oculomotor complex. In the cat, large numbers of retrogradely labeled cells were present in a small periaqueductal gray nucleus immediately dorsal to the caudal pole of the oculomotor complex, and a few labeled neurons were also dispersed through the caudal part of the oculomotor complex. Occasional labeled neurons were present in the contralateral superior colliculus in both species. The size and distribution of the labeled neurons within the intermediate gray differed dramatically in the two species. In the cat, the retrogradely labeled neurons were very large and occurred predominantly in the central region of the colliculus, while in the monkey, they were small to intermediate in size and were distributed more uniformly within the middle gray. Among the afferent populations present in the monkey, but not in the cat, was a group of scattered neurons in the ipsilateral rostral interstitial nucleus of the medial longitudinal fasciculus and a denser, bilateral population in the interstitial nucleus of Cajal.(ABSTRACT TRUNCATED AT 400 WORDS)
Abducens Nerve↗
Genetic variation of human mononuclear leukocyte lysosomal acid lipase activity. Relationship to atherosclerosis.
Lysosomal acid lipase activity was measured in mononuclear leukocytes of patients selected on the basis of premature cardiovascular disease, with or without hyperlipidemia. Enzyme activity was significantly lower in the patient population (4.8 +/- 1.3 nmol/min/mg protein, n = 190 males) than in an age-matched control population (5.4 +/- 1.3 nmol/min/mg protein, n = 124 males). There was no effect of hypercholesterolemia or hypertriglyceridemia on the enzyme activity. In the group of patients with normal plasma lipids (n = 77), 18% had mononuclear leukocyte acid lipase activity which fell below the control population 5th percentile, and in the range of enzyme activity observed in cells from obligate heterozygotes for inherited acid lipase deficiency (Wolman disease and cholesteryl ester storage disease). Studies of acid lipase activity in families of our patients provided evidence that an autosomal mutation is associated with (or responsible for) this reduced enzymatic activity and may represent an independent risk factor for the premature development of atherosclerosis.
Adult↗
Afferents to the flocculus of the cerebellum in the rhesus macaque as revealed by retrograde transport of horseradish peroxidase.
To investigate the afferent projections to the flocculus in a nonhuman primate, we injected horseradish peroxidase into one flocculus of six rhesus macaques (Macaca mulatta) and processed their brains according to the tetramethylbenzidine protocol to reveal retrogradely labeled neurons. Labeled neurons were found in a large set of nuclei within the rostral medulla and the pons. The greatest numbers of labeled neurons were in the vestibular complex and the nucleus prepositus hypoglossi. There were neurons labeled bilaterally throughout all the vestibular nuclei except the lateral vestibular nucleus, but most of the labeled neurons were in the caudal parts of the medial and inferior vestibular nuclei and in the central part of the superior vestibular nucleus; the nucleus prepositus was also labeled bilaterally, primarily caudally. Modest numbers of labeled neurons were found in the y-group, most ipsilaterally, and many neurons were labeled in the interstitial nucleus of the vestibular nerve. No labeled neurons were found in the vestibular ganglion following a large injection into the flocculus. A second large source of afferents to the flocculus was the medial, paramedial, and raphe reticular formation. Dense aggregates of labeled neurons were located in several pararaphe nuclei of the rostral medulla and the rostral pons and in the nucleus reticularis paramedianus of the medulla and several component nuclei of the nucleus reticularis tegmenti pontis bilaterally. Several groups of cells within and abutting upon the medial and rostral aspects of the abducens nucleus were labeled bilaterally. There was a modest projection from two parts of the pontine nuclei. Both a dorsal midline nucleus ventral to the nucleus reticularis tegmenti pontis and a collection of nuclei in a laminar region adjacent to the contralateral middle cerebellar peduncle contained labeled neurons whose numbers, while modest, were large compared to the projections to the flocculus in other animals. This generic difference may be due to the greater development of the smooth pursuit system in monkeys and the consequent need for a more substantial input from the cerebral cortex. As in other genera, the inferior olive projected to the flocculus via the dorsal cap of Kooy and the contiguous ventrolateral outgrowth. The projection was completely crossed and large injections labeled virtually every neuron in the dorsal cap, suggesting that the dorsal cap is the principal source of climbing fiber afferents.(ABSTRACT TRUNCATED AT 400 WORDS)
Abducens Nerve↗
Floccular efferents in the rhesus macaque as revealed by autoradiography and horseradish peroxidase.
To fulfill its putative role in short- and long-term modification of the vestibulo-ocular reflex, the flocculus of the cerebellum must send efferents to brainstem nuclei involved in the control of eye movements. In order to reveal the sites of these interactions, we determined the projections of the flocculus by autoradiography and orthograde transport of horseradish peroxidase in five rhesus macaques. Anterogradely labeled axons collected at the base of the injected folia and coursed caudally and medially between the middle cerebellar peduncle and the flocculus. They swept medially over the caudal surface of the middle cerebellar peduncle, over the dorsal surface of the cochlear nuclei, and then caudally along the lateral surface of the inferior cerebellar peduncle to pass over its dorsal surface in the cerebellopontine angle and terminate exclusively in the ipsilateral vestibular nuclei. Three contingents of axons could be differentiated. The axons of one group flowed caudally and medially into the y-group, which clearly received the densest floccular projection. Other, notably thicker, axons of this group continued rostrally and medially to terminate chiefly in the large-cell core of the superior vestibular nucleus. A second large contingent of thin axons streamed caudal and ventral to the y-group to form a compact tract adjacent to the lateral angle of the fourth ventricle and dorsal to the medial vestibular nucleus. Fibers from this tract (the angular bundle of Löwy) supplied a sizable projection to the rostral part of the medial vestibular nucleus and modest projection to the ventrolateral vestibular nucleus. A final group of fibers extended caudally and medially from the y-group in a plexus ventral to the dentate and interposed nuclei to terminate in the basal interstitial nucleus of the cerebellum (Langer, '85), a broadly distributed cerebellar nucleus on the roof of the fourth ventricle. The flocculus can affect vestibulo-ocular behavior only through these efferents to the vestibular nuclei and the basal interstitial nucleus of the cerebellum.
Afferent Pathways↗
[How bothersome is fiber bronchoscopy under local anesthesia?].
All the 79 (7.4%) complications of 1066 fiberoptic bronchoscopies performed under standardized topical anaesthesia in in- and outpatients were analyzed retrospectively. With the 4.9 mm bronchoscope the transnasal route was possible in all cases, and with the 6.0 mm bronchoscope in 92%. There were no deaths and no major complications, with the exception of one tension-pneumothorax, one pneumonia, one pulmonary edema and one 500 ml hemorrhage. The most frequent complications were minor hemorrhages (4.1%) which occurred mainly after biopsies and were rarely recognized by the patients. laryngospasms (1.5%) and bronchospasms (1.4%). The rate of complications was higher in patients with a FEV1 of less than 60% predicted (p = 0.02) and in patients with a pO2 below 50 mm Hg (p = 0.06). We recommend the administration of oxygen during fiberoptic bronchoscopy. Fever within 36 hours after bronchoscopy was observed in 12% and subsided without antibiotic therapy. In the light of these risks, patients should be informed prior to the procedure of the possible occurrence of shortness of breath, hemorrhage and fever.
Adult↗
Arrhythmia prophylaxis using propranolol after coronary artery surgery.
Sixty patients undergoing coronary artery bypass grafting operations with cold potassium cardioplegia as the method of myocardial preservation either received low-dose oral propranolol (10 mg every 6 hours; 28 patients) or served as controls (32 patients). The study period began after extubation and ended at the time of hospital discharge. On the fourth postoperative day, 24-hour Holter monitoring was performed to assess additional subtle differences in arrhythmias. The overall incidence of symptomatic postoperative arrhythmias was 31% in the control group: 6 patients (19%) had atrial fibrillation or flutter and 4 patients (12%), ventricular arrhythmias. By contrast, 1 patient (4%) in the propranolol group had atrial fibrillation, and no patient had ventricular arrhythmias. The difference in overall arrhythmia rates between the two groups is significant (p less than 0.025). Twenty-four-hour Holter monitoring demonstrated no additional differences in the frequency of simple or complex atrial or ventricular ectopy between the two groups. We conclude that the incidence of postoperative arrhythmias following coronary artery bypass operation is diminished by the oral administration of prophylactic low-dose propranolol. When compared with our previous study [1], in which the method of myocardial preservation was intermittent aortic cross-clamping and moderate hypothermia, there is no difference in the overall incidence of postoperative arrhythmias.
Arrhythmias, Cardiac↗
Low density lipoprotein metabolism and lipoprotein cholesterol content in southwestern American Indians.
The prevalence of ischemic heart disease is significantly lower in southwestern American Indians than in Caucasians. To investigate this difference, the metabolism of low density lipoprotein apoprotein (apo-LDL) and plasma lipoprotein cholesterol composition were studied in 10 southwestern American Indians and 5 Caucasian controls. The plasma concentration of LDL cholesterol in American Indians was 88 +/- 5 mg/dl (mean +/- SEM) and 111 +/- 7 mg/dl in Caucasians. The corresponding values of apo-LDL concentrations were 53 +/- 3 mg/dl and 77 +/- 4 mg/dl, respectively. Conversely, high density lipoprotein cholesterol (HDL) concentrations were significantly higher in American Indians (56 +/- 4 mg/dl) than in Caucasians (37 +/- 3 mg/dl). There were no statistically significant differences in the biological half-life of apo-LDL, calculated from the second exponential of the plasma die-away curve (3.06 +/- 0.15 days vs. 3.45 +/- 0.11 days), the fractional catabolic rate of apo-LDL (0.432 +/- 0.01 vs. 0.411 +/- 0.01), or the fraction of total exchangeable apo-LDL in the intravascular space (70 +/- 1 vs. 67 +/- 3%). As derived from the absolute catabolic rate under steady-state conditions, the synthetic rate of apo-LDL in American Indians was, however, significantly lower than in Caucasians (334.6 +/- 7.8 mg/m(2) per day vs. 507.2 +/- 6.7 mg/m(2) per day; P < 0.001). These data indicate that the lower levels of plasma LDL cholesterol and apo-LDL in American Indians are due to a reduced rate of apo-LDL synthesis rather than to differences in fractional catabolic rates. These differences, in combination with higher HDL cholesterol levels, may contribute to the lower prevalence of ischemic heart disease in American Indians.
Adult↗
[Matched-pair analysis--technic and results demonstrated on the example of breast cancer].
The matched pair analysis is a well-known, but rarely used method. This method is recommended for the following problems: preparation of a controlled clinical experiment based upon the results of a retrospective analysis of results of therapy; analysis of results from a controlled clinical experiment in sub-groups; influence of non-therapeutic factors on the prognosis; epidemiological problems and study of the course of diseases. A matched pair analysis of about 300 female patients with breast carcinoma failed to show significant differences between (a) radical mastectomy alone, (b) radical mastectomy followed by chemotherapy with cyclophosphamide, and (c) preoperative irradiation followed by radical mastectomy.
Breast Neoplasms↗