Regulation of succinate dehydrogenase: does the membrane environment change the catalytic activity of the enzyme?
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Catalysis↗
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Results for “Environment--changes”
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Climate and environment change in patients with chronic airway obstruction.
Psychological, clinical, and pulmonary physiological measurements were studied in ten patients with weather-sensitive chronic airway obstruction during one month in Gothenburg, Sweden, and immediately after for one month in the Canary Islands, a change to a drier and warmer climate. All patients improved according to psychological tests and claimed to be better. Objective measurements including peak expiratory flow rate, airway conductance, static lung volumes, and elastic lung recoil showed improvement in eight of ten patients, a change that we believe is due to the effect of climate.
Adult↗
Two largest national alliances fine-tune strategies as health care environment changes. Interview by Howard J. Anderson.
The nation's two largest alliances of not-for-profit hospitals and systems are refining their roles for the 1990s. American Health Care Systems (AmHS) and Voluntary Hospitals of America (VHA) are moving away from strategies designed for competition in the marketplace of the 1980s, and toward helping their members change the way they deliver health care in their communities. While AmHS is promoting its health care reform proposal, VHA sees its existing 29 regional organizations of hospitals as a potential infrastructure for the development of community-based, integrated networks of care as envisioned in the AHA's reform plan. Experts add that the alliances clearly have to go beyond group purchasing to serve the changing needs of their members.
Community-Institutional Relations↗
Strategic change in hospitals: an examination of the response of the acute care hospital to the turbulent environment of the 1980s.
Changes in strategies of hospitals responding to the turbulent health care environment of the 1980s are examined both in the aggregate and from the perspective of the individual hospital. The Miles and Snow typology is used to determine strategy type. Both investor-owned and not-for-profit hospitals were well represented in the broad mix of hospital types sampled. In addition, freestanding hospitals and members of multihospital systems were present in the sample. Last, hospitals of all sizes were included. Strategic change was evaluated by classifying hospitals by strategy type in each of two consecutive five-year time periods (1976 through 1980 and 1981 through 1985). Changes in reimbursement policies, the emergence of new technologies, changing consumer expectations, and new sources of competition made the environment for hospitals progressively more turbulent in the latter period and provided an opportune setting to evaluate strategic change. Results showed that a significant number of hospitals did change strategy as the environment changed, and in the direction anticipated. Logistic regression was used to determine whether prior strategy, type of ownership, system membership, or size would predict which hospitals would change strategy as the environment changed: only prior strategy was found to be a predictor of strategy change.
Economic Competition↗
Time-dependent fluorescence depolarization and lifetime studies of myosin subfragment-one in the presence of nucleotide and actin.
Time-dependent fluorescence depolarization and lifetime studies have been made on myosin subfragment 1 to obtain information about mobility changes and dye environment changes when different nucleotides are added. Data are reported for static and actively hydrolyzing systems containing G- and F-actin. Preliminary data indicate that myosin labeled with the fluorophore 1, 5 IAEDANS and treated with DTT preserves its actin-activated Vmax. S1 prepared in this manner gives lifetime changes which are nearly identical for all systems studied. S1 labeling without DTT addition gives a pattern of lifetimes similar, though not identical to ESR work. Either type of labeling produces no observable change in the polarization decay, and we set an upper limit of 15% length change for the elongate S1. An unusually long fluorescence decay lifetime for the S1-Mg++ ATP-G-actin system is found which may indicate a new acto-S1 state stabilized by G-actin. The method for obtaining the bound fraction of S1's in the presence of actin is presented and applied to the S1-F-actin-Mg++ ATP system. Qualitative agreement is obtained with other methods.
Actins↗
The role of thematic evaluation in program assessment: the case of the Community Clinical Oncology Program.
The evaluation of programs with multiple, and potentially conflicting, goals requires the integration of measures of goal achievement that often are not easily combined. One approach is the development of analytical themes which span the various goals of a particular program. The themes provide a mechanism by which the policy concerns of individuals with varying perspectives can be integrated into the evaluation framework. As well, the themes allow for flexibility in the development of new analysis as the program matures and environments change. This paper describes the application of the thematic approach to the evaluation of a complex, community-oriented cancer research program.
Clinical Trials as Topic↗
Epidemiology of dental caries.
The most recent epidemiological data on the prevalence of dental caries in children indicate a halting of the increasing levels in many developing countries and a continuing decrease in many highly industrialized countries of the world. However, a further fall in caries levels predicted for 5-yr-old children in the U.K. has not occurred and the decline in caries may have begun to level out. 'Polarization' of caries to a minority of high-risk individuals is occurring in the developed world, with 20-25% of children accounting for more than 50% of the disease. Socio-economic factors are important in determining the proportion of high-risk children in these countries. The multifactorial aetiology of caries allows a number of different interpretations to account for changes in the prevalence of the disease with time, in both the developing and developed countries. These changes are variously ascribed to alterations in dietary habits, especially the consumption of sugar; variations in the patterns of oral hygiene; increased contact with trace elements, especially fluoride, in the environment; changes in the ecology and/or virulence of oral and dental plaque microflora and alterations in the oral protective mechanisms including the immune status. The epidemiological evidence available on the relationship of all these social, environmental and other factors to changes in the prevalence levels of caries does not, however, fully explain all the changes that have been observed. The claim that caries is no longer a public health problem is premature, as it ignores the still high proportion of individuals with tooth decay throughout the world.
Adolescent↗
Platelet size and function in septic rats: changes in the adenylate pool.
Cecal ligation and puncture (CLP) were performed in rats. After 4 hr (early sepsis) and 16 hr (late sepsis), platelet morphology and function were studied. At 16 hr, platelet counts for the CLP group were significantly lower than for the sham-operated control group. Low maximum aggregation rates (MAR) and decreased platelet counts were elicited in platelet-rich plasma with 4 M ADP and 2 micrograms/ml collagen. However, with platelet counts equalized, MAR for the CLP group increased significantly, especially after 16 hr. The platelet-large cell rate and platelet distribution width decreased temporarily at 4 hr, then rose significantly at 16 hr. No significant changes were observed in the mean platelet volume after 4 hr, but there were significant increases after 16 hr. Total adenine nucleotide (TAN) levels within the platelets rose significantly in the CLP group, suggesting the appearance during the late sepsis of large, heavy platelets or adenine nucleotide-rich platelets. The platelet adenylate pool was divided into granular and cytoplasmic fractions, respectively characterized by ADP and ATP increases. However, no septicemia-related differences were noted in the degree of binding between goat antirat fibrinogen and platelet surface glycoprotein IIb/IIIa complex. Internal environment changes in the platelets indicated that during septicemia hyperfunctional or hypersensitive platelets with a latent capacity for active aggregation and release appeared in the circulation. Hypercoagulability in septicemia involves activation of coagulation factors, stimulation of the coagulation cascade, volume changes accompanying increased platelet TAN content, and changes in AN distribution in the two pools. These findings significantly increase our understanding of the transition from the prethrombotic state to thrombosis in septicemia.
Adenine Nucleotides↗
Demyelination, and remyelination by Schwann cells and oligodendrocytes after kainate-induced neuronal depletion in the central nervous system.
Excitotoxins are thought to kill neurons while sparing afferent fibers and axons of passage. The validity of this classical conclusion has recently been questioned by the demonstration of axonal demyelination. In addition, axons are submitted to a profound alteration of their glial environment. This work was, therefore, undertaken to reassess axonoglial interactions over time after an excitotoxic lesion in the rat. Ultrastructural studies were carried out in the ventrobasal thalamus two days to 18 months after neuronal depletion by in situ injections of kainic acid. In some cases, lemniscal afferents were identified by using anterograde transport of wheatgerm agglutinin conjugated to horseradish peroxidase from the dorsal column nuclei. Two and four days after kainate injection, numerous dying axons displaying typical signs of Wallerian degeneration were observed in a neuropile characterized by the loss of neuronal somata and dendrites, an increase in number of microglia/macrophages and the disappearance of astrocytes. Ten and 12 days after kainate injection, degenerating axons were no longer observed although myelin degeneration of otherwise unaltered axons was ongoing with an accumulation of myelin remnants in the neuropile. At 16 and 20 days, the demyelination process was apparently complete and axons of different diameters were sometimes packed together. One and two months after kainate injection, the axonal environment changed again: remyelination of large-caliber axons occurred at the same time as reactive astrocytes, oligodendrocytes and numerous Schwann cells appeared in the tissue. Schwann cell processes surrounded aggregates of axons of diverse calibers, ensheathed small ones and myelinated larger ones. Axons were also remyelinated by oligodendrocytes. Horseradish peroxidase-labeled lemniscal afferents could be myelinated by either of the two cell types. After three months, the neuropile exhibited an increase in number of hypertrophied astrocytes and the progressive loss of any other cellular or axonal element. At this stage, remaining Schwann cells were surrounded by a glia limitans formed by astrocytic processes. These data indicate that although excitotoxins are sparing the axons, they are having a profound and complex effect on the axonal environment. Demyelination occurs over the first weeks, accompanying the loss of astrocytes and oligodendrocytes. Axonal ensheathment and remyelination takes place in a second period, associated with the reappearance of oligodendrocytes and recruitment of numerous Schwann cells, while reactive astrocytes appear in the tissue at a slightly later time. Over the following months, astrocytes occupy a greater proportion of the neuron-depleted territory and other elements decrease in number.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
X-ray absorption spectroscopic studies of the high-spin iron(II) active site of isopenicillin N synthase: evidence for Fe-S interaction in the enzyme-substrate complex.
Isopenicillin N synthase from Cephalosporium acremonium (IPNS; M(r) 38.4K) is an Fe(2+)-requiring enzyme which catalyzes the oxidative conversion of (L-alpha-amino-delta-adipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N, with concomitant reduction of O2 to 2H2O. Chemical and spectroscopic data have suggested that catalysis proceeds via an enzyme complex of ACV bound to the iron through its cysteinyl thiolate [Baldwin, J. E., & Abraham, E. P. (1988) Nat. Prod. Rep. 5, 129-145; Chen, V. J., Orville, A. M., Harpel, M. R., Frolik, C. A., Surerus, K. K., Münck, E., & Lipscomb, J. D. (1989) J. Biol. Chem. 264, 21677-21681; Ming, L.-J., Que, L., Jr., Kriauciunas, A., Frolik, C. A., & Chen, V. J. (1991) Biochemistry 30, 11653-11659]. Here we have employed the technique of Fe K-edge extended X-ray absorption fine structure (EXAFS) to characterize the iron site and to seek direct evidence for or against the formation of an Fe-S interaction upon ACV binding. Our data collected in the absence of substrate and O2 are consistent with the iron center of IPNS being coordinated by only (N,O)-containing ligands in an approximately octahedral arrangement and with an average Fe-(N,O) distance of 2.15 +/- 0.02 A. Upon anaerobic binding of ACV, the iron coordination environment changes considerably, and the associated Fe EXAFS cannot be adequately simulated without incorporating an Fe-S interaction at 2.34 +/- 0.02 A along with four or five Fe-(N,O) interactions at 2.15 +/- 0.02 A.(ABSTRACT TRUNCATED AT 250 WORDS)
Acremonium↗
Persistent depression of rearing behavior in rats after extensive septal lesions.
Extensive septal lesions produced a persistent (76 days) reduction in rearing behavior which was not directly attributable to altered deprivation states, emotionality, activity levels, or competing behaviors and which occurred in familiar as well as various novel testing environments. Changes in visual, olfactory, or conspecific stimuli ameliorated or had no effect on the lesion effect. The results indicate that the septal area is importantly involved in normal rearing behavior and that lesion-induced alterations in responsiveness to some forms of stimulation may play a modulatory role in reduced rearing. It is also suggested that the septal area may constitute a portion of a neural system responsible for the initiation of this form of response.
Animals↗
Identification of adaptive changes in an evolving population of Escherichia coli: the role of changes with regulatory and highly pleiotropic effects.
A population of Escherichia coli initiated with a single clone developed extensive morphological and physiological polymorphism after being maintained for 773 generations in glucose-limited continuous culture. To understand the mechanisms of adaptation to this environment, total protein patterns of four adaptive clones and of the parent strains were examined by two-dimensional gel electrophoresis. Approximately 20% of the proteins (approximately 160 in absolute numbers) showed significantly different levels of expression in pairwise comparisons of parent and adapted clones. The extent of these changes points to the importance of mutations with regulatory and/or highly pleiotropic effects in the adaptive process. The four evolved clones all expressed fewer proteins than did the parent strain, supporting the hypothesis of energy conservation during evolutionary change. Forty-two proteins that could be assigned to known cellular functions were identified. The changes in some of them indicated that the evolved clones developed different adaptive mechanisms to glucose-limited environment. Changes were observed in the expression levels of proteins associated with translation, membrane composition, shock response, and active transport. A fraction of the changes could not be either explained or predicted from a consideration of the nature of the environment in which the clones evolved.
Adaptation, Biological↗
Hmong women: characteristics and birth outcomes, 1990.
Current demographic characteristics and pregnancy outcomes of immigrant Hmong women in a small town in southeastern United States were documented in a retrospective study. Interviews and review of existing records were used to determine prenatal practices and perceived problems. Sixteen health professionals and two women from the community were interviewed, and the labor and delivery records from 1985 to 1990 were reviewed for parity, child spacing, and health status of the women and newborns. The greatest concerns voiced by health caregivers were multiparity and the need for contraceptive compliance. Seventy-eight full-term infants were born to 64 women in five years, with 2 stillbirths. No eclampsia, diabetes, or Rh incompatibilities were noted. Evidence is limited that birth frequency or outcome for Hmong women is a problem. Their perinatal difficulties were thought to be sociocultural rather than medical. Further study of the effects of acculturation on maternal family position, perinatal risks, and birth outcomes is imperative as lifestyle and environment change for these immigrant women.
Adolescent↗
Computer-assisted three-dimensional reconstruction and simulations of vestibular macular neural connectivities.
The macular neuroepithelium is morphologically organized as a weighted neural network for parallel distributed processing of information. The network is continuous across the striola, where some type II hair cells synapse with calyces containing type I cells with tufts of opposite directional polarities. Whether other hair cell to calyx appositions that lack synapses interact because of intercellular potassium accumulation remains an open question. A functionally important inference of macular organization is that just as arrays of hair cells communicate an entire piece of information to a nerve fiber, so do macular subarrays of nerve fibers (not single units) carry the whole coded message to the brain stem. Moreover, the size of the network subarray can expand or become more limited depending upon the strength and/or duration of the input. It is the functioning of the network and its subarrays that must be understood if we are to learn how maculas carry out their work and adapt to new environments. Simulations of functioning maculas, or subparts, based on precise morphology and known physiology are useful tools to gain insights into macular information processing. The current simulations of afferent collateral electrical activity are a prelude to development of a 3-D model. The simulations demonstrate a relationship between geometry and function, with the diameter of the stem apparently being a major determinant of electrical activity transmitted to the base in the case of collaterals with short stems. Thus, while changes in synaptic number and/or size may be an important adaptive mechanism in an altered g environment, changes in diameter of the stem is another means of altering outflow. Research on the effects of microgravity should be extremely useful in examining the validity of this and other concepts of neural adaptation, since maculas are biological linear accelerometers ideally suited to the task. Maculas are also extremely interesting to study in detail because of the richness of connectivities and submicroscopic organization they present. Many of their features are common with more complex parts of the brain. It seems possible that knowledge of the three-dimensional geometric relationships operative in a functioning macula will contribute much to the understanding of the dynamics underlying more complex behavior. Computerized approaches greatly facilitate this task and provide an objective method of analysis. It is likely that, in the end, simple rules will be found to govern optimal neural architectural organization, even at higher cognitive levels. The architecture only appears complex because we do not yet grasp its meaning.(ABSTRACT TRUNCATED AT 400 WORDS)
Acoustic Maculae↗
Two point mutations in the transmembrane domain of P68gag-ros inactive its transforming activity and cause a delay in membrane association.
The transforming protein of the avian sarcoma virus UR2 is a 68-kDa transmembrane tyrosine protein kinase. We examined the relationship between membrane localization and transforming activity of P68 by changing Val-168-Val-169 in its hydrophobic domain into Asp-168-Glu-169. The resulting transmembrane (TM) mutant (P68TM) lost transforming activity toward chicken embryo fibroblasts (CEF). We found that the mutant protein was expressed and rapidly degraded into a smaller form which was still membrane associated and kinase active. The instability of the TM mutant protein is a phenomenon only manifested in CEF, because the same mutant protein was expressed with efficiency and stability similar to those of the wild-type protein in a transient expression system in COS cells. However, there are several differences between the wild-type and the TM mutant proteins in COS cells. The wild-type protein is more heavily phosphorylated and associated with membrane fractions in a cotranslational manner. It is enzymatically active when recovered from membrane fractions. The TM mutant protein is less phosphorylated, more labile toward protease degradation, and delayed in membrane association, with a lag period of 30 min or longer, and has little kinase activity when recovered from membrane fractions. Most of the kinase-active TM mutant protein was found in the cytosol fractions. Despite the delay, most of the TM protein in COS cells was found to be membrane associated, and its orientation on the cell surface was similar to that of the wild-type protein. It is probable that loss of the CEF-transforming activity of the TM mutant protein is due to its susceptibility to protease degradation resulting from improper membrane association of the newly synthesized product. The differences in the kinetics of membrane association and the distribution of kinase activity in COS cells might not be directly applicable in explaining the inability of the TM mutant to transform CEF but are intriguing as regards protein biosynthesis and translocation. The difference between CEF and COS cells implies that different factors or pathways are involved in the biosynthesis and processing of the TM mutant protein in these two cellular environments. Changes of P68TM in the kinetics of membrane association indicate that the transmembrane domain of ros, besides functioning as a membrane anchor, also plays a role in directing initial membrane association.
Animals↗
Development of stress-induced pituitary prolactin and TSH release in male rats.
Blood was collected from male rats of various ages under control conditions and after introduction of two stress factors. All animals were sacrificed between 15.00 and 16.00 h. Serum prolactin levels in immature male rats were found to be very low between birth and day 15 after birth. Neither exposure to a new environment, for example removal from the animal rooms for the duration of 10 min, nor exposure to concentrated ether vapour resulted in increased serum prolactin levels. Between day 20 and 35 basal serum prolactin levels were increased, they then fell at adult values. During this period of increasing serum prolactin levels pituitary prolactin release became stress-susceptable; i.e. elevated serum prolactin levels were observed after introduction of stress factors as in adult male rats. Serum TSH levels were found to be high between birth and day 10. Low TSH levels measured between day 15 and 40 and adult values were detected after day 40. Neither ether nor removal of the animals from their normal environment changed serum TSH levels at any age tested. The results indicate that the hypothalamo-pituitary in immature rats reacts in a similar way as that in adult animals from day 16-20 onwards. Serum TSH levels in these animals, however, are reduced, indicating that an increase in serum TSH is not necessary for normal processes of maturation.
Age Factors↗
Carboxyhaemoglobin saturation in relation to smoking and various occupational conditions.
The effects of smoking and occupational conditions on COHb saturation were studied among employees on traffic duty, in restaurants, in iron foundries, and in an office. The subjects were 139 smokers and 152 nonsmokers working in the same environments. Changes in COHb saturation were observed in samples of blood obtained before and after the working period. Samples of air were collected during the working hours in restaurants, in foundries and in office, 190 samples in all, for the determination of content of CO. Among the nonsmokers there was no change in COHb saturation in restaurants and in office work. On traffic duty and in iron foundries the increase was significant, but the values after work were less than half the permitted occupational threshold limit value (TLV) level of 6 per cent units. In the smoking group the mean values of COHb saturation before work were about twice the mean COHb saturation in the nonsmokers after work. In office work and in foundries the mean COHb saturations after the work exceeded the permitted TLV.
Adolescent↗
Lac Repressor. Fluorescence of the two tryptophans.
By comparing the fluorescence emission properties of the wild type lac repressor with two lac repressors altered at tryptophan 190 and 209, respectively, we show that tryptophan residue 209 has its environment changed, either by its own motion, or that of the surrounding amino acids when an inducer molecule is bound. Substitution of this tryptophan with other amino acids results in lac respressor molecules with reduced affinity for inducer molecules, indicating that the geometry at residue 209 affects the geometry of the inducer-binding site. From the results of potassium iodide quenching of fluorescence from the tryptophans, and from attempts to react the native lac repressor with dimethyl(2-hydroxy-5-nitrobenzyl) sulfonium bromide and 2-hydroxy-5-nitrobenzyl bromide, we propose that tryptophan residue 209 is involved in a conformational change of the protein upon binding of inducer, but does not come in direct contact with inducer.
Amino Acids↗