Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
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Carnitine is required for the transport of activated long chain fatty acids through the mitochondrial inner membrane. We measured the intracellular free calcium concentration [( Ca2+]i) by means of a calcium selective microelectrode in skeletal muscle biopsies obtained from nine patients in which myopathic carnitine deficiency (MCD) was diagnosed, and from six subjects with no evidence of neuromuscular disease. Intact intercostal muscle bundles were dissected and then split for electron microscopic studies and electrophysiological measurements. The [Ca2+]i in muscle fibers from MCD patients was 0.46 +/- 0.02 mumol.l-1 (mean +/- SEM) and 0.10 +/- 0.01 mumol.l-1 in control subjects. At the electron microscopic level, the predominant abnormality was the presence of lipid vacuoles between the myofibrils. These results show that in patients with myopathic carnitine deficiency there is a significant increase in the resting myoplasmic calcium concentration which might be related to a malfunction of some mechanisms responsible for the homeostasis of intracellular calcium.
Gen Physiol Biophys 1989 Apr
PMID:Intracellular free [Ca2+] in human skeletal muscle with myopathic carnitine deficiency. 277 61

We demonstrate that highly purified bullfrog (f) follicle-stimulating hormone (FSH) and luteinizing hormone (LH) bind specifically and significantly to a crude plasma membrane fraction of bullfrog liver. The other extragonadal organs of the bullfrog showed little or no specific binding. Specific bindings of 125I-fFSH and 125I-fLH to plasma membranes are saturable processes, and are time-, pH-, and temperature-dependent. Scatchard plots of fFSH and fLH were linear. The association constant of equilibrium (Ka) of the specific fFSH binding sites was 4.77 +/- 1.24 X 10(9)M-1 (mean +/- SEM) and the number of sites was 0.262 +/- 0.042 fmol/mg protein (mean +/- SEM). The Ka of the specific fLH binding sites was 5.38 +/- 1.27 X 10(9)M-1 (mean +/- SEM) and the number was 0.315 +/- 0.019 fmol/mg protein (mean +/- SEM). Competition experiments revealed that both fFSH and fLH use the same single class of binding sites. Binding of rat, chicken, bullfrog, and salmon gonadotropins to plasma membranes of the testis and liver of various vertebrates was studied. A significant degree of specific binding was detected only in combinations of bullfrog gonadotropins and amphibian livers. The concentration of adenosine 3'-5'-monophosphate (cAMP) in mince or primary culture cells of bullfrog liver was greatly increased by adding fFSH and fLH to the medium. Bullfrog LH was more potent than fFSH in increasing cAMP concentration, although they were not distinguished by specific binding sites. These data suggest that not only the gonads but also the liver is the target of gonadotropins in the bullfrog, although the final hepatic function controlled by gonadotropins remains unknown.
Gen Comp Endocrinol 1987 Nov
PMID:Receptors for native gonadotropins in amphibian liver. 282 51

1. The effects of atropine and glycopyrrolate on neuromuscular transmission and on muscle contraction, were studied, in the rat diaphragm preparation, by analyzing their effects on the indirectly (and directly)-elicited twitch (0.2 Hz), tetanic (50 Hz for 20 sec duration), post-tetanic twitch responses (at 5 sec after the tetanus), and on the phenomenon of post-tetanic twitch potentiation (PTP), which is thought to be of a presynaptic origin, i.e. due to increased transmitter release. 2. Atropine (0.001-10 microM) increased the indirectly-elicited twitch tension by 22 +/- 2.1% (control 0.9 +/- 0.1 g, P less than 0.02), the tetanus by 15 +/- 1.1% (control 3.9 +/- 0.7 g, P less than 0.05), the post-tetanic twitch response by 33 +/- 3.1% (control 1.2 +/- 0.1 g, P less than 0.01) and the PTP value by 36 +/- 1.9% (control 33 +/- 2.3%, P less than 0.01, means +/- SEM = 6). 3. Atropine (0.001-10 microM) had little effect on the directly-elicited twitch tension, but in high concentrations (e.g. 20 microM), it blocked the twitch tension. 4. In contrast, glycopyrrolate (0.1-100 microM) had little effect on the twitch tension (direct or indirect), but it significantly reduced the tetanus (by 38 +/- 3.5%, P less than 0.01), the post-tetanic twitch response (by 17 +/- 1.2%, P less than 0.05) and the PTP values (by 24 +/- 3.1% P less than 0.02). 5. In the presence of hemicholinium (1.3 microM) the responses to atropine and glycopyrrolate were altered (decreased), indicating a possible action on presynaptic mechanism of transmission. 6. It is concluded that atropine and glycopyrrolate produce different (opposite) effects at the rat neuromuscular junction, atropine enhances whereas glycopyrrolate depresses neuromuscular transmission. The effects of these two antimuscarinic drugs may be exerted at the presynaptic nerve terminals, i.e. on presynaptic muscarinic receptors, which are involved in the feedback mechanism of transmitter release.
Gen Pharmacol 1988
PMID:Effects of atropine and glycopyrrolate on neuromuscular transmission in the rat phrenic nerve-diaphragm preparation. 283 47

Currents were generated by depolarizing pulses in voltage-clamped, dissociated neurons from the CA1 region of adult guinea pig hippocampus in solutions containing 1 microm tetrodotoxin. When the extracellular potassium concentration was 100 mM, the currents reversed at -8.1 +/- 1.6 mV (n = 5), close to the calculated potassium equilibrium potential of -7 mV. The currents were depressed by 30 mM tetraethylammonium in the extracellular solution but were unaffected by 4-aminopyridine at concentrations of 0.5 or 1 mM. It was concluded that the currents were depolarization-activated potassium currents. Instantaneous current-voltage curves were nonlinear but could be fitted by a Goldman-Hodgkin-Katz equation with PNa/PK = 0.04. Conductance-voltage curves could be described by a Boltzmann-type equation: the average maximum conductance was 65.2 +/- 15.7 nS (n = 9) and the potential at which gK was half-maximal was -4.8 +/- 3.9 mV (mean +/- 1 SEM, n = 10). The relationship between the null potential and the extracellular potassium concentration was nonlinear and could be fitted by a Goldman-Hodgkin-Katz equation with PNa/PK = 0.04. The rising phase of potassium currents and the decay of tail currents could be fitted with exponentials with single time constants that varied with membrane potential. Potassium currents inactivated to a steady level with a time constant of approximately 450 ms that did not vary with potential. The currents were depressed by substituting cobalt or cadmium for extracellular calcium but similar effects were not obtained by substituting magnesium for calcium.
J Gen Physiol 1988 Aug
PMID:Potassium current activated by depolarization of dissociated neurons from adult guinea pig hippocampus. 284 59

One hypothesis that could account for the anxiogenic response to breathing air supplemented with carbon dioxide seen in panic anxiety patients is that panic patients might have abnormally high central medullary chemoreceptor sensitivity. Chemoreceptor sensitivity was assessed by using a rebreathing technique to measure the ventilatory response to CO2 in 14 medication-free patients with agoraphobia and panic attacks and 23 healthy subjects. Ventilatory response to CO2 was similar in patients and controls (mean +/- SEM, 1.58 +/- 0.16 vs 1.58 +/- 0.14 L/min/mm Hg), suggesting that abnormal chemoreceptor sensitivity does not explain the behavioral sensitivity of panic patients to CO2. Anxiety ratings increased markedly during rebreathing both in patients and controls; anxiety increases were significantly greater in patients than in healthy subjects matched for age, sex, and rebreathing duration. Alprazolam treatment in eight patients markedly attenuated anxiety increases during rebreathing. Differences in anxiogenic sensitivity to CO2 between patients and controls may be due to differences in the regulation of noradrenergic or other neuronal systems.
Arch Gen Psychiatry 1986 Sep
PMID:Carbon dioxide sensitivity in panic anxiety. Ventilatory and anxiogenic response to carbon dioxide in healthy subjects and patients with panic anxiety before and after alprazolam treatment. 309 80

The properties of a sex-steroid binding protein (SSBP) in the plasma of the American alligator, Alligator mississippiensis, were partially characterized. Alligator SSBP has a sedimentation coefficient of 4S in a 5-20% sucrose gradient. It binds to estradiol-17 beta (E2) and testosterone (T) with limited capacities and moderate affinities (association constant for [3H]E2 is 4.70 +/- 0.09 X 10(8) M-1 and for [3H]T is 1.05 +/- 0.07 X 10(8) M-1, mean +/- SEM of six determinations). Plasma SSBP level, as measured by plasma [3H]E2 binding capacity, varies from 30 to 140 nmol per liter plasma (nM) and was found to be dependent on the gender, sexual maturity, and reproductive state of the animal. Distinct annual fluctuations in plasma SSBP level were observed in female alligators. In adult females, plasma SSBP levels were high (122 +/- 6 nM) in the fall during the nonbreeding season and low (30-60 nM) in spring and early summer during the breeding season. A minimum (33 +/- 6 nM) was reached in mid-June coinciding with the time of oviposition and rapid decline in circulating estrogen levels. This decline in adult female plasma SSBP levels during the breeding season was not observed in immature females. On the contrary, plasma SSBP levels in immature females increased from 81 +/- 14 nM in April to 134 +/- 9 nM in June. Plasma SSBP levels in male alligators showed little changes throughout the entire breeding season; they remained within the range of 80-100 nM from March to June. We believe that seasonal fluctuations in plasma SSBP levels constitute part of the mechanism involved in the regulation of free steroid delivered to target organs in female alligators and that such a mechanism does not exist in male animals.
Gen Comp Endocrinol 1987 Jan
PMID:Plasma sex-steroid binding protein in a seasonally breeding reptile, Alligator mississippiensis. 310 Mar 87

Eight strains of Salmonella pullorum isolated from epidemiologically independent cases of pullorum disease (bacillary white diarrhoea) in young chickens possessed at least one large molecular mass plasmid in addition to smaller molecular mass plasmids. The 85 kb large plasmid, designated pBL001, of one of these strains was 'tagged' with an ampicillin resistance marker by the insertion of transposon Tn3. The plasmid was eliminated by passage in nutrient broth containing acridine orange. It was reintroduced into the strain from which it had been eliminated by mobilization using the F plasmid. Following oral inoculation of newly hatched Rhode Island Red chickens, the parent strain produced a high level of mortality (71%) with characteristic signs of pullorum disease. Following intramuscular inoculation of chickens of the same age, the bacterial LD50 was (log10 c.f.u.) 3.38 +/- 0.43 (mean +/- SEM). The derivative lacking pBL001 produced no mortality or morbidity when inoculated orally and the bacterial LD50 value increased to (log10 c.f.u.) 5.54 +/- 0.28. This increase was statistically significant (chi 2 = 13.6, P less than 0.01). Reintroduction of pBL001 restored virulence as gauged by oral inoculation of chickens (62% mortality) and by the intramuscular bacterial LD50 value (log10 c.f.u. = 3.78 +/- 0.25). These values were not significantly different to those produced by the parent strain (chi 2 = 0.59, P = 0.4 and chi 2 = 0.66, P = 0.5, respectively). Following oral inoculation, the pBL001-cured derivative was less invasive than the parent strain and following intramuscular inoculation it persisted for a shorter period than the parent strain in the liver, spleen and the leg muscle into which it had been inoculated. In addition, the parent strain, but not the pBL001-cured derivative, localized in large numbers in the myocardium where it produced lesions typical of pullorum disease. Both the parent strain and the pBL001-cured derivative were serum resistant in the presence of rabbit serum and grew equally well in chick serum and broth.
J Gen Microbiol 1988 Aug
PMID:The association between a large molecular mass plasmid and virulence in a strain of Salmonella pullorum. 325 8

Ecdysteroid levels detected by RIA in extracts of mature ovaries from Periplaneta americana increased approximately fourfold (53 +/- 10 to 184 +/- 38 ng/g; +/- SEM, n = 3) on treatment with Helix pomatia "sulphatase" enzymes. HPLC analysis showed that this increase in immunoreactivity resulted from the hydrolysis of six apolar compounds that cochromatographed with the ecdysteroid esters previously shown to be present in newly laid oothecae (A1, A2, A3, A4, A5, and A6; A. J. Slinger, L. N. Dinan, and R. E. Isaac (1986). Insect Biochem. 16 (i), 115-119). Intact ovaries cultured in saline were able to take up [3H]ecdysone from the medium and synthesize ecdysone esters, most of which cochromatographed with immunoreactive peaks from ovaries and oothecae. Crude homogenates and membranes prepared from mature ovaries were also able to esterify ecdysone in vitro. The enzyme activity associated with a high-speed pellet was greatly enhanced by the addition of coenzyme A fatty acyl esters, each reaction resulting in the synthesis of a single major metabolite. The three esters formed on incubating ecdysone with coenzyme A-palmitate, -lineate, and -oleate could be characterized by their retention times on HPLC which were identical to compounds A2, A5, and A6, respectively. These compounds were the three quantitatively important immunoreactive esters found in ovaries and newly laid oothecae. The data presented indicates that ovaries can esterify ecdysone with palmitic, linoleic, and oleic acids and that these apolar derivatives are transferred to the egg. The esters appear to be different from the ecdysone 22-fatty acyl esters that have been isolated from ticks and other insects.
Gen Comp Endocrinol 1988 Apr
PMID:Synthesis of apolar ecdysone esters by ovaries of the cockroach Periplaneta americana. 337 52

K contractures and two-microelectrode voltage-clamp techniques were used to measure inactivation of excitation-contraction coupling in small bundles of fibers from rat extensor digitorum longus (e.d.l.) and soleus muscles at 21 degrees C. The rate of spontaneous relaxation was faster in e.d.l. fibers: the time for 120 mM K contractures to decay to 50% of maximum tension was 9.8 +/- 0.5 s (mean +/- SEM) in e.d.l. and 16.8 +/- 1.7 s in soleus. The rate of decay depended on membrane potential: in e.d.l., the 50% decay time was 14.3 +/- 0.7 s for contractures in 80 mM K (Vm = 25 mV) and 4.9 +/- 0.4 s in 160 mM K (Vm = -3 mV). In contrast to activation, which occurred with less depolarization in soleus fibers, steady state inactivation required more depolarization: after 3 min at -40 mV in 40 mM K, the 200 mM K contracture amplitude in e.d.l. fell to 28 +/- 10% (n = 5) of control, but remained at 85 +/- 2% (n = 6) of control in soleus. These different inactivation properties in e.d.l. and soleus fibers were not influenced by the fact that the 200 mM K solution used to test for steady state inactivation produced contractures that were maximal in soleus fibers but submaximal in e.d.l.: a relatively similar depression was recorded in maximal (200 mM K) and submaximal (60 and 80 mM K) contracture tension. A steady state "pedestal" of tension was observed with maintained depolarization after K contracture relaxation and was larger in soleus than in e.d.l. fibers. The pedestal tension was attributed to the overlap between the activation and inactivation curves for tension vs. membrane potential, which was greater in soleus than in e.d.l. fibers. The K contracture results were confirmed with the two-microelectrode voltage clamp: the contraction threshold increased to more positive potentials at holding potentials of -50 mV in e.d.l. or -40 mV in soleus. At holding potentials of -30 mV in e.d.l. or 0 mV in soleus, contraction could not be evoked by 15-ms pulses to +20 mV. Both K contracture and voltage-clamp experiments revealed that activation in soleus fibers occurred with a smaller transient depolarization and was maintained with greater steady state depolarization than in e.d.l. fibers. The K contracture and voltage-clamp results are described by a model in which contraction depends on the formation of a threshold concentration of activator from a voltage-sensitive molecule that can exist in the precursor, activator, or inactive states.
J Gen Physiol 1988 May
PMID:Inactivation of excitation-contraction coupling in rat extensor digitorum longus and soleus muscles. 341 20

The relative affinities and maximum capacities of the classes of L-thyroxine (T4)- and 3,5,3'-triiodo-L-thyronine (T3)-binding sites in plasma of three species of salmonid teleost fish were determined by saturation analysis on miniature Sephadex G-25 columns at 20-21 degrees and kinetic data were analyzed by the multiligand, multisite LIGAND computer program. In plasma of rainbow trout (Salmo gairdneri) homologous ligand displacement indicated that both thyroid hormones (TH) bound to a minimum of two classes of saturable sites and at least one nonsaturable site. For T4 (n = 13) the relative site affinities were 0.61 +/- 0.08 (SEM) X 10(7) M-1 and 0.86 +/- 0.11 X 10(5) M-1 and the site capacities were 8.3 +/- 1.16 X 10(-7) M and 5.15 +/- 1.34 X 10(-5) M, respectively; for T3 (n = 14) the relative site affinities were 1.8 +/- 0.16 X 10(7) M-1 and 1.7 +/- 0.17 X 10(5) M-1 and the site capacities were 7.8 +/- 1.3 X 10(-7) M, respectively. The greater affinities of T3 than T4 for plasma binding sites would explain the lower proportion of free T3 than free T4 in trout plasma. Two-site models with comparable values for TH-binding parameters were determined for brook trout (Salvelinus fontinalis) and arctic charr (Salvelinus alpinus). The TH-binding parameters were uninfluenced by severe hemoglobin contamination of plasma, bleeding of fish 24 hr previously, or 2 weeks starvation. Heterologous ligand displacement (T4 displaced by T3 or T3 displaced by T4) on rainbow trout plasma suggested two low-affinity, high-capacity sites, one binding predominantly T4 and one binding predominantly T3: a high-affinity, low-capacity site binding T3 exclusively: and a high-affinity, low-capacity site binding T4 predominantly but also binding T3 with low affinity.
Gen Comp Endocrinol 1987 Feb
PMID:Kinetics of T4 and T3 binding to plasma sites in salmonid teleost fish. 381 50


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