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PubMed1999

Cytokine signals are sufficient for HIV-1 infection of resting human T lymphocytes.

Lentiviral vectors have been advocated to be effective vehicles for the delivery and stable expression of genes in nondividing primary cells. However, certain cell types, such as resting T lymphocytes, are resistant to infection with HIV-1. Establishing parameters for stable gene delivery into primary human lymphocytes and approaches to overcome the resistance of resting T cells to HIV infection may permit potential gene therapy applications, genetic studies of primary cells in vitro, and a better understanding of the stages of the lentiviral life cycle. Here we demonstrate that an HIV-1-derived vector can be used for stable delivery of genes into activated human T cells as well as natural killer and dendritic cells. Remarkably, a sizeable fraction of resting T cells was stably transduced with the HIV-1 vector when cultured with the cytokine interleukin (IL)-2, IL-4, IL-7, or IL-15, or, at a lower level, with IL-6, in the absence of any other stimuli. Resting T cells stimulated with these cytokines could also be infected with replication-competent HIV-1. To test the utility of this system for performing structure-function analysis in primary T cells, we introduced wild-type as well as a mutant form of murine CD28 into human T cells and showed a requirement for the CD28 cytoplasmic domain in costimulatory signaling. The ability to stably express genes of interest in primary T cells will be a valuable tool for genetic and structure-function studies that previously have been limited to transformed cell lines. In addition, the finding that cytokine signals are sufficient to permit transduction of resting T cells with HIV may be relevant for understanding mechanism of HIV-1 transmission and pathogenesis.

CD4-Positive T-Lymphocytes↗
PubMed1960

Some relations between action potential and resting potential of the lobster giant axon.

Experiments were performed to determine the quantitative relation existing between action potential and resting potential of the lobster giant axon. Resting potential changes were induced by either increasing the external potassium concentration or by reducing the external calcium concentration. For either treatment the action potential amplitude is proportional to the logarithm of the resting potential minus a constant. This constant is equivalent to the minimum resting potential at which a propagated spike is possible, and is larger for depolarization in low calcium than in high potassium. Thus the change in action potential per unit change in resting potential is greater in low external calcium than in high external potassium. Analog computer solutions to the Hodgkin-Huxley equations for squid axon membrane potentials show that, if the initial conditions are properly specified, the action potential is proportional to the logarithm of the potassium potential minus a constant. The experimental results and the analog computations suggest that reducing external calcium produces changes in the invertebrate axon that cannot be accounted for solely on the basis of alterations in the potassium potential.

Action Potentials↗
PubMed1966

Nonelectrolyte penetration and sodium fluxes through the axolemma of resting and stimulated medium sized axons of the squid Doryteuthis plei.

The penetration of (14)C-labeled erythritol, mannitol, and sucrose through the axolemma was determined in medium sized paired axons, one at rest and the other stimulated 25 times per sec. The resting permeabilities, in 10(-7) cm/sec, are erythritol, 2.9 +/- 0.3 (mean +/- SEM); mannitol, 2.3 +/- 0.4; and sucrose 0.9 +/- 0.1. In the stimulated axons they are: erythritol, 5.2 +/- 0.3; mannitol, 4.0 +/- 0.5; and sucrose, 1.8 +/- 0.3. Thus, the calculated permeabilities during activity (1 msec per impulse), in the same units, are: 100, 75, and 38, respectively. These changes in permeability are reversible. The effects of external potassium and sodium concentrations on erythritol penetration were also studied. At rest, erythritol penetration is independent of potassium and sodium concentrations. In the stimulated axons, erythritol penetration decreases when the extracellular sodium is diminished. Sodium influx (not the efflux) decreases during rest and activity when the extracellular sodium is diminished. The diminution during activity of erythritol and sodium entries in low sodium solutions may be related to a decrease of a drag effect of sodium ions on the nonelectrolyte molecules or to independent effects of the sodium concentration on sodium influx and the nonelectrolyte pathways. The axolemma discriminates among erythritol, mannitol, sucrose, and the different ionic species during rest and activity.

Alcohols↗
PubMed2004

Long HIV type 1 reverse transcripts can accumulate stably within resting CD4+ T cells while short ones are degraded.

We utilized quantitative methods to compare the efficiency of reverse transcription and stability of viral DNA within resting and activated T cells. Highly purified resting CD4(+) T cells and activated T cells from healthy donors were spinoculated with HIV-1(YU-2), then cultured in conditions that maintain both the viability and the quiescence of the resting cells. Spreading infection was suppressed, then kinetic PCR was used to relate the rates of synthesis of short (strong-stop, RU5) and long (gag or U3-gag second strand transfer) viral DNA to the mean number of virions initially bound to each type of cell. As shown previously, activated cells support an initial burst of high-level reverse transcription, which is then followed by a approximately 10-fold decay in cDNA levels over 4.5 days. In resting T cells, although the synthesis of late reverse transcripts was initially approximately 1000-fold less efficient than in activated T cells, the number of these cDNAs per bound input virion rose 10-fold as culture was extended to 4.5 days. The number of late reverse transcripts remained constant for 3 days after the addition of efavirinez, reflecting enhanced stability. In contrast, the short strong-step reverse transcripts were mostly degraded. Thus, late HIV-1 reverse transcripts can accumulate stably in resting T cells in the absence of detectable T cell activation. Defining the underlying basis for the stabilization of late reverse transcripts, and their associated nucleoprotein complexes, may be pertinent to the accumulation of reservoirs of latent HIV-1 in patients, and could provide a target for future therapies.

CD4-Positive T-Lymphocytes↗
PubMed1996

Cardiac systolic and diastolic function at rest and exercise in subclinical hypothyroidism: effect of thyroid hormone therapy.

Cardiac atrial and ventricular parameters were determined by Doppler two-dimensional echocardiography at rest and exercise in 8 patients with subclinical hypothyroidism (SCH) (6 women and 2 men; age range: 28-48 years) before and 3 months after achievement of a euthyroid state with incremental adjustment of L-thyroxine therapy. None of the patients had known heart disease. At 3 months of L-thyroxine therapy, TSH levels decreased from 14.8 +/- 9.4 mIU/L to 3.0 +/- 1.5 mIU/L and FTI increased from 7.1 +/- 1.8 to 8.1 +/- 1.9. The cardiac studies were performed at rest, and during incremental exercise load (50, 100, 150 W workload) on a Quinton exercise bicycle. No significant differences were found between the subclinical hypothyroid and euthyroid states in systolic blood pressure at rest (104.8 +/- 12.3 vs 105 +/- 10.1 mm Hg) and exercise (158 +/- 24.9 vs 158.5 +/- 20.9 mm Hg) or diastolic blood pressure at rest (70 +/- 4.7 vs 69 +/- 5.7 mm Hg) and exercise (86 +/- 11.4 vs 89.2 +/- 7.3 mm Hg). All echocardiographic atrial and ventricular parameters were similar before and during L-thyroxine therapy with the exception of a small but significant change in left ventricular diastolic dimension (4.5 +/- 0.3 vs 4.8 +/- 0.4 cm; p < 0.05). All Doppler parameters were not significantly affected by L-thyroxine therapy with the exception of preejection period at stage III exercise (51 +/- 17 vs 39 +/- 13 msec; p < 0.05). Preejection period at other stages of exercise showed trends toward similar differences between subclinical hypothyroidism and euthyroidism, but the differences were not statistically significant. We conclude that the cardiac structure and function overall remains for practical purposes normal in subclinical hypothyroidism. However, the latter may be responsible for a mild prolongation of the preejection period during exercise and a slightly smaller left ventricular diastolic dimension at rest, changes that may not be of clinical significance in patients without underlying heart disease.

Adult↗
PubMed1994

A general population survey of rest cramps.

Two hundred and eighteen subjects, out of 250 individuals taken from a general practice register, returned completed questionnaires giving details about rest cramps, and a further 15 were contacted by telephone. The overall prevalence of rest cramps in the survey population was 37%. The symptom was more prevalent in older subjects. Rest cramps were most commonly experienced in the muscles of the leg, in 83% of the 86 cramp sufferers. Symptoms were usually present at night (73%). On average cramp episodes lasted for 9 min (95%CI 6.7-11.2). Most cramps sufferers experienced symptoms infrequently, but 40% had cramp episodes more than three times per week and 6% complained of at least one episode per day or night. Twenty-one per cent of cramp sufferers described their symptoms as very distressing. A minority, 32% of the 86 cramp sufferers, had reported the symptoms to a general practitioner although the 86 subjects self-rated their health more negatively than the individuals without muscle cramps. There was a significant, positive association between rest cramps and symptoms of angina or intermittent claudication although these two factors only accounted for 12% of the variance, suggesting that peripheral vascular disease may play a relevant but limited role in the aetiology of rest cramps.

Aged↗
PubMed1998

Resting energy expenditure in children in a pediatric intensive care unit: comparison of Harris-Benedict and Talbot predictions with indirect calorimetry values.

The use of prediction equations has been recommended for calculating energy expenditure. We evaluated two equations that predict energy expenditure, each of which were corrected for two different stress factors, and compared the values obtained with those calculated by indirect calorimetry. The subjects were 55 critically ill children on mechanical ventilation. Basal metabolic rates were calculated with the Harris-Benedict and Talbot methods. Measured resting energy expenditure was 4.72 +/- 2.53 MJ/d. The average difference between measured resting energy expenditure and the Harris-Benedict prediction with a stress factor of 1.5 was -0.98 MJ/d, with an SD delta of 1.56 MJ/d and limits of agreement from -4.12 to 2.15; for a stress factor of 1.3 the average difference was -0.22 MJ/d, with an SD delta of 1.57 MJ/d and limits of agreement from -3.37 to 2.93. The average difference between measured resting energy expenditure and the Talbot prediction with a stress factor of 1.5 was -0.23 MJ/d, with an SD delta of 1.36 MJ/d and limits of agreement from -2.95 to 2.48; for a stress factor of 1.3, it was 0.42 MJ/d, with an SD delta of 1.24 MJ/d and limits of agreement from -2.04 to 2.92. These limits of agreement indicate large differences in energy expenditure between the measured value and the prediction estimated for some patients. Therefore, neither the Harris-Benedict nor the Talbot method will predict resting energy expenditure with acceptable precision for clinical use. Indirect calorimetry appears to be the only useful way of determining resting energy expenditure in these patients.

Adult↗
PubMed1978

The effect of beta-adrenoceptor and Ca2+ antagonist drugs on the hypoxia-induced increased in resting tension.

Using isolated, Langendorff-perfused, electrically-paced guinea-pig hearts, we have investigated the rise in resting tension that occurs when mammalian heart muscle becomes hypoxic. Substrate-depletion, tachycardia, hyperthyroidism, and inotropic interventions (ouabain, isoprenaline, and beta-receptor antagonists at concentrations which increase inotropic state) enhanced the rate of development of this increase in resting tension. 3.86 mumol.litre-1 propranolol, 0.22 to 2.20 mumol.litre-1 verapamil or removing Ca2+ from the extracellular phase at the start of the hypoxic episode prevented (or delayed) the rise in resting tension. Adding these same agents or removing Ca2+ from the extracellular phase after the hypoxia-induced rise in resting tension had started to develop failed to prevent its progression. These results provide some support for an hypothesis that the hypoxia-induced increase in resting tension is independent of an enhanced Ca2+ influx.

Adrenergic beta-Antagonists↗
PubMed1993

Angiotensin converting enzyme inhibition at rest and during exercise in congestive heart failure.

The haemodynamic effects of the sulfhydryl-containing angiotensin converting enzyme inhibitor, zofenopril, were studied in patients in New York Heart Association functional class II and III. Twenty-one clinically stable patients with coronary artery disease or cardiomyopathy completed a randomized double-blind treatment period of 2 months with either 15 mg zofenopril once daily or placebo. Regular therapy with digoxin and diuretic drugs was continued. Left ventricular volumes were measured by radionuclide angiography at rest and during submaximal bicycle exercise. Zofenopril significantly increased mean stroke volume at rest from 59 to 67 ml (48 vs 48 ml in the control group, 95% confidence interval of the difference 1 to 16 ml) and left ventricular ejection fraction at rest from 39 to 43% (30 vs 30% in the control group, 95% confidence interval of the difference 1 to 8%). No significant changes occurred in heart rate, cardiac output, and blood pressure at rest, and zofenopril did not result in haemodynamic alterations during exercise. Thus, 15 mg of the sulfhydryl-containing angiotensin converting enzyme inhibitor, zofenopril, administered once daily to patients with moderate heart failure increases left ventricular function at rest, but not during exercise.

Adult↗
PubMed1992

Spatial and temporal distribution of resting female mosquitoes (Diptera: Culicidae) in the coastal plain of North Carolina.

The spatial and temporal distribution of 28 species of female mosquitoes resting in natural (swamp, woods, and swamp-woods ecotone) and human-made (beneath bridges) habitats in blackwater stream-associated ecosystems in Duplin County, N.C., was determined by sampling with a D-Vac vacuum aspirator during 1984 and 1985. Two types of resting distributions were evident. In type one, species including Aedes atlanticus Dyar & Knab, Ae. canadensis (Theobald), Ae. triseriatus (Say), and Psorophora ferox (von Humboldt) rested predominantly on vegetation and were not collected beneath bridges. In type two, species including Anopheles punctipennis (Say), Culex erraticus (Dyar & Knab), Cx. peccator Dyar & Knab, Cx. pipiens L. and Cx. quinquefasciatus Say and their hybrids, Cx. restuans Theobald, Cx. territans Walker, and Uranotaenia sapphirina (Osten Sacken) rested on vegetation, in natural shelters in swamp habitats, and beneath bridges. Differences in the proportion of gravid mosquitoes among habitats were evident for Ae. canadensis, An. punctipennis, Cx. pipiens and Cx. quinquefasciatus and their hybrids, Cx. restuans, Cx. territans, Ps. ferox, and Ur. sapphirina, indicating that gonotrophic condition may influence resting site selection.

Analysis of Variance↗
PubMed1996

The centromere as a target for the induction of chromosome damage in resting and proliferating mammalian cells: assessment of mitomycin C-induced genetic damage at kinetochores and centromeres by a micronucleus test in mouse splenocytes.

The cytokinesis-block micronucleus assay (MN) on murine splenocytes was used for the estimation of chromosome damage in a resting cell population in vivo that can be induced to proliferate in vitro. Mitomycin C at different doses (10(-8), 6 x 10(-8), 10(-7), 6 x 10(-7) and 10(-6)M) was used to induce cytogenetic damage in resting and cycling splenocytes. Antikinetochore antibodies (CREST) and two-colour fluorescence in situ hybridization (FISH) with minor and major satellite DNA were applied. These approaches allowed the detailed characterization of the mechanisms by which MN originates, since it was possible to identify breaks induced in pericentric heterochromatic (resulting in MN containing the major but not the minor satellite DNA) or detachment/disruption of kinetochore (resulting in different frequencies of MN containing kinetochore or both probes). Based on the evidence that resting and cycling mouse splenocytes are characterized by different spatial distribution of centromeric regions, the hypothesis was tested that the damage induced by mutagens at centromeres is influenced by the phase of the cell cycle in which the cells are treated. Data presented here show that resting and cycling splenocytes are both sensitive to mitomycin C action, and indicate that this compound has an aneugenic potential, besides its strong clastogenic activity. In particular, results obtained after CREST and FISH characterization of MN differed when cells were treated during proliferation, suggesting a disruption/detachment of kinetochores induced by mitomycin C at this cell stage. Furthermore, under the same treatment condition the proportion of MN containing the major satellite DNA only was greater than expected on the basis of random breakage at this site. Treatment of resting cells produced aneugenic damage, but without evidence of disruption/detachment of kinetochores or preferential breakage at the centromere. These results indicate that the amount and type of chromosome damage induced by mitomycin C in mouse splenocytes differ in relation to the proliferative status of treated cells.

Animals↗
PubMed2000

REST-VP16 activates multiple neuronal differentiation genes in human NT2 cells.

The RE1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) can repress transcription of a battery of neuronal differentiation genes in non-neuronal cells by binding to a specific consensus DNA sequence present in their regulatory regions. However, REST/NRSF(-/-) mice suggest that the absence of REST/NRSF-dependent repression alone is not sufficient for the expression of these neuronal differentiation genes and that the presence of other promoter/enhancer-specific activators is required. Here we describe the construction of a recombinant transcription factor, REST-VP16, by replacing repressor domains of REST/NRSF with the activation domain of a viral activator VP16. In transient transfection experiments, REST-VP16 was found to operate through RE1 binding site/neuron-restrictive enhancer element (RE1/NRSE), activate plasmid-encoded neuronal promoters in various mammalian cell types and activate cellular REST/NRSF target genes, even in the absence of factors that are otherwise required to activate such genes. Efficient expression of REST-VP16 through adenoviral vectors in NT2 cells, which resemble human committed neuronal progenitor cells, was found to cause activation of multiple neuronal genes that are characteristic markers for neuronal differentiation. Thus, REST-VP16 could be used as a unique tool to study neuronal differentiation pathways and neuronal diseases that arise due to the deregulation of this process.

Adenoviridae↗
PubMed2006

Identification of the REST regulon reveals extensive transposable element-mediated binding site duplication.

The genome-wide mapping of gene-regulatory motifs remains a major goal that will facilitate the modelling of gene-regulatory networks and their evolution. The repressor element 1 is a long, conserved transcription factor-binding site which recruits the transcriptional repressor REST to numerous neuron-specific target genes. REST plays important roles in multiple biological processes and disease states. To map RE1 sites and target genes, we created a position specific scoring matrix representing the RE1 and used it to search the human and mouse genomes. We identified 1301 and 997 RE1s inhuman and mouse genomes, respectively, of which >40% are novel. By employing an ontological analysis we show that REST target genes are significantly enriched in a number of functional classes. Taking the novel REST target gene CACNA1A as an experimental model, we show that it can be regulated by multiple RE1s of different binding affinities, which are only partially conserved between human and mouse. A novel BLAST methodology indicated that many RE1s belong to closely related families. Most of these sequences are associated with transposable elements, leading us to propose that transposon-mediated duplication and insertion of RE1s has led to the acquisition of novel target genes by REST during evolution.

Animals↗
PubMed2005

Dobutamine stress echocardiography and the resting but not exercise electrocardiograph predict severe coronary artery disease in renal transplant candidates.

BACKGROUND: After renal transplantation half of all deaths are cardiac, so prior detection and treatment of severe coronary artery disease (CAD) is advocated. The aim of this study was to identify non-invasive predictors of severe CAD in a group of renal transplant candidates. METHODS: One hundred and twenty-five renal transplant candidates (mean age 52+/-12 years, 80 male, mean creatinine 608+/-272 micromol/l) were studied. All had coronary angiography, dobutamine stress echocardiography, and resting and exercise electrocardiograph (ECG). Severe CAD was defined as luminal stenosis >70% by visual estimation in at least one epicardial artery. The resting ECG was recorded as abnormal if there was evidence of pathological Q waves, left ventricular hypertrophy, ST depression or elevation > or=1 mm, T wave inversion or bundle branch block. Total exercise time, maximal ST segment change, maximal heart rate and systolic blood pressure, limiting symptoms and Duke score were calculated during the exercise ECG test. RESULTS: Of the patients, 36 (29%) had severe CAD, 55% were on dialysis and 39% were diabetic. Patients with severe CAD were significantly older (P<0.001), had higher total cholesterol (P = 0.05), higher CRP level (P = 0.05), larger left ventricular (LV), end systolic and end diastolic diameter (P = 0.007 for each), and lower LV ejection fraction (P = 0.01). A significantly higher percentage were diabetic (P = 0.05), had previous graft failure (P = 0.05), mitral annular calcification (P = 0.04), an abnormal resting ECG (P = 0.001) and positive stress echo result (P<0.001). Cardiac symptoms and exercise ECG parameters were not significantly different in the two groups. Stepwise logistic regression identified an abnormal resting ECG (OR 7, 95% CI 2, 34, P = 0.013) and positive stress echo result (OR 23, 95% CI 6, 88, P<0.001) as independent predictors of severe CAD. CONCLUSIONS: In selecting which potential renal transplant candidates should undergo coronary angiography, resting ECG and dobutamine stress echocardiography are the best predictors of severe CAD.

Adult↗
PubMed1997

Long-term effects of dual chamber pacing in patients with hypertrophic cardiomyopathy without outflow tract obstruction at rest.

BACKGROUND: Atrioventricular-synchronous pacing is beneficial in patients with hypertrophic obstructive cardiomyopathy. The effects of pacing in patients without significant left ventricular outflow tract obstruction at rest are, however, less well explored. This study compares the long-term outcome of pacing patients with and without significant left ventricular outflow tract obstruction at rest. METHODS: Forty-one patients with hypertrophic obstructive cardiomyopathy were studied, 19 with a left ventricular outflow tract gradient < 40 mmHg at rest, but exceeding 50 mmHg during provocation with isoproterenol (group A), and 22 with a left ventricular outflow tract obstruction > 40 mmHg at rest (group B). Before the implantation of a permanent pacemaker, the patients were studied according to a temporary pacing protocol. This included graded isoproterenol provocation of the left ventricular outflow tract obstruction, which was assessed by echo Doppler. Following permanent pacemaker implantation, the patients were regularly followed up with echo Doppler, exercise testing and monitoring of the clinical condition. RESULTS: Isoproterenol provocation was reproducible and the technique did not cause any clinically important side effects. Left ventricular outflow tract gradient reduction after chronic pacing did not differ between the two groups. In group A, it decreased from 98 +/- 30 mmHg in sinus rhythm to 42 +/- 26 mmHg during pacing. The corresponding values in group B were 87 +/- 40 mmHg to 36 +/- 24 mmHg. The clinical condition improved similarly in the two groups. Exercise capacity increased significantly and perceived dyspnoea and angina pectoris were significantly lower at submaximal levels of exercise after 6 months of pacing. CONCLUSION: Hypertrophic obstructive cardiomyopathy patients who only exhibit significant left ventricular outflow tract obstruction during provocation benefit as much from pacemaker treatment as do patients who already have significant obstruction at rest. Isoproterenol is a safe and reproducible method for pre-pacing evaluation of hypertrophic obstructive cardiomyopathy patients.

Adult↗
PubMed1985

Comparison of intravenous digital subtraction cineangiocardiography with conventional contrast ventriculography for the determination of the left ventricular volume at rest and during exercise.

Left ventricular volumes were determined by means of digital subtraction cineangiocardiography (DSA) which was performed in the right anterior oblique projection after contrast agent injection into the superior vena cava. Monoplane end-diastolic (EDV), end-systolic volumes (ESV), and ejection fraction (EF) were calculated using the 'area-length' method and were compared with the same parameters obtained by conventional left ventricular cineangiocardiography. A first group of 20 patients was studied at rest and a second group of 10 patients during bicycle exercise at a work load of 64 watts during 2 min, by DSA and conventional cineangiocardiography. Three different subtraction modes were evaluated: (1) mask mode subtraction (MMS), (2) time interval difference (TID) method and (3) a combination of MMS and TID called MMS + TID method. With the MMS method good correlations were obtained for EDV, ESV and EF at rest (r greater than 0.91) and during exercise (r greater than 0.91). The TID method showed only moderate correlations for patients at rest (r greater than 0.86) and during exercise (r greater than 0.79). Similar results as with MMS were achieved by the combined method (MMS + TID) at rest (r greater than 0.91) and during exercise (r greater than 0.91). Interobserver variability indicated a high reproducibility for all methods except for TID during exercise. It is concluded that DSA is an accurate technique for left ventricular volume determination not only at rest but also during exercise. The best results are obtained with MMS or MMS + TID methods, while left ventricular contour detection is easier and more convenient with MMS + TID.

Adult↗
PubMed2003

Age-related changes in the ultrastructure of the resting follicle pool in human ovaries.

Age-related decline of fertility in women is the result of the decline in both quantity and quality of the resting ovarian follicle pool. The aim of the present study was to determine whether the decline of follicle quality with age is reflected by ultrastructural changes in the resting follicle pool. Ovarian biopsy specimens were obtained by laparoscopy from seven healthy women aged 25-32 yr (young group) and from 11 healthy women aged 38-45 yr (advanced-age group). A total of 182 resting follicles from the young group were compared with 81 resting follicles from the advanced-age group for signs of age-related changes by transmission-electron microscopy. The ooplasmic fraction of vacuoles was increased (P = 0.02), and the fraction of mitochondria decreased (P = 0.005), in the advanced-age group. Also, the density of the mitochondrial matrix (P < 0.001) and the frequency of dilated smooth endoplasmic reticulum (SER; P = 0.001) and Golgi complex (P = 0.02) were increased with age. The frequencies of ruptured mitochondrial membranes (P = 0.001) and dilated SER (P = 0.003) were increased with age in the granulosa cells. Overall follicle-quality scores, which should reflect atretic changes, were not different for the young and advanced-age groups. In conclusion, in resting follicles, the morphological changes with age are different from the changes seen in quality decline by atresia. The morphological changes with age specifically involved the mitochondria, the SER, and the Golgi complex, and they may be the cause of atresia on initiation of follicular growth because of the substantial increase in metabolic requirements.

Adult↗
PubMed2003

Decrease in resting calcium and calcium entry associated with slow-to-fast transition in unloaded rat soleus muscle.

Using fura-2 and the manganese quenching technique, we show here that sarcolemmal permeability to cations (SP-Ca) of slow-twitch muscles is greater than that of fast-twitch ones. This appears to be related to a higher expression and/or activity of stretch-activated channels, whereas leak channel activities are similar. During hindlimb suspension (HU), we found highly correlated decreases in SPCa and resting calcium of soleus muscle toward values of extensor digitorum longus (EDL) muscle. This was significant as soon as 3 days of suspension, contrary to soleus muscle caffeine sensitivity and responsiveness that were not modified after this HU period. After 14 days of HU, SP-Ca, resting calcium, and caffeine response of soleus muscle became similar to that normally observed in EDL muscle. These results demonstrate that the correlated decreases in SP-Ca and resting calcium precede most functional changes due to HU. Given the known shortening of HU soleus muscle, we proposed that this could induce a decrease of SP-Ca and a consequent reduction of resting calcium. According to the crucial role of resting cytosolic free calcium in the maintenance and the adaptation of muscle phenotype, our results suggest that slow-to-fast transition of HU soleus muscle is calcium dependent.

Animals↗