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Biomedical subjects

A Keller

Publications and source records attributed to A Keller.

At least 109 records · Page 6Linked to original sources
PubMed1996

Postoperative irradiation treatment and bioresorbable implants in orthopaedic surgery: an experimental in vitro study.

The influence of applied radiation on the degradation of a polyglycolide (PGA) test specimen was studied in vitro. There was no significant difference in the time-dependent degradation behaviour between the irradiated test specimen and controls. Mandatory irradiation of an operation site following surgery therefore does not contradict the employment of bioresorbable implants in orthopaedic surgery.

Absorption↗
PubMed1996

Spectral analysis of ventricular fibrillation and closed-chest cardiopulmonary resuscitation.

This study was designed to assess the interference by closed-chest cardiopulmonary resuscitation (CPR) on the ventricular fibrillation (VF) ECG signal in a porcine model of cardiac arrest and to elucidate which variable of VF spectral analysis reflects best myocardial blood flow and resuscitation success during CPR. Fourteen domestic pigs were allocated to receive either 0.4 U/kg vasopressin (n = 7) or 10 ml saline (n = 7) after 4 min of VF and 3 min of CPR. Using radiolabeled microspheres, myocardial blood flow was determined during CPR before, and 90 s and 5 min after, drug administration. Using spectral analysis of VF, the median frequency, dominant frequency, edge frequency and amplitude of VF were determined simultaneously and before the first defibrillation attempt. Using filters in order to specify frequency ranges, stepwise elimination of mechanical artifacts resulting from CPR revealed that at a frequency bandpass of 4.3-35 Hz, median fibrillation frequency has a sensitivity, specificity, positive and negative predictive value of 100% to differentiate between resuscitated and non-resuscitated animals. The best correlation between myocardial blood flow and fibrillation frequency was found at a median frequency range of 4.3-35 Hz. We conclude that spectral analysis of VF can provide reliable information relating to successful resuscitation. In this model after elimination of oscillations due to mechanical CPR, median fibrillation frequency best reflects the probability of resuscitation success.

Analysis of Variance↗
PubMed1996

Expression of the neuron-specific enolase gene by rat oligodendroglial cells during their differentiation.

We have examined the regulation of neuron-specific gamma-enolase gene (NSE) expression in oligodendrocytes at various steps of their differentiation/maturation. We have demonstrated for the first time that NSE is expressed in oligodendroglial cells in vitro and in vivo, and only at a certain stage of differentiation. A heterogeneity of the gamma subunit was observed in cultured oligodendrocytes and the same one was found in adult rat brain. The level of gamma mRNA increased when precursor cells differentiated into oligodendrocytes. By contrast, no significant change in alpha-enolase gene expression was observed. High NSE (gamma gamma and alpha gamma) enolase activity was detected in cultured oligodendrocytes. Treatment with basic fibroblast growth factor, which stimulates the proliferation of oligodendrocyte precursor cells and reversibly blocks their differentiation, resulted in lower alpha gamma- and gamma gamma-enolase activities in these cells, but it enhanced alpha alpha-enolase activity slightly. These data indicate that gamma-enolase gene expression is associated with the differentiation of the oligodendrocytes and that it is repressed in adult fully mature cells.

Aging↗
PubMed1996

[Primary unrecognized gunshot wound in the frontal skull base].

BACKGROUND: Craniocerebral gunshot wounds demand a high degree of skill in clinical treatment. In addition to painstaking history, modern imaging techniques for preoperative diagnosis and interdisciplinary surgical treatment are important. CASE REPORT: Diagnosis and therapeutic principles are discussed on the basis of a case study of a 21-year-old soldier with an unusual craniocerebral gunshot wound.

Adult↗
PubMed1996

Lamivudine in children with human immunodeficiency virus infection: a phase I/II study. The National Cancer Institute Pediatric Branch-Human Immunodeficiency Virus Working Group.

The safety, tolerability, pharmacokinetic profile, and preliminary activity of lamivudine (2'-deoxy-3'-thiacytidine), a novel cytidine nucleoside analogue with antiretroviral activity, in human immunodeficiency virus (HIV)-infected children beyond the neonatal period were studied. Ninety children received dosages of 1-20 mg/kg/day. Pharmacokinetic evaluation demonstrated serum and cerebrospinal fluid concentrations that increased proportionally to dose. As of January 1994, 11 children had been withdrawn from study for disease progression and 10 because of possible lamivudine-related toxicity, and 6 had died. CD4 and CD8 cell counts remained stable over 24 weeks in therapy-naive children and decrease slightly in previously treated children. Quantitative immune complex-dissociated p24 antigen and HIV RNA were decreased significantly at 12 and 24 weeks. In vitro resistance to lamivudine was documented in sequential virus isolates from some patients by 12 weeks. Lamivudine was well-tolerated and exhibited virologic activity in children, although future use in children is likely to be in combination antiretroviral regimens.

Adolescent↗
PubMed1996

Effects of graded doses of vasopressin on median fibrillation frequency in a porcine model of cardiopulmonary resuscitation: results of a prospective, randomized, controlled trial.

OBJECTIVE: To assess the effects of graded doses of vasopressin vs. saline on median fibrillation frequency and defibrillation success in a porcine model of cardiopulmonary resuscitation. DESIGN: Prospective, randomized, controlled trial. SETTING: Animal laboratory in a university medical center. SUBJECTS: Twenty-eight domestic pigs (body weight between 26 and 31 kg), aged 12 to 14 wks. INTERVENTIONS AND MAIN RESULTS: After 4 mins of ventricular fibrillation and 3 mins of closed-chest cardiopulmonary resuscitation, the animals were allocated to receive either 0.2 U/kg of vasopressin (n = 7), 0.4 U/kg of vasopressin (n = 7), 0.8 U/kg of vasopressin (n = 7), or 10 mL of saline (n = 7, control group). Using radiolabeled microspheres, myocardial blood flow rates during cardiopulmonary resuscitation-before drug administration and 90 secs and 5 mins after drug administration-were as follows in the four groups (mean +/- SEM): 18.8 +/- 0.9, 17.2 +/- 1.1, and 14.6 +/- 1.4 mL/min/100 g in the control group; 17.8 +/- 2.2, 49.6 +/- 6.3 (p < .01 vs. control group), and 29.4 +/- 3.1 mL/min/100 g (p < .05 vs. control group) in the group receiving 0.2 U/kg of vasopressin; 17.1 +/- 1.0, 52.4 +/- 7.5 (p < .01 vs. control group), and 52.2 +/- 5.8 mL/min/100 g (p < .001 vs. control group) in the group receiving 0.4 U/kg of vasopressin; and 18.1 +/- 1.6, 94.9 +/- 9.2 (p < .001 vs. control group), and 57.2 +/- 6.3 mL/min/100 g (p < .001 vs. control group) in the group receiving 0.8 U/kg of vasopressin. Using spectral analysis, median frequencies of ventricular fibrillation-before drug administration and 90 secs and 5 mins after drug administration-were as follows in the four groups: 9.6 +/- 0.4, 8.5 +/- 0.8, and 7.2 +/- 1.0 Hz in the control group; 9.7 +/- 0.5, 12.9 +/- 0.8 (p < .01 vs. control group), and 12.7 +/- 0.8 Hz (p < .001 vs. control group) in the group receiving 0.2 U/kg of vasopressin; 10.3 +/- 0.2, 12.7 +/- 0.9 (p < .01 vs. control group), and 12.8 +/- 0.7 Hz (p < .001 vs. control group) in the group receiving 0.4 U/kg of vasopressin; and 10.0 +/- 0.9, 14.1 +/- 0.9 (p < .001 vs. control group), and 12.5 +/- 0.9 Hz (p < .001 vs. control group) in the group receiving 0.8 U/kg of vasopressin at the same points in time. Median frequency before the first defibrillation attempt was 12.3 +/- 0.4 Hz in the resuscitated animals (n = 19) and 8.2 +/- 1.2 Hz in the nonresuscitated animals (n = 9) (p < .001). CONCLUSIONS: This study contributes to the characterization of the effect of increasing global myocardial blood flow on median fibrillation frequency after administration of graded doses of vasopressin in a porcine model of ventricular fibrillation. Interventions such as vasopressor treatment that increase fibrillation frequency improve the chance of successful defibrillation.

Animals↗
PubMed1996

Cardiovascular function during the postresuscitation phase after cardiac arrest in pigs: a comparison of epinephrine versus vasopressin.

OBJECTIVE: The administration of vasopressin during cardiopulmonary resuscitation (CPR) provides significantly more vital organ blood flow when compared with epinephrine during cardiac arrest in pigs. The effects of this potent vasoconstrictor on postresuscitation cardiovascular function remain unknown. The purpose of this study was to compare the effects of vasopressin and epinephrine on cardiovascular function in the postresuscitation phase after CPR. DESIGN: Prospective, randomized, experimental study. SETTING: University research laboratory. SUBJECTS: Domestic pigs, 12 to 14 wks of age. INTERVENTIONS: Sixteen pigs were randomly allocated to receive either 0.045 mg/kg of epinephrine or 0.4 U/kg of vasopressin after 4 mins of cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, left ventricular contractility, and myocardial blood flow were measured for an interval of 240 mins after successful CPR. Differences between animals treated with epinephrine vs. vasopressin were most pronounced 15 mins after restoration of spontaneous circulation. At this time, mean aortic pressure was 64 +/- 6 (SEM) mm Hg in the epinephrine group and 84 +/- 6 mm Hg (p < .05) in the vasopressin group. Systemic vascular resistance was 1285 +/- 72 dyne.sec/cm5 in the epinephrine group and 2314 +/- 130 dyne.sec/cm5 (p < .001) in the vasopressin group. Cardiac index was 140 +/- 9 mL/min/kg in animals treated with epinephrine and 99 +/- 9 mL/min/kg (p < .01) in animals treated with vasopressin. Myocardial contractility (dp/ dtmax/P) was 52.8 +/- 3.4/sec with epinephrine as compared with 36.3 +/- 2.9 sec-1 (p < .01) with vasopressin. Left ventricular epicardial blood flow was 241 +/- 35 mL/min/100 g with epinephrine and 142 +/- 22 mL/min/100 g (p < .05) with vasopressin. Four hours after CPR, no significant differences were observed between groups. CONCLUSIONS: In the early postresuscitation phase, vasopressin provided higher systemic blood pressures and there was a reversible depressant effect on myocardial function when compared with epinephrine. Overall cardiovascular function was not irreversibly or critically impaired after the administration of vasopressin in this pig model of cardiac arrest.

Animals↗
PubMed1996

Reported alcohol use and behavior in long-distance runners.

Because alcohol may impair sports performance, we hypothesized there would be less drinking in serious recreational runners. We used mailed questionnaires to examine drinking patterns (2-wk quantity/frequency), scores on modified versions of the Michigan Alcoholism Screening Test (brief MAST [BMAST], short MAST [SMAST]), and parental history of problem drinking in 397 men and 144 women runners participating in a 20-mile race, compared with a nonexercising control population of 138 men and 119 women. A subset of 188 pairs (104 men, 84 women) were matched for gender, age, educational level, and marital status. We used chi-square analysis, paired t-test, and ANOVA. Male gender, running, and a family history for problem drinking predicted increased total alcohol consumption. We found that male runners (vs male controls) drank more 14.2 +/- 19.6 vs 5.4 +/- 7.6 drinks.wk-2, P = 0.004) and felt guilty about their drinking (26.6% vs 13.8%, P < 0.01). Men and women runners reported more occasions of drinking than matched controls (2.8 +/- 2.7 vs 2.0 +/- 2.3.wk-2, P = 0.004). Runners with scores on the BMAST (> or = 6) or SMAST (> or = 3) suggestive of a history of problem drinking drank less than controls with a similar score. Contrary to our hypothesis, running is associated with increased alcohol consumption, except in those who report a history of problem alcohol behavior.

Adult↗
PubMed1996

Release of endogenous vasopressors during and after cardiopulmonary resuscitation.

OBJECTIVE: To assess whether plasma endothelin, adrenaline, noradrenaline, arginine vasopressin, adrenocorticotropin, and cortisol concentrations were higher during cardiopulmonary resuscitation in patients in whom resuscitation was successful than in those in whom it failed, and to measure the concentrations of these hormones in the immediate post-resuscitation phase. DESIGN: Prospective, descriptive study. SETTING: Emergency medical service at a university hospital. PATIENTS: 60 patients with cardiac arrest out of hospital. INTERVENTIONS: Blood samples were drawn and blood pressure and heart rate were measured during cardiopulmonary resuscitation, before and after the first dose of adrenaline was given and at 5, 15, 30, and 60 minutes after the restoration of spontaneous circulation. Plasma hormone concentrations were measured by radio-immunoassays. RESULTS: 24 of the 60 patients were successfully resuscitated and admitted to hospital: 36 were not. During cardiopulmonary resuscitation before adrenaline was given, the plasma concentration of endothelin (mean (SEM)) in resuscitated and in not resuscitated patients was 4.3 (0.9) pg/ml and 5.5 (0.4) pg/ml respectively (NS), adrenaline was 14.1 (2.0) ng/ml and 25.3 (3.6) ng/ml (P < 0.01), noradrenaline was 5.0 (0.9 ng/ml) and 8.4 (1.1 ng/ml) (P < 0.05), arginine vasopressin was 193 (28) pg/ml and 70 (9) pg/ml (P < 0.001), adrenocorticotropin was 128 (34) pg/ml and 57 (6) pg/ml (P < 0.05), and cortisol was 18 (3) microgram/dl and 15 (2) microgram/dl (NS). During cardiopulmonary resuscitation after adrenaline was given endothelin in resuscitated and in not resuscitated patients was 4.0 (1.0) pg/ml and 5.3 (0.5) pg/ml (NS), adrenaline was 145 (16) ng/ml and 201 (21) ng/ml (P < 0.05), noradrenaline was 3.9 (0.9) ng/ml and 8.3 (1.1) ng/ml (P < 0.01), arginine vasopressin was 177 (27) pg/ml and 58 (9) pg/ml (P < 0.001), adrenocorticotropin was 234 (92) pg/ml and 85 (9) pg/ml (P < 0.001), and cortisol was 17 (2) microgram/dl and 13 (2) microgram/dl (NS). CONCLUSIONS: Despite a tremendous adrenosympathetic response, the lower arginine vasopressin and adrenocorticotropin concentrations during cardiopulmonary resuscitation in patients in whom resuscitation failed may influence vital organ perfusion and hence the success of resuscitation. Plasma concentrations of arginine vasopressin and adrenocorticotropin may have a more important effect on outcome than previously thought.

Adrenocorticotropic Hormone↗
PubMed1996

Cerebral oxygenation during cardiopulmonary resuscitation with epinephrine and vasopressin in pigs.

BACKGROUND AND PURPOSE: Administration of vasopressin during cardiopulmonary resuscitation (CPR) improves vital organ blood flow compared with epinephrine, but the effect of vasopressin on cerebral oxygenation and cerebral venous hypercarbia during CPR has not previously been studied. METHODS: Fourteen pigs were allocated to receive either epinephrine (0.2 mg/kg) or vasopressin (0.4 U/kg) after 4 minutes of ventricular fibrillation and 3 minutes of CPR. Cerebral blood flow was determined by radiolabeled microspheres, and arterial and cerebral venous blood gases were measured. RESULTS: Cerebral blood flow, measured before and 90 seconds and 5 minutes after drug administration, was 9 (3; 12), 25 (19; 27), and 18 (10; 23) mL/min per 100 g (median and 25th and 75th percentiles, respectively) in the epinephrine group and 12 (5; 16), 51 (48; 70), and 53 (45; 63) mL/min per 100 g in the vasopressin group (P<.05 at 90 seconds, P<.01 at 5 minutes between groups). Five minutes after drug administration, cerebral venous Pco2 was 63 (59; 68) mm Hg in the epinephrine group and 47 (43; 55) mm Hg in the vasopressin group (P<.01); at the same time cerebral venous pH was 7.18 (7.17; 7.20) and 7.26 (7.22; 7.36) (P<.01) in the epinephrine and vasopressin groups, respectively. Cerebral oxygen extraction ratio, calculated before and 90 seconds and 5 minutes after drug administration, was 0.42 (0.32; 0.57), 0.47 (0.41; 0.57), and 0.56 (0.56; 0.64) in the epinephrine group and 0.43 (0.38; 0.45), 0.38 (0.25; 0.44), and 0.35 (0.33; 0.49) in the vasopressin group (P<.05 at 90 seconds and 5 minutes). CONCLUSIONS: Compared with epinephrine, vasopressin not only increases cerebral blood flow but also improves cerebral oxygenation and decreases cerebral venous hypercarbia when administered during CPR in pigs.

Acid-Base Equilibrium↗
PubMed1996

Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease.

PURPOSE: To evaluate retrospectively the cumulative risk probability and factors correlated with renal dysfunction after allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From October 1984 to July 1994, 84 patients with malignant hematopoietic diseases received allogeneic BMT after conditioning with high-dose chemotherapy and total-body irradiation (TBI). Seventy-nine patients with normal renal function before conditioning are included in this study. Conditioning included high-dose cyclophosphamide without (n = 46) or with (n = 33) other agents (daunorubicin, busulfan, cytarabine, and thiotepa) followed by TBI. The TBI dose prescribed to the center of the abdomen was 10 Gy for 24 patients, 12 Gy for 32, and 13.5 Gy for 23. In vitro T-cell depletion was undertaken in 48 cases. The post-BMT nephrotoxicity of aminoglycosides, vancomycin, amphotericin, and cyclosporine was assessed. Time to renal dysfunction was defined as the time to a persistent increase of serum creatinine (SCr) level greater than 110 mumol/L. The potential influence of sex, age, diagnosis, chimerism, and graft-versus-host disease (GvHD) on renal dysfunction was also assessed. RESULTS: The 18-month probability of renal dysfunction-free survival (RDFS) for the whole group was 77%. Only TBI dose and presence of GvHD were significantly correlated with renal dysfunction by multivariate analysis. The 18-month probabilities of RDFS were 95%, 74%, and 55% for the patients conditioned with 10, 12, and 13.5 Gy, respectively. The 18-month RDFS probabilities were 88% and 61% for patients without and with GvHD, respectively. Combining both variables, we have defined two risk categories: low-risk (ie, 10 Gy TBI with/without GvHD and 12 Gy TBI without GvHD) and high-risk (ie, 12 Gy TBI with GvHD and 13.5 Gy TBI with/without GvHD). The predicted 18-month RDFS rates were 93% and 52% for the low- and high-risk groups, respectively. CONCLUSION: Renal dysfunction after allogeneic BMT is strongly related to the delivered TBI dose (and dose per fraction) and to the presence of GvHD. Renal shielding should be recommended if a TBI dose greater than 12 Gy (fractionated twice daily over 3 days) is to be prescribed. Furthermore, in those cases with a high risk of developing GvHD (eg, unrelated allogeneic BMT, absence of T-cell depletion), these data suggest that kidney doses greater than 10 Gy should be avoided.

Adolescent↗
PubMed1996

Resistance to (-)-2',3'-dideoxy-3'-thiacytidine (3TC) in HIV-1 isolated from paediatric patients.

We conducted detailed virological evaluations of 16 HIV-1-infected paediatric patients treated with 3TC (lamivudine) monotherapy. High-level phenotypic resistance against this compound (up to 2,500-fold) was seen in virtually all cases, usually within 8-12 weeks of initiation of therapy. This was concomitant with the appearance of the M184V mutation in viral reverse transcriptase, previously shown to be responsiblefor such resistance. Viral burden fell in virtually all cases after commencement of therapy, and remained below baseline in each instance studied, despite a rebound effect and the appearance of drug resistance. Viral isolates from some patients underwent a switch from a non-syncytium-inducing (NSI) to a syncytium-inducing (SI) phenotype during the course of the study, although no relationship was apparent between dose of drug employed, time to development of drug resistance or time of appearance of SI phenotype.

Anti-HIV Agents↗
PubMed1995

LTP in the barrel cortex of adult rats.

Intrinsic circuitry in the barrel cortex has been shown to be readily modifiable in response to changes in the patterns of sensory input, even in adult animals. It is believed that sensory experience modifies synaptic circuits by imposing specific patterns of repetitive presynaptic and postsynaptic coactivity, i.e. by LTP-like processes. However, the ability of intrinsic cynapses in the adult barrel cortex to express LTP has not been demonstrated. In slices from barrel cortex of adult rats, we show that input-specific LTP can be induced in the supragranular layers by tetanic stimulation of intracortical vertical and horizontal inputs.

2-Amino-5-phosphonovalerate↗
PubMed1995

Post-transfusion hepatitis revisited.

OBJECTIVE: To evaluate the risk of post-transfusion and postoperative non-A non-B hepatitis in Australia immediately before the introduction of screening for hepatitis C. DESIGN: Retrospective testing of blood samples from a prospective study of cardiac surgery patients. Samples were taken from transfusion recipients and non-transfused controls at regular intervals for 12 months after surgery during 1987-1989. For all donor, recipient and control samples, alanine aminotransferase (ALT) levels were measured and tests for antibody to hepatitis B (anti-HBc, anti-HBs) and, when available, to hepatitis C (anti-HCV) were performed. SETTING: Cardiac surgery units. PARTICIPANTS: Participants were included if they lived in the metropolitan area, and had not had a transfusion in the past year. MAIN OUTCOME MEASURES: Post-transfusion hepatitis (two consecutive samples showing raised ALT levels, > 90 IU/L with no other known cause); hepatitis C infection and carriage (antibody to hepatitis C). RESULTS: Post-transfusion hepatitis occurred in 1.1% of 736 recipients of blood not screened for hepatitis C (i.e., two cases per 1000 unscreened units given). No hepatitis occurred in 514 controls. Seven of the eight patients with post-transfusion hepatitis seroconverted to hepatitis C virus infection. Seven of the 26 anti-HCV-positive donations transmitted hepatitis C, six of these were positive by recombinant immunoblot assay (RIBA) (one by second generation testing only) and one was RIBA indeterminate. Nineteen were RIBA non-reactive; one transmitted hepatitis but the recipient did not develop anti-HCV, although hepatitis C RNA was detected in the donation. Serum ALT was raised in four of the six infective donations. CONCLUSIONS: Hepatitis C virus infection accounted for almost all cases of non-A non-B post-transfusion hepatitis. First generation anti-HCV tests detected about 85% of infective donations. Surrogate testing of donations by ALT or anti-HBc offers no additional advantage.

Alanine Transaminase↗
PubMed1995

Effects of insulin-like growth factor (IGF) binding proteins (BPs) -3 and -6 on DNA synthesis of rat osteoblasts: further evidence for a role of auto-/paracrine IGF I but not IGF II in stimulating osteoblast growth.

IGFBP-3 and IGFBP-6 were used to study whether both IGF I and IGF II play a role in auto-/paracrine stimulation of rat osteoblast growth. Both IGFBPs decreased basal DNA synthesis in neonatal rat calvaria cells but with different potencies. Consistent with their IGF binding affinities, IGFBP-3 blocked both IGF I- and IGF II-stimulated DNA synthesis, whereas IGFBP-6 preferentially blocked IGF II-stimulated DNA synthesis. These inhibitory effects of the two IGFBPs can be fully explained by the sequestration of IGFs. Because IGFBP-6 preferentially binds IGF II and is much less potent than IGFBP-3 in decreasing basal DNA synthesis in calvaria cells, IGF I but not IGF II appears to be an important auto-/paracrine stimulator of DNA synthesis.

Animals↗
PubMed1995

[Long-term therapy with a retard theophylline preparation].

The present study was conducted to investigate the therapeutic effect of long-term treatment with a slow-release theophylline preparation on the pulmonary functions FEV1 and peak exspiratory flow (PEF). A total of 908 patients took part in this open multicenter study. Treatment with the slow-release theophylline resulted in an increase of FEV1 and PEF of about 20% in asthma and between 11% and 14% in COPD. Apart from theophylline itself, the galenic nature of the slow-release formulation also contributed to the therapeutic effect.

Delayed-Action Preparations↗
PubMed1995

Transcriptional up-regulation of the mouse gene for the muscle-specific subunit of enolase during terminal differentiation of myogenic cells.

The glycolytic enzyme enolase (EC 4.2.1.11) exists as dimers formed from three structurally related subunits alpha, beta, and gamma, encoded by separate genes. The gene encoding the beta-subunit is expressed only in striated muscles. We have previously shown that the beta-enolase gene belongs to a small subset of muscle-specific genes showing transcriptional activity in cultured myoblasts, prior to withdrawal from the cell cycle. An increase in the level of beta-enolase mRNA occurs during terminal differentiation of myoblasts. To investigate the mechanisms underlying this increase, we have simultaneously estimated, under steady state conditions, the rate of synthesis and the stability of beta-enolase mRNA in proliferating C2.7 myoblasts as well as in differentiating myotubes. The method used is based on the isolation of newly synthesized RNA from the total RNA pool, following pulse-labeling of intact cells in the presence of 4-thiouridine. The results described here demonstrate a coordinate increase in newly synthesized and total beta-enolase mRNA, while the mRNA half-life, about 4 hr, remains unchanged in the course of terminal differentiation. The expression of the gene for insulin-like growth factor-II (IGF-II), a major positive regulator of myogenesis, was analyzed using the same approach. It is concluded that the up-regulation of beta-enolase as well as IGF-II gene expression in differentiating muscle cells reflects an increased rate of entry of newly synthesized mRNAs into the general pool of transcripts without changes in their respective half-lives.

Animals↗