Biomedical subjects
Publications and source records attributed to A Brunet.
A case of osteogenic thyroid carcinoma in a 68 years old male patient is reported. The WHO histopathological classification of such exceptional tumor is reminded. A review of the literature and the treatment modalities are discussed. Several etiological hypotheses are discussed.
The Mitogen Activated Protein Kinase (MAPK) module operates downstream of Ras to convey cell surface signals to the nucleus via the nuclear translocation of p42/p44 MAPKs. We have previously established that MAPK activation is obligatory and must persist in the G1 phase to allow resting fibroblasts to exit from G0 (Pagès et al., Proc. Natl. Acad. Sci.1993, 90, 8319-8323). It remained to be established whether MAPK activation was sufficient to trigger cell proliferation. To this aim, we generated and expressed in Chinese hamster lung fibroblasts, constitutively active mutants of hamster MAP kinase kinase (MAPKK). Three mutants: S218D, S222D and S218D/S222D in which we substituted the Raf1/MAPKKK-dependent regulatory phosphorylation sites by aspartic acid residues, displayed increased basal activity when expressed in fibroblasts. Two of them, S218D and S218D/S222D which have a basal activity higher than serum-stimulated wild type-MAPKK (respectively 2- and 5-fold), induced activation of p42 MAPK in growth factor-deprived cells. Interestingly, only these two mutants led to a growth factor-independent state as judged by early gene transcription (activation of the fos promoter), increased sensitivity to growth factors for reinitiation of DNA synthesis, autonomous cell cycling and rapid tumor formation in nude mice. Therefore we conclude that the downstream elements of the growth factor signalling cascade, MAPKK-MAPK, are both necessary and sufficient to promote growth factor signals and autonomous cell cycling in fibroblasts.
Capillarity, fibre types, fibre area and enzyme activities of different skeletal muscles (pectoralis, extensor digitorum longus), tibialis anterior, plantaris and the myocardium) were compared in Andean coot (Fulica americana peruviana) native to high altitude (Junín, Perú, 4200 m) and the same species nesting at sea level. Numbers of capillaries per square millimeter were higher in all high-altitude muscles when compared with sea-level muscles (P < 0.0001). Moreover, values for capillaries per fibre and capillaries in contact with each fibre were higher in digitorum and tibialis high-altitude muscles. Muscle fibres were classified as Type I, Type IIA or Type IIB on the basis of their myofibrillar ATPase pH lability. Pectoralis muscle of high-altitude and sea-level coots presented only fibres of Type IIA. In contrast, all the leg muscles studied showed a mosaic pattern of the three fibre types. Fibre areas were determined using a Leitz Texture Analysis System. Significant differences in fibre area were observed (P < 0.01) between high-altitude and sea-level muscles. Mean muscle fibre diameters were also lower in the high-altitude group than in the sea-level group. The enzyme activities studied were hexokinase, lactate dehydrogenase, citrate synthase and 3-hydroxyacyl-CoA-dehydrogenase. The oxidative capacity, as reflected by citrate synthetase and hydroxyacyl-CoA-dehydrogenase activities, was greater for myocardial and pectoralis than for leg muscles. However, analysis of maximal enzyme activities showed that there were no significant differences between the glycolytic and oxidative enzyme activities of high-altitude and sea-level coots.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitogen-activated protein kinases (p42mapk and p44mapk) are serine/threonine kinases that are activated rapidly in cells stimulated with various extracellular signals. This activation is mediated via MAP kinase kinase (p45mapkk), a dual specificity kinase which phosphorylates two key regulatory threonine and tyrosine residues of MAP kinases. We reported previously that the persistent phase of MAP kinase activation is essential for mitogenically stimulated cells to pass the "restriction point" of the cell cycle. Here, using specific polyclonal antibodies and transfection of epitope-tagged recombinant MAP kinases we demonstrate that these signaling protein kinases undergo distinct spatio-temporal localization in growth factor-stimulated cells. In G0-arrested hamster fibroblasts the activator p45mapkk and MAP kinases (p42mapk, p44mapk) are mainly cytoplasmic. Subsequent to mitogenic stimulation by serum or alpha-thrombin both MAP kinase isoforms translocate into the nucleus. This translocation is rapid (seen in 15 min), persistent (at least during the entire G1 period up to 6 h), reversible (by removal of the mitogenic stimulus) and apparently 'coupled' to the mitogenic potential; it does not occur in response to nonmitogenic agents such as alpha-thrombin-receptor synthetic peptides and phorbol esters that fail to activate MAP kinases persistently. When p42mapk and p44mapk are expressed stably at high levels, they are found in the nucleus of resting cells; this nuclear localization is also apparent with kinase-deficient mutants (p44mapk T192A or Y194F). In marked contrast the p45mapkk activator remains cytoplasmic even during prolonged growth factor stimulation and even after high expression levels achieved by transfection. We propose that the rapid and persistent nuclear transfer of p42mapk and p44mapk during the entire G0-G1 period is crucial for the function of these kinases in mediating the growth response.
Fifteen normotensive male subjects (age, 27.9 +/- 1.3 years) performed isometric contractions (handgrip) at 15, 30 and 50% maximal voluntary contraction respectively for 7, 3 and 1 min. The contractions were sustained with or without a cold pressor test of the same duration (immersion of one foot in water of 5.2 +/- 0.1 degrees C). At rest, under the influence of a cold pressor test for 3 min, the heart rate increased from 74.3 +/- 2.2 to 83.3 +/- 2.1 beats min-1 (P < 0.001) in less than 10 s, and returned to the control value in 3 min; on the contrary, at the end of 3 min of cold pressor test, the systolic blood pressure was still above the control value (135.5 +/- 4.2 and 121.0 +/- 3.2 mmHg, P < 0.001). During the contractions, there was no significant difference between heart rate and systolic blood pressure values obtained with or without cold pressor test. Similarly, there was no significant change in the concentrations of plasma catecholamines. This absence of cardiovascular effect of cold pressor test associated with isometric contraction (for three relative force levels) is probably due to the increasing importance of sympathetic cardiac activation produced by the contraction with respect to that produced by the cold pressor test, the absence of supplementary changes in total peripheral resistance and a partial reciprocal inhibition of pain produced by the simultaneous performance of these two tests.
The authors report their experience in closure of the pharynx following total laryngectomy or total pharyngolaryngectomy by mean of the TA 55 instrument. The technique is described stressing the particular point of good presentation of the mucosa and the importance of the crossing of the lines of staples when two clips are used. An analysis of 30 cases studies is presented with the results as of the date of removal of the nasogastric catheter and the percentage of fistula. This technique appears to be rapid, safer than conventional methods of closure and less complications have been encountered in this series.
The authors report the case of a 2 month old child in whom a coronary artery fistulae was diagnosed by colour Doppler echocardiography. Routine two-dimensional echocardiography showed a very dilated right coronary artery. Turbulent flow was detected in this vessel by pulsed Doppler echocardiography. Colour Doppler showed the fistulous connection to the inferior wall of the right ventricle. Until recently, this condition could only be diagnosed by selective angiography and coronary arteriography. Although there have been few reports in the literature, colour Doppler echocardiography would seem to be a significant advance in non-invasive diagnosis of abnormal connections of the coronary arteries. It allows the differential diagnosis of coronary aneurysm, ectopic coronary arteries and sinus of Valsalva aneurysms to be excluded. The patients can be followed up by colour Doppler echocardiography and anatomic information can be obtained to guide surgery, notably the site of drainage of the fistula. Coronary artery fistulae presenting clinically with a continuous murmer atypically situated for a patent ductus arteriosus are difficult to detect by conventional echocardiography and usually required cardiac catheterisation and angiography. Color Doppler echocardiography is a valuable non invasive diagnostic tool for this condition. The others report the case of a coronary artery cardiac fistula in a neonate diagnosed by color Doppler echocardiography.
The biochemical, histochemical, and structural changes induced by endurance training and long-term exposure to high altitude were studied in the diaphragm muscle of rats exposed to simulated altitude (HA: n = 16; Pb = 62 kPa, 463 Torr; 4000 m) and compared to animals maintained at sea-level (SL: n = 16). Half of the animals in each group were trained (T) by swimming for 12 weeks, the other half were kept sedentary (S). Except for a small decrease in type I fibres in the HA-S group (-7%, P < 0.05), in favour of type IIab and type IIb fibres, neither high-altitude exposure nor endurance training had an overall affect on fibre type distribution. The mean fibre cross-sectional area was found to be unaffected by altitude and/or chronic exercise. Capillary density was shown to be increased by both high-altitude exposure (P < 0.02) and training (P < 0.001), whereas capillary growth, estimated by the capillary/fibre ratio, was unaffected in both cases. Following endurance training, a modest increase in citrate synthase was shown to occur to the same extent in the HA-T and SL-T groups (+15% and +16% respectively, NS). Hexokinase increased following training (P < 0.05) and high-altitude exposure (P < 0.001). In normoxic and hypoxic animals, endurance training enhanced the ratio of the heart-specific lactate dehydrogenase isozyme LDH1 to total LDH activity (+59%, P < 0.01; +92%, P < 0.05 respectively). It may be hypothesized that the increased glucose phosphorylation capacity observed in diaphragm muscle contributes to the reduction of glycogen utilization during exercise.
After the promising results achieved with immunotherapy in disseminated malignant melanoma, a disease reported to show little response to chemotherapy, use of combination chemotherapy regimens with interferon or interleukin and interferon has been shown to provide higher response rates and responses of longer duration. A few phase I-II trials on monoclonal antibodies have also been reported. However, toxicity is substantial with these complex combination regimens.
The authors report two cases of brain tissue heterotopia in the nasopharynx, without other malformations and, in one of the cases, with a persistent craniopharyngeal canal opening onto the heterotopia. This exceptional malformation is very similar to brain heterotopia in the nose, or "nasal glioma", which is more frequent and less diversified at histology. The malformation is revealed by obstruction of the pharynx with respiratory distress immediately after birth or during the first weeks of life. Total surgical excision provides cure without sequelae. The diagnosis is based on histology. MRI is essential to the diagnostic and pretherapeutic evaluation, notably to avoid missing an ectopic hypophysis, but it is insufficient to diagnose a sphenoidal meningoencephalocele.
Skeletal muscle capillarity expressed as capillary density (CD), and number of capillaries per fibre (C/F), as well as the mean fibre cross-sectional area (FCSA), were determined in the extensor digitorum longus (EDL), plantaris (PLA) and soleus (SOL) muscles of four groups of eight rodents trained on a swimming exercise programme (T) or maintained sedentary (S), at sea level (SL) or at simulated altitude (HA), barometric pressure 61.7 kPa (463 torr) for 12 weeks. It was shown that both HA exposure and endurance training decreased body and skeletal muscles weights (P less than 0.001). However, neither HA exposure nor endurance training induce any variation in relative importance in the skeletal muscle mass. Altitude exposure and endurance training had increasing effects on CD in all muscles studied (P less than 0.001). This study confirms the fact that altitude exposure has no direct effect on capillary development. On the other hand, the capillary supply of the several slow- and fast-twitch skeletal muscles studied is increased by endurance training. This real enhancement in capillary network is ascertained by an increase in the C/F ratio (+7%, +26%, +16%, in PLA, EDL, and SOL muscles, respectively at sea level, and +19.5%, +30%, and +14% respectively at HA). These results indicate that the effects of chronic exercise on skeletal muscle capillarity estimated by the C/F ratio, are greater in an hypobaric environment than in a SL environment.
The effects of endurance training on the skeletal muscle of rats have been studied at sea level and simulated high altitude (4,000 m). Male Wistar rats were randomly assigned to one of four groups: exercise at sea level, exercise at simulated high altitude, sedentary at sea level, and sedentary at high altitude (n = 8 in each group). Training consisted of swimming for 1 h/day in water at 36 degrees C for 14 wk. Training and exposure to a high-altitude environment produced a decrease in body weight (P less than 0.001). There was a significant linear correlation between muscle mass and body weight in the animals of all groups (r = 0.89, P less than 0.001). High-altitude training enhanced the percentage of type IIa fibers in the extensor digitorum longus muscle (EDL, P less than 0.05) and deep portions of the plantaris muscle (dPLA, P less than 0.01). High-altitude training also increased the percentage of type IIab fibers in fast-twitch muscles. These muscles showed marked metabolic adaptations: training increased the activity levels of enzymes involved in the citric acid cycle (citrate synthase, CS) and the beta-oxidation of fatty acids (3 hydroxyacyl CoA dehydrogenase, HAD). This increase occurred mainly at high altitude (36 and 31% for HAD in EDL and PLA muscles; 24 and 31% for CS in EDL and PLA muscles). Training increased the activity of enzymes involved in glucose phosphorylation (hexokinase). High-altitude training decreased lactate dehydrogenase activity. Endurance training performed at high altitude and sea level increased the isozyme 1-to-total lactate dehydrogenase activity ratio to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of training and naftidrofuryl treatment were observed in 21-month-old Long-Evans rats. Rats were injected intraperitoneally twice daily for 8 weeks with 7 mg.kg-1 of naftidrofuryl acid (SN, TN), or with 7 mg.kg-1 fumaric acid (SC and TC) or used as solvent. Training groups (TC, TN) started a progressive 8-week training programme of treadmill exercise. The activities of lactate dehydrogenase (LDH), hexokinase (HK), citrate synthase (CS) and 3-hydroxyacyl-Co-A-dehydrogenase (HAD), were measured in Soleus (SOL), Extensor Digitorum Longus (EDL) and Diaphragm (DIA) muscles. The mean VO2max value was 65 ml.min-1.kg-1 for 21-month-old rats. The training protocol induced increases in the mean VO2max values in the TC and TN groups, 71.8 and 74.4 ml.min-1.kg-1. In sedentary groups (SN), naftidrofuryl increased enzymatic activities (HK, CS, HAD) in the three muscles examined. When the animals underwent 8 weeks of physical training, the enzymatic activities (HK, CS, HAD) increased in SOL, EDL and DIA. When training was combined with naftidrofuryl treatment the increases in enzymatic activities were greater than those induced by training alone. However, the total changes did not differ for the sum of the changes produced by each condition alone.
We tested a hypothesis from parallel distributed processing theory that highly hypnotizable subjects have greater connection strengths along verbal pathways and would show greater Stroop effects than low hypnotizable subjects. Using Cheesman & Merikle's (1986) paradigm, which varied cue visibility and probability, we assessed automatic and strategic effects on Stroop performance. Compared with 9 low and 9 moderately hypnotizable subjects, 9 highly hypnotizable ones showed significantly greater Stroop effects for both visible- and degraded-word trials. No strategic differences emerged for the 3 hypnotizability groups. These findings support the contention that highly hypnotizable persons have stronger verbal connection strengths than their moderately and low susceptible counterparts, and they may account for highly hypnotizable persons' propensity to disregard personal attributions and label their responses in hypnosis as being involuntary.
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We describe our technique of augmentation rhinoplasty with bone grafting. Degloving is used as the surgical access in collapsed noses, and midcolumellar incision allows further buildup of the nasal contour. A V cutting is made on the dorsum to receive the graft. A split skull graft is taken with a drill and an osteotome. The sculpted bone implant is maintained in position with a miniaturized screw. We compare various bone grafts and types of surgical access.
To examine how different kinds of activity affect the composition and contractile properties of aging skeletal muscle, old male rats were strength and swim trained. The mass of weights lifted during the strength training increased by 85 +/- 9% (P less than 0.05), which was accompanied by an increase by 32 +/- 5% (P less than 0.05) of the estimated force developed. The wet muscle weight of the soleus and the plantaris decreased significantly with age. The phenomenon was counteracted but not neutralized by the strength training. Twitch and tetanic tension also decreased significantly with age in both the soleus and plantaris muscle. This was avoided by the strength training. This training also significantly decreased time to peak tension and half-relaxation time of both muscles. The swim training increased the heart-to-body weight ratio by 21 +/- 5% (P less than 0.05) and the endurance of the soleus muscle. Time to peak tension and triosephosphate dehydrogenase activity of the plantaris muscle were strongly correlated (P less than 0.001) with myosin adenosinetriphosphatase activity. The results show that the composition and contractile properties of old skeletal muscle are considerably affected by strength training repeated during a substantial period of old age, whereas swim training only affects the endurance of the skeletal muscle.
Male Wistar rats were strength and swim trained during a substantial period of old age to determine the influence of aging and activity on the histochemical and metabolic characteristics of a predominantly slow (soleus) and a predominantly fast (plantaris) skeletal muscle. Strength training counteracted the age-related atrophy of the fibers and the age-induced changes in fiber-type distribution of both muscles. Swim training, on the other hand, was without any effect on these parameters. The activity of both mitochondrial and cytoplasmic enzymes became lower with aging in the soleus muscle, whereas only the activity of the cytoplasmic enzymes became lower in the plantaris. Strength training reduced the aerobic capacity of both muscles, whereas swim training had the opposite effect. Aging induced a lower glycogen concentration of the lateral gastrocnemius muscle. This was avoided by swim training. The phosphocreatine and adenosine 5'-triphosphate concentrations were unchanged with aging but became higher with strength training. The activity pattern, therefore, seems to have a considerable influence on the age-related modification of the histochemical and metabolic characteristics of skeletal muscles of the rat. The effect, however, is related to the recruitment pattern of the fiber populations and the form of activity.