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Biomedical subjects

F Haddad

Publications and source records attributed to F Haddad.

At least 91 records · Page 5Linked to original sources
PubMed1995

Control of beta-myosin heavy chain expression in systemic hypertension and caloric restriction in the rat heart.

In the rat left ventricle, both pressure overload induced by abdominal aortic constriction (Abcon) and caloric restriction (CR) induce an increase in the steady-state level of the beta-myosin heavy chain (MHC) protein and mRNA. Both models also induce a concomitant decrease in the alpha-MHC protein and mRNA. The goals of this study were to 1) determine if the changes in MHC expression in the models are due to altered transcription and 2) identify the relative levels of some key factors interacting with the regulatory regions of these genes. Female Sprague-Dawley rats were randomly assigned to the following groups: 1) normal control (NC), 2) Abcon, and 3) CR. After 5 wk of experimental manipulations, myocardial nuclei were isolated. These nuclei were used for 1) nuclear run-on assays or 2) nuclear extract, which was prepared and used for gel mobility shift assays (GMSAs). Nuclear run-on assays demonstrated that the increase in beta-MHC mRNA and protein expression in both Abcon and CR can be at least partially attributed to increased transcription. The concomitant decrease in alpha-MHC content can similarly be attributed to a decrease in transcription of this gene. Furthermore, GMSAs demonstrate that nuclear extract from each group interact differently with certain elements known to be important for expression in vitro. CR nuclear extracts have a 25.6 +/- 7.2% decrease (P < 0.05 vs. NC) in interaction with a thyroid-responsive element, a potential repressor of beta-MHC transcription.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Pressure-induced regulation of myosin expression in rodent heart.

A study was undertaken to determine how variations in chronic pressure overload imposed on the left ventricle (LV) regulate both its mass and the relative level of expression of the slow beta-myosin heavy chain (MHC) in rodents. Systemic mean arterial pressure was varied by the following interventions: 1) abdominal aortic constriction (AbCon), 2) unilateral nephrectomy coupled with salt and deoxycorticoacetate treatment (Nx-D), and 3) treatment with the angiotensin II-converting enzyme inhibitor captopril (50 mg.kg-1.day-1) in combination with the other interventions. Results showed that both AbCon and Nx-D induced significant elevations in both beta-MHC protein and mRNA expression relative to the control state. beta-MHC expression (protein and mRNA) strongly correlated with blood pressure as well as LV mass over a wide range. Although captopril treatment significantly reversed the elevations in mean arterial pressure, LV mass, and beta-MHC content in the AbCon group, it had very little effect on these variables in the Nx-D group. Collectively, the results demonstrate that the expression of beta-MHC in the rodent heart is strongly dependent on the arterial pressure imposed on LV. Although the underlying mechanisms have not been elucidated fully as to how alterations in blood pressure are translated to the regulation of the beta-MHC gene expression, these findings suggest that the renin-angiotensin system is not an obligatory factor for inducing cardiac hypertrophy or beta-MHC expression in some models of hypertension.

Animals↗
PubMed1995

Functional and cellular adaptations of rodent skeletal muscle to weightlessness.

Microgravity perturbs a wide variety of physiological systems. Specifically, skeletal muscle has been shown to undergo dramatic changes even during spaceflights of short durations. Despite a growing body of knowledge, many critical issues related to sarcomeric gene expression and the translation of this information into muscle function remain relatively unexplored. Ultimately, the types and quantities of contractile proteins present in skeletal muscle fibers determine muscle function. As shown in Figure 1, the pool of contractile proteins is determined by 4 important processes: i) transcription of sarcomeric genes; ii) translation of sarcomeric mRNA transcripts; iii) myofibrillar assembly; and iv) myofibrillar disassembly (i.e., protein degradation). Any factor(s) affecting one or more of these systems will ultimately impact skeletal muscle function. With respect to Figure 1, the objective of this paper is to provide a focused summary of the affects of short duration spaceflights on myosin composition of the soleus (SOL) muscle. This will be achieved by describing the affects of spaceflight upon: i) mechanical properties of skeletal muscle that are determined by the types and quantity of myosin; ii) myosin heavy chain (MHC) protein isoform composition; and ii) MHC mRNA isoform content. Data reported in this paper are from spaceflight missions having durations of 6 (PARE-02;2) and 14 days (SLS-2).

Animals↗
PubMed1995

Hemodynamic effects of pressure support ventilation following cardiac surgery.

Hemodynamic effects of pressure support ventilation (PSV) were assessed in 33 patients, after cardiac surgery. The patients, selected for their stable left ventricular and respiratory functions, underwent uncomplicated coronary artery bypass grafting. They all underwent the same anesthetic protocol, and an invasive hemodynamic monitoring. Eight to ten hours postoperatively, while all patients were fully awake, normothermic and hemodynamically stable, controlled ventilation (CV) was replaced by 3 levels of PSV (20, 10, 5 cm H2O). These levels were applied consecutively for 20 minutes each, before extubation. Hemodynamic and gas exchange data were recorded on CV, on each level of PSV, and on spontaneous breathing. The results were analyzed using ANOVA and Bonfferoni methods. No statistical significance could be noted between the five modes of ventilation as to hemodynamic parameters, arterial and mixed venous blood gases, and oxygen consumption (VO2). The only 2 parameters that reached statistical significance were central venous pressure and respiratory rate. Our study demonstrates that patients with stable cardiovascular and respiratory function can adapt to different levels of PSV without hemodynamic modifications or an increase in their VO2.

Adult↗
PubMed1994

Relationship of sweat electrolytes to apparent life-threatening events (ALTE): a case control study.

Twenty infants aged 25 days to 6 months who were consecutively investigated for apparent life-threatening events (ALTE) with negative results and 20 matched normal controls underwent an iontophoresis sweat test. A statistically significant elevated sweat potassium level (22.1 +/- 8.9 versus 12.4 +/- 6.5 mol/l) was noted in the ALTE patients compared with the control group (p < 0.001). No difference was found, however, between sweat sodium and chloride levels in the two groups. Na/K ratio in sweat was significantly different between the groups (p < 0.001). A between-groups discriminant analysis, using Na/K ratio as a discriminant variable, resulted in 80% accuracy in group assignment. A significant increase in sweat potassium concentration at night compared with day time was evident in ALTE patients. Elevated sweat potassium levels specifically characterized infants who experienced ALTE and may possibly indicate an underlying mechanism involving enhanced sympathetic activity.

Circadian Rhythm↗
PubMed1994

Effect of chronic energy deprivation on cardiac thyroid hormone receptor and myosin isoform expression.

Thyroid hormone (3,5,3'-triiodothyronine; T3) and its receptor (TR) play an important regulatory role for in vivo and in vitro cardiac myosin heavy chain (MHC) isoform gene expression by activating the alpha- and inhibiting the beta-MHC genes. Previous studies have shown that chronic energy deprivation (CED; 50% of normal caloric intake) in the rat impacts cardiac MHC protein expression and hemodynamic parameters in a pattern typically seen with hypothyroidism; yet, unlike hypothyroidism, circulating T3 levels are not depressed. Therefore, the goal of this study was to determine if the altered MHC isoform expression observed in CED is associated with altered TR expression, both at the mRNA and protein levels. Female rats weighing approximately 250 g were allocated into two groups, designated as normal control (NC) and CED. After 5 wk, the relative content of alpha-MHC protein and mRNA levels decreased in CED ventricles by 20% (P < 0.05). In contrast, the relative content of both beta-MHC protein and mRNA levels increased five- to sixfold in CED (P < 0.05). Although there were no changes in TR mRNA levels relative to 18S rRNA in CED, the total number of nuclear TRs decreased 3.5-fold in the CED group (P < 0.05), from a maximum binding capacity of 840 +/- 130 fmol/mg DNA in NC to 241 +/- 118 fmol/mg DNA in CED, with no change in the affinity of the receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Interaction of thyroid hormone and functional overload on skeletal muscle isomyosin expression.

This study examined the interaction of exogenous thyroid hormone 3,5,3'-triiodothyronine (T3) and functional overload on skeletal muscle myosin heavy chain (MHC) expression, studied at both the protein and mRNA level of analysis. Animals were allocated to the following groups: 1) normal control, 2) overload control, 3) hyperthyroid control, and 4) hyperthyroid+overload. Overload of the rat plantaris was accomplished by surgical removal of its synergists (soleus and gastrocnemius), and the animals were made hyperthyroid by injections of T3 (350 micrograms/kg every other day). After overload of 8 wk, muscle enlargement occurred by 53% for both overload groups (P < 0.05). This was accompanied by a 330 and 82% increase in the relative content of type I and IIa MHC, respectively, and a corresponding decrease by 16 and 44% in type IIx and IIb MHC, respectively, in the overload control group (P < 0.05 vs. normal control). Changes in the relative and absolute content of mRNA for these MHCs paralleled the protein response. Exogenous T3 completely reversed the upregulation of type I MHC and the downregulation of type IIx associated with overload at both the protein and mRNA level (P < 0.05). However, T3 was only partially effective in blunting the downregulation of IIb MHC and the upregulation of IIa MHC (protein and mRNA) accompanying the overload.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Interaction of chronic creatine depletion and muscle unloading: effects on postural locomotor muscles.

In some rodent skeletal muscles, hindlimb non-weight-bearing activity induces a shift in the expression of myosin heavy chains (MHCs) that favors the type II isoforms at the expense of type I. Chemically induced chronic creatine depletion results in isomyosin shifts favoring expression of type I MHCs. In this study, creatine depletion was induced separately and in combination with non-weight-bearing activity to determine if the response to lowering this metabolite would counter the MHC transitions expected from non-weight bearing. Creatine depletion was induced by feeding rats a diet supplemented with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Female Sprague-Dawley rats weighing 247 +/- 8 g were randomly assigned to four groups: 1) normal diet control, 2) beta-GPA control (BC), 3) normal diet suspended (NS), and 4) beta-GPA suspended (BS). BC and BS animals were fed a diet containing the creatine analogue for 68 days. Hindlimb non-weight bearing in BS and NS animals was accomplished by tail suspension for the final 30 days of this period. beta-GPA feeding lowered the creatine content of muscles sampled by 65%. Creatine depletion resulted in a 16% increase in citrate synthase activity in the soleus (SOL) and a 24% increase in the plantaris (PLN). In two postural muscles, the SOL and vastus intermedius (VI), tail suspension resulted in large decreases in the type I MHC expression and increases in type IIx and IIb MHCs. In two locomotor muscles, the PLN and medial gastrocnemius, type I MHC declined and type IIb increased with suspension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The effects of space flight on the contractile apparatus of antigravity muscles: implications for aging and deconditioning.

Previous studies have shown that the unloading of skeletal muscle, as occurring during exposure to space flight, exerts a profound effect on both the mass (cross sectional area) of skeletal muscle fibers and the relative expression of protein isoforms comprising the contractile system. Available information suggests that slow (type I) fibers, comprising chiefly the antigravity muscles of experimental animals, in addition to atrophying, undergo alterations in the type of myosin heavy chain (MHC) expressed such that faster isoforms become concomitantly expressed in a sub-population of slow fibers when insufficient force-bearing activity is maintained on the muscle. Consequently, these transformations in both mass and myosin heavy chain phenotype could exert a significant impact on the functional properties of skeletal muscle as manifest in the strength, contractile speed, and endurance scope of the muscle. To further explore these issues, a study was performed in which young adult male rats were exposed to zero gravity for six days, following which, the antigravity soleus muscle was examined for a) contractile properties, determined in situ and b) isomyosin expression, as studied using biochemical, molecular biology, and histochemical/immunohistochemical techniques.

Aging↗
PubMed1994

[Ischio-vertebral dysplasia (a dangerous syndrome for the spinal cord)].

PURPOSE OF STUDY: A previously unreported condition is defined, diagnostic features identified, and clinical course and treatment modalities presented. MATERIAL AND METHODS: This is a retrospective study of 11 patients with ischio-vertebral dysplasia (IVD), accomplished by record and radiographic review. RESULTS: 11 patients were included in the study group, age at presentation from 1 day to 33 yrs. Follow-up ranged from 5-30 yrs. Involvement of 3 successive generations (grandmother, mother and daughter) with similar findings was present in 1 family. Common features of IVD include: peculiar facies incomplete ossification of the ischial ramus, and a dysplasic scoliosis with a significant kyphotic element, constituting a rotatory dislocation. 2 patients followed from birth demonstrated the natural history of the condition, beginning without spinal deformity, and progressing to significant deformity. The spinal deformity was manageable surgically. The scoliosis ranged from 10 degrees to 235 degrees, and the kyphosis from 0 degrees to 200 degrees (the 10 and 0 being at day 1 of age). 6 patients incurred neurological sequelae, either spontaneously or associated with surgical treatment. 2 patients died, 1 due to cardiopulmonary failure at age 33; the 2nd was an infant with severe neurologic and cardiopulmonary complications due to the spinal deformity. Multiple surgical approaches to the problems were employed. Analysis of results permitted formulation of a logical and successful approach to the problem. Pre-op mean kyphosis = 112 degrees, post-op at maximum follow-up = 67 degrees. Deformity stabilization and neurologic normalcy was produced in every patient operated but 1. DISCUSSION: The characteristics of the syndrome are clear, as is the progressive nature of the deformity. The very high risk of neurologic involvement is emphasized. Before age 10, circumferencial fusion prevents progression and neurologic deterioration. Older patients require gradual correction by skeletal traction, followed by anterior concave strut stabilization and posterior fusion (with or without instrumentation). Extreme care is necessary for protection of the particularly vulnerable neurologic structures. Early stabilization and correction is recommended for prevention of the deterioration of cardiopulmonary function.

Abnormalities, Multiple↗
PubMed1993

Food restriction-induced transformations in cardiac functional and biochemical properties in rats.

The primary objective of this study was to ascertain if various degrees of marked chronic food restriction (FR) as well as the combination of FR and exercise training of moderate intensity induce changes in the functional properties of the heart that are consistent with previously reported findings indicative of downregulation of high-adenosinetriphosphatase V1 isomyosin expression. Adult female rodents were randomly assigned to one of four experimental groups: 1) free eating, 2) 50% food restricted, 3) 75% food restricted, or 4) 50% food restricted plus treadmill trained. Results show that FR induced significant depression in the functional properties (heart rate, left ventricular pressure, rate of pressure development, and double product) of the heart in all FR groups and that this depression in functional capacity corresponded to the degree of FR. These functional changes were accompanied by significant downregulation of the alpha- and upregulation of the beta-myosin heavy chain gene expressions, as studied at both the mRNA and protein levels. The exercise training induced further alterations in cardiac function; however, these alterations occurred independently of any shifts in isomyosin composition. These results suggest that although severe FR is a potent stimulus to transform both the biochemical and functional properties of the rodent heart, the underlying mechanism(s) concerning these adaptations remains unresolved.

Adenosine Triphosphatases↗
PubMed1993

Myosin heavy chain expression in rodent skeletal muscle: effects of exposure to zero gravity.

This study ascertained the effects of 9 days of zero gravity on the relative (percentage of total) and calculated absolute (mg/muscle) content of isomyosin expressed in both antigravity and locomotor skeletal muscle of ground control (CON) and flight-exposed (FL) rats. Results showed that although there were no differences in body weight between FL and CON animals, a significant reduction in muscle mass occurred in the vastus intermedius (VI) (P < 0.05) but not in the vastus lateralis (VL) or the tibialis anterior. Both total muscle protein and myofibril protein content were not different between the muscle regions examined in the FL and CON groups. In the VI, there were trends for reductions in the relative content of type I and IIa myosin heavy chains (MHCs) that were offset by increases in the relative content of both type IIb and possibly type IIx MHC protein (P > 0.05). mRNA levels were consistent with this pattern (P < 0.05). The same pattern held true for the red region of the VL as examined at both the protein and mRNA level (P < 0.05). When the atrophy process was examined, there were net reductions in the absolute content of both type I and IIa MHCs that were offset by calculated increases in type IIb MHC in both VI and red VL. Collectively, these findings suggest that there are both absolute and relative changes occurring in MHC expression in the "red" regions of antigravity skeletal muscle during exposure to zero gravity that could affect muscle function.

Animals↗
PubMed1992

Tuberculous peritonitis: an overlooked diagnosis.

Contrary to widespread belief, abdominal tuberculosis is not rare, nor is it confined to the poor or patients with active pulmonary tuberculosis. The disease must be considered in the differential diagnosis of abdominal pain.

Diagnosis, Differential↗