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Biomedical subjects

F Haddad

Publications and source records attributed to F Haddad.

At least 73 records · Page 4Linked to original sources

Interaction of thyroid state and denervation on skeletal myosin heavy chain expression.

The goal of this study was to examine the effects of altered thyroid state and denervation (Den) on skeletal myosin heavy chain (MHC) expression in the plantaris and soleus muscles. Rats were subjected to unilateral denervation (Den) and randomly assigned to one of three groups: (1) euthyroid; (2) hyperthyroid; (3) and hypothyroid. Denervation caused severe muscle atrophy and muscle-type specific MHC transformation. Denervation transformed the soleus to a faster muscle, and its effects required the presence of circulating thyroid hormone. In contrast, denervation transformed the plantaris to a slower muscle independently of thyroid state. Furthermore, thyroid hormone effects did not depend upon innervation status in the soleus, while they required the presence of the nerve in the plantaris. Collectively, these findings suggest that both thyroid hormone and intact nerve (a) differentially affect MHC transformations in fast and slow muscle; and (b) are important factors in regulating the optimal expression of both type I and IIB MHC genes. This research suggests that for patients with nerve damage and/or paralysis, both muscle mass and biochemical properties can also be affected by the thyroid state.

Animals↗

Role of thyroid hormone and insulin in control of cardiac isomyosin expression.

Previous studies show that both diabetes and thyroid state exert a strong regulatory influence on the pattern of rodent cardiac isomyosin expression. Therefore, we determined the separate and combined effects of thyroid hormone (T3) and insulin treatment on rodent cardiac myosin heavy chain (MHC) expression using a model of combined thyroid deficiency (Tx) and diabetes (D). The combination of Tx and D completely transformed cardiac isomyosin expression such that the fast alpha-myosin heavy chain (MHC) was completely repressed at both the protein and mRNA level of expression; whereas, the slow beta-MHC was upregulated to constitute 100% of the total MHC pool, based on both protein and mRNA analyses. Daily low doses of exogenous T3 treatment (3 micrograms/kg b.w. i.p.). in the absence of insulin treatment, partially restored expression of the alpha-MHC, while inhibiting expression of the beta-isoform. In contrast daily insulin treatment (4 U/rat), in the absence of exogenous T3 treatment, failed to exert any significant influence on the pattern of isomyosin expression in the thyroid-deficient diabetic rat model. Furthermore, when exogenous T3 was administered in conjunction with insulin, the effect on MHC mRNA expression was greater than that of T3 alone, thus suggesting the existence of interaction between T3 and insulin action in the regulation of MHC mRNA expression. Collectively, these findings suggest that: (a) thyroid state is a dominant regulator of cardiac isomyosin phenotype: and (b) insulin does not exert any regulatory influence on cardiac MHC expression in a severe thyroid deficient state, instead it requires a critical level of circulating T3 in order to be effective in blunting MHC transformation associated with diabetes. It is thus concluded that the regulation of cardiac MHC by insulin is a complex mechanism involving interaction of insulin with subcellular factors likely to have impact on the specific action of T3. This interaction is disrupted in the absence of sufficient thyroid hormone.

Animals↗

Effects of diabetes on rodent cardiac thyroid hormone receptor and isomyosin expression.

Previous studies show that diabetes induces marked transformations in cardiac myosin heavy chain (MHC) gene expression that are somehow linked to the cellular action of thyroid hormone 3,5,3'-triiodothyronine (T3). In this study, we tested the hypothesis that diabetes induces a reduced expression of thyroid hormone receptors (TRs), which are known to be important transcription factors interacting with thyroid response elements (TREs) in the promoter region of both alpha- and beta-MHC genes. Adult female rats were randomly assigned to either a normal control (NC) or diabetic (D) group. Three and/or six weeks after induction of diabetes via streptozotocin injection, the hearts of the animals were analyzed for MHC and TR mRNA isoforms expression, nuclear T3 binding, and nuclear extract interaction with a palindromic TRE. Results showed that diabetes induced significant alteration in alpha- and beta-MHC expression. Northern blot analyses indicated no diabetes-associated differences in TR isoform mRNA signals. Cardiac nuclear T3 binding studies suggested no differences in either the binding capacity or the equilibrium binding constant among the two groups, indicating no changes in either the number of nuclear TRs or their affinity for T3. Furthermore, gel mobility shift assays detected no difference between NC and D groups for cardiac nuclear extract binding to palindromic TRE. Collectively, these findings suggest that, whereas diabetes exerts a profound effect on cardiac isomyosin gene expression, the underlying mechanism, although dependent on factors linked to T3 function, does not involve alterations in TR expression.

Animals↗

Analysis of myosin heavy chain mRNA expression by RT-PCR.

An assay was developed for rapid and sensitive analysis of myosin heavy chain (MHC) mRNA expression in rodent skeletal muscle. Only 2 microg of total RNA were necessary for the simultaneous analysis of relative mRNA expression of six different MHC genes. We designed synthetic DNA fragments as internal standards, which contained the relevant primer sequences for the adult MHC mRNAs type I, IIa, IIx, IIb as well as the embryonic and neonatal MHC mRNAs. A known amount of the synthetic fragment was added to each polymerase chain reaction (PCR) and yielded a product of different size than the amplified MHC mRNA fragment. The ratio of amplified MHC fragment to synthetic fragment allowed us to calculate percentages of the gene expression of the different MHC genes in a given muscle sample. Comparison with the traditional Northern blot analysis demonstrated that our reverse transcriptase-PCR-based assay was reliable, fast, and quantitative over a wide range of relative MHC mRNA expression in a spectrum of adult and neonatal rat skeletal muscles. Furthermore, the high sensitivity of the assay made it very useful when only small quantities of tissue were available. Statistical analysis of the signals for each MHC isoform across the analyzed samples showed a highly significant correlation between the PCR and the Northern signals as Pearson correlation coefficients ranged between 0.77 and 0.96 (P < 0.005). This assay has potential use in analyzing small muscle samples such as biopsies and samples from pre- and/or neonatal stages of development.

Animals↗

[Neurologic manifestations in Behçet's disease. 16 cases in a cohort of 110 patients].

OBJECTIVE: To discuss neurological involvement of Behçet's disease and therapeutical possibilities. PATIENTS: Among 110 patients with Behçet's disease, 16 were found to have neurological involvement. All these patients fulfilled Japanese and International Study Group criteria for diagnosis of Behçet's disease. RESULTS: Central nervous system involvement was found in 15 patients and peripheral nervous system involvement in one. Meningoencephalitis and/or transverse myelitis were the most frequent features (69%) followed by tumor-like manifestations (13%); cerebral venous thrombosis was identified in 1 patient with occlusion of the left lateral sinus. Focal deficits were the major presenting signs and cranial paralysis were present in 19% of patients. In meningoencephalitis, the cerebrospinal fluid findings were lymphocytic pleocytosis and elevated protein level. Cerebral CT Scan, performed in 6 patients, was normal in 33% of cases. MRI, performed in 4, showed abnormal signals distributed over hemispheric white matter, the brainstem and the thalamus in one patient, an occlusion of the left lateral sinus in the second one and a tumor-like lesion in the third. MRI abnormalities were associated with concording clinical deficits. CONCLUSION: Neurological involvement in Behçet's disease con be classified into 3 clinical aspects: meningoencephalitis (and/or myelitis), cerebral venous thrombosis and tumor-like features. Corticosteroids, when prescribed early, are useful and are associated with better prognosis.

Adult↗

[Scleroderma with anomalies of the thyroid function. 7 cases].

Thyroid function, studied in 36 scleroderma patients revealed 7 abnormal cases: 6 hypothyroid patients secondary to autoimmune thyroiditis and 1 hyperthyroidism secondary to Graves' disease. In the hypothyroid subgroup, 3 cases presented a localized systemic sclerosis and the 3 others presented a diffuse systemic sclerosis; Sjögren syndrome was found in 2 of these patients. The hyperthyroid patient presented a diffuse systemic sclerosis. Because of the association between scleroderma and thyroid diseases, we suggest to perform thyroid screening regularly for all patients with systemic sclerosis.

Adult↗

[Inflammatory intestinal diseases and their extra-intestinal manifestations observed at Liban].

101 cases classified as inflammatory bowel disease at the Hôtel-Dieu de France Hospital between 1982 and 1994 were investigated. Files containing a sure diagnosis and complete clinical and biological investigations were included. 65 files were retained for the study: 48 cases had ulcerative colitis (UC), 17 had Crohn's disease (CD). UC averaged 4.7 admissions per 10,000 admissions to the hospital, while CD averaged 1.54 per 10,000. The UC/CD ratio was 2.8 and the Female/Male ratio was 1.4 for UC and 0.9 for CD. Medium follow-up was 6.4 years. 30% of our group was followed for more than 10 years. Overall frequency of extra-intestinal manifestations was similar to that reported worldwide. This is especially true for UC. However, no cases of ankylosing spondylitis, sclerosing cholangitis or erythema nodosum were found. One case of pyoderma gangrenosum was found in the series of CD. Extra-intestinal manifestations were found in 54% of UC patients and 94% of CD patients, probably because milder cases of this disease were misclassified as infectious diarrhea.

Adult↗

Influence of mechanical loading on myosin heavy-chain protein and mRNA isoform expression.

The overall objective of the studies reported herein was to examine the effects of high-resistance training on myosin heavy-chain (MHC) protein and mRNA isoform expression. The findings from these studies can be summarized as follows: 1) there was a substantial increase in the fast type IIX MHC protein isoform content of the trained red and white medial gastrocnemius muscles, but this did not occur until after the eighth training session (i.e., 16 days); 2) single-fiber analyses demonstrated that many so-called fast type IIB fibers contained small amounts of the fast type IIX MHC protein isoform and that the high-resistance training program altered the bias of fast type IIB-type IIX MHC protein isoform distribution in these fibers but did not increase the number of fibers that could be categorized as exclusively fast type IIX fibers; 3) the high-resistance training program produced a rapid (i.e., after two training sessions) elevation in the fast type IIX MHC mRNA isoform and a corresponding repression of the fast type IIB MHC mRNA isoform; and 4) the dose-response study revealed that as few as 10 contractions (40 s) per training session were capable of elevating the expression of the fast type IIX MHC mRNA isoform by approximately 250%. These collective findings demonstrate that high-resistance training is a powerful modulator of MHC protein isoforms and that pretranslational mechanisms are very sensitive to even small amounts of high-resistance training.

Animals↗

Microgravity-induced transformations of myosin isoforms and contractile properties of skeletal muscle.

This study examined the effects of microgravity (14 days) on 1) the contractile properties of the soleus (Sol), an antigravity skeletal muscle; and 2) the myosin heavy chain (MHC) protein and mRNA isoform content of the Sol, vastus intermedius (VI), plantaris (Plan), and tibialis anterior (TA) muscles. The force-velocity relationships of the flight Sol muscles had a significant reduction in maximal isometric tension (-37%) and a corresponding increase in maximal shortening velocity (+20%). Additionally, the force-frequency relationship of the flight Sol muscles was shifted to the right of the ground-based control group. Microgravity had the greatest effect on muscle fiber composition in the Sol muscle, with a reduction in slow muscle fibers and a corresponding increase in muscle fibers categorized as hybrid fibers. The estimated absolute MHC isoform content was altered to the greatest extent in the Sol and VI muscles, with significant decreases and elevations in the slow type I and fast type IIX MHC protein isoforms, respectively. Consistent with the protein data, both the flight Sol and VI muscles exhibited significant elevations in the fast type IIX MHC mRNA isoform. In contrast, however, the flight Plan and TA groups had significant increases in the fast type IIB MHC mRNA isoform content without corresponding changes at the protein level. The results of this study suggest that spaceflight of even short duration produces important changes in the contractile properties of antigravity skeletal muscle. These changes are mediated by alterations in MHC phenotype and reductions in muscle mass. In some instances, the alterations in MHC mRNA isoform content seemed to be uncoupled from those occurring at the protein level. This apparent uncoupling between mRNA and protein expression demonstrates that the effects of microgravity must be better understood at the transcriptional, translational, and post-translational levels.

Animals↗

Adaptive responses of hypertrophying skeletal muscle to endurance training.

We determined the effects of 6 wk of endurance running on citrate synthase (CS) activity and myosin heavy chain (MHC) expression in bilateral surgical-overloaded rodent fast-twitch plantaris and slow-twitch soleus muscles. The overload induced significant hypertrophy in both muscle types, and this response was enhanced by endurance training. The overload-induced compensatory hypertrophy was accompanied by a proportional increase in muscle CS content. Although endurance training produced significant increases in CS concentration in either muscle type of the normal-trained groups (P < 0.05), it was not effective in causing similar changes in the overloaded trained muscles. Also, overload of either the sedentary or trained groups produced an increase in slower MHC isoforms (i.e., type I in the soleus and types I and IIa in the plantaris) and a concomitant decrease in the faster MHC isoforms (type IIa in the soleus and IIb in the plantaris; P < 0.05), whereas endurance training alone produced the opposite effect, especially in the plantaris. Collectively, these data suggest that 1) increments in muscle oxidative enzyme content due to endurance training are compromised when a hypertrophying process is occurring concomitantly; and 2) the relative loading state imposed on the muscle during repetitive locomotor activity is critical in regulating the pattern of MHC plasticity.

Adaptation, Physiological↗

The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy.

Insulin-like growth factor-1 (IGF-1) is known to have anabolic effects on skeletal muscle cells. This study examined the time course of muscle hypertrophy and associated IGF-1 peptide and mRNA expression. Data were collected at 3, 7, 14, and 28 days after surgical removal of synergistic muscles of both normal and hypophysectomized (HX) animals. Overloading increased the plantaris (Plant) mass, myofiber size, and protein-to-body weight ratio in both groups (normal and HX; P < 0.05). Muscle IGF-1 peptide levels peaked at 3 (normal) and 7 (HX) days of overloading with maximum 4.1-fold (normal) and 6.2-fold (HX) increases. Increases in muscle IGF-1 preceded the hypertrophic response. Total DNA content of the overloaded Plant increased in both groups. There was a strong positive relationship between IGF-1 peptide and DNA content in the overloaded Plant from both groups. These results indicate that 1) the muscles from rats with both normal and severely depressed systemic levels of IGF-1 respond to functional overload with an increase in local IGF-1 expression and 2) this elevated IGF-1 may be contributing to the hypertrophy response, possibly via the mobilization of satellite cells to provide increases in muscle DNA.

Animals↗

[Nervous system brucellosis in Lebanon. Report of six cases].

The authors report 6 cases of nervous system brucellosis (3 males, 3 females) and present the different clinical features of this localization. Meningoencephalitis is observed in 4 patients and is associated with subarachnoid hemorrhage in one. Pure meningitis occurred in one case and acute myelitis in another one. Cerebrospinal fluid composition is studied in all these patients. Rifampicine associated with Cotrimoxazole, for at least 3 months, is very helpful in nervous system brucellosis because of their good central nervous system penetration but neurological sequelae are noted in one case of meningoencephalitis with chronic infection and in the case of myelitis.

Adolescent↗

[Coronary surgery in patients 70 years and older. Report of 70 cases].

Between January 1993 and January 1995, seventy patients over 70 years of age underwent coronary artery revascularization and were retrospectively reviewed. The anesthetic protocole, the surgical technique and the intraoperative myocardial protection were similar for all patients. Fourteen patients (19.8%) suffered major postoperative complications: stroke (3 cases), myocardial infarction (5 cases), left ventricular failure with intraaortic counter-pulsation (2 cases), gastrointestinal hemorrhage (2 cases), respiratory failure (2 cases). Thirty patients (42.6%) had minor complications with no impact on survival or hospital stay. Hospital mortality was 7.1% (5 patients) and was caused by left ventricular failure (2 cases), stroke (1 case), gastrointestinal hemorrhage (1 case), respiratory failure (1 case). Mortality was found to be correlated with preoperative renal failure, peripheral vascular disease and concomitant carotid endarterectomy. Patients remained in the cardiac surgery unit for 60 hours. The mean length of hospital stay was 8.2 days. Follow-up from 1 to 24 months revealed NYHA angina class I-II in 85% of the patients. These results are similar to other studies. We conclude that coronary artery revascularization in the elderly yields good results, with fair mortality and morbidity rates.

Aged↗

[Significance of TSH receptor antibody determination].

TSH receptor antibodies (TRAb) was performed by binding assay in seventy-seven patients (47 with Graves disease, 32 with other thyroid abnormalities). The sensitivity and specificity of our assay were respectively 81% and 96.5%. These results were similar to the results found in medical literature. The association of ophthalmopathy with Graves disease does not increase the sensitivity of the test. In this study we conclude that TRAb assay is of great interest in confirming the diagnosis and in the following of Graves disease.

Adolescent↗