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Biomedical subjects

M Sole

Publications and source records attributed to M Sole.

12 recordsLinked to original sources

Characterization of a strong positive cis-acting element of the human beta-myosin heavy chain gene in fetal rat heart cells.

A strong positive element within the proximal promoter region of the human beta-myosin heavy chain (beta-MHC) gene that is required for high level expression in primary cultures of fetal rat heart cells was localized by transient assays and DNase I footprinting to positions- 277/-298. Using gel shift studies, this sequence was found to bind specifically at high affinity (Kd approximately 4 x 10(-9) M) to a transcriptional factor (beta F1) found in nuclear extracts from rabbit heart. Dimethyl sulfate interference studies suggested that beta F1 may bind as a dimer to two hexameric imperfect direct repeats containing the consensus sequence 5'-(C/G)-T-G-(T/A)-G-G-3'. Gel shift analyses suggested that beta F1 is related to the M-CAT factor, which is known to control muscle-specific expression of the cardiac troponin T gene. A clustered mutation of the region between the putative binding half-sites and within the "M-CAT"-like domain abolished beta-MHC promoter activity. The sequence of the positive element also contains binding motifs for several transcriptional factors that regulate viral and cellular genes, including AP4, AP5, TEF-1, and MyoD-like proteins. When multiple copies of the beta-MHC element were inserted downstream from the transcriptional initiation site of the thymidine kinase gene, it did not act as a classical enhancer, showing some dependence upon orientation.

Animals

Bladder wash cytology and flow cytometry for the diagnosis of transitional cell carcinoma of the urinary bladder.

The role of bladder wash (BW) cytology and flow cytometry in the diagnosis of low-grade transitional cell carcinoma (TCC) of the bladder is yet to be demonstrated. We have studied a series of BW specimens by both conventional cytology and flow cytometry: there were 16 BW from patients with histologically proven TCC and 14 BW from patients with clinical suspicion of tumor or under follow-up for previous TCC in which no evidence of tumor was found by cystoscopy and multiple biopsies. As control group, 21 BW were studied from patients undergoing cystoscopy for causes other than TCC. In conclusion, the conventional cytologic study of BW specimens was highly sensitive for grade II-III TCC, but missed most grade I TCC; flow cytometric analysis did not improve significantly the detection rate in low-grade TCC.

Carcinoma, Transitional Cell

Ventricles as a major site of atrial natriuretic factor synthesis and release in cardiomyopathic hamsters with heart failure.

The aim of the present study was to correlate in cardiomyopathic hamsters with congestive heart failure the levels of atrial and ventricular atrial natriuretic factor (ANF) messenger RNA (mRNA) with immunoreactive ANF (IR-ANF) plasma levels and the relative amount of IR-ANF released by the whole heart versus isolated ventricles in the Langendorff preparation. High-performance liquid chromatography analysis of the forms of ANF present in plasma and in the Langendorff effluent of whole heart versus isolated ventricles was also performed. As previously found for cardiac IR-ANF, the levels of ANF mRNA decreased gradually in atria and increased in an analogous fashion in ventricles with the severity of congestive heart failure. Plasma IR-ANF levels (C-terminal) were more elevated in moderate than in severe congestive heart failure, as were the IR-ANF levels in the Langendorff effluent of the whole heart. On the contrary, the effluent of isolated ventricles from animals in severe heart failure yielded more IR-ANF than that from hamsters in moderate heart failure. Thus, while the isolated ventricles from controls contributed 35.8% of IR-ANF released by the whole heart, ventricles from hamsters in moderate heart failure contributed 17.5%, and those from hamsters in severe heart failure contributed 73.9%. These results indicate that atrial cardiocytes contribute more IR-ANF than their ventricular counterpart in moderate heart failure and that ventricles are a major source of plasma IR-ANF in severe heart failure. Analysis of IR-ANF from plasma and the Langendorff effluent from whole hearts and isolated ventricles revealed that the ventricles are the major source of the propeptide (and of its cleaved products) found in the circulation of cardiomyopathic hamsters. These results suggest that ANF synthesis and secretion do not increase conjointly in atria but do increase in ventricles during congestive heart failure.

Animals

Hereditary and acquired cardiomyopathies in experimental animals: mechanical, biochemical, and structural features.

Evidence has been presented regarding alterations of contractile behavior muscle biochemistry, and ulstrastructure during the course of the hereditary hamster cardiomyopathy. Also, preliminary structural and mechanical data were presented on the acquired cardiomyopathy of diabetes mellitus in experimental animals. In the hamster model, contractile performance, measured as isometric tension and rate of tension development, was shown to be depressed throughout the course of the disease, whereas normalized force-velocity relationships returned to normal only during the compensated stages of hypertrophy. Force-frequency relationships were depressed in myopathic muscles, indicating the presence of alterations in the muscle activation system, namely, the biochemical and functional integrity of the sarcoplasmic reticulum. Analysis of the contractile proteins in myopathic muscle has revealed depressions of Ca2+ activity in purified myosin in addition to an independently increased neutral protease activity that results in the specific degradation of LC2 of myosin. Sympathetic time and norepinephrine turnover increase progressively during the course of the disease. These changes are accompanied by decreasing tissue levels of neorepinephrine and increasing levels of dopamine, indicating a shift in the rate-limiting step for norepinephrine synthesis. Alterations were also noted in nuclear protein composition and serotonin levels. Microscopically, the myolytic and calcification changes that characterize the hamster cardiomyopathy have been confirmed. In addition, contraction bands and lysosomal changes have been observed that may relate to cateholamine hypersensitivity. In the experimental model of diabetic cardiomyopathy, a significant alteration in relaxation process was demonstrated despite the fact that peak tension development and its rate of development were unaltered. Also, the length dependence of contractile behavior was altered when compared to that of age-matched controls, indicating a potential loss of contractility reserve. When animals with combined hypertension and diabetes were studied, bothe contraction and relaxation processes were affected to a greater degree.

Actomyosin

Effect of acute and chronic renal denervation on renal function after release of unilateral ureteral obstruction in the rat.

The role of the renal nerves in determining renal function after relief of 24-h unilateral ureteral obstruction (UUO) was studied using clearance techniques in anaesthetized rats. Acute renal denervation during the first 1--2 h after relief of UUO resulted in a significant increase in glomerular filtration rate (GFR), renal plasma flow (RPF), urine flow, and sodium and potassium excretion, changes which were not seen in the sham-denervated postobstructive kidney. Acute denervation of sham-operated normal kidneys caused a similar natriuresis and diuresis but with no change in GFR or RPF. Chronic renal denervation 4--5 days before UUO denervated postobstructive controls, while chronic denervation alone was associated with a significantly higher urine flow and sodium excretion rate from the denervated kidney. The effectiveness of renal denervation was confirmed by demonstrating marked depletion of tissue catecholamines in the denervated kidney. It was concluded that renal nerve activity plays a significant but not a major role in the functional changes present after relief of UUO. Chronic renal denervation did not protect against the functional effects of unilateral ureteral obstruction.

Animals

[Aqueous humor flow measured by fluorophotometry. A comparative study of the effect of various beta-blocker eyedrops in patients with ocular hypertension].

A randomized double-blind study of aqueous humor flow and intraocular pressure measurements before and four hours after instillation of placebo and beta-blocker eyedrops, was carried out in 40 hypertensive patients. The treated and non-treated patients either did or didn't show an optic disc excavation and a visual field defect. Hypertensive patients with a previous tension treatment will stop therapy on a 3-week period up to an increase of their own ocular tension value greater than or equal to 3 mmHg. The intraocular pressure statistically decreased of 20.8% four hours after topical placebo, the aqueous humor flow remaining unchanged. In this study, timolol eyedrops induced a greater decrease of the aqueous humor flow (39%), followed equally by betaxolol (23.8%) and carteolol (20.42%). Timolol and betaxolol eyedrops equally induced a significant decrease of the intraocular pressure. There was no effect of carteolol on the intraocular pressure. The outflow facility was independent of the instilled beta-blocker eyedrop.

Adult

[2 fluorophotometric methods of measuring aqueous humor flow in hypertensive patients].

Two fluorophotometric methods, by instillation and oral route, allowed the aqueous humor flow measurement and apparent outflow resistance calculation in normal and hypertensive subjects. There was no statistically significant difference between the two methods in the aqueous humor flow of hypertensive patients and normal subjects. On the contrary, there was an increase of the outflow resistance in hypertensive patients in relation to normal subjects. Finally, oral route fluorophotometry allowed the individualization and calculation of a coefficient of aqueous humor production from the iris, which is statistically increased in hypertensive in comparison with normal subjects. Subsequent studies thanks to this fluorophotometric method by oral route, which interest is certain in treated hypertensive patients, should allow to determine the action site of the drug and to quantify its efficiency.

Administration, Oral