Search PubMed⌕ Search

Biomedical subjects

N Schmitt

Publications and source records attributed to N Schmitt.

At least 37 records · Page 2Linked to original sources

Muscle regeneration and mitochondrial calmitine increase in the dystrophic dy/dy mouse after intramuscular chlorpromazine injection.

We studied the effect of chlorpromazine injection on the gastrocnemius muscles of C57BL/6J dy/dy dystrophic mice. Changes in mitochondrial calmitine concentrations and differences in microscopy studies, fibre typing and morphometry were compared in gastrocnemius muscles of dystrophic and control mice before and 2 and 21 days after injection. In both cases, calmitine reduction associated with muscle degeneration was observed 2 days after drug injection. Calmitine then increased, reaching a level at day 21 nearly identical to that of controls before injection. This increase was associated with muscle regeneration. These results clearly indicate that dystrophic mouse muscle can regenerate calmitine after drug-induced damage.

Animals↗

Molecular cloning of human calmitine, a mitochondrial calcium binding protein, reveals identity with calsequestrine.

The cDNA of a mitochondrial calcium binding protein, "calmitine", has been cloned from a human skeletal muscle cDNA library. One cDNA of 1.8 kb has been isolated and sequenced. It encodes for a protein of 390 amino acid residues of 41,746 KDa and contains a leading peptide of 28 amino acids. The sequencing showed the possibility for 21 phosphorylation sites, 4 myristylation sites, and one N glycosylation site. Sequence comparison with other proteins revealed the identity of calmitine with calsequestrine, the sarcoplasmic reticulum low affinity, but high Ca2+ binding capacity, protein isolated in 1971. Subcellular fractionation showed a marked increase in these Ca2+ binding proteins in mitochondria as compared with the sarcoplasmic reticulum; furthermore the mitochondrial matrix is highly enriched with that protein. Therefore, our data either suggest a bicompartimentation of calmitine or indicate that the localization of calsequestrine should be reconsidered in the light of our data. Calmitine represents the Ca2+ reservoir of mitochondria, the function of which could be similar to what has been reported for calsequestrine in the sarcoplasmic reticulum.

Amino Acid Sequence↗

Mdx mouse skeletal muscle: could a mitochondrial factor be responsible for the absence of progressive necrosis?

We compared the myotoxic effect of chlorpromazine on mitochondria of gastrocnemius muscle in X-related muscular dystrophy (mdx) and control mice relative to changes in calmitine and calcium concentrations before and 3 and 6 days after a single injection of the drug. The results indicate that mdx mouse mitochondria are less sensitive to the myotoxic effect of chlorpromazine; calmitine and calcium binding were only slightly reduced compared to controls. Our observations indicate that the calmitine structure could differ in mdx and control mice with respect to calcium binding structures, and that the presence of calmitine in the mitochondria of mdx mouse skeletal muscle could explain why muscle degeneration does not occur in these animals. However, the muscles of patients with Duchenne muscular dystrophy (DMD) are lacking in calmitine and are subject to extensive progressive degeneration.

Animals↗

Effect of torbafylline on mitochondrial calmitine in mouse skeletal muscle regeneration after injection of a myotoxic drug.

The effect of torbafylline, a xanthine derivative (Hoechst, Werk Albert, Wiesbaden, Germany), was tested relative to changes in degeneration and subsequent regeneration processes in mouse gastrocnemius muscle induced by a single injection of chlorpromazine, a myotoxic drug. These processes were monitored by measuring changes in calmitine, a mitochondrial protein. We determined in our previous work that calmitine concentration decreases during degeneration and progressively increases during regeneration. In this study, we compared effects in torbafylline-treated mice with those in control mice treated with saline solution. The results show that regeneration is much faster with torbafylline treatment. Calmitine is decreased and returns quickly to normal in torbafylline-treated mice as compared to those treated with saline solution. Torbafylline might thus prove effective in stimulating muscle regeneration in myopathy.

Animals↗

Changes in mitochondrial calmitine and calcium in rat denervated skeletal muscle after injection of a myotoxic drug, chlorpromazine.

1. Calmitine and mitochondrial calcium were studied after injection of chlorpromazine into control and denervated gastrocnemius muscle in rat. 2. Calmitine decreased under the effect of chlorpromazine and then increased again. Regenerative capacity was more marked for denervated than control muscle. Calcium increased and then returned to its normal level in control muscle while remaining elevated in denervated muscle. 3. Thus, it would appear that calmitine synthesis can occur in the absence of innervation and that denervation, which probably causes disturbances in mitochondrial calcium regulation systems, may prevent total regeneration of muscle after an injury.

Animals↗

Degeneration and subsequent regeneration of mouse skeletal muscle after a single injection of chlorpromazine: changes in mitochondrial calmitine and calcium content.

We studied experimental models capable of showing muscle degeneration and subsequent regeneration and observed the changes in calmitine, calcium uptake and calcium concentration in mitochondria during these processes. The results presented here are based on the study of mitochondria of mouse skeletal muscle after a single intramuscular injection of chlorpromazine. This drug induces myotoxic effects followed by muscle regeneration. Our results show that the muscle degeneration process, as shown by histological studies, was associated with some changes in mitochondria: a decrease in calmitine, a calcium overload and a decrease in calcium uptake; the subsequent regeneration process was associated with an increase in calmitine, a decrease in calcium concentration and an increase in calcium uptake, these 3 parameters returning to normal values. It seems that there is a correlation between a decrease in calmitine and muscle degeneration, and an increase in calmitine and muscle regeneration, as shown by our biochemical and histological observations.

Animals↗

Capturing and clustering women's judgment policies: the case of hormonal therapy for menopause.

Two hundred sixty-five women estimated the likelihood that they would take estrogen plus progestin to alleviate menopausal symptoms when faced with hypothetical cases varying in degree of hot flashes and risk of osteoporosis and cancer. Clustering of their judgment policies revealed four groups of women with respect to their approach to this decision. These groups of women were significantly different from each other on educational level, perceived experience of stress, and attitudes toward menopause and use of medications. Willingness to take hormonal therapy across all cases was related to attitudes about, and knowledge of, menstruation, perceived stress, mother's experience with menstrual problems, severity of symptoms, and use of vitamins. While there have been previous attempts to cluster rater policies, the current study represents a novel attempt to understand the differences between people who appear to have different policies about a decision problem, in this case, whether or not to take hormone therapy to counter menopausal symptoms.

Attitude↗

The soluble receptor of interleukin 2 is not a serum marker of the autoimmune activity in type I diabetes mellitus.

In order to determine if soluble interleukin 2 receptor (IL2R) was useful as a marker in screening for early Type 1 diabetes and in monitoring immunological treatment, we assayed serum IL2R levels in 67 controls, 43 patients with newly diagnosed diabetes and 28 first degree relatives of diabetic patients (5 subjects were islet cell antibody positive). In 23 diabetes, specimens were analysed at 3 and 6 months after diagnosis whether or not cyclosporin A was administered. Seven patients were in a clinical trial using anti IL2R monoclonal antibody and cyclosporin A. Since IL2R level in the normal population is elevated in the first 5 years of life then decreases until adulthood (age:IL2R correlation between 0 and 15 years: r = -0.42, P less than 0.05), subjects were carefully matched in age. In recent onset diabetes, this negative correlation disappeared and IL2R levels tended to decrease particularly in younger subjects. In Type 1 prediabetic subjects presenting persistent islet-cell antibody serum IL2R was not elevated. During immunological treatment of recent onset diabetes, serum IL2R remained stable and was not modified by cyclosporin A. As expected IL2R became undetectable during treatment with anti IL2R MC Ab. But it rebounded when treatment was stopped with no effect on remission. We concluded that IL2R levels in Type 1 diabetic patients is not useful in screening autoimmune activity or in evaluating the effectiveness of immunosuppressors.

Adolescent↗

Calmitine: a calcium-binding mitochondrial protein specific for fast-twitch muscle fibers.

Mitochondrial fractions were isolated from fast-twitch (EDL), slow-twitch (soleus) and heart muscle of normal rat (WKY). Protein separation by electrophoresis and study of calcium-45 binding showed that a specific calcium protein (designated as calmitine) was present in the mitochondria of fast-twitch muscle but practically inexistent in slow-twitch and cardiac muscle. It seems to be related to calcium uptake by an energy-dependent mechanism.

Aging↗

Women's use of information regarding hormone replacement therapy.

For perimenopausal women, an important decision is whether or not to use hormone replacement therapy (HRT). The decision is complex because HRT involves judgment in weighing gains and losses related to physiological risk. Gains involve relief of hot flashes and prevention of osteoporosis; losses include cancer mortality and side effects of medication. A policy-capturing study of 283 perimenopausal women showed that the factor of most frequent concern was relief of hot flashes. Cluster analyses identified four major groups. Group 4 had an n of 9 and the lowest R2, making interpretation of data questionable. The largest group responded to hot flashes alone; the second to hot flashes and osteoporosis; and the third to hot flashes, somewhat to osteoporosis, but also to side effects of estrogen/progestin therapy. Results indicate nursing interventions should anticipate differences in women's concerns and tailor counseling appropriately.

Climacteric↗

Muscular dystrophy: possible role of mitochondrial deficiency in muscle degeneration processes.

We isolated mitochondria from fast-twitch (extensor digitorum longus) and slow-twitch (soleus) skeletal muscle of the adult rat in normal conditions and 45 days after denervation as well as from skeletal muscle (gastrocnemius) of control and dystrophic (C57BL6J dy/dy and mdx) mice. We searched for the presence of a calcium-specific mitochondrial protein (calmitine) and measured calcium uptake in mitochondria. Our results indicate a possible correlation between the quantity of calmitine present and calcium entry into mitochondria. Both these parameters were elevated in rat fast-twitch and mouse mixed muscle and very low in slow-twitch muscle. They were also very low in dystrophic mouse muscle (C57BL6J dy/dy) with extensive muscle degeneration, but on the contrary elevated in muscle (mdx) with no important signs of degeneration. Finally, we found a normal calmitine concentration and very low calcium uptake in rat extensor digitorum longus after 45 days of denervation. On the basis of these results, it is hypothesized that calmitine synthesis could be subject to neural influence, thus specific for fast-twitch muscle, and that it could be linked to mitochondrial calcium uptake. A decrease in uptake could disturb certain enzymatic activities related to ATP synthesis and bring about muscle degeneration by inhibiting such synthesis. This would occur in the context of reduced calmitine synthesis in the case of genetic anomalies and of inactivation of calmitine after neural disturbance in the case of denervation.

Animals↗

Age-related calmitine distribution in mitochondria of normal and mdx mouse skeletal muscle.

In our study, mitochondria were isolated from skeletal muscle in 3-, 5-, 6- and 16-week-old mdx and control mice. A deficit was observed in a calcium-specific mitochondrial protein (named "calmitine") in 3-, 5- and 6-week-old mdx mice but only in 3-week-old control mice. In addition, there was a correlation between the amounts of calmitine and calcium uptake in mitochondria: the latter remained low in 3-, 5- and 6-week-old mdx mice and was similar to controls in 16-week-old mdx mice (as was calmitine). A relationship is suggested between the deficit in calmitine (and calcium uptake in mitochondria) and the important signs of fiber degeneration presented by mdx mice between 3 and 6 weeks of age (a return to normal was observed subsequently).

Age Factors↗

Methods of analyzing physician practice patterns in hypertension.

A principal method of studying physician practice patterns has been to examine physicians' responses to brief written cases. We have compared this method with practice patterns of the same physicians derived from chart audit. Subjects were 98 family practice residents for whom data were available in actual patient encounters for the workup of asymptomatic hypertension. Short, carefully structured case reports using four cues were designed and a checklist similar to the one used for test ordering in practice was employed. Chart reviews and billing encounter forms were used for comparison. Results indicated residents ordered fewer tests in clinical practice, due, in part, to practice constraints not represented in the written cases. Physicians tend to make the diagnosis of hypertension incrementally in practice, with no one visit adequately representing the point of diagnosis. Studies based on data bases using a patient encounter as the unit of analysis in chronic disease such as hypertension may spuriously underestimate the actual number of tests ordered for the workup. Judgment cases may better reflect the patterns of use of information in a well-defined problem. Prediction of number of tests ordered in the clinical setting has not been established in this case.

Adult↗

[Angiography of hepatic angiomatosis in Rendu-Osler disease. Apropos of 3 cases].

The hepatic changes in hereditary hemorrhagic telangiectasia (Rendu Osler's disease) involve the extra- and intrahepatic vessels (enlarged hepatic artery, arteriovenous fistulas and inhomogeneous perfusion) and the hepatic parenchyma (fibrosis, telangiectasic cirrhosis). From three observations with liver involvement and imaged with angiography and dynamic CT, the authors emphasize on the role of the latter for detection of these changes, mostly arteriovenous fistulas.

Adult↗