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Biomedical subjects

F Fuchs

Publications and source records attributed to F Fuchs.

At least 37 records · Page 2Linked to original sources

Length-dependent effects of osmotic compression on skinned rabbit psoas muscle fibers.

The goal of this study was to characterize the interrelationship between sarcomere length and interfilament spacing in the control of Ca2+ sensitivity in skinned rabbit psoas muscle fibers. Measurements were made at sarcomere lengths 2.0, 2.7 and 3.4 microm. At 2.7 microm the fiber width was reduced by 17% relative to that at 2.0 microm and the pCa50 for force development was increased by approximately 0.3 pCa units. In the presence of 5% Dextran T-500 the fiber width at sarcomere length 2.0 microm was also decreased by 17% and the Ca2+ sensitivity was increased to the same value as at 2.7 microm. In contrast, at sarcomere length 2.7 microm the addition of as much as 10% Dextran T-500 had no effect on Ca2+ sensitivity. At sarcomere length 3.4 microm there was an additional 7% compression and the Ca2+ sensitivity was increased slightly (approximately 0.1 pCa units) relative to that at 2.7 microm. However at 3.4 microm the addition of 5% Dextran T-500 caused the Ca2+ sensitivity to decrease to the level seen at 2.0 microm. Given that the skinning process causes a swelling of the filament lattice it is evident that the relationship between sarcomere length and Ca2+ sensitivity observed in skinned fibers may not always be applicable to intact fibers. These data are consistent with measurements of Ca2+ in intact fibers which indicate that there might be a decline in Ca2+ sensitivity at long sarcomere lengths.

Animals↗

Changes in thiamin, riboflavin, niacin, beta-carotene, vitamins, C, A, D and E status of French Elderly Subjects during the first year of institutionalization.

Vitamin status was assessed in 26 recently institutionalized elderly subjects by combining dietary and biochemical measurements of thiamin, riboflavin, niacin, beta-carotene, vitamins C, A, D and E at admission (P1), and 1.5 (P2), 3.0 (P3), 4.5 (P4), 6.0 (P5), 12 (P6) months later. At admission, except for vitamin A, mean vitamin intakes were lower than the 1992 French Recommended Dietary Allowance. Thiamin, vitamins C, A and E status seemed nearly satisfactory as less than one-fourth of the population sample had blood values lower than the cut-off point for thiamin (erythrocyte thiamin pyrophosphate < 0.17 mumol/l), vitamin A (serum retinol < 1.05 mumol/l), vitamin C (serum vitamin C < 11.3 mumol/l) and vitamin E (serum alpha-tocopherol < 9.3 mumol/l) or higher than the cut-off point for thiamin (erythrocyte transketolase activity coefficient > 1.19). Almost half of the subjects for riboflavin, and almost all non supplemented subjects for vitamin D were in risk of vitamin deficiency (46% had an erythrocyte glutathione reductase activity coefficient > 1.19 and 72% had a plasma 25(OH)D3 < 25 nmol/l). During the study, vitamins status remained unchanged for riboflavin, niacin, vitamins A, D and E, improved for vitamin C (P = 0.004) or impaired for thiamin (P = 0.008). Thus, institutionalization seemed to have no effect on riboflavin, niacin, vitamins A, D and E status and a slight effect on thiamin and vitamin C status.

Aged↗

Folate status worsens in recently institutionalized elderly people without evidence of functional deterioration.

OBJECTIVE: To follow folate status, hematological and cognitive changes during the first year of institutionalization among elderly subjects. DESIGN: Prospective study. SETTING: Long-stay unit of the Dijon University Geriatric Hospital. SUBJECTS: Twenty women and four men older than 65 years admitted consecutively. MAIN OUTCOME MEASURES: Folate and vitamin B-6 dietary intake was evaluated by a five-day record on admission (day 1 or d 1), at day 45 (d 45), day 90 (d 90), day 135 (d 135), day 180 (d 180), day 360 (d 360). Circulating levels of folate, vitamin B-6, total homocysteine (tHcy), blood counts and cognitive performance were determined in parallel. RESULTS: From d 1 to d 360, mean folate and vitamin B-6 intakes remained below the French RDA and mean folate intakes decreased significantly (delta = 10.2%, p < 0.05). Mean plasma or erythrocyte folate decreased significantly (delta = 33.7%, p <0.05 and delta = -30.2%, p < 0.001, respectively) from d 1 to d 360; no significant change was observed for the other blood parameters. The incidence of folate deficiency increased (8% vs. 37% for plasma folate <6.8 nmol/L and 8% vs. 17% for erythrocyte folate <340 nmol/L) from d I to d 360. Mean plasma pyridoxal 5'-phosphate (PLP) remained <20 nmol/L during the one-year follow-up. There was no difference between genders for plasma tHcy. Although mean plasma tHcy was <14 micromol/L. plasma tHcy was >14 micromol/L in about one-third of the subjects. At each period, 50% or more subjects were anemic (Hct <35% in women and Hct <40% in men), but the anemia was normocytic (MCV <100 fL). Subjects had a moderate dementia at admission, and no change was observed during the study. CONCLUSIONS: Subjects were already vitamin B-6 deficient at admission. Folate status was impaired during the study. Low vitamin intakes were the main cause of vitamin B-6 deficiency and folate status deterioration. Hematology and mental status capacity were not aggravated by folate status deterioration. Plasma tHcy didn't appear to be an earlier predictor of folate deficiency.

Aged↗

Effect of ionic strength on length-dependent Ca(2+) activation in skinned cardiac muscle.

The length-dependence of myofilament Ca(2+) sensitivity is considered to be an important component of the steep force-length relationship in cardiac muscle (Frank-Starling relation). Recent studies suggest that Ca(2+) sensitivity is a function of the number of strong-binding cross-bridge interactions formed at a given sarcomere length. However, the length-dependent step in the thin filament activation process is still unknown. This study was designed to test the hypothesis that sarcomere length influences the transition of the thin filament from the unattached (blocked) state to the weakly bound (closed) state. This hypothesis was tested by determining the length-dependence of Ca(2+) sensitivity as a function of ionic strength in skinned bovine ventricular muscle. Previous studies have shown that reduction in ionic strength below a critical level, in the absence of Ca(2+), shifts the thin filament to the closed state. In this study normal Ca(2+) regulation was maintained at low ionic strength but the length-dependence of Ca(2+) sensitivity and the length-dependence of Ca(2+) binding were eliminated. These results are consistent with the hypothesis that the transition from the blocked to the closed state is a function of filament geometry as well as Ca(2+) and ionic strength.

Animals↗

Postpolio syndrome: poliovirus persistence is involved in the pathogenesis.

The pathogenesis of the postpolio syndrome (PPS) remains unclear. In this study we looked for poliovirus (PV) persistence in the CSF of 20 patients with PPS, in a control group including 20 patients with unrelated neurological diseases, and in 7 patients with stable poliomyelitis sequelae. CSF samples and sera were examined using reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of PV or other enterovirus genomes; this assay allows the detection from as little as 1 fg viral RNA. Sequencing of amplified products from 5 patients was performed. PV genomic sequences were detected in the CSF of 11 of 20 patients with PPS and in none of the control group. Sequencing in the 5' untranslated region confirmed the presence of mutated PV sequences. These findings suggest that PPS is related to the persistence of PV in the central nervous system.

Adult↗

[Food consumption of infants and young children in France in 1997].

BACKGROUND: In 1981 and 1989, two French nationwide food consumption surveys reported the dietary intakes of infants and toddlers. In 1997, another survey was conducted. POPULATION AND METHODS: Six-hundred and sixty, 1 to 30-month-old infants and children were recruited. Food records were completed by their parents during a 3-day period. Energy, proteins, carbohydrates, total lipids, minerals, vitamins, linoleic acid contents were calculated. Energy contribution of various food groups and the pattern of the distribution of the different meals were indicated. RESULTS: Between 1989 and 1997, the contribution of milk-based infant formulas increased at 4, 5, 7 and 8-9 months. From the age of 5 months, approximately 75% of the children had a protein intake twice as high as the official recommendations. Mean iron intakes were higher than those calculated in 1989 at the age of 7, 8-9 and 10-12 months. The average daily intake of linoleic acid was lower than the recommended daily allowance from the age of 6 months. CONCLUSION: Trends in dietary intakes between 1989 and 1997 indicated that the nutritional needs of French infants and toddlers are better covered as recommended by scientific committees. More effective efforts are needed for improvement of their nutritional status particularly for iron and essential fatty acids. For example, weaning foods should be introduced later and toddler's formulas should be used more systematically and longer.

Age Factors↗

Risk of Hepatitis A Infection among Young Travelers to Developing Countries: The Need for Vaccination.

In France, as in most industrialized countries, the seroprevalence of hepatitis A virus (HAV) infection decreases due to improvements in hygiene and sanitation, but is still frequent in developing countries.1 In a cohort of military recruits followed up in France, this rate fell from 50% in 1978 to 16% in 1994.2 It is likely, therefore, that young travelers from industrialized countries would not have prior immunity and would be more susceptible to HAV infection when visiting endemic areas.3 However, a safe and effective vaccine for hepatitis A has been available since 1992.4 To highlight the need for this vaccination in young people traveling to such countries, we report a cluster of cases of hepatitis A in a troop of French scouts after they visited a West African village.

Journal Article↗

Length-dependence of actin-myosin interaction in skinned cardiac muscle fibers in rigor.

It has been suggested that the length dependence of myofilament Ca2+ sensitivity and of Ca2+ binding to troponin C, observed over the ascending limb of the cardiac force-length curve, is based on variation in the number of interacting cross-bridges. This interaction would be reduced at short sarcomere length as a consequence of double overlap of oppositely polarized actin filaments and increased lateral separation of actin and myosin filaments. Based on current evidence, it is not clear to what extent the actin-myosin interaction is hindered at sarcomere lengths where Ca2+ sensitivity is reduced. We have used two biochemical assays to assess cross-bridge attachment in rigor muscle at sarcomere lengths corresponding to the ascending limb of the cardiac force-length curve. These are based on (1) the inhibition of K+-activated myosin ATPase by the complexation of actin with myosin, and (2) the enhancement of Ca2+ binding to troponin C by rigor bridge attachment to actin. Measurements were made with skinned fibers from bovine ventricle. As a check on our method, measurements were also made with skinned rabbit psoas muscle fibers. With both muscle types, a reduction in sarcomere length along the ascending limb of the force-length curve was associated with an increase in K+-activated ATPase activity and a reduction in Ca2+ binding to the regulatory sites of troponin C. These results indicate that actin-myosin interaction is significantly reduced at short sarcomere length.

Actins↗

Comparative sensitivities of Sabin and Mahoney poliovirus type 1 prototype strains and two recent isolates to low concentrations of glutaraldehyde.

Significant intratypic differences in the glutaraldehyde (GTA) sensitivity of echovirus isolates have been shown. While exploring ways to optimize the study of GTA sensitivity of enteroviruses, we also observed intratypic differences in poliovirus type 1 isolates collected in France. A suspension procedure was used for assessing the virucidal effect of GTA at low concentrations (< or = 0.10%) against purified viruses. Two recent isolates of poliovirus type 1 tested were first fully characterized by the PCR restriction fragment length polymorphism (RFLP) test. The RFLP pattern of clinical isolate 5617 was similar to that of poliovirus type 1 LS-c, 2ab (Sabin strain), confirming the vaccine origin of strain 5617. The RFLP pattern of strain 5915 recovered from sewage was different from that of the Mahoney strain, suggesting a genetic variation in this wild isolate. We then analyzed under the same controlled conditions the GTA sensitivities of both isolates and their respective prototype strains. The wild Mahoney and 5915 strains exhibited significantly lower sensitivities to GTA than did the vaccine Sabin and 5617 strains. The inactivation rates of clinical isolates 5617 and 5915 were very similar to those of their corresponding reference Sabin and Mahoney strains. Both the conformational structure of the capsid of each strain and the amino acid constitution of structural polypeptides could be involved in the variations observed. The relevance of our comparative sensitivity studies to standardization of virucidal tests is discussed.

Animals↗

Comparative study of poliovirus excretion after vaccination of infants with two oral polio vaccines prepared on Vero cells or on primary monkey kidney cells.

A comparative study was designed to assess the bioequivalence of 2 oral poliovaccines (OPV) produced on 2 different cell systems: primary monkey kidney (PMK) cells and the Vero cell line. The Vero cell line has been used to overcome the problem of obtaining a regular supply of high quality monkeys that are devoid of latent viruses. For this study, 9 children were vaccinated with PMK-OPV and 12 children with Vero-OPV. The comparison covered poliovirus excretion, reversion of polioviruses in the 5'-noncoding region, and immunogenicity. Major molecular markers in the 5'-noncoding region related to neurovirulence already had been identified at position 480 for type 1, position 481 for type 2, and position 472 for type 3 poliovirus. Two nucleic-acid based methods were designed for studying these positions: a RT-PCR followed by sequencing, which required preliminary culture and cloning; and a type-specific nested PCR followed by sequencing, which enabled direct detection and genotyping of polioviruses. Twenty-eight stool specimens were analyzed by this second method with no PCR inhibition problem. The use of Vero cell line did not modify the global pattern of poliovirus excretion, reversion frequency, or seroconversion. These results provide additional support for the use of the well-characterized Vero cell line in OPV manufacturing.

Animals↗

Sarcomere length versus interfilament spacing as determinants of cardiac myofilament Ca2+ sensitivity and Ca2+ binding.

The Ca2+ sensitivity of skinned cardiac muscle can be increased by either an increase in sarcomere length or osmotic compression of the myofilament lattice. The length-dependent change in Ca2+ sensitivity is considered to be an important component of the steep force-length relation along the ascending limb of the force-length curve (Frank-Starling relation). Since an increase in sarcomere length is accompanied by a reduction in the spacing between myosin and actin filaments it is not clear whether length-dependent changes in Ca2+ sensitivity are related to changes in sarcomere length, interfilament spacing or some combination of both. To obtain quantitative information on the relative contributions of these two parameters to the determination of Ca2+ sensitivity skinned bovine cardiac muscle bundles of varying sarcomere lengths (1.7-2.3 microns) were exposed to varying concentrations (0-5%) of Dextran T-500. Measurements were made of changes in muscle width in response to Dextran T-500 addition and both force-pCa curves and bound Ca(2+)-pCa curves were obtained as a function of sarcomere length and lattice compression. From the data obtained it was possible to compare Ca2+ sensitivity and Ca(2+)-troponin C affinity at different sarcomere lengths under conditions of changing interfilament spacing and constant interfilament spacing. Both Ca2+ sensitivity and Ca2+ binding correlated more closely with change in interfilament spacing than with change in sarcomere length. These results suggest that length-dependent force generation in cardiac muscle is based primarily on length-dependent changes in the separation between myosin and actin filaments.

Actin Cytoskeleton↗

A study on the mechanism of phalloidin-induced tension changes in skinned rabbit psoas muscle fibres.

The time course of phalloidin induced changes in isometric tension of partially activated skinned rabbit psoas fibres was studied as a function of both phalloidin concentration and time of pre-incubation with phalloidin. Upon addition of phalloidin to non-pretreated (control) fibres there was a fall in tension followed by an increase in tension. The latency of both parts of the response was inversely related to the phalloidin concentration in the range 40-130 microM phalloidin. By preincubating the fibres with phalloidin for varying periods of time it was possible to obtain responses which appeared to represent later portions of the control response. Thus after pre-treatment with 40 microM phalloidin in either rigor or relaxing solution for 5 min (the time corresponding to minimal tension in the control response) the tension response resembled that of the control, beginning from the vicinity of the minimum. The pattern of staining of the fibres by rhodamine-phalloidin was analysed by laser confocal microscopy to relate the mechanical response to phalloidin localization. If fibres were treated with rhodamine-phalloidin for 20-25 min there was a labelling of the I-Z-I segment with intense peaks of fluorescence at the Z-line and the ends of the I filaments. If fibres were pre-incubated for 5 min with phalloidin and then labelled with rhodamine-phalloidin the fluorescence at the Z-line and at the ends of the I filaments was suppressed and the peak of the fluorescence intensity was shifted toward the middle part of the I filament. The data indicate that the decrease in tension caused by phalloidin was associated with binding of phalloidin to the pointed ends of actin filament and the Z-line region, whereas the increase in tension occurred when phalloidin was bound along entire length of the actin filament.

Animals↗

Evidence of presence of poliovirus genomic sequences in cerebrospinal fluid from patients with postpolio syndrome.

The postpolio syndrome (PPS) is characterized by new neuromuscular symptoms occurring 30 to 40 years after the acute episode of poliomyelitis paralysis. The presence of the poliovirus RNA genome in the cerebrospinal fluid from 10 patients with PPS and from 23 control patients was sought by using reverse transcription and a PCR specific for polioviruses and/or other enteroviruses. Poliovirus-specific genomic sequences in the 5' untranslated region and in the capsid region (VP1) were detected by reverse transcription PCR in 5 of 10 patients with PPS but in none of the control patients. Sequencing confirmed the presence of mutated poliovirus sequences. This finding suggests persistent viral infection in the central nervous system related to the presence of poliovirus genomes.

Adult↗

Vitamin status of healthy subjects in Burgundy (France).

A nutrition survey was conducted in Burgundy (France) with a population sample of 337 middle-aged and healthy subjects (157 males and 180 females) recruited at a health examination center in 1985-1986. The status of beta-carotene, thiamin, riboflavin, folate, vitamin B6, B12, C, A, D, and E was assessed by means of 7-day food records and biochemical studies. Results were compared with two other recent nutritional surveys conducted in France: ESVITAF (control group only) and Val de Marne surveys. The dietary information collected for each subject was compared to the 1992 French Recommended Dietary Allowances (FRDA). Dietary vitamin intakes were higher in males than in females. Low vitamin intakes (< 1/2 FRDA) were found in 5% of males and 7% of females for thiamin, in 11% of males and 28% of females for vitamin B6, in 6% of males and 3% of females for vitamin C, in 87% of males and 91% of females for vitamin D, and in 8% of males and 13% of females for vitamin E. No subject had a vitamin intake < 1/2 FRDA for riboflavin, folate, vitamins A and B12. ESVITAF and Val de Marne studies also show low vitamin intakes for vitamin B6, thiamin, riboflavin, vitamins D and E. Biochemical status was examined using erythrocyte enzyme function and blood vitamin levels. The percent of subjects with deficient biochemical values was high for vitamin B6 (15% of all males and 20% of all females), and vitamin D (13% of all males, and 15% of all females). With regard to thiamin, riboflavin, vitamin C, folate, vitamin B12, vitamin A, and vitamin E, < 5% of subjects had values in the range of major vitamin deficiency. However, in both genders, except for vitamin C and vitamin A (only for females), low values corresponding to a moderate risk of vitamin deficiency was high for most vitamins. The incidence of a severe deficient vitamin status for thiamin and riboflavin was higher in Val de Marne than in Burgundy, or ESVITAF. In Val de Marne, the probability of a moderate risk of vitamin deficiency was high for thiamin, riboflavin, vitamin B6, vitamin A and vitamin E. Our results (as other studies performed in France and in other industrialized countries) raise the issue of the health significance of marginally deficient vitamin status.

Adolescent↗

Osmotic compression of skinned cardiac and skeletal muscle bundles: effects on force generation, Ca2+ sensitivity and Ca2+ binding.

Length-dependence of myofilament Ca2+ sensitivity is now considered to be an important component of the steep relationship between active force and sarcomere length along the ascending limb of the cardiac force-length curve. Studies with skinned cardiac muscle preparations have demonstrated that Ca(2+)-troponin C affinity is significantly increased as sarcomere length is increased over the range 1.7-2.3 microns. Increase in sarcomere length is accompanied by a reduction in interfilament spacing. In skinned fiber preparations from both cardiac and skeletal muscle osmotic compression of the filament lattice enhances myofilament Ca2+ sensitivity. This study was undertaken to evaluate the hypothesis that a change in filament separation may contribute to the length-dependent activation seen in cardiac muscle. Moderate reduction in interfilament spacing caused by exposure to Dextran T-500 (5-10%) produced an increase in force generation in both maximally activated and partially activated preparations of skinned bovine ventricular muscle. With fiber bundles of mean sarcomere length 1.7 microns the addition of 5% Dextran T-500 produced an increase in Ca2+ sensitivity of about 0.25 pCa units and a significant increase in Ca2+ binding in the pCa range (6.0-5.0) in which the single regulatory site of cardiac troponin C is titrated. This concentration of Dextran T-500 produced a reduction in fiber width equivalent to that produced by stretching fibers from sarcomere length 1.7 microns to sarcomere length 2.3 microns Osmotic compression of skinned rabbit psoas muscle fibers also enhanced Ca2+ sensitivity but there was no significant change in Ca(2+)-troponin C affinity. These data suggest that 1) an important component of length-dependent Ca2+ sensitivity in both cardiac and skeletal muscle is the change in interfilament spacing, and 2) in cardiac muscle a reduction in spacing, like increase in length, leads to a specific increase in Ca(2+)-troponin C affinity. Thus both filament overlap and filament separation contribute to the length dependence of Ca2+ sensitivity and Ca2+ binding in cardiac muscle.

Animals↗