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Biomedical subjects

F G Jennekens

Publications and source records attributed to F G Jennekens.

At least 73 records · Page 4Linked to original sources
PubMed1990

Oxidative phosphorylation in human muscle in patients with ocular myopathy and after general anaesthesia.

The fuel preference of human muscle mitochondria has been given. Substrates which are oxidized with low velocity cannot be used to detect defects in oxidative phosphorylation. After general anaesthesia, the oxygen uptake with the different substrates is much lower than after local analgesia. The latter was therefore used in the subsequent study. In 15 out of 18 patients with ocular myopathy, defects in oxidative phosphorylation could be detected in isolated muscle mitochondria prepared from freshly biopsied tissue. Measurement of the activity of segments of the respiratory chain in homogenate from frozen muscle showed no, or minor defects. In two of these patients showing exercise intolerance, decreased oxidation of NAD(+)-linked substrates and apparently normal mitochondrial DNA, further study revealed deficiency of pyruvate dehydrogenase in a girl with ptosis and a high Km of complex I for NADH in a man. Both patients responded to vitamin therapy.

Adolescent↗
PubMed1990

Prevention of cisplatin neurotoxicity with an ACTH(4-9) analogue in patients with ovarian cancer.

In a randomized, double-blind, placebo-controlled study, we assessed the efficacy of an ACTH(4-9) analogue, Org 2766, in the prevention of cisplatin neuropathy in 55 women with ovarian cancer. The analogue was given subcutaneously in a dose of 0.25 mg (low dose) or 1 mg (high dose) per square meter of body-surface area before and after treatment with cisplatin and cyclophosphamide (75 and 750 mg per square meter every three weeks). The threshold of vibration perception was used as the principal measure of neurotoxicity. After four cycles of chemotherapy, the mean (+/- SEM) threshold value for vibration perception in the placebo group increased from 0.67 +/- 0.12 to 1.61 +/- 0.43 microns of skin displacement (P less than 0.0001). In the high-dose treatment group, there was no increase in the threshold value after four cycles (from 0.54 +/- 0.12 to 0.50 +/- 0.06 micron). After six cycles of chemotherapy, the threshold value was 5.87 +/- 1.97 microns in the placebo group (more than an eight-fold increase from base line), as compared with 0.88 +/- 0.17 micron (less than a twofold increase) in the high-dose treatment group (P less than 0.005). In the high-dose group, fewer neurologic signs and symptoms were recorded than in the placebo group. With the lower dose of the analogue, these protective effects were less prominent. No side effects were seen after treatment with Org 2766. The rates of clinical response to chemotherapy were similar in all groups. These results suggest that Org 2766 can prevent or attenuate cisplatin neuropathy without adversely affecting the cytotoxic effect of the drug.

Adrenocorticotropic Hormone↗
PubMed1990

Morphological changes in the human end plate with age.

We carried out a light and electron microscopic study on end plates and related structures in external intercostal muscles from subjects aged between 4 and 77 years. Light microscopically end plates maintained the same size, did not increase in number and showed no sprouting of terminal axons, all indicating that major compensatory histological changes to maintain adequate neuromuscular transmission with age were not required. At the ultrastructural level end plates became more complex mainly at the postsynaptic side. The latter included increased length and branching of the postsynaptic membrane with enlargement of the postsynaptic area, and degeneration of junctional folds. However, some neuromuscular junctions (NMJs) showed little branching of the postsynaptic membrane, even in old age. At the presynaptic side nerve terminals with an irregular shape were noted in the aged. Schwann cell processes were seen to intrude into the primary synaptic cleft. From these data we suggest that degeneration of the postsynaptic membrane with consequent focal denervation of NMJs is a primary event in the age-related changes of end plates. The muscle fibres showed a minor degree of type grouping in old age doubtless due to loss of motor neurons with age.

Adult↗
PubMed1990

Lip-length and snout indices: methods for quantitative assessment of peri-oral facial muscle strength.

Two simple bedside methods for the assessment of perioral muscle function are described. Using a marking gauge, the width of the mouth can be measured easily and accurately. Lip-length (LL) and snout (S) indices are expressions of the degree to which the width of the mouth can be lengthened or shortened. Facial muscle weakness as present in patients with various neuromuscular diseases results in low values for both indices. LL- and S-indices are measured by 3 observers in 19 healthy volunteers. Interobserver variation is negligible for the LL-index and large for the S-index. Intraobserver variation is moderate for both indices but slightly smaller for the LL- than for the S-index. The LL-index is suited for the assessment of changes in peri-oral musculature in longitudinal investigations.

Adult↗
PubMed1989

Carnitine deficiency, mitochondrial dysfunction and the heart. Identical defect of oxidative phosphorylation in muscle mitochondria in cardiomyopathy due to carnitine loss and in Duchenne muscular dystrophy.

Cardiomyopathies are often caused by a metabolic defect. Carnitine deficiency and mitochondrial defects in the metabolism of acyl-CoA, including defects in oxidative phosphorylation, start the same circular mechanism of mitochondrial doom. Patients with cardiomyopathy due to carnitine loss are cured by carnitine supplementation. In such a patient we found defective oxidative phosphorylation in isolated muscle mitochondria. The stimulation of the respiratory rate with all substrates by ADP was decreased, probably the cause of inhibition of the adenine nucleotide translocator by accumulating long-chain acyl-CoA. The same condition was encountered in patients with Duchenne muscular dystrophy, who often get cardiomyopathy in the course of the disease process.

Acetyl Coenzyme A↗
PubMed1989

Perisynaptic satellite cells in human external intercostal muscle: a quantitative and qualitative study.

It is not known whether or not satellite cell nuclei are more common in the vicinity of motor endplates than in extrasynaptic regions of human muscle, as in animals. If so, perisynaptic satellite cells may have a role in preserving neuromuscular function. We compared the frequencies of satellite cell nuclei and of myonuclei in perisynaptic and extrasynaptic regions of human external intercostal muscle, and found an absolute as well as a relative increase of perisynaptic satellite cells. The mean frequency of satellite cell nuclei per sarcomere was 0.016 in perisynaptic and 0.00003 in extrasynaptic regions. The mean frequency of myonuclei per sarcomere was 0.098 in perisynaptic and 0.014 in extrasynaptic regions. We could not demonstrate any influence of aging on satellite cell distribution. Perisynaptic satellite cells had many processes, and some features suggested a more active state. These cells might add to the pool of junctional myonuclei for synthesis of acetylcholine-receptor molecules or help in the repair of the postsynaptic membrane. Alternatively, they may synthesize basal lamina substances that are specific for the endplate.

Adult↗
PubMed1989

Org.2766 stimulates collateral sprouting in the soleus muscle of the rat following partial denervation.

The influence of melanocortins on the process of collateral sprouting has been investigated in rat soleus muscle. The soleus muscle was partially denervated by transecting and ligating the L5 mixed nerve. Collateral sprouting was assessed by means of isometric twitch tension measurements of soleus motor units that remained following L5 transection. The smaller the number of remaining soleus motor units, the larger the extent of collateral sprouting. Seven days following partial denervation, the index of sprouting (ratio between twitch tension of motor units in partly denervated muscles and in normal muscles) was significantly increased by treatment with the ACTH4-9 analog Org.2766 (1 microgram/48 hours). This increase appeared to be present also 28 days following partial denervation. The electrophysiological results were confirmed by histological investigations. The results provide evidence that Org.2766 increases the motor neuron collateral sprouting capacity of peripheral nerve. Org.2766 did not induce muscle fiber hypertrophy.

Adrenocorticotropic Hormone↗
PubMed1989

A light and electron microscopical study of B-50 (GAP-43) in human intramuscular nerve and neuromuscular junctions during development.

The growth associated protein B-50 (GAP-43) is demonstrated in human intramuscular nerves and neuromuscular junctions by light microscopy and electron microscopy. Nearly all fetal endplates are shown to be immunoreactive for B-50. The percentage of B-50 positive endplates decreases significantly during the peri- and neonatal period, but in children and adults a low percentage of B-50 positive endplates remains present. These data indicate that also in the human peripheral nervous system the expression of B-50 is developmentally regulated.

Adult↗
PubMed1989

Vibration perception and thermoperception as quantitative measurements in the monitoring of cisplatin induced neurotoxicity.

In 20 ovarian cancer patients treated by cisplatin-based chemotherapy quantitative investigations of the vibration and the thermoperception were performed. Following the administration of cisplatin of 300 mg/m2 and more the vibration perception threshold (VPT) was shown to be significantly elevated in all patients, despite the absence of clinical symptoms and signs in a number of patients. The VPT returned within 8 months to its original level in the 2 patients who were followed after cessation of therapy (cumulative dose of cisplatin 450-525 mg/m2). The changes seen in hands and in feet were comparable. There was no significant difference between the left and the right hand side. Thermoperception thresholds did not change during the treatment period. This study shows that quantitative measurement of vibration perception thresholds in patients treated with cisplatin is a relatively simple, accurate and reliable technique. Measurement is only required at the hand. It is concluded that this technique is a valuable tool in the assessment of cisplatin neurotoxicity and may be used in the monitoring of drugs that claim to be of benefit in the prevention and treatment of this affliction.

Cisplatin↗
PubMed1989

Congenital paucity of secondary synaptic clefts (CPSC) syndrome in 2 adult sibs.

We studied 2 elderly sibs with a congenital form of myasthenia who had ptosis since early childhood. The extraocular muscles were weak and the proximal limb muscles became slowly weaker throughout life. Laboratory investigations of biopsies of intercostal muscle from these patients showed the following abnormalities: the amplitude of miniature end-plate potentials was small and the binding of 125I-alpha-bungarotoxin at the end-plate area was reduced, suggesting a considerable reduction of acetylcholine receptors (AChRs). Secondary synaptic clefts were scarce, whereas the number of end-plates per muscle fiber was increased. There was no indication of impaired transmitter release as the quantal content was within the range of controls. We conclude that these patients suffered from the congenital paucity of secondary synaptic clefts (CPSC) syndrome, described recently in 2 cases of myasthenic children, and suggest that the CPSC syndrome is a developmental disorder in which a deficiency of AChRs may be caused by a decreased clustering or insertion of AChRs. The increased number of end-plates per muscle fiber in both patients could serve as a compensatory mechanism.

Bungarotoxins↗
PubMed1988

A myasthenic syndrome with congenital paucity of secondary synaptic clefts: CPSC syndrome.

Two cases of a newly recognized myasthenic syndrome were investigated (CPSC syndrome). The course of the disease was observed for periods of 6 and 3 years. In infancy, exacerbations of the symptoms occurred during febrile illness, but thereafter the clinical course was stable and the children appeared to be only slightly handicapped. Biopsies were taken from the intercostal muscle in both patients. Microelectrode studies revealed small Mepp amplitudes. Light microscopy demonstrated predominance of type I fibers and focal type-grouping. There was a lowered cholinesterase activity and frequent branching of preterminal axons. Electron microscopy revealed that there were few, if any, folds of the postsynaptic membrane and that there were no signs of degeneration. Methods for localization of acetylcholine receptors (AChR) revealed a deficiency and altered distribution of AChRs at these postsynaptic membranes and the occurrence of extrajunctional AChRs in some muscle fibers. It is concluded that the syndrome is a clinicopathological entity, characterized morphologically by a congenital paucity of secondary synaptic clefts (CPSC syndrome).

Child↗
PubMed1988

Histological investigations of muscle atrophy and end plates in two critically ill patients with generalized weakness.

We describe pathological alterations at the light microscopical and ultrastructural level of motor end plates and muscle fibres in 2 critically ill patients with generalized muscular atrophy and weakness. Axonal degeneration of intramuscular nerve fibres was not conspicuous. The sural nerve in one patient showed only minor abnormalities. There was a marked atrophy of type 1 and especially type 2 muscle fibres. Nodal and ultraterminal nerve sprouts were seen in both biopsies. Motor end plates showed features of regeneration. They were enlarged in one patient. This patient was treated for a prolonged period with vecuronium bromide. Pharmacological denervation may explain the presence of fibrillation potentials, and, partially, of the histological abnormalities. Another factor which must be considered is inhibition of neuromuscular transmission by antibiotics. In addition to disuse atrophy and a minor degree of axonal neuropathy, the production of muscle proteolytic factors may be involved in the rapidly occurring massive loss of muscle fibre size in critically ill patients.

Atrophy↗
PubMed1988

Efficacy of the neuropeptide ORG.2766 in the prevention and treatment of cisplatin-induced neurotoxicity in rats.

In rats chronic systemic treatment with cisplatin results in a sensory neuropathy as evidenced by a reduction in the sensory conduction velocity in the sciatic nerve. Concomitant administration of the neurotrophic ACTH4-9 analog, ORG.2766, prevents the occurrence of the neuropathy. In addition, treatment with ORG.2766 stops further deterioration and improves recovery of an already established cisplatin-induced neuropathy. Furthermore, concomitant administration of ORG.2766 during a first cisplatin treatment period results in a better resistance against neurotoxicity in a second exposure period. Finally, ORG.2766 was shown not to hamper the anti-tumor effect of cisplatin in mice, carrying implanted tumor cells from a FMa human tumor line. These data are discussed in view of the potential clinical use of ORG.2766 in prevention and treatment of cisplatin-induced neuropathy.

Adenocarcinoma↗