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Biomedical subjects

H F Busch

Publications and source records attributed to H F Busch.

At least 55 records · Page 3Linked to original sources
PubMed1988

Exercise responses in patients with an enzyme deficiency in the mitochondrial respiratory chain.

Responses to exercise were obtained in six patients with a biochemically diagnosed enzyme deficiency at the level of NADH-CoQ reductase. The responses were compared with those of a control group, consisting of fourteen patients with inexplicable dyspnoea or muscle pain during exercise, for which no firm diagnosis could be established and of which the exercise responses were in the normal range. Metabolic, ventilatory and cardiological variables such as oxygen uptake (VO2), minute ventilation (VE), respiratory exchange ratio (R), heart rate (HR) and difference in blood lactate or base-excess (BE) between rest and maximal workload were measured during cycle ergometry from samples obtained in the last minutes of four minute periods, in which the load increased stepwise by 30 W per four minutes. The threshold of lactate metabolism (Tlact) was assumed to be equal to the threshold determined both by the VO2 at which the VE versus VO2 response started to deviate from a straight line and the ventilatory equivalent for oxygen (VE/VO2) showed a minimum (Tvent), Tvent was estimated from the mean of these values, obtained by linear and parabolic regression analysis respectively. In the patient group, mean values for symptom limited maximal VO2 (VO2,max,sl; % of VO2,max,ref), Tvent (% of VO2,max,ref) and R at maximal workload were 43, 17 and 1.23 against 85, 47 and 1.06 for the same variables in the control group, respectively. The differences were highly significant (p less than 0.001; p less than 0.005 for mean R difference). Mean maximal HR and mean change in blood lactate or BE were not significantly different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Defects in oxidative phosphorylation. Biochemical investigations in skeletal muscle and expression of the lesion in other cells.

Mitochondria are very vulnerable to genetic and environmental damage. If a patient is suspected of having a mitochondrial disease, elevated blood lactate, lowered blood free carnitine, abnormal urinary organic acids and carnitine esters and tissue histopathology may help with the diagnosis. For biochemical assessment of the defect, muscle is the tissue of choice even when involvement of other organs like heart or brain is more prominent. We have studied isolated muscle mitochondria and homogenates from muscle biopsies in 250 patients, and have detected in more than one third mitochondrial defects in oxidative phosphorylation, dehydrogenases, non-redox enzymes catalyzing synthesis of fuel molecules and in the carnitine system. Several patients showed more than one defect. We have selected eight patients to illustrate how a relatively simple series of investigations in both isolated mitochondria and homogenate can be used for the identification of defects in oxidative phosphorylation in a small amount of muscle (200 mg or more). Identification of the defect(s) is important since it may provide the basis for rational treatment. A minority of the patients recovered partly or completely, which is unique in treatment of inborn errors of subcellular organelles. An important aspect of mitochondrial dysfunction is the tissue specificity. The defect may be systemic but is often clinically expressed in only one or a few tissues. Rarely, tissue-specific defects can be understood on the basis of tissue-specificity of mitochondrial (iso-)enzymes. Mitochondrial deficiencies of all biotin enzymes and most CoA-linked enzymes are expressed in fibroblasts; most respiratory chain defects are not. When mitochondrial ATP synthesis has been compromised by a mitochondrial defect, secondary lesions may be generated by changes in mitochondrial protein synthesis, activated proteases and phospholipases, increased matrix CoA and resulting carnitine deficiency, decrease in Krebs cycle intermediates and increased free radical formation and lipid peroxidation.

Adolescent↗
PubMed1986

Pleocore disease. Multi-minicore disease and focal loss of cross striations.

We report clinical and morphological data on seven patients with a congenital myopathy as well as data concerning five parents. Classical myopathies such as rod disease, centronuclear myopathy or central core disease could be ruled out. Structural abnormalities of intracellular organelles or particulate inclusions were rare and insignificant. The most prominent and constant features were minicores and focal loss of cross striations, associated with a prevalence of type 1 fibres, increasing with the age at time of biopsy. A carrier state could not be defined in the five examined parents neither on clinical nor on morphological grounds. Although our group of patients could not clinically be distinguished from other congenital myopathies, the combination of the lesions allow their individualization as a subgroup of multicore or minicore disease under the already proposed denomination of pleocore disease [Martin and Busch, abstract in Zentralbl Allg Pathol 124:156 (1980)].

Adolescent↗
PubMed1986

Myopathy with abnormal mitochondria, transient low electron transport capacity in the respiratory chain, and absence of energy transduction at sites 1 and 2 in vitro.

A male adult with exercise-related myalgia and weakness from the age of 17 years, developed contractions after moderate exertion which were electrically silent. Triglyceride loading or prolonged fasting provoked excessive ketosis. His isolated muscle mitochondria had severe blockade of the respiratory chain, particularly of NADH-CoQ reductase. After 1.5 years a second biopsy was performed. The electron transport capacity of the respiratory chain was much improved, but now a lesion was observed in energy transduction of sites 1 and 2 of the respiratory chain. The unexpected abolishment of respiratory chain blockade was paralleled by only mild clinical improvement.

Adult↗
PubMed1985

Plasma and gamma-globulin infusion in chronic inflammatory polyneuropathy.

We treated 17 patients with chronic inflammatory polyneuropathy (CIP) with infusions of fresh-frozen plasma (FFP). Thirteen patients had a beneficial response: 12 improved considerably and one moderately. The first signs of improvement were seen within 8 days of the onset of treatment. None of these patients had had spontaneous remissions for 2 months prior to treatment, and none had received immunosuppressive medication during the plasma infusions. The treatment effect was short-lasting in 9 patients. Re-institution of the FFP infusions was always followed by improvement. The same effect could be achieved by intravenous gamma-globulin. We conclude that infusions with FFP, of which the IgG fraction is the effective part, may induce a rapid and clinically important improvement in patients with CIP.

Adolescent↗
PubMed1984

Uptake and stability of human and bovine acid alpha-glucosidase in cultured fibroblasts and skeletal muscle cells from glycogenosis type II patients.

Acid alpha-glucosidase (EC 3.2.1.20) was purified from human placenta and bovine testis by affinity chromatography using concanavalin A (conA) and Sephadex G 200. When added to the culture medium of human fibroblasts, the enzyme purified from bovine testis is taken up with a 200-fold higher efficiency than the enzyme from human placenta. Uptake of acid alpha-glucosidase from bovine testis is mediated by the mannose-6-phosphate receptor, whereas only a minor fraction of placental enzyme appears to be equipped with the mannose-6-phosphate recognition marker. Once internalized, both human and bovine acid alpha-glucosidase demonstrate a half-life of about 10 days in fibroblasts from control individuals and patients with different clinical forms of glycogenosis type II (Pompe's disease, acid alpha-glucosidase deficiency). Evidence is presented that the mannose-6-phosphate receptor is also present on the plasma membrane of the clonal myogenic skeletal muscle cell lines G8-1 and L6J1 (respectively from mouse and rat origin) and on cultured human skeletal muscle cells derived from a muscle biopsy. Addition of bovine testis acid alpha-glucosidase to skeletal muscle cell cultures from an adult patient with glycogenosis type II leads to complete correction of the enzyme deficiency.

Animals↗
PubMed1983

Hereditary neuralgic amyotrophy. Clinical, genetic, electrophysiological and histopathological studies.

Clinical, genetic, electrophysiological and histopathological studies in a four-generation family with hereditary neuralgic amyotrophy (HNA) are described. Clinically two kinds of attack could be distinguished: (1) the classical type with pain and weakness lasting for weeks to months, leaving atrophy and sometimes residual weakness; 2) attacks consisting of recurrent pain and weakness lasting for a few days and occurring about once a week for several months, also resulting in persisting atrophy and weakness. Genetically a strong association was found between HNA and hypotelorism, probably due to pleiotropism of one single gene. Close linkage with any of 29 genetic markers was not present. The electrophysiological findings indicated that a local process in the brachial plexus, possibly demyelination or a conduction block, was the primary pathophysiological mechanism. Nevertheless, the sural nerve of the index case, biopsied 5 months after the onset of an attack, showed a decreased number of myelinated nerve fibres per cross-sectional area. Apparently, other parts of the peripheral nervous system may be affected subclinically in an attack of brachial plexopathy. The central and peripheral nervous system of his mother, 30 years after her last attack of HNA, showed only nonspecific changes. Tomacula were not seen in either case. HNA and hereditary liability to pressure palsies (HLPP) are distinctly different disorders.

Adolescent↗
PubMed1983

Echocardiographic features in the cardiac type of glycogen storage disease II.

Clinical and echocardiographic findings of a six-month-old female with the cardiac variety of glycogen storage disease II type (Pompe's disease) are described. Obviously thickened right and left ventricular walls were detected with both M-mode and two-dimensional echocardiography. Echocardiographic features were similar to those seen in extreme hypertrophic cardiomyopathy. In combination with the clinical and biochemical features, this echocardiographic technique may be helpful in the early diagnosis of cardiac involvement in generalized glycogenosis.

Cardiomyopathy, Hypertrophic↗
PubMed1981

Autonomic nerve calcification and peripheral neuropathy in olivopontocerebellar atrophy.

This report concerns an unusual form of olivopontocerebellar atrophy (OPCA) of adult onset, inherited as an autosomal dominant. We examined 5 patients in one generation and performed neuropathological investigations in 3 of these. The clinical and pathological features were different from those of OPCA types I to V. Apart from olivopontocerebellar degeneration, there was dementia in 4, massive atrophy of the spinal cord in 3, and focal degeneration of the optic nerves in at least 1 case. The most remarkable findings were, however, the involvement of the peripheral nervous system and the abundant intrafascicular calcification in sympathetic nerve fibers and in their ganglia.

Atrophy↗
PubMed1981

Identification of heterozygotes for glycogenosis 2 (acid maltase deficiency).

In 21 obligate and 9 possible heterozygotes for acid maltase deficiency (AMD) (glycogenosis 2, Pompe's disease), different methods of identifying heterozygotes have been studied. Heterozygosity could not be demonstrated by physical examination, serum CPK assays, morphological examination of muscle biopsy (including light-microscopy, histochemistry and electron-microscopy), or by ultrastructural examination of a skin biopsy. Heterozygotes could be identified to a large, but still limited extent, by measuring the acid alpha-glucosidase activity in urine, cultivated fibroblasts, leucocytes, or skeletal muscle. Heterozygotes for the generalized from of AMD could not be distinguished from those for the muscular form. The limitations of heterozygote identification by means of enzyme assays are discussed, and some practical aspects for genetic counselling are mentioned.

Female↗
PubMed1981

A family with different clinical forms of acid maltase deficiency (glycogenosis type II): biochemical and genetic studies.

In the same family, the generalized or infantile form of acid maltase deficiency (glycogenosis type II, Pompe disease) and the muscular or adult-onset form affected different individuals. Autosomal-recessive inheritance for the two clinical forms was demonstrated in this family by assay of acid alpha-glucosidase in muscle, lymphocytes, cultured fibroblasts, and urine of asymptomatic relatives. Current biochemical techniques do not discriminate between persons heterozygous for the generalized form and those heterozygous for the muscular form. To explain the coexistence of both forms in the same family, the infant with the generalized form or her grandfather with the muscular form must have been a genetic compound of different mutant alleles for acid alpha-glucosidase.

Adult↗