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Biomedical subjects

J M Jacobs

Publications and source records attributed to J M Jacobs.

At least 91 records · Page 5Linked to original sources
PubMed1988

On internodal length.

A study has been made of changes in internodal lengths in rat tibial nerves and human sural nerves with age. Myelinated fibre counts on these nerves showed that maximum numbers were reached at an early stage of development. The slope of regression lines relating internodal length to fibre diameter was relatively flat at this stage, but became steeper with increasing age. Maximum internodal length in rat tibial nerve was closely related to growth of the limb bones. Whilst this study confirms that the largest fibres are subjected to hind limb growth for the greatest period, and therefore have the longest internodes, it does not support the generally accepted view that short internodes are the consequence of the later myelination of small fibres, and hence shorter period of extension due to growth.

Adolescent↗
PubMed1987

Oxidation of protoporphyrinogen to protoporphyrin, a step in chlorophyll and haem biosynthesis. Purification and partial characterization of the enzyme from barley organelles.

The protoporphyrinogen-oxidizing enzyme from Triton X-100 extracts of the mitochondrial and etioplast fractions of etiolated barley was purified by using ion-exchange and hydroxyapatite chromatography. The purified enzyme from both organelle fractions exhibited a Km of 5 microM and was labile to mild heat and acidification. The pH optimum (5-6) and the substrate-specificity (mesoporphyrinogen was oxidized as rapidly as protoporphyrinogen) revealed properties very different from the protoporphyrinogen-oxidizing enzyme of rat liver or yeast mitochondria, which is specific for protoporphyrinogen as substrate. The purest fractions showed a polypeptide band corresponding to an Mr of approx. 36,000 on SDS/polyacrylamide-gel electrophoresis. This is the first purification and characterization of the enzyme from a plant, and indicates no readily detectable differences between the enzyme isolated from mitochondrial or etioplast fractions, although only the latter organelle has the capacity for both haem and chlorophyll synthesis.

Chloroplasts↗
PubMed1987

Myelin changes in leprous neuropathy.

Myelin changes were observed in fibres of nerves from cases of leprosy. The myelin had a 'loosened' appearance caused by increased and irregular separation of the intraperiod line. 'Loosening' might affect all, or only some, of the lamellae forming a myelin sheath. There was a patchy distribution of fibres with abnormal myelin, and they were seen only in nerves showing other marked pathological changes including the presence of oedema. The appearances are suggestive of intramyelinic oedema which may be related to the presence of endoneurial oedema.

Humans↗
PubMed1987

Teased fibre studies in leprous neuropathy.

Nerve biopsies were taken from four cases of leprosy, which included borderline tuberculoid, borderline and lepromatous types. They were examined in 1-micron resin sections and in teased preparations. The most common finding in teased fibres from each leprosy type was paranodal demyelination affecting successive internodes. In transverse sections some fibres showed changes associated with axonal atrophy. Together, these findings suggest that demyelination in some cases may be secondary to axonal changes. In addition, there was evidence of focal areas of demyelination affecting whole internodes of many fibres at the same level across the nerve and which was possibly caused by local factors.

Biopsy↗
PubMed1987

Rat hepatic mitochondria are more sensitive to allyl alcohol than are those of mice.

The hepatotoxic effects of allyl alcohol with particular reference to mitochondrial morphology and function were compared in male CD1 mice and male CD rats 24 h after 0.05 ml/kg i.p. in corn oil. As already noted by others, allyl alcohol-treated rats usually showed histologic evidence of tissue necrosis when hematoxylin-eosin-stained tissue sections were examined whereas mouse tissue sections did not. The serum glutamic pyruvic transaminase (SGPT) activities were significantly elevated in both mice and rats but to a much greater extent in the latter. Pentobarbital sleeping time was significantly increased over that of corn oil control groups in rats but decreased in mice. In rats electron microscopy showed mitochondria which contained flocculent densities. State 4 respiration was not altered by allyl alcohol in rats, but state 3 respiration was significantly depressed indicating an absence of respiratory control and an inability to perform energy coupling. In allyl alcohol-treated mice the isolated mitochondria were found to be primarily in a condensed form. Except for the effect on pentobarbital sleeping time and SGPT, no other findings were different from those in control groups given only corn oil. When the dose of allyl alcohol in mice was increased to 0.15 ml/kg in an attempt to elicit more severe signs of hepatotoxicity, there was a high mortality in the first 24 h period without histologic evidence of liver necrosis. Thus, we confirm that at equivalent doses, male rats are more sensitive to the hepatotoxic effects of allyl alcohol than are male mice, and extend the generalization to the liver mitochondria of the 2 species.

1-Propanol↗
PubMed1987

Chronic demyelinating peripheral neuropathy associated with multifocal central nervous system demyelination.

A series of 6 cases is described in which a chronic demyelinating neuropathy was associated with a relapsing multifocal CNS disorder, the clinical features of which resembled multiple sclerosis. Multifocal CNS lesions were demonstrated by CT and MR imaging and the presence of CNS demyelination was indicated by prolonged central conduction times. These cases are discussed in relation to the occurrence of combined peripheral and central demyelination in chronic relapsing experimental allergic encephalomyelitis and neuritis.

Action Potentials↗
PubMed1986

Chronic demyelination in mouse peripheral nerve produced by lysophosphatidyl choline and X-irradiation: ultrastructural observations.

The effects of X-irradiation on demyelination and remyelination were studied in the peripheral nerve of the mouse. Three days after injection of lysophosphatidyl choline into one sciatic nerve, a 20 Gy dose of X-rays was administered to the hind limb. At survival times ranging from 4 days to 6 months after injection, the nerves were examined by light and electron microscopy. Removal of myelin debris was retarded and remyelination delayed or prevented. The myelin sheaths which did form were thin and the configuration of Schmidt-Lanterman incisures and nodes of Ranvier was abnormal. Some of the chronically demyelinated fibres formed focal node-like complexes: patches of finely granular material coated the inner aspect of the axolemma, the external surface was covered by slender processes of Schwann cell cytoplasm, and an electron-dense lamina was present in the enlarged periaxonal space. Elsewhere demyelinated axons and their ensheathing Schwann cells were separated by gap junctions or transverse bands. The present findings indicate that the morphological differentiation of structures thought to be characteristic of nodes of Ranvier can take place in the absence of remyelination.

Animals↗
PubMed1985

The pathology of amiodarone neurotoxicity. I. Experimental studies with reference to changes in other tissues.

Rats and mice were given amiodarone by mouth at doses of 50 mg/kg/day. The drug induced accumulations of lipids within lysosomes, leading to the formation of cytoplasmic bodies. These were found in many tissues, both nervous and nonnervous, but were excluded from regions with blood-brain or blood-nerve barriers. Of nervous system regions lying outside a vascular barrier, autonomic ganglia were the most affected, with large accumulations of lysosomal bodies in nerve cells and processes, and evidence of degenerative changes. the myenteric plexus was also involved. No significant changes were seen in peripheral nerves. A limited period of increased permeability caused by nerve crush, or due to immaturity of the blood-nerve barrier resulted in the short-lived appearance of drug-induced inclusions. The rate of regeneration of axons following nerve crush was not affected, although there were small defects in myelination.

Amiodarone↗
PubMed1985

The pathology of amiodarone neurotoxicity. II. Peripheral neuropathy in man.

Sural nerve changes are described in 2 cases of amiodarone neuropathy. Clinically, 1 patient developed a sensorimotor neuropathy, whereas in the other it was predominantly motor. Examination of sural nerves showed demyelination with only mild axonal loss. Cytoplasmic changes developed in Schwann cells of myelinated and unmyelinated axons, and involved loss of most recognizable organelles. These changes were associated with, and possibly preceded, myelin sheath breakdown. Inclusions, mainly of a lamellated type, were found in all cell types in the nerves. These inclusions, known to be lysosomal in origin, are a characteristic finding in amiodarone-induced neuropathy. The pathogenesis of the neuropathy is discussed, with particular reference to the findings in a parallel experimental study.

Adult↗
PubMed1985

Qualitative and quantitative morphology of human sural nerve at different ages.

A qualitative and quantitative study was made of 27 sural nerves obtained within 24 hours of death from human subjects without history of disease or ingestion of drugs known to affect peripheral nerve. Parameters studied included fascicular area, internodal length and diameter of teased fibres, density of myelinated and unmyelinated axons, and axonal and fibre diameter. The slope of internodal length-fibre diameter regression lines increased progressively during the first decade but thereafter remained relatively constant until about the age of 60 years, after which degeneration and regeneration, and demyelination and remyelination caused increasing variation in internodal length. Densities of myelinated and unmyelinated axons decreased markedly from birth to the end of the eighth decade, due to increasing size and separation of fibres during the first decade, and axonal degeneration and an increase in endoneurial collagen in the older age groups. Except during the first year of life, the diameter distribution of myelinated fibres was bimodal, the lower mode occurring at 3-5 microns in all age groups and the upper shifting progressively from 5-6 microns at 1 year to 9-12 microns after the first decade. g ratios were generally higher in small than in large fibres and showed increasing scatter with age. The distribution of unmyelinated axons was unimodal until the fifth decade; thereafter the number of fine calibre axons increased. Ageing was associated with reduplication of vascular, and thickening of perineurial, basement membranes.

Adolescent↗
PubMed1985

The induction of pulmonary phospholipidosis and the inhibition of lysosomal phospholipases by amiodarone.

Administration of high doses of amiodarone to young adult rats leads to phospholipidosis of the lung, with extensive phospholipid storage by type II pneumonocytes and alveolar macrophages. Biochemical analysis reveals an increase in the total phospholipid content of the lung and in the proportion of phosphatidylcholine. The cause of the phospholipidosis is suggested to be the inhibition of lysosomal phospholipases, responsible for catabolizing phospholipids. It is shown that amiodarone is a potent inhibitor of phospholipases prepared from the soluble fraction of adult rabbit lung lysosomes.

Amiodarone↗
PubMed1984

Effect of unsaturated fatty acids on protoporphyrinogen oxidation, a step in heme and chlorophyll synthesis in plant organelles.

Oleic acid stimulates enzymatic protoporphyrinogen oxidation by extracts of barley mitochondria and etioplasts. Greater stimulation occurred with Triton X-100 extracts which had been passed over a Sephacryl S-200 column than with crude Triton extracts, suggesting that purification may have removed a lipid factor required for optimal enzymatic activity. Palmitic acid, various phospholipids and detergents, or esters and alcohols of oleic acid did not substitute for free oleic acid. Linoleic acid caused a greater stimulation of protoporphyrinogen oxidation in both crude and purified barley organelle extracts and also caused a slow chemical oxidation of protoporphyrinogen. The stimulating effect of unsaturated fatty acids on enzymatic protoporphyrinogen oxidation may indicate a lipid requirement for this membrane bound enzyme or may also indicate involvement of unsaturated lipid oxidation in plant protoporphyrinogen oxidation.

Chlorophyll↗
PubMed1984

Protoporphyrinogen oxidation, an enzymatic step in heme and chlorophyll synthesis: partial characterization of the reaction in plant organelles and comparison with mammalian and bacterial systems.

High rates of oxidation of protoporphyrinogen to protoporphyrin were demonstrable in etioplasts, chloroplasts, and mitochondria from young barley shoots. Much lower rates were observed in chloroplasts from older barley or mature spinach, in mitochondria from potatoes or rat liver, and in membranes from the bacteria Escherichia coli and Rhodopseudomonas spheroides. The presence of high activity in cells capable of rapid synthesis of large amounts of chlorophyll suggests a role for this activity in chlorophyll synthesis. Characteristics of the plant protoporphyrinogen-oxidizing activity were compared to the activity in rat liver mitochondria. The activity in spinach chloroplasts exhibited a pH optimum of 7, which was lower than that of the mammalian enzyme. The plant activity was more sensitive to inhibition by glutathione or excess detergent, and was more readily inactivated at room temperature. The plant activity exhibited less specificity toward porphyrinogen substrates, oxidizing mesoporphyrinogen as rapidly as protoporphyrinogen. The mammalian enzyme oxidized mesoporphyrinogen slowly, and neither system oxidized coproporphyrinogen or uroporphyrinogen. Both the plant and the mammalian activity were bound to organelle membranes, but could be extracted with detergents. In contrast, activity from membranes of the bacteria E. coli and R. spheroides was inactivated by detergent treatment. The plant extracts could be fractionated with ammonium sulfate and retained activity after dialysis or Sephadex G-25 treatment, suggesting no readily dissociable cofactor. The activity extracted from spinach chloroplasts was mostly inactivated by trypsin digestion, which was additional evidence for the protein nature of the plant activity.

Animals↗
PubMed1984

Amiodarone lung toxicity: a human and experimental study.

This paper describes the pathology of pulmonary histiocytosis developing in a patient treated with amiodarone, and reports comparable changes in the lungs of rats and mice to which this drug had been administered. Ultrastructural studies indicate that the experimental lung changes are similar to those produced by iprindole and chlorphentermine. The patient also displayed focal necroses and an eosinophilic bronchiolitis; these may represent further effects of amiodarone on the lung.

Adult↗
PubMed1984

Changes in the compact myelin of single internodes during axonal atrophy.

Distal axonal atrophy was produced by proximal constriction of the tibial nerve in the rabbit. Transverse sections were studied by light and electron microscopy at 10 micron intervals along individual internodes of both atrophic and normal tibial nerve fibres. During axonal atrophy there were marked changes in axonal configuration at different levels within the territory of a single Schwann cell. These resulted in changes in the lengths of the axon perimeter and myelin spiral, without causing any alteration in the numbers of myelin lamellae or their spacing. Comparable changes in axon perimeter and myelin spiral length were seen in transverse sections through the paranodal and nuclear regions of normal fibres. These results show that local variations in axonal calibre or shape are associated with appropriate adjustments to the length of the myelin spiral, without a change in the number of lamellae, and thus of sheath thickness.

Animals↗
PubMed1983

Recovery of distal changes after nerve constriction by a ligature.

When ligatures were used to constrict the proximal tibial nerve in rabbits, nerve fibres distal to the site of constriction underwent a reduction in axonal and external fibre diameter, and in conduction velocity. Distal changes could be detected within 7-12 days of the onset of constriction; removal of the ligatures was followed by partial recovery. When paranodal myelin damage occurred in the distal tibial nerve, it showed the typical non-random distribution of secondary demyelination, with multiple paranodal defects on some fibres and complete sparing of others. These findings emphasize the role of the axon in the genesis of paranodal demyelination.

Animals↗
PubMed1983

Cryptogenic fibrosing alveolitis associated with peripheral neuropathy.

Eight patients who presented with fibrosing alveolitis and developed peripheral neuropathy are described. Seven had a positive rheumatoid factor, but only one had arthritis. The neuropathy affected both motor and sensory fibres. Two patients underwent peripheral nerve biopsy, one showing vasculitis and the other an axonal neuropathy. The two disorders responded differently to corticosteroid therapy, and immunosuppressant drugs may be useful in treating the neuropathy. The similarities of the patients suggests that this uncommon association is a real category.

Aged↗