Biomedical subjects

R H King

Publications and source records attributed to R H King.

At least 19 recordsLinked to original sources

PubMed1992

A freeze-fracture study of the perineurium in galactose neuropathy: morphological changes associated with endoneurial oedema.

Feeding rats with galactose as 40% of their diet results in peripheral nerve oedema related to the intrafascicular accumulation of galactitol and sodium. In this study, associated changes in the perineurium were examined by the freeze-fracture replication technique. Perineurial cells are linked by tight junctions (zonulae occludentes). In normal animals these are made up of anastomosing strands organized in a belt-like arrangement along the margins of continuous cells. The majority of the tight junctions in the galactose-fed animals displayed structural abnormalities. These ranged from slight separation of the strands to fragmentation and dispersal, with looping of isolated strands. Some of the tight junctions contained large dilated compartments within the junctional network. Short lengths of intramembranous particles, probably representing assembly or disassembly of tight junctional strands, were also observed. The membranes of perineurial cells normally possess numerous openings of caveolae. A quantitative assessment showed that the mean density of these caveolae openings was increased in the galactose-fed rats as compared with controls. The alterations in the tight junctions resemble those that have been produced experimentally in epithelia by subjecting them to abnormal osmotic gradients. They also resemble those seen in human diabetic neuropathy in which osmotic disturbances involving the perineurium have been considered to occur. If the alterations involve the inner layers of the perineurium, they are likely to impair its barrier function. The increased number of caveolae openings in galactose neuropathy may represent a reaction to the endoneurial oedema and indicate that the pinocytotic-like vesicles have a transport function.

Animals↗

PubMed1992

Growth hormone increases whole-body protein turnover in growing pigs.

Ten pigs with an average initial live weight of 65 kg were used to investigate the effects of daily exogenous porcine pituitary growth hormone (pGH; .1 mg.kg-1.d-1) for a 13-d period on N retention and whole-body protein turnover. Feed intake was restricted to both the control (treated with excipient) and pGH-treated groups to ensure that animals in each group consumed equal amounts. Whole-body protein turnover was estimated from the excretion of 15N in urinary urea and ammonia after a single oral dose of [15N]glycine. Nitrogen balance and whole-body N flux were increased by 35 to 40% with pGH treatment (P less than .001). Protein synthesis and breakdown were increased by 56 and 59% (P less than .001), respectively, in pGH-treated pigs relative to controls. These higher rates of protein turnover seemed to lower slightly the efficiency of the metabolic process for protein deposition. However, the absolute increment in protein synthesis rate was greater than that for breakdown, leading to the increased net N retention. Thus, pGH treatment improved the utilization of dietary amino acids for protein deposition.

Animals↗

PubMed1991

Shoulder disorders in the elderly: a community survey.

A community survey of identifiable symptomatic shoulder disorders in a sample of 644 elderly people over age 70 (318 male and 326 female) revealed a prevalence of 21%. Shoulder disorders were more common in women (25%, versus 17% in men). Approximately 70% of the cases of shoulder pain involved the rotator cuff. Fewer than 40% of the subjects sought medical attention for these symptoms. Increased medical awareness is needed, since the elderly often do not volunteer information about such symptoms.

Aged↗

PubMed1991

Freeze-fracture observations on normal and abnormal human perineurial tight junctions: alterations in diabetic polyneuropathy.

Perineurial cells in the human sural nerve possess tight junctions which in freeze-fracture replicas are seen to be composed of networks of branching and anastomosing P face strands and E face grooves. Isolated circular tight junctions (maculae occludentes) may represent attachment devices between adjacent perineurial lamellae. At the overlapping margins of the cells, a belt-like tight junction (zonula occludens) encircles the cells and is believed to comprise a paracellular diffusion barrier. As the permeability of the perineurium has been found to be altered in diabetic polyneuropathy, the zonulae occludentes have been studied. In freeze-fracture replicas from cases of diabetic polyneuropathy a mixed population of structurally normal and abnormal junctions was observed. In some, the strands were abnormally curved with reduced numbers of intersections, the intervening plasma membrane displaying prominent P face concavities and E face convexities. At other sites, the junctions were severely disorganized and represented by fragmented and isolated strands with few intersections and numerous free ends. These abnormalities resemble changes that have been produced experimentally in epithelial tight junctions by osmotic damage. The possibility is considered that similar mechanisms could result in the alterations of the perineurial tight junctions in diabetic polyneuropathy and account for its impaired permeability barrier properties.

Adult↗

PubMed1991

Peripheral neuropathy in the Chediak-Higashi syndrome.

The clinical features of a brother and sister with the Chediak-Higashi syndrome (CHS) are reported. Both showed evidence of a sensory neuropathy associated with central nervous system involvement. Nerve conduction studies indicated an "axonal" neuropathy. Sural nerve biopsy in the brother demonstrated a loss of myelinated nerve fibres, particularly those of larger size, and of unmyelinated axons. In contradistinction to some previous reports, giant lysosomes in Schwann cells were not observed and there were no inflammatory changes. Electron microscopy and teased-fibre studies showed no evidence of demyelination. It is concluded that the neuropathy of CHS is of axonal type. Its mechanism remains obscure.

Adult↗

PubMed1991

The clinical spectrum of peripheral neuropathies associated with benign monoclonal IgM, IgG and IgA paraproteinaemia. Comparative clinical, immunological and nerve biopsy findings.

Observations have been made on a consecutive series of 62 patients with peripheral neuropathy associated with benign monoclonal paraproteinaemia. The paraprotein class was IgM in 46 cases, IgG in 11 and IgA in 5. Although showing variations between patients, the clinical picture was similar for those with either IgM or IgG paraproteins, usually consisting of a late-onset, slowly progressive, distal sensorimotor demyelinating polyneuropathy, often with tremor and ataxia as prominent features. Tremor was slightly more common in patients with IgM paraproteins, in whom there was a male preponderance. The patients with both paraprotein classes were indistinguishable clinically and electrophysiologically from chronic idiopathic demyelinating polyneuropathy. In the 5 patients with an IgA paraprotein, there was a distal sensorimotor neuropathy in 4 which was demyelinating in 1. In 1 there was proximal demyelinating motor neuropathy. Immunoglobulin deposition on myelin was observed only in the patients with IgM paraproteinaemia, more commonly with a kappa light chain. No deposition of immunoglobulin in the endoneurium was seen. IgM deposits on the perineurium are a feature of normal nerve and were present in all cases. Widely spaced myelin was confined to cases with IgM paraproteins in which immunoglobulin deposition was detected on myelin. The response to treatment could not be assessed systematically but, in general, the patients with IgG and IgA paraproteins responded more satisfactorily (to corticosteroids, cytotoxic drugs, or plasma exchange) than did those with an IgM paraprotein.

Adult↗

PubMed1991

Sural nerve morphometry in diabetic autonomic and painful sensory neuropathy. A clinicopathological study.

Observations have been made on a selected series of insulin-dependent patients with neuropathy, subdivided into three groups: (1) severe autonomic neuropathy with an accompanying painless sensory neuropathy; (2) severe autonomic neuropathy with a chronic painful sensory neuropathy; and (3) chronic or acute painful sensory neuropathy with no autonomic neuropathy. All three groups showed a loss of large and small myelinated nerve fibres in sural nerve biopsy specimens which was greater in Groups 1 and 2. Regenerative activity was prominent in all three groups, but least in Group 3. Teased fibre studies showed evidence both of axonal regeneration and remyelination. Active fibre degeneration was rare. Measurements of g ratio (axon diameter:total fibre diameter) gave no indication of axonal atrophy. The density of unmyelinated axons was reduced in all three groups, as was their median diameter. Vibration sense threshold was positively correlated with the total number of myelinated fibres and thermal sensory threshold with median unmyelinated axon diameter but not with total unmyelinated axon numbers. No correlation between the occurrence of pain and active degeneration of myelinated fibres or with regenerative activity either in myelinated or unmyelinated axons was detectable. Assessment of differential loss of large or small myelinated nerve fibres was difficult because of the presence of large numbers of small regenerating myelinated axons. The results are discussed in relation to the concept of 'diabetic small fibre neuropathy' and the causation of pain in diabetic neuropathy.

Adult↗

PubMed1991

Experimental vitamin E deficiency in rats. Morphological and functional evidence of abnormal axonal transport secondary to free radical damage.

Morphological and functional studies have been performed on experimental vitamin E deficient rats. The predominant morphological change was axonal dystrophy and degeneration in the rostral parts of the dorsal columns, particularly in the gracile fasciculi. The dystrophic changes comprised focal axonal swellings containing accumulations of normal and abnormal organelles which included tubulovesicular structures probably derived from the smooth endoplasmic reticulum, mitochondria, dense lamellar bodies, neurofilaments, multifascicular bodies and lysosomes. Similar but lesser changes were observed in distal peripheral nerves. The appearances suggested a disturbance of axonal transport with a defect of 'turnaround' in the distal axons. Studies on the axonal transport of endogenous acetylcholinesterase showed an impairment both of fast anterograde and retrograde transport. The changes were considered to be secondary to the lack of the antioxidant effect of vitamin E as the neurological deficits could be reduced by the concomitant dietary administration of the synthetic antioxidant ethoxyquin and were markedly aggravated by the administration of polyunsaturated fatty acids. It is suggested that the neurological syndrome produced by vitamin E deficiency could be the result of damage to the function of mitochondria and other intra-axonal membranous structures which would interfer both with fast anterograde transport and 'turnaround' and lead to a distal axonal degeneration.

Acetylcholinesterase↗

PubMed1991

A freeze-fracture study of the perineurium in normal and protein-deprived rats.

Observations have been made using the freeze-fracture replication technique on the perineurium of normal and protein-deprived rats in which its permeability barrier function is known to be deficient. The perineurial cells of young normal rats possessed belt-like tight junctions (zonulae occludentes) at the borders and maculae occludentes at sites remote from their borders. In older rats, the zonulae occludentes were more prominent and the maculae occludentes relatively less frequent. No abnormalities were detected in the tight junctions of young rats with early induction of protein deficiency but this may have been related to sampling problems. In older severely protein-deficient animals, although many of the tight junctions were normal, some were abnormal and contained focal regions of dispersed strands. The density of caveolae in the surface membrane of the perineurial cells of older rats with severe protein deficiency was significantly greater than in the control animals. This provides support for the view that the pinocytotic-like vesicles of perineurial cells are involved in transport of substances across the cells. The increased numbers of caveolae in the protein deficient rats may reflect increased transcellular traffic. There were considerable differences in the density of P-face IMPs between the different perineurial lamellae, but the results did not allow a decision to be made as to whether there was a polarization of the cells between their endoneurial and epineurial aspects. No differences were detected in the density of P-face IMPs between the young control and protein-deprived rats. In the perineurium of the older rats with protein deficiency, IMP density was significantly greater in the E face than in the controls but not different in the P face. The delay in the development of enzymatic activity in the perineurium of protein-deficient rats that has been demonstrated histochemically is therefore not paralleled by a reduction in IMPs.

Animals↗

PubMed1991

Haemarthrosis due to fracture through amyloid deposits in bone in Portuguese familial amyloidosis.

A patient with Portuguese familial amyloid polyneuropathy who developed haemarthroses secondary to pathological fractures is described. Amyloid material was demonstrated on bone biopsy and confirmed immunohistochemically to be transthyretin (prealbumin). Although amyloid deposits in bone have been described in other types of amyloid, this is believed to be the first proved case of amyloid deposition resulting in pathological fracture in familial amyloidosis.

Adult↗

PubMed1991

Interrelationships between exogenous porcine somatotropin (PST) administration and dietary protein and energy intake on protein deposition capacity and energy metabolism of pigs.

Exogenous porcine somatotropin (PST) administration stimulates protein deposition and inhibits lipogenesis, resulting in dose-related improvements in growth performance and reduction of carcass fat content. However, the associated impacts of this technology on dietary nutrient requirements and energy partitioning between maintenance, protein, and fat remain unclear. Studies with pigs between 25 and 60 kg body weight indicate that, because of unknown improvements in amino acid utilization and(or) in the energy available for protein synthesis, only marginal increases in dietary protein percentage are required to support 20 to 25% improvements in protein deposition induced by PST administration. In contrast, an increased dietary protein concentration is required to support maximal protein deposition in pigs 60 to 100 kg. Exogenous PST administration increased the maintenance energy requirement and altered the relationship between energy intake and protein deposition, although the magnitude of these changes and the consequent effects on expression of dietary protein (amino acid) requirements was influenced by gender. Albeit limited, information suggests that PST alters nutrient demand at the tissue level. Information of this type will form the basis for rational decisions concerning the method for expression of dietary nutrient requirements (% vs g/d) for PST-treated pigs. Further quantitative information is required on the effects of PST dosage on the relationship of protein deposition to energy intake and on any underlying changes in amino acid utilization and metabolism.

Animals↗

PubMed1991

Neuroacanthocytosis. A clinical, haematological and pathological study of 19 cases.

Nineteen cases are described, including 12 cases from three different families and 7 nonfamilial cases, in which multisystem neurological disease was associated with acanthocytosis in peripheral blood and normal plasma lipoproteins. Mild acanthocytosis can easily be overlooked, and scanning electron microscopy may be helpful. Some neurologically asymptomatic relatives with significant acanthocytosis were identified during family screening, including some who were clinically affected. The mean age of onset was 32 (range 8-62) yrs and the clinical course was usually progressive but there was marked phenotypic variation. Cognitive impairment, psychiatric features and organic personality change occurred in over half the cases, and more than one-third had seizures. Orofaciolingual involuntary movements and pseudobulbar disturbance commonly caused dysphagia and dysarthria that was sometimes severe, but biting of the lips or tongue was rarely seen. Chorea was seen in almost all symptomatic cases but dystonia, tics, involuntary vocalizations and akinetic-rigid features also occurred. Two cases had no movement disorder at all. Computerized tomography often demonstrated cerebral atrophy. Caudate atrophy was seen less commonly, and nonspecific focal and symmetric signal abnormalities from the caudate or lentiform nuclei were seen by magnetic resonance imaging in 3 out of 4 cases. Depression or absence of tendon reflexes was noted in 13 cases and neurophysiological abnormalities often indicated an axonal neuropathy. Sural nerve biopsies from 3 cases showed evidence of a chronic axonal neuropathy with prominent regenerative activity, predominantly affecting the large diameter myelinated fibres. Serum creatine kinase activity was increased in 11 cases but without clinical evidence of a myopathy. Postmortem neuropathological examination in 1 case revealed extensive neuronal loss and gliosis affecting the corpus striatum, pallidum, and the substantia nigra, especially the pars reticulata. The cerebral cortex appeared spared and the spinal cord showed no evidence of anterior horn cell loss. Two examples of the McLeod phenotype, an X-linked abnormality of expression of Kell blood group antigens, were identified in a single family and included 1 female. The genetics of neuroacanthocytosis are unclear and probably heterogeneous, but the available pedigree data and the association with the McLeod phenotype suggest that there may be a locus for this disorder on the short arm of the X chromosome.

Acanthocytes↗

PubMed1990

Neurofibromatous neuropathy.

Three cases of chronic distal sensorimotor neuropathy are described in patients with neurofibromatosis. One had type 2 or central neurofibromatosis with a chromosome 22 deletion; the precise form of the disease was not established in the other two. A striking clinical feature was a diffuse nodular enlargement of the peripheral nerves. Nerve biopsies from all three cases demonstrated the presence of neurofibromatous pathology. Neurofibromatous neuropathy constitutes a rare manifestation of neurofibromatosis, related to diffuse neurofibromatous changes in the peripheral nerves.

Adult↗

PubMed1990

Relative growth and maturation of axon size and myelin thickness in the tibial nerve of the rat. 1. Normal animals.

Morphometric observations have been made on the medial plantar division of the tibial nerve (MPD) and on the motor branches of the tibial nerve to the calf muscles (MBC) in rats ranging in age from weaning (3 weeks) to 12 months. Axon size, assessed by measurements of circumference and cross-sectional area, increased rapidly until 3 months with further slight increases between 3 and 9 months and a slight fall between 9 and 12 months. Axon size distributions were unimodal throughout in the MPD but bimodal for the MBC except at 3 weeks. Distributions of myelin thickness were bimodal throughout for both nerves. Scatter plots of g ratios (axon diameter:total fibre diameter) confirmed the presence of two fibre populations: a group of small fibres with relatively thin myelin sheaths, and a group of larger fibres within which sheath thickness was relatively less on the larger than on the smaller axons. These two fibres populations were less easily separable in the MBC than in the MPD nerves. These results document morphometrically the normal growth changes in the rat tibial nerve and also provide control data for the analysis of the effects of experimental procedures on the growth and maturation of peripheral nerve fibres.

Aging↗

PubMed1990

Relative growth and maturation of axon size and myelin thickness in the tibial nerve of the rat. 2. Effect of streptozotocin-induced diabetes.

The relative changes in the growth and maturation of axon size and myelin thickness were studied in the medial plantar division of the tibial nerve in the lower leg and in the motor branches of the tibial nerve to the calf muscles in rats in which diabetes mellitus had been induced with streptozotocin at the time of weaning. Observations were made at 6 weeks and 3, 6, 9 and 12 months of diabetes for comparison with age-matched controls. Similar changes were observed in both nerves. Growth in body weight and skeletal growth was severely retarded from the time of induction of diabetes but at the 6-week stage axon size was not reduced, suggesting that neural growth may initially be relatively protected. At later stages axon size was consistently reduced in the diabetic animals as compared with the controls and showed an absolute reduction at 12 months, as compared with 9 months, that was greater than in the controls. Myelin thickness became reduced earlier and was more severely affected than axon size so that the fibers were relatively hypomyelinated. The myelin changes were greater in larger than in smaller fibers. The index of circularity of axons was reduced in the diabetic nerves. These results show that induction of diabetes in prepubertal rats produces effects on peripheral nerve fibers which differ from those resulting from diabetes induced in adult animals. The effects also differ between large and small nerve fibres. These observations may explain some of the disparate findings obtained in previous studies on experimental diabetes in rats.

Animals↗

PubMed1990

Cerebrotendinous xanthomatosis: clinical, electrophysiological and nerve biopsy findings, and response to treatment with chenodeoxycholic acid.

A 30-year-old patient with cerebrotendinous xanthomatosis was studied over a 6-year period. The clinical manifestations were cataracts, intellectual deterioration, ataxia, palatal and pharyngeal myoclonus, corticospinal tract damage and an electrophysiologically demonstrated sensorimotor peripheral neuropathy. Peripheral motor and sensory nerve conduction velocity was slowed. Sural nerve biopsy revealed reduced densities of both myelinated and unmyelinated axons and teased fibres showed evidence of axonal regeneration and some remyelination. The loss of myelinated nerve fibres particularly affected those of larger diameter, thus contributing to the slowing of nerve conduction. Chenodeoxycholic acid treatment for two separate periods of 10 and 6 months each increased nerve conduction velocity. This electrophysiological improvement was not matched by detectable clinical neurological improvement.

Adult↗

PubMed1990

Morphometry of endoneurial capillaries in diabetic sensory and autonomic neuropathy.

Nerve biopsies were obtained from 27 patients with diabetic neuropathy. All had a symmetric distal sensory and autonomic neuropathy or a purely sensory neuropathy. Mean age was 39.8 years (range 23-57 years). Two patients had Type 2 (non-insulin-dependent) diabetes mellitus and the remainder Type 1 (insulin-dependent) diabetes. Morphometric observations on endoneurial capillaries were compared with results from organ donor control cases and from patients with type 1 hereditary motor and sensory neuropathy. The area of the lumen of the capillaries did not differ between the three groups. The area occupied by the capillary endothelial cells in transverse section and the number of endothelial cell nuclei were increased both in the patients with diabetic neuropathy and hereditary motor and sensory neuropathy, as was the thickness of the surrounding basal laminal zone. 'Closure' of endoneurial capillaries in diabetic neuropathy, reported in another study, was not confirmed. Capillary density and nearest-neighbour distances were similar in the diabetic and organ donor control cases. Capillary density was reduced in the patients with hereditary motor and sensory neuropathy, this being related to increased fascicular area consequent upon the presence of hypertrophic changes. The presence of thickening of the pericapillary basal laminal zone and endothelial cell hyperplasia both in diabetic and hereditary motor and sensory neuropathy, the latter being a neuropathy in which a vascular basis can be discounted, makes it difficult to use such changes as an argument favouring a vascular cause for diabetic neuropathy. There were differences in the basal laminal zone between the diabetic and hereditary motor and sensory neuropathy cases suggesting that the reduplicated basal lamina was more persistent in the diabetic patients.

Adult↗

PubMed1990

Interaction of dietary protein content and exogenous porcine growth hormone administration on protein and lipid accretion rates in growing pigs.

Sixty-six intact male pigs were used to investigate the relationships between exogenous porcine growth (pGH) administration (0, excipient-treated, and .09 mg recombinant pGH.kg-1.d-1) and dietary protein content (8.3, 11.4, 14.5, 17.6, 20.7 and 23.8%) on protein and lipid accretion rates over the live weight range of 30 to 60 kg. Feed intakes were restricted (1.84 kg.pig-1.d-1) and pGH was administered daily by i.m. injection. Rate of protein deposition increased with increasing dietary protein up to 17.6 and 20.7%, respectively, for control and pGH-treated pigs; both growth and protein deposition were enhanced by pGH on the four higher protein diets but remained unaffected by pGH administration to pigs given the two lowest protein diets. Plasma IGF-I concentration was elevated by pGH administration in pigs given the four higher protein diets but unaffected by pGH with the two lowest protein diets. Rate of fat deposition was depressed on all dietary protein treatments by pGH administration; carcass fat content of control and pGH-treated pigs declined with each increase in dietary protein up to 17.6 and 23.8%, respectively. The results demonstrate that pGH acts independently on protein and lipid metabolism.

Adipose Tissue↗