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Biomedical subjects

S Hall

Publications and source records attributed to S Hall.

At least 19 recordsLinked to original sources

Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria granulocytes.

To investigate the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor in the granulocytes of paroxysmal nocturnal hemoglobinuria (PNH), the glycolipids of granulocytes from PNH patients and normal volunteers were biosynthetically labeled with [3H]mannose in the presence of tunicamycin. Extracted glycolipids were examined by thin-layer chromatography and compared with known biosynthetic intermediates. Normal granulocytes consistently showed [3H]mannose incorporation into the complete GPI core, several GPI biosynthetic intermediates, and dolichol phosphate mannose (DPM). The granulocytes of 10 patients with PNH that had no expression of CD55 and CD59 on greater than 95% of the cells were able to incorporate [3H]mannose into DPM, but were not able to incorporate detectable amounts into the complete GPI core. THus, PNH granulocytes do not synthesize detectable amounts of the complete GPI core and this defect likely accounts for the absence of GPI-linked membrane proteins on hematopoietic cells in this syndrome.

Antigens, CD

Subacute idiopathic demyelinating polyradiculoneuropathy.

Seven cases of subacute idiopathic demyelinating polyradiculoneuropathy had a monophasic illness characterized by progressive weakness of all four limbs that evolved during 4 to 8 weeks. Neurophysiological investigations implied demyelination in all seven cases. In two patients, sural nerve biopsy specimens that were taken showed macrophage-associated demyelination. All patients made substantial or complete recoveries with oral prednisolone (four cases) or without treatment (three cases). None of the patients required ventilation or had autonomic complications. These cases provide a link between the acute idiopathic demyelinating form of Guillain-Barré syndrome and chronic idiopathic demyelinating polyradiculoneuropathy.

Adult

Sural nerve biopsies in Guillain-Barre syndrome: axonal degeneration and macrophage-associated demyelination and absence of cytomegalovirus genome.

T-cell infiltration was detected by immunohistochemistry in only 2 of 10 sural nerve biopsies from patients with Guillain-Barré syndrome (GBS). The number of endoneurial macrophages, identified by the monoclonal antibody MAC 387, was increased, compared with the number in 10 cases of axonal neuropathy. Macrophage-associated demyelination was identified in 7 and axonal degeneration in 8 cases. Cytomegalovirus (CMV) genome was not detected with the polymerase chain reaction.

Adult

Regeneration of axons in the optic nerve of the adult Browman-Wyse (BW) mutant rat.

We have studied the regeneration of axons in the optic nerves of the BW rat in which both oligodendrocytes and CNS myelin are absent from a variable length of the proximal (retinal) end of the nerve. In the optic nerves of some of these animals, Schwann cells are present. Axons failed to regenerate in the exclusively astrocytic environment of the unmyelinated segment of BW optic nerves but readily regrew in the presence of Schwann cells even across the junctional zone and into the myelin debris filled distal segment. In the latter animals, the essential condition for regeneration was that the lesion was sited in a region of the nerve in which Schwann cells were resident. Regenerating fibres appeared to be sequestered within Schwann cell tubes although fibres traversed the neuropil intervening between the ends of discontinuous bundles of Schwann cell tubes, in both the proximal unmyelinated and myelin debris laden distal segments of the BW optic nerve. Regenerating axons never grew beyond the distal point of termination of the tubes. These observations demonstrate that central myelin is not an absolute requirement for regenerative failure, and that important contributing factors might include inhibition of astrocytes and/or absence of trophic factors. Regeneration presumably occurs in the BW optic nerve because trophic molecules are provided by resident Schwann cells, even in the presence of central myelin, oligodendrocytes and astrocytes. All the above experimental BW animals also have Schwann cells in their retinae which myelinate retinal ganglion cell axons in the fibre layer. Control animals comprised normal Long Evans Hooded rats, BW rats in which both retina and optic nerve were normal, and BW rats with Schwann cells in the retina but with normal, i.e. CNS myelinated, optic nerves. Regeneration was not observed in any of the control groups, demonstrating that, although the presence of Schwann cells in the retina may enhance the survival of retinal ganglion cells after crush, concomitant regrowth of axons cut in the optic nerve does not take place.

Animals

MRI, brain iron and experimental Parkinson's disease.

Abnormal levels of brain iron have been reported in parkinsonism, which is characterized principally by degeneration of dopaminergic (DA) nigrostriatal neurons. There are conflicting reports, however, of both increased and decreased iron in parkinsonism. An animal model of parkinsonism was used to clarify the contribution of the loss of nigrostriatal DAergic neurons to abnormal iron accumulations. In rats with 6-hydroxydopamine induced unilateral DA depletion, brain iron deposition and its day-to-day stability was studied in vivo using T2-weighted magnetic resonance imaging (MRI) scans taken on 4 consecutive days beginning 1-2 months post-surgery and post-mortem by Perls'-DAB histochemical stain. Unilateral DA depletion (parkinsonism model) produced large day-to-day fluctuations in T2 relaxation time in the striatum. The T2 relaxation time in Sham control rats was relatively minor. The uptake and transport of iron by intrinsic cells of the striatum may vary, and this variability may have been exaggerated by the destruction of DAergic nigrostriatal neurons, which are known to modulate the activity of the intrinsic cells. Inconsistent reports of increased or decreased iron in parkinsonism may reflect, in part, single time-point measures of widely fluctuating iron.

Animals

Interaction of regrowing PNS axons with transplanted aggregates of cultured CNS glia in vivo.

Aggregates of cultured neonatal mouse cerebellar astrocytes were implanted into adult mouse sciatic nerves. Two different experimental models were used: aggregates were either placed between proximal and distal stumps of totally transected nerves, or were placed in gaps in partially transected nerves in direct apposition with the cut surface of the proximal stumps. In the model where aggregates were not placed in contact with the proximal stump, regrowing axons rarely entered the aggregates. Where aggregates were placed in contact with the proximal stumps, axons entered the astrocyte-rich environment. Experimental depression of the supply of Schwann cells available to comigrate with regenerating axons proved to be unnecessary: astrocytes provided an alternative substrate for axons. Some axons became myelinated by oligodendrocytes which differentiated within the aggregates; however, few axons remained, unmyelinated, in long-term association with the transplanted astrocytes.

Animals

Pharmacological and biochemical properties of saxiphilin, a soluble saxitoxin-binding protein from the bullfrog (Rana catesbeiana).

Supernatant fractions of various tissues and plasma from the North American bullfrog, Rana catesbeiana, specifically bind saxitoxin with high affinity. Binding of [3H]saxitoxin to bullfrog plasma follows single-site behavior with an equilibrium dissociation constant of Kd = 0.16 +/- 0.03 nM at 0 degrees C and a maximum binding capacity of 380 +/- 60 pmole/ml plasma. High-affinity binding of [3H]saxitoxin is chemically specific since it is unaffected by tetrodotoxin and a variety of cationic peptides, amino acids and drugs. The structure-activity dependence of binding to this site was investigated with eight different natural and synthetic derivatives of saxitoxin. Substitution of the carbamoyl side chain or the C-12 beta-hydroxyl group of saxitoxin with a hydrogen atom had little effect on binding affinity, but addition of a hydroxyl group at the N-1 position decreased the binding affinity from 430- to 710-fold in three different molecular pairs. High performance size exclusion chromatography of supernatant from bullfrog skeletal muscle showed that the [3H]saxitoxin-binding component migrates with an apparent molecular weight of Mr = 74,000 +/- 8000 or a Stokes radius of 35 +/- 2A. The [3H]saxitoxin-binding protein in skeletal muscle extract or plasma is retained on a cation-exchange column at pH 6.0, suggesting that the protein contains a region of exposed basic residues. Column isoelectric focusing of a sample from plasma indicated that the protein has a basic isoelectric point near pH = 10.7.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphibian Proteins

Lung function abnormalities and decline of spirometry in scleroderma: an overrated danger?

To document the prevalence and progression of pulmonary involvement in scleroderma (systemic sclerosis including the CREST syndrome), the clinical notes and lung function records of 113 cases were reviewed. Lung function was normal in 39 cases, isolated impairment of DLCO was found in 38 patients, a restrictive defect was present in 27 cases and there was evidence of airflow obstruction in 9 cases. The median duration of symptoms was 10 years. Dyspnoea and an interstitial pattern on chest X-ray were associated with impaired lung function. Death during the period of review was significantly related to initial impairment of the DLCO. Sixty-six patients (53 women and 13 men) underwent repeat spirometry at least 1 year after initial testing. The rates of change in VC and FEV1 were no more rapid than would be expected for normal subjects. There was no significant difference in rates of change between men and women or between dyspnoeic patients and those who were asymptomatic. The extent of skin involvement and the presence of interstitial fibrosis on chest X-ray were unrelated to the rate of loss of lung function. It is concluded that most scleroderma patients in this study had abnormal lung function when first tested, but overall significant worsening of spirometry was not found.

Adolescent

Serial-position effects in paragraph recall following mild closed-head injury.

Serial-position effects were examined on a contextual memory task (paragraph recall) for patients with minor to mild closed-head injury and normal controls. Analysis indicated that at immediate recall, both normals and closed-head-injury patients have primacy and recency effects. With regard to total recall, however, the closed-head-injury patients remembered significantly fewer items than normal controls. The poorer performance of the minor to mild closed-head-injury group was not related to the duration from injury to neuropsychological evaluation and appears to be a lasting feature of memory performance following such injury. The pattern of serial-position effects was different between the groups. Normal controls showed slight recency and primacy effects and relatively better recall for the middle portions of the story, while patients with minor to mild closed-head injuries have prominent recency and primacy effects. Potential explanations for this pattern of performance are discussed.

Adult

The relationship between intelligence and memory following minor or mild closed head injury: greater impairment in memory than intelligence.

This study investigated the performance of patients with minor or mild closed head injury and age/education-matched normal controls on the Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the Wechsler Memory Scale-Revised (WMS-R). The results demonstrated that the control group had significantly higher scores than the patients with closed head injury on all WAIS-R and WMS-R index scores. Further analysis revealed that the patients with closed head injury showed a greater impairment in delayed memory when directly compared to intellectual performance that was not seen in the control group. These results are discussed in relation to findings in patients with more severe closed head injury, the construction of the WAIS-R and the WMS-R, and the performance patterns of the two groups.

Adult

A comparative study of carvedilol, slow-release nifedipine, and atenolol in the management of essential hypertension.

Carvedilol is a novel treatment for hypertension, having a balanced pharmacology of vasodilation and beta-receptor blockade. We present here the results of a three-way, multicenter, comparative study on the use of carvedilol, slow-release nifedipine, and atenolol in the management of essential hypertension. A total of 311 patients was entered into the study, of which 293 were randomized to one of the three treatment regimens. Full data are available on 255 patients. Systolic and diastolic blood pressure measurements, in both sitting and standing positions, were taken, together with the heart rate. There was no consistently significant difference between treatments with respect to blood pressure control. Differences in heart rate were more pronounced, with the reduction due to carvedilol being generally intermediate between nifedipine and atenolol. Further studies of carvedilol in hypertension, as well as other indications, are warranted.

Adolescent

Crystal arthritis: a clinician's view.

Arthritis, which can be acute, chronic or asymptomatic, is caused by a variety of crystal deposition in joints. The three main types of crystal arthritis are monosodium urate (gout), calcium pyrophosphate dihydrate, and calcium phosphate (usually hydroxyapatite). A clinical approach to diagnosis and management.

Adrenal Cortex Hormones

Actions of forskolin and isoprenaline on the separated myometrial layers of the guinea-pig uterus: influence of ovarian steroids and pregnancy.

Responses to forskolin and isoprenaline of electrically stimulated preparations of longitudinal and circular myometrium were compared. The guinea-pigs used were: untreated (dioestrous), ovarian steroid-treated, pregnant and post-partum. Forskolin inhibited electrically evoked contractions of both myometrial layers obtained from all groups; there was no change in its potency or its maximum effect (90-100% inhibition). The inhibition of contractions of longitudinal myometrium by isoprenaline was enhanced with steroid treatment, attaining a maximum in late pregnancy and immediately post-partum. In circular myometrium, there was no significant change in the potency of isoprenaline on tissues from ovarian steroid-treated animals. However, maximum potency as well as maximum response was observed in late pregnancy. Since the effects of isoprenaline but not of forskolin were modulated, we suggest that ovarian steroids and pregnancy may alter the coupling of beta-adrenoceptors to the adenylate cyclase system.

Animals

Relationship of glucocorticoid dosage to serum bone Gla-protein concentration in patients with rheumatologic disorders.

Serum bone Gla-protein (BGP) measurements in 50 rheumatic disease patients receiving long-term prednisone therapy revealed an inverse relationship (r = -0.71, P less than 0.001) between serum BGP levels and prednisone dosage. Multiple regression analysis demonstrated significant relationships (R2 = 0.72, P less than 0.001) between serum BGP1/2 and prednisone dosage, dosage2, serum creatinine, age, and an age-creatinine interaction. This model predicts the suppression of serum BGP with low dosages of steroids and 50% suppression with dosages of 20-25 mg/day.

Adolescent

Mitogenic action(s) of fluoride on osteoblast line cells: determinants of the response in vitro.

Clinically effective (osteogenic) concentrations of fluoride (5-30 microM) also have direct effects on skeletal tissues in vitro, to increase bone formation and osteoblast line cell proliferation. The effect on cell proliferation was specific for bone cells, modulated by systemic skeletal effectors, and dependent on (a) the [Pi] in the medium, (b) the presence of a bone cell mitogen, and (c) mitogen-responsive osteoprogenitor cells. Together, these data indicate that fluoride increases bone formation in vitro by increasing osteoprogenitor cell proliferation and that fluoride increases osteoprogenitor cell proliferation by enhancing the activity of bone cell mitogens.

Alkaline Phosphatase

Insectivory and social digestion in Drosophila.

It has long believed that Drosophila larvae feed almost entirely by ingesting yeast and possibly other microorganisms that are associated with fermenting fruits or other vegetable matter. However, we have discovered that the larvae of a number of Drosophila species can consume such diverse substrates as insect tissues, including the exoskeleton. Experiments reported here, which include raising sterile dechorionated eggs to adulthood on adult carcasses under axenic conditions, show that larvae can consume complex chitinous substrates directly without the assistance of microorganisms. We show that Drosophila larvae are able externally to digest amylose, cellulose, and chitin, without coming into physical contact with them. We conclude that not only do Drosophila larvae produce enzymes enabling them to digest a wide variety of substrates, but also these enzymes are egested onto the substrates so that at least some digestion, especially of large polymers, takes place externally. Finally, we suggest that the phenomenon of external digestion explains both the previously unexplained massiveness of Drosophila salivary glands and their chromosomes and the tendency of larvae to cluster, which may also be true of other dipterans.

Amylose