Biomedical subjects
A Patton
Publications and source records attributed to A Patton.
Six-point plan for supervision.
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Primary hypothyroidism with intracranial hypertension and pituitary hyperplasia.
A 12-year-old girl presented with primary hypothyroidism, secondary pituitary hyperplasia, and intracranial hypertension. Cranial computed tomography revealed a sellar mass with suprasellar extension. She responded to medical treatment. Intracranial hypertension may be associated with primary hypothyroidism prior to thyroxine treatment. Because significant pituitary hyperplasia can be associated with primary hypothyroidism, it is vital to have endocrine investigation prior to consideration of surgical removal of an apparent pituitary tumor.
Amyloid beta precursor protein and ubiquitin epitopes in human and experimental dystrophic axons. Ultrastructural localization.
Dystrophic axons (DA) represent a major pathological feature of several neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD) and Alzheimer disease. We have previously presented evidence that amyloid beta precursor protein (BPP) and ubiquitin (Ub) are present in DA of different origin. We have now characterized the immunoreactivity of DA experimentally induced in rat by the administration of parabromophenylacetylurea (BPAU) and examined the subcellular localization of Ub and BPP in BPAU-induced DA and in DA present in subjects affected by INAD. BPAU-induced DA strongly immunoreacted with antisera to Ub and to COOH- and NH2-terminal regions of BPP. Immunoblots of DA-enriched brain regions were consistent with an increase in the amount of Ub and BPP in DA. Moreover, BPAU-induced DA immunoreacted with antibodies to PGP 9.5, a neuronal-specific Ub COOH-terminal hydrolase, and to the inducible heat shock protein 70. Antigenic characterization also indicated that the tubulovesicular membranes within DA derived largely from the smooth endoplasmic reticulum rather than from the Golgi system or the synaptic vesicles. Subcellular immunolocalization of Ub and BPP in both INAD- and BPAU-induced DA revealed that Ub and BPP colocalize in granulovesicular material in both conditions. In INAD DA intense Ub immunoreactivity was also detected in nonmembranous electron dense structures that were present only in these DA, probably because of the chronic course of INAD. Although BPP immunostaining may be related to accumulation of BPP-containing membranes in DA, Ub immunostaining is likely to result from activation of the Ub system by the neuron in the attempt to remove excessive and possibly abnormal proteins. A similar pathogenesis can be postulated for DA of Alzheimer disease.
Axonal transport of two major components of the ubiquitin system: free ubiquitin and ubiquitin carboxyl-terminal hydrolase PGP 9.5.
Ubiquitin (Ub), a stress protein thought to target abnormal proteins for degradation, is present in abnormal structures that occur in neuronal perikarya and axons of degenerative diseases including Alzheimer disease. To begin to assess the role of the Ub system in the axon, we studied expression and axonal transport of Ub and other stress proteins, as well as of Ub carboxyl-terminal hydrolase PGP 9.5, in the rat visual system in normal conditions and following heat-shock (HS). In the retina, both the constitutive and inducible forms of HSPs 70 were expressed under normal conditions, while in the superior colliculus the inducible form was detected only following HS. Ub, PGP 9.5 and HSPs 70 were transported in the axon exclusively with the slow component b (SCb), known to carry cytoskeletal and cytoplasmic proteins. The exceedingly long time needed for stress proteins to reach distant axonal locales at the rate of SCb (approximately 3 mm/day) makes it unlikely that they could contribute significantly to the stress response at those sites.
Amyloid precursor protein and ubiquitin immunoreactivity in dystrophic axons is not unique to Alzheimer's disease.
A distinctive feature of Alzheimer's disease (AD) is the presence of dystrophic neurites that immunoreact with antibodies to amyloid precursor protein (APP) and ubiquitin (Ub). The authors examined dystrophic axons (DA) present in other chronic conditions such as familial infantile neuroaxonal dystrophy (INAD), aging, cystic fibrosis, and biliary obstruction as well as in conditions of shorter duration such as human immunodeficiency virus (HIV) leucoencephalopathy, infarction and radiation therapy to determine whether APP and Ub immunoreactivity was unique to the DA of AD. A large number of DA immunoreacted with antibodies to the A4, C- and N-terminal regions of APP as well as to Ub. Ub and APP immunoreactivities often, but not always, colocalized. "Acute" DA generally reacted more intensely and in larger number with antibodies to APP than to Ub, whereas the reverse was true for "chronic" DA. Structureless DA immunostained diffusely. In DA with cores or granules, the Ub immunoreaction was occasionally limited to these structures, whereas reaction with antibodies to APP was more diffuse. In view of the contention that impairment of proteolysis is the common pathogenetic step in the formation of DA, Ub immunoreactivity in all DA may indicate a vicarious attempt to degrade accumulated components through an activation of the Ub system. The role of APP in the formation of DA remains to be determined.
Giant axonopathy characterized by intermediate location of axonal enlargements and acceleration of neurofilament transport.
It has previously been shown that 2,5-hexanedione (2,5-HD) and its 3,4-dimethyl derivative (3,4-DMHD) induce neurofilamentous accumulations at prenodal sites in distal and proximal, respectively, regions of peripheral axons. For 2,5-HD, neurofilament (NF) transport is accelerated and this is thought to be directly related to the appearance of the axonal enlargements. For 3,4-DMHD, however, the rate of NF transport cannot be assessed owing to the very proximal position of NF accumulation. In the present study, it is shown that administration to rats of 3-methyl-2,5-hexanedione, the structural 'average' of 2,5-HD and 3,4-DMHD, induces NF accumulations at midway axonal positions of the sciatic and optic systems, and results in acceleration of NF in the sections of optic axons proximal to the enlargements. These results suggest that a common mechanism underlies all gamma-diketone neuropathies, and that the proximodistal pattern of axonal enlargements represents pharmacokinetic variables rather than differences in mode of action. The neurotoxicity of gamma-diketones probably arises from pyrrolation of lysine epsilon-amino groups in crucial regions of NF or related proteins responsible for maintaining the proper supramolecular organization of the cytoskeleton. Acceleration of NF transport appears to be a common characteristic of chemically induced axonopathies, regardless of location, and this is contrary to the theory that gamma-diketone-induced NF accumulation results primarily from a progressive cross-linking of NF occurring subsequent to pyrrole formation.
Axonal transport of neurofilament is accelerated in peripheral nerve during 2,5-hexanedione intoxication.
The neurotoxic compound 2,5-hexanedione (2,5-HD) causes an axonopathy characterized by the presence of neurofilament (NF)-containing enlargements in the preterminal segments of central and peripheral axons. The 2,5-HD axonopathy is a good model for human acquired and inherited giant axonal neuropathies. Recently, we reported that following 2,5-HD administration, axonal transport of NF is markedly and selectively accelerated in the primary visual system. We have now studied slow axonal transport in the sciatic system of rats intoxicated with 0.5% 2,5-HD in drinking water. Following radiolabeling, transported proteins were examined after polyacrylamide gel electrophoresis and fluorography. The bulk of radiolabeled NF subunits was located 30-50 mm from the spinal cord in 2,5-HD treated animals and 10-25 mm in controls. The rate of transport of the three NF subunits was 0.7 mm/day in controls and 1.2 mm/day in 2,5-HD treated animals. The rate of transport of tubulin was not significantly changed. Electrophysiological studies of soleus nerve and muscle showed no evidence of denervation after 6 weeks of intoxication. It is concluded that, following 2,5-HD administration, transport of NF is preferentially accelerated in both central and peripheral axons. A pathogenetic mechanism based on the acceleration of NF transport is proposed, which may explain the formation and the distal or proximal location of NF-containing axonal enlargements in giant axonopathies.
Muscarinic receptors: relationships among phosphoinositide breakdown, adenylate cyclase inhibition, in vitro detrusor muscle contractions and in vivo cystometrogram studies in guinea pig bladder.
The relationships between activation of muscarinic receptors in guinea pig bladder measured as carbachol-stimulated inositol phosphate (IP) accumulation, oxotremorine-induced adenylate cyclase (AC) inhibition and bladder detrusor smooth muscle contraction determined in vitro as well as in vivo in the slow filling cystometrogram (CMG), were analyzed from the potencies of a number of muscarinic antagonists to block these responses. Significant positive linear correlations were found among the inhibitory potencies of 10 muscarinic antagonists to inhibit phosphoinositide (PI) turnover and both detrusor muscle contraction in vitro, as well as peak intravesical bladder pressure in vivo in the CMG (r = 0.8, P less than .01). In contrast, there was no significant correlation between the potency of antagonists to block the AC inhibitory response and either in vitro or in vivo guinea pig bladder contractions (P greater than .05). Muscarinic agonists inhibited basal AC activity to a maximum of 20% in a GTP-dependent, Na+-sensitive manner and dose dependently stimulated both PI breakdown (3- to 4-fold) and isolated detrusor contractions. Again, a significant correlation (r = 0.9, P less than .01) was calculated among the potencies of seven muscarinic agonists to elicit PI turnover and in vitro muscle contraction, whereas no significant correlation was observed between their potencies to inhibit AC activity and contractile responses in vitro. Collectively, the data suggest that IP accumulation and presumably IP-induced Ca++ release may function as the transducing mechanism for cholinergic contraction of the urinary bladder.(ABSTRACT TRUNCATED AT 250 WORDS)
The influence of high carbohydrate diets on endurance running performance.
The purpose of the present study was to examine the influence of high carbohydrate (CHO) diets on recovery of endurance capacity following a treadmill run to exhaustion. Two high CHO diets were used, one in which the normal diet was supplemented with complex carbohydrates and the other in which supplementation was achieved with simple carbohydrates. The thirty recreational runners who took part in this study (fifteen men and fifteen women) completed weighed food intake diaries two to three weeks before the start of the study. From an analysis of this information each subject's 'normal diet' was prescribed before Trial 1 and then a supplemented diet before Trial 2. The aim was to achieve an increase in carbohydrate content to 70% in the diets of the two high CHO groups and an equivalent increase in energy intake by the Control group. The subjects were required to run to exhaustion on a treadmill at a speed equivalent to 70% VO2max on two occasions separated by 3 days. After Trial 1 the subjects were divided into three equal groups. The Complex CHO group (301 +/- 86 mg vs 507 +/- 120 mg) and Simple CHO group (265 +/- 45 mg vs 462 +/- 81 mg) increased their CHO intake by approximately 70% (p less than 0.05) during the 3 days before Trial 2 whereas the Control group increased their energy intake with additional protein and fat so as to match the energy intakes of the two CHO groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Who should give spiritual care?
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The metabolic challenge of the marathon.
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Retroactive inhibition, hypnosis, and hypnotic amnesia.
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Intraoperative sonography-guided removal of radiolucent foreign bodies.
This article reports our use of intraoperative sonography to guide in real time, the removal of radiolucent foreign bodies from five patients. Two of these patients had undergone previous unsuccessful attempts at surgical removal in the operating room. The technique is cost effective, readily available, and can be very helpful in locating difficult-to-find radiolucent foreign bodies at the time of surgery.