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Biomedical subjects

G T Patterson

Publications and source records attributed to G T Patterson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Comparison of cholinergic and neuromuscular toxicity following acute exposure to sarin and VX in rat.

Male Sprague-Dawley rats injected with a sublethal sc dosage of 110 micrograms/kg of sarin (isopropyl methylphosphonofluoridate), or 12 micrograms/kg of VX (S-(2-diisopropylaminoethyl) O-ethyl methylphosphonothioate), developed severe toxic signs within 5-15 min after sarin and 20-50 min after VX lasting for 5 to 7 hr. Myonecrotic lesions were seen in soleus and diaphragm muscles within 1 hr. A maximum number of lesions had developed after 24 hr, and lesions were also present in extensor digitorum longus (EDL) at this time. Regeneration of muscle fibers was slow since lesions were still evident past 7 days of treatment. Within 1 hr following VX, AChE activity was reduced to 8, 12, and 17% of control activity in soleus, diaphragm, and EDL, respectively, whereas with sarin the enzyme activity was reduced to 23, 48, and 82% of control. A still greater inhibition was seen 24 hr after sarin when AChE activity was reduced to 19, 13, and 43% in these muscles. In skeletal muscles the different molecular forms of AChE, such as 16 S, 12 S, 10 S, and 4 S vary in location and functional importance with the 16 S form highly concentrated at the neuromuscular junction. All forms in a given muscle were equally sensitive to the inhibitors. In EDL, sarin was the least effective in reducing AChE or its molecular forms. In the brain structures (cortex, brain stem, striatum, and hippocampus), AChE activity was reduced to 1-6% of control by sarin and VX with the exception that following VX striatal AChE was reduced to only 41% of control activity. AChE activity in the brain cortex following either of the agents was maximally affected (1%). A slow but significant recovery of brain AChE was evident after 24 hr and more so after Day 7. Butyrylcholinesterase (BuChE) activity was less sensitive to inhibition by both inhibitors compared to AChE activity and showed a rapid recovery. Based on the equitoxic doses (toxic signs of similar magnitude), VX was found to be 10 times more toxic than sarin. The mechanisms of this disparity may be due to differences in rate of uptake, circulation, susceptibility to hydrolysis, and reactivity with nonspecific binding sites.

Acetylcholinesterase↗
PubMed1991

The buccinator myomucosal island pedicle flap: anatomic study and case report.

The buccinator myomucosal island pedicle flap is a useful means of introducing relatively large amounts of vascularized mucosa into the oral cavity. Using cadaver dissections and clinical cases, the anatomy and clinical relevance of this tissue are defined. Emphasis is placed on the technical caveats and pitfalls of the procedure.

Adult↗
PubMed1990

Use of the coronal surgical incision for reconstruction of severe craniomaxillofacial injuries.

The coronal approach is a versatile surgical technique to expose the craniofacial skeleton. A retrospective clinical study on the use of this approach in treatment of craniomaxillofacial trauma in 28 patients was carried out. The study showed that this technique provides optimum exposure of the fracture sites, allowing for accurate anatomic reduction and fixation of the fractured segments and good cosmetic results in the incision site. The surgical technique, indications, and management and prevention of potential complications of the coronal approach are discussed.

Adolescent↗
PubMed1988

Macroglossia and ankyloglossia in Beckwith-Wiedemann syndrome.

Since the recognition of the Beckwith-Wiedemann syndrome was first noted in 1963, the number of associated anomalies has vastly increased. The rate of appearance of this abnormality is 1 in 13,5000 births. This article presents a case that includes macroglossia and ankyloglossia along with a bifid uvula and a submucous cleft of the palate. A discussion of treatment follows.

Ankylosis↗
PubMed1988

Prevention of diisopropylphosphorofluoridate (DFP)-induced skeletal muscle fiber lesions in rat.

The objective of the present investigation was to assess the comparative efficacy of prophylactic treatment with d-tubocurarine (d-TC) (0.075 mg/kg), atropine sulfate (16 mg/kg), and atropine methylnitrate (16 mg/kg), employed singly or in combination against the diisopropylphosphorofluoridate (DFP)-induced myopathy in rat. DFP (1.5 mg/kg, s.c.) produced signs of cholinergic toxicity with predominantly peripheral involvement manifest as severe muscle fasciculations beginning within 5-7 min and persisting in excess of 4-6 h. Maximal muscle fiber necrosis was observed within 24 h. Rats were protected against the apparent behavioural and morphological changes as well as electrophysiological signs of neuromuscular toxicity by all pretreatment agents. Combined pretreatment with d-TC (0.075 mg/kg, s.c.) and atropine methylnitrate (16 mg/kg, s.c.) was found to be most effective in attenuating DFP-induced muscle fiber necrosis as evidenced by complete absence of lesions and the prevention of DFP-induced hyperactivity in nerve and muscle. Significant protection was afforded by all pretreatment agents when given alone. It is suggested that the pretreatment agents act presynaptically by preventing drug-induced backfiring and muscle fasciculations possibly by reducing the release of acetylcholine (ACh). The protective drugs in the concentrations used had no significant effect on the normal characteristics of conduction and transmission.

Action Potentials↗
PubMed1988

Face imaging reconstructive morphography. A new method for physiognomic reconstruction.

A new method of facial identification--Face Imaging Reconstructive Morphography (FIRM)--is herein described. This method permits the construction of objective composites of facial features based on precise cephalometric measurements. The anthropometric measurements are derived from radiographic films taken by the Analytic Morphograph (KLS). FIRM is a rapid, objective, and reproducible method that is distinctly better than the current methods of forensic-anthropological identification.

Adult↗
PubMed1987

Biochemical and histochemical alterations following acute soman intoxication in the rat.

Rats injected with a nonlethal acute dose (100 micrograms/kg, sc) of soman (pinacolyl methylphosphonofluoridate) exhibited signs of anticholinesterase toxicity beginning at 5-15 min with increasing severity and lasting for 4-6 hr. Generalized tremors and seizure activity indicated comparatively greater involvement of the central cholinergic system than peripheral neuromuscular effects. During peak toxicity, all the brain regions tested showed more than 95% inhibition of acetylcholinesterase (AChE) activity. The cortex area was maximally affected (99% inhibition). Among skeletal muscles, soleus AChE was most severely affected (94%) and extensor digitorum longus (EDL) the least (72%). Inhibition of EDL AChE occurred at a much slower rate than in brain and other muscles. Significant recovery of AChE activity was seen by 48-72 hr after soman treatment in both brain and skeletal muscles. By Day 7, recovery was virtually complete in skeletal muscles but not in brain, although significant recovery had occurred by this time. Muscle fiber necrosis developed within 6 hr in the soleus and diaphragm, while no necrotic fibers were found in the EDL. The 16 S AChE molecular form showed the fastest recovery of the AChE isozymes in all three muscles. Full recovery was seen after 7 days in soleus and was increased to greater than control activity in diaphragm and EDL. The inhibition pattern of butyrylcholinesterase (BuChE) activity was similar to that described for AChE activity, but the recovery was comparatively faster. Carboxylesterase activity in plasma was decreased to less than 10% of control within 1 hr and recovered to 53% of control within 24 hr. No significant inhibition was seen in hepatic carboxylesterase activity. It can be concluded that soman-induced acute toxicity is directly related to the rate and degree of AChE inhibition. A significant amount of soman binds to non-AChE enzymes with serine sites such as BuChE and carboxylesterases.

Acetylcholinesterase↗
PubMed1987

Acute tabun toxicity; biochemical and histochemical consequences in brain and skeletal muscles of rat.

Male Sprague-Dawley rats injected s.c. with an acute non-lethal dose (200 micrograms/kg) of ethyl N,N-dimethylphosphoramidocyanidate (tabun) showed onset of hypercholinergic activity within 10-15 min. The maximal severity of toxicity signs was evident within 0.5-1 h and persisted for 6 h. Except for mild tremors no overt toxicity signs were evident after 24 h. Within 1 h a dramatic decline of acetylcholinesterase (AChE) activity occurred in all the brain structures (less than 3%) and skeletal muscles (less than 10% in soleus and hemi-diaphragm; and 32% in extensor digitorum longus (EDL)). No significant recovery was seen up to 48-72 h. Within 7 days rats became free of toxicity signs and AChE activity had recovered to about 40% in brain structures (except cortex, 14%) and 65-70% in skeletal muscles. Within 1 h the 16 S molecular form of AChE located at the neuromuscular junction was most severely inhibited in soleus, followed by hemi-diaphragm and least in the EDL, and had fully recovered in all the muscles when examined after day 7. Muscle fiber necrosis developed within 1-3 h in soleus and hemi-diaphragm and after a delay of 24 h in EDL. The highest number of necrotic lesions in all muscles was seen at 72 h with the hemi-diaphragm maximally affected and EDL the least. To determine detoxification of tabun by non-specific binding, the activity of butyrylcholinesterase (BuChE) and carboxylesterase (CarbE) was measured. The inhibition and recovery pattern of BuChE activity was quite similar to that of AChE, except that the rate of recovery was more rapid. Within 1 h the remaining activity of CarbE was 10% in plasma, about 30% in brain structures, and 79% in liver; recovery was complete within 7 days. The inhibition of BuChE and CarbE can serve as a protective mechanism against tabun toxicity by reducing the amount available for AChE inhibition. The prolonged AChE inhibition in muscle and brain may indicate storage of tabun and delayed release from non-enzymic sites. Since tabun is a cyanophosphorus compound, the toxic effects from the released cyanide (CN) could be another reason for the delayed recovery after tabun.

Acetylcholinesterase↗
PubMed1986

Serum regulation of acetylcholinesterase in cultured myotubes.

A large (20S) collagen-tailed form of acetylcholinesterase associated with the neuromuscular junction appears in cultures of chick embryo muscle cells when horse serum is withdrawn from the medium. In this report, 10-day-old cultures were incubated 2 days in serum-free medium or in medium containing either horse, bovine, fetal calf, chicken, heat-treated horse or chicken serum, low (less than 100K) or high (less than 100K) molecular weight fractions of horse serum, or fibronectin. Total acetylcholinesterase activity and activity of the 20S form increased in medium without serum, with fetal calf serum and with the low-molecular-weight fraction of horse serum. The largest increase occurred with fibronectin. The results suggest that a factor(s) greater than 100K in adult sera inhibits total acetylcholinesterase production and formation of the 20S form of the enzyme.

Acetylcholinesterase↗
PubMed1986

Mechanisms of toxicity and tolerance to diisopropylphosphorofluoridate at the neuromuscular junction of the rat.

Diisopropylphosphorofluoridate (DFP), an irreversible inhibitor of acetylcholinesterase (AChE) activity, when given as an acute dose (1.5 mg/kg, sc) caused fasciculations and induced necrosis in rat skeletal muscle fibers. No adaptation was seen to daily dosing of DFP (1.5 mg/kg, sc) since all rats died after the second or third injection. Daily dosing of DFP in a concentration (0.5 mg/kg, sc) that as a single dose did not cause symptoms, produced onset of fasciculations on the third day associated with a reduced number of muscle fiber lesions. Further administration of DFP (14 days) caused disappearance of fasciculations and loss of sensitivity to the necrotizing actions in all muscles tested (diaphragm, soleus, and extensor digitorum longus). Activity of all molecular forms of AChE was reduced to 20-24% of control when symptoms of cholinergic hyperactivity appeared. Continuous injections of DFP (0.5 mg/kg/day, sc) up to 14 days did not cause greater inhibition of AChE activity. Instead, recovery of enzyme activity, especially of the 4S and 10S forms, was seen. During this period choline acetyltransferase activity (ChAT) was increased in muscle (intramuscular nerves) while the postsynaptic nicotinic acetylcholine receptor (nAChR) density (Bmax) was decreased to 44% without a change in the affinity constant (KD). It is concluded that neuromuscular adaptation to DFP is caused by recovery of AChE activity due to de novo synthesis and reduction in the number of nAChR.

Acetylcholinesterase↗
PubMed1985

Mechanisms involved in the development of tolerance to DFP toxicity.

Rats treated daily with diisopropylfluorophosphate (DFP) (0.5 mg/kg, sc), an inhibitor of acetylcholinesterase (AChE) activity, exhibited the symptoms of cholinergic hyperactivity between Days 3 and 5 similar to those observed 15 min after a single acute dosage (1.5 mg/kg, sc). A significant (p less than 0.05) decrease in the activities of both AChE and cholinesterase (BuChE) (greater than 80%) occurred in muscles and in brain regions and of aliesterases in liver (greater than 92%) at this time. Further administration of DFP (0.5 mg/kg, for 7-14 days) led to behavioral tolerance, where symptoms of toxicity disappeared such as muscle fasciculations, tremors, and muscle necrosis. The activity of aliesterases in liver and AChE in muscles significantly (p less than 0.01) recovered, while no such recovery was seen in brain AChE. DFP toxicity was potentiated in rats that were pretreated with BuChE inhibitors, such as iso-OMPA (3 mg/kg, sc) or mipafox (0.05 mg/kg, sc), 30 min prior to DFP (0.5 mg/kg, sc). The severity of cholinergic hyperactivity and inhibition of aliesterase in liver, AChE and BuChE activity in brain and muscles was greater when compared to the effects of DFP alone. Both iso-OMPA and mipafox completely abolished the tolerance development to DFP, since no animal survived more than 5 days of combined treatment. The observed adaptation to DFP toxicity appears to be due to recovery of aliesterase, BuChE, and AChE activity as well as decreased nicotinic binding sites at the neuromuscular junction, as previously reported.

Acetylcholinesterase↗
PubMed1984

Drugs in muscular dystrophy of the chicken: corticosterone-21-acetate.

In a previous series of 22-day evaluations of 31 compounds, only corticosterone-21-acetate (C-21-A) increased righting ability of genetically dystrophic chickens to a greater extent than the standard of comparison, methysergide maleate. In the present study, C-21-A was subjected to longer-term trials of up to 48 days, and additional signs of the myopathy were examined. The highest doses of C-21-A increased righting ability for the duration of the trials, decreased the typically elevated plasma levels of creatine kinase (CK) activity by more than 80%, and improved morphology of the dystrophic pectoralis major muscle at the light microscopic level. The major adverse effect of C-21-A, reduction of body weight, was consistently observed at the relatively high doses needed to increase righting ability. That alone, however, could not account for increased righting ability, and plasma CK activity was decreased even at doses that did not reduce body weight. The results show that C-21-A is the most effective compound yet tested in this system and, perhaps more significantly, provides the first evidence that it is possible to identify compounds that improve muscle morphology in a hereditary myopathy using a short-term, step-wise system.

Animals↗
PubMed1983

Water deprivation: beneficial effect on muscular dystrophy in chickens.

Chicks affected with hereditary muscular dystrophy were deprived of water for 1 to 4 days at ages to 37 days ex ovo. Water deprivation partially alleviated impaired righting ability and reduced the typically elevated plasma creatine kinase activity by as much as 90%. Muscles from water-deprived chicks showed several qualitative histologic improvements, including decreased sarcoplasmic staining for acetylcholinesterase activity, reduced fiber diameters, and a decreased incidence of abnormally large rounded fibers, but retained the high degree of fiber diameter variability characteristic of dystrophic muscles. Feed deprivation reduced body weight to a similar extent as water deprivation but had lesser effects on creatine kinase activity and did not improve righting ability or muscle histology. Although the mechanism of the improvements is unknown, the magnitude and scope of the effects suggest that water deprivation beneficially alters a major abnormality in dystrophic chickens.

Animals↗