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Biomedical subjects

R Clark

Publications and source records attributed to R Clark.

At least 325 records · Page 18Linked to original sources
PubMed1986

Intermediate filament proteins in choroid plexus and ependyma and their tumors.

The intermediate filament protein types of normal choroid plexus and ependymal tissue and their putative tumors were investigated. In normal human choroid plexus tissue, but not in ependyma, keratin could be demonstrated immunohistochemically. By immunoblotting, keratins 8, 18, and 19 were found, but glial fibrillary acidic protein (GFAP) was absent. In mouse and rat, choroid plexus epithelium and ependymal lining cells were keratin-positive. In addition, many ependymal cells were vimentin-positive. Keratin was immunohistochemically found in three of four choroid plexus papillomas, two of two choroid plexus carcinomas, and the lining cells of three neuroepithelial cysts. GFAP-positive cells were present in some choroid plexus tumors. In contrast, none of the eight ependymomas contained keratin, but all were strongly positive for GFAP. The results show that choroid plexus lining cells and choroid plexus tumors have true epithelial characteristics in their cytoskeleton, in contrast to ependymomas, which do not show keratin positivity but show glial filaments, as would be seen in astrocytic tumors.

Adult↗
PubMed1986

Genetic and biochemical analysis of ras p21 structure.

We tested aspects of our model of the ras p21 structure using generic, biochemical, and immunologic approaches. First, we made a monoclonal antibody against a p21 region that is highly conserved and likely to be critical to p21 function. The antibody blocks p21 function in various cell systems. Its binding to p21 is completely blocked by guanine nucleotides, even though the region of p21 to which it binds does not seem to be part of the guanine nucleotide-binding site. We propose that the conformation of this critical region is modulated by nucleotide binding. Another interesting region of p21 includes amino acids 116 and 119, which seem to confer, in part, the specificity of p21 for guanine nucleotides. We made a series of mutants in this region and tested their ability to bind GTP, and such related purine nucleotides as XTP and diaminopurine nucleoside triphosphate. We were able to refine our model for guanine nucleotide interaction with p21 and to create mutant proteins with altered specificity for purine nucleotides. Finally, we tested rates of autophosphorylation of six position 12 mutants and conclude that amino acid 12 affects the positioning of bound nucleotides relative to sequences around amino acid 59.

Genes, ras↗
PubMed1986

Detection of activated Mr 21,000 protein, the product of ras oncogenes, using antibodies with specificity for amino acid 12.

Antisera raised to a set of chemically synthesized peptides spanning position 12 of ras Mr 21,000 protein (p21) (residues 5 to 17) were able to distinguish between different forms of p21 according to the amino acid at the twelfth codon. The peptide immunogens differed in one amino acid corresponding to position 12 of the protein; the substitutions were valine, serine, arginine, aspartate, alanine, or cysteine at this position. Normal p21 contains glycine at position 12; the other amino acid substitutions are those which would result from a single base change in codon 12 and may therefore be the activating mutations most likely to occur in human tumors. The peptide antisera were evaluated by the Western immunoblot procedure for reactivity with v-ki-ras p21 expressed in Escherichia coli containing the corresponding position 12 mutations. Five of the antisera reacted with p21, and of these, anti-serine, -valine, -arginine, and -aspartate peptide antibodies were specific for their cognate protein. Similar analysis using mammalian cells as sources of position 12 variant forms of p21 demonstrated the ability of these antisera to distinguish among their oncogenic forms of p21 differing by single amino acid substitutions.

Amino Acids↗
PubMed1986

Computer-assisted instruction in orthopedic biomechanics.

A computer-aided instructional (CAI) course in biomechanics was developed at the University of Texas Medical Branch in Galveston. This was used by our residents in preparation for the 1984 OITE. The course was developed on a 256K IBM personal computer with a color graphics board and color monitor. The course requires about 6 hours of user time to complete. The program was written in the Basic computer language and consists of a master and teaching program. The master program keeps track of the name of the user and his or her progress. The teaching program contains the chapters of biomechanical concepts with a quiz after each chapter. The chapters present the basic concepts of biomechanics with interactive color graphics. The quizzes contain about 20 board-type questions. Six residents voluntarily used the CAI and nine residents chose not to use the CAI. There was no difference in the two groups' outside reading of biomechanical texts or other methods of study. There was no statistical difference between the two groups 1983 OITE biomechanics score. There was also no statistical change in the nonusers' score from 1983 to 1984. The users, however, showed a statistically significant improvement (p less than .05) from the previous year. We conclude that with the wide use of properly developed CAI is an effective and efficient method to provide education for orthopedists.

Biomechanical Phenomena↗
PubMed1985

Control of myofibrillar ATPase activity and force in myodystrophic muscle.

Myofibrillar ATPase activity was measured as a function of the free calcium concentration in skeletal muscles of control and myodystrophic mice. In addition, the force developed in skinned extensor digitorum longus (EDL) fibers of control and myodystrophic mice was measured as a function of the free calcium concentration, and a histomorphometric study was performed on soleus and EDL muscles of control and myodystrophic mice. The results showed that the myofibrillar ATPase activity and the force-generating mechanisms of control and myodystrophic muscles were controlled to the same relative degree by equivalent concentrations of calcium ions. Upon maximal activation of the ATPase activities, we measured 18% less activity in myodystrophic muscles than in control muscles. Maximal activation of the force-generating capacity in skinned fibers showed there was no significant difference in force produced in the control compared to myodystrophic fibers. The histomorphometric study revealed no alteration in the relative distribution of different fiber types in myodystrophic compared to control muscles. However, the histomorphometry did reveal a larger slow (type 1) relative cellular area compared to total cross-sectional area in myodystrophic muscle than in controls. We propose that the lower ATPase activity but equal force-generating capacity of myodystrophic muscles compared to control muscles is due to myodystrophic muscles being composed of a greater fraction of myofibrils from slow (type 1) fibers than control muscles.

Adenosine Triphosphatases↗
PubMed1985

Nalbuphine.

Nalbuphine is a potent analgesic with a low side effect and dependence profile in animals and man. Nalbuphine is distinguished from other agonist/antagonist analgesics in having greater antagonist activity and fewer behavioral effects at analgesic doses than pentazocine, butorphanol or buprenorphine. At equi-analgesic doses, nalbuphine is quantitatively similar to nalorphine in regard to its large ratio of antagonist to analgetic activity. Clinical studies have confirmed this balance of strong antagonist to analgesic activity. Nalbuphine has been shown to effectively antagonize the respiratory depressant activity of narcotic analgesics while concomitantly adding to their analgetic responses. Unlike nalorphine or pentazocine, nalbuphine produces few overt behavioral or autonomic effects in animals at doses over 300 times its analgesic range. These findings are confirmed by clinical results which show that nalbuphine produces few psychotomimetic effects, even at elevated dose levels, in contrast to nalorphine or pentazocine. Nalbuphine produces limited respiratory depression in animals and in man. Significant cardiovascular effects have not been found. Nalbuphine was found to produce significantly less inhibition of gastrointestinal activity than any of the clinically useful narcotic or agonist/antagonist analgesics tested in animals. Nalbuphine's analgetic effects are reversed by naloxone doses similar to those which reverse nalorphine's agonist effects. Results in this and other tests suggest that nalbuphine is primarily a kappa-agonist/mu-antagonist analgesic. Unlike pentazocine or buprenorphine, nalbuphine does not suppress the narcotic abstinence syndrome in partly-withdrawn morphine-dependent animals or man. Rather, due to nalbuphine's strong antagonist activity, analgesic-range doses of nalbuphine severely exacerbate the withdrawal syndrome in partly-withdrawn mice, monkeys and humans. Nalbuphine also precipitates a strong abstinence response in non-withdrawn morphine-dependent animals and man. In post-addict humans, analgesic-range doses of nalbuphine are perceived as minimally morphine-like, but higher doses are judged to be progressively more nalorphine-like (i.e. dysphoric), which further limits nalbuphine's abuse potential in drug-seeking individuals. Primary dependence studies have demonstrated that physical dependence is possible at high dose levels that produce marked side effects. Other studies show that dependence is unlikely to be of significance within nalbuphine's usual analgesic range. Six-month studies in patients with chronic pain have confirmed that analgesic tolerance or physical dependence is uncommon.(ABSTRACT TRUNCATED AT 400 WORDS)

Analgesics↗
PubMed1985

Antibodies specific for amino acid 12 of the ras oncogene product inhibit GTP binding.

An antibody (anti-p21ser) was raised against a ras p21-related synthetic peptide and was able to recognize specifically the substitution of serine for glycine at amino acid 12 of p21. This substitution causes oncogenic activation of p21. Anti-p21ser was found to immunoprecipitate v-Ki-ras p21 and to strongly inhibit its ability to autophosphorylate and to bind GTP in an immunoabsorption assay. Furthermore, binding of the antibody to p21 was specifically inhibited by GTP or GDP, suggesting that amino acids around position 12 are part of the GTP/GDP binding site. These results, taken together with the observation that the microinjection of anti-p21ser into cells transformed by v-Ki-ras p21 causes a transient reversion of the cells to a normal phenotype [Feramisco, J. R., Clark, R., Wong, G., Arnheim, N., Milley, R. & McCormick, F. (1985) Nature (London) 314, 639-642], support the idea that interaction of p21 with guanine nucleotides is crucial to the transforming function of this protein.

Amino Acid Sequence↗
PubMed1985

Twice or four times daily beclomethasone dipropionate in mild stable asthma?

A double-blind cross-over study lasting 16 weeks was conducted to establish if a twice daily regimen of beclomethasone dipropionate (BDP) was as effective in controlling asthma as a four times daily regimen. The patient's need for inhaled steroids (100 mcg BDP qds) was confirmed prior to entering the study by deterioration of peak expiratory flow rates and/or increased bronchodilator usage during a single-blind placebo period of 6 weeks. Thirty six asthmatics were eligible to enter the study and completed both treatment periods. Daily record cards of symptom scores, four times daily peak expiratory flow rate measurements and inhaled bronchodilator usage were recorded throughout the study. There was no significant difference between the mean PEFR measurements taken four times each day and the variability in PEFR, between the two treatment groups. Symptom scores for cough, wheeze, breathlessness and overall disability also showed no significant difference. Symptomatic inhaler usage for the two groups was similar. Lung function measurements of FEV1, FVC and VC were almost identical; FEV1 being 2.1 l on twice daily regimen and 2.2 l on four times daily regimen. A slight variation was observed in PEFR taken at the end of each treatment period at the clinic visits, being 361 l/min on twice daily and 380 l/min on four times daily drug dosage. In stable asthmatics, the control of asthma measured both symptomatically and by daily lung function was independent of dosing schedule, but twice daily treatment may well lead to better compliance.

Adult↗
PubMed1985

Intermediate-filament proteins in parathyroid glands and parathyroid adenomas.

The intermediate-filament proteins of normal, hyperplastic, and adenomatous parathyroid glands were analyzed immunohistochemically and by immunoblotting with monospecific antibodies. In both normal and adenomatous parathyroid glands, we found keratins with molecular weights of 52, 45, and 40 kilodaltons (Nos. 8, 18, and 19, respectively). Vimentin proteins could be identified only in stromal cells, while glial fibrillary acidic protein was not found. In normal parathyroid glands, neurofilament positivity was seen only in nerve axons. In five of 15 parathyroid gland adenomas some keratin-positive cells expressed neurofilamentlike immunoreactivity also. In cytoskeletal extracts of one adenoma, the 200-kilodalton neurofilament protein was identified by immunoblotting. Thus it appears that some parathyroid gland adenoma cells may acquire neurofilament proteins and coexpress cytokeratin and neurofilament polypeptide in a way comparable with that reported in certain neuroendocrine tumors.

Adenoma↗
PubMed1985

Arthroscopic debridement of the knee for septic arthritis.

Sixteen knees with hematogenous septic arthritis in 12 adult patients were treated by arthroscopic decompression, debridement, and irrigation with motorized instruments plus suction drainage. Infectious disease consultants supervised the administration of intravenous antibiotics, and range-of-motion exercises were instituted when the drains were removed 48 hours after surgery. Patients were protected from bearing weight for six weeks. There were no treatment complications, and no patient required a repeated drainage procedure. Two patients died of diseases unrelated to knee infection. The 11 infected knees of the ten surviving patients were evaluated subjectively, functionally, objectively, and roentgenographically. With an average 34-month follow-up evaluation, all patients regained their preoperative functional status without loss of motion or roentgenographic evidence of cartilage loss. Arthroscopic debridement of the knee for septic arthritis is a safe, efficient method of joint decompression with minimal morbidity.

Adolescent↗
PubMed1984

Intraneuronal substance P contributes to the severity of experimental arthritis.

There is evidence that substance P is a peptide neurotransmitter of some unmyelinated primary afferent nociceptors and that its release from the peripheral terminals of primary afferent fibers mediates neurogenic inflammation. The investigators examined whether substance P also contributes to the severity of adjuvant-induced arthritis, an inflammatory disease in rats. They found that, in the rat, joints that developed more severe arthritis (ankles) were more densely innervated by substance P-containing primary afferent neurons than were joints that developed less severe arthritis (knees). Infusion of substance P into the knee increased the severity of arthritis; injection of a substance P receptor antagonist did not. These results suggest a significant physiological difference between joints that develop mild and severe arthritis and indicate that release of intraneuronal substance P in joints contributes to the severity of the arthritis.

Animals↗
PubMed1984

Primary radiation therapy for juvenile nasopharyngeal angiofibroma.

Evidence is presented of the effectiveness and relative lack of serious toxicity of external beam megavoltage radiation therapy (RT) as primary treatment for juvenile nasopharyngeal angiofibroma. The importance of careful radiological evaluation of tumor extent prior to irradiation is stressed, and only moderate dose RT is required. Fifty-five patients have been treated by RT and followed for from 3 to 26 years. Forty-four of 55 patients (80%) had permanent tumor control following a single course of 3000 cGy to 3500 cGy over 3 weeks. Surgical resection or a second course of RT controlled the tumor in all 11 patients in whom regrowth occurred. Angiofibromas involute slowly after RT so that 50% of patients still had visible masses in the nasopharynx 12 months after treatment, but only 10% had any visible abnormality 36 months after RT. Retreatment was necessary only if symptoms recurred, and continued follow-up showed that most asymptomatic nasopharyngeal masses resolved completely. Acute and late toxicity rates were low. Two patients developed tumors in the head or neck following RT. There was no significant clinical impairment of growth or endocrine function. A single course of external beam megavoltage radiation to 3000 cGy in 3 weeks is an effective first treatment for patients with juvenile nasopharyngeal angiofibroma.

Adolescent↗