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Biomedical subjects

C Adams

Publications and source records attributed to C Adams.

At least 163 records · Page 9Linked to original sources

Detection of human probombesin mRNA in neuroendocrine (small cell) carcinoma of the lung. In situ hybridization with cRNA probe.

The production of human bombesin (gastrin-releasing peptide), a peptide with mitogenic action, is a recognized feature of neuroendocrine (small cell) carcinoma of the lung. However, immunostaining of bombesin is not always possible in these tumors, probably because of poor storage mechanisms or rapid release of hormone. Molecular biological analysis of the gene encoding human bombesin has revealed the DNA sequence of human pro-bombesin. We have used in situ hybridization to study the expression of the human bombesin gene at the cellular level in small cell carcinoma of the lung. Probombesin cDNA was subcloned in pSP64 vector, linearized with Bam HI and transcribed in the presence of phosphorus 32(32P)-cytosine triphosphate (CTP) and SP6 polymerase. The cRNA probe was applied to tissue sections (from six cases of small cell carcinoma of the lung, freshly fixed in 4% paraformaldehyde), cell culture preparations (two different cell lines of small cell carcinoma), and cytologic specimens (smears of cells from three different cases of small cell carcinoma). Hybridization of probombesin mRNA was detected in tumor cells in all samples. Specificity of the signal was determined by control experiments, including the use of a probe which has a sequence identical to probombesin mRNA. Our results provide evidence for the expression of the bombesin gene in small cell carcinoma of the lung at a cellular level and show that probombesin mRNA is highly expressed in these tumors.

Bombesin↗

Non-isotopic RNA probes. Comparison between different labels and detection systems.

Several studies have shown the use of non-radioactive labelled DNA probes for in situ hybridisation, mainly to identify cellular DNA. In this study mRNA in situ hybridisation was performed on rat pituitary with biotinylated complementary (c) RNA probes for rat prolactin and growth hormone (GH), and compared with radioactive 35S-radiolabelled probes. Biotinylated cRNA probes were labelled with either biotin-11-UTP or with allylamine-UTP, the latter method being able to produce a higher yield of labelled RNA. Different detection systems were tested, and hybridisation signal was seen in cells of anterior pituitary with both types of biotinylated probes. The signals were detected using either avidin-biotin-complex with peroxidase (ABC), peroxidase-anti-peroxidase (PAP) or gold-silver methods. ABC peroxidase detected using glucose oxidase-diaminobenzidine (DAB)-nickel solution appeared to be the best method for detecting labelled RNA probes, with very strong signal and low background. The biotinylated probes were comparable in sensitivity to the radiolabelled probes in detecting prolactin and GH mRNAs in the anterior lobe of the rat pituitary. These results indicate an alternative methods of labelling and detection of biotinylated probes which could have a potential role in research and diagnostic techniques.

Allylamine↗

Neuron-specific enolase and its mRNA are highly expressed in large congenital nevi: a study using immunocytochemistry, biochemical assay, and in situ hybridization.

The malignant transformation of congenital nevocellular nevi, both large and small, is controversial and presents problems in management. The size of the lesion is taken to indicate potential malignant transformation, but this is an arbitrary scale. A more reliable biological indicator is needed to help predict the lesions at risk. Following the localization of neuron-specific enolase to most cells of the diffuse neuroendocrine system and their neoplasms (including benign and malignant melanocytic lesions), it has been suggested that its level is related to tumor activity. In a prospective trial, the presence of neuron-specific enolase immunoreactivity, its concentration, and gene expression in nevus cells were studied in 31 congenital melanocytic nevi of various sizes (1.5 cm to bathing trunk) using immunocytochemistry, biochemical assay, and in situ hybridization. Twenty-five of the 31 congenital nevi were immunoreeactive to neuron-specific enolase antiserum, with stronger immunostaining in the larger lesions. There is an apparent linear relationship between the size of the nevi and the level of neuron-specific enolase (expressed as nanograms per milligram protein). Neuron-specific enolase mRNA was highly expressed in most of the large congenital nevi (greater than 15 cm in diameter), as revealed by autoradiography following in situ hybridization. Our results show that neuron-specific enolase and its mRNA are expressed to a greater extent in large congenital nevi compared with the smaller lesions. This might prove to be a useful indicator of those lesions at risk of malignant transformation.

Adolescent↗

Superoxide dismutase inhibition of alkaline hemin-mediated O2 activation.

Inhibition of hemin-mediated O2 activation by bovine superoxide dismutase and the copper tetrammine complex has been examined. It is shown that the inhibitory effect of these species is not due to metabolism of O2-., but to a nonspecific inhibition of the process by the Cu2+ ion. We propose that the inhibition occurs at the level of electron transfer from NADH to iron in an analogous manner to that proposed for the Cu2+ inhibition of microsomal electron transfer.

Animals↗

Conversational characteristics of children with semantic-pragmatic disorder. I: Exchange structure, turntaking, repairs and cohesion.

Conversational samples were obtained from 57 children aged from 8 to 12 years with specific language impairment, and 67 control children aged from 4 to 12 years. Fourteen of the language-impaired children fitted the clinical description of semantic-pragmatic disorder. It was found that exchange structure, turntaking, conversational repair and use of cohesive devices could be assessed with adequate inter-rater and test-retest reliability. Children with semantic-pragmatic disorder produced more initiations than other children. Some of these children also violated turntaking rules by interrupting the conversational partner to an unusual degree. Use of cohesion was normal for children with semantic-pragmatic disorder, but limited in other language-impaired children. Analysis of conversations may be more useful than conventional language tests for identifying linguistic abnormalities in children with semantic-pragmatic disorder.

Child↗

Conversational characteristics of children with semantic-pragmatic disorder. II: What features lead to a judgement of inappropriacy?

Independent raters scanned transcribed conversations from 57 language-impaired children and 67 control children aged from 4 to 12 years and identified instances where the normal flow of conversation appeared to be disrupted because the child's utterance was in some way inappropriate. It was found that adequate inter-rater reliability could be obtained using this procedure. Furthermore, test-retest correlations for inappropriacy were significant, indicating that this is a stable conversational characteristic. The measure of inappropriacy decreased with age in control children, and it distinguished language-impaired from control children. Those identified as having 'semantic-pragmatic disorder' obtained particularly high scores. In a subsidiary analysis, inappropriate responses were subcategorised. A wide range of semantic, syntactic and pragmatic peculiarities was identified as leading to a sense of inappropriacy. Some instances of inappropriacy appeared to indicate cognitive rather than linguistic difficulties. Children with semantic-pragmatic disorder resembled younger normal children in that they frequently misunderstood the literal or implicit meaning of adult utterances and they violated normal rules of exchange structure. In other respects, however, the semantic-pragmatic group did not resemble normally developing children of any age. In particular, they tended to provide the listener with too much or too little information.

Child↗

[Evaluation of pulmonary arterial hypertension by Doppler echocardiography in chronic respiratory insufficiency].

The usefulness of doppler-echocardiography for the assessment of pulmonary arterial hypertension in patients with chronic respiratory failure was evaluated in 24 consecutive patients with chronic obstructive lung disease. Seventeen of these 24 patients (71 p. 100) who had tricuspid valve regurgitation analysable by the continuous wave doppler technique were selected as study group; they included 15 men and 2 women aged from 33 to 78 years (mean 63 years). The highest maximum velocity value (method A) or the maximum velocity value averaged on several cycles (method B) of the tricuspid regurgitation jet was used to calculate the right ventriculo-atrial pressure gradient, using Bernouilli's equation. Right atrial pressure was determined by three methods: haemodynamic measurement, clinical evaluation or attribution of an arbitrary 10 mmHg value. The pulsed doppler study of the pulmonary ejection flow included measurement of the acceleration time and calculation of the acceleration time/ejection time ratio. The usual echocardiographic parameters were measured. Catheterization was performed 2.5 days on average after the doppler study. Correlations between doppler examination and catheterization to evaluate the right ventricular systolic pressure were significant (p less than 0.001) and better with method B than with method A. Depending on the method employed to evaluate the right atrial pressure, the correlation coefficients obtained with method B were: 0.93 (haemodynamic measurement), 0.91 (clinical evaluation) and 0.88 (arbitrary value of 10 mmHg). The right ventricular systolic pressure evaluated by doppler ultrasound using method B and by clinical evaluation of the right atrial pressure was 47 +/- 12 mmHg (22 to 70 mmHg), as against 51 +/- 13 mmHg (28 to 74 mmHg) measured by catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[10-year outcome of aortocoronary bypass. Apropos of a consecutive series of 114 patients].

The cases of 114 consecutive patients undergoing saphenous vein coronary bypass surgery over 10 years ago were reviewed. The perioperative mortality was 2.6% and the incidence of non-fatal myocardial infarction in the same period was 6.1%. The 10 year survival rate was 80%; the most important prognostic factor for survival was left ventricular function (89% vs 51%; p less than 0.001). Other significant prognostic factors were the degree of revascularization (p less than 0.05) and the severity of the coronary artery disease (p less than 0.05). The incidence of recurrent ischaemia during follow-up depended mainly on the quality of myocardial revascularisation (p = 0.003). Taking into account the high proportion of patients with single vessel disease in this series (38.6%), our results were comparable with other reported studies of the same subject and the same period (1970-1976).

Adult↗

Ferriprotoporphyrin IX mediated oxygen activation/insertion reactions: the anerobic reduction of the aniline-Fe3+-microperoxidase-8 complex by NADH.

A spectrophotometric study of the reduction of the Fe3+ microperoxidase-8-aniline (Fe3+-MP-8-An) complex has been carried out. Addition of NADH to a solution of Fe3+-MP-8-An under strictly anerobic conditions results in the formation of a species with lambda max = 414 nm (Fe3+-MP-8-An lambda max 407 nm). The kinetics of formation of this species show an induction period (tau) which follows saturation kinetics with respect to [aniline] with Km(app) = 2.2 x 10(-3) mol dm-3, i.e., close to that obtained in the preceding paper from O2 consumption kinetics mediated by MP-8. Addition of an anerobic solution of the NADH reduced MP-8-An complex, to a saturated O2 solution at pH 12 in the presence of 0.5 mM NADH and aniline 10 mM results in the virtual elimination of the induction phase, which has previously characterized O2 consumption kinetics in ferriprotoporphyrin IX oxygen activation systems. The Arrhenius activation energy for the reduction of the Fe3+-MP-8-An complex is close to that observed for the first reductive step in the cyt P-450 O2 activation cycle. Anerobic reduction of Fe3+-MP-8 by sodium dithionite in 20% MeOH/Aq at pH 8 followed by anerobic titration of the Fe2+-MP-8 (lambda max 420.5 nm) with aniline at pH 12 gives rise to a species lambda max 415 with KD for the process = 4.4 x 10(-3) mol dm-3 (+/- 1.2 x 10(-3) mol dm-3).

Aniline Compounds↗

The effect of Goldmann applanation tonometry on automated static threshold perimetry.

Automated static threshold perimetry was performed in both eyes of 10 normal and 12 ocular hypertensive subjects treated with a topical beta-blocker, before and after Goldmann applanation tonometry of their right eyes. Both objective statistical comparison and subjective evaluation of the resultant visual fields showed no detrimental effect on visual field test results after applanation tonometry.

Adrenergic beta-Antagonists↗

Pelvic-floor musculature exercises in treatment of anatomical urinary stress incontinence.

The purpose of this study was to investigate the effects of pelvic-floor musculature exercises in the treatment of women with anatomical urinary stress incontinence. Fourteen female subjects, ranging in age from 33 to 67 years, participated in a four-week pelvic-floor musculature exercise program. Subjects underwent a pretraining urodynamic evaluation and were reexamined after four weeks of exercise training. Paired t tests of subjects' pretraining and posttraining values of bladder capacity, functional urethral length, and static urethral pressure profile showed no significant differences. Multivariate regression analysis demonstrated that the covariates of weight, motivation, and age did not significantly influence subjects' bladder capacity, functional urethral length, or static urethral pressure profile. Nine of the 14 subjects had a negative result on the posttraining urinary stress test (R = 0, p less than .01). The urinary stress test result was the only variable to change significantly from pretraining to posttraining measurements. All subjects reported posttraining improvement in control of urinary incontinence. A short-term exercise program for pelvic-floor musculature produced positive changes in subjects with anatomical urinary stress incontinence.

Adult↗

Neurogenic arthrogryposis multiplex congenita: clinical and muscle biopsy findings.

Thirteen cases of arthrogryposis multiplex congenita without evidence of spinal muscular atrophy, congenital muscular dystrophy, or structural myopathy were reviewed. Family history, consanguinity, pregnancy, delivery, number and severity of contractures, and outcome were evaluated. Laboratory investigations had been performed and a biopsy of muscle from an affected limb had been examined histochemically and by electron microscopy. Five biopsies showed fiber type 1 predominance and three had type 2 predominance. Patterns of fiber-type predominance may have resulted from altered neural influence leading to impaired maturation of type 1 or 2 motor units. Nine patients had been followed up for 3-8 years. Two were still not walking at age 8 years. For the 6 who were walking, the mean age at ambulation was 4.7 years. There was no deterioration in power. Muscle biopsy is recommended in arthrogryposis multiplex congenita. Identification of a probable neurogenic arthrogryposis multiplex congenita is important because the condition is not progressive and is apparently not transmitted genetically.

Arthrogryposis↗

A comparison of clinical and judicial procedures for reviewing requests for involuntary medication in New York.

The Rivers v. Katz decision substituted judicial review for administrative review of requests for involuntary medication of patients in New York State mental hospitals. This change, prompted by concern for the rights of involuntarily committed patients, did not delay or diminish the use of involuntary medication in a large state hospital. Advantages of judicial review include a better understanding by clinicians of the legal basis for involuntary medication and greater patient participation in the review procedure. Disadvantages include lack of an independent clinical review and increased costs.

Commitment of Persons with Psychiatric Disorders↗

[Acquired systemo-pulmonary fistula after pleurectomy responsible for a continuous thoracic murmur].

Systemo-pulmonary fistulae are rare. The case of a 27 year-old man, hospitalized for exploration of a continuous thoracic murmur, is reported. A right pleurectomy had been performed 2 years previously because of a recurrent spontaneous pneumothorax, and no murmur was present at that time. Angiography showed a systemo-pulmonary fistula with the right internal mammary artery and branches of the right axillary artery as afferent vessels, and the right pulmonary arteries and veins as efferent vessels. Blood gases measurements demonstrated a left-right shunt. The acquired nature of the fistula was suspected because of the history of right pleurectomy and the acquired nature of the murmur. There was no indication for surgery because of the complexity of the fistula and the absence of symptoms.

Adult↗

[Annulo-ectasing disease of the aorta: apropos of 10 cases].

Ten patients were investigated and operated for severe aortic regurgitation due to dystrophic aortic dilatation. This is the third commonest cause of pure aortic regurgitation (18 p. 100) operated at Necker Hospital during the same period. This condition, comprising aneurysm of the ascending aorta, dilatation of the aortic ring and dystrophic aortic valves, is often responsible for severe aortic regurgitation and is noteworthy because of the associated risk of aortic dissection. Cardiovascular surgery is indicated and usually includes replacement of the ascending thoracic aorta with aortic valve replacement.

Adult↗

Contrast sensitivity after epikeratophakia.

Epikeratophakia is a rapidly evolving surgical procedure for the refractive correction of aphakia. Even when Snellen acuity after epikeratophakia is normal, patients often report a subjective degradation of the visual image through the surgically corrected eye. To further define visual performance in the patient with optically successful epikeratophakia, we examined contrast sensitivity in two patients surgically corrected for monocular aphakia. Contrast thresholds were measured over a range of spatial frequencies using both computer-generated sinusoidal gratings and a commercially available wall chart system. The eye with epikeratophakia in each case was compared with the opposite normal eye with comparable acuity. One patient was also tested prospectively in the same eye both before and after surgery. Data demonstrate a depression of the contrast sensitivity function in the middle and high spatial frequencies induced by the placement of an epikeratophakia lenticule when compared with the normal eye or contact lens-corrected, preoperative aphakic eye with comparable good acuity. These findings may explain the subjective experience of epikeratophakia patients.

Adult↗

Effect of isomers of swainsonine on glycosidase activity and glycoprotein processing.

The chemical synthesis of swainsonine [(1S,2R,8R,8 alpha R)-trihydroxyindolizidine] from trans-1,4-dichloro-2-butene was previously described [Adams, C. E., Walker, F. J., & Sharpless, K. B. (1985) J. Org. Chem. 50, 420-424]. A modification of that synthesis provided two other isomers, referred to here as "Glc-swainsonine" [(1S,2S,8R,8 alpha R)-trihydroxyindolizidine] and "Ido-swainsonine" [(1S,2S,8S,8 alpha R)-trihydroxyindolizidine]. To determine whether these new compounds had biological activity, they were compared to swainsonine as inhibitors of a number of commercially available glycosidases. While swainsonine is a potent inhibitor of jack bean alpha-mannosidase but does not inhibit other glycosidases, its two isomers were inactive on alpha-mannosidase but did inhibit other enzymes. Thus, Glc-swainsonine was an inhibitor of the fungal alpha-glucosidase amyloglucosidase, and this inhibition was of a competitive nature (Ki = 5 X 10(-5) M) with respect to the substrate p-nitrophenyl alpha-D-glucopyranoside. This alkaloid also inhibited beta-glucosidase, but much less effectively than alpha-glucosidase. On the other hand, Ido-swainsonine was more effective toward beta-glucosidase than toward alpha-glucosidase, and this inhibition was also of a competitive nature. None of these inhibitors were effective against beta-mannosidase or alpha- or beta-galactosidase. Glc-swainsonine was also tested against the glycoprotein processing glycosidases. Surprisingly, in this respect, the alkaloid was like swainsonine in that it inhibited mannosidase II but had no effect or only slight effect on glucosidase I, glucosidase II, and mannosidase I. Glc-swainsonine also inhibited glycoprotein processing in cell culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗