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Biomedical subjects

R C Marshall

Publications and source records attributed to R C Marshall.

At least 19 recordsLinked to original sources

Structure and biochemistry of mammalian hard keratin.

In this review, the structure and biological formation of hard alpha-keratin are drawn together. The hard keratins comprising wool, hairs, quills, hooves, horns, nails and baleen contain partly alpha-helical polypeptides which show homology with epidermal polypeptides only in the helical regions. These polypeptides (about 32 chains) are organized into intermediate filaments (IFs) of 7.5 nm diameter which are embedded in variable amounts of a matrix of non-helical cystine-rich proteins and glycine-tyrosine-rich proteins. The total number of proteins may exceed 100. In addition keratins contain a variety of lipid components. Wool and hair are produced in follicles in a multistep procedure. In the lower levels of the follicle, IFs without associated matrix are found. Subsequently matrix proteins are laid down between the IFs and further synthesis takes place concurrently. Finally the proteins are insolubilized by the oxidative formation of disulphide bonds. Keratinized fibres shows considerable complexity and diversity in the structural arrangement of IFs and matrix within cortical cells. Typically the IFs show hexagonal packing or give a whorl-like appearance in cross-section.

Animals

The effect of flow on technetium-99m-teboroxime (SQ30217) and thallium-201 extraction and retention in rabbit heart.

In order to evaluate the accuracy of blood flow measurement, the single-pass extraction, retention/wash-out and relative net uptake of 99mTc-teboroxime (SQ30217) and 201Tl were evaluated and compared in 20 isolated blood-perfused rabbit hearts at coronary flow rates ranging from 0.49 to 2.85 ml/g wet wt min-1. The average peak extraction of 201Tl (+/- s.d.) (0.67 +/- 0.11) marginally exceeded that of SQ30217 (0.62 +/- 0.12) (p = 0.06). Flow significantly affected the maximum net extraction of 201Tl and the 40-min net extractions of both 201Tl and SQ30217. Unexpectedly, the rate of 201Tl myocardial washout was significantly faster (p less than 0.05) than SQ30217 washout at all flow rates evaluated. Increasing coronary blood flow rate was associated with a more rapid clearance of both tracers from the myocardium (p less than 0.05 for both comparisons). The slope of the linear correlations between relative net SQ30217 uptake versus flow and relative net 201Tl uptake versus flow were found to be similar for up to 10 min after isotope injection. These data were interpreted to indicate that: 1. Thallium-201 might be slightly better extracted than SQ30217. 2. SQ30217 is cleared more slowly from the myocardium. 3. Thallium-201 and SQ30217 appear to be comparable tracers of myocardial perfusion for up to 10 min after injection under the single-pass conditions currently employed. 4. Additional studies are needed to clarify myocardial SQ30217 kinetics.

Animals

Technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile and thallium-201 extraction, washout, and retention at varying coronary flow rates in rabbit heart.

Technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile (Tc-MIBI) and thallium-201 extraction, washout, and retention were investigated and compared in 20 isolated, isovolumic, retrograde blood-perfused rabbit hearts at flow rates ranging from 0.5 to 3.5 ml/g wet wt min-1 in the absence of tracer recirculation. Mean Tc-MIBI peak instantaneous extraction was lower (0.55 +/- 0.10, p less than 0.001) and more affected by flow rate (p less than 0.05) than 201Tl peak instantaneous extraction (0.83 +/- 0.06). In contrast, the rate of 201Tl washout was significantly faster (p less than 0.05) and initially more dependent on perfusion rate (p less than 0.05) than Tc-MIBI washout. Reflecting its higher peak instantaneous extraction, 201Tl retention was 55-79% higher immediately after isotope injection (p less than 0.001) than Tc-MIBI retention, and relative changes in maximal 201Tl net uptake correlated better (p less than 0.05) with relative flow changes than maximal Tc-MIBI net uptake. However, due to its faster washout rate, the superiority of thallium over Tc-MIBI as a perfusion indicator was lost within 10 minutes of tracer injection under the present single-pass experimental conditions. These data were interpreted to indicate that 1) Tc-MIBI is not as well extracted and has a slower washout rate than 201Tl; 2) varying the coronary flow rate has significant but divergent effects on the extraction, washout, and retention of Tc-MIBI and 201Tl; and 3) the present results support continued evaluation of Tc-MIBI as a possible perfusion indicator.

Animals

Korean hemorrhagic fever: environmental health and medical surveillance measures.

Throughout history, battles, campaigns, and wars have often been decided by diseases, rather than bullets and tacticians. During the Korean War, Korean hemorrhagic fever (KHF) afflicted several thousand allied soldiers and an unknown number of Communist soldiers. This disease, and other members of a closely related group, the hemorrhagic fevers with renal syndrome, represent a continuing worldwide military and civilian threat. Through inexpensive and flexible environmental health measures, and readily available medical surveillance and testing, it is now possible to reduce the risk from this disease. In this paper, we will outline various environmental health measures developed to reduce the risk of contracting KHF and the justification for their use. We will also discuss a medical surveillance and testing program designed to get at-risk and symptomatic individuals to definitive care quickly in order to reduce overall morbidity and mortality.

Environmental Monitoring

Idiosyncratic strategies in sentence production: a case report.

In their case study of a patient with selective apraxia of phonation, Marshall, Gandour, and Windsor (1988, Brain and Language, 35, 313-339) reported that many of his utterances were ill-formed syntactically. In this note, a detailed syntactic analysis of his speech is presented. Although the patient's syntax is deviant, it is seen to result from the application of certain consistent, identifiable, compensatory strategies. Moreover, it is shown that the particular, abnormal syntactic structures are internally consistent with his phonatory apraxia coupled with the normal rules of English prosody.

Aphasia

Home treatment for aphasic patients by trained nonprofessionals.

Thirty-seven aphasic men received 8-10 hr of individual treatment each week for 12 weeks from a home therapist (wife, friend, relative) who was trained and directed by a speech pathologist. Treatment was followed by 12 weeks of no treatment. Patients were evaluated at entry and at 6, 12, 18, and 24 weeks after entry with a battery of speech and language measures. The group made substantial progress on all measures during the 12 weeks of treatment and ceased to progress when treatment was discontinued. Progress for the home treatment patients did not differ significantly from that of patients who received 12 weeks of individual treatment from speech pathologists or from that of patients for whom treatment was deferred for 12 weeks. Patient selection, training of the home therapists, and other methodological aspects are described to assist speech pathologists in making decisions about the use of trained volunteers in aphasia treatment.

Aged

Selective impairment of phonation: a case study.

A 47-year-old right-handed man underwent craniotomy for clipping of an aneurism at the trifurcation of the left middle cerebral artery. Subsequently, he suffered a left hemisphere CVA after which his speech and language resembled that of Broca's aphasia with accompanying apraxia of speech. Medical, behavioral, and acoustical data amassed over a period of several months indicated numerous contraindications to traditional diagnoses of Broca's aphasia, apraxia of speech, and dysarthria. Ultimately, it was determined that the patient had a selective impairement of phonation or laryngeal apraxia. This was illustrated dramatically when he was taught to use an electrolarynx which allowed him to bypass his disrupted phonatory system. Speaking with the electrolarynx, the patient communicated normally. Any semblance of Broca's aphasia disappeared. Supralaryngeal articulation was normal; apraxia of speech behaviors were absent. This case report indicates that dissociation of oral and laryngeal gestures due to brain injury is possible. Mechanisms underlying such a dissociation for this case are reviewed. The possibility of discrete center lesions in the frontal motor association area causing different types of apraxia of speech is discussed.

Aphasia, Broca

Identification of persons at risk for sudden cardiac death.

Before any more progress is made in reducing the incidence of sudden cardiac death, our ability to identify those at risk must be refined further. The close association with coronary artery disease necessitates that the first step must be the identification of those with underlying coronary artery disease. This is underscored by the disturbing fact that, in many, sudden death is the first sign of coronary disease. An aggressive evaluation of those with significant risk factors appears justified. The second part of the problem is the identification of those with coronary artery disease who are at especially high risk. The current diagnostic modalities available suffer from a relative lack of specificity to be applied indiscriminately in light of the expense and morbidity of effective therapies (that is, coronary artery bypass surgery, antiarrhythmic drugs, implantable defibrillators, surgical or catheter ablation). At the present time, we can identify certain subsets that warrant aggressive therapy: survivors of sudden death events or sustained ventricular tachycardia, obstructive cardiomyopathies, aortic stenosis, left main coronary artery disease, and congenital QT prolongation. Less aggressive but also less specific therapies, such as beta-blockers in myocardial infarction survivors, can be given more indiscriminately. Ultimately, of course, the greatest impact will come from prevention of coronary artery disease.

Arrhythmias, Cardiac

Studies of developing human hair shaft cells in vitro.

Methods for studying aspects of hair formation in vitro have been devised on the basis of isolating developing hair shaft cells. These cells were obtained using a sterile microdissection technique. Plucked anagen follicles were dissected free of surrounding tissues (inner and outer root sheaths), and presumptive hair shaft cells (including germinal epithelia) were cultured directly on mammalian fibroblasts or in media preconditioned by fibroblasts. Specimens were cultured either as dispersions or in whole tissue pieces. Trypsinized whole tissue specimens in culture were sometimes observed to form increased bulk, while dispersed cells appeared to elongate and form larger colonies. In sections of these colonies examined by transmission electron microscopy, intracellular hard keratin intermediate filaments (IFs) together with IF-matrix hard keratin complexes were observed. Radiolabelled cysteine [35S] was added to cultures (3-20 days), showing a continuing but reduced synthesis of hard keratin IF proteins (low-sulfur) over the period of study. Matrix protein (high-sulfur) production was drastically reduced after 3 days. Monoclonal antibodies directed against hair keratin IF components were used in Western transfers and immunofluorescent studies to help assess the specificity of proteins synthesized in culture. Our observations indicate that, with some refinement, the presently described methods enable preparation of hair shaft precursor cells suitable for observing certain hair-forming processes in vitro.

Cells, Cultured

Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart.

The relationships between contractile function, myocardial oxygen consumption, and tissue high energy phosphate and lactate content were investigated during partial coronary flow disruption. The experimental preparation was an isolated, isovolumic retrograde blood-perfused rabbit heart. Both developed pressure (r = 0.94) and dp/dt (r = 0.95) exhibited strong linear correlations with myocardial oxygen consumption that were stable for up to 45 min after blood flow reduction. In contrast, tissue high energy phosphate content exhibited nonlinear relationships with both developed pressure and oxygen consumption such that systolic mechanical function and oxidative metabolism declined to 20 and 30% of control values, respectively, before significant abnormalities in myocardial high energy phosphate stores were observed. Similarly, developed pressure and oxygen consumption decreased to 36 and 48% of control, respectively, before abnormal tissue lactate content was detected. The results of this study indicate that: (a) mechanical function is closely related to the rate of oxidative energy production during partial coronary flow disruption, and (b) despite the development of significant contractile dysfunction, tissue high energy phosphate content remains at normal levels except under the most severely flow-deprived conditions. The preservation of tissue energy stores can be explained by the apparent coupling of contractile performance to oxidative energy production, which could function to maintain myocardial energy balance during partial coronary flow restriction.

Adenine Nucleotides

Response to exercise after withdrawal from chronic alcoholism.

To test for early evidence of alcoholic cardiomyopathy and to assess changes in exercise response after abstinence, 12 asymptomatic alcoholic men (group 1) underwent maximal upright bicycle exercise radionuclide ventriculography two to six days after alcohol withdrawal. Six of these patients (group 1A) had similar testing two to four weeks later. Six control subjects (group 2) had repeated exercise tests without isotope study. Group 1 left ventricular ejection fraction response (LVEF) was normal. LVEF at similar workloads did not differ in group 1A (p = NS). However, unlike group 2 results, the linear regression line relating double product to exercise stage in group 1A was higher at first exercise (p less than 0.05), probably due to the effects of alcohol withdrawal. We conclude that radionuclide left ventriculographic findings in these patients do not support the concept of a preclinical alcoholic cardiomyopathy made apparent by exercise, and exercise very early after alcohol withdrawal is associated with an increased myocardial oxygen demand at any given workload.

Adult

Myocardial energy production and consumption remain balanced during positive inotropic stimulation when coronary flow is restricted to basal rates in rabbit heart.

The effect on myocardial energy balance of increasing oxygen demand without altering basal myocardial perfusion rate was assessed in isolated, isovolumic, retrograde blood perfused rabbit hearts. Myocardial energy requirements were increased with paired stimulation. The capacity of rapid paired stimulation to increase mechanical energy consumption was demonstrated in the presence of increased perfusion with the rate X pressure product and oxygen consumption increasing 86 and 148%, respectively, compared with control values. In contrast, rapid paired stimulation under constant, basal flow conditions did not alter the rate X pressure product, while oxygen extraction and consumption increased only 40% relative to control. Myocardial ATP, creatine-phosphate, and lactate content were identical under control and constant flow-paired stimulation conditions. The results of this study indicate that no detectable energy imbalance was produced by rapid paired stimulation with flow held constant at basal rates. These results suggest that the myocardium does not increase mechanical energy expenditure in response to inotropic or rate stimulation in the presence of restricted flow reserve and are inconsistent with the concept of "demand-induced" or "relative" myocardial ischemia.

Adenosine Triphosphate

Self-monitoring behavior in a case of severe auditory agnosia with aphasia.

This case report describes an unusual combination of speech and language deficits secondary to bilateral infarctions in a 62-year-old woman. The patient was administered an extensive series of speech, language, and audiologic tests and was found to exhibit a fluent aphasia in which reading and writing were extremely well preserved in comparison to auditory comprehension and oral expression, and a severe auditory agnosia. In spite of her auditory processing deficits, the patient exhibited unexpected self-monitoring ability and the capacity to form acoustic images on visual tasks. The manner in which she corrected and attempted to correct her phonemic errors, while ignoring semantic errors, suggests that different mechanisms may underlie the monitoring of these errors.

Agnosia