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Biomedical subjects

D Welsh

Publications and source records attributed to D Welsh.

13 recordsLinked to original sources

A stereotactic technique for volumetric interstitial implantation in the brain.

Stereotaxis, a method of localizing a specific point using three dimensional coordinates, has greatly improved since the advent of computed tomography (CT). A simple, noninvasive stereotactic system which enables rapid, parallel placement of multiple interstitial catheters for treatment of malignant brain tumors has been developed. Departing from traditional stereotactic methods, the implantation procedure is performed in one stage--entirely in the CT suite. Perioperative nursing responsibilities include mastering the technical aspect of a high precision system as well as meeting the special needs of the patient undergoing this procedure. Initially developed for use in volumetric interstitial brachytherapy, the procedure is now being used in Phase II clinical trials of volumetric interstitial hyperthermia in the management of patients with intracranial malignancies.

Brachytherapy

Effect of running wheel availability on circadian patterns of sleep and wakefulness in mice.

Sleep/wake expression in mice varies predictably with circadian phase. Such circadian rhythms are known to depend on intact suprachiasmatic nuclei (SCN) in the hypothalamus, but the mechanism by which SCN activity modulates sleep/wake expression is unknown. This paper examines the possibility that circadian patterns of sleep/wake derive partly from circadian timing of waking behaviors that are incompatible with sleep, such as locomotor activity. Voluntary locomotor activity was restricted in five mice adapted to a running wheel by locking the wheel in place. Continuous electrographic monitoring of sleep and wakefulness over multiple circadian cycles revealed: (1) during the active phase, shorter wake bouts and more frequent bouts of sleep, resulting in greater sleep/wake fragmentation and more time spent asleep; (2) during the rest phase, a small compensatory reduction in NREM sleep; (3) reduced amplitude of circadian sleep/wake rhythms and a greater amount of sleep overall. Thus, voluntary locomotor activity has an important influence on sleep/wake expression in mice, and the normal circadian pattern of sleep/wake depends on circadian timing of activity. Previous reports of damped circadian sleep/wake rhythms in rodents may therefore be explained by coincident diminutions in locomotor activity associated with age or health status. Our results also support analogous findings in human subjects, and we propose that elderly humans may benefit from therapies that augment daytime activity.

Animals

CheA protein, a central regulator of bacterial chemotaxis, belongs to a family of proteins that control gene expression in response to changing environmental conditions.

During bacterial chemotaxis, the binding of stimulatory ligands to chemoreceptors at the cell periphery leads to a response at the flagellar motor. Three proteins appear to be required for receptor-mediated control of swimming behavior, the products of the cheA, cheW, and cheY genes. Here we present the complete nucleotide sequence of the Salmonella typhimurium cheA gene together with the purification and characterization of its protein product. The protein is a 73,000 Mr cytoplasmic constituent. Amino acid-sequence comparisons indicate that it belongs to a family of bacterial regulatory proteins including the products of the cpxA, dctB, envZ, ntrB, phoR, phoM, and virA genes. Each member of this family has a conserved domain of approximately equal to 200 residues within its C terminus. We have previously shown that another chemotaxis protein, CheY, represents a domain of protein structure that has been conserved within a second large family of bacterial regulatory proteins. Each protein of the CheA family seems to function as a regulator of a different CheY homologue. Although each pair of proteins appears to produce a specialized response to a distinct type of stimulus, the relationships in primary structure suggest that a similar molecular mechanism may be involved.

Amino Acid Sequence

The use of measured genotype information in the analysis of quantitative phenotypes in man. II. The role of the apolipoprotein E polymorphism in determining levels, variability, and covariability of cholesterol, betalipoprotein, and triglycerides in a sample of unrelated individuals.

Recent advances in molecular biology provide measures of genotypes at loci involved in lipid metabolism. Genotypes for apolipoprotein E (apo E) and quantitative levels of total plasma cholesterol, betalipoprotein, and triglycerides were measured in a sample of 223 unrelated individuals from Nancy, France. The frequencies of the epsilon 2, epsilon 3, and epsilon 4 alleles are 0.13, 0.74, and 0.13, respectively, in this sample. Significant differences among apo E genotypes were detected for these lipoprotein phenotypes. The average effect of the epsilon 2 allele was to reduce total plasma cholesterol and betalipoprotein levels by 0.52 mmol/L and 0.98, respectively, while the epsilon 4 allele raised these levels by 0.26 mmol/L and 0.61, respectively. Apo E genotype specific correlations suggest that this locus also has an effect on the coordinated metabolism between cholesterol and triglycerides. We infer that approximately 17% of the genetic variability in total plasma cholesterol may be attributable to this apo E polymorphism. No other single locus has been identified with such a large contribution to cardiovascular disease risk factors in the general population.

Alleles

Palliative topical and systemic misonidazole with low-dose irradiation for recurrent carcinoma of the cervix uteri.

This report concerns a determinate series of 11 patients with progressive recurrent cancer of the cervix uteri, who were treated with misonidazole (1 g) applied locally for 24 hours and an oral dose of 2.9 g/m2 four hours before a single mid-plane dose of 5.00 Gy. Four of 11 (36%) remained free of disease at one year. It is suggested that this is largely a hypoxic cell cytotoxic effect and is a useful method of palliation.

Carcinoma, Squamous Cell

Reaction times to weak test lights.

Maloney and Wandell [Vision Res. 24, 633-640 (1984)] describe a model of the response of a single visual channel to weak test lights. The initial channel response is a linearly filtered version of the stimulus. The filter output is randomly sampled over time. Each time a sample occurs there is some probability--increasing with the magnitude of the sampled response--that a discrete detection event is generated. Maloney and Wandell derive the statistics of the detection events. In this paper we test the hypothesis that the reaction time responses to the presence of a weak test light are initiated at the first detection event. This permits us to extend the application of the model to lights that are slightly above threshold, but still within the linear operating range of the visual system. We test a parameter-free prediction of the model proposed by maloney and Wandell for lights detected by this statistic. The data are in agreement with the prediction.

Humans

Adaptation in the long-wavelength pathways.

We describe and test predictions of a model of long-wavelength test sensitivity upon large, uniform backgrounds. The model explains changes in sensitivity in the red-green detection pathways strictly based upon losses of sensitivity in the receptors. We derive the prediction that field mixture data for field-mixtures of mu1 (fixed) and an addend, mu 2, must follow the same shape on different intensities of the fixed background, mu 1. This prediction is not in good agreement with the measurements.

Adaptation, Ocular

Stage I cervical carcinoma: local experience in Port Elizabeth with 5-year follow-up.

Seventeen patients who presented with stage i squamous carcinoma of the cervix between 1969 and 1974 are reviewed. Thirteen of the patients were treated by means of radical irradiation, 3 by Wertheim's hysterectomy and 1 by a simple hysterectomy and postoperative pelvic irradiation. Two patients died 2 years after presentation, 1 from metastases and 1 from unrelated causes. The remaining 15 patients were well with no evidence of malignancy 5 years after presentation.

Adult

Transcription of killer virion double-stranded RNA in vitro.

Intracellular virions of stationary phase ethanol-grown cells of a killer strain of Saccharomyces cerevisiae contain encapsulated M (1.1 x 10(6) dalton) and L (3.2 x 10(6) dalton) double-stranded RNA plasmids. These virions also contain RNA polymerase activity which catalyzes the synthesis of full-length, single-stranded, asymmetric transcripts (denoted m and l) of the virion double-stranded RNAs. Product m is made by M-containing particles and shows complete sequence homology to M but not to L. Product l is made by L-containing particles and shows complete homology only to L. The products show no self-homology, indicating asymmetric transcription. Therefore, the polymerase appears to function in vitro as a double-stranded RNA transcriptase. The lack of sequence homology between M and L is confirmed.

Base Sequence

The diagnosis and treatment of intramuscular hemangiomas of the masseter muscle.

Two cases of hemangioma of the masseter muscle are presented with a review of the literature. The possibility of an intramuscular hemangioma should be considered in any lateral facial swelling, particularly one anterior to the parotid. Total excision of the hemangioma with a margin of normal muscle is recommended. The approach utilized by the authors is a preauricular incision with elevation of a flap lateral to the parotid gland. This provides an excellent exposure for removal of the tumor with minimal risk to the facial nerve and minimal cosmetic deformity.

Blood Vessels