PubMed HealthSearch

Biomedical subjects

C Spencer

Publications and source records attributed to C Spencer.

At least 19 recordsLinked to original sources

Complementary DNA synthesis in situ: methods and applications.

In situ transcription is the synthesis of cDNA within cells. This chapter has illustrated some of the application of IST to the study of gene expression in complex cell environments. While the importance of transcription in modulating cellular activity has been long appreciated, the role of translational control mechanisms in regulating central nervous system functioning is just beginning to be recognized. Previous limitations in the availability of tissue have made it difficult to construct cDNA libraries from defined cell populations, to examine translational control, and to quantitate differences in the amount of mRNA for many distinct mRNAs in the same sample. In situ transcription facilitates all of these procedures, making it possible to characterize aspects of gene regulation that were previously difficult. Indeed, taken to its furthest extreme it is now possible to characterize gene expression in single live cells. This level of analysis allows basic questions, such as How different morphologically identical cells are at the level of gene expression, and How synaptic connectivity and glial interactions influence gene expression in single cells, to be experimentally approached. The ability to characterize gene expression in small amounts of tissue and single cells is critical to gaining an understanding of the contribution of specific cell types to the physiology of the central nervous system.

Animals

Sequences in the human c-myc P2 promoter affect the elongation and premature termination of transcripts initiated from the upstream P1 promoter.

A conditional block to transcription elongation provides one mechanism for controlling the steady-state levels of c-myc RNA in mammalian cells. Although prematurely terminated c-myc RNAs are not detectable in mammalian cells, truncated c-myc RNAs with 3' ends that map near the end of the first exon are transcribed from human c-myc templates injected into Xenopus oocytes germinal vesicles. A series of linker scanner and deletion mutants within the c-myc P2 promoter was tested in the Xenopus oocyte injection assay to determine the potential contribution of promoter elements to the elongation or premature termination of c-myc transcription. Although this analysis failed to identify sequences in the P2 promoter that significantly affect the elongation or termination of P2-initiated transcripts, our results suggest that sequences within the P2 promoter contribute to the premature termination of transcripts initiated at the upstream P1 promoter. A subset of these sequences is essential for the efficient elongation of P1-initiated transcripts through intrinsic sites of termination at the end of exon 1. These sequences affect P1 elongation when they are downstream of the site of initiation, and we hypothesize that they may be analogous to a class of prokaryotic elements required for antitermination.

Animals

The T cell receptor in autoimmune diseases.

Autoimmunity is likely the cause of a variety of diseases including systemic lupus erythematosus, rheumatoid arthritis and diabetes. Normally, the body's immune system serves as a defense against a variety of conditions, including, injury, infection and neoplasm. However, for reasons that are currently unclear, the normal regulation of the immune system can breakdown resulting in autoaggressive responses. T cells, especially CD4+ cells, appear to play a predominant role in most autoimmune diseases. We summarize our workshop which focussed on the role of the T cells in autoimmune diseases. We summarize our workshop which focussed on the role of the T cells in autoimmune diseases; the T cell receptor in autoantigen recognition (emphasizing the role of selective T cell receptor V regions in the autoimmune response); and a discussion of possible therapeutic interventions.

Animals

How do uncompensated care pools affect the level and type of care? Results from New York State.

Uncompensated care pools have been used by several states in their attempt to aid hospitals and increase the volume of care provided to patients without health insurance. We examined the uncompensated care pool used in New York State between 1983 and 1987. Our primary interest was to estimate the impact of the pools on the level and type of care provided to uninsured patients. Our results indicate that hospitals responded to the pools by increasing the volume of care provided to uninsured patients. Without the pools, over 30,000 fewer adjusted hospital admissions would have been provided to the uninsured in a typical year. Many of these newly purchased admissions were for "nondiscretionary" medical care, suggesting that beneficial care to the indigent was rationed prior to the introduction of the uncompensated care pools.

Charities

Stargazer: a new neurological mutant on chromosome 15 in the mouse with prolonged cortical seizures.

We report here the initial description of the inheritance pattern, linkage mapping, and electroclinical phenotype of a recessive mutation on mouse Chromosome 15, stargazer (stg), that produces epilepsy. The salient epileptic phenotype is a syndrome of spontaneous, prolonged, generalized spike-wave cortical discharges with behavioral arrest. A second, complex, seizure pattern featuring movements during the discharge can also appear. The stg/stg mutant phenotype confirms the general principal that inherited epilepsies sharing similar cortical excitability patterns can be transmitted by single gene loci residing on different chromosomes and provides new evidence that the severity of seizure expression depends on the specific mutant gene affected.

Animals

The development of 3- to 6-year-olds' map using ability: the relative importance of landmarks and map alignment.

Previous research (e.g., Bluestein & Acredolo, 1979) has demonstrated that children as young as 3 or 4 years of age can use simple maps, if the maps are aligned, and has suggested that when such young children use a map, they rely on the information provided about landmarks. The support for this suggestion, however, comes from research with older children. Our experiment was designed to find out how 3- to 6-year-olds used a map and whether they could use maps that were not aligned. The children were asked to find a hidden toy in a mapped layout that showed the toy's position and included a single landmark. The maps were either aligned or rotated 90 degrees, 180 degrees, or 270 degrees relative to the layout. The results showed that young children could use the maps, even when they were not aligned with the layout, and that they relied on landmark information to do so.

Aptitude

Immunomagnetic microsphere mediated purging of cALLa positive leukemic cells from bone marrow for autologous reinfusion.

Bone marrow from sixteen patients with cALLa positive ALL have been treated with a monoclonal antibody (MoAb) cocktail which includes DuALL-1 (CD9), WCMH15.14 (CD10) and HD-37 (CD19). Following antibody treatment, marrows were incubated (30 minutes) with anti-murine-IgG1 (Fc) coated magnetic microbeads and passed through a graded magnetic field chamber. Two problems have had to be addressed: (1) More marrow cells must be processed than in marrows from patients with neuroblastoma, for which the separation chamber was originally developed, requiring the use of more beads, causing occlusion of the chamber's collection surface. This has been corrected by using a large surface area pre-magnet for the elimination of excess microbeads prior to processing in the main chamber; (2) Up-modulation (up to 40% positive cells) of the CD9 associated antigen has been detected. To avoid difficulty, marrows are being routinely screened prior to harvest for purging, and purging is delayed for patients with elevated CD9 levels. Eight patients have been reinfused, with no morbidity or mortality associated with the purging or other ex vivo handling of the marrow.

Antibodies, Monoclonal

Transporting bone marrow for in vitro purging before autologous reinfusion.

We describe the procedures employed for transporting bone marrow to and from a central facility. Marrow has been harvested from 80 patients with neuroblastoma, at 16 centers which are geographically dispersed throughout North America. Marrow from the outside transplant centers was packed on wet ice or cold packs in insulated containers, and transported by commercial carriers or chartered aircraft to the central processing laboratory. Post processed marrows were frozen in liquid nitrogen and returned by commercial carrier to the referring institution. In comparing transported with non-transported but similarly treated marrows, no differences were found in any of the following parameters: (1) CFU-GM recovery, (2) fraction viable cells at thawing, or (3) time to engraftment in patients. We conclude the transportation of harvested marrows to a central purging facility is safe. Based on this experience, we propose a set of standards, which, if adhered to, will insure the continued safe processing, shipping, and storage of bone marrow in all centers so engaged.

Bone Marrow Transplantation

Immobilization of polar bears (Ursus maritimus) with Telazol in the Canadian Arctic.

In 1986, 213 polar bears (Ursus maritimus) were immobilized with Telazol on the sea ice of the eastern Beaufort Sea during April and May, and 106 along the western coast of Hudson Bay near Churchill, Manitoba (Canada) in September. No animals died from handling. The efficacy of this drug at different seasons and the physiological responses of the immobilized bears were compared. A single injection of 8 to 9 mg of Telazol per kg of body weight gave a rapid full immobilization with satisfactory analgesia, and faster recovery than other drugs for which there is no antagonist. The reactions of the bears could be reliably and easily interpreted from a safe distance before the animal was approached. There was a wide range of tolerance to high dosages and bears appeared able to thermoregulate while immobilized. The mortality rate due to handling was lower than with any other drug used to date.

Anesthetics

Measurement and analysis of intraservice work.

The work that physicians perform represents a major resource input to medical services and procedures. In this article we describe the concepts of work and its dimensions, as well as the methods developed to measure them. We also describe the design and results of a national probability survey of physicians in 18 specialties. We present the results--estimated values of work and its dimensions--for selected services. Our findings indicate that physicians can give reliable and valid ratings of work and that we can model this work as a function of four dimensions: time, mental effort and judgment, technical skill and physical effort, and stress. Analyzing the complex functional relationship between work and these four dimensions shows that all four dimensions are important and statistically significant in predicting work. Time is a more important dimension in predicting work for medical specialties than for surgical specialties, with the estimated regression coefficients between .3 and .5 and .2 and .3, respectively. In contrast, technical skill is a more important dimension in predicting work in surgical specialties than for medical specialties, with the estimated regression coefficients between .3 and .5 and .2 and .3, respectively. Finally, we found that an exponential equation of the four dimensions precisely describes total work.

Clinical Competence

The relation of thyroid indices in the critically ill patient to prognosis and nutritional factors.

Thyroid indices and nutritional assessment values were measured in 73 critically ill euthyroid patients within 48 hours of admission to the medical or surgical intensive care unit. Significantly increased rates of mortality were observed among patients with decreased T3 or T4 levels or elevated T3UR or rT3 values. Alterations in thyroid function tests were associated with changes in certain putative nutritional indices, including serum albumin and transferrin concentrations, triceps skin fold and skin test reactivity. The data indicated that thyroid parameters measured early in the critical phase of illness are predictive of subsequent outcome. The pathogenesis of altered thyroid hormone metabolism is unknown, but nutritional deprivation may be an important contributing factor.

Adolescent

Time course and frequency dependence of synaptic vesicle depletion and recovery in electrically stimulated sympathetic ganglia.

The mammalian superior cervical sympathetic ganglion has been extensively used to study the kinetics of ACh metabolism and release. The present investigation examined the time course of changes in the number of synaptic vesicles and abundance of plasma membrane at preganglionic nerve terminals using stimulation protocols similar to those used in previous biochemical and electrophysiological studies. Continuous stimulation of the preganglionic trunk to the cat superior cervical ganglion in vivo produced an initially rapid fall in the number of clear synaptic vesicles followed by a subsequent plateau. Reciprocal changes in plasma membrane occurred with a similar time course. The plateau phase is interpreted as a steady-state where vesicle exocytosis is balanced by the rate of vesicle reformation from plasma membrane. During quiescent recovery, restoration of normal resting ultrastructure is initially rapid but slows with time as vesicle number and plasma membrane abundance approach pre-stimulation values, indicating that the rate of vesicle reformation at the end of stimulation is high and proportional to the number of vesicles incorporated into the plasma membrane. These results are interpreted as consistent with the 'vesicle hypothesis' of neurotransmitter release.

Acetylcholine

Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients.

Thyrotropin (TSH) concentrations were measured in 1580 hospitalized patients and 109 normal persons. Using the mean +/- 3 SD limits of the log values for the controls (0.35-6.7 milli-int. units/L), the proportion of abnormal TSH results in the hospitalized patients was 17.2%. TSH was undetectable (less than 0.1 milli-int. unit/L) in 3.1% of patients, suggesting hyperthyroidism, and high (greater than 20 milli-int. units/L) in 1.6%, suggesting hypothyroidism. On follow-up of 329 patients, 62% with abnormal TSH (less than 0.35 or greater than 6.7 milli-int. units/L) and 38% with normal TSH concentrations, only 24% of those with undetectable TSH had thyroid disease: 36% of them were being treated with glucocorticoids and 40% had nonthyroidal illness (NTI). Although half the patients with TSH greater than 20 milli-int. units/L had thyroid disease, 45% of patients had high TSH values associated with NTI. TSH concentrations usually returned towards normal when patients' therapy with glucocorticoids was discontinued or they recovered from NTI. TSH test sensitivity appeared good when the mean +/- 3 SD limits of the reference population were used, i.e., no cases of hyper- or hypothyroidism, as identified by free thyroxin index (FT4I), were missed. However, TSH test specificity was inferior to that of the FT4I test (90.7% vs 92.3%), although specificity could be improved to 97.0% if the wider TSH reference limits of 0.1 to 20 milli-int. units/L were used--limits considered pathological if applied to outpatients. Evidently, different reference intervals for TSH are needed for hospitalized and nonhospitalized patients. We conclude that a "sensitive TSH assay" is not a cost-effective thyroid screening test for hospitalized patients as compared with the FT4I.

Adult

Treatment of degenerative spondylolisthesis.

The purpose of this article is to evaluate three surgical approaches to the treatment of degenerative spondylolisthesis. A review of 107 surgically treated cases were used to select a group of patients who met the following criteria: No previous spine surgery, no involvement in litigation, and no significant lesions at other levels of the spine. Adequate follow-up. The selected group of 47 surgically treated cases of degenerative spondylolisthesis had follow-up of 2-7 years. Three surgical approaches to the treatment of degenerative spondylolisthesis were analyzed. A relatively small patient group with a wide posterior decompression, at the level of the slip, sacrificing the articular processes had good to excellent results in only 33% of the cases. A second group with a midline posterior decompression with preservation of the articular processes had 80% good to excellent results after 2 years. The third group with a midline decompression and preservation of the articular processes had an added intertransverse process fusion between the olisthetic levels. This group had 90% good to excellent results. The conclusion is that a posterior decompression with preservation of the articular processes plus a transverse process fusion at the involved level is the preferred method of treatment for degenerative spondylolisthesis without regard to age.

Aged