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Biomedical subjects

R G Smith

Publications and source records attributed to R G Smith.

At least 289 records · Page 16Linked to original sources

Radiologic appearance of the Jarvik artificial heart implant and its thoracic complications.

The principles of total artificial heart devices, their radiologic appearance, and the complications associated with their use have become increasingly relevant as these devices are used more often in patients with end-stage cardiac disease. The Jarvik artificial heart implant is the one used most frequently. Intrathoracic complications related to its use were evaluated radiographically in seven patients undergoing implantation at our institution. Because of the relatively large size of the device, complications from compression of the left lung are common. Four of the seven patients had prolonged atelectasis of the left lower lobe and two had major vascular compression (pulmonary veins in the left lung in one and the inferior vena cava in another). Other chest complications were infection in the surgical site (three patients), mediastinal bleeding (one patient), and extensive fibrous adhesions around the device, making explantation difficult (one patient). All seven patients had pulmonary edema before surgery, which regressed over several days after surgery. Radiographs readily display the major components of the Jarvik heart and are valuable for detecting pulmonary complications associated with its use.

Adult↗

Architecture of rod and cone circuits to the on-beta ganglion cell.

Photoreceptors connect to the on-beta ganglion cell through parallel circuits involving rod bipolar (RB) and cone bipolar (CB) neurons. We estimated for a small patch in the area centralis of one retina the 3-dimensional architecture of both circuits. This was accomplished by reconstructing neurons and synapses from electron micrographs of 189 serial sections. There were (per mm2) 27,000 cones, 450,000 rods, 6500 CBb1, 30,300 RB, 4100 All amacrines, and 2000 on-beta ganglion cells. The tangential spread of processes was determined for each cell type, and, with the densities, this allowed us to calculate the potential convergence and divergence of each array upon the next. The actual numbers of cells converging and diverging were estimated from serial sections, as were the approximate numbers of chemical synapses involved. The cone bipolar circuit showed narrow convergence and divergence: 16 cones----4 CBb1----1 on-beta 1 cone----1 CBb1----1.2 on-beta This circuit is thought to contribute significantly to the on-beta cell's photopic receptive field because the CBb1 has a center-surround receptive field whose center diameter is greater than the spacing between adjacent CBb1s. Consequently, the receptive fields of the CBb1s converging on a beta cell are probably largely concentric and thus mutually reinforcing in their contributions to the on-beta. The rod bipolar circuit showed a wider convergence and divergence: 1500 rods----100 RB----5 AII----4 CBb1----1 on-beta 1 rod----2 RB----5 AII----8 CBb1----2----2 on-beta The 1500 rods converging via this circuit account for the spatial extent of the beta cell's dark-adapted receptive field. This convergence also accounts for the ganglion cell's maintained discharge, which is thought to arise from about 6 quantal "dark events" per second. This many dark events would appear in the ganglion cell if each rod in the circuit contributed 0.004 dark events per second, and this is close to what has been measured in monkey rods (Baylor et al., 1984). Divergence in this circuit serves to expand the number of copies of the quantal signal (1 rod----8 CBb1) and so to engage large numbers of chemical synapses that provide amplification. Reconvergence at the last stage (8 CBb1----2 on-beta) may reduce (by signal averaging) the synaptic noise that would otherwise accumulate along the pathway.

Animals↗

Serum and urinary magnesium, calcium and copper levels in insulin-dependent diabetic women.

Eighteen insulin-dependent diabetic (IDD) and 15 healthy control women participated in a study of the relationship between glycemic control or renal function measurements and the levels of magnesium, calcium and copper in the serum and urine. In the IDD women glycosylated hemoglobin averaged 9.8 +/- 0.5% and the fasting plasma glucose was 1.89 +/- 0.19 g/L. The glomerular filtration rate, approximated from creatinine clearance, averaged 125 +/- 16 ml/min in the IDD women in comparison to 82 +/- 4 ml/min in the controls. IDD women had lower serum (p less than 0.001) and higher urinary (p less than 0.01) magnesium levels than did the controls; serum and urinary copper levels and serum ceruloplasmin levels all were higher (p less than 0.01) in the IDD women. There was no difference in either serum or urinary calcium levels between the two groups. In the IDD women serum magnesium was related to urinary glucose (r = -0.758, p less than 0.01) and to glycosylated hemoglobin (r = -0.603, p less than 0.01); none of the other measurements of serum or urinary minerals was related to measures of glucose control. Urinary calcium and copper levels, but not urinary magnesium, were correlated with the glomerular filtration rate (r = 0.476, p less than 0.05 and r = 0.554, p less than 0.05, respectively). The results of this study suggest that IDD alters the utilization of magnesium, calcium, and copper, but that these three minerals are not affected in the same way by physiological changes associated with the disease.

Adolescent↗

Partial characterization of a unique growth factor secreted by human Sertoli cells.

Human Sertoli cells were grown in a serum-free environment, and the Sertoli cell conditioned medium (hSCCM) was tested for mitogenic activity. The presence of a potent growth factor(s), termed Sertoli cell secreted growth factor (SCSGF), in hSCCM was confirmed and supports previous observations based on experiments using rat SCCM. Mitogenicity of hSCSGF was demonstrated in cell proliferation assays with the A431 (human epidermoid carcinoma) cell line and in [methyl-3H]-thymidine incorporation (DNA synthesis) assays with the Swiss 3T3 (mouse embryo fibroblast) cell line. In a dose-dependent manner, hSCSGF stimulated A431 cell growth up to 4-fold over control values (P less than 0.0001) and stimulated thymidine incorporation up to 4.5-fold over control values (P less than 0.0002). Importantly, SCSGF stimulated A431 proliferation 2-fold over control values (P less than 0.0002) in the presence of 5% serum. With the exception of rat SCSGF, human SCSGF is the only growth factor known to stimulate A431 cells. SCSGF also demonstrated epidermal growth factor (EGF)-like activity based upon displacement of EGF from its receptor in a radioreceptor assay. However, SCSGF is not EGF since it is a potent stimulator of A431 cells, whereas EGF is inhibitory. The growth factor was stable to heat, freeze-thaw, acid (pH 3), and trypsin treatment. Furthermore, it did not bind heparin agarose and is thus distinct from the endothelial cell growth factor family. High-pressure liquid chromatography on size exclusion (TSK G2000 SW) columns revealed an approximate size of 8000 daltons. Human SCSGF is a unique growth factor and may play a key role in the regulation of normal spermatogenesis.

Blood↗

Long distance transport of cardiac patients in extremis: the mobile intensive care (MOBI) concept.

Critically ill cardiac patients may require transport to distant centers. Their clinical demands often exceed the capabilities of land or air ambulance services. To provide this service, a new, safe, and cost-effective concept for transport of the critically ill was developed. A mobile intensive care unit system (MOBI) was developed with support capabilities of an intra-aortic balloon pump, defibrillator, ventilator, pulse oximeter, multiple infusion pumps, and pressure and EKG monitoring. Eleven patients in cardiogenic shock, all with multidrip inotropic therapy, eight requiring intra-aortic balloon pump, three of whom were on the ventilator, were transported. Six patients were transported in aircraft, with the longest transport over 2,000 mi. Five patients were transported by ground ambulance. All patients survived the transport: no complications were attributed to the transport process. The system is cost effective since slight modification is required in regular ambulance or chartered aircraft to provide the highest level of care.

Aircraft↗

Rod bipolar array in the cat retina: pattern of input from rods and GABA-accumulating amacrine cells.

The potential and actual connections between rod and rod bipolar arrays in the area centralis of the cat retina were studied by electron microscopy of serial ultrathin sections. In the region studied there were about 378,000 rods/mm2 and 36,000-47,000 rod bipolars/mm2. The tangential spread of rod bipolar dendrites was 11.2 microns in diameter, and the "coverage factor" for the rod bipolar cell was 3.5-4.6. We estimate that about 37 rods potentially converge on a rod bipolar cell and that one rod potentially diverges to about four rod bipolar cells. The actual connections, however, are less than this by about half: 16-20 rods actually converge on a bipolar cell and one rod actually diverges to slightly less than two rod bipolar cells. The degree of convergence appears to reflect a compromise between the need to signal graded stimulus intensities (requiring wide convergence) and the need to maintain a good signal/noise ratio (requiring narrow convergence). Amacrine varicosities that provide reciprocal contact at the rod bipolar dyad were studied in serial electron microscopic autoradiograms following intraocular administration of 3H-GABA or 3H-glycine. More that 90% of the reciprocal amacrine processes accumulated GABA in a specific fashion. This information, in conjunction with Nelson's recordings from the rod bipolar and amacrine cells postsynaptic at the dyad (Nelson et al: Invest. Ophthalmol. 15:946-953, '76; Kolb and Nelson: Vision Res. 23:301-312, '83), suggests that feedback at the rod bipolar output might be positive.

Animals↗

Glucocorticoid effects on growth, and androgen receptor concentrations in DDT1MF-2 cell lines.

The DDT1MF-2 smooth muscle tumor cell line contains receptors for and is differentially sensitive to androgens and glucocorticoids. Androgens stimulate and glucocorticoids inhibit growth. We now confirm that the latter involves the induction of a block in the G1 phase of the cell cycle. We have developed and characterized in vitro and in vivo a glucocorticoid resistant variant of this cell line, the DDT1MF-2-GR. Glucocorticoids specifically inhibit androgen induced androgen receptor augmentation in DDT1MF-2 cells, but not in the GR variant suggesting that growth inhibition is related to inhibition of androgen receptor augmentation. However, under optimal conditions for cell proliferation, when glucocorticoid inhibited growth is relieved by the exogenous addition of platelet derived growth factor, androgen receptor augmentation is still suppressed. Thus, androgen induced elevation in androgen receptor concentrations is not a prerequisite for cell proliferation. These results imply that in androgen responsive cells, although androgen stimulation of growth can be blocked by antagonism of androgen receptor mediated events, the antagonism can be bypassed by supplying the cells with exogenous growth factors. These results provoke speculation on how cells, which are dependent upon androgens for growth, become autonomous.

Animals↗

Terminal deoxynucleotidyl transferase (TdT)-containing peripheral blood mononuclear cells during remission of acute lymphoblastic leukemia: low sensitivity and specificity prevent accurate prediction of relapse.

Serial samples of peripheral blood were obtained from 75 children with acute lymphoblastic leukemia in remission. An immunofluorescence assay was used to quantitate TdT-containing (terminal deoxynucleotidyl transferase-containing) cells in the mononuclear leukocyte fraction of these specimens. Nine relapses in 8 patients were preceded by elevations (0.12-0.70%) in peripheral blood terminal deoxynucleotidyl transferase-containing cells noted 1-33 weeks prior to relapse. No such elevations were observed prior to 6 relapses in 4 patients. Peripheral blood terminal transferase deoxynucleotidyl-containing cells were elevated (0.12-0.61%) in 22 children who did not relapse over a 5-82 week period of observation. The sensitivity (67%) and specificity (68%) of this assay are inadequate to establish which patients have minimal residual leukemia.

Child↗

Montage: a system for three-dimensional reconstruction by personal computer.

This paper describes a simplified system for serial section three-dimensional (3-D) reconstruction. A set of 9 software programs runs on a standard personal computer and produces camera-ready illustrations suitable for publication. The user enters trace points on a digitizing tablet from sections that have been already aligned. A 3-D view of the reconstructed object is generated which can be displayed with hidden lines removed. Analysis of volume, surface area and autoradiographic grain density are performed automatically. A relational database query language allows display and analysis of a selected subset of the data. The system runs under the UNIX operating system which allows the programs to be easily transported to new hardware or modified for other purposes.

Animals↗

Monoclonal antibodies that recognize a broad range of mammalian terminal deoxynucleotidyl transferases.

Terminal deoxynucleotidyl transferase (TdT) is a useful marker for lymphocyte precursors in the bone marrow and thymus and for lymphoblastic leukemia and lymphoma cells. To simplify and enhance the detection and phenotypic analysis of these cells, we sought to develop monoclonal antibodies to this enzyme. In order to obtain antibodies that bind a variety of mammalian TdTs, mice were immunized with bovine TdT and the hybridoma secretions were screened by immunofluorescence assays on cultured TdT-positive and negative human lymphoblasts. Four monoclonal antibodies which bound specifically to TdT-positive lymphoblasts were characterized in detail. All four antibodies immunoprecipitated the native 60 kd TdT molecule from extracts of TdT-positive human lymphoblasts and bound specifically in immunoblot assays to the 43.8 and 11 kd proteolytic fragments of bovine thymus TdT. To assess whether the antibodies bound to related or distinct epitopes on bovine TdT, we measured the displacement of radiolabeled antibody from the immobilized enzyme by an excess of unlabeled heterologous antibody. These studies revealed that three of the antibodies competed for the same determinant on bovine TdT, while one antibody reacted with a distinct epitope. Antibody binding to either epitope, however, partially inhibited the enzymatic activity of bovine TdT. Specificity for TdT was tested by immunofluorescence and competition radioimmunoassays. In these assays, the antibodies did not stain a variety of known TdT-negative human hematopoietic cells and cell lines. both normal and neoplastic, nor were the antibodies displaced from purified bovine TdT by extracts of these TdT-negative cells. These results confirmed the cross-reactivity of the antibodies with human and bovine TdT. To assess cross-reactivity with TdT from other species, extracts of rabbit, mouse, and rat thymus were prepared and shown to specifically displace the antibodies from bovine TdT. Thus, these antibodies bound to TdT derived from at least five mammalian species. To determine whether these antibodies could be used to detect small subpopulations of TdT-positive cells, mixtures of TdT-positive and negative cells were prepared and stained with fluorescein conjugates of the antibodies. When assayed by flow cytometry, a population of 1% TdT-positive cells was easily detectable. We conclude that these monoclonal antibodies should be useful for the enumeration and analysis of TdT-positive cells in normal and neoplastic hematopoietic tissues from several mammalian sources, including man.

Animals↗

Medical assessment of elderly persons prior to a move to residential care: a review of seven years' experience in Edinburgh.

Assessment prior to a move to residential care has been carried out by the Departments of Geriatric Medicine in the Lothian Region for many years. Results have been reviewed over 7 years in one Department; 688 people were assessed; 7% were placed in alternative accommodation as a result of the assessment and a further 15% were offered specialist advice. The workload was 50 assessments per 10,000 population over 65 years per year. Of these, 58% were already known to the geriatrician and 23% were seen as part of the normal work of the department. It was concluded that the benefits of assessment make the extra work involved well worth while.

Aged↗

Prescribing patterns observed in registered nursing homes and long-stay geriatric wards.

Details of medication prescribed to 400 elderly patients in 18 registered nursing homes and 233 patients in 11 long-stay geriatric wards were obtained. Excluding laxatives, there was a mean of 2.15 medications prescribed for the long-stay patients, compared to 2.62 items for the nursing-home population. There was apparent over-prescribing of certain drugs within the nursing-home population.

Aged↗