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Biomedical subjects

C A Miller

Publications and source records attributed to C A Miller.

At least 163 records · Page 9Linked to original sources

Productivity and selected indicators of care in maternity and infant care and children and youth projects according to sponsorship.

Bureau Common Reporting Requirements (BCRR) data tapes for Fiscal Year 1980 were analyzed to determine whether the type of sponsoring agency influenced the productivity or indicators of care of Maternity and Infant Care and Children and Youth Projects. Sponsors were classified as either health department or non-health department, health department or major medical center, or public or private in three separate sets of analyses. Some of these analyses indicated that special projects that were either health department or public agency sponsored were more likely to have more non-medical patient encounters and more health education and social work staff for a given level of expenditures. Although publicly sponsored projects employed fewer physician equivalents than did the non-public projects, those physicians were more productive. Despite these differences in encounters, staffing, and utilization of physicians, there were no differences in available measures of the process of care between categories of projects in any of the analyses.

Child↗

Detection of bacteria by hybridization of rRNA with DNA-latex and immunodetection of hybrids.

A novel nucleic acid hybridization assay with a DNA probe immobilized on 1.25-micron-diameter latex particles was developed. Hybridization of the immobilized probe DNA with sample rRNA was complete in 10 to 15 min. Alkaline phosphatase-labeled anti-DNA-RNA was allowed to bind to the DNA-RNA hybrids on the latex particles. Then the latex was collected on a small glass fiber filter pad, and bound alkaline phosphatase was quantitated by reflectance rate measurement. The method detected a broad range of bacterial species and had a detection limit of 500 cells per assay. The assay was used to screen urine samples for bacteriuria and had a sensitivity of 96.2% compared with conventional culture at a decision level of greater than or equal to 10(4) CFU/ml. The hybridization method could have broad application to the detection of bacteria and viruses.

Bacteria↗

The immature and the mature myocardium. Responses to multidose crystalloid cardioplegia.

This study was designed to determine whether multidose St. Thomas' Hospital cardioplegic solution is as effective for preservation of the immature myocardium during ischemia as it is for the mature myocardium. An isolated working heart model was used. Sets of six hearts from immature (3 to 4 weeks, 500 gm) and mature (24 weeks, 2 kg) rabbits were subjected to 60, 90, or 120 minutes of ischemia. Myocardial protection consisted of infusion of cardioplegic solution every 30 minutes at 4 degrees C in a dose of 10 ml/kg of animal weight and maintenance of hypothermia at 10 degrees C by immersion in a cold saline bath. The percent recovery of preischemic aortic flow was lower in the immature than the mature hearts after 90 minutes (60.3% +/- 7.4% versus 101.8% +/- 4.3%) and after 120 minutes (57.4% +/- 10.6% versus 91.1% +/- 13.6%) of ischemia (results expressed as mean value +/- standard error of the mean, p less than 0.05). There were no differences between the mature and the immature hearts in the recovery of heart rate, left atrial pressure, mean aortic pressure, or glycogen stores. Adenosine triphosphate levels measured at the end of the experiment were not different from control in the immature hearts subjected to 60 or 90 minutes of ischemia, but did decline after 120 minutes of ischemia (18.5 +/- 0.8, 16.9 +/- 1.3, 16.6 +/- 0.6 versus 12.3 +/- 1.8 mumol/gm dry weight, p less than 0.05). Adenosine triphosphate levels in the mature hearts were lower than control in hearts subjected to 60, 90, and 120 minutes of ischemia (18.0 +/- 1.2 versus 13.6 +/- 1.1, 12.8 +/- 0.9, 13.7 +/- 1.5 mumol/gm dry weight, p less than 0.05). Multidose St. Thomas' Hospital cardioplegia does not provide adequate preservation of hemodynamic function in the immature rabbit heart, even though myocardial high-energy stores are well preserved. Additional work is necessary to clarify the mechanism of this finding and to develop appropriate methods for protection of the immature myocardium.

Adenosine Triphosphate↗

Identification of an arginine vasopressin-like diuretic hormone from Locusta migratoria.

We have identified two neuropeptides (F1 and F2) from suboesophageal and thoracic ganglia of Locusta migratoria, which we isolated earlier based on their immunological similarity to arginine vasopressin. The more abundant and hydrophilic factor, F1, has sequence Cys-Leu-Ile-Thr-Asn-Cys-Pro-Arg-Gly-NH2, but its biological role is unknown. The less abundant factor, F2, is an antiparallel dimer of F1, and functions as a diuretic hormone of this species. It appears to act through the intermediacy of cyclic AMP. The properties of the native neuropeptides were identical with those of samples synthesized from appropriately protected L-amino acids.

Amino Acid Sequence↗

Structures and biological activities of three synaptic antagonists from orb weaver spider venom.

The venom of Argiope aurantia, an orb weaver spider, contains a mixture of low molecular weight "argiotoxins", which block neuromuscular transmission in insects. Complete structure elucidation of three argiotoxins reveals common features; a hydrophilic, basic domain of arginine, a polyamine and asparagine is connected to an aromatic moiety contributed either by 4-hydroxyindole-3-acetic acid or 2,4-dihydroxyphenylacetic acid. Structural assignments of two argiotoxins are verified by chemical synthesis. The argiotoxins cause reversible paralysis when injected into insects and this is correlated with a stimulus-dependent inhibition of skeletal neuromuscular transmission at submicromolar concentrations.

Animals↗

Monoclonal antibody identification of subpopulations of cerebral cortical neurons affected in Alzheimer disease.

Neuronal degeneration is one of the hallmarks of Alzheimer disease (AD). Given the paucity of molecular markers available for the identification of neuronal subtypes, the specificity of neuronal loss within the cerebral cortex has been difficult to evaluate. With a panel of four monoclonal antibodies (mAbs) applied to central nervous system tissues from AD patients, we have immunocytochemically identified a population of vulnerable cortical neurons; a subpopulation of pyramidal neurons is recognized by mABs 3F12 and 44.1 in the hippocampus and neocortex, and clusters of multipolar neurons in the entorhinal cortex reactive with mAb 44.1 show selective degeneration. Closely adjacent stellate-like neurons in these regions, identified by mAB 6A2, show striking preservation in AD. The neurons recognized by mAbs 3F12 and 44.1, to the best of our knowledge, do not comprise a single known neurotransmitter system. mAb 3A4 identifies a phosphorylated antigen that is undetectable in normal brain but accumulates early in the course of AD in somas of vulnerable neurons. Antigen 3A4 is distinct from material reactive with thioflavin S or antibody generated against paired helical filaments. Initially, antigen 3A4 is localized to neurons in the entorhinal cortex and subiculum, later in the association neocortex, and, ultimately in cases of long duration, in primary sensory cortical regions. mAb 3F12 recognizes multiple bands on immunoblots of homogenates of normal and AD cortical tissues, whereas mAb 3A4 does not bind to immunoblots containing neurofilament proteins or brain homogenates from AD patients. Ultrastructurally, antigen 3A4 is localized to paired helical filaments. Using these mAbs, further molecular characterization of the affected cortical neurons is now possible.

Alzheimer Disease↗

Optic-nerve degeneration in Alzheimer's disease.

Alzheimer's disease is a dementing disorder of unknown cause in which there is degeneration of neuronal subpopulations in the central nervous system. In postmortem studies, we found widespread axonal degeneration in the optic nerves of 8 of 10 patients with Alzheimer's disease. The retinas of four of the patients were also examined histologically, and three had a reduction in the number of ganglion cells and in the thickness of the nerve-fiber layer. There was no retinal neurofibrillary degeneration or amyloid angiopathy, which are typically seen in the brains of patients with Alzheimer's disease. The changes we observed in the patients with Alzheimer's disease were clearly distinguishable from the findings in 10 age-matched controls and represent a sensory-system degeneration that occurs in Alzheimer's disease. Study of the retina in patients with this disease may be helpful diagnostically, and isolation of the affected ganglion cells may facilitate molecular analysis of the disorder.

Aged↗

Steroid-induced remission in primary malignant lymphoma of the central nervous system.

A case of primary malignant lymphoma of the central nervous system is described in which lesions seen on computed tomography scans disappeared, and clinical remissions occurred with the administration of corticosteroids. The tumor affected the region of the fourth ventricle and parietal and frontal lobes. In our patient, three remissions occurred over a span of 24 months, each in conjunction with corticosteroid administration. This supports other observations that steroids alter the natural history of primary malignant lymphoma of the central nervous system, leading to both radiologic and clinical remissions.

Adrenal Cortex Hormones↗

Cyclic nucleotide-dependent protein kinases in the lower esophageal sphincter.

The characteristics and regulation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent and guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinases (PKs) in opossum, canine, and human lower esophageal sphincter (LES) were investigated. As measured by the incorporation of 32P from [gamma-32P]adenosine 5'-triphosphate (ATP) into histone, LES homogenates from all three species contained three distinct types of PK: cAMP-dependent PK, cGMP-dependent PK, and cyclic nucleotide-independent PK. In all three species, cAMP-dependent PK comprised approximately 80%, cGMP-dependent PK comprised approximately 10%, and cyclic nucleotide-independent PK comprised approximately 10% of the total PK activity in the LES. Diethylaminoethyl-sepharose column chromatography of the supernatant fraction of opossum LES homogenates revealed that of the total cAMP-dependent PK, 10% was Type I and 90% was Type II. In contrast, equal amounts of Type I and Type II cAMP-dependent PK were present in both the human and canine LES. Isoproterenol-induced relaxation of the isolated opossum LES was accompanied by an increase in cAMP content and an activation of cAMP-dependent PK. The results of this study support the proposal that cyclic nucleotides and cyclic nucleotide-dependent PKs regulate LES tone.

Adenosine Triphosphate↗

Selective modifications of cellular proteins in intratumoral subpopulations of human colonic carcinoma cells.

Molecular alterations of cellular proteins were assessed in three previously described subpopulations of human colon carcinoma cells that were originally isolated from a single human primary colon carcinoma. The subpopulations designated HCT 116b, HCT 116, and HCT 116a exhibited significant differences in their expression of several biological properties. Immunoautoradiographic analysis of membrane components, fractionated by SDS-PAGE and electrophoretically transferred onto nitrocellulose sheets, distinguished the most aggressive tumor cell subpopulation from the intermediate and least aggressive subpopulations. An elevated expression of antigens of molecular weight in the range of 116-120 kd, 92 kd, 55-66 kd, and 31 kd was found to be associated with the most aggressive subpopulation of HCT 116a cells. The binding pattern of RCA I and WGA lectins to membrane components, fractionated by SDS-PAGE and fixed on nitrocellulose, also distinguished the three subpopulations of cells. Elevated bindings of RCA I to 80-92 kd components of HCT 116b cells and elevated bindings of WGA to 120 kd components of HCT 116a cells distinguished the three subpopulations from one another. Analysis of cellular phosphoprotein profiles, following labeling of the cells with 32Pi in the presence of phosphate-free medium, further distinguished the most aggressive subpopulation from the intermediate and least aggressive subpopulations. High level of phosphorylation of 120 kd and 250 kd nuclear components, 30 and 90 kd cytosolic components, and low level of phosphorylation of lower molecular weight membrane components were found to be associated with the most aggressive subpopulation. It is concluded that differences in the expression of membrane antigens, differences in the glycosylation of membrane components, and the selective phosphorylation and/or dephosphorylation of cellular proteins exist in subpopulations of intratumoral colonic carcinoma cells with different biological properties. These biochemical alterations of cellular proteins may play an important role in the generation of phenotypic diversity and heterogeneity of malignant cells.

Antigens, Neoplasm↗

Observations on the perioperative management of aneurysmal subarachnoid hemorrhage.

Thirty-two patients with aneurysmal subarachnoid hemorrhage (SAH) were managed according to a protocol based on pain control and hemodynamic manipulation, monitored by an arterial line and Swan-Ganz catheter. Hemodynamic parameters were adjusted to four clinical situations. 1) For the unoperated patient with no neurological deficit, the regimen aims to maintain pulmonary wedge pressure (PWP) at 10 to 12 mm Hg, and the cardiac index (CI) and blood pressure (BP) at normal levels. 2) For the unoperated patient presenting with or developing neurological deficit, the PWP is increased until the deficit is reversed or the CI falls; the CI is high, and the BP normal. 3) For the postoperative patient with no neurological deficit, the PWP is maintained at 12 to 14 mm Hg, the CI is a high normal, and the BP is normal. 4) For the postoperative patient developing neurological deficit but showing no surgical complication on the computerized tomography scan, the PWP is increased until the deficit is reversed or the CI falls; the CI is high and the BP is increased with vasopressors if necessary. Fourteen patients developed neurological deficits either preoperatively, postoperatively, or both. Neurological deficits were repeatedly reversed by increasing the PWP, as measured hourly. In several patients an optimal wedge pressure was determined, below which deficits would reappear. In one patient whose neurological deficit was reversed on several occasions by increasing the PWP, the optimal PWP rose after each episode until it reached 22 mm Hg. Detailed event-related analysis of these patients' course illustrates these phenomena well. The optimal PWP varied from patient to patient, but ranged most frequently from 14 to 16 mm Hg. Meticulous monitoring of the patients' neurological status coupled with prompt correction of low PWP (assuming an adequate CI) has proven to be an effective way to prevent and reverse neurological deficits following aneurysmal SAH.

Adult↗

Management of cervical radiculopathy.

Cervical monoradiculopathy occurs most commonly at C5-6 and C6-7. It is due mostly to acute herniation of nuclear material. The syndrome often responds to conservative prescription but when surgery is indicated, the results are good. The neurologic examination is the most specific and sensitive clinical test. Acute radiculopathies due to herniated nucleus are, in our hands, best approached via a posterior muscle-splitting incision. Chronic radiculopathies due to osteophyte formation may be approached either anteriorly or posteriorly. Reflex discogenic pain requiring anterior fusion exist but are less common. These patients must be carefully screened because of the functional factors involved.

Cervical Vertebrae↗

Selective nuclear protein phosphorylation/dephosphorylation in subpopulations of human colonic carcinoma cells.

The nuclear protein and phosphoprotein profiles from 3 subpopulations of human colonic carcinoma cells which expressed different levels of neoplastic properties were characterized by two-dimensional electrophoresis. The silver stained nuclear protein profiles were found to be remarkably similar among the subpopulations. However, 2 types of nuclear proteins were found to be selectively modified by phosphorylation/dephosphorylation reactions. The dephosphorylation of type I and the phosphorylation of type II nuclear proteins were found to be associated with the HCT 116a subpopulation which expressed a high level of neoplastic properties. Conversely, the phosphorylation of type I and the dephosphorylation of type II nuclear proteins were found to be associated with the HCT 116b subpopulation, which expressed a low level of neoplastic properties. The HCT 116 subpopulation, which expressed an intermediate level of neoplastic properties, was found to possess an intermediate phosphoprotein profile relative to that of the other two subpopulations. Selective modification of cellular proteins by phosphorylation/dephosphorylation reactions may be involved in the generation of tumor cell diversity and heterogeneity.

Autoradiography↗

Juvenile hormone titre and regulation in the cockroach Diploptera punctata.

Titres of juvenile hormone (JH) have been determined in both hemolymph and whole body extracts of female Diploptera punctata during the first gonotrophic cycle using a method employing gas chromatography/mass spectrometry for qualitative and quantitative analysis. JH III is the sole JH found in both adult and last instar D. punctata. Maximum values of approximately 1500 ng/ml (approximately 6 microM) were observed at the middle of the gonotrophic cycle, when basal oocyte growth rate was greatest. Changes in rates of JH release in vitro by corpora allata paralleled closely the changes in JH titre, suggesting that biosynthesis is a major regulator of titre. JH levels per animal were calculated from observed JH titres, and at certain time points in the gonotrophic cycle JH obtained from analysis of whole bodies were significantly greater than those predicted from hemolymph titres. These results suggest the existence of a nonhemolymph JH pool in D. punctata. Decay in JH titre after allatectomy of 5 day females has also been studied. Following a rapid initial decline, the rate of decay slowed appreciably 4 h post-operation. Thus, use of a first-order rate constant to estimate half-life of JH significantly underestimated the longevity of the hormone. The apparent persistence of JH following allatectomy may be due to the existence of a nonhemolymph JH pool.

Animals↗

Annual stability in the levels of lymphocyte subpopulations identified by monoclonal antibodies in blood of healthy individuals.

The absolute numbers and percentages of lymphocytes, monocytes, and lymphocyte subpopulations in the blood mononuclear cells were examined monthly in two healthy individuals over a 22-month period. The object of this study was to determine whether the levels of lymphocyte subpopulations identified by monoclonal antibodies, Leu4+ (T), Leu3+ (helper T), Leu2+ (suppressor/cytotoxic T), and Leu7+ (natural killer) cells, were stable during the year for healthy donors. The results were analyzed by the cosiner method to estimate the rhythmicity of these subpopulations. The number of lymphocytes varied, showing a moderate circannual rhythm with a peak in early summer, whereas the number of monocytes also varied but its variation did not show a specific rhythm. The absolute numbers of T-lymphocyte subpopulations and Leu3+ and Leu2+ cells showed a covariation, with a peak in early summer in parallel with the circannual rhythm of total lymphocyte counts. A subpopulation of granular lymphocytes with natural killer function, Leu7+ cells, also showed a significant variation during the year. Of particular interest is that Leu3/Leu2 ratios were considerably stable during the year. The two-time point examination of these lymphocyte markers including HB-2+ B cells in August and January in 15 normal donors did not show any significant differences, although the mean values were slightly higher in summer. The stability and variability of these lymphocyte markers are displayed graphically and the details of these variations are listed.

Adult↗