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Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 523 records · Page 29Linked to original sources
PubMed1985

Technetium-99m low density lipoproteins: preparation and biodistribution.

The focal uptake by human atherosclerotic lesions of 125I bound to low density lipoproteins (LDL) can be demonstrated by external imaging. However, 125I has poor imaging characteristics. Therefore, we have developed a technique for labeling LDL with technetium. To facilitate analysis, LDL was first labeled with 99mTc, by reduction of TcO4- with dithionite in the presence of the protein. The labeled LDL was stable to electrophoresis, ultracentrifugation, and passage in vivo. This technique was repeated with minor modification with 99mTc to prepare [99mTc] LDL for use as an imaging agent. Its biodistribution in 16 rabbits was similar to that of [125I] LDL and it allowed high resolution external imaging of LDL uptake by tissues, including the injured, healing, arterial wall, and the adrenal cortex.

Animals↗
PubMed1985

How do doctors discuss do-not-resuscitate orders?

Although patient preferences are important in decisions about "do not resuscitate" (DNR) orders, little is known about how physicians discuss these orders with patients. We asked 15 physicians to simulate discussing such orders with a patient. We found a striking variation in whether physicians explicitly asked for patient preferences, how they described cardiopulmonary resuscitation (CPR) and its possible outcomes and whether they made a recommendation to the patient about DNR orders. There was no pattern to the different amounts of information presented about CPR. Physicians gave conflicting reasons for how they individualized discussions with patients. Awareness of such different behaviors may stimulate physicians to examine what they say to patients about this sensitive and important topic and why they say it.

Disclosure↗
PubMed1984

[Tinea nigra. 1st clinical case in Uruguay].

The first case in Uruguay of 'tinea nigra' is described in a 44-year-old male patient with a maculous pigmented lesion on the right foot. It represents the most meridional case of the disease yet recorded in South America. Exophiala werneckii was isolated in cultures (strain 1905 IHM).

Adult↗
PubMed1984

Phosphorylation in vivo of rat hepatic glucocorticoid receptor.

Rat liver glucocorticoid receptors were labeled in vivo with [32P]orthophosphate. In the last two fractionation procedures leading to purified, molybdate-stabilized, unactivated receptor complex, bound [32P] coeluted with peaks of bound [3H]triamcinolone acetonide. SDS-gel electrophoresis revealed [32P] labeled 90K and 24K bands. The lower molecular weight band is heavily phosphorylated and it could be either a component of the unactivated receptor or a degradation product.

Animals↗
PubMed1984

Purification of the unactivated glucocorticoid receptor and its subsequent in vitro activation.

The unactivated, molybdate-stabilized rat hepatic glucocorticoid receptor has been purified approximately 4000-fold, as calculated by specific radioactivity, by affinity chromatography using a deoxycorticosterone-derivatized agarose, gel filtration on Bio-Gel A-1.5m agarose, and DEAE-cellulose chromatography. The final receptor sediments at 9-10 S in low salt (40 mM KCl) glycerol gradients containing molybdate. Elevated salt concentrations up to 1 M KCl reduce the sedimentation coefficient to 8-9 S. The final DEAE-cellulose eluted complexes exhibit a Stokes radius of 7.3 nm, a value similar to that reported for receptors in crude cytosol. From the hydrodynamic parameters an apparent Mr = 303,000 can be calculated for the steroid-receptor complex. Analysis of the receptor-containing fractions from DEAE-cellulose chromatography by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrates the occurrence of a major Mr = 90,000 protein band which closely followed the distribution of bound radioactivity. Two other proteins corresponding to Mr = 41,000 and 40,000 also exhibit the same distribution pattern. Saturation of cytosolic specific binding sites with unlabeled triamcinolone acetonide prior to receptor purification results in the disappearance of these three proteins from the DEAE-cellulose chromatogram. Furthermore, a Mr = 24,000 component, which is eluted from DEAE-cellulose at a salt concentration higher than that of the bound radioactivity peak itself, also disappears. These observations argue that the Mr = 90,000, 41,000, 40,000, and 24,000 components are related as components or degradation products of the unactivated, molybdate-stabilized rat hepatic glucocorticoid-receptor complex. Studies on the in vitro activation of purified steroid-receptor complexes have revealed that Sephadex G-25 gel filtration and warming (25 degrees C for 30 min) enables purified receptors to become activated judged by ability to bind to DNA-cellulose but to a lower extent than observed for receptors in crude tissue homogenates. A DNA-cellulose binding capacity, similar to that shown by crude liver cytosolic receptor under the same conditions, can be conferred on the purified complexes only in a reconstituted system in which crude cytosol has been added. Molybdate is shown to completely inhibit activation induced by gel-filtration and offers significant protection against heat-induced activation both in highly purified and reconstituted systems. The activation inhibitory effect of molybdate has also been confirmed by DEAE-cellulose chromatography.

Animals↗
PubMed1984

Collagen: the organic matrix of bone.

Collagen is the principal organic matrix in bone. The triple helical region of the molecule is 1014 amino acids long. In fibrils these molecules are staggered axially by integers of 234 residues or 68 nm (D). This axial shift occurs by self-assembly and can be understood in terms of a periodicity in the occurrence of apolar and polar residues in the amino acid sequence. Because the molecular length L = 4.47 D, there are gaps 1.5 X 36.5 nm regularly arrayed throughout the fibrils. The three-dimensional molecular arrangement is a quasi-hexagonal lattice with three distinct values for the principal interplanar spacings. Analysis of the intensity distribution in the medium-angle X-ray diffraction patterns from tendons has produced the following picture of the molecular arrangement in fibrils (Fraser et al. 1983). The molecular helices have a coherent length of 32 nm and are tilted parallel to a specific place within the lattice. A regular azimuthal interaction exists between these helices. This crystalline region could be the overlap region with a non-crystalline gap region. However, the gap is still regular axially and the molecular helices retain their structure; their lateral packing is perturbed although they retain a 'gap'. Neutron and X-ray scattering experiments have shown that calcium hydroxyapatite crystals occur in the gap and are nucleated at a specific though unknown location within the gap. The c-axis of the apatite crystals is parallel to the fibril axis and its length c = 0.688 nm is close to the axial periodicity in a protein with an extended beta-conformation. If the telopeptides at the end of a collagen molecule do have this conformation they would either have a highly heterogeneous conformation or exist in a folded manner because the overall length of the telopeptides is shorter than a regular collagen repeat of 0.029 nm would allow.

Amino Acid Sequence↗
PubMed1984

Pneumoconiosis associated with exposure to glass and abrasive particles.

A patient with a history of decorating glass fixtures by means of abrasive etching presented with a disease characterized by diffuse infiltrates on chest roentgenogram and restriction and diffusion impairment on pulmonary function testing. Mineralogic analysis of biopsied pulmonary lesions showed particles consistent in composition to the glasses etched and abrasives used. The former particles were noncrystalline. Silicate mineral phases were identified as well, these displaying crystalline properties. Previous studies of workers exposed to abrasives, ie, silicon carbide and emery (as a form of corundum) suggest slight pneumoconiotic risk exists; this is also the case for workers exposed to forms of industrially made glass. The question is raised as to whether there exists, in this present case, an etiological association between exposure to respirable glassy particles and the development of pulmonary scarring.

Aluminum↗
PubMed1984

The expressed lysozyme-specific B cell repertoire. I. Heterogeneity in the monoclonal anti-hen egg white lysozyme specificity repertoire, and its difference from the in situ repertoire.

A panel of closely and distantly related lysozymes and lysozyme-peptide fragments were utilized in assessing the specificity repertoire of murine anti-hen egg white lysozyme hybridomas. The 44 monoclonal antibodies could be divided into a minimum of 18 fine specificity groups in tests using the lysozyme panel. Two hybridoma products were specific for epitopes containing amino acids 68 and 121, respectively; and another was specific for an epitopes containing amino acids 113-114. Several hybridomas demonstrated unique heteroclitic binding, for example, to bob-white lysozyme (BEL), but not other closely related lysozymes, suggesting lysine at position 68 in BEL as an important residue of recognition. Radioimmunoassay using lysozyme peptides bound to plastic plates specified the regional specificity of 6 additional antibodies of the 44. A comparison of the specificities of monoclonal antibodies with antibody produced in vivo showed some major differences suggesting that those cells proceeding on to antibody formation in the regulatory milieu of the whole animal are a selected subpopulation.

Animals↗
PubMed1984

Immunodominant protein epitopes. I. Induction of suppression to hen egg white lysozyme is obliterated by removal of the first three N-terminal amino acids.

The lack of response to hen egg white lysozyme (HEL) by C57BL (H-2b) mice has been demonstrated previously to be related to the induction of suppressor T (Ts) cells which recognize the amino terminal region of HEL. In this report, the nature of the protein determinant required for Ts cell induction is more precisely detailed using des-1,2,3-HEL (AP-HEL) prepared with an aminopeptidase purified from Aeromonas proteolytica . Remarkably, the removal of just these three amino acids obliterates the ability of HEL to induce Ts cells specific for HEL. Additionally, in contrast to HEL, AP-HEL is able to prime for an in vitro T cell proliferative response to either AP-HEL or HEL. Thus, removal of a very limited region of a protein antigen can drastically alter its immunogenic properties.

Animals↗
PubMed1984

Immunodominant protein epitopes. II. The primary antibody response to hen egg white lysozyme requires and focuses upon a unique N-terminal epitope.

The antibody response to a defined protein antigen, hen egg white lysozyme (HEL) has been investigated using an aminopeptidase-treated HEL molecule, des-1,2,3-HEL (AP-HEL). Surprisingly, removal of these three N-terminal residues eliminates an epitope which is a dominant B cell determinant recognized in the primary antibody response to HEL. Thus, the initial antibody response focuses on a very small region of the molecule. Even more striking is the observation that removal of this epitope markedly reduces the immunogenicity of HEL. Therefore, the epitope is not only the focus of the primary antibody response, but is essential for the initiation of the response. This report demonstrates that a selective mechanism must be activated during the response to this protein antigen. Of the multitude of B cell determinants present on HEL, only a limited number are focused upon by the immune system.

Amino Acid Sequence↗
PubMed1984

Selective reversal of H-2 linked genetic unresponsiveness to lysozymes. I. Non-H-2 gene(s) closely linked to the Ir-2 locus on chromosome 2 permit(s) an antilysozyme response in H-2b mice.

Genes outside of the mouse major histocompatibility complex (H-2) were found to be capable of specifically reversing the previously described nonresponsiveness to hen egg-white lysozyme (HEL) owing to H-2b immune response (Ir) genes. C3H.SW, BALB.B, and C57L, all of the H-2b haplotype, showed responsiveness to HEL, but not to human lysozyme (HUL). Mapping of the reversing gene(s) was attempted by testing H-2b recombinant inbred (RI) strains of mice carrying C3H, BALB, and C57L non-H-2 genes. Analysis of the strain distribution pattern of responsiveness with both CXB and BXH RI strains was consistent with the location of the responsible site within the H-3 region on chromosome 2. The anti-HEL proliferative responsiveness in two H-3 congenic strains of mice, B10.C(28NX)SN and B10.C-H-3cH-3a, that have BALB/c genes within the H-3 region confirmed the mapping, as well as localized the reversing gene(s) near the Ir-2 gene. The data are discussed with regard to the site of expression of the reversing gene(s) and its mechanism of action.

Animals↗
PubMed1984

Delayed recovery of behavior after anesthesia in rats.

UNLABELLED: Early, complete recovery from general anesthesia is of importance for outpatients, in resuscitation research and in behavior testing of neonates. A model was designed to study behavior during the first week of recovery from anesthesia in rats, using two methods: spontaneous and unrestrained locomotor activity was tested and passive avoidance of electroshock was studied in a two session, one trial model. Neurologic deficit and ease of handling were also tested. After anesthesia with halothane 1-2% in N2O/O2 for 30 min, spontaneous activity was reduced, compared with unanesthetized rats, for up to at least 48 h. On day 6 post-anesthesia, locomotor activity was recovered, and, on days 4 and 5, passive avoidance was unchanged. Neurologic deficits were absent after the first hour of recovery and ease of handling was unchanged. CONCLUSION: Halothane and nitrous oxide have prolonged effects on locomotor behavior beyond the immediate post-anesthesia recovery period, at a time when neurologic deficit testing does not reveal any abnormalities. The model is suitable for the comparison of recovery from different anesthesia techniques in rats.

Anesthesia, General↗
PubMed1984

Asphyxia, cardiac arrest and resuscitation in rats. II. Long term behavioral changes.

This study in 53 rats was conducted to investigate a mild insult, sensitive parameter model in contrast to a severe insult, severe damage model of brain resuscitation. Up to now, the latter approach, which causes neuropathologic changes and neurological abnormalities, has not provided unequivocal data on pharmacological measures to ameliorate post-anoxic brain damage, because of logistical difficulties and many extracranial complicating factors. As tracheotomy and oral intubation in rats proved impractical in studies on recovery from asphyxia, transtracheal jet ventilation was tested in 14 rats as a measure for effective prolonged and reversible control of airway and ventilation. Subsequently, in 37 other rats we studied, during the first post-insult week, the effects of anesthesia, with or without 6 min asphyxia, on behavior, i.e. unrestrained spontaneous locomotor activity and two sessions of one-trial passive avoidance. Transtracheal jet ventilation proved a reliable method for reversible and prolonged controlled ventilation in rats. Spontaneous locomotor activity was affected for at least 48 h after anesthesia and differently so after asphyxia. Passive avoidance was affected only after asphyxia. The recovery of behavior was delayed for days, whereas the recovery of neurologic deficits was only delayed for several post-asphyxia hours. The asphyxiated rats showed hyper-excitability for at least 2 weeks. The existence of abnormal behavior during recovery from mild anoxic-ischemic insults to the brain provides parameters for evaluation of therapies of the post-resuscitation disease in a model without the difficulties encountered in models with severe insults, which made post-insult intensive care necessary. The mild insult, sensitive parameter model is promising and further work in this direction is indicated.

Animals↗
PubMed1984

Fixed-tissue binding of fluorescein-conjugated concanavalin A to malignant melanomas versus nevi.

Concanavalin A (con A) is a plant-derived lectin that has the capability of agglutinating malignant cells in vitro. We studied the binding of fluorescein isothiocyanate-conjugated con A to formalin-fixed, paraffin-embedded malignant melanomas and nevocellular nevi. Both malignant melanoma cells and nevus cells emitted partial or circumferential, cytoplasmic rim, apple green fluorescence. There was no demonstrable difference between fluorescence distribution or intensity between the two groups. Control, unstained tissue specimens yielded a brilliant nuclear and nucleolar yellow-green autofluorescence, which is peculiar to melanoma cells and rare to absent in nevus cells. Fluorescein isothiocyanate-conjugated con A provided no clear differentiation between malignant melanomas and nevocellular nevi in fixed tissue. However, characteristic melanoma cell autofluorescence may prove to be of benefit for differentiating malignant melanocytic from benign nevocytic lesions.

Binding Sites↗