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Biomedical subjects

D K Miller

Publications and source records attributed to D K Miller.

At least 145 records · Page 8Linked to original sources
PubMed1981

Antihistaminics, local anesthetics, and other amines as antiviral agents.

A number of lipophilic amines of diverse chemical structure, including antihistaminics, local anesthetics, and chloroquine, were found to exhibit similar kinetics in inhibiting the infection of BHK cells by vesicular stomatitis virus. The inhibition occurred prior to both primary and secondary RNA transcription but following transfer from the cell surface to an intracellular site, presumed to be the lysosomes. A similar inhibition, by these agents, of infection by Sendai, influenza strain WSN, and Semliki Forest viruses suggested a lysosomal involvement in infection by these viruses as well.

Amines↗
PubMed1980

Reconstituted G protein-lipid vesicles from vesicular stomatitis virus and their inhibition of VSV infection.

The single glycoprotein (G) of vesiclar stomatitis virus (VSV) was isolated in nearly quantitative yield by extraction of the purified virions with 0.05 M octyl-beta-D- glucoside (OG) in 0.01 M sodium phosphate, pH 8.0. The extract contained essentially all of the viral phospholipids and glycolipids, and was free of other essentially all of the viral phospholipids and glycolipids, and was free of other viral proteins. Dialysis to remove OG resulted in the formation of G protein-viral lipid vesicles having a lipid-G protein ratio similar to that of the intact virions. The vesicles were 250-1,000 A in diameter, with a "fuzzy" external layer also similar to that of intact virions. The vesicles were predominantly unilamellar and sealed, with both phosphatidyl ethanolamine and gangliosides symmetrically distributed in the bilayer. G protein was asymmetrically oriented, with about 80 percent accessible to exogenous protease. Addition of soybean phospholipid to the viral extract before dialysis resulted in vesicles that incorporated viral proteins and lipids quantitatively, but that were markedly decreased in buoyant density. The G neutralized protein-lipid vesicles were effective in eliciting specific anti-G antibodies that neutralized viral infectivity. Competitive radioimmunoassay showed that both reconstituted vesicles and a soluble form of G protein (Gs) were indistinguishable from purified VSV in their antibody binding properties. Addition of G protein-lipid vesicles of BHK-21 cells before, or simultaneously with, infection by VSV inhibited viral infectivity, as measured by two independent techniques (viral RNA production in the presence of actinomycin D and a neutral red assay of cell viability). The total inhibitory activity of G protein in the vesicular form was, however, less than 5 percent of that found for intact virus particles that have been inactivated by ultraviolet light irradiation. Gs was inactive as an inhibitor as determined by the RNA production assay.

Animals↗
PubMed1980

Inhibition of vesicular stomatitis virus infection by spike glycoprotein. Evidence for an intracellular, G protein-requiring step.

In an assay measuring virus-directed RNA synthesis, infection of BHK cells by a standard test dose of vesicular stomatitis virus (VSV) was inhibited by ultraviolet light-irradiated wt VSV and by ts 045, one of a number of thermolabile, temperature-sensitive G protein mutants of VSV. After heat treatment for 1 h at 45 degrees C, the thermolabile mutants were no longer able to inhibit the VSV infection. In contrast, the thermolabile M protein mutant ts G31 and the nonthermolabile G protein mutant ts 044 could still inhibit the test VSV dose. Thus, the presence of G protein in its native conformation was necessary for inhibition of infection. There was little difference in the binding to cells or the internalization to a trypsin-resistant state of ts 045 or wt VSV before and after heat treatment, and there was no evidence of specific saturable receptors on the cell surface. None of the irradiated virions at concentrations that gave maximal inhibition of infection could prevent binding of infectious VSV to, or internalization by, BHK cells. The G protein-specific inhibition, therefore, did not occur at the cell surface but must have occurred at some intracellular site, which has been suggested to be the lysome. The lysosomal inhibitor chloroquine, when added with the infecting virus, completely inhibited VSV infection at all multiplicities of infection tested, and it gave 50% inhibition when added to 1.5 h after infection. The possible importance of the lysosome in the intracellular pathway of infection is discussed.

Animals↗
PubMed1979

Loss of strain specificity of the TA3-St subline: evidence for the role of epiglycanin in mouse allogeneic tumor growth.

We described the in vivo conversion of the strain-specific ascites murine mammary adenocarcinoma subline TA3-St to a new ascites subline designated TA3-MM. This conversion occurred during passage in a syngeneic A/HeHa mouse infected with pneumonia-producing microorganisms. The mode number of chromosomes of the TA3-MM cell (82) was greater than that of the parental TA3-St cell (69) or the other non-strain-specific subline TA3-Ha (42). The TA3-MM subline could grow in and kill mice of various allogeneic strains. In addition, the TA3-MM cell possessed numerous receptors for the lectin of Vicia graminea seeds, which were hardly detectable at the surface of the parent TA3-St subline but were present in abundance at the cell surface of the non-strain-specific subline TA3-Ha. These lectin receptors of the TA3-Ha cell were previously demonstrated to be present in a unique high-molecular-weight endogenous cell surface glycoprotein termed epiglycanin. The V. gramines lectin receptors on the new TA3-MM subline also were present on an epiglycanin-like molecule. This finding provides further evidence for the hypothesis that allogeneic growth in the TA3 system is a direct result of these membrane glycoproteins.

Adenocarcinoma↗
PubMed1979

Isolation and partial characterization of an epiglycanin-like glycoprotein from a new non-strain-specific subline of TA3 murine mammary adenocarcinoma.

A new non-strain-specific ascites subline of the TA3 mammary adenocarcinoma TA3-MM, which arose in vivo from the strain-specific TA3-St subline during an acute respiratory illness of the syngeneic mouse strain A/HeHa hosts, possessed at its surface a glycoprotein not found on the parent TA3-St cell. This glycoprotein, termed TA3-MM epiglycanin, was characterized by a high molecular weight (500,000), by potent inhibition of hemagglutination by the Vicia gramines lectin, and by carbohydrate and amino acid compositions nearly identical to those of the glycoprotein epiglycanin present at the surface of the allotransplantable TA3-Ha ascites cell. By electron microscopic examination, TA3-MM epiglycanin appeared as long extended rods with widths (2.5 nm) and lengths (450--500 nm) similar to those of TA3-Ha epiglycanin. Incubation of each of two sublines of the TA3-MM ascites cell, TA3-MM/1 and TA3-MM/2, with a modified trypsin followed by column chromatography produced approximately 1.0- and 0.2-fold as much epiglycanin-like material, respectively, as was obtained from the TA3--a ascites cell. Continuous growth of the TA3-MM cell in suspension culture resulted in an almost complete disappearance of epiglycanin in a manner demonstrated earlier for the TA3-Ha cell grown under similar conditions. Allotransplantability in the TA3-MM cell may be due, at least in part, to masking a histocompatibility antigens by epiglycanin-like molecules.

Amino Acids↗
PubMed1977

Hemodynamic response to submaximal exercise after dehydration and rehydration in high school wrestlers.

Cardiac output (Q), heart rate (HR), stoke volume (SV), and arteriovenous oxygen difference (AVD) were measured in 16 high school wrestlers during submaximal work (65%Vo2 Max) at normal weight (T1), after a four or five percent weight loss (T2), and following one hour of rehydration (T3). Weight losses were accomplished over 48 hours by fluid and food restriction as well as intermittent exercise. An ad libitum volume and commercial glucose-electrolyte solution was used to rehydrate the subjects. At T2 the mean weight loss was 4.6%, with the average plasma deficit estimated to be 4.9%. Under these conditions significantly higher HR and lower SV were observed during standardized exercise. Although Q was 7.8% lower and AVD was 7.3% higher after dehydration, neither change was statistically significant. Following rehydration all dependent variables returned to near T1 levels. It was concluded that despite a short rehydration period, the cardiovascular dynamics of these high school wrestlers rapidly returned to normal during moderately heavy work because of the small plasma changes that accompanied the 48-hour weight loss.

Adolescent↗
PubMed1975

Sexual counseling with spinal cord-injured clients.

Spinal cord-injured clients have many fears and misapprehension about their sexual functioning. Common beliefs include: (a) disabled men cannot sexually satisfy able-bodied women; and (b) cord-injured persons cannot have sexual intercourse. Such misapprehensions can be helped by the counselor's willingness to discuss sexual issues openly. Clients need a clear and accurate picture of the facts, as well as encouragement and support to help them rediscover their sexuality. Spinal cord injury does not mean sexual incapacity. Given a knowing and patient partner, most clients can enjoy a satisfying sex life.

Attitude of Health Personnel↗
PubMed1975

Reversible loss in suspension culture of a major cell-surface glycoprotein of the TA3-Ha mouse tumor.

A major cell-surface glycoprotein of the TA3-Ha ascites mammary adenocarcinoma diminished during transfer from ascites growth to cell growth in suspension culture. A sensitive, hemagglutination-inhibition assay that used a lectin from Vicia graminea seeds indicated approximately a 50% loss after 7-10 days of culture and a 90% loss after 2 months. These findings were corroborated by carbohydrate and amino acid analysis with gas-liquid chromatography of trypsin glycopeptides released from the cell surface. Repassage of the cultured cells in vivo caused the reappearance of the surface glycoprotein.

Adenocarcinoma↗
PubMed1975

Therapeutic groups for patients with spinal cord injuries.

A preliminary study was conducted to determine the effectiveness of therapeutic patient groups in a rehabilitation setting. A spinal cord knowledge "Inventory" test was designed to evaluate the success of the group method in disseminating information to patients. The first part of this test assesses the patient's knowledge about body physiology and functioning, health care, and community resources. The second part attempts to evaluate the patient's feelings regarding his body image, sexual attractiveness, and family relationships. The test was administered to 31 spinal cord injured patients upon admission and again just prior to discharge. Eighteen patients participated in a therapeutic patient group, which met twice a week for a month. The other group did not participate in such sessions. The purpose of the meetings was to help the patient adjust to his disability by exchanging commonly needed information and discussing experiences and feelings. Initial results suggest that therapeutic groups can provide an effective means for imparting information to patients. The test also indicates that many patients experience changes in their attitudes and feelings around such sensitive areas as personal worth and self-esteem.

Adolescent↗
PubMedDate not supplied

Achieving consensus on withdrawing or withholding care for critically ill patients.

OBJECTIVE: To examine the decision-making process to withhold or stop life support. DESIGN: Survey. SETTING: Medical intensive care unit of a tertiary care center. PARTICIPANTS: Physicians and families of 15 critically ill patients; in seven cases patients also participated. MEASUREMENTS: Meetings between physicians and family members concerning a decision to withhold or stop treatment of a critically ill family member were tape-recorded. Transcriptions of the meetings were analyzed for 1) process: how the physician introduced the need for a decision, framed the likely outcomes of options, and closed on a decision; 2) what decision was made; and 3) the outcome; died, discharged home, or discharged to another institution. RESULTS: The concept of "patient's wishes" was a central orientation point for the negotiation of consensus regarding withholding or withdrawing therapy even when the patient was not a participant. Physicians tended to provide a direct and unambiguous introduction, give equal weights to options during decision framing, but narrow the options during decision closure to correspond to their judgments. Not every decision was consistent with the physician's judgment. CONCLUSIONS: Decision making to withhold or withdraw life-support therapy from critically ill persons involves complex, difficult processes. Successful management of the tension among life extension, quality of life, patient autonomy, and social justice requires better understanding of these processes.

Adult↗
PubMedDate not supplied

Determining transition probabilities: confusion and suggestions.

Confusion regarding proper use of the terms rate and risk persists in the literature. This has implications for the proper modeling of prognosis and transition between health states in decision analysis and related techniques. The issue is complicated by the plethora of terms related to rate and risk. Although the suggestion to use the terms force and probability as substitutes for rate and risk has some appeal, the change in terminology by itself is unlikely to solve all the confusion or misuse of terms. This paper clarifies the proper definitions and estimations of rates and risks and suggests critical factors for the decision analyst to remember when using, modeling, or interpreting transition rates and risks.

Actuarial Analysis↗