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Biomedical subjects

J E Morgan

Publications and source records attributed to J E Morgan.

At least 127 records · Page 7Linked to original sources
PubMed1990

Reliability of cell counts and protein determinations in serial bronchoalveolar lavage procedures performed on healthy volunteers.

We measured the variability in volume, total cells, cell types, and proteins in the bronchoalveolar lavage fluid recovered from 10 volunteers (five smokers, five non-smokers) lavaged repeatedly over a three-year period. Thirty lavages were performed using a rigorously standardized approach. Differential counts on the cytospin preparations were performed by three independent readers and interobserver variability in the interpretation of these counts measured. Variability in interpreting the cellular counts was less in smokers than non-smokers and decreased as the number of cells of any particular type increased. Only one reader interpreting the mean percentage of cells recovered of one cell type (neutrophils) in only one smoking group, the nonsmokers, was significantly different from the other two. There was also considerable variability in bronchoalveolar lavage fluid total protein, albumin, IgG, and IgA. Expressing albumin and IgG as a percentage of total protein recovered and expressing IgA and albumin as a ratio in nonsmokers lessened the variability of these parameters. Mean and standard deviations of the cellular and protein concentrations showed that large differences in these parameters would be necessary in order to attribute these changes to changes in the underlying pulmonary status. Excessive variability in nearly all parameters in this group without recognized lung disease challenges the usefulness of this test in the clinical assessment of patients serially followed because of underlying lung disease.

Adult↗
PubMed1990

Dystrophin expression and genotypic analysis of two cases of benign X linked myopathy (McLeod's syndrome).

DNA extraction and Southern blot analysis of two cases of McLeod's syndrome showed restriction fragments identical to normal controls using probes from the Xp21 (1-2) region, in contrast to striking deletions found in two other McLeod phenotypes studied in the USA. The McLeod locus is adjacent to Duchenne muscular dystrophy (DMD) and dystrophin immunocytochemistry showed that expression is normal in muscle from the two McLeod cases in spite of the mild DMD-like myopathy.

Blotting, Southern↗
PubMed1990

Therapeutic drug monitoring: improved performance through educational intervention.

A pilot study done at our institution and previous studies in the literature indicate that therapeutic drug monitoring (TDM) is frequently performed without a proper indication. In addition, samples are often improperly collected or interpreted by physicians. The purpose of this study was to determine if a pharmacy-based educational intervention could positively influence the performance of TDM in a teaching institution. A cost-savings analysis on the reduction of drug levels not indicated or improperly sampled was also performed. The study consisted of a preliminary data collection period, an educational intervention, and a postintervention data collection period. The pre- and posteducational intervention periods consisted of a 1-month concurrent review of aminoglycosides, digoxin, and theophylline serum levels. The educational intervention consisted of in-service programs and newsletter. There were 188 and 211 serum drug levels analyzed during the pre- and postintervention periods, respectively. Overall, the educational intervention significantly increased the number of drug levels obtained for rational indications, correctly sampled and appropriately interpreted by physicians (p less than 0.001, chi 2 analysis). Cost savings associated with this program was +2,788 in patient charges (+559 in hospital costs) per month. This study demonstrated that TDM may be significantly improved through education.

Aged↗
PubMed1989

Electron transfer between cytochrome a and copper A in cytochrome c oxidase: a perturbed equilibrium study.

Intramolecular electron transfer in partially reduced cytochrome c oxidase has been studied by the perturbed equilibrium method. We have prepared a three-electron-reduced, CO-inhibited form of the enzyme in which cytochrome a and copper A are partially reduced and in an intramolecular redox equilibrium. When these samples were irradiated with a nitrogen laser (0.6-ns, 1.0-mJ pulses) to photodissociate the bound CO, changes in absorbance at 598 and 830 nm were observed which were consistent with a fast electron transfer from cytochrome a to copper A. The absorbance changes at 598 nm gave an apparent rate of 17,000 +/- 2000 s-1 (1 sigma), at pH 7.0 and 25.5 degrees C. These changes were not observed in either the CO mixed-valence or the CO-inhibited fully reduced forms of the enzyme. The rate was fastest at about pH 8.0, falling off toward both lower and higher pHs. There was a small but clear temperature dependence. The process was also observed in the cytochrome c-cytochrome c oxidase high-affinity complex. The electron equilibration measured between cytochrome a and copper A is far faster than any rate measured or inferred previously for this process.

Animals↗
PubMed1989

Studies of histidine phosphorylation by a nuclear protein histidine kinase show that histidine-75 in histone H4 is masked in nucleosome core particles and in chromatin.

Histone H4 is a good substrate in vitro for the protein histidine kinase activity found both in Physarum polycephalum nuclear extracts and in Saccharomyces cerevisiae cell extracts. However, histone H4 in nucleosome core particles is not a substrate for these kinases. Isolated chromatin was also not a substrate for the protein histidine kinase. The results significantly limit possible interpretations of histidine phosphorylation on histone H4 in vivo and provide a new, sharper focus for future work. In addition, a polynucleotide kinase activity was identified in the Physarum extracts.

Animals↗
PubMed1989

Conversion of mdx myofibres from dystrophin-negative to -positive by injection of normal myoblasts.

An important corollary to the recent advances in our understanding of the primary cause of Duchenne muscular dystrophy, is the validation of genuine genetic homologues as animal models of the disease in which potential therapies can be tested. The persistent skeletal muscle necrosis that characterizes human Duchenne muscular dystrophy is also seen in the mdx mouse and is, in both, a consequence of a deficiency of dystrophin, probably within the muscle fibres themselves. As injected muscle precursor cells of one genotype can fuse with host muscle fibres of a different genotype and express the donor genes, we decided to test grafts of normal muscle precursor cells to see if they could induce synthesis of dystrophin in innately dystrophin-deficient mdx muscle fibres. We show that injected normal muscle precursor cells can fuse with pre-existing or regenerating mdx muscle fibres to render many of these fibres dystrophin-positive and so to partially or wholly rescue them from their biochemical defect.

Animals↗
PubMed1989

Mdx muscle grafts retain the mdx phenotype in normal hosts.

Whole muscle grafts were made between mdx and normal mice to investigate whether the mdx myopathic lesion is intrinsic to mdx muscle or is a property of its environment. Grafts were examined between 20 and 101 days. Unequivocal necrotic muscle fibers and/or newly formed basophilic myotubes were noted in 8 of 16 grafts of mdx muscle made in normal hosts but in none of 16 grafts of normal muscle made in mdx hosts. In older grafts, the proportion of centrally nucleated fibers and variability of fiber diameter were both higher in mdx muscle grafted into normal hosts than in normal muscle grafted into either mdx or normal hosts. Analysis of the glucose-6-phosphate isomerase (GPI) isoenzyme content of the grafts indicated that the muscle formed was predominantly of donor origin. These findings provide evidence that the mdx lesion is a primary myopathy rather than secondary to an extramuscular primary lesion.

Animals↗
PubMed1989

The effect of lead incorporation on the elemental composition of earthworm (Annelida, Oligochaeta) chloragosome granules.

The elemental compositions of chloragosome 'granules' in the earthworm Lumbricus rubellus living in non-polluted (Dinas Powys) and heavily Pb-polluted (Wemyss) soils were determined by fully quantitative electron probe X-ray microanalysis. P, Ca, S and Zn were the major elemental components of the chloragosomes. High Pb concentrations were found in chloragosomes of Wemyss animals; Pb was not detected in chloragosomes of Dinas Powys animals. Partial correlation and regression analysis indicated that the in vivo accumulation of Pb by chloragosomes was accompanied by diminished chloragosomal Ca concentrations. Pb is bound by P-containing ligand(s) in the chloragosome matrix. The sequestration of Pb by chloragosomes results in the detoxification of the metal by accumulative immobilization.

Animals↗
PubMed1989

Zinc sequestration by earthworm (Annelida: Oligochaeta) chloragocytes. An in vivo investigation using fully quantitative electron probe X-ray micro-analysis.

The elemental compositions of chloragosome "granules" in the earthworm Lumbricus rubellus living in non-polluted and heavily Zn-polluted soils were determined by fully quantitative electron probe X-ray microanalysis. P, Ca, S and Zn were the major elemental components of the chloragosomes. The in vivo accumulation of Zn by the chloragosomes was accompanied by diminished chloragosomal Ca concentrations. Zn was apparently bound by at least two ligand pools (Pool 1 = uncharacterised; Pool 2 = P-containing ligands, binding approximately 45% and 55% of the Zn, respectively) in the "control" chloragosomes. In Zn-contaminated chloragosomes, most (approximately 70%) was bound by P-containing ligand(s) but some (less than 1%) was also bound by S-containing ligands. It is suggested that the sequestration of Zn in chloragosomes results in the detoxification of the metal by accumulative immobilisation.

Animals↗
PubMed1989

T cells expressing high levels of non-major histocompatibility complex (MHC)-restricted cytotoxicity are present in early and late clinical phases of human immunodeficiency virus 1 (HIV-1) infection.

Cytotoxic cells appear to play an important role in host defense against viral infection. In HIV-1 infection there is an expansion of the Leu7-positive lymphocyte population which is associated with cytotoxic activity. Since a form of non-MHC-restricted T-cell cytotoxicity [lectin-dependent cell cytotoxicity (LDCC)] has been reported to be mediated by CD3+Leu7+ cells, we evaluated LDCC and Leu7-positive lymphocyte populations in HIV-1-infected subjects and healthy controls. Both LDCC and percentages of Leu7+CD3+ and Leu7+CD2+ cells were increased in HIV-1-infected individuals as compared to controls. However, the CD3+Leu7+ lymphocyte population was increased to a greater degree than the CD8+Leu7+ population and a minor Leu7+ cell population (Leu7+CD4+) was expanded in the early stages of infection. Lectin-dependent cell cytotoxicity was positively correlated with the percentages of Leu7+CD3+ cells. Thus T-cells with the capacity to mediate high levels of non-MHC-restricted cytotoxicity are present in increased proportions in HIV-1-infected individuals and persist in advanced disease. Further studies are required to see if these cells participate in HIV-specific cytotoxicity or reflect an aberrant, ineffective, or immunologically detrimental response to the virus.

Antibodies, Monoclonal↗
PubMed1989

Immunologic assessment of a cluster of asymptomatic HTLV-I-infected individuals in New Orleans.

PURPOSE: Although clusters of individuals infected with the human T-cell lymphotrophic virus type I (HTLV-I) have been identified in the United States, no systematic evaluation of the immunologic status of these persons has been reported. We therefore studied a group of 11 HTLV-I-infected former intravenous drug abusers who were long-term participants in a methadone maintenance program in New Orleans, Louisiana, to determine the effects of HTLV-I and chronic opiate use on immunity. PATIENTS AND METHODS: Mitogenic responses and results of serologic studies, cell phenotype analysis, and cytotoxicity assays were compared to those in two other HTLV-I seronegative groups: a similar group of 17 methadone users and 15 healthy age-, sex-, and race-matched control subjects. All study participants were seronegative for human immunodeficiency virus type 1. RESULTS: Percentages and numbers of total T lymphocytes (CD2+,CD3+), T-suppressor/cytotoxic lymphocytes (CD8+), cytotoxic lymphocytes (Leu7+, Leu11+, NKH-1+) and B lymphocytes (B4+) were similar among the study groups. Although percentages and numbers of total T-helper lymphocytes (CD4+) were also similar among the groups, HTLV-I-infected subjects had higher percentages and proportions of helper/inducer cells (CD4:4B4+) than did HTLV-I seronegative methadone users. Both methadone using groups had decreased percentages and numbers of suppressor/inducer T lymphocytes (CD4:2H4+). Major histocompatibility complex unrestricted T-cell cytotoxicity (lectin-dependent cellular cytotoxicity), natural killer cell function, and mitogenic responses to the T-cell mitogen phytohemagglutin were similar among the three study groups. Pokeweed mitogen responses were severely depressed in the HTLV-I-infected population. CONCLUSIONS: We conclude that HTLV-I infection is associated with abnormalities in T-cell-dependent B-cell proliferative responses. Furthermore, both long-term methadone use and HTLV-I infection are associated with abnormalities in the distribution of CD4+ cell subpopulations. The increase in the helper/inducer and T-cell cell populations and decrease in the pokeweed mitogenic response noted in HTLV-I-infected subjects appear to be markers for infection with this retrovirus.

Adult↗
PubMed1989

Studies of spontaneous proliferation of mononuclear cells in human immunodeficiency virus (HIV-1)-infected individuals.

We evaluated the ability of mononuclear cell populations from 56 hemophiliac subjects, 69 homosexuals, and 32 control subjects to proliferate spontaneously in vitro. Levels of spontaneous proliferation (SP) were not significantly different among homosexuals or hemophiliac subjects when they were grouped as asymptomatic human immunodeficiency virus (HIV) seronegative, asymptomatic seropositive, persistent generalized lymphadenopathy, acquired immunodeficiency syndrome-related complex, or acquired immunodeficiency syndrome groups. There was, however, a stepwise increase in levels of SP corresponding with progression of disease in both patient groups. No correlations were noted between SP and CD8+ cell populations or mitogenic responses in study subjects, but SP correlated inversely to percentages and numbers of CD4+ lymphocytes. Depletion of CD4+ cells from mononuclear cell populations of HIV-infected subjects decreased SP. Thus, in HIV-1-infected subjects, SP increases as HIV-1-related disease progresses and appears to be CD4 dependent.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Species-specific shrimp allergens: RAST and RAST-inhibition studies.

Two edible shrimp species are widely available in Louisiana, Penaeus setifecus (white shrimp) and Penaeus aztecus (brown shrimp). Some sensitive individuals report only occasional allergic symptoms after shrimp ingestion, suggesting that there may be species-specific allergens. To investigate this possibility, we evaluated shrimp species-specific reactivity in 31 individuals with a history of immediate hypersensitivity reactions after shrimp ingestion with skin prick tests and RASTs with white and brown shrimp extracts. On selected individuals, RAST-inhibition studies were performed with white shrimp and/or brown shrimp-coupled disks, with white and/or brown shrimp extracts as inhibiting allergen. Positive skin tests to both types of extract were observed in 77% (23/30) of the subjects; one individual reacted to brown shrimp extract only. Elevated RASTs to both extracts were observed in 16/31 study participants; one subject reacted only to white shrimp extracts and two subjects to brown shrimp extract alone. Sera from two individuals tested by RAST inhibition recognized qualitatively different allergens in brown and white shrimp extracts, supporting the hypothesis that there are species-specific shrimp allergens. Species specificity is important because it may explain the intermittent symptoms of some study subjects. The percentage of shrimp-sensitive subjects testing positive by skin test and RAST can be increased by use of extracts from more than one species of shrimp.

Adult↗
PubMed1989

Food specific skin-test reactivity in atopic subjects.

It has been proposed that a permanent or transitory increase in gut permeability is an important facet in the development of food allergy. If this occurs, then individuals with a history of a specific food allergy should have a higher incidence of immunological reactivity to other food allergens as compared to food tolerant subjects. To test this hypothesis, we evaluated the prevalence of food-specific IgE responses by skin-prick testing in 60 individuals. Subjects were classified by a history of food allergy (shrimp hypersensitivity) and atopic status. Prevalence of skin-prick test reactivity to shrimp and a panel of nine other food extracts was determined. Skin-test reactivity to shrimp was related both a history of shrimp sensitivity and atopic status. However, the prevalence of skin-test reactivity to other foods was not related to clinical history of shrimp allergy, although it was related to atopy. A subset of subjects with shrimp allergy had multiple positive skin reactions to many of the nine other foods. This reactivity was associated with a history of pulmonary symptoms following shrimp ingestion. In general our results do not support non-specific increases in gut permeability being important in the development of food allergy.

Adolescent↗
PubMed1989

Drug allergy documentation by physicians, nurses, and medical students.

The completeness and accuracy of drug allergy documentation by medical residents, medical students, and primary-care nurses in a 450-bed teaching hospital were assessed, along with patients' knowledge of their drug allergy status. During a three-month period, the current admission notes written by medical residents, medical students, and primary-care nurses for adult medicine patients with drug allergies were reviewed by a pharmacy student. Patients with drug allergies were identified by the presence of drug hypersensitivity labels on the front of the medical charts. The student collected information about each reaction and determined whether it was a true allergic reaction, a nonallergic adverse reaction, or unclassifiable. A second pharmacy student interviewed the same patients whose medical charts had been reviewed and asked seven open-ended questions about the allergy status of each patient. For the 49 patients included in the study, 75 drugs were listed as allergens on the front of the patients' charts and 78 drugs were reported as allergens during patient interviews; only 66 of those drugs were identified both on the charts and by the patients. Approximately 20% of the health-care professionals failed to document the drug allergies in their admission notes. Although the majority of patients could recall the dosage form of the offending drug, the time that had elapsed between administration of the drug and appearance of symptoms, and how long ago the reaction had occurred, none of this information was recorded by the health-care professionals. Incomplete documentation of the drug allergy status of patients in our hospital does not appear to be related to patients' inability to provide accurate information.

Documentation↗
PubMed1988

Heat treatment of cytochrome c oxidase perturbs the CuA site and affects proton pumping behavior.

It has been previously reported that mild heat treatment (43 degrees C for ca. 60 min) abolishes the proton pumping activity of cytochrome c oxidase while leaving the oxidase activity and cytochromes a and a3 unperturbed [Sone, N., & Nicholls, P. (1984) Biochemistry 23, 6550-6554]. We herein describe the effects of this heat treatment on the electron paramagnetic resonance (EPR) and optical absorption signatures of the redox-active metal centers in the enzyme. We find that heat treatment of the oxidized enzyme causes a local structural perturbation at the CuA site. After heat treatment, the enzyme sample contains three subpopulations, each of which has a different structure at CuA. These include (i) native CuA, (ii) a type 2 copper species similar to the one produced by chemical modification by p-(hydroxymercuri)benzoate (pHMB) [Gelles, J., & Chan, S. I. (1985) Biochemistry 24, 3963-3972], and (iii) a novel type 1 copper species. In addition to changes at the CuA site, we find that heat treatment results in accelerated cyanide binding and the removal of subunit III. If the cytochrome c oxidase is heat treated while fully reduced, none of these changes are observed except for subunit III depletion. Furthermore, partial (CO mixed-valence derivative) reduction of the enzyme as well as ligand binding to cytochrome a3 also protects the enzyme against the heat-induced changes, indicating that the oxygen binding site plays a role in stabilizing the CuA site against structural perturbations.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1988

Partial correction of an inherited biochemical defect of skeletal muscle by grafts of normal muscle precursor cells.

We have attempted to use allografts of normal muscle precursor cells (mpc) to insert donor nuclei, containing a normal genome, into growing or regenerating skeletal muscle fibres of mice with an inherited deficiency of the enzyme phosphorylase kinase (PhK). Analysis of the glucose-6-phosphate isomerase (GPI) isoenzymes of treated muscles showed that myonuclei of donor origin became incorporated into host muscle fibres in 8 of 9 regenerating autografts, but PhK activity was found only in the 3 grafts into which the largest numbers (1-3 x 10(6)) of mpc had been implanted. Following injection of normal mpc into growing PhK-deficient skeletal muscle, mosaic fibres containing myonuclei of donor origin were detected in only 11 of 192 muscles examined from 64 mice, but, of these 11 muscles, 5 contained PhK activity detectable by two separate assays in a further 4 muscles activity was detected by one or other assay.

Animals↗