Search PubMed⌕ Search

Biomedical subjects

M A Johnson

Publications and source records attributed to M A Johnson.

At least 235 records · Page 13Linked to original sources
PubMed1995

Presentation and clinical investigation of mitochondrial respiratory chain disease. A study of 51 patients.

Defects of the mitochondrial respiratory chain are associated with a great variety of clinical disorders. Whilst recognition of these conditions is increasing, the need for sophisticated biochemical and molecular studies has tended to limit both their investigation and diagnosis to a few specialist centres. Using a group of 51 patients with histochemically, biochemically and/or genetically defined respiratory chain defects, we have examined both the clinical heterogeneity of these disorders and how they may be investigated most effectively in non-specialist centres. We evaluated the use of the following routinely available clinical investigations--fasting intermediary metabolites (lactate, pyruvate, ketone bodies, etc.) in blood and cerebrospinal fluid, serum creatine kinase estimation, EMG, EEG, CT, MRI and histological/histochemical muscle biopsy analysis. Our studies show that, in addition to well-recognized syndromes (e.g. chronic progressive external ophthalmoplegia, mitochondrial encephalopathy lactic acidosis and stroke like episodes, and myoclonus epilepsy with ragged red-fibres, a significant number of patients present with non-specific encephalopathic disorders. Furthermore, even within those categories of respiratory chain disease which have been genetically defined, a wide variation of presenting symptoms and signs were found. Where there was initial doubt concerning the diagnosis, the following clinical features were helpful in suggesting respiratory chain disease: ophthalmoplegia; a maternal pattern of inheritance; the presence of myopathy or deafness in association with encephalopathy. Of the clinical investigations we assessed, elevated lactate in blood or cerebrospinal fluid and low density lesions in the basal ganglia were helpful in identifying patients with respiratory chain dysfunction. Histochemical analysis of muscle was, however, the single most useful investigation being diagnostic in patients with chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome and myopathy, and of significant importance in patients presenting primarily with central nervous system disease. The results of our study are used to discuss the most appropriate approach to diagnosis of this group of disorders.

Adolescent↗
PubMed1995

Edhazardia aedis (Microspora: Culicosporidae) effects on the reproductive capacity of Aedes aegypti (Diptera: Culicidae).

The influence of the microsporidium Edhazardia aedis (Kudo) on the survival and reproduction of its mosquito host, Aedes aegypti (L.), was studied in the laboratory. Survival, fecundity, egg hatch, and percentage of emergence for 4 gonotrophic cycles were compared for control and infected mosquitoes. Control females oviposited an average of 123.1 eggs over 4 gonotrophic cycles, 86.1% of which hatched, whereas infected females laid an average of 38.0 eggs with a 69.3% hatch. Emergence in progeny of infected female Ae. aegypti was significantly less than for control mosquitoes in all gonotrophic cycles. The reproductive capacity (Ro) for control and infected adults was 168.4 and 4.1, respectively, representing a decrease of 98.2%. Overall infection levels in progeny of infected females was 95.7%, of which 46.6% were lethal, larval infections. Infected female survivors were capable of initiating infections in F2 progeny. Wing length, often used as an indicator of fitness, was not significantly different between infected and control adults.

Aedes↗
PubMed1995

Distinct HIV-1 long terminal repeat quasispecies present in nervous tissues compared to that in lung, blood and lymphoid tissues of an AIDS patient.

OBJECTIVE: To investigate the phylogenetic relationship of HIV-1 proviral long terminal repeat (LTR) variants present in postmortem samples of lymph node, spleen, lung, dorsal root ganglion and spinal cord as well as in the peripheral blood of an HIV-1-infected patient dying with AIDS. DESIGN AND METHODS: Postmortem tissues were studied by a combination of histology, cell culture and molecular analyses. The patient had a stable CD4 count of 10 x 10(6)/I during the 12 months preceding death. A 540 base-pair fragment of the LTR including U3/R/U5 was amplified using polymerase chain reaction on proviral DNA from the five postmortem tissues and peripheral blood mononuclear cells obtained 2 months prior to death. The population of viral variants was determined by sequencing at least five plasmid clones of the amplicons. The relationship between the variants present in different body sites was investigated using molecular phylogeny methods. RESULTS: HIV-1 was present in all organs analysed and correlated with the presence of abnormal histology. Genetic variation leading to divergence from the consensus sequence was more frequently present in characterized transcription factor binding sites within the LTR (P < 0.0001) although the HIV-1 LTR quasispecies in the different body sites showed similar, relatively low levels of divergence (intra-organ median heterogeneity ranging from 0.0094 to 0.017). Phylogenetic analysis showed that the spinal cord and dorsal root ganglion harboured an LTR population genetically distinct from that present in other organs and more closely related to a previously characterized neurotropic strain of HIV (strain JRcsf). CONCLUSION: The independent clustering of HIV-1 LTR variants present in spinal cord and dorsal root ganglion shows that HIV-1 LTR evolution can occur in a compartmentalized fashion. The data show that the LTR is an important region to analyse in sequence variation studies of HIV since it may play a role in nervous tissue adaptation of HIV-1 and neuropathogenicity. Outgrowth of HIV-1 LTR variants that are most fit for the utilization of tissue-specific transcription factors can occur in the nervous tissue.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Antagonism of the effects of clonidine by the alpha 2-adrenoceptor antagonist, fluparoxan.

1. The effects of fluparoxan, an alpha 2-adrenoceptor antagonist, on the pharmacodynamic changes induced by clonidine were investigated in this placebo-controlled, double-blind, two-period, cross-over study in 16 healthy male volunteers (aged 19 to 44 years). 2. Subjects received either fluparoxan or placebo, twice-daily for 5 1/2 days (11 doses). One hour after the first and last dose of each treatment period, clonidine (200 micrograms) was infused intravenously over 5 min. 3. Indices of clonidine-mediated pharmacodynamic responses (growth hormone secretion, bradycardia, hypotension, xerostomia and sedation) were taken before and after clonidine infusion. Growth hormone secretion was assessed by quantifying serum growth hormone concentrations; sedation was assessed by both visual analogue scales (VAS) and by a visual psychomotor response meter, measuring critical flicker fusion (CFF). 4. The majority of subjects reported minor adverse events such as lethargy, headache and dry mouth following clonidine infusion. All adverse events were likely to be related to clonidine, as they occurred consistently between treatment groups. Fluparoxan has, however, in previous studies been reported to cause headache and light-headedness. 5. Prior to the clonidine infusion, fluparoxan caused small but statistically significant increases in systolic blood pressure (4 mm Hg) and salivary flow (approximately 30%) after both single and repeated doses. A small increase in heart rate (2 beats min-1) was seen after a single dose which was also statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Changes to alveolar macrophage phenotype in HIV infected individuals with normal CD4 counts and no respiratory disease.

BACKGROUND: It has previously been shown that HIV infected individuals with pneumonitis have identifiable abnormalities in alveolar macrophages obtained by bronchoalveolar lavage (BAL). In particular, alterations in the expression of alveolar macrophage surface antigens associated with macrophage function have been reported. To determine whether these changes reflect HIV infection or the respiratory episode itself, a population of HIV infected patients with no respiratory disease was studied. METHODS: Twenty two HIV antibody positive individuals with a peripheral blood CD4 count of > 400/microliters and 10 healthy volunteer controls underwent bronchoscopy and BAL. Cytospin preparations from the recovered cells were stained using immunoperoxidase and double immunofluorescence techniques with monoclonal antibodies RFD1, RFD7, EBM11/CD68 (mature macrophages), UCHM1/CD14 (monocyte marker), and HLA-DR (RFDR1). Differential cell counts were also performed. RESULTS: There was an increase in overall alveolar macrophage HLA-DR expression in the HIV population. This was not reflected in a change in the percentage of cells staining CD14 (monocytes) or CD68 (mature macrophages) positive. The relative proportions of cells staining RFD1 + RFD7- (inducer cells), RFD1 - RFD7+ (effector cells), and RFD1 + RFD7+ (suppressive cells) were unchanged between HIV and control groups. CONCLUSIONS: In a population of HIV infected individuals with normal CD4 counts and no respiratory disease there was an increase in overall alveolar macrophage HLA-DR expression which occurred independently of any alteration in the relative proportions of alveolar macrophage subpopulations.

AIDS-Related Complex↗
PubMed1995

Intestinal disaccharidase activity in human immunodeficiency virus disease.

BACKGROUND: The relationship between disaccharidase activity, progression of human immunodeficiency virus (HIV) disease, and diarrhoea and weight loss was investigated. METHODS: Forty-six HIV-positive patients ingested a solution of lactose, palatinose, sucrose, and lactulose after 24 h of dietary exclusion and overnight fasting, after which urine was collected for 10 h. Urinary disaccharide (activity) ratios-lactose/lactulose (L/LL), palatinose/lactulose (P/LL), and sucrose/lactulose (S/LL)-were measured by thin-layer chromatography. RESULTS: There was a significant decrease in disaccharidase activity (L/LL, P/LL, and S/LL) with advancing clinical stage of HIV disease (p < 0.05, Wilcoxon rank sum test) as well as decreasing CD4 count (p < 0.05, Spearman correlation). Patients with weight loss/diarrhoea also had significantly (p < 0.05) decreased disaccharidase activity compared with control but not as compared with AIDS patients. Anti-retroviral therapy did not influence disaccharidase activity. CONCLUSION: Impairment of disaccharidase activity occurs with advancing HIV disease, but its role in HIV patients with weight loss and diarrhoea remains to be determined.

Adult↗
PubMed1995

Modelling the relative metabolic occurrence of alkyl-nitrogen bond cleavage using structure-reactivity maps.

Over a broad range of tertiary N-methyl amines, whenever alkyl-nitrogen bond cleavage was observed, N-demethylation was also observed. Alkyl-nitrogen bond cleavage in rings, alkyl-nitrogen bond cleavage if the carbon of the N-dealkylation reaction-site is in a ring and the nitrogen atom of the reaction-site is not in a ring, and dedimethylamination are not likely to occur relative to N-demethylation. Structure-reactivity relationships for other N-dealkylations, such as N-debenzylation, N-dethiophenation, and N-dedimethylaminoethylation of tertiary amines were evident from a visual inspection of the structure-reactivity map. Structure-reactivity maps proved to be a useful tool for ascertaining structural environments influencing the relative occurrence of alkyl-nitrogen bond cleavage in tertiary N-methyl amines.

Biotransformation↗
PubMed1995

Sequence characteristics of a gene in infectious laryngotracheitis virus homologous to glycoprotein D of herpes simplex virus.

An infectious laryngotracheitis virus (ILTV, gallid herpesvirus 1) gene homologous to glycoprotein D of herpes simplex virus (HSV) was identified and characterized by its nucleotide and derived amino acid sequence. The ILTV gD gene is located in the unique short region (U(s)) and contains an open reading frame capable of specifying a polypeptide of 380 amino acids, including N- and C- terminal hydrophobic domains consistent with signal and anchor regions respectively, and no potential sites for N-glycosylation. Alignment of the amino acid sequence with those published for HSV gD, equine herpesvirus type 1 (EHV-1) gD, pseudorabies virus (PRV) gp50, Marek's disease virus (MDV) gD, herpesvirus of turkeys (HVT) gD and bovine herpesvirus type 1 (BHV-1) gD showed similarities over the N-terminal region, with the greatest differences occurring in the C-terminal. The identical positioning of 6 cysteine residues supports the hypothesis of common ancestry of herpesvirus family (McGeoch, 1990) and is consistent with the essential role of this glycoprotein.

Amino Acid Sequence↗
PubMed1995

Extra-adrenal pheochromocytoma in pregnancy: ultrasonography and magnetic resonance imaging findings.

The authors describe a 24-year-old woman with extra-adrenal pheochromocytoma during pregnancy. Initial ultrasonography (US) at 27 weeks gestational age failed to show the pheochromocytoma, which was subsequently found by US at 35 weeks gestational age. Magnetic resonance imaging (MRI) provided diagnostic confirmation, as well as important information used by the obstetrician and the surgeon in operative planning.

Abdominal Neoplasms↗
PubMed1995

Presence of CD3+CD8+Bcl-2(low) lymphocytes undergoing apoptosis and activated macrophages in lymph nodes of HIV-1+ patients.

Infection with human immunodeficiency virus 1 causes profound changes in the lymph nodes of infected patients. In particular, large numbers of CD8+CD45RO+ T cells infiltrate both the paracortex and the germinal centers. These cells contained the cytotoxic granule-associated protein TIA-1 but showed no detectable levels of perforin and shared the same characteristics of the expanded, activated, short-lived CD8+ population found during acute viral infections. These cells expressed low levels of Bcl-2 and are likely to be short-lived in vivo as evidenced by the direct observation of CD8+ apoptotic cells in the paracortical areas of the infected nodes. Changes in the paracortical nonlymphoid populations were also seen. There were reactive changes in the blood vessels, and the macrophage population was expanded and activated. Furthermore, apoptotic bodies were seen in the cytoplasm of the activated CD68+RFD-7+RFD-1+ macrophages pointing to the phagocytic capacity of these cells and their role in the clearance of the apoptotic cells from the tissues. These observations suggest that the persistance of CD8+ population in human immunodeficiency virus 1 infection is not a result of the presence of an abnormal CD8+ population but rather a result of an inappropriate over-stimulation of the CD8+ cells.

Adult↗
PubMed1994

HHV-6 in AIDS.

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗
PubMed1994

Biosynthesis of monoterpenes: partial purification, characterization, and mechanism of action of 1,8-cineole synthase.

Geranyl pyrophosphate: 1,8-cineole cyclase (cineole synthase) catalyzes the conversion of geranyl pyrophosphate to the symmetrical monoterpene ether 1,8-cineole (1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane) by a process thought to involve the initial isomerization of the substrate to the tertiary allylic isomer, linalyl pyrophosphate, and cyclization of this bound intermediate to the alpha-terpinyl carbocation that is subsequently captured by water and undergoes heterocyclization to the remaining double bond. The enzyme was isolated from the secretory cells of the glandular trichomes of Salvia officinalis (garden sage) and partially purified, and the properties of this monoterpene cyclase, previously determined in crude cell-free extracts, were reexamined. These properties (pH optimum, divalent metal ion requirement, molecular weight, pI) were similar to those determined previously with the exception of substrate utilization; geranyl pyrophosphate was shown to be a more efficient substrate than the cis-isomer, neryl pyrophosphate, in the absence of competing phosphatase activity that contaminated earlier preparations of this enzyme. As with other monoterpene cyclases of herbaceous species, cineole synthase was inhibited by cysteine- and histidine-directed reagents, and protection against inactivation was provided by the substrate-metal ion complex. Studies with 18O-labeled acyclic precursors and H(2)18O, followed by mass spectrometric analysis of the product, confirmed that water was the sole source of the ether oxygen atom of 1,8-cineole. The electrophilic nature of the coupled isomerization-cyclization reaction was examined with a series of substrate and intermediate analogues. The overall stereochemistry of the cyclization of geranyl pyrophosphate to the symmetrical monoterpene was established by determining the enantioselectivity for (3R)- or (3S)-linalyl pyrophosphate as an alternative substrate and by oxidation of [3-3H]1,8-cineole, derived from [1-3H]geranyl pyrophosphate, to (+/-)-3-keto-1,8-cineole and radio-GLC separation of diastereomeric ketal derivatives to determine the labeled enantiomer.

Carbon-Carbon Lyases↗
PubMed1994

Electrophysiologic and electroretinographic evidence for photoreceptor dysfunction as a toxic effect of digoxin.

PURPOSE: To investigate photoreceptor dysfunction caused by digoxin toxicity. METHODS: First, a patient who experienced toxic side effects from digoxin was studied acutely by serial electroretinography and later during convalescence. Second, the light responses of isolated photoreceptors exposed to varying amounts of digoxin were studied in vitro. RESULTS: Electroretinographic amplitudes were reduced and implicit times were delayed when digoxin levels were elevated and recovered slowly after return to normal digoxin levels. Isolated photoreceptors exhibited concentration-dependent reductions in the magnitude of the light response during digoxin exposure, suggesting reduction in the dark current due to blockade of the sodium-potassium-adenosine triphosphatase pump. Cones were about 50-fold more sensitive than rods. CONCLUSIONS: Reversible rod and cone dysfunction occur during exposure to toxic levels of digoxin. Photoreceptor dysfunction is probably due to the diminution of the dark current in response to the sodium-potassium-adenosine triphosphatase blockade.

Ambystoma↗
PubMed1994

Methodologic dependence of electroretinogram oscillatory potential amplitudes.

The International Society for Clinical Electrophysiology of Vision (ISCEV) protocol for eliciting oscillatory potentials uses a considerably lower flash intensity and a different preconditioning stimulus than the only oscillatory potential protocol used to predict progression of diabetic retinopathy. To determine if the ISCEV protocol will be useful in predicting progression of diabetic retinopathy, summed oscillatory potential amplitudes were measured by both protocols in a population of diabetics. Summed oscillatory potential amplitudes measured by the ISCEV protocol, although smaller, are highly correlated with the summed oscillatory potential amplitudes measured with the higher-intensity flash. Thus, summed oscillatory potential amplitudes measured with the ISCEV protocol should be useful in predicting outcome in diabetic retinopathy. Different signal processing filters used to extract oscillatory potentials from the electroretinogram waveform have a small, but significant, effect on summed oscillatory potential amplitude. Use of the caliper-square method or the summed peak-to-trough method for measuring oscillatory potential heights had an insignificant effect on measured oscillatory potential amplitude.

Adult↗
PubMed1994

An analysis of the relative occurrence of N-demethylation and N-oxidation in xenobiotic metabolism using structure-reactivity maps.

The relative occurrence of N-demethylation and N-oxidation in a structurally diverse set of N-methyl tertiary amines was examined using structure-reactivity maps. A structure-reactivity map of the data indicated important structural features useful for predicting the relative occurrence of these reactions. A steric index which describes the degree of steric hinderance at the N-methyl reaction site is defined. A QSAR between the relative occurrence of N-demethylation and N-oxidation of N-methyl tertiary amines and the steric index was developed.

Animals↗
PubMed1994

Cytotoxic T lymphocyte and antibody responses generated in rhesus monkeys immunized with retroviral vector-transduced fibroblasts expressing human immunodeficiency virus type-1 IIIB ENV/REV proteins.

The immune response against human immunodeficiency virus type-1 (HIV-1) is believed to play a role in controlling the early stages of disease progression. The cellular immune response, in particular cytotoxic T lymphocyte (CTL) activity, may be important for eliminating virally infected cells in HIV-1-infected individuals. Genetic immunization using retroviral vectors provides an effective means of introducing antigens into the antigen presentation pathways for T cell stimulation. A nonreplicating, amphotropic murine retroviral vector containing the HIV-1 IIIB env gene has been used to transduce primary rhesus monkey fibroblasts for the expression of HIV-1 antigenic determinants. Rhesus monkeys were immunized with four doses of either vector-transduced autologous fibroblasts (VTAF) expressing the HIV-1 IIIB ENV/REV proteins or nontransduced autologous fibroblasts (NTAF) administered at 2-week intervals. The animals were evaluated for both the induction of HIV-1-specific immune responses and potential toxicity associated with this ex vivo treatment. The VTAF-immunized monkeys generated CTL responses specific for HIV-1 ENV/REV expressing autologous target cells, whereas, NTAF-immunized monkeys showed negligible CTL activity. The cytotoxic activity was mediated by CD8+, major histocompatibility complex (MHC)-restricted CTL. In addition, antibody responses directed against the HIV-1 gp120 protein were also detected in the sera of VTAF-immunized monkeys. Clinical and histopathological evaluation of immunized monkeys showed no evidence of significant adverse events. Several animals that received either VTAF or NTAF had detectable anti-cytoplasmic antibodies, but were not positive for anti-nuclear antibodies or rheumatoid factor. Subsequent evaluation of renal, synovial, and hepatic tissue samples from these monkeys revealed no autoimmune disease-associated lesions. This study demonstrates the safety and ability of autologous retroviral vector-transduced cells expressing HIV-1 IIIB ENV/REV proteins to stimulate immune responses in a non-human primate model, and provides a basis for this form of genetic immunization in HIV-infected humans.

AIDS Vaccines↗
PubMed1994

Iron nutriture in elderly individuals.

The purpose of this review is to examine current research on the iron status of the elderly and factors that influence the body burden of iron. Studies of noninstitutionalized elderly individuals report mean iron intakes that meet current Recommended Dietary Allowances for iron. Dietary practices that may decrease iron bioavailability, and hence iron stores in the body, include low intakes of ascorbic acid or high intakes of calcium, and decreased consumption of highly available iron from meat, fish, and poultry. Although not well documented, the effect of age on iron absorption and iron excretion appears to be small, and body stores of iron increase with age. It is difficult to estimate the prevalence of iron deficiency in elderly persons, because impaired iron status can be the result of iron deficiency or chronic disease. Further study is necessary to determine whether red blood cell ferritin and serum transferrin receptors may be useful biochemical markers to differentiate the anemia of chronic disease from iron deficiency anemia. Hereditary hemochromatosis is a genetic disease that greatly increases the body burden of iron and the risk of hepatic disease among homozygotes. Because iron deficiency or iron excess may impair health, the role of iron in diseases associated with aging such as depressed immune response, neurological dysfunction, cancer, and heart disease is discussed.

Absorption↗