Biomedical subjects

M A Johnson

Publications and source records attributed to M A Johnson.

At least 253 records · Page 14Linked to original sources

PubMed1994

Lymphocyte activation in HIV-1 infection. II. Functional defects of CD28- T cells.

OBJECTIVES AND DESIGN: The expression of the accessory molecule CD28 was compared in various populations of T and natural killer (NK) cells from HIV-1-negative and HIV-1-positive individuals and correlated with activation using mitogens in vitro. METHODS: Multiparameter flow cytometric analysis using combinations of CD3 CD28 and other markers was performed together with absolute cell counting in peripheral blood. Blast transformation and proliferative responses were also quantitated using the Cytoronabsolute after stimulation with phytohaemagglutinin (PHA) and anti-CD3. CD28- cells were also purified to confirm the observations. RESULTS: In HIV-1-negative individuals > 90% of CD3+ T cells were CD28+ and responded to stimulation, while CD3- CD16+ CD57+ NK-like cells were CD28- and failed to respond. In HIV-1-positive individuals the expression of CD28 was greatly reduced and the proportion of CD3+CD28- T cells expanded. CD8 lymphocytosis was caused entirely by the accumulation of CD28- T cells and many of these expressed activation markers human lymphocyte antigen-DR, CD38 and CD45RO on their membrane and molecules such as TIA-1 and perforin, associated with cytolytic function, in their cytoplasm. The strong positive correlation (r = 0.66) between the lack of CD28 expression and the poor proliferation from HIV-1-positive individuals was confirmed by demonstrating that only CD28+ cells transformed into lymphoblasts and proliferated. Although the CD28- including CD3+ T cells transiently expressed CD25 (interleukin-2R alpha), they did not undergo blastogenesis or activation measured by bromodeoxyuridine uptake and died after 3-4 days in culture. These observations were confirmed in costimulation experiments with anti-CD2 and anti-CD28. CONCLUSION: In HIV-1 infection activated CD3+CD28- T cells accumulate but are unresponsive to mitogens and anti-CD28. These cells appear to represent terminally differentiated effector cells which fail to respond to further stimuli because of the absence of a CD28 second signal.

Adult↗

PubMed1994

Effects of high-dose oral acyclovir on herpesvirus disease and survival in patients with advanced HIV disease: a double-blind, placebo-controlled study. European-Australian Acyclovir Study Group.

OBJECTIVE: To determine the efficacy of high-dose oral acyclovir in preventing cytomegalovirus (CMV) and other herpesvirus disease in patients with advanced HIV disease and to evaluate its effect on patient survival. DESIGN: Double-blind, placebo-controlled randomized trial of up to 1 year's therapy. SETTING: Outpatient clinics in 16 hospitals in Europe and Australia. PARTICIPANTS: A total of 302 patients with Centers for Disease Control and Prevention stage IV HIV disease, seropositive for CMV and with CD4+ lymphocyte counts < or = 150 x 10(6)/l. INTERVENTIONS: Oral acyclovir (800 mg, four times daily) or matching placebo for 48 weeks. MAIN OUTCOME MEASURES: Time to development of CMV and other herpesvirus disease. Following the results of another study, the protocol was amended to make survival a second major endpoint. RESULTS: Acyclovir failed to reduce the incidence of CMV disease: the probability of developing CMV disease at 1 year was 0.24 and 0.23 in the placebo and acyclovir groups, respectively (P = 0.53). However, acyclovir significantly reduced the probability of dying at 1 year of follow-up (from 0.39 to 0.23; P = 0.018). As expected, acyclovir significantly reduced the incidence and frequency of herpes simplex virus disease. There were no notable differences between treatment groups in clinically adverse experiences and no changes in haematological parameters to indicate clinically significant drug-induced toxicity. CONCLUSIONS: High-dose acyclovir failed to reduce the incidence of CMV disease, but significantly reduced the probability of dying at 1 year of follow-up.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Flow cytometric analysis of the stimulatory response of T cell subsets from normal and HIV-1+ individuals to various mitogenic stimuli in vitro.

A novel technique is described which allows the study of the responses of T cell subpopulations stimulated in bulk cultures without interfering with cell-cell interactions. The number and phenotype of lymphoblasts developing following stimulation with phytohaemagglutinin (PHA), anti-CD3, staphylococcal protein A (SPA) and pokeweed mitogen (PWM) was determined in HIV-1- and HIV-1+ patients using a new five-parameter flow cytometric method. We found that normal T cells responded faster to PHA than to any of the other mitogens tested. The peak of the PHA response occurred on day 3, followed by anti-CD3 and SPA on day 4 and PWM mitogen on day 5. Although PHA and anti-CD3 stimulated up to 95% and 80% of lymphocytes, respectively, SPA and PWM stimulated only 40% and 30% of cells, respectively. A defective T cell response was observed in lymphocytes cultured from asymptomatic HIV-1+ patients compared with negative controls. This loss of response was related to a selective mortality of T cells following mitogenic stimulation, referred to as activation-associated lymphocyte death (AALD). The results showed that stronger mitogens (PHA and anti-CD3) induced AALD in a larger proportion (50-60%) of T cells than weaker mitogens such as SPA and PWM (30-40%), and that AALD affected different lymphocyte subsets to different extents. AALD occurred more frequently in total CD8+ and CD45RO+ T cells compared with CD4+ and CD45RA+ T cells, but memory CD4+ T cells were the population most severely affected in samples from HIV-1+ donors.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Transrectal ultrasound versus magnetic resonance imaging in the estimation of prostatic volume.

OBJECTIVE: To establish which method of determining prostatic volume (transrectal ultrasound [TRUS] or magnetic resonance imaging [MRI]) and which calculation formula give the most exact and least variable results; to determine the size and the source of the variability: and to establish which method is the more sensitive to drug-induced changes in prostate volume. PATIENTS AND METHODS: Prostatic size was estimated by TRUS and MRI in 21 patients treated medically (either active treatment or placebo) for benign prostatic hyperplasia. Each patient was examined at baseline, and after 3 months and 6 months of treatment. Prostatic volume was calculated at every visit using different formulae proposed in the literature. RESULTS: With some of these formulae, including the classical ellipsoid formula, there was a strong correlation (r > 0.8) between TRUS and MRI volume estimates. For others the correlation was much weaker, suggesting unreliability. MRI gave a significantly larger volume than TRUS because of larger values for the cephalocaudal and anteroposterior diameters. For patients on placebo the visit-to-visit variability of the prostate volume was 10-12% of the mean volume, whether calculated by TRUS or MRI. Part of this variability was apparently due to natural variation of prostate size. CONCLUSION: The classical ellipsoid formula is adequate for determining prostate volume. MRI and TRUS give different volumes. Visit-to-visit variability is similar for both methods and is partly due to real, natural variation. MRI is better able than TRUS to detect drug-induced changes in prostate volume.

Double-Blind Method↗

PubMed1994

Individual foods and food group patterns of the oldest old.

This study compares the dietary patterns of centenarians (n = 85) with sexagenarians (n = 76) and octogenarians (n = 83). A Daily Diet Diary was developed to code the responses of the 24-hour dietary recalls. Centenarians and octogenarians consumed a more varied (P < 0.05) diet, with higher (P < 0.01) consumption frequencies of milk and grains, and fewer (P < 0.01) skipped breakfasts than sexagenarians. However, centenarians also consumed high fat foods (P < 0.01), such as whole milk and biscuits, and coffee (P < 0.5) more frequently than the two younger cohorts. Several of the variations found in the food patterns among the three age groups may reflect cohort differences, rather than true antecedents for longevity.

Age Factors↗

PubMed1994

The influence of rural/urban residence on health in the oldest-old.

Differences between rural (n = 18) and urban (n = 66) centenarians are examined across the following variables: physical health, activities of daily living, mental health, and life satisfaction. Results demonstrate higher levels of morale in rural residents and higher levels of functional health as exhibited by urban elders. Qualitative data support trends of increased degrees of independence among the rural participants. The absence of robust differences in rural and urban centenarians is discussed in terms of a leveling-off effect.

Activities of Daily Living↗

PubMed1994

Nephrogenic diabetes insipidus secondary to lithium therapy in the postoperative patient: a case report.

Nephrogenic diabetes insipidus (NDI) presents a rarely encountered but challenging fluid management problem in the perioperative period. This case is that of a patient with a perforated duodenal ulcer and previously undiagnosed NDI who received standard preoperative and postoperative hydration with normal saline, causing hypernatremia and an inappropriate diuresis. The resulting hypernatremia and hyperosmolality required aggressive hypotonic fluid replacement to return to preoperative values. Though refractory to 1-desamino-8-D-argenine-vasopressin (dDAVP), thiazide diuretics and nonsteroidal anti-inflammatory agents have a role in managing selected patients. Early diagnosis with careful fluid and electrolyte management are critical in successful management of these patients in the perioperative period.

Adult↗

PubMed1993

Electroretinographic findings in iris neovascularization due to acute central retinal vein occlusion.

Electroretinograms (ERGs) were recorded in 94 patients with central retinal vein occlusion (CRVO). Of these 94, 11 had neovascularization of the iris (NVI) at the time of testing, 25 later developed NVI, and 58 did not develop NVI during a follow-up period that varied from 1 1/2 to 5 years. The ERG recorded at the patient's presentation visit predicted the occurrence of NVI in these patients with high sensitivity and specificity. The most predictive ERG parameters were the semi-saturation constant from intensity-response analysis (log K), and the implicit times of the scotopic a- and b-waves and the scotopic 30-Hz flicker response. These parameters were highly correlated, suggesting that the functional mechanism that places eyes at risk for NVI in CRVO is unidimensional. Paradoxically, the most likely candidate for this mechanism is photoreceptor sensitivity loss due to ischemia.

Acute Disease↗

PubMed1993

Predicting outcome in central retinal vein occlusion using the flicker electroretinogram.

OBJECTIVE: To evaluate the usefulness of the 30-Hz flicker electroretinogram (ERG) in predicting outcome in patients with central retinal vein occlusion using an automated system previously developed to measure parameters of the flicker ERG and using information about the a priori probability of developing neovascularization of the iris in central retinal vein occlusion. METHODS: Amplitude and timing were extracted from 30-Hz flicker ERGs of 76 patients with acute central retinal vein occlusion from a previous study. The ability of the ERG to predict the development of neovascularization of the iris based on derived parameters was measured using the area under the receiver operating characteristic curve. RESULTS: The predictive ability of the 30-Hz ERG amplitude, as judged by a two-alternative forced-choice procedure, was 92%. The corresponding value for implicit time was 89%. Using Bayes' theorem, we computed the probability of developing neovascularization of the iris based on a single 30-Hz flicker ERG measurement at initial patient presentation. CONCLUSIONS: The 30-Hz flicker ERG provides useful information about the patients with central retinal vein occlusion.

Dark Adaptation↗

PubMed1993

Cytochrome c oxidase activity in single muscle fibers: assay techniques and diagnostic applications.

Microphotometric enzyme assay was used to study cytochrome c oxidase activity in single human skeletal muscle fibers. The assay techniques combine the precise localization of enzyme activity provided by histochemical methodology with the precise quantitation of a sensitive assay system. Abnormalities of cytochrome c oxidase were investigated using microphotometric enzyme assay in 12 patients with Kearns-Sayre syndrome, chronic progressive external ophthalmoplegia, or Leigh's syndrome. Control values were obtained using muscle biopsy specimens from 20 juvenile and 18 adult subjects with no evidence of neuromuscular disease. In the patients with Leigh's syndrome due to cytochrome c oxidase deficiency, the abnormality was found to be expressed uniformly throughout the muscle fiber population. In contrast, patients with Kearns-Sayre syndrome or chronic progressive external ophthalmoplegia showed abnormal heterogeneity of cytochrome c oxidase activity. In many cases, extreme degrees of variability were seen, with fibers containing high activity adjacent to fibers with no detectable activity. Mitochondrial DNA analysis showed that most of the patients with Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia had major rearrangements of mitochondrial DNA. It was concluded that the extreme variability of cytochrome c oxidase activity detected using microphotometric enzyme assay was an indicator of a probable abnormality of mitochondrial DNA. Conversely, cytochrome c oxidase defects in muscle which show a homogeneous distribution are more likely to be associated with defects of the nuclear genome.

Adolescent↗

PubMed1993

The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy. II. Correlation of phenotype with genetic and protein abnormalities.

We have correlated a detailed clinical assessment of 67 patients with proven Becker muscular dystrophy with the results from genetic and protein analyses. There was an overall deletion frequency of 80%, rising to 92.6% in the large group of patients defined on clinical grounds as being of "typically" mild severity. The deletions in this group were all clustered in the region of the gene between exons 45 and 59; the most common deletion was of exons 45-47 and all but one started at exon 45. No similar deletions were seen in the patients with more severe disease, in whom the diverse genetic defects included a duplication and a very large deletion. Dystrophin patterns in the "typical" group were also very characteristic, and in both groups were as predicted from the genetic defect, the size of deletions being inversely proportional to the size of the protein produced.

Adolescent↗

PubMed1993

The variability of the b-wave of the electroretinogram with stimulus luminance.

We measured the variability of the b-wave of the electroretinogram as a function of stimulus luminance in two young normal individuals. We also estimated b-wave variability by examining residuals from Naka-Rushton curves fit to intensity-response data. The change of variability with amplitude was similar with both techniques. The standard deviation of b-wave amplitude rose with b-wave amplitude at low stimulus intensities. At higher intensities, the standard deviation of b-wave amplitude became constant. The point at which the standard deviation became constant was Log K for the eye, as determined by fitting the data with the Naka-Rushton equation. These changes suggest that the mechanisms underlying the growth of the b-wave with luminance change near Log K.

Adult↗

PubMed1993

The care and fitting of Naka-Rushton functions to electroretinographic intensity-response data.

We developed an automated system to estimate parameters of the Naka-Rushton function based on a heuristic model of the electroretinogram intensity-response series. Data from a population of patients with central retinal vein occlusion were used to examine the ability of the derived parameters to predict the development of neovascularization of the iris. The predictive performance of this automated system in central retinal vein occlusion is comparable to that of a human expert.

Adult↗

PubMed1993

Use of lambda gt11 and monoclonal antibodies to map the gene for the 60,000 dalton glycoprotein of infectious laryngotracheitis virus.

To localize the gene encoding the 60 kD glycoprotein (gp60) of infectious laryngotracheitis virus (ILTV), a library of the ILTV genome was constructed in the lambda gt11 expression vector. Twelve recombinant bacteriophages expressing gp60 epitopes as fusion products with beta-galactosidase were detected by immunoscreening with monoclonal antibodies specific for gp60. The ILTV DNA sequence contained in one of these recombinants lambda 24-4 was used as a hybridization probe for mapping the insert sequence on the viral genome. The gene for the gp60 was located at map unit 0.72-0.77 in the unique long region (UL) of the ILTV genome. The DNA sequence of the 1.2 kb insert of lambda 24-4 containing the gp60 epitope was determined. The majority of deduced gp60 amino acid sequence has no homology with any of the known alphaherpesvirus glycoproteins.

Amino Acid Sequence↗

PubMed1993

HIV infection in women.

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AIDS-Related Opportunistic Infections↗

PubMed1993

Identification of an infectious laryngotracheitis virus gene encoding an immunogenic protein with a predicted M(r) of 32 kilodaltons.

The nucleotide sequence of an infectious laryngotracheitis virus (ILTV) gene which maps immediately upstream from the glycoprotein 60 (gp60) gene was determined. The gene, designated p32, encodes a predicted polypeptide of 298 amino acids with an estimated M(r) of 32,000 daltons. The predicted protein sequence has four potential N-glycosylation sites and a signal sequence at the N-terminal region. Amino acid residues in the NH2-terminal region of the p32 protein exhibit similarity to glycoprotein X (gX) of pseudorabies virus (PRV) and its homolog in equine herpesvirus type 1 (EHV-1). Within the conserved (N-terminus) region, one putative N-linked glycosylation site and four cysteine residues are aligned in these proteins. These common structural features of the gX-like proteins were also found in glycoprotein G (gG) of human herpes simplex virus type 2 (HSV-2) and equine herpesvirus type 4 (EHV-4). High level bacterial production of the p32 protein was achieved by cloning the p32 open reading frame into a pGEX-2T expression vector. Western blot analysis of the fusion protein produced in E. coli using immune chicken sera confirms that p32 protein is of viral origin and is an immunogen in birds with infectious laryngotracheitis (ILT). An antiserum from chicken immunized with the fusion protein detected a substantial amount of p32 protein in the medium of ILTV-infected cells in Western blotting. Moreover tunicamycin treatment of cells infected with the virus indicated that p32 was glycosylated. This allows us to conclude that p32 is a glycoprotein and like gX of PRV accumulates in the medium of infected cells.

Amino Acid Sequence↗

PubMed1993

The effect of starting time on dexamethasone suppression test results in horses.

This study was conducted to investigate the effect of starting time on dexamethasone suppression test results in horses. Eight adult horses were used throughout the trial. Baseline cortisol levels were established by collecting cortisol levels twice daily, at 8:00 A.M. and 8:00 P.M. for 4 consecutive days. Morning baseline cortisol levels were 46.3 +/- 5.94 ng/ml, and evening baseline cortisol levels were 32.8 +/- 5.59 ng/ml. Although lower, the evening cortisol levels were not statistically different (P = 0.154) from the morning levels. Dexamethasone suppression tests initiated at either 9:00 A.M. or 9:00 P.M. were performed by collected a control blood sample, administering either 0.044 mg/kg dexamethasone or its vehicle intravenously and then collecting additional blood samples at 6, 12, 24, 36, and 48 hr after treatment. Mean cortisol levels at hr 0, 6, 12, 24, 36, and 48 after a dexamethasone injection given at 9:00 A.M. were 55.6 +/- 3.08, 6.4 +/- 2.05, 0.73 +/- 0.48, 11.0 +/- 5.82, 12.6 +/- 4.30, and 40.5 +/- 5.38 ng/ml respectively. Mean cortisol levels at hr 0, 6, 12, 24, 36, and 48 hr after a dexamethasone injection given at 9:00 P.M. were 45.0 +/- 6.03, 4.5 +/- 1.28, 0.20 +/- 0.12, 4.5 +/- 2.49, 23.4 +/- 5.88, and 29.5 +/- 6.61 ng/ml respectively. There was no statistical difference in cortisol values between A.M. and P.M. initiated tests at any hour post dexamethasone administration. There was no decrease in cortisol level after administration of dexamethasone vehicle.

Analysis of Variance↗

PubMed1993

Variability in clinical, genetic and protein abnormalities in manifesting carriers of Duchenne and Becker muscular dystrophy.

We have analysed the results of clinical assessment, X-inactivation status, deletion screening and dystrophin analysis in eight manifesting carriers of Duchenne and Becker muscular dystrophy (DMD and BMD). Only two had a prior family history of X-linked muscle disease, all had normal karyotypes and none were twins. Presentation varied from 2 to 25 yr and progression varied from a DMD-like severity to a very mild BMD-like course. In one girl the initial symptoms were restricted to learning difficulties. Where methods for assessing X-inactivation were informative, three patients showed an abnormal pattern. However, in one patient, the obligate carrier daughter of a BMD patient who had presented at the age of 2 yr, X-inactivation appeared normal in lymphocytes and muscle. While dystrophin analysis seems to be reliable in identifying manifesting carriers of DMD and BMD, the relationship between X-inactivation status, dystrophin analysis and phenotype is not simple.

Adolescent↗