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Biomedical subjects

G Brown

Publications and source records attributed to G Brown.

At least 199 records · Page 11Linked to original sources
PubMed1995

What benefit can be derived from treating normocholesterolemic patients with coronary artery disease?

Controversy still remains regarding the possible clinical or arteriographic benefit of intensive lipid-altering therapy in patients who have coronary artery disease and apparently normal lipid levels. Resolution of this controversy appears to depend on an improved understanding of the role of variables other than total or low density lipoprotein cholesterol levels. A comparison of the "normolipidemic" subgroup of The Familial Atherosclerosis Treatment Study patients and The Harvard Atherosclerosis Reversibility Project patients indicates that low levels of high density lipoprotein cholesterol and elevated levels of apolipoprotein B appear to increase considerably the likelihood of benefit from intensive lipid-altering therapy. Other risk-related variables such as systolic blood pressure and lipoprotein(a) further contribute to the prediction of risk and possibly to the potential for treatment benefit.

Adult↗
PubMed1995

Down-regulation but not phosphorylation of stathmin is associated with induction of HL60 cell growth arrest and differentiation by physiological agents.

Stathmin is a cytosolic phosphoprotein that has an important but, as yet, undefined role in cell proliferation and differentiation. Induction of growth arrest and differentiation of HL60 cells to monocytes by phorbol 12-myristate 13-acetate is associated with rapid phosphorylation of the protein. Stathmin phosphorylation was not seen when HL60 cells were induced to differentiate to monocytes, by 1 alpha, 25-dihydroxyvitamin D3, and to neutrophils, by all-trans retinoic acid and granulocyte colony stimulating factor. In all the above instances, stathmin expression was down-regulated. Thus, increased stathmin phosphorylation is not required for cell growth arrest or differentiation or down-regulation of stathmin expression.

Blotting, Western↗
PubMed1995

Intracellular heteroplasmy for disease-associated point mutations in mtDNA: implications for disease expression and evidence for mitotic segregation of heteroplasmic units of mtDNA.

Studies in vitro have shown that a respiratory-deficient phenotype is expressed by cells when the proportion of mtDNA with a disease-associated mutation exceeds a threshold level, but analysis of tissues from patients with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) have failed to show a consistent relationship between the degree of heteroplasmy and biochemical expression of the defect. One possible explanation for this phenomenon is that there is variation of heteroplasmy between individual cells that is not adequately reflected by the mean heteroplasmy for a tissue. We have confirmed this by study of fibroblast clones from subjects heteroplasmic for the MELAS 3243 (A-->G) mtDNA mutation. Similar observations were made with fibroblast clones derived from two subjects heteroplasmic for the 11778 (G-->A) mtDNA mutation of Leber's hereditary optic neuropathy. For the MELAS 3243 mutation, the distribution of mutant mtDNA between different cells was not randomly distributed about the mean, suggesting that selection against cells with high proportions of mutant mtDNA had occurred. To explore the way in which heteroplasmic mtDNA segregates in mitosis we followed the distribution of heteroplasmy between clones over approximately 15 generations. There was either no change or a decrease in the variance of intercellular heteroplasmy for the MELAS 3243 mutation, which is most consistent with segregation of heteroplasmic units of multiple mtDNA molecules in mitosis. After mitochondria from one of the MELAS 3243 fibroblast cultures were transferred to a mitochondrial DNA-free (rho0) cell line derived from osteosarcoma cells by cytoplast fusion, the mean level and intercellular distribution of heteroplasmy was unchanged. We interpret this as evidence that somatic segregation (rather than nuclear background or cell differentiation state) is the primary determinant of the level of heteroplasmy.

Adolescent↗
PubMed1995

Variation in mitochondrial DNA levels in muscle from normal controls. Is depletion of mtDNA in patients with mitochondrial myopathy a distinct clinical syndrome.

Recent studies have identified a group of patients with cytochrome oxidase (COX) deficiency presenting in infancy associated with a deficiency of mtDNA in muscle or other affected tissue (Moraes et al 1991). We used a novel approach to compare the level of mitochondrial (mtDNA) compared to nuclear DNA in skeletal muscle from a group of patients and controls, based on dot blots that were hybridized with a mtDNA probe labelled with 35S[dCTP] and a reference nuclear DNA probe labelled with [32P]dCTP. The ratio of mtDNA to nuclear DNA varied in samples from different muscles of the same individual. Secondly, fetal muscle had very low levels of mtDNA compared to nuclear DNA, and data from older controls (cross-sectional rather than sequential) suggest that this increases rapidly over the first 3 months after birth and thereafter more slowly. Four patients with COX deficiency had levels of mtDNA that were below the age-specific range defined by 'normal' quadriceps muscle. The clinical features to two of these patients were similar to earlier case reports of mtDNA depletion. In three patients the clinical course was relatively benign compared to cases that have previously been described. Levels of mtDNA in skeletal muscle from some patients with other forms of muscle disease were also found to be low, suggesting that mtDNA depletion, possibly related to depletion of mitochondria, may be a relatively non-specific response of muscle to various pathological processes. However, there does appear to be a distinctive group of young patients with reduced cytochrome oxidase activity in muscle, in whom marked mtDNA depletion reflects the primary defect.

Adolescent↗
PubMed1995

Performance of the Gen-Probe amplified Mycobacterium tuberculosis direct test in a laboratory that infrequently isolates Mycobacterium tuberculosis.

The performance of the Gen-Probe Mycobacterium tuberculosis direct (MTD) test was assessed in a laboratory whose specimens were derived from a population with a low prevalence (1.3%) of tuberculosis. A total of 339 specimens from 113 patients were included in the study. Nine of 10 MTD positive samples were culture positive (smear positive, n = 7; smear negative, n = 1; smear not ordered, n = 2). The 10th MTD-positive sample, which was smear and culture negative, was from a patient whose two other study specimens were smear and culture positive and who had a clinical history consistent with tuberculosis. Prior to and following resolution of discrepant results, the sensitivities and specificities of the MTD test relative to culture were 100 and 99.7% and 100 and 100%, respectively.

Bacteriological Techniques↗
PubMed1995

Characterization and distribution of epidermal growth factor receptors in the skin and wool follicles of the sheep fetus during development.

We have determined the binding affinity and capacity and relative distribution of epidermal growth factor (EGF) receptors in the skin of the Merino sheep fetus before and during the development of the wool follicle population. Autoradiography of tissue sections incubated with [125I]EGF revealed that label was confined predominantly to the epidermis and dermoepidermal junction before follicle formation, at 30 and 55 d of gestation. During follicle initiation (Days 60 to 65), receptor activity was distributed over the epidermis, including the epidermal aggregations of primordia at the dermoepidermal junction. However, receptor concentrations, as revealed by grain counts of autoradiographs, were reduced in these regions when compared with 55-d skin. The receptor distribution over the epidermis and its derivatives did not alter during subsequent follicle development, although the intensity of labeling increased as the follicles matured. Specific receptor binding was not observed above background levels in the dermis and dermal papillae during all stages of follicle development. At follicle maturation, EGF receptors were widely distributed over the cells of the epidermis and the epidermal derivatives of the cutaneous appendages but were particularly localized in the sebaceous glands and outer root sheath (see also Wynn et al. 1989). EGF immunoreactive material has also been found at these sites (du Cros et al. 1992), suggesting an autocrine role for EGF in the regulation of cell function. It is likely that the differentiation-promoting activities of EGF may predominate over those of growth, because the receptor-bearing cells were not members of rapidly proliferating populations.

Animals↗
PubMed1995

Inflammatory pseudotumours in children: CT and ultrasound appearances with histopathological correlation.

Inflammatory pseudotumour is an uncommon benign lesion that presents in children and young adults. The rarity of these lesions, particularly at extrapulmonary sites, has resulted in poor documentation of its radiological manifestations. The casenotes, radiology and histology of five patients with inflammatory pseudotumour were reviewed. Two lesions were intra-abdominal, one oesophageal, one intrapulmonary and one lower limb. CT demonstrated inflammatory pseudotumours as well circumscribed masses of soft tissue density producing displacement of surrounding structures rather than local invasion. Sonography depicted these lesions as well defined masses with homogeneous echo patterns. Surgical removal resulted in dramatic symptomatic improvement.

Bronchial Diseases↗
PubMed1995

The role of intravenous contrast enhancement in magnetic resonance imaging of prostatic carcinoma.

Although magnetic resonance imaging (MRI) has been shown to be a promising technique for staging prostatic carcinoma, its accuracy in detection of extraprostatic spread and seminal vesical invasion is subject to considerable error. The role of dynamic MRI, following bolus intravenous contrast medium, in depicting carcinoma of the prostate was evaluated and the information provided by this technique compared with unenhanced images. Spin-echo T1-weighted, T2-weighted, bolus contrast enhanced and delayed post-contrast enhanced T1-weighted images were obtained in 20 patients with histologically proven adenocarcinoma of the prostate. Tumour was identified in all of the patients studied. When compared with unenhanced and delayed post-contrast enhanced images, dynamic bolus contrast enhanced images enabled the best definition of tumour within the gland in 50% of patients and demonstrated extracapsular spread more clearly in 80% of patients. It is concluded that dynamic bolus contrast enhancement may be useful in selected patients with prostatic carcinoma by enabling tumour margins to be depicted more clearly.

Aged↗
PubMed1995

Stathmin is expressed by the proliferating hepatocytes during liver regeneration.

Aim-To determine the liver cell populations that express the phylogenetically conserved cytosolic protein stathmin during liver regeneration.Methods-Double immunostaining for stathmin and the Ki67 antigen was performed on sections of formaldehyde fixed, paraffin wax embedded tissues from 31 liver specimens. These included a variety of disease conditions characterised by some degree of hepatocyte regeneration. Quantitative western blot analysis was performed on 22 of these specimens.Results-Variable amounts of stathmin protein were detected by western blotting in all of the specimens examined. Stathmin was not detected in three cases of histologically normal liver. On immunostaining, stathmin was demonstrated in a proportion of hepatocytes as well as lymphoid inflammatory cells and other tissue elements. In all cases most of these stathmin positive cells showed nuclear positivity for the Ki67 antigen.Conclusions-Stathmin is expressed by proliferating hepatocytes but not by resting hepatocytes. Thus, it is likely that the protein has a function important to cell proliferation as opposed to cell differentiation.

Journal Article↗
PubMed1995

Use of dreams in therapy: a survey of clinicians in private practice.

A literature review indicated a dearth of research on how dreams are used in therapeutic settings so a questionnaire was sent to a random sample of 500 members of the Florida Psychological Association to assess (a) the extent of dream use in therapy, (b) theoretical approaches applied to dream interpretation, and (c) basis for experience and expertise in dream work. Of the 500 potential clinicians, 228 returned survey forms for a response rate of 46%. Analysis indicated that 83% of the respondents used dream material at least occasionally in their practice and that Freudian and Gestalt approaches were most often used in dream interpretation. Interestingly, most respondents gained their 'experience' in dream work through self-study and continuing education workshops and seminars.

Adult↗
PubMed1995

Safety, immunogenicity, and pilot efficacy of Plasmodium falciparum sporozoite and asexual blood-stage combination vaccine in Swiss adults.

This study was part of a larger program to develop a vaccine effective against Plasmodium falciparum infection caused by sporozoites and clinical malaria caused by asexual blood stages. In a phase 1 study of safety and immunogenicity, two recombinant proteins (Ro 46-2717, a circumsporozoite [CS] protein) construct with a molecular mass of 35 kD, and Ro 46-2924, a merozoite surface antigen [MSA-2] construct with a molecular mass of 25 kD) adsorbed onto alum were injected in two low (20 micrograms) or two high (100 micrograms) doses in the right and left deltoid muscles of 33 healthy Swiss volunteers; six other volunteers received a placebo (alum alone). Twenty-six participants reported 51 immunization-related adverse events, mainly pain at the injection site. Mean antibody titers to CS protein and MSA-2 in an indirect immunofluorescence assay peaked four weeks after the second immunization without evidence of boosting (i.e., sharp increase in titer). By that time, 56% and 31% of the vaccinees seroconverted to CS protein and MSA-2, respectively, with the increase in MSA-2 titer being weaker than that for the CS protein. After a third immunization, five vaccinees volunteered to be challenged by three or four infective bites of Anopheles stephensi. Prepatent and incubation periods in all five were comparable with unvaccinated historic controls challenged under similar conditions, and all had symptoms of clinical falciparum malaria. We conclude that the vaccine components were safe and immunogenic but there was no evidence that this immunization regimen with the CS protein plus MSA-2 component was able to prevent infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Minimizing aminoglycoside toxicity by prescriber notification of prolonged therapy.

The development of aminoglycoside toxicity has been reported related to duration of exposure. To potentially reduce the duration of exposure to aminoglycosides, pharmacists documented, via a permanent note in the patient health record, the exposure and potential associated risks of any patient who received greater than 10 consecutive days or 20 days total within 3 months of aminoglycoside therapy at this institution. The impact of the notification on further aminoglycoside exposure was evaluated over two 6-month periods. Notification was successful in ending further aminoglycoside exposure in 25 of 57 patients. Continued aminoglycoside therapy primarily involved treatment of febrile neutropenia and endocarditis. Prevention of toxicity was suggested in the second evaluation period in which none of the patients, having therapy altered by the notification, developed toxicity versus 13 of the 40 other patients who developed a rise in serum creatinine concentration or a reduction in hearing acuity. The methodology that produced these positive results should be easily transferable to other institutions.

Aminoglycosides↗
PubMed1995

Particular combinations of signals, by retinoic acid and 1 alpha, 25 dihydroxyvitamin D3, promote apoptosis of HL60 cells.

The promyeloid cell line HL60, when grown in serum-free medium, is induced to differentiate towards either neutrophils or monocytes by treatment with particular concentrations of 9-cis retinoic acid (9-cis RA) and 1 alpha, 25 dihydroxyvitamin D3 (D3). We have investigated whether treatment of HL60 cells with 9-cis RA and D3 can lead to growth arrest and a failure to undergo cell differentiation. This occurred in two circumstances and HL60 cells died rapidly by apoptosis. First, treatment with 5 x 10(-7) M 9-cis RA and 1.25 x 10(-9)-3.1 x 10(-10) M D3 promoted growth arrest and apoptosis of HL60 cells. The amount of 9-cis RA alone promoted significant neutrophil differentiation of HL60 cells. The amounts of D3 alone promoted a very low level of monocyte differentiation. Treatment with each agent alone did not result in increased levels of apoptosis. Second, HL60 cells were treated with concentrations of 9-cis RA (5 x 10(-7) M) and D3 (3.9 x 10(-14) M) that were appropriate for induction of neutrophil differentiation. At the time when they were undergoing commitment to the neutrophil pathway of differentiation (days 1-2), an amount of D3 (1 x 10(-7) M) that promotes monocyte differentiation was added to the cultures. HL60 cells failed to differentiate and died by apoptosis. Hence, certain combinations of signals, elicited by 9-cis RA and D3, promote apoptosis of HL60 cells. This finding has important implications for the use of retinoids and D3 in differentiation therapy.

Apoptosis↗
PubMed1995

Stathmin expression is a feature of proliferating cells of most, if not all, cell lineages.

BACKGROUND: Stathmin is a phylogenetically conserved protein which was identified initially as a prominent cytosolic protein in hemopoietic cells, endocrine cells, brain, and testis. In these tissues, it has been suggested that the level of stathmin expression is important in development and cell proliferation. Furthermore, stathmin phosphorylation appears to be involved in the regulation of cell growth arrest, terminal differentiation, and hormone secretion. Elevated levels of expression of stathmin have been described in leukemia and lymphoma cells. The aim of this study was to characterize the distribution of cells that express the stathmin protein in a wide variety of normal human and rodent tissues. EXPERIMENTAL DESIGN: First, antisera against a synthetic stathmin peptide have been raised in rabbits and the specificity of these antisera confirmed by their reactivity with stathmin on 1-dimensional and 2-dimensional Western blots. Second, the most appropriate means of fixing tissues in order to stain stathmin has been investigated. Finally, using the optimized conditions of tissue fixation, the antisera have been used to immunostain sections taken from a wide variety of tissues. RESULTS: Immunopositivity was found in cells of all the lineages studied, with the stained cells present within the proliferating compartment of tissues. Conversely, most nonproliferating mature cells did not stain with the antisera to stathmin. The only nonproliferating cells that appeared to express stathmin were a subpopulation of glial cells, neurons, and anterior pituitary cells. CONCLUSIONS: It is proposed that stathmin is necessary for cell proliferation in most, or all, cell lineages and that its primary function relates to some aspect of cell division.

Animals↗
PubMed1995

Evaluation of myocardial infarction therapy at a Canadian tertiary referral hospital.

OBJECTIVE: To evaluate the appropriateness of acute and postmyocardial infarction (MI) treatment. DESIGN: A retrospective chart review. SETTING: Tertiary care teaching hospital. PATIENTS: All patients admitted with a potential MI or who experienced an MI during their hospital stay from November 18, 1991 to September 20, 1992. RESULTS: For acute treatment, thrombolytics, acetylsalicylic acid (ASA) and intravenous beta-blockers were used in 82%, 96% and 39% of eligible patients with a median time delay of 1.4, 4.4 and 1.8 h, respectively. For post-MI treatment, ASA, oral beta-blockers, warfarin and angiotensin-converting enzyme inhibitors were used in 93%, 68%, 50% and 71% of eligible patients, respectively. CONCLUSIONS: ASA use was considered acceptable while the other therapies were underused. The time delays in the initiation of therapies were also considered longer than desirable. Ongoing audit may aid in improving the quality of care in future patients with an MI.

Adrenergic beta-Antagonists↗