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Biomedical subjects

J Levy

Publications and source records attributed to J Levy.

At least 235 records · Page 13Linked to original sources
PubMed1993

Photodynamic elimination of clonogenic Ph+ chronic myeloid leukemia cells.

Benzoporphyrin derivative (BPD) and light is a potent photosensitizer. We investigated this modality as a means to selectively eliminate clonogenic Ph(+) chronic myeloid leukemia (CML) cells. BPD at 10 ng/ml and 10.8 J/cm2 broad spectrum light eliminates from 5 to 6 logs of Ph(+) EM-2 cells. Long-term marrow culture studies of treated mixtures of normal and CML cells indicate that multipotent progenitor cell viability is retained while cells transcribing BCR-ABL are not detected. We conclude that BPD and light may offer a means of providing CML autografts potentially free of Ph(+) clonogenic cells.

Adult↗
PubMed1993

Pediatric femur fractures: an overview of treatment.

Femur fractures in the pediatric population are common injuries which may be either isolated or associated with polytrauma. The orthopedist is faced with treatment options ranging from skin traction to more aggressive methods, including internal or external fixation. We review the pros and cons of current treatment options. A simple treatment algorithm based on age of the patient, other associated injuries, and open vs closed injury is presented.

Adolescent↗
PubMed1993

Podocytic cytoskeletal disaggregation and basement-membrane detachment in puromycin aminonucleoside nephrosis.

Puromycin aminonucleoside--(PAN) treated rats develop acute nephrotic syndrome, mimicking human minimal lesion disease. In PAN nephrosis, podocyte detachment from the glomerular basement membrane (GBM) is the most likely cause of massive proteinuria in this model. To elucidate further the mechanisms of PAN-induced cellular dysfunction, new methods were employed to visualize podocyte cytoskeletal aggregation and to measure fibrillar attachment to the GBM. Adult Sprague-Dawley rats (n = 4/group) received a single tail-vein injection of PAN (75 mg/kg). On days 1, 2, 3, and 5 following injection, 24-hour urine collections were obtained for creatinine clearance, albuminuria, and total proteinuria. Then kidneys from each group were fixed by perfusion. Podocytic cytoskeleton was visualized by scanning electron microscopy. Subepithelial GBM staining and attachment fiber number, observed on digitized images of transmission electron micrographs, were quantitated with computer-based density analysis. A significant reduction in attachment fiber number in the GBM lamina rara externa occurred by day 5. On scanning electron micrographs, the secondary and tertiary podocytic processes were observed to be formed by highly aggregated cytoskeleton, which became partially disaggregated by day 3, was totally absent by day 5, and normalized by day 20. Immunogold staining revealed that actin and vinculin localized to the tertiary podocytic processes in the normal state were dispersed into the cell body following PAN. Podocyte cytoskeletal disaggregation precedes, and detachment from the GBM occurs simultaneously with, the onset of massive proteinuria in the PAN model.

Actins↗
PubMed1992

Childhood living conditions and Helicobacter pylori seropositivity in adult life.

Infection with Helicobacter pylori increases an individual's risk of peptic ulceration and gastric cancer. In the developed world, prevalence of infection rises with age and varies with social class. We used a cross-sectional study design to test the hypothesis that H pylori infection would be more closely associated with childhood living conditions than with current socioeconomic status. Prevalence of IgG antibodies against H pylori was determined with an enzyme-linked immunosorbent assay in 215 subjects (median age 46 years, range 18-82) attending a health-screening clinic in London. Seropositivity varied from 9% (age less than 30) to 67% (greater than or equal to 70). Subjects were asked about their living conditions at present and when they were aged 8 years. Absence of a fixed hot-water supply (p = 0.0005) and domestic crowding (p = 0.0005) in childhood were powerful independent risk factors for current infection with H pylori. Among current living conditions, only the number of children living in the household was independently associated with H pylori infection (p = 0.004). Most British adults infected with H pylori probably became infected by household contact in childhood.

Adult↗
PubMed1992

Direct effects of luteinizing hormone-releasing hormone agonists and antagonists on MCF-7 mammary cancer cells.

The binding of luteinizing hormone-releasing hormone (LH-RH) analogues to the human mammary tumor cell line MCF-7 and their effect on the cell proliferation was studied to elucidate their direct action on estrogen-dependent mammary tumors. The growth rate of these cells was doubled by the addition of 1 nM estradiol to cells maintained in an estrogen-deficient medium. Although the basal growth rate was only slightly inhibited by the LH-RH antagonist [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-RH (SB-75), the estrogen-stimulated growth was completely abolished by the antagonist. In contrast, the LH-RH agonist buserelin stimulated cell growth in estrogen-deficient medium, whereas it had no effect in the presence of estrogen. 125I-labeled buserelin was used for the measurement of LH-RH receptors on MCF-7 cells. A Scatchard plot analysis of buserelin-specific binding revealed a nonlinear plot, which suggested the presence of one high-affinity binding site with a Kd of 1.4 +/- 1.0 nM and the remaining sites with low affinity (Kd = 1.3 +/- 1.0 microM). The binding of 125I-labeled buserelin was displaced equally well by unlabeled buserelin and by the LH-RH antagonist SB-75, suggesting that both analogues are bound to the same receptor. When parallel experiments were performed with 125I-labeled SB-75, the binding was displaced by unlabeled SB-75 and other antagonists, but only partially displaced by unlabeled buserelin. The results suggest that in these mammary tumor cells there is a LH-RH antagonist binding site that is not recognizable by LH-RH agonists. This hypothesis was tested by measuring cell growth in the presence of both agonists and antagonists. It was found that SB-75 inhibited the stimulation of growth by buserelin, but buserelin did not prevent the inhibition by the antagonist of the estrogen-dependent growth. These results suggest that antagonists directly inhibit mammary tumor growth, not only by competing with LH-RH high-affinity receptors, but also by other mechanisms mediated by low-affinity antagonist binding sites.

Antineoplastic Agents↗
PubMed1992

Determination of yohimbine and its two hydroxylated metabolites in humans by high-performance liquid chromatography and mass spectral analysis.

The existence of at least two metabolites of yohimbine (YO) in humans is demonstrated. Combined high-performance liquid chromatographic (HPLC), NMR and mass spectral analyses permitted them to be identified as hydroxylated metabolites at the C-10 and C-11 positions. A normal-phase HPLC method allowing the simultaneous determination of YO and its main metabolite, 11-hydroxyyohimbine (11-OHYO), in biological samples is described. This assay was performed using a LiChrosorb Si 60 column and a mobile phase consisting of 0.02 M sodium acetate (pH 5)-methanol (5:95, v/v) at a flow-rate of 1 ml/min. Detection was achieved by a fluorimetric method (excitation at 280 nm and emission at 320 nm). The extraction yields of YO, 10-OHYO and 11-OHYO from plasma were 91.8, 45.3 and 17.8%, respectively, and their respective within-day reproducibilities were 3.8, 1.4 and 5.9%. The between-day reproducibility for YO at the concentrations of 1 and 10 ng/ml were 8.9 and 6.4%, respectively. The accuracy of the method for YO at concentrations of 1 and 10 ng/ml were 5.1 and 2.3%, respectively. The limits of determination of YO, 10-OHYO and 11-OHYO were 0.1, 0.5 and 1 ng/ml, respectively. The method was used in bioavailability study of YO following oral and intravenous administration in humans.

Biological Availability↗
PubMed1992

Integrated plasma cortisol concentration in children with asthma receiving long-term inhaled corticosteroids.

We assessed the effect of long-term therapy with inhaled beclomethasone dipropionate (BDP) on the pituitary-adrenal axis, by measuring the integrated concentration (IC) of plasma cortisol in eight children with asthma (age, 6-16 years) who regularly used inhaled BDP in doses ranging from 8 to 26.5 micrograms/kg (200-450 micrograms/day) for 6 months to 4 years. The control group included six children (age, 6-16 years) who had the IC of plasma cortisol measured as part of an endocrinological evaluation and were found to be healthy. Cortisol concentration was measured in blood samples collected continuously over a 24-hr period. Mean IC of plasma cortisol in the study group was significantly lower than in the healthy controls (mean +/- SD, 4.9 +/- 3.3 vs 9.1 +/- 1.9 micrograms/mL; P less than 0.02). Cortisol response to 0.25 mg ACTH (iv) was abnormal in one of the eight BDP-treated patients. No correlation was found between IC of plasma cortisol and the BDP dose, severity of asthma, height percentile, or the Tanner stage. We conclude that long-term therapy, even with relatively conventional doses of inhaled BDP may cause reduction in the normal physiological secretion of cortisol. The clinical relevance of low IC of plasma cortisol is not clear, but it may reflect partial suppression of the pituitary-adrenal axis.

Administration, Inhalation↗
PubMed1992

Campylobacter enteritis in Portugal: epidemiological features and biological markers.

From 1984 to 1989, stool samples from 2811 gastroenteritis cases were examined for the presence of Campylobacter jejuni and C. Coli, Salmonella, Shigella and Yersinia species. Isolation rates were: Campylobacter jejuni and C. Coli, 5.3%, Salmonella spp., 14.8%, Shigella spp., 4.6% and Yersinia enterocolitica, 1.1%. Age group distribution analysis shows a higher Campylobacter isolation rate in children under one year of age. Seasonal distribution revealed a peak incidence in winter as in other Mediterranean countries. Predominant biotypes were C. jejuni I (51%), C. jejuni II (21.5%) and C. coli I (18.8%). Antimicrobial susceptibility testing did not reveal resistance to erythromycin. Thirty of the strains harboured plasmids with 7 different profiles.

Adolescent↗
PubMed1992

Visual field differences for clockwise and counterclockwise mental rotation.

Geometric line drawings were presented to normal subjects in the left visual field (LVF) or right visual field (RVF) at various degrees of rotation from a centrally presented vertical standard. The task of the subject was to indicate with a reaction time (RT) response whether the laterally presented stimulus could be rotated into the vertical standard or if it was a rotated mirror image of the standard. In Study 1, an overall right hemisphere superiority was found for RT and accuracy on match trials. Most interestingly, interactions between Visual Field and Rotation Angle for the match accuracy data and between Visual Field and Direction of Rotation (clockwise or counterclockwise) for the match RT slopes were found. These interactions suggested that clockwise rotations were more readily performed in the LVF and counterclockwise rotations in the RVF, consistent with other literature for mental rotation. The purpose of Study 2 was to replicate this finding of visual field differences for rotation direction using a design in which direction and degree of rotation were varied orthogonally. No main effect of Visual Field was found. However, significant interactions between Visual Field and Rotation Angle were found for both RT and accuracy, confirming the presence of visual field differences for rotation direction in a new sample of subjects. These differences were discussed in terms of the possibly greater relevance of medially directed stimuli and a possible hemispheric bias for rotation direction, and in terms of interhemispheric transmission factors.

Adolescent↗
PubMed1992

Guanine nucleotide modulation of high affinity gonadotropin-releasing hormone receptors in rat mammary tumors.

We previously suggested that gonadotropin-releasing-hormone (GnRH) analogues activate the phosphoinositide pathway in rat mammary tumor membranes. In the present study we analyzed the binding of GnRH analogues to these membranes and assessed its modulation by guanine nucleotides. [125I]Buserelin (a GnRH superagonist) binding is specific because it is displaced only by GnRH analogues. Scatchard plot analysis reveals high affinity binding sites (Kd = 2.5 +/- 0.8 nM, Bmax = 250 +/- 120 fmol/mg membrane protein) and low affinity binding sites (Kd 1.1 +/- 0.3 microM, Bmax = 200 +/- 105 pmol/mg membrane protein). Guanine nucleotides increased the ED50 of [125I]buserelin displacement, and almost completely eliminated the high affinity binding. Similar results were obtained with [125I]D-Trp6-GnRH--another GnRH superagonist. The inhibition of buserelin binding by guanine nucleotides was specific for nucleotides that interact with G-binding proteins and was dose-dependent with a maximal effect at 10 microM GTP gamma S. Kinetic analysis of buserelin binding revealed that the dissociation rate increased at least 4-fold in the presence of 10 microM GTP gamma S. These results support the hypothesis that GnRH analogues interact directly with mammary tumors and activate a G-protein-dependent transducing mechanism.

Animals↗
PubMed1992

Gonadotropin-releasing hormone specific binding sites in normal and malignant renal tissue.

Renal cell carcinoma has been reported to contain estrogen and progesterone receptors. Thus, it has been suggested that these tumors are hormone dependent in a similar manner described for the breast and prostate cancers. It has been recently shown that mammary and prostate tumor cells contain gonadotropin-releasing hormone (GnRH) receptors and are growth inhibited directly by GnRH antagonists. In this study we examined for the presence of GnRH, estrogen and progesterone receptors in normal and malignant renal tissues. Estrogen receptors were found both in the normal and malignant kidney while progesterone receptors were present only in the normal tissue. Specific binding of [125I]buserelin, a GnRH agonist, was evident in renal carcinoma and in normal kidney and was displaced with equal efficiency by unlabeled buserelin and by D-Trp6-GnRH, but not by unrelated peptides such as thyrotropin releasing hormone and oxytocin. The non-linear scatchard curve obtained for buserelin binding, suggests the presence of at least two binding sites, one with high affinity in the nanomolar range and another in the micromolar range.

Buserelin↗
PubMed1992

Photodynamic inactivation of retrovirus by benzoporphyrin derivative: a feline leukemia virus model.

The ability of a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), and either broad-spectrum (400-1200 nm) or narrow-band (600-700 nm) red light to kill feline leukemia virus (FeLV) and FeLV-infected cat T cells (cell line 3201) was investigated in culture medium containing fetal calf serum and in blood from infected cats. A molecular clone of FeLV, 61E, is minimally pathogenic and productively infects 3201 cells while causing no change in rate of cell division, viability, or size. Active virus (either free or within infected cells) was quantified by using a limiting dilution assay that involved cocultivation of test samples with naive 3201 cells, after which either the polymerase chain reaction or a reverse transcriptase assay was used to detect the presence of virus. It was shown that 61E-infected T cells in culture were slightly more sensitive to photodynamic killing than were uninfected cells. Infected cells and free virus were eliminated from whole blood taken from infected cats by using 4 micrograms per mL of BPD-MA and 40 J per cm2 of red light. These results correlate well with previous results with BPD-MA and vesicular stomatitis virus in whole human blood and suggest that this photosensitizer is a promising agent for the elimination of retroviruses that are either free or located within infected cells in blood.

Animals↗
PubMed1992

A protective role of 1,25-dihydroxyvitamin D3 in chemically induced rat colon carcinogenesis.

The intriguing observation has been made that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] receptors are present in tissues not involved in calcium homeostasis and that 1,25(OH)2D3 exerts an antiproliferative, differentiation-promoting action in a variety of cancer cell lines, including cells of the large intestine. It was therefore deemed of interest to study 1,25(OH)2D3 expression and biological activity in a murine model of colon carcinogenesis. Colon carcinogenesis was induced in male rats by the sequential administration of 1,2-dimethylhydrazine dihydrochloride (DMH). Levels and binding characteristics of 1,25(OH)2D3 receptors were assessed in control and DMH-treated rat colonic mucosal high-speed supernatants. In concurrent studies, 1,25(OH)2D3 was administered (s.c., 400 ng/rat) prior to, together with and after DMH challenge and the activity of ornithine decarboxylase (ODC), a growth-related DMH-induced enzyme, was determined in colonic cytosols. Serum Ca2+ levels were measured concurrently. Rats submitted to identical treatment schedules were killed 10 weeks after termination of DMH administration and the whole colon was opened and examined for tumors. The results show that (i) rat colonic mucosa possesses a single class of high-affinity 1,25(OH)2D3 receptors; (ii) DMH administration provokes a marked reduction (50%) in 1,25(OH)2D3 binding sites without affecting Kd values; (iii) DMH administered concurrently with 1,25(OH)2D3 suppressed the vitamin D-induced hypercalcemia and restored serum Ca2+ concentrations to basal levels; and (iv) 1,25(OH)2D3 delivered prior to DMH challenge obliterated the typical DMH-induced early colonic ODC activity peak and markedly reduced (50%) the number of colon adenocarcinomas. The present findings indicate that a colon-specific potent carcinogen interferes with the biological expression of 1,25(OH)2D3 and that vitamin D administered prior to a carcinogenic insult is able to reduce significantly the incidence of colon tumors, presumably acting as an antiproliferative or differentiation-promoting agent.

1,2-Dimethylhydrazine↗