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Biomedical subjects

J Gil

Publications and source records attributed to J Gil.

At least 163 records · Page 9Linked to original sources

Postnatal growth of lung parenchyma in the piglet: morphometry correlated with mechanics.

BACKGROUND: A previous study of piglet lung growth (Mansell et. al. 1989. J. Appl. Physiol., 67:1422-1427) showed transient stiffness to changes in shape and volume immediately after birth. Later, elastic recoil was found to increase as the lung grew in weight and volume. The present study uses morphometry to test possible structural correlates of these two mechanical changes. METHODS: Piglet lungs were fixed near full inflation via the airways during the immediate newborn period (6-12 hours, n = 3), at 3-5 days (n = 6), 25-30 days (n = 5), and 80-85 days (n = 3). Morphometry comprised arithmetic and harmonic mean thicknesses of alveolar septae and average mean surface curvature. Measurements of curvature and airspace volume were combined to differentiate alveolar expansion from septal proliferation as mechanisms for volumetric growth. RESULTS: The unique mechanical behavior of the newborn lungs was associated with relatively thick alveolar septae. Marked thinning of the septae and resolution of the stiffness to shape and volume change had occurred by 3-5 days. An increase in elastic recoil during the first postnatal month was found to be associated with simple airspace expansion. The second and third months were characterized by septal proliferation and increase in arithmetic mean septal thickness but elastic recoil did not increase further. Harmonic mean septal thickness and airspace volume per gram of lung tissue did not change over the course of the study. CONCLUSIONS: 1) A relative stiffness to shape and volume change in freshly newborn piglet lungs is associated with relatively thick alveolar septal walls; 2) postnatal development of piglet lung parenchyma involves septal lengthening and thinning followed by septal proliferation; 3) the initial phase of septal lengthening, rather than the later phase of septal proliferation, is associated with increase in parenchymal recoil.

Animals↗

A patient with antineutrophil cytoplasmic antibody-negative pulmonary capillaritis and circulating primed neutrophils.

We describe an antineutrophil cytoplasmic antibody-negative patient with capillaritis, acute respiratory failure, and primed neutrophils circulating systemically. Thoracoscopic lung biopsy showed capillary destruction, with neutrophils infiltrating the lung interstitium and air spaces but no alveolar damage or hemorrhage. We suggest that this atypical, limited form of pulmonary injury may occur when circulating neutrophils are primed, but, in the absence of an activating factor, not fully activated.

Antibodies, Antineutrophil Cytoplasmic↗

Effect of body position on gas exchange in patients with unilateral pleural effusion: influence of effusion volume.

The objective of this study was to evaluate the effect of lateral body position on gas exchange in patients with unilateral pleural effusion, with special reference to the influence of effusion volume. Thirty consecutive patients with unilateral pleural effusion, without evidence of parenchymal pulmonary involvement, were entered into the study. Arterial blood gas tensions (PaO2, PaCO2) were randomly measured in both right and left lateral decubitus body positions, while breathing room air. To assess the influence of the effusion volume, roentgenographic and functional parameters were used. Among the latter, FVC, FEV1, TLC and RV were determined. The influence of the presence or absence of pleuritic pain on gas exchange was also assessed. There was no significant difference in PaCO2 between right and left lateral decubitus body positions (31.1 +/- 4.2 vs. 31.0 +/- 4.5 mmHg). The differences in PaO2 between the two body positions ranged from 0.5-25 mmHg (mean 9.3 +/- 6.6 mmHg). Mean PaO2 with the normal-side (control) down (PaO2-N) (81.4 +/- 8.5 mmHg) was higher, but without significant statistical difference, than mean PaO2 with the effusion-side down (PaO2-E) (78.0 +/- 12.5 mmHg). PaO2-N was higher than PaO2-E in 22 of 30 patients (conventional), and lower in eight patients (paradoxical). No consistent relationship was found for alterations in PaO2 in different positions with the volume of effusion, either when estimated by a roentgenographic method or when using spirometric or plethysmographic values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hepatosplenic gamma-delta T-cell malignant lymphoma: report of the first case in childhood, including molecular minimal residual disease follow-up.

We report the first case of T-cell gamma delta+ hepatosplenic malignant lymphoma in childhood. Tumour-specific oligoprobes were developed against the single V1-J1 rearrangement of the delta T-cell receptor (TCR) gene in order to perform minimal residual disease (MRD) studies. Molecular analysis in serial bone marrow samples proved to be of predictive value concerning the clinical outcome. Clonotypic DNA was not detected in peripheral blood during the course of the disease until a refractory terminal leukaemic phase took place 18 months after the diagnosis. This case demonstrates the usefulness of MRD studies to monitor the course of disease in at least some subsets of peripheral T-cell lymphomas.

Base Sequence↗

Effect of zidovudine on human fetal lung development.

Zidovudine (AZT) is currently used to treat human immunodeficiency virus (HIV)-positive women during pregnancy to prevent the prenatal transmission of HIV type 1 (HIV-1). However, AZT not only inhibits HIV replication but also affects the DNA polymerases of human cells; hence AZT is not recommended during the first trimester of pregnancy. The lung is a unique organ because it continues to grow and develop throughout fetal life. Using a human fetal lung organ culture system, we sought to determine the effect of AZT on morphogenesis and epithelial cytodifferentiation of developing alveoli. Lung tissues from three fetuses, 14-15 weeks gestational age, were grown in culture for 24 hours (day 0). AZT at a concentration of either 0.4, 4.0, 8.0, or 40.0 mumol/L was added on days 1, 5, and 10 of growth. The cultures were interrupted on days 6 and 15 and examined by light and electron microscopy for alveolar saccular development, interstitial thinning, and epithelial cell differentiation. On day 6 of growth the treated cultures demonstrated fewer alveolar saccules and a thicker, more cellular interstitium compared to the controls. After 15 days of growth the cultures treated with 0.4 mumol/L of AZT appeared structurally similar to the controls. The cultures treated with AZT concentrations of 4.0 to 40.0 mumol/L appeared unchanged from day 6, implying arrested maturation of the culture. However, epithelial cell differentiation was unaffected. We conclude that AZT at concentrations of 4.0 mumol/L and greater affects the structural development of the human fetal lung in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation↗

Computerized interactive morphometry in the differential diagnosis of irradiated prostates.

Radiation therapy is becoming a treatment of choice for many patients with prostatic carcinoma. Distinguishing radiation change in prostate glands from carcinoma may be difficult. In this study we objectively assessed, by morphometric methods, the nuclear characteristics of benign and malignant prostates with a history of radiation treatment (125I implant with or without prior external beam radiation). This is part of our continuing efforts to achieve difficult differential diagnoses by analyzing perimeter, diameter and nuclear profile area of cells or interest and applying methods of statistical classification. Biopsies were performed 18-36 months following implant therapy. Eleven cases with residual prostate tumor constituted the malignant group. These were compared to 20 benign cases (benign glands in the 11 carcinoma cases plus 9 other cases with no residual carcinoma). Immunohistochemical staining with keratin 903 was performed on all cases. Differences in the nuclear parameters were most evident in the average nuclear profile areas (32.5 microns 2 for the malignant groups vs. 39.6 for the benign) and in the mean maximal cord length (diameter) (7.4 microns for the malignant group vs. 9.0 for the benign). Classification, however, is based on the size distribution plots of nuclear profile areas, which, in the malignant cases, had a sharper peak at lower value, while the benign cases had higher value and a broader peak with a trailing off into the larger values. This study emphasized the marked nuclear alterations that occur in irradiated prostates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Phosphorylation of the MARCKS family of protein kinase C substrates in human B chronic lymphocytic leukemia cells.

Incubation of B chronic lymphocytic leukemia (B-CLL) cells with phorbol esters resulted in the phosphorylation of three Triton-soluble, heat-stable, acidic proteins with apparent M(r) of 80 KDa, 60 KDa and 43 KDa. The characteristics of the three proteins suggested that they could be related to the myristoylated, alanine-rich, C-kinase substrate (MARCKS). p80 was immunoprecipitated with an antibody against the N-terminal peptide of MARCKS. p43 co-migrated with mouse MRP/Mac-MARCKS (MARCKS-related protein). p60 is the most prominent substrate of protein kinase C in B-CLL cells.

Amino Acid Sequence↗

Inhibition of bone marrow-derived natural suppressor activity by glucocorticoids and its reversal by IFN-gamma or IL-2.

Natural suppressor (NS) activity is mediated by cells (NS cells) of bone marrow origin with ability to suppress nonspecifically proliferative responses of lymphocytes. Here we show that pharmacologic concentrations (10(-6)-10(-8) M) of glucocorticoids (GC) greatly inhibit NS activity, as detected by coculturing bone marrow and spleen cells stimulated with B cell (LPS) or T cell (concanavalin A) mitogens. Progesterone antagonizes GC-mediated inhibition of NS activity, suggesting that GC were acting through a receptor-dependent mechanism. A prior treatment of NS cells with GC (10(-5) M) has no effect on the NS activity mediated by these cells. GC are required in culture during the first 24 hr of the suppressor assay. Addition of low amounts of IFN-gamma to GC-treated cultures fully reverses NS cell-mediated suppression. IL-2 produces a reversion as well, while addition of IL-3 or IL-4 does not prevent the GC effect. Neutralizing anti-IFN-gamma antibodies, but not anti-IL-2 or anti-TGF-beta, greatly inhibit NS activity in absence of GC. Taken together, these results indicate that GC inhibit NS activity by impairing endogenous cytokine production required to obtain successful NS cell activation, and not by acting directly on NS cells (i.e., inhibiting the secretion of putative NS factors). Among the cytokines involved in NS cell activation, IFN-gamma appears to be critical, since its addition readily overrides the GC effect and its neutralization results in strong inhibition of NS activity.

Animals↗

Control of fructose 2,6-bisphosphate metabolism by different mitogenic signals in Swiss 3T3 fibroblasts.

The mitogenic signals that control fructose 2,6-bisphosphate metabolism in murine Swiss 3T3 fibroblasts have been studied. Bombesin, vasopressin, insulin, protein kinase C activation by phorbol esters, or increase in the intracellular cAMP concentration by forskolin induced an increase in fructose 2,6-bisphosphate levels. When the cells were incubated in the presence of insulin or phorbol esters, an increase in the Vmax of 6-phosphofructo-2-kinase activity was observed. However, forskolin did not produce this effect. The increase in 6-phosphofructo-2-kinase activity elicited by phorbol 12,13-dibutyrate was blocked by cycloheximide. In contrast, the effect of insulin did not require protein synthesis. This study demonstrates that different mitogenic signal transduction pathways control the levels of fructose 2,6-bisphosphate. The high rate of glycolysis in proliferating Swiss 3T3 cells may be explained by an increase in the levels of this regulatory metabolite.

3T3 Cells↗

Reduction of annexin-V (placental anticoagulant protein-I) on placental villi of women with antiphospholipid antibodies and recurrent spontaneous abortion.

OBJECTIVE: The mechanism by which antiphospholipid antibodies are associated with pregnancy loss and thromboembolic conditions has yet to be elucidated. Annexin-V, an anticoagulant phospholipid-binding protein, is normally present in syncytiotrophoblasts lining the placental villi, where it may play a role in the maintenance of intervillous blood fluidity. We therefore investigated the distribution of annexin-V in placentas of patients with antiphospholipid antibodies in situ and then used short-term villous cultures to study the direct effect of antiphospholipid antibodies on the immunolocation of annexin-V. STUDY DESIGN: We performed a blinded study by means of computerized morphometric analysis of placental tissues that were stained for annexin-V with affinity-purified polyclonal antibody in an avidin-biotin peroxidase system. The distribution of villous surface annexin-V on cross sections of placentas of patients with antiphospholipid antibodies was compared with that of placentas from patients with uncomplicated pregnancies, elective abortions, and pregnancy losses not associated with antiphospholipid antibodies (n = 8 for each group). We quantitated villous surface annexin-V in cultured placental villi that were incubated with antiphospholipid antibodies immunoglobulin G compared with normal immunoglobulin G and measured annexin-V levels by enzyme-linked immunosorbent assay in conditioned media and in the villi. RESULTS: The mean villous surface annexin-V of the group with antiphospholipid antibodies was 26.2% +/- 17% (SD) versus 93.9% +/- 5.7% in the normal control group (p < 0.0001). Villi from patients undergoing elective abortions and with pregnancy losses that were not attributed to antiphospholipid antibodies also showed higher mean villous surface annexin-V levels (86.9% +/- 10.6% and 83.5% +/- 11.3%, respectively, p < 0.0001). Organ culture of normal placental villi with affinity-purified immunoglobulin G from patients with antiphospholipid antibodies showed a dose-dependent decrease of villous surface annexin-V over a concentration range of 1.5 micrograms/ml to 1.5 mg/ml. Annexin-V concentrations in conditioned media were significantly lower in the presence of antiphospholipid antibodies immunoglobulin G compared with normal immunoglobulin G (49.4 +/- 8.9 ng/gm wet weight vs 57.2 +/- 11.5 ng/gm, respectively, p < 0.05). In contrast, the mean level of annexin-V in placental villi incubated with antiphospholipid antibodies immunoglobulin G was greater than in villi incubated with normal immunoglobulin G, 1328 +/- 130 ng/gm wet weight versus 1183 +/- 165 ng/gm (p < 0.02). CONCLUSIONS: Patients with antiphospholipid antibodies and a history of previous pregnancy losses have a significant reduction in annexin-V immunostaining on placental villous surfaces, and antiphospholipid antibodies immunoglobulin G can directly decrease levels of villous surface annexin-V on cultured placental villi. Assays of annexin-V in the conditioned media and cell pellets of cultured placental villi suggest that the mechanism for antiphospholipid antibodies-mediated reduced annexin-V surface staining is an inhibition of annexin-V transport to the villous surface rather than displacement by antiphospholipid antibodies from the surface. This antiphospholipid antibodies-induced deficiency of placental surface annexin-V may contribute to the placental thrombosis observed in these patients.

Abortion, Habitual↗

Semi-automatic quantitation of nucleolar organizer regions in non-Hodgkin's lymphomas.

Nucleolar organizer regions may be useful in the diagnosis and classification of non-Hodgkin's lymphomas. In this study of 46 cases we applied morphometric analysis with quantitation of physical descriptors of the nuclear profile (area, perimeter) and both number and area of stained nucleolar organizers therein enclosed to a series of lymphomas and benign lymphoid infiltrates. While nuclear outlines were manually traced small organizer regions within the nuclear profiles were semi-automatically outlined by a thresholding procedure subjected to manual override. This results in determination of number, area and perimeter of organizer regions. Data were corrected for section thickness effects and a stereologic (three-dimensional) analysis was additionally performed. We found an increase in mean number and area of nucleolar organizers per nucleus in high grade lymphomas compared to benign infiltrates and lower grade lymphomas. Volume and thickness corrected data showed a decrease in organizer number with concomitant increase in organizer volume in the higher grade lymphomas. Multivariate analysis of the cases, previously classified histologically, showed that clear resolution could be obtained, on the basis of physical descriptors, both between as well as within groups of the three tumor grades.

Humans↗

Nuclear diffuseness as a measure of texture: definition and application to the computer-assisted diagnosis of parathyroid adenoma and carcinoma.

A measure of texture, the nuclear diffuseness, was formulated for use in biological classification, and specifically to characterize quantitatively chromatin texture. Nuclear diffuseness corresponds to the amount of local intensity variation in the digitized image of a nuclear profile. As a setting in which to test the efficacy of nuclear diffuseness as a diagnostic tool, the identification of parathyroid adenoma and carcinoma was considered. Digitized images of sections of parathyroid chief cell nuclei were obtained from 16 biopsies, and the nuclear diffuseness, as well as other morphometric descriptors, were computed. With just the average nuclear diffuseness and average nuclear profile area, jackknife (leave-one-out) classification using an artificial neural network was able to diagnose correctly and unambiguously the condition (normal, parathyroid adenoma, or parathyroid carcinoma) in 15 of 16 cases. In one case, the neural network assigned a higher weight to the correct diagnosis, but was unable to distinguish between normal and adenoma conclusively.

Adenoma↗

Effect of acute lithium administration on pyroglutamyl-aminopeptidase I activity in several brain areas of the rat.

Lithium (CAS 7439-93-2) is widely accepted as an effective treatment in acute mania. A considerable body of literature exists on the effects of lithium on the central nervous system. However, the neurochemical mechanism of the ion action remains still relatively obscure. In the present work, the effect of acute lithium administration on pyroglutamyl-aminopeptidase I activity in discrete areas of the rat brain, including the hypothalamic-pituitary axis, is described. Increases of the enzyme activity in the striatum and the hypothalamus after lithium treatment were observed. It is suggested that this enzyme activity plays a part in the lithium action mechanism, possibly through the regulation of the activity of TRH (Thyrotropin Releasing Hormone) and/or histidyl-proline diketopiperazine.

Animals↗

Lung metastases from prostatic carcinoma: orchidectomy-induced remission in two patients.

Two patients with pulmonary metastases from a prostatic carcinoma are described. When first seen by the pulmonary physician, respiratory symptoms were predominant and diagnosis of the primary site was not yet made. Orchidectomy achieved an impressive response with regression of symptoms and radiological lesions within weeks. Since metastatic deposits from prostatic origin may respond promptly to endocrine manipulation, this possibility must be taken into account in the evaluation of any patient with pulmonary metastases of unknown origin.

Adenocarcinoma↗

Ovarian dysplasia: nuclear texture analysis.

BACKGROUND: Ovarian dysplasia has been defined by histologic and morphometric studies focusing on architectural and nuclear profile changes. A new technique is used to enhance the accuracy of this diagnosis by a quantitative evaluation of the nuclear texture that represents the nuclear chromatin pattern on which conventional diagnoses of malignancy are usually made. METHODS: Histologic sections from 35 ovaries classified as malignant (12), dysplastic (12), and normal (11) were evaluated by tracing boundaries of nuclear profiles and measuring "textons" (texture primitives) with a histogram analysis of three zones of gray level densities (called for simplification white, gray, and dark). The average combined area was tabulated for specimens with the same diagnosis, and linear regression plots compared the texton area with total nuclear area. RESULTS: The dimensions of textons originally hidden inside the chromatin and revealed by histograms were found to be closely clustered in normal epithelium, and increasingly dissociated from the containing nucleus as the lesion progressed from dysplastic to malignant. The statistical multivariate analysis including nine parameters correctly classified the three diagnostic categories as normal, dysplastic, and malignant. CONCLUSIONS: Computerized image analysis of nuclear texture adds accuracy to the recently elaborated morphometric methods to define ovarian dysplasia, a potential precursor of ovarian carcinoma.

Cell Nucleus↗

Brain soluble and membrane-bound Tyr-aminopeptidase activities during the stages of estrous and proestrous in the female rat.

Brain Tyr-aminopeptidase activity levels during two stages of the rat estrous cycle (estrous and proestrous), are described in this research. The study includes the activities of the soluble and the membrane-bound forms. Soluble Tyr-aminopeptidase activity shows a significant increase during the proestrous stage in the hypothalamus. The complete membrane-bound activity did not significantly change at any point. However, a significant rise was found in the membrane-bound puromycin insensitive aminopeptidase activity in the hypothalamus and the pituitary gland during the proestrous phase.

Aminopeptidases↗