Lung abscess complicating post-varicella pneumonia.
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Chickenpox↗
Biomedical subjects
E Lazar
Publications and source records attributed to E Lazar.
Unusual localisation of an ectopic pregnancy.
We present a case of ectopic pregnancy with a peculiar localisation: beneath the peritoneal serosa covering the anterior wall of the uterus, at the level of the uterovesical pouch. The case raised some diagnostic and management problems for the medical team. Considerations are made concerning the etiopathology of this unusual form of ectopic pregnancy.
Adult↗
The influences of age, retinal topography, and gender on retinal degeneration in the Fischer 344 rat.
The Fischer 344 (F344) rat is presently the animal of choice for age-related research. The existence of an age-related retinal degeneration was reported previously in the males of this strain, but a gender comparison has not been performed. In this study, histological and morphometric measurements of the retina related to age, retinal topography, and gender were made on 3- to 24-month-old animals. The thicknesses of the outer nuclear layer (ONL) and the photoreceptor layer (PRL) were measured from sagittal sections at six loci. Retinas of both sexes showed steady decline with age in the thicknesses of the ONL and PRL at all locations. An important finding was the presence, after 12 months of age, of a drastically accelerated rate of peripheral retinal degeneration seen only in male subjects. Females showed a less dramatic rate of peripheral degeneration which did not begin until after 18 months of age. In addition, two other forms of retinal degeneration were found--cystoid degeneration was found earlier and more frequently in the male, while a paving-stone type of degeneration was found in both sexes. These two types of lesions were preferentially, but not exclusively found in the peripheral retina. In conclusion, the F344 rat offers a convenient model to study a pattern of retinal degeneration affected by the combination of gender, regional and age-related factors.
Aging↗
Free vascularized fibular grafts: radiographic evidence of remodeling and hypertrophy.
OBJECTIVE: A study was undertaken to determine the growth potential and radiographic appearance of a free vascularized fibular graft as it responds to the mechanical and physiologic features of its new environment. MATERIALS AND METHODS: In a 10-year period, 30 patients underwent reconstruction of a large skeletal defect with a vascularized fibular graft. Radiographic studies were adequate for assessing sequential changes in 21 patients. Hypertrophy was evaluated by serial measurements of the periosteal and endosteal dimensions and was assessed with respect to age, sex, duration and location of the graft, the indication for reconstruction, and fixation apparatus. RESULTS: Hypertrophy of vascularized bone grafts is not rare. Among 21 vascularized fibular grafts, a measurable degree of hypertrophy was found in eight. Hypertrophy was caused by periosteal formation of new bone. The amount of hypertrophy could be considerable; in some cases it reached 2 cm of new cortical bone, resulting in an unusual radiographic appearance of marked cortical thickening. The amount of hypertrophy was greatest in young males, but was independent of diagnosis and site, and could be seen even in grafts bridged by metallic plates. CONCLUSION: Hypertrophy of vascularized bone grafts is a relatively frequent finding and has distinctive radiographic features. It is unclear why hypertrophy occurs to a much greater extent in some grafts than in others.
Adolescent↗
Transplantation of Y79 cells into rat eyes: an in vivo model of human retinoblastomas.
PURPOSE: To develop an in vivo model of human retinoblastoma by returning cultured Y79 retinoblastoma cells to the retinal environment of a widely available laboratory animal. In so doing, to study the survival, integration, and invasive characteristics expressed by tumoral cells grafted into an intraocular milieu from which these progenitor cells originated more than 20 years ago. METHODS: Using the retinal grafting method of Lazar and del Cerro, Y79 cells were injected under direct visualization into the subretinal space of Fischer 344 rats. The host rats included 36 animals that received daily injections of cyclosporin A and 4 that did not. All hosts were sacrificed 30 to 60 days after transplantation. RESULTS: Clinical examination showed vitreal invasion by masses of flocculent white material or the intravitreal formation of solid tumors. Histologic examination showed these formations to be outgrowths of grafted tumoral cells into the host retina and vitreal cavity. Highly anaplastic tumoral cells were also found lodged in subretinal and intraretinal locations. There were signs of continued and intense cell division within the grafts, with no indication of cell-mediated host reaction against the grafted cells. CONCLUSIONS: After intraretinal xenografting, human Y79 retinoblastoma cells retain a highly tumoral nature despite many years of in vitro propagation. When xenografted, these cells survive, grow, and express their malignancy within the retina of the common laboratory rat protected by a moderate immunosuppressive regimen. This partial immunosuppression is a requirement for the xenografts to prosper. This model offers a valuable opportunity to study in vivo the cellular and molecular biology of this and other human retinoblastomas, and it may facilitate the evaluation of antitumoral treatments.
Animals↗
TGF-alpha production correlates with tumorigenicity in clones of the SW613-S human colon carcinoma cell line.
The c-myc gene is amplified and the c-Ki-ras gene is mutated in the SW613-S human colon carcinoma cell line. Two cell types with different levels of c-myc amplification are present in the SW613-S cell population and representative cell clones can be isolated. The clones with a high level of amplification and expression of the c-myc gene are tumorigenic in nude mice whereas those with a low level are not. The tumorigenic clones secrete transforming growth factor alpha (TGF-alpha) in the culture medium whereas the non-tumorigenic clones do not produce any detectable amount. Accordingly the level of TGF-alpha mRNA is higher and the transcription rate of the gene is increased in the tumorigenic clones. The acquisition of the tumorigenic phenotype by cells of non-tumorigenic clones, following introduction of c-myc gene copies by transfection, is accompanied by an increase in the steady-state level of TGF-alpha mRNA. These findings suggest a role for an elevated level of TGF-alpha production in the tumorigenic phenotype of SW613-S cells. The possibility that this role is indirect is discussed.
Animals↗
Intraretinal xenografts of differentiated human retinoblastoma cells integrate with the host retina.
We report on the successful use of chemically modified Y79 human retinoblastoma cells for intraretinal xenografting into damaged adult mammalian eyes. Y79 cells were exposed in vitro to retinoic acid/butyrate to induce differentiation. Using a multisite transplantation method, the suspension was injected into the subretinal space of Fischer 344 rats. The survival, integration, and differentiation potential of these cells was studied, following their return to the intraocular milieu from which the progenitor cells originated. The grafted cells survived and differentiated into immature photoreceptor elements in the subretinal and intraretinal locations, as multiple clusters of rosette-forming cells intimately attached to the host neuroretina. The differentiation process included development of synaptic connectivity of the ribbon type with the surrounding neuropil. No signs of renewed cell division were found within grafts performed on 42 rat eyes, and there was no indication of cell-mediated host reaction against the transplants. This study indicates that tumorigenicity can be suppressed in mitotically arrested Y79 cells, and that these cells are capable of undergoing differentiation in vivo. This provides evidence of the remarkable differentiation properties of human retinoblastomas while indicating that Y79 cells may ultimately be able to substitute for fetal cells in experimental retinal transplantation.
Animals↗
Human immunodeficiency virus type 1 infection of neural xenografts.
Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.
AIDS Dementia Complex↗
Photoreceptor differentiation in retinal xenografts of fetal monkey retina.
Although the potential of retinal grafts to provide the host eye with rod cells is presently well established, the possibility of grafting cone photoreceptors has not been documented. In this study, the neural retinas of two Cebus apella monkey fetuses were xenografted into immunosuppressed Fischer 344 adult rats. Histological analysis showed intimate apposition between the grafted donor cells and the neighboring host rat retina. The transplanted cells survived well and often overgrew the boundaries of the host retina, expanding into the host vitreous cavity. These cells formed histogenetically differentiated structures predominantly populated by the photoreceptors. When transplanted into a foreign environment, donor cells formed inner segments which exhibited the basic morphology of cells developed in situ. This study demonstrates that embryonic monkey neural retina is a viable source of xenograft material. It also indicates that an advanced embryonic stage is not a deterrent to survival and differentiation of grafted primate neuroretinal cells. The successful transplantation of these cells, especially under the relatively adverse conditions of a xenograft, raises the hope that retinal transplantation may in fact be a useful technique for repairing both rod and cone function in damaged retinas of higher animals including humans.
Animals↗
A new procedure for multiple intraretinal transplantation into mammalian eyes.
A new method of intraretinal grafting is described which avoids opening the globe and allows direct visual control of the transplant by observing placement of the graft through the host pupil. A microsyringe with a bevelled needle partially ensheathed in plastic tubing in order to limit penetration was used to inject dissociated donor cells into 2 to 4 pre-selected points of the sub-retinal space of adult rats. The needle tip was inserted through the scleral and choroidal tissue, and observed through the animal's pupil as it reached into the sub-retinal space. Donor cells were then injected into several sites of the retina. Results, using ophthalmoscopy as well as light and electron microscopy, confirmed the atraumatic nature of this technique and the survival of grafted cells. Intraretinal injection of colloidal carbon visually illustrated the effectiveness of this method in covering an extended portion of the host retina. The procedure, which is virtually free of complications has enabled us to perform multisite intra-ocular grafting in a safe, easy, and reliable fashion, under direct visual control.
Anesthesia↗
Intraretinal grafting restores visual function in light-blinded rats.
In seeing rats light flashes inhibit acoustic startle reflexes at short lead times. In contrast, visually impaired (light-blinded) rats show an early phase of exaggerated reflex expression, revealing the presence of pathological visual processing, and then an aberrant late phase of delayed inhibition. Grafting fetal retinal cells into the damaged retina entirely removed reflex facilitation and restored a modest degree of properly timed and statistically significant reflex inhibition. This restoration of visually-mediated behaviour, observed in two independent groups, reveals that intraretinal grafts provide useful information to blinded hosts.
Acoustic Stimulation↗
Intraocular transplantation of cell layers derived from neonatal rat retina.
The goal of this study was to determine whether cell layers derived from either the inner or outer regions of the neonatal rat retina had the capacity to grow and differentiate when transplanted into the adult retina of the same species and, if so, whether there would be differences between the grafts originated from the two different cell populations. Two different tracers were used to label donor cells and to identify them following transplantation. Firstly, at postnatal day (PND) 2, the pups received bilateral injections of rhodamine-labeled microspheres in the superior colliculus in order to label retrogradely the retinal ganglion cells. From the day of birth until the day of sacrifice (PND 4), the donors received daily injections of [3H]thymidine to label the nuclei of dividing cells. At PND 4 the animals were sacrificed and the retinas isolated. Following brief enzymatic treatment, the inner and outer retinal regions were separated from each other using filter membranes. Cells derived from each of the two moieties were transplanted separately into the eyes of adult host animals of the same strain. After survival times ranging from 3 to 44 days, the host eyes were enucleated and prepared for examination using both light and electron microscopic methods. Both retinal regions gave viable transplants. Unexpectedly, the transplants derived from the inner zone of the retina survived better than those derived from the outer zone, despite the fact that the highest number of undifferentiated and mitotically active cells occurred in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
In vivo staining of the mammalian retina by means of a simple fluorescent method.
Intraocular injections of microliter volumes of a solution containing the fluorescent stain Fluoro-Gold produces an intense and long-lasting in vivo stain of the cells forming the neural retina of rats and mice. The label is incorporated by the neuro-retinal cells, while other intraocular structures such as the lens, iris, ciliary processes and even the optic nerve head exclude it. The fluorophore can be easily demonstrated under epi-illumination by means of commonly used fluorescence filter combinations. The stain has proven to be compatible with cryostat sectioning and with plastic embedding. Furthermore, electron dense lysosomal and lamellar bodies in retinal neurons which have incorporated the stain may provide a means for identification of Fluoro-Gold labeled cells at the electron microscopic level which is consistent with previous results. Intraocular injection of Fluoro-Gold fills the need for a reliable, simple, and robust in vivo and in toto stain of the neural retina.
Animals↗
Celiprolol in systemic hypertension.
The safety and efficacy of orally administered celiprolol, a new beta 1-selective adrenergic blocking drug with peripheral beta 2-agonist properties, were assessed in 91 patients with mild to moderate systemic hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg without medication) using a placebo-controlled, double-blind, randomized, titration-to-effect study design. All patients received placebo for 4 weeks and were then randomized to receive placebo (n = 46) or once-daily celiprolol (n = 45), which was titrated every 2 weeks (200, 400, 600 mg/day) over a 6-week period to achieve a reduction in supine diastolic BP to less than or equal to 90 mm Hg. Plasma lipids and lipoproteins were also assessed at baseline, during placebo and after randomization to active therapy in a subgroup of patients. Compared with placebo, celiprolol reduced supine and standing BP (reduction of supine BP -0.4/-2.1 mm Hg with placebo, -5.7/-6.4 with celiprolol, p less than 0.05; reduction of standing BP -1.7/-1.0 with placebo, -7.2/-4.9 with celiprolol, p less than 0.05). Supine heart rate was reduced by 6.8 beats/min with celiprolol compared with 2.0 beats/min with placebo (p less than 0.05). No differences were seen when the effects of placebo and celiprolol on plasma lipoproteins were compared. Celiprolol is a safe, effective and well tolerated once-daily antihypertensive drug and has no detrimental effects on plasma lipids.
Antihypertensive Agents↗
Sustained high-dose nitroglycerin transcutaneous patch therapy in angina pectoris: evidence for attenuation of effect over time.
The safety and efficacy of using continuous high-dose transcutaneous nitroglycerin in doses up to 100 mg/24 hours in chronic stable angina was assessed in 20 patients using serial treadmill testing. Patients had first to show a response to sublingual nitroglycerin with a 20% improvement in exercise time. All patients were then titrated with 20 mg (40 cm2), 60 mg (120 cm2), 80 mg (160 cm2) or 100 mg (200 cm2) patches, until intolerable headache in association with a 10 mmHg reduction in blood pressure and a ten-beat increment in heart rate. Drug was then discontinued for 2 days and patients underwent three repeat stress tests to reestablish a consistent drug-free baseline. Patients were then randomized in double-blind fashion to receive either active patch (N = 11) in previous titration dose or placebo patch (N = 9), with treadmill tests performed at 0 (1 hour after previous patch removal), 4, and 24 hours after patch application at baseline and at weeks 1 and 2. Venous blood was obtained for measurement of plasma nitroglycerin levels. After the first 24 hours of active patch therapy, there was a significant reduction in systolic blood pressure (P = .05), a significant increase in heart rate (P = .01), and a minor increase in exercise tolerance (P = .06) compared to placebo. At weeks 1 and 2, there was an attenuation of drug effect in all of these parameters. Plasma nitroglycerin levels demonstrated consistently high plasma levels over each 24-hour dosing interval, on day 1, week 1, and week 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Cutaneous↗
Transforming growth factor alpha: an aromatic side chain at position 38 is essential for biological activity.
Site-directed mutagenesis has been performed in the human transforming growth factor alpha gene. When tyrosine 38 is mutated into phenylalanine or tryptophane, biological activity is retained. In contrast, other alterations between cysteine 34 and cysteine 43 and disruption of disulfide bonds 8 to 21 and 34 to 43 resulted in loss of activities. The presence of an aromatic side chain at position 38 of transforming growth factor alpha seems to be essential for its activity.
Amino Acid Sequence↗
Intraretinal transplantation for rod-cell replacement in light-damaged retinas.
Blindness from retinal disease is often the consequence of extensive damage to the photoreceptor cell population, while other cell types which form the neural retina are relatively spared. In this setting, transplantation of photoreceptor cells could offer hope for the restoration of some degree of visual function. We tested the feasibility of this approach by transplanting immature retinal cells into the eyes of adult rats affected by late stage phototoxic retinopathy, which are almost totally devoid of photoreceptor cells. Dissociated neuroretinal cells from newborn rats were injected into the hosts' retinas. These cells were labelled with the fluorescent tracer Fast-blue for identification within the host eye. Survival time ranged from 3 to 100 post-transplantation days. Fundus examination of light-irradiated eyes showed pallor caused by a considerable reduction of the retino-choroidal vascular bed after light irradiation. Histologically the hosts exhibited decimation of the elements forming the outer layers throughout the entire retina. As visualized by light and electron microscopic procedures, we report the differentiation of clusters of transplanted photoreceptor cells, and the integration of these cells within the adjacent areas of the host retina. Fluorescence microscopy showed these clusters to be formed by fluorescently labelled cells developing in intimate contact with the unlabelled host retina. Electron microscopically it was possible to determine that these photoreceptors had established synaptic contacts. These observations indicate that successful transplantation of immature retinal cells is feasible into adult eyes that have suffered extensive retino-choroidal damage. These findings also support the concept that retinal transplantation is a procedure which may open new avenues into the study of retinal repair.
Animals↗
Retinal transplants for cell replacement in phototoxic retinal degeneration.
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Amidines↗