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Biomedical subjects

Z Friedman

Publications and source records attributed to Z Friedman.

At least 37 records · Page 2Linked to original sources

Adrenergic drug effects on cyclic AMP in cultured human trabecular meshwork cells.

Cyclic AMP production in the presence or absence of various adrenergic agonists and antagonists was determined in cultured human trabecular cells using a gammaflow automated radioimmunoassay that allowed multiple simultaneous experiments and reproducible results. Adrenergic agonists and antagonists showed activation and inhibition constants consistent with the presence of beta2-receptors: Ka of isoproterenol < epinephrine < norepinephrine < phenylephrine; Ki of timolol < betaxolol < celiprolol < atenolol. Selective ICI antagonists showed beta2-specificity.

Adrenergic beta-Agonists↗

A splice variant of trkB and brain-derived neurotrophic factor are co-expressed in retinal pigmented epithelial cells and promote differentiated characteristics.

There is evidence suggesting reciprocal trophic interactions between photoreceptors and the retinal pigmented epithelium (RPE), but the factors involved have not been identified. In this study, we investigated the hypothesis that one or more known neurotrophic factors act upon the RPE. Cultured human and freshly isolated bovine RPE cells demonstrated saturable specific binding for [125I]labeled BDNF, NT-4/5 and NT-3 with little specific binding for CNTF and none for NGF. Cross-competition experiments showed that BDNF is the preferred ligand and cross-linking of [125I]BDNF resulted in a doublet at 160 kd that was increased in RPE cells incubated in all-trans retinoic acid. There was basal phosphorylation of a 145 kd protein recognized by an anti-trk antibody that was increased in RPE cells pulsed with BDNF. RT-PCR with primers spanning the transmembrane domain demonstrated that RPE cells express trkB mRNA lacking a region homologous to exon 9 of chicken trkB, a splice variant that has been demonstrated to preferentially interact with BDNF. Northern blots demonstrated that cultured RPE cells also express mRNA for BDNF. BDNF did not stimulate proliferation or increase survival of RPE cells in serum-free medium, but promoted a differentiated morphology and increased the expression of cellular retinaldehyde binding protein, a marker of the differentiated state in RPE cells. An RPE cell line that spontaneously shows differentiated features showed a high level of BDNF mRNA. These data demonstrate that RPE cells express a short splice variant of trkB whose activation correlates with expression of differentiated characteristics and the cells themselves are capable of producing a ligand for the receptors. Signaling through trkB could play a role in differentiation of RPE cells during development and maintenance of the differentiated state in adult RPE.

Animals↗

[Progression of diabetic retinopathy after cataract extraction].

A prospective study of the effect of cataract extraction with intraocular lens implantation on the course of diabetic retinopathy (DR) in 44 patients (59 eyes) was carried out. It showed that in the 1-3 years following surgery, there was progression of DR (including development of newly formed retinopathy) in 35% of the patients (28.8% of eyes). Progression was more marked in patients with pre-operative bilateral DR compared to those without bilateral DR (77% and 16% respectively). Insulin dependence did not play a role in progression. Final visual acuity was better in patients without pre-operative DR, as well as in eyes without progressive retinopathy.

Aged↗

The instantaneous measurement of multiple Doppler spectra in the investigation of ovarian masses.

The use of Doppler indices of tumor vascularity as markers for malignancy has been a subject of debate, with inconsistencies in specificity and sensitivity as well as in the diagnostic cut-off values. Part of the discrepancy might be explained by the limited number of vessels selected within the tumor for Doppler evaluation. A typical sample of three or four vessels may not be sufficiently large for correct representation of the vasculature of the tumor, which may contain many vessels. The existing conventional Doppler (color and spectral) techniques clearly have limitations. We present here a novel Doppler modality, namely two-dimensional spectral Doppler imaging (SDI), which allows the acquisition of many Doppler spectra within a few seconds. The operator selects a region of interest within a color Doppler image. The Doppler sequence is initiated and the entire selected region is automatically scanned for about 20 s until all spectral Doppler data have been acquired and processed. The system computer generates a color-coded map of the desired Doppler indices overlaid on the gray-scale image. The system also displays a cumulative histogram or a table of the requested Doppler index from all the sections in the tissue. The whole process is automatically performed by the system computer, without any need for operator intervention. The system provides the examiner with a 'fishing net' for Doppler indices, instead of the 'fishing hook' used in current techniques.

Female↗

Cutaneous larva migrans, sacroileitis, and optic neuritis caused by an unidentified organism acquired in Thailand.

We report the case of a 32-year-old pregnant woman with an unidentified intraocular parasite. The parasite, which had been acquired in Thailand, caused cutaneous larva migrans, sacroileitis, and 2 years later optic neuritis and panuveitis. The patient was successfully treated with ivermectin and albendazole. The diagnostic possibilities of this peculiar presentation are discussed. Parasitic infections are a leading cause of medical problems in travelers to tropical countries.1 While most parasites cause gastrointestinal problems, some may migrate throughout the body and lodge in critical organs. Ocular parasitic infections may occur by direct inoculation onto the eye,2 or incidentally during systemic migration. Subconjunctival parasites are easily diagnosed by removal and careful microscopic examination.3 Parasites, which lodge within the eye, are more difficult to diagnose, especially if not removed. In this report we describe a patient who presented with an intraocular parasite causing optic neuritis and panuveitis, 2 years after travel to Thailand.

Adult↗

Multigated simultaneous spectral Doppler imaging: a new ultrasound modality.

BACKGROUND: Spectral Doppler ultrasound, an important diagnostic tool for the functional assessment of various organs, as yet has no major use in prenatal diagnosis due to the conventional technique's limitation of analyzing only one site at a time. Our aim was to develop a new modality that shows simultaneous studies of multiple sites in a vascular area, which should provide improved assessment of hemodynamic status of vascular systems. TECHNIQUE: The new Doppler modality features automatic acquisition and analysis of blood flow in multiple sites over a large area. The quantitative Doppler data are presented as color-coded maps of the spectral Doppler indices overlaid on the gray-scale sonographic images and as histograms of indices distribution. EXPERIENCE: Serial sequences of Doppler measurements in the umbilical artery were taken in 14 women. The reproducibility of the new modality was confirmed. CONCLUSION: Our new Doppler modality provides reproducible and reliable data. This method is a viable alternative to the traditional Doppler ultrasound and might offer better assessment of feto-placental circulation.

Female↗

A simplified technique for extraction of subluxated lenses in young patients.

The authors describe a simplified and safer technique for surgical removal of hereditary or idiopathic soft subluxated lenses. Five eyes of three patients underwent intercapsular aspiration of the lens material. A side-port cannula was introduced through the pars plicata while the eyes were pressurized by an anterior chamber maintainer. This was followed by anterior vitrectomy and capsulectomy. With this technique, the risk of vitreous loss, which can occur with an anterior approach, and the risk of the spread of lens particles into the vitreous, which can occur with a lensectomy with a vitrectomy probe, are avoided. Postoperatively, optical correction was achieved with a contact lens in the two children and with an anterior chamber intraocular lens in the adult. Final visual acuity was 6/9 or better in all eyes. No surgical or other complication occurred during 2 to 4 years of follow-up. A soft subluxated lens can be removed without the risks of vitreous loss or spread of lens particles into the vitreous, reducing the probability of severe complications.

Acetylcholine↗

The Abbreviated Injury Scale. A valuable tool for forensic documentation of trauma.

Anatomic trauma scoring systems are fundamental to trauma research. The Abbreviated Injury Scale (AIS) and its derivative, the Injury Severity Score (ISS), are the most frequently used scales. We assessed the applicability of the AIS and the ISS systems for postmortem forensic documentation of trauma. In a prospective study, all trauma autopsies performed between January 1 and June 30, 1993, were coded according to the AIS and ISS method. All cases were reviewed by a consultant in forensic medicine and a traumatologist. Cases were grouped in three categories according to ISS values: 0-14, 16-66, and 75. These categories represent minor, major, and incompatible-with-life injuries, respectively. All autopsy findings in which ISS was < or = 14 were peer-reviewed to establish mechanism and cause of death. In the 6-month period, 279 trauma-related autopsies were studied. Age at death averaged 37.1 +/- 18.7 (mean +/- SD). Eighty-six percent of the victims were male. Penetrating trauma was the mechanism of injury in 67%. ISS was 0-14 in 19 cases, 16-66 in 150 cases, and 75 in 110 cases. In conclusion, AIS and ISS scoring systems are applicable to trauma forensic documentation. Using these methods for coding postmortem findings may help in establishing a database for trauma research, and this information could constitute a major part of continuous quality improvement of trauma management. Low ISS values may serve as a warning, sometimes indicating preventable death.

Abbreviated Injury Scale↗

[Medical kits in Army physicians' vehicles].

Physicians' medical kits (PMK) were distributed to 50 physicians, graduates of an advanced trauma life support course. The kits were always to be present in the physicians' designated vehicles, enabling them to provide advanced life support at the earliest possible stage (the "golden hour"). The kits have equipment for advanced airway intervention and management, chest trauma management (chest tube insertion, etc.) and fluid administration. To help assess the impact of the PMK and its cost effectiveness, questionnaires were sent to the physicians involved, of whom 35/50 responded. The questions included 2 subjects: the presence of the kit in the car and details of its use for injuries. The kit was present at all times in the cars of all except 1 of 31 physicians. 7 (22.5%) of them used the kit in 50 incidents which involved 74 injured persons. The injuries were caused by road accidents in 54 cases, in 17 by terrorist activity, and 3 cases involved heart attacks and cardiac resuscitation. Distribution of the PMK among army physicians appears to be valuable in the field, and before hospitalization.

Automobiles↗

Platelet-derived growth factor is an autocrine growth stimulator in retinal pigmented epithelial cells.

The retinal pigmented epithelium (RPE) plays a major role in normal and exaggerated retinal wound repair; the latter can result in epiretinal membrane formation and loss of vision. The RPE forms a stable monolayer of highly differentiated cells that proliferates only during wound repair. The mechanism underlying the change to the proliferating phenotype is unknown. When grown on a plastic substratum, cultured RPE cells mimic the proliferating phenotype in situ; they escape density arrest and proliferate in serum-free medium. In this study, we have demonstrated that a platelet-derived growth factor (PDGF) autocrine loop is involved in RPE growth in serum-free medium, because: (1) RPE cells secrete PDGF into their media and express PDGF receptors; (2) the PDGF receptors on RPE cells are autophosphorylated in serum-free medium and suramin, an agent that displaces PDGF and other growth factors from their receptors, blocks the autophosphorylation; and (3) a neutralizing antibody to PDGF significantly decreases RPE growth in serum-free medium. When a linear scrape is made in an RPE monolayer, the cells migrate and proliferate to fill in the gap mimicking wound repair in situ. Cells along the edge of the scrape show increased expression of PDGF and PDGF-beta receptors, and increased staining for proliferating cell nuclear antigen. Immunohistochemistry and in situ hybridization demonstrate expression of PDGF in ganglion cells and cells of retinal blood vessels. PDGF is not detected in the outer retina or RPE in untreated eyes, but is detected in RPE participating in wound repair, either adjacent to laser burns or underlying retinal detachment. PDGF and PDGF receptors are also expressed in RPE in epiretinal membranes removed during vitreous surgery. These data suggest that PDGF is an autocrine stimulator of growth in RPE that plays a role in retinal wound repair and epiretinal membrane formation.

Animals↗

The course of nonproliferative diabetic retinopathy following ECCE with posterior chamber IOL implantation.

A prospective study on the effect of ECCE + IOL implantation on the course of diabetic retinopathy (DR) in 59 eyes showed that in one to three years following surgery, progression of DR, including the development of newly formed one, occurred in 28.8% of the eyes. This was more marked in patient with IDDM (IDDM-46%, NIDDM-24%) as well as in eyes with pre-operative BDR (pre-operative BDR-62.5%, no pre-operative BDR-16.3%). Final visual acuity was better in eyes without pre-operative DR as well as in eyes that did not show progression of the retinopathy.

Aged↗

A new technique for improved diagnosis of local placental abnormalities: Fourier analysis of intraplacental waveforms.

A new method to diagnose localized placental lesions is introduced. The method involves Fourier analysis of intraplacental and umbilical Doppler velocity waveforms. It is shown, using a theoretical model based on an electrical transmission line approach, that intraplacental waveforms that are of higher pulsatilities than those in the umbilical artery indicate placental abnormalities. The method was applied in a series of cases with normal umbilical waveforms in which placental abnormalities were diagnosed. The method promises to be more sensitive and specific than analyzing umbilical waveforms alone as it does not depend on uncertain threshold values.

Adult↗

[Pneumatic-retinopexy scleral buckling for retinal detachment].

30 eyes with rhegmatogenous retinal detachment due to retinal tear at the upper half of the circumference or due to a macular hole underwent SF6 gas injection into the vitreous. In 25 eyes (83%) the retina had re-attached 1-2 days following the injection and the tear was then photocoagulated. Final visual acuity was 6/12 or better in 13 eyes, 6/15-6/20 in 4 eyes, 6/30-6/60 in 8 eyes and less than 6/60 in 5 eyes, 3 of which had a macular hole. There was no morbidity or irritation compared to conventional scleral buckling, and the functional results were better. 4 of the 5 failures underwent successful surgery. In only 1 eye the retina could not be attached by surgery. Pneumatic retinopexy can substitute for surgery in selected cases of retinal detachment.

Gases↗

Human retinal pigment epithelial cells possess V1 vasopressin receptors.

Membrane preparations of cultured human retinal pigment epithelial (RPE) cells were incubated with various concentrations of [3H]arginine vasopressin (AVP) in the presence and absence of 10 microM nonradioactive AVP. Saturable, specific binding to a single site with a Kd of 6.2 nM and Bmax of 111 fmol/mg protein was detected. Vasopressin had no effect on RPE cyclic AMP levels measured by radioimmunoassay. Intracellular calcium fluxes were measured by spectrofluorometry of RPE cell suspensions preloaded with quin 2. The baseline cytosolic calcium level was 217 +/- 20 nM, and AVP caused a concentration-dependent increase in this level with a 3.5-fold maximal response at 10(-6) M and an EC50 of 120 nM. The production of inositol phosphates was measured in RPE preloaded with [3H]myoinositol, and AVP caused a concentration-dependent increase in their production with a 2.1-fold maximal response at 10(-5) M and an EC50 of 80 nM. A specific vasopressin receptor antagonist, SKF 101926, prevented the AVP-induced increase in calcium mobilization and inositol phosphate production in RPE. These data suggest that RPE cells possess V1 AVP receptors coupled to calcium mobilization and inositol phosphate metabolism.

Aminoquinolines↗

Human retinal pigment epithelial cells in culture possess A2-adenosine receptors.

Adenosine agonists cause a marked stimulation in cyclic AMP accumulation in whole human retinal pigment epithelial (RPE) cells in the presence of adenosine deaminase and papaverine, a phosphodiesterase inhibitor. N-Ethylcarboxamidoadenosine (NECA) stimulates cyclic AMP accumulation 16.1-fold above basal with an EC50 of 2.5 x 10(-7) M. It is also an effective (1.9-fold) stimulator of adenylate cyclase activity in RPE membrane preparations and a modest (1.22-fold) stimulator in the presence of forskolin in RPE cell membranes prepared from freshly isolated porcine RPE. N6-Cyclopentyladenosine (CPA) and N6-phenylisopropyladenosine (PIA) also increase cyclic AMP levels with EC50s of 4.9 x 10(6) M (8.9-fold above basal) and 3.5 x 10(-6) M (8.0-fold above basal) respectively. This potency order (NECA greater than PIA greater than CPA) is typical of A2-adenosine receptors. The relatively A1-selective agonists 10(-7) M indicating that RPE cells do not have A1-receptors which inhibit adenylate cyclase. Three adenosine receptor antagonists, BW-A1433U, 8-cyclopentyltheophylline and 8-sulfophenyltheophylline, blocked the NECA-induced stimulation of cyclic AMP accumulation with IC50s of 0.36 microM, 1.5 microM, and 75 microM respectively. Since alteration of cAMP levels has been demonstrated to affect several RPE functions, including cell migration, resorption of subretinal fluid, and phagocytosis, adenosine may play a significant regulatory role in RPE.

Adenosine↗

Effects of betaxolol/timolol on epinephrine stimulated cyclic-AMP levels in human trabecular meshwork cells.

The effects of timolol and betaxolol were compared for blocking beta agonist stimulation of cyclic-AMP in cultured human trabecular meshwork cells. Epinephrine (10(-5) M) produced a large and rapid increase in HTM cyclic-AMP; timolol (10(-6) M), at concentrations readily achieved in the aqueous humor after 0.5% eyedrops, completely blocked this effect. Recovery from timolol treatment appeared to be relatively slow, with only a 30-40% recovery observed by 9 hours. In comparison, betaxolol (10(-6) M) produced a smaller blockade of the epinephrine effects; a rapid recovery from the betaxolol effects was observed, with a greater than half-maximal response to epinephrine observed 15 minutes after removal of this beta blocker. These findings may help to explain the clinical observations of an outflow facility effect of epinephrine when used in combination protocols with betaxolol, but not with timolol.

Betaxolol↗