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Biomedical subjects

V T Tran

Publications and source records attributed to V T Tran.

At least 19 recordsLinked to original sources

Modeling the electrophoresis of rigid polyions: application to lysozyme.

An algorithm is developed to determine the electrophoretic mobility of a rigid polyion modeled as a low dielectric volume element of arbitrary shape containing an arbitrary charge distribution. The solvent is modeled as a high dielectric continuum with salt distributed according to the linearized Poisson Boltzmann equation. Account is also taken of a Stern layer that separates the molecular surface and the surface of hydrodynamic shear, or Stern surface. Relaxation of the ion atmosphere because of the presence of the external field is ignored. The electrostatic and hydrodynamic problems are both solved by boundary element methods. The procedure is first applied to spherical polyions containing monopolar, dipolar, and quadrupolar charge distributions, and calculated mobilities are found to be in excellent agreement with the theory of Yoon and Kim. It is then applied to lysozyme by using models that account for the detailed shape and charge distribution of the enzyme. For reasonable choices of the molecular and Stern surfaces, calculated and experimental mobilities are found to be in fair agreement with each other. However, if a pH independent Stern layer (or, equivalently, translational diffusion constant, Dt) is assumed, the calculated mobilities exhibit a stronger pH dependence than is observed experimentally. A small increase in Dt with increasing pH could correct this discrepancy.

Algorithms

[Uveitis in the elderly].

BACKGROUND: There is only scarce information available in the literature on uveitis of older patients. The aim of this study was to study this age group in greater detail. PATIENTS AND METHODS: 435 patients were seen in the uveitis clinic of the University Eye Hospital Jules Gonin from January 1990 to March 1993. We analysed here the 94 (21.8%) patients that presented a first episode of uveitis after the age of sixty. RESULTS: This collective was characterised by an increased frequency of the anatomic diagnosis of panuveitis (p < 0.0001), and of the specific diagnosis of zoster uveitis (p < 0.0001), sarcoidosis (p < 0.0001), uveitis associated with scleritis (p < 0.05) and granulomatous anterior uveitis (p < 0.01). The frequency of diagnosis of intermediate uveitis was significantly reduced (p < 0.034) as were the specific diagnosis of HLA-B27 positive acute anterior uveitis (p < 0.001), pars planitis (p < 0.08) and non granulomatous anterior uveitis (p < 0.01). Reiter's uveitis, Possner-Schlossmann Syndrome, Behçet's uveitis, Vogt-Koyanagi-Harada disease and Toxoplasmosis retinochoroiditis were never diagnosed in this group of elderly patients. The proportion of defined specific diagnosis (75.5%) was comparable to the group of patients of less than 60 years old. CONCLUSION: As can be seen from our data, epidemiological characteristics of old age uveitis differ markedly from younger patients which should influence the diagnostic approach in these patients.

Aged

[Indications and complications of systemic corticosteroid therapy in treatment of uveitis].

PURPOSE: Systemic steroids is often the first choice of immunosuppressive therapy for severe endogenous uveitis. The aim of this study was to analyse the indications of steroid therapy, complications and side-effects. PATIENTS AND METHODS: Charts from all patients that received oral steroid therapy were reviewed for this purpose and a questionnaire was sent out to all patients to record their subjective complaints. RESULTS: From January 1990 to March 1993, 63 out of the 435 new patients seen at the uveitis clinic received oral prednisone. In 4 cases severe complications occurred that did however not lead to discontinuation of therapy. In 2 cases of intolerance cyclosporine (CsA) had to be added to the treatment regimen to lower the steroid doses and in one case steroids had to be stopped because of intolerance. The questionnaire showed a high rate of subjective side-effects to steroids. CONCLUSIONS: In our collective oral steroids were associated with complications, intolerance and side-effects in a high proportion of cases. It is important to explain the possible side-effects to the patient before starting the therapy. The preventable collateral effects like weight gain and decalcification should be addressed by diet recommendations and modern calcium sparing therapy.

Administration, Oral

Intravenous cefazolin in penetrating eye injuries. Treatment of experimental posttraumatic endophthalmitis.

The use of intravenous antibiotics as prophylaxis in penetrating eye injuries is strictly empiric and not based on scientific data supporting their use. To determine the efficacy of prophylactic intravenous cefazolin in penetrating eye injuries, a rabbit model of posttraumatic endophthalmitis was developed. Forty rabbits received penetrating eye injuries followed immediately by an intravitreal inoculum of live Staphylococcus epidermidis. The rabbits then were randomly divided into four groups: group 1 received three doses of intravenous cefazolin; group 2 received six doses, and group 3 received nine doses; group 4 received no treatment and served as controls. All control rabbits developed 4+ vitreitis; rabbits receiving three doses of the antibiotic developed 2+ vitreitis, and those receiving six or nine doses of cefazolin showed no vitreous inflammation (P < or = 0.0001). Histologic examination of control eyes showed an exuberant reaction with formation of retrolental membranes, vitreous abscess, and retinal detachment. Eyes treated with nine doses of cefazolin were devoid of inflammatory cells. These findings suggest that intravenous cefazolin is effective in preventing the development of posttraumatic endophthalmitis in a rabbit model.

Animals

Defective lens fiber differentiation and pancreatic tumorigenesis caused by ectopic expression of the cellular retinoic acid-binding protein I.

All-trans retinoic acid, a metabolite of retinol, is a possible morphogen in vertebrate development. Two classes of cellular proteins, which specifically bind all-trans retinoic acid, are thought to mediate its action: the nuclear retinoic acid receptors (RAR alpha, beta, gamma), and the cytoplasmic binding proteins known as cellular retinoic acid-binding proteins I and II (CRABP I and II). The function of the retinoic acid receptors is to regulate gene transcription by binding to DNA in conjunction with the nuclear retinoid X receptors (RXR alpha, beta, gamma), which in turn have 9-cis retinoic acid as a ligand. Several lines of evidence suggest that the role of the cellular retinoic acid-binding proteins is to control the concentration of free retinoic acid reaching the nucleus in a given cell. Here, we have addressed the role of the cellular retinoic acid-binding protein I in development by ectopically expressing it in the mouse lens, under the control of the alpha A-crystallin promoter. We show that this ectopic expression interferes with the development of the lens and with the differentiation of the secondary lens fiber cells, causing cataract formation. These results suggest that correct regulation of intracellular retinoic acid concentration is required for normal eye development. In addition, the generated transgenic mice also present expression of the transgene in the pancreas and develop pancreatic carcinomas, suggesting that overexpression of the cellular retinoic acid-binding protein is the cause of the tumors. These results taken together provide evidence for a role of the cellular retinoic acid-binding protein in development and cell differentiation. The relevance of these findings to the possible role of the cellular retinoic acid-binding proteins in the transduction of the retinoic acid signal is discussed.

Animals

Vitrectomy for perforating eye injuries from shotgun pellets.

Pars plana vitrectomy and scleral buckling were performed on 22 eyes of 19 patients for treatment of perforating eye injuries from shotgun pellets. We reviewed the intraoperative findings at the time of vitrectomy to determine what factors might influence final visual acuity. The presence of a total retinal detachment at vitrectomy portended a poor prognosis when compared with eyes without total retinal detachment, as only one of ten eyes with total retinal detachment obtained useful vision (P = .002). Preoperative separation of the posterior vitreous was associated with a favorable outcome when compared with the absence of posterior vitreous detachment (P = .035), as ten of 16 eyes with posterior vitreous detachment at the time of vitrectomy ultimately achieved functional vision. The locations of the exit wounds did not affect visual success in the overall series of patients. However, in the patients who achieved visual success, exit wounds outside the vascular arcades were more likely to be associated with final visual acuities of, or better than, 20/70 than were those within the arcades (P = .022). Other prognostic factors, such as the number of perforations and the use of cryotherapy, were also examined for their effects on final visual outcome. However, these factors did not appear to affect visual outcome statistically.

Adolescent

Postnatal development of the ciliary body and pars plana. A morphometric study in childhood.

The ciliary body of the human eye serves many vital functions and provides important access to the posterior segment of the globe in vitreoretinal surgery. Although embryogenesis and prenatal development of the ciliary body have been well documented, continuing development of the ciliary body during early childhood has not been studied extensively. We determined the lengths of the ciliary body and pars plana in 76 normal eyes of subjects who ranged in age from 1 week to 6 years. The ciliary body was found to be of substantial length soon after birth; it measured a mean of 3.06 mm nasally and 3.31 mm temporally. Three quarters of the final length of the ciliary body at adulthood was achieved by age 24 months. The growth of the ciliary body is discussed in relation to the growth of the eye.

Age Factors

Human retinal pigment epithelial cells possess beta 2-adrenergic receptors.

Beta-adrenergic receptors on cultured human retinal pigment epithelium were demonstrated by the binding of [125I]cyanopindolol. Its pharmacologic specificity was also examined. Specific [125I]cyanopindolol binding was saturable, with a dissociation constant of 130 pM and a receptor density of 12 fmol per one-half million cells, which is equivalent to 14,000 receptor sites per retinal pigment epithelial cell. Agonists competed for specific [125I]cyanopindolol binding, with the following rank order of potencies: (-)-isoproterenol > (-)-epinephrine > (-)-norepinephrine. Beta 2-selective antagonist ICI-118551 was approximately 3 log orders more potent than the beta 1-selective antagonist, betaxolol. These receptors were also coupled to an adenylate cyclase. These results suggest strongly that cultured human retinal pigment epithelial cells possess beta 2-adrenergic receptors. The potential significance of these findings with regard to retinal pigment epithelial functions is discussed herein.

Adenylyl Cyclases

Differential localization of dopamine D1 and D2 receptors in rat retina.

Dopamine interacts with distinct receptors on different target neurons in the rat retina. Dopamine receptors were labeled in the rat retina by autoradiography using 3H-SCH-23390 and 3H-spiperone binding to retinal sections. The 3H-SCH-23390 binding to D1 receptors was most concentrated in the inner plexiform, inner nuclear, and ganglion cell layers; it was absent from the outer nuclear layer and the photoreceptor inner and outer segments. Competition studies indicated that 3H-SCH-23390 binding to the inner retina was inhibited with high affinities by the D1-specific agonist and antagonist, SKF-38393 and SCH-23390. The D2-specific compounds were ineffective in competing for 3H-SCH-23390 binding. The 3H-spiperone binding to D2 receptors, however, was most concentrated in the photoreceptor inner and outer segments and in the outer nuclear layer. The D2-specific agonist and antagonists, such as quinpirole, sulpiride, and eticlopride, competed for 3H-binding with high affinities; SCH-23390 and SKF-38393 were ineffective. The D2 receptors on the photoreceptors had a high affinity for clozapine but lower affinities for the modified benzamides. This is characteristic of a novel subtype of D2 receptors. Thus, D1 and D2 dopamine receptors are localized differentially in the rat retina to mediate different physiologic effects of dopamine.

Animals

Guanine nucleotide-binding regulatory proteins in retinal pigment epithelial cells.

The expression of GTP-binding regulatory proteins (G proteins) in retinal pigment epithelial (RPE) cells was analyzed by RNA blot hybridization and cDNA amplification. Both adult and fetal human RPE cells contain mRNA for multiple G protein alpha subunits (G alpha) including Gs alpha, Gi-1 alpha, Gi-2 alpha, Gi-3 alpha, and Gz alpha (or Gx alpha), where Gs and Gi are proteins that stimulate or inhibit adenylyl cyclase, respectively, and Gz is a protein that may mediate pertussis toxin-insensitive events. Other G alpha-related mRNA transcripts were detected in fetal RPE cells by low-stringency hybridization to Gi-2 alpha and Gs alpha protein-coding cDNA probes. The diversity of G proteins in RPE cells was further studied by cDNA amplification with reverse transcriptase and the polymerase chain reaction. This approach revealed that, besides the above mentioned members of the G alpha gene family, at least two other G alpha subunits are expressed in RPE cells. Human retinal cDNA clones that encode one of the additional G alpha subunits were isolated and characterized. The results indicate that this G alpha subunit belongs to a separate subfamily of G proteins that may be insensitive to inhibition by pertussis toxin.

Amino Acid Sequence

A clinical comparison of the Oculab Tono-Pen with the Goldmann applanation tonometer in eyes filled with silicone oil.

Intraocular pressure in 21 eyes filled with silicone oil was measured with two different instruments: the Oculab Tono-Pen and a Goldmann applanation tonometer mounted to a slit lamp biomicroscope. Intraocular pressure ranged from 2 mmHg to 28 mmHg, and the mean difference between readings obtained from the two instruments was 0.64, which was not statistically significant. These results suggest that the Oculab Tono-Pen is an effective instrument with which to measure intraocular pressure in silicone-filled eye.

Cataract Extraction

Somatostatin binding sites in human and monkey brain: localization and characterization.

A radioiodinated analogue of somatostatin 28, 125I [Leu8,D-Trp22,Tyr25] SS-28, was used to localize and characterize somatostatin binding sites in both human and monkey brain. High-affinity binding sites (approximately 1 nM) were found in cerebral cortex. The highest binding was in cerebral cortex with intermediate binding found in hippocampus, striatum, and amygdala and low binding in hypothalamus and brainstem. There was a rough correlation between somatostatin receptor binding and concentrations of somatostatin-like immunoreactivity (SLI) in human brain. Somatostatin receptors were stable for up to 24 h in an animal model simulating human autopsy conditions and there was no correlation between postmortem interval and receptor binding in human brain. Pharmacologic characterization in human cortex showed that there was a correlation between the inhibition of receptor binding by somatostatin analogues and their known abilities to inhibit growth hormone secretion. These findings demonstrate that a highly specific membrane-associated receptor for somatostatin is present in both monkey and human brain. Examination of somatostatin receptor binding in Alzheimer's disease and Huntington's disease may improve understanding of the role of somatostatin in both these illnesses.

Animals

Reduced numbers of somatostatin receptors in the cerebral cortex in Alzheimer's disease.

Somatostatin receptor concentrations were measured in patients with Alzheimer's disease and controls. In the frontal cortex (Brodmann areas 6, 9, and 10) and temporal cortex (Brodmann area 21), the concentrations of somatostatin in receptors in the patients were reduced to approximately 50 percent of control values. A 40 percent reduction was seen in the hippocampus, while no significant changes were found in the cingulate cortex, postcentral gyrus, temporal pole, and superior temporal gyrus. Scatchard analysis showed a reduction in receptor number rather than a change in affinity. Somatostatin-like immunoreactivity was significantly reduced in both the frontal and temporal cortex. Somatostatin-like immunoreactivity was linearly related to somatostatin-receptor binding in the cortices of Alzheimer's patients. These findings may reflect degeneration of postsynaptic neurons or cortical afferents in the patients' cerebral cortices. Alternatively, decreased somatostatin-like immunoreactivity in Alzheimer's disease might indicate increased release of somatostatin and down regulation of postsynaptic receptors.

Adult

Two types of somatostatin receptors differentiated by cyclic somatostatin analogs.

Somatostatin receptors in rat brain, pituitary, and pancreas were labeled with two radioiodinated analogs of somatostatins 14 and 28. Two cyclic analogs of somatostatin, SMS201-995 and cyclo(Ala-Cys-Phe-D-Trp-Lys-Thr-Cys), showed biphasic displacement of binding to somatostatin receptors by these radioligands. In contrast, all other somatostatin analogs, including somatostatin-14, competed for the receptor sites with monophasic displacement of radioligand receptor binding. Thus two types of somatostatin receptors were identified. It was found that the pituitary and pancreas have predominantly one type of somatostatin receptor whereas the brain has both, and that different regions of the brain have various proportions of the two types. These findings suggest methods to characterize other types of somatostatin receptors subserving somatostatin's diverse physiological functions, including a potential role in cognitive function and extrapyramidal motor system control.

Animals

[Salmonella osteomyelitis in sickle cell anemia].

Case report of a 28-year old black sickle cell anemia patient with salmonella osteomyelitis of the radius. Aside from sickle cell anemia patients this skeletal complication of enteric salmonellosis is an extreme rarity. Description of the typical roentgenological features including intracortical fissures and sequestration.

Adult

[3H]doxepin interactions with histamine H1-receptors and other sites in guinea pig and rat brain homogenates.

[3H]Doxepin, a tricyclic antidepressant, binds to brain homogenates with two saturable components. The high affinity component, with a dissociation constant (KD) of 0.26 nM, is associated with histamine H1-receptors. This high affinity binding shows stereospecificity in that d-chlorpheniramine is 100 times more potent than the pharmacologically less active l-isomer. Its drug specificity and regional variation closely parallel those exhibited by [3H]mepyramine binding. The drug specificity of the low affinity component is distinct from that of histamine H1-receptors, with no stereospecificity for chlorpheniramine isomers. Furthermore, all the H1-histamine antagonists tested display micromolar potency at the low-affinity doxepin sites but nanomolar potency at the high-affinity doxepin sites associated with a physiological histamine H1-receptor. The drug specificity of the low affinity site does not correspond to that of any known neurotransmitter receptor. Tricyclic antidepressants display IC50 values of 30-600 nM for the inhibition of [3H]doxepin binding to the low-affinity component with most values in the 0.1-0.3 microM affinity range.

Animals