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M Adamian

Publications and source records attributed to M Adamian.

34 records · Page 2Linked to original sources
PubMed1999

Focal wall overstretching after high-pressure coronary stent implantation does not influence restenosis.

To determine if vessel wall overstretching during coronary stenting is associated with a higher restenosis rate, the intravascular ultrasound morphological evaluation was performed following ultrasound criteria. A total of 468 lesions with successful coronary Palmaz-Schatz stenting guided by intravascular ultrasound were classified into the no overstretching group (n = 295) and the overstretching group (n = 147). There were 26 lesions not classifiable due to the poststent morphology. Balloon-to-vessel ratio was 1.12 +/- 0.17 in the no focal overstretching group and 1. 20 +/- 0.20 in the overstretching group (P < 0.0002). Follow-up angiogram was performed in 77% of no focal overstretching group and in 75% of the focal overstretching group. The restenosis rate of the no focal overstretching group was 19.8% and 20.9% in the focal overstretching group, respectively (P = 0.65). Focal overstretching was more frequent following balloon oversizing. No increase in restenosis rate, found in focal overstretched stented lesions, leads us to the hypothesis of a regulation of smooth-muscle-cell proliferation activated by the normalization of blood flow and of shear stress, when stent implantation succeeds in optimally improving the lumen. Cathet. Cardiovasc. Intervent. 48:24-30, 1999.

Coronary Angiography↗
PubMed1998

Histopathologic and immunohistochemical study of an autopsy eye with X-linked cone degeneration.

We performed a histopathologic and immunohistochemical study of eyes obtained at autopsy of an 84-year-old man from a family with X-linked cone degeneration in which affected members have a 6.5-kilobase deletion in the red cone pigment gene. At his most recent ocular examination, at age 71 years, this patient had had a visual acuity of 20/200 OU, fundus changes suggestive of macular degeneration, borderline-normal full-field rod electroretinograms, and profoundly reduced full-field cone electroretinograms. Histopathologic examination demonstrated marked loss of cone and rod photoreceptors and the retinal pigment epithelium in the central macula. The peripheral cone population was reduced, while the peripheral rod population was relatively preserved. Immunohistochemical examination with an antibody to both red and green cone opsin and an antibody to blue cone opsin disclosed a prominent loss of the red and green cone population and preservation of the blue cone population. These findings show that a defect in the red cone pigment gene can result in extensive degeneration of the red and green cone population across the retina.

Aged↗
PubMed1998

Histopathologic and immunohistochemical study of dominant cone degeneration.

PURPOSE: To report the histopathologic and immunohistochemical findings in autosomal dominant cone degeneration. METHODS: The autopsy eyes of a 75-year-old man with autosomal dominant cone degeneration were studied with both light and electron microscopy. In addition, immunofluorescent studies using antibodies to cone opsins and cone alpha transducin were performed. RESULTS: Histopathologic examination of the fovea disclosed loss of photoreceptors and attenuated retinal pigment epithelium. Reduced numbers of cones could be seen in the parafovea, and only occasional cones were visible in the periphery; rods were preserved in the periphery. CONCLUSION: The histopathologic and immunohistochemical findings in this case of dominantly inherited cone degeneration correlate well with the loss of cone function and preservation of normal or nearly normal rod function upon clinical examination. This condition affects red, green, and blue cones.

Aged↗
PubMed1997

Molecular characterization of abLIM, a novel actin-binding and double zinc finger protein.

Molecules that couple the actin-based cytoskeleton to intracellular signaling pathways are central to the processes of cellular morphogenesis and differentiation. We have characterized a novel protein, the actin-binding LIM (abLIM) protein, which could mediate such interactions between actin filaments and cytoplasmic targets. abLIM protein consists of a COOH-terminal cytoskeletal domain that is fused to an NH2-terminal domain consisting of four double zinc finger motifs. The cytoskeletal domain is approximately 50% identical to erythrocyte dematin, an actin-bundling protein of the red cell membrane skeleton, while the zinc finger domains conform to the LIM motif consensus sequence. In vitro expression studies demonstrate that abLIM protein can bind to F-actin through the dematin-like domain. Transcripts corresponding to three distinct isoforms have a widespread tissue distribution. However, a polypeptide corresponding to the full-length isoform is found exclusively in the retina and is enriched in biochemical extracts of retinal rod inner segments. abLIM protein also undergoes extensive phosphorylation in light-adapted retinas in vivo, and its developmental expression in the retina coincides with the elaboration of photoreceptor inner and outer segments. Based on the composite primary structure of abLIM protein, actin-binding capacity, potential regulation via phosphorylation, and isoform expression pattern, we speculate that abLIM may play a general role in bridging the actin-based cytoskeleton with an array of potential LIM protein-binding partners. The developmental time course of abLIM expression in the retina suggests that the retina-specific isoform may have a specialized role in the development or elaboration of photoreceptor inner and outer segments.

Actins↗
PubMed1996

Clinical and histopathologic findings in clumped pigmentary retinal degeneration.

OBJECTIVE: To describe the clinical and histopathologic features of clumped pigmentary retinal degeneration (CPRD). DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Twenty-four patients, aged 7 to 83 years, were identified from the medical record filed of the Berman-Gund Laboratory, Boston, Mass, as having the clinical features of CPRD. The autopsy eye from a 56-year-old man with CPRD was studied with light and electron microscopy. MAIN OUTCOME MEASURES: Visual acuities, visual fields, dark-adaptation thresholds, and results of electroretinograms; histopathologic study of an autopsy eye. RESULTS: The functional deficit of patients with CPRD seems to be similar to that of patients with typical retinitis pigmentosa. Different degrees of severity were observed among patients of similar age. The histopathologic data showed that the clinically distinct areas of clumped pigment are due to excessive accumulation of melanin granules in retinal pigment epithelial cells. CONCLUSION: Based on the distinct clinical and histopathologic appearance, CPRD should be considered as a separate form of retinal degeneration.

Adolescent↗
PubMed1994

Rhodopsin accumulation at abnormal sites in retinas of mice with a human P23H rhodopsin transgene.

PURPOSE: To investigate the mechanism by which photoreceptors degenerate in transgenic mice carrying a mutant human rhodopsin gene (P23H). METHODS: The temporal and spatial pattern of the retinal degeneration caused by P23H rhodopsin was mapped using immunocytochemistry with rhodopsin-specific antibodies. The subcellular localizations of rhodopsin, transducin, and rod cGMP phosphodiesterase (PDE) were also determined, and rhodopsin localization was compared among P23H transgenic mice, rd mice, and Royal College of Surgeons (RCS) rats. RESULTS: In transgenic mice that express P23H rhodopsin, photoreceptors are lost centrally by postnatal day 10. As the retina degenerates, rhodopsin accumulates in the outer nuclear layer and within the photoreceptor synaptic terminals. The P23H transgenic retinas also show an accumulation of transducin and PDE within the outer plexiform layer. In contrast, other types of hereditary retinal degenerations studied show a similar pattern of rhodopsin accumulation in the outer nuclear layer but not in the outer plexiform layer of the retina. CONCLUSIONS: The pattern of degeneration in the P23H transgenic retina is consistent with a model in which the centrally located, first-born photoreceptors are the first to die. In contrast to other animal models for hereditary retinal degeneration (rd, RCS), a novel feature of the P23H degeneration is an accumulation of rhodopsin, transducin, and PDE within the outer plexiform layer of the retina. One hypothesis to explain this observation is that P23H rhodopsin is routed intracellularly through a pathway not used by normal rhodopsin. Nonmutant forms of the peripheral transducing proteins normally associated with disk membrane, such as transducin and PDE, may accompany the aberrantly routed rhodopsin.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1994

In vivo transfer of a reporter gene to the retina mediated by an adenoviral vector.

PURPOSE: The ability of replication-deficient adenovirus to mediate gene transfer to retinal cells was evaluated. METHODS: A replication-deficient adenoviral vector, AdCMV beta A.ntlacZ, which contains the bacterial beta-galactosidase (lacZ) reporter gene, was injected into the subretinal space of normal, rd, and rds strains of mice at various ages. The efficiency and duration of transgene expression were assessed by histochemical examination and transmission electron microscopy. RESULTS: AdCMV beta A.ntlacZ was effective in mediating gene transfer to the retinal pigment epithelial cells, rod and cone photoreceptor cells, and cells in the inner nuclear layer of the retina for periods of up to 1 month. Gene transfer to retinal pigment epithelial cells occurred at much lower viral titers than was required for gene transfer to photoreceptor cells. The extent to which photoreceptor cells could be transduced varied with the age of the animals and the conditions of the photoreceptor cells: greater numbers of photoreceptor cells were transduced in 5- to 7-day-old pups and in mice at the initial stages of photoreceptor degeneration than in normal adult mice. No evidence of gross pathogenic effects or viremia in recipient mice was observed. CONCLUSIONS: Replication-deficient adenovirus mediates transfer and expression of a foreign gene in retinal pigment epithelial and photoreceptor cells. Gene transfer to photoreceptor cells is enhanced in developing retinas or at the predegenerate stage of photoreceptors in genetically programmed retinal degeneration.

Adenoviruses, Human↗
PubMed1993

Olivopontocerebellar atrophy with retinal degeneration. An electroretinographic and histopathologic investigation.

BACKGROUND: Olivopontocerebellar atrophy is an uncommon disorder with variable clinical manifestations that affects the cerebellum, the spinocerebellar tracts, and other structures of the brainstem. A deficiency of glutamate dehydrogenase, which results in an excess of glutamate, has been suggested to play a role in the pathogenesis of olivopontocerebellar atrophy. In experimental animals, toxic levels of glutamate are known to cause a selective loss of the b-wave on electroretinographic (ERG) testing and a degeneration of the inner retinal layers. One of the subtypes of olivopontocerebellar atrophy, type II, according to Harding's classification, is associated with retinal degeneration. METHODS: The authors describe the ophthalmologic and ERG findings in a family with olivopontocerebellar atrophy type II. Histopathologic study of an eye from a 6-year-old family member who died of severe neurologic deterioration secondary to olivopontocerebellar atrophy type II was performed. RESULTS: Electroretinographic changes may be present in affected family members who are entirely asymptomatic and have a normal ophthalmologic evaluation. The changes on the ERG in one patient suggest that cone dysfunction is one of the subtle changes that may be seen in olivopontocerebellar atrophy type II. Our ERG results did not show a selective loss of the b-wave but instead showed a loss of both the a-wave and b-wave in affected family members. Results of light and electron microscopic examination showed diffuse and extensive degeneration of the photoreceptors involving both rods and cones, the most prominent changes being present in the macula. An amorphous debris, presumably degenerated photoreceptors, was noted between the outer nuclear layer and retinal pigment epithelium. CONCLUSION: Patients with olivopontocerebellar atrophy type II have photoreceptor abnormalities as revealed in abnormal ERGs seen in many patients and histopathologic study of an autopsy eye from an affected 6-year-old boy. Our results do not support the hypothesis that glutamate toxicity may be responsible for the development of retinal degeneration in this condition.

Adult↗
PubMed1992

Ultrastructural findings in an autopsy eye from a patient with Usher's syndrome type II.

We studied an eye taken at autopsy from a 55-year-old woman with retinitis pigmentosa and partial deafness (Usher's syndrome type II). Two years before her death, her visual acuity was R.E.: 20/80 and L.E.: 20/50, and visual fields were constricted to a 30- to 40-degree diameter with a V4e white test light. Both rods and cones were present across the retina except for areas of the midperiphery; remaining photoreceptors had shortened or disrupted outer segments, or both, and some cones had inclusion bodies in inner segments. In the macula, most of the connecting cilia of photoreceptors appeared abnormal, with either extra microtubules or an apparent disruption of the nexin link between doublet microtubules. The pigment epithelium was abnormal across the eye, with diminished apical microvilli and basal infoldings of the plasma membrane. Possible mechanisms by which abnormal cilia could lead to photoreceptor cell death are considered.

Female↗
PubMed1991

Cytoskeletal specializations at the rod photoreceptor distal tip.

We have examined microtubules and microtubule-like elements within the toad rod photoreceptor outer segment in order to define regional specializations of the photoreceptor cytoskeleton. "Ciliary" microtubules were localized within the rod outer segment (ROS) by using thin section electron microscopy, immunofluorescence, and rapid-freeze deep-etch microscopy. All three methods showed that ciliary microtubules stop short of the extreme ROS distal tip, although abundant microtubule-like structures distinct from the ciliary microtubules were found within the distal 10-15 microns of the ROS tip. These heretofore undescribed "distal ROS tubules" are clustered at the clefts or incisures of the disk membrane stack and resemble microtubules in overall size and shape, although they are not closely related antigenically to tubulin. The distal ROS tubules are more abundant in green rods than red rods and vary in number during the daily light/dark cycle. Quantitation of these tubules at two time points during the light/dark cycle suggests that there are three- to fourfold more tubules in the ROS tip one hour after light onset than one hour before light onset. Retinas prevented from normal disk membrane shedding by separation of the retina from the adjacent pigment epithelium, failed to develop increased numbers of tubules after light onset. This suggests that the newly described distal ROS tubules may modulate or be modulated by light-induced interactions between the photoreceptors and pigment epithelium, such as those that occur during the disk shedding phase of membrane turnover.

Animals↗
PubMed1991

A 52 kD cytoskeletal protein from retinal rod photoreceptors is related to erythrocyte dematin.

A novel cytoskeletal antigen, RET52, has been identified in the mouse retina. This 52 kD polypeptide is antigenically related to dematin (band 4.9), an actin-bundling phosphoprotein component of the erythrocyte membrane skeleton. Like dematin, RET52 is also a substrate for cAMP-dependent protein kinase. Within the retina, RET52 is primarily concentrated in two regions-the rod inner segment and the outer synaptic layers-although the developmental expression of RET52 differs in these areas. RET52 is present at birth in the inner segment, but appears about the time of initial synapse formation (postnatal day 4-6) in the outer plexiform layer. No differences in RET52 expression have been detected in early-stage mouse retinas with the retinal degeneration (rd) phenotype. RET52 localization, developmental expression, homologies to dematin, and in vitro phosphorylation pattern suggest a possible role for cytoskeleton-associated proteins in the initiation or control of disk membrane assembly and/or synapse formation in the rod photoreceptor.

Animals↗
PubMed1987

Characterization of retinal pigment epithelial cells cultured on microporous filters.

Retinal pigment epithelium (RPE) cultured on microporous filter supports was compared to RPE cultured on plastic and evaluated for features characteristic of RPE in vivo. RPE cells grown on filters were cuboidal, formed junctional complex structures between cells, and had elaborate microvilli and basal infoldings similar to RPE in vivo, while RPE grown on plastic also formed intercellular junctions but appeared squamous and had few microvilli and basal infoldings. RPE grown on filters or plastic secreted an extracellular matrix at the basal surface and ingested isolated rat rod outer segments at the apical surface. RPE grown on filters coated with laminin or fibronectin became confluent more rapidly than RPE grown on uncoated filters, while RPE grown at the same density on filters coated with collagen type I did not become confluent. The laminin and fibronectin coatings did not alter the RPE cell morphology; however, cells seeded on collagen-coated filters grew in large disorganized clusters. RPE grown on laminin-coated filters formed functional tight junctions as evidenced by the capacity of RPE monolayers to prevent the bulk flow of medium and the passage of trypan blue across the filter. Radiolabeled sucrose and inulin were used to measure the paracellular flux through the tight junctions between cells. The passage of these tracers was linear over time, with the lower molecular weight tracer, sucrose, passing through the monolayer more readily than inulin. Values for the flux of radiolabeled bovine serum albumin across RPE monolayers fell between values for sucrose and inulin. The results from these studies show that RPE monolayers cultured on laminin-coated filters maintain a morphology similar to that of RPE in vivo, are capable of ingesting rod outer segments, and form a selectively permeable barrier to various tracers. This culture system should be useful for studies of transepithelial transport, secretion, endocytosis and exocytosis that require independent control of the extracellular environment at the apical and basolateral cell surfaces.

Animals↗
PubMed1983

Ultrastructure of the eye of a euphausiid crustacean.

The compound eye of the Antarctic euphausiid Euphausia superba is a spherical clear zone eye. The dioptric system consists of a hexagonally-faceted cornea, two corneagenous cells, two crystalline cone cells which form the bipartite crystalline cone, and two accessory cone cells. The dioptric system of each ommatidium is separated from that of adjacent ommatidia by six distal pigment cells and a basement membrane. The proximal tip of the crystalline cone is cupped by the distal ends of the seven retinula cells whose nuclei are arranged in a staggered array slightly distal to the middle of the clear zone. In the distal half of the clear zone, each narrow retinula cell column is surrounded by large proximal extensions of the six distal pigment cells. The pigment cells narrow more proximally and terminate at the proximal basement membrane. A specialized axial channel complex extends from the crystalline cone through the clear zone, and is continuous with a conical refractive element which caps the distal end of the rhabdom. The rhabdom is fused, and made up of alternating highly birefringent layers of orthogonally-oriented microvilli. It is surrounded by a narrow extra-cellular space which is continuous with the distal refractive element and a second conical refractive element at the proximal end of the rhabdom.

Animals↗
PubMedDate not supplied

Short- and intermediate-term results of (32)P radioactive beta-emitting stent implantation in patients with coronary artery disease: The Milan Dose-Response Study.

BACKGROUND: Radioactive (32)P beta-emitting stents have been shown to reduce intrastent neointimal hyperplasia in a substantial dose-related manner in the animal model. The aim of this dose-response study was to evaluate, in the clinical setting, the safety and efficacy at 6-month follow-up of this approach to reducing restenosis. METHODS AND RESULTS: A total of 122 (32)P radioactive beta-emitting stents (initially the Palmaz-Schatz and later the BX Isostent) with an activity level of 0.75 to 3.0 microCi (group 1), 3.0 to 6.0 microCi (group 2), and 6.0 to 12.0 microCi (group 3) were implanted in 91 lesions in 82 patients. There were no procedural events. At 6-month follow-up, no deaths had occurred, and only 1 patient had stent thrombosis. Pure intrastent binary restenosis was 16% in group 1, 3% in group 2, and 0% in group 3. However, intralesion restenosis was 52% in group 1, 41% in group 2, and 50% in group 3. CONCLUSIONS: The use of (32)P radioactive beta-emitting stents in patients with CAD is feasible. At 6-month follow-up, intrastent neointimal hyperplasia was reduced in a dose-related manner. However, in the 3 groups, intralesion restenosis was high because of a high late lumen loss in the reference segments at the stent edges, possibly as a result of a low activity level of radiation at the edges of the stent combined with an aggressive approach to stenting. We called this "edge effect" the "candy wrapper."

Analysis of Variance↗