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Biomedical subjects

J A Foster

Publications and source records attributed to J A Foster.

At least 55 records · Page 3Linked to original sources

Reconstruction of the irradiated contracted socket with an expanded superficial temporalis fascial flap.

PURPOSE: To describe the reconstruction of an irradiated contracted socket with an expanded superficial temporalis fascial flap and oral mucosa. METHODS: A superficial temporalis fascial flap was first expanded with tissue expansion techniques and then rotated into the orbit to revascularize the socket. The mucosal surface of the socket was secondarily grafted with buccal and hard palate mucosa. RESULTS: The expanded superficial temporalis fascial flap was used to revascularize the socket for grafting with hard palate and buccal mucosa. This resulted in the successful retention of an ocular prosthesis. CONCLUSION: The expanded superficial temporalis fascial flap is a useful technique in reconstruction of the contracted socket.

Child, Preschool↗

Direct orbital manometry in patients with thyroid-associated orbitopathy.

PURPOSE: To determine orbital tissue tension and orbital compartment compliance in patients with and without thyroid-associated orbitopathy (TAO). DESIGN: Prospective case series. PARTICIPANTS: Orbits of patients with TAO (18 orbits) and control patients without TAO (35 orbits) were studied. METHODS: An orbital manometer was designed to directly measure orbital tissue tension in patients undergoing ocular or orbital surgery. MAIN OUTCOME MEASURES: Tissue tension was recorded before, during, and for 5 minutes after a 5-ml retrobulbar injection of anesthetic. Orbital compliance was calculated as change in volume divided by change in tissue tension. RESULTS: Resting orbital tissue tension was 4.4 +/- 2.2 mmHg (mean +/- SD) in normal orbits and 9.7 +/- 4.8 mmHg in orbits of TAO patients (P = 0.0005) Following retrobulbar injection, orbital tissue tension rose to 12.0 +/- 3.6 mmHg (P = 0.0000000000000006 compared with baseline) in the control group and to 36.3 +/- 15.2 mmHg in the TAO group (P = 0.0000007 compared with baseline, and P = 0.000008 TAO group versus control group). Orbital compartment compliance was 0.80 +/- 0.50 ml/mmHg in the control group and 0.27 +/- 0.21 ml/mmHg in the TAO group (P = 0.00001). Resting orbital tissue tension in 8 TAO orbits with compressive optic neuropathy was 12.4 +/- 4.9 mmHg, and was 7.8 +/- 3.5 mmHg in 10 orbits of TAO patients without compressive optic neuropathy (P < 0.05). No adverse events occurred. CONCLUSIONS: Retrobulbar injection causes consistent measurable changes in orbital tissue tension. Orbital manometry safely demonstrated higher orbital tissue tension and lower orbital compartment compliance in the orbits of TAO patients versus those of normal subjects. Resting orbital tissue tension was higher in the orbits of TAO patients with compressive optic neuropathy than in those orbits without. Compressive optic neuropathy may partially result from an orbital compartment syndrome in some patients with TAO. Directly assessing orbital dynamics in vivo may prove useful as an adjunct in the clinical evaluation of patients with TAO and other orbital disorders.

Aged↗

Selegiline effects on cocaine-induced changes in medial temporal lobe metabolism and subjective ratings of euphoria.

To test the effect of selegiline, a specific monoamine oxidase B (MAO-B) inhibitor, on the cerebral metabolic and euphorigenic effects of cocaine in experienced users, eight cocaine-dependent (CD) subjects were evaluated using a within-subjects design. Each subject participated in two pairs of [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans (baseline scan followed 24 h later by a second scan obtained in conjunction with a 40-mg cocaine infusion) performed before and after a 1-week period of daily treatment with 10 mg selegiline administered orally. The hippocampus and amygdala were evaluated because of their hypothesized involvement in the addiction process, and the thalamus was evaluated as a comparison region. Following 7 days of selegiline treatment, the magnitude of the subjective euphoria ("high") produced by cocaine infusion was reduced by 40% (cocaine by selegiline interaction F = 7.15, df = 1.21, p = .014). Selegiline treatment also altered glucose utilization (normalized against whole brain counts) in the two limbic regions, but not the thalamus. In the amygdala, the effects of cocaine differed, depending upon whether or not patients were being treated with selegiline (cocaine by selegiline interaction F = 4.67, df = 1,19.8, p = .043). A different effect was observed in the hippocampus, where selegiline treatment decreased metabolic activity irrespective of whether cocaine was given (main effect F = 7.70, df = 1.20, p = .012). The concomitant changes in both the subjective experience of the "high" and normalized amygdala glucose utilization after selegiline treatment, suggest that a relationship exists between cocaine-induced euphoria and limbic metabolism. The data suggest that selegiline may be a useful adjunct in the treatment of cocaine dependence.

Adult↗

The role of NF-1 factors in regulation of elastin gene transcription.

The -195- to -500-bp region of the human elastin promoter has been shown to convey high activity in neonatal rat aortic smooth muscle cell and pulmonary fibroblast cell cultures. In addition, this region has been implicated in controlling the differential basal level of elastin transcription in these two cell types. The overall goal of this study was to define the positive element(s) within the -195- to - 500-bp region and to identify the trans-acting factors binding to this sequence. A combination of deletion and linker scan mutational analyses localizes the positive element between -401 and -415 bp. Gel shift analyses demonstrate that the positive element binds NF-1 family members. Co-transfection of a CTF1 expression vector in Drosophila Schneider cells shows the ability of an NF-1 family member to activate elastin promoter activity through this site. Comparative Western and Southwestern blot analyses of nuclear extracts isolated from SMC and lung fibroblasts lay the foundation for possible differential regulation of elastin transcriptional levels via cell specific expression of different NF-1 family members.

Animals↗

Codon optimization, genetic insulation, and an rtTA reporter improve performance of the tetracycline switch.

The objective of this work was to further develop a tetracycline repressor (TetR) protein system that allows control of transgene expression. First, to circumvent the need for a binary approach, a single plasmid design was constructed and tested in tissue culture. To indirectly assay integrations that express the synthetic transcription factor (rtTA), a bicistronic gene was built which included an internal ribosome entry site (IRES) and a green fluorescent protein coding region (GFP) on the same expression cassette as the coding region of rtTA (pTetGREEN). This construct did not produce fluorescent colonies when stably integrated and provided minimal expression of GFP in the face of adequate expression of rtTA. The coding region for TetR was then altered by introducing 156 silent point mutations to simulate mammalian genes. Replacement of wild-type TetR gene (tetR) in pTetGREEN with 'mammalianized' tetR provided GFP expression. Adjustment of codon usage in the tetR region of rtTA nearly doubled the expression level of functional rtTA. To increase the number of rtTA expressing lines, the chicken egg-white lysozyme matrix attachment region (MAR) was introduced into the single plasmid design just upstream of the tetracycline operators (tetO). Inclusion of the MAR doubled the number of colonies that expressed rtTA (44% vs 88%). With the modifications described here, the number of lines that express rtTA and provide induction from a single plasmid design can be increased by the inclusion of a MAR and the level of rtTA expression can be further increased by adjusting the base composition of the TetR coding region. The MAR also insulates the inducible gene from the promoter driving rtTA.

Amino Acid Sequence↗

Upper lid blepharoplasty.

Upper lid blepharoplasty is the most common cosmetic procedure performed in men and women. The eyes are the most important aesthetic facial unit and also a sensitive projector of facial aging changes. Patients will complain about tired eyes, sad eyes, or extra tissue around the eyes. Dermatochalasis, fat herniation or protrusion, brow ptosis, and eyelid ptosis secondary to disinsertion or dehiscence of the levator aponeurosis all contribute to a patient's perceptions of the need for upper lid blepharoplasty. In this article we discuss aging changes in the periocular region in Asian and Caucasian type eyelids and in male and female patients. Traditional upper lid blepharoplasty techniques, indications for surgery, psychological considerations in candidates for cosmetic surgery, and frequently encountered complications are also covered.

Anesthesia, Local↗

Direct orbital manometry in healthy patients.

PURPOSE: To determine orbital tissue tension and orbital compartment compliance in normal patients. METHODS: An orbital manometer was designed to directly measure orbital tissue tension before, during, and after a 5-ml retrobulbar injection of anesthetic in patients undergoing ocular surgery. Tissue tension was recorded for 5 minutes after the injection. Orbital compliance was calculated as change in volume divided by change in pressure. Data were collected from 18 normal orbits. RESULTS: Resting orbital tissue tension was 4.0 +/- 1.5 mmHg (mean +/- standard deviation). After retrobulbar injection, orbital tissue tension rose to 11.6 +/- 2.6 mmHg (p = 0.00000000009 compared with baseline). After 5 minutes, tissue tension declined to 6.6 +/- 1.9 mmHg (p = 0.00000001 compared with preinjection and p = 0.00002 compared with postinjection). Orbital compartment compliance was 0.74 +/- 0.31 ml/mmHg. No adverse events occurred. CONCLUSIONS: The authors' orbital manometer safely determined orbital tissue tension and orbital compartment compliance in normal orbits. Retrobulbar injection causes consistent measurable changes in orbital tissue tension. Directly assessing orbital dynamics in vivo may prove useful both as an adjunct in the clinical evaluation of patients with disorders resulting in an orbital compartment syndrome as well as in assessing the risk of retrobulbar injection in orbits at greater risk for complications from this procedure.

Anesthetics, Local↗

Hard palate mucosal grafts in the treatment of the contracted socket.

PURPOSE: The treatment of the traumatic contracted anophthalmic socket is challenging. The ability to wear an ocular prosthesis may require multiple operations to replace orbital volume, mucosa, or both. Hard palate mucosal grafts are a logical choice to augment mucosa and volume in the reconstruction of a contracted socket. METHODS: Ten patients with severely contracted sockets underwent socket reconstruction using hard palate mucosal grafts. The mucosal surface lining the contracted sockets was undermined and recessed toward the lid margins. Hard palate mucosal grafts that were harvested freehand and by using a radiofrequency instrument were placed in the socket fundus and sutured to the recessed mucosal edges. Forniceal sutures were placed full thickness through the lids, and custom conformers were placed in the sockets. In six patients, fixation sutures were passed through the conformer, fornices, and full thickness through the lid. In four patients, temporary tarsorrhaphies were placed for a minimum of 4 weeks postoperatively. RESULTS: Postoperatively, 8 of the 10 patients were able to wear an ocular prosthesis comfortably. Cosmesis was acceptable. Two patients had recurrent socket contracture and were unable to wear a prosthesis. CONCLUSIONS: Hard palate mucosal grafts are a useful option in the surgical rehabilitation of contracted sockets. A mucosal surface, resistance to contracture, ease of harvesting, and ability for additional harvesting are advantages over other graft materials.

Adult↗

The zebrafish swimbladder: A simple model for lung elastin injury and repair.

In this communication we offer data to suggest that the zebrafish swimbladder may provide a simple model of elastin injury and repair which is amenable to genetic analysis and pertinent to lung physiology. In situ hybridization of zebrafish embryos illustrated that elastin gene expression is evident in the developing gut tract prior to swimbladder morphogenesis. Northern blot analysis demonstrated that the major zebrafish elastin mRNA is 2.0 kb which is significantly smaller than its higher vertebrate counterpart. Amino acid analysis of alkali-resistant protein from the anterior chamber of the adult zebrafish swimbladder showed a composition similar to higher vertebrate elastins including significant amounts of desmosine crosslinks. Electron microscopic investigations of the swimbladder wall indicate a simple structure with an inner layer of elastin fibers. Elastase delivery to the swimbladder in vitro resulted in significant fragmentation of elastin in the anterior chamber providing an environment for studying elastin repair within the tissue.

Air Sacs↗

The mechanism of action of steroidogenic acute regulatory protein (StAR). StAR acts on the outside of mitochondria to stimulate steroidogenesis.

Steroidogenic acute regulatory protein (StAR) plays an essential role in steroidogenesis, facilitating delivery of cholesterol to cytochrome P450scc on the inner mitochondrial membrane. StAR is synthesized in the cytoplasm and is subsequently imported by mitochondria and processed to a mature form by cleavage of the NH2-terminal mitochondrial targeting sequence. To explore the mechanism of StAR action, we produced 6-histidine-tagged N-62 StAR (His-tag StAR) constructs lacking the NH2-terminal 62 amino acids that encode the mitochondrial targeting sequence and examined their steroidogenic activity in intact cells and on isolated mitochondria. His-tag StAR proteins stimulated pregnenolone synthesis to the same extent as wild-type StAR when expressed in COS-1 cells transfected with the cholesterol side-chain cleavage system. His-tag StAR was diffusely distributed in the cytoplasm of transfected COS-1 cells whereas wild-type StAR was localized to mitochondria. There was no evidence at the light or electron microscope levels for selective localization of His-tag StAR protein to mitochondrial membranes. In vitro import assays demonstrated that wild-type StAR preprotein was imported and processed to mature protein that was protected from subsequent trypsin treatment. In contrast, His-tag StAR was not imported and protein associated with mitochondria was sensitive to trypsin. Using metabolically labeled COS-1 cells transfected with wild-type or His-tag StAR constructs, we confirmed that wild-type StAR preprotein was imported and processed by mitochondria, whereas His-tag StAR remained largely cytosolic and unprocessed. To determine whether cytosolic factors are required for StAR action, we developed an assay system using washed mitochondria isolated from bovine corpora lutea and purified recombinant His-tag StAR proteins expressed in Escherichia coli. Recombinant His-tag StAR stimulated pregnenolone production in a dose- and time-dependent manner, functioning at nanomolar concentrations. A point mutant of StAR (A218V) that causes lipoid congenital adrenal hyperplasia was incorporated into the His-tag protein. This mutant was steroidogenically inactive in COS-1 cells and on isolated mitochondria. Our observations conclusively document that StAR acts on the outside of mitochondria, independent of mitochondrial import, and in the absence of cytosol. The ability to produce bioactive recombinant StAR protein paves the way for refined structural studies of StAR and StAR mutants.

Animals↗

Elastogenesis in the developing chick lung is transcriptionally regulated.

The overall goals of this study were to establish the level at which elastin gene expression is regulated during chick lung embryogenesis and to identify the temporal and spatial relationships among elastogenesis, smooth muscle cell differentiation, and cell proliferation. A comparison of lung elastin mRNA and transcriptional levels during embryogenesis shows that elastin expression is developmentally regulated at the transcriptional level. The increase in elastogenic activity occurs during the late stages of lung embryogenesis and coincides with terminal maturation of the tertiary bronchi. In situ hybridization analysis demonstrates that the increase in elastin mRNA expression is confined to the tertiary bronchial respiratory subunits, connective tissue septa, and supporting vasculature of the lung parenchyma. Immunohistochemical localization of smooth muscle cell alpha-actin and tropoelastin suggests that alpha-actin-immunoreactive cells of the lung parenchyma are a major contributor to the increase in elastin expression during embryogenesis. This observation is also reflected by Northern blot analysis, which demonstrates a temporal coincidence in the increase of both alpha-actin and elastin mRNA levels. Histone mRNA expression, which was used as an index of cellular proliferation, reveals a level and spatial pattern inversely related to that of the elastin transcript. Tissue transfections of chick lungs isolated from 18-day embryos with various elastin gene deletion/reporter constructs illustrate that the elastin promoter is not promiscuous within a tissue environment and that sequences spanning the -500 to +2 region are capable of directing promoter activity spatially comparable to the endogenous elastin gene.

Actins↗

Intraoperative tissue expansion in eyelid reconstruction.

OBJECTIVE: Chronic tissue expansion is a well-accepted modality for increasing available tissue for reconstructive surgery. In rapid intraoperative tissue expansion (RITE), a tissue expander is used intraoperatively to increase the available tissue area for defect closure. The use of the ubiquitous and inexpensive Foley catheter has previously been reported as a tissue expander in RITE. In this paper, the authors examine the application of the Foley catheter for RITE in oculoplastic surgery. DESIGN: Case series. PARTICIPANTS: Twenty-six patients (ages 50 to 87) with eyelid defects from various causes underwent reconstruction using RITE. INTERVENTION: Using this technique, the tip of a #14 French Foley catheter is trimmed, keeping the balloon intact. The balloon is inserted under a skin-muscle flap. Counter traction is applied, and the balloon is filled with saline until the flap blanches. The balloon is inflated twice for 5 minutes with a 1- to 2-minute rest period between expansions. This provides increased tissue area for reconstruction of periocular defects. MAIN OUTCOME MEASURES: The linear extent of the eyelid defect was measured prior to and after expansion with RITE. A comparison was made between the two measurements. RESULTS: The linear extent of the eyelid margin defect decreased by 36% after RITE. CONCLUSIONS: Rapid intraoperative tissue expansion with a Foley catheter is a means of providing increased tissue area for reconstructive surgery of the eyelids and periorbital region. This technique provides excellent tissue match for color, texture, and thickness. The technique decreases the size of the incised and undermined skin-muscle flap and the tension needed for wound closure.

Aged↗

Targeting of a germ cell-specific type 1 hexokinase lacking a porin-binding domain to the mitochondria as well as to the head and fibrous sheath of murine spermatozoa.

Multiple isoforms of type 1 hexokinase (HK1) are transcribed during spermatogenesis in the mouse, including at least three that are presumably germ cell specific: HK1-sa, HK1-sb, and HK1-sc. Each of these predicted proteins contains a common, germ cell-specific sequence that replaces the porin-binding domain found in somatic HK1. Although HK1 protein is present in mature sperm and is tyrosine phosphorylated, it is not known whether the various potential isoforms are differentially translated and localized within the developing germ cells and mature sperm. Using antipeptide antisera against unique regions of HK1-sa and HK1-sb, it was demonstrated that these isoforms were not found in pachytene spermatocytes, round spermatids, condensing spermatids, or sperm, suggesting that HK1-sa and HK1-sb are not translated during spermatogenesis. Immunoreactivity was detected in protein from round spermatids, condensing spermatids, and mature sperm using an antipeptide antiserum against the common, germ cell-specific region, suggesting that HK1-sc was the only germ cell-specific isoform present in these cells. Two-dimensional SDS-PAGE suggested that all of the sperm HK1-sc was tyrosine phosphorylated, and that the somatic HK1 isoform was not present. Immunoelectron microscopy revealed that HK1-sc was associated with the mitochondria and with the fibrous sheath of the flagellum and was found in discrete clusters in the region of the membranes of the sperm head. The unusual distribution of HK1-sc in sperm suggests novel functions, such as extramitochondrial energy production, and also demonstrates that a hexokinase without a classical porin-binding domain can localize to mitochondria.

Amino Acid Sequence↗

Cosmetic indications for botulinum A toxin.

This article describes the use of botulinum toxin type A in the cosmetic treatment of facial wrinkles. Injection techniques, volumes, and concentration of the botulinum A toxin are described for various types of facial wrinkles.

Botulinum Toxins, Type A↗

The endoscopic browlift for forehead rejuvenation.

Since its initial description by Vasconez et al in 1992, the endoscopic browlift has evolved into a popular method for addressing brow ptosis and forehead rejuvenation. The advantages of fewer incisions, less postoperative swelling, alopecia and prolonged scalp anesthesia, and more rapid rehabilitation have provided greater patient acceptance than the traditional coronal approach. Unlike the coronal browlift where the amount of elevation is determined by the amount of skin excised, the elevation in the endoscopic browlift is determined by periosteal release at the arcus marginalis and forehead flap fixation. Though equipment costs are greater and a learning curve exists, the endoscopic browlift offers the oculoplastic surgeon additional beneficial options in the management of brow ptosis.

Endoscopy↗

Effects of code growth and parsimony pressure on populations in genetic programming.

Parsimony pressure, the explicit penalization of larger programs, has been increasingly used as a means of controlling code growth in genetic programming. However, in many cases parsimony pressure degrades the performance of the genetic program. In this paper we show that poor average results with parsimony pressure are a result of "failed" populations that overshadow the results of populations that incorporate parsimony pressure successfully. Additionally, we show that the effect of parsimony pressure can be measured by calculating the relationship between program size and performance within the population. This measure can be used as a partial indicator of success or failure for individual populations.

Biological Evolution↗

Assembly of AKAP82, a protein kinase A anchor protein, into the fibrous sheath of mouse sperm.

The assembly of the mammalian sperm flagellum is a complex developmental event requiring the sequential activation of genes encoding the component parts and the coordinated assembly of these proteins during the differentiation of the haploid spermatid. In this study, the mechanism underlying the assembly of the fibrous sheath surrounding the axoneme was examined. The subject of the study was the major fibrous sheath protein of the mouse sperm flagellum, AKAP82, a member of the A Kinase Anchor Protein (AKAP) family of polypeptides that bind the regulatory (RII) subunit of protein kinase A (PK-A). Immunoelectron microscopy demonstrated that AKAP82 is present throughout the transverse ribs and longitudinal columns of the fibrous sheath. Since AKAP82 is initially synthesized as a precursor (pro-AKAP82) during spermiogenesis, an antiserum was raised against a peptide from the processed region of pro-AKAP82 (M(r) 97,000). In immunoblotting experiments, the antibody detected pro-AKAP82 in condensing spermatids but not in epididymal sperm. In addition, two other immunoreactive proteins of M(r) 109,000 (p109) and M(r) 26,000 (p26, representing the "pro" domain of the precursor) were present in epididymal sperm. Alkaline phosphatase treatment of epididymal sperm proteins demonstrated that p109 was a phosphorylated form of pro-AKAP82 that remained in sperm. By immunofluorescence, pro-AKAP82 was localized to the entire length of the principal piece in testicular sperm, while in epididymal sperm p109 and p26 were present only in the proximal portion of the principal piece. Pro-AKAP82 was solubilized when germ cells were extracted with Triton X-100. However, in sperm, both AKAP82 and p109 were almost totally resistant to these extraction conditions and remained in the particulate fraction even after extraction with Triton and dithiothreitol. Similar to pro-AKAP82, the RII subunit of PK-A was present in the Triton X-100-soluble fraction of developing germ cells. In sperm, much of the RII also became particulate, consistent with the hypothesis that AKAP82 anchors RII in the flagellum. These data indicate that pro-AKAP82 is synthesized in the cell body, transported down the axoneme to its site of assembly in the fibrous sheath, and then proteolytically clipped to form mature AKAP82.

Animals↗

AM67, a secretory component of the guinea pig sperm acrosomal matrix, is related to mouse sperm protein sp56 and the complement component 4-binding proteins.

The guinea pig sperm acrosomal matrix is the dense core of the acrosome and is likely to be important in acrosome biogenesis and fertilization. Isolated acrosomal matrices are composed of a limited number of major bands when analyzed by SDS-polyacrylamide gel electrophoresis, among which is a Mr 67,000 protein that we have termed AM67. Indirect immunofluorescence demonstrated that AM67 is localized to the apical segment of the cauda epididymal sperm acrosome. Immunoelectron microscopy further refined the localization of AM67 to the M1 (dorsal bulge) domain within the acrosome. Using a polymerase chain reaction product based upon tryptic peptide sequences from AM67, a lambdagt11 guinea pig testis cDNA library was screened to yield two cDNA clones that encode the AM67 peptides. Northern analysis revealed that AM67 is transcribed as a 1. 9-kilobase testis-specific mRNA. The complete AM67 sequence encodes a prepropolypeptide of 533 amino acids with a calculated Mr of 59, 768. Following cleavage of a probable signal sequence, the polypeptide was predicted to have a Mr of 56,851 and seven consensus sites for asparagine-linked glycosylation. The deduced amino acid sequence of AM67 is most similar to those of the mouse sperm protein sp56 and the alpha-subunits of complement component 4-binding proteins from various mammalian species. Although mouse sp56 has been reported to be a cell-surface receptor for the murine zona pellucida glycoprotein ZP3, standard immunoelectron microscopy using the anti-sp56 monoclonal antibody 7C5 detected sp56 within the mouse sperm acrosome, but failed to detect sp56 on the surface of acrosome-intact mouse sperm. Furthermore, acrosomal labeling was detected in mouse sperm prepared for immunofluorescence using paraformaldehyde fixation, but was not observed with live unfixed sperm. Thus, the finding that sp56 is present within the acrosome provides further support that sp56 and AM67 are orthologues and suggests that sp56 may function in acrosomal matrix-zona pellucida interactions during and immediately following the acrosome reaction in the mouse.

Acrosome↗