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Biomedical subjects

J A Foster

Publications and source records attributed to J A Foster.

At least 19 recordsLinked to original sources

Expression of a killer cell receptor-like gene in plastic regions of the central nervous system.

A property common to the immune system and the nervous system is regulation by a highly complex and adaptable network of cellular interactions. Major histocompatibility complex (MHC) class I molecules, which are ligands of antigen-specific receptors on CD8 T cells and of inhibitory receptors on natural killer cells, have an important and surprising role in the control of activity-dependent neuronal plasticity in the central nervous system (CNS). While expression of MHC class I molecules in neurons has been reported, corresponding immune receptors have not been identified in the CNS. Here we show selective expression of a gene related to killer cell immunoglobulin-like receptor (KIR) genes in subregions of the mouse brain where synaptic plasticity and neurogenesis occur, including olfactory bulbs, rostral migratory stream and dentate gyrus of hippocampus. These results suggest new functions for KIR-like molecules in the CNS.

Animals↗

Botulinum toxin type a for dysthyroid upper eyelid retraction.

PURPOSE: To evaluate the safety and efficacy of botulinum toxin type A for treatment of eyelid retraction resulting from thyroid eye disease (TED) during the inflammatory phase of the condition. METHODS: In this prospective, nonrandomized case series, 18 patients with inflammatory eyelid retraction caused by active TED received botulinum toxin type A injection (10, 5, or 2.5 U) for treatment of upper eyelid retraction. Botulinum toxin type A (Allergan, Irvine, CA, U.S.A.) was injected transconjunctivally just above the superior tarsal border in the elevator complex of the upper eyelid. RESULTS: Seventeen of 18 patients (94%) demonstrated a reduced marginal reflex distance (MRD1) after botulinum toxin injection. The average change in MRD1 of the treated eyelid after injection was -2.35 mm (range, 0 to -8.0 mm). Of the 27 eyelids injected, 33% had a 0- to 1-mm drop in eyelid height, 30% had a 1.5- to 2-mm decrease, 22% had a 2.5- to 3-mm decrease, and 15% had a greater than 3-mm decrease in eyelid height. None of the treated eyelids were noted to increase in height. One patient showed no alteration inafter treatment. One patient had clinically MRD1 significant ptosis and one patient reported worsening of preexisting diplopia after injection. Three patients undergoing unilateral injection had relative contralateral eyelid elevation. All untoward effects resolved spontaneously without sequelae. CONCLUSIONS: : Botulinum toxin type A may be used in the inflammatory stage of thyroid eye disease to improve upper eyelid retraction. Individual response to treatment is variable, but this modality should be considered as a temporizing measure until stability for surgery is reached.

Adult↗

Nasolacrimal obstruction secondary to I(131) therapy.

PURPOSE: To report the finding of nasolacrimal drainage system obstruction associated with I(131) therapy for thyroid carcinoma from an updated and expanded cohort. METHODS: Patients with a history of epithelial derived thyroid carcinoma who had tearing were offered referral for evaluation by an oculoplastic surgeon. Patients underwent nasolacrimal probing and irrigation procedures with localization of their nasolacrimal obstruction. Therapy for the site of obstruction was instituted. RESULTS: Clinically significant tearing was identified in 26 patients, all of whom had previously undergone I(131) therapy (n = 563). Nineteen patients were evaluated and confirmed to have nasolacrimal drainage system obstruction; 7 have yet to be formally evaluated. Areas of obstruction included nasolacrimal duct, common canaliculus, and, rarely, distal upper and lower canaliculi. Patients were treated with a variety of modalities including silicone intubation, balloon dacryoplasty, dacryocystorhinostomy, and conjunctival dacryocystorhinostomy. CONCLUSIONS: The use of I(131) for thyroid carcinoma is associated with a 3.4% incidence of documented nasolacrimal drainage obstruction and an overall 4.6% incidence of documented or suspected obstruction. The true incidence may be higher, since - I(131) treated individuals were neither systematically evaluated nor questioned about tearing. It has yet to be established if the obstructions result from local toxicity caused by the passive flow of radioactive iodine containing tears through these tissues or the active uptake and concentration of I(131) in lacrimal drainage system tissues through the sodium/iodide supporter.

Adolescent↗

Intracerebroventricular but not intravenous interleukin-1beta induces widespread vascular-mediated leukocyte infiltration and immune signal mRNA expression followed by brain-wide glial activation.

Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that appears in brain and cerebrospinal fluid following peripheral immune challenges and central infections or injury. We examined the consequences of i.c.v. infusion of IL-1beta on mRNA expression of several immune markers and on recruitment of peripheral leukocytes. Awake rats were infused with IL-1beta (100 ng/rat) into the lateral ventricle, and 0.5, 2, 4, 8, 12, or 24 h later, animals were killed and their fresh-frozen brains processed for in situ hybridization and immunohistochemistry. Widespread vascular expression of inhibitory factor kappa(B)alpha (Ikappa(B)alpha, marker of nuclear factor kappa(B)alpha transcriptional activity) and inducible cyclooxygenase (COX-2) mRNAs at 0.5-2 h was credited to movement of IL-1beta along ventricular, subarachnoid, and perivascular pathways to target endothelia that express type 1 IL-1 receptor mRNA. Induction of monocyte chemoattractant protein-1 mRNA and intercellular adhesion molecule-1 (ICAM-1) immunostaining on endothelia began at 0.5-2 h. Leukocytes (neutrophils and monocytes, recognized by morphology and CD45 and ED1 immunostaining) appeared in meninges and blood vessels at 2-4 h and diffusely penetrated the parenchyma at 8-24 h. The leukocytes strongly expressed IL-1beta and inducible nitric oxide synthase mRNAs. Beginning at 4-12 h, astrocytes (glial acidic fibrillary protein mRNA and protein and c-fos mRNA) and microglia (ionized calcium-binding adaptor molecule 1 mRNA and protein) showed widespread activation. Other rats received i.v. IL-1beta (6 microg/kg). Their brains showed induction of Ikappa(B)alpha and COX-2 mRNAs in the vasculature at 2 h but none of the other sequelae. In summary, our data indicate that IL-1beta in the cerebrospinal fluid reaches its target receptors on the endothelia via perivascular volume transmission, up-regulates ICAM-1, and triggers a targeted leukocyte emigration and widespread glial activation stimulated perhaps by pro-inflammatory molecules expressed by leukocytes. The dramatic difference between i.c.v. and i.v. routes of administration underscores the potency of IL-1beta within the brain to dynamically affect the cellular trafficking component of 'immune privilege'.

Animals↗

The role of IDA scintigraphy in the follow-up of liver disease in patients with cystic fibrosis.

The main aim of this study was to investigate the role of N-(2,4,6 trimethyl-3-bromophenylcarbamoylmethyl) iminodiacetic acid (IDA; Mebrofenin) scintigraphy in follow-up assessments of the biliary system in patients with cystic fibrosis associated liver disease. Fourteen patients from a study published in 1996 were re-examined after a mean interval of 4.7 years from their initial study, in which diisopropylphenyl carboxymethyl iminodiacetic acid (DISIDA) was used. The results of ultrasound, liver function tests and clinical examination were also compared. Twelve of the patients had been treated with ursodeoxycholic acid and taurine in the interim. Five subjects' IDA examinations showed a slight improvement on follow-up, six deteriorated, two were unchanged, whilst one demonstrated a 'mixed picture'. Overall, nine patients deteriorated in one or more of the tests. No patient showed a decline in all four investigations and only two in three. There was poor correlation between the various follow-up examinations, with different patients showing a decline in some tests but not others. This may be due to the mixture of functional and anatomical studies utilized, their differing sensitivies, and the fact that deterioration in one did not necessarily affect another. In conclusion, follow-up of hepatobiliary disease in patients with cystic fibrosis cannot be encompassed by one method alone. If early detection of disease progression would affect management, patients will continue to require a number of investigations rather than a single test.

Adolescent↗

Molecular evaluation of two major human sperm fibrous sheath proteins, pro-hAKAP82 and hAKAP82, in stump tail sperm.

OBJECTIVE: To determine whether mutations in the pro-hAKAP82 gene and the resulting pro-hAKAP82 and hAKAP82 proteins were associated with the infertility seen in a patient with stump tail sperm. DESIGN: Case report. SETTING: Academic research and teaching environment, tertiary care hospital. PATIENT(S): A single, infertile Caucasian male diagnosed with essentially 100% stump tail sperm. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Electrophoresis, silver staining, and immunoblotting of patient and control sperm proteins; RII (type II regulatory subunit of protein kinase-A) overlay assay of patient and control sperm proteins, partial DNA sequence analysis of patient's pro-hAKAP82 gene; indirect immunofluorescence and immunogold electron microscopy of patient and control sperm. RESULTS(S): No significant abnormalities in the size or amount of pro-hAKAP82 and hAKAP82 or in the ability of these proteins to bind the regulatory subunit of protein kinase-A were identified in the patient's sperm. Partial sequence analysis of the patient's pro-hAKAP82 gene was identical to the published normal sequence. Indirect immunofluorescence and immunoelectron microscopy of sperm localized pro-hAKAP82/hAKAP82 to the sperm flagellum and demonstrated that the proteins were present in a disorganized, amorphous region, which apparently represented the fibrous sheath. CONCLUSION(S): These results suggest that, although pro-hAKAP82 and hAKAP82 localize to the correct structural component of the flagellum and are not directly responsible for the stump tail phenotype, they are unable to assemble normally into the fibrous sheath. Although this study did not identify abnormalities in the pro-hAKAP82 gene or its resulting proteins in a patient with stump tail sperm, several regions of the gene and protein remain to be examined.

A Kinase Anchor Proteins↗

Lipid peroxidation-mediated oxidative stress and dopamine neuronal apoptosis in the substantia nigra during development.

The cellular pathways underlying naturally occurring neuronal apoptosis in the rat substantia nigra (SN) during the perinatal period remain largely unknown. Determining the mediators of this process in development may shed light on causes of premature neuronal death in adult neurodegenerative disorders, including the loss of dopamine neurons in Parkinson's disease. In the present study, we investigated whether lipid peroxidation-mediated oxidative stress mediates developmental death of nigral neurons by (1) establishing the profile of lipid peroxidation and other oxidative stress markers throughout the postnatal period both in the SN and striatum, and (2) examining whether the inhibitor of lipid peroxidation, alpha-tocopherol, protects these neurons from death. In addition to monitoring, the level of lipid peroxidation throughout development, we also measured the activities of three antioxidant enzymes, namely superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). We have shown that lipid peroxidation and SOD activity progressively increased from postnatal day (PND) 3 to PND 42 in both SN and striatum. During this period, GPx activity remained stable, while catalase activity transiently increased at PND 8 only in the SN. Furthermore, alpha-tocopherol treatment from embryonic day 18 to PND 2 did not reduce the number of apoptotic neurons at PND 3. These results do not support the hypothesis that lipid peroxidation-mediated oxidative stress is the major mediator of nigral dopamine neuronal apoptosis during the perinatal period.

Animals↗

Evolutionary computation.

Evolution does not require DNA, or even living organisms. In computer science, the field known as 'evolutionary computation' uses evolution as an algorithmic tool, implementing random variation, reproduction and selection by altering and moving data within a computer. This harnesses the power of evolution as an alternative to the more traditional ways to design software or hardware. Research into evolutionary computation should be of interest to geneticists, as evolved programs often reveal properties - such as robustness and non-expressed DNA - that are analogous to many biological phenomena.

Algorithms↗

Inverted pyramidal biopsy.

We describe a biopsy technique that is simple, rapid, and effective for numerous cutaneous lesions. The inverted pyramidal biopsy (IPB) creates an acute geometric tissue defect with an apex located in the dermis. A cosmetically pleasing result, while still providing adequate tissue to render a histologic description and diagnosis, is obtained. The technique can also be employed to remove a host of benign lesions, including dermatofibroma, fibrous papules, and chalazion, among others.

Biopsy↗

Electrosurgical standing cutaneous cone modification.

BACKGROUND: Tissue redundancy manifesting as a standing cutaneous cone is a common surgical problem. OBJECTIVE: To describe the use of electrosurgery to modify standing cutaneous cones. METHODS: Electrical current is applied via an electrosurgical needle to deep dermis and subcutaneous fat. The superficial dermis and epidermis are left undisturbed. In properly selected standing cones, correction of the standing cone is achieved without scar lengthening. RESULTS: Use of the technique can provide standing cone correction without lengthening the surgical scar. There has been no increase in wound failure or infection with the described technique. CONCLUSION: Electrosurgical modification complements existing surgical techniques for standing cutaneous cone repair.

Cicatrix↗

Effect of 131 iodine therapy on the course of Graves' ophthalmopathy: a quantitative analysis of extraocular muscle volumes using orbital magnetic resonance imaging.

There remains uncertainty as to the effect of radioactive iodine (131I) therapy on the associated ophthalmopathy (GO). Twenty newly diagnosed patients with Graves' hyperthyroidism treated with 131I (median dose, 15.5 mCi) were followed with ophthalmologic evaluations (OE) and magnetic resonance imaging (MRI) at baseline, 2, and 6 months, and with OE alone at 3 years. For MRI, the superior, inferior, and medial rectus muscle volumes and total muscle volumes (TMV) were measured. Replacement levothyroxine was initiated as low thyroxine (T4) levels were noted. At baseline, 10 patients (50%) showed evidence of mild GO by OE and/or MRI. There was a significant difference in TMV between the 20 patients with Graves' hyperthyroidism and 10 controls (mean +/- standard error [SE]; 2,652 +/- 118 vs. 2,046 +/- 96 mm3; P = 0.002) and between the 10 patients with and 10 without GO (3,006 +/- 96 vs. 2,298 +/- 61 mm3; P = 0.001). TMV correlated with the Hertel score (r = 0.56, P = 0.01). TMV showed no significant change at 2 or 6 months posttreatment. The inferior rectus volume increased slightly at 2 months posttreatment (P = 0.03) but remained stable at 6 months. Furthermore, no significant changes occurred in Hertel scores or in clinical assessments up to 3 years posttreatment and none showed worsening or new development of GO. In conclusion, our results show no significant risk for radioiodine-induced initiation or progression of mild GO.

Adult↗

Differential release of guinea pig sperm acrosomal components during exocytosis.

The contents of the sperm acrosome are compartmentalized at the biochemical and morphological levels. Biochemically, the acrosome can be considered to be comprised of two compartments: one consisting of readily soluble proteins and one containing a particulate acrosomal matrix. To test the hypothesis that compartmentalization affects the release of acrosomal components during the course of secretion in guinea pig sperm, we examined the relationship between the presence of specific proteins and acrosomal status and monitored the recovery of acrosomal constituents in the medium surrounding sperm induced to undergo exocytosis with the ionophore A23187. Cysteine-rich secretory protein 2 (CRISP-2), a soluble component of the acrosome, was rapidly lost from the acrosome soon after ionophore treatment. However, acrosomal matrix components remained associated with the sperm for longer periods. AM67, a matrix component and the guinea pig orthologue of the mouse sperm zona pellucida-binding protein sp56, was released at a slower rate than was CRISP-2 but at a faster rate than were two other matrix proteins, AM50 and proacrosin. Coincident with their release from the sperm, AM50 and proacrosin were posttranslationally modified, probably by proteolysis. The release of proacrosin from the matrix appears associated with the conversion of this protein to the enzymatically active acrosin protease. These results provide strong support for the hypothesis that compartmentalization plays a significant role in regulating the release of proteins during the course of acrosomal exocytosis. Acrosomal matrix proteins remain associated with the sperm for prolonged periods of time following the induction of acrosomal exocytosis, suggesting that transitional acrosomal intermediates may have significant functions in the fertilization process.

Acrosin↗

Flap minimization via peripheral recruitment.

PURPOSE: To describe tissue-conserving modifications to traditional flap design such as the use of beveled incisions and the pattern of the incisions. These techniques should maintain flap viability and enhance cosmesis. METHODS: We describe the techniques of peripheral flap recruitment. RESULTS: Flaps conformed to reduced geometry, beveled incisions and bases, and tapered ends maximize vascularity. Peripheral tissues are recruited to fill primary defects; smaller flaps thus can be used to fill larger defects. Additionally, this flap design enhances cosmetic results and maintains a high probability for flap survival. CONCLUSION: The described novel flap design has many potential advantages over traditional designs. Correctly applied, these flap techniques spare tissue, decrease scarification, trauma and bleeding, and reduce the need for secondary procedures. Potential drawbacks of this flap design include temporary anatomic distortion especially over rounded structures such as the nose. Complications are minimal.

Ear Diseases↗

Functional components of basic fibroblast growth factor signaling that inhibit lung elastin gene expression.

Previously, we have demonstrated that basic fibroblast growth factor (bFGF) decreases elastin gene transcription in confluent rat lung fibroblasts via the binding of a Fra-1-c-Jun heterodimer to an activator protein-1-cAMP response element in the distal region of the elastin promoter. In the present study, we show that bFGF activates the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2, resulting in the translocation of phosphorylated extracellular signal-regulated kinase 1/2 into the nucleus followed by increased binding of Elk-1 to the serum response element of the c-Fos promoter, transient induction of c-Fos mRNA, and sustained induction of Fra-1 mRNA. The addition of PD-98059, an inhibitor of mitogen-activated protein kinase kinase, abrogates the bFGF-dependent repression of elastin mRNA expression. Comparative analyses of confluent and subconfluent fibroblast cultures reveal significant differences in elastin mRNA levels and activator protein-1 protein factors involved in the regulation of elastin transcription. These findings suggest that bFGF modulates specific cellular events that are dependent on the state of the cell and provide a rationale for the differential responses that can be expected in development and injury or repair situations.

Animals↗

Series spiral advancement flap: an alternative to the ellipse.

BACKGROUND: Surgical excision of skin lesions is a common dermatologic procedure. OBJECTIVE: An alternative to the elliptical excision is described. METHODS: We present an excisional technique that creates a series of nonepidermal outwardly spiraling flaps. The surgical defect is closed with specially tunneled absorbable suture. RESULTS: There has been no increase in infectious complications or wound failures compared with standard ellipses. Proper patient and lesion selection aids in obtaining an acceptable outcome. CONCLUSION: The series spiral advancement flap has the potential to become a useful and common surgical technique.

Dermatologic Surgical Procedures↗

Neurons expressing NADPH-diaphorase in the developing human spinal cord.

The present study used nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry to identify populations of neurons containing nitric oxide synthase and to describe their putative migration during development of the human spinal cord. As early as week 6 (W6) of gestation, diaphorase expression was observed in sympathetic preganglionic neurons (SPNs) and interneurons of the ventral horn. As development proceeded, the SPNs translocated dorsally to form the intermediolateral nucleus, and the interneurons remained scattered throughout the ventral horn. In addition to the dorsal translocation of SPNs, a unique dorsomedially directed migratory pathway was observed. At later stages of development, other groups of SPNs were identified laterally in the lateral funiculus and medially in the intercalated and central autonomic regions. In addition, two "U-shaped" groups of diaphorase-labeled cells were identified around the ventral ventricular zone at W7. Cells of these groups appeared to translocate dorsally over the next weeks and presumably give rise to interneurons within the deep dorsal horn and surrounding the central canal. Furthermore, during W7-14 of gestation, the deep dorsal horn contained a number of diaphorase-positive cells, whereas the superficial dorsal horn was relatively free of staining. These data demonstrate that nitric oxide is present very early in human spinal cord development and that two unique cell migrations initially observed in rodents have now been identified in humans. Furthermore, nitric oxide may be expressed in some populations of neurons as they migrate to their final positions, suggesting that this molecule may play a role in neuronal development.

Anterior Horn Cells↗

NADPH-diaphorase reveals presumptive sympathetic primary afferents in the developing human spinal cord.

Numerous studies have elucidated two visceral afferent pathways in the spinal cord of mammals, the lateral collateral pathway (LCP) and the medial collateral pathway (MCP). The present study utilized NADPH-diaphorase histochemistry to visualize afferent pathways in the developing human thoracolumbar spinal cord. Diaphorase-positive fiber bundles, strikingly similar to the previously defined LCP and MCP, were observed coursing along the lateral and medial aspects of the dorsal horn to the base of the dorsal horn, the intermediate gray, and/or the dorsal commissure. Furthermore, some axons forming the MCP crossed in the dorsal commissure to the contralateral side of the spinal cord. In addition, axons projecting in the LCP often appeared to terminate within clusters of diaphorase-labeled sympathetic preganglionic neurons, supporting the concept that monosynaptic connections may exist between primary afferents and autonomic motor neurons. Thus, nitric oxide may be involved in both afferent and efferent neurons in reflex pathways of the human sympathetic nervous system.

Adrenergic Fibers↗

Evidence of deprenyl-insensitive apoptosis of nigral dopamine neurons during development.

Apoptosis of dopamine neurons occurs naturally in the substantia nigra during development, culminating in approximately 30% loss of these cells during the perinatal period. Deprenyl, independent of its monoamine oxidase (MAO)-B inhibitory properties, can prevent dopamine neuronal apoptosis in models of neurodegeneration. Our current study demonstrate that apoptotic death of dopamine neurons during development is insensitive to daily treatment of pregnant mothers and then newborns with deprenyl (0.1, 1, or 10 mg/kg). This result is not due to poor crossing of the placental and blood-brain barriers, since deprenyl caused a dose-dependent inhibition of brain MAO-B activity in pups at birth. Determining the pathway(s) leading to deprenyl-insensitive apoptosis of nigral dopamine neurons in development may shed light on mechanisms underlying the premature death of dopamine neurons in neurodegenerative disorders.

Animals↗