Biomedical subjects

J A Foster

Publications and source records attributed to J A Foster.

At least 73 records · Page 4Linked to original sources

PubMed1997

Stability of tacrolimus in an extemporaneously compounded oral liquid.

The stability of tacrolimus in an extemporaneously compounded oral liquid formulation was studied. A suspension was prepared by mixing the contents of commercially available 5-mg capsules of tacrolimus with equal amounts of Ora-Plus and Simple Syrup, NF, to make a final volume of 60 mL. The final concentration of tacrolimus in the suspension was 0.5 mg/mL. Six identical suspensions were prepared, placed in three glass and three plastic amber prescription bottles, and stored at room temperature (24-26 degrees C). Immediately after preparation and at 7, 15, 30, 45, and 56 days, samples were removed and assayed in duplicate by stability-indicating high-performance liquid chromatography. At least 98% of the initial tacrolimus concentrations remained in all suspensions throughout the study period. Color, order, and pH did not change appreciably over the study period. Tacrolimus 0.5 mg/mL compounded extemporaneously in equal amounts of Ora-Plus and Simple Syrup, NF, was stable at 24-26 degrees C for at least 56 days in both glass and plastic amber prescription bottles.

Capsules↗

PubMed1997

Mitomycin C treatment for conjunctival-corneal intraepithelial neoplasia: a multicenter experience.

OBJECTIVE: The purpose of the study is to evaluate the efficacy and risks of topical mitomycin C (MMC) for conjunctival-corneal intraepithelial neoplasia (CCIN). DESIGN: The study design was a clinical case series of CCIN. PARTICIPANTS: Seventeen patients, 16 with biopsy-confirmed CCIN and 1 with invasive squamous cell carcinoma (SCC), were included in the study. INTERVENTION: Patients received topical drops of MMC 0.02% to 0.04% four times daily from 7 to 28 days. Retreatment was done in cases of lesion recurrence. MAIN OUTCOME MEASURES: The size of the CCIN before and after the treatment and ocular complications post-MMC application were evaluated. RESULTS: Ten patients remained disease-free after one course of MMC application. In one case, residual CCIN remained very small without regrowth. In the one patient with invasive SCC and in five patients with CCIN, regrowth occurred within 6 months of the first treatment. After retreatment, invasive SCC and CCIN in an additional two patients were eradicated. In two cases, although the size of the lesions decreased after two and three applications of MMC, regrowth occurred, and the CCIN returned to its original size. In the final case, limited recurrence has occurred and no retreatment has been done. The complications of MMC use included mild-to-moderate conjunctival hyperemia and mild allergy, which resolved after discontinuation of the treatment. Severe pain manifested when treatment was longer than 14 days. CONCLUSIONS: Application of topical MMC is an efficient treatment for most but not all cases of CCIN.

Administration, Topical↗

PubMed1997

Computed tomography in lacrimal outflow obstruction.

BACKGROUND: Acquired nasolacrimal duct obstruction is a common ophthalmologic problem. Despite widespread understanding of treatments available for nasolacrimal duct obstruction, few authors have commented on its etiology. Because the nasolacrimal system is anatomically related to important nasal and sinus structures, the authors postulated that acquired nasolacrimal duct obstruction and its complications might occur simultaneous to, and possibly as a consequence of, rhinologic or sinus disease. MATERIALS AND METHODS: Twenty-three patients with acquired nasolacrimal duct obstruction and 100 control patients were evaluated by coronal computed tomography for evidence of sinus disease or nasal abnormalities. Specifically, five findings were noted: ostiomeatal complex disease, ethmoidal opacification, agger nasi cell opacification, concha bullosa, and nasal septal deviation. RESULTS: Overall, 20 (87%) patients with acquired nasolacrimal duct obstruction demonstrated one or more radiologic finding of sinus disease or rhinologic abnormality whereas 63 (63%) control subjects exhibited these findings. This difference was determined to be statistically significant (P < 0.05). A statistically significant higher incidence of ethmoidal opacification, agger nasi cell opacification, and nasal septal deviation was observed in patients with nasolacrimal outflow obstruction than in controls. Differences in the incidence of ostiomeatal complex disease and concha bullosa were not found to be statistically significant. CONCLUSION: These data demonstrate a correlation between computed tomography findings of sinus disease or nasal abnormality and the presence of acquired nasolacrimal outflow obstruction. This association between radiologic evidence of sinorhinologic disorders and lacrimal outflow obstruction may imply that dacryocystitis, like sinus disease, may be produced by disease of the lateral nasal wall. When evaluating a patient with acquired nasolacrimal duct obstruction, the physician should consider evaluation for concomitant nasal and sinus disease.

Humans↗

PubMed1997

Differential induction of heat shock mRNA in oligodendrocytes, microglia, and astrocytes following hyperthermia.

A time course analysis of hsp70 mRNA induction in response to a physiologically relevant increase in body temperature of 2.6 degrees C was performed in the rabbit forebrain. A protocol that combined in situ hybridization and cytochemistry on the same tissue section was employed to identify reactive glial cell types. Cytochemical markers for astrocytes, microglia, and oligodendrocytes were utilized in combination with a DIG-labelled hsp70 riboprobe, which permitted mRNA localization at high resolution. Four glial cell body-enriched regions of the rabbit forebrain were examined, namely, cortical layer 1, hippocampal fissure, corpus callosum, and fimbria. Maximal hsp70 mRNA induction was observed in 2 and 3 h hyperthermic animals. The colocalization analysis demonstrated that hsp70 mRNA was induced in oligodendrocytes and microglia, but not in forebrain GFAP positive astrocytes. In addition, cell counts were performed which showed that almost all oligodendrocytes induced hsp70 mRNA while a subpopulation of microglial cells responded. These data are consistent with the notion that oligodendrocytes, microglia, and astrocytes exhibit distinct thresholds for activation of the heat shock response following a physiologically relevant increase in body temperature.

Animals↗

PubMed1997

MR evaluation of age-related increase of brain iron in young adult and older normal males.

The purposes of this study were to extend the investigation of age-related increases in brain iron to a younger age group, replicate previously published results, and further evaluate the validity of a novel noninvasive magnetic resonance (MR) method for measuring tissue iron (ferritin) levels with specificity. The method consists of measuring the dependence of tissue transverse relaxation rates (R2) on the field strength of MR instruments. Two MR instruments operating at 1.5 and 0.5 T were used to measure the field-dependent R2 increase (FDRI) in the frontal white matter, caudate, putamen, and globus pallidus. A group of 13 normal adult males (ages 21-77), with seven subjects below and six above age 35, was examined. As expected from postmortem and prior FDRI data, robust and significant age-related increases in FDRI were observed in the caudate, putamen, and globus pallidus, with the globus pallidus FDRI increasing sharply in the second decade and reaching a plateau after age 30. In addition, we replicated previous reports showing very high correlations between FDRI and published brain iron levels for the four regions examined. The data replicate and extend previous FDRI observations on brain aging and are consistent with postmortem data on age-related increases in brain iron. These results are relevant to the investigation of age-related neurodegenerative diseases in which iron may catalyze toxic free radical reactions.

Adult↗

PubMed1997

Travel with infants and children.

This article reviews the special needs of infants and children when traveling abroad. It addresses the importance of planning ahead, obtaining immunizations, and assessing possible risks while traveling. Also, this article reviews types of disease that can be acquired during travel and the follow-up care of children when they return home.

Aftercare↗

PubMed1997

Developmental regulation of elastin gene expression.

Developmental regulation of elastin gene expression appears to be exerted primarily at the transcriptional level. Although the elastin gene promoter possesses features of "housekeeping" genes, these characteristics do not preclude transcriptional regulation as shown with a number of other gene promoters of this class. Direct evidence for transcriptional regulation has been obtained by nuclear run-on analysis of nuclei isolated from developing lung and aortic tissues and indirectly through elastin promoter activity in transgenic mice and transient tissue transfections of embryonic lung and aortic tissues. Although several different modulators have been proposed to control the developmental activation of elastin gene expression, only insulin-like growth factor I has been experimentally linked to increased transcription by in vivo studies. This link is specific for aortic smooth muscle cells in which cell cycle control appears intimately associated with elastogenesis. Recent studies suggest that progress in understanding developmental activation of the elastin gene lies in transgenic models and organ transfection assays that assess the direct relevancy of the modulators and cis- and trans-acting factors involved.

Animals↗

PubMed1996

Intracellular localization of heat shock mRNAs (hsc70 and hsp70) to neural cell bodies and processes in the control and hyperthermic rabbit brain.

Heat shock proteins are essential cellular proteins that may play important roles in cellular repair and/or protection. This report focuses on the expression of two members of the hsp70 multigene family, namely, constitutive hsc70 mRNA and stress-inducible hsp70 mRNA in the control and hyperthermic rabbit brain. The intracellular localization of these heat shock mRNAs was examined using high-resolution nonradioactive in situ hybridization. The distribution of hsc70 mRNA and hsp70 mRNA was examined in (1) neuronal cell bodies and their dendritic processes and (2) oligodendrocytes and their cellular processes. In control animals, hsc70 mRNA was detected in the apical dendritic processes and cell bodies of cortical layer II and V neurons, CA3 and CA4 neurons, deep cerebellar neurons, and brainstem neurons. A time course analysis of hsc70 mRNA, after a physiologically relevant increase in body temperature of 2.6 degrees C, revealed more distal transport of this constitutive message into dendrites of these neuronal populations. In the same neuronal populations, basal levels of hsp70 mRNA were observed in the cell body; however, this mRNA was not detected in dendritic processes in control or hyperthermic animals. After hyperthermia, hsp70 mRNA was strongly induced in oligodendrocytes and transported to the processes of these glial cells. The localization of heat shock messages in the processes of these neural cell types could provide a mechanism for local control of synthesis of heat shock proteins in cellular compartments that are remote from the cell body.

Animals↗

PubMed1996

Insulin-like growth factor-I regulates transcription of the elastin gene through a putative retinoblastoma control element. A role for Sp3 acting as a repressor of elastin gene transcription.

Previous studies have demonstrated that insulin-like growth factor-I (IGF-I) increases elastin gene transcription in aortic smooth muscle cells and that this up-regulation is accompanied by a loss of protein binding to the proximal promoter. Sp1 has been identified as one of the factors whose binding is lost, and in the present study we show that Sp3 binding is also abrogated by IGF-I, but in a selected manner. In functional analyses using Drosophila SL-2 cells, Sp1 expression can drive transcription from the elastin proximal promoter, while co-expression of Sp3 results in a repression of Sp1 activity. Footprint and gel shift analyses position the IGF-I responsive sequences to a putative retinoblastoma control element (RCE). Mutation of the putative RCE sequence as assessed by transient transfection of smooth muscle cells results in an increase in reporter activity equal in magnitude to that conferred by IGF-I on the wild type promoter. Together these results support the hypothesis that IGF-I-mediated increase in elastin transcription occurs via a mechanism of derepression involving the abrogation of a repressor that appears to be Sp3 binding to the RCE.

Animals↗

PubMed1996

Elastase release of basic fibroblast growth factor in pulmonary fibroblast cultures results in down-regulation of elastin gene transcription. A role for basic fibroblast growth factor in regulating lung repair.

We have reported previously that a factor released by elastase treatment of pulmonary fibroblast cultures is capable of down-regulating elastin gene expression. In the present study we have pursued the identification of the factor released by elastase treatment and the characterization of the level of elastin gene expression at which this factor exerts its effect. We have found by immunologic and biochemical procedures that elastase treatment results in the release of basic fibroblast growth factor (bFGF) that is bound within the matrix. Both purified bFGF and bFGF released by elastase from cell matrices decrease the transcriptional level of the elastin gene by 70-80% within 24 h. Transient transfections of pulmonary fibroblasts with a series of elastin promoter deletion constructs show that the region of the elastin gene responsive to bFGF is located within sequences spanning -900 to -200 base pairs. The biological implications of these findings coupled with our previous report are significant, since they demonstrate that elastase digestion of pulmonary fibroblast matrices not only results in the proteolysis of elastin but also results in the release of a potent regulator of elastin gene transcription whose activity can influence repair mechanisms.

Animals↗

PubMed1996

Autoantigen 1 of the guinea pig sperm acrosome is the homologue of mouse Tpx-1 and human TPX1 and is a member of the cysteine-rich secretory protein (CRISP) family.

We have cloned and sequenced cDNAs encoding autoantigen 1 (AA1), a testis-specific protein and the major autoantigen of the guinea pig sperm acrosome. The cDNA predicts a precursor protein of 244 amino acids including a 21 amino acid hydrophobic, secretory signal sequence. The mature polypeptide is predicted to have a molecular mass of 24,891 Daltons which agrees with the experimentally determined molecular weight of 25,000. Consistent with previous studies demonstrating that AA1 is not a glycoprotein, the predicted amino acid sequence contained no canonical sites for N-linked glycosylation. Comparison with other sequences showed that AA1 is the guinea pig homologue of the testis-specific protein Tpx-1 in mice and TPX1 in humans. AA1 also showed significant amino acid sequence homology with other cysteine-rich secretory proteins (CRISP's): rat and mouse acidic epididymal glycoproteins (AEG; also known as proteins D/E in rats) and helothermine, a toxin from the Mexican beaded lizard. In addition, AA1 had a lesser degree of homology with antigen 5 (vespid wasp venom), PR-1 (a plant pathogenesis related protein), and GliPR (a protein identified in human gliomas). Northern analysis of RNA from purified guinea pig spermatogenic cells showed that a 1.5 kb message was first detected in pachytene spermatocytes, was strongest in round spermatids, and was detected at a low level in condensing spermatids. Immunoblot analysis and metabolic labeling data of AA1 in spermatogenic cells showed that the protein was synthesized as early as the pachytene spermatocyte stage of spermatogenesis. Thus, the patterns of AA1 mRNA and protein expression during spermatogenesis are similar to the expression of other acrosomal mRNAs and proteins that are first detected meiotically.

Acrosome↗

PubMed1996

Computer simulation of transposable element evolution: random template and strict master models.

It has been proposed that the most extensively studied mammalian retrotransposons replicate by some form of a master template model. This conclusion has been drawn largely from DNA sequence analysis and is based on phylogenetic tree topology, the presence and ordering of shared variants, the degree of divergence between elements within a subfamily, and the shape of the distribution of pairwise differences between elements. To investigate how robust these parameters are as predictors of the model of transposition, computer simulations of the two most extreme transposition models, the Random Template Model and the Strict Master Model, were carried out. A prototype of a computer simulator for studying retrotransposition is presented. The simulator is a versatile digital workbench that maintains DNA sequence data and allows manipulation of a range of factors including reverse transcriptase and in situ mutation rates, transposition template, and transposition rate. All parameters previously used as predictors of the model of transposition were markedly different for the two extreme models when evaluated using large sample sizes of sequences from experiments simulating up to 15 million years of evolution.

Animals↗

PubMed1996

Obesity as a cause of mechanical entropion.

PURPOSE: Although lower eyelid entropion can result from many conditions, obesity is not a generally recognized factor. We treated a case of recurrent severe entropion that was a result of morbid obesity in a patient with de Morsier's syndrome. METHODS: The patient underwent surgery on both lower eyelids. RESULTS: The entropion was corrected by advancing the lower eyelid retractors and debulking the subcutaneous tissue in the lower eyelids. CONCLUSIONS: Mechanical entropion can occur as a rare complication of morbid obesity and may respond to surgical procedures that address its cause.

Abnormalities, Multiple↗

PubMed1996

The efficacy of topical metronidazole in the treatment of ocular rosacea.

PURPOSE: The purpose of the study is to investigate the efficacy of metronidazole topical gel in the treatment of ocular rosacea. METHODS: Ten patients with ocular rosacea were treated prospectively with lid hygiene and topical metronidazole applied to the lid margin in one eye and lid hygiene alone in the fellow eye. The treatment period was 12 weeks. A masked observer graded the ocular findings at the initial visit and at the conclusion of the treatment period. Pretreatment scores were compared with post-treatment scores with respect to ocular surface, eyelid margin, and combined eyelid plus ocular surface. RESULTS: Eight of ten treated eyes improved, whereas only five of ten control eyes improved. There was a statistically significant improvement in the eyelid score in both the treated and control groups (P = 0.003, P = 0.025, respectively), but no significant improvement in the ocular surface score in either group. When the pretreatment and post-treatment eyelid and ocular surface scores were combined, there was a significant improvement in the treated eyes but not in the control eyes (P = 0.022, P = 0.10, respectively). No adverse effects of the metronidazole treatment were encountered in this study. CONCLUSION: Metronidazole topical gel may be a safe and effective means of treating rosacea blepharitis.

Administration, Topical↗

PubMed1996

The use of botulinum A toxin to ameliorate facial kinetic frown lines.

PURPOSE: External photography and subjective response were used to evaluate the use of botulinum A toxin to diminish glabellar kinetic folds. METHODS: Eleven patients with glabellar folds and midline forehead wrinkling received one to four injections of 0.1 ml of 100 U/1 ml botulinum A toxin. The injections were given into the procerus or corrugator muscles or both. The number of injections corresponded to the wrinkle lines in each patient. The patients were examined and photographed just before the injections and at 7 to 10 days after the injections. Treatment efficacy was judged by photographic evaluation and by the patient's subjective evaluation of the effect of the treatment. RESULTS: Photographic evaluation showed objective improvement in the glabellar wrinkling in 6 of 11 patients in relaxed facial position and in all 11 patients during contraction of the periocular mulscles. Ten of the 11 patients reported satisfaction with their cosmetic results and indicated that they would choose to have the procedure done again. CONCLUSIONS: The results of this study suggest that botulinum A toxin is a safe and effective treatment for glabellar folds.

Adult↗

PubMed1996

Results of dacryoscintigraphy in massage of the congenitally blocked nasolacrimal duct.

Between November 1990 and November 1993, 580 children with lacrimal outflow obstruction were examined at the Children's Hospital of Philadelphia. After excluding patients previously treated for nasolacrimal duct obstruction, we obtained a prospectively selected series of 20 children for this study. These patients underwent dacryoscintigraphy before and immediately after lacrimal sac massage to investigate the effect of external compression on fluid movement within the lacrimal outflow system. In 12 patients, tracer did not enter the lacrimal outflow system on the side(s) of obstruction. The absence of radiopharmaceutical correlated with clinical obstruction. In eight patients, tracer was noted to enter the lacrimal sac. After massage of the lacrimal sac, we observed progression of the tracer in five of the eight subjects. In these eight subjects, the pre- and postmassage tear column measurements showed a relative increase of 34.3%. Massage of eight clinically normal ducts showed a relative increase of 2.4% (p = 0.06). We conclude that progression of the tear column after lacrimal massage can be demonstrated on dacryoscintigraphy.

Child, Preschool↗

PubMed1995

Localization of constitutive and hyperthermia-inducible heat shock mRNAs (hsc70 and hsp70) in the rabbit cerebellum and brainstem by non-radioactive in situ hybridization.

Neural expression of constitutive hsc70 mRNA and hyperthermia-inducible hsp70 mRNA is examined using radioactive and non-radioactive in situ hybridization procedures. A strong induction of hsp70 mRNA was noted in cell populations in cerebellar layers and in the brainstem which demonstrated expression of mRNA encoding proteolipid protein, an oligodendrocyte marker. The non-radioactive in situ hybridization procedure using digoxigenin (DIG)-UTP-labeled riboprobes permitted improved signal localization, and stress-inducible hsp70 mRNA was detected at the cytoplasmic cap areas of individual oligodendrocytes. Cell types which express constitutive members of the hsc/hsp70 multigene family were also identified. Neurons in the brainstem and in the deep white matter and molecular layer of the cerebellum showed expression of hsc70 mRNA while signal was not detected in adjacent glial cells. A neuron-specific enolase riboprobe aided in the identification of neuronal cell types. The non-radioactive DIG riboprobe revealed that hsc70 mRNA was highly localized to the cytoplasm of individual neurons. High constitutive levels of hsc70 in certain neurons may dampen hsp70 induction after hyperthermia in these cell populations.

Animals↗

PubMed1995

Transcriptional regulation of the elastin gene by insulin-like growth factor-I involves disruption of Sp1 binding. Evidence for the role of Rb in mediating Sp1 binding in aortic smooth muscle cells.

We have recently identified a novel element (EFE 5/6) in the human elastin gene promoter that modulates the ability of insulin-like growth factor I (IGF-I) to up-regulate elastin gene transcription in aortic smooth muscle cells. In the present study, we have pursued the identification of those nuclear proteins binding to the EFE 5/6 element and affected by IGF-I treatment. Chelation inactivation and metal reactivation experiments together with supershift gel analyses demonstrated that Sp1 was one of the proteins affected by IGF-I. Southwestern and Western analyses showed that Sp1 was present in IGF-I nuclear extracts and capable of binding DNA after fractionation. Addition of retinoblastoma gene product (Rb) antibody mimicked the effect of IGF-I in gel shift analysis, suggesting that Sp1 binding may be regulated by an inhibitor normally associated with Rb. The fact that the phosphorylation state of Rb was affected by IGF-I was shown by Western blot analysis. The control smooth muscle cells transcribed the elastin gene at a high level without addition of IGF-I, so it is likely that disruption of Sp1 binding is the first step in allowing the binding of a more potent activating factor.

Animals↗