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P Snyder

Publications and source records attributed to P Snyder.

At least 19 recordsLinked to original sources
PubMed2001

Quantitative analysis of epithelial cell aggregation in the simple metazoan Hydra reveals a switch from homotypic to heterotypic cell interactions.

Hydra, a member of the diploblastic phylum Cnidaria, exhibits the most basic type of organized metazoan tissues. Two unicellular sheets of polarized epithelial cells - ectoderm and endoderm - form a double layer throughout the body column. The double layer can be reestablished from single-cell suspensions by tissue-specific cell-sorting processes. However, the underlying pattern of interactions between ectodermal and endodermal epithelial cells responsible for double-layer formation is unclear. By analyzing cell interactions in a quantitative adhesion assay using mechanically dissociated Hydra epithelial cells, we show that aggregation proceeds in two steps. First, homotypic interactions within ectodermal epithelial cells (ecto-ecto) and within endodermal epithelial cells (endo-endo) form homotypic cell clusters. Second, at an aggregate size of about ten epithelial cells/cluster, ectodermal and endodermal clusters start to form heterotypic aggregates. Homotypic ecto-ecto interactions are inhibited by a polyclonal anti-Hydra membrane antiserum, and under these conditions homotypic endo-endo interactions do not proceed beyond a size of about ten epithelial cells/cluster. These data suggest that homotypic cell clusters reduce their initial homotypic affinity and acquire a new heterotypic affinity. A link between cell adhesion and cell signaling in early Hydra aggregates is discussed.

Animals↗
PubMed2000

WNT signalling molecules act in axis formation in the diploblastic metazoan Hydra.

Members of the Wnt/wingless family of secreted proteins act as short-range inducers and long-range organizers during axis formation, organogenesis and tumorigenesis in many developing tissues. Wnt signalling pathways are conserved in nematodes, insects and vertebrates. Despite its developmental significance, the evolutionary origin of Wnt signalling is unclear. Here we describe the molecular characterization of members of the Wnt signalling pathway--Wnt, Dishevelled, GSK3, beta-Catenin and Tcf/Lef--in Hydra, a member of the evolutionarily old metazoan phylum Cnidaria. Wnt and Tcf are expressed in the putative Hydra head organizer, the upper part of the hypostome. Wnt, beta-Catenin and Tcf are transcriptionally upregulated when head organizers are established early in bud formation and head regeneration. Wnt and Tcf expression domains also define head organizers created by de novo pattern formation in aggregates. Our results indicate that Wnt signalling may be involved in axis formation in Hydra and support the idea that it was central in the evolution of axial differentiation in early multicellular animals.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Overexpression of the EphA2 tyrosine kinase in prostate cancer.

BACKGROUND: Molecules that are highly expressed by human prostate cancers may serve as therapeutically relevant targets or tumor markers. Tyrosine kinases are frequently overexpressed in metastatic tumor cells and this prompted us to screen for tyrosine kinases that are overexpressed in prostate cancer cells. METHODS: Expression levels of the EphA2 receptor tyrosine kinase were determined by Western blot analysis in canine and human prostate cancer cell lines and in immortalized and transformed variants of 267B1 prostatic epithelial cells. EphA2 levels in benign human prostate and prostate cancers were also determined in formalin-fixed, paraffin-embedded tissues using immunohistochemical staining. RESULTS: Metastatic prostate cancer cells overexpressed EphA2 by 10-100 fold as compared with non-invasive prostatic epithelial cells. EphA2 immunoreactivity in vivo was also significantly greater in human prostate cancers as compared with benign prostate epithelium. CONCLUSIONS: The EphA2 receptor tyrosine kinase is differentially expressed in human and canine prostate cancer cell lines and overexpressed in human prostate cancers as compared with benign prostate tissues. Metastasis-derived canine prostate carcinoma cell lines overexpress EphA2 and may provide pre-clinical models to further evaluate the role of EphA2 in prostate carcinogenesis. Further investigations are needed to determine the utility of EphA2 as a tumor marker and a novel target in human prostate cancer.

Animals↗
PubMed1999

Pathways: a culturally appropriate obesity-prevention program for American Indian schoolchildren.

Pathways, a culturally appropriate obesity prevention study for third-, fourth-, and fifth-grade American Indian schoolchildren includes an intervention that promotes increased physical activity and healthful eating behaviors. The Pathways intervention, developed through a collaboration of universities and American Indian nations, schools, and families, focuses on individual, behavioral, and environmental factors and merges constructs from social learning theory with American Indian customs and practices. We describe the Pathways program developed during 3 y of feasibility testing in American Indian schools, with special emphasis on the activities developed for the third grade; review the theoretical and cultural underpinnings of the program; outline the construction process of the intervention; detail the curriculum and physical education components of the intervention; and summarize the formative assessment and the school food service and family components of the intervention.

Asian People↗
PubMed1999

The Pathways study: a model for lowering the fat in school meals.

We describe the development and implementation of the Pathways school food service intervention during the feasibility phase of the Pathways study. The purpose of the intervention was to lower the amount of fat in school meals to 30% of energy to promote obesity prevention in third- through fifth-grade students. The Pathways nutrition staff and the food service intervention staff worked together to develop 5 interrelated components to implement the intervention. These components were nutrient guidelines, 8 skill-building behavioral guidelines, hands-on materials, twice yearly trainings, and monthly visits to the kitchens by the Pathways nutrition staff. The components were developed and implemented over 18 mo in a pilot intervention in 4 schools. The results of an initial process evaluation showed that 3 of the 4 schools had implemented 6 of the 8 behavioral guidelines. In an analysis of 5 d of school menus from 3 control schools, the lunch menus averaged from 34% to 40% of energy from fat; when the menus were analyzed by using the food preparation and serving methods in the behavioral guidelines, they averaged 31% of energy from total fat. This unique approach of 5 interrelated food service intervention components was accepted in the schools and is now being implemented in the full-scale phase of the Pathways study in 40 schools for 5 y.

Asian People↗
PubMed1999

Process evaluation in a multisite, primary obesity-prevention trial in American Indian schoolchildren.

We describe the development, implementation, and use of the process evaluation component of a multisite, primary obesity prevention trial for American Indian schoolchildren. We describe the development and pilot testing of the instruments, provide some examples of the criteria for instrument selection, and provide examples of how process evaluation results were used to document and refine intervention components. The theoretical and applied framework of the process evaluation was based on diffusion theory, social learning theory, and the desire for triangulation of multiple modes of data collection. The primary objectives of the process evaluation were to systematically document the training process, content, and implementation of 4 components of the intervention. The process evaluation was developed and implemented collaboratively so that it met the needs of both the evaluators and those who would be implementing the intervention components. Process evaluation results revealed that observation and structured interviews provided the most informative data; however, these methods were the most expensive and time consuming and required the highest level of skill to undertake. Although the literature is full of idealism regarding the uses of process evaluation for formative and summative purposes, in reality, many persons are sensitive to having their work evaluated in such an in-depth, context-based manner as is described. For this reason, use of structured, quantitative, highly objective tools may be more effective than qualitative methods, which appear to be more dependent on the skills and biases of the researcher and the context in which they are used.

Asian People↗
PubMed1998

Octreotide as primary therapy for acromegaly.

The effects of octreotide (up to 5 yr) as primary treatment in 26 patients with acromegaly were compared with those in 81 patients with acromegaly who received octreotide as secondary or adjunctive therapy after previous surgery and/or pituitary radiation. These patients were part of a multicenter study that took place between 1989-1995. The study was divided into 3 phases beginning with a 1-month placebo-controlled treatment period followed by a 1-month washout period. In the second phase, patients were randomized to treatment with either 100 or 250 micrograms octreotide, sc, every 8 h for 6 months. Octreotide was then discontinued for 1 month and reinitiated at the lower dose for a total mean treatment duration of 39 months. The dose was titrated by each investigator to improve each patient's individual response, which included improvement in symptoms and signs of acromegaly as well as reduction of GH and insulin-like growth factor I (IGF-I) into the normal range. In the second phase of the study, in which patients were randomized to either 100 or 250 micrograms octreotide, three times daily, mean integrated GH and IGF-I concentrations after 3 and 6 months were equivalent in the primary and secondary treatment groups. During long term open label treatment, mean GH fell from 32.7 +/- 5.2 to 6.0 +/- 1.7 micrograms/L 2 h after octreotide injection in the primary therapy group and remained suppressed for a mean period of 24 months (range, 3-60 months). The mean final daily dose was 777 micrograms. In the patients receiving secondary treatment, mean GH fell from 30.2 +/- 7.6 to 5.6 +/- 1.1 micrograms/L after 3 months and remained suppressed for the remainder of the study (average dose, 635 micrograms daily). Mean IGF-I concentrations fell from 5.2 +/- 0.5 x 10(3) U/L (primary treatment group) and 4.7 +/- 0.4 x 10(3) U/L (secondary treatment group) to a mean of 2.2 +/- 0.3 x 10(3) U/L in both groups after 3 months of open label treatment and remained suppressed. IGF-I was reduced into the normal range during at least half of the study visits in 68% of the primary treatment group and in 62% of the secondary treatment group. Patients whose GH levels fell to at least 2 SD below the baseline mean GH were considered responders. There was no significant difference in the percentage of responders in the primary and secondary treatment groups (70% vs. 61%), nor was there a statistical difference in the mean GH concentrations between the groups. Symptoms of headache, increased perspiration, fatigue, and joint pain were reported at baseline by 46%, 73%, 69%, and 85%, respectively, of patients in the primary therapy group and improved during 3 yr of octreotide treatment in 50-100%. Similarly, these acromegaly-related symptoms were reported by 62%, 58%, 78%, and 60% of patients in the secondary therapy group, and improvement was noted in 62-88%. Pituitary magnetic resonance imaging scans were available in 13 of 26 patients in the primary treatment group before and after 6 months of octreotide treatment. Tumor shrinkage was observed in 6 of 13 patients, with reduction in tumor volume greater than 25% in only 3. Of 6 patients with documented tumor shrinkage, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 5 patients. The degree of tumor shrinkage did not correlate with the percent reduction in IGF-I or GH. In summary, octreotide was equally effective in 26 previously untreated acromegalic patients (primary treatment group) and 81 patients previously treated with either surgery or pituitary radiation (secondary treatment group). These observations call into question the current practice of surgical resection of all newly diagnosed GH-secreting pituitary adenomas regardless of the likelihood of cure. (AB

Acromegaly↗
PubMed1998

Effects of human intravenous immunoglobulin on canine monocytes and lymphocytes.

OBJECTIVE: To evaluate interactions of human intravenous immunoglobulin (IVIG) with canine lymphocytes and monocytes. SAMPLE POPULATION: Heparinized blood samples from 4 clinically normal Beagles. PROCEDURE: Binding ability of IVIG to canine lymphocytes and monocytes was measured by flow cytometry and an indirect immunofluorescent assay. Dual-staining fluorescent assays were done to determine lymphocyte subsets that bind IVIG. Competitive assays were done, using intact canine IgG and Fc fragments, and inhibition of binding was compared with that of F(ab)2 fragments. Ability of IVIG to inhibit phagocytosis of antibody-coated canine RBC also was determined, using a canine mononuclear cell phagocytic assay. RESULTS: IVIG concentrations (10, 1, 0.1, and 0.01 mg/ml) bound to (mean+/-SD) 99.6+/-0.4, 92.4+/-6.1, 20.4+/-24.6 and 2.0+/-5.1 % of canine lymphocytes, respectively, Dual staining analyses with IVIG and canine lymphocyte markers indicated that IVIG bound to CD4, CD8, and B lymphocytes. The aforementioned 4 IVIG concentrations bound to 98.0+/-2.1, 85.5+/-13.5, 64.7+/-32.8, and 26.5+/-17.1 % of monocytes, respectively. Inhibition of IVIG (0.01 mg/ml) binding to monocytes was significant (P< 0.05) in the presence of 1 and 10 mg of canine IgG/ml and 1 mg of canine Fc fragments/ml. In the presence of F(ab')2 fragments of canine IgG, inhibition was not significant, suggesting that binding is Fc mediated. Co-culturing of monocytes, opsonized RBC, and the 4 concentrations of IVIG and no IVIG resulted in 11.8+/-5.1, 27.7+/-12.3, 31.8+15.1, 53.8+/-6.7, and 45 + 12% of the monocytes containing RBC, respectively. Phagocytosis inhibition was significant (P < 0.05) at an IVIG concentration of 10 mg/ml. CONCLUSIONS: IVIG binds to canine lymphocytes and monocytes; binding to the latter is Fc mediated. IVIG also inhibits Fc-mediated phagocytosis of antibody-coated RBC. CLINICAL RELEVANCE: Owing to its ability to inhibit Fc-mediated phagocytosis of antibody-coated RBC, IVIG may be an effective short-term treatment for dogs with immune-mediated hemolytic anemia.

Animals↗
PubMed1995

The contributions of proprioceptive deficits, muscle function, and anatomic laxity to functional instability of the ankle.

Functional instability is a common complication following an acute ankle sprain. Three potential contributing factors underlying the ankle which chronically gives way are proprioceptive deficits, muscle weakness, and ligamentous laxity. This study's purpose was to document the presence or absence of these concerns in a sample of subjects with unilateral functional ankle instability. Both ankles of 42 subjects were randomly assessed for passive movement sense into inversion and generation of peak torque by the evertors isokinetically. Thirty-four subjects were available for documentation of talar tilt of both ankles through inversion stress radiographs. Analysis found significantly greater mean values for passive movement sense and talar tilt for the involved ankles compared with the uninvolved, while no significant strength differences in peak torque of the evertors were present. Fifty-eight percent of the sample demonstrated clinical impairments in at least one of these three categories. In conclusion, deficits in passive movement sense and anatomic stability are greater concerns than strength deficits when managing the ankle with functional instability.

Adolescent↗
PubMed1994

Transurethral electrical bladder stimulation: a followup report.

Transurethral electrical bladder stimulation (TEBS) initially proposed to rehabilitate the neurogenic bladder has been promoted in the United States since the mid 1980s. The ultimate goal of TEBS is volitional voiding. Since January 1989 we performed 938 sessions of stimulation comprising 64 TEBS series in 25 patients with neurogenic bladders. A cystometrogram was performed before each series of stimulation to monitor progress, and at the time of this review parental impressions of the stimulation were obtained by a telephone interview questionnaire. The initial evaluation cystometrogram before stimulation revealed that 18 patients (72%) had bladder contractions. After TEBS 24 patients (96%) manifest contractions. Before stimulation only 3 children sensed the contractions, while during stimulation half of the patients perceived the contractions. A cystometrogram performed before each series demonstrated a greater than 20% increase in the age adjusted bladder capacity in 6 of the 18 patients (33%) with serial studies. Improvements in the end filling pressure defined by clinically significant decreases were observed in 5 of these patients (28%). Results of the telephone questionnaire revealed that the parents perceived a benefit from stimulation more often than the urodynamic studies could confirm. In our experience TEBS is a time-consuming, labor intensive technique. The limited urodynamic benefits our patients achieved have not materially altered the daily voiding regimen and, because of these factors, we are not enrolling any new patients in our TEBS program.

Adolescent↗
PubMed1993

Characterization of translational frame exception patients in Duchenne/Becker muscular dystrophy.

The clinical progression of Duchenne muscular dystrophy (DMD) patients with deletions can be predicted in 93% of cases by whether the deletion maintains or disrupts the translational reading frame (frameshift hypothesis). We have identified and studied a number of patients who have deletions that do not conform to the translational frame hypothesis. The most common exception to the frameshift hypothesis is the deletion of exons 3 to 7 which disrupts the translational reading frame. We identified a Becker muscular dystrophy (BMD) patient, an intermediate, and a DMD patient with this deletion. In all three cases, dystrophin was detected and localized to the membrane. One DMD patient with an inframe deletion of exons 4-18 produced no dystrophin. One patient with a mild intermediate phenotype and a deletion of exon 45, which shifts the reading frame, produced no dystrophin. Two patients with large inframe deletions had discordant phenotypes (exons 3-41, DMD; exons 13-48, BMD), but both produced dystrophin that localized to the sarcolemma. The DMD patient, 113, indicates that dystrophin with an intact carboxy terminus can be produced in Duchenne patients at levels equivalent to some Beckers. The dystrophin analysis from these patients, together with patients reported in the literature, indicate that more than one domain can localize dystrophin to the sarcolemma. Lastly, the data shows that although most patients show correlation of clinical severity to molecular data, there are rare patients which do not conform.

Adolescent↗
PubMed1993

Kennedy's disease: a clinicopathologic correlation with mutations in the androgen receptor gene.

We confirmed a mutation of the androgen receptor gene as the cause for Kennedy's disease, also called "X-linked recessive spinal and bulbar muscular atrophy" or "bulbospinal neuronopathy." The mutation is characterized by an increased size of a polymorphic tandem CAG repeat within the first exon of the gene. The study population consisted of 17 patients from seven families (five distinct kinships and two isolated cases). Two patients were as yet asymptomatic and had normal examinations. Four carrier females showed the mutant as well as the normal allele; none showed clinical features of Kennedy's disease. There was no large expansion of the mutation observed in three generations of one family. Phenotypic expression between and within families was variable and not related to the size of the mutation. This contrasts with the gene mutations found in myotonic dystrophy and fragile X syndrome, where increased severity of disease correlates with the number of tandem triplet repeats. The findings reported here appear to explain the failure to find genetic anticipation in Kennedy's disease. The DNA test for Kennedy's disease can now be used for definitive diagnosis and carrier detection. In addition, mutation analysis allows early detection, which has implications for potential treatment.

Creatine Kinase↗
PubMed1992

Transurethral electrical bladder stimulation: initial results.

Transurethral electrical bladder stimulation to rehabilitate the neurogenic bladder initially proposed by Katona has been promoted in the United States by Kaplan and Richards since the mid 1980s. Encouraged by their results, 2 1/2 years ago we instituted a program patterned on their experience. Since January 1989 we performed transurethral electrical bladder stimulation in 21 patients ranging in age from 4 months to 26 years. The cause of the neurogenic bladder was myelomeningocele in 16 patients, lipomeningocele in 4 and an incomplete spinal cord injury in 1. The stimulation was performed using equipment supplied by Kaplan and Richards, and the stimulation protocol followed their recommendations. The treatments were delivered in daily sessions of 90 minutes with about 20 sessions in a series. Of the patients 11 have undergone 1,6 have finished 2 and 4 have completed 3 series of stimulation. The ultimate objective of the program is to achieve volitional voiding. To reach that goal the stimulation must engender a bladder contraction that must then be perceived and ultimately controlled. Of our patients 20 (95%) achieved bladder contractions during stimulation, including 12 (60%) who had either a definite (7) or probable (5) sense of these contractions. To date, only 1 patient has started the biofeedback program to attempt to modify detrusor activity and he is presently wet on clean intermittent catheterization. Parents of 5 other children report minor positive changes in the child's perception of the bladder activity. Three patients noticed an improvement in the bowel program, although the effect only lasted during the month of stimulation in 1. Cystometrograms were performed before each series of treatments. Of the 10 patients with serial studies 2 had significant increases in bladder capacity and 3 demonstrated a clinically significant decrease in the end filling pressures. We have seen limited encouraging results from transurethral electrical bladder stimulation. This is a time-consuming, labor intensive program, and the parents and patients need to be informed of the actual potential for dramatic improvements.

Adolescent↗