Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancer types exhibiting microsatellite instability. Using intron primers previously reported for examination of the entire coding region of the TGFbetaRII gene, 29 sporadic gastric cancers were screened with non-radioactive single strand conformation polymorphism and subsequent DNA sequencing analysis. Mutations of the TGFbetaRII gene were detected in three out of 29 tumors (10%). Two cases showed deletions in a polyadenine tract in both alleles and was positively associated with replication error. One case had an insertion of GA dinucleotide sequence in one allele. Mutations of the TGFbetaRII gene were restricted to exon 3 and other coding regions were not affected. Loss of heterozygosity was detected by analyzing a polymorphic site in intron 2. Three out of nine (33%) informative cases, which were all of intestinal type and advanced cases, showed loss of heterozygosity but neither TGFbetaRII mutation nor replication error was found in these cases. Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different extent in the gastric cancer with genetically abnormal transforming growth factor. Although the numbers studied are small, homozygous (A)10 deletion or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and progression of at least some part of sporadic gastric cancer.      

The duration of phorbol-inducible ErbB2 tyrosine dephosphorylation parallels that of receptor endocytosis rather than threonine-686 phosphorylation: implications for the physiological role of protein kinase C in growth factor receptor signalling

Tumour cell growth may be accelerated by protein kinase C (PKC) agonists such as phorbol esters and receptor tyrosine kinases, but receptor tyrosine kinases are in turn desensitized to growth factors by PKC agonists. To clarify this apparent PKC bifunctionality, we have used phosphoantibodies to determine the relationship between PKC- dependent phosphorylation events affecting the ErbB2 oncoprotein in G8/DHFR 3T3 cells. Neither the kinetics nor the extent of phorbol- induced juxtamembrane domain (Thr686) phosphorylation vary directly with C-terminal (Tyr1222) dephosphorylation, with Tyr1222 continuing to be dephosphorylated long after Thr686 phosphorylation has also declined. Platelet-derived growth factor (PDGF) mimics the short-term effects of phorbol on Thr686 and Tyr1222 phosphorylation, and confocal microscopy reveals that both of these PKC agonists induce rapid internalization of PKC-modified ErbB2. Phorbol causes sustained cytoplasmic accumulation of PKC-phosphorylated receptors, however, whereas PDGF triggers the appearance of this ErbB2 subset only briefly. Metabolic labelling and co-precipitation studies fail to implicate heterologous molecules in either the tyrosine dephosphorylation or internalization of PKC-modified ErbB2. Taken in the context of earlier juxtamembrane domain mutagenesis studies, these findings indicate that phorbol-activated PKC may desensitize growth factor receptors to extracellular ligands solely by triggering sustained receptor internalization. We submit that PKC-dependent juxtamembrane domain phosphorylation represents a physiological mechanism for shortening the duration and enhancing the specificity of growth factor signalling by promoting internalization of liganded and unliganded receptors, respectively.      

Intracranial chondroma of the occipital lobe

A case report of an intracranial chondroma is discussed with emphasis on magnetic resonance imaging.     

Using an immunization registry: effect on practice costs and time.

INTRODUCTION: Immunization registries can consolidate immunization records scattered among different providers, allowing immunization documentation for legal purposes, generation of needed-immunization lists, inventory management, and outreach for underimmunized children. They have been endorsed by the Centers for Disease Control and Prevention and health professionals as a means of sustaining high immunization rates. However, some providers perceive the cost of registry use as a barrier to participation. We sought to determine the effects of registry use on cost and time. METHODS: We used a pre-post design and a cost-accounting approach to measure labor costs and time for immunization-related activities possibly affected by registry use before development of a regional registry in Colorado and after the registry was being fully used. Two rural family practices, 2 rural community health centers (CHCs), 3 urban pediatric practices, and 2 rural public health agencies participated in both periods. RESULTS: Cost per shot increased slightly in the postregistry period for private practices and CHCs ($0.56 per shot in 2001 dollars) and public health agencies ($0.38). Since costs can increase for several reasons, including salary increases above inflation, we analyzed time spent per shot and found that staff time decreased for private practices and CHCs but increased substantially for public health agencies. CONCLUSIONS: The study findings suggest to private practices that registry participation can provide a net benefit by making the vaccination process more efficient and, absent above-average salary increases, less costly. Public health agencies, however, would have to rely exclusively on the registry and eschew the use of paper vaccination records to realize efficiencies seen by other practice types.     

Quality improvement in immunization delivery following an unsuccessful immunization recall.

OBJECTIVES: Within a clinic serving disadvantaged children, 1) to evaluate a multifaceted quality improvement (QI) project to improve immunization (IZ) up-to-date (UTD) rates and 2) to assess the efficacy of IZ reminder/recall performed following QI. METHODS: A year-long QI project followed by a trial of reminder/recall. QI interventions were targeted at previously identified barriers to IZ and were designed specifically to improve the efficacy of reminder/recall. QI interventions were designed to 1) increase the use of medical record releases to document IZs received elsewhere; 2) improve the accuracy of parental contact information; and 3) reduce missed opportunities by utilizing chart prompts, provider education, and provider reminders. Following QI, we conducted a randomized trial of reminder/recall. RESULTS: UTD rates for 7-11 month olds increased from 21% before the QI project to 52% after (P <.0001); rates for 12-18 month olds increased from 16% before QI to 44% after (P <.0001); 19-25 month olds 18% before to 33% after (P <.001). After QI, an average of 61 records per month were updated with IZs received elsewhere. However, the accuracy of parental contact information worsened (29% unreachable before QI vs 44% after, P <.001) and missed opportunities did not improve (8% before vs 6% after, P = not significant [NS]). A subsequent trial of reminder/recall did not increase UTD rates, with 17% of recalled children brought UTD vs 16% of controls (P = NS). CONCLUSIONS: Clinic-based QI increased documented UTD rates in a disadvantaged patient population. However, IZ reminder/recall did not further increase UTD rates above the rates achieved by the QI process.     

Neurodevelopmental changes of fetal pain

Pain in the developing fetus is controversial because of the difficulty in measuring and interpreting pain during gestation. It has received increased attention lately because of recently introduced legislation that would require consideration of fetal pain during intentional termination of pregnancy. During development, sensory fibers are abundant by 20 weeks; a functional spinal reflex is present by 19 weeks; connections to the thalamus are present by 20 weeks; and connections to subplate neurons are present by 17 weeks with intensive differentiation by 25 weeks. These cells are important developmentally, but decline as a result of natural apoptosis. Mature thalamocortical projections are not present until 29 to 30 weeks, which has led many to believe the fetus does not experience emotional "pain" until then. Pain requires both nociception and emotional reaction or interpretation. Nociception causes physiologic stress, which in turn causes increases in catecholamines, cortisol, and other stress hormones. Physiological stress is different from the emotional pain felt by the more mature fetus or infant, and this stress is mitigated by pain medication such as opiates. The plasticity of the developing brain makes it vulnerable to the stressors that cause long-term developmental changes, ultimately leading to adverse neurological outcomes. Whereas evidence for conscious pain perception is indirect, evidence for the subconscious incorporation of pain into neurological development and plasticity is incontrovertible. Scientific data, not religious or political conviction, should guide the desperately needed research in this field. In the meantime, it seems prudent to avoid pain during gestation.     

Insights in Public Health: Developing the Ho‘ouna Pono Substance Use Prevention Curriculum: Collaborating with Hawaiian Youth and Communities

This article briefly outlines a collaboration among communities on Hawai‘i Island and a university-based research team to develop, implement, and evaluate a school-based substance use prevention curriculum called Ho‘ouna Pono. In addition to providing a rationale for the project, the goal of this paper is fourfold. First, an overview of the Ho‘ouna Pono research results to date (2007–2013) is provided. Second, within this overview, the ways in which selected results informed program development are highlighted. Third, the curriculum is briefly described, and finally, the role of the students and community in the video production is described.