Conditional activation of Pik3ca(H1047R) in a knock-in mouse model promotes mammary tumorigenesis and emergence of mutations.

Oncogenic mutations in PIK3CA, which encodes the phosphoinositide-3-kinase (PI3K) catalytic subunit p110α, occur in ∼25% of human breast cancers. In this study, we report the development of a knock-in mouse model for breast cancer where the endogenous Pik3ca allele was modified to allow tissue-specific conditional expression of a frequently found Pik3ca(H1047R) (Pik3ca(e20H1047R)) mutant allele. We found that activation of the latent Pik3ca(H1047R) allele resulted in breast tumors with multiple histological types. Whole-exome analysis of the Pik3ca(H1047R)-driven mammary tumors identified multiple mutations, including Trp53 mutations that appeared spontaneously during the development of adenocarinoma and spindle cell tumors. Further, we used this model to test the efficacy of GDC-0941, a PI3K inhibitor, in clinical development, and showed that the tumors respond to PI3K inhibition.

Illness representations and coping as predictors of emotional well-being in adolescents with type 1 diabetes.

OBJECTIVES: To test whether coping acts to mediate the relationships between illness representations and emotional well-being in adolescents with diabetes. METHODS: Seventy adolescents between 11 and 18 years of age were asked to complete the Diabetes Illness Representations Questionnaire (DIRQ), the Well-being Questionnaire, and the Kidcope. RESULTS: Perceived impact, identity, and cognitive restructuring were significant independent predictors for depressive symptomatology. For anxiety, perceived impact and identity were significant predictors, and for positive emotional well-being, treatment effectiveness to control diabetes was the only significant predictor. Multiple regression analyses indicated that coping did not mediate the association between illness representations and positive emotional well-being. CONCLUSIONS: Perceived impact was consistently associated with participants' indices of negative emotional well-being. Contrary to the hypothesized model, coping did not mediate the association between illness representations and emotional well-being in this sample.

Midgut exopeptidase activities in Aedes aegypti are induced by blood feeding.

Midgut extracts from Aedes aegypti females exhibited hydrolytic activities against synthetic substrates for carboxypeptidase A, carboxyopeptidase B and leucine-aminopeptidase. The three activities showed a broad pH optimum, with maximum activities at pH between 6.5 and 8.5. Enzymatic activities were further characterized by testing the effects of a variety of protease inhibitors. Captopril and 1-10-phenantroline inhibited the activities of carboxypeptidases A and B, while leuhistin, amastatin and bestatin inhibited aminopeptidase activity. Exopeptidase activities were induced by a blood meal and the highest activities were found during the peak of trypsin activity, about 20-24h after feeding. An amino acid meal failed to induce significant increases in any of the three exopeptidase activities. The amounts of exopeptidase activities induced were proportional to the protein concentration of the meal. The addition of soy-trypsin inhibitor to the protein meal blocked the post-feeding induction of exopeptidases. The features of the induction of synthesis of the three exopeptidase activities resembled the induction of synthesis of late trypsin during the second phase of digestion.

Neuroendocrine factors affecting the steady-state levels of early trypsin mRNA in Aedes aegypti.

Transcription of the early trypsin gene occurs in the midgut after adult emergence under control of juvenile hormone (JH). We tested the hypothesis that factors that affect the steady-state levels of early trypsin mRNA do so by influencing the levels of JH. We investigated the effect of ingesting different meals on early trypsin mRNA levels as well as on JH levels. We also studied how early trypsin mRNA levels changed when the midgut was isolated from different components of the neuroendocrine system by abdominal ligation and decapitation. Early trypsin transcripts levels are high in unfed females; feeding different meals had three distinct effects on the changes of steady-state levels of early trypsin mRNA: (1) blood and protein meals caused the level to decrease drastically and remained low for at least 24 h; (2) amino acid meals caused a transient decrease in the mRNA level, but it returned to high levels after 12-18 h; and (3) sugar, latex and saline meals had no effect on the early trypsin mRNA steady-state levels. The changes in JH levels after ingesting blood and amino acid meals show profiles resembling the changes in early trypsin mRNA levels for the corresponding meal. Decapitation at 1, 2 and 3 days after emergence does not affect the steady-state levels of early trypsin in unfed females. In contrast, 24 h after feeding, transcript levels were significantly higher in decapitated females when compared with non-decapitated fed females. We propose that the changes in the steady-state levels of early trypsin mRNA observed after the ingestion of different meals, ligations and decapitations are generated by changes in the levels of juvenile hormone.

Recombinant juvenile hormone esterase, an effective tool for modifying juvenile hormone-dependent expression of the early trypsin gene in mosquitoes.

The study of the changes in the steady-state levels of the early trypsin (ET) messenger RNA (mRNA) was used as a sensitive assay for measuring the effects of recombinant juvenile hormone esterase (rJHE) on juvenile hormone (JH)-dependent gene expression in mosquitoes. ET is a female-specific protease present in the midgut of the yellow fever mosquito Aedes aegypti during the first few hours after ingestion of a blood meal. Transcription of the early trypsin gene is part of the normal postemergence maturation of the midgut in the adult female, and it is regulated by JH. JHE was cloned from Heliothis virescens and expressed in a baculovirus vector. Injection of rJHE into mosquitoes resulted in an increase of JHE activity in the haemolymph. Injection of rJHE into newly emerged adult females delayed the normal increase in steady-state levels of ET mRNA observed in controls. Topically applied methoprene (a JH analogue) reversed the effect of rJHE. Injection of increasing concentrations of rJHE into 3-day-old unfed females resulted in a dose-dependent decrease in the steady-state levels of ET mRNA after 24 h. The effect of rJHE was transient, once the enzyme was cleared (72 h after injection), the steady-state levels of ET mRNA were restored. The injection of rJHE is an effective tool for modifying JH-dependent expression of the early trypsin gene in mosquitoes.

Microcatheter adhesion of cyanoacrylates: comparison of normal butyl cyanoacrylate to 2-hexyl cyanoacrylate.

PURPOSE: To compare the catheter adhesion properties of 2-hexyl cyanoacrylate (Neuracryl M), a new agent, to those of normal butyl cyanoacrylate (Histoacryl), the most widely used liquid acrylic agent for microcatheter embolization. MATERIALS AND METHODS: 2-hexyl cyanoacrylate (Neuracryl M1) was tested in pure form and mixed with either a proprietary polymerization retardant/contrast agent (Neuracryl M2) or ethiodized oil (Ethiodol). Histoacryl was tested in pure form and mixed with Ethiodol. The cyanoacrylate mixtures were injected through microcatheters into wells partially filled with heparinized whole blood. The cyanoacrylates were allowed to polymerize around the microcatheter tips for 1-3 minutes. The microcatheters were then pulled at a constant rate until they were extracted from the polymerized cyanoacrylates. The peak forces required for extraction were recorded. RESULTS: The peak forces required to extract the microcatheters from either pure Histoacryl or Histoacryl mixed with 33% Ethiodol were significantly higher (P < .01; P < .05) than those for pure Neuracryl M1. When Neuracryl M1 and M2 were mixed together (as intended for clinical use), the force required for microcatheter extraction was significantly lower than that for either pure Histoacryl, Histoacryl mixed with 33% Ethiodol, or Neuracryl M1 alone (P < .01; P < .01; P < .01, respectively). The force required to extract microcatheters from the Neuracryl M1 and M2 mixture was not, however, significantly different from that of Histoacryl mixed with 50% Ethiodol. The force of extraction for the Neuracryl M1 and 50% Ethiodol mixture was below our ability to obtain precise measurements. CONCLUSION: When Neuracryl M1 was mixed with its proprietary polymerization retardant/contrast agent (Neuracryl M2), catheter adhesion was not significantly different from that of Histoacryl mixed with 50% Ethiodol, a mixture common in clinical use. When Neuracryl M1 was tested alone or mixed with Ethiodol (not intended by the manufacturer), catheter adhesion was significantly decreased relative to pure Histoacryl or equivalent mixtures of Histoacryl and Ethiodol.

Extradural aneurysms.

Extradural aneurysms have distinct characteristics from their intradural counterparts. Most extradural aneurysms cannot be treated by direct surgical exposure and clip ligation or by direct endovascular means without parent vessel sacrifice. Arterial occlusion with or without bypass grafting remains the traditional treatment. Controversy about the "best" or "proper" technique of arterial balloon test occlusion is rivaled only by that of the necessity for bypass grafting when apparent tolerance for arterial occlusion has been demonstrated.

Current concepts and controversies in imaging of renal cystic diseases.

Renal cystic disease compromises a diverse group of inherited and acquired entities. This article reviews the clinical, pathologic, and radiologic findings of eight renal cystic diseases. For each entity, the current concepts of pathogenesis and pathophysiology are discussed. When appropriate, controversies concerning terminology, management, and malignant potentials are addressed. Renal cystic diseases that are discussed include autosomal dominant and autosomal recessive polycystic kidney disease, medullary sponge kidney, medullary cystic disease, multicystic, dysplastic kidney, von Hippel-Lindau disease, acquired cystic kidney disease, and tuberous sclerosis.

Renal cystic diseases.

Renal cystic disease comprises a mixed group of heritable, developmental, and acquired disorders. Because of their diverse etiology, histology, and clinical presentation, no single scheme of classification has gained acceptance. Conditions include autosomal dominant polycystic kidney disease, acquired renal cystic disease, medullary sponge kidney, autosomal recessive polycystic kidney disease, multicystic dysplastic kidney, medullary cystic disease, tuberous sclerosis, cysts of the renal sinus, and von Hippel-Lindau's disease. An awareness of the pathology of each cystic disease is helpful in the understanding of the corresponding radiological images. Imaging techniques used in evaluating renal cystic disease include intravenous urography, sonography, CT, MRI, nuclear medicine, and renal angiography. Many types of cystic disease show similar imaging features. Meticulous attention to subtle radiological findings is therefore essential for reaching a correct diagnosis. Imaging features requiring analysis include whether the cysts are unilateral or bilateral, renal size and functional status, cyst distribution in the kidneys, and the presence of hemorrhagic and calcified renal cysts, solid renal masses, renal sinus cysts, and cysts in adjacent organs. Radiological findings should be carefully correlated with clinical features such as patient age, family history, symptoms, physical findings, and renal functional status before a diagnosis is attempted.

CT diagnosis of splenic vein occlusion: imaging features, etiology and clinical manifestations.

BACKGROUND: Previous reports have described the computed tomographic (CT) appearance of collateral veins following splenic vein occlusion (SVO). This retrospective study was performed to determine the etiology, clinical manifestations, and accuracy of CT diagnosis in patients with this entity. METHODS: A computer search of radiology reports for a 1-year period found 52 patients with SVO diagnosed by absence of visualization of the splenic vein accompanied by the formation of the expected perigastric collateral veins. Clinical data were reviewed for sequela of SVO and clinical impact of the diagnosis. RESULTS: In 12 cases, other studies confirmed the CT diagnosis of SVO. In no case was the CT diagnosis proved to be incorrect by other imaging studies. Angiographic records found five additional cases with SVO not diagnosed by CT, but two of five had convincing CT evidence of SVO noted upon reevaluation by the authors. Review of clinical data showed heme-positive stool in six, of which three had significant gastrointestinal hemorrhage. Splenic infarction occurred in two cases. CONCLUSIONS: Our data indicate that SVO is more common than previously suspected and usually remains clinically silent, but CT appears to be highly specific and fairly sensitive for its diagnosis.

Volume of the spleen in children as measured on CT scans: normal standards as a function of body weight.

OBJECTIVE: The purpose of this study was to develop standards for the normal volume of the spleen in children as measured on CT scans. SUBJECTS AND METHODS: CT scans were used to measure the volume of the spleen in 48 children (30 boys and 18 girls), 1 day to 18 years old (mean and median ages were 8.2 and 7.8 years, respectively). Children who had underlying malignant tumors, infection, hematologic diseases, or other conditions that could alter splenic size were excluded. The area of the spleen on each axial section was determined by tracing its outline on the CT monitor and measuring the area of the region of interest. The area of the spleen on each section was multiplied by the slice thickness to calculate the volume of the spleen for each section. The total volume of the spleen was then determined by adding the individual volumes for each of the sections through the spleen. This method of calculating splenic volume has been validated in previous studies in adult subjects. The volume of the spleen was analyzed as a function of both body weight and age. RESULTS: The volume of the spleen correlated better with body weight than with age. The best regression model (r = .85) was a linear relationship as follows: splenic volume (cm3) = 0.7 + [4.6 x weight (kg)]. Using these data and a regression model, we generated standards for normal volume of the spleen as a function of body weight (with 95% tolerance intervals). CONCLUSION: We have developed CT standards for normal splenic volume in children. These standards can be used to objectively measure the size of the spleen in children who have clinically suspected splenomegaly.

Ilio-psoas abscess in neonates.

We report two cases of primary ilio-psoas abscess in neonates diagnosed by CT and sonography. Ilio-psoas abscess is extremely uncommon in this age group.