PubMed Health⌕ Search

Biomedical subjects

T J Carroll

Publications and source records attributed to T J Carroll.

34 records · Page 2Linked to original sources

Synergism between Pax-8 and lim-1 in embryonic kidney development.

Pax genes encode a family of highly conserved DNA-binding transcription factors. These proteins play key roles in regulating a number of vertebrate and invertebrate developmental processes. Mutations in Pax-6 result in eye defects in flies, mice, and humans, and ectopic expression of this gene can trigger the development of ectopic compound eyes in flies. Likewise, mutation of other Pax genes in vertebrates results in the failure of specific differentiation programs-Pax-1 causes skeletal defects; Pax-2, kidney defects; Pax-3 or Pax-7, neural crest defects; Pax-4, pancreatic beta-cell defects; Pax-5, B-cell defects; Pax-8, thyroid defects; and Pax-9, tooth defects. Although this class of genes is obviously required for the normal differentiation of a number of distinct organ systems, they have not previously been demonstrated to be capable of directing the embryonic development of organs in vertebrates. In this report, it is demonstrated that Pax-8 plays such a role in the establishment of the Xenopus embryonic kidney, the pronephros. However, in order to efficiently direct cells to form pronephric kidneys, XPax-8 requires cofactors, one of which may be the homeobox transcription factor Xlim-1. These two genes are initially expressed in overlapping domains in late gastrulae, and cells expressing both genes will go on to form the kidney. Ectopic expression of either gene alone has a moderate effect on pronephric patterning, while coexpression of XPax-8 plus Xlim-1 results in the development of embryonic kidneys of up to five times normal complexity and also leads to the development of ectopic pronephric tubules. This effect was synergistic rather than additive. XPax-2 can also synergize with Xlim-1, but the expression profile of this gene indicates that it normally functions later in pronephric development than does XPax-8. Together these data indicate that the interaction between XPax-8 and Xlim-1 is a key early step in the establishment of the pronephric primordium.

Amino Acid Sequence↗

Dynamic patterns of gene expression in the developing pronephros of Xenopus laevis.

Data from gene ablation studies in mice have indicated critical roles for Lim-1, Wnt4, WT-1, and Pax-2 in the coordination and execution of kidney patterning and differentiation. However, the precise roles of these molecules, their ordering within a genetic hierarchy, and the manner in which they contribute to establishing the fates of cells of each of the components of the nephron have yet to be elucidated in any system. In this report, the temporal and spatial expression patterns of these genes within the Xenopus pronephric system were examined in detail by single- and double-probe in situ hybridization. We describe restrictions of these gene expression patterns within the pronephros which indicate a model for the partitioning of the common pronephric anlage into its three component parts--the tubules, the glomus, and the duct.

Animals↗

Contrast-enhanced MR angiography of the carotid bifurcation.

With contrast-enhanced MR angiographic techniques, a T1-shortening contrast agent is injected into the blood stream. Imaging during the first pass of the contrast agent permits acquisition of a high-contrast MR angiogram. Scan parameters such as flip angle, repetition time, echo time, and scan duration, and injection parameters, such as dose and rate, must be carefully chosen to achieve maximum contrast between blood vessels and stationary tissues. A critical parameter affecting image quality is the timing of the acquisition relative to the injection. If the collection of the center of k-space does not coincide with peak arterial concentration, artifacts, reduced SNR, and venous enhancement may result. Several techniques have been developed to address the timing issue. Post-processing techniques such as subtracting a pre-contrast image from a post-contrast angiogram can be used to improve image quality. Intravascular contrast agents that may also lead to improved image quality are currently being developed.

Angiography, Digital Subtraction↗

Design and validation of a motion stage for in vitro MR experiments.

A computer-controlled motion stage was designed to facilitate motion studies and simulations of cardiac magnetic resonance (MR) experiments. The stage was constructed to move a phantom of up to 6 kg at velocities up to 15 cm/sec along a two-dimensional trajectory within an MR scanner. The operation of the motion stage was validated and found to be accurate to within 0.08 cm in displacement and 1.5 cm/sec in velocity (root-mean-square error). No image degradation was observed.J. Magn. Reson. Imaging 1999;10:972-977.

Artifacts↗

Precocious expression of the Wilms' tumor gene xWT1 inhibits embryonic kidney development in Xenopus laevis.

The tumor suppressor WT1 has been demonstrated to have a wide variety of activities in vitro and is required for metanephric development in vivo. In the experiments presented here, the Xenopus pronephros was used as a simple model system to examine the activity of Xenopus WT1 (xWT1) during kidney development. xWT1 was ectopically expressed in Xenopus embryos by mRNA injection and found to inhibit pronephric tubule development. Confocal microscopy confirmed this observation and revealed that the inhibition was the result of a failure to form a pronephric anlage of appropriate size rather than a defect in epithelialization. Examination of Xlim-1 expression, an early molecular marker of pronephric specification, in tailbud embryos indicated that injected xWT1 mRNA inhibited pronephric specification prior to any overt sign of morphogenesis (Xenopus stage 21). These results suggest that xWT1 may act to repress tubule-specific gene expression in the portion of the pronephros fated to form its vascular structure, the glomus.

Animals↗

Resistance training frequency: strength and myosin heavy chain responses to two and three bouts per week.

Seventeen subjects performed resistance training of the leg extensor and flexor muscle groups two (2/wk) or three (3/wk) times per week. Changes in the relative myosin heavy chain (MHC) isoform contents (I, IIa and IIx) of the vastus lateralis and isometric, isokinetic and squat-lift one-repetition maximum (1 RM) strength were compared between conditions after both a common training period (6 weeks) and number of training sessions (18). After 6 weeks and 18 sessions (9 weeks for the 2/wk group), increments in 1RM strength for the 3/wk and 2/wk groups were similar [effect size (ES) differences approximately 0.3, 3/wk > 2/wk], whereas the 2/wk group presented greater isokinetic (ES differences = 0.3-1.2) and isometric (ES differences approximately 0.7) strength increases than the 3/wk condition. A significant (P < 0.05) increase in MHC IIa percentage was evident for the 2/wk group after 18 sessions. Both training groups exhibited a trend towards a reduction in the relative MHC IIx and an increase in MHC IIa contents (ES range = 0.5-1.24). However, correlations between changes in the strength and MHC profiles were weak (r2: 0.0-0.5). Thus, isometric and isokinetic strength responses to variations in training frequency differed from 1RM strength responses, and changes in strength were not strongly related to alterations in relative MHC content.

Adolescent↗

Model systems for the study of kidney development: use of the pronephros in the analysis of organ induction and patterning.

Most vertebrate organs, once formed, continue to perform the function for which they were generated until the death of the organism. The kidney is a notable exception to this rule. Vertebrates, even those that do not undergo metamorphosis, utilize a progression of more complex kidneys as they grow and develop. This is presumably due to the changing conditions to which the organism must respond to retain what Homer Smith referred to as our physiological freedom. To quote, "Recognizing that we have the kind of blood we have because we have the kind of kidneys we have, we must acknowledge that our kidneys constitute the major foundation of our physiological freedom. Only because they work the way they do has it become possible for us to have bones, muscles, glands, and brains. Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one can say that the kidneys make the stuff of philosophy itself" ("From Fish to Philosopher," Little, Brown and Co., Boston, 1953). Different kidneys are used to make the stuff of philosophy at different stages of development depending on the age and needs of the organism, rather than the usual approach of simply making embryonic organs larger as the animal grows. Although evolution has provided the higher vertebrates with complex adult kidneys, they continue to utilize simple kidneys in embryogenesis. In lower vertebrates with simple adult kidneys, even more simple versions are used during early developmental stages. In this review the anatomy, development, and gene expression patterns of the embryonic kidney, the pronephros, will be described and compared to the more complex kidney forms. Despite some differences in anatomy, similar developmental pathways seem to be responsible for the induction and the response to induction in both evanescent and permanent kidney forms. Gene expression patterns can, therefore, be added to the morphological and functional data indicating that all forms of the kidney are closely related structures. Given the similarities between the development of simple and complex kidneys, the embryonic kidneys may be an ideal model system in which to investigate the genesis of multicomponent organ systems.

Animals↗

Wilms' tumor suppressor gene is involved in the development of disparate kidney forms: evidence from expression in the Xenopus pronephros.

The Wilms' tumor suppressor gene (WT1) is required for the formation of the mammalian metanephros, or adult kidney, and for the normal development of the mesonephros, the major mammalian embryonic kidney. In this report the isolation of a Xenopus gene closely related to the mammalian WT1 gene in both sequence and splicing pattern is described. Expression of this gene, xWT1, is restricted to the developing nephric system until late tadpole stages, which expression also begins to be observed in the heart. Within the nephric system, expression is observed in the dorsal portion of the splanchnic lateral plate in tailbud embryos, and in the glomus of early tadpoles. No expression is observed in the pronephric tubules or pronephric duct. The WT1 gene is therefore expressed in a similar temporal and spatial pattern in the vascularized portion of the amphibian pronephroi and in the mammalian metanephroi, arguing that it probably plays a similar crucial role in the morphogenesis of these very different kidney forms. The absence of expression in the developing pronephric tubules indicates that xWT1 is not required for the epithelialization of the tubular portion of the pronephros.

Animals↗

Prostate carcinoma metastatic to ureter.

Since carcinoma of the prostate usually metastasizes to pelvic lymph nodes or to bone or by direct extension, a discrete metastatic papillary lesion involving the ureter is unusual. We report such a case in a fifty-three-year-old man. Review of the literature has identified 11 other cases of carcinoma of the prostate metastatic to the ureter. None of the previously reported cases, however, described a discrete papillary intraluminal tumor in which there was no direct extension outside the ureteral wall. In addition, small foci of tumor were within intraluminal lymphatics as well as within the ureterovesical resection margin. These findings together with immunoperoxidase results confirm the unusual behavior and presentation of metastatic prostate carcinoma involving the ureter. Later a bladder tumor developed and histology again revealed metastatic prostate carcinoma.

Adenocarcinoma↗

Neoplastic angioendotheliomatosis: immunopathologic and morphologic evidence for intravascular malignant lymphomatosis.

Neoplastic angioendotheliomatosis (NAE) is a rare entity characterized by multifocal, intravascular proliferation of large pleomorphic cells within small vessels of most organs, with a particular affinity for the central nervous system. Clinically, patients with NAE present with focal neurologic signs and a progressive decline in mental status, followed by death in a few months. The histogenesis of NAE is controversial but has been previously thought to represent a malignant proliferation of endothelial cells. Three autopsy cases with clinical and histologic features of NAE were investigated by electron microscopic, standard histochemical, and immunohistochemical technics that included the use of three panleukocyte monoclonal antibodies (PLA), the endothelial-cell-specific reagents, FVIII-RAG anti-sera and Ulex europaeus agglutinin (UEA), and muramidase. The NAE cells in all three cases were stained positively by the PLA, whereas the adjacent endothelial cells and not the NAE cells were stained by FVIII-RAG and UEA. Muramidase by immunoperoxidase technic and nonspecific esterase (chloracetate) were not present in NAE cells. These results indicate that NAE is a leukocyte-derived neoplasm and not a malignant endothelial cell neoplasm. Based on these findings and on a review of the literature, it is proposed that NAE represents intravascular malignant lymphomatosis (IML). IML appears to be a primary manifestation and/or a major secondary form of disseminated malignant lymphoma. This would explain the spectrum of findings in previously reported cases.

Adult↗

Myelodysplastic syndromes. A clinical and pathologic analysis of 109 cases.

A total of 109 patients with myelodysplastic syndromes (MDS) was analyzed to determine the clinical and pathologic features of the five recently defined French-American-British Cooperative Group (FAB) subtypes, and to assess the utility of this classification system in predicting survival, evolution to acute nonlymphocytic leukemia (ANLL), and cause of death. All patients with MDS presented with anemia; additional cytopenias were present in patients with refractory anemia with excess blasts (RAEB), chronic myelomonocytic leukemia (CMML) and refractory anemia with excess blasts in transformation to ANLL (RAEB/Tr). Thirty-two patients received some form of antileukemic therapy for MDS. ANLL developed in 16 of the 77 remaining untreated patients, including 18% (2/11), 0% (0/21), 22% (5/23), 33% (2/6), and 44% (7/16) of patients with refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), RAEB, CMML, and RAEB/Tr, respectively (P = 0.02). The FAB subtype was highly predictive of survival with median survivals ranging from 71 months for RARS to 5 months for RAEB/Tr (P = less than 0.0001). Patients with RAEB, CMML, and RAEB/Tr frequently died of direct consequences of MDS, while patients with RA and especially RARS generally survived or died from unrelated disorders (P = less than 0.0001). MDS encompass a spectrum of disorders. RA and RARS, are relatively indolent and often do not lead to the patient's demise. RAEB, CMML, and RAEB/Tr are aggressive disorders which are often responsible for the patient's death whether or not actual progression to overt leukemia occurs. FAB subtype predicts survival, evolution to ANLL, and cause of death, although the five morphologic subtypes appear to separate into only two disease groups, especially with regard to survival and cause of death.

Aged↗

Nonendemic adult T-cell leukemia/lymphoma in the United States: report of two cases and review of the literature.

Adult T-cell leukemia/lymphoma (ATLL) is a recently described distinct clinicopathologic entity characterized by a leukemic or lymphomatous proliferation of hyperlobulated peripheral T-cells, which is usually widespread at presentation and is associated with infection by a type C retrovirus. ATLL rarely is described outside of endemic regions, which include southwestern Japan, the Caribbean region, and the southeastern United States. The authors report the clinical, pathologic, and immunologic features of two cases of nonendemic ATLL that occurred in patients from the midwest United States. One patient was a 16-year-old white girl from rural Iowa, and the other was a 46-year-old white man from rural Minnesota. The features of 13 other probable nonendemic ATLL cases from the United States were compiled and reviewed. In the United States, nonendemic ATLL occurred in widespread geographic locations, affected mostly white people, and was characterized by an aggressive course with generalized adenopathy, blood and bone marrow involvement, and hepatosplenomegaly at presentation. Skin involvement was present in one-fourth of the patients. Hypercalcemia was rare. Although antibodies to type C retrovirus were detected in three of the five patients tested, the available data is not sufficient to establish a conclusive association between nonendemic ATLL and type C retrovirus infection.

Adolescent↗

Studies of the endothelial origin of cells in systemic angioendotheliomatosis and other vascular lesions of the brain and meninges using ulex europaeus lectin stains.

Ulex europaeus agglutinin I (UEA-I) is a plant lectin which binds specifically to alpha-L-fucose moieties on the surface glycoproteins of human endothelial cells. The binding is completely inhibited by preincubation of the lectin with fucose. UEA-I can be conjugated directly to fluorescein or peroxidase and can be used to stain endothelium of paraffin embedded tissues. UEA-I staining was evaluated on normal and infarcted brain, systemic angioendotheliomatosis, metastatic epidural angiosarcoma, hemangioendothelioma, hemangioblastoma, angioblastic meningioma of both the hemangioblastic and hemangiopericytic types, and vascular meningioma. The endothelium, but not neuropil of normal and infarcted brain was positive for UEA-I. The tumor cells of hemangioendothelioma and angiosarcoma also stained. However, no staining was seen in malignant intravascular cells of angioendotheliomatosis, the stromal cells of hemangioblastoma, or pericytes of angioblastic meningioma. It is concluded that the malignant cells in angioendotheliomatosis, the stromal cells of hemangioblastoma and the pericytes of angioblastic meningioma do not produce surface glycoproteins characteristic of endothelial cells.

Brain Neoplasms↗