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D S Hartman

Publications and source records attributed to D S Hartman.

At least 37 records · Page 2Linked to original sources

Nerve growth factor-induced differentiation in neuroblastoma cells expressing TrkA but lacking p75NGFR.

Nerve growth factor (NGF) binds to two distinct cell surface receptors, TrkA, which is a receptor tyrosine kinase, and p75NGFR, whose role in NGF-induced signal transduction remains unclear. We have found that human neuroblastoma IMR-32 cells express TrkA, but p75NGFR expression was not detectable in these cells by northern blot analysis, immunoblotting, or chemical crosslinking experiments. Despite the lack of p75NGFR expression, subnanomolar concentrations of recombinant human NGF induced neurite outgrowth, tyrosine phosphorylation, and immediate early gene expression in these cells. These results strongly suggest that NGF-induced neuronal differentiation in IMR-32 cells is initiated through TrkA in the absence of p75NGFR. Thus, IMR-32 cells may provide a model for studying neurotrophic effects of NGF on adult striatal cholinergic neurons, which also lack p75NGFR expression.

Adult↗

Interactive method of informing patients of the risks of intravenous contrast media.

PURPOSE: To evaluate interactive computer-based informed consent for use of contrast material versus the same information in a written format. MATERIALS AND METHODS: Patients (n = 160) referred for radiologic examination with intravenous contrast material were block randomized (sex, age, and previous exposure to contrast material) into two groups and were provided either written or computer-based (video) informed consent. RESULTS: The female patients in the video group scored better on the test than those in the group with the written consent form. Male patients attained equivalent scores with both types of consent. The video took an average of 1.6 minutes longer to complete, probably because the majority of patients chose to be informed of every risk of intravenous contrast material. CONCLUSION: This project demonstrates that a video format for informed consent before use of intravenous contrast material offers a good alternative to the written consent form.

Comprehension↗

Renal oncocytoma and carcinoma: failure of differentiation with CT.

The authors studied the hypothesis that oncocytoma and adenocarcinoma of the kidney can be differentiated with computed tomographic (CT) criteria and that differences would become more apparent as tumors enlarged. On contrast material-enhanced scans, homogeneous attenuation throughout the tumor and a central, sharply marginated, stellate area of low attenuation were considered predictors of oncocytoma. Any area of decreased attenuation in the tumor except for a stellate, central area was used as a predictor of adenocarcinoma. Among oncocytomas larger than 3 cm in diameter, 67% exhibited the criteria for oncocytoma and 33% met the criterion for adenocarcinoma; among smaller oncocytomas, the respective results were 82% and 18%. Among adenocarcinomas larger than 3 cm in diameter, 84% fulfilled the criterion for malignancy and 16% were incorrectly predicted to be oncocytomas; among smaller adenocarcinomas, the respective results were 58% and 42%. The authors conclude that the CT criteria used are poor predictors of the diagnosis of oncocytoma or adenocarcinoma regardless of tumor size.

Adenoma↗

Multiple trkA proteins in PC12 cells bind NGF with a slow association rate.

Rat pheochromocytoma (PC12) cells express two distinct nerve growth factor receptors (NGFRs), p75NGFR and trkA (p140trk). In addition to these receptors, by using 125I-mNGF affinity labeling and BS3 chemical cross-linking of PC12 cell protein, we have identified two additional trkA protein bands with apparent molecular weights of 220,000 and 300,000. These bands contain trkA, but were not immunoprecipitated by p75NGFR-specific antisera, suggesting that they do not represent trkA/p75NGFR protein complexes. The 220-kDa trkA band apparently represents trkA with alternate post-translational modification. The appearance of the 300-kDa trkA band was dependent on cross-linker concentration and could be diminished in the presence of reducing agents, suggesting that it represents a trkA dimer. All trkA bands were phosphorylated on tyrosine residues when bound to mNGF, suggesting that they participate in NGF-induced signal transduction. NGF binding kinetics to all three trkA bands were indistinguishable, with slow dissociation rates, and a slow association rate that required approximately 1 h to reach equilibrium levels at 4 degrees C. All three trkA bands bound the related neurotrophin brain-derived neurotrophic factor and neurotrophin-3 with a profile characteristic of trkA.

Animals↗

Renal cystic disease in multisystem conditions.

Five renal cystic diseases have significant extrarenal manifestations: autosomal dominant polycystic kidney disease (ADPCK), autosomal recessive polycystic kidney disease (ARDCK), tuberous sclerosis (TS), von Hippel-Lindau Syndrome (VHL), and medullary cystic disease (MCD). Knowledge of these extrarenal manifestations is important since they may precede, present simultaneously, or follow the onset of the renal cystic disease. This article discusses the most significant extrarenal manifestations of these five renal cystic diseases: (1) ADPCK: hepatic cysts and cardiovascular abnormalities; (2) ARDCK: portal hypertension; (3) TS: hamartoma-like tumors of other organs; (4) VHL: central nervous system hemangioblastomas and paragangliomas; and (5) MCD: congenital hepatic fibrosis. Detecting extrarenal manifestations may be helpful (1) in confirming the renal cystic disease; (2) in thoroughly evaluating the patient with known renal cystic disease, and (3) if they antedate the renal cystic disease, their presence will alert the radiologist to evaluate the kidneys.

Adult↗

Retroaortic left renal vein in testicular cancer patient: potential staging and treatment pitfall.

A 20-year-old man was diagnosed with a left mixed germ cell testicular tumor and clinical staging with computerized tomography suggested left para-aortic subhilar retroperitoneal adenopathy. The patient received 4 cycles of cisplatin, vinblastine and bleomycin chemotherapy but the mass in the left renal hilus area remained unchanged. Subsequent retroperitoneal lymphadenectomy revealed the mass to be a retroaoritc left renal vein type 2. Further confusion occurred during followup in differentiating this anomaly from recurrent neoplasm necessitating evaluation by magnetic resonance imaging. Retroaortic left renal vein represents a potential imaging pitfall in testicular cancer that may facilitate suboptimal staging, treatment and followup.

Adult↗

From the archives of the AFIP. Leiomyosarcoma of the retroperitoneum and inferior vena cava: radiologic-pathologic correlation.

Leiomyosarcoma is the second most common primary retroperitoneal tumor in adults. Retroperitoneal leiomyosarcoma exhibits three major growth patterns: (a) completely extravascular (extraluminal) (62% of cases), (b) completely intravascular (intraluminal) (5% of cases), and (c) extra- and intraluminal (33% of cases). The usual clinical manifestation is a large abdominal mass. Intraluminal leiomyosarcoma may be accompanied by symptoms referable to venous thrombosis. The variable gross features and potential for intravascular extension result in various radiologic appearances, the most common being a large, partially necrotic soft-tissue mass in the retroperitoneum with or without extension into the inferior vena cava. Computed tomography and magnetic resonance imaging typically show a nonfatty, necrotic retroperitoneal mass and a vascular component when it is present. Ultrasound and angiography may also be useful, especially if vascular involvement is suspected from other imaging studies. Treatment of choice is surgical excision, which is frequently impossible due to the invasiveness of the tumor. Prognosis is related to extent of invasion and the adequacy of resection. Long-term prognosis is poor, and most patients die of local recurrence or distant metastasis.

Angiography↗

Cystic renal masses: usefulness of the Bosniak classification.

To determine the usefulness of the Bosniak classification of cystic renal masses, the computed tomographic (CT) and ultrasound findings of 16 pathologically proven cystic renal masses were retrospectively reviewed. All imaging studies were reviewed and categorized utilizing the Bosniak classification without knowledge of the final pathologic diagnosis. There were no category I lesions (classical simple cyst), four category II (minimally complicated), seven category III lesions (more complicated), and five category IV lesions (probable malignant). All category II lesions were benign, all category IV lesions were malignant. Of the seven category III lesions, three were benign and four were malignant. We conclude that the Bosniak classification is extremely useful in the management of cystic renal masses.

Female↗

Efficiency of acetylcholine receptor subunit assembly and its regulation by cAMP.

Assembly of nicotinic acetylcholine receptor (AChR) subunits was investigated using mouse fibroblast cell lines stably expressing either Torpedo (All-11) or mouse (AM-4) alpha, beta, gamma, and delta AChR subunits. Both cell lines produce fully functional cell surface AChRs. We find that two independent treatments, lower temperature and increased intracellular cAMP can increase AChR expression by increasing the efficiency of subunit assembly. Previously, we showed that the rate of degradation of individual subunits was decreased as the temperature was lowered and that Torpedo AChR expression was acutely temperature sensitive, requiring temperatures lower than 37 degrees C. We find that Torpedo AChR assembly efficiency increases 56-fold as the temperature is decreased from 37 to 20 degrees C. To determine how much of this is a temperature effect on degradation, mouse AChR assembly efficiencies were determined and found to be only approximately fourfold more efficient at 20 than at 37 degrees C. With reduced temperatures, we can achieve assembly efficiencies of Torpedo AChR in fibroblasts of 20-35%. Mouse AChR in muscle cells is also approximately 30% and we obtain approximately 30% assembly efficiency of mouse AChR in fibroblasts (with reduced temperatures, this value approaches 100%). Forskolin, an agent which increases intracellular cAMP levels, increased subunit assembly efficiencies twofold with a corresponding increase in cell surface AChR. Pulse-chase experiments and immunofluorescence microscopy indicate that oligomer assembly occurs in the ER and that AChR oligomers remain in the ER until released to the cell surface. Once released, AChRs move rapidly through the Golgi membrane to the plasma membrane. Forskolin does not alter the intracellular distribution of AChR. Our results indicate that cell surface expression of AChR can be regulated at the level of subunit assembly and suggest a mechanism for the cAMP-induced increase in AChR expression.

Acetylglucosaminidase↗

Extracellular synaptic factors induce clustering of acetylcholine receptors stably expressed in fibroblasts.

The clustering of nicotinic acetylcholine receptors (AChRs) is one of the first events observed during formation of the neuromuscular junction. To determine the mechanism involved in AChR clustering, we established a nonmuscle cell line (mouse fibroblast L cells) that stably expresses just one muscle-specific gene product, the AChR. We have shown that when Torpedo californica AChRs are expressed in fibroblasts, their immunological, biochemical, and electrophysiological properties all indicate that fully functional cell surface AChRs are produced. In the present study, the cell surface distribution and stability of Torpedo AChRs expressed in fibroblasts (AChR-fibroblasts) were analyzed and shown to be similar to nonclustered AChRs expressed in muscle cells. AChR-fibroblasts incubated with antibodies directed against the AChR induced the formation of small AChR microclusters (less than 0.5 micron 2) and caused an increase in the internalization rate and degradation of surface AChRs (antigenic modulation) in a manner similar to that observed in muscle cells. Two disparate sources of AChR clustering factors, extracellular matrix isolated from Torpedo electric organ and conditioned media from a rodent neuroblastoma-glioma hybrid cell line, each induced large (1-3 microns 2), stable AChR clusters with no change in the level of surface AChR expression. By exploiting the temperature-sensitive nature of Torpedo AChR assembly, we were able to demonstrate that factor-induced clusters were produced by mobilization of preexisting surface AChRs, not by directed insertion of newly synthesized AChRs. AChR clusters were never observed in the absence of extracellular synaptic factors. Our results suggest that these factors can interact directly with the AChR.

Animals↗

From the Archives of the AFIP. Xanthogranulomatous pyelonephritis.

Xanthogranulomatous pyelonephritis is a form of chronic infection of the kidney and surrounding tissues characterized by destruction and replacement of renal parenchyma by lipid-laden macrophages. Gross pathologic features include massive renal enlargement, lithiasis, peripelvic fibrosis, hydronephrosis, and lobulated yellow masses replacing renal parenchyma. Typically, the disease is diffuse and has characteristic imaging features. Less commonly, the process is focal and is difficult to differentiate from malignant disease on radiologic studies. Ultrasound demonstrates renal enlargement with multiple anechoic or hypoechoic masses replacing the normal corticomedullary differentiation and a contracted pelvis. Peripelvic fibrosis may obscure acoustic shadowing from a central staghorn calculus. On computed tomographic scans, a staghorn calculus may be seen in a contracted renal pelvis of an enlarged kidney, with characteristic low-attenuation, peripherally enhancing rounded masses. Extrarenal extension of the inflammatory process is frequently seen.

Adult↗

Current status of imaging indeterminate renal masses.

In 1986 Bosniak proposed a classification of cysts and cystic renal masses in an attempt to define precisely the radiologic findings for lesions not requiring further evaluation and for those that should be explored surgically in an attempt to salvage normal renal parenchyma. This classification has been extremely useful in expanding the number of patients treated conservatively. The following entities can be considered benign and require no further evaluation: the classic simple cyst (Bosniak category 1), a cyst with benign calcification (see Fig. 1A and B), a hyperdense cyst (see Fig. 2), and a cyst with thin (less than or equal to 1mm) septations (see Fig. 5A; Bosniak category 2). When any of the following features are present, further evaluation is warranted: aggressive calcifications (see Fig. 1C-E), abnormal density not fulfilling the criteria of a hyperdense cyst (see Figs. 3 and 4), or nodular septations (see Fig. 5B and C), or wall thickening (see Fig. 7; Bosniak) category 3). Small masses that cannot be characterized accurately also require further evaluation. Multiloculated masses(see Fig. 9) require surgery (Bosniak category 3). Most cases of multiple localized renal cysts can be distinguished from multiloculated masses and do not require surgery (see Fig. 10). Evaluation of cyst fluid by MR imaging has not been proved reliable in differentiating benign and malignant masses. MR imaging will become more useful when its spatial resolution equals that of CT. Masses that remain indeterminate after careful evaluation by ultrasonography and CT scanning can be evaluated additionally by angiography or cyst puncture. Management options for persistent enigmatic masses include follow-up radiologic studies, exploration, local excision, and nephrectomy.

Carcinoma, Renal Cell↗

Coexpression of two distinct muscle acetylcholine receptor alpha-subunits during development.

The nicotinic acetylcholine receptor is a ligand-gated channel that mediates signalling at the vertebrate neuromuscular junction. It is a pentameric complex of four different subunits, assembled with a stoichiometry of alpha 2 beta gamma delta. Muscle-like alpha-subunits have been cloned from Torpedo, mouse, calf, rat, chicken, human and Xenopus, and only a single alpha-subunit complementary DNA from each species has been detected. We report here the cloning and characterization of a second muscle alpha-subunit cDNA from Xenopus, and show that this and a previously reported Xenopus alpha-subunit cDNA are encoded by distinct genes. The novel alpha-subunit reported here is expressed uniquely in oocytes; but both types of alpha-subunit are coexpressed throughout muscle development. This latter observation indicates that the expression of these two alpha-subunits is different from a previously reported developmental 'subunit-switch' mechanism used to generate channel diversity.

Amino Acid Sequence↗