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R J Wechsler

Publications and source records attributed to R J Wechsler.

At least 19 recordsLinked to original sources

src-family tyrosine kinase p55fgr is expressed in murine splenic B cells and is activated in response to antigen receptor cross-linking.

Stimulation of the B cell Ag receptor (BCR) triggers a complex cascade of intracellular signals that lead to activation, proliferation, and differentiation. One of the earliest and most critical events following Ag receptor cross-linking is the activation of receptor-associated tyrosine kinases, which phosphorylate a variety of substrates involved in transducing signals generated through the receptor. Several tyrosine kinases have been shown to be associated with the BCR, including the src family members Lyn, Fyn, Blk, and Lck and the non-src kinase Syk. Here we describe another src family kinase expressed in B cells, p55fgr. Although previous studies have suggested that Fgr expression in the mouse is restricted to cells of the myeloid lineage, we demonstrate that highly purified murine splenic B cells express the kinase as well. We also show that Fgr, like other B cell kinases, is activated in response to cross-linking of the Ag receptor. Unlike these other kinases, however, Fgr does not appear to be physically associated with the receptor, and does not become activated until several minutes after stimulation. Moreover, we find that Fgr is associated with a distinct set of cellular proteins. On the basis of these studies, we hypothesize that Fgr may play a unique role in the BCR-associated signaling pathway.

Animals

Immature B lymphocytes are deficient in expression of the src-family kinases p59fyn and p55fgr1.

Unlike mature B cells, immature B cells are highly sensitive to tolerance induction and do not proliferate in response to stimulation through their Ag receptors. Our previous studies have suggested that this differential responsiveness is caused by differences in Ag receptor-proximal signaling pathways. Because many of these pathways are regulated by tyrosine phosphorylation, we have compared the expression and activity of tyrosine kinases in immature and mature B cells. Consistent with previous studies, we demonstrate that mature B cells express syk, lyn, blk, hck, and fyn; in addition, we find that they express significant amounts of the src-family kinase p55fgr. Immature B cells from day-3 mouse spleen show similar expression and activity of syk, lyn, blk, and hck. However, these cells have marked deficiencies in fyn and fgr expression. Differential expression of fyn and fgr is also observed in immature cells from the bone marrow, indicating that this phenotype is characteristic of the immature stage of B cell development. High levels of fyn and fgr are detectable in splenic B cells beginning at 4 wk of age, coincident with the appearance of cells that proliferate in response to receptor cross-linking. These observations indicate that expression of the src-family kinases fyn and fgr is regulated developmentally in murine B lymphocytes. Moreover, they suggest that these kinases may be important for mature B cell responses to Ag receptor stimulation, and that their absence may contribute to the unresponsiveness and tolerance susceptibility of immature B cells.

Animals

Threshold selection for CT angiography shaded surface display of the renal arteries.

The purpose of this study was to define objective criteria to calculate a tissue segmentation threshold for shaded surface display (SSD) rendering of the renal arteries with computed tomography angiography. Contrast-enhanced spiral CT scans were obtained through the renal arteries of nine patients. Six sets of SSD images were rendered for each patient with lower threshold values ranging from 80 to 130 Hounsfield units (HU) by increments of 10 HU. Visceral organ enhancement was measured in the aorta, liver, spleen, pancreas, and kidney. The segmentation threshold for each patient was determined by evaluation of the SSD images alone as well as by comparison with conventional arteriograms. The ideal threshold, as shown by comparison with conventional arteriography, was better correlated with a threshold value selected by qualitative evaluation of SSD images alone (rs = .42), than with measured enhancement in visceral organs (rs = -.289 to .009). The degree of stenosis was overestimated in a single renal artery (1 of 18) because of an inappropriate threshold selected by evaluation of the SSD images alone. In comparison with a segmentation threshold calculated from measured enhancement of visceral organs, a segmentation threshold selected by qualitative evaluation of the resulting SSD images is more likely to approximate the ideal threshold. Given the subjective nature of such threshold selection, further evaluation is warranted to determine whether threshold selection may result in inaccurate grading of stenosis.

Adult

Superior hypogastric plexus block for chronic pelvic pain in the presence of endometriosis: CT techniques and results.

PURPOSE: To evaluate the use of superior hypogastric plexus block with computed tomographic (CT) guidance in patients with endometriosis and chronic pelvic pain. MATERIALS AND METHODS: Seven blocks were performed on an outpatient basis in five women with endometriosis and pelvic pain. In the first four patients, one or two 20-gauge, 15-cm needles were placed anterior to the spine at the common iliac bifurcation from a posterior approach. In the fifth patient, the block was performed from an anterior approach with a single needle. RESULTS: One procedure resulted in mild pain relief, three in considerable pain relief, one in complete midline pain relief with no change in the lateral pain, and one in complete pain relief. One procedure was terminated because anesthetic was injected into the peritoneal cavity. There were no other complications. CONCLUSION: CT-guided superior hypogastric plexus block is easily performed and can be used to assess whether chronic pelvic pain can be attenuated by blocking the superior hypogastric plexus.

Adult

The radiologic and pathologic spectrum of biliary hamartomas.

OBJECTIVE: The purpose of our study was to correlate the spectrum of radiologic and pathologic findings in a series of patients with biliary hamartomas and known extrahepatic malignancy. MATERIALS AND METHODS: Biliary hamartomas were diagnosed in 18 patients with a primary malignant lesion who had liver biopsy for evaluation of possible metastatic disease. Prebiopsy imaging studies included CT in 16 patients and sonography in 11. Imaging studies were reviewed retrospectively and correlated with findings at surgery and on pathologic examination. The hamartomas were classified histologically by the degree of cystic dilatation of bile ducts within the lesion. RESULTS: Radiologically, biliary hamartomas presented a spectrum of findings including one or two circumscribed lesions (5-10 mm in diameter) in four patients; multiple (about five) lesions (approximately 5 mm each) in one patient; innumerable tiny, nearly uniform (2-5 mm) lesions in two patients; and innumerable lesions of varying size (2-15 mm) in three patients. Among the patients with innumerable lesions, the nodules were either uniformly or nonuniformly distributed throughout the liver. In all cases, the lesions were hypodense on contrast-enhanced CT scans and hypoechoic on sonograms. In eight patients, the lesions were not visible by imaging but biopsies were done at surgery when single or multiple tiny nodules were noted on the liver surface. The diagnosis was made by either wedge or core-needle biopsy; fine-needle aspirations were nondiagnostic. Pathologic examination revealed single or multiple hamartomas of varying sizes ranging from solid to largely cystic lesions; the degree of cystic dilatation did not correlate with imaging findings. Visibility on imaging correlated with larger lesion size; small surface lesions were usually occult. CONCLUSION: Biliary hamartomas cause single or multiple nonspecific hepatic lesions that may mimic metastases. This diagnosis should be considered in patients with a primary malignant tumor when single or multiple small hepatic lesions are seen, regardless of uniformity of size or distribution.

Adult

Tarsal coalition: depiction and characterization with CT and MR imaging.

PURPOSE: To compare computed tomography (CT) and magnetic resonance (MR) imaging in the detection, localization, and characterization of tarsal coalitions. MATERIALS AND METHODS: Preoperative CT and MR images were obtained for 10 feet in nine patients (eight male and one female patients), aged 11-18 years who were unresponsive to conservative therapy. Results from two blinded readers were compared with results from surgery. RESULTS: Five calcaneonavicular and four medial subtalar coalitions were found at surgery. One patient had synovitis. CT depicted six coalitions and four were characterized correctly, but the fibrous coalitions were not characterized correctly. MR depicted all coalitions and seven were characterized correctly, including the fibrous coalitions. At MR imaging, proliferative synovitis was incorrectly characterized as a fibrous coalition. CONCLUSION: These results suggest that MR imaging depicts all coalitions but may not be able to help differentiate synovitis from fibrous coalitions and that CT has limitations in the depiction of fibrous coalitions.

Adolescent

Breast implants: incidental findings on CT.

The mammographic, sonographic, and MR appearances of both normal and abnormal breast implants have been described. Breast implants are occasionally seen on chest CT scans obtained for other reasons; however, we know of no published reports on the CT findings in a series of patients with breast implants. We present a retrospective review of CT findings in 18 patients with 27 breast implants that illustrates the spectrum of findings that can be seen in asymptomatic patients.

Breast

CT done 4-6 hr after CT arterial portography: value in detecting hepatic tumors and differentiating from other hepatic perfusion defects.

OBJECTIVE: Nontumorous perfusion defects occur during CT arterial portography (CTAP) as normal variants or in cirrhosis, focal fatty infiltration, and portal vein obstruction. The purpose of this study was to determine whether delayed CT 4-6 hr after CTAP improves sensitivity to hepatic tumors and differentiates them from other hepatic perfusion defects. SUBJECTS AND METHODS: CTAP was done at 1-cm increments on 26 patients for evaluation of hepatic tumors. Delayed CT scans were obtained 4-6 hr later in all patients. Two observers retrospectively reviewed the CT scans obtained during CTAP and recorded size, shape, and location of suspected hepatic tumors. Confidence levels were assigned for each tumor. The delayed CT scan was then interpreted in conjunction with the CT scans obtained during CTAP, and confidence levels were reassigned. Surgical correlation was obtained for all patients. In the 26 patients, 86 masses were found at surgery. The sensitivity and number of false-positives for both CTAP alone and CTAP combined with delayed CT were compared with a two-tailed Student t-test. Receiver-operating-characteristic analysis also was performed. RESULTS: CTAP detected 73 (85%) of the 86 hepatic masses. Delayed CT had no effect on the sensitivity of CTAP. However, adding delayed CT decreased the total number of false-positives by 11, a statistically significant difference (p < .05). Receiver-operating-characteristic analysis revealed a significantly greater (p < .05) area under the curve (Az index) of 0.927 +/- 0.025 for CTAP combined with delayed CT compared with 0.886 +/- 0.032 for CTAP alone. Delayed CT was most useful for larger (> 1 cm) wedge-shaped perfusion defects and least useful for smaller (< 1 cm) round defects. CONCLUSION: Delayed CT has no effect in detecting tumors but may be useful for differentiating tumors from other hepatic perfusion defects seen on CTAP. The greatest benefit of delayed CT is in evaluating regions obscured by large wedge-shaped perfusion defects on CT scans obtained during CTAP.

Colorectal Neoplasms

Gastric stump lymphoma.

Lymphoma occurring in the post-operative stomach would appear to be very rare with only five previously recorded cases. In three of these, focal lymphoid hyperplasia or pseudolymphoma had been found at the time of the original ulcer surgery, or at subsequent biopsies of the gastric stump or anastomotic sites. These latter three cases developed lymphoma within 11 years of the ulcer surgery as against the 20 years or longer generally found in cases of gastric stump carcinoma. Two cases presenting with gastric stump lymphoma approximately 20 years after Billroth 2 partial gastrectomy are reported. In neither of these two cases, nor in the other two patients previously recorded with post-operative gastric lymphoma 20 or more years following gastric surgery, was luminal focal lymphoid hyperplasia reported at the time of the original gastric surgery. It is postulated that these two small groups may have developed lymphoma due to differing malignant stimuli.

Gastrectomy

Endogenous expression of delta on the surface of WEHI-231. Characterization of its expression and signaling properties.

WEHI-231 is a murine B cell lymphoma that has been used extensively as a model for the immature stage B cell and its functional response to Ag receptor cross-linking as a model for immature B cell tolerance. This cell line expresses sIgM, CD5, and FcR gamma, but lacks the B cell-specific isoform of CD45 (B220). This study demonstrates for the first time that WEHI-231, in contrast to classically defined immature B cells, expresses delta on its surface. Analysis of delta on WEHI-231 revealed structural differences with respect to that on BAL-17 or primary splenic B cells. Although the m.w. of delta on the latter two B cell populations was similar, delta on WEHI-231 manifested a marked increase in its apparent m.w. deduced by SDS-PAGE. This difference was found to be due primarily to differential N-linked glycosylation. Signal transduction through the endogenous sIgD on WEHI-231 was investigated. In contrast to cross-linking of sIgM, cross-linking of the endogenous surface IgD on WEHI-231 was unable to generate a negative growth response in these cells. This inability may be due to uncoupling from normal surface Ig signaling pathways. The signaling properties of the endogenous sIgD on WEHI-231 differ from that on primary B cells and other sIgD-expressing cell lines. Whereas sIgD on splenic B lymphocytes or the mature B cell line BAL-17 is coupled to inositol phospholipid hydrolysis and calcium mobilization, cross-linking of sIgD on WEHI-231 failed to elicit these events, although induced changes in tyrosine phosphorylation were observed. Thus, endogenous expression of surface IgD on WEHI-231 is inconsistent with its representing the classically defined immature stage B cell. The structural and signaling differences associated with delta on these cells suggest the potential for developmentally regulated delta function and model for study of sIgD signal transduction.

Animals

Pulmonary calcinosis following orthotopic liver transplantation.

Pulmonary opacities following orthotopic liver transplantation (OLT) are frequent due to pneumonia, infarction, or pulmonary edema. Metastatic pulmonary calcifications are present as persistent opacities that may mimic these conditions. In a series of 91 patients who underwent OLT, chest radiographs of 77 were reviewed and pulmonary calcinosis was seen in 4 (5.2%). Pulmonary calcinosis may be due to a variety of conditions, including dystrophic calcification in damaged lung and primary or secondary hyperparathyroidism. In this series, patients with pulmonary calcinosis had significantly higher levels of serum phosphate and calcium postoperatively and had received more intraoperative platelets and other blood products containing exogenous calcium than other patients. Pulmonary calcinosis should be considered in patients following OLT when stable, nonspecific pulmonary opacities are present. CT or radionuclide studies will aid in confirming this diagnosis.

Adolescent

Cost containment in the use of low-osmolar contrast agents: effect of guidelines, monitoring, and feedback mechanisms.

PURPOSE: To describe a program for controlling intravenous use of low-osmolar contrast agents (LOCAs). MATERIALS AND METHODS: The department of radiology at the authors' institution adopted a policy of selective use of intravenously administered LOCAs. Clinical indications for LOCA use were specified after consultation with the administration, risk managers, legal department, and ethics committee of the hospital. The guidelines were then publicized throughout the department and hospital, and a contrast agent data form was developed to collect data on all cases. Monitoring mechanisms were instituted. RESULTS: Over the next 23 months, 11,373 patients received intravenous iodinated contrast agents, of whom 28.1% were deemed to be at high risk and were given LOCAs. Monthly tracking showed no evidence of a trend toward increasing use of LOCAs. CONCLUSION: Clear definition of use guidelines, close monitoring, and feedback can stabilize LOCA use at acceptably low levels.

Adult

Localization of peripheral pulmonary nodules for thoracoscopic excision: value of CT-guided wire placement.

OBJECTIVE: One of the indications for the rapidly expanding use of thoracoscopic surgery as an alternative to thoracotomy is the excision of peripheral lung nodules. Nodules judged too small or too far from the pleural surface to be seen or palpated during thoracoscopy must be localized beforehand. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous placement of spring hookwires to localize such nodules before video-assisted thoracoscopy. SUBJECTS AND METHODS: Under CT guidance, 17 nodules in 14 patients were preoperatively localized with the Kopans breast lesion localization system. Three patients who had solitary nodules had thoracoscopic resections for diagnosis because a previous transthoracic needle or transbronchial biopsy had been unsuccessful. Four patients who had lesions less than 8 mm in diameter had thoracoscopic biopsies because transthoracic fine-needle aspiration biopsy was not likely to be diagnostic. Seven patients, who had a total of 10 nodules, had therapeutic wedge resections of either limited metastases or a second bronchogenic carcinoma. Mean nodule diameter was 10 mm (range, 3-20 mm). The mean distance from nodule to costal pleura was 9 mm (range, 0-25 mm). At the end of the procedure, wire placement was confirmed by CT scanning. After thoracoscopy, the surgeons were questioned about the stability and utility of each hookwire localization. RESULTS: In all 17 procedures, a hookwire was placed successfully. In one case, the wire dislodged before thoracoscopy (after a 6-hr preoperative delay and severe bending of the wire during induction of anesthesia). In 16 of the 17 resections, the surgeon thought that thoracoscopic identification of the lesion would not have been possible without hookwire localization. Only one localization, across a major fissure, required placement of a second wire to localize a nodule. Wire-related complications included two instances of serious pain, five cases of clinically insignificant pneumothorax, and one large pneumothorax requiring drainage before a second nodule in the same lung was localized. CT scanning showed presumed local pulmonary hemorrhage in six cases without hemoptysis or hemothorax. CONCLUSION: CT-guided hookwire localization is easily and safely performed and permits thoracoscopic resection of lung nodules, which might otherwise be impossible.

Adult

Computed tomography of talocalcaneal coalition: imaging techniques.

The diagnosis of symptomatic talocalcaneal coalition requires an imaging study that demonstrates precise anatomic detail. Computed tomography affords the best method for the diagnosis. This essay reviews the computed tomographic anatomy of talocalcaneal coalitions in several projections and stresses the routine use of the angled coronal and direct sagittal projections.

Adolescent

Actinomycosis and nocardiosis of the lung.

Actinomyces and Nocardia species are frequently overlooked pulmonary pathogens until their presence is histologically proved. These infections often are not considered in the differential diagnosis of lung disease because of the spectrum of their presentation, the similarity of their appearance to other granulomatous or neoplastic diseases, and coexistence of these infections with other pulmonary conditions. Pulmonary actinomycosis is characterized by pulmonary consolidation, frequently with cavitation and spread to contiguous tissues without regard for normal anatomic barriers. The appearance often is confused with that of bronchogenic carcinoma or other granulomatous infections, especially tuberculosis. Pulmonary nocardiosis most frequently develops in immunocompromised patients, and the incidence of this infection is increasing. The radiographic manifestations of nocardiosis are pleomorphic, but early recognition is essential to initiate appropriate therapy.

Actinomycosis

Suprahepatic circumcaval ring: CT finding after orthotopic liver transplantation.

A suprahepatic circumcaval ring or arc was noted on computed tomographic (CT) scans in 20 of 37 patients who had undergone 42 orthotopic liver transplantations. The patients were divided into two groups, depending on the presence or absence of this finding. The amounts of blood products transfused intraoperatively and the levels of serum calcium, phosphate, and calcium phosphate product after transplantation were determined for each group. Liver graft function was evaluated on the basis of postoperative levels of serum bilirubin, albumin, and aminotransferase. The levels of serum calcium and calcium phosphate product were higher in patients with the circumcaval ring. This group had received substantially more fresh frozen plasma and platelets at surgery. There was no difference in liver graft function between the two groups. In one case, pathologic examination demonstrated calcification within circumcaval fibrotic tissue. A suprahepatic circumcaval ring is a common finding at CT performed after liver transplantation and is probably related to elevated perioperative serum calcium levels and tissue injury. Surgeons should be made aware of this finding before performing repeat transplantation, since calcification at a potential anastomotic site may make surgery more difficult.

Adolescent