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Biomedical subjects

E Levine

Publications and source records attributed to E Levine.

At least 19 recordsLinked to original sources
PubMed1995

Glycosylphosphatidylinositol-modified murine B7-1 and B7-2 retain costimulator function.

Glycosylphosphatidylinositol (GPI)-modified variants of murine B7-1 and B7-2 cell surface costimulators were produced via chimerization with alternative GPI-modification signal sequences from decay-accelerating factor (DAF). GPI anchorage was verified by demonstrating phosphatidylinositol-specific phospholipase C (PI-PLC) sensitivity of the chimeric polypeptides in both immunofluorescence/flow-cytometric and immunoprecipitation analyses. The various GPI-modified chimeric B7-1:DAF and B7-2:DAF polypeptides were shown to retain costimulator function, in both an in vitro proliferation assay and an in vivo triggering of cytotoxicity assay. The findings indicate that costimulator function for both B7-1 and B7-2 is not dependent upon native hydrophobic transmembrane anchorage. Moreover, the functionality of the GPI-modified variants in enhancing the immunogenicity of the murine T lymphoma line EL-4 suggests a novel route for generating APC-centered immunotherapeutics, including cellular cancer vaccines, that is based upon protein transfer of GPI-modified costimulators.

Animals↗
PubMed1995

Therapy for inflammatory breast cancer: impact of doxorubicin-based therapy.

BACKGROUND: Inflammatory breast cancer (IBC) carries an ominous prognosis. Before 1988, women with IBC at our institution were treated with neoadjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with or without vincristine and prednisone (CMF/VP). After 1988, women with IBC were treated with cyclophosphamide, doxorubicin, and 5-fluorouracil (FAC). This study compares these two regimens with regard to response and survival. METHODS: The records of all women presenting between January 1973 and December 1991 with a stage IIIB (T4d, any N, MO) breast cancer with proven dermal lymphatic invasion by tumor cells were reviewed retrospectively. RESULTS: The study comprised 38 women; 28 received CMF (22 CMF, 6 CMF/VP), and 10 received FAC. The overall response rate to induction chemotherapy in the CMF/VP group was 57% (40% PR, 17% CR), and 100% (60% PR, 40% CR) in the FAC group. The median overall survival for women receiving CMF/VP was 18 months compared with 30 months for women receiving FAC (p = 0.02). The median disease-free survivals for the CMF/VP and FAC groups were 6 and 24 months, respectively (p < 0.001). When comparing responders and nonresponders with CMF/VP induction therapy, the responders had a significantly longer overall median survival (24 versus 10 months) (p < 0.001) and disease-free median survival (8 versus 2 months) (p < 0.001). All of the five patients remaining alive received FAC with 80% (four of five) having a complete response. These four patients subsequently underwent mastectomy and radiation. CONCLUSION: This study suggests that a doxorubicin-containing chemotherapy regimen improves overall and disease-free median survivals when compared with the previously used CMF combination in the treatment of IBC. A favorable response to induction chemotherapy also appeared to be associated with an improved survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Phase I study of paclitaxel and carboplatin: implications for trials in head and neck cancer.

An ongoing phase I and pharmacokinetic trial of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with carboplatin is evaluating the maximum tolerated dose (MTD) of a 3-hour paclitaxel infusion combined with fixed doses of carboplatin in previously treated and untreated patients with a variety of advanced cancers. A patient's previous treatment status determines the fixed carboplatin dose: target area under the concentration-time curves of 4.0 and 4.5 mg.min/mL in previously treated and untreated patients, respectively. Studies 1 and 2 entered previously treated patients to establish the paclitaxel MTD without and with cytokine support: study 1 established 135 mg/m2 paclitaxel as the MTD without such support. In study 2, granulocyte colony-stimulating factor is administered, and the MTD has not yet been reached with paclitaxel doses of 135 mg/m2 to 230 mg/m2 assessed thus far and 250 mg/m2 now being evaluated. Objective responses have been seen in three of five patients with squamous cell carcinoma of the head and neck and in patients with non-small cell lung cancer and metastatic cancer of unknown primary site as well. Myelosuppression has been the dose-limiting toxicity, although significant nausea and vomiting and myalgia have been documented occasionally. Paclitaxel apparently has nonlinear pharmacokinetics with a beta half-life of 6.7 hours (SD +/- 1.3 hours). Future trials of paclitaxel/carboplatin will address the management of squamous cell carcinoma of the head and neck and non-small cell carcinoma of the lung.

Adenocarcinoma↗
PubMed1994

Selective disruption of E-cadherin function in early Xenopus embryos by a dominant negative mutant.

E-cadherin function was disrupted in vivo in developing Xenopus laevis embryos through the expression of a mutant E-cadherin protein lacking its cytoplasmic tail. This truncated form of E-cadherin was designed to act as a dominant negative mutant by competing with the extracellular interactions of wild-type endogenous E-cadherin. Expression of truncated E-cadherin in the early embryo causes lesions to develop in the ectoderm during gastrulation. In contrast, expression of a similarly truncated N-cadherin protein failed to cause the lesions. The ectodermal defect caused by the truncated E-cadherin is rescued by overexpression of wild-type E-cadherin, by co-injection of full-length E-cadherin RNA along with the RNA for the truncated form. Overexpression of full-length C-cadherin, however, is unable to compensate for the disruption of E-cadherin function and can actually cause similar ectodermal lesions when injected alone, suggesting that there is a specific requirement for E-cadherin. Therefore, E-cadherin seems to be specifically required for maintaining the integrity of the ectoderm during epiboly in the gastrulating Xenopus embryo. Differential cadherin expression reflects, therefore, the requirement for distinct adhesive properties during different morphogenetic cell behaviors.

Amino Acid Sequence↗
PubMed1994

Needs assessment for advanced practice nurses for the uniformed services.

An assessment was made of the need for advanced practice nurses (APNs) in the uniformed services of the Department of Defense and the United States Public Health Service. The purpose of the assessment was to determine the role of the Graduate School of Nursing (GSN) at the Uniformed Services University of the Health Sciences in educating APNs for the uniformed services. The assessment focused on three categories of APNs: certified registered nurse anesthetists (CRNAs), certified nurse-midwives (CNMs), and nurse practitioners (NPs). The assessment found that current authorizations for APNs in the three military services exceeded inventory by 192 APNs: 148 CRNAs, 4 CNMs, and 40 NPs. In addition, losses through attrition in fiscal year 1993 were 154 APNs: 97 CRNAs, 7 CNMs, and 50 NPs. Thus, there is a need for educational support to prepare APNs for the uniformed services. The GSN can usefully supplement other educational programs in meeting this need.

Education, Nursing↗
PubMed1994

Acute renal and urinary tract disease.

Patients with acute urinary tract disorders often present with acute abdominal symptoms. Sonography and CT are often the first investigations performed when the clinical nature of the symptoms is unclear. However, excretory urography and cystography, scintigraphy, and angiography all play useful roles in evaluating patients with acute urinary tract disorders. Patients with suspected acute renal obstruction due to ureteric calculi are best assessed by excretory urography. If the latter study is contraindicated, sonography with duplex Doppler analysis of small intra-renal arteries may suggest the diagnosis by showing a dilated collecting system and an elevated resistive index. Patients with acute renal trauma are best imaged by CT, although excretory urography is an appropriate alternative if a mild exclusively renal injury is suspected. Patients with refractory acute renal infections require imaging to identify either pyonephrosis or large renal or perinephric abscesses that require immediate intervention. CT and sonography are most useful for identifying these complications. Acute renal vascular disorders, including renal hemorrhage, renal infarction, and renal vein thrombosis are readily diagnosed by contrast-enhanced CT. Both sonography and MR imaging help in the diagnosis of acute renal vein thrombosis. Most acute bladder disorders are diagnosed clinically. Cystography, however, is essential for the diagnosis of traumatic bladder rupture. Pelvic CT is a useful alternative to cystography for diagnosing bladder rupture in patients who undergo CT as their first imaging study because of suspected head or abdominal injuries.

Abdomen, Acute↗
PubMed1993

Left ventricular outflow tract obstruction following repair of pneumococcal mitral annular abscess.

An unusual case of a mitral annular abscess caused by Streptococcus pneumoniae was diagnosed by transesophageal echocardiography. The patient underwent surgical resection of the abscess and developed outflow tract obstruction. This is an unusual complication of the surgical procedure. The outflow tract obstruction may have been due to anterior displacement of the mitral valve by the abscess.

Abscess↗
PubMed1992

Past pregnancy is associated with axillary node involvement in women with breast cancer.

In 186 women with breast cancer, there was a progressive increase in the proportion of axillary nodal involvement as the number of pregnancies increased from zero to two or more (P = 0.026). Logistic regression analysis demonstrated that this effect was independent of the known relationship of age and tumor size to nodal involvement. Race and history of breast feeding had no influence on nodal involvement.

Axilla↗
PubMed1992

Renal cell carcinoma in uremic acquired renal cystic disease: incidence, detection, and management.

Patients with end-stage kidney disease, particularly those treated with dialysis, have an increased risk of renal cell carcinoma. Renal cell carcinoma may also develop in the native kidneys of renal transplant recipients with good graft function many years after transplantation. Recent studies suggest that the incidence of renal carcinoma among dialysis patients is 3-6 times greater than in the general population. However, annual imaging of the native kidneys of all dialysis patients is not justified because it has not been shown to have a significant effect on patient outcome. Screening may, however, be useful in selected patients with good general medical conditions and who have known risk factors for renal carcinoma.

Carcinoma, Renal Cell↗
PubMed1992

Lymphangioma presenting as a small renal mass during childhood.

Renal lymphangioma is a very rare lesion. A case of lymphangioma that presented as a small, hyperechoic renal mass on sonography in a child is reported. On CT, the lesion appeared as a low-density, enhancing renal mass. Despite its rarity, lymphangioma should be considered in the differential diagnosis of such a lesion. A suspected lymphangioma may be evaluated by percutaneous biopsy.

Acute Disease↗
PubMed1992

Familial pheochromocytomas with unusual associations.

Pheochromocytoma occurs in a familial pattern in approximately 10% of patients. Although most familial pheochromocytomas are an expression of the genetic abnormality of neuroectodermal dysplasia or the genetic syndrome of multiple endocrine neoplasia, some familial pheochromocytomas occur without associated disease. Two patients with familial pheochromocytoma are described. One had an extraadrenal tumor, producing severe renal artery stenosis and in whose family pheochromocytomas were found in three successive generations. A second had multiple pheochromocytomas associated with von Hippel-Lindau disease and a family member with multiple endocrine neoplasia type 2. The combinations and permutations of these genetic entities form discrete syndromes, with other peculiar interrelationships, pathologically related to an aberration in the migration, growth, and differentiation of the neural crest cells, and emphasizing their common neuroectodermal origin. The unique features that characterize the familial pheochromocytomas and cause diagnostic and therapeutic challenges are reviewed.

Adrenal Gland Neoplasms↗
PubMed1992

Renal infarction associated with an extraadrenal pheochromocytoma.

A patient with an abdominal extraadrenal pheochromocytoma showed computed tomography findings of renal infarction. Selective angiography of the affected kidney showed no evidence of arterial occlusion or emboli. We postulate that the renal infarcts were caused by reversible severe vasospasm associated with high systemic blood levels of norepinephrine and angiotensin II.

Angiography↗
PubMed1992

Mutational analysis of gap junction formation.

The paired oocyte cell-cell channel assay was used to investigate the mechanisms involved in the process of formation of gap junction channels. Single oocytes, injected with connexin-specific mRNAs, accumulate a pool of precursors from which cell-cell channels can form rapidly upon pairing. Several lines of evidence, including immunohistochemistry and surface labeling, indicate that part of this precursor pool is located in the cell membrane, probably in the form of closed hemichannels. The homophilic binding of hemichannels to each other can be mimicked by synthetic peptides representing the extracellular loop sequences of connexin32. The peptides specifically suppress channel formation. A crucial role is established for the six cysteines in the extracellular domains that are conserved in all vertebrate gap junction proteins. Change of any of these cysteines into serines results in absolute loss of function of the mutant connexin. The effects of thiol-specific reagents on channel formation suggest that docking and/or opening of channels involves disulfide exchange. Several of the variable amino acids in the extracellular loop sequences were found to determine specificity of connexin-connexin interactions.

Amino Acid Sequence↗
PubMed1992

Calcified renal stones and cyst calcifications in autosomal dominant polycystic kidney disease: clinical and CT study in 84 patients.

Although renal calculi and cyst calcifications occur commonly in patients with autosomal dominant polycystic kidney disease (ADPKD), their true frequency is unknown because it is difficult to distinguish between the two with excretory urography and sonography. A detailed analysis of renal calcifications in ADPKD based on CT findings has not been performed. Accordingly, we retrospectively evaluated clinical and CT findings in 84 patients with ADPKD to determine the frequency of calculi and cyst calcifications, the relationship of these abnormalities to symptoms, and possible factors in their pathogenesis. Of the 84 patients, 53 had both IV contrast-enhanced and unenhanced CT scans and 31 had unenhanced scans only. We examined unenhanced CT scans of all 84 patients for renal calcifications. However, we classified renal calcifications into stones and cyst calcifications in only the 53 patients, because it is often difficult to distinguish between the two when only unenhanced scans are available. Of 84 patients, 18 (21%) had passed renal calculi or had stones treated surgically and 42 (50%) had renal calcifications on CT. Of the 53 patients who had both enhanced and unenhanced CT scans, 19 (36%) had renal calculi on CT. Patients with stones had significantly higher frequencies of previous flank pain (68% vs 35%) and of urinary tract infections (63% vs 18%) than did those without calculi. Cyst calcifications occurred in 13 (25%) of 53 patients and were probably a consequence of cyst hemorrhage. Cyst calcifications were found significantly more often in older patients with larger kidneys and worse renal function. We conclude that renal stones have a high rate of occurrence among patients with ADPKD and are a significant cause of morbidity in this disorder. Cyst calcification is also common in patients with ADPKD, particularly those with more advanced cystic disease.

Adolescent↗