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Biomedical subjects

T Ebert

Publications and source records attributed to T Ebert.

12 recordsLinked to original sources

Monoclonal antibody Due ABC 3 directed against transitional cell carcinoma. I. Production, specificity analysis, and preliminary characterization of the antigen.

The development of the hybridoma technology allows the identification of tumor associated antigens with monoclonal antibodies (mAbs). Employing this technology mAb Due ABC 3 was obtained by immunization of a BALB/c mouse with bladder tumor cell line SW 1710 and subsequent cell fusion of spleen cells with P3. X63.Ag8.653 mouse myeloma cells. MAb Due ABC 3, an IgM antibody, was found to recognize an antigen present in the membrane of tumor cells in 25 out of 28 (89%) transitional cell carcinoma specimens but rarely (three out of 25 specimens, 12%) on normal urothelial cells. Cross reactions were seen with proximal tubular epithelium of the kidney and seven out of 12 renal cell carcinomas examined. Furthermore, the antigen was expressed by granulocytes, some gastrointestinal epithelia, ovarian and breast carcinoma. The antigen recognized by mAb Due ABC 3 was stable to fixation with formaldehyde and paraffin emmbedding, different proteases, alkaline treatment and heat exposure up to 70C. Antigenicity was abandoned by incubation with periodate but not with neuraminidase treatment. The antigen could be extracted with chloroform/methanol suggesting the involvement of a glycolipid. Immuno-thin layer chromatography revealed a single lipid band reacting with mAb Due ABC 3 but not with anti-CD15, directed against the Lewis X antigen. Although not tumor-specific, mAbs directed against differentiation antigens may be of value for the investigation of cell transformations as well as for diagnostic use.

Animals

Assessment of clinical skills of residents utilizing standardized patients. A follow-up study and recommendations for application.

OBJECTIVE: To determine the reliability and validity of "standardized patients" to assess clinical performance of internal medicine residents. DESIGN: Each resident spent 2 half-days interacting with 19 standardized patients (nonphysicians taught to portray patients in a reproducible fashion). Each resident was asked to obtain focused histories, perform relevant physical examinations, and provide patient education or counseling. At the end of each 10- to 15-minute encounter, the resident was asked to identify positive findings on physical examination and to prioritize a differential diagnosis. Other, more traditional indicators of clinical skills were also obtained. PARTICIPANTS: Three hundred ten residents from nineteen internal medicine training programs in the New England region of the United States. RESULTS: Reproducible estimates of data gathering and interviewing skills were achieved with 1 day of testing. Validity analyses were difficult to interpret because of the lack of an external "gold standard." However, faculty judgments of performance from reviewing videotapes corresponded with standardized-patient-based scores. Differences in group performance were also demonstrated across years of training and between U.S. or Canadian and foreign medical graduates. CONCLUSIONS: Systematic and effective procedures for developing standardized-patient-based test materials and for training standardized patients have been developed. This technique is best used for measuring data gathering and interviewing skills. Correlations with commonly used evaluation methods were generally low; this may be because standardized patients measure different skills. Local use of this technique by residency programs and the development of regional consortia sharing resources, costs, and expertise are advocated.

Clinical Competence

Monoclonal antibody Due ABC 3 directed against transitional cell carcinoma. II. Prospective trial on the diagnostic value of immunocytology using monoclonal antibody Due ABC 3.

Recently, the development of monoclonal antibody Due ABC 3 directed against transitional cell carcinoma has been reported. With this monoclonal antibody an in vitro test system for diagnosis and followup of patients with transitional cell carcinoma has been developed. The clinical value of this assay, designated as quantitative immunocytology, was evaluated in a prospective trial and compared to conventional cytology. We investigated 74 voided urine specimens obtained from patients with histologically proved transitional cell carcinoma and 60 specimens from donors without clinical evidence of transitional cell carcinoma. Sensitivity was 66% versus 47% for immunocytology and conventional cytology. Specificity of conventional cytology (92%) was higher compared to immunocytology (58%). Statistical analysis demonstrated a significantly higher sensitivity of the combined analysis of conventional cytology and immunocytology (p less than 0.001) compared to conventional cytology alone, without significant differences in specificity. The results obtained with immunocytology were impaired by the great number of nonevaluable specimens. Poor preservation of cells, severe pyuria or an insufficient number of urothelial cells prevented evaluation in 25% of the cases, while only 6% could not be evaluated by conventional cytology. The ability of immunocytology to improve the sensitivity of conventional cytology makes this technique a promising adjunct to the noninvasive diagnosis of transitional cell carcinoma.

Antibodies, Monoclonal

Accuracy of imaging modalities in staging the local extent of prostate cancer.

In this study, none of the evaluated clinical staging methods was found to predict reliably the presence or absence of extracapsular growth of histologically proved carcinoma of the prostate. In this respect, digital rectal examination, transrectal ultrasound, CT, and MR imaging cannot contribute to treatment decisions in localized prostate cancer. Further studies are under way to determine the value of 7.5-MHz scanners in transrectal ultrasound and high-resolution surface coils in MR imaging.

Biopsy

Establishment and characterization of human renal cancer and normal kidney cell lines.

We have reviewed our laboratory's efforts to establish continuous human renal cancer cell lines. During the 16-year period of 1972 through 1987, 498 successive attempts resulted in establishment of 63 renal cancer cell lines. Of these lines, 46 were derived from primary kidney tumors and 17 from metastatic sites (lung, brain, bone, and lymph node). Forty-three of these lines have been characterized with regard to morphology, growth kinetics, anchorage-independent growth, tumorigenicity in athymic nude mice, and expression of kidney cell surface antigens. These results were compared with data from primary short term cultures of normal kidney epithelium. The overall success rate of establishing continuous renal cancer cell lines was 12.7%. In general, no significant difference in success was noted based on whether the specimen was derived from a primary or a metastatic lesion. However, all successfully established lines were derived from tumors exhibiting clinically "aggressive" behavior. All cell lines expressed proximal tubular cell differentiation antigens. Significant morphological heterogeneity was observed among normal kidney as well as kidney cancer cell lines in vitro. No significant difference in doubling time was found between cell lines of renal cancer and passage 1 cultures of normal kidney epithelium. Twenty-one of 30 (70%) lines assayed formed clones on soft agar and 26 of 33 (79%) lines grew in athymic mice. Among the 25 lines which were assayed for both soft agar growth and tumorigenicity in nude mice, this pair of phenotypic traits were concordant in 17 lines (60%). Four lines (16%) grew on agar but not in mice, while four other lines (16%) failed to grow in agar but were tumorigenic in mice.

Animals

Immunodiagnosis of renal cell carcinoma.

Development of immunoassays for the diagnosis of RCC offers significant promise of improved clinical treatment of this disease. While this promise remains to be fulfilled, there is reason to believe that advances will soon be forthcoming. MABs have defined numerous kidney-associated antigens. In at least one instance (ADAbp), an immunoassay has already been established that aids in the diagnosis of benign renal diseases. A similar approach may also be useful in renal cancer. Likewise, in at least one instance a previously undefined peptide (the HHM factor) has been closed and sequenced. Synthesis of this peptide and production of antibodies to it cannot be far off. Measurement of this peptide and/or of the many other aberrantly produced peptides associated with this cancer may be anticipated to improve substantially our ability to diagnose early and, therefore, cure renal cancer.

Antibodies, Monoclonal

[Biological markers in renal cell carcinoma].

The development of immunoassays for the diagnosis of renal cancer promises significant improvements in clinical treatment. Monoclonal antibodies have defined numerous kidney-associated antigens. In at least one instance (ADAbp), an immunoassay has already been established that is helpful in the diagnosis of benign renal diseases. A similar approach may also be useful in renal cancer. Similarly, in at least one instance a previously undefined peptide (HHM factor) has been cloned and sequenced. Synthesis of this peptide and the production of antibodies to it is imminent. The possibility of measuring this peptide and/or the many other aberrantly produced peptides associated with this cancer would presumably mean a substantial improvement in early diagnosis and therefore cure rates in renal cancer. The final role of chromosome changes in the diagnosis and determination of prognosis cannot yet be defined.

Biomarkers, Tumor

The conservative treatment of osteonecrosis of the femoral head. A comparison of core decompression and pulsing electromagnetic fields.

Once roentgenographic changes are apparent, osteonecrosis of the femoral head in the adult generally progresses to osteoarthritis within two to three years. A variety of conservative surgical procedures have been devised to conserve the femoral head with varying success. This study examines the effectiveness of pulsing electromagnetic fields and core decompression in the treatment of osteonecrosis of the femoral head. Both techniques reduce the incidence of clinical and roentgenographic progression. Exposure to pulsing electromagnetic fields appears to be more effective in hips with Ficat II lesions than in hips with more advanced lesions.

Adult

[Complications and late sequelae following radical cystectomy and supravesicle urinary diversion].

Until recently radical cystectomy combined with urinary diversion was only justified by most urologists as a therapeutic measure for the management of bladder cancer, when other forms of treatment failed controlling the disease. This attitude was mainly based on a high morbidity and mortality rate of up to 20% of the cases. Improved selection of the patients, progress in improving preoperatively the physical conditions of the patients, intra- and post-operative intensive care and improvement of the surgical technique have contributed considerably to reduce the risks of this procedure. Effective preparation of the small and large bowel, early anticoagulation and digitalis medication as well as an efficient antibiotic treatment starting intraoperatively, and optimal parenteral hyperalimentation are of particular importance. Adjuvant preoperative radiation therapy and a simultaneously performed pelvic lymph node dissection do not contribute to an increased morbidity or mortality rate. Taking into account all available preventive measures, the mortality rate of about 20% 20 years ago has been reduced to about 1-5% at present.

Follow-Up Studies