Epitope mapping of prostate-specific antigen with monoclonal antibodies

Prostate-specific antigen (PSA) is a widely used marker for screening and monitoring prostate cancer. We identified and characterized the epitopes of two anti-PSA monoclonal antibodies (mAbs) designated B80 and B87. The epitopes were initially mapped as nonoverlapping by developing a sandwich immunoassay to measure PSA with the two anti-PSA mAbs. The two antibodies do not cross-react with homologous pancreatic kallikrein, but recognize epitopes unique to PSA. B80 and B87 can recognize both free and complexed PSA and hence measure total PSA. Epitope scanning and bacteriophage peptide library affinity selection procedures were used to identify and locate an epitope on PSA. A possible epitope for B80 was identified as being located on or near PSA amino acid residues 50-58 (-GRH-SLFHP-). The epitope for B87 was likely on an exposed nonlinear conformational determinant, unique to PSA, and not masked by the binding of B80 or alpha 1-antichymotrypsin.     

The prevention and treatment of postoperative thrombosis of the deep veins of the lower extremities (II. Treatment)

Defining the most appropriate conditions for strengthening the retention of endothelial cells (ECs) by small-diameter prosthetic endothelialized grafts is indispensable to their clinical application. The incubation time after seeding is one of the most important factors in EC retention. The effects of different postincubation times (0, 2, 4, 8, 16, 24, and 36 hr) on EC monolayers on two different types of graft, fibronectin-coated expanded polytetrafluoroethylene (ePTFE) and collagen-coated knitted Dacron grafts (4 mm x 5 cm) were examined. In situ counting of ECs on the grafts was performed by light microscopy. The percentage cell retention was calculated by dividing the cell counts for grafts exposed to pulsatile flow for 90 min by those for control grafts. To characterize the EC coverage of the grafts, scanning electron microscopy was also performed. The average cell density of control grafts ranged from 5.59 +/- 1.1 to 6.69 +/- 1.5 x 10(4) cells/cm2 and did not differ according to the kind of graft or incubation time. The knitted Dacron grafts showed the maximal cell retention (88 +/- 5%) after incubation for 8 hr, whereas ePTFE grafts did so after 24 hr (83 +/- 6%). Scanning electron microscopic examination after incubation for 8 hr revealed that the density of human ECs on the surfaces of ePTFE and Dacron grafts differed, although there was no morphological difference between the ECs on the two types of graft. Knitted Dacron grafts achieved a high percentage retention in a shorter time than ePTFE grafts.     

Metastatic vertebral disease in children

We retrospectively reviewed 19 children with osseous vertebral metastases. The average age was 10.9 years at diagnosis of the primary tumor and 11.2 years at diagnosis of metastasis. The location of the multiple metastases was cervical (three), thoracic (14), and lumbar (10). Treatment consisted of chemotherapy (19), radiation therapy (12), and operation (seven). Ten children died at an average of 13 months after diagnosis of the primary tumor; nine are alive at an average of 72 months after diagnosis. All four children treated with chemotherapy, spinal radiation, and laminectomy, and who survived > 2 months, developed deformity. In this particular situation, we encourage consideration of spinal stabilization when it is appropriately coordinated with radiation and chemotherapy.     

Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer

CONTEXT: Interstitial radiation (implant) therapy is used to treat clinically localized adenocarcinoma of the prostate, but how it compares with other treatments is not known. OBJECTIVE: To estimate control of prostate-specific antigen (PSA) after radical prostatectomy (RP), external beam radiation (RT), or implant with or without neoadjuvant androgen deprivation therapy in patients with clinically localized prostate cancer. DESIGN: Retrospective cohort study of outcome data compared using Cox regression multivariable analyses. SETTING AND PATIENTS: A total of 1872 men treated between January 1989 and October 1997 with an RP (n = 888) or implant with or without neoadjuvant androgen deprivation therapy (n = 218) at the Hospital of the University of Pennsylvania, Philadelphia, or RT (n = 766) at the Joint Center for Radiation Therapy, Boston, Mass, were enrolled. MAIN OUTCOME MEASURE: Actuarial freedom from PSA failure (defined as PSA outcome). RESULTS: The relative risk (RR) of PSA failure in low-risk patients (stage T1c, T2a and PSA level < or =10 ng/mL and Gleason score < or =6) treated using RT, implant plus androgen deprivation therapy, or implant therapy was 1.1 (95% confidence interval [CI], 0.5-2.7), 0.5 (95% CI, 0.1-1.9), and 1.1 (95% CI, 0.3-3.6), respectively, compared with those patients treated with RP. The RRs of PSA failure in the intermediate-risk patients (stage T2b or Gleason score of 7 or PSA level >10 and < or =20 ng/mL) and high-risk patients (stage T2c or PSA level >20 ng/mL or Gleason score > or =8) treated with implant compared with RP were 3.1 (95% CI, 1.5-6.1) and 3.0 (95% CI, 1.8-5.0), respectively. The addition of androgen deprivation to implant therapy did not improve PSA outcome in high-risk patients but resulted in a PSA outcome that was not statistically different compared with the results obtained using RP or RT in intermediate-risk patients. These results were unchanged when patients were stratified using the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through 6 vs 7 vs 8 through 10. CONCLUSIONS: Low-risk patients had estimates of 5-year PSA outcome after treatment with RP, RT, or implant with or without neoadjuvant androgen deprivation that were not statistically different, whereas intermediate- and high-risk patients treated with RP or RT did better then those treated by implant. Prospective randomized trials are needed to verify these findings.     

Coupled B-snake grids and constrained thin-plate splines for analysis of 2-D tissue deformations from tagged MRI

Magnetic resonance imaging (MRI) is unique in its ability to noninvasively and selectively alter tissue magnetization and create tagged patterns within a deforming body such as the heart muscle. The resulting patterns define a time-varying curvilinear coordinate system on the tissue, which we track with coupled B-snake grids. B-spline bases provide local control of shape, compact representation, and parametric continuity. Efficient spline warps are proposed which warp an area in the plane such that two embedded snake grids obtained from two tagged frames are brought into registration, interpolating a dense displacement vector field. The reconstructed vector field adheres to the known displacement information at the intersections, forces corresponding snakes to be warped into one another, and for all other points in the plane, where no information is available, a C1 continuous vector field is interpolated. The implementation proposed in this paper improves on our previous variational-based implementation and generalizes warp methods to include biologically relevant contiguous open curves, in addition to standard landmark points. The methods are validated with a cardiac motion simulator, in addition to in-vivo tagging data sets.     

Measurement of sialyl transferase activity and serum glycoproteins in malignant and beningn (hyperparathyroid) hypercalcemia

Serum sialyl tranferase activity (STA) and protein bound carbohydrate were measured in hypercalcemic patients with surgically documented hyperparathyroidism (n = 15) or with cancer without skeletal metastases (n = 10). Precipitable protein-bound sialic acid and hexosamine, but not neutral hexoses or fucose were significantly (P less than 0.025) increased 40% and 21% respectively, in the perchlorate treated sera of cancer patients. Measurements of some specific serum glycoproteins by radial immunodiffusion assay were also different (P less than 0.05). Mean seromucoid protein was almost twice as great in the group with cancer (P less than 0.005), but four of these values overlapped those from the patients with hyperparathyroidism. The mean STA was 21.1 (range, 9.0-46.8) activity units in the patients with the cancer and 9.2 (range 1.0-17.8) in the patients with hyperparathyroidism (P less than 0.005). Six of the patients with cancer had values above the upper limit of the group with hyperparathyroidism. A discriminant function generated from these data correctly classified all the patients with hyperparathyroidism and 70% of those with cancer. Measurements of seromucoid and STA deserve further consideration as a way to discriminate some cases of hypercalcemia.