W C Waltzer

Sheba Medical Center, Gan, Tel Aviv, Israel

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Publications (100)179.02 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The presence of tumor infiltrating lymphocytes (TIL) has been attributed to the host cell mediated immune response against the evolving malignancy. However, due to specific evasive and escape mechanisms, the immune competent cells are rendered ineffective. One such mechanism may be the production of immune suppressor substance(s), inhibiting lymphocyte proliferation, and subsequently, their transformation into effector cells. To evaluate a possible impact of RCC extract on lectin and alloantigen-induced proliferation of TIL and peripheral blood lymphocytes (PBL) from renal cell carcinoma (RCC) patients and from healthy control human subjects. Tumor extract and TIL were derived from 13 patients with RCC undergoing radical nephrectomy. Tumor infiltrating lymphocytes and PBL from these patients were activated with Concanavalin A (Con-A), Phytohemoglutinine (PHA) or Pokeweed (PW) and the rate of blastogenesis was measured by (3)H Thymidine incorporation. The same procedure was used in assay with PBL from control healthy blood donors. There was a significant reduction (88.6%) in the proliferative response to ConA of TIL compared to PBL from the same patients (P = 0.007). A similar decrease was seen following stimulation by PHA (85.8%, P = 0.01) and PW mitogen (78.5%, P = 0.001). A 79.5% decrease in response level of TIL to alloantigens compared to PBL from RCC patients (P = 0.021), was observed. Lectin induced proliferative response of RCC patients was significantly lower in the presence of RCC extract (82.9%) compared to normal kidney extract (P = 0.008). Alloantigenic stimulation of healthy individual PBL was also decreased significantly in the presence of RCC extract (92.9%, P = 0.0001) compared to normal kidney extract. Similarly, lectin induced stimulation of healthy control PBL in the presence of RCC extract was significantly lower (83.2%, P = 0.003). Our data suggest that RCC extract contains an immune suppressive substance(s), capable of inhibiting lymphocyte proliferative response of tumor infiltrating lymphocytes as well as of PBL from patients and healthy individuals alike. This may be one of the mechanisms by which the tumor evades the transformation of lymphocytes into effector killer cells, and thus affects the biological inter-relationship between tumor and host. Identification of this substance and its gene may provide an effective anti-tumoral treatment modality.
    Urologic Oncology 01/2003; 21(1):27-32. · 3.36 Impact Factor
  • Transplantation Proceedings 01/2003; 34(8):3180-2. · 0.95 Impact Factor
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    ABSTRACT: As manifested by the presence of immune competent cells, failure to control the progression of renal cell carcinoma by a local immune response attests to impaired local cell mediated immunity. To test this hypothesis we compared the expression of T-cell activation markers in renal cell carcinoma infiltrating lymphocytes with the expression of activation markers of peripheral blood lymphocytes in the same patients. Tumor infiltrating lymphocytes were harvested from a patient with renal cell carcinoma undergoing radical nephrectomy. Peripheral blood was obtained before surgery. Tumor infiltrating and peripheral blood lymphocytes were incubated with monoclonal antibodies defining specific differentiation and activation markers on the cell surface, and analyzed by flow cytometry. Cell subsets are expressed as a fraction of the total number of mononuclear cells. The T-cell subset level was significantly higher in peripheral blood than in renal cell carcinoma tissue of the same patient. However, the level of activated T-cell subset expressing HLA-DR was significantly higher in renal cell carcinoma tissue than in peripheral blood. The levels of interleukin-2 receptor and transferrin receptors expressing T-cell subsets were also significantly higher in carcinoma tissue than in peripheral blood. Natural killer cells were found in significantly higher proportions in renal cell carcinoma than in peripheral blood. These results point to significant activation of T, B and natural killer tumor infiltrating lymphocytes. The inability of tumor infiltrating lymphocytes to mount an effective immune response to renal cell carcinoma may be secondary to the presence of suppressive factors in the tumor that prevent tumor infiltrating lymphocytes from transforming into effector cells. These factors may be particularly valuable for the further study of renal cell carcinoma-host interactivity.
    The Journal of Urology 12/2002; 168(5):2216-9. · 3.75 Impact Factor
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    ABSTRACT: Acute rejection is associated with the activation of helper and cytotoxic cells. A shifting balance between the suppressor/inducer CD45+ CD4+ and T helper/inducer (CD4+CD45-) cells may be responsible for the transition from quiescence to overt rejection. We examined the kinetics of CD45 expression on CD4+ T cells in renal allograft recipients from pretransplant values to acute rejection and after reversal of rejection, searching for a shift in balance between helper/inducer and suppressor/inducer cell subsets. Using two color flow cytometry, the peripheral blood levels of CD4+, CD4+CD45- [T helper/inducer (Thi)], CD4+CD45+ [T suppressor/inducer (Tsi)], CD3+, and CD8+ T cells subsets and their interrelationships, were determined in 49 patients prior to transplantation, and in 10 of them, during acute rejection and after its reversal. Results were analyzed and compared to data obtained from 10 healthy blood donors. Acute rejection was associated with a significant decline in CD45+ CD4+ expression compared to quiescent phase (22% +/- 3.7% vs. 26.5% +/- 3.2%, p = 0.05) and controls (29.5% +/- 6.2%, p = 0.01). No difference was observed compared to pretransplant levels (19.9% +/- 3.2%, p = ns). CD45-/CD45+ (Thi/Tsi) ratio was lowest during quiescence (0.75) compared to rejection (0.97, p = 0.05), in controls (0.98, p = 0.05) and pretransplant values (1.4, p = 0.01). Acute rejection was characterized by higher Thi/CD8+ and lower Tsi/CD8+ ratio (103 and 88 respectively, p = 0.045), compared to clinical quiescence (104 and 116 respectively, p = 0.039). These data suggest that acute rejection is associated with down regulation of CD4+CD45+ suppressor/inducer subset. This shift may account for the transition from quiescence to overt rejection, concurring with reports on CD4+CD45 regulatory function.
    International Urology and Nephrology 11/2002; 34(4):555-8. · 1.29 Impact Factor
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    ABSTRACT: Tumor infiltrating lymphocytes (TIL) in colorectal cancer are a manifestation of local, cell mediated immune response to the malignant tumor. Tumor progression is due to impairment of the host ability to control tumor growth. Several studies suggested possible causes for such impairment, however, the precise factor(s) underlying such malfunction is uncertain. To compare the possible effects of colorectal cancer (CRC) and normal colonic mucosa extracts on lectin induced blastogenesis of the same patients' peripheral blood lymphocytes (PBL) proliferation. CRC and normal mucosa extracts were obtained from 3 patients undergoing curative surgery for colon adenocarcinoma. Proliferation assays used PBL from the CRC patients, incubated with Concanavalin A (ConA) and Phytohemoglobin (PHA) in the presence of CRC or normal mucosa extract and in medium alone. Proliferation was measured by H3 Thymidine incorporation following 48 hours on incubation. Exposure of ConA induced PBL proliferation assay to CRC extract yielded a 98.7% inhibition measured by counts/minute (cpm) of incorporated H3 Thymidine compared to normal colonic mucosa extract (1,214 +/- 594 cpm vs. 95,335 +/- 6,997 cpm respectively, p = 0.0018). PHA stimulated proliferation exposed to CRC extract showed a 99.7% decrease in blastogenic activity compared to normal mucosa extract (362 +/- 175 cpm vs. 62,375 +/- 16,591 cpm respectively, p = 0.0234). These preliminary results suggest that CRC extract contain factor(s) capable of profoundly inhibiting lectin induced proliferation of PBL. Shedding of suppressor substances may be one of the possible mechanisms by which the tumor evades the effector arm of the cell-mediated immune response. Characterization of such factors may aid in intratumor, local and systemic cellular immune response reconstitution.
    Harefuah 11/2002; 141(10):862-4, 932.
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    ABSTRACT: Mucormycosis is a rare opportunistic infection that complicates chronic debilitating diseases and immunosuppressed solid-organ transplant recipients. We present a case of life-threatening pulmonary mucormycosis in a diabetic renal allograft recipient who survived with reasonable renal function. Early recognition of this entity and prompt use of bronchoalveolar lavage (BAL) are critical to the outcome. Antifungal therapy combined with early surgical excision of infected, necrotic tissue appears to be the preferred course of action. Judicious withholding of immunosuppressants until fungemia cleared did not jeopardize allograft function.
    American Journal of Kidney Diseases 01/2002; 38(6):E37. · 5.76 Impact Factor
  • K Malinowski, H Ye, W C Waltzer
    Transplantation Proceedings 07/2000; 32(4):773-5. · 0.95 Impact Factor
  • Transplantation Proceedings 02/1997; 29(1-2):839-41. · 0.95 Impact Factor
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    ABSTRACT: Cases of immunoglobulin A heavy chain and kappa light chain deposition disease are rare and their clinical presentations vary. We report one patient with histopathologic and clinical findings of a microangiopathic glomerulonephritis due to immunoglobulin A-kappa deposition. Ultrastructural studies revealed highly ordered deposits in the capillary lumen, mesangium, and basement membrane. The disease recurred at 2.5 years after a cadaveric kidney transplantation. Pulse steroid therapy was repeatedly effective in retarding further progression of renal deterioration in this patient.
    American Journal of Kidney Diseases 02/1995; 25(1):75-8. · 5.76 Impact Factor
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    ABSTRACT: With the appropriate combined use of different immune monitoring techniques, it is possible to derive sensitive diagnostic parameters for the transplant surgeon. However, the core biopsy or cytological examination of the graft continues to represent the gold standard for evaluating the specificity and sensitivity of these methods. With the development of newer monoclonal antibodies and a better understanding of the impact of immune processes on the behavior of various activation linked, T cell associated surface antigens, one may be able to secure further valuable information, with enhanced diagnostic and prognostic accuracy.
    The Journal of Urology 11/1994; 152(4):1070-6. · 3.75 Impact Factor
  • W C Waltzer
    Seminars in urology 06/1994; 12(2):84-8.
  • Transplantation Proceedings 05/1994; 26(2):936-7. · 0.95 Impact Factor
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    ABSTRACT: The dialysis population has grown rapidly in the past decade, as a consequence of government support for catastrophic illness and broadening of the indications for patient selection. Progress in the management of patients on hemodialysis has resulted in a steady increase in the number of surviving long-term patients with end stage renal disease. As a result, this population includes large numbers of older subjects, as well as individuals with systemic diseases, in whom establishment and maintenance of adequate vascular access is particularly difficult. The success of vascular access in the elderly patients depends upon proper selection of the type and location of the A-V fistula, and upon prompt and aggressive management of any developing complications. While experience with transplantation in elderly patients has significantly improved in recent years, careful evaluation of the elderly potential allograft recipient may improve patient and graft survival, by identifying those patients in whom the risk involved may be prohibitive. In addition, growing knowledge and judicious use of immunosuppressive medications have further improved the outcome following transplantation. In the absence of any obvious contraindications, transplantation is a safe, effective treatment modality for end-stage renal disease in elderly patients.
    Geriatric Nephrology and Urology 02/1994; 4(1).
  • Transplantation Proceedings 01/1994; 25(6):3320-4. · 0.95 Impact Factor
  • Transplantation Proceedings 01/1994; 25(6):3328-33. · 0.95 Impact Factor
  • S T Jao, W C Waltzer, F Miller, F T Rapaport
    Transplantation Proceedings 05/1993; 25(2):2133-5. · 0.95 Impact Factor
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    ABSTRACT: This study compares the cellular events in excised rejected renal allografts (RKT), with concurrent data in the peripheral blood (PB) in the same patients. The kidney transplants were obtained from recipients after rejections crises that were refractory to treatment. Two-color flow cytometry data was used for quantitation of cell subset profiles and quantitation of the density of individual lymphocyte surface antigen(s). The level of CD3DR-positive T cells in RKT was significantly higher than in PB. This difference ranged from 3 to 19-fold increases. There was an even more pronounced increase in CD8CD57 cell subset levels in RKT versus PB. In parallel with these findings, there was a 15-fold greater mean density of the CD8CD57 markers on T cells in RKT, when compared with the same cells in PB. The density of CD8 and of DR markers on CD3+ cells was also significantly higher (4-fold in each instance) in RKT. These data point to a homing of CD8CD57 cells with corresponding increases in the density of these markers in acutely rejected renal allografts, with only a relative decrease of this cell subset in peripheral blood. The appearance of a high preponderance of CD8CD57 cells in the renal allograft at the time of a rejection crisis may constitute a particularly severe prognostic sign regarding the reversibility of the response after treatment with steroids and/or monoclonal antibodies.
    Transplantation 01/1993; 54(6):1013-7. · 3.78 Impact Factor
  • Transplantation Proceedings 05/1992; 24(2):755-6. · 0.95 Impact Factor
  • Transplantation Proceedings 05/1992; 24(2):752-4. · 0.95 Impact Factor
  • Transplantation Proceedings 09/1991; 23(4):2301-3. · 0.95 Impact Factor

Publication Stats

263 Citations
179.02 Total Impact Points


  • 2003
    • Sheba Medical Center
      Gan, Tel Aviv, Israel
  • 1983–2003
    • Stony Brook University
      • • Department of Urology
      • • Department of Surgery
      • • Department of Medicine
      • • Health Sciences Center
      Stony Brook, NY, United States
  • 1987–2002
    • State University of New York
      New York City, New York, United States
    • Kitasato University
      Edo, Tōkyō, Japan