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Biomedical subjects

A D Jacobs

Publications and source records attributed to A D Jacobs.

At least 19 recordsLinked to original sources

Staving off cynicism.

Explore the source record for details and available documents.

Attitude of Health Personnel↗

Pigmented subcutaneous spindle cell tumors in native gizzard shad (Dorosoma cepedianum).

An epizootic of pigmented subcutaneous spindle cell tumors affected nearly 25% of the adult gizzard shad (Dorosoma cepedianum) sampled from Lake of the Arbuckles in central Oklahoma over a 2 year period. Grossly, the tumors were primarily distributed over the head, trunk and fins as superficial raised masses that were almost always darkly pigmented. Histologically, they were located in the dermis, had a variable amount of connective tissue, and consisted of cells in a variety of forms and arrangements. Most tumors were composed of fusiform or spindle cells arranged in wavy bundles, whirling patterns or interwoven fascicles. Pigmentation was attributed to large dense deposits of melanin or to scattered individual melanin-containing cells. Immunohistochemical detection of proliferating cell nuclear antigen revealed a high proliferative activity in the spindle cells. Electron microscopy showed that the tumors were composed of several cell types, including host reactive cells, melanocytes in stages of maturity, and fibroblast-like cells. Tumor cells had neither cell-to-cell junctions nor an external lamina. Although the cell of origin of the tumors was not identified, evidence points toward melanocytes or, possibly, nerve sheath cells. However, an origin from fibroblasts or some other poorly differentiated cell cannot be ruled out. The etiology of the tumors was not determined. Fractionation of lake water and sediment samples followed by GC-MS analysis revealed no carcinogenic compounds. A retroviral etiology is unlikely because assays for reverse transcriptase in tumor homogenates were negative, and no evidence of viral particles was found in specimens examined by electron microscopy.

Animals↗

Efficacy of intensive chemotherapy for acute myelogenous leukemia associated with a preleukemic syndrome.

One hundred ninety-six patients with acute myelogenous leukemia (AML) were treated with intensive induction chemotherapy using similar daunorubicin/cytarabine/thioguanine regimens. Treatment results of 44 patients who had a documented preleukemic syndrome or cytopenia present for more than 2 months before developing over AML were compared with 152 patients with de novo AML. Eighteen (41%) patients with preleukemia evolving into AML achieved complete remission compared with 111 (73%) patients with de novo AML (P less than .01). Patients with preleukemia-AML had a significantly longer period to recovery of granulocytes. Multivariate analysis indicated that presence of a previous preleukemic syndrome and advancing age were independent poor prognostic indicators for achieving remission. For patients who achieved remission, disease-free survival and overall survival were also inferior for patients with previous preleukemia; disease-free survival was 17 +/- 17% at 3 years compared with 29 +/- 10% in patients with de novo AML (P = .02). These data indicate that intensive chemotherapy has limited efficacy in patients with AML following a preleukemic syndrome. Durable remissions may be achieved in some patients.

Age Factors↗

Evolving therapy of hairy cell leukemia.

The rationale for antileukemic therapy in hairy cell leukemia is to reduce the significant risk of infection and other potential serious complications. Corticosteroids have limited value; both corticosteroids and chemotherapy are associated with substantial risks of infection. The mainstay of therapy has been splenectomy. Improvement is seen in 50% to 70% of patients with cytopenias; although the impact of splenectomy on survival has not been clearly demonstrated, prolonged hematologic improvement can occur. Splenectomy presumably alleviates the pancytopenic effect of hypersplenism by removing the preferred site of leukemic cell proliferation. Human interferon represents a major advance in management. Favorable results with natural leukocyte alpha interferon have been confirmed by data with biosynthetic (recombinant) alpha interferon. Importantly, the incidence of infection has been clearly shown to decrease, suggesting improved survival in patients with advanced hairy cell leukemia. Many questions regarding interferon therapy remain unanswered, including optimal dose, optimal duration, and maintenance therapy after maximal response. The mechanism of action is unclear, but possibly interferon modulates as yet unidentified lymphokines or growth factors. In vitro evidence suggests a direct antiproliferative effect of type I interferon on hairy cells. Preliminary data suggest that although toxicity issues, including induction of immunodeficiency and renal insufficiency require further clarification, deoxycoformycin, an adenosine deaminase inhibitor, is also highly effective and holds substantial promise as an important therapeutic modality.

Adrenal Cortex Hormones↗

Induction of acute corneal allograft rejection by alpha-2 interferon.

A 38-year-old man who underwent corneal transplantation in 1973 for treatment of a keratoconus is described. In 1982, hairy cell leukemia was diagnosed and he was treated with splenectomy followed by chlorambucil and androgen therapy. In April 1984, treatment with alpha-2 interferon was begun, and two weeks later, evidence of acute corneal allograft rejection developed. The allograft rejection responded to temporary discontinuation of alpha-interferon and the administration of topical corticosteroid. Treatment with interferon was resumed, and he has subsequently had no clinical evidence of rejection. Although the mechanism of antineoplastic activity of alpha-interferon in hairy cell leukemia is unknown, the observations described in this report suggest that clinically important immune phenomena may occur in patients undergoing interferon therapy.

Adult↗

The UCLA experience with type I interferons in hairy cell leukemia.

Fifty-one patients have been entered on clinical trials of interferon in hairy cell leukemia. Hematological improvement was seen in 23 (96%) patients treated with recombinant alpha-2b-interferon, nine patients (69%) treated with lymphoblastoid alpha-N1-interferon, and, thus far, in five (71%) patients beginning therapy with recombinant beta-serine-interferon. All patients showing improvement have done so within 1 year and most within 6 months. Rapidity of response, duration of follow-up, and toxicity data are presented.

California↗

Pure red cell aplasia characterized by erythropoietic maturation arrest. Response to anti-thymocyte globulin.

Pure red cell aplasia is a syndrome characterized by markedly decreased erythropoiesis. On bone marrow examination, there are typically less than 0.5 percent erythroblasts, but sometimes a picture of maturation arrest can be seen. This report describes a patient with maturation arrest of erythropoiesis at the basophilic normoblast stage who had a response to an eight-day course of anti-thymocyte globulin with a return of normal erythropoiesis.

Adult↗

Bone marrow changes in patients with hairy cell leukemia treated by recombinant alpha 2-interferon.

Bone marrow specimens from 21 patients with hairy cell leukemia (HCL) who were entered into a program to study the efficacy of treatment with recombinant alpha 2-interferon were evaluated. Patients were treated with the interferon, 2 X 10(6) U/m2 subcutaneously three times weekly, and were scheduled to undergo bone marrow aspiration and biopsy at study entry and after three (21 patients) and six (16 patients) months of treatment. Bone marrow samples after three months of treatment showed an overall decline in cellularity, from an average of 77 +/- 20 to 57 +/- 22 per cent, with a marked decrease in the percentage of neoplastic mass (from 87 +/- 9 to 59 +/- 24 per cent). The bone marrow changes were associated with significant improvement in hematologic values, including hemoglobin levels and granulocyte and platelet counts. The bone marrow changes and improved hematologic values remained stable with continuation of interferon therapy. However complete bone marrow remission did not occur in any of the patients after three or six months of interferon therapy. The HCL cell mass in more than 60 per cent of the patients remained at or above 50 per cent of the marrow cellularity and dropped to less than 25 per cent in 14 per cent of the patients. In all of the patients increased amounts of reticulin fibers were identified in the bone marrow prior to therapy, and 89 per cent of bone marrow aspirations failed (dry tap). The amounts of reticulin fibers remained increased in most of the patients (91 per cent), with a high incidence of dry taps (73 per cent), after therapy. Interferon therapy also changed the tartrate-resistant acid phosphatase(TRAP)-positive HCL cells to TRAP-negative, suggesting inhibition of activity and/or production of TRAP in HCL cells.

Acid Phosphatase↗

Recombinant alpha-2-interferon for hairy cell leukemia.

Twenty-two patients with hairy cell leukemia were treated with biosynthetic (recombinant) alpha-2-interferon in an open-label, single-arm efficacy study. Patients received 2 X 10(6) U/m2 recombinant alpha-2-interferon three times weekly. Therapy was well tolerated subjectively with minimal short-term hematologic toxicity. Two patients had bacterial infections during the period of study, and one patient experienced a short-lived readily reversible rejection of a corneal transplant. Statistical comparison of the mean hematologic indices at study entry and after three to six months of therapy with recombinant alpha-2-interferon indicates a significant improvement in hemoglobin, granulocyte, and platelet counts. Bone marrow biopsies in six of 14 patients after six months of therapy showed a greater than 50% decrease in the infiltration of leukemia cells. We conclude that recombinant alpha-2-interferon is highly effective therapy for hairy cell leukemia.

Adult↗

Acute transformation of chronic lymphocytic leukemia.

A patient with chronic lymphocytic leukemia had typical cell morphology and a characteristic clinical course for 7 years. He then developed progressive disease with a rapidly rising WBC which proved resistant to chemotherapy. The cells resembled lymphoblasts. Immunoperoxidase studies demonstrated identical immunoglobulin light and heavy chains on the surface of both mature lymphocytes and lymphoblasts. Using a recently described monoclonal antibody, B5, a "blast" antigen was demonstrated on the lymphoblast cell surface, but not on the mature lymphocytes. On the basis of morphological and immunological studies, we suggest that the patient's malignant clone transformed from chronic lymphocytic leukemia to acute lymphoblastic leukemia.

Cell Transformation, Neoplastic↗

Acute myelogenous leukemia following radiation therapy and chemotherapy for osteogenic sarcoma.

Patients receiving ionizing radiation therapy or cytotoxic chemotherapy are at increased risk of developing acute myelogenous leukemia. Ten cases of therapy-linked myelogenous leukemia have been reported in patients with sarcoma, and we report here the first case in a patient who received combined-modality therapy for treatment of an osteogenic sarcoma. As treatment for this disease becomes more intensive and survival improves, the incidence of leukemia following therapy for osteogenic sarcoma may increase.

Adult↗