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Biomedical subjects

A D Ho

Publications and source records attributed to A D Ho.

At least 217 records · Page 12Linked to original sources
PubMed1987

Differentiation changes in cord blood T lymphocytes induced by synthetic C-terminal peptides of thymosin alpha 1.

Thymosin fraction 5 and its component thymosin alpha 1 has been reported to play a regulatory role in the later stages of T lymphocyte differentiation. Previous studies from our group have also demonstrated that thymosin fraction 5 can induce changes in purine degradative enzymes and in surface antigenic markers of cord blood lymphocytes, which have been shown to be immature compared with normal adult lymphocytes. Birr et al., have shown that the C-terminal region of thymosin alpha 1 is essential for the biological activity. In this study, the effects of these synthetic peptide fragments on cord blood T lymphocytes were studied. After incubation with different peptide sequences, cord blood lymphocytes were analysed for surface antigenic markers (OKT4/OKT8) and for purine degradative enzymes (PNP, 5 NT). In the range of 1.3 X 10 to 1.3 X 10(-5)M, one of the eleven peptides examined (sequence 13-19) exhibited activity approximately equal to that of the parent peptide thymosin alpha 1: increase in activity of 5'NT (p less than 0.01) and reduction of cells positive for OKT4 (p less than 0.01). Another sequence (20-28) was able to induce an increase in 5'NT only and a third one (20-25) a reduction of cells positive for OKT4. The results obtained in this study confirm that the C-terminal region contains molecular signals for T cell differentiation.

5'-Nucleotidase↗
PubMed1987

A prospective multicenter trial with human recombinant alpha 2c-interferon in hairy cell leukemia before and after splenectomy.

Our multicenter study on the treatment of hairy cell leukemia (HCL) started in December 1984 and the present data cover the time up to June 30, 1986. Ninety-seven patients were enrolled. For induction of response daily doses (6 micrograms) of low dose human recombinant alpha 2c-interferon (arg) was chosen. Further dose reduction (3 micrograms) was possible for patients who improved within the first 3-4 weeks. Patients with known risk factors started at lower doses (0.6 microgram daily). As infections are known to be the main cause of death in HCL, splenectomy was not mandatory before treatment. Thirty-nine patients received treatment with interferon. Nevertheless, infections remained the major cause of death in the study. The protocol did not prevent fatal infections in nine of the 34 splenectomized patients. The regimen proved safe for all but one of the nonsplenectomized patients. According to this experience, new criteria are needed for the choice of primary treatment in HCL. In our opinion splenectomy should become restricted to selected cases.

Antineoplastic Agents↗
PubMed1986

Enzymes of purine metabolism in hairy cell leukemia.

Differences in activities of the purine degradative enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'-nucleotidase (5'NT), have been observed among different classes of lymphoid malignancies. Recent studies have shown that hairy cell leukemia (HCL) may respond to treatment with the ADA inhibitor, 2-deoxycoformycin. This study demonstrates that the cells of HCL have significantly lower levels of ADA and 5'NT (P always less than 0.01) when compared to levels in normal B- or T-lymphocytes, but have higher levels of PNP (P less than 0.001 for both comparisons). Recent studies have shown that when treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), cells of B-cell chronic lymphatic leukemia (B-CLL) acquire phenotypic characters of HCL. The authors have therefore also investigated the changes in enzyme pattern of B-CLL after incubation with TPA B-CLL cells are characterized by low levels of ADA, PNP, and 5'-NT, but TPA caused a marked increase in PNP activity (P less than 0.001, t test for paired samples), a pattern similar to HCL. The results from biochemical studies are thus in accordance with the hypothesis that HCL cells are more mature than B-CLL cells. The special enzyme profile of HCL suggests that a PNP inhibitor might also be effective in the treatment of this disease.

5'-Nucleotidase↗
PubMed1986

[Results with the use of the M-2 protocol in plasmacytoma].

99 patients with multiple myeloma were treated over a period of 6 1/2 years; 62 of these were initially treated with vincristine, carmustine, cyclophosphamide, melphalan and prednisone: M 2-Protocol. Response to this therapy was assessed after three therapy cycles had been completed, which had been given at intervals of 5-6 weeks. In patients responding to the therapy, treatment was continued until a maximum regression of the paraproteins was achieved. By the end of May 1985, the data of 52 patients could be evaluated, in 31 (60%) of whom remission was observed. Median survival time of all patients was 27 months. In 18 patients with "complete" remission the median has not yet been reached after 40 months. In 13 patients with partial remission, the median survival time was 36 months. In patients with complete remission, the median remission period was 26.5 months, in patients with partial remission 13.9 months.

Adult↗
PubMed1986

Non-Hodgkin's lymphoma resembling polyposis coli. A case report.

In a 72-year-old patient with cervical non-Hodgkin's lymphoma, colonoscopy was performed in response to a positive result of a test for occult blood (Hemoccult). The examination revealed lesions throughout the whole of the colon, resembling polyposis coli. Histopathologic examination of the polypoid lesions disclosed an intermediate-grade non-Hodgkin's lymphoma (centrocytoma), which was identical to the histology of the cervical lymphoma. Regression of the lesions following chemotherapy, was observed by endoscopy and in the biopsy specimens. Clinical features and treatment of gastrointestinal lymphomas are discussed.

Aged↗
PubMed1986

Purine degradative enzymes and immunological phenotypes in chronic B-lymphocytic leukaemia: indications that leukaemic immunocytoma is a separate entity.

Investigations of the purine degradative enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and ecto-5'-nucleotidase (5'NT) have been shown to be of value in defining subsets of lymphoid malignancies. We have studied the activities of these enzymes in the circulating malignant cells of 35 patients with chronic B lymphocytic leukaemia and have correlated the biochemical data with immunological phenotypes. Classification of the cases into those without evidence of secretory activity ('true' CLL, 14 patients) and those with cytoplasmic immunoglobulin (CIg) ('immunocytoma'; 21 patients) revealed that immunocytomas are phenotypically and biochemically associated with more mature features. Malignant cells without CIg were characterized by low activities of ADA, PNP and 5'NT. In malignant cells with evidence of secretory activity (immunocytoma), low activity of ADA was also observed, but the activities of PNP and 5'NT were relatively high and approached the range of normal B lymphocytes. The differences in PNP (P less than 0.05) and in 5'NT (P less than 0.01) between these two groups were significant. Phenotypically the cells without CIg were predominantly associated with IgM (+k light chains) as surface membrane immunoglobulin (SmIg) whereas expression of IgG was more often observed in the leukaemic cells with CIg. No correlation between enzyme patterns and the stage of the disease was apparent. Thus both biochemical and immunological criteria show that cases of CLL vary within a range of maturity and that those with CIg might be more mature in the B cell axis. The present study emphasizes the value of purine enzyme studies in defining subsets of B cell neoplasia.

5'-Nucleotidase↗
PubMed1986

Mitoxantrone and VP-16 in refractory acute myelogenous leukemia.

Phase I/II-studies suggested that mitoxantrone is effective in the treatment of acute leukemia. In this study we have investigated its efficacy in combination with VP-16 in patients with refractory acute myelogenous leukemia. The regimen consists of: mitoxantrone 10 mg/m2/day i.v. from days 1 to 5, VP-16 100 mg/m2/day as short infusion from days 1 to 3. A dosis escalation of VP-16 was attempted. As of August 1985, 27 patients have been enrolled in the study and 21 patients are now evaluable. Of these 21 patients, 6 (28.6%) have achieved complete remission including 3 with primary refractory disease, 2 with early relapse (less than 6 months after CR), and 1 with relapse under maintenance therapy. Two other patients have attained a partial remission. Toxicity was mild and, except one case of early death, no life threatening complications were observed. This combination seems to be an active regimen in refractory acute myelogenous leukemia and its incorporation in front line therapy seems warranted.

Adolescent↗
PubMed1986

Autologous transplantation of blood-derived hemopoietic stem cells after myeloablative therapy in a patient with Burkitt's lymphoma.

A patient with Burkitt's lymphoma in complete remission received myeloablative consolidation treatment with superfractionated total body irradation (1,320 rad) and cyclophosphamide (200 mg/kg) followed by autologous transplantation of previously harvested and cryopreserved blood-derived hemopoietic stem cells. Seven successive leukaphereses were performed to yield a total of 55.2 X 10(9) mononuclear cells (MNC) comprising 15.1 X 10(6) CFU-GM or 4.34 X 10(6) CFU-GEMM. Following autologous blood stem cell transplantation (ABSCT), reconstitution of all cell lines occurred very rapidly, ie, 1,000 leucocytes per microL were reached after nine days, 500 granulocytes and 50,000 platelets per microL after ten days. B cells reached normal values around day 35 post-transplantation. CFU-GM first appeared in the circulating blood exhibiting an enormous overshoot. Some days later CFU-GM also appeared in the marrow. The kinetics and pattern of hemopoietic reconstitution after myeloablative treatment and ABSCT provide clear evidence that blood-derived hemopoietic stem cells are capable of completely restoring hemopoietic function in man. A possible reconstitutive advantage of blood over marrow-derived stem cells is discussed.

Adult↗
PubMed1986

Combination therapy with mitoxantrone and etoposide in refractory acute myelogenous leukemia.

We have investigated the efficacy of mitoxantrone in combination with etoposide in patients with refractory acute myelogenous leukemia. The regimen consisted of 10 mg/m2/day of mitoxantrone given iv on Days 1-5; and 100 mg/m2/day of etoposide as short infusion, initially on Days 1-3 and extended to Days 4 and 5 as appropriate. Of the 26 patients treated with this combination, nine (34.6%) have achieved complete remission and two have achieved partial remission. The median duration of continuous complete remission was 85 days (range, 21-183+). Toxicity was mild and only one case of early death was observed. This combination seems to be an active regimen in refractory acute myelogenous leukemia, and its incorporation in front-line therapy seems warranted.

Adult↗
PubMed1985

[Plasmacytomas without paraproteins].

Rare plasmocytomas without paraprotein (frequency less than 1%) can present a diagnostic trap. Three observations give grounds for drawing attention to misinterpretation of symptoms and the problematic nature of the diagnosis. In one patient, a monoclonal immunoglobulin (kappa light-chains) was detectable in the bone-marrow myeloma cells (non-excretory plasmacytoma). In a further patient no paraprotein could be found in the myeloma cells (non-secretory plasmacytoma) despite repeated investigations. An additional unusual feature in a third patient was the simultaneous presence of chronic lymphocytic leukaemia; his plasmocytoma was first detected at autopsy.

Adult↗
PubMed1985

[Long-term observations of Wegener's disease. Results of treating recurrences].

Four patients with Wegener's disease (three women; one man) were followed from three to eleven years. Patient 1 has been free of recurrence for 11 years, six of them without treatment. Patient 2 had a probable recurrence after seven years, six of them without treatment. Patient 3 had a recurrence after 11 years (ten without treatment) requiring renewed treatment, with good response. Patient 4 (male) has required continued treatment with cyclophosphamide and prednisone for the last three years.

Adult↗
PubMed1985

Mitoxantrone in the treatment of relapsed and refractory acute leukemia.

Twenty-four patients with acute leukemia or blast crisis (BC) of chronic myelocytic leukemia (CML) in relapse or refractory to standard chemotherapy, were eligible for treatment with mitoxantrone. Mitoxantrone (Novantrone; dihydroxyanthracenedione) was administered in a dose of 8-13 mg/m2 on five consecutive days. Five of 20 evaluable patients were induced into complete remission, one patient achieved a partial remission. Side-effects included moderate to severe bone marrow suppression, moderate mucositis and hair loss. No cardiotoxicity was observed. We believe that mitoxantrone is an active agent in the treatment of acute leukemia and suggest further studies in combination chemotherapy.

Acute Disease↗
PubMed1985

Respiratory distress as primary symptom of relapse in a patient with non-Hodgkin lymphoma.

A report on a 74-year old woman with high-grade malignant non-Hodgkin lymphoma in clinical remission, who suddenly developed episodes of severe dyspnea and wheezing. Clinical and roentgenographic investigations including tomography of the trachea failed to demonstrate any lesion. Fiberoptic bronchoscopy revealed and endotracheal, polyp-like lymphoma 3 cm above the carina, which was immediately operated. Other sites of relapse (submandibular lymph-nodes) were found 2 weeks after the operation. Second-line chemotherapy (IMVP 16) was able to induce a second remission.

Aged↗
PubMed1985

Treatment of acute myeloid leukemia developing after a myelodysplastic phase with low dose arabinosyl cytosine.

Patients with acute myeloid leukemia (AML) secondary to myelodysplastic phase respond poorly to standard chemotherapy designed for AML. As arabinosyl cytosine (Ara-C) at low-dose has been reported to achieve promising results in certain forms of AML, we have applied the low-dose (10 mg m-2/12 h subcutaneously for 14-24 days) regimen in 11 patients with AML secondary to myelodysplastic syndromes. Though a complete remission could be achieved in 2 patients and a short partial remission in 2 further patients, complications are severe and often life threatening. The amount of hematological supportive care required often exceeded that needed for patients treated by conventional TAD regimen. Moreover, survival of the responders did not seem to be longer than that of non-responders. A review of the literature showed that the results of this low-dose Ara-C regimen might be more promising in patients in the myelodysplastic phase and in those with de novo acute leukemia.

Aged↗
PubMed1985

Terminal differentiation of cord blood lymphocytes induced by thymosin fraction 5 and thymosin alpha 1.

Cord blood lymphocytes (CBL) have been shown to be functionally immature compared with normal circulating adult lymphocytes (NAL). Differentiation of T cells is associated with changes in surface antigenic markers and in the pattern of purine degradative enzymes. Previous studies have demonstrated that thymosin fraction 5 (TMS-F5) and thymosin alpha 1 (TMS-alpha 1) can induce in vitro differentiation of murine T-cell precursors and human thymocytes. We have investigated the effects of TMS-F5 and TMS-alpha 1 on the pattern of the purine degradative enzymes adenosine deaminase, purine nucleoside phosphorylase, and ecto-5'-nucleotidase (5'NT) of CBL and on the phenotypic markers from the OKT series 3, 4, 8 and 11. Other than a significantly reduced level of 5'NT activity (P less than 0.001) and an elevated percentage of OKT4+ cells (P less than 0.01), CBL demonstrated the same immunological and biochemical patterns as NAL. Incubation of CBL with TMS-F5 (150 micrograms/ml) and TMS-alpha 1 (1 microgram/ml) for 40 h caused a significant rise in 5'NT level and decrease of cells positive for OKT4, resulting in a pattern characteristic of NAL. Thus TMS-F5 might induce the terminal differentiation of CBL, and TMS-alpha 1 seemed to be the active component.

5'-Nucleotidase↗
PubMed1985

Mitoxantrone in the treatment of relapsed and refractory acute leukemia.

Twenty-four patients with acute leukemia and blast crisis of chronic myelocytic leukemia in relapse or refractory to standard chemotherapy were eligible for treatment with mitoxantrone. Mitoxantrone was administered in a dose of 8-13 mg/m2 on five consecutive days. 5 of 20 evaluable patients were induced into complete remission, 1 patient achieved a partial remission. Side effects included moderate to severe bone marrow suppression, moderate mucositis and hair loss. No cardiotoxicity was observed. We believe that mitoxantrone is an active agent in the treatment of acute leukemia and suggest further studies in combination chemotherapy.

Acute Disease↗