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Biomedical subjects

A Zander

Publications and source records attributed to A Zander.

At least 73 records · Page 4Linked to original sources
PubMed1991

Absent or rare human immunodeficiency virus infection of bone marrow stem/progenitor cells in vivo.

An important question in human immunodeficiency virus (HIV) pathogenesis is whether HIV-infected bone marrow CD34+ stem/progenitor cells serve as a significant reservoir of virus in HIV-infected individuals. Our data indicate that infection of bone marrow stem/progenitor cells with HIV occurs rarely, if ever, in vivo. In the present study, CD34+ cells were immunomagnetically purified from the bone marrow of HIV-seropositive individuals, and purified cells or colony-forming cells of the granulocyte/macrophage lineage were analyzed for HIV proviral DNA by the polymerase chain reaction. No HIV DNA was detected in colony-forming cells of the granulocyte/macrophage lineage from HIV-positive patients. Furthermore, no virus was found in CD34(+)-enriched cells from six of seven samples from asymptomatic HIV-infected individuals and four of four samples from patients with AIDS-related complex or AIDS. Thus, infected stem cells are not a major source of persistent HIV and do not account for hematopoietic suppression. These findings have positive implications for the concept of marrow reconstitution with autologous stem cells, genetically engineered for HIV resistance, following marrow-ablative antiviral therapy.

DNA, Viral↗
PubMed1987

Monosomy 21, partial duplication of chromosome 11, and structural abnormality of chromosome 1q21 in a case of lymphoma developing in a transplant recipient: characteristic abnormalities of secondary lymphoma?

Cytogenetic analysis by QFQ-banding of direct preparation of a testicular mass from a patient with secondary lymphoma revealed a modal chromosome number of 45,XY, including structural and numerical anomalies. The most consistent anomalies were the monosomy 21, duplication of the long arm of #11, and structural anomaly associated with chromosome #1 in band q21.

Adult↗
PubMed1986

High dose therapy and autologous marrow transplantation as salvage treatment for patients with diffuse large cell lymphoma.

Twenty-nine patients with diffuse large cell lymphoma who failed traditional chemotherapy were treated with high dose chemotherapy with or without total body irradiation followed by infusion of cryopreserved autologous marrow. Complete response was achieved in 11/29 patients (38%), partial response in 13/29 patients (45%) and 5/29 patients (17%) had no response. Six complete responders remain well and free of disease for 5+, 6+, 9+, 10+, 18+ and 25+ months, 3 relapsed at 2, 3 and 8 months after marrow infusion, and 2 died from infectious complications. Complete response was seen more frequently with the absence of bulky tumor (70 vs 21%, P = 0.03), a total body irradiation containing regimen (52 vs 0%, P = 0.03), a history of complete remission with initial chemotherapy (55% vs. 9%, P = 0.03), and a performance status greater than or equal to 80 (56 vs 15%, P = 0.06). High dose therapy had a high response rate (83%) in resistant diffuse large cell lymphoma and yielded durable complete responses in a minority of these patients.

Adolescent↗
PubMed1986

High-dose intensification therapy with autologous bone marrow support for limited small-cell bronchogenic carcinoma.

The efficacy and toxicity of high-dose chemotherapy with autologous bone marrow transplantation (ABMT) was studied in 32 patients with untreated limited small-cell bronchogenic carcinoma (SCBC). Ten patients received three courses of induction therapy consisting of vincristine (VCR) (1.5 mg X 2), ifosfamide (5 g/m2), and Adriamycin (Ad; Adria Laboratories, Columbus, Ohio) (60 mg/m2). Patients then received two courses of intensification therapy with cyclophosphamide (CYT) (4.5 g/m2), 4' demethyl-epipodophyllotoxin-d-D-ethylidene glucoside (VP-16-213) (600 mg/m2) and VCR (2 mg) with ABMT. Another 22 patients received induction therapy with VCR, CYT (600 mg/m2), Ad (50 mg/m2), and VP-16-213 (180 mg/m2). All 22 patients also received intensification therapy of the same dose of CYT (4.5 g/m2) and VP-16-213 (600 mg/m2). Nine patients also received high-dose methotrexate (MTX), four patients received Ad (40 to 60 mg/m2), and two patients received both Ad and MTX. After intensification, patients received elective prophylactic brain irradiation (3,000 rad) and chest irradiation (5,000 rad). After induction therapy, there were 13 (41%) complete remissions (CR) and 17 (53%) partial remissions (PR). After intensification therapy, there were 22 CRs (69%) and 10 PRs (31%). Median survival for all patients was 14 months (range, 5 to 59+). Of the 13 patients who received intensification therapy in CR, five remain disease free (DF), four for 4 years or longer. Of the nine patients to achieve CR with intensification, only one is DF. No patient died during intensification. In conclusion, intensification with high-dose chemotherapy can increase the CR rate, and this approach is most likely to show long-term benefits in patients with minimal disease (CR) at the beginning of intensification therapy.

Adult↗
PubMed1986

Potential drugs for elimination of acute lymphatic leukemia cells from autologous bone marrow.

Five drugs, selected because of minimal in vivo myelotoxicity, have been investigated for inhibition of the growth of three acute lymphatic leukemia-derived cell lines. Granulocyte-macrophage colony-forming units (GM-CFU) inhibition with these five drugs after 60-min incubation was first established. Drug concentrations giving up to 90% kill of GM-CFU were then used. Spirogermanium and L-asparaginase did not have an effect on any of the three cell lines under the culture conditions tested, while 4-hydroperoxycyclophosphamide (4-HC) and vincristine inhibited the growth of all three cell lines tested, and bleomycin inhibited the growth of two cell lines. In addition to 4-HC, bleomycin and vincristine should be considered as possible agents in eliminating leukemic cells from autologous marrow grafts. These drugs also deserve further investigation in clonal systems.

Antineoplastic Agents↗
PubMed1986

High-dose melphalan with autologous bone marrow transplantation for multiple myeloma.

A large dose of melphalan was given to 23 patients with advanced multiple myeloma that was refractory to multiple prior treatments. Sixteen patients received a dose of 80 to 100 mg/m2, and seven were given 140 mg/m2 followed by autologous bone marrow infusion. Tumor mass was reduced by more than 75% in 14 patients, including four who died of bone marrow aplasia. Serious infections were prevented in six of seven patients who received autologous bone marrow. The marked cytoreduction in patients with previously refractory disease indicated the apparent drug resistance could be overcome by dose escalation. However, short remission times in most responding patients were consistent with rapid regrowth of primordial tumor cells with high proliferative activity. Although high-dose melphalan was of limited benefit to patients with refractory myeloma, further studies are necessary to clarify its role during earlier phases of disease.

Adult↗
PubMed1985

Ag-NOR staining in human chromosomes: differential staining in normal and leukemic bone-marrow samples.

A silver staining technique developed by Goodpasture and Bloom (1975) stains a specific protein associated with the activity of ribosomal cistrons during the preceding interphase. By counting the number of chromosomes with darkly stained nucleolus organizer regions (NORs), the number of active NORs per metaphase can be determined. A comparison of NOR activity in bone-marrow cells from leukemic patients in different stages of disease with that of bone marrow from normal, healthy individuals was conducted and differential NOR activity was detected. The control group showed significantly lower NOR activity when compared with a group of patients with acute lymphocytic leukemia (ALL). These preliminary data indicate that this simple cytochemical technique can be effectively used to differentiate between normal and ALL bone-marrow samples.

Bone Marrow↗
PubMed1984

Mycobacterial pulmonary infections after allogeneic bone marrow transplantation.

Allogeneic bone marrow transplant recipients are prone to pulmonary infections caused by a wide spectrum of organisms. Nonetheless, the recognition of lung disease caused by Mycobacterium tuberculosis in two patients and Mycobacterium avium-intracellulare in a third patient at the University of Texas M. D. Anderson Hospital represents the first report of these agents occurring in allogeneic marrow recipients. Diagnosis can be difficult due to atypical presentations, initial negative culture results, and the presence of more than one pathogen in these compromised hosts. In the case involving Mycobacterium avium-intracellulare infection, culture of material obtained by bronchoscopy established the diagnosis when repeated sputum samples showed no growth. A vigorous search for mycobacteria is suggested in allogeneic bone marrow transplant recipients with pulmonary infections.

Adult↗
PubMed1984

Obstructive lung disease after allogeneic bone marrow transplantation.

We report the cases of 3 patients with marked dyspnea and an obstructive ventilation disorder associated with chronic graft-versus-host disease after allogeneic bone marrow transplantation. This disorder was characterized by recurrent pulmonary infections and colonization of the lower respiratory tract by Pseudomonas aeruginosa. Two patients have shown rapidly progressive deterioration with death following due to respiratory failure. Intensive therapy with antibiotics, bronchodilators, high-dose steroids, and azathioprine was not effective in arresting the malignant course of this disorder.

Adult↗
PubMed1983

High-dose chemotherapy and autologous bone marrow transplantation for the treatment of small cell lung carcinoma.

Fourteen patients with untreated small cell bronchogenic carcinoma were treated initially with 2 chemotherapy courses of cyclophosphamide (1.5 g/m2 days 1-3), 4-dimethyl epipodophylloxtin (200 mg/m2 days 1-3), vincristine (1.5 mg/m2 days 1 and 3), and with Adriamycin (80 mg/m2 day 1) in 8 patients and without Adriamycin in 6 patients. To modify hematopoietic toxicity from these high doses of chemotherapy, autologous marrow collected and frozen before storage was thawed and infused after each of these high-dose therapies. After this therapy patients received prophylactic brain irradiation (3000 rad), 4 courses of usual doses of these same drugs and then 5000 rad chest irradiation if there was still evidence of disease (PR) or randomized to radiation if in complete remission (CR). Response rate was high, with 54% CR and 46% PR, a total of 100%. However, a median response duration of 41 weeks and median survival of 56 weeks, are similar to other chemotherapy programs. Toxicity was mild except for cardiac arrhythmias when Adriamycin was included. The reasons for no therapeutic increment are discussed.

Aged↗
PubMed1982

Antibody-dependent cell-mediated cytotoxicity in human cancer: characterization of patient leukocyte activity and treatment effects.

Antibody-dependent cell-mediated cytotoxicity (ADCC), medicated by peripheral blood Hypaque-Ficoll separated mononuclear cells, was studied in humans using chicken erythrocytes (CRBC) incubated in a 1:1200 dilution of rabbit anti-CRBC and human B erythrocytes (HRBC) incubation in a 1:20 dilution of isoantibody. At the optimal target effector ratio of 3:1, ADCC to both CRBC and HRBC was significantly higher than normal in 27 lung cancer, 18 malignant melanoma, and seven colon cancer patients, but not in 20 breast cancer patients. Chemotherapy (single-agent or combination) in 12 patients did not effect ADCC in vitro but significantly suppressed ADCC to both targets after only four or five days of therapy in vivo (ADCC to CRBC, 47.4 to 24.1% lysis: ADCC to HRBC, 48.1 to 16.3% lysis). Immunotherapy with intravenous (IV) corynebacterium parvum or IV methanol extraction residue of BCG (MER) boosted ADCC to both targets within four to seven days of the first dose. It was found that ADCC to HRBC but not to CRBC was completely absent in three cases of active hairy cell leukemia but was present in two cases in remission. The ADCC to HRBC showed an age-dependent increase in both the 51 normal subject and the cancer patients. This was not observed for ADCC to CRBC. The ADCC to CRBC was mediated mainly by an Fc-receptor-positive, nonadherent, small lymphocyte, and ADCC to HRBC was mediated entirely by an adherent monocyte. The ADCC did not correlate significantly with the H3 thymidine incorporation of peripheral blood mononuclear cells, cultured without stimulation for either one or seven days. It also did not correlate with the number of residual granulocytes in the mononuclear cell suspensions. Measurement of ADCC is a useful method of characterizing host defense in malignant disease and its modification by therapy.

Age Factors↗