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Biomedical subjects

M Cline

Publications and source records attributed to M Cline.

26 records · Page 2Linked to original sources
PubMed1985

Human alpha-lymphoblastoid interferon. A phase I study including pharmacokinetics and effects on hematologic stem cells (CFU-GMs).

Human alpha lymphoblastoid interferon (Wellferon) was administered to 33 patients in a phase I study. Patients received Wellferon intramuscularly every 12 hours for 14 doses in nine dosage levels ranging from 0.75 X 10(6) units to 50.0 X 10(6) units. Toxicity tended to be dose dependent and included fever/chills, malaise, hematologic toxicity, and digestive tract toxicity. Thirty X 10(6) u q 12 h was felt to be the maximum tolerated dose. Three partial responses (renal cell carcinoma, diffuse histiocytic lymphoma, Hodgkin's disease) were achieved. Interferon rapidly (2 to 3 hours after the initial injection) reached peak serum levels which varied generally with dose and exceeded 500 u/ml at the 30 and 50 X 10(6) u dosages. Multiple doses of interferon resulted in cumulative peak levels substantially higher than first dose levels (greater than 500 u/ml at dosages greater than 3 X 10(6) u/ml and greater than 1,500 u/ml at dosages greater than or equal to 18 X 10(6) u). Interferon given at high dosages persisted up to 10 days beyond the final injection. Despite hematologic toxicity, inhibition of CFU-GM was not seen.

Dose-Response Relationship, Drug↗
PubMed1983

Comparison of Naegleria fowleri and Naegleria gruberi cultivated in the same nutrient medium.

The human pathogenic amoeboflagellate Naegleria fowleri and the nonpathogenic species N. gruberi can be cultivated axenically but usually in different media. Naegleria fowleri 6088 has been adapted to grow in Balamuth H-4 medium, usually used to propagate N. gruberi nB81, and nB81 has been adapted to grow in supplemented Nelson's medium, usually used to propagate N. fowleri. N. gruberi nB81, grown in either medium, enflagellated 135 to 150 min after subculture to non-nutrient amoeba saline, whereas 6088 required 225 min. Naegleria gruberi nB81 grown in either medium was agglutinated by 100 micrograms concanavalin A/ml, whereas N. fowleri 6088 was not. Naegleria fowleri and N. gruberi grown in Nelson's medium became rounded to a greater extent upon chilling at 5 degrees C and remained rounded longer than Naegleria grown in Balamuth medium. The specificity of the surface antigens was an inherent characteristic of each species and not dependent upon the propagating medium, but Naegleria grown in Nelson's medium was agglutinated more reproducibly and more effectively by antiserum. N. gruberi was somewhat more resistant to acriflavine, actinomycin D, cycloheximide, or tetracycline than N. fowleri, regardless of the culture medium. Naegleria fowleri 6088 grown in Nelson's medium, however, was more resistant to actinomycin D, daunomycin, mithramycin, sulfamethoxazole, or tyrocidine than 6088 grown in Balamuth medium. There are limitations on the validity of comparisons of N. fowleri and N. gruberi based upon cultures grown in different media.

Agglutination Tests↗
PubMed1981

In vitro analysis of the contributions of adherent cell layer and recharging population to hemopoietic cell proliferation in long-term bone marrow cultures.

Cell proliferation in long-term suspension cultures of mouse bone marrow was studied. Bone marrow cells were maintained on irradiated or conventional non-irradiated semiallogeneic adherent feeder layers and the origin of the proliferating cells was investigated by using the unique T6 chromosome marker. In cultures containing irradiated feeder layers total cell numbers were less at the first week after "recharging," but the levels soon reached those of conventional non-irradiated cultures. At the first weeks after recharging, proliferating cells, maintained on conventional non-irradiated feeder layers, originated mainly from the adherent layer. The contribution of the recharging population to the proliferating cell population increased with time. In contrast, the proliferating cells grown on irradiated adherent layers originated mainly from recharging population from the first week after recharging. The origin of the nonadherent CFUs and their development in F1 hybrid mice and mice of syngeneic strains was also examined. The pluripotent stem cells grown on non-irradiated feeder layers were derived mainly from the adherent layer.

Animals↗
PubMed1981

Prevention of graft rejection following bone marrow transplantation.

Bone marrow transplantation from an HLA-identical sibling is increasingly used in the treatment of severe aplastic anemia. One major problem with this approach is graft rejection that occurs in 25%-60% of patients conditioned for transplantation with cyclophosphamide. At most transplant centers it has been difficult to accurately identify patients at high risk for graft rejection. We studied a conditioning regimen of cyclophosphamide (200 mg per kg) and low-dose total body irradiation (3 Gy; equivalent to 300 rad) in 23 consecutive unselected patients with aplastic anemia followed for a minimum of 6 mo. There was only one episode of graft rejection. Graft-versus-host disease and interstitial pneumonitis were not increased by the more intensive conditioning regimen. Actuarial survival was 61% at 1 yr and 49% at 2.5 yr. Cyclophosphamide and low-dose total body irradiation is an effective conditioning regimen in patients with aplastic anemia. It may be particularly useful when accurate predictive tests of graft rejection are not available as is the case in most transplant centers.

Actuarial Analysis↗
PubMed1979

Human myeloid precursors forming colonies in diffusion chambers expresses the Ia-like antigen.

Normal human bone marrow contains cells capable of forming myeloid colonies (CFU-DG) in fibrin clots in diffusion chambers placed in the peritoneal cavity of cyclophosphamide-treated mice. Evidence has accumulated indicating that these colony-forming cells represent an earlier stem cell than the granulocyte-monocyte precursor cell (CFU-C) assayed in soft agar. We provide data showing that these stem cells express the "Ia-like" or DR antigen. In the presence of rabbit Ia antiserum at a titer of 1:300, all CFU-DG were inhibited. Cytotoxicity was complement-dependent. Data are also presented that suggest that the megakaryocyte stem cell also expresses the Ia antigen.

Absorption↗
PubMed1978

Acute lymphocytic leukemia-associated cell membrane antigen.

Antisera were raised in New Zealand White rabbits against non-B, non-T acute lymphocytic leukemia (ALL) cells coated with antilymphocyte serum. Following minimal absorption with chronic lymphocytic leukemia (CLL) cells, the antiserum reacted mainly with non-B, non-T ALL cells. The following numbers of patients had leukemia cells that reacted with the ALL antisera: 13 of 18 with ALL, 3 of 27 with acute myelocytic leukemia, 1 of 8 with chronic myelocytic leukemia (CML), and 0 of 12 with CLL. The positive CML was a patient in CML blast crisis. Normal peripheral blood B- and T-lymphocytes and normal bone marrow were negative. Reactions of the anti-ALL serum (136K) were compared with the reactions of a rabbit anti-B-cell antiserum (63K) that reacted with approximately 70% of leukemia cells. Cultured lymphoblastoid cell lines from normal donors were negative by both cytotoxicity and immunofluorescence tests. However, by immunofluorescence testing, 8 of 17 known malignant lines from a variety of lymphoproliferative disorders were positive; 4 of these lines were of T-cell origin. By immunoprecipitation and polyacrylamide gel electrophoresis, the ALL antigen appeared to consist of a single polypeptide chain of approximately 98,000 daltons. The anti-ALL antiserum was not cytotoxic for normal myeloid stem cells (colony-forming units).

Adult↗
PubMedDate not supplied

Effect of progestin on the ovarian epithelium of macaques: cancer prevention through apoptosis?

OBJECTIVE: The apoptosis pathway is a vital mechanism in vivo that functions to eradicate genetically damaged cells prone to malignancy. The purpose of this study was to determine whether oral contraceptives, which confer significant protection against subsequent epithelial ovarian cancer, induce apoptosis in the ovarian epithelium. METHODS: Female cynomolgus macaques (N = 75) were randomized to receive a diet for 35 months containing either no hormones, the oral contraceptive Triphasil (Wyeth-Ayerst Laboratories, Philadelphia, PA), the estrogenic component of Triphasil (ethinyl estradiol) alone, or the progestin component of Triphasil (levonorgestrel) alone, each administered in a cyclic fashion. At study termination, the animals underwent ovariectomy and the ovarian epithelium was examined morphologically and immunohistochemically for apoptosis. The percentage of ovarian epithelial cells undergoing apoptosis was measured in each animal and compared between the treatment groups. RESULTS: The median percentage of ovarian epithelial cells undergoing apoptosis by treatment was control (3.8%), ethinyl estradiol (1.8%), Triphasil (14.5%), and levonorgestrel (24.9%). Compared with control and ethinyl estradiol-treated monkeys, a statistically significant increase in the proportion of apoptotic cells was noted in the ovarian epithelium of monkeys treated with the oral contraceptive Triphasil (P < or = .01) or levonorgestrel (P < .001), with a maximal effect (six-fold) seen in the group treated with levonorgestrel alone. CONCLUSION: Oral contraceptive progestin induces apoptosis in the ovarian epithelium. Given the importance of the apoptosis pathway for cancer prevention, an effective chemopreventive strategy may be possible using progestins or other agents that selectively induce apoptosis in the ovarian epithelium to prevent the development of ovarian cancer.

Animals↗