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Biomedical subjects

J Steinberg

Publications and source records attributed to J Steinberg.

At least 91 records · Page 5Linked to original sources
PubMed1984

Mitoxantrone in malignant lymphoma.

Two phase II trials of mitoxantrone in refractory malignant lymphoma have been conducted. In the first of these, mitoxantrone (5 mg/m2) was given weekly for 6 weeks, and in the second, 14 mg/m2 was administered every 3 weeks. The first trial was conducted by the Southeastern Cancer Study Group (SECSG), and the second was a multicenter trial sponsored by Lederle Laboratories. Of the 80 patients entered in the SECSG trial, 47 could be evaluated for response and 43 for toxicity. Granulocyte nadirs below 1.9 X 10(9)/L were recorded in 18 patients. Four partial responses and no complete responses were obtained. These results contrast with those of the high dose study in which 41 patients were entered, and 28 of these were evaluated for response. Responses were obtained in 15 patients (2 complete, 13 partial). Side effects on this 3 weekly dose regimen were minimal. WBC nadirs ranged from 1 to 4.3 X 10(9) cells/L (mean 2.5 X 10(9)/L). Three patients experienced mild nausea and vomiting, and two had mild alopecia. These preliminary data indicate that mitoxantrone has significant activity in malignant lymphoma. All of the responding patients had received extensive prior therapy, many of them with anthracyclines in combination or as single agents. The higher response rate to mitoxantrone given at 14 mg/m2 every 3 weeks suggests that careful consideration should be given to dose when this drug is examined further in phase III trials.

Anthraquinones↗
PubMed1981

[Active evaluation].

Explore the source record for details and available documents.

Educational Measurement↗
PubMed1980

The detection of DNA-binding proteins by protein blotting.

A method, called "protein blotting," for the detection of DNA-binding proteins is described. Proteins are separated on an SDA-polyacrylamide gel. The gel is sandwiched between 2 nitrocellulose filters and the proteins allowed to diffuse out of the gel and onto the filters. The proteins are tightly bound to each filter, producing a replica of the original gel pattern. The replica is used to detect DNA-binding proteins, RNA-binding proteins or histone-binding proteins by incubation of the filter with [32P]DNA, [125I]RNA, or [125I] histone. Evidence is also presented that specific protein-DNA interactions may be detected by this technique; under appropriate conditions, the lac repressor binds only to DNA containing the lac operator. Strategies for the detection of specific protein-DNA interactions are discussed.

Carrier Proteins↗
PubMed1980

Dextran sulphate induced arthritis in rabbits.

Persistent effects of a short course of intra-articular dextran sulphate, dextrans, or chondroitin sulphate were examined in rabbit knees. Only dextran sulphate produced gross arthritis, associated with high synovial acid phosphatase and beta-glucuronidase activities. Synovial degradative capacity in synovium-cartilage cocultures was increased 2-fold by dextran sulphate and 1.5-fold by chondroitin sulphate treatments. Stimulation of cartilage breakdown in vitro paralleled the content of synovial marker enzyme at death of the animal, but the 2 responses could be dissociated.

Animals↗
PubMed1979

A tissue-culture model of cartilage breakdown in rheumatoid arthritis. Quantitative aspects of proteoglycan release.

1. The destruction of articular cartilage in human rheumatoid and other arthritides is the result of diverse mechanical, inflammatory and local cellular factors. A tissue-culture model for studying cartilage-synovial interactions that may be involved in the final common pathway of joint destruction is described. 2. Matrix breakdown was studied in vitro by using bovine nasal-cartilage discs cultivated in contact with synovium. Synovia were obtained from human and animal sources. Human tissue came from patients with ;classical' rheumatoid arthritis, and animal tissue from rabbits with antigen-induced arthritis. 3. Cartilage discs increased their proteoglycan content 2-3-fold during 8 days in culture. Proteoglycan was also released into culture medium, approx. 70% arising from cartilage breakdown. 4. Synovial explants from human rheumatoid and rabbit antigen-induced arthritis produced equivalent stimulation of proteoglycan release. After an initial lag phase, the breakdown rate rose abruptly to a maximum, resulting in a 2-fold increase of proteoglycan accumulation in culture medium after 8-10 days. 5. High-molecular-weight products shed into culture media were characterized chromatographically and by differential enzymic digestion. Proteoglycan-chondroitin sulphate accounted for 90% of the released polyanion, and its partial degradation in the presence of synovial explants was consistent with limited proteolytic cleavage. 6. Rheumatoid synovium applied to dead cartilage increased the basal rate of proteoglycan release. Living cartilage was capable of more extensive autolysis, even in the absence of synovium. However, optimal proteoglycan release required the interaction of living synovium with live cartilage. These findings support the view that a significant component of cartilage breakdown may be chondrocyte-mediated.

Animals↗
PubMed1979

A tissue culture model of cartilage breakdown in rheumatoid arthritis. III. Effects of antirheumatic drugs.

The effects of hydrocortisone, indomethacin, and gold thiomalate on proteoglycan release were assessed in bovine nasal cartilage-rheumatoid synovium cocultures. Of the three agents, only hydrocortisone consistently inhibited both basal and synovium-stimulated cartilage breakdown. Hydrocortisone responsivity was a direct function of the degradative capacity of synovial specimens, and this was equally well demonstrated both in patients receiving long-term therapy and those given perioperative glucocorticoid therapy. The data are consistent with significant hydrocortisone inhibition of lysosomal enzyme-mediated degradation of cartilage.

Arthritis, Rheumatoid↗
PubMed1979

The low ionic strength reaction of human blood: relationship between the binding of serum immunoglobulin and complement of red blood cells and surface charge of the cells.

Using the sucrose haemolysis reaction of Hartmann & Jenkins (1966) as a basic model, the low ionic strength reaction (LISR) of human blood was studied to determine: (1) serum Ig uptake by RBC with saline elution and 125I-IgG uptake, and (2) complement fixation (CF) to RBC with lysis of PNH cells and C3H/C4 antiglobulin haemagglutination (AH) of normal cells. The saline eluates were found to contain IgG and IgM with traces of IgA; their pH optima for the uptake by RBC were 6.0 +/- 0.5, 5.5 +/- 0.5 and c 5.0 respectively. The ratio of bound IgG to IgM was linearly related to the uptake pH. Both C4 AH and lysis were found to be optimum at pH 6.0--7.5, whereas the maximum C3 AH was at pH 6.0 +/- 0.5. The LISR performed at a constant pH (6.1 +/- 0.1) showed that an increasing concentration of neuraminidase (VCN) used in pretreatment of RBC was associated with a decrease in both IgG uptake and CF activity. A maximum VCN effect reduced the Ig uptake to c 20% of normal and abolished almost all the CF activity. An impaired LISR to various degrees was also observed with RBC pretreated with ficin, papain, bromelin, trypsin or protamine, and RBC from two individuals of En(a-) type. Preincubation of serum at LIS with and without RBC resulted in respectively a 'complete' and partial consumption of C in the fluid phase. The latter was not enhanced or inhibited by the addition of VCN-treated RBC for preincubation. A hypothesis is proposed suggesting that in the LSR the Ig uptake by RBC is an electrostatic interaction of the oppositely charged RBC and Ig and the CF to RBC results from C activation by the cell-bound IgG and IgM. In addition, a pH-dependent inactivation of the cell-bound C3 in the LISR is demonstrated.

Complement Fixation Tests↗
PubMed1979

C3d antiglobulin haemagglutination of human red blood cells. A demonstration of two types of cell-bound C3d by means of typsin digestion.

Washed human red blood cells from blood collected in EDTA were tested by Auto-Analyzer for a percentage of maximum antiglobulin haemagglutination (AH) using monospecific antisera to human C3d and C3c. The cells from normal persons were found to be agglutinated by anti-C3d but not by anti-C3c. To a fixed dilution of antiserum, the normal C3d AH values (X +/- 2 SD) were 34 +/- 19% for adult cells (n = 29) and 14 +/- 19% for cord cells (n = 19); the difference was significant (P less than 0.0001). By pretreatment of these cells with trypsin the C3d AH was either completely abolished or markedly reduced. Its difference between the adult and cord cells was eliminated as the observed values were 4 +/- 7% and 3 +/- 4% respectively (P = 0.15). The supernatant fluid of cell-trypsin mixture, treated with trypsin inhibitors, was found to be inhibitory to C3d AH but not to C3c AH. In contrast, the AH of C3d-coated red blood cells resulting from complement fixation in vivo (ie, cold agglutinin disease) or in vitro (eg, sucrose water reaction) was resistant to trypsin treatment. The difference between the trypsin-sensitive and trypsin-resistant cell-bound C3d is postulated to be at its attachment mechanism to the cell membranes. In addition, both the advantage and limitation of using trypsinised cells for C3d antiglobulin tests are demonstrated.

Adult↗
PubMed1978

Collagen turnover and the growth state in 3T6 fibroblast cultures.

The metabolic turnover of collagen in 3T6 fibroblast cultures was studied at various stages of growth by compartmental analysis of hydroxyproline content and of the conversion of radioactive proline to hydroxyproline. Quantitative and radioactive hydroxyproline measurements were directly parallel, although the latter method was more sensitive in demonstrating collagen synthesis in all phases of growth. Hydroxyproline formation as an index of collagen synthesis was abruptly accelerated at the time of confluence, and was well maintained at the new rate despite a gradual decline in the rate of general protein synthesis. Ethanol fractionation of growth medium proved superior to perchloric acid extraction in providing a pool of soluble hydroxyproline clearly derived from collagen degradation. Breakdown products were released at a constant rate per cell in all growth phases and accumulated to high levels in continuous culture. The fractional rate of collagen breakdown (percentage of hydroxyproline radioactivity) was highest in early logarithmic growth. Its gradual decline as cultures aged reflected the increased hydroxyproline content and improved stability of collagen under these conditions.

Cell Division↗
PubMed1974

Role of sarcoplasmic reticulum phospholipids in calcium ion binding activity.

The relationship between sarcoplasmic reticulum phospholipid and Ca(2+) binding by sarcoplasmic reticulum membranes was explored. Ca(2+) bound in the absence of ATP was defined as "ATP-independent Ca(2+) binding," and the additional amount of Ca(2+) bound in the presence of ATP was defined as "ATP-dependent Ca(2+) binding." The latter was found to be very sensitive to the loss of sarcoplasmic reticulum phospholipid; the amount of Ca(2+) bound was reduced when as little as 3% of the phospholipid was destroyed by phospholipase C. Further destruction of membrane phospholipid up to a 40% loss caused little or no further reduction of this Ca(2+) binding. However, when the destruction of phospholipid exceeded 40%, further loss of this Ca(2+) binding occurred, and there was an almost complete loss of this function when more than 60% of the sarcoplasmic reticulum phospholipid was destroyed.

Adenosine Triphosphate↗