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Biomedical subjects

P Nathan

Publications and source records attributed to P Nathan.

At least 37 records · Page 2Linked to original sources
PubMed1987

Anti-proliferative effects of interferons on Daudi Burkitt lymphoma cells: induction of cell differentiation and loss of response to autocrine growth factors.

Treatment of Daudi B-lymphoblastoid cells with low concentrations of either natural or recombinant human alpha-interferons inhibits cell proliferation and modulates the expression of a number of cell-surface antigens. Using a panel of monoclonal antibodies (MAbs) identifying determinants expressed at the surface of normal plasma cells, and polyclonal antibodies against surface and cytoplasmic immunoglobulin, we have found that growth inhibition is accompanied by plasmacytoid differentiation. Assays of growth stimulation of heterologous cells indicate that the culture medium from interferon-treated Daudi cells contains substantially more B-cell growth factor activity than that from control cells. However, the interferon-treated cells exhibit an impaired ability to respond to both these autocrine factors and exogenous factors produced by another Burkitt lymphoma line. These findings show that, in the case of Daudi cells, growth inhibition by interferons is closely associated with both terminal differentiation and a refractoriness to growth factors. In this system IFN-alpha may therefore be considered to be a B-cell differentiation factor, suggesting a possible basis for the anti-proliferative effects observed with certain human B-cell malignancies.

Antibodies, Monoclonal↗
PubMed1987

A monoclonal antibody recognizes a human nuclear protein resembling Xenopus oocyte nucleoplasmin.

The monoclonal antibody 10BG2 (IgG3) was derived from a mouse immunized with human pre B cells. In immunofluorescence studies the antibody revealed a human nuclear-associated determinant, which in interphase cells was entirely restricted to the nucleus. In metaphase cells 10BG2 antigen was detected throughout the cytoplasm with intensified staining at the periphery of chromosomes. 10BG2 antibody stained all human normal and transformed cells tested. In contrast, the antibody did not stain mouse 3T3 cells or Chinese hamster ovary (CHO) cells. Electrophoresis under denaturing and non-denaturing conditions revealed the 10BG2 antigen to be a 130 X 10(3) to 140 X 10(3) Mr protein with a subunit molecular weight of 29.5 X 10(3). This suggests the protein is at least a tetramer. On two-dimensional gels the 10BG2 antigen had a streaked appearance and separated into two isoelectric variants (pI5.2, 5.4). The protein was also shown to be phosphorylated and thermostable, and remained in solution at pH 3.6. 10BG2 antigen was highly soluble in aqueous buffers and co-migrated on non-denaturing gels with the nucleosome-assembly protein, nucleoplasmin, purified from Xenopus oocytes. The similarity of 10BG2 antigen to nucleoplasmin is discussed.

Animals↗
PubMed1986

Differential localization of membrane receptor chemotaxis proteins in the Caulobacter predivisional cell.

The methyl-accepting chemotaxis proteins (MCPs) are membrane receptors that initiate signal transduction to the flagellar rotor upon ligand binding. The synthesis of these proteins occurs only in the Caulobacter crescentus predivisional cell coincident with the biosynthesis of the polar flagellum. Both the flagellum and the MCPs are partitioned to only one daughter cell, the swarmer cell, upon division. We report the results of experiments designed to determine the distribution of these MCPs within swarmer cells and predivisional cells. Flagellated and non-flagellated vesicles were prepared from these cells by immunoaffinity chromatography and the level of MCPs that had been labeled either in vivo or in vitro with methyl-3H was determined. Small membrane vesicles from swarmer cells contained [methyl-3H]MCPs both in the flagellated and non-flagellated vesicles, which indicates that the region immediately surrounding the flagellum, as well as the rest of the surface of the swarmer cell, contains [methyl-3H]MCP. Thus, the MCPs are not specifically localized to the immediate vicinity of the flagellar rotor. The distribution of MCPs was examined in flagellated and non-flagellated vesicles isolated from predivisional cells. The analysis of small predivisional vesicles showed that the MCP content is higher in the flagellated vesicles, and analysis of large flagellated vesicles showed that the MCPs are positioned preferentially in the swarmer cell portion of the predivisional cell. This positional bias of MCPs within predivisional cells could reflect either a large compartment or membrane domain within the incipient swarmer cell, or a gradient of MCPs, with the highest concentration in the vicinity of the flagellum.

Autoradiography↗
PubMed1986

Autocrine growth of human B lymphocytes: maintained response to autostimulatory factors is the special feature of immortalization by Epstein-Barr virus--a hypothesis.

The autocrine growth profile of human B lymphocytes transformed with Epstein-Barr virus (EBV) was found to comprise three distinct components: a B-cell growth factor (BCGF); an interleukin-1 (IL-1)-like activity; an activity requiring cell-to-cell contact for its action. Observations on the inhibition of the EBV-carrying Daudi lymphoma line by alpha-interferon indicated that loss of response to these autostimulatory factors was underlying growth cessation. Furthermore, a putative receptor for BCGF was found to be down-regulated on B cells stimulated with non-transforming mitogens but constitutively expressed following EBV-transformation. Taken together with recent evidence that normal B cells produce autostimulatory factors, these findings suggest that the special feature of autocrine growth by EBV-immortalized cells is a maintenance of what should normally be a transient phenotype, possibly through deregulation of receptor expression. This hypothesis is discussed.

B-Lymphocytes↗
PubMed1986

An evaluation of Aquaphor Gauze dressing in burned children.

Aquaphor Gauze was evaluated as a dressing for skin graft donor sites, for partial thickness burn injuries and for split thickness skin grafts. Control dressings consisted of: fine mesh gauze for skin graft donor sites. silver sulphadiazine (Silvadene) on coarse mesh gauze for the partial thickness burns, and nitrofurazone cream (Furacin) on fine mesh gauze for the skin grafts. The Aquaphor Gauze was found to be inferior to the fine mesh gauze for donor site dressings. No statistically significant difference was identified between Aquaphor Gauze and controls for the treatment of partial thickness burns. As a dressing for skin grafts the Aquaphor Gauze was significantly superior to the control dressing as measured by graft take and reduced patient pain. We would recommend that Aquaphor Gauze be used as a dressing for skin grafts where the risk of infection is not excessive.

Adolescent↗
PubMed1985

Drug-loaded synthetic dressings: effect on contraction, epithelialization, and collagen synthesis of deep second-degree experimental burns.

The effect of drug-loaded synthetic dressings on the contraction, epithelialization, and collagen synthesis of deep second-degree burns was followed for 21 days in 44 guinea pigs. Two symmetrical burns were inflicted on the back of each animal; the animals were then divided at random into the following test groups: Group 1 (n = 10), a prefabricated, precut, pliable, and noncracking dressing designated as Dimac (DM), versus Dimac plus 2% silver sulfadiazine (DM+); Group 2 (n = 10), Hydron loaded with 2% silver sulfadiazine (HAgS) one versus fine mesh gauze and 1% silver-sulfadiazine cream (GAgS); Group 3 (n = 12), Hydron (Hyd) versus fine mesh gauze (G); Group 4 (n = 4), fine mesh gauze versus Telfa (Tel); Group 5 (n = 6), Telfa versus Telfa; Group 6 (n = 2), gauze versus gauze. Epithelialization and contraction rates were measured at dressing changes on postburn days 6, 12, 18, and 21, with a computerized sonic digitizer. Collagen biosynthesis was measured from the wound scar on PBD 21 and expressed as relative collagen biosynthesis. Contraction on PBDs 18 to 21 was significantly lower (p less than 0.05) in the DM and DM+ treated burns. Epithelialization of the DM and DM+ treated groups on PBD 21 was significantly (p less than 0.05) higher than in the Hyd, HAgS, GAgS, and Tel treated burns, and did not differ from the G treated wounds. The relative collagen biosynthesis method was inapplicable to this burn wound model.

Animals↗
PubMed1984

Treatment for children of volatile psychotic adults in the adult psychiatric setting.

The authors describe a unique program for the treatment of troubled children of adult psychiatric patients at a Veterans Administration hospital. The location of this program within the adult setting greatly facilitated the successful treatment of these children. The program can also be a valuable addition to the treatment of adult patients, especially patients who are chronically ill and emotionally volatile and have been particularly difficult to treat.

Adult↗
PubMed1983

The microclimate chamber: the effect of continuous topical administration of 96% oxygen and 75% relative humidity on the healing rate of experimental deep burns.

The healing rate of small experimental burns continuously treated topically with 96% O2 and 75% relative humidity was followed for 25 days. Serial image photographic magnifications (tenfold throughout) of the wounds enabled precise measurements of their size by means of a polar planimeter. Healing rate was expressed as decreased percentile of wound size on a given day compared to the initial area. The mean percentages of healing +/- SEM of the humidified O2 treated wounds on postburn days 6, 11, and 16 were 31.25 +/- 6.15, 82.09 +/- 3.52, and 98.29 +/- 1.46, respectively, and those for the control wounds were 7.08 +/- 2.20, 47.68 +/- 3.39, and 84.41 +/- 1.38, respectively. Analysis of variance revealed highly significant differences in the healing rate between O2-humidity-treated and control wounds (p less than 0.005). The results indicate that topical treatment with 96% O2 and 75% relative humidity improved healing of experimental burns in guinea pigs.

Administration, Topical↗
PubMed1982

A silicone-nylon laminated dressing (IP-758) for closure of excised or débrided burn wounds.

A synthetic dressing (IP-758) consisting of a silicone membrane with a laminated layer of nylon fabric was evaluated in patients as a substitute for biological materials to cover excised areas of burn wounds. During a 3-day interval, the tissue developed a tightly adherent bond to the synthetic dressing. The IP-758 conformed to irregularly-shaped regions and stretched with the movements of the wound surface. Seventeen burned children from 3 to 12 years of age and 1 adult are included in this study. In 12 cases, the mean area covered with the synthetic ranged from approximately 39 to 118 cm2. The average dressing remained in place for 3 days and was replaced once. Microbiological sampling (wet swab technique) of the area under the IP-758 after application of second dressing was compared with open control sites treated with topical antibiotics. The results with Staphylococcus aureus, a frequent contaminant, were similar for the two test areas. The IP-758 site in 6 patients contained an average of 10 3 S. aureus per swab test. Immediately following removal of the adherent IP-758 and control of local bleeding, the wounds in most patients provided excellent sites for autografts. The IP-758 dressing is well-tolerated, elastic and adherent to the burn wound permitting maturation of the wound to readily accept autografts.

Adult↗
PubMed1982

A clinical study of antimicrobial agents delivered to burn wounds from a drug-loaded synthetic dressing.

This report is of an investigation of the release of antimicrobial agents from a solid barrier dressing when applied to second- and third-degree burn wounds. The synthetic dressings were formed by a mixture of polyethylene glycol-400 (PEG), poly-2-hydroxethyl methacrylate (PHEMA) and one of the test drugs: silver sulfadiazine (AgSD), gentamicin, silver nitrate, or nitrofurazone. The dressings were formed directly on the burn wounds of 33 patients from a paste prepared from a mixture of PEG-PHEMA and drug. These dressings remained in place for 3 days, covering 12 to 64 square inches of the wound. In six patients, the entire burn wounds were covered with the dressings in which the treated areas were each about 200 square inches. The use of drug-loaded synthetic dressings extended to cover major portions of the burn wounds reduced the work required for nursing care and lessened patient discomfort.

Adolescent↗
PubMed1982

Circular organization of the DNA synthetic pathway in Caulobacter crescentus.

Genetic analysis of the cell cycle of Caulobacter crescentus has identified a DNA synthetic pathway and a cell division pathway (M. A. Osley and A. Newton, J. Mol. Biol. 138:109-128, 1980). The results presented here show that in double-shift experiments the function of the PC2076 gene product, which is required for the initiation of DNA synthesis, depends on completion of a late stage of chromosome replication in the previous cell cycle. These findings suggest a circular organization of steps in the DNA synthetic pathway in C. crescentus.

Bacteria↗
PubMed1982

Release of estradiol from fetal bovine serum by rat thymus, spleen, kidney, lung and lung macrophage cultures.

High levels of estradiol (E2) were detected by radioimmunoassay (RIA) in supernatants of rat thymus and spleen, kidney, lung and lung macrophages cultured in the presence of fetal bovine serum(FBS). A competitive inhibitor of E2 synthesis and no effect on the production of E2 by thymic cultures. Acid hydrolysis of estrogen conjugates in FBS released enough free E2 to account for the high level found in culture supernatants. Removal of free estrogens and estrogen conjugates by charcoal stripping the serum before addition to media of rat tissues by hydrolysis of estrogen conjugates in FBS.

Androstatrienes↗
PubMed1981

Localized and systemic hypersensitivity reactions to human seminal fluid.

Reaginic humoral antibodies to human seminal plasma were present in two women with systemic reactions. In one patient, IgE antibodies were demonstrated by direct skin tests, leukocyte histamine release, passive transfer to a nonallergic human recipient, the radioallergosorbent test, inhibition of the radioallergosorbent test and neutralization of passive transfer antibodies. A similar mechanism was established in the other case by direct skin tests and antigen-induced leukocyte histamine release. Sephadex G-100 fraction 2, derived from human seminal plasma, showed greater reaginic activity than other chromatographic fractions. Two other patients with histories of localized reactions did not develop humoral antibodies but did evince cell-mediated immunity to seminal fluid antigens. One patient with localized reactions also had significant titers of IgM and IgG sperm agglutinating antibodies to seminal plasma. Both reaginic and cell-mediated sensitization to human sperm extract were also observed in this series of patients. Histocompatibility leukocyte antigen (HLA) typing of all patients and their sexual partners showed a marked degree of shared histocompatibility focus antigens in members of each of two couples.

Female↗
PubMed1981

Control of experimental burn wound infections: comparative delivery of the antimicrobial agent (silver sulfadiazine) either from a cream base or from a solid synthetic dressing.

This report demonstrates prolonged effective release of silver sulfadiazine (AgSD) to experimental burns in rats from a solid dressing by mixtures of polyethylene glycol-400 and poly-2-hydroxyethyl methacrylate. The synthetic dressing, incorporating the antimicrobial drug, may be formed either directly on the burn wound or prepared as a preformed sheet and applied to the wound after it was contaminated with bacteria. The level of silver in the blood following treatment of the burn wound with topical AgSD (Silvadene, Marion Labs) is significantly less when the drug is presented in the dressing than when the drug is applied in a cream base; the concentration of the sulfadiazine moiety in the blood is similar for the two drug preparations. Improved survival of the burned and contaminated rats and reduced nursing care were observed in the burned animals when the synthetic dressing was used to deliver the drug relative to the results when the AgSD was applied in a cream base by standard procedures.

Animals↗