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P Nathan

Publications and source records attributed to P Nathan.

At least 19 recordsLinked to original sources
PubMed1996

The human IL-11 receptor requires gp130 for signalling: demonstration by molecular cloning of the receptor.

We describe the molecular cloning of a cDNA for the alpha chain of the human IL-11 receptor (IL-11R alpha) and demonstrate the requirement of either the human or mouse gp130 molecule for signalling. cDNA clones encoding IL-11R alpha were isolated from a bone marrow cDNA library using a fragment from the murine IL-11R alpha as a probe. The human receptor was predicted to consist of 422 amino acids and was found to share 84% identity with the murine protein. In the extra-cellular region it exhibited a single hemopoietin domain with conserved cysteine residues and WSTWS motif. The transmembrane region was followed by a short cytoplasmic tail which did not contain a tyrosine kinase domain. Interaction of the human IL-11R alpha with murine gp130 was demonstrated: expression of the human IL-11R alpha in murine M1 cells which constitutively express murine gp130 (and murine LIF receptor), resulted in the generation of specific high-affinity binding sites for IL-11 (Kd = 250 pM). In addition, expression of the human IL-11R alpha in these cells permitted the induction of macrophage differentiation in response to IL-11. These results suggested that the human IL-11R alpha chain was able to form a functional receptor complex in association with murine gp130. The requirement of gp130 for signalling was confirmed by expression of the human IL-11R alpha in Ba/F3 cells. BaF3 cells that expressed the human IL-11R alpha alone showed binding of radiolabelled IL-11 but no proliferative response. Introduction of human gp130 into these cells resulted in high-affinity IL-11 binding sites and IL-11 dependent cellular proliferation. Thus these results demonstrated the absolute requirement of gp130 for signalling.

Amino Acid Sequence↗
PubMed1995

Vasodilatory state of decompensated cirrhosis: relation to hepatic dysfunction, ascites, and vasoactive substances.

The objective of this study was to determine the relations between the hallmark circulatory finding of decompensated cirrhosis, a reduced systemic vascular resistance (SVR), and the indices of hepatic decompensation, the accumulation of ascites, and the concentrations of various vasoactive substances. At a university-affiliated teaching hospital, eighteen hospitalized patients with cirrhosis and 18 age- and sex-matched healthy subjects were used. This was a case-control study. Measurements included cardiac dimensions and indices derived from echocardiograms and Doppler studies, abdominal ultrasound estimates of ascites, indices of hepatic function, and various serum (S) and urinary (U) substances. Results showed that cirrhotics had increased left atrial and left ventricular dimensions, left ventricular mass, heart rate, cardiac output (CO), transvalvular velocities, and a decreased SVR. SVR was related to hepatic dysfunction, as reflected by an abnormal prothrombin time ratio (r = -0.64, p = 0.006), and also related to overall severity of liver disease as estimated by the Child-Pugh score (r = -0.53, p = 0.044). Although cirrhotics with ascites generally had a reduced SVR, estimates of ascites were directly related to SVR (r = 0.57, p = 0.03) and inversely related to CO (r = -0.53, p = 0.04). Concentrations of S and U digoxin-like immunoreactive substance (DLIS) were also increased, but the concentrations of S glucagon and estradiol were not elevated. The accumulations of S and U DLIS, S glucagon, and S estradiol were all related to hepatic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Mood disorders in children with oppositional defiant disorder: a pilot study.

The nature and prevalence of comorbid mood disorders were explored in a group of 28 latency-age children diagnosed with oppositional defiant disorder. Findings are preliminary in nature but suggest that children with oppositional defiant disorder are at significant risk for low-grade depressive illness and that this may commonly be overlooked in the presence of their primary disorder's more overt symptoms.

Child↗
PubMed1993

Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma.

The search for tumour-specific markers is one of the chief goals in cancer biology. We show that the translocation t(12;16)(q13:p11) in malignant myxoid liposarcoma can be a fusion of the CHOP dominant negative transcription factor gene with a novel gene, FUS, which can result in fusion of the FUS glycine-rich protein with the whole CHOP coding region. The data support the concept that protein fusion may commonly occur in solid tumours resulting in tumour-specific markers of potential clinical importance. The data also indicate the importance of transcription disruption in the pathogenesis of solid tumours.

Amino Acid Sequence↗
PubMed1992

Symptomatic angina secondary to coronary-subclavian steal syndrome treated successfully by percutaneous transluminal angioplasty of the subclavian artery.

Subclavian artery stenosis causing severely symptomatic angina in a patient with a previous left internal mammary artery bypass to the left anterior descending artery was treated successfully with percutaneous transluminal angioplasty. Baseline arteriography clearly revealed subclavian and coronary steal by evidence of competitive flow of nonopacified blood from the left vertebral artery. Although there was a difference of only 15 mm Hg between the right and left brachial arteries, there was a palpable difference in the upstroke of these pulses. The stenosis in the subclavian artery was successfully dilated with percutaneous transluminal angioplasty. Angiographic evidence of subclavian steal resolved following balloon dilatation, and the patient's angina was completely resolved.

Aged↗
PubMed1991

Varieties of sentence comprehension deficits: a case study.

In recent publications, Grodzinsky (1984, 1986, 1990) has offered a new theory of the disruption of sentence comprehension in so-called agrammatic aphasics. In these works Grodzinsky contends that his account, which is based in various ways on the formal apparatus of current syntactic theory (Chomsky, 1981), is an accurate and explanatory characterization of the preserved language of all those who present with both agrammatic sentence production and asyntactic sentence comprehension. We argue that this claim is not in accord with the facts. We present a detailed case study of the sentence comprehension performance of a patient who is clinically categorized as agrammatic. This patient's performance on full and truncated passives, and on subject- and object-cleft sentences fails each of Grodzinsky's predictions for these sentence types. We argue that whether there exists any patient who does exhibit the predicted performance pattern is also in serious doubt.

Aphasia, Broca↗
PubMed1988

Plasma proteolytic activity following burns.

Because a number of metabolic events which are triggered by proteolysis in the bloodstream are activated following trauma, net proteolytic activity (P.A.) in the plasma of 37 pediatric burned patients was measured. The P.A. assay involved incubating plasma with a radioiodinated protein substrate and counting the isotopic activity of the hydrolyzed fragments in the acid-soluble fraction. In patients, plasma P.A. increased in direct proportion to the extent of burn injury. To examine additional trends in plasma P.A. suggested by the patient P.A. data, we measured plasma P.A. in a burned rat model: circulating P.A. was significantly elevated at 6 hours and until at least 2 weeks postburn; infection with Pseudomonas and use of the proteolytic debriding agent, Travase, each further elevated this activity; the plasma P.A. was not directly derived from the burn site. We postulate that this elevated circulating P.A. triggers some of the pathologic as well as some physiologic sequelae which follow burn trauma.

Adolescent↗
PubMed1988

Identification of two new cell division genes that affect a high-molecular-weight penicillin-binding protein in Caulobacter crescentus.

Penicillin-binding proteins (PBPs) are membrane proteins associated with the synthesis of the bacterial cell wall. We report the characterization of 14 PBPs in Caulobacter crescentus, using in vivo and in vitro penicillin-binding assays and experiments to determine their possible role in cell division. New conditional cell cycle mutants were isolated by selecting cephalosporin-C-resistant mutants of the beta-lactamase strain SC1107 at 30 degrees C that are also defective in cell division at 37 degrees C. They fall into two classes, represented by strains PC8002 and PC8003. Strain PC8002 produced short cells arrested at all stages of cell division at 37 degrees C and was found to contain a high-molecular-weight PBP 1B which was temperature sensitive when assayed in vivo and in vitro. Strain PC8003 was blocked at an early stage of cell division and formed tightly coiled, unpinched filaments. This cephalosporin-C-resistant strain was also defective in PBP 1B, but only when assayed in vivo. PBP 1B behaved like a high-affinity PBP, and in competition assays, beta-lactams that induced filamentation bound preferentially to PBP 1B. These results and the phenotype of mutant PC8002 suggest that PBP 1B is required for cell division, as well as for cell growth, in C. crescentus. The behavior of strain PC8003 suggests that it contains a conditionally defective gene product that interacts in some way with PBP 1B at an early stage of cell division. None of the mutants showed an allele-specific PBP pattern when assayed in vitro at the nonpermissive temperature, but all of them displayed temperature-sensitive PBP 1C (102 kilodaltons) activity. Thus, it appears that PBP 1C is inhibited at 37 degree C as a consequence of filamentous growth.

Anti-Bacterial Agents↗
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↗