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Biomedical subjects

E Rosen

Publications and source records attributed to E Rosen.

At least 19 recordsLinked to original sources
PubMed1992

Hepatocyte growth factor is a synergistic factor for the growth of hematopoietic progenitor cells.

Bone marrow (BM) stromal cells, which include macrophages, fibroblasts, endothelial cells, and adipocytes, have been shown to produce several factors that modulate the growth of BM progenitors. Hepatocyte growth factor (HGF) is a fibroblast-derived factor and has recently been shown to be a ligand for the c-met proto-oncogene, a member of the receptor class of tyrosine kinases. c-met messenger RNA (mRNA) is predominantly expressed in epithelial cells, but has been detected in several murine hematopoietic progenitor cell lines, suggesting that HGF and met might function during hematopoiesis. Here, BM cells were found to express both met mRNA and protein. Moreover, HGF was shown to synergize with interleukin-3 and granulocyte-macrophage colony-stimulating factor to stimulate colony formation of hematopoietic progenitor cells in vitro. These results show that, in addition to its activity on epithelial cells, HGF is a new member of the functionally related group of factors that modulate hematopoiesis.

Animals↗
PubMed1992

Binding of scatter factor to epithelial cell membrane protein: identification of its receptor.

Binding of scatter factor (SF) to the surface protein of Madin-Darby canine kidney (MDCK) cells was investigated. The factor has a specific affinity for membrane proteins of MDCK cells and could be purified 10-20-fold using a membrane protein-affinity chromatographic procedure. The binding was pH- and salt-dependent. The factor did not bind to columns prepared with membrane proteins from non responder cells or with bovine serum albumin. Further purification to homogeneity was achieved using reverse phase and immunoaffinity chromatography. The factor dissociated into 92, 62 and 34/32 kDa bands on SDS-PAGE under reducing conditions. A 230 kDa protein band, the receptor-SF complex, was observed when radiolabeled SF was crosslinked to surface proteins of MDCK cells and the complexes were subjected to electrophoresis. The binding of radiolabeled SF to the MDCK cells was decreased in presence of excess unlabeled SF. These observations suggest that the binding of SF to surface proteins of MDCK cells is specific and occurs predominantly to a 150 kDa protein.

Animals↗
PubMed1992

Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells.

The proto-oncogene c-MET encodes a transmembrane tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF stimulates the proliferation and motility of various cell types. Because HGF/SF is also a melanocyte mitogen, we investigated the biological role of HGF/SF, including c-Met expression, activation and signal transduction, in normal and malignant human melanocytes. We show that HGF/SF is mitogenic in the presence of synergistic factors, such as basic fibroblast growth factor (bFGF) and mast cell growth factor (MGF) and that, by itself, it stimulates the motility of normal human melanocytes. The ligand also maintained high levels of tyrosinase activity and melanin content in theses cells. Signal transduction by HGF/SF included phosphorylation of tyrosyl residues on c-Met, a cascade of tyrosine phosphorylations on several other proteins and activation of microtubule-associated protein kinase/extracellular signal-regulated kinase. Met expression and activity are normal in human melanomas, and constitutive activity of HGF/SF in retrovirally infected autonomously proliferative mouse melanocytes is insufficient to confer the malignant phenotype. Our findings suggest that activation of Met in response to HGF/SF may contribute to malignant progression synergistically with the aberrant expression of bFGF in malignant melanocytes and that, in addition, the peptide may promote dispersion of factor-dependent melanocytes from early stages of primary melanomas to ectopic sites.

Animals↗
PubMed1991

The development of adolescent sexual intimacy: implications for counseling.

This paper proposes a perspective for understanding the development of adolescent sexual intimacy. A "transitional stage" is described in which adolescents, driven by a variety of developmental needs influenced by external forces such as peers and family, experiment with sexual behaviors. The completion of the transitional stage results in the adolescent's ability to achieve "relational" sexual intimacy, which is also described. The problems and implications for counseling associated with the biophysiological and family dynamic influences on the development of adolescent sexual intimacy are discussed.

Adolescent↗
PubMed1989

Expression of human plasminogen cDNA in a baculovirus vector-infected insect cell system.

A cDNA that encodes the human plasminogen (HPg) amino acid sequence has been inserted adjacent to the polyhedrin promoter in the genome of the baculovirus, Autographa californica nuclear polyhedrosis virus, which was then used to infect cultured cells of the farm armyworm, Spodoptera frugiperda. Under the conditions of cell growth employed, recombinant (rec)-HPg was secreted into the medium after 24 h postinfection (p.i.), at which point virtually no rec-HPg antigen remained inside the cells. At 48 h p.i., a maximal level of intact rec-HPg was present in the medium, which underwent substantial proteolytic digestion after that time. The rec-HPg produced by this expression system possessed a molecular weight equivalent to that of plasma [Glu1]-plasminogen. In addition, the rec-HPg adsorbed to Sepharose-lysine, and was eluted with epsilon-aminocaproic acid (EACA). The recombinant protein also interacted with polyclonal antibodies generated to plasma HPg, as well as with a monoclonal antibody directed against a distinct region (kringle 1-3) of the plasma HPg molecule. Finally, the insect-expressed rec-HPg was activatable to plasmin (HPm) by urokinase. The results demonstrate that this expression system produces a full-length functional single-chain rec-HPg, which can be isolated intact from the culture medium, with some consideration for the temporal events that occur in secretion and longer-term degradation of the protein. The fact that this rec-HPg was converted to HPm with a plasminogen activator, and that it interacted with anti-plasma HPg polyclonal and monoclonal antibodies, as well as with the ligand, EACA, indicates that the molecule retains many of its important functional properties and is folded in an integral manner.

Animals↗
PubMed1989

Transposon mutagenesis of baculoviruses: analysis of Trichoplusia ni transposon IFP2 insertions within the FP-locus of nuclear polyhedrosis viruses.

The transposable IFP2 element of Trichoplusia ni was originally isolated as a host DNA insertion in spontaneous FP mutants of Galleria mellonella or Autographa californica nuclear polyhedrosis viruses (NPVs). The termini of IFP2 insertions from five independently isolated FP mutants were sequenced. In all cases IFP2 is flanked by 13-bp terminal inverted repeats and has additional inverted repeats of 19 bp in length located asymmetrically with respect to the ends of the element. Insertion of IFP2 into the viral genome always generated a duplication of the tetranucleotide target site, TTAA. There was an apparent preference for insertion within a 12-bp A + T-rich imperfect palindromic sequence surrounding the target site. Sequence analysis of three independent IFP2 elements revealed an internal domain of 2.475 kb containing an RNA polymerase II promoter region and two large open reading frames. Primer extension analysis of IFP2-specific mRNA positioned the 5' terminus of the transcript. The element is present in DNA isolated from T. ni cell lines TN-368 and TN-5B1, but is not apparent in DNAs isolated from the TN-R2 cell line or our laboratory colony of T. ni larvae, suggesting IFP2 was recently introduced into the T. ni genome.

Base Sequence↗
PubMed1988

Senior adult sexuality in age segregated and age integrated communities.

Middle-income older adults who select to reside in age-segregated (AS) leisure-type retirement communities exhibit significantly more sexual interest, sexual activities, and liberal sexual attitudes than do middle-income older adults residing in age-integrated (AI) mainstream communities. Data from 314 respondents on a senior adult sexuality scale were subjected to a discriminant analysis. Sexual activities and traditional sexual interests respectively make the strongest contribution to the group differences. The implications of these findings are discussed.

Aged↗
PubMed1988

Nursing staff response to a facility's relocation.

RESPONSE RATE--approximately 200 questionnaires were distributed and 101 were returned and collated. The response rate was 51 percent. ORIENTATION--the results were as follows: 89 percent of staff surveyed attended orientation; many staff took more than one tour (55.6 percent had two or more), which may be an important factor in adjustment; 75.2 percent indicated tht orientation was relevant, and those who did not recommended more specific unit orientation; and 31 percent said there was too much information and perhaps this should be examined in future orientation programs. OMISSIONS--many commented that specific, hands-on orientation to the equipment such as telephones and the call system would have been beneficial, as well as orientation to their own specific unit. Smaller orientation groups would also seem to be warranted in light of this information. COMMUNICATION CONCERNING THE MOVE--approximately 79 percent of the staff attended at least one staff meeting prior to the move, and 78 percent knew of the moving schedule. However, subsequent (and frequent) changes in this schedule were mentioned as a source of frustration. About 13 percent indicated a need for more staff input into the move and would suggest more open forums or discussion groups to solicit input as a way of increasing staff participation and commitment to the move. A need for frequent, reliable written communication was mentioned frequently as misinformation or word-of-mouth information led to unnecessary frustrations. It is interesting to note that approximately 80 percent of respondents had no suggestions to improve communication, and it is difficult to know whether this may indicate satisfaction with communication mechanisms or a lack of ideas on how to improve the situation. SENSE OF PREPAREDNESS FOR THE MOVE--80.4 percent gave a high rating to indicate how prepared they felt regarding the move, which is really very positive. PROBLEMS ADJUSTING TO NEW ENVIRONMENT--most of the responses (48%) related to problems with communication systems, particularly the phone system, problems with the phone listing book and lack of directional signs. Suggestions for facilitating adjustment closely followed the above responses in that more and better signs, and more effective means for directing staff, patients and visitors, were frequently cited. CURRENT FRUSTRATIONS--respondents were asked to detail ongoing and current frustrations. Environmental concerns such as excessively dry air and the cleanliness of the building were noted and earmarked for further investigation. It is worthy of note that concerns relating to nurse staffing were mentioned very infrequently both during and after the move.

Anxiety↗
PubMed1987

Gene regulation during dedifferentiation in Dictyostelium discoideum.

During development of Dictyostelium discoideum, cells acquire the capacity to rapidly recapitulate morphogenesis. Therefore, when cells at the loose aggregate stage are disaggregated and challenged to reaggregate, they do so in a tenth of the original time. If loose aggregate cells are disaggregated and resuspended in buffered dextrose solution (erasure medium), they retain the capacity of rapid recapitulation for 80 min, then completely lose this capacity in a single, synchronous step referred to as the "erasure event." The erasure event sets in motion a program of dedifferentiation during which cells lose developmentally acquired characteristics at different times. The erasure event is inhibited by the addition of 10(-4) M cAMP to erasure medium. The synthesis of 33 growth-associated polypeptides, the synthesis of 53 development-associated polypeptides, and the level of 2 development-associated RNAs have been monitored during the erasure program and in cultures inhibited from erasing by the addition of 10(-4) M cAMP. Growth-associated polypeptides begin to be resynthesized and development-associated polypeptides exhibit dramatic decreases in rate of synthesis at different times throughout the first 240 min in erasure medium. Inhibiting the erasure event with cAMP has no major effect in the resynthesis of the majority of growth-associated polypeptides. Only one growth-associated polypeptide, V28, is completely inhibited by cAMP, suggesting that it may play a role in the erasure process. In contrast, inhibiting the erasure event with cAMP has a marked effect on the synthesis of development-associated polypeptides, causing a dramatic reduction in the rate at which synthesis decreases for 6 polypeptides, and completely inhibits the decrease in the synthetic rate of 8 polypeptides. The two development-associated RNAs, 16G1 and 10C3, exhibit two distinctly different patterns of loss during erasure, but in both cases cAMP added at time zero of the erasure process dramatically retards or inhibits loss. In addition, when cAMP is added just prior to the erasure event, it inhibits the erasure event and stimulates a rapid increase in the level of 16G1 RNA back to the developmental level. The level of 16G1 RNA then remains at this level for at least 400 min. When cAMP is added after the erasure event, it causes a low, transient increase in the level of 16G1 RNA. These results are considered both in relation to the program of erasure, and in relation to the role of cAMP in the expression of developmental genes during the forward program of development.

Cell Differentiation↗
PubMed1985

Radiotherapy for prostate carcinoma: the JCRT experience (1968-1978). II. Factors related to tumor control and complications.

We have analyzed treatment failure and complications as a function of radiotherapy technique and other factors in 229 patients irradiated for prostate carcinoma from 1968-1978. Thirty-four patients (15%) developed clinical evidence of local-regional recurrence. In about one-quarter of these recurrences, there was a component of ureteral obstruction, possibly due to marginal miss in the seminal vesicles. Although different parameters of treatment technique were not significantly correlated with local failure, there was a trend toward higher failure rates for Stage B and C patients when the length and/or width of the conedown field was less than 8 cm (p = 0.27 and 0.25, respectively). As in other recent studies, patients with Stage C disease who had undergone trans-urethral resection of the prostate had a lower disease-free survival rate than patients who had only needle biopsy (39 vs. 65% at 5 years, p = 0.055). The use of larger initial fields treating the pelvic lymph nodes did not result in better local tumor control or better overall control. However, the use of larger fields did result in a higher rate of significant complications (8.7 vs. 1.6% for fields greater than or equal to 150 cm2 or less than 150 cm2, respectively, p = 0.013). In view of the higher complication rate and the absence of convincing evidence of benefit for whole pelvic treatment, irradiation of all pelvic lymph nodes can be questioned.

Carcinoma↗
PubMed1983

An unusual transposon encoding heat shock inducible and developmentally regulated transcripts in Dictyostelium.

We have isolated and characterized a transposable element from Dictyostelium discoideum denoted Tdd-1. There are approximately 50 complete copies of the element per haploid genome and approximately 100-150 partial elements. Southern blots of DNA from different Dictyostelium discoideum strains show that Tdd-1 is a mobile element. Tdd-1 is 4.9 kb long, with 313 bp inverted repeats. These repeats lie near the termini, but unlike other transposable elements one end of Tdd-1 extends 36 bp past the repeat and the other extends 1 bp. Tdd-1 encodes a series of developmentally regulated transcripts, all with the same polarity, that increase dramatically in abundance after approximately 10 hr of development. We have also identified a heat shock inducible transcript of the opposite polarity.

Animals↗
PubMed1983

Pulmonary edema occurring after isoxsuprine and dexamethasone treatment for preterm labor: Case report.

A case of maternal pulmonary edema occurring in a patient in the 32nd week of gestation is presented. This was our first case of pulmonary edema seen during a period of five years' usage of isoxsuprine in the treatment of premature labor. The patient presented was 28 years old, gravida 2, para 1, admitted to the maternity ward with premature uterine contractions. Her past history eliminate cardiac or pulmonary disease. Isoxsuprine therapy was begun with initial dose of 0.04 mg/min. and increased to 0.32 mg/min., the total dose administered was 560 mg during 48 hours. During this period she was given in dexamethasone 24 mg. Fluid balance on the first day of the treatment was +1.7 liters and on the second day +5.2 liters. Forty-eight hours from the commencement of the treatment, the patient experienced shortness of breath and chest pain. Physical examination disclosed wet rales over both lungs, sinus tachycardia and tachypnea. Laboratory examination disclosed hypopotassemia of 3 mEq/liter, hypoxemia (PO2 of 80 torr on 0.5 FiO2 face mask) with mild hyperventilation 28 torr PCO2 with normal ph 7.43. Recognition of the early signs of pulmonary edema enable swift clinical diagnosis and steps to be taken to prevent disasterous condition due to progressive hypoxemia. The prompt treatment in this complication includes discontinuation of isoxsuprine and fluid administration, placement of the patient in an erect position, intravenous furosemid 40 mg, oxygen supplement by face mask and 25 mg of meperidine. The patient's condition dramatically improved though the lung fields became completely clear from wet rales only eight hours from the start of dyspneic attack.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1980

Toxicologic evaluation of streptozotocin (NSC 85998) in mice, dogs and monkeys.

Single intravenous doses of CDF1 mice, and single and five daily intravenous treatment schedules in beagle dogs and rhesus monkeys were used to evaluate the toxicity of Streptozotocin (SZN). The major target organs in the three species were liver, kidney, lymphoid tissue and pancreatic islet beta cells. Moderate bone marrow depression and gastrointestinal toxicity were observed in the large animal species after lethal doses. Monkeys were less sensitive than the dog to the hepatotoxic effects of SZN and clinical signs of liver dysfunction were more severe in dogs after multiple doses. Microscopic lesions in the renal proximal convoluted tubules were present in the three species; these lesions appeared to be irreversible for dogs. The toxic effect on the endocrine pancreas was manifest by hyperglycemia, glucosuria, islet atrophy and beta cell degranulation. Multiple dose regimens were less toxic than single doses in dogs and monkeys in terms of the total dose received.

Animals↗