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Biomedical subjects

R Rosenfeld

Publications and source records attributed to R Rosenfeld.

At least 73 records · Page 4Linked to original sources
PubMed1993

Partition of plasmid R1: a computer simulation.

A computer-simulated population of individual Escherichia coli cells harboring plasmid R1 parA+/parB- has been used to analyze three possible modes of plasmid segregation: equi-partition, in which plasmids are partitioned equally to daughter cells at cell division; single-site inheritance, in which the products of the most recent replication event are partitioned equally and the remaining plasmids are distributed randomly; and pair-site partition, in which a single, randomly chosen plasmid is actively partitioned to each daughter cell at division and the rest are distributed randomly. Comparison between predicted and experimental plasmid loss-frequency enabled us to rule out the first of these models as a likely mode of action in R1 but was inconclusive regarding the other two. The parA region would therefore seem to partition actively only one pair of plasmids to each daughter cell, the precise selection rule involved remaining unresolved. This question is not easily decided with current technology, as we show, but our simulation results also predict that the isolation of rep(Ts) mutants will provide an experimental system in which a clear distinction is possible between two plasmids that are the products of the most recent replication event and two that are chosen strictly at random.

Computer Simulation↗
PubMed1993

Zinc fingers: conserved properties that can distinguish between spurious and actual DNA-binding motifs.

The zinc finger, one of the major structural motifs used for sequence specific DNA binding, has been identified in many regulatory proteins. By analogy, involvement in nucleic acid recognition has been implied for proteins that contain two cysteines and two histidines, spaced in accordance with the zinc finger motif. In this study we identify sequence dependent characteristics that are conserved in the DNA-binding zinc fingers and are probably required for a functional DNA-binding zinc finger. Examination of the conserved properties in view of the solved three dimensional structure of a zinc finger, confirms the importance of most of these properties. The absence of the identified physical-chemical characteristics from CCHH containing sequences of non-DNA binding proteins suggest that they can be used to distinguish between spurious and actual DNA binding zinc fingers.

Amino Acid Sequence↗
PubMed1993

The growth hormone and somatomedin axis in short children with osteogenesis imperfecta.

Growth deficiency is a cardinal feature of severe osteogenesis imperfecta (OI) and a frequent feature of mild to moderate forms of this disease. We have investigated the status of hormones related to growth in 22 short prepubertal children, 13 males and 9 females, with various types of OI. Ten children had Sillence type III OI, 10 had type IV, and 2 had type I. Evaluation included GRH stimulation, three standard GH provocative tests (arginine-insulin tolerance test, L-dopa), 24-h sampling for measurement of unstimulated GH secretion and a somatomedin-C generation test. None of these children had GH deficiency by standard criteria. We found that 9 OI children had decreased responsiveness to GRH, similar to the GRH response of GH-deficient children. Overall, however, mean 24-h GH values and mean peak GH response to provocative agents of OI children were within the normal range. In the somatomedin generation test, the OI children as a group showed a blunted response, with 13 of 22 having less than a 2-fold stimulation of somatomedin-C by GH. This suggested resistance of the liver and other somatomedin-C secreting tissues to GH. The group with blunted insulin-like growth factor-I response did not correlate significantly with the group with decreased GRH response. To investigate the responsiveness of OI bone to growth stimulation, six OI children with less than average integrated GH secretion were enrolled in a pilot study in which one child received exogenous GH and six received clonidine for at least 6 months. The child treated with exogenous GH and three of six treated with clonidine experienced at least a 4.7 cm/yr increase over their pretreatment growth rates. Growth response could not be predicted from baseline studies. We conclude that abnormalities of the GH-somatomedin axis exist in some children with OI. Administration of GH or clonidine may augment growth rates in OI children; however, the effect of these agents on final stature is unknown.

Adolescent↗
PubMed1992

Effect of axis II diagnoses on treatment outcome with clomipramine in 55 patients with obsessive-compulsive disorder.

We used the Structured Interview for DSM-III Personality Disorders to diagnose DSM-III personality disorders systematically in 55 patients with obsessive-compulsive disorder in the active-treatment cell of a controlled trial of clomipramine hydrochloride. Patients with a cluster A personality disorder had significantly higher obsessive-compulsive disorder severity scores at baseline, and the number of personality disorders was strongly related to baseline severity of obsessive-compulsive disorder symptoms. At the conclusion of the 12-week study, we found no significant difference in treatment outcome with clomipramine between those patients with at least one personality disorder and those with no personality disorders. However, the presence of schizotypal, borderline, and avoidant personality disorders, along with total number of personality disorders, did predict poorer treatment outcome. These variables were strongly related to having at least one cluster A personality disorder diagnosis, which was also a strong predictor of poorer outcome. Implications of these findings are discussed.

Adult↗
PubMed1991

Insulin-like growth factors: the ovarian connection.

A large body of information now supports the existence of a complete intraovarian insulin-like growth factor (IGF) system replete with ligands, receptors, and binding proteins. Although much remains to be learned, the emerging consensus would suggest that the intraovarian IGF system is concerned largely with the amplification of gonadotrophin hormonal action for the facilitation of follicular growth and development. Future studies are likely to address the central issue of indispensability and the documentation of a meaningful in vivo role for this and related putative intraovarian regulators.

Animals↗
PubMed1991

Insulin-like growth factor I as an intraovarian regulator: basic and clinical implications.

Although much remains to be learned with respect to the possible relevance of IGF-I to ovarian physiology, it may be possible at this time to tentatively formulate possible functions of IGF-I in this connection: 1. Amplification of gonadotropin hormonal action--a key requirement given the exponential nature of follicular development. 2. Integration of follicular development--an essential facet concerned with the coordination of granulosa-theca cooperation. 3. Selection of dominant follicle(s)--a speculative proposition assuming timely and selective activation of the IGF-I system in "chosen" follicles. Aside from its possible role(s) in the course of established follicular cycles, IGF-I (and/or IGF-II) may also participate in the very formation of the follicular apparatus during the late fetal/early neonatal period. Although the ovary is gonadotropin-independent at that time, we previously showed that IGF-I may well interact with VIPergic input now implicated in the morphodifferentiation of the follicular apparatus. Similarly, IGF-I may be concerned with the promotion of juvenile and early pubertal follicular gonadotropin (FSH) levels; ovarian IGF-I may have a bearing on the puberty-promoting effect of growth hormone. Indeed, an association appears to exist between isolated growth hormone deficiency and delayed puberty in both rodents and human subjects, a process reversed by systemic growth hormone replacement therapy. Given that ovarian IGF-I and its receptor may be growth hormone-dependent, it is tempting to speculate that the ability of growth hormone to accelerate pubertal maturation may be due, at least in part, to the promotion of ovarian IGF-I production and reception with the consequent local potentiation of gonadotropin action.

Animals↗
PubMed1990

Clomipramine and obsessive compulsive disorder: a placebo-controlled double-blind study of 32 patients.

Thirty-two nondepressed patients with obsessive compulsive disorder were randomly assigned to treatment with clomipramine (N = 16) or placebo (N = 16) in a 10-week double-blind study. Of the 15 patients who received at least 3 weeks of clomipramine treatment, 11 (73%) improved, 5 (33%) improved by more than 50%, and none worsened. Only 2 (12.5%) of the 16 placebo-treated patients improved, 1 (6%) by more than 50%; two (13%) worsened. Clomipramine treatment was associated with statistically significant improvement on several measures of obsessive compulsive symptoms. Side effects were more frequent and severe with clomipramine than with placebo. Although most patients tolerated clomipramine well, 3 discontinued treatment because of side effects.

Adult↗
PubMed1989

Characterization of the receptor for insulin-like growth factor II in bone cells.

We have previously shown that insulin-like growth factor II (IGF-II) is produced by bone cells and that IGF-II stimulates cell proliferation and collagen synthesis in bone cells. We now extend these in vitro findings by demonstrating specific IGF-II binding to bone cells derived from newborn mouse calvaria and embryonic chick calvaria. The kinetics of [125I] IGF-II binding in embryonic chick calvaria cells showed time and temperature dependence. Scatchard analysis of [125I]IGF-II binding to chick calvaria cells showed an apparent Kd of 1.4 x 10(-10) M, with a calculated receptor site concentration of 40,000/cell. The specificity characteristics showed that IGF-II was significantly more potent than IGF-I or insulin in displacing IGF-II tracer. Competition for binding of [125I]IGF-II by unlabeled IGF-II showed a dose-dependent displacement between 0.5 and 25 ng/ml. Fifty percent displacement of [125I]IGF-II binding to chick and mouse calvarial cells was achieved at 1-2 ng/ml; 90% of specific binding of [125I]IGF-II was displaceable in the presence of 125 ng/ml of unlabeled IGF-II. IGF-I showed less than 5% cross reactivity for displacement of [125I]IGF-II binding to chick and mouse bone cells. Type II receptor inhibitory antibodies, R-II-PAB1 inhibited the binding of [125I]IGF-II to mouse bone cells and H-35 rat hepatoma cells (which contain type II but not type I receptors) in a dose-dependent manner. R-II-PAB1 also inhibited basal cell proliferation as well as IGF-II-, IGF-I-, and fibroblast growth factor (FGF)-induced cell proliferation in mouse bone cells. In chick calvaria bone cells and TE89 human osteosarcoma cells, R-II-PABI inhibited neither binding of [125I]IGF-II nor IGF-II-induced cell proliferation. These results together with our findings that IGF-II increased chick bone cell proliferation in the presence of maximal doses of IGF-I suggest that at least part of the mitogenic action of IGF-II is mediated through type II rather than type I receptors in bone cells.

Animals↗