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Biomedical subjects

L Silverman

Publications and source records attributed to L Silverman.

At least 19 recordsLinked to original sources
PubMed1992

del(5q) in acute lymphoblastic leukemia with biphenotypic and early progenitor phenotype.

We report three patients with acute lymphoblastic leukemia with biphenotypic and early progenitor phenotype who had del(5q). In the first patient, the del(5q) was the sole abnormality; in the second patient, the del(5q) was interpreted as subclonal evolutionary event; while in the third patient, the rearrangement was transiently present 7 months following the diagnosis of Ph-positive ALL, while the patient was in clinical remission. Review of the literature indicates that del(5q) is rare in ALL. In contrast to its presence in AML, del(5q) in ALL is not an adverse prognostic indicator, and it appears to be more frequent in children.

Adolescent↗
PubMed1992

Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides.

Three-dimensional structures of complexes of the SH2 domain of the v-src oncogene product with two phosphotyrosyl peptides have been determined by X-ray crystallography at resolutions of 1.5 and 2.0 A, respectively. A central antiparallel beta-sheet in the structure is flanked by two alpha-helices, with peptide binding mediated by the sheet, intervening loops and one of the helices. The specific recognition of phosphotyrosine involves amino-aromatic interactions between lysine and arginine side chains and the ring system in addition to hydrogen-bonding interactions with the phosphate.

Amino Acid Sequence↗
PubMed1992

Chromosome 21 rearrangement in acute biphenotypic leukemia.

A patient with myelodysplastic syndrome (MDS) and a 47,XY,+21 karyotype at diagnosis, was documented to have a clonal chromosome 21 rearrangement, i(21q), four months before transformation to acute biphenotypic leukemia. For 4 months after transformation, isochromosome 21 persisted while the patient was receiving treatment with zidovudine. Vitamin D3 was added to zidovudine for an additional month, during which time the trisomy 21 clone reappeared as the predominant cell population. The unique aspects of this patient are the atypical evolution of chromosome 21, the transformation to biphenotypic leukemia, and the occurrence of i(21q) associated with biphenotypic leukemia evolving from an MDS.

Anemia, Refractory, with Excess of Blasts↗
PubMed1992

Lysine residues form an integral component of a novel NH2-terminal membrane targeting motif for myristylated pp60v-src.

Association of pp60v-src with the plasma membrane is fundamental to generation of the transformed phenotype. Although myristylation of pp60v-src is required for interaction with a membrane-bound receptor, the importance of NH2-terminal amino acids in receptor binding has not yet been uncoupled from their role in signaling myristylation. Using chimeric src proteins, peptides identical or related to the NH2 terminus of src, and site-directed mutagenesis, we demonstrate that NH2-terminal lysines in conjunction with myristate are essential for membrane localization. Subsequent to NH2-terminal interaction with the "src receptor," internal regions of the src protein also participate in membrane binding. This novel NH2-terminal motif and internal contact mechanism may direct other members of the src family of tyrosine kinases to their membrane receptors.

Amino Acid Sequence↗
PubMed1991

Chemotherapy of metastatic Merkel cell cancer.

Out of 16 cases of Merkel cell cancer identified in the records of the Mt. Sinai Medical Center or affiliates, 11 patients developed systemic metastases. Literature review confirms the substantial possibility of dissemination. Both in our series and in the literature, cytotoxic chemotherapy produced a high rate of usually short-lived response, although one of our patients with disseminated metastases achieved complete remission for two years.

Adult↗
PubMed1989

Mechanisms of T cell activation by the calcium ionophore ionomycin.

We have investigated signaling mechanisms that may underlie the T cell mitogenic properties of the Ca2+ ionophore ionomycin. Ionomycin induces highly purified resting human T cells to proliferate in the presence of monocytes with accompanying IL-2R expression and IL-2 synthesis. Treatment of T cells with ionomycin triggers the hydrolysis of phosphoinositides, as evidenced by the accumulation of the hydrolytic by-products phosphatidic acid and inositol phosphates. Ionomycin also induces the activation of protein kinase C (PKC), as demonstrated by the auto-phosphorylation of PKC and the phosphorylation of the PKC target proteins CD4 and CD8. Ionomycin synergizes with PMA in enhancing the activation of PKC. It is concluded that, in addition to its putative activation of Ca2+/calmodulin-dependent signaling pathways, ionomycin induces the hydrolysis of phosphoinositides and the activation of PKC in human T cells. The synergy of ionomycin with phorbol esters in triggering T cell activation may relate, at least in part, to enhanced activation of PKC.

Calcium↗
PubMed1989

Increased permissivity of monkey cells to human adenovirus multiplication is affected by culturing conditions and correlates with both synthesis of virion fiber protein and altered splicing of its mRNA.

Human adenoviruses (Ad2) grow poorly in CV-1 (monkey) cells, resulting in an abortive infection. During abortive infections synthesis of the fiber protein is approximately 100-fold depressed compared to its synthesis in CV-1 cells productively infected with a host range mutant of adenovirus (Ad2hr400), while the corresponding mRNA is reduced only 10-fold. We found that passage of CV-1 cells under modified culture conditions resulted in loss of restrictiveness for Ad2 growth. As cells became more permissive, fiber polypeptide synthesis was enhanced although fiber mRNA levels did not necessarily increase. Analysis of the 5' ends of fiber message isolated from cells in various stages of permissivity showed a direct correlation between efficient synthesis of the fiber protein and an altered splicing pattern of the fiber message.

Adenoviruses, Human↗
PubMed1989

Characterization of the translational defect to fiber synthesis in monkey cells abortively infected with human adenovirus: role of ancillary leaders.

Synthesis of the fiber protein of human adenovirus serotype 2 (Ad2) is 100-fold lower in abortively infected monkey cells, compared with productive infections, despite only a 5- to 10-fold reduction in fiber mRNA levels. Previously Anderson and Klessig (Proc. Natl. Acad Sci. USA 81:4023-4027, 1984) demonstrated a direct correlation between the productive nature of the infection, efficient synthesis of the fiber protein in vivo, and the presence of the x or y ancillary leaders on 10 to 25% of fiber messages. To determine at what level in translation these leaders might be important, the relative rate of initiation and elongation of each class of fiber message was assessed. The presence of the y ancillary leader in productively infected cells increased the rate of initiation about twofold, although translational elongation was similar on all fiber messages. However, the rate of elongation of all fiber messages was threefold slower in abortively infected than in productively infected cells. This reduced elongation rate in abortive infections was specific for fiber. The similar distribution of fiber mRNAs on polysomes in both infections suggests that initiation must also be partially blocked in abortive infections. Since the majority of the fiber mRNA even in productive infections did not contain the ancillary leaders, the initiation and elongation defects in the abortive infection cannot be fully explained by the absence of these leaders. Therefore, other factors in the infected cell must be influencing the rate of translation.

Adenoviruses, Human↗
PubMed1988

Clinical and genetic investigation in autosomal dominant limb-girdle muscular dystrophy.

Limb-girdle muscular dystrophy is a syndrome of progressive myopathic weakness affecting shoulder and hip girdle and proximal arm and leg muscles. The disease occurs either sporadically or inherited as an autosomal recessive trait. Autosomal dominant inheritance is rare. We report a large family with apparent autosomal dominant inheritance. Sixteen members were affected with a disease characterized by proximal weakness, leg greater than arm, onset in the third decade, elevated CK and CK MB levels, and myopathic EMGs and muscle biopsies. Linkage analysis revealed no conclusive linkage.

Adolescent↗
PubMed1987

Androgen-binding levels in a sexually dimorphic muscle of Xenopus laevis.

The larynx of adult South African clawed frogs, Xenopus laevis, is larger in males than in females and hypertrophies in adult females and juveniles in response to androgen. Sexual dimorphism and androgen sensitivity suggest that the larynx is a testosterone target tissue. Saturation analysis of androgen (R1881) binding in laryngeal cytosol revealed an approximately threefold quantitative difference between male and female androgen-binding levels (36.4 vs 11.5 fm/mg protein). By contrast, as measured by one-point assay, androgen-binding levels in thigh muscle of either males or females were between 0 and 4 fm/mg protein with no apparent sex difference. Competition studies indicated that dihydrotestosterone was the most effective competitor for R1881 binding activity in the larynx. Saturation analysis showed the binding activity to be saturable and of high affinity (apparent Kd 0.46 nM in the male and 0.38 nM in the female). After 1 month of testosterone treatment, female binding levels averaged 16.6 fm/mg protein with a Kd of 0.49 nM, within the range for normal females. In males castrated for 4 months, binding levels were 52 fm/mg protein. After 1 year of castration, binding levels were 25 fm/mg protein. We conclude that laryngeal muscle is an androgen target tissue with sexually dimorphic levels of binding in adults.

Androgens↗
PubMed1985

Dimethylsulfoxide-induced changes in a rat prostate adenocarcinoma.

A variety of agents can induce mammalian tumor cell lines to acquire characteristics of the normal cell counterpart. Dimethylsulfoxide (DMSO) has been an effective differentiating agent in many tumor cell lines. In the present study a Dunning rat prostate tumor subline, MAT LyLu, available as an in vitro continuous cell culture was treated with 2.25% DMSO (vol/vol). Treated MAT LyLu cells had a decreased growth rate, saturation density, and clonogenicity, an increased doubling time, and alterations in enzyme activity and tumorigenicity when compared to untreated MAT LyLu cells. The cell viability of treated cells at the saturation density was greater than 90%. MAT LyLu cells treated with DMSO and then removed from DMSO (posttreated) when compared to untreated cells had similar growth rates, doubling times, clonogenicities, enzyme activities, and tumorigenicities. Posttreated MAT LyLu cells had a different growth pattern than untreated MAT LyLu cells. Posttreated cell viability at saturation density was greater than 90%. This investigation demonstrated that a rat prostate adenocarcinoma grown in medium containing 2.25% DMSO acquired characteristics consistent with differentiated prostate cells. Posttreated MAT LyLu cells were similar in many characteristics to untreated cells but were not identical. The alterations noted were not cytotoxic and were not completely reversible. The results of this study correlated with the observations of other investigators who have studied mammalian tumor cell lines exposed to DMSO.

Adenocarcinoma↗
PubMed1985

Further data on the effects of subliminal symbiotic stimulation on schizophrenics.

This investigation further examined the effects of activating unconscious symbiotic fantasies in schizophrenics. One hundred twenty-eight hospitalized schizophrenic men who qualified as "relatively differentiated" on the Adjective Rating Scale were randomly assigned to four groups. Each group was assessed for pathological thinking, pathological nonverbal behavior, and self-esteem before and after the subliminal exposure of an experimental and control stimulus. The control stimulus for all groups was the message PEOPLE ARE WALKING and the experimental stimuli were the messages MOMMY AND I ARE ONE, MOMMY IS ALWAYS WITH ME, MOMMY FEEDS ME WELL, and I CANNOT HURT MOMMY (one for each group). One half of each group was subliminally exposed to verbal messages only and one half to verbal messages accompanied by congruent pictures. The first stimulus (MOMMY AND I ARE ONE) was intended to activate unconscious symbiotic fantasies that in a number of prior studies reduced pathology in groups of relatively differentiated schizophrenics. The other stimuli were intended to activate reassuring unconscious fantasies about "mommy" that were not specifically symbiosis-related. Only the MOMMY AND I ARE ONE stimulus led to more adaptive behavior and did so on all three dependent variables. This supported the supposition, also borne out in two other studies, that it is specifically symbiosis-related gratifications that are ameliorative for schizophrenics. The above results were considerably stronger for the subgroup that was exposed to a picture accompanying the MOMMY AND I ARE ONE message. This was viewed as probably the result of the pictorial representation serving as a concretization of the more abstract verbal message and as such being more relevant to the relatively primitive mode of thinking in schizophrenia.

Adolescent↗
PubMed1985

Synthesis of the Ad2+ND5-specified 42K protein is regulated posttranscriptionally in abortively infected monkey cells.

In abortive infections of monkey cells by Ad2+ND5, the synthesis of the simian virus 40-specific 42,000-molecular-weight (42K) protein was reduced approximately 10-fold compared with a productive coinfection by Ad2+ND5 plus Ad2hr400 and about 20-fold compared with productive infections by Ad2+ND5 plus simian virus 40 or by Ad2+ND2 alone. However, the level of Ad2+ND5-specific mRNA was depressed twofold or less in abortive infections compared with productive infections. Moreover, the 42K mRNA isolated from abortive Ad2+ND5 infections translated in vitro with the same efficiency as the mRNA isolated from productive coinfections. This is analogous to the block to synthesis of the adenovirus fiber polypeptide in monkey cells (Anderson and Klessig, J. Mol. Appl. Genet. 2:31-43, 1983). Also like fiber protein, the increased level of the 42K protein found in productive infections was due to enhanced synthesis, not increased stability of the protein. Our results suggest that the synthesis of the Ad2+ND5-specified 42K protein and the adenovirus fiber protein are regulated in similar posttranscriptional manners.

Adenoviruses, Human↗
PubMed1985

Oncodevelopmental enzymes of the Dunning rat prostatic adenocarcinoma.

In this paper, data are presented which demonstrate that adenylate kinase and creatine kinase are oncodevelopmental enzymes in the rat prostate. The Dunning tumor (dorsal rat prostate) was used as a model system; four sublines of the tumor (R3327-H, R3327-AT, MAT Lu, and MAT LyLu) were studied. The tumor lines were maintained as solid tumors in syngeneic rats (Copenhagen) and as monolayers in tissue culture. The appearance of adenylate kinase with malignant transformation of the dorsal prostate was demonstrated. The disappearance of the CK-M subunit of creatine kinase and decreasing levels of creatine kinase were demonstrated with increasing anaplasia. The lactate dehydrogenase (LDH) concentration increased with increasing anaplasia, and the LDH isoenzyme pattern shifted to a more glycolytic pattern (LDH-4, LDH-5). The malignant isoenzyme pattern was reversible with the use of a differentiating agent (dimethyl sulfoxide). Prostates from neonatal rats and castrated adult male rats exhibited patterns of creatine kinase and adenylate kinase similar to those of the undifferentiated tumor. The oncofetal isoenzyme pattern of the castrated rat prostate was reversible with physiological levels of exogenous testosterone.

Adenocarcinoma↗
PubMed1978

Linkage of the endogenous avian leukosis virus genome of virus-producing chicken cells to inhibitory cellular DNA sequences.

The endogenous avian leukosis virus genome of uninfected virus-producing(V+) chicken embryo fibroblasts appears to be inefficiently transcribed and is noninfectious in transfection assays of high molecular weight DNA. We previously proposed that the endogenous virus genome was linked to a cis-acting control element which inhibited its transcription and, consequently, interfered with transfection by endogenous viral DNA. We now report that DNA of uninfected V+ cells is infectious at a low level when sheared to the approximate size of the virus genome. These results suggest that the endogenous virus genome of uninfected V+ chicken cells can be converted to an infectious form by separating it from adjacent cellular DNA sequences, as predicted by the cis-acting control element model.

Animals↗