Mucocele of the sphenoid sinus due to an osteoma.
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Bone Neoplasms↗
Biomedical subjects
Y Ben-David
Publications and source records attributed to Y Ben-David.
TGF-beta mediated G1 arrest in a human melanoma cell line lacking p15INK4B: evidence for cooperation between p21Cip1/WAF1 and p27Kip1.
We have studied TGF-beta mediated G1 arrest in WM35, an early stage human melanoma cell line. These cells have lost p15INK4B expression through loss of one chromosome 9 and rearrangement of the other. In asynchronously growing WM35, TGF-beta caused reductions in cyclin D1, cyclin A and cdk4 proteins and their associated kinase activities and an increase in both p21Cip1/WAF1 and p27Kip1. These findings were confirmed in cells released from quiescence in the presence of TGF-beta, in which TGF-beta inhibited or delayed the reduction in the cdk inhibitors that normally occurs in late G1. In contrast to observations in other cell types, there was an increased association of both p21Cip1/WAF1 and p27Kip1 with cyclin D1/cdk4 and with cyclin E/cdk2 during TGF-beta mediated arrest of asynchronously growing cells. Upregulation of p21Cip1/WAF1 preceded that of p27Kip1. Furthermore, p21Cip1/WAF1 and p27Kip1 were not present in the same cdk complexes but bound distinct populations of target cdk molecules. Both p21Cip1/WAF1 and p27Kip1 immunoprecipitates from asynchronously growing cells contained active kinase complexes. These KIP-associated kinase activities were reduced in TGF-beta arrested cells. It has been proposed that in TGF-beta arrested epithelial cells, up-regulation of p15INK4B and of p15INK4B binding to cdk4 serves to destabilize the association of p27Kip1 with cyclin D1/cdk4, promoting p27Kip1 binding and inhibition of cyclin E/cdk2. Our findings demonstrate that this is not a universal mechanism of G1 arrest by TGF-beta. In TGF-beta arrested WM35, which lack p15INK4B, the increased p21Cip1/WAF1 may serve a similar function to that of p15INK4B: initiating kinase inhibition and providing an additional mechanism to supplement the effect of p27Kip1 on G1 cyclin/cdks.
Carrier Proteins↗
Mass spectrometric characterization of sequence-specific complexes of DNA and transcription factor PU.1 DNA binding domain.
Electrospray ionization mass spectrometry (ESI-MS) has been used to study the noncovalent interaction of the 13.5-kDa DNA binding domain of PU.1 (PU.1-DBD) with specific double-stranded DNA (dsDNA) target molecules. Mixtures of PU.1-DBD protein and wild-type target DNA sequence yielded ESI-MS spectra showing only protein-dsDNA complex ions of 1:1 stoichiometry and free dsDNA. When PU.1-DBD protein, wild type target DNA, and a mutant target DNA lacking the consensus sequence were mixed, only the 1:1 complex with the wild-type DNA was observed, consistent with gel electrophoresis mobility shift assay results, demonstrating the observation of sequence-specific protein-dsDNA complexes using ESI-MS.
Binding Sites↗
Multiple features of advanced melanoma recapitulated in tumorigenic variants of early stage (radial growth phase) human melanoma cell lines: evidence for a dominant phenotype.
The vast majority of primary human cutaneous melanomas undergo a slow and gradual progression from a clinically indolent, curable radial growth phase (RGP) to a malignant vertical growth phase. We sought to develop a way of isolating genetically related malignant variants from a benign RGP human melanoma, called WM35. The parent and variants were then used as a model system to examine to what extent the expression of clinically and biologically relevant phenotypic features characteristic of advanced melanomas are associated with (and thus perhaps causative of) such a malignant conversion. Such a model system could also be used as a means of eventually identifying genetic alterations and cellular changes involved in the malignant switch in melanoma progression. To develop such a model, we subjected WM35 cells to retroviral insertional mutagenesis, which was followed by selection for progressive growth of solid tumors in nude mice. Highly aggressive and phenotypically stable tumorigenic variants were derived which contained at least four integrated proviruses. In contrast to the parental WM35 cells, these cell lines expressed several phenotypic features characteristic of naturally derived, advanced-stage malignant melanoma cells. Thus, in addition to tumor-forming ability in nude mice, the variants were growth factor and anchorage independent, overexpressed the MUC18 adhesion molecule, and lost responsiveness to the growth-inhibitory effect of several cytokines, including interleukin 6, transforming growth factor beta, interleukin 1beta, and tumor necrosis factor-alpha. Tumorigenicity and "multicytokine resistance" were dominant traits since in somatic cell hybrids between the parental cells and a tumorigenic subline no suppressive effect of the former cell population was observed. These findings suggest that one or more dominantly acting genetic alterations might be involved in this progression of RGP melanoma cells. The identity of such alterations remains to be determined.
Animals↗
Activation of the erythropoietin gene in the majority of F-MuLV-induced erythroleukemias results in growth factor independence and enhanced tumorigenicity.
Retroviral insertional activation of Fli-1 is the first detectable genetic alteration associated with F-MuLV-induced primary erythroleukemias, while mutations within p53 are only observed in Epo-dependent (ED) cell lines derived from syngeneic mice serially transplanted with F-MuLV-induced primary erythroleukemias. In this study we have determined the mechanism of growth factor independence in several Epo-independent (EI) cell lines established from adult mice previously injected with ED-erythroleukemia cell lines or serially transplanted primary tumor cells. Here we have shown constitutive expression of the Epo gene in 12 of 15 (80%) EI-erythroleukemia cell lines. Among these 12 cell lines, eight were shown to possess clonal rearrangement of the Epo gene which could be detected in the tumors used to establish the majority of these EI-cell lines. Analysis of the pattern of proviral integration revealed that the activation of the Epo gene in these cell lines is independent of retroviral insertional mutagenesis, but apparently the result of genomic rearrangements. Furthermore, the acquisition of growth factor independence by these leukemic cells confers a selective growth advantage in vivo and is associated with enhanced tumorigenicity. Together these observations suggest that the activation of the Epo gene in the large majority of these F-MuLV-induced erythroleukemic cell lines establishes an autocrine loop resulting in the constitutive activation of the Epo receptor signal transduction pathway, thereby conferring a growth and survival advantage in vito and in vitro.
Animals↗
Do Frenzel glasses have a place in the modern electronystagmography laboratory?
Electronystagmography (ENG) is generally performed with the patient's eyes closed to prevent visual fixation. In this way, direct observation of eye movements is impossible. By means of Frenzel glasses (FG), the direct observation of eye movements is possible, but the effectiveness of visual fixation suppression and the diagnostic contribution of FG must still be studied. One hundred seven patients with vertigo participated in this study. Each patient underwent a complete ENG test under two fixation modalities: (a) closed eyes and (b) open eyes with FG. The spontaneous nystagmus and the Hallpike test did not show any significant difference between the two fixation modalities. The slow-phase velocity of nystagmus with the caloric test was significantly greater with closed eyes, but the pattern of nystagmus with FG fixation was more tooth-shaped and regular than that with closed eyes. It is concluded that using FG when performing an ENG may improve its diagnostic value.
Adolescent↗
p53-independent tumor growth and in vitro cell survival for F-MuLV-induced erythroleukemias.
Retroviral insertional activation of the Fli-1 proto-oncogene is the first genetic event associated with the induction of erythroleukemias by the Friend murine leukemia virus (F-MuLV). Mutations within p53, which are only detected in cell lines established from transplanted tumors, have been previously shown to be associated with the immortalization of erythroleukemic cells in culture. In this study, we have demonstrated that primary erythroleukemic cells grown in liquid culture undergo rapid apoptosis independent of the stabilization of wild-type p53 protein. Further confirmation that the programmed cell death observed for liquid-cultured F-MuLV-induced primary erythroleukemic cells is largely p53 independent was provided by experimentation with a transgenic mouse line containing multiple copies of the dominant negative mutant p53Pro-193 allele. Erythroleukemic cells taken from tumor-bearing transgenic mice expressing high levels of the mutant p53Pro-193 undergo programmed cell death in culture in a manner that is largely identical to that observed for tumor cells derived from nontransgenic littermates. Furthermore, the rate of development of F-MuLV-induced erythroleukemias for both p53Pro-193-transgenic and nontransgenic littermates are similar. Moreover, cytogenetic analysis indicates that primary erythroleukemia cells are diploid, whereas chromosomal aberrations were observed in all established cell lines. These results are consistent with the notion that mutations within the p53 tumor suppressor gene affect genomic stability, subsequently leading to changes in gene expression that are associated with the immortalization of erythroid progenitor cells.
Animals↗
[The stria vascularis of the inner ear and its normal structural variations].
The ultrastructural effects of gentamicin on the stria vascularis of the inner ear of guinea pigs were studied by transmission electron microscopy. In a single specimen of an isolated, inner ear we found an unexpected variation in the structure of the stria vascularis in a normal, pigmented, guinea pig not treated with ototoxic drugs. There were prominent, wide protrusions from the apical surfaces of marginal cells into the endolymphatic space. This finding has not been previously reported and was seen in only 1 of 7 animals studied. It may be considered a normal structural variation, and is not pathological change in the stria vascularis due to ototoxic drugs.
Animals↗
Retroviral insertional mutagenesis as a strategy for the identification of genes associated with cis-diamminedichloroplatinum(II) resistance.
Expression of resistance to cis-diamminedichloroplatinum(II) (CDDP), one of the most effective chemotherapeutic drugs used to treat a variety of malignancies, remains a serious obstacle for improving cancer treatment. To study possible genetic mechanisms underlying the development of CDDP resistance, we have adopted the approach of retroviral insertional mutagenesis. An early-stage CDDP-sensitive human melanoma cell line, WM35, was infected with a defective amphotropic murine retrovirus (murine stem cell virus), and the pooled cells were subsequently selected for CDDP-resistant variants. Nine CDDP-resistant clones independently derived from murine stem cell virus-infected WM35 cells were analyzed and it was found that five of these clones acquired an identical retroviral integration site, designated as CDDP resistance locus 1 (CRL-1), as revealed by isolation of retroviral flanking sequences. Furthermore, using the flanking sequence as probe, we have detected a 3.5-4.0-kilobase message, the expression of which is strongly increased in clones carrying a rearranged CRL-1 locus. These results strongly suggest that overexpression of CRL-1 confers resistance to CDDP in these clones. In addition, the present study indicates that retroviral insertional mutagenesis represents a potential strategy to identify genes responsible for CDDP resistance and possibly other chemotherapeutic drugs as well.
Cisplatin↗
Meta-analysis comparing cisplatin total dose intensity and survival.
OBJECTIVE: To determine the relationship between total dose intensity (TDI) of cisplatin/carboplatin, total dose intensity of all chemotherapy drugs (GDI) and median survival (MS) in stage III-IV ovarian cancer patients. METHODS: Over 700 studies from the English literature were reviewed. Prospective clinical trials that had at least one arm treating patients with cisplatin/carboplatin and provided data on both MS and dose and schedule of chemotherapy were included. Dose intensity (DI), TDI, and GDI were calculated for each study arm. To explore possible relationships, several linear regression models were fitted with MS as the dependent variable and DI, TDI, GDI, and other known prognostic factors as the independent variables. RESULTS: Sixty-one study arms were analyzed including 4118 patients. No significant correlation was found between DI and TDI of cisplatin and MS (P = 0.90 and P = 0.11 respectively). Of the 10 variables tested, proportion of patients optimally debulked (%OD), proportion of mucinous tumor, and GDI were found to have a significant correlation to MS. All studies with a GDI less than 20 and %OD < 20 had a MS less than 20 months. On the other hand 77% of studies have a MS greater than 20 months when GDI is > 20 and %OD > 20%. We found single-agent chemotherapy had the worst outcome and there was very little difference between two or more drugs for percentage of studies with > 20 months MS, (56.5% vs 63.3% respectively). CONCLUSIONS: From this meta-analysis we believe that both GDI and %OD are important factors that determine outcome in terms of median survival.
Antineoplastic Agents↗
Idiopathic Subjective Tinnitus Treated by Amitriptyline Hydrochloride/Biofeedback.
The efficiency of two treatment modalities for subjective/idiopathic tinnitus (SIT): biofeedback (BF) and amitriptyline hydrochloride (AT) was investigated in 225 randomly selected subjects. Findings show that after 10 weeks of treatment in the BF group, 43.5% of the patients reported an improvement of tinnitus during activity. In the AT group, 27.5% of patients reported subjective improvement of tinnitus at rest although only 15.8% of the AT patients reported improvement during activity. Biofeedback during rest had a significantly better effect on tinnitus disturbance than AT. No objective diminishment of tinnitus loudness was found as a result of any of the treatment modalities. We believe that BF can help tinnitus patients especially during periods of rest and we also suggest trying tricyclic antidepressant drugs such as AT for treatment of tinnitus patients, in small doses, however, to minimize the side effects of this drug. Subjective tinnitus (ST) is one of the most common and yet most unclear of otologic symptoms.(1-4) ST can accompany any type of hearing loss including both sensorineural as well as conductive hearing loss, and may originate from any part of the auditory pathway.(1,5) Treatment of ST must be primarily directed to the basic illness diagnosed after a thorough general ear-nose-throat and neurologic evaluation.(6) Severity of ST is evaluated both objectively, by determining the pitch and intensity of the tinnitus,(7) and subjectively as described by the patient. Because of the relatively high incidence of ST and in some patients, the severe personal reaction to it, many different treatments have been suggested, but generally only small to moderate success has been achieved in reducing tinnitus and its consequences, if any at all.(8) In this study we examined the effect of two treatment modalities: amitriptyline hydro-chloride and biofeedback.
Journal Article↗
Amnionitis and premature delivery with intact amniotic membranes involving Staphylococcus aureus. A case report.
Subclinical infection is suspected to be an important etiologic factor in the initiation of preterm labor in women with intact membranes. We present a case of acute clinical chorioamnionitis followed by preterm labor and fetal distress in a woman with intact membranes. The bacteriologic data on the mother and neonate clearly identified coagulase-positive Staphylococcus aureus as the etiologic factor.
Adult↗
Double-balloon instillation device for second-trimester abortion. Outcome in 340 consecutive cases.
For the past five years we have used a double-balloon device for extraovular instillation of prostaglandin solution for termination of midtrimester pregnancy. In 340 consecutive cases a success rate of 91% (abortions within 24 hours) was achieved, with a mean instillation-to-abortion interval of 17.5 +/- 6.5 (SD) hours in nulliparas versus 12.8 +/- 6.1 in multiparas (P < .005). The instillation of continuous, low-dose prostaglandin solution into the extraovular space resulted in very few side effects and no complications. Furthermore, the technique was used successfully in women who had undergone one or more cesarean sections in the past. The use of prostaglandin E2 (PGE2) resulted in shorter instillation-to-abortion intervals than did prostaglandin F2 alpha (P < .01); 500 micrograms/h of PGE2 solution was needed in nulliparas, whereas 250 sufficed in multiparas.
Abortion, Induced↗
[Chronic otitis media].
Results of middle ear operations performed between 1984-1989 were analyzed. The operations included 139 simple mastoidectomies, 68 radical mastoidectomies, and 41 simple mastoidectomies with tympanoplasty. 342 tympanoplasties were also performed, 51 in children up to 14 years old and 291 in those over 14. We conclude that the Schuller view and CT are not conclusive as to the presence of cholesteatoma, and cannot be relied on without other confirmation in planning the type of operation. Of patients with cholesteatoma who underwent simple mastoidectomy, in 21.1% the cholesteatoma recurred and revision or radical mastoidectomy was necessary. When the Eustachian tube was patent, the graft took in more than 90% of cases. Fibrin glue did not affect the results of tympanoplasty or myringoplasty. Graft take was similar in those under and over the age of 14. Tympanoplasty in children has a good chance of succeeding, and enables most to return to a normal life (including swimming).
Adolescent↗
Retroviral integration within the Fli-2 locus results in inactivation of the erythroid transcription factor NF-E2 in Friend erythroleukemias: evidence that NF-E2 is essential for globin expression.
Activation of either Fli-1 or Spi-1 members of the ets family of transcription factors as a result of retroviral insertion and mutational inactivation of the p53 tumor suppressor gene play essential roles in the multistage erythroleukemias induced in mice by various strains of Friend virus. We have previously identified another common site for provirus integration, designated Fli-2 (Friend leukemia integration 2), in some erythroleukemia clones induced either by Friend murine leukemia virus (F-MuLV) or by the polycythemia-inducing strain of Friend virus complex (FV-P). Here we show that genomic sequences adjacent to Fli-2 correspond to the coding region of the erythroid-specific DNA binding protein NF-E2 p45. In one erythroleukemia cell line the expression of NF-E2 p45 is undetectable due to proviral integration in one allele and loss of the other allele. The complete loss of NF-E2 p45 in this cell line is associated with a drastic reduction in expression of the alpha- and beta-globin genes that were partially restored by reintroduction of the NF-E2 p45 gene. Taken together, these results provide direct evidence that NF-E2 gene is essential for globin transcription and suggest that perturbation in expression of this transcription factor may contribute to erythroleukemia progression.
Animals↗
The A1 and A1B proteins of heterogeneous nuclear ribonucleoparticles modulate 5' splice site selection in vivo.
Recent in vitro results suggest that the heterogeneous nuclear ribonucleoparticle (hnRNP) A1 protein modulates alternative splicing by favoring distal 5' splice site (5'SS) selection and exon skipping. We used a mouse erythroleukemia (MEL) cell line (CB3C7) deficient in the expression of hnRNP A1 to test whether variations in hnRNP A1 and AlB protein levels affected alternative splicing in vivo. In contrast to A1-expressing MEL cell lines, CB3C7 cells preferentially selected the proximal 13S and 12S 5'SS on the adenovirus E1A pre-mRNA. Transiently expressing the A1 or A1B cDNA in CB3C7 cells shifted 5'SS selection toward the more distal 9S donor site. A1 protein synthesis was required for this effect since the expression of a mutated A1 cDNA did not affect 5'SS selection. These results demonstrate that in vivo variations in hnRNP A1 protein levels can influence 5'SS selection.
Alternative Splicing↗
[Supravoltage irradiation as a cause of maxillary fibrosarcoma].
Therapeutic doses of supravoltage radiation are not commonly thought to be carcinogenic and post-irradiation fibrosarcoma of the head and neck regions is rare. We present a 43-year-old man with post-irradiation fibrosarcoma of the maxilla, who had had supravoltage radiation 12 years before for nasopharyngeal carcinoma.
Adult↗