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PubMed2004

Tuberculous acute mastoiditis--a rare diagnosis. A case report.

Tuberculous acute mastoiditis (TAM) is a rare inflammatory infective condition of the mastoid process that can be difficult to diagnose. We presente the case of a 65-year-old women with earache, ear purulent discharge and tenderness of the mastoid tip after long time of medical therapy. Mastoidectomy with attico-antrotomy revealed chronic granulations with an osteitic process of mastoid and tympanic cavity with intact ossicular chain. Standard medical therapy resulted with prompt healing. Despite its rarity, diagnosis of TAM is often delayed, with potentially danger for severe complications.

Aged↗

PubMed1992

Bioconversion of tamoxifen by microbes.

Screening studies of tamoxifen (TAM) have shown that only one culture, Streptomyces rimosus ATCC 2234 was able to metabolize tamoxifen to 4-hydroxy tamoxifen (OHT) which was obtained in a 10% yield and chemically identified by 2 D nmr spectroscopy. A number of microorganisms were capable of biotransforming TAM to tamoxifen-N-oxide (TNO), and desmethyltamoxifen (DMT). The chemical identity of the isolated metabolites was achieved using gas chromatography/mass spectrometry and different nmr spectroscopic techniques.

Bacteria↗

PubMed2004

Adjuvant therapy of melanoma patients (stage II, III): a pilot immuno-toxicological study.

A pilot study was conducted to assess the tolerability and the effect on host immunity of a post-surgery adjuvant treatment of melanoma patients with an anti-angiogenic agent, Tamoxifen (TAM, 20 mg/die p.o., daily), combined with immunomodulating cytokines, i.e. recombinant interleukin-2 (IL-2, 4 MUI/m2 s.c., day 8,10,12) and alpha-2b-interferon (IFN, 3 MUI/m2 i.m., day 15,17,19), starting a new cycle on day 21, for a total of 12 cycles. Fifty patients (pts) entered into the study, 27 males and 23 females with a median age of 55 years (range 25-75), performance status (ECOG) 0 with melanoma stage IIA (12 patients), stage IIB (28 patients), stage III (10 patients). Preliminary in vitro studies showed that TAM does not interfere with up-regulation of natural immunity induced by IFN, IL-2, or IFN + IL-2 in normal peripheral blood mononuclear cells (MNC). The clinical study indicates that the protocol was well tolerated. Increase of NK and LAK activity of patient MNC was observed on day 15. The mean disease-free interval was 10 months and 40 pts were alive at 5 years of follow-up. Further investigations should be performed to test effectiveness of this protocol in a randomized study.

Adult↗

PubMed2005

Potential of endogenous estrogen receptor beta to influence the selective ER modulator ERbeta complex.

The ratio of estrogen receptor beta (ERbeta) to ERalpha can alter the estrogen-like properties of tamoxifen. Transient transfection of ERbeta cDNA into cells can decrease the estrogen-like properties of the ERalpha:tamoxifen complex, whereas an increase in the amount of ERbeta is associated with tamoxifen-resistant breast cancer. We have addressed each of these hypotheses by examining well characterized laboratory models. We determined whether changes in endogenous ERbeta are responsible for the estrogen-like or antiestrogenic properties of tamoxifen or raloxifene in MDA-MB-231 cells transfected with cDNAs for ERalpha or mutants D351G, D351Y. We found that the amount of ERbeta mRNA in separate, stable transfectants of mutant ERalpha cDNA was always < 2% of ERalpha. Since at least a 50:50 mixture of ERalpha:ERbeta is needed to silence the tamoxifen:ERalpha complex, we conclude that insufficient ERbeta mRNA is available for selective ER modulation in stable transfectants of D351G and D351Y ERalpha. Similarly, to test the hypothesis that ERbeta is up-regulated and plays an important role during the development of tamoxifen-stimulated tumor growth, we quantitatively analyzed ERbeta and ERalpha mRNA in tamoxifen-naïve (MCF-7:E2, ECC1:E2) and tamoxifen-stimulated tumors (MCF-7:TAM, EnCa 101:TAM). We found that ERbeta mRNA levels were not significantly elevated in tamoxifen-stimulated tumors and the ERalpha mRNA remained over 99% out of all ER species for all the tumors tested. The same results were also obtained when mRNA levels of ERbeta and ERalpha in a series of tamoxifen-naïve and tamoxifen-resistant breast cancer was analyzed. We conclude that endogenous ERbeta may not play a dominant role in the modulation of the tamoxifen ERalpha complex, or in the development of tamoxifen-stimulated resistant tumor growth.

Animals↗

PubMed2006

[Detection of estrogenic effects of nonylphenol and bisphenol A in vitro reporter gene-based assays].

OBJECTIVE: To explore the estrogenic effects and disruptive mechanism of NP and BPA by reporter gene-based assays we developed. METHODS: pERE-Luc plamid was generated by inserting estrogen response element (ERE) fragment into MCS of pGL3-promoter vector. MCF7 cells were cotransfected with pERE-Luc and phRL-SV40 using Sofast transfection reagent. The cells then treated with 17beta-estradiol (E2), tamoxifen (Tam), nonylphenol(NP) and bisphenol A (BPA) and expression of the repoter gene in the cell lysates was assayed using Dual-Lucferase reporter assay system. RESULTS: The pERE-Luc plasmid was constructed. Luciferase activities of MCF7 cells transfected pERE-Luc showed dose-responed realitionship with E2. 1 x 10(-11) mol/L E2 could induce the expression of reporter gene and 1 x 10(-9) mol/L E2 resulted in the largest luciferase activity. E2 couldn't induce the luciferase activity without pERE-Luc. Tam is a complete antagonist, inhibited the E2-induced luciferase expression. NP induced the luciferase activity at concertrations > 1 x 10(-6) mol/L, BPA induced the luciferase activity at concertrations > 1 x 10(-6) mol/L. The estrogenic activity of NP was more than BPA. CONCLUSION: The assay we established is usful, NP and BPA showed estrogenic activities.

Benzhydryl Compounds↗

PubMed1991

New alloplastic tympanic membrane material.

For patients with a totally empty middle ear a total alloplastic middle ear prosthesis (TAM) has been developed consisting of a macroporous hydroxyapatite canal-wall segment as a foundation system from which a dense hydroxyapatite ossicular chain is suspended. To connect the ossicular chain, we developed an alloplastic tympanic membrane made from a polymer. Light microscopy, morphometry, and autoradiography as well as various electron microscopy techniques were used in this study to evaluate the biocompatibility of Polyactive, a polyether polyester copolymer, after implantation in the rat middle ear. After between 2 and 4 weeks, implants were completely covered by tympanic-membrane epidermis and epithelium. Polyactive provoked a mild foreign-body reaction, showed a degradation rate of 54 percent after 1 year, and was nontoxic. Growth of fibrous tissue and bone into Polyactive copolymer indicated appropriate implant fixation by mechanical interlocking. The fixation of Polyactive by ingrowth of bone is promising, not only in terms of the amount of bone but also in terms of the bone/polymer interface. The latter is indicative of bonding osteogenesis in a way similar to that reported for hydroxyapatite implants. The results of this study showed that Polyactive copolymer is suitable as a degradable alloplastic tympanic membrane, both as a temporary scaffolding for the repair of tympanic membrane perforations and as a tympanic membrane in the TAM.

Animals↗

PubMed2006

[Management of soft tissue defects in the region of finger PIP joints by means of pedicular skin flaps taken from abdomen].

Management of soft tissue defects in the region of finger PIP joints makes a serious operative problem. Commonly recommended skin plastics require a wide experience in hand surgery. There is also lack of a comprehensive doctrine of surgical therapy depending on the extent of the mutilations. The paper presents the results of treatment of 17 mutilated fingers of 11 patients (8 men, 3 females) treated over the period of 2 years (2002-2004). The method applied was pediculated skin flaps taken from an abdomen. According to the extent of lesions three groups of patients were created. Eight patients were treated as emergencies, three appeared from 4 to 11 weeks after the accident. Flaps were cut off after 20.4 days on average. The secondary plastic was performed after the following 9.5 weeks. In 2 patients tendon plastics were performed. Fingers were mobilized during the whole period of the therapy. No complications in healing of the flaps were observed. The functional results were assessed 6 months on average after the primary operation. The average TAM and TPM were evaluated as follows: group I (no, or minor tendon lesions) TAM--186 degrees, group II.

Abdomen↗

PubMedDate not supplied

[Prognostic significance of macrophage infiltration in laryngeal carcinoma].

We investigated the relationships between tumor associated macrofages (TAM) and tumor tissues and their possible prognostic significance in a laringeal carcinomas of patients operated in our Department for sovraglottic or total laringectomy. In our analysis we found a positive trend in Grade 3, but we could not find any correlations in the other cases. That shows that TAM have antithetic activities in the life of neoplasia.

Cell Movement↗

PubMed1990

[Transient abnormal myelopoiesis followed by acute leukemia in children with Down syndrome].

This report describes three cases with Down's syndrome. These cases initially had transient abnormal myelopoiesis (TAM), from which they recovered spontaneously. They finally developed into overt acute leukemia characterized by an increase of blasts, hepatosplenomegaly, and elevated lactic dehydrogenase. Of these three cases, one was thought to have ANLL, which broke out 5 months after spontaneous remission. The other two had ALL, each occurring 8 and 9 years later. Chromosomal abnormality, in addition to trisomy 21, was detected in blast cells from one of the patients with acute leukemia. All three patients with acute leukemia experienced complete remission. However, two of the three patients relapsed and died. It is noted in the literature that remission is permanent in most cases of TAM, and is rarely terminated by leukemic relapse. In view of our observations, the importance of following up on such patients who evidence apparent remission of their leukemia-like disorder is emphasized.

Bone Marrow↗

PubMed1990

[Tissue polypeptide antigen liberation and proliferation of MCF-7 cells after synchronization with hydroxytamoxifen and rescue with estradiol].

The kinetic of release of the tissular polypeptide antigen (TPA) by MCF-7 cells synchronised by sequential treatment with hydroxytamoxifen (OH-TAM) and 17 beta-estradiol has been studied. The present findings confirm the proliferative effect of estradiol on MCF-7 cells, with a shortening of the doubling time (TD) (22.2 h versus 24.8 h) and an increase in the growing fraction (Fc) (94% versus 81%) when compared with the same parameters measured in cells rescued from OH-TAM but not treated with estradiol. In addition, the action of estradiol was followed by a simultaneous increase in the amount of TPA in the culture medium related with the phases G2/M and G1 of the mitotic cycle. This phenomenon seems to be the reason for the steplike shape of the TPA released curves. The experimental results suggest that in MCF-7 cells the sequential combination of antiestrogenic agents and estrogens leads to a cellular synchronization. Furthermore this synchronization is maintained for at least 3 cycles of cell division.

Antigens↗

PubMed1989

Factors of the extrinsic pathway of blood coagulation in tumour associated macrophages.

Despite the growing evidence implicating intratumoural fibrin formation in the progression of malignant tumours, the origin of coagulation factors that participate in extravascular clotting has not been elucidated. Using immunohistochemical methods we attempted to detect and localize clotting factors of extrinsic pathway in different human malignant tumours. Coagulation factors II, V, VII and X (FII, FV, FVII and FX) were detected in a huge number of cells showing spindle-shaped or stellate morphology. By double immunohistochemical labellings it was demonstrated that cells containing these clotting factors express monocyte/macrophage differentiation marker antigens recognized by Leu M3, Ki M7 and DAKO-macrophage monoclonal antibodies, i.e. they represent monocyte-derived, phagocytic tumour associated macrophages (TAMs). These findings suggest that TAMs can be viewed as clot cells, which in addition to the initiation of extravascular clotting by expressing procoagulant activity can also provide all the components necessary for the extrinsic thrombin formation.

Animals↗

PubMed1989

Comparison of benefit from UCH/RNID single-channel extracochlear implant and tactile acoustic monitor.

A 53-year-old, post-lingually totally deafened adult was evaluated six months post-operatively to compare the benefits of a UCH/RNID single-channel extra cochlear implant and a Tactile Acoustic Monitor (TAM). The TAM provided information giving clues to the prosodic features of rhythm and length of sounds. The cochlear implant provided information on pitch changes as well as the above prosodic features. The patient was able to use this additional information to obtain improved speech discrimination and environmental information.

Cochlear Implants↗

PubMed1987

Histamine and growth: interaction of antiestrogen binding site ligands with a novel histamine site that may be associated with calcium channels.

N,N-Diethyl-2-[(4-phenylmethyl)-phenoxy]ethanamine hydrochloride (DPPE) is a novel paradiphenylmethane derivative with antiproliferative and antiestrogenic properties. Like tamoxifen (TAM), DPPE binds to the microsomal antiestrogen binding site with high affinity (Kd approximately 50 nM), but, conversely, not to estrogen receptor or calmodulin. We now demonstrate that DPPE competes for [3H]histamine binding in rat cerebral cortex with an affinity (Ki = 4.5 +/- 2.6 X 10(-6) M) significantly greater than that of the H1 antagonist pyrilamine (Ki = 7.2 +/- 2.2 X 10(-5) M), despite the previous demonstration that pyrilamine is up to 1000 times more potent than DPPE in antagonizing histamine-induced contraction in canine tracheal smooth muscle. DPPE demonstrates antiproliferative activity against MCF-7 cells at concentrations between 1 X 10(-7) and 1 X 10(-5) M; the IC50 value of DPPE for growth inhibition at 7 days in this assay is 5 X 10(-6) M, a value equivalent to its Ki value for histamine binding. DPPE also competes for [3H]verapamil binding in membranes from whole rat brain with an affinity equal to that for verapamil (Kd = 4.0 +/- 1.8 X 10(-7) M); however, verapamil competes for [3H]DPPE binding in brain membranes and rat liver microsomes with an affinity markedly lower (Ki approximately 1 X 10(-4) M) than that of DPPE, suggesting allosteric interactions between the verapamil and DPPE sites. Unlike DPPE, verapamil is not antiproliferative in vitro against MCF-7 cells at concentrations up 1 X 10(-5) M, but, like DPPE, is cytotoxic at concentrations of 1 X 10(-4) M. In immature oophorectomized rats, verapamil or DPPE alone is antiuterotropic; however, verapamil shows no antagonism of exogenous estradiol on uterine growth, as opposed to DPPE which is a partial antagonist. Thus, the antiproliferative and antiestrogenic properties of DPPE either are not associated with calcium channel antagonism, or result from a qualitatively different effect on channels than verapamil. The in vitro antiproliferative effect of DPPE (7.5 X 10(-6) M) on MCF-7 cells at 72 h is significantly reversed by 10 mM L-histidine (70.2 +/- 12.6% reversal) and L-methionine (92.4 +/- 11.1% reversal), but not by L-ornithine, L-arginine, L-phenylalanine, or exogenous histamine. At lower concentrations of TAM (0.75 X 10(-6) M), where growth inhibition is estrogen-reversible, L-ornithine, but not L-histidine or L-methionine, causes significant reversal of growth inhibition (66.8 +/- 13.3%; p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Generation of new oncogenic murine retroviruses by cotransfection of cloned AKR and MH2 proviruses.

We have obtained a set of oncogenic recombinant retroviruses, the 3RV complex, by cotransfecting murine fibroblasts (SC-1 cells) with plasmids containing the cloned genomes of the avian MH2 and murine AKR viruses. The transfected culture (TAM-2) was shown to release murine transforming viruses by means of reverse transcription and focus formation assays. Analysis of TAM-2 intracellular RNA revealed new transcripts hybridizing with the oncogenes myc and mil and cross-hybridizing with an AKR probe. The biological activity of the 3RV complex was tested for the induction of murine macrophage proliferation in the absence of exogenous growth factors, a property described as the result of mil and myc cooperativity. Cell-free supernatants from 3RV transformed fibroblasts were indeed able to induce the proliferation of macrophage-like cells from murine bone marrow and spleen primary cultures. Such cultures were capable of continuous growth and showed independence from exogenous myeloid growth factors. The cells expressed antigenic markers and functional properties specific of the monocytic-macrophage lineage. These results suggest that transfection-induced recombination could be a novel way to generate biologically active recombinant retroviruses.

Animals↗

PubMed1988

Demonstration of a novel tumor-killing factor secreted from human macrophage-monocyte hybridomas.

We constructed human macrophage-monocyte hybridomas between a thymidine kinase-deficient human macrophage-like cell line, designated as TAM-2, and human peripheral blood monocytes in order for the study of cytokines from human monocytes. The hybrid and macrophage-monocyte nature of the growing cells was confirmed by the following facts: 1) All of the hybridomas established possess TK activity, whereas the TAM-2 cells are TK negative. 2) Most but not all of the hybridomas express the MaG-1 Ag which was shown to be a human macrophage-granulocyte specific Ag, but not T- and B-specific Ag. In the assay for cytokine, a few of the hybridomas produced a novel tumor-killing factor (TKF) after stimulation with PMA, polypeptone, and retinoic acid. Chemical nature of the TKF from the 3-63 hybrid clone was characterized and compared to those of well-known TNF and lymphotoxin. The TKF from a hybridoma was basic protein and had binding capacity to Con A-Sepharose, whereas TNF had an opposite nature. Moreover, TKF activity was not neutralized by both a murine monoclonal antibody against human TNF and rabbit antisera against human lymphotoxin. Thus, these results strongly indicate that the TKF is a novel TKF produced by human monocytic cells.

Cell Fusion↗

PubMed1987

[Proliferation kinetics of MCF-7 cell cultures. II. Synchronization and cell recruitment induced by hormones].

The culture of MCF-7 cells in well known experimental conditions and the analysis of the cellular uptake of 3HTdR under the influence of estrogens (17-beta-E2) and antiestrogens (OH-TAM) at precise concentration levels (10(-6)/10(-9) M) have made possible the study of the growing kinetic process of the cellular cultured population and the determination of the action of such hormonal preparations on the same process. The main findings are as follows: the growing rate of the cultured cells appears to slow down in presence of OH-TAM; the reason for this slowing growth seems to be the "blockade" of the cultured cells in the last part of G1 phase, a phenomenon that has proved to be dose-dependent; by the stimulating effect of the 17-beta-E2, the MCF-7 cells, synchronized in G1, progress simultaneously in their vital cycle during, at least, three divisory cycles; and this "recruitment" effect seems to be characteristic of the estrogen since the synchronization process fades or disappears when the 17-beta-E2 is absent from the culture medium.

Cell Division↗

PubMed1985

Amplification of immune T lymphocyte function in situ: the identification of active components of the immunologic network during tumor rejection.

Previous data had indicated that sarcoma-bearing mice receiving combination therapy consisting of a single i.p. injection of cytoxan (CY) and an i.v. injection of tumor-sensitized T cells (immune cells) rejected the neoplasm. The reaction was immunologically specific and dependent on donor T cells. This report is concerned with the hypothesis that the transfer of immune cells results in the amplification of T cell responses at the tumor site. Using C57BL/6J mice bearing the syngeneic rhabdomyosarcoma MCA/76-9, we show that 6 to 9 days after combination therapy those components usually associated with the immunologic network were present at the tumor site. Tumor-associated macrophages (TAM) and lymphocytes (TAL) were shown to produce IL 1 and IL 2, respectively. The TAM expressed Ir gene products (Ia) and were able to present the synthetic polymer GAT to specifically sensitized lymphocytes. In addition, it was demonstrated by in situ labeling with 3H-TdR that lymphocytes associated with the regressing tumors were proliferating. The peak incorporation occurred 7 days after therapy, 24 hr before a significant increase in the T cell content of the tumors. The data indicate that those facets of the immunologic network necessary for amplification were present at the site of rejection.

Animals↗

PubMed1979

Echocardiographic aortic root motion in ventricular volume overload and the effect of mitral incompetence.

Echocardiographic aortic root motion in systole was studied in 57 patients: 13 normal subjects, 4 patients with left ventricular (LV) volume overload due to anaemia, 16 patients with mitral incompetence, 13 with aortic incompetence and 11 with mitral stenosis. In normal subjects, patients with mitral stenosis and in patients with LV volume overload, in whom the increased stroke volume was ejected forwards into the ascending aorta (anaemia, aortic incompetence) the amplitude of motion of the posterior aortic wall (vp), the aortic widening fraction (AWF) and total aortic motion (TAM) were increased. In mitral incompetence, however, despite the large increase in total LV stroke index, there was a decrease in vp (P less than 0.01), AWF (P less than 0.001) and TAM (P less than 0.001), and the decrease in aortic motion for a given stroke index was related to the mitral regurgitant fraction, indicating that aortic wall movement in systole depended predominantly on forward ejection of the LV stroke volume. Reduced echocardiographic aortic root motion and widening during systole are useful echocardiographic signs of mitral regurgitation.

Anemia↗