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J Pinkas

Publications and source records attributed to J Pinkas.

12 recordsLinked to original sources
PubMed2001

Synthesis and structural characterization of functionalized dimeric aluminophosphonates and a monomeric gallophosphonate anion.

Reaction of t-BuP(O)(OSiMe(3))(OH) with Me(3)Al leads to the formation of [Me(2)Al(mu-O)(2)P(OSiMe(3))(t-Bu)](2) (1) whereas Me(2)AlCl reacts with Ph(2)P(O)(OH) to yield [(Cl)(Me)Al(mu-O)(2)PPh(2)](2) (2). These compounds represent the first examples of functionalized dimeric four-ring type aluminophosphonate systems. The double four-ring type gallophosphonate, namely, [t-BuPO(3)GaMe](4), reacts with n-Bu(4)NHF(2) under ambient conditions, resulting in the formation of a monomeric gallophosphonate [n-Bu(4)N][MeGa[t-BuPO(2)(OH)](3)] (3). These derivatives have been adequately characterized using various spectroscopic techniques and X-ray diffraction studies.

Journal Article↗
PubMed2000

Cytoplasmic sequestration and functional repression of p53 in the mammary epithelium is reversed by hormonal treatment.

Proper function of the p53 tumor suppressor gene is critical for inhibiting tumor development in a broad spectrum of tissues. Although the mammary gland is highly susceptible to tumor formation, the functional status of p53 in the normal tissue had not been investigated. Therefore, expression, localization, and activity of p53 were examined in normal mammary tissues. High levels of p53 protein were found expressed in the cytoplasm of the ductal epithelium of the quiescent mammary gland. Ionizing radiation failed to recruit p53 to the nucleus, and p53-dependent responses were minimal. However, transient hormonal stimulation resulted in nuclear accumulation of p53, an induction of p21/WAF1, and a 5-fold increase in apoptosis after ionizing radiation. Therefore, the functional state of wild-type p53 in the mammary epithelium can be regulated by hormonal stimuli.

Animals↗
PubMed1999

Expression of MDM2 during mammary tumorigenesis.

The MDM2 oncoprotein encodes a 90 kDa nuclear phosphoprotein capable of abrogating the growth suppressive functions of p53 and pRb tumor suppressor proteins by direct interaction. Alternative splicing of MDM2 protein coding sequences has been documented during tumor progression in human ovarian and bladder carcinomas. The aim of this study was to determine whether alternative splicing of MDM2 occurs during breast tumorigenesis in mice and humans and whether protein coding sequences were affected. Specimens representing normal and malignant breast tissues from the murine D2 mammary tumor model system and human breast carcinomas were examined. Three distinct mdm2 mRNA transcripts of 3.3, 1.6 and 1.5 kb were detected in normal and malignant murine mammary tissues by Northern blot analysis using a full-length mdm2 cDNA probe. Additional Northern blot analysis using a probe derived from exon 12 of murine mdm2 demonstrated that the 1.5 and 1.6 kb transcripts lack sequences encoding the C-terminus of the protein. No evidence of internal deletions of protein coding sequences of mdm2 was detected in any of the normal mammary tissues or D2 murine mammary tumors examined by reverse transcription PCR (RT-PCR). Three distinct MDM2 transcripts of 6.7, 4.7 and 1.9 kb were detected in malignant human breast tissue by Northern blot analysis using a cDNA probe specific for the complete open reading frame of human MDM2. However, a cDNA probe specific for the last exon of human MDM2 hybridized only to the 6.7 and 4.7 kb transcripts, demonstrating that the 1.9 kb transcript lacked protein coding sequences contained in exon 12. Similarly, no internal deletions were detected in a panel of malignant human breast tissues using RT-PCR and analogous primers within human MDM2. Therefore, breast tumors differ from other solid tumors reported previously in that no internal deletions of MDM2 protein coding sequences were observed. However, the data document the presence of multiple MDM2 mRNA transcripts in both normal and malignant breast tissues. A subset of MDM2 transcripts were shown to lack the last exon which contains sequences coding for the RING and zinc fingers and domains which are targets for caspase-3 mediated proteolytic degradation and are required to target p53 for proteosomal degradation.

Alternative Splicing↗
PubMed1999

Regulation of p53 and its targets during involution of the mammary gland.

Post-lactational involution of the mammary gland provides a system in which to study the expression and function of genes that regulate apoptosis in the context of a normal tissue. The functions of the p53 tumor suppressor gene have been extensively studied as a mediator of apoptosis in response to DNA damage, but its regulation in normal physiologic processes has been poorly characterized. Expression of p53 mRNA was shown to be among the first genes to be induced in mammary tissue following weaning of neonates. Although involution proceeds in the absence of a functional p53 gene, it is delayed compared to normal individuals. Therefore, involution can be viewed as biphasic with initial responses being sensitive to p53, whereas secondary responses being p53-independent. These observations can be exploited to determine the subset of genes that are p53-responsive and that mediate the effects of p53 in normal mammary tissue.

Animals↗
PubMed1998

Delayed involution of the mammary epithelium in BALB/c-p53null mice.

In mammals, weaning of neonates and subsequent milk stasis initiates removal of the secretory epithelium of the mammary gland by apoptosis. The p53 tumor suppressor gene is induced rapidly following weaning of neonates, but its role in the process of involution has not been defined. Therefore, experiments were performed to identify the cell types in which the p53 gene is expressed during involution and determine the consequences of its absence in BALB/c-p53null mice. Both p53 mRNA and protein were detected in the mammary epithelium within 48 h following weaning and resulted in an eightfold increase in levels of p21WAF1 mRNA. Induction of p21WAF1 mRNA was absent in BALB/c-p53null mice, and therefore, was shown to be p53-dependent. The BALB/c-p53null mice exhibited delayed involution of the mammary epithelium, as measured by 60% greater epithelial area compared to BALB/c-p53(wt) mice through 5 days post-weaning. The delay was transient with no differences being apparent at 7 days post-weaning. Expression of the stromal protease stromelysin-1 was unaffected by the absence of p53 suggesting that stromal responses were intact. These data demonstrate that p53 participates in the first stage of involution initiated by the epithelium itself, but does not affect the second phase during which stromal proteases are induced.

Animals↗
PubMed1998

Induction of heat shock protein 27 by hydroxyurea and its relationship to experimental metastasis.

Treatment of tumor cells with hydroxyurea (HU) has been shown to increase the experimental metastatic potential of these cells. We have previously described the induction of stress proteins (antioxidants) by HU in B16 murine melanoma cells and their relationship to the metastatic process. We have now investigated the induction by HU of another set of stress proteins, the heat shock proteins, and their role in experimental metastasis. HU markedly increased the cellular content of heat shock protein (hsp) 27 but not of hsp 90, 72/73, or 60 as measured by immunoblotting. The induction of hsp27 protein was preceded by a specific increase in hsp27 mRNA. Furthermore, HU-treated cells were more thermotolerant. To investigate the functional role of hsp27, human hsp27 cDNA was constitutively overexpressed in B16 cells at levels seen in HU-treated cells. In separate experiments, we induced a global increase in hsps by heat shock. Neither the hsp27 transfectants nor the heat-shocked cells demonstrated an increase in their experimental metastatic capacity. We conclude that hsp27 protein is increased by HU by the specific induction of hsp27 mRNA in B16 melanoma cells but increased hsp27 protein is not responsible for the increase in experimental metastasis. Since high levels of hsp27 are associated with metastatic disease in breast and ovarian cancers, but not in our experimental system, the functional role of hsp27 in metastasis requires further study.

Animals↗
PubMed1993

Role of antioxidant enzymes in the induction of increased experimental metastasis by hydroxyurea.

BACKGROUND: Treatment of tumor cells with hydroxyurea and other DNA-damaging agents has been shown to increase the experimental metastatic potential of these cells. PURPOSE: We sought to elucidate some of the biochemical and genetic changes that promote tumor cell metastasis in hydroxyurea-treated cells. We hypothesized that drug treatment induces resistance to oxidative damage and that elimination of this resistance reverses the drug-induced experimental metastatic capabilities of tumor cells. METHODS: We examined the effect of hydroxyurea treatment on B16 melanoma cells with respect to experimental metastatic potential, resistance to hydrogen peroxide (H2O2), glutathione peroxidase activity and messenger RNA (mRNA) level, glutathione reductase activity, glutathione levels, glutathione-S-transferase activity, and catalase activity and mRNA level. RESULTS: Hydroxyurea-treated cells were transiently more metastatic following intravenous injection in syngeneic mice and transiently more resistant than untreated cells to exogenous H2O2. Hydroxyurea-induced experimental metastases and H2O2 resistance were eliminated by depletion of intracellular glutathione with buthionine sulfoximine. Glutathione peroxidase activity and mRNA level, glutathione reductase activity, and reduced glutathione levels were all transiently increased in hydroxyurea-treated cells, whereas the increase in glutathione-S-transferase activity was sustained. Catalase activity was modestly increased with no increase in its mRNA levels. CONCLUSIONS: In B16 melanoma cells, experimental metastasis induced by hydroxyurea appears to depend on a process that requires glutathione. Hydroxyurea treatment also induces resistance to exogenous H2O2, which may be due to induction of glutathione and antioxidant enzyme activity. IMPLICATIONS: The role of antioxidants in B16 melanoma cells offers new insights into the metastatic process and the cellular response to chemotherapy.

Animals↗
PubMed1987

Heating rabbit joint by microwave applicator.

Heating the joint to high temperatures using a microwave device may inhibit metabolic activity of the synovial tissue and enable higher penetration of antiinflammatory drugs into the joint cavity. To measure the temperature distribution of local thermotherapy, the hind joints of eight rabbits were heated by a 915 MHz microwave power source, using a special applicator. Temperatures of 44.0 +/- 2.8C, 36.1 +/- 3.8C, 39.6 +/- 2.3C, and 35.2 +/- 1.5C were measured after heating in the joint cavity, cartilage, muscle, and skin, respectively. The only significant increase in the temperature was recorded in the heated joint cavity (p less than 0.01). This new microwave device can be a therapeutic tool in treating joint diseases because of its advantage of heating the target organ only, eg, synovium, while sparing the adjacent tissues.

Animals↗
PubMed1985

Detection of cross-reactive anti-DNA antibody idiotypes in the serum of systemic lupus erythematosus patients and of their relatives.

Two common cross-reacting anti-DNA antibody idiotypes designated 16/6 and 32/15, previously identified in the serum of patients who have systemic lupus erythematosus, were found in 24% and 7%, respectively, of 147 first-degree relatives. These findings imply that high-frequency germ-line genes exist among lupus relatives, as well as patients. These dominant or public anti-DNA antibody idiotypes are not likely to be pathogenic factors, but are probably a genetically associated phenomenon.

Antibodies, Antinuclear↗