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J Liebmann

Publications and source records attributed to J Liebmann.

At least 37 records · Page 2Linked to original sources
PubMed1994

The influence of Cremophor EL on the cell cycle effects of paclitaxel (Taxol) in human tumor cell lines.

We have performed DNA flow analysis, mitotic index studies, time-lapse photography, and paclitaxel uptake studies of human tumor cell lines exposed to paclitaxel. DNA flow analysis demonstrated that cells began accumulating in G2/M within 6 hrs of exposure to paclitaxel; by 12 hrs over 50% of cells accumulated in G2/M at all concentrations tested. After 24 hrs of exposure to 10 nM paclitaxel, cells underwent non-uniform mitotic division resulting in multinucleated cells. Of cells treated with 30 nM to 1000 nM paclitaxel, 75% to 85% remained blocked in G2/M for up to 72 hrs. Although a large proportion of cells treated with higher concentrations of paclitaxel (10,000 nM) was blocked in G2/M, a significant proportion (10% to 40%) of these cells was also in G1. Cells exposed to lower concentrations of paclitaxel (10 nM to 1000 nM) in medium containing 0.135% (v/v) Cremophor EL also had a relatively large proportion in G1. Mitotic index studies demonstrated that the paclitaxel-induced G2/M block was initially a mitotic block and that cells remained in mitosis for up to 24 hrs. With additional time of exposure to paclitaxel, mitotic index and time-lapse studies indicated that cells attempted to complete mitosis; however, cytokinesis was inhibited and cells became multinucleated. Time-lapse photography revealed that paclitaxel markedly prolonged the time in mitosis from 0.5 hr to 15 hr. High levels of Cremophor EL (0.135% v/v) markedly reduced the number of cells in mitosis but did not alter the mitotic delay induced by paclitaxel. 3H-paclitaxel uptake studies revealed that high concentrations of Cremophor EL did reduce the rate of uptake of paclitaxel into cells but had little effect on total paclitaxel accumulation. These results confirm that paclitaxel has striking effects on the cell cycle and show that high concentrations of Cremophor EL are capable of inducing a cell cycle block distinct from the mitotic block seen with paclitaxel. These results also demonstrate that cells exposed to paclitaxel for longer than 24 hours attempt to complete mitosis but the process of cytokinesis is inhibited. Together with cytotoxicity data, these results indicate that entry into and exit out of mitosis are prerequisites for paclitaxel cytotoxicity.

Adenocarcinoma↗
PubMed1994

Pharmacokinetic properties of nitroxide-labeled albumin in mice.

We have conjugated bovine serum albumin (BSA) with a pyrrolidinyl nitroxide and report on the in vivo pharmacokinetic properties of this conjugate in mice. In vivo EPR measurements of nitroxide were obtained after intravenous injection of 30 mg of labeled BSA by analysis of the nitroxide signal from the tails of mice. Following in vivo nitroxide measurements, the animals were sacrificed by exsanguination and organs were removed for determination of nitroxide levels. The level of nitroxide as determined by in vivo measurements declined exponentially with time and had a half-life (t1/2) of 7 hours. Blood nitroxide levels also declined exponentially with time with an initial t1/2 of 70 minutes and a terminal t1/2 of 10 hours. Nitroxide concentration varied among different organs; no nitroxide was detected within brain whereas lung had high concentrations of nitroxide. Liver and kidney both had relatively low levels of oxidized nitroxide, though total nitroxide (reduced plus oxidized) accumulated in the kidneys with time. Nitroxide-labeled BSA was well tolerated by the mice, is relatively stable, and is mainly confined to the intravascular space. Nitroxide-labeled albumin may be useful as a contrast agent for MRI or EPR imaging.

Animals↗
PubMed1994

Ultrasound biomicroscopy in pigment dispersion syndrome.

PURPOSE: To examine the positional relations of the iris, lens, ciliary processes, and zonules in eyes with the pigment dispersion syndrome (PDS). METHODS: High-resolution, anterior segment ultrasound biomicroscopy was performed on 16 untreated eyes of 11 patients with PDS. Scanning was repeated on four eyes after miotic treatment and four eyes after laser iridotomy. RESULTS: Mid-peripheral iris concavity could be demonstrated in 56%, irido-zonular contact in 25%, and irido-ciliary process contact in 75% of untreated eyes with PDS. Repeat scanning after laser iridotomy or pilocarpine therapy showed resolution of the iris concavity and irido-zonular contact in all eyes receiving these therapies. Irido-ciliary process contact persisted in some eyes. CONCLUSION: The authors' findings demonstrate the structural relations among the iris, lens, zonules, and ciliary processes in vivo that characterize the PDS. Miotic therapy and laser iridotomy eliminate the iris concavity in all patients with this finding, supporting the hypothesis of reverse pupillary block. Irido-ciliary process contact may be another mechanism causing release of pigment. This issue merits further clinical and histologic study.

Adolescent↗
PubMed1994

Protection from lethal irradiation by the combination of stem cell factor and tempol.

Cytokines that stimulate growth and differentiation of hematopoietic precursor cells have been used as protectors in vivo against ionizing radiation. Recently, we have shown that the nitroxide tempol is also an effective radiation protector in vivo. The purpose of the present study was to determine if the combination of tempol with stem cell factor (SCF, c-kit ligand) would provide enhanced radiation protection in C57 mice compared with the protection afforded by either agent alone. Mice were exposed to whole-body irradiation and assessed for survival at 30 days after irradiation. No control mice survived doses of more than 9 Gy. Treatment of mice before and after radiation with SCF alone (100 micrograms/kg at -20 h, -4 h and +4 h) protected mice from radiation at doses of as high as 10 Gy (76% survival). Tempol (350 mg/kg) given 10 min prior to radiation was a radioprotector at 9 Gy (55% survival). The combination of SCF and tempol increased the survival of mice exposed to radiation doses up to 11 Gy (32% survival for the combination vs 4% for SCF alone and 0% for tempol alone; P < 0.001 for the combination vs either agent alone). Lower doses of SCF alone (1 microgram/kg) or tempol alone (275 mg/kg) did not protect mice from radiation. However, the combination of these reduced doses of SCF and tempol protected mice from lethal irradiation at 10 Gy. Stem cell factor and tempol given either singly or together were well tolerated by the animals. These data show that SCF and tempol are radiation protectors and that their radioprotective effects are more than additive when the agents are given together.

Animals↗
PubMed1994

[Methanol formation in vitro and in vivo (methanol formation after pectin administration)].

1. In the course of 34 days the detectable methanol concentration in freshly squeezed grapefruit and organ juices as well as in grapefruit and orange juice mixes increased to a maximum level of approximately 600 mg/kg. This increase could already be detected at the beginning of the examination i.e. as early as 1 or 2 days after squeezing the fruit juices. At the beginning of the experiments the methanol concentrations were between 10 and 270 mg/kg. 2. After the consumption of pectin (40 g on one day and 2 x 40 g on two days) blood or serum-methanol values respectively were observed which were clearly above the level of chronic alcohol abuse (10 mg/kg). After the ingestion of ethanol (0.5 g/kg bodyweight) the serum-methanol concentration increased even further.

Adult↗
PubMed1994

Cycloheximide inhibits the cytotoxicity of paclitaxel (Taxol).

Treatment of human breast (MCF-7) and lung (A549) adenocarcinoma cell lines with 10 micrograms/ml cycloheximide provided substantial protection from paclitaxel-induced cytotoxicity. Addition of cycloheximide to cells at 0, 6, 12 or 18 h into a 24 h exposure to paclitaxel resulted in cytotoxicity similar to that found in cells treated with paclitaxel alone for only 0, 6, 12 or 18 h, respectively. DNA flow cytometry showed that paclitaxel blocked cells in G2/M. Mitotic index studies demonstrated that paclitaxel arrested cells in mitosis and that prolonged exposure to paclitaxel resulted in the development of multiple micronuclei. Concurrent incubation of cells in cycloheximide prevented the development of a G2/M block, mitotic arrest and micronuclei formation. The addition of cycloheximide to cells at 6 or 12 h into a 24 h exposure to paclitaxel reduced the degree of G2/M block to that produced by incubation of cells in paclitaxel alone for only 6 or 12 h. Mitotic index studies confirmed that cells treated with cycloheximide during paclitaxel exposure had a marked reduction in the percentage of cells in mitosis. However, the percentage of paclitaxel-treated cells which had multiple micronuclei was increased in cells treated with cycloheximide. These results indicate that entry into mitosis is a prerequisite for paclitaxel-induced cytotoxicity and that cycloheximide reduces cytotoxicity due to paclitaxel by preventing cells from entering mitosis. However, once cells have entered mitosis in the presence of paclitaxel, protein synthesis is not required for the development of multiple micronuclei and cytotoxicity.

Adenocarcinoma↗
PubMed1994

Measurement of ultrasound biomicroscopy images: intraobserver and interobserver reliability.

PURPOSE: To evaluate intraobserver and interobserver reproducibility of measurement of images obtained during ultrasound biomicroscopy. METHODS: Four anterior segment images of four normal patients were obtained by a single examiner. The measurements of three independent observers were compared to assess interobserver reproducibility in quantifying the images. Thirteen different anterior segment parameters were measured by each observer on each image. Intraobserver and interobserver reproducibility of measurement were assessed by calculating the coefficient of variation for each individual observer and by using the F test to detect a difference among observers. RESULTS: Intraobserver reproducibility was high. Interobserver reproducibility for the measured parameters varied considerably and was affected by subjective interpretation of visualized anatomic landmarks. CONCLUSIONS: The optimal parameters for quantitative ultrasound biomicroscopy require refinement. Measurements of alterable parameters are best measured presently by a single observer. Ultrasound biomicroscopy has the potential to elucidate anatomic relationships underlying much anterior segment disease, but caution in interpreting quantitative differences is warranted.

Anterior Eye Segment↗
PubMed1993

Alterations in cell membrane permeability by the lentivirus lytic peptide (LLP-1) of HIV-1 transmembrane protein.

Previously we reported that synthetic peptide homologs of an amphipathic region (designated the lentivirus lytic peptide, or LLP-1) near the carboxy terminus of HIV-1 transmembrane protein (TM) were toxic for both prokaryotic and eukaryotic cells when added exogenously to cell cultures. We postulated that these peptides may exert their toxic effects in much the same manner as natural cytolytic peptides such as magainins, cecropins, and melittin by forming pores through cellular membranes. Here we show the results of 51Cr-release assays and membrane flux measurements of peptide treated cells that support our hypothesis. We have also tested a limited panel of LLP-1 peptide analogs in these assays and found that relatively minor alterations in peptide charge or amphipathicity in the parent HIV LLP-1 sequence resulted in total loss of membrane perturbative properties. These results demonstrate that the peptide homolog of HIV-1 LLP-1 can indeed perturb membranes by forming pores of defined size in cytoplasmic membranes. Furthermore, the analog studies described here reveal that the amphipathy and high positive charge of this protein segment are required for the membrane perturbative properties.

Amino Acid Sequence↗
PubMed1993

Ultrasound biomicroscopy in pseudophakic malignant glaucoma.

BACKGROUND: Malignant glaucoma (ciliary block glaucoma; aqueous misdirection glaucoma) is an incompletely understood, rare and serious complication of intraocular surgery. METHODS: A woman with pseudophakic malignant glaucoma underwent successful neodymium: YAG (Nd:YAG) laser photodisruption of the anterior hyaloid face with resolution of the glaucoma. High-resolution ultrasound biomicroscopy was used to image the anterior segment and anterior chamber angle before and after laser surgery. RESULTS: Ultrasound biomicroscopy provided cross-sectional images of the iris, posterior chamber intraocular lens (IOL), and ciliary body and their relative positions before and after resolution of the malignant glaucoma. Anterior rotation of the ciliary body and anterior chamber shallowing normalized after rupture of the anterior hyaloid face. CONCLUSION: High-resolution ultrasound biomicroscopy provided images consistent with accepted concepts of the pathophysiology of this disease and offers great promise for the future elucidation of the anatomic mechanisms underlying various forms of glaucoma.

Aged↗
PubMed1993

Argon laser trabeculoplasty in pigmentary glaucoma.

PURPOSE: To evaluate the long-term effect of argon laser trabeculoplasty (ALT) in pigmentary glaucoma. METHODS: The authors retrospectively analyzed results of ALT in 32 eyes of 32 patients with medically uncontrolled pigmentary glaucoma. Data were longitudinally adjusted to normalize the disparity in time of follow-up and evaluated by life-table analysis. RESULTS: Mean age (+/- standard deviation) was 45.1 +/- 13.1 years (range, 23-72 years) (males, 46.3 +/- 13.7 years; females, 42.9 +/- 12.2 years). Mean baseline intraocular pressure (IOP) was 27.8 +/- 5.3 mmHg. Mean follow-up time was 33.0 +/- 5.0 months (range, 1 week [immediate failures] to 96 months). Three eyes were lost to follow-up at 3 months. Eleven eyes required trabeculectomy between 1 week (2 eyes) and 37 months after laser treatment. Life-table analysis indicated a cumulative success for all eyes of 80% at 1 year, 62% at 2 years, and 45% at 6 years. Mean IOP was significantly reduced (P < 0.001; paired Student's t test) for male and female eyes at all intervals calculated. Age was a significant factor in determining time to failure. CONCLUSION: Argon laser trabeculoplasty is effective in pigmentary glaucoma. Younger patients had a greater chance of success than older patients at all intervals. This became highly significant (P < 0.001) after 3 years.

Adult↗
PubMed1993

Ocular hypotony and choroidal effusion following bleb needling.

A choroidal effusion, hypotony, and a shallow anterior chamber developed in a patient following a transconjunctival needling revision of an encapsulated filtering bleb. While choroidal effusions occur frequently following filtration surgery, to our knowledge, this complication has not been previously reported following a filtering bleb needle revision.

Choroid Diseases↗
PubMed1992

Lattice degeneration of the retina and the pigment dispersion syndrome.

Retinal detachment occurs more frequently in patients with pigment dispersion syndrome. We evaluated the incidence of peripheral retinal abnormalities known to predispose to rhegmatogenous retinal detachment in a consecutive series of 60 patients with pigment dispersion syndrome with or without glaucoma. Lattice degeneration was present in at least one eye of 12 patients (20%). Seven patients had bilateral lesions. Full-thickness retinal breaks were found in seven patients (11.7%) and two patients (3.3%) had asymptomatic rhegmatogenous retinal detachments that required scleral buckle procedures. The incidence of lattice degeneration and full-thickness retinal breaks appears to be increased in this group of patients, and may be responsible for the increased risk of rhegmatogenous detachment.

Adult↗
PubMed1992

Identification of nitroxide radioprotectors.

The nitroxide Tempol, a stable free radical, has recently been shown to protect mammalian cells against several forms of oxidative stress including radiation-induced cytotoxicity. To extend this observation, six additional water-soluble nitroxides with different structural features were evaluated for potential radioprotective properties using Chinese hamster V79 cells and clonogenic assays. Nitroxides (10 mM) were added 10 min prior to radiation exposure and full radiation dose-response curves were determined. In addition to Tempol, five of the six nitroxides afforded in vitro radioprotection. The best protectors were found to be the positively charged nitroxides, Tempamine and 3-aminomethyl-PROXYL, with protection factors of 2.3 and 2.4, respectively, compared with Tempol, which had a protection factor of 1.3. 3-Carboxy-PROXYL, a negatively charged nitroxide, provided minimal protection. DNA binding characteristics as studied by nonequilibrium dialysis of DNA with each of the nitroxides demonstrated that Tempamine and 3-amino-methyl-PROXYL bound more strongly to DNA than did Tempol. Since DNA is assumed to be the target of radiation-induced cytotoxicity, differences in protection may be explained by variabilities in affinity of the protector for the target. This study establishes nitroxides as a general class of new nonthiol radioprotectors and suggests other parameters that may be exploited to find even better nitroxide-induced radioprotection.

Animals↗