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Biomedical subjects

Y Zou

Publications and source records attributed to Y Zou.

At least 199 records · Page 11Linked to original sources
PubMed1995

Comparison of four methods to generate immunoreactive fragments of a murine monoclonal antibody OC859 against human ovarian epithelial cancer antigen.

In the present study, four different proteases (pepsin, papain, bromelain and ficin) were screened with a murine monoclonal antibody OC859, in order to verify whether different digestion procedures could improve yield and stability of the F(ab')2 or Fab fragments. The yields of F(ab')2 or Fab fragments from digestion with pepsin, papain, bromelain and ficin were respectively 20.3 +/- 2.0%, 50.5 +/- 5.0%, 74.4 +/- 2.7% and 82.8 +/- 10.2% of the theoretical maximum. Immunoreactivity in a noncompetitive solid-phase radioimmunoassay (SPRIA) of the fragments generated by the four proteases were respectively 10 +/- 5%, 36 +/- 5%, 60 +/- 6% and 75 +/- 6% of the intact OC859 IgG. These results suggested that the fragmentation of OC859 with ficin gave a higher yield of superior immunoreactive fragments.

Animals↗
PubMed1995

Nd: YAG laser lysis of the fibrinous membrane and remnant substance on the anterior surface of intraocular lens.

PURPOSE: To determine the effects of Nd: YAG laser to disrupt the fibrinous membrane and remnant substance on the anterior surface of intraocular lens. METHODS: Nd: YAG laser was applied on 23 cases of fibrinous membrane formation and 8 cases of remnant substance on the anterior surface of intraocular lenses (IOL) which had not responded well to steroid therapy. Eighteen cases were male and 13 female. The mean age was 49.7 years (range, 5 approximately 78 years). The interval between IOL implantation and laser therapy was 0.5 approximately 30 months in the fibrinous membrane cases and 3 approximately 10 days in the remnant substance cases. The energy applied was 0.8 approximately 3.0 mJ/exp. with 2 approximately 112 exposures. Mean follow-up period was 3.6 months. RESULTS: Complications during therapy included only 2 cases of slight iris bleeding. Visual acuity after therapy was improved 1 line in 16 cases, 2 lines in 11 cases, 3 lines in 1 case, 4 lines in 1 case and 5 lines in 2 cases. No post-therapy complication was found. CONCLUSIONS: Nd: YAG laser lysis is an effective alternative to remove the fibrinous membrane and remnant substances on the anterior surface of IOL.

Adolescent↗
PubMed1995

Primary posterior chamber intraocular lens implantation in traumatic cataract with posterior capsule breaks.

BACKGROUND: In patients with incomplete posterior capsule support, posterior chamber intraocular lenses (PC-IOLs) were implanted with both haptics transscleral fixation. This causes more damage to the eye and may result in more complications. In patients with small posterior breaks, non-fixation or single haptic fixation may be adequate. METHODS: Thirty-two consecutive patients of traumatic cataract with posterior capsule breaks caused by penetrating eye trauma were retrospected. Posterior chamber intraocular lenses were implanted in all these patients with three techniques, ie, without fixation, with single haptic fixation and with both haptics fixation. The selection of the technique was based on the position and size of the posterior capsule. The follow-up period was 21 days to 28 months (mean, 15.2 months). RESULTS: Intra-operative problems included ciliary body bleeding (two patients, 6.25%) and enlargement of posterior capsule breaks (2 patients, 6.25%). Postoperative visual acuity was 0.5 or better (corrected) in 28 case (87.5%) and 0.1-0.4 in four patients (12.5%). Postoperative complications included hyphema (6 eyes, 18.8%), transient intraocular pressure elevation (6 eyes, 18.8%), transient hypotention (7 eyes, 21.8%). Postoperative IOL position were good except one case of IOL tilt. No pupillary capture or endophthalmitis was found. CONCLUSIONS: Not all PC-IOLs have to be fixed by two haptics. In patients with small posterior capsule breaks, PC-IOL may not be fixed or fixed by only one haptics.

Adolescent↗
PubMed1995

Preclinical toxicity of liposome-incorporated annamycin: selective bone marrow toxicity with lack of cardiotoxicity.

Annamycin (Ann) is a new lipophilic anthracycline antibiotic with a marked ability to circumvent typical multidrug resistance both in vitro and in vivo. Because of its high affinity for lipid membranes and very low solubility in water, Ann has been prepared in a submicron liposome formulation (L-Ann) that is currently being investigated in a Phase I clinical study. We studied the preclinical toxicity of L-Ann in mice and beagle dogs and compared it with that of free Ann in suspension and the parent compound doxorubicin (Dox). In mice, free Ann was about twice as toxic as Dox (LD50 after a single i.v. bolus administration, 8.8 versus 19.9 mg/kg; P < 0.01). The liposomal carrier reduced Ann toxicity by 2-fold (LD50, 15.74 mg/kg for L-Ann versus 8.8 mg/kg for free Ann; P < 0.01). Granulocytopenia was the main toxicity of Ann, either free or liposome incorporated, and was much more profound than with an equitoxic dose of Dox as assessed by blood counts and pathological studies. In chronic mouse studies, L-Ann was remarkably less cardiotoxic than Dox. Cumulative toxicity with the weekly administration of a given fraction of the subacute LD10 was markedly higher with Dox than with L-Ann as assessed by body weight and mortality studies. L-Ann also had less vesicant toxicity than Dox after intradermal administration in mice. Beagle dogs tolerated the mouse-equivalent LD10 dose of L-Ann (1.4 mg/kg) with no side effects, changes in the hematological and biochemical blood parameters, or pathological changes. Our results indicate that: (a) L-Ann is more selectively myelotoxic than Dox and is noncardiotoxic; (b) the liposome carrier plays a major role in the favorable toxicity profile of L-Ann; and (c) the standard one-tenth of the LD10 should be a safe starting dose for Phase I clinical trials with L-Ann in humans.

Animals↗
PubMed1994

Sequence specificity of DNA-DNA interstrand cross-link formation by cisplatin and dinuclear platinum complexes.

The sequence specificity of interstrand cross-links induced in DNA by mononuclear and dinuclear platinum complexes in a 49-base-pair DNA duplex has been determined directly. This new assay takes advantage of the fact that 3'-->5' exonuclease digestion of randomly platinated DNA produces a pool of fragments of different lengths. This treatment allows identification of the spectrum of adducts impeding the exonuclease scission. Interstrand cross-linked adducts produce fragments that may remain complementary in the proximity of the binding site. As a result, these fragments may act as primer templates for extension upon subsequent treatment with a DNA polymerase. This extension increases the size of the oligonucleotide fragments, which may be evidenced by a more slowly migrating band on a sequencing gel. Concomitantly, the original band corresponding to the digested cross-link decreases in intensity. Therefore, comparison of a sequencing gel after digestion only and after the "digestion-extension" treatment should show the disappearance, or diminished band intensity, of only those fragments with interstrand cross-links. This approach was applied to the analysis of DNA interstrand cross-links formed by cis-[PtCl2(NH3)2] (cis-DDP) and [(trans-PtCl(NH3)2)2H2N(CH2)4NH2]Cl2. Cis-DDP was confirmed to form interstrand cross-links at d(GC) sequences but, interestingly, interstrand cross-links predominated in a sequence GCGG, with possible 1,3-intrastrand but no 1,2-intrastrand cross-links forming. The dinuclear compound formed 1,2, 1,3, and 1,4 DNA interstrand cross-links between guanines on opposite strands. In 1,3 and 1,4 cross-links, the guanines are separated by one and two base pairs, respectively, whereas a 1,2 cross-link is formed from guanines on neighboring base pairs.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Antitumor activity of free and liposome-entrapped annamycin, a lipophilic anthracycline antibiotic with non-cross-resistance properties.

The lipophilic anthracycline antibiotic annamycin (Ann) was entrapped in liposomes of different size [median diameter: 1.64 microns, multilamellar liposomal Ann (L-Ann); 0.030 micron, small unilamellar Ann (S-Ann)] with > 90% entrapment efficiency and tested in vitro against four pairs of sensitive and multidrug-resistant (MDR) tumor cell lines and in vivo by the i.v. route in five tumor models: advanced s.c. B16 melanoma; s.c. M5076 reticulosarcoma; lung metastases of Lewis lung carcinoma; and s.c. KB and KB-V1 xenografts in nude mice. Predetermined optimal doses of the different formulations were used and the results were compared with doxorubicin (Dox). In vitro, Ann, either in suspension in 10% dimethyl sulfoxide (F-Ann) (1 mg/ml) or entrapped in liposomes, was able to partially overcome resistance in all four pairs of sensitive and MDR KB, 8226, P388, and CEM cell lines (resistance indexes 63, 269, 333, and 356 for Dox versus 4, 5, 19, and 8.7 for L-Ann, respectively). In vivo, both F-Ann and liposome-entrapped Ann were slightly more effective than Dox in inhibiting the growth of advanced s.c. B16 melanoma tumors. L-Ann was markedly more effective than Dox and moderately more effective than F-Ann in prolonging the life span of animals bearing s.c. M5076 and lung metastases of Lewis lung carcinoma tumors. All drugs were equally effective at optimal doses in delaying the growth of s.c. KB xenografts, whereas all Ann formulations were markedly more effective than Dox in delaying the growth of s.c. KB-V1 (MDR) xenografts. In all in vivo experiments, S-Ann was consistently more effective than L-Ann and L-Ann was more effective than F-Ann. These results indicate that (a) Ann is more effective than Dox by the i.v. route against several tumor models and that MDR tumors are partially not cross-resistant to Ann both in vitro and in vivo, (b) liposomes enhance the in vivo antitumor properties of Ann, and (c) small liposomes are more effective than large liposomes in enhancing Ann antitumor activity.

Animals↗
PubMed1994

Cellular pharmacology of the partially non-cross-resistant anthracycline annamycin entrapped in liposomes in KB and KB-V1 cells.

The in vitro cytotoxicity, cellular pharmacology, and DNA lesions induced by the lipophilic anthracycline annamycin (Ann) were studied in KB and KB-V1 (multidrug-resistant) cells. Ann was tested in suspension in saline and 10% dimethylsulfoxide (DMSO: final concentration, 0.05%-0.5%) or entrapped in multilamellar liposomes (median size, 1.57 microns). Doxorubicin (Dox) was about twice as cytotoxic as Ann or liposome-entrapped Ann (L-Ann) against KB cells. Both Ann and L-Ann displayed a partial lack of cross-resistance with Dox (resistance indices: > 60 for Dox, 4.7 for Ann, 4.0 for L-Ann). Accumulation of Ann in KB and KB-V1 cells was consistently about 2-3 and 10-20 times higher, respectively, than that of Dox. Cellular retention of Ann in KB and KB-V1 cells was about 2 and 30 times higher, respectively, than that of Dox as a result of the different efflux patterns of the two drugs: Dox was not effluxed from KB cells but was significantly effluxed from KB-V1 cells (66% at 1 h, whereas Ann efflux was similar in both cell lines (about 50% at 1 h). Dox retention in KB-V1 cells was increased by a factor of 2 in the presence of verapamil or cyclosporine A, but Ann retention was not. In addition, accumulation of Dox in KB-V1 cells was enhanced by the metabolic inhibitor deoxyglucose/azide and the membrane carboxylic ionophore monensin, whereas accumulation of Ann was not affected by either agent. All these findings indicate significant differences in the cellular transmembrane transport systems between Dox and Ann and suggest that Ann efflux is not mediated by P-glycoprotein. Liposome entrapment reduced by a factor of 1.3-2.0 the cellular accumulation of Ann without affecting its cytotoxicity. As compared with Dox, both Ann and L-Ann induced 3 times more DNA double- and single-strand breaks in KB cells. In KB-V1 cells, Dox did not induce DNA damage, whereas the extent of DNA breaks induced by both Ann and L-Ann was similar to that induced by Dox in KB cells. Our results indicate (1) that the lack of cross-resistance between Ann and Dox is associated with a markedly enhanced accumulation and retention of Ann in KB-V1 cells and (2) that the type of liposomes used does not significantly affect the cellular effects of Ann.

Antibiotics, Antineoplastic↗
PubMed1993

Ligand effects on platinum binding to DNA. A comparison of DNA binding properties for cis- and trans-[PtCl2(amine)2] (amine = NH3, pyridine).

The DNA binding properties of cis- and trans-[PtCl2(pyridine)2] have been examined and compared with their NH3 analogs, cis- and trans-DDP. The presence of a planar ligand reduces the rates of DNA binding but does not greatly affect the overall conformation of CT DNA, as measured by circular dichroism spectroscopy. The sequence specificity of trans-[PtCl2(py)2] includes alternating purine-pyrimidine sequences. The sequence specificity is further different between the two pyridine isomers, and the steric effects of two cis-pyridine groups are demonstrated by the appearance of relatively few binding sites in the 49-bp duplex. The effects of the pyridine ligand are further manifested by a greatly enhanced DNA-DNA interstrand cross-linking efficiency for the trans isomer, with a cross-link per adduct frequency of between 0.14 and 0.23, depending on the rb of the sample. The unwinding of closed circular pUC19 DNA by trans-[PtCl2(pyridine)2] is also more efficient than that by either DDP isomer, with an unwinding angle calculated at phi = 17 degrees (compare cis-DDP with phi = 13 degrees and trans-DDP with phi = 9-10 degrees). In contrast, little unwinding is induced by cis-[PtCl2(pyridine)2], with phi = 4 degrees. These results in particular invert the standard cis/trans structure-activity relationships observed previously for [PtCl2(NH3)2]. The results are discussed with respect to the previously demonstrated effect of activation of the trans-platinum geometry using sterically hindered ligands.

Base Sequence↗
PubMed1993

Enhanced therapeutic effect against liver W256 carcinosarcoma with temperature-sensitive liposomal adriamycin administered into the hepatic artery.

The antitumor activity of Adriamycin encapsulated in temperature-sensitive liposomes combined with local hyperthermia (HT) was tested in rats bearing well-developed liver W256 carcinosarcoma tumors. Two h after rats received Adriamycin encapsulated in temperature-sensitive liposomes via either the hepatic artery (i.a.) or the femoral vein (i.v.) or free Adriamycin i.a., liver HT was applied at 42 degrees C for 6 min. In animals treated with liposomal Adriamycin i.a., HT resulted in a 38% reduction in the tumor volume ratio and a 2.2-fold increase in the life span of the animals. In animals treated with liposomal Adriamycin i.v. or free Adriamycin i.a., HT did not alter the tumor volume ratio or life span of the animals. Administration i.a. of liposomal Adriamycin markedly increased the tumor drug levels (4-14-fold), reduced the systemic distribution of the drug, and slowed the drug decrease from both the tumor and liver compared with animals treated i.v.. Liver HT in animals treated with liposomal Adriamycin i.a. further increased tumor drug levels by 1.5-2.6-fold, further slowed the drug decrease from the tumor, and resulted in a dissociation of the parallel decrease of drug and lipid from the tumor. This latter effect was not observed in the other groups. These pharmacological findings combined with the lack of beneficial effect from HT in animals treated with free Adriamycin i.a. or liposomal Adriamycin i.v. suggest that i.a. administration of Adriamycin encapsulated in temperature-sensitive liposomes results in a significant retention of intact liposomes in the tumor vasculature that are able to release the encapsulated drug into the tumor cell compartment upon raising the temperature to the phase transition level.

Animals↗
PubMed1993

Near-infrared spectrophotometric monitoring of stroke-related changes in the protein and lipid composition of whole gerbil brains.

Strokes are a critical problem in the U.S. that affect more than 500,000 people annually. Research into the causes of stroke and testing of drug therapies to reduce ischemic and postischemic damage to the brain is frustrated by an inability to continuously follow the physical and chemical events that occur during ischemia and reperfusion in vivo. Near-IR spectrometry is used in this paper to observe stroke-induced changes in the lipids and proteins of whole brain samples and in intact subjects. The examination of whole brains is made possible by a combination of hardware and software techniques designed to make the sample presentation to the spectrometer more reproducible. Near-IR spectrophotometry of brain tissue discriminates between adult (3-4 months of age) and aged (18-20 months of age) brains as well as between brains exposed to 5- and 10-min ischemia. The near-IR analytical method has many applications in aging and stroke research, including the noninvasive determination of age from brain spectra obtained transcranially, simultaneous multicomponent analysis of lipids and proteins, and quantification of edema.

Aging↗