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J Liu

Publications and source records attributed to J Liu.

At least 649 records · Page 36Linked to original sources
PubMed2000

Novel genomic imbalances in embryonal rhabdomyosarcoma revealed by comparative genomic hybridization and fluorescence in situ hybridization: an intergroup rhabdomyosarcoma study.

A comparative genomic hybridization (CGH) approach provides identification of genomic gains and losses in a tumor specimen in a single experiment. Only 11 embryonal rhabdomyosarcomas (E-RMS) have previously been subjected to CGH. The underlying genetic events in this histologic subtype are not well defined. In this investigation, 12 E-RMS specimens from 10 patients entered into Intergroup Rhabdomyosarcoma Study (IRS) I-IV and two local patients were analyzed by CGH and fluorescence in situ hybridization (FISH). Gains of chromosomes or chromosomal regions 2 (50%), 7 (42%), 8 (67%), 11 (42%), 12 (58%), 13q21 (33%), and 20 (33%) and losses of 1p35-36.3 (42%), 6 (33%), 9q22 (33%), 14q21-32 (25%), and 17 (25%) were most prominent. Chromosomal regions 1p35-36.3 and 9q22 represent novel regions of loss. Importantly, loss of 9q22 corresponds to the locus of a putative tumor suppressor gene (PTCH), which has been shown to play a role in rhabdomyosarcoma in a mouse model of Gorlin syndrome. Loss of 1p36 corresponds to the locus for PAX7, a paired box containing gene characteristically altered in alveolar rhabdomyosarcoma. Moreover, loss of 1p36 is prominent in another common pediatric soft tissue tumor, neuroblastoma. Gains of 2, 7, 8, 12, and 13 and loss of 14 were seen in the sole prior E-RMS CGH series; thus, these data provide important confirmatory results. In contrast to this previous study, however loss, not gain, of chromosome 17 was observed in the current study. Chromosome 17 loss correlates well with previous descriptions of frequent allelic loss of 17p (TP53) in E-RMS. In summary, CGH and FISH analyses of 12 E-RMS specimens revealed novel genomic imbalances that may be useful in directing further molecular studies for the determination of E-RMS critically involved genes.

Adolescent↗
PubMed2000

Effect of osmotic stress on the developmental competence of germinal vesicle and metaphase II stage bovine cumulus oocyte complexes and its relevance to cryopreservation.

The effects of osmotic stress on germinal vesicle (GV) and metaphase II (MII) stage bovine cumulus oocyte complexes (COCs) were evaluated by first exposing them to various anisotonic NaCl solutions (75, 150, 600, 1200, 2400, and 4800 +/- 5 mOsm/kg) for 10 min and then returning them to isotonic TL-Hepes solution (270 +/- 5 mOsm/kg) at 20 +/- 2 degrees C. Percentages of oocyte maturation, fertilization, polyspermy, cleavage, and blastocyst formation were measured as endpoints. Exposure to anisotonic conditions had a significant (P < 0.05) effect on the developmental competence of both GV and bovine MII COCs. Oocytes at the GV stage were more sensitive to anisotonic stress than MII oocytes (P < 0.05). None of the GV oocytes developed to the blastocyst stage after exposure to hypertonic conditions (2400 or 4800 mOsm solutions), while exposure to hypotonic conditions (75 or 150 mOsm solutions) resulted in significantly lower (P < 0.05) blastocyst formation (9% and 13%, respectively) compared to the isotonic control (25%). A dramatic decrease to 4% development to blastocyst was observed for MII oocytes following exposure to a 4800 mOsm solution. Blastocyst formation of MII oocytes which were exposed to 75, 150, 600, 1200, or 2400 mOsm solutions were similar (15%, 20%, 18%, 14%, and 13%, respectively; P > 0.05), but lower (P < 0.05) than those in the control group (29%). Exposing GV oocytes to anisotonic conditions increased polyspermic fertilization (P < 0.05), although MII oocytes were not similarly affected (P > 0.05). These data support the hypothesis that osmotic stress is detrimental to bovine oocytes and must be considered when developing optimized cryopreservation procedures for these cells. Mol. Reprod. Dev. 55:212-219, 2000.

Animals↗
PubMed2000

Inactivation of MMAC1 in bladder transitional-cell carcinoma cell lines and specimens.

We recently limited the location of a candidate tumor suppressor gene in invasive (T3a/b) bladder transitional-cell carcinoma (TCC) to a 2.5-cM region at chromosome 10q23.3. This region harbors the MMAC1/PTEN/TEP1 gene (referred to hereafter as MMAC1), a dual-phosphatase tumor-suppressor gene frequently inactivated in variety of malignant tumors. In the present study, we examined whether MMAC1 is a target for inactivation by mutations and deletions in bladder TCC cell lines and specimens. MMAC1 was inactivated by homozygous deletions and mutations in three (27%) of 11 bladder cancer cell lines. One cell line, UC-3, had homozygous deletions, and two other cell lines, T-24 and UC-9, had missense mutations. T-24 had also a nonsense mutation. However, none of the 33 bladder TCC specimens examined had a mutation or deletion in the coding region. These results suggest that MMAC1 is not the primary target for inactivation in bladder TCC and that another gene, in close proximity to the MMAC1 locus, within this region of frequent allelic losses, may be the target for inactivation.

Carcinoma, Transitional Cell↗
PubMed2000

Crystalline versus amorphous content of lumaxistrade mark analog XP280 using X-ray and electron diffraction methods.

In the course of the development of Lumaxistrade mark (roxifiban), the physical state of XP280 (the besylate salt of the active metabolites of roxifiban) and SC887 (the mesylate salt of the free base of roxifiban) were characterized. Powder X-ray diffraction patterns of XP280 were ambiguous in that a high degree of background signal was present and potentially indicative of the existence of an amorphous phase. Herein the results of combined synchrotron X-ray diffraction and electron microscopy (diffraction and imaging) studies on XP280 and SC887 are reported. The combination of these two techniques allowed an unambiguous assessment of the crystallinity, as well as determination of four of the unit cell parameters of XP280 and complete determination of the unit cell parameters for SC887.

Amidines↗
PubMed2000

Cell size and the morphogenesis of wing hairs in Drosophila.

Almost all epidermal cells on the Drosophila wing produce a single cuticular hair. This is formed in the pupae from a microvillus-like cell projection called the prehair. Previous experiments have shown the existence of two mechanisms that ensure that only a single hair is made. One is the restriction of prehair initiation to a small subregion of the cell by the action of the frizzled tissue polarity pathway. The second is a system that ensures the integrity of the prehair. Mutations and drugs that inhibit the actin cytoskeleton lead to the splitting of a single prehair into multiple smaller hairs. We report that large polyploid cells produce multiple hairs both because they form multiple independent prehair initiation centers and because the larger than normal hairs these cells produce have a tendency to split. We show that reducing cell size by starvation partially suppresses the phenotype seen in polyploid cells and that increasing apical cell surface area by mechanical stretching also results in the formation of multiple prehair initiation centers. We also show that the frizzled tissue polarity pathway is functional in large polyploid cells even if it is unable to restrict prehair initiation to a small region of the cell. We conclude that both of these cellular systems are limited in their ability to scale to accommodate larger cell size.

Animals↗
PubMed2000

Oncostatin M suppresses EGF-mediated protein tyrosine phosphorylation in breast cancer cells.

The effect of oncostatin M (OM) on epidermal growth factor (EGF)-mediated protein tyrosine phosphorylation in an infiltrating ductal breast carcinoma cell line, H3922, was investigated by Western blot analysis. Pretreatment of H3922 cells with OM for 72 h suppressed EGF-stimulated protein tyrosine phosphorylation signals by 77%. Interestingly, pretreatment with OM for 6 or 48 h had little effect on these signals. EGF-mediated tyrosine phosphorylation of EGF receptor (EGFR) was suppressed by 55% in 72-h OM pretreated H3922 cells. No reduction in EGFR protein expression was detected in these cells. Flow cytometric analysis verified that OM does not suppress EGFR expression. The effect of OM could not be attributed to induction of protein tyrosine phosphatases. An H3922 subclone cell line, designated H3922-8, was found to exhibit no proliferative response to treatment with EGF. However, EGF-mediated protein tyrosine phosphorylation was detected in these cells. Radioligand EGF binding studies comparing H3922 to H3922-8 cells indicated that the clonal cells apparently lack high affinity EGF receptors. The mechanism by which OM suppresses EGF-mediated tyrosine phosphorylation has not been completely characterized. However, the suppressive effect occurs regardless of whether the cells are acutely responsive (H3922) or virtually unresponsive (H3922-8) to EGF stimulation of cell growth.

Breast Neoplasms↗
PubMed2000

In vivo expression of the interleukin 4 receptor alpha by astrocytes in epilepsy cerebral cortex.

We reported previously that non-neoplastic astrocytes (derived from brain tissues of patients with epilepsy) expressed interleukin 4 receptor alpha (IL-4Ralpha) and responded to interleukin 4 (IL-4) in culture. To determine whether reactivity of cultured astrocytes was relevant to primary tissue, we investigated IL-4Ralpha expression in specimens of non-neoplastic cerebral cortex removed for surgical treatment of intractable epilepsy compared to specimens of glial tumours, which have been reported to contain IL-4Ralpha. Freshly frozen tissues from eight cases (four epilepsy, four malignant astrocytoma) were evaluated for IL-4Ralpha expression by reverse-transcriptase polymerase chain reaction (RT-PCR), Southern blotting, and double-labelled immunohistochemistry with antibodies to IL-4Ralpha and glial fibrillary acidic protein (GFAP). IL-4Ralpha mRNA was detectable in both non-neoplastic and neoplastic tissues, whereas interleukin 2 receptor gamma chain (IL-2Rgammac) mRNA was not found. By immunohistochemistry, IL-4Ralpha protein co-localized to cells displaying GFAP and astrocytic morphology in epilepsy tissues. As anticipated, IL-4Ralpha was detectable in astrocytoma, but, surprisingly, was also observed in GFAP-positive, non-neoplastic "reactive" astrocytes adjacent to tumour. Results are consistent with the concept that non-neoplastic epilepsy astrocytes express IL-4Ralpha in situ, thus confirming in vitro studies and implying IL-4 sensitivity in vivo.

Actins↗
PubMed2000

DNA/dendrimer complexes mediate gene transfer into murine cardiac transplants ex vivo.

Starburst polyamidoamine dendrimers are synthetic polymers with unique structural and physical characteristics suitable for DNA gene transfer. Our previous studies demonstrated that Starburst dendrimers augment plasmid-mediated gene transfer efficiency in a nonvascularized, cardiac transplantation model. In this study, the fifth generation of ethylenediamine core dendrimer was investigated for its ability to enhance gene transfer and expression in a clinically relevant murine vascularized heart transplantation model. The plasmid pMP6A-beta-gal, encoding beta-galactosidase (beta-Gal), was incubated with dendrimers to form complexes. The complexes were perfused via the coronary arteries during donor graft harvesting, and reporter gene expression was determined by quantitative evaluation of X-Gal staining. The grafts infused with pMP6A-beta-gal/dendrimer complexes showed beta-Gal expression in myocytes from 7 to 14 days. A number of variables for transfer of the DNA/dendrimer complexes were tested, including DNA:dendrimer charge ratios, concentrations of DNA and dendrimer, preservation solutions, ischemic time, and enhancement of vascular permeability by serotonin, papaverine, and VEGF administration. The results showed that DNA/dendrimer complexes containing 20 microg of DNA and 260 microg of dendrimer (1:20 charge ratio) in a total volume of 200 microl resulted in highest gene expression in the grafts. The results also showed that prolonged incubation (cold ischemic time) to 2 h and pretreatment with serotonin further enhanced gene expression.

Animals↗
PubMed2000

The change of interleukin-6 and tumor necrosis factor in patients with obstructive sleep apnea syndrome.

The levels of lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) expression in culture of peripheral blood mononuclear cells (PBMC) and the plasma levels of IL-6 and TNF-alpha in the patients with obstructive sleep apnea syndrome (OSAS) were measured and the relationship between OSAS and IL-6 or TNF-alpha expression studied. Both IL-6 and TNF-alpha were detected by using ELISA in 22 patients with OSAS and 16 normal controls. The levels of LPS-induced IL-6 (787.82 +/- 151.97 pg/ml) and TNF-alpha (4165.45 +/- 1501.43 pg/ml) expression in the supernatant of the culture of PBMC and plasma level of IL-6 (50.67 +/- 4.70 pg/ml) and TNF-alpha (299.09 +/- 43.57 pg/ml) in the patients with OSAS were significantly higher than those in the normal controls (in the supernatant of the culture of PBMC: 562.69 +/- 197.54 pg/ml and 1596.25 +/- 403.08 pg/ml respectively; in the plasma; 12.69 +/- 2.75 pg/ml and 101.88 +/- 21.27 pg/ml respectively). There were significantly positive correlation between the levels of IL-6 and TNF-alpha and the percentage of time of apnea and hyponea, as well as the percentage of time spending at SaO2 below 90% in the total sleep time. It was concluded that LPS-induced IL-6 and TNF-alpha levels as well as plasma IL-6 and TNF-alpha levels in the patients with OSAS were up-regulated, which may be associated with the pathogenesis of OSAS.

Adult↗
PubMed2000

Study on gastric empty disorder after the gastric ulcer healing and therapeutic effect of cisapride.

Gastric emptying time of liquid meal was detected by using ultrasonography in 28 gastric ulcer patients with continual or recurrent dyspepsia symptoms after the ulcer healing. Sixteen out of 28 patients (57.1%) with a delay of gastric emptying time (T1/2) were randomly divided into two groups: 8 cases were treated with cisapride 5 mg three times a day and 8 cases with cisapride 10 mg three times a day respectively. The results showed that cisapride could relieve the symptoms with the effective rate being 68.8% in the two groups. T1/2 in the patients after treatment with cisapride was significantly shorter than before treatment (P < 0.001). It was concluded that there is a delay of T1/2 in some patients with gastric ulcer healing. Cisapride could promote gastric empty of liquid meal and relieve the symptoms efficiently. The effect of lower dose of cisapride is similar to that of higher dose.

Adult↗
PubMed2000

Co-culture of early embryo with human decidual stromal cells in vitro by improvement of early embryo development.

An early embryo co-culture system with human decidual stromal cells was established to study its effect on early embryonic cleavage and growth in vitro. Three hundred and eight 2-cell mouse embryos were co-cultured with human decidual stromal cell monolayer in MEM + 0.4% bovine serum albumin (BSA) and 163 embryos cultured in MEM + 15% FCS alone as control. Among the mouse 2-cell embryos co-cultured with human decidual stromal cells, 72.73% developed to the morula stage and 67.21% cavitated to blastocysts with 59.74% hatching, as compared with 61.34% to morula stage, 48.47% to blastocysts and none hatching in the controls, respectively. Co-cultured embryos cleaved slightly faster than controls and showed no or less fragmentation than those in the control. These results suggested that human decidual stromal cells can support early embryonic development and yield a reasonable number of embryos with good quality up to blastocyst stage.

Adult↗
PubMed2000

Synthesis and characterization of stereospecific 1-propargyl-2-(dimethoxymethyl)-1-cyclohexanols.

Stereochemical isomers with hydroxy groups were synthesized by reacting 2-(dimethoxymethyl)cyclohexanone with propargylmagnesium bromide. The stereo chemical structures were identified by NMR spectral interpretation and the geometry optimization. To assist the NMR interpretation, geometry optimization based on semi-empirical AM1 and PM3 methods was applied. Throughout this study, the structures of the two isomers were all determined and 1H and 13C NMR spectra were fully assigned. It was proven that the less polar isomer is an axial alcohol and the more polar one is an equatorial alcohol.

Alkynes↗
PubMed2000

In-vitro antibacterial activities of cefpiramide and other broad-spectrum antibiotics against 440 clinical isolates in China.

The in-vitro antibacterial activity of cefpiramide was compared with those of 15 other broad-spectrum cephalosporins. A total of 440 clinical strains of bacteria, including 9 bacterial species, were isolated from our hospital in 1998. The minimum inhibitory concentrations (MICs) of cefpiramide and five other antibiotics were determined for each species, using the agar-dilution method. The MIC of cefpiramide for Escherichia coli and Klebsiella pneumoniae was higher than those of three other third-generation cephalosporins, (ie, cefoperazone, ceftazidime, and ceftriaxone). Fifty-one percent (26/51) of Enterobacter cloacae isolates were resistant to cefpiramide. Cefoperazone/sulbactam and cefepime had greater activity against E. cloacae (resistance, 3.9% and 19.6%, respectively) than cefpiramide. Cefpiramide was more active against Pseudomonas aeruginosa (resistance rates, 12%) than cefoperazone, ceftazidime, ceftriaxone, aztreonam, and cefepime. Cefpiramide-resistant P. aeruginosa strains were resistant to ceftazidime, but 27% of ceftazidime-resistant strains were susceptible to cefpiramide; 15.3% of cefpiramide-resistant S. maltophilia strains were also susceptible to ceftazidime, but 50% of ceftazidime-resistant strains were still susceptible to cefpiramide. Cefoperazone/sulbactam was the most active agent against Acinetobacter baumannii, showing a resistance rate of 2%. Ampicillin/sulbactam, ceftazidime, and cefpiramide were the second most active agents, and about 50% of the tested strains were susceptible to these three antibiotics. Cefpiramide had an activity comparable to that of all tested beta-lactams against oxacillin-susceptible Staphylococcus aureus (MIC90, 2 microg/ml). Against Streptococcus pneumoniae and Haemophilus influenzae, cefpiramide had good activity, with an MIC90 concentration at which 90% of the strain was inhibited of 1 microg/ml and 0.5 microg/ml, respectively. These results indicated that cefpiramide was more active against glucose non-fermenting bacteria than against Enterobacteriaceae, and was very active against oxacillin-susceptible Staphylo-coccus aureus, S. pneumoniae, and H. influenzae. Thus, cefpiramide may be a good choice of drug for the treatment of patients with infections with glucose non-fermenting bacteria and community acquired infections.

Cefazolin↗
PubMed2000

Effect of auranofin, an antirheumatic drug, on neutrophil apoptosis.

OBJECTIVE: The effects of auranofin (AF) on apoptosis and on the biological functions of neutrophils were investigated. METHODS: Neutrophils were incubated with various concentrations of AF for different periods. Cell viability was determined by the MTS assay and apoptosis was evaluated by flow cytometric analysis of propidium iodide (PI)- staining of the nuclei and annexin-V staining of phosphatidylserine in the cell membrane. The effect of AF on the expression of adhesion molecules (CD62L and CD11b/CD18) and on the generation of O2- by neutrophils was also determined. RESULTS: At a low concentration (1 microM), AF significantly prolonged neutrophil survival by delaying spontaneous apoptosis. Neutrophils incubated with AF for 12 and 24 hours maintained the capacity to express adhesion molecules and generate O2-. In contrast, a higher AF concentration (5 microM) shortened neutrophil survival by the induction of cell necrosis. CONCLUSION: Although the biological significance of inhibitory effect of AF on neutrophil apoptosis remains unclear, it seems to be unlikely that AF exerts the anti-inflammatory effect in vivo by directly suppressing neutrophil functions. Since AF has a wide range of effects on leukocytes, its therapeutic benefit in rheumatoid arthritis may be mediated in a complex manner.

Annexin A5↗
PubMed2000

Interleukin-13 sensitivity and receptor phenotypes of human glial cell lines: non-neoplastic glia and low-grade astrocytoma differ from malignant glioma.

Many of the actions and receptor components of interleukin-13 (IL-13), a pleiotrophic cytokine with immunotherapeutic potential, are shared with IL-4. Because human low-grade astrocytoma cells express IL-4 receptors and their growth is arrested by IL-4, we speculated that IL-13 sensitivity and receptor expression might also be present. The purpose of the current study was to investigate IL-13 receptor components and sensitivity in a series of glial cell lines derived from adult human non-neoplastic cerebral cortex, low-grade astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. Unlike peripheral blood lymphocytes (PBL), glial cells did not express IL-2 receptor gamma chain. IL-13 receptor alpha-1 (IL-13Ralpha1), however, was present in 11/13 glial lines and PBL. Deficient cell lines were all glioblastoma-derived. All anaplastic astrocytoma and glioblastoma but not other glial lines or PBL expressed IL-13 receptor alpha-2 (IL-13Ralpha2). In non-neoplastic glia, low-grade, and anaplastic astrocytoma, IL-13 decreased DNA synthesis, an effect reversible with antibody to IL-4Ralpha. Results indicate that low-grade astrocytoma cells resemble non-neoplastic glia in terms of IL-13 sensitivity and IL-4Ralpha/IL-13Ralpha1 receptor profile but alterations occur with malignant progression. Glioblastoma cells were uniformly insensitive to IL-13 and, unlike other glia, failed to phosphorylate STAT6 after IL-13 challenge. Data suggest that IL-13 and analysis of IL-13 receptors may have clinical application in glial tumors.

Astrocytoma↗
PubMed2000

The riboflavin-mediated photooxidation of doxorubicin.

PURPOSE: Previously, it was shown that exposing doxorubicin (ADR) to 365 nm light resulted in the loss of its cytotoxic activity as well as its absorbance at 480 nm. These processes were much enhanced when mediated by riboflavin. In the present study we investigated the quantitative and qualitative aspects of riboflavin-mediated photodegradation of ADR. METHODS: ADR solutions containing variable concentrations of riboflavin and other agents were exposed to 365 nm light for variable time periods and then the absorbance spectrum of ADR was measured by a double beam spectrophotometer. These measurements were used to calculate the half-time of the ADR degradation process. The degraded ADR solutions were analyzed by chromatography and mass spectrometry. RESULTS: Analysis of the riboflavin effect indicated that a maximal rate of photolytic degradation of ADR was obtained only after most of the ADR molecules had formed bimolecular complexes with riboflavin. The retardation of lumichrome formation by ADR and the inhibition of ADR bleaching by excess of ascorbic acid suggested that ADR was degraded by a photooxidation process. Similar spectral changes occurred when ADR was exposed to strong oxidizers such as sodium hypochlorite and dipotassium hexachloroiridate. Cyclic voltammetry revealed that the oxidation-reduction process of ADR was not electrochemically reversible and therefore the oxidation potential could not be determined accurately; however its value should be between 0.23 and 0.78 V. Analysis of the photooxidative process revealed that it was not mediated by the formation of singlet oxygen, superoxide anion radicals, hydrogen peroxide or hydroxyl radicals, and it is suggested that ADR was oxidized directly by the excited triplet riboflavin. The mass spectrograms and the HPLC chromatograms of photooxidized ADR indicate that the central ring of ADR was opened and that 3-methoxysalicylic acid was produced by this cleavage. CONCLUSIONS: The riboflavin-mediated photodegradation of ADR is an oxidative process resulting in the cleavage of the anthraquinone moiety. 3-Methoxysalicylic acid was identified as one of the resulting fragments. It is possible that some of the large fractions of the ADR metabolites that are non-fluorescent are the result of an in vivo oxidation of ADR and that 3-methoxysalicylic acid may play a role in the different biological activities of ADR.

Antibiotics, Antineoplastic↗
PubMed2000

Advanced glycation endproduct-modified superoxide dismutase-1 (SOD1)-positive inclusions are common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutations and transgenic mice expressing human SOD1 with a G85R mutation.

To clarify the biological significance of the neuronal Lewy body-like hyaline inclusions and astrocytic hyaline inclusions characteristically found in patients with familial amyotrophic lateral sclerosis with superoxide dismutase-1 (SOD1) gene mutations and in transgenic mice expressing human SOD1 with G85R mutation, the detailed protein composition in both types of inclusions was immunohistochemically analyzed using 45 different antibodies. Both types of inclusions had very strong immunoreactivity for SOD1. The SOD1-positive inclusions in both cell types were also immunoreactive for the insoluble advanced glycation endproducts (AGEs) such as Nepsilon-(carboxymethyl)lysine (CML), pyrraline and pentosidine: both inclusions in both conditions were ultrastructurally composed of the granule-coated fibrils that had immunoreactivities to CML and pyrraline. Both types of inclusions were negative for stress-response proteins (SRPs), 4-hydroxy-2-nonenal (HNE), acrolein, nitric oxide synthases (NOSs) and nitrotyrosine as representative markers of oxidative stress. The neurons and astrocytes of the normal individuals and non-transgenic mice showed no significant immunoreactivity for SOD1, AGEs, SRPs, HNE, acrolein, NOSs or nitrotyrosine. Our results suggest that a portion of the SOD1 composing both type of inclusions, probably toxic mutant SOD1, is modified by the AGEs, and that the formation of the AGE-modified SOD1 is one of the mechanisms responsible for the aggregation involving no significant oxidative mechanisms.

Adult↗