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Biomedical subjects

W W Li

Publications and source records attributed to W W Li.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of visual acuity outcomes in predominantly classic vs occult lesions in age-related macular degeneration treated with photodynamic therapy.

PURPOSE: To determine if patients with occult with no classic and predominantly classic (PC) choroidal neovascular membranes have clinically equivalent visual outcomes after treatment with photodynamic therapy (PDT) with verteporfin. METHODS: This is a retrospective, observational cohort study. Two hundred and seventy-seven consecutive patients with occult or PC choroidal neovascularization secondary to age-related macular degeneration treated with PDT were included. The main outcome was the difference in mean change in Early Treatment of Diabetic Retinopathy Study (ETDRS) acuity lost from baseline in occult vs PC lesions, with the minimal clinically important difference (MCID) set at 7.5 letters. RESULTS: At baseline, 131 patients had occult and 146 had PC choroidal neovascularization. Twelve-month follow-up data were available for 94 occult and 110 PC participants. Occult patients lost an average of 8.7 letters (1.9 lines), and patients in the PC group an average of 10.0 ETDRS letters (two lines) over 12 months. The mean letters lost at 12 months was not significantly different between the groups, and the MCID was not detected (difference=1.3 letters; P=0.411; 95% confidence interval (-2.3, 5.6)). Patients with occult lesions required a mean of 2.99 treatments vs a mean of 2.96 treatments in the PC group (out of a possible 4; P=0.172). CONCLUSION: We were not able to detect a clinically important difference in mean change in visual acuity with PDT treatment between patients with occult and PC lesions.

Aged↗
PubMed2004

Pharmaceutical care and community pharmacists' understanding of bisphosphonate dosing information.

OBJECTIVES: To evaluate pharmacists' knowledge of approved dosing information for cyclic etidronate, alendronate and risedronate in the treatment of postmenopausal osteoporosis; and to assess its relationship to demographic and pharmaceutical care factors. DESIGN: Fax-back questionnaire to evaluate pharmacists' knowledge of approved bisphosphonate dosing information and their involvement in pharmaceutical/patient care activities through independent indices. SETTING: Community pharmacies in both urban and rural settings in British Columbia. PARTICIPANTS: Pharmacies surveyed with 22% response rate (163 pharmacists), 47% male and 54% owners/managers. Most were independent (31%) or volunteer chain (28%) pharmacies. MEASUREMENTS AND MAIN RESULTS: Mean bisphosphonate dosing knowledge score was 76 +/- 11% (mean +/- SD). Mean scores (+/-SD) for questions pertaining to alendronate (92 +/- 13%) were higher than risedronate (81 +/- 26%) and etidronate (48 +/- 19). Pharmacists were least familiar with approved dosing instructions regarding the lack of need to remain upright after etidronate dosing, spacing out of etidronate from food/antacids/calcium/vitamins, and whether risedronate may be taken at bedtime. Factors found to affect pharmacists' bisphosphonate knowledge scores included employment in higher volume pharmacies and greater number of years in practice. Pharmacists in the upper tertile of pharmaceutical care index scores had similar bisphosphonate knowledge scores to those delivering less pharmaceutical care. Pharmacist gender, being owner/manager, and continuing education hours were not significantly associated with higher knowledge or pharmaceutical care scores. CONCLUSIONS: There is a wide range of knowledge of bisphosphonate dosing and delivery of pharmaceutical care amongst community pharmacists surveyed. Given the importance of proper bisphosphonate dosing to optimize drug absorption and to minimize toxicity, pharmacist education should be a priority.

Alendronate↗
PubMed2004

The role of MAP kinases in rapid gene induction after lesioning of the rat sciatic nerve.

Lesion of the sciatic nerve caused a rapid activation of p38MAP kinase in the injured nerve adjacent to the site of transection. This activation was detectable 3 min after lesioning, increased during the next 15 min and remained high for several hours. Erk1/2 activation was also observed as early as 15 min after lesioning. Activation of these MAP kinases was seen in both the external sheaths and the endoneurium. The separation of the external sheaths from the endoneurium accelerated the p38MAP kinase activation. To evaluate whether the injury-activated MAP kinase cascades are implicated in the rapid gene induction observed after nerve lesion, experiments were performed with an ex vivo model. Segments of sciatic nerves were incubated in oxygenated Krebs-Ringer buffer. MAP kinases were activated at 15 min and remained active after 6 h. Induction of mRNA was also observed for nerve growth factor (NGF), interleukin 6 (IL-6), leukaemia inhibitory factor (LIF) and deiodinases of type 2 (D2) and type 3 (D3). Thus, the ex vivo model mimics events occurring in the animal after nerve section. Finally, nerve segments were incubated in the presence of specific inhibitors of Erk1/2 activation (U0126) and of p38MAP kinase activity (SB203580). U0126 inhibited D3, LIF and to a lesser extent NGF mRNA induction, but did not affect significantly the induction of D2 and IL-6 mRNAs. SB203580 inhibited the expression of the genes for D3 and LIF. We conclude that MAP kinase cascades, activated by nerve transection, are involved in the rapid gene induction in the nerve.

Animals↗
PubMed2001

Proliferation and apoptosis in the epithelium of the developing human cornea and conjunctiva.

To determine the distribution of proliferating and apoptotic cells in the human cornea during prenatal and early postnatal development, we examined sections of the bulbar conjunctiva, the limbus as well as the central and peripheral cornea between 11 weeks of gestation and 6 months after birth. The objective was to localize dividing cells by proliferating cell nuclear antigen-like immunoreactivity (PCNA-LI) and apoptotic cells by terminal transferase-mediated nick-end labeling (TUNEL). Before the 17th gestational week, PCNA-LI was absent in all 4 regions examined, indicating negligible cell proliferation during early development. After 20 weeks, strong PCNA-labeling was observed in all regions examined suggestive of high proliferative activity not only in the limbus and the bulbar conjunctiva, but also in the central and peripheral cornea. This rise in proliferative activity was followed by a steady decline: after 28 weeks, anti-PCNA staining gradually disappeared in the central and peripheral cornea, so that, at 6 months after birth, it was confined to the limbus and the bulbar conjunctiva, resembling the picture described for the adult cornea. TUNEL-positive cells were virtually absent in all 4 regions examined before the 38th gestational week. Apoptotic cells only started to appear at 38 weeks; at this stage, they were confined to the bulbar conjunctival epithelium. At 6 months after birth, TUNEL-positive cells were observed in the bulbar conjunctival epithelium and the entire cornea; the limbus, however remained devoid of apoptotic cells throughout the entire prenatal and early postnatal period. The present study for the first time localizes proliferating and apoptotic cells in the epithelium of the developing human cornea. Three stages of development can be distinguished: Minimal proliferation (until 17th week), vigorous proliferation over the entire cornea including the limbus and the bulbar conjunctiva (until 28th week) and gradual decrease in proliferative activity (after 28th week) accompanied by the appearance of apoptotic cells.

Aging↗
PubMed2001

Conserved key amino acid positions (CKAAPs) derived from the analysis of common substructures in proteins.

An all-against-all protein structure comparison using the Combinatorial Extension (CE) algorithm applied to a representative set of PDB structures revealed a gallery of common substructures in proteins (http://cl.sdsc.edu/ce.html). These substructures represent commonly identified folds, domains, or components thereof. Most of the subsequences forming these similar substructures have no significant sequence similarity. We present a method to identify conserved amino acid positions and residue-dependent property clusters within these subsequences starting with structure alignments. Each of the subsequences is aligned to its homologues in SWALL, a nonredundant protein sequence database. The most similar sequences are purged into a common frequency matrix, and weighted homologues of each one of the subsequences are used in scoring for conserved key amino acid positions (CKAAPs). We have set the top 20% of the high-scoring positions in each substructure to be CKAAPs. It is hypothesized that CKAAPs may be responsible for the common folding patterns in either a local or global view of the protein-folding pathway. Where a significant number of structures exist, CKAAPs have also been identified in structure alignments of complete polypeptide chains from the same protein family or superfamily. Evidence to support the presence of CKAAPs comes from other computational approaches and experimental studies of mutation and protein-folding experiments, notably the Paracelsus challenge. Finally, the structural environment of CKAAPs versus non-CKAAPs is examined for solvent accessibility, hydrogen bonding, and secondary structure. The identification of CKAAPs has important implications for protein engineering, fold recognition, modeling, and structure prediction studies and is dependent on the availability of structures and an accurate structure alignment methodology. Proteins 2001;42:148-163.

Algorithms↗
PubMed2001

CKAAPs DB: a conserved key amino acid positions database.

The Conserved Key Amino Acid Positions DataBase (CKAAPs DB) provides access to an analysis of structurally similar proteins with dissimilar sequences where key residues within a common fold are identified. The derivation and significance of CKAAPs starting from pairwise structure alignments is described fully in Reddy et al. [Reddy,B.V.B., Li,W.W., Shindyalov,I.N. and Bourne,P.E. (2000) PROTEINS:, in press]. The CKAAPs identified from this theoretical analysis are provided to experimentalists and theoreticians for potential use in protein engineering and modeling. It has been suggested that CKAAPs may be crucial features for protein folding, structural stability and function. Over 170 substructures, as defined by the Combinatorial Extension (CE) database, which are found in approximately 3000 representative polypeptide chains have been analyzed and are available in the CKAAPs DB. CKAAPs DB also provides CKAAPs of the representative set of proteins derived from the CE and FSSP databases. Thus the database contains over 5000 representative poly-peptide chains, covering all known structures in the PDB. A web interface to a relational database permits fast retrieval of structure-sequence alignments, CKAAPs and associated statistics. Users may query by PDB ID, protein name, function and Enzyme Classification number. Users may also submit protein alignments of their own to obtain CKAAPs. An interface to display CKAAPs on each structure from a web browser is also being implemented. CKAAPs DB is maintained by the San Diego Supercomputer Center and accessible at the URL http://ckaaps.sdsc.edu.

Algorithms↗
PubMed2001

Indocyanine green staining and removal of internal limiting membrane in macular hole surgery: histology and outcome.

PURPOSE: To report the surgical technique, outcome, and histologic findings involving indocyanine green staining and removal of internal limiting membrane in primary macular hole surgery. METHODS: Prospectively, consecutive patients with idiopathic macular hole or myopic macular hole with retinal detachment were recruited. After pars plana vitrectomy and epiretinal membrane removal, the internal limiting membrane was stained and removed. The specimens were stained using hematoxylin and eosin and periodic acid-Schiff. Immunohistochemical staining was also performed for glial fibrillary acidic protein, vimentin, type I and type IV collagen, and actin. RESULTS: Among 10 patients (10 eyes) in the study, nine eyes had stage 3 or 4 macular hole. Four of them had chronic macular hole. The tenth patient had retinal detachment resulting from a myopic macular hole. Postoperatively, all cases had closure of macular hole without an elevated edge and the retina was attached. Seven patients had improvement of 2 or more Snellen lines, whereas visual acuity remained the same for the other three patients. In six eyes in which complete histologic examinations were feasible, internal limiting membrane was confirmed and two eyes also had a small amount of epiretinal membrane. Myofibrocytes in internal limiting membrane, either scattered or as a single layer, were found in three cases. CONCLUSIONS: Removal of indocyanine green--stained internal limiting membrane around idiopathic macular hole or myopic macular hole with retinal detachment is confirmed with histology and may contribute to macular hole closure and retinal reattachment.

Actins↗
PubMed2001

Angiotensin II increases urokinase-type plasminogen activator expression and induces aneurysm in the abdominal aorta of apolipoprotein E-deficient mice.

Urokinase-type plasminogen activator (uPA) is increased in human abdominal aortic aneurysm (AAA). Chronic infusion of angiotensin II (Ang II) results in AAA in apolipoprotein E-deficient mice. We tested the hypothesis that Ang II infusion results in an elevation of uPA expression contributing to aneurysm formation. Ang II or vehicle was infused by osmotic pumps into apoE-KO mice. All mice treated with Ang II developed a localized expansion of the suprarenal aorta (75% increase in outer diameter), accompanied by an elevation of blood pressure (22 mmHg), compared to the vehicle-treated group. Histological examination of the dilated aortic segment revealed similarities to human AAA including focal elastin fragmentation, macrophage infiltration, and intravascular hemorrhage. Ang II treatment resulted in a 13-fold increase in the expression of uPA mRNA in the AAA segment in contrast to a twofold increase in the atherosclerotic aortic arch. Increased uPA protein was detected in the abdominal aorta as early as 10 days after Ang II infusion before significant aorta expansion. Thus, Ang II infusion results in macrophage infiltration, increased uPA activity, and aneurysm formation in the abdominal aorta of apoE-KO mice. These data are consistent with a causal role for uPA in the pathogenesis of AAA.

Angiotensin II↗
PubMed2001

Type 2 deiodinase in the peripheral nervous system: induction in the sciatic nerve after injury.

Thyroid hormones are essential for the development and function of the brain and also for the maturation and repair of the peripheral nervous system. In the brain, most of the 3,5,3'-triiodothyronine is locally produced by 5'-deiodination of thyroxine catalyzed by the type 2 deiodinase. The absence of any information about thyroid hormone metabolism in the peripheral nervous system prompted us to study the expression of type 2 deiodinase (mRNA and activity) in the peripheral nervous system. Expression of type 2 deiodinase mRNA was very low in the sciatic nerve of rats until day 5 after birth, then increased from day 10 to 35-45 and gradually decreased afterwards, down to the low basal levels observed in the adult. A lesion of the sciatic nerve in the adult induced an increase in type 2 deiodinase mRNA and activity. After a cryolesion, the stimulation was observed as early as 4 h and mRNA levels increased until 24-48 h, then gradually declined down to basal levels around 28 days, when regeneration and functional recovery were completed. After a permanent transection, up-regulation of type 2 deiodinase persisted in both proximal and distal segments until the end of the experiment (28 days). Transection and cryolesion were also followed by increased type 2 deiodinase mRNA expression in the ipsilateral L4/L6 dorsal root ganglia within 24 h. Both mRNA and activity were found in the peripheral nerve sheaths but not in the internal compartment of the intact or injured nerve. Cultured fibroblasts from the sciatic nerve expressed type 2 deiodinase 4 h after stimulation by 10 microM forskolin, whereas purified Schwann cells did not. The present study provides evidence that the peripheral nervous system has its own system responsible for the local production of 3,5,3'-triiodothyronine, which may play a key role during the regeneration process.

Aging↗
PubMed2001

Analysis of temporal and spatial dichotomous PM air samples in the El Paso-Cd. Juarez air quality basin.

This paper presents and discusses the results obtained from the gravimetric and chemical analyses of the 24-hr average dichotomous samples collected from five sites in the El Paso-Cd. Juarez air quality basin between August 1999 and March 2000. Gravimetric analysis was performed to determine the temporal and spatial variations of PM2.5 (particulate matter less than 2.5 microm in diameter) and PM25-10 (particulate matter less than 10 pm but greater than 2.5 microm in diameter) mass concentrations. The results indicate that approximately 25% of the PM10 (i.e., PM25 + PM25-10) concentration is composed of PM2.5. Concurrent measurements of hourly PM concentrations and wind speed showed strong diurnal patterns of the regional PM pollution. Results of X-ray fluorescence (XRF) elemental analyses were compared to similar but limited studies performed by the Texas Natural Resource Conservation Commission (TNRCC) in 1990 and 1997. Major elements from geologic sources-Al, Si, Ca, Na, K, Fe, and Ti-accounted for 35% of the total mass concentrations in the PM2.5-10 fraction, indicating that geologic sources in the area are the dominant PM sources. Levels of toxic trace elements, mainly considered as products of anthropogenic activities, have decreased significantly from those observed in 1990 and 1997.

Air Pollutants↗
PubMed2001

Association of human beta-herpesviruses with the development of cervical cancer: bystanders or cofactors.

BACKGROUND/AIM: Human papillomaviruses (HPVs) are important, but not sufficient, for the development of cervical cancer. All three human beta-herpesviruses--cytomegalovirus (CMV) and human herpesviruses (HHV) types 6 and 7--have been detected in the cervix. In addition, CMV and HHV-6 can interact with HPVs in vivo. This study examined the possible role of beta-herpesviruses in cervical cancer development. METHODS: HPV, CMV, HHV-6, and HHV-7 were detected by the polymerase chain reaction using cervical scrapes taken at colposcopy from 388 women. HPV types were identified using restriction fragment length polymorphisms. Colposcopy guided biopsies were taken from abnormal areas, and the histological findings were regarded as the final diagnoses. The associations between herpesvirus infection and the degree of cervical lesion were analysed with respect to HPV status. RESULTS: Of the 388 women, 51.8% had a normal cervix, 14.4% had cervical intraepithelial neoplasia grade 1 (CIN1), 8.2% had CIN2, 19.3% had CIN3, and 6.2% had invasive carcinoma. Overall, the positive rates for high, intermediate, and low risk HPVs were 18.8%, 21.4%, and 5.2%, respectively. Fifteen patients harboured HPVs for which the genotype could not be identified. Positive rates for CMV, HHV-6, and HHV-7 were 9.5%, 3.6%, and 3.4%, respectively. HPV positive patients carried a higher risk for high grade lesions (CIN2/3 or carcinoma) (odds ratio (OR), 5.24; 95% confidence interval (CI), 3.19 to 8.62; chi 2 = 51.79; p < 0.001), whereas those positive for CMV, HHV-6, or HHV-7 did not. Thirteen of 131 patients with high grade lesions had HPV/herpesvirus coinfections, but no association with the cervical lesion was noted. Furthermore, positive rates for herpesviruses among HPV negative, high/intermediate risk HPV negative, and high risk HPV negative subgroups were similarly low and without a significant association. CONCLUSIONS: The ubiquitous nature of herpesviruses may pose difficulty in elucidating their pathogenic role. These results indicate that CMV, HHV-6, and HHV-7 are bystanders rather than cofactors in the oncogenesis of cervical cancer.

Adolescent↗
PubMed2001

Induction of type 3 iodothyronine deiodinase by nerve injury in the rat peripheral nervous system.

Thyroid hormones are essential for the development and repair of the peripheral nervous system. The type 2 deiodinase, which is responsible for the activation of T(4) into T(3), is induced in injured sciatic nerve. To obtain information on the type 3 deiodinase (D3) responsible for the degradation of thyroid hormones, we looked for its expression (mRNA and activity) in the sciatic nerve after injury. D3 was undetectable in the intact sciatic nerve of adult rats, but was rapidly and highly increased in the distal and proximal segments after nerve lesion. After cryolesion, D3 up-regulation disappeared after 3 d in the proximal segment, whereas it was sustained for 10 d in the distal segment, then declined to reach basal levels after 28 d, when functional recovery was completed. After a transsection preventing the nerve regeneration, up-regulation of D3 persisted up to 28 d at high levels in the distal segment. D3 was expressed in peripheral connective sheaths and in the internal endoneural compartment. D3 mRNA was inducible by 12-O-tetradecanoylphorbol-13-acetate in cultured fibroblasts or Schwann cells. In conclusion, induction of D3 in the peripheral nervous system after injury may play an important role during the regeneration process by adjusting intracellular T(3) levels.

Animals↗
PubMed2001

Sensitivity of soft tissue sarcoma cell lines to chemotherapeutic agents: identification of ecteinascidin-743 as a potent cytotoxic agent.

The cytotoxic effects of ecteinascidin-743(ET-743), a novel marine natural product, were evaluated and compared with that of clinically used anticancer agents methotrexate, doxorubicin, etoposide, and paclitaxel in eight human soft tissue sarcoma (STS) cell lines. HT-1080, a fibrosarcoma cell line, and HS-42, a malignant mesodermal cell line, were the most sensitive of the cell lines to methotrexate, doxorubicin, etoposide, and paclitaxel. Other cell lines (IC50s) varied considerably and were more resistant to these agents. ET-743 was more potent than any of these agents, with IC50s in the pM range in all of the cell lines. Cytotoxicity of ET-743 was dose- and time-related (4-72 h exposure). Cytotoxic concentrations of ET-743 produced a S/G2 block in all of the cell lines tested. Three colon adenocarcinoma cell lines, HCT-8, HT-29, and HCT-116, and one breast cancer cell line, MCF-7, were 1-2 logs less sensitive to ET-743 than the STS cell lines. Cell lines were also characterized as to expression of oncogenes and tumor suppressor genes to attempt to correlate sensitivity of these cell lines to ET-743 and other chemotherapeutic agents. All of the cell lines except M8805, a malignant fibrous histiocytoma cell line, had mutations in p53 and/or overexpressed the MDM2 protein. Only HS-18, a liposarcoma cell line, lacked expression of the retinoblastoma protein. None of the cell lines had detectable expression of P-glycoprotein as measured by immunohistochemistry. ET-743 is an extremely potent cytotoxic agent against human STS cell lines and is being evaluated as an antitumor agent in this disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Sequence-dependent enhancement of cytotoxicity produced by ecteinascidin 743 (ET-743) with doxorubicin or paclitaxel in soft tissue sarcoma cells.

Ecteinascidin 743 (ET-743) is a potent antitumor agent from the Caribbean tunicate Ecteinascidin turbinata and is presently in clinical trials for human cancers. To better understand how ET-743 might be used clinically, the present study used SRB assays to examine the cytotoxicity resulting from combining ET-743 with three other antineoplastic agents: doxorubicin (DXR), trimetrexate, and paclitaxel in different administration schedules in two soft tissue sarcoma cell lines, HT-1080 and HS-18, in vitro. Concurrent exposure of ET-743 with DXR resulted in synergistic interactions in both cell lines. Addition of ET-743 for 24 h before DXR was the most effective cytotoxic regimen against both cell lines. Morphological study by fluorescence microscopy revealed that combination treatment of both cells with ET-743 and DXR induced apoptosis. Exposure to paclitaxel before ET-743 was also an effective regimen. These results encourage studies of the combination of ET-743 and DXR in the treatment of soft tissue sarcoma, because each of these agents have activity in this disease.

Antineoplastic Agents↗
PubMed2000

The flathead mutation causes CNS-specific developmental abnormalities and apoptosis.

We describe a new mutation, flathead (fh), that arose spontaneously in an inbred colony of Wistar rats. The mutation is autosomal recessive, and the behavioral phenotype of fh/fh rats includes spontaneous seizures, tremor, impaired coordination, and premature death. A striking feature of the fh mutation is a dramatic reduction in brain size (40% of normal at birth). In contrast, no abnormalities are evident in the peripheral nervous system or in other tissues outside of the CNS. Although bromodeoxyuridine incorporation assays indicate that the rate of cell proliferation in the fh/fh cortex is similar to that of unaffected animals, in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin end-labeling assays reveal a dramatic increase in apoptotic cell death beginning after embryonic day 16 (E16). At E18 there is a 20-fold increase in cell death in the ventricular zone of fh/fh neocortex, and at postnatal day 1 (P1), the number of apoptotic cells is still two times that of normal. However, by P8 the extent of cell death in fh/fh is comparable to that of unaffected littermates, indicating that the reduction in brain growth is caused by abnormally high apoptosis during a discrete developmental period. Late-developing structures such as the cerebellum, neocortex, hippocampus, and retina are most severely affected by the fh mutation. Within these structures, later-generated neuronal populations are selectively depleted. Together, these results suggest that the flathead gene is essential for a developmental event required for the generation and maturation of late-born cell populations in the brain.

Animals↗
PubMed2000

The clinical manipulation of angiogenesis: pathology, side-effects, surprises, and opportunities with novel human therapies.

The first phase of angiogenesis research has provided knowledge of the basic pathobiology of angiogenesis and its manipulation in models, mouse, and man. The first line of therapeutic substances has been devised and is now in clinical trials. New lessons are being learned from clinical observations. Unexpected side-effects are being noted, particularly affecting the nervous system. Other side-effects may be anticipated from a sound knowledge of clinical pathology and recognition of the commonality of angiogenesis to multiple disease mechanisms, but these may be tolerable or avoidable. Angiogenesis researchers await further feedback and ideas from the clinic to stimulate the next phase of basic and applied research.

Angiogenesis Inducing Agents↗
PubMed2000

Changes of cytochemical markers in the conjunctival and corneal epithelium after corneal debridement.

1. The aim of this study was to determine the epithelial changes of the conjunctiva and cornea up to 7 days after corneal debridement and the changes highlighted included (1) proliferation, (2) production of growth factor, (3) changes in calcium binding protein marker, (4) production of cytokine, and (5) maturity of the regeneration corneal epithelium. 2. The cytochemical changes of the corneal and conjunctival epithelia of rabbit were analyzed up to 7 days after debridement. 3. An increase in proliferating cell nuclear antigen (PCNA) was observed in the limbal epithelia 12 hr after lesion and reached a peak by 48 hr. 4. Some proliferating limbal cells also contained epidermal growth factor (EGF) beginning 24 hr after injury. The early limbal cell proliferation and the EGF production and their persistence until 7 days after lesion were likely involved with the process of regeneration. 5. Other positive markers appeared after lesion included tumor necrosis factor (TNFalpha) and calcium binding proteins S100A and S100B, which appeared mainly within the first 48 hr after lesion and then started to decline. The short appearance and the relatively small quantity of TNFalpha indicated that this cytokine was probably not very important in the repair process and its appearance might be related to the injury induced. The presence of S100A and S100B could be associated with both cell death after injury and the proliferation of new epithelium. 6. The cornea epithelium was still immature 7 days after lesion in that it still contained cytokeratin. 7. In conclusion, the critical hours of peak conjunctival and corneal changes after corneal debridement were in the first 2 days.

Animals↗