Interaction of epidermal growth factor, Ca2+, and matrix metalloproteinase-9 in primary keratinocyte migration

Elevations of epidermal growth factor (EGF) and Ca²⁺ concentrations in the wound site are associated with reepithelialization during wound healing. In addition, Ca²⁺ and EGF can both induce increases in matrix metalloproteinase‐9 (MMP‐9) synthesis. However, little is known about the interplay of these events in regulating the migration properties of primary keratinocytes on collagen I, the most abundant extracellular matrix component in the skin. We found that EGF stimulated both chemokinetic and chemotactic migration of primary keratinocytes on collagen I; however, MMP‐9 was required for EGF‐stimulated chemotaxis but not EGF‐stimulated chemokinesis. Calcium at 0.5 mM stimulated chemokinetic migration of keratinocytes. Together, Ca²⁺ and EGF stimulated higher levels of chemokinesis than either stimulus alone. Furthermore, Ca²⁺ could restore the ability of keratinocytes from MMP‐9 null mice to undergo EGF‐stimulated chemotaxis. The phosphatidylinositol‐3 kinase inhibitor LY294002 inhibited both EGF‐ and Ca²⁺‐stimulated chemokinetic migration. In contrast, the MEK inhibitor PD98059 blocked Ca²⁺‐ but not EGF‐stimulated chemokinetic migration of keratinocytes. A combination of PD98059 and LY294002 was required to inhibit Ca²⁺ enhancement of EGF‐stimulated migration completely. Calcium‐stimulated chemokinesis was completely blocked by either the protein kinase C‐α inhibitor Gö6976 or the src/fyn inhibitor PP2. Using primary keratinocytes, our results showed how the combined action of Ca²⁺, EGF, and MMP‐9 regulated the contributions of extracellular‐regulated kinase and phosphatidylinositol‐3 kinase toward chemokinetic and chemotactic migration of keratinocytes.     

Variation of multifocal electroretinogram with axial length

INTRODUCTION: The first-order kernel response of multifocal electroretinogram (mfERG) decreases in myopia. A recent study indicates that the flash ERG is also reduced with increased axial length. The aim of this study was to investigate the variations in the first-order response (K1) and the first slice of second-order response (K2.1) across the retina for different axial lengths. METHODS: Thirty healthy subjects with axial length from 23.72 to 28.13 mm (spherical equivalent refractive errors from plano to -10.50 D) were recruited for mfERG measurement using VERIS 4.0. All subjects were fully corrected after cycloplegic refraction and pupils were dilated prior to mfERG recording. There is one trough, n1, and one peak, p1, in the K1 response and three troughs, n1, n2, n3, and three peaks, p1, p2, p3, in the K2.1 response. The amplitudes and implicit times of K1 and K2.1 responses were analysed to determine the characteristic of the responses across retina and the correlation to axial length. RESULTS: The amplitudes of p1 (in the first-order kernel-K1) decreased in the central region and the paracentral region (ring 3) as the axial length increased. The central retinal region showed high rates of reduction in both n1 and p1 (in K1). The amplitudes of n1p1 and n2p2 (in the first slice of the second-order kernel-K2.1) were reduced in the paracentral region (from ring 2 to ring 5) as axial length increased. The average n1 and p1 in K1, and n1p1 and n2p2 in K2.1 mfERG responses are decreased in amplitude by 6-10% per millimetre elongation of axial length. CONCLUSION: Eyes with longer axial lengths, usually with high myopia, have a weaker mfERG response and this attenuation is across the measured retina (from central to paracentral regions) but different kernel responses show a different pattern of attenuation at different retinal eccentricities. The weaker mfERG responses may be related to the morphological changes associated with increased axial length.     

Laparoscopic repair of recurrent childhood inguinal hernias after open herniotomy

Background Open repair of recurrent paediatric inguinal hernias (IH) is difficult and there is definite risk of damaging the vas deferens and testicular vessels during dissection of the previous open herniotomy field. Laparoscopic repair (LR) has the benefit of avoiding the previous operative site. Method Records of patients with recurrent IH that had LR after open repair were reviewed and evaluated retrospectively. The results were compared with data from cases in which the LR method was used in the initial IH repair. Results From September 2002 to October 2005, four boys and one girl (mean age 58.8 months) were treated in our institution for recurrent IH after open repair. Operative time, success rate and complications did not show any statistically significant difference when compared with our previous prospectively collected data for primary repairs. Conclusion Laparoscopic repair is the preferred operation for recurrent childhood IH after open repair.     

Pentasomy 8q in Myelodysplasia

Trisomy 8 and, less commonly tetrasomy 8, are karyotypic aberrations found in myeloid malignancies. We describe a unique case of acute myeloid leukemia with partial pentasomy 8 resulting from duplication of isochromosome 8q, and discuss its possible roles in leukemogenesis.     

Phase I trial of piroxicam in 62 dogs bearing naturally occurring tumors

Summary Piroxicam, a nonsteroidal antiinflammatory drug, was given to 62 dogs bearing naturally occurring tumors in a phase I clinical trial. Dose escalation was performed, with oral doses ranging from 0.5 mg/kg every 48 h (q48h) to 1.5 mg/kg q48h being tested. Dose-limiting gastromestinal irritation/ulceration occurred in all four animals that received 1.5 mg/kg q48h. The maximum tolerated dose was 1 mg/kg q48h. Subclinical renal papillary necrosis occurred in two dogs (initial dosages, 1 and 1.5 mg/kg q48h, respectively). Following dose escalation, an additional group of dogs was treated with 0.3 mg/kg piroxicam q24h per os, the accepted canine dosage prior to this trial. Inclusion of this treatment group enabled evaluation of the toxicity of and tumor response to a daily dosage regimen. No complete remissions occurred in this trial. Partial remission was documented in three of ten dogs exhibiting transitional-cell carcinoma, in three of five animals bearing squamous-cell carcinoma, in one of three dogs displaying mammary adenocarcinoma, and in the one dog that exhibited a transmissible venereal tumor. The results of this study support the additional evaluation of piroxicam in a phase II clinical trial in dogs bearing naturally occurring tumors.This investigation was supported by Pfizer Inc.     

Comparison of two-dimensional vs three-dimensional camera systems in laparoscopic surgery

Background: The lack of depth perception and spatial orientation in video vision are the drawbacks of laparoscopic surgery. The advent of a three-dimensional camera system enables surgeons to regain binocular vision and may be advantageous in complex laparoscopic procedures. Methods: We prospectively studied two groups of surgeons (with and without experiences in laparoscopic surgery) who performed a designated standardized laparoscopic task using a two-dimensional camera system (Olympus OTV-S4) vs a three-dimensional camera system (Baxter-V. Mueller VS7700) and compared their time performances. Results: The results suggested that only experience in laparoscopic surgery had significant effect on individual's performance. We could not demonstrate any superiority of the 3D system over the 2D system. However, two-thirds of the surgeons commented that the depth perception did improve. Conclusions: With further refinement of the technology, the 3D system may improve its potential in laparoscopic surgery.     

High performance liquid chromatographic characterisation and quantitation of p-aminobenzoic acid N-acetylation in Chinese subjects

p-Aminobenzoic acid (PABA), p-acetamidobenzoic acid (PADB) and p-aminohippuric acid (PAH) have been separated and determined by a reversed phase, isocratic high performance liquid chromatographic (HPLC) procedure simultaneously. The mobile phase, at 1.5 ml min-1, used was 10 mM sodium hydrogen phosphate buffer, pH 3.5, containing 40% methanol. The eluent was detected at 270 nm. Linear relationship was obtained from 0 to 2.0 micrograms ml-1 of each compound with the corresponding peak-height ratio using p-methylamino-benzoic acid (PMAB) as the internal standard. Urine samples were obtained from healthy Chinese volunteers after oral dosing of 200 mg PABA which was used as a model substance for metabolic investigation of N-acetylation and other conjugation reactions. The 24 hour urinary recovery, from 43 healthy subjects, of PABA, PABA-COOH conjugates, PADB and PADB-COOH conjugates were (mean +/- S.D.) 2.9 +/- 1.5%, 5.2 +/- 3.3%, 13.9 +/- 4.0% and 42.9 +/- 9.8% of the ingested dose respectively. These accounted for 64.9 +/- 12.0% of total dose ingested in 24 hour. In contrast to previously reported findings on one Caucasian subject, no PAH was identified in the urine, and N-acetylation was the major route of metabolism of PABA apart from conjugation at the -COOH group in this group of Chinese volunteers. It is proposed that PABA metabolism may be a useful probe to study ethnic and geographic variation in N-acetylation.     

Further characterization of ts1-8, a mutant of herpes simplex virus type 1.

Our initial characterization of a herpes simplex virus type 1, temperature sensitive host shutoff mutant, called ts1-8, revealed that it has a low plaquing efficiency and exhibits a defect in the shutoff of host polypeptide synthesis and host DNA replication at the nonpermissive temperature of 39.5 degrees C. Using intratypic marker rescue experiments the ts plaquing mutation was mapped to a 557 bp region. Sequence analysis and complementation studies revealed that the low plaquing efficiency phenotype is due to a mutation in the glycoprotein B gene converting Pro-357 to Ser. This novel tsgB mutation is located in a conserved region of gB and it is distinct from the delayed host shutoff mutation (dhs).     

Nasal septum lesions caused by chromium exposure among chromium electroplating workers

A chromium electroplating worker, suffering from epistaxis during work, was found to have nasal septum perforation. To determine the etiology and prevalence of nasal septum lesions, we conducted a survey of seven chromium electroplating factories and examined 79 workers. Forty workers from three aluminum electroplating factories were also enrolled as the reference group. Subjects were thoroughly examined by an otolaryngologist and each of them provided a blood and urine sample. A questionnaire interview regarding symptoms of the upper respiratory tract, past medical history, life style, and work history was also conducted. Air chromium concentrations were measured by taking area samples for 4–6 hours. Based on field observation and chromium measurements, we divided chromium electroplating into three different exposure zones: workers directly dealing with electroplating tanks (n = 31), other process workers (n = 29), and office workers and drivers (n = 19). Among the 79 chromium electroplating workers, there were 16 cases of nasal septum perforation, and 42 with either scar formation or ulceration; 10 chromium electroplating workers developed skin ulcers after performing chrome plating. No workers from aluminum electroplating factories had any nasal septum or skin abnormalities. There was a consistent trend between the degree of chromium exposure and the signs and symptoms related to the nose, throat, and skin. Immediate improvement of occupational hygiene is warranted.