Biomedical subjects

J A Anderson

Publications and source records attributed to J A Anderson.

At least 91 records · Page 5Linked to original sources

PubMed1995

Scar tissue orientation in unsutured and sutured corneal wound healing.

AIMS: This study aimed to evaluate stromal wound healing morphology in short term unsutured compared with sutured corneal wounds, to define regional variation in healing within radial keratotomy wounds. METHODS: Stromal scar tissue orientation (fibroblast and collagen fibre orientation) was analysed in unsutured and adjacent sutured keratotomy wounds in monkeys, 2 to 9 weeks after surgery, using light and transmission electron microscopy. RESULTS: At 2 to 4 weeks, scar tissue orientation was transverse to the wound edge in unsutured wounds, but sagittal in sutured wounds. At 5 to 9 weeks, a reorientation of scar tissue sagittal to the wound was seen in the unsutured wounds, proceeding from the posterior to anterior wound regions. In sutured wounds, a scar tissue reorientation transverse to the wound was seen, proceeding from the anterior wound region in a posterior direction. CONCLUSIONS: Within the same cornea, sutured and unsutured wounds showed opposite patterns of healing. Sutured wounds initially healed more slowly, but obtained pseudolamellar continuity over time. In contrast, healing of unsutured wounds was characterised by an early approximation towards lamellar repair that was followed by an ineffective reorganisation of the scar. This latter pattern of healing, that may be associated with a variable weakening of the wound, may relate to the clinical findings of unpredictability and/or progression of refractive effect following radial keratotomy.

Animals↗

PubMed1995

Immunohistochemical analysis of unsutured and sutured corneal wound healing.

In the unsutured partial thickness penetrating wounds of the cornea, the epithelium migrates over the wounded stromal surface prior to the onset of stromal regeneration. To determine the possible affects of the epithelial ingrowth on the organization of the stromal scar tissues, the healing of unsutured and sutured wounds was compared immunohistochemically. Immunostaining patterns for fibronectin, types III, VI and VII collagen, keratan sulfate proteoglycan (KSPG), and intermediate filament-associated protein (IFAP 130) in fibroblasts, were analyzed in unsutured and adjacent sutured keratotomy wounds in monkeys, at 2-9 weeks after surgery. At 2-4 weeks, fibronectin, type III and type VI collagen showed a lamellar interweaving pattern across unsutured wounds that was absent in sutured wounds. Type VII collagen was detected along the entire depth of regenerated stroma in unsutured wounds, but not in sutured wounds indicating that the epithelium had formerly been present in the regenerated stroma in unsutured wounds. Fibroblasts in both types of wounds expressed IFAP 130, but staining was more pronounced in sutured wounds. At 5-9 weeks, cellular re-activation, as judged from the expression for IFAP 130, was concomitant with a loss of lamellar interweaving with fibronectin, type III and type VI collagen across unsutured wounds, and proceeded in a posterior to anterior direction. In contrast, in sutured wounds, lamellar interweaving was established in anterior to posterior direction. At all postoperative times, unsutured and sutured wounds showed minimal staining for KSPG in the anterior scar.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

In vitro model for corneal wound healing; organ-cultured human corneas.

Healing of linear, non-perforating thermal burns was studied in 56 human corneas in an air/liquid organ culture system in serum free medium or in media supplemented with 10% fetal bovine serum, 10% human serum or 10% human plasma. The extent of epithelial wound healing was determined by measuring epithelial growth into the wound using digitized computer scanning of light micrographs of 1 micron sections. The cross-sectional area of this epithelial growth entering the wound was significantly greater for corneas incubated with either human serum (16,350 +/- 12,088 microns 2/day; p < 0.0001) or human plasma (20,571 +/- 12,276 microns 2/day; p = 0.0004) than for those incubated in serum free (1,784 +/- 1,957 microns 2/day) medium. There was no significant difference between epithelial growth in the serum free and fetal bovine serum supplemented (3,779 +/- 2,580 microns 2/day) media or between that in human serum and human plasma supplemented media. The thickness of the epithelium adjacent to the wound was greater in corneas cultured in fetal bovine serum supplemented media than in corneas cultured in the presence of human serum. Similarly, the build-up of epithelium at the wound edge for corneas in either serum free or fetal bovine serum supplemented media was significantly greater than for either human serum or human plasma supplemented media. The percentage of basal epithelial nuclei which incorporated bromodeoxyuridine (BrdU) increased during the first three days of culture when it reached a plateau. Comparison of paired wounded and unwounded corneas showed that wounding stimulated an increase in DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Basement Membrane↗

PubMed1995

3-D computer models of human keratocytes.

We constructed three separate three-dimensional (3-D) models from serial high voltage electron micrographs (HVEM) of five human keratocytes. The serial micrographs were digitized using HVEM-3D software and a digitizing tablet on a personal computer system. After the models were constructed, we added surface and volume data using another computer program, SYNU. Hard copies of selected orientations of the model were obtained with a laser printer, by color photographs of the computer monitor, by direct imaging from the computer file, or by video recording. The first model was constructed from 73 serial sections of two activated keratoconus keratocytes next to a break in Bowman's layer (BL). Two adjacent keratocytes from the same cornea, but located away from disruptions in BL, made up the second model. The third model was created from approximately 106 serial sections of a normal human keratocyte cultured in an attached collagen gel. Examination of these 3-D models created from HVEM micrographs showed striking differences in keratocyte morphology and cell/matrix interactions related to corneal disease.

Adult↗

PubMed1995

Mechanisms in adverse reactions to food. The brain.

Specific chemical mediator release such as histamine and the prostaglandins (PG2a or PGD2) associated with headaches has been found in a few patients who were repeatedly challenged with specific foods, using DBPCFC techniques.

Adult↗

PubMed1994

Variation in healing throughout the depth of long-term, unsutured, corneal wounds in human autopsy specimens and monkeys.

OBJECTIVE: To determine regional differences in stromal wound healing morphologic features in long-term radial keratotomy wounds. METHODS: Unsutured, semiradial, nonperforating wounds in seven monkeys and 10 human autopsy specimens obtained 3.5 to 52 months after surgery were analyzed using light, transmission, and fluorescent microscopy. RESULTS: Monkeys showed fast healing, whereas all human specimens had one or more incisions containing a superficial epithelial plug. Completely healed wounds in both models had fibroblast orientation and ultrastructural "pseudolamellar" (ie, colinear collagen fiber) continuity across the anterior wound, compared with disorganization of the midposterior scar. CONCLUSIONS: Regional differences in healing rates, mechanical factors associated with epithelial plug elimination, intrinsic tissue characteristics, and/or induction of pseudolamellar repair by the epithelial plug may explain variation in healing within an unsutured corneal wound.

Adult↗

PubMed1994

H-ras oncogene mutation and human papillomavirus infection in oral carcinomas.

OBJECTIVE: Previous in vitro studies have demonstrated that transfection of an activated ras gene induces malignant transformation in epithelial cell lines infected with the human papillomavirus (HPV). The results of these studies support the hypothesis that HPV may cooperate with an activated ras gene in epithelial tumor carcinogenesis. To test this hypothesis in head and neck cancers, we screened 35 oral carcinomas for the presence of HPV DNA and for a mutated H-ras gene. DESIGN: The design of the study was screening survey type. Twenty-seven oral squamous cell carcinomas and eight verrucous carcinomas were analyzed for the presence of HPV DNA using the polymerase chain reaction, followed by Southern blot and probe hybridization. The tumors were also screened for point mutations of the H-ras gene using the polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Six (22%) of the 27 oral squamous cell carcinomas demonstrated point mutation in the H-ras gene. In addition, six tumors (22%) were positive for HPV DNA, with three tumors (11%) demonstrating both HPV DNA and H-ras gene point mutation. While the rate of simultaneous HPV infection and ras gene activation by point mutation was 11% in oral squamous cell carcinomas, 25% of oral verrucous carcinomas contained both HPV DNA and mutation in the H-ras gene. CONCLUSIONS: These results suggest a stronger association between HPV infection and activation of the H-ras gene in oral verrucous carcinomas. These results continue to confirm the multihit hypothesis of tumorigenesis and suggest that in some cases of oral cancer at least two of these events are H-ras gene mutation and HPV infection.

Adult↗

PubMed1994

Developmental toxicity of the HMG-CoA reductase inhibitor, atorvastatin, in rats and rabbits.

The developmental toxicity of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, atorvastatin, was investigated in pregnant rats and rabbits given daily oral doses during organogenesis. Rats received 0, 10, 100, or 300 mg/kg on days 6-15 of gestation, and rabbits received 0, 10, 50, or 100 mg/kg on days 6-18 of gestation. Maternal and fetal parameters were evaluated on day 20 (rats) or 29 (rabbits) of gestation. Live fetuses were examined for external, visceral, and skeletal malformations and variations. At 300 mg/kg in rats, 1 treatment-related death occurred on day 12 of gestation, and maternal body weight gain and food consumption were decreased during treatment (43% and 23%, respectively). In addition, 1 animal at 300 mg/kg had total litter resorption. Increased postimplantation loss (not statistically significant) and slightly decreased fetal body weight (statistically significant only in males) were also observed at 300 mg/kg. There were no significant differences between treated and control groups in the incidence of fetal malformations or variations. No maternal or developmental toxicity was observed in rats at 10 or 100 mg/kg. In rabbits, marked maternal toxicity (7 deaths, body weight loss during and after treatment, and decreased food consumption) and abortion occurred at 100 mg/kg. At 50 mg/kg, maternal toxicity (2 deaths and 72% body weight gain suppression) and abortion also occurred. There were no treatment-related effects on live litter size or sex ratio. At 50 and 100 mg/kg, nonstatistically significant increases in postimplantation loss and decreases in gravid uterine weight were observed, and at 100 mg/kg, decreases in fetal body weight were observed relative to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

PubMed1994

Developmental toxicity studies in mice, rats, and rabbits with the anticonvulsant gabapentin.

The developmental toxicity of the anticonvulsant agent gabapentin was evaluated in mice, rats, and rabbits treated by gavage throughout organogenesis. Mice received 500, 1000, or 3000 mg/kg on gestation days (GD) 6-15 and rats and rabbits received 60, 300, or 1500 mg/kg on GD 6-15 (rats) or 6-18 (rabbits). Additional groups received an equivalent volume of the vehicle, 0.8% methylcellulose, or remained untreated. All dams were observed daily for clinical signs of toxicity. In mice, body weights and food consumption were recorded on GD 0, 6, 12, 15, and 18 while in rats and rabbits these parameters were evaluated daily. Near term (mouse, GD 18; rat, GD 20; and rabbit, GD 29) each female was euthanatized, necropsies were performed, and litter and fetal data were collected. Live fetuses were examined for external, visceral, and skeletal variations and malformations. No adverse maternal or fetal effects were observed in mice or rats given doses up to 1500 or 3000 mg/kg, respectively. No treatment-related maternal or fetal effects were apparent in rabbits given 60 or 300 mg/kg. At 1500 mg/kg, one rabbit died, four others aborted, and reduced food consumption and body weight gain were observed. No other reproductive, litter, or fetal parameters were affected, except that the incidence of visceral variations in rat fetuses was slightly but statistically significantly increased at 1500 mg/kg due to a slight increase in the incidence of dilated renal pelvis. This finding was not considered biologically significant because this degree of variability has been seen in this strain of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

PubMed1994

Interleukin-2-induced lymphocyte infiltration of multiple organs is differentially suppressed by soluble tumor necrosis factor receptor.

Interleukin-2 (IL-2) mediates the regression of metastatic cancer, but clinical application is restricted by associated toxicities. Previous studies implicate tumor necrosis factor (TNF) as an important mediator of certain IL-2-induced toxicities. We hypothesized that soluble TNF receptor (sTNFr), a TNF antagonist, would alter lymphocyte trafficking into normal tissues and ameliorate IL-2-induced toxicity. Four groups of C57BL/6 mice were treated for 4 days with intraperitoneal injections of 100,000 IU IL-2 alone, 100,000 IU IL-2 and 30 micrograms sTNFr combined, 30 micrograms sTNFr alone, or equal volumes of saline. Animal activity was graded and blood obtained for SGPT and SGOT. At necropsy, organs were harvested for wet:dry ratios as a measurement of organ edema. The lung, liver, and thymus were examined histologically for lymphocytic infiltration and graded on a scale of 1 to 5. IL-2-treated groups had a statistically significant increase in organ edema, lymphocytic infiltration into the lung and liver, liver enzyme elevation, and pancytopenia when compared with controls. Soluble TNFr significantly suppressed IL-2-induced pulmonary lymphocytic infiltration and associated serum lymphopenia without significant alteration of other IL-2-induced effects. These data implicate TNF as a mediator of the pulmonary lymphocytic infiltration and of lymphopenia that accompanies IL-2 therapy and further suggest that alternative mechanisms are involved in other IL-2-induced deleterious effects.

Animals↗

PubMed1994

Tumor necrosis factor causes microvascular protein leakage independently of neutrophils or mast cells.

Tumor necrosis factor-alpha (TNF-alpha) has been implicated as an important mediator in the development of multiple system organ failure after either severe injury or infection. Using the rat cremaster muscle, we previously showed that systemically administered TNF-alpha caused hypotension, tachypnea, and microvascular protein leakage in association with leukocyte-endothelial adherence. In the current study, we hypothesized that topical administration of TNF-alpha to the cremaster muscle would cause microvascular protein leakage independent of changes in hemodynamic parameters. In addition, histological methods were used to study the role of neutrophils and mast cells in the TNF-alpha-induced microvascular protein leakage. Topically applied low-dose (1 ng/ml) TNF-alpha caused microvascular leakage in the cremaster, without changes in central hemodynamic parameters, but high-dose TNF-alpha (10 ng/ml) did not cause protein leakage. Histological studies did not demonstrate evidence of either neutrophil adhesion or mast cell degranulation in topically applied TNF-alpha-treated cremasters compared to controls. These data suggest that TNF-alpha-induced macromolecular leakage is a dose-dependent phenomenon which can occur independently of neutrophils or mast cell degranulation.

Animals↗

PubMed1994

Inward and outward rectifying potassium currents in Saccharomyces cerevisiae mediated by endogenous and heterelogously expressed ion channels.

Disruption of genes encoding endogenous transport proteins in Saccharomyces cerevisiae has facilitated the recent cloning, by functional expression, of cDNAs encoding K+ channels and amino acid transporters from the plant Arabidopsis thaliana [1-4]. In the present study, we demonstrate in whole-cell patch clamp experiments that the inability of trk1deltatrk2delta mutants of S. cerevisiae to grow on submillimolar K+ correlates with the lack of K+ inward currents, which are present in wild-type cells, and that transformation of the trk1deltatrk2delta double-deletion mutant with KAT1 from Arabidopsis thaliana restores this phenotype by encoding a plasma membrane protein that allows large K+ inward currents. Similar K+ inward currents are induced by transformation of a trk1 mutant with AKT1 from A. thaliana.

Arabidopsis↗

PubMed1994

A comparison of reflection and transmission ultrasonic techniques for measurement of cancellous bone elasticity.

A reflection ultrasonic technique, which offers several advantages over transmission ultrasonic techniques, has been described for elastic property measurement of bone. Ultrasonic velocities from specimens of cancellous bone were compared using a reflection ultrasound technique and the more traditional transmission ultrasonic technique. The two techniques were found to yield velocities which were reasonably well correlated (r2 = 0.74). However, a statistical difference was found between the line of identity and the regression between transmission and reflection velocities (due to an offset in the intercept). In spite of differences in intercept between velocities measured by the two techniques, significant correlation was found between the two methods, suggesting that the reflection technique can measure wave velocities meaningful to bone elasticity.

Animals↗

PubMed1994

Composition of coronary atherosclerotic plaque in the intima and media affects intravascular ultrasound measurements of intimal thickness.

OBJECTIVES: The purpose of this study was to evaluate how intravascular ultrasound-determined thickness and reflectivity of the inner echogenic layer of coronary artery plaque is affected by changes in collagen, elastin, proteoglycan, calcium and lipid content in the intima and media. BACKGROUND: Coronary artery plaque often results in disruption of the internal elastic lamina and in increased collagen in the media as well as increased intimal lipid, calcium and proteoglycan content. How these factors affect intravascular ultrasound-derived measurements of intimal thickness are unknown. METHODS: Twenty-one coronary artery segments from 10 patients with varying degrees of coronary artery disease were obtained fresh and unfixed at autopsy. Intravascular ultrasound (30-MHz, 3.5F catheter) was performed at regions in the vessel where a three-layered region was evident. Quantitative measurements of inner echogenic and deeper echolucent layer thickness were determined as well as estimates of ultrasound reflectivity and compared with histologic measurements of intimal and medial thickness and collagen, proteoglycan, lipid and calcium content. RESULTS: In plaque > 300 microns thick and equivalent histologic levels of collagen, inner echogenic layer reflectivity was greater in regions with a greater amount of calcium and proteoglycan and lesser amounts of lipid. Inner echogenic layer thickness correlated well with intimal thickness but had the best correlation with intimal and medial thickness when medial collagen content was increased (r = 0.89). The median observed difference between intimal and inner echogenic thickness was 160 (p < 0.05 compared with zero), whereas the median observed difference between inner echogenic thickness and intimal plus medial thickness when medial collagen content was increased was 60 (not significantly different from zero). CONCLUSIONS: The inner echogenic layer of human coronary artery plaque may represent both intima and media. The echolucent layer by ultrasound may represent only the basal section of the media that does not contain high collagen content.

Adult↗

PubMed1994

Human excimer laser keratectomy. Clinical and histopathologic correlations.

PURPOSE: To understand the healing capabilities of the diseased human cornea after excimer laser photoablation by morphologic analysis of laser-treated corneas. METHODS: Twelve corneal specimens were obtained 5 to 16 months after lamellar or full-thickness keratoplasty following phototherapeutic keratectomy for undercorrected myopic epikeratoplasty (2 eyes), corneal leukomas (2 eyes), herpes zoster corneal scarring (1 eye), band keratopathy (2 eyes), adenoviral subepithelial opacity (1 eye), keratoconus (1 eye), herpes simplex corneal scarring (2 eyes), granular corneal dystrophy (1 eye), and recurrent lattice dystrophy (1 eye). The morphology of the corneas was examined by light and electron microscopy. RESULTS: Epithelial hyperplasia, abnormal epithelial attachment, and disorganized stromal matrices were observed. Evidence of residual disease frequently observed in these specimens indicated that the pathology either was not excised at the time of laser keratectomy or was recurrent. CONCLUSIONS: The response of the diseased cornea to excimer laser treatment has similar characteristics to the responses previously observed in animal studies. Incomplete ablation of diseased tissue and/or recurrence of the initial disease was the major reason for failure of the treatment. Possible causes for the inability to remove diseased tissues and superficial scars with the excimer laser include (1) insufficiently achieved ablation depth and/or diameter and (2) decreased laser ablation rates of scarred cornea.

Adult↗

PubMed1994

Antibiotic drug allergy in children.

Cutaneous reactions to penicillin-type antibiotics are usually caused by IgE-mediated reactions directed toward the beta-lactam ring (in penicillin, ampicillin-amoxicillin, and cephalosporins). These allergic reactions may be reliably diagnosed (96% to 99% of the time) with a battery of skin tests derived from penicillin. A few individuals have been identified in Spain, and now Canada, who react to side chains of the beta-lactam antibiotics (and not the beta-lactam ring). Nonallergic cutaneous or systemic reactions to trimethoprim sulfamethoxazole (TMP-SMX) are now an emerging problem among HIV-infected patients. Life-threatening reactions have been described in HIV-infected infants who were rechallenged with TMP-SMX. New 10-day and 48-hour desensitization procedures have been used successfully in some TMP-SMX-reactive patients. Stevens-Johnson syndrome and Lyell's syndrome (toxic epidermal necrolysis) are the most serious of the antibiotic-associated cutaneous reactions. These reactions may be caused by an immune reaction similar to graft-versus-host syndrome. Corticosteroids have been shown to be helpful in the management of Stevens-Johnson syndrome. Although the mortality of toxic epidermal necrolysis is usually high, several children with this disorder have been successfully treated in a burn unit.

Anti-Bacterial Agents↗

PubMed1994

Smoking among health professionals.

A cross-sectional prospective study was conducted between the period December 1991 and November 1992, to identify the extent of smoking among practising doctors and other health professionals in general hospitals and health clinics in Al-Ain, United Arab Emirates. The study population consisted of 300 health professionals (doctors, specialists both clinical and non-clinical, pharmacists and dentists). They were handed self-administered questionnaires adapted from the World Health Organization standard questionnaire on smoking among health professionals. Among the responding 268 (89%) health professionals 197 (73.5%) were men, and 71 (26.5%) women. Among the men health professionals 86 (43.7%) were current smokers, 24 (12.2%) were ex-smokers and 87 (44.2%) were non-smokers, while among the women health professionals 4 (5.6%) were smokers, 1 (1.4%) was an ex-smoker and 66 (93%) were non-smokers. Doctors were uniformly aware of the detrimental effects of smoking, particularly its association with lung cancer, coronary artery disease, chronic bronchitis, and laryngeal cancer, and this was the major reason for their abstaining or wanting to quit the habit. The relationship of smoking with bladder cancer, soft tissue lesion (mouth and lip) and neonatal death was not well appreciated. Counselling patients about the hazards of smoking was practised significantly less often by doctors who smoked. The majority (83.6%) expressed the need for specific training for counselling patients to stop smoking. The options favoured by the health professionals for preventing smoking included a ban on tobacco advertising, specific health warnings on cigarette packets and restriction on smoking in public places, particularly in hospitals and clinics.

Adult↗

PubMed1994

Heterologous expression of K+ channels in Saccharomyces cerevisiae: strategies for molecular analysis of structure and function.

The ability to express heterologous proteins in K+ uptake-defective strains of Saccharomyces cerevisiae can be exploited to identify cDNAs encoding heterologous K+ channels. Moreover, the ability of heterologous potassium channels like KAT1 and AKT1 to suppress completely the conditional negative growth phenotype of S. cerevisiae cells containing mutations in TRK1 or TRK1 and TRK2 opens the field of plant K+ channel biology to molecular approaches. Owing to the efficiency of modern techniques in molecular biology structure/function studies of K+ channels involving site-directed mutagenesis suffer, if anything, from the ability to produce more mutations than can be easily analyzed by electrophysiological techniques. The microbial aspects of S. cerevisiae offer the opportunity to greatly increase the efficiency of screening for functionally altered K+ channels. S. cerevisiae cells deleted for both TRK1 and TRK2 provide a desirable genetic background for investigating the effects of mutations in K+ channels since they can be assessed over a very broad functional range. For example, since the wild-type KAT1 K+ channel reduces the potassium requirement of trk1 delta trk2 delta cells from approximately 50 mM to less than 50 microM, the function of mutant channels can be assessed over a 1,000-fold range in concentration of the permeant ion. We have developed this system using a mutagenesis scheme that alters the amino acid sequence of the presumed pore region of KAT1. Regions of three amino acids in length can be saturated with substitutions and efficiently screened for function using this system. In addition, by testing the mutants for growth on media containing the appropriate competing ions, an in vivo indication of ion selectivity can be obtained. Saturation mutagenesis of the highly conserved GYG sequence in the channel pore reveals that few structural changes are tolerated if K+ selectivity is to be maintained. On the other hand, many of the mutants allow K+ permeation through the channel.

Amino Acid Sequence↗