PubMed Health⌕ Search

Biomedical subjects

W Garner

Publications and source records attributed to W Garner.

18 recordsLinked to original sources
PubMed2000

The relationship between rabbit lens optical quality and sutural anatomy after vitrectomy.

This study was conducted first, to characterize structural changes in rabbit lenses after vitrectomy; and second, to assess whether such changes correlate with a quantifiable compromise in optical function. Unilateral, partial vitrectomies were performed on 2.5 month old Dutch Belted rabbits (n = 64). Age matched non-operated rabbits (n = 32) were used as controls. Lenses were analysed by correlative structural (light, scanning electron microscopic and three-dimensional computer-assisted drawings) and optical (low power helium-neon laser scan) analysis at 1.5, 3, 6 and 12 months post-surgery (n = 16 lenses from operated animals and n = 8 lenses from non-operated controls at each time point). Results demonstrate that in rabbits lens growth, or fiber formation, is compromised after vitrectomy. From 1.5 to 12 months after surgery, lenses had progressively more crooked posterior line sutures with sub-branches of increasing size and number in successive growth shells. Quantification of lens optical quality specifically along and/or between these atypical suture branches and sub-branches revealed a significant increase in focal length variability (sharpness of focus) after vitrectomy. A peripheral zone of fibers with abnormal posterior ends was produced surrounding the pre-surgical lens mass. This additional zone of aberrant fibers was associated with a quantifiable degradation in lens optics. Studies on the prevention of post-vitrectomy lens changes in this rabbit model may yield useful information applicable to the human condition.

Animals↗
PubMed1997

Heparin-binding ligands mediate autocrine epidermal growth factor receptor activation In skin organ culture.

Exogenous EGF and TGF-alpha accelerate wound healing, but treatment effects are often modest. Using short-term human skin organ culture, we found that autocrine EGF receptor activation could account for this observation. Amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) transcripts were rapidly and markedly induced, whereas EGF and TGF-alpha mRNAs were undetectable or only slightly increased. Vascular permeability factor and keratin 6 transcripts were also strongly induced, albeit with a >/= 3 h delay relative to HB-EGF and amphiregulin. All four transcripts were upregulated in actual healing skin wounds, HB-EGF and keratin 6 being the most prominent. The highly EGF receptor-specific tyrosine kinase inhibitor PD153035 strongly inhibited induction of all four transcripts in organ culture, as well as release of immunoreactive HB-EGF into the medium. These effects were confirmed using the anti-EGF receptor mAb 225 IgG. Neither PD153035 nor 225 IgG was toxic to keratinocytes, as judged by calcein-AM uptake. PD153035 completely abrogated the proliferative phase of keratinocyte outgrowth in skin explant cultures, whereas it had no effect on the antecedent migratory phase. Based on these results, we conclude that EGF receptor activation by highly inducible, keratinocyte-derived heparin-binding ligands is an important mechanism for amplification and transmission of the cutaneous wound healing signal.

Adult↗
PubMed1997

Neuronal thread protein gene modulation with cerebral infarction.

Neuronal thread proteins (NTP) are a family of phosphoproteins expressed during neuritic sprouting. The 15 to 18 kD NTP cluster is associated with development and neuronal differentiation, whereas the 21 kD and 39 to 42 kD species are overexpressed in Alzheimer's disease, correlating with neurodegenerative sprouting and synaptic disconnection. Empirical observations suggested that NTP might also be modulated with central nervous system injury and stroke. In this study of both human and experimental (rat) focal cerebral infarcts, in situ hybridization and immunocytochemical staining revealed NTP gene expression up-regulated in perifocal neurons. These findings were confirmed by quantitative Northern and Western blot analyses. Moreover, Western blot analysis demonstrated selectively increased expression of the 15 to 18 kD NTP species during the acute, subacute, and healing phases of cerebral infarction in both humans and experimental animals, corresponding with the expected period of neuronal repair. These results suggest an additional role for the 15 to 18 kD NTP species in neuritic sprouting required for neuronal regeneration after injury in the mature central nervous system.

Adult↗
PubMed1995

Fibroblast responses to cytokines are maintained during aging.

Impaired wound healing in older individuals may result from a global deficit of fibroblast activity or a decreased response of aged fibroblasts to stimulation by inflammatory cytokines. Twenty-eight fibroblast cell strains were developed from normal human skin aged 3 days to 84 years. Mitogenic response to cytokines, epidermal growth factor, tumor necrosis factor-alpha, platelet-derived growth factor or fetal bovine serum was determined using a 4-hour 3H-thymidine incorporation assay. Synthesis of collagen and noncollagen proteins was determined basally and in response to transforming growth factor-beta using a 6-hour 3H-proline incorporation assay. Neither the mitogenic response to cytokine stimulation (p > 0.3) nor the synthesis of collagen and noncollagen protein after transforming growth factor-beta stimulation (p > 0.4) varied with the age of the cell donor. Individual cell lines' response to cytokine stimulation varied widely, reflecting differences commonly seen in patients' wound-healing abilities. Cellular responses to wound-healing cytokines are preserved as people age. Abnormalities in wound healing in older patients may be the result of altered immune initiation of healing or the cumulative result of concomitant disease.

Adolescent↗
PubMed1995

Increased types I and III collagen and transforming growth factor-beta 1 mRNA and protein in hypertrophic burn scar.

Hypertrophic scar is the result of abnormal healing that often follows thermal injury. Hypertrophic scar is characterized by excessive dermal fibrosis and scarring. Five cases of human hypertrophic scar were compared with normal skin using in situ hybridization to localize mRNAs for procollagen types I and III and transforming growth factor-beta 1. Expression of type I procollagen and TGF-beta 1 were also examined with immunohistochemistry. The results demonstrated a significant increase in the expression of mRNA for types I and III procollagen and type I procollagen protein by fibroblasts in hypertrophic scar compared with normal skin. In all cases of hypertrophic scar, significant numbers of cells expressed TGF-beta 1 mRNA or peptide. Neither TGF-beta 1 mRNA nor protein was detected in control tissues. These results suggest a profound increase in production and expression of types I and III collagen mRNA by the fibroblasts in hypertrophic scar. This may result from increased TGF-beta 1 production, through paracrine and autocrine pathways, as have been described for this fibrogenic cytokine.

Base Sequence↗
PubMed1994

The role of xanthine oxidase and xanthine dehydrogenase in skin ischemia.

The importance of sequential events which lead to skin necrosis has significant implications in trauma, vascular injury, and wound healing. In this series of experiments, we tested the hypothesis that xanthine oxidase (XO) activity was increased along an ischemic gradient of a skin flap and that the XO enzyme activity correlated with an increase in neutrophils. There were two animal groups in which the skin flaps were raised and assayed at 0, 1, or 6 hr. In the other group, they were created as bipedicle flaps for 7 days, before the distal attachment was divided and the tissue assayed. In the acutely raised flaps, some animals were treated with the XO inhibitor, allopurinol. Xanthine dehydrogenase (XD) and XO activity was measured with a fluorometric pterin assay and neutrophil concentration was measured using a myeloperoxidase marker. In this model, there was consistent skin necrosis in the distal end of the skin flap (48 +/- 8%). The data showed that both XD and XO activity in the distal ends was statistically significantly increased over the sham control or proximal ends of the skin flaps at 1 hr (P < 0.05). XO activity remained elevated in the distal ends at 6 hr. Allopurinol significantly reduced the neutrophil concentrations in the distal ends of the skin flaps when compared to untreated animals (P < 0.05). Moreover, allopurinol reduced skin necrosis to 12 +/- 1%. Preconditioning of the skin flap reduced the XO activity to sham control levels. The observations implicate XO activity as source of free radical injury in skin necrosis seen in random skin flaps.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗
PubMed1990

Skin grafting: dermal components in inhibition of wound contraction.

The inhibition of wound contraction by skin grafting is widely accepted but poorly understood. We used an experimental model of contraction to study the effect of dermal organization, cellularity, and collagen matrix on contraction inhibition. Wound beds covered with inverted and collagen matrix grafts contracted at the same rate as full-thickness grafts. Heat denaturation diminished this ability. Partial-thickness grafts derived from papillary or reticular dermis inhibited contraction to an equal degree. Inhibition of contraction appears to relate to the amount of intact dermal collagen matrix transferred, and not to another component of a full-thickness graft.

Animals↗
PubMed1988

Portable chest roentgenography and computed tomography in critically ill patients.

Computed tomography (CT) of the chest offers improved resolution and sensitivity for evaluating chest pathologic conditions compared with other imaging techniques. Intensive care unit patients with portable chest findings that diverge from the clinical course may actually have severe intrathoracic disease that can be detected with CT. Our three patients demonstrate chest CT can aid in the diagnosis of significant intrathoracic pathologic conditions which have been significantly underestimated by portable chest roentgenography. We discuss the reasons for this improved detectability by CT, as well as suggest alternative techniques that can be performed at the bedside in patients whose initial portable chest roentgenogram and clinical course do not correlate.

Adult↗
PubMed1988

Airway pressure release ventilation (APRV). A human trial.

After operative coronary revascularization, 14 consenting adults received conventional positive pressure ventilation (PPV). When they were hemodynamically stable, data were collected during PPV and then during airway pressure release ventilation (APRV). During APRV, airway pressure (Paw) was reduced periodically at the lowest frequency which produced normal PaCO2. As anesthesia resolved, the rate of APRV breaths was decreased until patients breathed only with CPAP. During PPV and APRV, pHa, PaO2/FIO2, and hemodynamic variables were similar. All patients were weaned from APRV without complication. Optimal ventilator design for patients with acute lung injury would provide CPAP as a primary intervention and secondarily would augment alveolar ventilation. The APRV supported oxygenation and ventilation in patients with mild acute lung injury, yet with much lower peak airway pressure than produced by PPV.

Airway Resistance↗
PubMed1985

Validity and reproducibility of the Cooperative Cataract Research Group (CCRG) cataract classification system.

The validity and reproducibility with which six classifiers [one experienced (L.T.C.), and five novices (W.G., F.G., W.W., J.W. and O.W.)] used the CCRG cataract classification system was assessed. The validity of index classifications was assessed by computing sensitivities and pairwise interclass correlations between experienced and novice classifiers using the former's classification as the standard. The number of unordered combinations of terms in the CCRG's classification was reduced by combining cortical terms according to the CCRG's accepted system of staged simplification. The number of combinations of terms at each stage is as follows: Stage I (greater than 1000); II (127); III (63); IV (15); V (7); VI and VII (3) and VIII (2). Excellent agreement was obtained between the experienced and novice classifiers for Stages VII and VIII of the classification, good agreement for Stages V and VI and poor agreement for Stages IV, III and II (sensitivities of 97, 96, 72, 59, 40, 24 and 20% respectively). Good agreement was also achieved for the classifications of single lenticular regions, except for subcapsular regions. The intra- and interobserver reproducibility was assessed by computing the Kappa statistic to (1) compare classifications between novice observers and (2) compare repeat classifications made by the same observer by viewing the same cataract once on each of three different days. The novice classifiers had excellent intraobserver reproducibility for Stages VII and VIII (Kappas of 0.87 and 0.97 respectively), good reproducibility for Stages IV, V and VI (Kappas of 0.53, 0.62 and 0.62, respectively) and marginal reproducibility for stages II and III (Kappas of 0.39 and 0.40, respectively). The intraobserver reproducibility of the experienced classifier was superior to the others for virtually all characteristics with excellent reproducibility for Stages IV, V, VI, VII and VIII with Kappas of 0.79, 0.90, 1.0, 1.0 and 1.0, respectively and good reproducibility for Stages II and III (Kappas of 0.55 and 0.64, respectively). These results indicate that the simplified CCRG cataract classification system (Stages IV-VIII) passes the minimum standards for reproducibility. The performance of the experienced classifier far exceeds the minimum standards and indicates the feasibility of improving classifier performance with training and practice.

Cataract↗
PubMed1985

cAMP-dependent phosphorylation of bovine lens alpha-crystallin.

This communication reports that the A1 and B1 chains of bovine lens alpha-crystallin are phosphorylated. The conclusion is based on the following evidence: (i) When soluble preparations from lens cortex are incubated with [gamma-32P]ATP, a cAMP-dependent labeling of a high molecular weight protein is obtained. (ii) After NaDodSO4/PAGE, the label is found in two bands with Mr 22,000 and 20,000, corresponding to the B and A chains of alpha-crystallin, respectively. (iii) Isoelectric focusing indicates that the radioactivity is almost exclusively in bands with pI values of 5.58 and 6.70, corresponding to the A1 and B1 chains, respectively. (iv) Similar results are obtained in experiments of [32P]orthophosphate incorporation in lens organ culture. (v) Analyses of the digested protein indicate the label is exclusively in phosphoserine. (vi) 31P NMR analyses of native, proteolytically digested, and urea-treated alpha-crystallin gives a chemical shift of 4.6 ppm relative to 85% H3PO4 at pH 7.4, suggesting that the phosphate is covalently bound to a serine in the protein. An abundance of approximately one phosphate per four or five monomer units was found. (vii) Similar results were obtained by chemical analyses of independently prepared alpha-crystallin samples. The results are consistent with the view that the A1 and B1 chains arise as result of the phosphorylation of directly synthesized A2 and B2 polypeptides. It is suggested that this metabolically controlled phosphorylation may be associated with the terminal differentiation of the lens epithelial cell and the intracellular organization of the lens fiber cell.

Animals↗
PubMedDate not supplied

Psychosocial modifiers of immunocompetence in medical students.

This study addressed the effects of a naturally occurring stressor on components of the immune response. Blood was drawn twice from 75 first-year medical students, with a baseline sample taken one month before their final examinations and a stress sample drawn on the first day of final examinations. Median splits on scores from the Holmes--Rahe Social Readjustment Rating Scale and the UCLA Loneliness Scale produced a 2 X 2 X 2 repeated measures ANOVA when combined with the trials variable. Natural killer (NK) cell activity declined significantly from the first to the second sample. High scorers on stressful life events and loneliness had significantly lower levels of NK activity. Total plasma IgA increased significantly from the first to second sample, while plasma IgG and IgM, C-reactive protein, and salivary IgA did not change significantly.

Adult↗
PubMedDate not supplied

Urinary cortisol levels, cellular immunocompetency, and loneliness in psychiatric inpatients.

This study examined the associations among loneliness, stressful life events, urinary cortisol levels, and immunocompetency. Blood and urine were obtained from 33 psychiatric inpatients on the day after admission, at which time the patients completed the UCLA Loneliness Scale, the Psychiatric Epidemiology Research Interview Life Events Scale (PERI), and the MMPI. Patients who scored above the median on loneliness had significantly higher urinary cortisol levels. The high loneliness group also had significantly lower levels of natural killer cell activity, as well as a poorer T-lymphocyte response to phytohemagglutinin. The high loneliness subjects described themselves as more distressed than the low loneliness group on the MMPI. There were no consistent significant effects on either the immunologic measures or the MMPI associated with the PERI.

Adolescent↗