Exact solution of a one-dimensional deterministic sandpile model.
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Journal Article↗
Biomedical subjects
D Chang
Publications and source records attributed to D Chang.
Haemophilus aphrophilus bleb infection after a mitomycin trabeculectomy.
BACKGROUND: Haemophilus aphrophilus is a rare cause of ocular infection. It has been reported once as a cause of late-onset endophthalmitis in a patient with an inadvertent bleb after cataract surgery. We present a case of Haemophilus aphrophilus bleb infection after a mitomycin trabeculectomy. METHODS: A 56-year-old woman presented with a bleb infection 10 weeks after a mitomycin C augmented trabeculectomy at a University tertiary referral practice of one of the authors (GET). The causative organism was Haemophilus aphrophilus, identified by the Toronto Public Health Laboratory, Ontario, Canada. RESULTS: The bleb infection resolved following topical, subconjunctival and intravenous antibiotic therapy. A formal bleb revision was required to repair a persistent bleb leak. CONCLUSION: Patients who have had trabeculectomies augmented with mitomycin C may be predisposed to bleb infection with unusual organisms. Prompt diagnosis and treatment is necessary to control the infection. Increased awareness and communication with laboratory personnel may increase the isolation of this fastidious organism.
Anti-Bacterial Agents↗
Interactions of pulmonary surfactant protein D (SP-D) with human blood leukocytes.
Surfactant protein D (SP-D) is believed to contribute to nonimmune host defense within the alveoli and distal airways of the lung. SP-D molecules can bind to specific carbohydrates on the surface of bacterial, fungal, and viral organisms and can also interact with membrane glycoconjugates expressed by alveolar macrophages. Because neutrophils (PMN) and monocytes are recruited into the airspaces in association with many types of infection or lung injury, we examined the interactions of these cells with purified natural and recombinant SP-Ds, using a modified Boyden chamber assay and checkerboard analysis. Natural or recombinant rat SP-D (approximately 10(-9) to 10(-13) M) showed dose-dependent effects on human PMN and monocyte migration with a maximal response at a SP-D concentration of 5 ng/ml (approximately 10(-11) M). The migratory response was comparable to that obtained with the optimum concentration of FMLP (10(-8) M). HL-60 cells, after induction of differentiation with DMSO, responded to SP-D with the same dose-response as neutrophils. The effects of SP-D were abrogated by the simultaneous addition of SP-D to the upper chamber or by the addition of antibodies to the carboxy-terminal lectin domain. Migration toward SP-D was markedly inhibited (< 10% of controls) by 10 mM maltose but was not significantly inhibited by to 50 mM lactose. These studies establish that SP-D can bind to specific sites on neutrophils and monocytes and strongly suggest that these interactions involve the saccharide binding domains of SP-D.
Animals↗
Neu differentiation factor upregulates epidermal migration and integrin expression in excisional wounds.
Neu differentiation factor (NDF) is a 44-kD glycoprotein which was isolated from ras-transformed rat fibroblasts and indirectly induces tyrosine phosphorylation of the HER-2/neu receptor via binding to either the HER-3 or HER-4 receptor. NDF contains a receptor binding epidermal growth factor (EGF)-like domain and is a member of the EGF family. There are multiple different isoforms of NDF which arise by alternative splicing of a single gene. To date, in vivo biologic activities have not been demonstrated for any NDF isoform. Since NDF, HER-2/neu, and HER-3 are present in skin, and other EGF family members can influence wound keratinocytes in vivo, we investigated whether NDF would stimulate epidermal migration and proliferation in a rabbit ear model of excisional wound repair. In this model, recombinant human NDF-alpha 2 (rhNDF-alpha 2), applied once at the time of wounding, induced a highly significant increase in both epidermal migration and epidermal thickness at doses ranging from 4 to 40 micrograms/cm2. In contrast, rhNDF-alpha 1, rhNDF-beta 1, and rhNDF-beta 2 had no apparent biologic effects in this model. rhNDF-alpha 2 also induced increased neoepidermal expression of alpha 5 and alpha 6 integrins, two of the earliest integrins to appear during epidermal migration. In addition, rhNDF-alpha 2-treated wounds exhibited increased neoepidermal expression of cytokeratin 10 and filaggrin, both epidermal differentiation markers. NDF alpha isoforms were expressed in dermal fibroblasts of wounded and unwounded skin, while both HER-2/neu and HER-3 were expressed in unwounded epidermis and dermal adnexa. In wounds, HER-2/neu expression was markedly decreased in the wound neoepidermis while neoepidermal HER-3 expression was markedly upregulated. Taken together, these results suggest that endogenous NDF-alpha 2 may function as a paracrine mediator directing initial epidermal migration during cutaneous tissue repair.
Animals↗
Surfactant protein D interacts with Pneumocystis carinii and mediates organism adherence to alveolar macrophages.
Pneumocystis carinii interacts with glycoproteins present in the lower respiratory tract through its mannose-rich surface antigen complex termed gpA. Surfactant protein D (SP-D) is a recently described component of the airspace lining material that possesses a calcium-dependent lectin domain capable of interacting with glycoconjugates present on microorganisms and leukocytes. Accordingly, we evaluated the extent and localization of SP-D in the lower respiratory tract during Pneumocystis pneumonia in an immunosuppressed rat model and examined its role in modulating interaction of P. carinii with macrophages. We report that SP-D is a major component of the alveolar exudates that typify P. carinii pneumonia and is present bound to the surface of P. carinii organisms in vivo. We further demonstrate that SP-D binds to P. carinii through saccharide-mediated interactions with gpA present on the surface of the organism. Lastly, we show that SP-D augments binding of P. carinii to alveolar macrophages, but does not significantly enhance macrophage phagocytosis of the organism. The interaction of SP-D with gpA represents an additional important component of the host-parasite relationship during P. carinii pneumonia.
Animals↗
Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.
Some human chronic dermal wounds treated with recombinant platelet-derived growth factor-BB (rPDGF-BB) show increased healing coupled with fibroblast activation and granulation tissue formation. To determine whether endogenous PDGF is associated with healing and nonhealing dermal ulcer phenotypes, we developed monoclonal antibodies capable of recognizing the three isoforms of PDGF, AA, AB, and BB dimers, and capable of discriminating between two alternatively spliced A chain transcripts. We detected little PDGF isoform expression in normal skin and in nonhealing dermal ulcers. In contrast, in surgically created acute wounds and chronic ulcers treated with rPDGF-BB, markedly upregulated levels of PDGF-AA (long form) were found. In both types of wounds, increased PDGF-AA was detected primarily in capillaries and fibroblasts, although in rPDGF-BB-treated chronic wounds, widespread expression of PDGF-AA was somewhat delayed. With continued treatment, the long form of PDGF-AA, which can preferentially bind extracellular matrix, was expressed only in capillaries, while fibroblasts began synthesizing the short form of PDGF-AA. Within capillaries, all endothelial cells and varying numbers of pericytes and smooth muscle cells contained PDGF-AA. In all wounds, macrophages and keratinocytes were not a major contributor. While PDGF-BB and PDGF-AB were present in a minority of healing wounds, they were usually present at lower levels than PDGF-AA. PDGF-beta receptors, which bind only PDGF-BB and not other isoforms, were found in normal skin and granulation tissue, providing a molecular basis for treating human chronic wounds with exogenous rPDGF-BB.
Adult↗
Effect of lifting belts, foot movement, and lift asymmetry on trunk motions.
Whether or not lifting belts protect workers from injury is a topic of considerable interest in industry. Not only is the protective effect uncertain, but the biomechanical basis for belt function is unclear. The objective of this study was to determine if lifting belts provide a means for controlling trunk motions during asymmetric material-handling tasks. We recruited 16 nursing personnel as experienced lifters to participate in two lifting sessions. A lifting belt was worn in one session and for a week prior to this session during the subjects' routine work activities. Each session required 42 lifts, distributed across three asymmetry conditions (0, 45, and 90 deg) and temporally spaced 30 s apart. Foot motion was not permitted in half the lifts. Results indicated that during lifting, lateral bending and twisting motions were reduced by both the lifting belt and foot motion; the most pronounced effect was observed at 90 deg of asymmetry. Trunk motions in the sagittal plane during lifting were not affected by the lifting belt. These results appear to support the use of lifting belts in asymmetric lifting conditions, but more research is needed to determine whether the muscles in the torso benefit from the reduced motion or are working harder to overcome this resistance to motion, causing increased internal loads on the spine during asymmetric material-handling tasks.
Adult↗
Abdominal computed tomographic scan in the selection of patients with mucinous peritoneal carcinomatosis for cytoreductive surgery.
BACKGROUND: Cytoreductive surgery and intraperitoneal chemotherapy have been used to treat peritoneal carcinomatosis. A complete surgical resection is required for optimal results to be achieved. This study evaluated the preoperative computed tomographic (CT) findings in patients with mucinous peritoneal carcinomatosis in order to predict the probability of a complete resection. STUDY DESIGN: Computed tomographic scans of the abdomen and pelvis were reviewed retrospectively in 45 patients with a diagnosis of mucinous peritoneal carcinomatosis who were treated with surgery and intraperitoneal chemotherapy. According to the completeness of cytoreduction, patients were divided into two groups. Patients in the first group (n = 25) had complete cytoreduction (CR) with no tumor deposits 2.5 mm in diameter or larger left behind. The surgical resection of tumor was incomplete in the second group of patients (n = 20). Sixteen CT parameters were initially examined in each group of patients and statistically evaluated according to the completeness of the cytoreductive surgical procedure. RESULTS: The incidences of six CT findings were significantly different in the two groups of patients. These findings were: tumor volume in small bowel mesentery (p < 0.001), tumor volume in proximal jejunum (p = 0.003), tumor volume in distal jejunum (p = 0.002), tumor volume in proximal ileum (p = 0.003), mesentery configuration (p < 0.001), and obstruction of bowel segments by tumor (p < 0.001). A statistical approach using a tree-structured diagram showed that patients with both obstruction of bowel segments by tumor and tumor diameter greater than 0.5 cm on small bowel surfaces exclusive of distal ileum on preoperative CT scan, had an 88 percent probability of incomplete resection. Patients without these two CT findings had a 92 percent probability of complete resection. CONCLUSIONS: This study shows that selection criteria for patients with mucinous peritoneal carcinomatosis are available on a preoperative CT scan of the abdomen and pelvis. Patients whose scans show obstruction of bowel segments by tumor and tumor diameter greater than 0.5 cm on small bowel surfaces exclusive of distal ileum are unlikely to be candidates for cytoreductive surgery for the treatment of peritoneal carcinomatosis.
Adenocarcinoma, Mucinous↗
Surfactant protein-D modulates interaction of Pneumocystis carinii with alveolar macrophages.
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Animals↗
ARIA is concentrated in nerve terminals at neuromuscular junctions and at other synapses.
Skeletal muscle ACh receptors (AChRs) accumulate at neuromuscular junctions (nmjs) at least partly because of the selective induction of AChR subunit genes in subsynaptic myotube nuclei by the motor nerve terminal. Additionally, mammalian AChRs undergo a postnatal change in subunit composition from embryonic (alpha 2 beta gamma delta) to adult (alpha 2 beta epsilon delta) forms, a switch that also depends on innervation. ARIA, a protein purified from chicken brains based on its ability to induce AChR synthesis in primary chick muscle cells, is a strong candidate for being the molecule responsible for these early developmental events. ARIA mRNA has been detected in embryonic motor neurons during synapse formation, and the gene continues to be expressed postnatally. In this report, we provide evidence that ARIA-like immunoreactivity is concentrated in rat motor nerve terminals from early postnatal ages, and that it can be detected in motor neurons in E18 embryos. ARIA is also detectable in axons within colchicine-treated sciatic nerves, suggesting that the protein in the nerve terminal has been transported from the cell body. ARIA mRNA is present in, but not restricted to, cholinergic neurons. Likewise, we report here that ARIA-like immunoreactivity is present in some noncholinergic central synapses. We also present evidence that isoforms of ARIA are differentially distributed among functionally distinct classes of neurons.
Animals↗
Aniseikonia, metamorphopsia and perceived entoptic pattern: some effects of a macular epiretinal membrane, and the subsequent spontaneous separation of the membrane.
Following cryo surgery for retinal hole repair, visual effects in the senior author's eyes were caused by an epiretinal membrane. Subjectively, metamorphopsia was noted, and entoptically perceived radial striae were observed centred near fixation. After subsequent cataract surgery, metamorphopsia was not detectable. Several months later, the centre of the striate entoptic pattern was observed to be centered several degrees from fixation. Concurrently, loss of contrast in the central visual field was noted. In time, both the entoptic pattern and the contrast effects became less visible (contrast improved much faster). The epiretinal membrane had spontaneously separated from the fovea. Repeated measurements of aniseikonia were obtained before cataract surgery, and after cataract surgery both prior to, and after the separation of the epiretinal membrane. Inferences are drawn.
Aniseikonia↗
ErbB-3 and ErbB-4 function as the respective low and high affinity receptors of all Neu differentiation factor/heregulin isoforms.
Neu differentiation factor (NDF or heregulin) elevates tyrosine phosphorylation of the ErbB-2 receptor tyrosine kinase, and it was, therefore, thought to function as a ligand of this receptor. However, several lines of evidence raised the possibility that the interaction between NDF and ErbB-2 involves another molecule, which belongs to the family of epidermal growth factor receptors. To address this question we constructed soluble chimeric proteins between alkaline phosphatase and the extracellular domains of ErbB-2 and either ErbB-3 or ErbB-4, two newly recognized members of the epidermal growth factor receptor family. Using the soluble proteins we found that beta isoforms of NDF specifically bind to the ErbB-3 and ErbB-4 receptors but not to the soluble ErbB-2 protein. When ectopically expressed in monkey fibroblasts, the full-length ErbB-3 and ErbB-4 receptors conferred specific binding to NDF. In these cells ErbB-3 displayed lower ligand binding affinity than ErbB-4, but like the latter receptor it preferred to bind the beta isoform over the alpha class of NDFs. These results indicate that both ErbB-3 and ErbB-4 function as physiological receptors of all NDF isoforms and suggest that a still unknown ligand of ErbB-2 exists.
Amino Acid Sequence↗
Brain neurons and glial cells express Neu differentiation factor/heregulin: a survival factor for astrocytes.
Neu differentiation factor (NDF, also called heregulin) was isolated from mesenchymal cells on the basis of its ability to elevate phosphorylation of ErbB proteins. Earlier in situ hybridization analysis showed that NDF was transcribed predominantly in the central nervous system during embryonic development. To gain insights into the role of NDF in brain we analyzed its distribution by immunohistochemistry and in situ hybridization. Late-gestation (day 17) rat embryos displayed high NDF immunoreactivity in both motor (e.g., putamen) and limbic (e.g., septum) regions. Lower levels of the factor were exhibited by adult brain, except for the cerebellum, where NDF expression was increased postnatally. Both neurons and glial cells were identified by immunohistochemistry as NDF-producing cells (e.g., pyramidal neurons in the cerebral cortex and glial cells in the corpus callosum). By establishment of primary cultures of rat brain cells we confirmed that NDF was expressed in neurons as well as in astrocytes. In addition, by using such primary cultures we observed that NDF treatment exerted only a limited mitogenic effect, which was accompanied by significant acceleration of astrocyte maturation. Furthermore, long-term incubation with the factor specifically protected astrocytes from apoptosis, implying that NDF functions in brain as a survival and maturation factor for astrocytes.
Animals↗
Molecular structure of pulmonary surfactant protein D (SP-D).
Previous studies have shown that pulmonary surfactant protein D (SP-D) is composed of a 43-kDa polypeptide with a short NH2-terminal domain, a collagen sequence, and a COOH-terminal C-type lectin domain. In the present studies, ultrastructural and biochemical techniques were used to examine the quaternary structure of native rat SP-D (rSP-D). Electron microscopy of freeze-dried preparations demonstrated a highly homogeneous population of molecules with four identical rod-like arms (46 nm in length), each with an 8-9-nm diameter globular terminal expansion. The arms, which are similar in diameter to the type I collagen helix (approximately 4 nm), emanate from the central "hub" in two pairs that closely parallel each other for their first 10 nm. This structure is consistent with hydrodynamic studies that predict an highly asymmetric and extended molecule (f/f0 = 3.26) with a large Stokes radius (Rs = 18 nm). Pepsin digestion gave glycosylated, trimeric collagenous fragments (43 +/- 4 nm, 17 kDa/chain). Trimeric subunits containing intact triple helical domains were also liberated from SP-D dodecamers by sulfhydryl reduction under non-denaturing conditions. Digestion of rSP-D with bacterial collagenase generated a COOH-terminal carbohydrate binding fragment and a smaller peptide (approximately 12 kDa, unreduced) that contains interchain disulfide bonds. Electron microscopy also demonstrated higher orders of multimerization, with as many as 8 molecules associated at the hub. These studies demonstrate that SP-D is assembled as homopolymers of four identical trimeric subunits, that interactions between the amino-terminal domains of the trimers are stabilized by interchain disulfide bonds, and that SP-D molecules can associate to form complex multimolecular assemblies.
Amino Acid Sequence↗
Recombinant pulmonary surfactant protein D. Post-translational modification and molecular assembly.
Pulmonary surfactant protein D (SP-D) is a member of a family of collagenous C-type lectins that includes the serum mannose binding proteins and surfactant protein A. Recent studies have shown that rat SP-D (rSP-D) molecules are assembled as tetramers of trimeric subunits (12 mers) and that dodecamers can participate in higher orders of molecular assembly involving interactions of the amino-terminal peptide domains. In order to further study the assembly of SP-D in vitro, Chinese hamster ovary K1 cells were transfected with a full-length rat SP-D cDNA, and stable transfectants with high levels of SP-D production (approximately 6 x 10(6) dodecamers/cell/24 h) were obtained using a glutamine synthetase selection system. The secreted molecules (RrSP-D), which were purified by affinity chromatography on maltosyl-agarose, comigrated with rSP-D on SDS-polyacrylamide gel electrophoresis in the presence and absence of reduction, and coeluted with rSP-D dodecamers from 4% agarose. The major bacterial collagenase-resistant peptide showed a decreased mobility on reduction consistent with the formation of intrachain disulfide bonds. A 17-kDa pepsin-resistant fragment was isolated following overnight digestion with pepsin at 27 degrees C, confirming the formation of a triple helical domain comparable in size and thermal stability to that of natural SP-D. The expressed protein contained sialylated endoglycosidase F-sensitive carbohydrate; amino acid analysis of acid and alkaline hydrolysates demonstrated essentially normal levels of hydroxyproline, hydroxylysine, and hydroxylysine-glycosides. Electron microscopic studies showed a molecular structure indistinguishable from lung SP-D, with a similar small subpopulation of molecules showing higher orders of multimerization. Solid-phase neoglycoprotein binding assays gave the same saccharide inhibition profile as natural rat SP-D, and both proteins showed efficient saccharide-dependent agglutination of Escherichia coli. These studies demonstrate that a single genetically distinct chain type can account for the various and complex molecular assemblies of SP-D, and further verify the potential physiologic significance of the disulfide-bonded multimers and higher aggregates isolated from rat, bovine, and human lung lavage.
Agglutination↗
Status epilepticus results in reversible neuronal injury in infant rat hippocampus: novel use of a marker.
Despite ready induction of severe limbic status epilepticus by systemic kainic acid (KA) in infant rats, excitotoxic neuronal injury has not been observed. The mechanisms of this resistance of the immature hippocampus to excitotoxicity are unknown. Acid fuchsin stain has been used as a marker of irreversibly injured neurons in the adult brain. We speculated that the dye might map reversibly injured neurons in the infant. Subsequent to KA-induced status epilepticus in 11-day-old rats, acid fuchsin stain was evident in the hippocampal CA3, CA1, dentate gyrus and hilus by 24 h, peaked at 48 h and disappeared by 6 days, without evidence for neuronal loss. Acid fuchsin may be a useful tool for delineating the distribution of reversibly injured immature neurons in experimental seizure paradigms.
Animals↗
Disposition and metabolism of Ro 24-4736 in the rat.
Ro 24-4736, a new platelet activating factor antagonist, is currently under preclinical and clinical development. The tissue distribution of the 14C-label in male rats following a single intravenous dose of 1.0 mg/kg of 14C-Ro 24-4736 indicated appreciable uptake by the liver, kidney, heart and gastrointestinal tract. Peak plasma and tissue concentrations were seen at 5 minutes after dosing except for the small intestine (4 hrs) and abdominal fat, stomach and large intestine (4 hrs). Thereafter, the 14C-label rapidly declined in all tissues. At 48 hours, only 3.5% of the dose was present in the tissues, and 6.1% in the lumen of the gastrointestinal tracts. The excretion of 14C was essentially completed; 94% of the administered 14C was excreted in the feces and 4.0% in the urine. Overall recoveries of the administered 14C label ranged from 96 to 116%. The purified major 14C-labelled component in the fecal extracts yielded essentially the same NMR spectrum as authentic Ro 24-4736 which accounted for 11% of the dose. In vitro incubations of Ro 24-4736 with rat liver 9S supernatant in an NADPH generating system produced two metabolites. NMR spectra indicated that one metabolite was hydroxylated at carbon-1 while the other one contained a hydroxyl at carbon-10 of the parent molecule. Interestingly, the sites of hydroxylation were at carbons C1, and C10 bearing the protons guarding the bay area of the phenanthrenoid ring, rather than carbons of the phenyl-methyl-thienotriazolodiazepine moiety.
Animals↗
A prospective study of vancomycin pharmacokinetics and dosage requirements in pediatric cancer patients.
Pharmacokinetics of vancomycin and dosage requirements were evaluated prospectively in 28 pediatric cancer patients 9 months to 13 years of age. The predictive performance of a two-compartment Bayesian forecasting program was also evaluated. A mean (+/- SD) daily dosage of 75 +/- 22 mg/kg/day was necessary to attain a mean peak serum vancomycin concentration (SVC) of 23.1 +/- 5.8 mg/liter and a mean trough SVC of 6.2 +/- 2.3 mg/liter. Mean vancomycin clearance, volume of distribution and serum half-life were 0.153 +/- 0.033 liter/hour/kg, 0.63 +/- 0.08 liter/kg and 2.95 +/- 0.48 hours. Final peak SVCs, which reflected the last dosage regimens received, were predicted with minimal bias (mean prediction error, -1.2 mg/liter) and accurate precision (root mean-squared prediction error, 2.0 mg/liter) whereas trough SVCs were predicted with even smaller bias (mean prediction error, -0.1 mg/liter) and greater precision (root mean-squared prediction error, 0.8 mg/liter). This study showed that pediatric cancer patients with normal renal function required vancomycin dosage regimens substantially greater than the standard 40 mg/kg/day to attain the desired SVCs.
Adolescent↗