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PubMed2003

Dynamics and energetics of single-step hole transport in DNA hairpins.

The dynamics of single-step hole transport processes have been investigated in a number of DNA conjugates possessing a stilbenedicarboxamide electron acceptor, a guanine primary donor, and several secondary donors. Rate constants for both forward and return hole transport between the primary and secondary donor are obtained from kinetic modeling of the nanosecond transient absorption decay profiles of the stilbene anion radical. The kinetic model requires that the hole be localized on either the primary or the secondary donor and not delocalized over both the primary and the secondary donor. Rate constants for hole transport are found to be dependent upon the identity of the secondary donor, the intervening bases, and the location of the secondary donor in the same strand as the primary donor or in the complementary strand. Rate constants for hole transport are much slower than those for the superexchange process used to inject the hole on the primary donor. This difference is attributed to the larger solvent reorganization energy for charge transport versus charge separation. The hole transport rate constants obtained in these experiments are consistent with experimental data for single-step hole transport from other transient absorption studies. Their relevance to long-distance hole migration over tens of base pairs remains to be determined. The forward and return hole transport rate constants provide equilibrium constants and free energies for hole transport equilibria. Secondary GG and GGG donors are found to form very shallow hole traps, whereas the nucleobase deazaguanine forms a relatively deep hole trap. This conclusion is in accord with selected strand cleavage data and thus appears to be representative of the behavior of holes in duplex DNA. Our results are discussed in the context of current theoretical models of hole transport in DNA.

Base Pairing↗

PubMedDate not supplied

Pigment granule migration in crustacean photoreceptors requires calcium.

We have investigated the role of calcium in the regulation of pigment granule migration in photoreceptors of the semi-terrestrial crab, Sesarma cinereum. Isolated crab eyes (eyecup plus eyestalk) were maintained in crustacean Ringer either prepared normally or calcium-free plus 50 mM EGTA. Pigment granule movement was indirectly observed by monitoring reflectance from the eye during light stimuli using intracellular optical physiological techniques. Electroretinograms (ERGs) were also measured during light stimuli. EGTA treatment caused gradual loss of centripetal migration of pigment granules (normally leading to pupillary closure), and photoreceptors eventually became locked in the open-pupil, dark-adapted state despite repeated stimuli. In contrast, ERG responses continued throughout EGTA treatment, although the size and shape of the response was altered. Normal ERG responses and pigment granule movements returned after replacing EGTA-Ringer with normal-calcium medium. These results suggest that centripetal migration of pigment granules in crustacean photoreceptors requires calcium.

Animals↗

PubMedDate not supplied

[Effects of a controlled Staphylococcus aureus infection on the renewal of endoalveolar cells].

We have studied, in rats, the influence of the intratracheal injection of 30 X 10(6) Staphylococcus aureus upon the differential count and renewal of the cell populations extracted by pulmonary lavage. In vivo labelling of alveolar macrophages was performed by intratracheal injection of 125I iododeoxyuridine, and the evolution of the labelled population was quantitatively followed up after scheduled sacrifice. Dividing cells were also identified at all times in the lavage population, after incorporation of (3H)-thymidine in vitro and autoradiography. The injection of Staphylococcus aureus induced an acute inflammatory process followed by the migration of polymorphonuclears, lymphocytes and macrophages mainly during the first 24 hours. Later on, no viable bacteria were observed and the cell populations returned to control values. Kinetic parameters were found varying as a function of the cell type. The early increase of macrophages was mainly produced by the migration of monocytes, which exhibited a shorter lifespan in alveolus than did resident macrophages. The inflammatory reaction observed, whilst inducing a considerable modification of the cell distributions, did not significantly modify the lifespan of macrophages located within alveolus before the aggression.

Animals↗

PubMedDate not supplied

Travelers' compliance to prophylactic measures and behavior during stay abroad: results of a retrospective study of subjects returning to a travel medicine center in Italy.

BACKGROUND: Many sources of health advice are consulted by travelers, but in Europe, only 35% go to a travel clinic. Travel to countries outside Europe increases daily, and from 2001 to 2004, there was a marked increase in the number of travelers from the Florentine area crossing the borders (+18.0%), taking a plane (+81.4% of international travelers in Pisa airport), and applying to the Centre of Travel and Migration Medicine (CTMM) (+96%). METHODS: An anonymous survey was carried out at CTMM among those travelers returning to complete vaccinations for which the first dose had been given before going abroad. The survey included questions on vaccination status, adherence to recommended antimalaria prophylaxis, occurrence of other health problems, and food and drink consumption. RESULTS: The study population (which represents a "best case scenario") was composed of 1,237 subjects and had a very high compliance to the proposed questionnaire (95%). Approximately 55% of travelers took malaria chemoprophylactic measures, and 88% of them followed the indications given. Approximately 28% reported one or more secondary effects following antimalarial medication, and approximately 69% reported constant attention regarding safe consumption of food and drinks. Notwithstanding these measures, 236 cases of travelers' diarrhea were reported. CONCLUSIONS: Our results are conditioned by the self-selection of the study population (those who seek advice are likely to follow it through). However, since no certainty exists about other sources of health advice for the remainder of the traveler population in our region, both the importance of counseling offered by travel clinics as well as the recommendation to the ever-increasing number of travelers to consult these clinics are stressed.

Adult↗

PubMed2026

Preoperative Proximal Migration of the Radial Head as an Independent Predictor of Suboptimal Outcomes After Osteochondral Autograft Transplantation for Capitellar Osteochondritis Dissecans: A Retrospective Cohort Study.

BACKGROUND: Osteochondral autograft transplantation (OAT) is widely performed for capitellar osteochondritis dissecans (OCD). However, preoperative predictors of suboptimal postoperative outcomes remain unclear. PURPOSE/HYPOTHESIS: The authors aimed to evaluate clinical outcomes after OAT for capitellar OCD and identify preoperative risk factors associated with suboptimal outcomes. They hypothesized that radiographic indicators of disease severity, including preoperative proximal migration of the radial head, lesion size, and lateral wall disruption, would be associated with suboptimal postoperative clinical outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The records of adolescent athletes who underwent OAT for capitellar OCD with a minimum 2-year follow-up were retrospectively reviewed. Clinical outcomes included elbow range of motion (ROM) and Timmerman-Andrews (T-A) score. A suboptimal outcome was defined as a postoperative T-A score <160. Preoperative radiographs were used to measure proximal migration of the radial head relative to the coronoid process, hypertrophy of the radial head, OCD lesion area, and a 5-grade lateral wall disruption classification; measurement reliability was assessed. Multivariate logistic regression analysis was performed to identify independent predictors of a suboptimal outcome, and receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for proximal migration. RESULTS: A total of 69 elbows (mean age, 13.6 years; mean follow-up, 48 months) were included. ROM and T-A scores improved significantly after OAT, and all athletes returned to any sports. Of these, 50 elbows (72%) achieved good outcomes, whereas 19 (28%) had suboptimal outcomes. Preoperative proximal migration was significantly greater in the suboptimal outcome group compared with the good outcome group (mean, 2.1 ± 2.3 vs 0.5 ± 1.7 mm; P = .002), as were lesion area (mean, 70 ± 16 vs 58 ± 20 mm2; P = .02) and lateral wall disruption grade (median, 5 vs 3; P = .01). On multivariate analysis, proximal migration of the radial head was the only independent predictor of a suboptimal outcome (adjusted OR, 1.47 per 1-mm increase; 95% CI, 1.03-2.09; P = .033). ROC analysis showed an area under the curve of 0.72 with an optimal cutoff of 2.2 mm (sensitivity, 56%; specificity, 84%). CONCLUSION: OAT resulted in significant clinical improvement in adolescents with capitellar OCD; however, 28% of patients were classified as having suboptimal outcomes. Preoperative proximal migration of the radial head is an independent predictor of a suboptimal postoperative outcome. A value >2.2 mm may indicate advanced radiocapitellar incongruity, a condition in which OAT may be less effective.

Humans↗

PubMed2003

Computational model of the migrating motor complex of the small intestine.

The migrating motor complex (MMC) is a cyclic motor pattern with several phases enacted over the entire length of the small intestine. This motor pattern is initiated and coordinated by the enteric nervous system and modulated by extrinsic factors. Because in vitro preparations of the MMC do not exist, it has not been possible to determine the intrinsic nerve circuits that manage this motor pattern. We have used computer simulation to explore the possibility that the controlling circuit is the network of AH/Dogiel type II (AH) neurons. The basis of the model is that recurrent connections between AH neurons cause local circuits to enter a high-firing-rate state that provides the maximal motor drive observed in phase III of the MMC. This also drives adjacent segments of the network causing slow migration. Delayed negative feedback within the circuit, provided by activity-dependent synaptic depression, forces the network to return to rest after passage of phase III. The anal direction of propagation is a result of slight anal bias observed in projections of AH neurons. The model relates properties of neurons to properties of the MMC cycle: phase III migration speed is governed by neuron excitability, MMC cycle length is governed by the rate of recovery of synaptic efficacy, and phase III duration is governed by duration of slow excitatory postsynaptic potentials in AH neurons. In addition, the model makes experimental predictions that can be tested using standard techniques.

Algorithms↗

PubMed1994

Migration of so-called naive and memory T lymphocytes from blood to lymph in the rat. The influence of IFN-gamma on the circulation pattern.

It has been suggested that naive T lymphocytes migrate directly from the blood into the lymph nodes, whereas memory T lymphocytes arrive via the afferent lymphatics. However, these routes were defined indirectly by determining only the frequencies of naive and memory T lymphocytes in the afferent and efferent lymph of sheep. In this study naive (CD45RC+) and memory (CD45RC-) CD4+ lymphocytes obtained by thoracic duct cannulation of the rat were injected i.v. and their reappearance in the thoracic duct lymph (efferent lymph) was monitored in absolute numbers over 5 days. In addition, it was investigated whether continuous application of IFN-gamma influences the migration of the two subsets differently. After i.v. injection both naive and memory T lymphocytes returned to the thoracic duct in considerable numbers and with similar kinetic patterns. Interestingly, within 5 days at least 25% of memory phenotype lymphocytes converted to naive phenotype lymphocytes. When naive and memory T lymphocytes were injected in animals receiving a continuous IFN-gamma infusion, only the reappearance of the naive T lymphocytes but not that of memory T lymphocytes in the thoracic duct lymph was reduced. Thus, by investigating the migration of labeled lymphocytes, data were obtained that contradict conclusions drawn by analyzing preferential accumulation of lymphocyte subsets only. Our results suggest that in unstimulated animals naive and memory thoracic duct lymphocytes migrate at a similar tempo and to a comparable extent from the blood via the lymph node into the efferent lymph. IFN-gamma only influences the traffic of naive lymphocytes, indicating that the migration of the two populations is regulated by different mechanisms.

Animals↗

PubMed2000

Mapping the pathways for O2 entry into and exit from myoglobin.

The effects of mutagenesis on geminate and bimolecular O2 rebinding to 90 mutants at 27 different positions were used to map pathways for ligand movement into and out of sperm whale myoglobin. By analogy to a baseball glove, the protein "catches" and then "holds" incoming ligand molecules long enough to allow bond formation with the iron atom. Opening of the glove occurs by outward movements of the distal histidine (His(64)), and the ligands are trapped in the interior "webbing" of the distal pocket, in the space surrounded by Ile(28), Leu(29), Leu(32), Val(68), and Ile(107). The size of this pocket is a major determinant of the rate of ligand entry into the protein. Immediately after photo- or thermal dissociation, O2 moves away from the iron into this interior pocket. The majority of the dissociated ligands return to the active site and either rebind to the iron atom or escape through the His(64) gate. A fraction of the ligands migrate further away from the heme group into cavities that have been defined as Xe binding sites 4 and 1; however, most of these ligands also return to the distal pocket, and net escape through the interior of wild-type myoglobin is <20-25%.

Animals↗

PubMed2006

Strongyloides stercoralis: risks posed to immigrant patients in an Australian tertiary referral centre.

BACKGROUND: Strongyloides stercoralis is a nematode human parasite with a global prevalence that is able to maintain a prolonged infestation by means of its autoinfective life cycle. Immunosuppression may result in a life-threatening hyperinfection syndrome. Recent changes in migration have resulted in the arrival of many immigrants from endemic areas. As to whether physicians are alert to the risks of strongyloidiasis in these patient groups is unclear. The aim of the study was to assess the risks posed by chronic strongyloidiasis in patients presenting to a tertiary referral centre and the need for screening of immigrant patients before immunosuppression. METHODS: The study comprised a retrospective review of cases of strongyloidiasis presenting to the Alfred Hospital, Melbourne. Thirty-three cases were diagnosed by either positive serology or faecal microscopy between January 1998 and January 2005. The medical records for 29 cases were examined with regard to demographics, clinical features and complications. RESULTS: Two major groups were identified: immigrants (17) and returned travellers (11). Six immigrants, but no returned traveller, developed a hyperinfective syndrome. Five immigrants received immunosuppressive therapies before developing symptoms of hyperinfection and this was complicated by life-threatening sepsis in two patients. Diagnosis was frequently delayed in the immigrant group who were significantly more likely to present with respiratory symptoms. Four immigrants and two returned travellers were treated with corticosteroids for symptoms that were probably related to larval migration. CONCLUSION: Before giving immunosuppressive therapies, patients with a history of potential exposure must be investigated for strongyloidiasis and consideration given to empirical treatment.

Adult↗

PubMed1989

Enhancement of vinculin synthesis by migrating stratified squamous epithelium.

A 110-115-kD protein is present at levels 27-fold higher in migratory epithelium in the rat cornea than in stationary epithelium. This protein represents 2.7% of the total protein in migratory epithelium 6-h postabrasion wound and 0.1% of the total protein in stationary epithelium. Our findings demonstrate that this 110-115-kD protein is vinculin. In Western blots comparing proteins from migratory and control epithelium, antibody against vinculin cross-reacted with the 110-115-kD protein. Using immunoslot blots, vinculin was determined to be present at maximal levels 6 h postabrasion wound, at levels 22- and 8-fold higher than control at 18 and 48 h, respectively, returning to control levels 72 h postwounding. Vinculin was also localized by indirect immunohistochemistry in migrating corneal epithelium. 3-mm scrape wounds were allowed to heal in vivo for 20 h. In flat mounts of these whole wounded corneas, vinculin was localized as punctate spots in the leading edge of migrating epithelium. In cryostat sections, vinculin was localized as punctate spots along the basal cell membranes of the migrating sheet adjacent to the basement membrane and in patches between cells as well as diffusely throughout the cell. Only very diffuse localization with occasional punctate spots between adjacent superficial cells was present in stationary epithelium. The increased synthesis of vinculin during migration and the localization of vinculin at the leading edge of migratory epithelium suggest that vinculin may be involved in cell-cell and cell-substrate adhesion as the sheet of epithelium migrates to cover a wound.

Animals↗

PubMed1995

Shifts in the concentrations of magnesium and calcium in early porcine and rat wound fluids activate the cell migratory response.

Accruing evidence indicates that the levels of extracellular Mg2+ and Ca2+ can have a distinct impact on the adhesive and migratory activities of many cell types. The physiological relevance of these observations, however, has remained largely unexplored. In the present study, wound fluids collected throughout the early stages of cutaneous wound repair were examined for possible Mg2+ and Ca2+ fluctuations. Early in the process, when cell migration into the wound site is initiated, Mg2+ is elevated and Ca2+ is reduced (Mg2+:Ca2+ = 1). As wound healing progresses, wound fluid concentrations of Mg2+ and Ca2+ begin to return to normal plasma levels (Mg2+:Ca2+ = 0.4). When macrophages, keratinocytes, fibroblasts, and endothelial cells were exposed to dialyzed wound fluid, the migration stimulated by undialyzed wound fluid was lost. Addition back to dialyzed wound fluid of 24 h, postinjury concentrations of Mg2+ and Ca2+ restored all migratory stimulus. This observed migration is approximately twofold greater than when normal plasma Mg2+ and Ca2+ concentrations are present. Changes in the levels of Mg2+ and Ca2+ in wound fluid occur during the same period that inflammatory cells, keratinocytes, fibroblasts, and neovasculature have been shown to migrate during wound healing in vivo. Together, these data suggest that the impact of these changes on integrins and E-cadherin may play a direct role in the activation and maintenance of the migratory phenotypes of the cells involved in the wound healing process.

Animals↗

PubMed1990

Gastrointestinal motor effects of erythromycin.

We studied the small intestinal motor effects of oral and intravenous (iv) erythromycin in 10 conscious dogs. After control recordings with placebo, oral or iv erythromycin was given at 40% of the migrating motor complex (MMC) cycle. Recordings were made after administration until normal contractile activity had returned or 12 h postdrug administration. Low doses initiated a premature MMC. High doses, however, prolonged the MMC cycle length. Erythromycin reduced the MMC propagation velocity at all doses. Both oral and iv erythromycin induced amyogenesia. During this pattern, electrical control activity was obliterated in the proximal and destabilized in the distal small intestine. Erythromycin also increased the incidence of retrograde giant contractions (RGCs) and vomiting. These effects occurred within the first 2 h after oral and within the first 30 min after iv administration. The incidence of giant migrating contractions (GMCs) increased significantly from 5 to 12 h but not from 0 to 5 h after administration. The distance of origination of GMCs from the ileocolonic junction was significantly increased from 5 to 12 h. The amplitude ratio, duration, and velocity of migration of GMCs induced after erythromycin were similar to control values. Clusters of coordinated antral and duodenal contractions also occurred early after administration. Our findings suggest that erythromycin has multiple motor effects on the stomach and small intestine. Diarrhea, abdominal cramping, and vomiting associated with erythromycin may be related to increased incidence of GMCs and RGCs. Erythromycin has a biphasic effect on MMC cycle length, initiating premature MMCs at low doses and prolonging their cycle length at higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed2001

Fragmentation of riverine systems: the genetic effects of dams on bull trout (Salvelinus confluentus) in the Clark Fork River system.

Migratory bull trout (Salvelinus confluentus) historically spawned in tributaries of the Clark Fork River, Montana and inhabited Lake Pend Oreille as subadult and adult fish. However, in 1952 Cabinet Gorge Dam was constructed without fish passage facilities disrupting the connectivity of this system. Since the construction of this dam, bull trout populations in upstream tributaries have been in decline. Each year adult bull trout return to the base of Cabinet Gorge Dam when most migratory bull trout begin their spawning migration. However, the origin of these fish is uncertain. We used eight microsatellite loci to compare bull trout collected at the base of Cabinet Gorge Dam to fish sampled from both above and further downstream from the dam. Our data indicate that Cabinet Gorge bull trout are most likely individuals that hatched in above-dam tributaries, reared in Lake Pend Oreille, and could not return to their natal tributaries to spawn. This suggests that the risk of outbreeding depression associated with passing adults over dams in the Clark Fork system is minimal compared to the potential genetic and demographic benefits to populations located above the dams.

Animals↗

PubMed1989

Breast-feeding intentions and practice among Hispanic mothers in southern California.

Breast-feeding intentions, breast-feeding in the hospital, and breast-feeding at home were studied among 132 Hispanic mothers participating in the Expanded Food and Nutrition Education Program in southern California. There was not a large difference between total breast-feeding intention (77.7%) and total breast-feeding practice (63.8%). However, the 67.7% intention of exclusive breast-feeding drastically decreased to 19.7% and 17.2% in the hospital and at home, respectively. Formula supplementation, increased by 4.5 times from intention to practice. Exclusive formula feeding increased from 10.0% to approximately 37.0% in the hospital and at home. Stepwise logistic regression identified that the likelihood of intending breast-feeding was greater for mothers who migrated from Mexico than for mothers born in the United States (odds ratio 4.75). The likelihood of breast-feeding practice was greater for mothers who initiated breast-feeding within the first 10 hours after birth as opposed to 11 or more hours (odds ratio 1.27), for mothers who had a vaginal rather than cesarean delivery (odds ratio 12.76), for mothers who did not return to work postpartum as opposed to working mothers (odds ratio 28.26), and for mothers who migrated from Mexico compared with mothers born in the United States (odds ratio 8.54). The importance of assessing and supporting mothers' breast-feeding intentions in the pre- and post-partum period is documented. Training in the clinical aspects of breast-feeding and improvement of hospital protocols is recommended. Mothers intending to breast-feed should be identified and supported.

Adult↗

PubMed1995

Basic fibroblast growth factor is a signal for the initiation of centrosome redistribution to the front of migrating endothelial cells at the edge of an in vitro wound.

Rapid, efficient repair of the endothelium following focal endothelial wounding and denudation is regulated by a complex series of cellular processes. Directed cell migration, an early essential event in repair, is thought to be initiated by centrosome redistribution toward the front of the cell prior to the onset of migration. As such, centrosomal polarity may be an important regulatory event in directed endothelial cell migration. Little is known about the regulation of this process. To study this further, in vitro wounds were created down the middle of confluent porcine aortic endothelial monolayers by mechanical denudation. Conditioned media collected 1 hour after wounding contained basic fibroblast growth factor (bFGF). Antibodies directed against bFGF added to the cultures at the time of wounding significantly inhibited cell migration and transiently inhibited centrosome redistribution. When transcription was transiently inhibited with actinomycin D, present at 1 hour before and for 1 hour after wounding, the cells moved more slowly (5.2 +/- 2.8 versus 22.7 +/- 5.7 microns/h for control), taking five times longer for the wound to close. Throughout this period, centrosomes did not reorient to the front of the cells. When either recombinant bFGF or conditioned medium collected from control cultures at 1 hour after wounding was added 23 hours after actinomycin D was washed out (at which time RNA synthesis returned to control levels), the centrosomes redistributed to the front of the cells, and cells migrated at a rapid rate (17.2 +/- 4.2 microns/h), similar to control. However, the recombinant bFGF or conditioned media had no effect when added immediately after actinomycin D was removed, ie, when RNA synthesis was still inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

A simplified model of spatiotemporal population dynamics.

This paper is an extension of the model of population growth and migration originally developed by H. Hotelling in 1921. This model consists of two ingredients, a logistic growth function and a linear spatial diffusion term. The author notes that the saturation population can be affected by the development of new technology and that improvements in transportation have increased the possibilities for migration. "Basic nonlinearities are introduced by use of a production technology with increasing-decreasing returns to scale. It is demonstrated how industrial takeoffs, population transitions, and agglomerative spatial patterns can emerge by changing the model parameters."

Conservation of Natural Resources↗

PubMed2003

Effect of prolonged hyperdynamic endotoxemia on jejunal motility in fasted and enterally fed pigs.

OBJECTIVE: To determine the effects of hyperdynamic endotoxemia on the motility of the small intestine. SUMMARY BACKGROUND DATA: Motility disorders of the gastrointestinal tract are a common complication of sepsis. It has been suggested that gram-negative endotoxin plays a role in the pathogenesis of the accompanying diarrhea frequently observed. METHODS: Pigs were infused with lipopolysaccharide for a 24-hour period. During this fasting period jejunal motility was measured using ambulatory manometry. One and 4 days after cessation of endotoxin, pigs were enterally fed, and again motility was recorded. RESULTS: Hyperdynamic endotoxemia was achieved in this model. Manometric pressure recordings revealed that endotoxin infusion accelerated the migrating motor complex (MMC) migration along the jejunum. Also, a simultaneous increase in MMC cycling frequency was observed in the endotoxin-treated group. Elevated MMC migration velocity and cycling frequency were maintained the following day after endotoxin during feeding and returned to basal values 4 days after endotoxin. CONCLUSIONS: A small dose of continuously infused endotoxin significantly provokes jejunal motility disturbances that may contribute to diarrhea.

Animals↗

PubMed1991

Direct evidence for spatial and temporal regulation of transforming growth factor beta 1 expression during cutaneous wound healing.

The expression of transforming growth factor (TGF beta 1) protein in human and porcine skin has been analyzed by immunohistochemistry with two polyclonal antibodies (anti-CC and anti-LC) following cutaneous injury. The anti-LC antibody binds intracellular TGF beta 1 constitutively expressed in the nonproliferating, differentiated suprabasal keratinocytes in the epidermis of normal human skin, while the anti-CC antibody does not react with the form of TGF beta 1 present in normal skin as previously shown. TGF beta 1 may play a role in wound healing as suggested by its effect on multiple cell types in vitro and its acceleration of wound repair in animals. We have evaluated the natural expression and localization of TGF beta 1 protein in situ during initiation, progression, and resolution of the wound healing response in two models of cutaneous injury: the human suction blister and the dermatome excision of partial thickness procine skin. Anti-CC reactive TGF beta 1 in the epidermis is rapidly induced within 5 minutes following injury and progresses outward from the site of injury. The induction reflects a structural or conformational change in TGF beta 1 protein and can be blocked by the protease inhibitor leupeptin or by EDTA, suggesting a change in TGF beta 1 activity. One day post-injury anti-CC reactive TGF beta 1 is present in all epidermal keratinocytes adjacent to the wound including the basal cells. This corresponds temporally to the transient block of the basal keratinocyte mitotic burst following epithelial injury. Three to 4 days post-injury anti-CC reactive TGF beta 1 is localized around the suprabasal keratinocytes, in blood vessels, and in the papillary dermis in cellular infiltrates. The exclusion of TGF beta 1 from the rapidly proliferating basal cells and its extracellular association with suprabasal keratinocytes may represent physiological compartmentation of TGF beta 1 activity. Anti-CC staining is strong in the leading edge of the migrating epithelial sheet. The constitutive anti-LC reactivity with suprabasal keratinocytes seen in normal epidermis is neither relocalized nor abolished adjacent to the injury, but anti-LC staining is absent in the keratinocytes migrating within the wound. As the wound healing response resolves and the skin returns to normal, anti-CC reactive TGF beta 1 disappears while constitutive anti-LC reactive TGF beta 1 persists. Thus, changes in the structure or conformation of TGF beta 1, its localization, and perhaps its activity vary in a spatial and temporal manner following cutaneous injury and correlate with physiological changes during wound healing.

Animals↗