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PubMed1998

The influence of radiographic contrast media on some granulocyte functions.

Radiographic CM are used to change the X-ray absorption of tissue. They have been used since the 1930's and today four main types are available. All these CM are derived from one original structure: the 2,4,6 triiodobenzoic acid with the substituents in positions 1,2 and 5 as a carboxylic group or amides. According to the nature of the substituents and the number of aromatic rings, the four different types of CM can be identified. Three of the four types of CM are hyperosmolar, some of the ionic CM contain meglumine and all CM contain calcium disodium EDTA. To fulfil their role in host defence, circulatory PMN must adhere to endothelium of capillaries and venules adjacent to the inflammatory locus, migrate through the vessel wall to the area of inflammation, phagocytose opsonized bacteria, kill ingested organisms and, finally, inactivate their own toxic products to prevent damage to normal tissue. CM should be biologically inert, but many physiological and pathophysiological effects have been described. This review deals with the present knowledge about the influence of CM on PMN. This thesis presents results of the effects of the four main types of CM on PMN exocytosis of elastase and lactoferrin, adherence to nylon fibers, chemotaxis under agarose and phagocytosis of latex particles, as well after in vitro exposure of CM to PMN and after intravascular injection of CM. After in vitro exposure of CM to whole blood, a dose-dependent fall in lactoferrin and elastase concentration was observed, statistically significant for diatrizoate and ioxaglate at high concentrations. I.v. injection of iohexol or ioxaglate resulted in small, although statistical, decreases in lactoferrin concentration in plasma. No differences between the CM groups were seen. PMN adherence to nylon fibers after incubation of CM with whole blood or isolated PMNs was inhibited. The most inhibitive agents were the ionic CM diatrizoate and ioxaglate. The meglumine ion was found to contribute to the inhibitive effect of diatrizoate upon adherence. Following i.v. injection of iohexol or ioxaglate, increased numbers of PMNs, in combination with decreased adherence, were noted with ioxaglate, and the opposite with iohexol. Immediately after arteriography with iohexol and ioxaglate, a small increase of PMN count, in combination with decreased adherence, could be seen. An inhibition of adherence will result in a shift from the marginal to the circulatory pool of PMNs and thus an increase in PMN count. Although statistically significant the changes were minor. A pronounced increase in PMN count was seen 2-5 hours after arteriography in combination with a decrease in adherence. These changes may be due to a release of glucocorticoids from the adrenals in response to the procedure and/or the injection of CM. CMs do not act as chemoattractants. However, when CM are added to the chemoattractant N-fMLP in the under agarose assay, the number of PMNs migrating (density) was lowered, while the distance migrated by the leading front was not affected except for diatrizoate that almost abolished migration. When diatrizoate was added to PMNs, a dose-dependent inhibition was observed. Following i.v. injection of CM, no changes in PMN chemotaxis or changes in the chemoattractive potential of serum could be demonstrated compared to the baseline levels. The ability of PMNs to ingest latex particles after incubation with CM was inhibited in a dose-dependent way. The most inhibitive agents were diatrizoate and ioxaglate. A solution containing the same amount of disodium calcium EDTA as the CM solutions inhibited phagocytosis significantly, although less than the CM solution. Improved phagocytosis was observed in hyperosmolar environments due to NaCl or mannitol at osmolarities higher than 369 mOsm. I.v. injection of ioxaglate or iohexol inhibited the phagocytosis of latex particles by PMNs. The impairment was most pronounced immediately after the injection, and had almost returned to ba

Cell Adhesion↗
PubMed1992

Perforation and intravesical erosion of a ventriculoperitoneal shunt in a child with an augmentation cystoplasty.

Bladder augmentation has evolved into a common method of management in children with a low capacity and/or poorly compliant bladder secondary to a neuropathic condition. We report on a 4-year-old girl with myelodysplasia who presented with sepsis and who had a perforation of the augmented bladder, which was surgically repaired. She returned for evaluation 1 month after she was discharged from the hospital when the distal component of the ventriculoperitoneal shunt was noted to protrude per urethram after clean catheterization. Distal shunt replacement with prolonged bladder drainage successfully resolved this perforation of the augmented bladder. The patient has had no further difficulties. We discuss the diagnosis and management of this case with reference to the current literature regarding complications of augmentation cystoplasty.

Cerebrospinal Fluid Shunts↗
PubMed1996

Japan's growing economic activities and the attainment patterns of foreign-born Japanese workers in the United States, 1979 to 1989.

"This study examines the impact of the economic activities of Japan in the United States on the socioeconomic attainments of foreign-born Japanese male workers in 1979 and 1989. It demonstrates that working in wholesale trade, finance and manufacturing industries, three major sectors of Japanese investment in America, provided foreign-born male Japanese workers with the highest likelihood of assuming managerial positions. Moreover, the managerial occupation in turn provided the Japanese workers with the highest earnings returns. This pattern is consistent over time and by length of residence. The results suggest the importance of Japan's economic globalization since the 1970s in explaining the socioeconomic attainment patterns of foreign-born Japanese workers in the United States."

Americas↗
PubMed1987

Changes in neural cell adhesion molecule (NCAM) structure during vertebrate neural development.

Changes in carbohydrate and polypeptide form of the neural cell adhesion molecule (NCAM) have been documented during the development of central nervous system tissue in both chicken and frog. The carbohydrate variations reflect a high and low content of polysialic acid, and for the two vertebrates examined the expression of these forms is similar. At very early stages of neural development NCAM with a low content of polysialic acid is present, during histogenesis of the central nervous system NCAM with a high content of polysialic acid dominates, and there is a gradual return to NCAM with a low content of polysialic acid as the animals approach maturity. In contrast, the order of expression of the major NCAM polypeptide forms is different in the chicken and frog. These findings suggest that changes in sialic acid are a fundamental aspect of the function of NCAM in development, whereas NCAM polypeptide differences may affect events associated with a particular vertebrate. Studies have demonstrated that a decreased sialic acid content enhances the adhesion properties of NCAM. On this basis, we propose that NCAM with a low content of polysialic acid functions both to maintain integrity of neuroepithelium during morphogenesis of the early embryo and to stabilize differentiated structures in the adult, while the decreased adhesive function of NCAM with a high content of polysialic acid provides more plasticity in cell interactions during cell migration, axon outgrowth, and formation of neural circuits.

Animals↗
PubMed1999

Modulation of fibronectin expression in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis.

Fibronectin (FN), a large family of plasma and extracellular matrix (ECM) glycoproteins, plays an important role in leukocyte migration. In normal central nervous system (CNS), a fine and delicate mesh of FN is virtually restricted to the basal membrane of cerebral blood vessels and to the glial limitans externa. Experimental autoimmune encephalomyelitis (EAE), an inflammatory CNS demyelinating disease, was induced in Lewis rats with a spinal cord homogenate. During the preclinical phase and the onset of the disease, marked immunolabelling was observed on the endothelial luminal surface and basal lamina of spinal cord and brainstem microvasculature. In the paralytic phase, a discrete labelling was evident in blood vessels of spinal cord and brainstem associated or not with an inflammatory infiltrate. Conversely, intense immunolabelling was present in cerebral and cerebellar blood vessels, which were still free from inflammatory cuffs. Shortly after clinical recovery minimal labelling was observed in a few blood vessels. Brainstem and spinal cord returned to normal, but numerous inflammatory foci and demyelination were still evident near the ventricle walls, in the cerebral cortex and in the cerebellum. Intense expression of FN in brain vessels ascending from the spinal cord towards the encephalon preceded the appearance of inflammatory cells but faded away after the establishment of the inflammatory cuff. These results indicate an important role for FN in the pathogenesis of CNS inflammatory demyelinating events occurring during EAF.

Animals↗
PubMed2006

Local understandings of, and responses to, HIV: rural-urban migrants in Tanzania.

Migration is an important process of change for rural populations in developing countries. Migration is a primary cause of behaviour change-by their very act of migrating, migrants are different from those who do not migrate. The focus of the current study is male rural-urban migration in Tanzania and its interaction with sexual behaviour. The analysis presents results from a comparison with individual-level analyses of two populations, one (composed of recent rural-urban migrants) in an urban area and one made up of residents in a rural area. Detailed migration histories (n=96 rural-urban migrants) and in-depth interviews form the basis of the analysis. Three key research questions are addressed: How does the sexual behaviour of migrants differ from that of rural residents? How do HIV knowledge levels vary between rural-urban migrants and rural residents? What factors are associated with either intentions of behaviour change or reported behaviour? The results are counter-intuitive: rural-urban migrants-both married and unmarried-are not having sex in town. Despite limited understanding of the nature of HIV, the migrant population studied here regulates its behaviour in a way that reflects local understandings of the disease. This finding is important, not least because it challenges the view that HIV in sub-Saharan Africa is largely transmitted to rural areas by return migrants. Maasai rural-urban migrants in Tanzania-both married and unmarried-are not having sex in town. The policy and service provision implications of the results are explored.

Adult↗
PubMed2002

Transient CD44 variant isoform expression and reduction in CD4(+)/CD25(+) regulatory T cells in C3H/HeJ mice with alopecia areata.

Alopecia areata, an autoimmune disease affecting anagen stage hair follicles, can be induced by grafting spontaneous alopecia areata affected skin to normal-haired C3H/HeJ mice. As the onset of alopecia areata can be significantly retarded by anti-CD44 variant isoform 10 treatment, it was interesting to explore the underlying disease mechanism. Two weeks after transplanting alopecia areata affected skin, expression of CD44 variant isoforms 3, 6, 7, and 10 was strikingly upregulated as compared with sham-grafted mice. By 6 wk after grafting, CD44 variant isoform levels had returned to normal, whereas in draining lymph nodes, CD44 variant isoform expression was slightly decreased. Leukocytes in the skin of mice with chronic alopecia areata expressed a hematopoietic isoform of CD44 and CD44 variant isoform 6 at an elevated level, but CD44 variant isoform 3 expression was reduced. Cytokine expression in leukocytes of chronic alopecia areata affected skin was higher than in normal-haired controls. Cytokine expression also increased postsurgery in sham and alopecia areata grafted mice, but remained elevated only in mice receiving alopecia areata affected skin. Finally, from the skin of mice with chronic alopecia areata and of mice transplanted with alopecia areata affected skin, an increased number of CD4(+) and CD8(+) cells, but a strongly decreased number of CD4(+)/CD25(+) regulatory T cells was recovered. Thus, expression of CD44 variant isoforms is important for the migration of leukocytes during the initial period of alopecia areata. CD44, however, is apparently not involved in the maintenance of the disease state, which is characterized by high cytokine expression levels, an increased number of CD4(+) and CD8+ cells, but a low level of CD4(+)/CD25(+) suppressor cells.

Alopecia Areata↗
PubMed1995

Epidermal growth factor stimulates the restitution of rat gastric mucosa in vitro.

Epidermal growth factor (EGF) is mitogenic to gastric mucosal cells, protects against gastric mucosal injury induced by ulcerogenic agents, and stimulates cell migration in many systems. Restitution, the rapid re-establishment of mucosal integrity following damage, involves epithelial cell migration and can be monitored by measuring the transmucosal potential difference (PD) of tissue mounted in an Ussing chamber. The role of EGF in restitution is poorly characterized. To assess the effect of exogenous EGF on restitution, samples of rat gastric mucosa were mounted in an Ussing chamber with a solution of 10 nM EGF bathing either the mucosal or serosal surface. Matched control tissues from the same animals were untreated. Mucosal damage was induced by exposure of tissues to hyperosmolar sodium chloride. Restitution following injury was monitored by measuring the recovery of transmucosal PD, which reflects the degree of mucosal integrity. Undamaged mucosa maintained a PD of approximately -30 mV for several hours (mucosa negative with respect to serosa). Mucosal exposure to 1.2 M NaCl for 2 min reduced the PD to near 0 mV. Thereafter, the PD returned in approximately 60 min to plateau at a value representing maximal recovery. Tissues mucosally treated with 10 nM EGF recovered following damage to a maximum of 60.2 +/- 5.1% of pre-exposure PD, while matched controls recovered to only 46.2 +/- 5.8%, a significant difference. Tissues serosally treated with EGF recovered to 61.0 +/- 3.2% and matched controls recovered to 51.1 +/- 2.9%, also a significant difference. These results suggest that both serosally and mucosally applied EGF stimulates the restitution of rat gastric mucosa in vitro.

Animals↗
PubMed1987

Income distributional effects on factor returns.

"In this work an attempt [is] made to model the distributional effects of the brain drain in the recipient country in terms of an inflow of sector-specific skilled labor in a three factor, two goods model. Although only one variant of this model has been examined, it is sufficient to demonstrate its rich potentiality for purposes of immigration policy analysis relative to the traditional model and other modifications in the literature." (SUMMARY IN FRE AND SPA)

Demography↗
PubMed1979

Social urbanization in the Cauca Valley, Colombia.

"This paper treats aspects of the urbanization of the countryside occurring in southern Colombia. It focuses on those urban-emanating forces that provide rural people with a perspective of 'city' life. The impact of such things as the construction (or improvement) of roads, the role of the media, return visits by ex-villagers, and the urban visiting of country people [is] discussed in terms of social urbanization. This presentation renews the call for eschewing bipolar models for studying migration/urbanization in favor of a broader and more holistic perspective. Furthermore, this article suggests that urbanization is another manifestation of a type of dependency relationship."

Americas↗
PubMed1989

Drug use among Puerto Rican youth: an exploration of generational status differences.

An analysis of the relationship between generational status, or a migrational experience, and adolescent drug use takes advantage of a natural experiment--the migration of Puerto Ricans to the continental United States and their immigration back to the island. Although researchers have studied different sources of variation in adolescent drug use behavior, few have examined the drug use experience of the same ethnic group in varying sociocultural settings. The present study focused on the drug use involvement of four generational status groups of Puerto Rican adolescents in two different settings--New York City and San Juan, Puerto Rico. The groups surveyed in New York City were: New York Ricans (New York City-born Puerto Ricans) and New York migrants (island-born Puerto Rican adolescents). The two groups identified in Puerto Rico were: Puerto Rican islanders (adolescents who had never lived outside of Puerto Rico) and Puerto Rican immigrants (New York City-born youngsters of Puerto Rican parentage whose families had returned to live on the island). In this study, it was hypothesized that the more the perceived environment dimensions of the different generational status groups have characteristics conducive to drug use, the greater the drug use involvement of the groups will be. The analysis confirmed that the drug use involvement of the four groups of Puerto Rican adolescents paralleled the exposure of the groups to a host society, New York City, which has a higher prevalence of adolescent drug use than the culture of origin, Puerto Rico. In addition, it was found that the longer New York migrants lived in New York City, the greater was their drug use involvement. The roles of various other sociodemographic factors (i.e. gender, grade level, family structure and socioeconomic status) in relation to adolescent drug use were also investigated. Two important conditional relationships were documented. First, the impact of length of time living in New York City varied with the adolescent's gender, with higher risk of drug involvement observed for female migrants. Second, socioeconomic status was associated with Puerto Rican adolescents' drug use involvement in the New York City subgroups, but not among the students in Puerto Rico.

Adolescent↗
PubMed1991

Isolation, characterization, and quantitative analysis of ceruloplasmin from horses.

Ceruloplasmin (Cp) was isolated from fresh equine plasma by precipitation, cellulose chromatography, and improved ion-exchange chromatography. Purified equine Cp is a glycoprotein having a molecular weight of approximately 115,000. In electrophoresis, equine Cp migrated to the alpha 1-globulin region, its isoelectric point was about 4.15 and consisted of about 890 amino acid residues. Serum Cp concentration was measured by use of the single radial immunodiffusion method. In clinically normal horses, the mean (+/- SD) serum Cp concentration of newborn foals was 2.87 +/- 0.40 mg/ml and that of 3-month-old foals was 5.02 +/- 0.92 mg/ml, which was similar to the adult value. It reached a peak of 6.06 +/- 0.74 mg/ml in 2-year-old horses. The Cp concentration in mares was not statistically different for the perinatal period, but it decreased immediately before and after delivery. Concentration of Cp increased at 6 days after IM administration of turpentine oil, castration, or jejunojejunostomy in adult horses, and increased to peak values twice as high as baseline values at 7 to 14 days, returning to baseline values at 28 days after treatment. We concluded that equine serum Cp is an acute-phase reactive protein increased in the intermediary or later phase of acute inflammation.

Aging↗
PubMed2006

Invasion of an exotic forb impacts reproductive success and site fidelity of a migratory songbird.

Although exotic plant invasions threaten natural systems worldwide, we know little about the specific ecological impacts of invaders, including the magnitude of effects and underlying mechanisms. Exotic plants are likely to impact higher trophic levels when they overrun native plant communities, affecting habitat quality for breeding songbirds by altering food availability and/or nest predation levels. We studied chipping sparrows (Spizella passerina) breeding in savannas that were either dominated by native vegetation or invaded by spotted knapweed (Centaurea maculosa), an exotic forb that substantially reduces diversity and abundance of native herbaceous plant species. Chipping sparrows primarily nest in trees but forage on the ground, consuming seeds and arthropods. We found that predation rates did not differ between nests at knapweed and native sites. However, initiation of first nests was delayed at knapweed versus native sites, an effect frequently associated with low food availability. Our seasonal fecundity model indicated that breeding delays could translate to diminished fecundity, including dramatic declines in the incidence of double brooding. Site fidelity of breeding adults was also substantially reduced in knapweed compared to native habitats, as measured by return rates and shifts in territory locations between years. Declines in reproductive success and site fidelity were greater for yearling versus older birds, and knapweed invasion appeared to exacerbate differences between age classes. In addition, grasshoppers, which represent an important prey resource, were substantially reduced in knapweed versus native habitats. Our results strongly suggest that knapweed invasion can impact chipping sparrow populations by reducing food availability. Food chain effects may be an important mechanism by which strong plant invaders impact songbirds and other consumers.

Animal Migration↗
PubMed2000

Determination of temporal expression patterns for multiple genes in the rat carotid artery injury model.

Vascular injury induces extensive alteration to the extracellular matrix (ECM). These changes contribute to lesion formation and promote cell migration and proliferation. To elucidate ECM response to arterial injury, we used real-time polymerase chain reaction monitoring to quantitate the expression levels of 81 genes involved in the synthesis and breakdown of ECM as well as receptors and signaling proteins that communicate and respond to ECM molecules. The temporal regulation of gene expression in the carotid was measured at 1, 3, 5, 7, 9, 14, and 28 days postinjury. Among the 68 genes that showed detectable expression by our method, 47 (69%) were significantly induced or repressed over time, confirming the extensive ECM gene response in this model. More ECM-related genes (31) were regulated at day 1 than at any other time point, and the number of regulated genes decreased over time. However, 14 of the genes were still induced or repressed at day 28, indicating that return to preinjury expression patterns did not occur and no new steady state was achieved over 28 days. In spite of the large number of changes in gene expression, only a small number of expression patterns was observed, suggesting that ECM-related genes could potentially be coregulated.

Animals↗
PubMed1999

AneuRx stent graft versus open surgical repair of abdominal aortic aneurysms: multicenter prospective clinical trial.

The results of a prospective, nonrandomized, multicenter clinical trial that compared endovascular stent graft exclusion of abdominal aortic aneurysms with open surgical repair are presented. During an 18-month period, 250 patients with infrarenal aneurysms underwent treatment at 12 study sites-190 patients underwent endovascular repair using the Medtronic AneuRx stent graft (Sunnyvale, Calif), and 60 underwent open surgical repair. There was no significant difference in operative mortality rates between the groups. The patients who underwent stent grafting had significant reductions in blood loss, time to extubation, and days in the intensive care unit and in the hospital, with an earlier return to function. The major morbidity rate was reduced from 23% in the surgery group to 12% (P <. 05) in the stent graft group. There was no difference in the combined morbidity/mortality rates between the two groups. Primary technical success at the time of discharge for the patients with stent grafts was 77%, largely as a result of a 21% endoleak rate. At 1 month, the endoleak rate had decreased to 9%. There was no difference in the primary or secondary procedure success rates at 30 days between the surgery and stent graft groups. The primary graft patency rate at 6 months was 98% in the surgery group and 97% in the stent graft group. The aneurysm exclusion rate at 1 month and 6 months was 100% in patients who underwent surgery and 91% in patients who underwent stent grafting. Stent graft migration occurred in three patients and resulted in late endoleaks; each endoleak was corrected by means of endovascular placement of a stent graft extender cuff. There have been no aneurysm ruptures and no surgical conversions to open repair in the stent graft group. Stent graft repair compares favorably with open surgical repair, with a reduced morbidity rate, shortened hospital stays, and satisfactory short term outcomes.

Aged↗
PubMed2001

Intrauterine contraception--what now and what next?

Rising each year by around 85 million, we have started this millennium with over 6,000 million, mostly utterly destitute, human beings on a finite planet. We will never meet human needs without stabilizing human numbers. In the sexual arena, all human beings (but especially the males of the species) are very bad at using their brains and their genitalia at the same time, i.e. putting the knowledge in their head about risks of conception or of sexually transmitted infections into appropriate preventive action when sexually aroused! Therefore, a very useful criterion for choice of methods all through the various stages of reproductive life is 'forgettability'. This is a great 'plus' point for the intrauterine route, especially the levonorgestrel intrauterine system (LNG-IUS). Its main contraceptive effects are local, by endometrial suppression and changes to the cervical mucus and uterotubal fluid, which impair sperm migration. The blood levels of levonorgestrel are about one-quarter of the peak levels in users of the progestin-only pill, and so gestagenic symptoms are uncommon and ovarian function is little altered. Most women continue to ovulate and, in the remainder, sufficient estrogen for health is produced from the ovary even if they become amenorrheic, as many do; this is primarily a local end-organ effect and should be seen as a benefit. Postmenopausal estradiol levels have not been detected, even in those who have no uterine bleeding. Although usable by selected nulliparae, the LNG-IUS is a particularly good choice for the parous woman, for whom I maintain it represents the future already here, which is not recognized by many providers. It has unsurpassed efficacy; 99.5% of women have not conceived after 5 years of use. Return of fertility is rapid and appears to be complete. Combining the best features of hormonal and intrauterine contraception without most ofthe problems of either, it fundamentally 'rewrites the textbooks' about intrauterine devices. Its gynecological benefits are impressive: the LNG-IUS user can expect a dramatic reduction in amount and, after the first few months, in duration of blood loss. Dysmenorrhea is also greatly benefited, in most cases. In summary, the LNG-IUS fulfils many of the criteria for an 'ideal' contraceptive. Adverse side-effects are few and, in general, they are not in the category 'hazardous'. Regarding the inconvenience of the first weeks of light post-insertion bleeding and the early-phase low incidence ofsteroidal side-effects, forewarned is forearmed!

Administration, Intravaginal↗
PubMedDate not supplied

Mortality and morbidity among Rwandan refugees repatriated from Zaire, November, 1996.

INTRODUCTION: Following renewed ethnic violence at the end of September 1996, conflict between Tutsi rebels and the Zairian army spread to North Kivu, Zaire where approximately 700,000 Rwandan Hutu refugees resided following the 1994 genocide. After a major rebel offensive against the camps' militia groups on 15 November, a massive movement of refugees towards Rwanda through Goma town, the capital of North Kivu, began. Massive population movements such as this are likely to be associated with substantial mortality and morbidity. OBJECTIVE: To study patterns of mortality, morbidity, and health care associated with the Rwandan refugee population repatriation during November 1996. METHODS: This study observed the functioning of the health-care facilities in the Gisenyi District in Rwanda and the Goma District in Zaire, and surveyed mortality and morbidity among Rwandan refugees returning from Zaire to Rwanda. Patterns of mortality, morbidity, and health care were measured mainly by mortality and health centre consultation rates. RESULTS: Between 15 and 21 November 1996, 553,000 refugees returned to Rwanda and 4,530 (8.2/1,000 refugees) consultations took place at the border dispensary (watery diarrhea, 63%; bloody diarrhea, 1%). There were 129 (0.2/1,000) surgical admissions (72% soft tissue trauma) to the Gisenyi hospital in the subsequent two weeks. The average number of consultations from the 13 health centres during the same period was 500/day. Overall, the recorded death rate was 0.5/10,000 (all associated with diarrhea). A total of 3,586 bodies were identified in the refugee camps and surrounding areas of Goma, almost all the result of trauma. Many had died in the weeks before the exodus. Health centres were overwhelmed and many of the deficiencies in provision of health care identified in 1994 again were evident. CONCLUSIONS: Non-violent death rates were low, a reflection of the population's health status prior to migration and immunity acquired from the 1994 cholera outbreak. Health facilities were over stretched, principally because of depleted numbers of local, health-care workers associated with the 1994 genocide. Health-care facilities running parallel to the existing health-care system functioned most effectively.

Adolescent↗
PubMedDate not supplied

Spatial and temporal expression of transforming growth factor-beta isoforms during ovine excisional and incisional wound repair.

To elucidate the role for transforming growth factor-beta isoforms (beta(1), -beta(2), and -beta(3)) in wound repair, we used isoform-specific antibodies to detect the spatial and temporal expression of the latent and mature/active transforming growth factor-beta isoforms by immunohistochemical localization through 21 days after excisional and incisional wounding of ovine skin. Although incisional and excisional wounds showed similar patterns of transforming growth factor-beta immunoreactivity, we found a differential temporal and spatial expression of the latent and mature transforming growth factor-beta isoforms throughout wound repair. Specifically, 1 day after wounding, there was a marked increase in transforming growth factor-beta isoforms in the epithelium adjacent to the wound, epidermal appendages, and the cells and matrix of the granulation tissue. At this time, transforming growth factor-beta(3) isoform was the most abundant. Most notably, the epidermis adjacent to the wound was intensely immunoreactive for all transforming growth factor-beta isoforms 1 day after injury. However, the migrating epithelium, derived from both the hair follicles and the wound margins, was completely devoid of immunoreactive transforming growth factor-beta until reepithelialization was complete. Within the inflammatory exudate, there was a distinct band of leukocytes that was immunoreactive for transforming growth factor-beta(2) and -beta(3) 1 day after injury and 1 day later for transforming growth factor-beta(1). Although transforming growth factor-beta(1) and -beta(2), latent transforming growth factor-beta(2), transforming growth factor-beta(3), and latent transforming growth factor-beta(3) immunostaining was present in the numerous fibroblasts and other dermal cells, latent transforming growth factor-beta(1) was only associated with the extracellular matrix. In general, immunoreactivity remained high until day 7 after wounding and slowly subsided over time. However, by day 21, immunostaining had not returned to normal and the original wound was replete with immunoreactive fibroblasts and a dense, immunostained extracellular matrix. Thus, although the dynamic presence of transforming growth factor-beta isoforms exemplifies its positive role in the wound repair process, its persistence together with its known potent effects on matrix accumulation, supports its role in scar formation.

Journal Article↗