Transport of IgA immune complexes across epithelial membranes: new concepts in mucosal immunity.
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Biomedical subjects
Publications and source records attributed to J K Robinson.
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BACKGROUND: Initiation of sun protection strategies can be promoted, to some extent, by educational efforts, but little is known about the merit of continuing education interventions in sustaining the desired behaviors or adding new behaviors. This prospective study clarifies the choices individuals make among the four strategies that allow them to maintain lifestyle changes. METHODS: From 1983 to 1987, the population received education about sun protection coupled with the removal of a nonmelanoma skin cancer. One year later, their choice of sun protection methods was determined. Then annually from 1985 to 1989, they received written recommendations about sun protection for a period of 2-6 years after the initial education. The maintenance, cessation, and addition to the initial sun protection behaviors were ascertained by a questionnaire, as was the intention to change. Frequency of physician visits and development of subsequent nonmelanoma skin cancer were evaluated by medical chart review for the 2-6 year phase of continued education. RESULTS: One percent of the population consisting mostly of women described ceasing tanning after 2-6 years of education. The population related a greater use of protective clothing and/or sunscreen with an SPF of 15 or greater as their reported restrictions on outdoor activities ceased. An emerging new strategy of some of the population (n = 185) was the use of sunscreens with an SPF less than 15 in association with attempts to deliberately tan and longer daily outdoor exposure. Neither frequency of physician visits nor numbers of subsequent nonmelanoma skin cancers influenced continuation or addition of sun protection behaviors. CONCLUSIONS: While the greatest reported change in behavior was temporarily associated with educational intervention linked to removal of the skin cancer, continued educational efforts may have recruited some individuals to cease tanning and encouraged others to adopt the use of protective clothing or more frequent sunscreen use as they were unable to maintain the limitations on outdoor activities. It is not possible to structure a control group restricted from mass media education; therefore, the effectiveness of specific behavior-directed education cannot be precisely determined. Nonetheless, the population described using knowledge to develop compensation sun protection strategies that preserved lifestyle.
Two experiments were conducted to determine whether lesions affecting limited areas of the thalamus can impair the performance of rats on a spatial delayed-nonmatching-to-sample (DNMTS) task trained before surgery. In Experiment 1, DNMTS was not affected by lesions produced by injecting 5 microliters of 1 mM N-methyl-D-aspartate into either the midline thalamus (n = 16) or bilaterally 1.0 mm from the midline (n = 16). In experiment 2, radio-frequency lesions were made 1.0 mm lateral to the midline at 3 anterior-posterior locations that destroyed the full rostral-caudal extent of the lateral internal medullary lamina (L-IML; n = 8), or at single anterior-posterior locations that destroyed either the anterior (n = 8) or posterior (n = 8) portions of the L-IML site. Although complete L-IML lesions disrupted DNMTS performance to an extent comparable to that of another study (Mair & Lacourse, 1992), lesions that were restricted to either the anterior or posterior portion of the L-IML site had no significant effect on this task.
We examined the ganglioside content of normal human keratinocytes and basal cell carcinomas (BCC). The total ganglioside content of the epidermis was 0.098 +/- 0.01 microgram lipid-bound sialic acid/mg dry weight. GM3 was the predominant ganglioside of epidermis. GM2 and GD3 were also found in significant amounts. Polysialylated gangliosides were identified in only small amounts. In contrast to all other body locations, breast epidermis showed large amounts of GM1. The total ganglioside content of nodular and sclerosing facial BCC was approximately 3.5 times that of normal facial epidermis. This marked elevation of total ganglioside was not affected by dermal ganglioside contamination, because the total ganglioside content of the dermis was similar to that of the epidermis. The relative percentage of GM2 was significantly decreased, whereas the relative percentage of GM3 was slightly decreased in BCC. 9-O-acetyl-GD3 was present in the BCC, but not in normal epidermis or dermis. 9-O-acetyl-GD3 may be a surface marker for BCC. Furthermore, the alterations in amount and composition of individual gangliosides on neoplastic membranes may lead to novel therapeutic interventions.
This 36-month prospective study of a group of 61 people at high risk to develop multiple basal cell carcinomas (BCC) examined the circulating lymphocyte subsets of the population, patterns of sun exposure, and the longitudinal development of basal cell carcinoma. Sun exposure status was highly correlated with immune status defined by the CD4/CD8 T-lymphocyte ratio. There were significantly more BCC at 18 and 36 months in the 35 patients with high sun exposure and low CD4/CD8 ratio than in the 20 patients with low sun exposure and high CD4/CD8 ratio. A multivariate analysis assessed the relative importance of prior basal cell carcinoma, sun exposure, and immune status on the development of the skin cancer. Basal cell carcinoma developing in the previous 18 months and sun exposure during those 18 months were the first and second most important variables in determining development of basal cell carcinoma during the next 18 months. CD4/CD8 ratio had no additional predictive ability once prior skin cancers and sun exposure were accounted for. A low ratio of CD4/CD8 cells correlated with high sun exposure during the preceding 18 months.
Seven human immunodeficiency virus-(HIV) positive patients with biopsy proved extensive facial molluscum contagiosum were treated with trichloroacetic acid peels. Peels were performed with 25 to 50% trichloroacetic acid (average 35%) and were repeated every 2 weeks as needed. A total of 15 peels were performed with an average reduction in lesion counts of 40.5% (range 0 to 90%). No spread of molluscum lesions, scarring, or secondary infection developed at 2 months' follow-up. Trichloroacetic acid peeling in concentrations of 35% or less appears to be a safe, effective, adjuvant therapy in the treatment of extensive molluscum contagiosum in immunocompromised patients.
Estimates are that 180,000 cases of breast cancer will be diagnosed in 1992. Breast conservation therapy is becoming the treatment of choice for many women. Physicians providing long-term care for these women must be aware of the cutaneous presentations of local metastatic or recurrent disease, including inflammatory, nodular, telangiectatic and scirrhous variants. In addition, radiation changes, as well as the development of a secondary malignancy at the site of previous radiation therapy, must be distinguished from metastatic breast lesions.
Rats were trained on a spatial delayed-nonmatching-to-sample (DNMTS) task and assigned by block randomization to one of four treatments: pyrithiamine-induced thiamine deficiency (PTD), PTD with administration of MK-801 after 12 days, control with MK-801 treatment, and control without MK-801. After 15 days of treatment followed by 21 days of recovery, the PTD rats showed significant deficits for DNMTS accuracy at retention intervals (RI) that ranged from 3.0 s to 15.0 s, the RIs that produced 75% accuracy on DNMTS in staircase training, and the rate at which a novel radial arm maze task was learned. The PTD-treated rats had consistent lesions in the thalamus and the mammillary bodies. MK-801 protected rats from both behavioral deficits and brain lesions (assessed quantitatively and qualitatively) that were produced by the PTD treatment.
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The polymeric immunoglobulin receptor (pIgR) on mucosal epithelial cells binds dimeric IgA (dIgA) on the basolateral surface and mediates transport of dIgA to the apical surface. Using Madin-Darby canine kidney epithelial cells stably transfected with pIgR cDNA, we found that soluble immune complexes (ICs) of 125I-labeled rat monoclonal antidinitrophenyl (DNP) dIgA (125I-dIgA) and DNP/biotin-bovine serum albumin were transported from the basolateral to the apical surface and then released. Monomeric IgA ICs were not transported, consistent with the specificity of pIgR for polymeric immunoglobulins. Essentially all the 125I-dIgA in apical culture supernatants was streptavidin precipitable, indicating that dIgA remained bound to antigen during transcytosis. While both dIgA and dIgA ICs bound pIgR with equal affinity (Kd approximately 8 nM), the number of high-affinity binding sites per cell was 2- to 3-fold greater for dIgA than for dIgA ICs. The extent of endocytosis of dIgA and dIgA ICs was correlated with the number of high-affinity binding sites. SDS/PAGE analysis of intracellular dIgA and dIgA ICs demonstrated that in both cases IgA remained undegraded during transport. The results suggest that the pathways of epithelial transcytosis of free dIgA and dIgA ICs are the same. Given the high population density of mucosal IgA plasma cells and the enormous surface area of pIgR-expressing mucosal epithelium, it is likely that significant local transcytosis of IgA ICs occurs in vivo. Such a process would allow direct elimination of IgA ICs at the mucosal sites where they are likely to form, thus providing an important defense function for IgA.
Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy, usually on the genitalia, that almost always extends beyond clinically apparent margins. Recurrences after standard methods of surgical excision are notoriously frequent; effective treatment with Mohs micrographic surgery was first reported in 1979. It has since been suggested this malignancy may be multifocal, and reports of recurrences after resection with micrographic surgery have appeared. The authors report six cases treated with Mohs surgery, two of which recurred. They also present data on 42 additional cases obtained from a written survey of members of the American College of Mohs Micrographic Surgery and comparison cases selected from the literature. The recurrence rate after micrographic surgery appears to be at least as low as that after conventional surgical excision with vertical frozen section or paraffin section margin control. Mohs micrographic surgery allows for maximal tissue sparing of critical anatomic structures and is performed under local anesthesia as an outpatient; because of this, it may be superior to conventional surgical excision. A scheme for management of this malignancy is presented. Surgeons should be aware radical excision is not needed for most cases of extramammary Paget's disease and very long-term patient follow-up is required.
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The presence of immunoreactive epidermal growth factor receptors in human skin tumors was investigated using the indirect immunoperoxidase technique. Sixteen basal cell carcinomas and 11 squamous cell carcinomas were evaluated. All of the specimens studied were receptor positive. In 70% of the specimens there was prominent staining of the cell membranes. In 54% of the nodular basal cell carcinoma specimens there was increased staining at the periphery of the tumor cell masses.
Nonsurgical and nonradiation therapy for nonmelanoma skin cancer is focusing on immunotherapy, recombinant human gene products, localized delivery of radiant energy, photodynamic therapy, and retinoids. Although they are not currently practical for widespread application to nonmelanoma skin cancer, there is good reason to hope for significant therapeutic advances in these areas, which will make successful nonsurgical therapy widely available.
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Following cancer resection of the nasal unit, nasal valve malfunction is manifested by the symptoms of nasal stuffiness or difficulty getting air into the nostril. These symptoms occur in cases in which the resection is in the alar crease at the junction with the lateral sidewall of the nose. Wound scar contracture elevates the alar margin and causes the alar and lateral cartilages to move inward forming a visible and palpable shelf on the lateral wall of the nasal vestibule. This displacement of the alar and lateral cartilages and the rigid scar formed between these cartilages render the nasal valve immobile. Since it is easier to prevent nasal valve malfunction than to repair it later, wounds that bridge the alar crease or are located in either the alae or lateral sidewall and come within 1 mm of the alar crease with a total diameter of 1.0 cm should be repaired to prevent nasal valve malfunction. In the process of repairing deep defects, the overlapping region of the lateral crus of the alar cartilage and the lateral cartilage may be stabilized by a conchal cartilage graft. This cartilage graft may be used in combination with reconstruction of the nasal skin with a forehead flap and repair of the nasal lining. In the event that the nasal lining is intact, the cartilage graft may be used with a full-thickness skin graft.
Pigeons were exposed to fixed-time food schedules of 30, 120, and 480 sec with two reinforcer magnitudes at each. Attack behavior against a rear-projected conspecific image was assessed at each interfood/reinforcer magnitude combination. For seven of eight subjects, attack rate was related to interfood interval by an inverted-U or bitonic function. The larger reinforcer magnitude typically induced more attack than the smaller.
The history of tissue expansion, technique, indications, and complications are reviewed. A detailed review of delayed tissue expansion's histologic, biochemical, biomechanical, and physiologic changes in the skin is given. There is a net gain in epidermal tissue during delayed expansion. Recent experimental and clinical experience suggests that expansion for 1 to 2 weeks is just as effective as longer delayed expansion for 6 to 8 weeks. A new deviation from standard technique, intraoperative tissue expansion, may have significant implications for dermatologic surgery. Intraoperative tissue expansion is explored in relation to other commonly used techniques of intraoperative load cycling.