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Biomedical subjects

A F Wells

Publications and source records attributed to A F Wells.

11 recordsLinked to original sources
PubMed1992

Correlation between increased hyaluronan localized in arthritic synovium and the presence of proliferating cells. A role for macrophage-derived factors.

OBJECTIVE: To determine whether the increased levels of circulating hyaluronan seen in patients with arthritis also occur locally. METHODS: Biopsy specimens of normal synovium and synovium from patients with various arthropathies were studied using histochemical and immunohistochemical staining procedures, to determine the tissue distribution of hyaluronan and infiltrating cells. RESULTS: Hyaluronan was found in increased concentrations in inflamed tissues, and was co-localized in sites containing Ki-67+ cells. In vitro analyses showed that macrophage-released factors increased hyaluronan production by fibroblasts. Hydrocortisone inhibited this in vitro production of hyaluronan. CONCLUSION: Edema and swelling seen in inflamed joints may be due to the presence of large amounts of hyaluronan. One possible mechanism of action of corticosteroids in the alleviation of acute joint inflammation may occur via the inhibition of hyaluronan production.

Arthritis↗
PubMed1991

Localization of hyaluronan in various muscular tissues. A morphological study in the rat.

The histochemical distribution of hyaluronan (hyaluronic acid, HYA) was analysed in various types of muscles in the rat by use of a hyaluronan-binding protein (HABP) and the avidin-biotin/peroxidase complex staining procedure. Microwave-aided fixation was used to retain the extracellular location of the glycosaminoglycan. In skeletal muscles, HYA was detected in the connective tissue sheath surrounding the muscles (epimysium), in the septa subdividing the muscle fibre bundles (perimysium) and in the connective tissue surrounding each muscle fibre (endomysium). HYA was heterogeneously distributed in all striated muscles. In skeletal muscles with small fibre dimensions (e.g., the lateral rectus muscle of the eye and the middle ear muscles), HYA was predominantly accumulated around the individual muscle fibres. Perivascular and perineural connective tissue formations were distinctly HYA-positive. In cardiac muscles, HYA was randomly distributed around the branching and interconnecting muscle fibres. In comparison, smooth muscle tissue was devoid of HYA.

Animals↗
PubMed1991

Cytokine gene expression: analysis using northern blotting, polymerase chain reaction and in situ hybridization.

We describe here the use of northern blotting, PCR and in situ hybridization for the analysis of cytokine gene expression. These techniques, each with their advantages and disadvantages, have been used to monitor cytokine gene expression in sites of immune reactivity and in the developing thymus. Whilst expression of a gene usually correlates well with protein production from that gene, this may not always be the case. The development of methods to analyze protein production in situ, for instance by immunohistochemistry, together with analysis of mRNA expression will allow us to begin to understand the role of cytokines within the immune system of the intact animal.

Animals↗
PubMed1991

Lung hyaluronan during development: a quantitative and morphological study.

Hyaluronan, an important constituent of developmental interstitium in fetal lungs, mediates cell-to-cell interactions and thereby directs migrating cells. Furthermore, because of the polyionic nature of the molecule, hyaluronan forms open, hydrated matrices that provide channels for migrating cells. This hydrated matrix undergoes contraction before birth. However, continued growth of the lung in the perinatal period requires newly synthesized hyaluronan. This study's purpose was to elucidate the changes in lung hyaluronan concentration and distribution in the perinatal period. We studied rabbits at days -6, -4, -2, -1, 0, +2, and +4 with respect to term, as well as adult rabbits. We found that hyaluronan concentration was highest in the youngest fetuses studied [682 +/- 115 micrograms/g dry wt (means +/- SD)]. However, hyaluronan concentration decreased to 129 +/- 12 micrograms/g dry wt just before birth then returned to 366 +/- 111 micrograms/g dry wt at day +4; these values were similar to adult values. We found hyaluronan staining decreased during late gestation, particularly in the interalveolar region. In the postnatal period, hyaluronan staining increased in the visceral pleura and, to a lesser extent, beneath the epithelium of the bronchioles. Hyaluronan did not reaccumulate in the interalveolar region in the postnatal period. Our data suggest a change in the predominant role of lung hyaluronan during the perinatal period. Before term, hyaluronan facilitates morphogenesis. However, hyaluronan's major role in neonatal lung is most likely in regulation of fluid balance in interstitium.

Animals↗
PubMed1991

Localization of hyaluronan in regions of the human female reproductive tract.

Accumulation of hyaluronan has previously been observed in various organs as an inflammatory response. To study the presumed connection between infertility due to a tubal factor and inflammation, we performed an analysis of the hyaluronan distribution in biopsy specimens from the female reproductive tract, using a biotinylated hyaluronan binding protein (HABP) as a histochemical probe. In normal specimens hyaluronan was localized in the dense, irregular connective tissue surrounding blood vessels of various sizes. Smooth muscle and columnar epithelium were devoid of hyaluronan. The isthmic part of the normal Fallopian tube showed moderately intense staining of the entire lamina propria, whereas normal fimbriae stained weakly. No cyclic changes in hyaluronan content were observed. In biopsy specimens from women with infertility due to a tubal factor, intense staining, stronger than in normal tubes, was detected in the adhesions and in the lamina propria of sactosalpinx. This may indicate that infertility due to a tubal factor is associated with an ongoing inflammatory and/or proliferative process.

Biopsy↗
PubMed1991

Histochemical localization of hyaluronan in psoriasis, allergic contact dermatitis and normal skin.

In suction blister fluid from active psoriatic lesions we have previously found elevated concentrations of hyaluronan. The aim of this investigation was to study the localization of hyaluronan with a histochemical method, in biopsy specimens from lesions of 13 patients with progressive psoriasis. Ten normal subjects and seven patients with allergic contact dermatitis were also studied. In normal epidermis the highest intensity of hyaluronan staining was found in the intercellular spaces in the middle and upper spinous layer, whereas the staining was much weaker in the basal layer. No hyaluronan was detected in the granular layer or in the orthokeratotic stratum corneum. In the dermis there was pronounced staining of the papillary dermis and around the sebaceous glands, sweat glands, hair follicles and blood vessels. In six of the 16 specimens from psoriatic lesions the normal epidermal meshwork of hyaluronan was partly absent and replaced by diffuse staining of both the spinous and the basal layer. In the remaining ten of these 16 specimens the same type of meshwork was found in stratum spinosum as in normal skin. The parakeratotic stratum corneum contained hyaluronan, in contrast to the normal stratum corneum, where no hyaluronan was present. The pattern of hyaluronan staining in the dermis of the psoriatic lesions did not differ from that in normal dermis. In the majority of the allergic patch test reactions the junction was less distinct than in normal skin between dermis and epidermis and the normal hyaluronan pattern of the basal layer was abolished and replaced by a diffuse staining throughout the layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The localization of hyaluronan in normal and rejected human kidneys.

Hyaluronan (HYA) is a large glycosaminoglycan with a high capacity to immobilize water. Increased levels of HYA have previously been observed in plasma as well as in affected tissues in various inflammatory conditions. The morphological localization of HYA has, however, not been described in normal or rejected human kidneys. Using a recently developed method for localization of HYA in tissue sections by means of a biotin-labeled hyaluronan binding protein used as a probe, we have now investigated the distribution of HYA in normal and irreversibly rejected human kidneys. In the normal kidney HYA was essentially confined to the medulla. In the rejected kidneys increased amounts of HYA were observed primarily in the cortex and in sclerotic vessels. Incubating tissue sections with hyaluronidase abolished the staining for HYA, showing the specificity of the staining procedure. The increased amounts of HYA of the rejected kidney may play a role in local edema formation, and thereby alter graft function.

Connective Tissue↗
PubMed1989

Systemic injection of group A streptococcal peptidoglycan-polysaccharide complexes elicits persistent neutrophilia and monocytosis associated with polyarthritis in rats.

The perpetuation of inflammatory changes within joints elicited by persisting, poorly biodegradable group A streptococcal cell walls (peptidoglycan-polysaccharide complexes [PG-PS]) is well documented. Chronic changes in the bloodstream induced by PG-PS have not been described previously. We demonstrated that leukocytosis occurs within 3 days after intraperitoneal injection of PG-PS and remains elevated 20 weeks later. Chronic neutrophilia, monocytosis, and lymphocytosis were observed in all experiments. Chronic changes in platelet, erythrocyte, and reticulocyte counts were not seen. The newly documented leukocytosis, lasting for months after PG-PS administration, provided a circulating pool of leukocytes that may participate in chronic inflammatory events in the joint. Although the central role of the macrophage in PG-PS-mediated inflammation has been emphasized (F. G. Dalldorf, W. J. Cromartie, S. K. Anderle, R. L. Clark, and J. H. Schwab, Am. J. Pathol. 100:383-402, 1980), the polymorphonuclear cell may be involved in periods of exacerbation of streptococcal cell wall-mediated polyarthritis. This was supported by our observations that neutrophilia and monocytosis correlate well with the degree of chronic joint inflammation.

Animals↗
PubMedDate not supplied

Expression of an interferon-gamma-like substance in normal and transplanted rat heart tissue.

The presence of interferon-gamma-like molecules has been reported not only in lymphocytes, but also in certain nerve cells and in normal skeletal muscle. We have studied the reactivity of the anti-interferon-gamma monoclonal antibody DB1 with frozen sections of normal and transplanted rat hearts. Cardiac grafts from PVG donor rats were transplanted to syngeneic PVG recipients or allogeneic Wistar/Kyoto recipient rats with the use of an accessory cervical heart transplantation technique. The allogeneic heart transplants were harvested 4 days and the syngeneic grafts 4 weeks after transplantation. In normal hearts there was a weak but distinct reactivity with the anti-interferon-gamma antibody in most muscle cells. In addition, some lymphocytes and the Purkinje fibers were positive. Hearts transplanted over an allogeneic barrier revealed that staining for interferon-gamma on muscle cells was substantially increased whereas no or only a moderate increase in the anti-interferon-gamma staining was seen in hearts transplanted to syngeneic recipients. These data indicate that interferon-gamma present in rat myocyte may be involved in the pathophysiology of graft rejection and also suggest that interferon-gamma may be of importance for the function of normal rat heart muscle cells.

Animals↗