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Biomedical subjects

M Malmström

Publications and source records attributed to M Malmström.

At least 19 recordsLinked to original sources

Quantitative assessment of mast cells in recurrent aphthous ulcers (RAU).

Previous studies on the frequency of mast cells (MCs) in recurrent aphthous ulcers (RAU) have yielded conflicting results. Monoclonal antibodies specific for tryptase (AA1) and anti-IgE (polyclonal antibody) were used to identify density and distribution of MCs in an immunohistochemical study of RAU (n=15), induced oral traumatic ulcers (TUs) (n=9), and control clinically healthy oral mucosa (n=15). Results were quantified by means of a VIDAS image analyzer. In all sections studied, IgE-positive cells showed similar frequency and distribution to tryptase-positive MCs. In RAU lesions, numerous tryptase-positive MCs were found in the sub-epithelial lamina propria, but MC numbers in the epithelium were low and present only in some RAU biopsies. MCs were also more numerous in RAU-inflammatory infiltrates (118+/-31 cells/mm2) than those seen in TU-inflammatory infiltrates (75+/-18 cells/mm2, P<0.001). MC activation/degranulation, as judged by diffuse extracellular tryptase staining, was a common feature within RAU-inflammatory infiltrates and at RAU-inflammatory infiltrates-connective tissue interfaces, which were often associated with connective tissue disruption. MC counts in the RAU connective tissue, lateral to the inflammatory infiltrates, were significantly greater than in the connective tissue of TUs and of control biopsies (124+/-36 vs 73+/-13 vs 69+/-21 cells/mm2, respectively; P<0.001). Overall, MCs were significantly increased in aphthae (116+/-26 cells/mm2) compared with TU lesions (72+/-11 cells/mm2, P<0.001) and controls (71+/-16 cells/mm2, P<0.001). In conclusion, MC numbers are increased in a typical topographical pattern, and the local MCs show signs of activation/degranulation suggesting active involvement of this cell type in RAU pathogenesis.

Adult

Indices of need and social deprivation for primary health care.

This study aimed to examine two indices of need, the underprivileged area (UPA) score and a Swedish Care Need Index (CNI, in Swedish vårdbehovsindex) with weightings from British and Swedish GPs respectively, and an index of material deprivation, Townsend score at SAMS (Small Area Market Statistics) level and at municipality level for the whole of Sweden. One third of primary health care physicians from the whole of Sweden received a questionnaire about their workload. CNI, UPA and Townsend scores were calculated using information from the Swedish census of 1990 and the registers of unemployment and migration for 1992. The Swedish GPs weighted some of the variables quite differently from the GPs in the UK. This may be important, especially at the SAMS level. The GPs in both countries considered that older people living alone contributed most to their workload. However, in Sweden the physicians ranked foreign-born people high compared with the English doctors, and in England the GPs ranked children under five years much higher than the doctors in Sweden. The correlation between the scores was high.

Adolescent

Factor XIIIa-positive dendrocytes are increased in number and size in recurrent aphthous ulcers (RAU).

The factor XIIIa-positive (FXIIIa+) cell is a potent antigen-presenting cell, which has been described as increasing in numbers in various chronic inflammatory conditions. The purpose of this study was to investigate the distribution and frequency of FXIIIa+ cells in acute recurrent aphthous ulcer (RAU) lesions compared with induced traumatic ulcer (TU) lesions and with clinically healthy oral mucosa. Samples were labeled with polyclonal rabbit anti-human FXIIIa antibodies in avidin-biotin-peroxidase complex (ABC) staining. Most of the FXIIIa-immunoreactive cells in TUs and normal mucosa were spindle-shaped, whereas a relatively large, dendritic-like cell was predominant in RAU lesions. FXIIIa+ cells were quite frequent within mononuclear cell-rich inflammatory cell infiltrates and in perivascular areas in RAU lesions. In contrast, FXIIIa+ cells were not found in mucosal epithelium or in the neutrophil-rich areas. RAU mononuclear cell-rich inflammatory cell infiltrates appeared to have greater numbers of positively stained cells than the TU-inflammatory cell infiltrates (199 +/- 67 vs 110 +/- 31 cells/mm2, P < 0.001). Overall, FXIIIa+ dendrocytes were increased in numbers, and apparently also in size, in RAU lesions (274 +/- 68/mm2) as compared to controls (177 +/- 74/mm2, P < 0.01), and to TU lesions (183 +/- 50 mm2, P < 0.01). Interestingly, relatively high numbers of FXIIIa+ dendrocytes were also found in deep connective tissue in RAU sections compared with TUs (281 +/- 80 vs 166 +/- 57, P < 0.01). The characteristic changes in the size and shape of individual FXIIIa+ cells, their typical distribution and increase in frequency in RAU lesions indicate active involvement in the local pathogenic mechanisms. Localization to perivascular areas/inflammatory cell infiltrates would be compatible with a role in antigen presentation.

Acute Disease

Intraepithelial lymphocytes bearing the gamma/delta receptor in the oral and jejunal mucosa in patients with dermatitis herpetiformis.

Lymphocytes bearing T cell receptor (TcR) gamma/delta are increased in the jejunal mucosa of patients with dermatitis herpetiformis (DH) and coeliac disease. In this study, we examined whether increased numbers of gamma/delta TcR positive lymphocytes occur in the oral mucosa of patients with DH. Oral and jejunal mucosal biopsies were taken from 13 newly diagnosed and 13 gluten free diet (GFD)-treated patients with DH. Monoclonal antibodies and avidin-biotin peroxidase method was used for staining, and TcR positive cells were counted from the buccal and jejunal epithelium. Very few gamma/delta TcR positive lymphocytes were seen in the buccal epithelium of untreated or GFD-treated DH patients (median 0.4 and 0.3 cells/mm2), whereas alpha/beta TcR positive lymphocytes were frequent in both groups of DH patients (154 and 250 cells/mm2) and healthy controls (135 cells/mm2). The numbers of gamma/delta TcR positive intraepithelial lymphocytes were significantly increased in the jejunum of both untreated (43 cells/mm) and GFD-treated (27 cells/mm) DH patients compared to control patients (2.2 cells/mm). The present study did not, therefore, disclose any evidence for active recruitment of gamma/delta TcR positive lymphocytes in the oral epithelium, but showed substantial amounts of intraepithelial alpha/beta TcR positive lymphocytes both in DH patients and healthy controls.

Adult

Epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor in labial salivary glands in Sjögren's syndrome.

OBJECTIVE: Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) affect cells through binding to a shared EGF receptor (EGF-R), which is a transmembrane protein with tyrosine kinase activity. They exert trophic effects on vascular endothelial, salivary acinar, and ductal and mucosal epithelial cells. In Sjögren's syndrome (SS) focal sialadenitis leads to salivary gland tissue damage, diminished salivary flow, and changes in the oral epithelium, a complex referred to as xerostomia. We compared the localization of EGF, TGF-alpha, and EGF-R in labial salivary glands in SS and in healthy controls. METHODS: Labial salivary gland tissues of 12 patients with SS and 7 healthy controls were stained with the immunohistochemical peroxidase-antiperoxidase method for EGF, TGF-alpha, and EGF-R. RESULTS: Immunoreactivity for both EGF and TGF-alpha was found in endothelial cells of blood vessels and in some ductal epithelial cells. TGF-alpha, but not EGF, was also found in some acinar cells. EGF-R was found in endothelial, acinar, and salivary duct epithelial cells. There was no difference in the expression of EGF-R between diseased and healthy specimens, but both EGF and TGF-alpha were diminished in SS. CONCLUSION: The interrelated localization of EGF-R and its ligands, EGF and TGF-alpha, suggests an autocrine, juxtacrine, and paracrine mitogenic/trophic role for them and thus a role in the maintenance of the secretory and excretory cells of the normal salivary glands. The trophic effects on acinar cells seem not to be mediated by EGF, but more likely by TGF-alpha. The diminished expression of EGF and TGF-alpha indicates a failure of this trophic system in SS, which may contribute to the acinar atrophy and secondary changes thereof, including atrophy of the oral mucosa.

Adolescent

Salivary and serum IgA antigliadin antibodies in dermatitis herpetiformis.

Serum IgA class antigliadin antibodies (IgA-AGA) are increased in untreated patients with coeliac disease and dermatitis herpetiformis (DH), and it has been suggested that salivary IgA-AGA measurements could be used as a non-invasive screening test for gluten-sensitive enteropathy. In the present study salivary and serum IgA-AGA were measured by an ELISA test in 10 untreated patients with DH. The results were compared to IgA-AGA levels in nine patients with DH on a long-term gluten-free diet (GFD) and in 20 healthy control subjects on an ordinary diet. The mean serum but not salivary IgA-AGA concentrations were significantly higher in the untreated than in the patients with DH on a long-term GFD. When the 10 untreated patients with DH adhered to a GFD for 3 months, the rash disappeared and the mean serum IgA-AGA decreased to normal levels, but no change was found in the mean salivary IgA-AGA concentration. These results show that serum but not salivary IgA-AGA measurements are suitable for monitoring GFD treatment in patients with DH. The discrepancy between the serum and salivary IgA-AGA concentrations suggests that systemic and salivary IgA-AGA responses are controlled separately.

Adult

Transforming growth factor beta 2 in labial salivary glands in Sjögren's syndrome.

OBJECTIVE: To compare the distribution and the amount of transforming growth factor beta (TGF beta) in labial salivary glands (LSG) in patients with Sjögren's syndrome (SS) and healthy controls. METHODS: LSG from SS patients (n = 10) and healthy controls (n = 6) were labelled with peroxidase-antiperoxidase staining for TGF beta 2, which was quantitated in image analysis using Video Interactive Display System software. RESULTS: In all LSGs in SS and healthy controls, TGF beta 2 was found in endothelial cells of the capillaries and in the capsular and stromal fibroblasts. In LSGs in SS, TGF beta 2 was also found in some lymphocytes in the inflammatory cell foci and in fibroblasts in fibrotic areas. The TGF beta 2 staining index (microns 2/mm2 tissue) was greater in SS than in control LSGs (3670 (SEM 430) v 2061 (176); p < 0.01), with no difference between the primary and secondary forms of SS (p > 0.05). CONCLUSION: The localisation and the level of expression of TGF beta 2 indicate its involvement in local tissue fibrosis, and may reflect attempts at immunosuppression.

Adult

Effect of tetracyclines on collagenase activity in patients with recurrent aphthous ulcers.

Human neutrophil-type (MMP-8) and fibroblast-type (MMP-1) interstitial collagenase, and their inhibition by tetracyclines in saliva from patients with recurrent aphthous ulcers (RAU) or aphthae, were studied by means of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and enzymological analyses. In the salivary specimens obtained from patients with aphthae, collagenase was found in endogenously active form and was predominantly of MMP-8 type. Topical rinsing treatment with chlortetracycline (Aureomycin) alleviated the discomfort caused by the lesions but did not reduce salivary collagenase amounts; however in vitro, doxycycline inhibited salivary collagenase totally.

Adolescent

Collagenase and stromelysin in recurrent aphthous ulcers (RAU).

Six patients with recurrent aphthous ulcers were studied for the presence of matrix metalloproteinases (MMP) 1, 3, and 8 in the lesions and in the clinically unaffected control mucosa obtained from the opposite side. MMP-type specific antisera were applied in the avidin-biotin-peroxidase complex staining method. Neutrophil-type collagenase (MMP-8) was found intracellularly in the connective tissue under the necrotized epithelium, and also laterally to the ulcer in association with the basement membrane. Fibroblast-type collagenase (MMP-1) and stromelysin (MMP-3) were found in the epithelial cells adjacent to the ulcerous lesion. They were found also in the endothelium of capillary blood vessels and postcapillary venules and also in some macrophage- and fibroblast-like mononuclear cells in the lamina propria laterally to the ulcer. A small number of MMP-1 and MMP-3 positive cells were noted in the control biopsies obtained from the clinically uninvolved control mucosa. These findings suggest regional differences in the distribution of the two main collagenases, implying distinct roles in tissue destruction and remodeling.

Adult

Peripheral nerves and mast cells in normal buccal mucosa.

The topographical distribution and relation to mast cells of PGP 9.5 (protein gene product 9.5, a major cytoplasmic neuron-specific protein with ubiquitin C-terminal hydrolase activity) and neurofilament (intermediate neuron-specific cytoskeletal filaments) in normal human buccal mucosa was studied in five healthy volunteers. Morphometric analysis disclosed the densest innervation to be in the middle layers of the lamina propria, with a mean number of 5.9-6.1 PGP 9.5 and/or neurofilament-immunoreactive nerve fiber profiles per one mm2. In contrast, the mean mast cell number decreased from 110/mm2 to 46/mm2 from superficial to deep lamina propria, being 69-72/mm2 in the most densely innervated middle layers. Only 16-17% of all fiber profiles contained substance P and 51-54% calcitonin gene-related peptide (CGRP). Finally, analysis of the spatial relationship between nerve fiber profiles and mast cells in a double staining procedure disclosed no preferential neuron-effector associations. All these findings suggest that such a relationship does not exist between peripheral nerves and mast cells in normal buccal mucosa.

Adolescent

Peptide-containing nerves in labial salivary glands in Sjögren's syndrome.

OBJECTIVE: The presence and spatial distribution of peptide-containing nerves in labial salivary glands from 10 Sjögren's syndrome patients were compared with those in salivary glands from 7 healthy controls. METHODS: Immunoperoxidase staining was used to demonstrate vasoactive intestinal peptide (VIP)-immunoreactive (IR) fibers, postganglionic sympathetic fibers containing the C-flanking peptide of neuropeptide Y (CPON), and sensory fibers containing calcitonin gene-related peptide (CGRP) and substance P. RESULTS: Acini, intralobular ducts, small arteries, and postcapillary veins were richly innervated by VIP-IR fibers, whereas CPON-, CGRP-, and substance P-IR fibers were restricted to blood vessels. Peptide-containing nerves were found surrounding, but not in the middle of, the highly inflamed mononuclear cell areas. CONCLUSION: This topologic distribution suggests involvement of VIP-IR fibers in vascular, motor, and secretory components of the reflex salivary secretion, whereas the distribution and the vasoactive actions of CPON, CGRP, and substance P suggest a role in the regulation of the salivary gland circulation, and thus of transcapillary flow. Excessive release may contribute to a neurogenic inflammation. Local depletion and absence of trophic neuropeptide stimuli may contribute to acinar atrophy.

C-Peptide

Distribution of adhesion receptors in recurrent oral ulcers.

When activated under physiologic or pathologic conditions leukocytes adhere to one another or to other cell types. Adhesion receptors mediate these interactions. In the study reported here, the distribution of the adhesion receptors LFA-1 (CD11a/CD18), ICAM-1 (CD54), CD2 and LFA-3 (CD58) in recurrent oral ulcers (ROU) were studied. Nine tissue specimens from five female patients (mean age 33 yr, age range 21-40 yr) with ROU were studied using the avidin-biotin-peroxidase complex (ABC) method. The main mononuclear cell infiltrations were in lamina propria (LP) and the epithelium next to the basement membrane (BM), laterally to the ulcers. In this area, ICAM-1 was strongly expressed in capillaries and in postcapillary venules. LFA-1, LFA-3 and CD2 were expressed in 65 +/- 1.1%, 70 +/- 16% and 80 +/- 1%, respectively, of all mononuclear cells. The findings indicate that LFA-1/ICAM-1 and CD2/LFA-3 interactions may play roles in cell to cell adhesion events in ROU.

Adult

Topology of innervation of labial salivary glands by protein gene product 9.5 and synaptophysin immunoreactive nerves in patients with Sjögren's syndrome.

Glandular secretion and integrity, local blood flow, salivary secretion, pain perception and neurogenic inflammation can all be controlled by the nervous system. Therefore, the pattern of innervation of labial salivary glands (LSG) was studied in 10 patients with Sjögren's syndrome using neuronal markers: protein gene product 9.5 (PGP 9.5), a cytoplasmic, noncytoskeletal epitope and synaptophysin, a glycoprotein present in presynaptic vesicles. PGP 9.5 immunoreactive nerve fibers were found surrounding the acini, salivary ducts and blood vessels. The rich innervation of LSG was even more evident in immunofluorescence stained sections analyzed using confocal laser scanning imaging. Synaptophysin immunoreactive nerve endings and preterminal varicosities also demarcated the LSG acini. Furthermore, in the small foci, PGP 9.5 and synaptophysin immunoreactive nerve fibers were found amid inflammatory mononuclear cells and in extensive inflammatory areas nerve fibers were found in the peripheral parts of such infiltrates. This suggests a possible neurogenic influence on the local cellular inflammation. When LSG patient samples were compared to unaffected glands from 7 controls, acinar atrophy was found in the areas devoid of a local delivery system of neurogenic trophic stimuli, suggesting this as a possible cause of glandular degeneration. It may become necessary to incorporate this neglected, but existing system into our current view on the local but possibly centrally controlled or influenced pathogenetic mechanisms of Sjögren's syndrome.

Humans

Immune-inflammatory cells in recurrent oral ulcers (ROU).

Tissue lesions from eight patients with recurrent oral ulcers (ROU) were subjected to detailed immunohistopathologic studies. In five patients, a specimen of an unaffected area from the opposite site was obtained. The main inflammatory cells in situ were CD3 positive T lymphocytes, with CD4 cells forming approximately half (range 30-60%) and CD8 cells 20% (range 10-30%) of all cells. CD19 positive B lymphocytes formed 5-12% of all cells. Furthermore, 45% (range 15-65%) of all lymphoid cells had signs of previous antigenous contact and had helper/inducer CDw29 type. Suppressor/inducer CD45R cells formed only about 20% (range 7-50%) of all cells. Although this observation suggests involvement of antigen as a causative and/or triggering stimulus, elements of a non-specific inflammatory response were observed as well. Endogenous peroxidase-positive neutrophils were present at the ulcer site, and were occasionally observed intravascularly and in the extracellular matrix in areas characterized by inflammatory mononuclear cell infiltrates. Although the proportion of endogenous peroxidase-positive, recently recruited monocytes was low, CD11b and nonspecific esterase-positive mature tissue macrophages formed about 14% (range 5-35%) of all inflammatory cells in situ, particularly at the periphery of the lymphoid cell infiltrates. Mast cells were also observed in all samples studied, forming 2-5% of inflammatory cells in the richly vascularized connective tissue beneath the basement membrane. In the specimens from clinically unaffected areas, inflammatory cells were rare. Our observations stress the multifaceted nature and participation of multiple effector systems in the local tissue pathogenesis of ROU.

Adult

Localization of lysozyme mRNA in the labial salivary glands by in situ hybridization in Sjögren's syndrome.

In this study, lysozyme mRNA in labial salivary glands has been localized with in situ hybridization technique using 35S-labeled hen lysozyme cDNA (cDNALZM) as a hybridization probe in normals and in patients with Sjögren's syndrome, 35S-DNALZM:mRNA hybrids were detected only in acinar serous cells, although lysozyme was identified in ductal cells using immunohistochemical techniques. Our results suggest that the serous acinar cells are the only site of lysozyme synthesis in small salivary glands. The presence of lysozyme in ductal cells may be a result of reabsorption from the saliva or concentration from the blood or surrounding tissues.

Autoradiography

A six-year follow-up study of sports-related dental injuries in children and adolescents.

The records were analyzed of 106 patients with sports-related dental traumas treated in 1983 at the public oral surgery unit in Helsinki, Finland; 51 were examined six years after injury. The mean age was 11.8 years (range 7-24 years). The woman/man ratio was 1:3. In 39% of cases, the injuries had arisen from ice hockey or skating; 30% happened during school hours; 80% were uncomplicated crown fractures, concussions or subluxations. During the six-year follow-up, of 80 teeth in 51 patients, root resorption was found in 6 teeth (7.5%), periapical lesions were noted in 2 teeth (2.5%), and obliteration of the pulp was seen in 4 teeth (5%). Three teeth (3.7%) had suffered loss of vitality. The pulp had been extirpated in 13 of the traumatized teeth (16%). In all, 13.7% of the patients were found to have complications six years later. The results showed that long follow-up periods are needed after dental injury.

Adolescent