[Prima--25 years of waiting for general practitioners!].
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Family Practice↗
Biomedical subjects
M Kallioinen
Publications and source records attributed to M Kallioinen.
Systemic therapy with estrogen or estrogen with progestin has no effect on skin collagen in postmenopausal women.
OBJECTIVES: To investigate the effect of estrogen alone or combined with progestin on the amount and synthesis of skin collagen in postmenopausal women. METHODS: Forty-three early postmenopausal women were enrolled into this open, non-randomized parallel-groups study. Fifteen women received a continuous oral dose of 2 mg of 17 beta-estradiol and 1 mg of norethisterone acetate daily and 14 women an oral dose of 2 mg estradiol valerate daily. Fourteen subjects served as controls. The histology and type I and III procollagen immunohistochemistry of the skin, skin thickness, the amount of total collagen determined by a colorimetric method and the synthesis of type I and III collagens determined by analysing procollagen propeptides in the suction blister fluid were studied before the treatment and at 6 and 12 months. The proportional area of elastic fibers and the thickness of the epidermis were assessed from the sections obtained before the treatment and at 12 months, with computerized image analysis. RESULTS: Skin thickness, the amount and rate of collagen synthesis, the proportional area of elastic fibers and the thickness of the epidermis were not affected by either 17 beta-estradiol and 1 mg of norethisterone acetate or 2 mg of estradiol valerate. No histological or immunohistological changes were detected in the skin specimens during the 12-month treatment period compared to the baseline or to the skin specimens of the control group. CONCLUSIONS: A 1-year treatment with systemic estrogen alone or combined with progestin does not change the amount of collagen or the rate of collagen synthesis in postmenopausal women.
Administration, Oral↗
A homozygous nonsense mutation and a combination of two mutations of the Wilson disease gene in patients with different lysyl oxidase activities in cultured fibroblasts.
Wilson disease is a rare autosomal recessive disease of copper metabolism. The gene for Wilson disease was characterized recently and has been predicted to encode a copper-transporting ATPase highly homologous to the protein encoded by the gene of Menkes disease. In this study, the genetic mutations of two Finnish patients with Wilson disease were investigated. One patient was homozygous for a novel nonsense mutation in exon 4, while the other was a compound heterozygote. Lysyl oxidase (EC 1.4.3.13) is an extracellular copper enzyme with deficient activity in Menkes disease. The levels of lysyl oxidase activity in cultured skin fibroblasts from these Wilson disease patients were also measured.
Adult↗
Ehlers-Danlos type IV: non-invasive techniques as diagnostic support.
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Adult↗
Multicellular origin of tenascin in skin tumors--an in situ hybridization study.
Tenascin mRNA expression was studied by an in situ hybridization method in 27 skin tumors. Tenascin synthesis was increased in all skin tumors when compared to uninvolved skin but there was variation in the site of cellular synthesis between different types of tumors. In melanocytic nevi and precancerous keratinocyte lesions, tenascin seemed to be of epidermal or stromal origin. In basal cell carcinoma, squamous cell carcinoma and malignant melanoma, there was tenascin synthesis also in tumor cells. These findings are in concordance with earlier studies which suggest a role of tenascin as an anti-adhesive and motility-promoting factor in malignant skin tumors.
Basal Cell Carcinoma↗
P53 accumulation, deoxyribonucleic acid ploidy and progression of bladder cancer.
PURPOSE: The alterations in deoxyribonucleic acid (DNA) ploidy and p53 expression during progression of bladder cancer were determined. MATERIALS AND METHODS: p53 Expression and DNA ploidy were studied in 51 patients with transitional cell carcinoma of the bladder (mean followup 5 years). Of 29 primarily superficial tumors (stages Ta and T1) 17 became subsequently invasive (greater than stage T2) within an average of 4 years (group 2) and 12 recurred superficially with no sign of progression during a mean followup of 10.8 years (group 1). Of the patients 22 had metastatic disease (group 3). Samples of tumors at diagnosis and recurrence or progression were analyzed by immunohistochemistry and flow cytometry. RESULTS: p53 Accumulation was detected at diagnosis in 29 of the 51 patients (57%), including 3 of 12 (25%) in group 1, 5 of 17 (29%) in group 2 and 14 of 22 (64%) in group 3. The p values for the differences between groups 1 and 3, and 2 and 3 were 0.07 and 0.054, respectively. Abnormal DNA contents were noted in 3 of 12 (25%), 11 of 17 (65%) and 16 of 22 (73%) patients in groups 1 to 3, respectively, and the differences between groups 1 and 2, and 1 and 3 were statistically significant. Using these 2 genetic markers, we found genetic progression to be uncommon in groups 1 and 3, whereas in group 2 an initially negative p53 staining became positive at invasion into the muscle in 5 of 12 patients (42%). CONCLUSIONS: The tumors in patients with superficial recurrences are mostly diploid and negative for p53, and those with metastasis are nondiploid and positive for p53 from the beginning, while further genetic progression is uncommon. However, p53 tends to accumulate frequently when the tumor begins to invade the muscle. There seems to be a need for caution against under staging an apparent stage T1 tumor that is positive for p53.
Carcinoma, Transitional Cell↗
Erythema elevatum diutinum in association with coeliac disease.
Erythema elevatum diutinum (EED) has been described in association with several immunological or infectious diseases. We describe a female patient who presented with clinically and histologically typical EED in whom previously undiagnosed coeliac disease was found. Appearance of EED lesions was preceded by widespread joint pains. In extensive laboratory tests, the only abnormal findings were an elevated erythrocyte sedimentation rate (ESR) and decreased haemoglobin and folic acid levels. Later, IgA and IgG type antireticulin and antigliadin antibodies were detected. Serum total IgA was elevated but no paraproteinaemia was found. In lesional skin, granular deposits of IgA and C3 were seen at the dermo-epidermal junction. A duodenal biopsy revealed total villous atrophy. Dapsone treatment was partly effective but complete healing of the EED lesions was achieved only after the introduction of a strict gluten-free diet. The patient has now remained symptom-free on the diet for 1.5 years.
Celiac Disease↗
Effect of topical tretinoin on non-sun-exposed human skin connective tissue: induction of tenascin but no major effect on collagen metabolism.
The effects of topical tretinoin on collagen synthesis and degradation were studied in 29 volunteers. The subjects applied 0.1% tretinoin cream on their non-sun-exposed abdominal skin once a day for 1 week (n = 10) (experiment 1) or twice a day for 2 weeks (n = 8) (experiment 2) or once a day for 2 months (n = 11) (experiment 3). After the treatments, suction blisters were induced and amino-terminal propeptides of type I and III procollagens (PINP, PIIINP, respectively) (experiments 1 and 3) and carboxy-terminal propeptide of type I procollagen (PICP) (experiment 2) were assayed as an index of de novo collagen synthesis by radioimmunoassays. Matrix metalloproteases 2 (MMP-2) and 9 (MMP-9) were assayed by the zymography method in experiment 2. In experiment 3, histology, immunohistochemistry of type I and III procollagens, tenascin, mRNA levels of type I collagen alpha 1-chain [alpha 1 (I)], interstitial collagenase (MMP-1), MMP-2, MMP-9 by slot-blot analysis and the levels of alpha 1 (I) collagen mRNA by a quantitative polymerase chain reaction method were studied. The proportional area of elastic fibres visualized in Verhoeff-stained sections was analysed by computerized digital image analysis. The results indicated that treatment with topical tretinoin does not markedly induce de novo synthesis of collagen in vivo or affect matrix metalloproteases. In the immunohistochemical staining, tenascin was increased in the papillary dermis. As it has been suggested that tretinoin could counteract the atrophogenic effect of corticoids on the dermis, the effect of a combination of betamethasone-17-valerate (once a day) and tretinoin (once a day) on the propeptide levels was also studied. Betamethasone alone caused a 60% decrease in the concentrations of PINP and PIIINP, and a similar decrease was found after the combination treatment, indicating that topical tretinoin administered during short treatment periods does not counteract the inhibitory effect of a potent corticoid on collagen propeptides.
Abdomen↗
Matrix metalloproteinase-2 (72 kD type IV collagenase) expression occurs in the early stage of human melanocytic tumour progression and may have prognostic value.
Matrix metalloproteinase-2 (MMP-2), a member of the matrix metalloproteinase family, participates in degradation of the pericellular and extracellular matrix during neoplastic growth and metastasis. Experimental data have substantiated its role in melanoma invasion, but there is no information at present concerning its expression in histological specimens from human melanocytic tumors. This study describes the occurrence and immunolocalization of MMP-2 in human melanocytic lesions, defining distinct steps in melanoma progression. Paraffin-embedded sections from 118 melanocytic lesions were immunostained using a specific antibody to 72 kD type IV collagenase. The material included 34 common naevocellular naevi, 14 dysplastic naevi, 21 in situ melanomas, 20 primary malignant melanomas, and 29 melanoma metastases. Intracytoplasmic MMP-2 immunoreactive protein was found in the 'naevocytic nests' of common naevi, in junctional naevus cells, and in melanoma cells. The surrounding normal skin stained negatively, except for occasional macrophages, sweat glands, and hair follicles. The number of MMP-2-positive cells increased with decreasing architectural organization and increasing atypia in the melanocytic lesions. The MMP-2 positivity in the primary and subcutaneous melanoma lesions correlated with later haematogenous metastasis. The data suggest that MMP-2 expression is an early event in melanocytic tumour progression, but is nevertheless prognostic for haematogenous metastasis in melanoma.
Adult↗
Increased collagen propeptides in the skin of a scleredema patient but no change in re-epithelialisation rate.
Scleredema is a rare disease, affecting the skin connective tissue with increased amounts of collagen and glycosaminoglycans. In the present study, the collagen synthesis and re-epithelialisation rate were measured from a 64-year-old male patient, who rapidly developed extensive tightening of the skin, without any underlying disease. The skin was thickened at several sites when measured with ultrasound, and the histology revealed accumulation of glycosaminoglycans and collagen bundles. The collagen synthesis rate was measured from suction blisters induced on two different sites of the skin before the treatment and three times later up to 6 months after the treatment with a systemic steroid was started. The aminoterminal propeptide of type I collagen (PINP) was increased manifold in the affected skin when compared with the controls, indicating active collagen deposition in vivo. Systemic steroid medication with high doses (over 20 mg/d) decreased both the type I and the type III collagen propeptide levels. The time schedule of the decreases in the propeptides in the thickened, affected skin and in the clinically normal-looking skin varied, and especially in the thickened skin in the abdomen the decrease in PINP was noted only after 3 months of prednisolone therapy. When the prednisolone dose was only 10 mg daily, the propeptides were again up-regulated, perhaps reflecting the natural course of the disease. The re-epithelialisation rates at two different sites of the patient were similar to those in the controls, suggesting that even massive fibrosis with active deposition of collagen does not alter the basal rate of re-epithelialisation in the skin. In conclusion, collagen synthesis is markedly elevated in scleredema, leading to fibrosis of the skin. A recently developed method utilizing assays of collagen propeptides from suction blister fluid allows monitoring of the collagen synthesis and detection of changes in the collagen synthesis during the treatment of fibrotic disorders.
Abdomen↗
Non-erythroid spectrin (fodrin) in cutaneous tumours: diminished in cell membranes, increased in the cytoplasm.
The expression and distribution of non-erythroid spectrin (alpha-fodrin), a basic protein of the cell membrane skeleton, was investigated by immunohistochemical methods in 42 cutaneous tumours. The suprabasal keratinocytes of the normal epidermis showed plasma membrane-associated spectrin. The basal cells of the normal epidermis, seborrhoeic keratosis, and basal cell carcinoma, revealed both intracytoplasmic and membrane-bound spectrin. In squamous cell carcinoma, the expression of spectrin was heterogeneous and mostly intracytoplasmic. The dysplastic cells of solar keratosis expressed no spectrin at all. In various types of melanocytic naevi, intracytoplasmic and discontinuous membrane-bound spectrin was found in most tumour cells. Malignant melanomas showed a heterogeneous intracytoplasmic staining for spectrin, or were negative. The results indicate a diminished amount, or a total lack, of membrane-bound spectrin with increasing depolarization and proliferation of cells in solar keratosis and pigment cell tumours, but a partial preservation in polarized cells of basal cell carcinoma. The increase and heterogeneity, in cytoplasmic spectrin, of squamous cell carcinoma and malignant melanoma seemed to be associated with the less differentiated, invasive cells of these malignant tumours.
Basal Cell Carcinoma↗
Destruction of the epithelial anchoring system in lichen planus.
To find out whether the epithelial anchoring system shows any alterations in lichen planus, we examined the distribution of type VII collagen, alpha 6 beta 4 integrin, and kalinin in lesions of lichen planus. These molecules were chosen because they are structural components of anchoring fibrils, hemidesmosome-associated complexes, and anchoring filaments. The localization of type VII collagen in lichen planus was strikingly different from that in nonaffected mucosa or dermis or in other mucocutaneous lesions. In the normal mucosa, type VII collagen was localized only at the basement membrane zone. In lichen planus, type VII collagen was present not only in the basement membrane area but also in streaked patterns deep in the connective tissue. The hemidesmosome-associated complex, alpha 6 beta 4 integrin, was localized at the basal aspect of basal epithelial cells of nonaffected sites, but was diffuse and discontinuous in lichen planus lesions. Most of the basal keratinocytes, however, stained for this integrin. Kalinin staining was discontinuous in lichen planus lesions. Often, finger-like projections of kalinin staining were found protruding into the connective tissue stroma. Kalinin was localized at the basement membrane zone of the nonaffected tissue and other mucocutaneous lesions. These results indicate that in cutaneous and mucosal lichen planus, the epithelial anchoring system is disturbed.
Antigens, Surface↗
Expression of cytokeratins in regenerating human epidermis.
The expression of cytokeratin polypeptides in regenerating human epidermis was immunohistochemically examined during re-epithelization of suction blisters. The regenerating basal and suprabasal epidermis expressed keratin polypeptides K13, K14, K16 and K18, which are not present in normal suprabasal epidermis. On the contrary, K10, a normal constituent of terminally differentiated keratinocytes, was lacking from the epidermis until the ninth day of re-epithelization. The findings indicate changes similar to other hyperproliferative states (expression of K16), basal-like features (expression of K14), or properties reminiscent of fetal skin (K13 and K18) in the newly formed epidermis. Monoclonal antibodies for cytokeratins and a technique using suction blisters seemed to be a suitable methodology for the study of epidermal regeneration in normal skin. The technique may also have advantages in the investigation of keratin expression in diseased skin.
Adult↗
Adhesion molecules in the nickel allergic reaction.
Nickel is the major cause of allergic contact dermatitis, and to increase our understanding of this immune reaction we studied changes in the expression of adhesion molecules on mononuclear cells during nickel stimulation in vivo and in vitro. Nickel-induced lymphocyte cultures were used in vitro, the cells being examined with monoclonal antibodies (Mabs) and by flow cytometry. Mononuclear cells from skin biopsies of in vivo cutaneous nickel reactions were studied with Mabs and immunohistochemistry. The expression of adhesion molecules in vitro was differential: the number of cells carrying CD11c, CD29, CDw49b, CDw49d, CDw49e, CDw49f, CD54, CD56 and ELAM-1 being significantly overrepresented among the nickel-induced lymphoblasts whereas the number of blasts carrying CD44 was underrepresented and those of CD11a, CD18, CD58 and LAM-1 remained unchanged. CD4+ cells gained adhesion molecules during nickel-induced blast transformation whereas CD8+ cells lost most of their adhesion molecules. The in vivo results were in agreement with the in vitro ones except that CDw49b, CDw49f, CD56 and ELAM-1 could not be detected in a 96-hour nickel reaction in vivo. In conclusion, the nickel allergic reaction favors the expression of certain adhesion molecules, and this expression is induced on CD4+ cells while CD8+ cells tend to lose such molecules. The changes were more sensitively detected with the in vitro method.
CD4-Positive T-Lymphocytes↗
Neurofibromin: expression by normal human keratinocytes in vivo and in vitro and in epidermal malignancies.
BACKGROUND: Neurofibromin is the product of the NF1 gene, the mutations of which have been linked with type 1 neurofibromatosis. The expression of neurofibromin in human skin has not been analyzed in detail. EXPERIMENTAL DESIGN: Polyclonal Ab were raised against synthetic peptides corresponding to three different sites of neurofibromin. One of the Ab selectively recognized type II neurofibromin. The localization of neurofibromin was first studied in normal human skin. Further studies concentrated on neurofibromin expression in basal cell and squamous cell carcinomas. Reverse transcription-PCR (RT-PCR) and molecular hybridizations and immunocytochemistry were used to characterize the expression of neurofibromin in cultured keratinocytes. RESULTS: All neurofibromin-specific Ab immunolabeled the epidermis. The basal keratinocytes displayed the most prominent immunosignal for type II neurofibromin. RT-PCR demonstrated the presence of both type I and II neurofibromin mRNA transcripts in cultured keratinocytes. Keratinocytes induced to differentiate and to arrest division by a high (1.4 mM) Ca2+ concentration of the culture medium displayed a down-regulation of neurofibromin expression at the mRNA and protein levels. This was most strikingly demonstrated by a reduction of immunoreactivity for type II neurofibromin. Basal cell carcinomas displayed a weak immunosignal for type II neurofibromin. In contrast, particularly the central areas of squamous cell carcinoma, islands were intensely immunolabeled. CONCLUSIONS: The results suggest that neurofibromin acts as a regulator of the basal keratinocytes in normal skin and that cultured keratinocytes offer a human model for studies aimed to elucidate the regulation of neurofibromin gene expression. Furthermore, aberrations in neurofibromin expression may play a role in the pathogenesis of epidermal cancers.
Amino Acid Sequence↗
Development of the neurocranium after transsutural fixing by new, resorbable poly-L-lactide miniplates. A comparison to fixing with the common titanium miniplates.
The right coronal sutures of twelve (12) newborn rabbits were fixed with commercially available, self-reinforced poly-L-lactide miniplates, with eight (8) rabbits sham treated with titanium miniplate fixation as reference experiments, in order to demonstrate the possible effects on skull growth. After six (6) months follow-up, both types of plate were detected to have caused a similar asymmetry in the neurocranium. Therefore, in our opinion, fixing across growing sutures, even with the new biodegradable devices, should be avoided.
Animals↗
Pachydermoperiostosis: analysis of the connective tissue abnormality in one family.
BACKGROUND: Pachydermoperiostosis (PDP) is a rare hereditary disease characterized by hyperostosis, clubbing of fingers, coarse skin, and abnormalities in other organs, such as the gastrointestinal tract. Previous studies have disclosed several abnormalities in the connective tissue in these patients. OBJECTIVE: The purpose of the study was to investigate connective tissue abnormalities in one family with PDP. METHODS: Clinical features were evaluated; x-ray, immunohistochemical, and electronmicroscopic studies were performed; and markers of collagen metabolism and lysosomal enzymes were determined. RESULTS: Immunohistochemical and ultrastructural studies revealed accumulation of tenascin, glycosaminoglycans, and fibrillar material in apparently disorganized microfibrils of elastic fibers. Osteocalcin levels in the serum were increased, but synthesis and degradation markers of collagen in the serum were not altered. No evidence of a lysosomal enzyme deficiency was found. CONCLUSION: Acidic mucopolysaccharides and some fibrillar material accumulate in the dermis of patients with PDP. Increased levels of osteocalcin in serum indicate higher osteoblastic activity. Markers of synthesis and degradation of collagen were not altered.
Acid Phosphatase↗
Increased tenascin expression in melanocytic tumors.
Tenascin is a large extracellular matrix glycoprotein which is widely distributed in normal, hyperplastic and neoplastic tissues. Its function is unknown but it has been associated with the epithelial-stromal interactions, such as cell adhesion and movement which take place, e.g. in morphogenesis, cellular proliferation and neoplasia. In this study, we investigated tenascin expression in 70 benign, dysplastic and malignant melanocytic tumors by using immunohistochemistry and monoclonal anti-tenascin 143DB7C8 antibody on paraffin sections. In all types of benign nevi, both intradermal, compound and junctional, there was a moderate expression of tenascin at the dermoepidermal junction and in the papillary dermis. In dysplastic nevi, the fibrotic areas in the papillary dermis also showed a moderate staining for tenascin. Invasive malignant melanomas showed the strongest expression of tenascin. In addition to the staining at the dermo-epidermal junction and in the papillary dermis, there was a variable expression of tenascin in the reticular dermis. Intracytoplasmic tenascin was detected both in primary melanomas and melanoma metastases. In conclusion, we have shown that tenascin expression is moderately increased in benign and dysplastic melanocytic tumors and greatly increased in malignant melanomas and melanoma metastases. The function of tenascin may be related to the cellular-stromal interactions and it is possibly associated with the proliferation and spread of the melanocytic tumors.
Biopsy↗