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Biomedical subjects

J Karvonen

Publications and source records attributed to J Karvonen.

At least 19 recordsLinked to original sources

Increased collagen synthesis in psoriasis in vivo.

Psoriasis is an inflammatory skin disease of unknown a etiology which also involves changes in dermal elements. Previous in vitro studies have shown an increased collagen synthesis rate in cultured fibroblasts. In this study collagen synthesis was studied in vivo in the uninvolved skin of psoriatic patients using a newly developed method in which collagen propeptides were measured in suction blister fluid. Both type I and type III collagen synthesis rates, as measured in terms of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP), were increased about two-fold in uninvolved psoriatic skin as compared with controls, the mean level of PICP being 870 and 457 micrograms, respectively (P < 0.001), and of PIIINP being 294 and 124 micrograms, respectively (P < 0.01). The increased collagen synthesis rate was also confirmed by in situ hybridization using specific probes. Collagen mRNAs were found to be particularly abundant in psoriatic patients, who also demonstrated a high collagen synthesis rate when assayed by measuring collagen propeptides. The increased rate of collagen synthesis in the uninvolved psoriatic skin seemed not to be related to the severity of the disease or to various treatments such as UVB, PUVA, retinoids or cytostatic drugs, but seemed more likely to be due to the psoriasis itself. Interestingly, skin thickness was not increased in the patients with psoriasis, even though collagen synthesis was markedly elevated, perhaps suggesting that in psoriasis the turnover rate of collagen is enhanced.

Adult

Lesional psoriatic epidermis displays reduced neurofibromin immunoreactivity.

Neurofibromin enhances the inactivation of protooncogene p21ras and has been suggested to function as a regulator of cell growth and differentiation. In normal skin, neurofibromin is particularly abundant in the basal keratinocytes of epidermis. The present study utilized antibodies raised against two synthetic peptides corresponding to different regions of neurofibromin. One of the antibodies recognized all forms of neurofibromin and the other was specific for type II neurofibromin. The following specimens were analyzed for neurofibromin immunoreactivity: 1) skin of apparently healthy volunteers, 2) active lesions of 15 psoriatic patients, 3) apparently healthy skin of the same patients at the time of the active phase of the disease, and 4) the previously lesional areas after anti-psoriatic treatment of the same patients. The presence of neurofibromin mRNA in normal epidermis and in keratinocytes cultured from normal skin was demonstrated by reverse transcriptase-polymerase chain reaction or by Northern hybridization. In marked contrast to normal epidermis, active psoriatic lesions were characterized by a weak immunosignal for types I and II neurofibromin in the basal cell layer of the epidermis. Previously lesional, clinically healed areas displayed variable, yet clearly detectable, expression of neurofibromin. Our results demonstrate that the epidermis of psoriatic lesions displays reduced immunostaining for type I and II neurofibromins compared to normal epidermis, and that neurofibromin immunoreactivity is partially restored concomitant with clinical healing of the lesions. The question whether the changes in neurofibromin expression in psoriasis are causal or consequential with respect to the pathogenesis of psoriasis remains to be elucidated.

Adolescent

Topical mometasone furoate and betamethasone-17-valerate decrease collagen synthesis to a similar extent in human skin in vivo.

Topical corticosteroids are used extensively to treat inflammatory skin diseases. Long-term use, however, may be associated with adverse effects such as skin atrophy. New steroids have been developed with the objective of increasing efficacy and reducing the incidence of adverse effects. Mometasone furoate (MMF) is one of these new derivatives. The aim of our study was to compare the effects of MMF and betamethasone-17-valerate (BM-17-valerate) on collagen synthesis in human skin in vivo. Fifteen healthy male volunteers applied MMF, BM-17-valerate and vehicle for 1 week to different areas of abdominal skin. Suction blisters were raised on these areas, and a control site, and procollagen propeptide (PICP, PINP, PIIINP) levels in the suction blister fluid were measured by radioimmunoassay. Skin thickness was measured ultrasonically by Dermascan A at the end of the treatment period. The levels of the three propeptides in suction blister fluid were reduced to similar extent by MMF and BM-17-valerate. The 1-week treatment period had no detectable influence on skin thickness. We conclude that MMF and BM-17-valerate decrease collagen synthesis to the same extent in human skin in vivo.

Administration, Topical

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

Two antireflux operations: floppy versus standard Nissen fundoplication.

The effects of fundic mobilization in Nissen fundoplication on belching ability, abdominal gas volume, bloating and flatus were assessed in a prospective, randomized study of 25 patients with refractory gastro-oesophageal reflux disease. Reflux was cured regardless of fundic mobilization. Subjective ability to belch was restored to preoperative in 73% of the patients with fundic mobilization, compared to 50% without. About 10% in both groups totally lost their ability to belch. Disturbance from flatus increased postoperatively slightly in both groups, but from bloating it remained the same or even diminished. The residual intra-abdominal radioactivity (median (interquartile range)) after provoked belching was preoperatively 8.9% (4.4-12.0) with and 13.2% (6.8-15.2) without fundic mobilization, compared to 36.7% (31.1-40.9) of the controls (P < 0.05). After fundoplication this residual activity was normalized in both study groups. Disturbance from postoperative bloating or flatus were not related to the ability of belching. Preoperatively symptomatic patients tended to have more complaints postoperatively. In conclusion, fundic mobilization restored belching ability slightly more effectively without compromising antireflux efficacy, but there did not seem to be any advantage regarding flatus or bloating.

Adult

Cell-type related and spatial variation in the expression of integrins in cutaneous tumors.

Integrins constitute a group of transmembrane proteins which mediate cell-cell and cell-matrix interactions. Previous studies have shown both increased and decreased expression of integrins in relation to malignancy and invasion. In the present study, we investigated integrin distribution in cutaneous tumors by using monoclonal antibodies on frozen tissue sections. Antibodies to integrin subunits alpha v, alpha 3, alpha 4, alpha 5, alpha 6, beta 1 and beta 3 were used. The study was designed to explore (i) the association between integrin expression and the tumor type, and (ii) the effect on the integrin expression of the location of the tumor, i.e. whether it grows intraepidermally or within various compartments of the dermis (papillary or reticular). Beta 1, beta 3 and alpha 3 were strongly or moderately expressed in the epithelial and stromal cells of basal cell carcinomas (BCC), seborrheic keratoses, solar keratoses, dermatofibromas (DF), and showed a variable expression in the nevic cells of benign and dysplastic nevocellular nevi. alpha v and in alpha 5 appeared strongly expressed in the stromal cells of BCC and DF, while only a focal, often weak staining was seen in nevic cells and in the epithelial cells of BCCs. In some nevocellular nevi, they were only expressed, together with alpha 4, in the deep-seated nevic cells in the reticular dermis. alpha 6 was expressed by tumor cells of BCCs and nevocellular nevi only within the dermo-epidermal junction. In seborrheic keratosis and solar keratosis a basement membrane-associated staining pattern for alpha 6 was seen in the basal cell layer, with focal discontinuities in solar keratosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal

Mononuclear cell subsets in the nickel-allergic reaction in vitro and in vivo.

Nickel is the major cause of metal-induced contact allergy. To understand the mechanism of its immune reaction, we studied changes in lymphocyte surface markers during nickel challenge in both allergic and healthy subjects using an in vitro nickel reaction in which the lymphocytes of allergic subjects divide when they are stimulated with nickel sulfate. The lymphocytes were labeled with monoclonal antibodies (MAbs) to cell-surface antigens and studied by flow cytometry. Mononuclear cells from the nickel reaction in vivo were studied from skin biopsy specimens using MAbs and avidin-biotin immunohistochemistry. Nickel-induced lymphoblast transformation occurred in vitro only in cells from nickel-allergic subjects. CD4+ cells and CD45RO+ cells were overrepresented among the lymphoblasts of nickel-sensitive subjects, whereas CD8+ and CD8+CD11b+ and CD4+CD45R+ cells were underrepresented. The lymphoblasts contained T cells with the following activation markers: CD25, HLA-DR, CD26, CD71, Ki-67, and activation-associated antigen detected by the MAb, M21C5, but they were CD30-. CD16+ cells were overrepresented among the lymphoblasts. Nickel-reacting T cells used predominantly the T cell receptor, alpha beta-heterodimer, but no preferential selection of either V beta 5, V beta 6, or V beta 8 was observed. The phenotypes of nickel-reacting cells from cutaneous biopsy specimens were in agreement with the in vitro results.

Antigens, Differentiation

Alcohol and smoking: risk factors for infectious eczematoid dermatitis?

Risk factors for infectious eczematoid dermatitis (IED) were analyzed in a study of males aged 19-50 years. The subjects were 43 IED patients and 226 controls with other skin diseases from the dermatological outpatient clinics of three University Hospitals in Finland. The patients' lifestyles were assessed by a self-administered questionnaire pertaining to two specified periods: the period 12 months before the onset of the skin disease and the period 12 months before the examination date. Recalled mean alcohol intake before the onset of the skin disease was 39.2 g/day for the IED patients and 17.1 g/day for the controls (p = 0.04). The average number of cigarettes smoked daily was 17.7 for the IED patients and 10.4 for the control patients (p = 0.001). The IED patients significantly reduced their alcohol intake after the onset of the skin disease. In logistic regression analysis, IED associated with alcohol intake and smoking but not with coffee consumption, life events, age, marital status, or social group. The odds ratio for IED at an alcohol intake of 50 g/day as against no intake, was 1.7 (95% confidence interval 1.03-2.7), and the odds ratio at a tobacco consumption rate of 20 cigarettes/day as against no use of tobacco, was 2.1 (1.2-3.7). We conclude that alcohol intake and smoking appear to be risk factors for infectious eczematoid dermatitis among males.

Adult

Comparison of intravenous diclofenac, indomethacin and oxycodone as post-operative analgesics in patients undergoing knee surgery.

The non-steroidal anti-inflammatory drugs diclofenac, indomethacin and oxycodone were compared in the treatment of pain after arthroscopy or arthrotomy of the knee in a double-blind, randomized trial. A single and, if needed, a repeated dose of one of the following six dose and drug alternatives was given intravenously for post-operative pain relief: diclofenac 37.5 mg or 75 mg, indomethacin 25 mg or 50 mg and oxycodone 5 mg or 10 mg. Oxycodone 5 mg i.v. was used as a rescue medication whenever the patient needed further pain relief after the two doses of the trial drugs. The observation period was 14 h. In the diclofenac group the patients needed significantly less trial and rescue analgesics than in the indomethacin (P less than 0.001) and oxycodone (P less than 0.05) groups, the latter groups being equal in this respect. Both the duration from the first trial drug infusion to the second trial medication and to the first rescue medication were significantly longer in the diclofenac group than in the indomethacin group (P less than 0.05 and less than 0.01, respectively).

Adult

Alcohol intake: a risk factor for psoriasis in young and middle aged men?

OBJECTIVE: To clarify the nature of the association between alcohol intake and psoriasis. DESIGN: Case-control study of men aged 19-50 with onset of skin disease in 1976 or later. SETTING: Outpatient clinics of the departments of dermatology of the university central hospitals in Helsinki, Oulu, and Tampere from September 1987 to April 1989. SUBJECTS: 144 Patients with psoriasis and 285 unmatched controls with other skin diseases. MAIN OUTCOME MEASURES: Results of clinical examination and self administered questionnaire assessing lifestyle and alcohol intake during two specified periods--namely, 12 months before the onset of skin disease and 12 months before the date of examination. RESULTS: Recalled mean alcohol intake before the onset of skin diseases was 42.9 g/day among the patients with psoriasis and 21.0 g/day among the controls. In logistic regression analysis psoriasis was associated with alcohol intake but not with coffee consumption, smoking, age, marital state, or social group. The odds ratio for psoriasis at an alcohol intake of 100 g/day compared with no intake was 2.2 (95% confidence interval 1.3 to 3.9). The controls decreased their alcohol intake after the onset of the disease but the group with psoriasis did not. Analysis of serum enzyme values showed that gamma-glutamyltransferase activity was significantly correlated with alcohol intake (r = 0.35), the mean activity being 75.0 U/l among patients with psoriasis and 41.9 U/l among controls. CONCLUSIONS: Alcohol is a risk factor for psoriasis in young and middle aged men, and psoriasis may sustain drinking.

Adult

Segmental neurofibromatosis: immunocytochemical analysis of cutaneous lesions.

Cutaneous lesions from three patients with segmental neurofibromatosis were evaluated. Routine histologic studies revealed the presence of redimentary neural structures within an abundant collagenous matrix. The majority of the cells in all three cases expressed S-100 protein, suggesting their identity as Schwann cells. The stromal component stained positively for fibronectin and type IV collagen; the latter indicated the presence of basement membrane material. Embedded in the tumor mass were glandular epithelial structures that stained with epithelial membrane antigen antibody. Staining for factor VIII-related antigen revealed vascular endothelium and multiple scattered mast cells. In one case strands of cells stained with antibodies to desmin, suggesting muscle cell differentiation. This case may represent a distinct subset of neurofibromas.

Adult

Effect of long-term PUVA treatment of psoriasis on the collagen and elastin gene expression and growth of skin fibroblasts in vitro.

The proliferation rate, collagen metabolism and collagen and elastin messenger-RNA levels were studied in fibroblasts derived from patients who had received many courses of either systemic 8-methoxypsoralen or topical trioxsalen PUVA treatment. The proliferation rate of fibroblasts as measured by the incorporation of 3H-thymidine or by cellular division was decreased in those obtained from patients who had PUVA treatment as compared with controls. Collagen synthesis was slightly increased in the cells from PUVA-treated patients, but the relative collagen synthesis and the ratio between types I and III collagen were unchanged. The levels of collagen and elastin mRNAs were increased in fibroblasts derived from the PUVA-treated patients. No significant differences in histology or immunochemistry could be found in the biopsies taken from topical and systemic PUVA-treated patients.

Adult

Changes in running speed, blood lactic acid concentration and hormone balance during sprint training performed at an altitude of 1860 metres.

The development of results of five national level sprinters (Group A) was followed up during a training period of two weeks at an altitude of 1860 m aiming at increase of strength and speed and after it. Changes in anaerobic capacity were monitored by making blood lactic acid determinations, and occurrence of any overstrain by serum testosterone, cortisol, growth hormone and SHBG (sex hormone binding globulin) determinations. A control group (Group B) trained simultaneously according to a similar programme at sea level. Maximal 150 m running speeds increased in Group A significantly during the two weeks at the altitude of 1860 m (p less than 0.001). No such increase was observable in Group B. Maximal 300 m running speeds and maximal lactic acid concentrations after running did not increase significantly in either group. Serum hormone levels did not change significantly either, in either group. Training at an altitude of 1860 m to increase strength and speed significantly improved results at the shorter distance of 150 m but had not significant effects on anaerobic capacity or on serum testosterone, cortisol, growth hormone or SHBG levels.

Adult