Biomedical subjects

T Kinnunen

Publications and source records attributed to T Kinnunen.

32 records · Page 2Linked to original sources

PubMed1998

N-syndecan and HB-GAM (heparin-binding growth-associated molecule) associate with early axonal tracts in the rat brain.

Heparin-Binding Growth-Associated Molecule (HB-GAM)/pleiotrophin is an 18 kDa extracellular matrix- and cell-surface-associated protein shown to enhance neurite outgrowth of perinatal forebrain neurones in vitro. The heparan sulphate proteoglycan N-syndecan (Raulo et al., 1994) has been isolated as a receptor/coreceptor for the HB-GAM. We have investigated, whether HB-GAM and N-syndecan could have a similar role in neurite outgrowth and axon guidance in early axonal tracts of brain. In the present study N-syndecan was found to be spatiotemporally associated with the developing axonal tracts already on embryonic day 9 in rat, as revealed by coexpression with class III beta-tubulin, which is one of the earliest neuronal markers (Easter et al., 1993; Brittis et al., 1995). Later, N-syndecan and HB-GAM were detected in the first afferent serotonergic projections arising from the pontine raphe nuclei. The expression pattern of HB-GAM peaked in the developing rhombencephalon at embryonic stage (E) 13-14. At the same time, N-syndecan was expressed in the developing raphe neurones growing neurites towards the diencephalon along HB-GAM immunoreactive pathways. When rhombencephalic neurones were cultured on decreasing concentrations of substrate-bound HB-GAM, E13 neurones showed a significantly better neurite outgrowth response than E11, E16 or E18 neurones. The neurite outgrowth of raphe neurones in vitro was inhibited by adding soluble heparin or N-syndecan into the culture medium, whereas addition of chondroitin sulphate had no effect. In a simple pathway assay, E13 raphe neurones selectively preferred attaching and growing neurites on pathways containing HB-GAM as compared with regions containing either laminin or fibronectin alone. Our results suggest that HB-GAM may function as a developmentally regulated cue for rhombencephalic neurones that possess N-syndecan on their cell membrane.

Animals↗

PubMed1998

Regulation of mRNA localization by transmembrane signalling: local interaction of HB-GAM (heparin-binding growth-associated molecule) with the cell surface localizes beta-actin mRNA.

Localization of mRNAs is currently thought to be partially responsible for molecular sorting to specific compartments within the cell. In mammalian cells the best-studied example is the beta-actin mRNA that is localized to the cell processes, and its localization is necessary in migratory responses of cells. It is reasonable to assume that mRNA localization within cells is coupled to transmembrane signalling due to extracellular factors, but little is known about such putative mechanisms. We show here that HB-GAM, an extracellular matrix-associated factor that enhances migratory responses in cells, is able to localize beta-actin mRNA when locally applied to cells via microbeads. The HB-GAM-induced mRNA localization is specifically inhibited by low concentrations of heparin and by heparitinase treatment of cells, showing that cell-surface heparin-type glycans are required for the effect. The finding that soluble N-syndecan is also inhibitory suggests that the transmembrane proteoglycan N-syndecan, previously identified as an HB-GAM receptor, is involved in the mRNA-localizing effect of HB-GAM. Inhibition of the mRNA localization by the src-kinase inhibitor PP1 is compatible with an N-syndecan-mediated effect since the receptor function of N-syndecan has been recently found to depend on the src-kinase signalling pathway. The mRNA-localizing activity of N-syndecan is also suggested by the finding that affinity-purified anti-N-syndecan antibodies coated on microbeads are able to localize beta-actin mRNA.

Actins↗

PubMed1996

Neurite outgrowth in brain neurons induced by heparin-binding growth-associated molecule (HB-GAM) depends on the specific interaction of HB-GAM with heparan sulfate at the cell surface.

Heparin-binding growth-associated molecule (HB-GAM) is a cell-surface- and extracellular matrix-associated protein that lines developing axons in vivo and promotes neurite outgrowth in vitro. Because N-syndecan (syndecan-3) was found to function as a receptor in HB-GAM-induced neurite outgrowth, we have now studied whether the heparan sulfate side chains of N-syndecan play a role in HB-GAM-neuron interactions. N-Syndecan from postnatal rat brain was found to inhibit HB-GAM-induced but not laminin-induced neurite outgrowth when added to the assay media. The inhibitory activity was abolished by treating N-syndecan with heparitinase, but it was retained in N-syndecan-derived free glycosaminoglycan chains, suggesting that N-syndecan heparan sulfate at the cell surface is involved in HB-GAM-induced neurite outgrowth. Binding to HB-GAM and inhibition of neurite outgrowth was observed with heparin-related polysaccharides only; galactosaminoglycans were inactive. Significant inhibition of neurite outgrowth was induced by heparin and by N-syndecan heparan sulfate but not by heparan sulfates from other sources. A minimum of 10 monosaccharide residues were required for HB-GAM-induced neurite outgrowth. Experiments with selectively desulfated heparins indicated that 2-O-sulfated iduronic acid units, in particular, are of importance to the interaction with HB-GAM, were implicated to a lesser extent. Structural analysis of N-syndecan from 6-day-old rat brain indicated that the heparan sulfate chains contain sequences of contiguous, N-sulfated disaccharide units with an unusually high proportion (82%) of 2-O-sulfated iduronic acid residues. We suggest that this property of N-syndecan heparan sulfate is essential for HB-GAM binding and induction of neurite outgrowth.

Animals↗

PubMed1996

Depression and smoking cessation: characteristics of depressed smokers and effects of nicotine replacement.

Previous research has linked depression to difficulties in smoking cessation. The authors followed 269 smokers who attempted to quit smoking for 3 months. Participants were given nicotine gum (2 or 4 mg) or placebo gum and brief counseling. The study found that 34% of the smokers met the criterion for current depression using the Center for Epidemiological Studies Depression Scale. Depressed smokers relapsed significantly earlier than the nondepressed. Nicotine gum was significantly more effective than placebo gum among all smokers. The benefits of nicotine gum were particularly apparent among the depressed. Only 12.5% of depressed smokers quit successfully with placebo gum for 3 months, whereas 29.5% quit with nicotine gum. Depressed smokers reported more stress, less coping resources, more physical and psychological symptoms, and more frequent smoking in the presence of negative affect than did the nondepressed.

Adaptation, Psychological↗

PubMed1996

Hypnotic amnesia and learning: a dissociation interpretation.

The effect of hypnotically induced amnesia on positive transfer learning was examined within the conceptual framework of dissociation theory. An Experimental group learned two paired-associates word lists that contained highly similar (between the two lists) stimulus words. After learning the first list, subjects were given suggestions for amnesia for that list. Control group 1 learned the same two lists without amnesia suggestions. Control group 2, with amnesia suggestions following the first list, learned two lists that contained dissimilar stimulus words. All subjects remained hypnotized throughout the session. Positive transfer between the two lists was demonstrated for the Experimental group and for Control group 1, but not for Control group 2. The results are viewed as consistent with predictions from dissociation theory.

Amnesia↗

PubMed1996

Nicotine gum dose and weight gain after smoking cessation.

The authors examined weight gain in 79 abstinent cigarette smokers during treatment with placebo or with 2 mg or 4 mg of nicotine gum. Results indicated that nicotine gum suppressed weight gain in a linear fashion with increasing nicotine dose. At 90 days postcessation, placebo gum users gained 3.7 kg, 2-mg gum users gained 2.1 kg, and 4-mg gum users gained 1.7 kg. Assessment of nicotine replacement by means of pre- and postcessation salivary continue levels revealed that smokers who replaced a greater percentage of their baseline continue levels during treatment gained less weight. Percentage of baseline cotinine replaced remained related to weight gain after the number of pieces of gum used was controlled. Implications for smokers hoping to minimize postcessation weight gain are discussed.

Adult↗

PubMed1995

Urges to smoke during the first month of abstinence: relationship to relapse and predictors.

The urges to smoke reported by 215 former smokers were measured 1 day, 7 days, 14 days and 30 days after they quit to examine: (a) the time course of smoking urges, (b) the relationship of urges to relapse, and (c) predictors of urges to smoke. Urges to smoke were strongest 1 day after quitting, and decreased at each subsequent measurement point. Urges were a powerful predictor of relapse. At each of the four assessment points, abstinent subjects who reported stronger urges to smoke were more likely to relapse by the next measurement point. Urges to smoke at a given day (e.g., day 1) were consistently the best predictors of the persistence of urges at the next assessment (e.g., day 7). Greater negative emotion (e.g., anxiety, sadness, anger, and confusion) and psychosocial stress also predicted stronger urges to smoke. Nicotine gum significantly reduced urges during week 1 post-cessation. Clinical implications of the findings are discussed.

Adult↗

PubMed1994

Is the hypnotized subject lying?

Do the verbal reports of deeply hypnotized Ss truthfully reflect their subjective experiences of hypnotic suggestions? Experiment 1 established that the electrodermal skin conductance response (SCR) provides an effective method for detecting deception in the laboratory equally well in hypnotized and nonhypnotized Ss. In Experiment 2, deeply hypnotized and simulating Ss were administered a number of hypnotic suggestions in a typical hypnotic session, without mention of deception, and were questioned about their experiences while SCR measures were recorded concurrently. Results indicate that 89% of the hypnotized Ss' reports met the criterion for truthfulness, whereas only 35% of the simulators' reports met this criterion. Implications for the theory of hypnosis are discussed.

Adult↗

PubMed1992

Collagen synthesis in granuloma annulare.

Previous research has demonstrated active collagen synthesis in granuloma annulare (GA), a mainly degenerative disease of the skin. The present investigation is aimed to characterize details of the collagen synthesis and its regulation. Northern and in situ hybridization techniques and immunohistochemical methods are used to identify type I and type III collagen synthesis, regulation-associated polypeptides TGF-beta, Il-1 alpha, and Il-1 beta and an extracellular matrix protein tenascin, as well as lymphohistiocytic cells present in GA lesions. High mRNA levels of both pro-alpha 1 (I) and pro-alpha 1 (III) collagens were detected in GA lesions. In situ hybridization with cDNA probes revealed active fibroblasts with signals for both type I and III collagen mRNA around GA lesions. Some TGF-beta expression was found within the areas of inflammatory cells. Immunohistochemically, most of the mononuclear/lymphatic cells were CD3+ T cells. The helper/inducer phenotype (CD4+) was common among them, but there were no T-suppressor (CD8) cells. CD1+ cells were few in number, as were cells with activation or proliferation markers (CD26, CD30, and Ki67 antigens). Il-1 alpha- and Il-1 beta-positive lymphocytes/monocytes as well as interleukin-2 receptor containing cells were detected around the lesions, i.e., in the same areas as collagen-synthesizing fibroblasts. Another possible association with the regulation of collagen synthesis was the finding of an accumulation of tenascin, a growth-promoting extracellular matrix protein, in the surroundings of the GA lesions. We suggest that the firmly established and seemingly well-regulated type I and type III collagen synthesis presents a reparative phenomenon in the cutaneous lesions of GA.

Adult↗

PubMed1992

Moisturizers prevent irritant dermatitis.

The purpose of this study was to investigate the ability of eight different moisturizers to prevent irritant dermatitis. Twelve healthy female students washed the outer aspect of their upper arms with a liquid detergent for one minute twice a day for one week. Seven skin creams and one skin oil were applied to 3 x 7 cm areas of the left upper arm just after each washing, while the right upper arm was left untreated. Transepidermal water loss (TEWL) (mean) increased from 7.1 to 9.3 g/m2/h (p less than 0.001) and laser-Doppler flowmetry (LDF) value (mean) decreased from 11.8 to 10.8 arbitrary units (N.S.) in the left upper arm, but there was no statistical difference between the eight moisturizers. During the second week of the study, the test subjects did not continue washing their arms. Eight areas (3 x 7 cm) of the right upper arm were treated with the moisturizers twice a day. The mean TEWL value decreased from 20.3 to 8.6 (p less than 0.0011) over 7 days, but there were no significant differences between the individual moisturizers. The laser-Doppler values showed the same trend as the TEWL values. In conclusion, regular use of emollients prevented irritant dermatitis from a detergent.

Adult↗

PubMed1991

Antibacterial and antifungal properties of propylene glycol, hexylene glycol, and 1,3-butylene glycol in vitro.

The antimicrobial properties of three glycols, - propylene glycol, hexylene glycol, and 1,3-butylene glycol - against Candida albicans, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes A, Streptococcus mitis, and E. coli were studied in vitro. Within 20 h, 10% and 30% hexylene glycol in fresh tryptic soy broth were able to kill all the micro-organisms listed above. Five percent hexylene glycol showed some antimicrobial properties but the 1% agent had no effect. Thirty percent 1,3-butylene glycol and 30% propylene glycol were approximately as effective as 10% HG. The results speak in favour of using hexylene glycol in cosmetic and dermatological vehicles instead of propylene glycol and 1,3-butylene glycol.

Anti-Bacterial Agents↗

PubMed1991

Collagen biosynthesis in lichen sclerosus et atrophicus studied by biochemical and in situ hybridization techniques.

Collagen was studied by biochemical and immunohistochemical techniques and by in situ hybridization in four patients with lichen sclerosus et atrophicus (LSA). The solubility of collagen in acetic acid and pepsin was increased in the lesional skin of the LSA patients when compared with their non-affected skin or samples from control subjects, indicating that a marked proportion of the collagen was newly synthesized. Collagen synthesis was slightly increased in fibroblasts derived from the lesional skin of the LSA patients. In situ hybridization with human sequence-specific cDNAs to type I procollagen demonstrated active fibroblasts in lesional skin of LSA patients, further confirming a high level of collagen synthesis in LSA. Remarkably, active fibroblasts were not associated with inflammatory cell infiltrates noted in LSA skin nor did they express transforming growth factor beta(TGF beta 1). Our results indicate that despite the degeneration of connective tissue, there is an active regeneration process in LSA with significant collagen synthesis.

Aged↗

PubMed1989

Skin reactions to hexylene glycol.

Hexylene glycol (HG), which has been used for years in industrial chemicals and cosmetics, has recently been introduced in topical corticosteroids. We studied the irritant and sensitizing properties of HG in eczema patients. HG at 50% or 30% and propylene glycol (PG) at 30% in water were patch tested in 823 eczema patients subjected to routine patch testing. Oedema and erythema reactions from HG occurred in 2.8% of the patients. The corresponding result for PG was 3.8%. 50% HG equalled 30% PG in producing a visible reaction. In patch tests with dilution series, 2 patients reacted to 1% HG, but in both cases ROAT with HG remained negative. One other patient with a 3+ patch test reaction to both 30% PG and 50% HG had a positive ROAT result to 30% HG in water and to 5% PG in a cream base. PG, but not HG, increased transepidermal water loss both in atopic normal-looking skin and among healthy controls. The present results suggest that HG is less irritating that PG under occlusion, but that delayed contact allergic reactions may occur.

Adult↗

PubMed1989

Biochemical and immunohistochemical comparison of collagen in granuloma annulare and skin sarcoidosis.

Collagen was studied by biochemical and immunohistochemical means in 5 patients with granuloma annulare (GA) and 3 with cutaneous sarcoidosis (SA). The solubility of collagen from the lesional skin in acetic acid was higher than that of collagen from unaffected skin from both patients and control subjects. Collagen concentration in the skin lesions, measured in terms of hydroxyproline content, was reduced in 3 patients with granuloma annulare and one with sarcoidosis, but the ratio of type III/I collagen was unchanged vis-à-vis non-affected skin. The collagen concentration in non-affected skin of both GA and SA-patients was also lower than in controls. The most typical immunohistochemical finding was the association of type III procollagen and fibronectin with granulomas in the lesional skin of both GA and SA cases. The activity of prolyl hydroxylase, a key enzyme in collagen biosynthesis, was markedly increased in the lesional skin, indicating that collagen synthesis in vivo was also increased. Surprisingly, collagen synthesis was not increased in cell culture studies. This could be due to cell selection as observed previously in scleroderma. Another possibility could be that various mediators released in vivo from inflammatory cells activate fibroblasts. However, when cells are subcultivated, this effect is not maintained. In conclusion, marked changes in collagen could be observed in granuloma annulare and skin sarcoidosis, reflecting increased turnover of collagen in vivo.

Adult↗