Distribution of placental protein 14 in tissues and body fluids during pregnancy

Summary. Placental protein 14 (PP14) levels were measured in serum samples from non-pregnant and pregnant women. amniotic fluid, cord blood, and extracts of placenta, decidua and fetal membranes. The levels were low (15–40 μg/ l ) in serum of non-pregnant women. In four pregnancies following in-vitro fertilization, the serum PP14 levels started to rise 2–12 days after embryo replacement. In normal pregnancy, the highest serum PP14 concentrations (up to 2200 μg/l) were detected between 6 and 12 weeks. After 16 weeks the level decreased and plateaued at 24 weeks to around 200 μg/l. In amniotic fluid, the highest PP14 levels (232 mg/l) were found between 12 and 20 weeks, being considerably higher than those in maternal serum throughout pregnancy. In cord blood, the levels were low (15–22 μg/l) or undetectable. In early pregnancy decidua. the PP14 content was higher (41–160 mg/g total protein) than in late pregnancy decidua (60–2700 μg/g total protein). In amnion and chorion laeve, the PP14 concentration varied from 50 to 750 and 50 to 1000 μg/g protein, respectively. Early pregnancy placenta contained 0-25-15 mg/g and late pregnancy placenta 3–430 μg/g protein of PP14. These results show that the levels of PP14 in pregnancy serum have a similar profile to hCG, but in contrast to other placental proteins, the amniotic fluid PP14 levels are remarkably high. This may be explained by suggesting that decidua is a source of PP14.     

Serum steroid sulphates in ichthyosis

Serum concentrations of pregnenolone sulphate, dehydroepiandrosterone sulphate and 5-androstene-3 beta,17 beta-diol sulphate were measured by radioimmunoassays in twelve patients with various types of ichthyosis. In X-linked ichthyosis (n = 5), ichthyosis vulgaris (n = 5) and lamellar ichthyosis (n = 1), steroid sulphates were not significantly higher than in the control subjects. In one baby with ichthyosiform erythroderma and associated deafness serum 5 -androstene-3 beta,17 beta-diol sulphate concentration was about 60 fold higher (31 microgram/ml) than the mean of the control children. The other steroid sulphate levels were normal in this baby. These results indicate that it is not possible to demonstrate the steroid sulphatase deficiency in X-linked ichthyosis by determining blood steroid sulphates. The cause of the high 5-androstene-3 beta,17 beta-diol sulphate concentration in the baby with ichthyosiform erythroderma needs further evaluation.     

New aspects of the mechanism of corticosteroid–induced dermal atrophy

Glucocorticoids are effective for the treatment of various inflammatory skin diseases, but their long-term use may lead to serious side-effects such as osteoporosis and skin atrophy. The incidence of skin atrophy following application of potent corticosteroids is especially high among children and the elderly. During recent years the effects of glucocorticoids on connective tissue have been elucidated, and it is evident that skin atrophy is mostly due to a decrease in collagen synthesis. Since collagen is the most abundant protein in the skin, the inhibition of its synthesis leads to atrophy. This review discusses the molecular mechanisms of glucocorticosteroid-induced skin atrophy and therapeutic possibilities.     

Recovery of human skin collagen synthesis after short-term topical corticosteroid treatment and comparison between young and old subjects

Summary In the present study, the recovery of the collagen synthesis rate after topical potent glucocorticoid treatment in the human skin in vivo was investigated. In the first experiment, two age groups were compared: young subjects with an age range of 21–26 years (mean 23), and old subjects, aged 55–70 years (mean 64). Twenty healthy male volunteers applied betamethasone-17-valerate to their abdominal skin for 3 days twice a day. Suction blisters were induced on the treated areas, and on the opposite side (healthy non-treated skin), of the abdominal skin on the day following the discontinuation of the treatment, and on the second and seventh day. In another experiment, suction blisters were induced after the treatment and 2 weeks later on the treated area and on healthy skin, in eight male volunteers. In both experiments, the aminoterminal propeptides of type I and III collagens (PINP and PIIINP, respectively) were measured radioimmunologically from the suction blister fluid. Corticosteroid treatment decreased the collagen synthesis in both age groups after a 3-day treatment period, and essentially no recovery in the collagen synthesis could be seen during a 1-week corticoid-free period. The inhibition and downregulation of collagen synthesis in the corticoid-treated skin was similar in both young and old subjects, up to 7 days after the treatment. During the 2-week corticoid-free period, collagen synthesis was recovered to about 50% of the level seen in the non-treated skin. Indicating that collagen synthesis is not completely normalized in the human skin even during a 2-week corticoid-free period.     

Expression of cytokeratins in regenerating human epidermis

The expression of cytokeratin polypeptides in regenerating human epidermis was immunohistochemically examined during re-epithlization 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 suitable methodology for the study of epidermal regeneration in normal skin. The technique may also advantages in the investigation of keratin expression in diseased skin.     

Demonstration of cellular retinoic acid binding protein in cultured human skin fibroblasts

Previous studies have indicated that retinoids, such as all-trans-retinoic acid and 13-cis-retinoic acid, can modulate connective tissue metabolism in human skin fibroblast cultures. Such effects could be mediated through binding of these retinoids to specific cellular binding proteins. In the present study we have demonstrated cellular retinoic acid binding protein using both whole cell and cytosol binding assays with [3H]all-trans-retinoic acid or [3H]13-cis-retinoic acid as the ligand. Specific binding of [3H]all-trans-retinoic acid could be demonstrated by both techniques and the binding could be displaced by unlabelled all-trans-retinoic acid and 13-cis-retinoic acid, but not by retinol or RO-10-9359 (etretinate) in a 100-fold excess. Gel filtration chromatography of the cytosol proteins after incubation with [3H]all-trans-retinoic acid demonstrated that the specific binding protein had an apparent molecular weight of approximately 15 000 daltons. Thus, the cellular retinoic acid binding protein demonstrated in human skin fibroblasts may mediate the effects of the retinoids on connective tissue metabolism in these cells.     

A local potent glucocorticosteroid decreases the induction of galactosylhydroxylysyl glucosyltransferase in suction blisters but has no effect on basement membrane structures

The effects of local glucocorticosteroid treatment on collagen biosynthesis and basement membrane components were studied in suction blisters in human abdominal skin. Pretreatment with clobetasol-17-propionate, applied three times a day for 4 days, did not affect the activity of galactosylhydroxylysyl glucosyltransferase (GGT) in fresh blisters but post-blistering treatment for 3 days with the steroid markedly inhibited the increase of this enzyme activity during the initial phases of re-epithelialization. The GGT activity was over 50% lower in steroid-treated blisters compared with control values. Protein concentrations and blister fluid volumes were also significantly decreased in healing 3-day blisters after steroid treatment. These results suggest that local glucocorticosteroid decreases either the synthesis of GGT or its release from the tissue into the blister fluid. The treatment did not affect the blister histology nor the early process of re-epithelialization. Immunohistochemically, type IV and V collagens and laminin of the basement membrane zone were similarly located in blisters of steroid-treated and placebo-treated skin, suggesting that local glucocorticosteroid does not affect the integrity of the basement membrane.     

Postmyocardial Infarction Patients Susceptible to Ventricular Tachycardia Show Increased T Wave Dispersion Independent of Delayed Ventricular Conduction

Arrhythmia Markers After Myocardial Infarction. Introduction: Experimentally, both delayed ventricular conduction and nonhomogeneous ventricular repolarization contribute to reentrant arrhythmias. We tested the hypothesis that increased T wave dispersion is independent of delayed ventricular conduction associated with arrhythmia vulnerability in postmyocardial infarction (post-MI) patients.
Methods and Results: We studied 32 post-MI patients with clinical or inducible monomorphic ventricular tachycardia (VT group), 28 post-MI patients without arrhythmias (MI group), and 13 healthy controls, using magnetocardiographic (MCG) mapping with signal averaging. Twelve-lead ECG was the reference. Filtered QRS duration (fQRS) and T wave peak to T wave end interval (TPE) were used as measures of ventricular conduction and nonhomogeneity in ventricular repolarization, respectively. In MCG, the VT group showed the longest fQRS (  135 ± 34  msec vs  114 ± 22  msec in the MI group;  P = 0.012  ). Mean TPE and maximum TPE in VT versus MI groups were  78 ± 9  msec versus  70 ± 6  msec (  P < 0.001  ) and  117 ± 23  msec versus  104 ± 19  msec (  P = 0.020  ), respectively. Maximum TPE did not correlate with fQRS in the VT group (  r = 0.063; P = NS  ) but did correlate in the MI group (  r = 0.396; P = 0.037  ). For identification of post-MI patients prone to VT, selection of cutoff values for fQRS > 140 msec and mean TPE > 81 msec gave sensitivity and specificity of 41% and 89%, and 31% and 96%, respectively. Their combination increased sensitivity to 63% while maintaining 89% specificity.
Conclusion: Post-MI patients susceptible to VT show increased T wave dispersion independent of delayed ventricular conduction.     

Application of machine vision to assess involved surface in patients with psoriasis

An objective method is still lacking in the quantitative assessment of psoriasis severity. The purpose of this study was to examine whether computer image analysis (CIA) by a new colour segmentation method can be used as an objective method of estimating involved surface area in patients with psoriasis. Involved surface area in psoriasis was assessed from colour photographs covering the same areas as the psoriasis area and severity index (PASI) scores of 26 patients by human observers from different medical professional groups and by CIA. The reliability of CIA was tested with reference analysis by colouring manually the involved areas in the images with the aid of projected slides. The surface area estimates by the different methods were compared with each other and the resulting effects on the PASI score were assessed. The agreement between the reference analysis and the image analysis was high, especially on trunk areas, but the cylindrical shape of the limbs resulted in some difficulties in assessing involved skin area. The human eye estimates differed from the image analysis ones in almost one-third of the cases and mostly when psoriasis affected under 30% of the skin surface area. Both over-and underestimates emerged, but overestimates were more common. Error estimates had a significant effect on the PASI score. The CIA method seems to be reliable and practicable in estimating the actual surface of psoriasis. The method has the disadvantage of being time-consuming (photographing, processing of pictures) and technically demanding. Further development of this method should make it faster in the future.