Expression of intermediate filament proteins in the inner ear of the dancer mouse mutant

The expression of intermediate filaments (using well defined monoclonal antibodies to detect neurofilaments, vimentin, and cytokeratins nos. 8 and 18) was analysed in the inner ear of the dancer mouse mutant (with a morphogenetic type of inner ear defect) and compared with that in the normal CBA/CBA mouse. A similar pattern of immunoreactivity was found in the two mouse strains.     

The impact of education and occupation on the employment status of cancer survivors

We explored the effect of a diagnosis of cancer on employment according to cancer type, education, occupation, age, gender, mother tongue (Swedish or Finnish), calendar time and hospital district. All 12,542 new cancer cases diagnosed in 1987-1988 and 1992-1993, aged 15-60 years at the time of the diagnosis were identified from the Finnish Cancer Registry. The employment rate of the cancer survivors 2-3 years after the diagnosis was only 9% lower than their gender- and age-matched referents. However, we found that education and occupation modified the effect of cancer on the employment; the difference between cancer survivors and their referents in the probability of being employed was greater in the lower than in the higher educational groups. A modifying effect of education on the probability of employment was found among people with cancer of the lung, stomach, rectum and cervix uteri and those with cancers of the nervous system.     

Timing and effect of fissure sealants on permanent molars: a study in Finland and Sweden

Fissure sealants are frequently used in the Nordic countries for the prevention of caries in children. The aim here was to analyse their use and effect on dental health in children and adolescents in Finland and Sweden. A retrospective longitudinal population-based study was performed in northern Finland and Sweden, where different strategies have been adopted for sealing teeth. The timing of sealant and restoration placements up to 18 years was studied in representative samples of subjects born in the early 1980s in Kemi, Oulu, Raahe and Tornio in Finland (n = 908) and compared with a random sample of subjects from Norrbotten, Sweden (n = 634). A sensitive survival analysis method was applied to all the permanent molars separately (Virtanen et al. 1996). About 80-90% of molars had been sealed in the Finnish subjects, and approximately 30% in the Swedish cases, employing selective criteria. The filling increments were statistically significantly higher in Sweden than in Finland, although the differences were not of the same magnitude as the reduction in sealants. More than 30% of first molars and 50% of second molars had not been treated, i.e. were without sealants or fillings, by the end of the follow-up in Sweden, compared with 10% and 20%, respectively, in Finland. Fissure sealants were effective in preventing caries in molars in children and adolescents, and the use of selective criteria for targeting this treatment can yield savings in effort and costs in a low caries situation, although more research is needed to find the optimum cost-effective strategy.     

State of vigilance,oestrogen replacement therapy,and lipid profile as modifiers of nocturnal movement-induced heart rate responses

Study objectives: To investigate the body movement‐associated heart rate responses during sleep in postmenopausal women and to evaluate the possible effect of transdermal oestrogen replacement therapy and metabolic factors on these responses. Design: A prospective double‐blind cross‐over placebo‐controlled trial. Setting: A university sleep research unit. Patients: Seventy‐one healthy postmenopausal women. Methods: The subjects underwent a whole‐night polysomnography including an electrocardiogram (ECG) and a sensitive whole‐body movement sensor channel. Body movements of 2–15 s duration with an artefact‐free ECG were identified and heart rate was automatically analysed for 30 s before and 60 s after movement. The movement‐induced reflex tachycardia and the following rebound bradycardia were measured for the awake state, non‐rapid eye movement (REM) sleep and REM sleep. Indices of the heart rate response correlated with age, body mass index (BMI) and high‐density lipoprotein (HDL)/low‐density lipoprotein (LDL) cholesterol ratio. Results: The tachycardia response to a body movement was stronger during sleep than in the awake state, being strongest in REM sleep. The rebound bradycardia following a tachycardia response was relatively similar in REM and in the awake states, but attenuated in non‐REM sleep. Oestrogen did not influence the heart rate response. Increasing age and BMI attenuated the response, while an increase in the HDL/LDL cholesterol ratio enhanced the rebound bradycardia response. Conclusions: Sleep powerfully modulates the rapid cardiac autonomic responses to internal stressors. Postmenopausal hormone replacement therapy does not influence these responses, but they are strongly modulated by lipid metabolism and closely correlated with age and BMI.     

Maternal midtrimester serum AFP and free beta-hCG levels in in vitro fertilization twin pregnancies

We aimed to compare the levels of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG) levels as multiples of the median (MoM) values between spontaneous and in vitro fertilized (IVF) twin pregnancies. The control group of spontaneous singleton pregnancies was used for calculating the gestational age specific median levels of the values. Within a cohort of 19 310 pregnancies, 145 twin pregnancies were identified. The data were collected from Down syndrome (DS) screening programmes in four University catchment areas in Finland between 1994-98. Maternal midtrimester serum marker levels were measured across gestational weeks 14-18. There were no fetal chromosome anomalies in either of the twin groups or the singleton group. Serum AFP of 145 and beta-hCG values of 39 spontaneous twin pregnancies were compared to the values of 6548 singleton pregnancies. In IVF twins 30 AFP and 29 beta-hCG values were compared to the levels of the control group. Both AFP and beta-hCG values were twice as high in the spontaneous twin pregnancies (medians 2.18 and 1.83 MoM respectively) as in the singleton group (medians 1.00 and 1.00 MoM respectively). In IVF twin pregnancies beta-hCG levels were higher (median 2.20 MoM) than in spontaneous twins (p=0.08), whereas no significant difference was found in AFP levels (2.30 MoM). In conclusion, the higher levels of beta-hCG levels in IVF twin pregnancies should be considered in DS screening to avoid high false positive rates.     

Nemosis of fibroblasts is inhibited by benign HaCaT keratinocytes but promoted by malignant HaCaT cells

Cell–cell clustering of fibroblasts, called nemosis, leads to a massive growth factor, proteolytic and proinflammatory response. Culturing fibroblasts in conditioned medium collected from HaCaT keratinocyte cell panel representing different stages of skin carcinogenesis had a differential effect on fibroblast nemosis. Non-malignant keratinocytes had a nemosis-inhibiting effect on fibroblasts as seen by inhibition of COX-2 protein expression. Conditioned medium from malignant cells promoted fibroblast nemosis by inducing higher levels of COX-2, HGF/SF and VEGF. Even a small amount of malignant medium converted the inhibitory effect of benign medium, whereas non-malignant medium neutralized the nemosis-promoting effect of malignant medium. In collagen co-cultures benign keratinocytes caused a nemosis-inhibiting effect on fibroblast spheroids by inhibiting COX-2 induction, while with malignant keratinocytes myofibroblastic differentiation of fibroblasts was seen.     

Phenotypic/genotypic correlations in patients with epidermolytic hyperkeratosis and the effects of retinoid therapy on keratin expression

Dominant-negative mutations in the KRT1 and KRT10 genes cause epidermolytic hyperkeratosis, a rare form of ichthyosis sometimes associated with palmoplantar keratoderma. Although there is no permanent cure, some patients improve on retinoid therapy. More knowledge is needed, however, about the mechanism of action of retinoids and the genotypic/phenotypic correlations in this disease. Thirteen patients from 10 families with generalized disease and 2 sporadic patients with nevoid lesions were studied, probably representing most of the patients in Sweden and Norway. All patients, except one nevoid case, were known to have KRT1 or KRT10 mutations. Those with mutated keratin 1 (K1) invariably had associated keratoderma (n=6). In contrast, only 1 of 7 patients with K10 mutations had this problem (p = 0.0047). Five out of 6 patients with KRT10 mutations benefited from treatment with oral acitretin (5-25mg/day) or topical tretinoin/tazarotene, but none of the patients with KRT1 mutations derived any benefit. Quantitative analysis of K1 and K10 mRNA in skin biopsies obtained before and after retinoid therapy (n=8) showed no consistent down-regulation of mutated keratin that would explain the therapeutic outcome. Instead, the mRNA expression of K2e (a normal constituent of the upper epidermis) diminished especially in nonresponders. In contrast, K4 mRNA and protein (marker of retinoid bioactivity in normal epidermis) increased in almost all retinoid-treated patients. In conclusion, our study confirms a strong association between KRT1 mutations and palmoplantar keratoderma. Retinoid therapy is particularly effective in patients with KRT10 mutations possibly because they are less vulnerable to a down-regulation of K2e, potentially functioning as a substitute for the mutated protein in patients with KRT1 mutations.