Early development of synchrony in cortical activations in the human.

Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates.

Service screening mammography reduces breast cancer mortality among elderly women in Turku.

OBJECTIVES: The aim of this study was to assess the effects of service screening mammography on breast carcinoma incidence and refined mortality among women aged 55-69 at entry in three cities employing different screening policies. METHODS: Since 1987, the city of Turku, Finland, has provided service screening mammography for women aged 55-69 at entry (in 1987), and Tampere provided screening for women aged 55-59 at entry, whereas Helsinki did not screen any of these age groups. The incidence of breast carcinoma during the screening period 1987-97 in women born in 1918-32 (1918-22, 1923-27, 1928-32) was compared with incidence during the pre-screening period 1976-86 in women born in 1907-21 (1907-11, 1912-16, 1917-21) in each city. The follow-up for mortality was four years longer. RESULTS: Breast carcinoma incidence was 31-38% higher in the screening period in all three cities irrespective of screening. In breast carcinoma mortality, no significant changes were seen in Helsinki or Tampere. In Turku, a 36% mortality reduction (relative risk [RR] 0.64; 95% confidence interval [CI] 0.47-0.88; P=0.007) in the whole study population and a 47% reduction in women aged 65-69 at entry (RR 0.53; 95% CI 0.28-0.99; P=0.047) were seen. CONCLUSIONS: The incidence of breast carcinoma increased in all study cities irrespective of screening. The comprehensive screening programme in Turku including women aged 55-69 at entry was associated with a significant reduction in breast carcinoma mortality. The pronounced decrease in mortality in the oldest age group (65-69 years at entry) also indicated that women of this age group greatly benefit from mammography screening.

Empty nests in the great tit (Parus major) and the pied flycatcher (Ficedula hypoleuca) in a polluted area.

Great tits (Parus major) are sometimes found to incubate in their nests even though the nests contain no eggs. This phenomenon has been observed in different parts of Europe (Sweden, Finland, UK, Netherlands, Germany) and it has become more common during the 1980s. We analysed the occurrence of empty nests in P. major and in pied flycatcher (Ficedula hypoleuca) in SW Finland from 6-year data collected in a polluted area around a copper smelter which emits large quantities of sulphuric oxides and heavy metals. Among first broods 3.3% of P. major females incubated in empty nests. Incubation on empty nests was not observed in F. hypoleuca, but in this species 2.4% of the nests remained without eggs. In both species empty nests were more common close to the pollution source than farther away. Histopathological analyses in P. major suggest that there are diverse reasons for the incapability of a female to lay. One out of five P. major females captured from incubating in an empty nest had dark cysts in her oviduct. Two P. major females had very scanty medullary bone tissue in their tibiotarsus and tarsometatarsus and one female showed exceptionally high concentrations of lead in her bone tissue. We conclude that air pollutants enhance the number of empty nests especially in F. hypoleuca, but cannot wholly explain the phenomenon in P. major.

Mammography screening interval and the frequency of interval cancers in a population-based screening.

In a population-based mammography screening, 129,731 examinations were carried out among 36,000 women aged 40-74 in the city of Turku, Finland, in the period 1987-94. Women older than 50 were screened at 2-year intervals, and those younger than 50 at either 1-year or 3-year intervals, depending on their year of birth. Screen-detected breast cancers numbered 385 and, during the same time period, 154 women were diagnosed with breast cancer outside screening in the same age group in the same city, and 100 interval cancers were detected. Two hundred and fifty (67%) of the screen-detected cancers were of post-surgical stage I compared with 45 (45%) of the interval cancers and 52 (34%) of the cancers found outside screening (P<0.0001). However, among women aged 40-49 the frequency of stage I cancers did not differ significantly among screen-detected cancers, interval cancers and cancers found outside screening (50%, 42% and 44% respectively; P=0.73). Invasive interval cancers were more frequent among women aged 40-49 if screening was done at either 1-year (27%) or 3-year intervals (39%) than in older women screened at 2-year intervals (18%; P=0.08 and P=0.0009 respectively). Even if adjusted for the primary tumour size, screen-detected cancers had smaller S-phase fractions than interval cancers or control cancers (P=0.01), but no difference in the S-phase fraction size was found between cancers of women younger than 50 and those older than this (P=0.13). We conclude that more interval cancers were found among women younger than 50 than among those older than 50 and that this could not be explained by the rate of cancer cell proliferation.

Immunolocalization of cystatin A in condylomatous and dysplastic lesions of the human uterine cervix: correlation with the presence and type of human papillomavirus infection.

Cystatin A is the major cysteine proteinase inhibitor in human squamous epithelia. We investigated the occurrence of cystatin A in normal, condylomatous, and dysplastic lesions of the cervix with or without human papillomavirus (HPV) infection. Cystatin A was detected by immunohistochemistry and HPV infection by DNA hybridization techniques. In the normal uterine cervix, cystatin A was seen throughout the epithelium, except in the basal and parabasal cell layers. In condylomatous lesions, the staining intensity was similar to that in normal epithelium. In low-grade cervical intraepithelial neoplasias (CINs), reduced staining was seen in the lower third of the epithelium; in high-grade CINs, a reduction in staining intensity was also seen in the middle and upper thirds. Cystatin A staining in epithelia and nuclei was negative in highly cellular and poorly differentiated CIN III. The cytoplasmic staining of cystatin A did not correlate with presence or type of HPV DNA. In the high-grade CINs infected with HPV types 16 and 18, however, cystatin A staining was more often confined to the nuclear compartment.

Ultrasound propagation speed in arthritic synovial tissue.

Ultrasonic properties of knee synovial tissues destroyed by arthritis were studied by analysing 40 tissue specimens from 21 patients using an ultrasound echo meter and an optical microscope. The idea was to compare pathological findings to ultrasound propagation speeds, and to try to find any relation between them. The fresh specimens were first measured by the echo meter to collect data for statistical calculations of the propagation speed vs. different pathological properties. Before pathological studies, the specimens were fixed in formalin solution. The connective and fat tissues were evaluated within a resolution of 5% and expressed in percentages (0-100%). Inflammatory cells, edema and villus formation were also evaluated. As results, we obtained several charts of ultrasound propagation speed and their trends in the function of different properties. It could be seen that the trend of the propagation speed increased from 1515 m/s to 1565 m/s when the percentage amount of connective tissue increased from 30% to 90%. The trend of the speed decreased from 1560 m/s to 1480 m/s when the share of fat tissue increased from 0 to 60%. The same phenomenon is already well known from some other tissues. A special new result was that the speed varied in a remarkable range of 1490-1660 m/s in samples of 0% fat and high connective tissue content. The overall average of the ultrasound propagation speed in the specimens was 1548 m/s, and the average of the standard deviations of measurements (each specimen was measured at least twice) of each tissue specimen was 8.3 m/s.

Segmental mediolytic arteritis--electronmicroscopic and immunohistochemical study.

We examined specimens of human gastroepiploic artery aneurysm from a patient having several visceral aneurysms using electronmicroscopic and immunohistochemical techniques. The histopathological and ultrastructural findings confirmed the diagnosis of segmental mediolytic arteritis. Arterial smooth muscle cells from the gastroepiploic artery contained cytoplasmic vacuoles, media was thin and the internal elastic membrane showed distortion. X-ray microanalysis revealed calcium deposits in the medial extracellular space. Antigenic determinants of human immunoglobulins, fibrinogen, complement C3a and factor VIII were demonstrated in the injured artery wall, suggesting that immunocomplexes deposited in the artery wall may be associated with local injury. These findings support the role of autoimmune disorders in the pathogenesis of segmental mediolytic arteritis.

Aggressiveness of breast cancers found with and without screening.

OBJECTIVE: To examine how breast cancers found by mammographic screening differ from those found outside screening. DESIGN: Comparative cohort study. SETTING: Turku, southwestern Finland. PATIENTS: 126 women aged 40-74 years with breast cancer detected during the first round of mammographic screening in 1987-90 and 125 women within the same age range with breast cancer detected outside screening during the same period. MAIN OUTCOME MEASURES: Primary tumour size, axillary nodal status, histological features, oestrogen and progesterone receptor concentrations, ploidy, and S phase fraction. RESULTS: Compared with the controls women with cancers detected by screening had a smaller primary tumour (57 (46%) screened v 11 (10%) controls had tumours less than or equal to 11 mm in diameter, p less than 0.0001), and less often had axillary nodal metastases (104 (83%) screened v 71 (57%) controls node negative, p less than 0.0001). After adjustment for the smaller size of the primary tumour compared with control cancers, those cancers detected by screening were less likely to have axillary nodal metastases (odds ratio 0.44, 95% confidence interval 0.23 to 0.84), poor histological differentiation (0.20, 0.08 to 0.49), high mitotic counts (0.38, 0.15 to 0.97), tumour necrosis (0.45, 0.22 to 0.93) or to be of the ductal histological type (0.46, 0.22 to 0.95). They had low oestrogen receptor (0.29, 0.12 to 0.70) and progesterone receptor (0.35, 0.17 to 0.92) concentrations less often and had smaller S phase fractions (0.72, 0.55 to 0.96) than control cancers. CONCLUSIONS: Even after adjustment for the smaller size of screen detected breast cancers, their histological and cytometric features suggest low malignant potential. They may also be less likely to metastasise to axillary lymph nodes than cancers found outside screening.

Risk factors for screen-detected breast cancer. A case-control study.

Risk factors for breast cancer (BC) detected in mammography screening were sought using a questionnaire among 31,927 women aged from 40 to 74 years who attended screening. Data from 204 women with screen-detected BC were compared with those of 612 controls who did not have BC in screening. Mothers of women with BC had more often BC than those of the controls (8% vs. 3%, odds ratio, OR, 3.18, 95% CI 1.59-6.35). Women with screen-detected BC were older at their first childbirth (25.7 years vs. 24.7 years, OR 1.61, 1.14-2.33), and younger at menarche (13.6 years vs. 13.8 years, OR 1.38, 1.00-1.91), but there was no significant difference in the body mass index, number of pregnancies, breast size, smoking, or in the use of contraceptive pills between the cases and the controls. In multivariate logistic regression analyses, late age at the first childbirth, BC in the mother, and early age at menarche were independent risk factors for screen-detected BC but they appear to be of limited value in targeting screening in the female population aged from 40 to 74 in order to improve its cost-effectiveness.

Cystatin A and B in the development of human squamous epithelia.

The expression of cystatin A (Acid cysteine proteinase inhibitor) and B (Neutral cysteine proteinase inhibitor) during human embryogenesis was studied immunohistochemically by using the PAP-complex method. Both inhibitors were visible first in the developing mucosal tissue at the age of about 9 weeks. In the fetal epidermis (periderm), cystatin B was demonstrated at the age of 11 weeks and cystatin A at 12 weeks. In these young fetuses, the staining was visible in the basal cells, whereas in fetuses older than 17 weeks the staining of both inhibitors diminished in the basal cells. In the skin of 17 to 25 weeks old fetuses, the epidermal staining of cystatin B become weaker than that of cystatin A, and at the age of about 26 weeks, cystatin B disappeared totally. At this stage, cystatin A was localized in the cytoplasm of the middle to upper cell layers of the epidermis. In the squamous epithelia of the mucosal tissues, the staining of the both inhibitors reached their maximal intensity when the fetuses were about 16 weeks old. At the mature fetuses, infants as well as adults, both cystatin A and B seemed to be present in wet squamous epithelia while in the epidermis only cystatin A was expressed.

Campylobacter-like organisms and gastritis: histopathology, bile reflux, and gastric fluid composition.

We studied a prospective series of 107 randomly chosen dyspepsia patients without gastric ulcer for the association of spiral Campylobacter-like organisms (CLO) with features of antral and fundal gastritis and duodenogastric reflux. CLO were observed in 38% of the patients. The scores for all classes of inflammatory cells in both antral and body mucosa were significantly higher in the CLO-positive patients than in the CLO-negative ones (p less than 0.001), and foveolar hyperplasia was also associated with CLO (p less than 0.05). Metaplasia and glandular atrophy in the antral mucosa were significantly commoner in the CLO-positive group (p less than 0.05 and p less than 0.01, respectively). The body gastritis score correlated significantly with age in the CLO-negative patients (R = 0.33, p less than 0.01) but not in the CLO-positive ones. There were no significant differences between the groups with regard to duodenogastric reflux or intragastric pH. The results confirm that CLO are associated with gastritis, most notably superficial gastritis in the body and atrophic gastritis in the antrum, but their aetiological significance remains to be proved.

Gastric carcinoids with minimal or no macroscopic lesion in patients with pernicious anemia.

In a series of 44 patients with pernicious anemia examined by gastroscopy, three cases of gastric carcinoids were found. During the same ten-year period about 11,000 gastroscopies were performed on patients not suffering from pernicious anemia, and only one case of gastric carcinoid was detected. In two of the cases no endoscopic lesion was seen and the carcinoid was detectable only at histological examination, while in one case an unusual combination of carcinoid tumor and tubular adenoma in the same polyp was found. Most of the carcinoids arose in atrophic body mucosa, but in one case the mucosa around the carcinoid showed antral properties. One patient had slightly elevated values of pancreatic polypeptide, while no hormonal activity was found in others. No growth or spread of the carcinoid was observed during follow-up. It is suggested that the same pathogenetic factors may operate in the genesis of gastric carcinoid and gastric carcinoma in patients with pernicious anemia.

Immunohistochemical localization of epidermal basement membrane laminin and type IV collagen in bullous lesions of dermatitis herpetiformis.

Antibodies against the human basement membrane proteins, laminin and the 7-S domain of type IV collagen, were used to study the epidermal basement membrane in lesional skin from four patients with dermatitis herpetiformis. The staining pattern of both antigens was mostly fragmented and sometimes absent on papillary microabscesses, but when present it was attached to the epidermal basal cells. On papillary microblisters and larger blisters the staining of both antigens showed discontinuities and was located in the floor of the blister, except for two cases where tiny fragments of laminin staining were also seen in the roof of larger blisters. These results suggest that blister formation in dermatitis herpetiformis takes place between the epidermal basal cells and the basement membrane.

[Behavior of small molecular cysteine proteinase inhibitors in lung cancers and surrounding tissue]. / Das Verhalten der kleinmolekularen Cysteinproteinase-Inhibitoren in Lungencarcinomen und den sie umgebenden Geweben.

In this work, we have studied the occurrence of acid and neutral cysteine proteinase inhibitors in 3 histologically different lung cancers. The acid cysteine proteinase inhibitor ( ACPI ) seems to be associated to squamous differentiation as our previous observations have shown. As a new observation we could show that the neutral cysteine proteinase inhibitor ( NCPI ) was localized in alveolar macrophages.

Occurrence of acid and neutral cysteine proteinase inhibitors in epidermal malignancies: immunohistochemical study.

Acid cysteine proteinase inhibitor ( ACPI ) and neutral cysteine proteinase inhibitor ( NCPI ) were localized in human epidermal malignancies by the unlabelled peroxidase-antiperoxidase complex method. Basaliomas did not contain ACPI or NCPI . In spinous, metatypic , and clear cell carcinomas of the epidermis, both inhibitors were located in the cytoplasm and sometimes on the cell membranes of the differentiated carcinoma cells. The inhibitors were not seen in the 1 or 2 most "basal" cells layers of the carcinoma islets. The locations of both inhibitors were similar, and the staining for ACPI was usually more intense than staining that NCPI .

Acid and neutral cysteine proteinase inhibitor in normal uterine portio and in squamo-epithelial metaplasia, dysplasias and infiltrative carcinoma of the uterine portio.

Acid cysteine proteinase inhibitor (ACPI) and neutral cysteine proteinase inhibitor (NCPI) were localized in formalin-fixed normal human uterine portio as well as in the squamous cell carcinoma and dysplasias of the uterine portio. The peroxidase-antiperoxidase technique was used. In the squamous epithelium of normal uterine portio, ACPI and NCPI were localized in the cells of the upper and middle layers, mainly in the cytoplasm. In the precursors of cancer, immunoreactivity for ACPI and NCPI declined, and neither of the inhibitors was demonstrable immunohistochemically in the anaplastic squamo-epithelial carcinoma of the uterine portio. Our results suggest that ACPI and NCPI are associated with squamo-epithelial differentiation and that they may also be of significance for the regulation of cysteine proteinase activity in normal tissue and malignant growth.