Effect of maternal tobacco smoking or exposure to second-hand smoke on the levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine of mother and the first urine of newborn.

Tobacco smoking during pregnancy is associated with a variety of negative consequences not only for the mother, but also for the developing fetus. Many studies have shown that carcinogens contained in tobacco smoke permeate across the placenta, and are found in fetus. The aim of the study was to determine the prenatal exposure to tobacco-specific carcinogenic N-nitrosamines on the basis of measurements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine of smoking and second-hand smoke (SHS) exposed women and in the first urine of their newborns. A questionnaire documenting demographics and socio-economical data, smoking habits and exposure to SHS was completed by 121 delivering women near or at term. Maternal concentrations of cotinine and NNAL were measured in urine of the mother and the first urine of her newborn infant by liquid chromatography tandem mass spectrometry (LC/MS/MS). The mean concentration of cotinine was 439.2 ng/mg creatinine and NNAL concentration in urine of smoking women was 74.0 pg/mg creatinine, and for her newborn 78.6 pg/mg creatinine. Among mothers exposed to SHS, cotinine and NNAL mean concentration were 23.1 ng/mg creatinine, and 26.4 pg/mg creatinine. In newborns of SHS exposed mothers during pregnancy the mean concentration of NNAL was 34.1 pg/mg creatinine, respectively. Active tobacco smoking as well as passive exposure to smoking during pregnancy is an important source of tobacco specific N-nitrosamines to the fetuses as evidenced by increased concentrations of this carcinogen. Determination of NNAL in maternal urine samples can be a useful biomarker of prenatal exposure of newborn to carcinogenic nitrosamines.

Assessment of relations between clinical outcome of ischemic stroke and activity of inflammatory processes in the acute phase based on examination of selected parameters.

BACKGROUND AND PURPOSES: Inflammatory factors play an important role in the pathogenesis of ischemic stroke. They may influence circulation during the acute phase of stroke and enhance the ischemic region. MATERIALS AND METHODS: We examined 51 patients--36 patients in the early stage of stroke, i.e. the first 24 h after onset. Of these, 15 patients had infection and 21 had no infection during the week preceding stroke. There were 15 patients with noninflammatory diseases in the control group. We analyzed parameters of inflammation such as: activity of serum chitotriosidase by fluorimetric assay, C-reactive proteins (CRP), number of white body cells (WBCs), IgG and fibrinogen. We also assessed the neurological stage according to the Scandinavian Stroke Scale (SSS). RESULTS: In our study, we observed a statistically significant difference (p < 0.05) in the activity of most parameters of inflammation. This difference could be seen in the levels of CRP, number of WBCs and the activity of chitotriosidase, apart from IgG and fibrinogen, between the control group and groups with versus without infection. A significantly increased level of CRP (p < 0.0005) and fibrinogen (p > 0.01) was found on the first day in the stroke group as compared to the control group. The neurological stage on day 4 after stroke, assessed according to the SSS, was significantly worse in the group of patients with infection before stroke than in stroke patients without infection (p < 0.008). CONCLUSION: These results suggest the importance of active inflammatory processes in the pathogenesis of stroke. We observed increased activity of chitotioridase, a parameter of the inflammatory process, in stroke. This study is one more proof that inflammatory processes caused by infection may influence the occurrence of stroke and worsen its outcome. It could be another step towards understanding immunological processes during the acute phase of stroke. The study may also help establish new diagnostic and therapeutic strategies and could be a useful tool for prophylaxis.

Factors predicting early stroke fatality in Poland. Preliminary report of the Polish National Stroke Registry.

Poland has one of the highest rates of death due to stroke in Europe, which, in contrast to many industrialized countries, has not changed since at least 1984. To improve this unfavorable situation, the entire approach to stroke management needs to be recognized. For this purpose, an analysis of stroke epidemiology regarding regional differences was one of the the strategic points of the Polish National Project of Stroke Prevention and Treatment. The Polish National Stroke Registry was maintained from 1 January to 31 December 2000 in 59 Neurological Department in all 16 districts of Poland. In total 11,107 patients were included: 11% with intracerebral hemorrhage, 63.4% with ischemic stroke, and 25.6% with unclassified stroke. Computed tomography (CT) was performed in 73.6% of patients. Analysis of in-hospital deaths showed great differences between the centers (from 8% to 36%). According to multifactorial analysis, not only well-known predictors of early death (decrease in consciousness at the onset of stroke, decrease in functional state prior to stroke, and severity of stroke) influence the prognosis. In centers with high risk of death, CT, especially CT on admission, was performed significantly less often (4.2% vs. 62.6%), early rehabilitation was delayed (38.3% vs. 73.4%), and secondary prevention treatment was prescribed to fewer patients (antiplatelettherapy 36.4% vs. 77.4%; antithrombotic therapy 4.9% vs. 13%).

Major histocompatibility complex class II (MHC II) expression in the normal and pathological human foetal spinal cord.

The ability of the specific immune response of organisms is determined by the possibility of synthesis, transport and presentation of the major histocompatibility complex class II (MHC II) molecules on the surface of antigen-presenting cells. MHC II molecules are responsible for the binding, transport and presentation of a foreign antigen to helper T lymphocytes. They also stimulate the multiplication of specific B lymphocytes and determine the type of antibodies produced. The expression of MHC II molecules on the cellular surface of the spinal cord in cervical, thoracic, lumbar and sacral regions was studied on 30 normal human foetuses between 11 and 22 weeks of gestation (GW) and 9 foetuses with genetic defects (Down syndrome, mucopolysaccharidosis, mucoviscidosis or Nori's syndrome) between 17 and 22 GW. The immunocytochemical presence of MHC II molecules was found in all regions of the spinal cord in both groups of foetuses, normal and pathological, during the whole interval under study. The molecules were dispersed in the grey and white matter of the spinal cord and located most frequently on the surface of cells, near the central canal and blood vessels. These cells corresponded morphologically and immunocytochemically with amoeboid and ramified microglia. No differences in MHC II expression between the spinal cord regions or between normal foetuses and those with genetic defects were noted. It seems likely that such an early occurrence of MHC II expression in the spinal cord of foetuses with normal development, as well as the absence of abnormalities in this expression in foetuses with genetic defects, may indicate the significant role of these molecules in the immunological protection of the foetus and thus ensuring normal embryogenesis.

Lewy body variant of Alzheimer's disease and Alzheimer's disease: a comparative immunohistochemical study.

Immunohistochemistry (IHC) and ultrastructural study were performed on 19 demented autopsy cases of sporadic Alzheimer's disease (AD). Semiquantitative IHC assessment of the pathological changes, according to the criteria of the Consortium to Establish a Registry of Alzheimer's Disease (CERAD) and the Consortium on Dementia with Lewy Bodies, showed morphological hallmarks of AD in 18 demented patients. It was found that 11 of these cases fulfilled criteria for "pure" AD, whereas the remaining 7 cases, with mixed findings, Lewy bodies (LBs) and Lewy-related dystrophic neurites, neuritic plaques (NP) and sometimes neurofibrillary tangles (NFT), met the criteria for Lewy body variant of Alzheimer's disease (LBV). One case with brain stem and cortical LBs but without NP and NFT was finally diagnosed as a pure form of dementia with Lewy bodies (DLB). Regional distribution and semiquantitative assessment frequency of alpha-synuclein-immunoreactive LBs, tau-immunoreactive NFT and beta-amyloid immunoreactive senile plaques, were compared between LBVand AD. Ultrastructural examination confirmed the filamental structure of cortical LBs. In conclusion, IHC study including antibody to alpha-synuclein, the sensitive marker for Lewy bodies, revealed the coexistence of brain stem and cortical LBs and pathological features of AD in a great part of dementia cases. Patients with mixed, LBs, NP and sometimes NFT pathology, fulfilled neuropathological CERAD criteria for LBV. Semiquantitative comparative IHC study, according to LBs- and NFT-scores and CERAD NP-scores showed in the LBV group a significantly lower frequency of NFT coexisting with neocortical LBs than in the group with pure form of AD.

Quantitative evaluation of intranuclear inclusions in SSPE: correlation with disease duration.

Three types of intranuclear inclusions in neurones, oligodendrocytes and astrocytes were quantitatively evaluated by electron microscopy in the autopsy material derived from six cases of subacute sclerosing panencephalitis (SSPE) with different duration of disease. Viral nucleocapsids were found in neurones and oligodendrocytes with the highest incidence (about 38% of nuclei) in two acute cases (adolescent), whereas in two subacute cases only 10% of nuclei of these cells contained nucleocapsids. However, in one acute case (child) and one chronic case, no nucleocapsids were detected at all, despite very intensive study. Two other types of intranuclear inclusions--nuclear bodies (NBs) and granulofilamentous inclusions (GFs) were present in astrocytic nuclei in all cases. Nuclear bodies were found the most frequently (about 66%) in cases of a several-week-long duration, and their incidence decreased with the extended duration of the disease. In the case of a seven-year-long duration, about 31% of nuclei contained NBs. The incidence of certain types of NBs varied also in individual groups of cases, and the same applied to the occurrence of cellular nuclei with different numbers of NBs. Nuclear bodies types IVand V occurred with similar frequency, regardless of the disease duration. The highest incidence of nucleocapsids and NBs was accompanied by the highest (about 25%) frequency of GF in astrocytic nuclei. The incidence of the latter declined with the prolonged duration of the disease, and in the chronic case it was about 16 times lower than in acute cases. In some acute and subacute cases, GF occurred together with NBs. Astrocytic nuclei with both types of inclusions occurred with a similar frequency (about 1.6-1.8%).

Neurones and microglia in central nervous system immune response to degenerative processes. Part 1: Alzheimer's disease and Lewy body variant of Alzheimer's disease. Quantitative study.

The quantitative correlation between neurone loss and brain immune response, assessed by intensity of microglia inflammatory reaction in cortical association area and limbic cortex, was investigated and compared in previously immunohistochemistry (IHC) and ultrastructural confirmed 11 cases of Alzheimer's disease (AD), 7 cases mixed form of Dementia with AD findings and Lewy bodies (AD/DLB) reported, in accordance with Consortium on Dementia, as Lewy body variant of AD (LBV) and 6 non-demented autopsy control cases from 63 to 86 years old. In the present work we investigated association and limbic cortical areas linked with memory mechanisms; there are regions characterised by early distribution of IHC confirmed AD and DLB/AD (LBV) markers, as well as a substantial physiological stability of neurone pool regardless of age. The results indicated that AD and LBV differ in their neurone loss intensity and inflammatory reaction, with much higher intensity in AD. In Alzheimer's disease, neurone loss in association temporal cortex made up 51% of control values with simultaneous 8-fold increase in the density of MHC II-positive activated microglia, whereas in LBV, both the loss of neurone density and the increase in activated microglia density, was not so high (up to 41% and 4-5-fold, respectively). Changes in the limbic cortex were less pronounced. A strong correlation in the clinical material between neurone loss and microglia activation in both processes, especially in AD (r = 0.73), speaks in favour of the hypothesis on the neuronal immune surveillance and arousal of immune brain response in conditions of declining control, due to significant neurone loss in the neurodegenerative process. The inflammatory reaction of MHC II-immunoreactive microglia, concomitant with neurodegenerative process, seems to be a consequence of increased immune response due to loss of neurones and weakening of their control upon immunosurveillance in central nervous system.

Ultrastructural changes in neuronal and glial cells in subacute sclerosing panencephalitis: correlation with disease duration.

This paper presents ultrastructural changes in neuronal and glial cells with special reference to intranuclear inclusion bodies in subacute sclerosing panencephalitis (SSPE) with different duration (from several weeks to seven years). Brain autopsy at ultrastructural level revealed the nucleocapsids of paramyxovirus in neuronal and oligodendroglial nuclei in 4 of 6 SSPE cases under study. Nucleocapsids of measles virus were present in two cases of disease lasting several weeks and in two cases with disease duration of two years, while abundant nuclear bodies and granulofilamentous inclusions in astrocytic nuclei were found in all cases. Occasionally, both granulofilamentous inclusions and complex nuclear bodies occurred in the same astrocytic nucleus. Only in the case lasting seven years they were not observed. It is likely that there is a structural and morphological relationship between these two types of inclusions present in astrocytic nuclei. Nuclear bodies and granulofilamentous inclusions were common and independent of the presence or absence of virus nucleocapsids. In the case of SSPE with a seven-year duration but without viral nucleocapsids in neuronal and oligodendroglial nuclei, neuronal tangles were observed.

Major histocompatibility complex class II expression in the frontal and temporal lobes in the human fetus during development.

Antigen-presenting cells (APCs) that show the expression of major histocompatibility complex (MHC) class II molecules in adult persons are related to an early phase of immunological response. These molecules are responsible for the binding, transport, and presentation of a foreign antigen to helper T lymphocytes and determine the type of antibodies produced. They also stimulate the multiplication of specific B lymphocytes and participate in the elimination of autoreactive lymphocytes and maturation of T lymphocytes. Cells with MHC II molecules expressed on their surface were observed in the frontal and temporal lobes of 30 brains of human fetuses with normal development between gestation weeks (GW) 11 and 22. MHC II expression was noted during the whole interval under study. Its immunocytochemical localization was noted on the surface of the cerebral meninges cells, in the choroid plexus of the lateral ventricle and blood vessel lumen, and in ameboid microglia (AM) and ramified microglia (RM) cells in both cerebral lobes of the human fetus. The expression of MHC II that occurred on the cells of the central nervous system (CNS) already in GW 11 may be evidence not only of an early capability of immunological protection of the fetal nervous system, but also of a significant role potentially played by this system in normal embryogenesis. Despite continuous controversy over the cellular lineage of microglia origin, the expression of MHC II on AM and RM cells indicates its mesodermal origin, as in other APCs.

Major histocompatibility complex class II (MHC II) expression during the development of human fetal cerebral occipital lobe, cerebellum, and hematopoietic organs.

In adults, under physiological conditions proteins of the major histocompatibility complex, class II (MHC II) molecules are synthesized and then presented on the surface of the cells known under a common name as antigen presenting cells (APCs). Dendritic cells (DCs), microglia, macrophages, ameboid microglia and lymphocytes B are qualified as APCs. The aim of present study was to evaluate the expression of MHC II molecules in the central nervous system (CNS) and hematopoietic organs during the fetal development. Observations were made on the cerebral occipital lobe, cerebellum, thymus, spleen and liver of 30 normal human fetuses, between 11 and 22 week of gestation (GW). Histological, histochemical and immunohistochemical techniques were used to identify cells with expression of MHC II molecules. In the brain, MHC II molecules were detected on macrophages/ameboid microglia in meninges, choroid plexus and single cells of ramified microglia in deeper layers of the cortex and white matter. In the other organs besides macrophages and dendritic cells, MHC II molecules were also immunopositive in thymic epithelial cells, and in the spleen and liver also in other cells of stroma and lobule. The expression of MHC II molecules on so extensive population of cells, at an early stage of the fetal development, may evidence their significant involvement in histogenesis and morphogenesis. It seems that in adults the complex of MHC II with protein is originated from the foreign antigen. On the contrary, during normal fetal development the complex of MHC II with protein origins most probably from the fetus own structures.

Ischemic strokes are more severe in Poland than in the United States.

Case fatality rates for stroke were ascertained prospectively in two regional catchment hospitals in Poland and 36 teaching hospitals in the US University Hospital Consortium. Case fatality rates in Poland (23.9%) were higher than in the United States (7.5%). Angina, atrial fibrillation, and congestive heart failure were more frequent in Polish stroke patients (40%, 26%, and 25%, respectively) than in US patients (17%, 12%, and 10%). Stroke severity as indicated by higher frequencies of hemiplegia, disordered consciousness, dysphagia, and aphasia was greater in Poland (19%, 39%, 28%, and 42%, respectively) than the United States (11%, 13%, 14%, and 26%).

[A sporadic case of Creutzfeldt-Jakob disease with peculiar neuropathological lesions]. / Sporadyczny przypadek choroby Creutzfeldta-Jakoba o szczególnym obrazie neuropatologicznym.

The authors report a case of Creutzfeldt-Jakob disease in a man aged 60 years from a family without a history of similar disease. The disease extended over 11 months. In the clinical picture initially equilibrium disturbances and dementia with psychotic symptoms predominated, EEG pattern was not typical of CJD. Neuropathological examination revealed extensive spongiform lesions in the cortex of all cerebral lobes, in striatum and substantia nigra, moreover a considerable number of kuru plaques was found in cerebellar cortex. The authors consider that the case meets the criteria accepted for the sporadic form of CJD but believe that the final differentiation from the Gerstmann-Streussler-Scheinker syndrome should be based on genetic studies.

Dysembryoplastic neuroepithelial tumor. A case report.

Dysembryoplastic neuroepithelial tumor (DNT) is a rare, benign tumor encountered in the cortex. It is characterized by the presence of cells of different histogenesis. Due to its mixed nature (glial-neuronal), WHO histological classification of brain tumors included it into the group of neuronal and glial-neuronal mixed tumors. Case of tumor in a 19-year-old woman experiencing for three years seizure of temporal lobe epilepsy is presented. A cranial magnetic resonance imaging (MRI) showed "pseudocystic" tumor in temporal lobe. Histological and immunocytochemical examinations of the tumor fragment removed during surgery revealed large numbers of neuronalglial nodules occurring in the cerebral cortex. Columns of glial-neuronal structures crossing parallely to the cortex surface, surrounded by oligodendrocyte-like cells (OLC) were a characteristic feature of the tumor texture. In the tumor interstitium, "floating" maturated, dysplastic-free ganglionic cells were visible in numerous bright spaces. In addition, numerous lobuliform--structured areas consisted of oligodendrocyte-like cells. Oligodendrocyte-like cells were characterized by positive immunoreaction to the presence of S-100 protein and synaptophysin. Basing on clinical manifestation and histopathological findings dysembryoplastic neuroepithelial tumor was diagnosed.

Anticardiolipin antibodies are an independent risk factor for ischemic stroke.

Our aim was to determine if anticardiolipin antibodies are an independent risk factor for ischemic stroke and to determine their influence on stroke type and clinical outcome. We prospectively studied 194 consecutive patients with ischemic stroke admitted within 48 h of stroke. A control group consisted of 100, age and sex matched, healthy individuals. Neurological and functional status was assessed on admission, at 30 days, and at 1 year. IgG anticardiolipin antibodies were significantly more frequent in stroke patients (25.3%) than controls (6%, p < 0.05). A multivariate analysis suggested that anticardiolipin antibodies are an independent risk factor for ischemic stroke in addition to hypertension and atrial fibrillation (RR = 2.94, p < 0.05). Elevated IgG anticardiolipin antibodies were associated with cognitive impairment as measured by the Mini Mental State Examination at 30 days and at 1 year. IgG anticardiolipin antibodies did not correlate with stroke recurrence, or mortality at 30 days or 1 year.

Ultrastructural changes in substantia nigra and striatum observed on a mouse model of Parkinson's disease induced by MPTP administration.

The study was carried out on a mouse model of Parkinson's disease induced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-neurotoxin which damages dopaminergic neurons in substantia nigra. Occurrence of dark degenerated neurons was the most prominent ultrastructural change. They were characterized by the progressive condensation of cytoplasm and nuclear chromatin as well as by the light mitochondria and dilated cisternae of Golgi apparatus. Dark degenerated neurons were found particularly often on the 7th day after toxication, however on the last day of the observation, only a few neurons showed the features of dark degeneration. It is likely that degenerative changes led to death in the part of neurons only.

Microglia and neuritic plaques in familial Alzheimer's disease induced by a new mutation of presenilin-1 gene. An ultrastructural study.

The results of the ultrastructural study of the brains of two sisters with familial Alzheimer's disease (AD) induced by a new mutation of presenilin-1 (PS-1) gene who died at the young age (35 and 37 years) are presented. In both cases, the changes typical of AD with particularly large number of neuritic plaques (NPs) were found. Microglial cells were located between amyloid core and neurites. At the ultrastructural level, the content of microglial cytoplasm was differentiated (amyloid fibrils or/and phagocytic bodies). This may suggest that microglial cells participate in forming of amyloid fibrils and/or phagocytosis of amyloid.

Border zone neovascularization in cerebral ischemic infarct.

Immunocytochemical and quantitative studies on vascular reaction (angiogenesis) in cortical border zone of infarct were undertaken. Intensity and temporal profile of angiogenesis was assessed in 60 patients aged between 48 and 69 (younger group), and between 70 and 92 (older group), with cerebral infarct in the area of middle cerebral artery vascularization, who died during the first six weeks following the stroke. We have found that angiogenesis was a multistage process in which four stages were distinguished: phase of primary activation of endothelial cells, two consecutive phases of active angiogenesis and final phase of only sporadic proliferation of vessels. The distinction of phases in a multiphase angiogenic cascade helped us to evaluate the correlation with survival time and the age of patients. The most pronounced intensification of angiogenesis and increased density of CD 31 positive capillaries in penumbra were observed in the second phase, especially in younger patients. The duration of the penumbral neovascularization decreased in the older age patient. Our results indicate that sprouting angiogenesis is a quantitatively significant source of vessels in the cerebral infarct border zone. However, non-therapeutically stimulated angiogenesis developed only 3-4 days after the stroke, that is beyond the period of reversible changes in ischemic penumbra recognized as a "therapeutical window" in the human brain. The angiogenic therapy opens a new way towards the revascularization of ischemic brain infarct.

The comparison of microglia maturation in different structures of the human nervous system.

The aim of the study was to find out whether differences in morphology and time-sequence of microglia appearance in course of development of the phylogenetically different structures of the central nervous system (CNS) in normal human fetus do exist. An attempt was also made to evaluate quantitatively the development of microglial cells in comparison to astroglia, taking into account their role in the structural and immunological maturation of the CNS. The study was performed on CNS tissue of frontal lobes, mesencephalon and cerebellum from 72 fetuses between 8 and 22 week of gestation (GW). Histochemical and immunohistochemical reactions were used as basic study methods. A quantitative evaluation of developing microglia and astroglia in all investigated structures was performed by counting the mean number of cells per 1 mm2. Morphological and ultrastructural patterns of the three basic types of microglia; ameboid, ramified active and ramified resting, were characterized. It was indicated that they emerge at the same time in all structures under study, except the ameboid microglia arising earlier in the mesencephalon. A quantitative evaluation revealed that the number of ameboid microglial cells decreased slightly in an early stage of fetal development. The number of ramified microglial cells between 11 and 22 GW increased in all structures. The highest values of ramified microglia were found in mesencephalon, and the lowest in white matter of cerebellum. The number of astroglial cells exceeded the increase in ramified microglia by several times in all structures.

[Carotid artery disease in patients with ischemic stroke. Results of year-long observation conducted within the framework of prospective epidemiological studies, Warsaw, 1991-1992]. / Zwezenie tetnicy szyjnej wewnetrznej u chorych z niedokrwiennym udarem mózgu. Wyniki rocznej obserwacji prowadzonej w ramach prospektywnych badan epidemiologicznych, Warszawa 1991-1992.

A cohort of 297 patients with ischaemic stroke were followed for one year. Doppler ultrasonography, done in 219 patients (109 women and 110 men), aged 68.0 +/- 12.6, revealed a concomitant carotid artery occlusive disease (CAD) in 76 patients (34.7%), 34 women and 42 men, aged 66.5 +/- 11.1, 45 of them had high grade stenosis (> 75%) or occlusion. Claudication, myocardial infarction and hypercholesterolaemia diagnosed before the onset of stroke was found more often in patients with CAD, 11.1%, 22.2% and 4.4% was versus 2.8%, 12.3% and 1.4% in patients without CAD. Prevalence of other stroke risk factors, hypertension, diabetes, angina in both groups of patients was similar. Severe stenosis or occlusion was diagnosed more often among men (58%) and among smokers (55%), in the group of patients without CAD than 48% and 42% respectively. The onset of stroke was preceded more often by TIA--24% in group with CAD, versus 17% in patients without CAD. Neurological state on admission, test by Stroke Severity Scale and Weakness Score according to SDB, was similar in both groups of patients but prognosis was worst among patients with CAD, 13.5% of them developed recurrent stroke versus 7% in group without CAD. In Kaplan-Meier analysis one year cumulative survival rates were lower in the group of the patients with severe stenosis or occlusion.