The histone-encoding genes in Schizosaccharomyces pombe were physically mapped by hybridisation to filters containing cosmid and P1 genomic libraries. The H2A.2 gene and the H2A.1-H2B.1 gene pair mapped between the ade6 and rikI genes on chromosome III. The three H4-H3 gene pairs were mapped to three different regions by a H4.1 probe. Southern analysis of clones from each region revealed the positions of the three H4-H3 gene pairs. H4.1-H3.1 was localised to chromosome I between the mei2 and rad1 genes; H4.2-H3.2 mapped between rad3 and cdc2 on chromosome II; H4.3-H3.3 was localised to a region between the nuc1 and puc1 genes on chromosome II.

Blotting, Southern↗

PubMedDate not supplied

Dynamics of Ia-expressing cells and T lymphocytes of different subsets during experimental allergic neuritis in Lewis rats.

Inflammatory cells were characterized by immunohistochemistry, utilizing monoclonal antibodies against cell surface antigens in frozen sections of sciatic nerves and nerve roots of Lewis rats, sacrificed during the course of experimental allergic neuritis. Large numbers of Ia-expressing irregular macrophage-like/dendritic cells, as well as W 3/13 reactive T lymphocytes of both W 3/25 reactive helper and ox8 reactive suppressor/cytotoxic phenotypes were seen within afflicted peripheral nervous tissue at the start of clinical symptoms and at the height of the disease. T lymphocytes of both helper and suppressor/cytotoxic phenotypes decreased concomitant with clinical recovery. During this period demyelination was still extensive and Ia-expressing macrophage-like/dendritic cells were abundant.

Animals↗

PubMedDate not supplied

Effect of monoamine reuptake inhibiting antidepressants on major histocompatibility complex expression on macrophages in normal rats and rats with experimental allergic neuritis (EAN).

This study examined the modulation of IFN-gamma induced MHC class I and II expression on normal Lewis rats and rats with EAN peritoneal macrophages cultured in the absence or presence of 10(-4)-10(-8) M of the 5-HT reuptake inhibiting antidepressants zimeldine, and its metabolites norzimeldine and cpp200 oxalate as well as the antidepressants clomipramine and imipramine, in addition amitriptyline, nortriptyline and maprotiline in EAN rats. In normal rats, MHC class I expression was suppressed by the antidepressants zimeldine, norzimeldine and cpp200 oxalate at concentrations up to 10(-5) M. At concentrations between 10(-6) to 10(-8) M, the same drugs significantly enhanced MHC class expression. Clomipramine at 10(-8) M and imipramine at 10(-6)-10(-7) M enhanced MHC class I expression, while the MHC class II expression was not significantly influenced by concentrations < or = 10(-5) M of these two drugs. In EAN rats, MHC class I expression was enhanced by zimeldine, cpp200, imipramine, and nortriptyline at 10(-5)-10(-8) M, amitriptyline at 10(-5)-10(-7) M as well as by norzimeldine and clomipramine at 10(-6) M-10(-8) M. However, maprotiline at 10(-4)-10(-6) M suppressed class I expression in the presence of 0.5 U/ml and 1.0 U/ml of IFN-gamma. MHC class II expression was suppressed by cpp200 and clomipramine at 10(-4)-10(-5) M in presence of 0.5 U/ml of IFN-gamma. At concentrations < 10(-5) M most tested drugs significantly enhanced IFN-gamma induced MHC class II expression. Compared to the results in normal rats, drug effects on EAN macrophages were more pronounced and reached higher levels of significance. The 5-HT reuptake inhibiting antidepressants also exerted a modulatory effect on MHC class I and II in EAN rat macrophages even in the absence of IFN-gamma. The modulatory effect of antidepressant drugs on IFN-gamma induced MHC class I and II expression may contribute to their influence on demyelinating autoimmune diseases, and may have implications for their clinical use.

Amitriptyline↗

PubMedDate not supplied

Demonstration in children of oligoclonal IgG bands in unconcentrated CSF using agarose isoelectric focusing and immunolabeling.

Agarose isoelectric focusing, followed by protein transfer to cellulose nitrate membrane and double-antibody avidin-biotin peroxidase staining (avidin-biotin agarose isoelectric focusing), was used to demonstrate oligoclonal IgG bands in unconcentrated cerebrospinal fluid (CSF) and serum; 161 consecutive pediatric patients, ages 6 months to 16 years with a variety of mainly neurologic disorders, were studied. The procedure was standardized for agarose isoelectric focusing (AIF) using 5 microliter specimens containing 125 ng of IgG. Oligoclonal bands were found in the CSF of 12% of the patients; bands were found simultaneously in the CSF and serum of 10% of the patients, mostly those with nervous system infections, but also those with central nervous system tumors, seizures, or migraine. In about 50% of positive cases, oligoclonal bands constituted the only CSF abnormality, reflecting an abnormal humoral immune response within the CSF-central nervous system compartment. Avidin-biotin AIF can be recommended as an integrated part of routine CSF examinations in children.

Adolescent↗

PubMedDate not supplied

Current gene-mapping strategies in experimental models of multiple sclerosis.

Both family-based linkage analyses and population-based association studies have failed to identify disease-regulatory non-human leucocyte antigen genes of importance in multiple sclerosis (MS). Instead, investigators have employed experimental models, which offer major advantages in genetic studies. We summarize the current main methodologies used and the status of both the human and experimental approaches. Why is it important to find genes regulating MS? There is an immense number of cellular and molecular interactions defined in the immunological field and it is very difficult to unravel those that are critical to an inflammatory disease, such as MS, by classical hypothesis-driven research. Unbiased genetics defines evolutionary conserved gene polymorphisms and pathways regulated by these genes, which are central in the pathogenesis. These, in turn, are of interest as therapeutic targets and pharmacogenetic markers.

Animals↗

PubMedDate not supplied

Uptake and retrograde axonal transport of horseradish peroxidase in normal and axotomized motor neurons during postnatal development.

The axonal uptake and somatopetal transport of horseradish peroxidase (HRP) was studied during early postnatal development of facial neurons in mice and rats. HRP injected systemically or locally into the muscles of the vibrissae, diffused into the region of the immature neuromuscular junction and was incorporated into vesicles in the axon terminals on the first and third postnatal days, at a time when synaptic vesicles were already present. HRP later was found in the nerve cell bodies of the facial nucleus in the brain stem indicating a somatopetal transport of the tracer in axons. The response of facial neurons to nerve transection changed from rapid neuronal death to prolonged survival between the 6th and 10th postnatal day. HRP was transferred to nerve cell bodies after topical application to the proximal stump of transected facial nerves in rats 3 days-of-age. In the perikaryon it was localized to vesicles and vacuoles with no signs of leakage into the cytoplasm. In the light of our findings different hypotheses for the mechanism of the neuronal death in the immature animals are discussed.

Aging↗

PubMedDate not supplied

Neuronal uptake of iron: somatopetal axonal transport and fate of cationized and native ferritin, and iron-dextran after intramuscular injections.

Mice were injected into the muscles of the vibrissae with native ferritin (NF), cationized ferritin (CF) and iron-dextran. CF adsorbed on to the surface of the axon terminal at the neuromuscular junction, while NF did not. Both CF and NF were incorporated into vesicles and vacuoles at the synapse, but CF uptake was detected after injections at much lower concentrations than NF. In contrast to NF, CF was also found histochemically in cell bodies of facial neurones after a single i.m. injection, showing that the electrical charge of a molecule is one factor of importance for its potential to be incorporated in axons and transported somatopetally. Repeated i.m. injection of iron-dextran into suckling mice resulted in a marked iron load of Schwann cells and nerve cell bodies. This produced no signs of toxicity and the nerve fibre developed normally. Iron had disappeared from the nerve cell bodies after 25 days, while in Schwann cells it still persisted after 223 days.

Animals↗

PubMedDate not supplied

Clinical features and prognosis in young adults with infratentorial infarcts.

BACKGROUND AND PURPOSE: Many comprehensive descriptions of the clinical spectrum of infratentorial infarcts in elderly patients and with a retrospective design have been published. The aim of this study was to describe the clinical characteristics and prognosis in young patients with isolated infratentorial infarcts. METHODS: In a prospective series of 105 patients aged 18-44 years with cerebral infarction 24 had a brainstem or cerebellar infarction. The patient selection was validated in a population-based epidemiological survey. The patients were assessed acutely and at 4 and 12 months after onset. Extensive evaluation included CT and MRI scans, angiography, ultrasonic duplex scanning, transesophageal echocardiography and a chemistry panel including hematologic testing. The modified Rankin scale and NIH stroke scale were used for assessment of disability and neurological dysfunction. RESULTS: Eighteen patients had a cerebellar infarct (posterior inferior cerebellar artery territory in 9 patients, superior cerebellar artery in 6, anterior inferior cerebellar artery in 2, nonterritorial in 1). Two patients had lateral medullary infarcts and 2 isolated pontine infarcts. In 2 patients MRI was normal despite repeated investigations. Hearing loss and tinnitus were the only explicit symptoms for superior cerebellar artery infarcts, but it was otherwise impossible to classify each case to a vascular territory according to clinical characteristics. The age-specific incidence of isolated cerebellar infarction was 1.8/100,000/year. The presumed causes were arterial dissection in 8 patients, idiopathic in 7, cardioembolic in 5, oral contraceptive use in 3 and protein S deficiency in 1 patient. One patient died during the acute phase and another developed a locked-in syndrome. At follow-up, 1 patient had a transitory ischemic attack and 1 a silent cerebral infarction. Twenty-two patients had a favorable outcome according to the modified Rankin scale (grade 0-2) and the NIH scale. CONCLUSIONS: Cerebellar infarctions are frequent among young stroke patients in northern Sweden. Arterial dissection is the prevailing stroke mechanism in infratentorial infarcts. The prognosis is favorable regarding motor impairment but cognitive deficits may prevent return to work.

Adolescent↗

PubMedDate not supplied

Activity in the hypothalamic-pituitary-adrenal axis and delirium.

Glucocorticoid hormones are important for coping with stress but may have deleterious effects on mood and memory during prolonged excessive secretion. A key abnormality related to cortisol excess in delirium seems to be abnormal 'shut-off' of the hypothalamic-pituitary-adrenal (HPA) axis tested by the dexamethasone suppression test. In experimental models, the hippocampal formation is of prime importance for normal HPA axis shut-off. In this brain area, a close interaction between neurotransmittors, notably acetylcholine, serotonin and noradrenaline, and glucocorticoid receptors, is present and possibly relevant for the development of delirium in elderly patients with stroke and neurodegenerative brain diseases.

Animals↗