Angiotensinogen promoter and angiotensinogen II receptor type 1 gene polymorphisms and incidence of ischemic stroke and neurologic phenotype in Fabry disease

Abstract

Context: Stroke and/or white matter lesions (WMLs) are significant in Fabry disease. Polymorphisms of angiotensinogen (AGT), AGT Promoter and angiotensinogen II receptor type 1 (AGTR1) are correlated with WMLs.

Objectives: We compared AGT. AGT Promoter and AGTR1 genotypes to stroke incidence, Fabry-specific [Mainz Severity Score Index (MSSI)] severity score, and neurologic sub-score (n-MSSI).

Methods: Sixty-three Fabry patients and 49 matched controls plus historic controls were genotyped. Institutional Review Board approval was received.

Results. C and/or CC alleles of AGT Promoter and AGTR1 were significantly correlated with stroke and n-MSSI.

Discussion/conclusion: Findings are suggestive of role of AGT Promoter and AGTR1 genotypes in Fabry phenotypes.     

Seminalplasmin: A protein with many biological properties

Proteins present in the seminal plasma of mammals are known to influence functions associated with ejaculated spermatozoa such as motility, capacitation, acrosome reaction and fertilising ability. The proteins isolated and characterised so far influence only one of the above functions of spermatozoa. Seminalplasmin, a protein isolated from the seminal plasma of bull is exceptional in that it influences many of the above spermatozoal functions. It is also a potent antimicrobial protein and capable of lysing microbial and mammalian cells. The physiological function of seminalplasmin as nature's own antifertility agent is discussed.     

Sodium-Dependent Proline Uptake in the Rat Hippocampal Formation: Association with Ipsilateral-Commissural Projections of CA3 Pyramidal

Na+-dependent uptake of L-[3H]proline was measured in a crude synaptosomal preparation from the entire rat hippocampal formation or from isolated hippocampal regions. Among hippocampal regions, Na+-dependent proline uptake was significantly greater in areas CA1 and CA2-CA3-CA4 than in the fascia dentata, whereas there was no marked regional difference in the distribution of Na+-dependent gamma-[14C]aminobutyric acid ([14C]GABA) uptake. A bilateral kainic acid lesion, which destroyed most of the CA3 hippocampal pyramidal cells, reduced Na+-dependent proline uptake by an average of 41% in area CA1 and 52% in area CA2-CA3-CA4, without affecting the Na+-dependent uptake of GABA. In the fascia dentata, neither proline nor GABA uptake was significantly altered. Kinetic studies suggested that hippocampal synaptosomes take up proline by both a high-affinity (KT = 6.7 microM) and a low-affinity (KT = 290 microM) Na+-dependent process, whereas L-[14C]glutamate is taken up predominantly by a high-affinity (KT = 6.1 microM) process. A bilateral kainic acid lesion reduced the Vmax of high-affinity proline uptake by an average of 72%, the Vmax of low-affinity proline uptake by 44%, and the Vmax of high affinity glutamate uptake by 43%, without significantly changing the affinity of the transport carriers for substrate. Ipsilateral-commissural projections of CA3 hippocampal pyramidal cells appear to possess nearly as great a capacity for taking up proline as for taking up glutamate, a probable transmitter of these pathways. Therefore proline may play an important role in transmission at synapses made by the CA3-derived Schaffer collateral, commissural, and ipsilateral associational fibers.     

Segregation of viral double-stranded and single-stranded DNA molecules in nuclei of adenovirus infected cells as revealed by electron microscope in situ hybridization.

Formation of progeny viruses in the nuclei of HeLa cells infected with adenovirus type 5 was studied at the ultrastructural level by in situ hybridization techniques allowing specific detection of either viral double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA). Prior to the initiation of replication of viral genomes, infective DNA molecules which entered the nucleus of the target cell were randomly distributed among host chromatin fibers including nucleolus-associated chromatin. They were double-stranded, that is, without single-strand breaks. Such association of viral DNA with host condensed chromatin also occurred in mitosis. The initiation of viral genome replication occurred simultaneously with the appearance in the nucleoplasm of small fibrillar regions containing intermingled viral dsDNA and ssDNA. Later, at the intermediate stage of nuclear transformation, viral dsDNA and ssDNA molecules were almost entirely separated into two contiguous substructures. At this stage, viruses were observed occasionally in the vicinity of viral ssDNA accumulation sites. Still later, an additional substructure developed in the centre of the nucleus which consisted of large quantities of viral dsDNA, traces of viral ssDNA and abundant viruses. Portions of viral ssDNA were attached to some viruses even at late stage of nuclear transformation, an association which strongly suggests the occurrence of encapsidation of at least some of the viral genomes while they are still engaged in replication.     

Desipramine Binding: Relationship to Central and Sympathetic Noradrenergic Activity

We examined the effects of treatments affecting norepinephrine release on the number of norepinephrine reuptake recognition sites as reflected by desipramine binding. To do this, we used manipulations having similar presynaptic but contrasting postsynaptic effects. Presynaptic inhibition by 6-hydroxydopamine lesion or by clonidine, and postsynaptic receptor stimulation by isoproterenol, reduced desipramine binding. Presynaptic stimulation by d-amphetamine and postsynaptic receptor blockade by prazosin increased desipramine binding. Similar effects and binding properties were seen in cerebral cortex, heart, and soleus muscle. After unilateral noradrenergic lesions, reduction in desipramine binding correlated with reduction in norepinephrine uptake. These results show that norepinephrine reuptake appears to be regulated by transmitter release regardless of effects on postsynaptic transmission, and that this regulation is analogous in the central and sympathetic nervous systems.     

Cuticular lesions induced in grass shrimp exposed to hexavalent chromium

Adult grass shrimp were exposed to four concentrations (0.5, 1.0, 2.0 and 4.0 ppm) of hexavalent chromium for 28 days. At the end of the exposure period, over 50% of the surviving shrimp possessed cuticular lesions that had many of the gross characteristics of “shell disease.” These lesions were usually associated with articulations of the appendages and abdomen. Furthermore, it was found that at increasing levels of chromium exposure, there was a proportionate increase in the loss of limbs such that nearly 50% of the limbs were lost in grass shrimp exposed to the highest test concentration of chromium. Histological and ultrastructural examination of numerous lesions demonstrated a range of degenerative features within the subcuticular epithelium that included cytoplasmic vacuolization, mitochondrial swelling, chromatin emargination, and the presence of unusual nuclear inclusions that appear to indicate direct chromium toxicity. Additionally, a marked retardation in new epicuticle and exocuticle formation was observed in viable tissues associated with lesions in late premolt shrimp. It is proposed that chromium interferes with the normal functions of subcuticular epithelium, particularly cuticle formation, and subsequently causes structural weaknesses or perforations to develop in the cuticle of newly moted shrimp. Because of these chromium-induced exoskeletal deficiencies, a viaduct for pathogenic organisms (e.g., bacteria) and direct chromium influx is formed that perpetuates lesion development.     

Different long-term effects of bilateral and unilateral nucleus basalis lesions on rat cerebral cortical neurotransmitter content

Young adult rats received either unilateral or bilateral ibotenic acid infusions in their nucleus basalis, destroying most of the cholinesterase-staining neurons in that region. Cerebral cortex levels of choline acetyltransferase, somatostatin, neuropeptide Y, and monoamines were then assayed 2.5 and 10 months after bilateral lesions, or, 2.5, 10, and 14 months after unilateral lesions. Entorhinal and cerebral cortex levels of several amino acid transmitters were also measured. As expected, choline acetyltransferase activity was decreased in the frontal cortex ipsilateral to the ibotenic acid infusion in unilaterally or bilaterally lesioned animals. Parietal cortex concentrations of somatostatin and neuropeptide Y were altered by lesioning in a complicated, time-dependent manner. Thus, while unilateral lesions transiently decreased or had no effect on these neuropeptide levels, bilateral lesions elevated the level of each neuropeptide by over 100% at 10 months. Other cortical transmitter systems investigated appeared to be less affected by nucleus basalis-lesions. Unilateral lesions had no effect on prefrontal cortex norepinephrine, serotonin, or dopamine content at 14 months post-lesioning. These different neurochemical effects of unilateral and bilateral nucleus basalis lesions may be important for developing a model for the trans-synaptic effects of cortical cholinergic deafferentation.     

Effects of Chronic Basic Fibroblast Growth Factor Administration to Rats with Partial Flmbrial Transections on Presynaptic Cholinergic Parameters and Muscarinic Receptors in the Hippocampus: Comparison with Nerve Growth Factor

Abstract: The present study compares the effects of chronic administration of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) on various hippocampal cholinergic parameters in rats with partial unilateral fimbrial transections. Lesions resulted in marked reductions of several presynaptic cholinergic parameters: choline acetyltransferase (ChAT) activity (by 50%), [³H]-acetylcholine ([³H]ACh) synthesis (by 59%), basal and ve-ratridine (1 μM)-evoked [³H]ACh release (by 44 and 57%, respectively), and [³H]vesamicol binding site densities (by 35%). In addition, [³H]AF-DX 116/muscarinic M₂ binding site densities were also modestly decreased (by 23%). In contrast, [³H]pirenzepine/muscarinic M₁ and [³H]AF-DX 384/muscarinic M₂/M₄ binding site densities were not altered by the lesions, nor were they affected by any of the treatments. Intracerebroventricular administration of bFGF (10 ng, every other day, for 21 days) partially prevented the lesion-induced deficit in hippocampal ChAT activity, an effect that was not markedly different from that measured in the NGF-treated (1 μg intracerebroventricularly, every other day, for 21 days) rats. In rats treated with a combination of bFGF and NGF, ChAT activity was not different from that in rats treated with the individual factors alone. In contrast, the lesion-induced deficits in the other cholinergic parameters were not attenuated by bFGF treatment, although they were at least partially prevented by NGF administration. To determine whether higher concentrations of bFGF are necessary to affect cholinergic parameters other than hippocampal ChAT activity, rats were treated with 1 μg (every other day, 21 days) of the growth factor. In this group of rats, detrimental effects of bFGF, manifested by an increased death rate (46%), and marked reductions in body weight of the survivors, were observed. In addition, this concentration of bFGF appeared to exacerbate the lesion-induced reduction in [³H]ACh synthesis by hippocampal slices; [³H]ACh synthesis in lesioned hippocampi represented 36 and 52% of that in contralateral unlesioned hippocampi for the bFGF-treated and control groups, respectively. In conclusion, although bFGF administration attenuates the deficit in hippocampal ChAT activity induced by partial fimbrial transections, this does not appear to translate into enhanced functional capacity of the cholinergic terminals. This is clearly in contrast to NGF, which enhances not only hippocampal ChAT activity, but also other parameters indicative of increased function in the cholinergic terminals.     

Relationships between mutans streptococci and perceived treatment need of primary root-caries lesions.

A total of 447 primary root-caries lesions from 169 dental patients was studied to determine the relationships between mutans streptococci and the perceived treatment need of primary root-caries lesions. Samples of this altered dentine for microbiological culture were obtained. Lesions were classified into 5 treatment categories; soft and restore, leathery and restore, leathery and debride of caries, leathery and treat chemotherapeutically, and hard, to receive no treatment. The total numbers of mutans streptococci decreased significantly with decreased treatment need. The percentage of mutans streptococci from lesions requiring no treatment was significantly less than from lesions requiring treatment. The frequency of isolation of mutans streptococci was significantly greater from lesions requiring more treatment. Significantly more lesions containing > 10² mutans streptococci were distributed in the groups with a greater perceived treatment need or with larger dimensions occlusogingivally and/or mesio-distally or bucco-lingually or with a closer proximity to the gingival margin.