Neuronal ceroid lipofuscinosis: clinical and morphologic findings in nine affected Polish Owczarek Nizinny (PON) dogs

OBJECTIVE: The aim of this study was to characterize the clinical and morphologic features of neuronal ceroid lipofuscinosis (NCL) in the Polish Owczarek Nizinny (PON) breed of dog. ANIMALS: Nine Swedish PON dogs of both sexes were included in the study. PROCEDURE: All dogs underwent a detailed clinical evaluation, with emphasis on ophthalmic exams. Histopathology and electron microscopy were performed on the eyes, brain and various internal organs. Immunohistochemical staining for detection of sphingolipid activator proteins (SAPs) and mitochondrial ATP synthase (SCMAS) was performed on the eyes and brain. RESULTS: The dogs showed behavioral abnormalities, motor disturbances and visual impairment or blindness. Pupillary responses were abnormal while fundus changes varied from normal to severe retinal atrophy. Electroretinography (ERG) showed variable changes, from slight alterations in the process of dark adaptation to severely reduced or nonrecordable ERG a- and b-wave amplitudes. Histopathology revealed intracytoplasmic storage bodies within neurons of the brain and in retinal cells, especially the retinal pigment epithelium (RPE). Round to oval granular type of inclusion bodies, known as granular osmiophilic dense deposits (GRODS), were found in neuronal cells in the brain and in the retina. Immunohistochemistry identified the storage material in the brain and retina as consisting of SAPs. CONCLUSION: The presently described NCL disease in PON dogs shows similarities to previously recorded cases in the Miniature Schnauzer. The closest human equivalent to this disease is infantile NCL (CLN1), in which the major stored proteins are SAPs and the ultrastructure of the inclusion bodies of neuronal cells is granular.     

Necrosis of hippocampus and piriform lobe in 38 domestic cats with seizures: a retrospective study on clinical and pathologic findings

The clinical records of 38 cats (1985-1995) with a neuropathologically confirmed diagnosis of necrosis of the hippocampus and occasionally the lobus piriformis were evaluated retrospectively. There was no sex or breed predisposition. Most cats were between 1 and 6 years of age (mean age 35 months) and had either generalized or complex-partial seizures of acute onset and rapid progression. The seizures had a tendency to become recurrent and to present as clusters or even status epilepticus later in the course of the disease. Fourteen cats died spontaneously, and 24 were euthanized. Histopathologic examination revealed bilateral lesions restricted to the hippocampus and occasionally the lobus piriformis. The lesions seemed to reflect different stages of the disease and consisted of acute neuronal degeneration to complete malacia, affecting mainly the layer of the large pyramidal cells but sometimes also the neurons of the dentate gyrus and the piriform lobe. The clinical, neuropathologic, and epidemiologic findings suggest that the seizures in these cats were triggered by primary structural brain damage, perhaps resulting from excitotoxicity. The cause remains unknown, but epidemiologic analysis suggests an environmental factor, probably a toxin.     

基于神经网络的树叶识别系统研究

在林业系统注册树木种类时,通常采用大量树叶上的可见外形特点来辨别数目繁多的树木种类。针对此问题,本文提出了基于神经网络的树叶识别方法,该方法建立并管理一个分等级的树叶图像体系,通过对不同种类树叶的边缘提取来识别每种树叶的特征点,从而得到树叶的外部轮廓来区分树木种类:给出了相应的改进型神经网络算法,并给出详细的论述过程:最后,通过Java语言给出了系统实现并做了大量的数值仿真。结果证明本文方法是可行有效的。图4表1参8。     

Polyneuropathy associated with forage sources in Norwegian horses

BACKGROUND: Cases of hindlimb digital extensor weakness of unknown etiology have been observed in Norway since 1995. HYPOTHESIS: We hypothesized that the observed bilateral extensor weakness was attributable to neuropathy of the distal nerves and that this was related to environmental factors, possibly dietary. ANIMALS: Seventy-five horses with digital extensor weakness occurring from 1995 to 2004 are described. METHODS: Eleven horses were examined at The Norwegian School of Veterinary Science, and the medical records of 64 horses seen in ambulatory practice were reviewed. RESULTS: There was no apparent sex, age, or breed predilection, but the majority were horses kept for pleasure or breeding purposes. Clinical signs varied from intermittent knuckling of the hindlimbs to paraplegia. Some horses showed no or only slow progression of signs, whereas others developed severe signs within hours. No other neurologic deficits were detected in any of the horses. Epidemiologic data and laboratory results were not supportive of an infectious etiology. The only common factor for all affected horses seemed to be feeding big bale silage or, occasionally, hay of poor microbiologic quality. Forty of the 75 horses were euthanized. Histopathologic examination of peripheral nervous tissue was performed in 22 horses, all of which had neuronal fiber degeneration. The majority of horses with mild signs recovered after 5-6 months of rest. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical signs correlated with polyneuropathy involving sciatic nerves.     

一维Theta-神经元网络中规则单放电行波解的讨论

本文主要讨论一维Theta-神经元网络中的规则单放电行波解。首先从理论上论证了通过控制网络中细胞之间的耦合作用时间可得到网络中的单放电行波解;其次通过数值模拟对结果加以验证。     

The effect of administration of 2-iminobiotin at birth on growth rates, morbidity and mortality in piglets under farm conditions

It has since long been demonstrated that perinatal asphyxia in pigs can result in perinatal mortality, decreased viability/vitality at birth and reduced survival rates until 10 days of age. In human perinatology much interest is presently focussed on strategies to prevent adverse outcome arising from birth asphyxia. Given the rather high perinatal and postnatal losses in the pig industry, it is very interesting to explore rescue strategies to reduce adverse effects of postischemic organ damage caused by perinatal asphyxia also in newborn piglets.

The aim of this study was to determine the effects of postnatal treatment of piglets with 2-IminoBiotin (2-IB), a selective inhibitor of neuronal and inducible NitricOxideSynthase (nNOS and iNOS), under farm conditions on postnatal growth rates, morbidity and mortality.

In total 81 piglets from 15 litters were used. Immediately after birth, blood was collected from the umbilical artery and piglets were alternately assigned to either a control (saline) or drug (2-IB; 0.18 mg/kg bodyweight every 4 h during 24 h) group. Administration of control or drug started with an intravenous injection in the umbilical vein immediately after birth, followed by 6 intraperitoneal injections at 4 h intervals, starting 4 h after the intravenous injection. Piglets were checked for growth, morbidity and mortality until the experiment was finished (average age: 44 days).

Postnatal treatment with 2-IB resulted in significantly increased growth rates at 10 days of age (P = 0.02) (165 g/day compared to 140 g/day in controls), independently of health status and birth weight. At weaning 2-IB treated piglets tended to show higher growth rates (P = 0.06). Growth rates at the end of the experiment, morbidity and mortality were not affected by treatment.

It is hypothesized that 2-IB reduces the rather limited, nearly ‘physiological’ harmful effects occurring in the gastrointestinal tract, resulting from a short period of hypoxia-ischemia experienced during birth. This might explain the significantly increased growth rates at 10 days of life in 2-IB treated piglets. Selective inhibition of nNOS and iNOS might also result in increased availability of l-arginine for protein synthesis in newborns resulting in higher postnatal growth rates. However these issues need further investigations.

In conclusion, this study showed a positive effect of immediate postpartum administration of 2-IB during the first day after birth on growth rates up to 10 days of age. Furthermore, no negative effects of 2-IB treatment on piglet health and survival were found.     

两个不动点的神经网络模型行波解的存在唯一性的数值模拟

本文主要研究神经网络模型行波解的存在唯一性,运用Matlab软件对存在两个不动点的情况进行行波解与存在唯一波速的数值模拟.     

Effect of cyclooxygenase 2 on hippocampal neuronal damage induced by aluminum in rats

AIM:To study the relationship between cyclooxygenase 2(COX-2) and the damage of hippocampal neurons by aluminum overload in rats. METHODS:Newborn SD rats(less than 24 h) were used to establish the model of primary culture of hippocampal neurons. The neurons were treated with aluminum at concentration of 200 μmol/L. The techniques of RNA interference(RNAi) and cell transfection were used to study the role of COX-2 in hippocampal neuron. Following RNAi by cell transfection, Western blotting analysis was used to determine the protein expression of COX-2. Cell growth was assayed by the method of MTT. The pathological changes of the neurons were observed by fluorescence labeling. The activity of superoxide dismutase(SOD) and lactate dehydrogenase(LDH), and the content of malondialdehyde(MDA) were detected for evaluating cell damage. RESULTS:COX-2 RNAi by cell transfection significantly decreased the protein expression of COX-2 without changing the neuronal pathomorphology, cell viability, SOD activity and MDA content. However, it obviously improved livability and SOD activity of the hippocampal neurons, which were aluminum-overloaded. Inhibition of COX-2 expression also reduced the leakage of LDH and the content of MDA, and ameliorated the pathological changes in neurons. CONCLUSION:Moderate silence of COX-2 expression not only significantly affects the morphological changes and physiological functions of hippocampal neurons, but also prevents the neurons from aluminum-induced damages.     

兔脑nNOS阳性神经元的形态、结构和分布规律

利用SABC免疫组织化学方法，对兔脑神经型一氧化氮合酶(nNOS)阳性神经元的形态、结构及分布规律进行了系统研究，结果表明：① nNOS阳性神经元呈深棕色，着色主要在胞质内，细胞核处较为浅淡；神经元胞体形态多种多样，有三角形、圆形、椭圆形、梭形等，神经元突起有一个或者数个；nNOS阳性神经纤维大多呈棕色串珠样，有些区域的阳性纤维交错分布，相互交织成网状。②家兔的各个脑区均有nNOS阳性神经元和神经纤维出现,其中在大脑皮质、小脑、丘脑下部、中脑和脑桥广泛分布，延髓分布极少。③nNOS阳性神经元，在仔兔时就已基本发育到成年兔水平，以后随着年龄增长逐渐发育成熟至衰老，到2岁龄（老年兔）时就出现了显著的衰老变化，即密度减小，表达强度减弱，第一级突起数减少，最长突起长度变短等。结果提示：nNOS阳性神经元及其催化产生的NO在家兔神经系统的发育和神经调控中起重要作用。     

GM2 Gangliosidosis in Shiba Inu Dogs with an In‐Frame Deletion in HEXB

Consistent with a tentative diagnosis of neuronal ceroid lipofuscinosis (NCL), autofluorescent cytoplasmic storage bodies were found in neurons from the brains of 2 related Shiba Inu dogs with a young‐adult onset, progressive neurodegenerative disease. Unexpectedly, no potentially causal NCL‐related variants were identified in a whole‐genome sequence generated with DNA from 1 of the affected dogs. Instead, the whole‐genome sequence contained a homozygous 3 base pair (bp) deletion in a coding region of HEXB. The other affected dog also was homozygous for this 3‐bp deletion. Mutations in the human HEXB ortholog cause Sandhoff disease, a type of GM2 gangliosidosis. Thin‐layer chromatography confirmed that GM2 ganglioside had accumulated in an affected Shiba Inu brain. Enzymatic analysis confirmed that the GM2 gangliosidosis resulted from a deficiency in the HEXB encoded protein and not from a deficiency in products from HEXA or GM2A, which are known alternative causes of GM2 gangliosidosis. We conclude that the homozygous 3‐bp deletion in HEXB is the likely cause of the Shiba Inu neurodegenerative disease and that whole‐genome sequencing can lead to the early identification of potentially disease‐causing DNA variants thereby refocusing subsequent diagnostic analyses toward confirming or refuting candidate variant causality.