Neuropathologic effects developing after administration of tetanus toxin to several rat brain structures]

Neuropathological syndromes following local tetanus toxin (TT) injection into different rat brain structures were studied. As demonstrated, there arose specific neuropathological signs dissimilar to those developing with different TT localization, i.e. as a rule the action of TT in the given brain parts was local. Experiments carried out confirmed the theory of the generator mechanisms of the neuropathological syndromes according to which specific manifestations of the corresponding syndrome were due to the localization of a generator of pathologically-enhanced excitation in definite brain structures.     

Modeling neuropathologic syndromes by creating generators of pathologically enhanced excitation in the hypothalamus of rabbits

In the experiments on free behavior rabbits, tetanus toxin was injected into "pacemaker" motivational emotiogenic regions of the hypothalamus to form generators of pathologically enhanced excitation; this produced stable, long-term disorders in motivational-emotional behavior. The changes were manifested by intensification of the feeding behavior activity, including increase of the "secondary motivational reactions", intensification of the motor activity, excessive number of automatic masticatory movements, appearance of aggression, fear reaction and corresponding vegetative changes. The character of these reactions depended on the site of the toxin administration and on its dose. Formation of long-term generators of the pathologically enhanced excitation in the "pacemaker" motivational-emotiogenic centers of the hypothalamus by tetanus toxin can be used the modelling of psychopathological states in animals. The data obtained on the new model have confirmed the theory of generative mechanisms of neuropathological syndromes characterized by hyperactivity of the systems.     

肺癌转移与中医脏象理论相关性分析

目的:分析肺癌转移与中医脏象理论的相关性。方法:回顾性选择我院收治的102例晚期肺癌转移患者为研究对象,统计患者的转移灶所属部位,并参照《中医内科学》对患者的中医临床证候进行判定。分别统计各证型患者肺癌转移的单器官及首发转移器官的分布、肺癌转移各单器官及首发转移器官的证型分布情况。结果:各证型患者肺癌转移的单器官及首发转移器官分布率比较,差异具有统计学意义(P0.05)。同时,肺癌转移各单器官及首发转移器官的证型分布率比较,差异具有统计学意义(P0.05)。结论:根据肺癌患者的中医临床证候可判断其病灶转移方向,同时,根据肺癌患者的转移灶所属部位可判断其中医临床证型。     

Effects of destruction and activation of limbic structures on formation of convulsive and emotional disorders during picrotoxin kindling

In the experiments on rats it was shown that the picrotoxin kindling, which consists of the progressive increasing of convulsive reactions during daily systemic administration of picrotoxin in subconvulsive dosages results also in the development of the pathologically enhanced defensive reactions. The destruction of hippocampal structures by kainic acid prevented the seizure syndrome, while their activation due to blood injection in hippocampus promoted its development; under these conditions the kindling of pathologically enhanced defensive reactions was not significantly changed. Bilateral amygdalar destruction significantly attenuated the development of pathologically increased defensive behavior; under these conditions the seizure syndrome was not significantly changed. The data are discussed on the theory of generator, and systemic mechanisms of neuropathologic syndromes and show that picrotoxin kindling results in the formation of two different pathologic systems which cause the development of two mentioned syndromes: seizure syndrome and syndrome of pathologically enhanced defensive behavior.     

Parkinson’s disease: clinical aspects

Parkinsonism is a clinical syndrome characterized by akinesia, muscular rigidity, and resting tremor. The most frequent cause of parkinsonism is Parkinsons disease (PD). Progressive loss of substantia nigra neurons together with the occurrence of Lewy bodies are considered essential neuropathological features of PD. Recent neuropathological studies suggest that nigral degeneration is only part of a more extended brain degeneration that starts in the medulla oblongata and then spreads to the mesencephalon and cerebral cortex. Correspondingly, the clinical symptoms occurring in PD go far beyond parkinsonism. Depending on the disease stage, autonomic dysfunction, olfactory disturbances, depression, and dementia are frequently encountered in PD. These neuropathological and clinical observations have major implications for future research in PD. In particular, the analysis of the properties that the neuronal cell types involved in PD have in common and that might make them susceptible to degeneration is essential.     

Effect of electric stimulation of the caudate nucleus on the foci of epileptic activity in the cerebral cortex

It was shown in the acute experiments on rats that caudate nucleus is one of the main structures of brain antiepileptic system. It was noted that reduction of the influence of activating cerebral structures is a tool for abolishing the proepileptic effects which occur in some cases under conditions of electrical stimulations of neostriatum. Results of the investigation confirm G. N. Kryzhanovsky theory of a role of system-antisystem interrelations in suppression of neuropathological syndromes as a result of system hyperactivity.     

Genetic modulation of senescent phenotypes in Homo sapiens

Single-gene mutations can produce human progeroid syndromes--phenotypes that mimic usual or "normative" aging. These can be divided into two classes--those that have their impacts upon multiple organs and tissues (segmental progeroid syndromes) and those that have their major impacts upon a single organ or tissue (unimodal progeroid syndromes). The prototypic example of the former is the Werner syndrome, a condition caused by mutations of the RecQ family of DNA helicases. Research on the Werner syndrome and a surprising number of other progeroid syndromes support the importance of the maintenance of genomic stability as a partial antidote to aging. The prototypic examples of the latter are Alzheimer type dementias. The three gene products that cause rare autosomal-dominant early-onset varieties of these disorders all participate in the modulation of the beta amyloid precursor protein. They thus support the importance of the maintenance of proper protein processing and folding as a partial antidote to aging.     

Description,nomenclature, and mapping of a novel cerebello-renal syndrome with the molar tooth malformation

Cerebello-oculo-renal syndromes (CORSs) and Joubert syndrome (JS) are clinically and genetically heterogeneous autosomal recessive syndromes that share a complex neuroradiological malformation resembling a molar tooth on brain axial images, a condition referred to as "molar tooth on imaging" (MTI) or the "molar tooth sign." The current literature on these syndromes is complex, with overlapping and incomplete phenotypes that complicate the selection of clinically homogeneous cases for genetic purposes. So far, only one locus (JBTS1 on 9q34) has been mapped, in two families with JS. Here, we describe a large consanguineous family with JS and nephronophthisis, representing a novel cerebello-renal phenotype. We have mapped this condition to the pericentromeric region of chromosome 11 and have named the locus "CORS2." The acronym "CORS" is proposed for all loci associated with JS, CORSs, and related phenotypes sharing the MTI, because this neuroradiological sign seems to be the unifying feature of these clinically heterogeneous syndromes.     

Proteus syndrome: Clinical profile of six patients and review of literature

OBJECTIVE:

Proteus syndrome (PS) is characterized by patchy or segmental overgrowth and hyperplasia of multiple tissues and organs, along with susceptibility to development of tumors. Very few cases are reported in literature from developing countries. Due to certain overlapping features with other overgrowth syndromes, diagnosis is usually delayed. Our aim was to describe clinical profile of this rare condition in six patients.

MATERIALS AND METHODS:

Retrospective case sheet review of patients followed in a Pediatric Genetic and Metabolic clinic at a tertiary care institute of North India with a diagnosis of hemihypertrophy/overgrowth syndrome.

RESULTS:

Six cases presented with asymmetric overgrowth and peculiar features suggestive of PS were included in this study. Age at presentation was 2 months to 10 years; two were males and four were females. Hemihypertrophy was noticed in only one case at birth, and focal overgrowths in rest of other patients were seen later during childhood.

CONCLUSION:

Due to certain overlapping features with other overgrowth syndromes, diagnosis of PS is usually delayed. Pediatricians are the first persons who come across such patients and they should be aware about this rare condition.     

In vivo and in vitro studies with agents that cause quasi-morphine withdrawal syndromes

Compounds that elicit a "quasi-morphine withdrawal syndrome" (QMWS) after acute administration to rats constitute a new class of behavior-modifying agent. In studying the pharmacological bases of quasi-opiate withdrawal syndromes, we found that the dihydrocodeinone, RX 336-M, a standard QMWS-inducing agent, caused a naloxone-insensitive increase in twitch tension on the field-stimulated rat was deferens preparation. In contrast, IBMX (3-isobutyl-1-methylxanthine), the historical inducer of quasi-abstinence in rats, gave a naloxone-insensitive decrease in twitch tension. Tolerance developed to the "wet-dog" shakes elicited by twice-daily s.c. injections of RX 336-M or IBMX in rats for 5 or 15 days, respectively. The parallel development of tolerance to the in vitro effects of these compounds could not be demonstrated.     

Epigenetic deregulation of genomic imprinting in human disorders and following assisted reproduction

Imprinted genes play important roles in the regulation of growth and development, and several have been shown to influence behavior. Their allele-specific expression depends on inheritance from either the mother or the father, and is regulated by "imprinting control regions" (ICRs). ICRs are controlled by DNA methylation, which is present on one of the two parental alleles only. These allelic methylation marks are established in either the female or the male germline, following the erasure of preexisting DNA methylation in the primordial germ cells. After fertilization, the allelic DNA methylation at ICRs is maintained in all somatic cells of the developing embryo. This epigenetic "life cycle" of imprinting (germline erasure, germline establishment, and somatic maintenance) can be disrupted in several human diseases, including Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS), Angelman syndrome and Hydatidiform mole. In the neurodevelopmental Rett syndrome, the way the ICR mediates imprinted expression is perturbed. Recent studies indicate that assisted reproduction technologies (ART) can sometimes affect the epigenetic cycle of imprinting as well, and that this gives rise to imprinting disease syndromes. This finding warrants careful monitoring of the epigenetic effects, and absolute risks, of currently used and novel reproduction technologies.     

Prolongation of sleep following creation of a generator of pathologically enhanced excitation in the orbital cortex

Acute experiments on cats showed that injection of tetanus toxin into the orbital cortex (which destroys various types of inhibition) resulted in the formation of a local generator of pathologically enhanced excitation in this cortex area. Chronic experiments showed that cats with such a generator in the orbital cortex developed pathological changes of sleep, expressed in reduction of the duration of wakefulness and development of the slow-wave and paradoxical sleep phases being, retained. The results of this investigation confirm the view on the participation of the orbitofrontal cortex in sleep induction. They are in favour of the general conception on the role of the determinant structure in the nervous system activity and the theory of the generator mechanisms of the neuropathological syndromes characterized by the hyperactivity of the system.     

Hirsutism: common clinical problem or index of serious disease?

Hirsutism is a clinical condition commonly encountered in the practice of primary care medicine. The etiology and the age of the patient when it occurs vary widely. Causes range from a basic illness or condition (drug exposure, smoking, idiopathic, and obesity) to complex and serious diseases (Cushing's syndrome, neoplasms, congenital adrenal hyperplasia, insulin-resistance syndromes, hyperprolactinemia, polycystic ovary syndrome, and hyperthecosis). Hirsutism may appear in childhood as well as in older persons. Some drugs (oral contraceptives, L-thyroxine, danazol, and diazoxide), tobacco smoke, some syndromes (polycystic ovary syndrome, obesity, insulin resistance, hyperprolactinemia, hyperthecosis, congenital adrenal hyperplasia, and idiopathic), and some neoplasms (adrenal or ovarian) may lead to hirsutism. The most frequently defined "causes" of hirsutism are polycystic ovary syndrome and idiopathic hirsutism. In hirsutism of gradual onset, hyperprolactinemia, insulin-resistance syndromes, hyperthecosis, polycystic ovary syndrome, and idiopathic hirsutism may be responsible. Cushing's syndrome, neoplasms, and congenital adrenal hyperplasia should be suspected if there has been rapid onset.     

Commonality of molecular mechanisms of neuroplasticity and neuropathology: integrative approach

Analysis of our own data and of the results from other groups brings about a concept concerning community of the basic molecular mechanisms involved in neuroplasticity and neuropathology at different levels. Along with the fundamental significance of this idea for understanding of processes taking place both in normal brain and in neuropathological conditions, the concept is of principal importance for practical application. Failure in development of the "pathogenetically directed" approaches to treatment of neural diseases (e. g. stroke) are, in particular, related to the neglecting of identity of the basic molecular mechanism underlying both normal brain functioning and neuropathological conditions resulting in intervention into these common mechanisms (NMDA receptors blockade, inhibitor of the so called "apoptotic" proteases).     

A decade of modeling Alzheimer's disease in transgenic mice

It has been over a decade since the first Alzheimer's disease (AD) transgenic mouse models were reported. These models have enabled dramatic advances in our understanding of the pathogenic mechanism in AD and of potential therapeutic approaches to tackling the inexorable clinical progression of the disease. In this article, we discuss the current status of AD mouse models and focus on recent work that has examined the development of the neuropathological lesions observed in AD (plaques and tangles). The relationship between these lesions, neurodegeneration and development of the clinical syndrome will be explored.     

Limb mammary syndrome: a new genetic disorder with mammary hypoplasia, ectrodactyly, and other Hand/Foot anomalies maps to human chromosome 3q27.

We report on a large Dutch family with a syndrome characterized by severe hand and/or foot anomalies, and hypoplasia/aplasia of the mammary gland and nipple. Less frequent findings include lacrimal-duct atresia, nail dysplasia, hypohydrosis, hypodontia, and cleft palate with or without bifid uvula. This combination of symptoms has not been reported previously, although there is overlap with the ulnar mammary syndrome (UMS) and with ectrodactyly, ectodermal dysplasia, and clefting syndrome. Allelism with UMS and other related syndromes was excluded by linkage studies with markers from the relevant chromosomal regions. A genomewide screening with polymorphic markers allowed the localization of the genetic defect to the subtelomeric region of chromosome 3q. Haplotype analysis reduced the critical region to a 3-cM interval of chromosome 3q27. This chromosomal segment has not been implicated previously in disorders with defective development of limbs and/or mammary tissue. Therefore, we propose to call this apparently new disorder "limb mammary syndrome" (LMS). The SOX2 gene at 3q27 might be considered an excellent candidate gene for LMS because the corresponding protein stimulates expression of FGF4, an important signaling molecule during limb outgrowth and development. However, no mutations were found in the SOX2 open reading frame, thus excluding its involvement in LMS.     

On the occurrence of macroorchidism and mental handicap in the Aarskog syndrome

In this report we present follow-up on two moderately mentally retarded boys with Aarskog syndrome. As 22 other mentally normal Aarskog patients these two boys presented a catch-up after a delayed puberty with a final adult height of 160 cm. A remarkable finding was the development of macroorchidism in two mentally retarded Aarskog patients. The pathogenesis of macroorchidism in the fragile X syndrome and in other X-linked mental retardation syndromes is discussed.     

先天性心脏病相关综合征的遗传学研究

先天性心脏病(congenitalheartdisease,CHD)是儿科常见的疾病,现已发现约有300多种临床综合征伴有CHD.对Alagille综合征、CHARGE联合征、Holt-Oram综合征、Noonan综合征、Turner综合征、VACTERL联合征、Williams综合征、22q11缺失综合征和13、18、21三体综合征与CHD相关流行病学、临床表型、遗传病因和诊断及其再发风险进行了综述,为产前和产后临床诊断,了解疾病预后和再发概率提供资料.     

Sex-Specific Effects of High Fat Diet on Indices of Metabolic Syndrome in 3xTg-AD Mice: Implications for Alzheimer's Disease

Multiple factors of metabolic syndrome have been implicated in the pathogenesis of Alzheimer''s disease (AD), including abdominal obesity, insulin resistance, endocrine dysfunction and dyslipidemia. High fat diet, a common experimental model of obesity and metabolic syndrome, has been shown to accelerate cognitive decline and AD-related neuropathology in animal models. However, sex interacts with the metabolic outcomes of high fat diet and, therefore, may alter neuropathological consequences of dietary manipulations. This study examines the effects of sex and high fat diet on metabolic and AD-related neuropathological outcomes in 3xTg-AD mice. Three month-old male and female 3xTg-AD mice were fed either standard or high fat diets for 4 months. Obesity was observed in all high fat fed mice; however, ectopic fat accumulation, hyperglycemia and hyperinsulinemia were observed only in males. Interestingly, despite the different metabolic outcomes of high fat diet, the neuropathological consequences were similar: both male and female mice maintained under high fat diet exhibited significant worsening in behavioral performance and hippocampal accumulation of β-amyloid protein. Because high fat diet resulted in obesity and increased AD-like pathology in both sexes, these data support a role of obesity-related factors in promoting AD pathogenesis.