Organization of dopamine D1 and D2 receptors in human striatum: receptor autoradiographic studies in Huntington's disease and schizophrenia

The technique of quantitative autoradiography was used to examine the effects of Huntington's disease (HD) and schizophrenia on the organization of striatal dopamine (DA) D1 and D2 receptors. Whereas the striatum of HD cases showed a reduction in the density of D1 ([3H]SCH 23390) and D2 ([3H]spiroperidol) receptors, the patterning of D2 receptor loss did not match that of the D1 receptor loss. The HD loss of D1 D1 receptors (65%) is far greater than the loss of D2 receptors (28%). Whereas there was a dorsal-ventral gradient of effect on both receptor subtypes, the effects of HD on D2 receptors in the ventral putamen (PUT) and nucleus accumben septi (NAS) were minimal. Similarly, muscarinic M1 and M2 receptors demonstrate different patterns of alteration in HD. The M2 subtype, labeled with [3H]N-methylscopolamine (in the presence of excess pirenzepine to occlude M1 sites), was depleted far more than the M1 receptor subtype, labeled with [3H]pirenzepine. Although the effects of HD on [3H]mazindol labeling of DA terminals were more heterogeneous, there appeared to be a relative preservation of this afferent input to the striatum of the HD cases. In the schizophrenic cases, our autoradiographic studies confirm previous reports of an elevation of D2 receptor density in the striata of many schizophrenics. This increase was evident even though two of the three cases were known to have not been treated with neuroleptics, and the third case may also have been drug naive. However, the increase was far greater in the NAS (164%) and ventral PUT (173%) than more dorsally in the striatum (68%). The density of D1 receptors and DA terminals labeled with [3H]mazindol in the striatum of schizophrenics was not significantly different from that of control cases. Thus in both HD and schizophrenia, the ratio of D2/D1 receptors is altered in favor of the D2 population, particularly in the NAS.     

A VIP antagonist distinguishes VIP receptors on spinal cord cells and lymphocytes

Vasoactive intestinal peptide (VIP) is a neuropeptide which also interacts with cells of the immune system. The paucity of specific VIP receptor antagonists has hampered studies of possible receptor heterogeneity and of VIP function. To aid in achieving these goals, a new VIP antagonist, a hybrid between neurotensin and VIP, has been synthesized. This peptide interacted with VIP receptors on spinal cord cells with an affinity 10-fold greater than VIP itself. In contrast, 1000-fold higher concentrations of the antagonist were required to displace labeled VIP from its receptor on lymphoid cells as compared to VIP itself, suggesting VIP receptor heterogeneity between immune and spinal cord cells.     

Randomized placebo-controlled trial comparing montelukast and cetirizine for treating perennial allergic rhinitis in children aged 2–6 yr

Leukotriene receptor antagonists (LTRAs) were recently added to the method of treating allergic rhinitis (AR). However, in children under 6 yr old, there has been no study about its efficacy in treating AR. We aim to compare the clinical efficacy of montelukast, cetirizine and placebo in the treatment of children from 2 to 6 yr old with perennial allergic rhinitis (PAR), to see if there are any significant differences. Sixty children were selected and treated with montelukast, or cetirizine, or placebo once daily. The efficacy of the three agents was compared with the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Total Symptom Score (TSS) by diary. In addition, we also examined serum IgE, serum eosinophil cationic protein (ECP), blood eosinophil counts, nasal airway resistance (NAR) and eosinophil percentage in nasal smears. The results revealed that both montelukast and cetirizine were significantly efficacious compared with placebo in NAR, eosinophil percentage in nasal smears, PRQLQ, TSS and all symptom items except nasal itching, throat itching and tearing. For nasal itching, only cetirizine was significantly efficacious. On the other hand, for night sleep quality, montelukast was significantly superior to cetirizine.     

TLR4 Asp299Gly、Thr399Ile基因多态性对变应性哮喘的发病及IgE水平的影响

目的　探讨TLR4 (toll likereceptor 4 )Asp2 99Gly、Thr399Ile基因多态性对变应性哮喘的发病和血浆IgE水平的影响。方法　利用聚合酶链反应 限制性片段长度多态性分析技术 (PCR RFLP) ,对 1 97例变应性哮喘患者和 1 5 6例健康人进行TLR4的Asp2 99Gly、Thr399Ile两位点的基因型检测。同时利用免疫发光法检测血浆IgE的水平。结果　 1 97例变应性哮喘患者TLR4基因Asp2 99Gly位点Asp Asp、Asp Gly和Gly Gly的基因型频率为 0 .81 7、0 .1 4 7和 0 .0 36 ,与正常对照组相比差异无统计学意义 (χ2 =0 .0 32 ,P =0 .984 ) ;但变应性哮喘患者Gly Gly、Asp Gly基因型血浆总IgE对数值 ( x±s:2 .6 1 5± 0 .6 0 0 1 ,n =36 )与Asp Asp基因型血浆总IgE对数值 ( x±s:2 .2 4 0± 0 .6 894 ,n =1 6 1 )相比较高 ,差异有统计学意义 (P =0 .0 0 2 )。TLR4基因Thr399Ile位点Thr Thr、Thr Ile和Ile Ile的基因型频率为 0 .970、0 .0 2 0和 0 .0 1 0 ,与正常对照组相比差异无统计学意义 (χ2 =0 .6 2 0 ,P =0 .733) ;变应性哮喘患者Ile Ile、Thr Ile基因型血浆总IgE对数值 ( x±s:2 .4 1 7± 0 .4 4 2 3,n =6 )与Thr Thr基因型血浆总IgE对数值 ( x±s:2 .30 5± 0 .6 94 9,n =1 91 )相比差异无统计学意义 (P =0 .5 71 )。     

力竭运动后大鼠海马脑区谷氨酸受体NR2A蛋白含量和基因表达的变化

目的:观察力竭运动前后大鼠脑中海马谷氨酸受体NR2A蛋白含量和基因表达的变化,探讨其与运动性疲劳的可能联系。方法:50只SD雄性大鼠,随机分为安静对照组(S,n=10),力竭运动后即刻组(AE1,n=10),力竭运动后恢复0.5小时组(AE2,n=10),力竭运动后恢复3小时组(AE3,n=10)和力竭运动后恢复24小时组(AE4,n=10)。分别采用免疫印迹法和RT-PCR法测定一次性力竭运动后大鼠脑中海马谷氨酸受体NR2A蛋白含量和基因表达。结果:与安静对照组相比,力竭运动后即刻,大鼠NR2A蛋白含量明显升高,而mRNA表达显著减少;恢复0.5小时后,蛋白含量略有下降,mRNA表达显著增加;恢复3小时后蛋白含量显著下降,mRNA表达继续增加;恢复24小时后蛋白含量恢复到安静时水平,mRNA表达则减少至恢复0.5小时后水平。结论:力竭运动后即刻及恢复过程中,大鼠脑中海马谷氨酸受体NR2A蛋白含量及mRNA表达变化趋势不同,提示基因表达对蛋白含量的调控可能具有延迟性。     

ALS and SAD-like nicotinic acetylcholine receptor subunit genes are widely distributed in insects

Segments of nicotinic acetylcholine receptor α sub-unit genes have been isolated from a panel of insect species by polymerase chain reaction, using degenerate oligonucleotide primers designed to recognize conserved regions of the Drosophila melanogaster ALS and SAO genes. The amplified segments encode elements of typical a-subunits anticipated to play roles in ligand binding and ion channel formation. Each is also clearly either ALS or SAD-like. The predicted protein sequences display extremely high levels of conservation (over 85% for each subtype) even though derived from very distantly related insect species.     

胰腺癌细胞的增殖同膜脂质饱和度,膜胰岛素受体的关系

外源性表皮生长因子(或生长抑素)能促进(或抑制)胰腺癌细胞的增殖。胰腺癌细胞增殖速率的高低与细胞膜脂质饱和度的降、升;与膜胰岛素受体数量的增减密切相关。测定细胞膜脂质饱和度和胰岛素受体数量,是判断胰腺癌增殖状态的灵敏指标,有一定临床价值。     

Postnatal development of the hamster coclea. I. Growth of hair cells and the organ of Corti

A morphometric analysis of the developing organ of Corti and its component hair cells was carried out in an age-graded series of Syrian golden hamsters with the aid of scanning electron microscopy. The purpose was to establish a quantitative framework that would provide insight into the rules and principles by which the mammalian cochlea attains its adult proportions. This study examined postnatal development at two day intervals from birth to 22 days after birth. Our analysis included measures of cochlear length and hair cell numbers as well as measures of hair cell sizes in each of five sectors along the cochlear spiral. Our results demonstrate several principles of cochlear development: (1) The full two and one-fourths turns seen in the adult cochlea are already present at birth, but the cochlea continues to elongate for the next 10–12 days. (2) Development of hair cells in the apex generally lags behind that in the base. Whereas the stereocilia and apical margins of hair cells are clearly defined in the basal turn, they become well defined in the apex only postnatally. (3) Growth in cochlear length occurs mainly by increases in cell size rather than in cell numbers; although hair cells do increase in numbers during the first 4 days of cochlear growth, this increase involves addition of hair cells only to preexisting regions of the cochlear apex. Moreover, the full complement of hair cells is established 6 days before the full size of the cochlea is attained; in contrast, hair cell growth occurs at all positions along the cochlear spiral and spans the entire period of cochlear elongation. (4) The period of hair cell growth exceeds the period of organ of Corti growth and appears to be possible by decreases in intercellular spacing, primarily in the apical region of the cochlea; inner and outer hair cell growth was complete between 16 and 18 days after birth. (5) Inner and outer hair cell neighbors remain virtually constant at different ages indicating that the spatial relationships between the two hair cell populations is preserved as the cochlea grows. (6) Comparison with previous developmental studies of auditory function in the hamster reveals that the age of 16 days after birth, when hair cells attain their mature sizes, coincides with the onset of brainstem auditory evoked responses. Growth of hair cell somas alone, however, cannot explain either the subsequent maturation of evoked potential thresholds or changes in frequency representation in the developing cochlea. © Wiley-Liss, Inc.     

血清白细胞介素－2受体的测定在脑血管性痴呆诊治中意义的探讨

目的 :检测脑血管性痴呆患者血清中可溶性白细胞介素 - 2 (s IL- 2 R)水平 ,评价 s IL- 2 R的测定在诊治脑血管性痴呆中的价值。方法 :采用双抗体夹心的 EL ISA法检测脑血管性痴呆患者血清中 s IL- 2 R的水平。结果 :脑血管性痴呆患者血清中的 s IL- 2 R水平较健康对照组显著增高 ,两组比较差异非常显著 (P <0 .0 1)。结论 :检测脑血管性痴呆患者血清中 s IL- 2 R水平 ,有助于了解患者的免疫功能变化及疗效观察     

Stress during gestation alters postpartum maternal care and the development of the offspring in a rodent model.

BACKGROUND: Epidemiological studies suggest that environmental adversity can alter parental care and thus influence child development. We addressed the question of whether stressors can directly affect parental behavior using a rodent model of stable, individual differences in maternal behavior. METHODS: Lactating rat mothers were characterized as high or low in pup-directed licking/grooming (LG) behavior, rebred, and subjected to 7 days of intermittent stress or control conditions during gestation. Female rats were mated a third time without any subsequent intervention. Maternal behavior, oxytocin receptor (OTR) binding, and offspring behavior were examined. RESULTS: Stress reduced OTR levels and pup LG of high LG mothers to levels comparable with those of low LG mothers. The adult offspring of the gestational stress/high LG mothers resembled those of low LG mothers on behavioral measures of anxiety and maternal behavior, as well as OTR levels. The results of the third mating revealed an enduring effect of gestational stress on both mother and offspring maternal LG. CONCLUSIONS: These findings suggest that stress can directly alter maternal care through the neuroendocrine systems that normally regulate this behavior. Thus, the effects of environmental adversity can be transmitted across generations through a nongenomic mechanism involving maternal care.