Beitrag zur Extrakardialen Digitaliswirkung (Kohlenhydrathaushalt)

Ohne Zusammenfassung     

Amphetamine-induced anorexia: analysis with hypothalamic lesions and knife cuts

The present study examined the hypotheses that the midlateral perifornical region of the hypothalamus (PFH), at the level of the ventromedial nucleus, plays a crucial role in amphetamine (AMPH)-induced anorexia and that mediating fibers ascending to this brain region follow a midlateral course through the caudal hypothalamus. Electrolytic lesions that destroyed the PFH region attenuated the feeding suppression induced by intraperitoneal administration of AMPH. Lesions placed anterior, dorsal, or medial to this region, in contrast, did not decrease AMPH's effect. The medially-placed paraventricular nucleus lesion, in fact, enhanced drug response. Midlateral coronal wire-knife cuts in the caudal hypothalamus also attenuated AMPH anorexia. The crucial midlateral caudal hypothalamic cut also disrupted anorexia induced by direct injection of AMPH into the PFH area. The results obtained from the lesion data support the hypothesis that the PFH region is essential to AMPH's suppressive effect upon feeding, and the KC data suggest that crucial catecholamine fibers mediating this drug response ascend specifically through the midlateral portion of the hypothalamus.     

Mapping of breakpoints, and relationship to BCR-ABL RNA expression, in Philadelphia-chromosome-positive chronic myeloid leukaemia patients with a breakpoint around exon 14 (b3) of the BCR gene

The BCR gene, on chromosome 22, is involved in the Philadelphia (Ph1) chromosome which is a characteristic cytogenetic marker of chronic myeloid leukaemia (CML). Breakpoints in CML occur within the M-bcr region (5.8 kb) which encompasses exons 12-15 (b1-b4), and the M-bcr can be conveniently divided into five zones by restriction mapping. One of these zones (3) contains exon b3 which can be either present or absent from the hybrid mRNA, even if it is present in the chimaeric gene. We have mapped the breakpoints around BCR exon b3 and related this to the type of RNA splice site expressed, in CML patients at diagnosis. Breakpoints within zone 3 were restriction mapped to one of six sub-zones and the site related to the type of RNA splice site. Two clusters of breakpoints within zone 3 were observed. One cluster was located around exon b3 and often resulted in deletion of exon b3 from the chimaeric gene. The majority of this cluster expressed b2-a2 spliced RNA, usually as a consequence of a deletion removing exon b3. The second cluster occurred within two sub-zones that spanned an Alu sequence, and 90% of this cluster exhibited b3-a2 spliced RNA. Furthermore, a greater number of patients had entered blast crisis if the RNA contained BCR exon b3 (8 of 10 patients), compared to those with b2-a2 spliced RNA (3 of 12 patients). The high degree of heterogeneity in the site of the breakpoint within zone 3 of the M-bcr, combined with the type of BCR-ABL hybrid mRNA expressed, further implicates BCR exon b3 in the pathogenesis of CML.     

Medial hypothalamic serotonin: effects on deprivation and norepinephrine-induced eating

Evidence to date suggests an inhibitory role for serotonin (5-HT) in the regulation of feeding behavior. In the present study, hypothalamic 5-HT was investigated for its anorexic potency under different feeding conditions. In fasted rats, 5-HT (1.1-4.4 micrograms) injected into the hypothalamic paraventricular nucleus (PVN), produced a reliable dose-dependent reduction in food consumption. Under satiated conditions, this inhibitory effect was significantly larger and apparent at lower doses (down to 0.1 micrograms), in animals induced to eat by PVN injection of norepinephrine (NE). Tests with receptor antagonists, injected into the PVN immediately prior to 5-HT, revealed a dose-dependent blockade of 5-HT's action by the serotonergic blockers, metergoline, methysergide and cinanserin. While the effect of 5-HT was somewhat attenuated by administration of certain beta-adrenergic and phenothiazine-type dopamine receptor antagonists, 5-HT was totally resistant to the actions of more selective dopamine blockers and of the cholinergic and histaminergic antagonists, atropine and dexbrompheniramine. PVN injection of various serotonergic compounds, known to inhibit feeding when peripherally administered, also suppressed NE-induced feeding in a dose-related manner (fluoxetine = dl-norfenfluramine greater than quipazine greater than chlorimipramine greater than dl-fenfluramine). Further tests with PVN administration of the dextro isomer and metabolite of fenfluramine showed a considerably stronger inhibitory effect with d-norfenfluramine as compared to dexfenfluramine, and a particular effectiveness of peripherally injected dexfenfluramine in NE-injected rats, at doses at least 10-fold higher than centrally effective doses.(ABSTRACT TRUNCATED AT 250 WORDS)     

THE IN VITRO PRODUCTION OF ANTIBODY BY DELAYED PHASE CORNEAL LIMBAL LYMPHOID FOCI

The intracorneal inoculation of a sufficient quantity of a soluble protein antigen into the eye of a rabbit produces a biphasic allergic reaction in that cornea. The earlier stage, characterized by a diffuse corneal clouding, is a manifestation of delayed hypersensitivity and is accompanied by a limbal infiltrate composed predominantly of lymphocytic-mononuclear elements. The later response, known as the Wessely Phenomenon, is a ring of opacification in the cornea which is visible in the gross. This reaction is dependent upon the presence of specific circulating antibodies and is therefore classified among the immediate types of hypersensitivity. It is accompanied by a dense limbal infiltration of plasma cells. Intervening between the two reactions is a period of several days during which the eye appears relatively normal. Explants containing large numbers of infiltrating lymphocytic-mononuclear elements were removed from the corneal-scleral junction of experimental eyes during the height of the delayed type hypersensitivity reaction and maintained in vitro in tissue culture. At a later date the overlay fluid in which the explants were maintained was shown to contain specific humoral antibodies, demonstrating the capability of cells present at a delayed reaction for the later production of antibodies. The possible linkage of the two modes of immune phenomena is discussed.     

胶原海绵复合新生大鼠原代心肌细胞构建工程化心肌组织

目的:探索以胶原海绵为支架、新生大鼠原代心肌细胞为种子细胞,于体外构建工程化心肌组织的方法。方法:实验于2005-12/2006-11在解放军第四军医大学西京医院心内科实验室完成。Ⅰ型胶原海绵剪切成方形片状(2.0cm×1.4cm×0.2cm),经60Co照射消毒,于DMEM培养液中水化1h左右。另取1d龄SD大鼠心脏,剪成小碎块,然后用2.5g/L胰蛋白酶于37℃中消化,吸取上清至含胎牛血清的DMEM中,重复消化四五次,用差速贴壁法除去大部分成纤维细胞,将细胞沉淀用DMEM培养液以2×109L-1的密度悬浮备用。将上述的心肌细胞悬液1mL缓慢滴注于玻璃模型中的胶原海绵上,然后置于细胞培养中培养。肉眼及显微镜主要观察工程化心肌组织在培养期间的自发收缩情况,包括收缩的部位、强度、频率、一致性以及收缩随时间变化的情况。苏木精-伊红染色观察工程化心肌组织内胶原纤维的变化,细胞形态,胞核的形状及细胞之间的连接。免疫组织化学染色和透射电镜观察工程化心肌组织片的形态和功能。结果:①细胞接种于胶原海绵上1d后,细胞/胶原复合物的凝胶化过程基本完毕,体积保持恒定,维持至培养结束,第3天细胞/胶原复合物局部出现点片状自发收缩,第5天整个细胞/胶原复合物出现同步化自发收缩,收缩频率61～199次/min。2周后37.5%的工程化心肌组织的自发收缩活动减弱,但75%的工程化心肌组织的自发收缩活动持续至培养结束。②苏木精-伊红染色、免疫组织化学染色和透射电子显微镜显示,工程化心肌组织内细胞间连接广泛存在,细胞多呈纵向分布,胞核呈长圆形,胞浆内α-肌节肌动蛋白阳性,胞内肌原纤维排列整齐,可见到心肌特异性的肌小节结构和Z线,多数细胞具有分化的心肌细胞表型。结论:用新生大鼠原代心肌细胞为种子细胞、以Ⅰ型胶原海绵为支架材料,构建出的工程化心肌组织,于体外可长时间持续自发收缩,该细胞/胶原复合物的形态结构与生理功能均类似于成熟大鼠心肌组织。