Analysis of the thermolytic action of ICV neurotensin in the rat at different ambient temperatures

Intracerebroventricular (ICV) cannulae were implanted chronically in adult female Sprague Dawley rats for central injection of neurotensin (NT) or artificial CSP vehicle. During experiments carried out at 48 hr intervals, the body temperature of each rat was monitored continuously by a thermistor probe inserted in the colon. At an ambient temperature of 22°C, NT infused ICV in a threshold dose of 1.5 μg caused a mean maximum fall of 0.9°C in the rats' body temperature. This decline in core temperature was enhanced further to 1.4°C when the rats were exposed to an ambient temperature of 4°C for 1.0 hr immediately after the NT infusion. Similarly, when the rats were exposed to 34°, 36° or 40°C, again for 1.0 hr directly after NT administration, core temperature increased to a maximum of 0.3° to 0.6° during this interval. The maximum hyperthermic response following the control ICV infusion of CSF in rats exposed to the same elevated ambient temperatures was slightly greater (0.2–0.3°C) than that after infusion of NT, because of the initial thermolytic effect produced by the peptide. However, the respective slope of each rise in body temperature in both NT and CSF groups during exposure to all three warm temperatures was nevertheless identical. Overall, the results show that in the animal given NT centrally the core temperature tends to follow the ambient temperature, either cold or warm. Thus, it is concluded that NT possesses a clear-cut poikilothermic action on the central neutral systems underlying the control of body temperature. Therefore, it remains uncertain whether NT in fact could play any role in the mechanism within the diencephalon which mediates normal thermoregulatory function.     

Fully automated synthesis procedure of 4-[18F]fluorobenzaldehyde by commercial synthesizer: Amino-oxi peptide labelling prosthetic group

Automatic synthesis of 4-[18F]fluorobenzaldehyde has been developed by a commercially available TRACERlab™ FX_F−N synthesis module to be used as prosthetic group for amino-oxy functionalized peptide labelling in clinical routine application. In addition a handmade purification device (HPD) has been setup to perform automatic cartridge purification as well as to back-up the reactor where one-pot synthesis is not applicable. Cartridges for solid phase extraction such as C18, C8, phenyl has been tested to best perform purification as well as activity recovery. Radiochemical yield (RCY) at end of synthesis (EOS) was in average 67% after about 45 min (90% decay corrected at EOB). The RCY of the entire procedure was 54% with a radiochemical purity above 99%.     

Peptides from pigeon cerebrum: Two-dimensional fingerprinting and amino acid analysis

The number and heterogeneity of endogenous peptides from pigeon cerebrum were studied by two-dimensional peptide fingerprinting. A highly consistent pattern of 8–9 peptides in the 1000–5000 molecular weight range was obtained from each cerebral sample. Amino acid analysis of the peptide material indicated that 30% of the identified residues were dicarboxylic amino acids and 30% were aliphatic amino acids. There was no evidence for the presence of arginine or half-cystine in the peptide fraction.     

肿瘤浸润性淋巴细胞识别的人黑色素瘤特异性抗原肽的研究

从人黑色素瘤细胞中分离人白细胞抗原（ＨＬＡ－Ａ２）相关多肽，并对ＨＬＡ－Ａ２限制性肿瘤浸润性淋巴细胞（ＴＩＬ）识别的黑色素瘤特异性抗原肽进行研究。方法ＴＩＬ来源于ＨＬＡ－Ａ２＋黑色素瘤病人的周围淋巴结。通过去垢剂溶解细胞和亲和层析法从人黑色素瘤细胞中制备ＨＬＡ－Ａ２分子及相关多肽，并经酸处理和反相－高效液相色谱（ＲＰ－ＨＰＬＣ）分离得到不同多肽组份，将其与抗原加工缺陷的ＨＬＡ－Ａ２＋细胞Ｔ２反应，进行重建ＴＩＬ识别的人黑色素瘤特异表位测定。结果ＴＩＬ对自身或同种异体的ＨＬＡ－Ａ２＋的黑色素瘤细胞具有杀伤作用，而对ＨＬＡ－Ａ２－的黑色素瘤细胞和ＨＬＡ－Ａ２＋的非黑色素瘤细胞无作用。从ＲＰ－ＨＰＬＣ分离不同组份的重建试验中，发现有三个活性高峰值。结论具有活性的多肽分子与ＨＬＡ－Ａ２限制性ＴＩＬ识别的人黑色素瘤特异性抗原肽有关。     

Cholecystokinin-8-like-immunoreactive fibers in rat lumbosacral autonomic regions are sexually dimorphic and altered by a reduction of androgen receptors

Cholecystokinin-8-like-immunoreactive (CCK-8-LI) fibers in laminae VII and X of the rat lumbosacral spinal cord demarcate the position of preganglionic autonomic neurons. This investigation reveals that adult male Sprague-Dawley, or King-Holtzman/Sprague-Dawley rats contain more CCK-8-LI fibers in lumbosacral laminae VII and X than adult females. Furthermore, testicular feminization mutation male rats (which lack 85-90% of their functional androgen receptors) contain fewer CCK-8-LI fibers than normal male or female rats, with the amount of CCK-8-LI being reduced to a greater extent in the sympathetic vs. the parasympathetic regions of the lumbosacral spinal cord. Thus, CCK-8-LI in testicular feminization mutation male rats has a distinctly female-like pattern. These results suggest that testosterone is a regulatory factor for CCK-8-LI fibers found in laminae VII and X of the lumbosacral spinal cord. Sexual dimorphism in lumbosacral CCK-8-LI fibers may contribute to modulating the final common pathway which differentially regulates the reproductive organs and stereotypic reproductive behavior, and may be involved with the sex differences described for pain.     

大鼠肠缺血/再灌注损伤时血浆ET、CGRP水平的变化及PLA_2阻断剂的影响

Wistar大鼠肠缺血／再灌注损伤后，血浆ET、CGRP水平明显升高（P＜0．05，P＜0．01）。PLA2阻断剂氯喹、消炎痛、三氟拉嗪于缺血／再灌注损伤前应用可明显延长损伤大鼠的存活时间，减轻肠缺血／再灌注时远端脏器肺组织的损伤，同时降低血浆ET、明显升高血浆CGRP水平。上述结果提示：ET、CGRP参与缺血／再灌注损伤过程。PLA2阻断剂可抑制损伤时ET释放，并通过某些环节促进机体释放CGRP，这可能是它们在此条件下，对机体保护作用的机制之一。     

Neurotransmitter and neuromodulator systems of the rat inferior colliculus and auditory brainstem studied by in situ hybridization

This study was concerned with the distribution of a variety of putative neuromodulator and neurotransmitter systems in auditory regions of the rat brainstem using in situ hybridization histochemistry. Serial brain sections were screened for the presence of mRNAs for (i) precursors of the neuroactive substances cholecystokinin, somatostatin, proenkephalin and substance P (preprotachykinin), (ii) glutamic acid decarboxylase, the key synthesizing enzyme for GABA, or (iii) subunits l, 2 and 3 of the GABA_A receptor. Detectable message for all of these probes was found in at least one auditory brainstem area. There were clear differences in the distribution of the various mRNAs in subregions of the inferior colliculus, superior olivary complex, lateral lemniscus and cochlear nucleus. Cells expressing mRNA for glutamic acid decarboxylase were most prominent in the inferior colliculus, but were also present in all lower auditory brainstem nuclei, except the medial superior olivary nucleus and medial nucleus of trapezoid body. The mRNA for GABA_A1 receptor subunits was detectable in all auditory regions investigated, although at different levels of expression. GABA_A2 and 3 mRNA signals were seen in inferior colliculus, lateral lemniscus and in almost all superior olivary complex regions, but in fewer cells and at lower levels than the GABA_A1 subtype. Moderate to high levels of preprocholecystokinin mRNA expression were seen in all subregions of the inferior colliculus. In other auditory brainstem areas, preprocholecystokinin mRNA levels were either low or absent. With regard to mRNAs for the neuroactive peptides somatostatin, preprotachykinin and preproenkephalin, all were expressed in the inferior colliculus but there were differences in their cellular distribution. For example, there were almost no preprotachykinin mRNA expressing cells in the central nucleus of inferior colliculus and levels of somatostatin mRNA were especially high in the dorsal cortex and in layer 3 of the external cortex of inferior colliculus. There were also differences in the pattern of expression of these mRNAs in the various brainstem auditory nuclei; there was no preprotachykinin mRNA in any part of the superior olivary complex, only somatostatin mRNA was found in the ventral cochlear nucleus, and expression of preproenkephalin mRNA was pronounced in the ventral nucleus of the trapezoid body and the rostral periolivary zone. The data are considered in light of the connectivity and functional organization of the auditory brainstem.     

抗肿瘤生物活性肽研究进展

 生物活性肽（bioactive peptide）是指具有特殊生理功能的肽类物质。生物活性肽的结构可以从简单的二肽到较大分子的多肽[1]。1902 年，伦敦大学医学院的 Bayliss 和 Startling从动物的胃肠中发现了一种能引起胰腺分泌活动的物质，称为分泌素，这是人类第一次发现生物活性肽类物质[2]。此后，随着现代生物技术和化学技术的应用，反相高效液相色谱、快速原子轰击质谱测定法（fast atom bombardment mass spectromentry）、二维核磁共振（two dimension nuclear magnetic resonance）等技术的发展，对生物活性肽，特别是抗肿瘤活性肽的研究取得了很大进展，本文对此予以综述，并展望抗肿瘤生物活性肽开发利用的前景。     

Cerebral and cerebellar gangliocytomas: a morphological study of nine cases

Hypothalamic gangliocytomas have been shown to contain immunoreactivity for hypophysiotropic peptides and some have been associated with endocrine dysfunction. Extrahypothalamic gangliocytomas are usually not associated with endocrine abnormalities. We studied nine cerebral or cerebellar gangliocytomas from six men and three women; none of the patients had detectable alterations of endocrine homeostasis. On histological examination, the tumor cells resembled hypothalamic neurons. Electron microscopy disclosed the presence of dense-core vesicles in neuronal cytoplasm and processes resembling Herring bodies, and there were synaptic contacts between tumor cells. All but two tumors contained immunocytochemical positivity for at least one peptide hormone or amine; these included somatostatin, corticotropin-releasing hormone, -endorphin, galanin, vasoactive intestinal peptide, calcitonin, serotonin, catecholamines or met-enkephalin. These tumors have been thought to represent neoplasms arising in ectopic autonomic neural tissue. Their morphological features, their similarity to hypothalamic gangliocytomas and the multiple immunoreactivities shown here suggest that they can be regarded as tumors of peptidergic neurons that are widely distributed throughout the central nervous system.This work was supported in part by grants of the Medical Research Council of Canada (SA, KK)