Testicular metastasis of primary cecal carcinoid tumor

Testicular carcinoids are rare and the majority are of primary testicular origin. Testicular carcinoids can also be secondary from extra-testicular primary tumors, but the incidence is even less common. The case described here is a patient who initially had an infiltrating cecal carcinoid with hepatic metastasis. Following surgery, he was managed with octreotide and had close monitoring of the levels of serum serotonin and its urinary metabolite. He experienced a fairly indolent clinical course and 5 years after excision of the primary cecal carcinoid, his hepatic lesion has virtually been unchanged. However, he developed a secondary testicular metastasis. He has otherwise remained well, without evidence of metastases elsewhere on imaging studies.     

Divergent effects of prostaglandin receptor signaling on neuronal survival

Induction of cyclooxygenase-2 (COX-2) with production of prostaglandins occurs in a wide spectrum of acute and chronic neurodegenerative diseases and is associated with neuronal death. Inhibition of the COX-2 pathway and downstream production of prostaglandins protect neurons in rodent models of cerebral ischemia and neurodegeneration. Recent studies investigating the functions of selected prostaglandin receptor pathways in mediating COX-2 neurotoxicity have demonstrated both toxic and paradoxically neuroprotective effects of several receptors in models of excitotoxicity. In this study, we investigate the functions of additional prostaglandin receptors not previously characterized in organotypic models of glutamate excitotoxicity. We find that PGD₂, PGI₂, and PGF_2α receptors protect motor neurons in an organotypic spinal cord model of amyotrophic lateral sclerosis (ALS). In addition, PGI₂ and TXA₂ receptors rescue CA1 neurons in an organotypic hippocampal model of N-methyl-d-aspartate excitotoxicity. However, in a model of inflammation induced by lipopolysaccharide, prostaglandin receptors previously found to be protective in excitotoxicity now cause CA1 neuronal death. Taken together, these studies identify novel eicosanoid receptor signaling pathways that mediate neuronal protection in excitotoxic paradigms; these data also support the emerging hypothesis that the toxic/protective effects of eicosanoid signaling on neuronal viability diverge significantly depending on whether excitotoxicity or inflammation predominates as the underlying toxic stimulus.     

Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions

Heterotrimeric G proteins mediate asymmetric division of Drosophila neuroblasts. Free Gbetagamma appears to be crucial for the generation of an asymmetric mitotic spindle and consequently daughter cells of distinct size. However, how Gbetagamma is released from the inactive heterotrimer remains unclear. Here we show that Locomotion defects (Loco) interacts and colocalizes with Galphai and, through its GoLoco motif, acts as a guanine nucleotide dissociation inhibitor (GDI) for Galphai. Simultaneous removal of the two GoLoco motif proteins, Loco and Pins, results in defects that are essentially indistinguishable from those observed in Gbeta13F or Ggamma1 mutants, suggesting that Loco and Pins act synergistically to release free Gbetagamma in neuroblasts. Furthermore, the RGS domain of Loco can also accelerate the GTPase activity of Galphai to regulate the equilibrium between the GDP- and the GTP-bound forms of Galphai. Thus, Loco can potentially regulate heterotrimeric G-protein signaling via two distinct modes of action during Drosophila neuroblast asymmetric divisions.     

Activation of the parapyramidal region in the ventral medulla stimulates gastric acid secretion through vagal pathways in rats

Neurons synthesizing thyrotropin-releasing hormone, substance P and serotonin in the medullary caudal raphe nuclei project to the dorsal vagal complex and play a role in the central vagal regulation of gastric function. Neurons in the parapyramidal region in the ventral medulla share similar biochemical coding and projections as those in the caudal raphe nuclei. The role of the parapyramidal region in the autonomic regulation of gastric acid secretion was investigated in urethane-anesthetized rats. Unilateral microinjection of kainate into the parapyramidal region at 10, 15 and 20 ng induced a dose-related stimulation of gastric acid secretion (net increases: 22.2+/-11.2, 40.5+/-8.5 and 89.8+/-19.4 micromol/60 min, respectively), while injection of vehicle had no effect (net change: -0.1+/-1.4 micromol/60 min). Time-course studies showed a nine-fold peak increase over basal at 30 min after parapyramidal injection of kainate (20 ng) and acid secretion returned to basal level at 70 min. Microinjections of kainate (15-20 ng) outside the parapyramidal region or into the parapyramidal region in vagotomized rats had no effect. Exposure to cold (4 degrees C) for 2 h, which is known to induce vagally mediated gastric secretory and motor responses through medullary thyrotropin-releasing hormone pathways, increased the number of Fos-positive cells in the caudal, middle and rostral parts of the parapyramidal region to 4.3+/-0.4, 9.4+/-0.9 and 18.4+/-1.6/section, respectively, compared with 0.1+/-0. 1, 0.1+/-0.0 and 0.7+/-0.6/section, respectively, in rats maintained at room temperature. Most of the Fos-labeled cells co-expressed pro-thyrotropin-releasing hormone messenger RNA signal and/or were serotonin immunoreactive. These data show that chemical activation of neurons in the parapyramidal region results in a vagal-dependent stimulation of gastric acid secretion and that acute cold exposure activates parapyramidal neurons containing pro-thyrotropin-releasing hormone and/or serotonin, suggesting a potential role of the parapyramidal region, in addition to the caudal raphe nuclei, as medullary sites involved in the vagal regulation of gastric function.     

大鼠脊髓损伤后NGF及其受体TrkA在运动神经元及神经胶质细胞表达的变化

为探讨脊髓损伤后运动神经元及神经胶质细胞内神经生长因子(NGF)及其高亲和力受体(TrkA)表达的变化,用改良Allen重击法损伤SCI组动物T12脊髓,按伤后存活时间再将动物分为脊髓损1 d组、2 d组和5 d组。各组动物的脊髓切片经ABC法免疫组织化学染色,用光镜观察TrkA及NGF在脊髓前角运动神经元表达的变化和胶质纤维酸性蛋白(GFAP)及NGF免疫反应阳性胶质细胞的反应性增生程度,并进行图像分析。结果显示:脊髓损伤后前角运动神经元TrkA及NGF的表达随脊髓损伤后动物存活时间的延长逐渐上调;脊髓白质和灰质内尤其是皮质脊髓束内GFAP及NGF阳性胶质细胞明显增生;与此同时,室管膜细胞内亦可见明显的NGF免疫反应产物。上述结果表明,脊髓损伤可刺激脊髓前角运动神经元表达TrkA及NGF,通过自分泌维持受损神经元的存活;损伤部位反应性增生的胶质细胞亦可产生NGF,通过旁分泌作用于脊髓前角运动神经元或皮质脊髓束的轴突末梢,以维持运动神经元的存活及促进皮质脊髓束的再生;适时补充外源性神经营养素或改变损伤局部的微环境将有利于受损脊髓的修复和再生。     

A tctex1-Ca2+ channel complex for selective surface expression of Ca2+ channels in neurons

Voltage-gated Ca(2+) channels (VGCCs) are important in regulating a variety of cellular functions in neurons. It remains poorly understood how VGCCs with different functions are sorted within neurons. Here we show that the t-complex testis-expressed 1 (tctex1) protein, a light-chain subunit of the dynein motor complex, interacts directly and selectively with N- and P/Q-type Ca(2+) channels, but not L-type Ca(2+) channels. The interaction is insensitive to Ca(2+). Overexpression in hippocampal neurons of a channel fragment containing the binding domain for tctex1 significantly decreases the surface expression of endogenous N- and P/Q-type Ca(2+) channels but not L-type Ca(2+) channels, as determined by immunostaining. Furthermore, disruption of the tctex1-Ca(2+) channel interaction significantly reduces the Ca(2+) current density in hippocampal neurons. These results underscore the importance of the specific tctex1-channel interaction in determining sorting and trafficking of neuronal Ca(2+) channels with different functionalities.     

Comparison of two single-chain antibodies that neutralize canine parvovirus: analysis of an antibody-combining site and mechanisms of neutralization

We cloned the heavy- and light-chain variable domains of two monoclonal antibodies that recognize each of the two major neutralizing antigenic sites of the canine parvovirus (CPV) capsid. After expression in Escherichia coli as single-chain variable domains (scFv) with glycine-serine linker sequences, both scFv bound CPV capsids with the same specificity as the intact IgG, but with 10- to 20-fold lower avidity. Both scFvs neutralized CPV infectivity with efficiency similar to that of the IgG. Although both IgGs inhibited hemagglutination by CPV, only one scFv was inhibiting. The binding of one of the antibodies has previously been analyzed by cryoelectron microscopic reconstruction and the epitope-binding residues predicted. Mutagenesis of predicted contact residues in three heavy-chain complementarity-determining regions (CDR) showed that mutants of CDR1 or CDR3 reduced the binding of the scFv by about 10-fold compared with the wild-type scFv, while no effect was seen for one mutant of CDR2. The levels of neutralization of CPV and of hemagglutination inhibition by the scFv mutants were proportional to their reduction in binding affinity compared with the wild type. Neither scFv blocked virus binding to host cells, but they both caused aggregation of the capsids and appeared to affect the process of infection after virus uptake into the cells.     

Molecular cloning and expression of a novel alternative splice variant of BRDT gene

In this study, a human adult testis cDNA microarray was constructed and hybridized with (33)P-labeled human adult testis, embryo testis and sperm cDNA probes, respectively. A novel alternative splice variant of BRDT gene, named BRDT-NY, presumably involved in testicular function was cloned. It was expressed 3.96-fold more in human adult than embryo testis and also expressed in human spermatozoa. Similarly, RT-PCR revealed a differential expression pattern of this gene in human adult testes and fetal testes. The full length of BRDT-NY was 3438 bp and contained a 2883 bp open reading frame, encoding a 960-amino-acid protein. Sequence analysis showed that it has two bromodomains in N-terminal of the protein. Multiple tissue RT-PCR results showed that BRDT-NY was exclusively expressed in testis. mRNA expression of BRDT-NY gene was deleted in some azoospermic patients' testes. These experiments suggested that BRDT-NY gene may have an important role in the process of spermatogenesis and may be correlated with male infertility.     

125I-白细胞介素-8在小鼠体内的分布研究

为了解白细胞介素 - 8的体内行为 ,用 Bolton- Hunter法对 IL- 8进行 1 2 5I标记 ,并测定它在小鼠体内的分布 ;得到了 1 2 5I- IL- 8在小鼠血、心、肝、肺、肾、骨、脾等脏器中的分布以及它在血液中的快相半排期 T1 /2α为 0 .3 2 h和慢相半排期 T1 /2β为 8.0 1h。1 2 5I- IL- 8主要通过肾排除