Clonal mixing, clonal restriction, and specification of cell types in the developing rat olfactory bulb

To understand the clonal relationship of various olfactory bulb (OB) cell types, OB progenitor cells were infected at embryonic day (E) 14, E15, and E17 with retroviral libraries encoding alkaline phosphatase or beta-galactosidase. After survival to postnatal day 10-15, sibling relationships were identified by polymerase chain reaction DNA amplification of distinct sequences in the retroviral constructs. Within the OB, clonal progeny dispersed widely in all directions. In sharp contrast, however, clonal dispersion between the OB and neocortex was not observed, although occasional clonal dispersion between the OB and pyriform and hippocampal regions could not be excluded. Most clones (84%) contained a single cell type, especially after E17 injections, suggesting the existence of either restricted precursors, or multipotential progenitors instructed by a restricted cellular environment. Mixed OB clones (16%) contained multiple cell types in the OB, or occasionally glial or neuronal cells outside the OB, demonstrating the existence of multipotential OB progenitors, likely at a stage before formation of the olfactory rostral migratory stream. Surprisingly, OB glial cells were not labeled, suggesting distinct lineages or perhaps distinct migratory paths for glia and neurons into the OB. A hierarchical cell lineage is proposed that involves a multipotential progenitor that gives rise to potentially more limited progenitors.     

The processing of secretogranin II in the peripheral nervous system: release of secretoneurin from porcine sympathetic nerve terminals

The distribution of secretoneurin (SN), a peptide derived from secretogranin II (SgII), in the coeliac ganglion, the splenic nerve and the spleen was examined by immunohistochemistry. In the ganglion, SN immunoreactivity (IR) was unevenly distributed. Positive nerve terminals densely surrounded some postganglionic perikarya in which also intense SN-IR was present. In the crushed splenic nerves, intense immunoreactivities appeared proximal (but to a less extent also distal) to the crush of the nerve. Analysis by cytofluorimetric scanning (CFS) demonstrated that SN-IR and neuropeptide Y immunoreactivity (NPY-IR) were predominant in the axons proximal to the crush representing anterogradely transported components. Using radioimmunoassay (RIA) we demonstrated that upon electrical stimulation (10 Hz, 1 min) of the splenic nerve, significant amounts of SN-IR (64.2+/-2.3 fmol) were released together with NA (4. 1x106+/-0.2 fmol) and NPY (330.0+/-7.2 fmol) from the isolated perfused porcine spleen. To evaluate the processing of SgII in sympathetic neurons, boiled tissue extracts (coeliac ganglia and splenic nerve) and boiled spleen perfusate (used as a suitable source for vesicle derived peptides) were analysed by gel filtration chromatography followed by SN-RIA. In all cases immunoreactivity was present solely as SN, indicating that SgII was fully processed to the free peptide. The evidence that SN is transported to the nerve terminals and is released from the porcine spleen upon nerve stimulation, suggests that it may modulate adrenergic neurotransmission and may also play a role in the neuroimmune communication.     

Synthetic retinoid CD437 induces S-phase arrest and apoptosis in human prostate cancer cells LNCaP and PC-3

BACKGROUND: Exposure of prostate carcinoma cell lines to retinoids, which function through the classical retinoic acid nuclear receptor, (RARs) or retinoid X receptors (RXRs), results in minimal cytostatic inhibition of cell proliferation. METHODS: Growth inhibition and various regulatory responses were investigated in two human prostate carcinoma cell lines (LNCaP and PC-3) treated with or without a synthetic retinoid, CD 437. RESULTS: Incubation of prostate carcinoma cell lines with a novel retinoid CD437 resulted in the marked inhibition of proliferation. LNCaP and PC-3 possessed IC50 values for CD437 of 375 nM and 550 nM, respectively. Incubation with 1 microM CD437 for 24 hr resulted in 100% and 60% inhibition of growth in LNCaP and PC-3 cells, respectively. Simultaneously, cell flow cytometric analyses revealed a dramatic increase of the cell population in S phase, in both LNCaP (from 38.6% up to 86.7%) and PC-3 (27.9% to 55.7%), and a decreased proportion of cells in G2 phase, in LNCaP (from 23.7% down to 1.2%) and PC-3 (14.9% to 2.2%), indicating a significant S-phase arrest. The cell growth inhibition and S-phase arrest in these cells were followed by apoptosis, as revealed by the acquisition of the characteristic cell morphology including the appearance of apoptotic bodies, and further confirmed by cellular DNA fragmentation. CD437-induced-S phase arrest was associated with upregulated mRNA levels of p21waf1/cip1/sdi1 in both LNCaP (p53+/+) and PC-3 (53-/-) cells. CONCLUSIONS: CD437 represents a unique retinoid that induces S-phase arrest and apoptosis in both androgen-dependent (LNCaP) and -independent (PC-3) human prostate cancer cells, suggesting a potential role of CD437 in the treatment of human prostate cancer.     

肉毒碱治疗TPN大鼠肝脂肪变性的研究

目的 探讨在全胃肠外营养（ＴＰＮ）中补充肉毒碱减轻肝脂肪变性的作用。方法 １８只正常Ｗｉｓｔａｒ大鼠和１９只肝硬化Ｗｉｓｔａｒ大鼠分别随机分为６组,Ａ１组、Ａ２组,自由进食和进水（各６只）;Ｂ１组、Ｂ２组,ＴＰＮ（分别６只、７只）;Ｃ１组、 ,ＴＰＮ加肉毒碱（各６只）。各组实验结束后测肝功能,肝脂肪及行肝脏的组织学检查。结果 ＴＰＮ组肝内脂肪显著２,ＴＰＮ＋肉毒碱组肝内脂肪明显减少。结论 在ＴＰＮ     

不同生物相容性的透析膜对红细胞免疫功能的影响

目的：了解血液透析病人透析过程中红细胞免疫功能指标的动态改变及不同生物相容性的透析膜对其变化的影响。方法：分别采用铜仿膜（Ｃｕ膜）、聚砜膜（ＰＳ膜）、聚甲基丙烯酸甲酯膜（ＰＭＭＡ膜）,观察了透析过程中不同时相的红细胞免疫功能指标ＲＢＣ－Ｃ３ｂ和ＲＢＣ－ＩＣ的变化。结果：尿毒症病人的 ＲＢＣ－Ｃ３ｂ显著下降, ＲＢＣ－ＩＣ显著增高。透析开始后,早期 ＲＢＣ－Ｃ３ｂ进一步下降,其后逐渐上升;而 ＲＢＣ－ＩＣ早期逐渐增加,其后逐渐稳定。结论：Ｃｕ膜能明显地影响红细胞的免疫功能; Ｐｓ膜次之; ＰＭＭＡ膜对其影响最小。     

Discovery of novel non-peptide CCR1 receptor antagonists

Ligands for the CCR1 receptor (MIP-1alpha and RANTES) have been implicated in a number of chronic inflammatory diseases, most notably multiple sclerosis and rheumatoid arthritis. Because these ligands share a common receptor, CCR1, we sought to discover antagonists for this receptor as an approach to treating these disorders. A novel series of 4-hydroxypiperidines has been discovered by high throughput screening (HTS) which potently inhibits the binding of MIP-1alpha and RANTES to the recombinant human CCR1 chemokine receptor. The structure-activity relationships of various segments of this template are described as the initial HTS lead 1 was optimized synthetically to the highly potent receptor antagonist 6s. This compound has been shown to have at least 200-fold selectivity for inhibition of CCR1 over other human 7-TM receptors, including other chemokine receptors. In addition, data obtained from in vitro functional assays demonstrate the functional antagonism of compound 6s and structurally related analogues against the CCR1 receptor in a concentration dependent manner. The discovery and optimization of potent and selective CCR1 receptor antagonists represented by compound 6s potentially represent a novel approach to the treatment of chronic inflammatory diseases.     

Alterations of striatal monoamine metabolites in young rats following pre- and postnatal lead exposure

Dam rats were given lead (0, 0.58, 1.76, and 5.27 mmol/l) containing water ad lib from day 16 of gestation to weaning of the offspring on day 21 postpartum. The pups continued drinking the same lead containing water until the postnatal day 30. At the 30th day postpartum, the pups in each lead treated group were divided into four groups. The first group contains six male pups (PN30M). The second, third, and fourth groups contain six female pups (PN30F, PN60a, PN60b), respectively. The six female pups from control group formed the fifth group (PN60c). PN60a continued drinking the same lead-containing water until the postnatal day 60. PN60b were dosed with distilled water instead of lead-containing water from the 30th day to the 60th day postpartum. PN60c began to expose to 5.27 mmol Pb/l from the 30th day to the 60th day postpartum. The rats in PN30M and PN30F were decapitated on the 30th day postartum, whereas PN60a, PN60b, and PN60c were decapitated on the 60th day postpartum. The contents of metabolites of monoamine neurotransmitters: homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyin-doleacetic acid (5-HIAA) in striatum were determined using high performance liquid chromatography with electrochemical detection (HPLC-ECD). There were significant increases in the concentrations of HVA (1.58 ± 0.30 vs. 1.17 ± 0.12 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30M, p < 0.01; and 1.44 ± 0.08 vs. 1.17 ± 0.10 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN60a, p < 0.05) and DOPAC (2.39 ± 0.25, 2.47 ± 0.28, 2.39 ± 0.44 vs. 1.82 ± 0.24 ng/mg wet tissue in three lead treated groups of PN60a, p < 0.05). The significant decreases in the concentration of MHPG (37.33 ± 5.53, 32.02 ± 6.87, 33.31 ± 2.41 vs. 43.85 ± 4.93 ng/mg wet tissue in the 0.58 mmol Pb/l group of PN60a, p < 0.05; in the 1.76 and the 5.27 mmol Pb/l group of PN60a, p < 0.01) and 5-HIAA (0.23 ± 0.04 vs. 0.38 ± 0.05 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30M, p < 0.05; 0.26 ± 0.09 vs. 0.45 ± 0.09 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30F, p < 0.05; 0.31 ± 0.08 vs. 0.44 ± 0.08 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN60a, p < 0.05) were observed. No significant changes in the concentration of monoamine metabolites were observed either in rats of PN60b or PN60c. The results demonstrated the disturbances of monoamine metabolism in the striatum of developmental lead exposed rats.     

Another CT sign of sinonasal polyposis: truncation of the bony middle turbinate

In order to study the features of sinonasal polyposis (SNP) on CT, 100 consecutive coronasal sinus CT examinations done for chronic inflamamtory sinonasal disease were reviewed. The CT findings of the 27 fully documented SNPs were analyzed. All our SNPs were bilateral. There was a strong tendency for extensive involvement. Nasal polyps were seen in 22 of 27 (81%); bony trabecular deossification in 23 of 27 (85%); widening of infundibulum in 26 of 27(96%). We discovered a new sign truncation of the bony middle turbinate, where the bulbous part of bony middle turbinate was missing, in 51 of 26 (58 %) of SNP patients without a previous history of middle turbinectomy, 12 of 15(80%) were bilateral. The one SNP patient (1 of 27) with previous middle turbinectomy was not regarded to be real truncation. Truncation of the bony middle turbinate is a characteristic and easily recognizable ancillary sign, and is not seen in other patterns of sinusitis. Together with other features on coronal sinus CT, this adds diagnostic confidence in diagnosing sinonasal polyposis. Correspondence to: E. Y. Liang     

A discussion of jaws relation in complete denture restoration]

We studied jaws relation of 8 edentulous patients after complete denture restoration by using Digital Sirognathograph (D-SGG).The results indicated that the maximum intercuspation occlusion (i.e.CO or MCP) is not commonly coincident with the CRO,and the discrepancy is statistically significant.The CO is anterior to the CRO by 0.72+/-0.39mm,and it may vary significantly in different closures of the same patient. This implies that the termination of the occlusion with neuromusculature is not strictly precise and constant,but alters in a corresponding range.So,it seems reasonable to develop a "freedom of centric" in the range of 0.72+/-0.39mm anterior to the CRO.The physiological functional occlusion,therefore,is restricted to neither of the CO nor the CRO, but is guided between the two.