国际间合作遏制青光眼:2008年3月6日第一届"世界青光眼日"

众所周知,青光眼是全球第二位可治疗的致盲性眼病.作为不可逆盲的重要原因,其防治已成为重要的公共卫生问题,其在世界各国致盲眼病的排名不断攀升[1].尽管在发展中国家及发达国家,白内障和年龄相关性黄斑变性分别是首位的致盲原因,但在发达国家有一半的青光眼患者不知道自己患有青光眼[2],发展中国家中则有超过90%的青光眼患者对自己的疾病一无所知,甚至从未听说过青光眼.尽管对青光眼危险因素的理解有所进步,但对这一状况的改善并不明显.青光眼尽管可以发生于任何年龄,但在老年人更常见,其患病率随着年龄增长而增加.预计到2020年,全世界将有7960万人患有青光眼,其中1120万人最终可能发展为双眼盲[1].     

The occipitoparietal pathway of the macaque monkey: comparison of pyramidal cell morphology in layer III of functionally related cortical visual areas

The dendritic morphology of pyramidal cells located at the base of layer III in the primary visual area (V1), the second visual area (V2), the middle temporal area (MT), the ventral portion of the lateral intraparietal area (LIPv) and in the portion of cytoarchitectonic area 7a within the anterior bank of the superior temporal sulcus was revealed by injecting neurons with Lucifer Yellow in fixed, flattened slices of macaque monkey visual cortex. These areas correspond to different levels of the occipitoparietal cortical 'stream', which processes information related to motion and spatial relationships in the visual field. The tissue was immunocytochemically processed to obtain a light-stable diaminobenzidine reaction product, revealing the dendritic morphology in fine detail. Retrogradely labelled MT- projecting neurons in supragranular V1 (layer IIIc of Hassler's nomenclature, corresponding to Brodmann's layer IVb) were predominantly pyramidal, although many spiny multipolar (stellate) cells were also found. The average basal dendritic field area of pyramidal neurons in sublamina IIIc of V1 was significantly smaller than that in the homologous layer of V2, within the cytochrome oxidase-rich thick stripes. Furthermore, the average basal dendritic field areas of V1 and V2 pyramidal neurons were significantly smaller than those of neurons in MT, LIPv and area 7a. There was no difference in basal dendritic field area between layer III pyramidal neurons in areas MT, LIPv and 7a. While the shape of most basal dendritic fields was circularly symmetrical in the dimension tangential to the cortical layers, there were significant biases in complexity, with dendritic branches tending to cluster along particular axes. Sholl analysis revealed that the dendritic fields of neurons in areas MT, LIPv and 7a were significantly more complex (i.e. had a larger number of branches) than those of V1 or V2 neurons. Analysis of basal dendritic spine densities revealed regional variations along the dendrites, with peak densities being observed 40-130 microns from the cell body, depending on the visual area. The peak spine density of layer III pyramidal neurons in V1 was lower than that observed in V2, MT or LIPv, which were all similar. Pyramidal neurons in area 7a had the greatest peak spine density, which was on average 1.7 times that found in V1. Calculations based on the average spine density and number of dendritic branches at different distances from the cell body demonstrated a serial increase in the total number of basal dendritic spines per neuron at successive stations of the occipitoparietal pathway. Our observations, comparing dendritic fields of neurons in the homologous cortical layer at different levels of a physiologically defined 'stream', indicate changes in pyramidal cell morphology between functionally related areas. The relatively large, complex, spine-dense dendritic fields of layer III pyramidal cells in rostral areas of the occipitoparietal pathway allow these cells to sample a greater number of more diverse inputs in comparison with cells in 'lower' areas of the proposed hierarchy.      

Hepatitis B and C in doctors and dentists in Nigeria

We surveyed a random sample (n = 75) of doctors and dentists at University College Hospital, Ibadan, Nigeria. They were offered anonymous testing for hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAG), antibodies to hepatitis B core antigen (anti-HBc) and to hepatitis C virus (anti-HCV), by enzyme immunoassay. The results suggest a high prevalence of hepatitis B virus (HBV) with a high potential of transmissibility, as well as a high prevalence of HCV infection. The majority of the doctors and dentists use universal precaution for protection against viral hepatitis on < 50% of the occasions when they carry out procedures on their patients. Infection with HBV was associated with type of specialty (surgeons, dentists) and lack of HBV vaccination (p < 0.05). After logistic regression, these factors were independently associated with HBV infection (p < 0.05). Sixty (80%) had not received prior HBV vaccination. Unvaccinated personnel were more likely to be surgeons, dentists, < 37 years of age, and have fewer years of professional activity (p < 0.05). After logistic regression, only fewer years of professional activity remained independently associated with lack of vaccination (p < 0.05). To reduce the occupational exposure of HBV, universal precautions must be rigorously adhered to when the doctors and dentists carry out procedures on their patients, and all health-care workers should be vaccinated with HBV vaccine and the HCV vaccine, when it becomes available.      

Relationship between tumor necrosis factor-α and liver fibrosis

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Hepatitis B virus DNA in the serum of Sardinian blood donors negative for the hepatitis B surface antigen

The high endemicity of hepatitis B virus (HBV) infection and liver disease in Sardinia led us to assess the occurrence of HBV DNA in 1,411 sera of two selected groups of hepatitis B surface antigen (HBsAg)- negative blood donors: 793 with abnormal serum alanine aminotransferase (ALT) and 618 with normal serum ALT values (determined during routine testing of their blood donation). HBV DNA sequences were detected by dot-blot hybridization in 68 of 793 subjects (9%) with abnormal ALT but only in three of 618 subjects (0.5%) with normal ALT. HBV-core antibody (anti-HBc) was detected in 338 of 793 subjects (43%) with abnormal ALT as well as in 125 of 618 subjects (20.2%) with normal ALT. Among the 71 subjects positive for serum HBV DNA, 22 (31%) were positive for anti- HBc, while 49 (69%) were negative for all serologic markers of HBV infection. Thus, a high frequency of anti-HBc in apparently healthy HBsAg-negative individuals and a high prevalence of serum HBV DNA in the absence of immunologic markers of HBV infection suggest the existence of genetic variants of HBV that may be responsible for some of the presumed NANB hepatitis encountered in Sardinia and possibly other areas of high endemicity for HBV.     

Early detection of antibodies against rDNA-produced HIV proteins with a flow cytometric assay

There is evidence that some human immunodeficiency virus (HIV)-infected individuals have prolonged periods of seronegativity. A flow cytometric immunoreactive bead (IRB) assay is described for quantitative, simultaneous, and early detection of antibodies to HIV. Polystyrene beads of four diameters, each size coated with a different HIV recombinant DNA-produced protein (p24, p31, gp41, or gp120), bound anti- HIV antibodies detected with fluorescent antiglobulin. The IRB assay was performed on a panel of blood donor samples, many giving consistently false-positive enzyme immunoassay (EIA) and indeterminant Western blot (WB) results. The IRB assay proved as sensitive and more specific than currently licensed EIA and WB tests. Results on serial samples from eight HIV-infected individuals indicated that quantitation of anti-p24 by IRB assay may be useful in monitoring disease progression. Sequential pre- and post-EIA seroconversion sera from 35 HIV-infected homosexual men were tested by the IRB assay using IgM- and IgG-specific fluorescent probes. All 35 cases were IRB assay positive for at least one rDNA-p either before (17 of 35, 49%) or at the time of EIA positivity. Eleven cases (31%) initially had only IgM anti-HIV, primarily to gp41 (17%). In two individuals, the IgM response was detected at least 18 months before EIA seroconversion. The IRB assay is a widely applicable analytic procedure, potentially useful in pretransfusion anti-HIV screening of blood.     

Chloride transport in primary cultures of rabbit colonocytes at different stages of development

BACKGROUND & AIMS: Ontogeny of colonic Cl- transport and its regulation has been characterized inadequately. The aim of this report was to study developmental changes in Cl- transport in primary cultures of rabbit distal colonocytes. METHODS: Colonocytes from newborn (7-9 days old), weanling (25-28 days old), and adult (6 months old) rabbits were cultured for 24 hours on a collagen IV matrix, and Cl- transport was measured using the fluoroprobe 6-methoxyquinolyl acetoethyl ester. RESULTS: Cl- permeabilities were dependent on [Cl-]o with maximal rates (in millimoles per liter per second) at [Cl-]o = 75 mmol/L (newborns; 0.15 +/- 0.04; weanlings; 0.2 +/- 0.02; and adults, 0.32 +/- 0.06). Influx was inhibited significantly by the Cl- channel (50 mumol/L diphenylamine-2-carboxylate) and the Na(+)-K(+)- 2Cl- cotransport (10 mumol/L furosemide) inhibitors. The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent secretagogues, prostaglandin E1 (1 mumol/L), forskolin (1 mumol/L), and 8-bromo-cAMP (100 mumol/L), and the protein kinase C activator, phorbol 12-13 dibutyrate (1 mumol/L), increased Cl- influx significantly in all groups with adults showing greatest stimulation. However, taurodeoxycholate (0.025-1 mmol/L) had an effect only in the adult and the guanosine 3',5'-cyclic monophosphate (cGMP) activators STa and 8-bromo-cGMP had no effect. CONCLUSIONS: Rabbit distal colonocytes possess inhibitor-sensitive Cl- permeabilities even in neonates. However, the ontogeny of their regulation depends on the secretagogue-signaling pathway. (Gastroenterology 1996 Dec;111(6):1541-50)     

Electroporation of synthetic oligodeoxynucleotides: a novel technique for ex vivo bone marrow purging

Recent data suggest that tumor cells contaminating reinfused bone marrow may contribute to relapse in patients undergoing autologous bone marrow transplantation. Purging strategies that are able to remove these contaminating tumor cells need to be developed. This study describes how electroporation (EP) can be used to improve intracellular delivery of synthetic antisense oligodeoxynucleotides (ODNs), thereby enhancing their ability to suppress a target protein. Antisense ODNs that were introduced into cells by EP led to immediate suppression of targeted c-myc protein; this was associated with rapid cell death in the diffuse histiocytic lymphoma, U937; Burkitt's lymphoma, ST486; breast carcinoma, MCF-7; and Ewing's sarcoma, CHP-100, cell lines. Electroporation was found to have little or no detrimental effect on cells responsible for murine hematopoietic long-term reconstitution as determined from in vivo competitive repopulation studies. Using human c- myc-directed antisense ODNs as a model for the application of this approach to bone marrow purging, selective killing of human lymphoma U937 cells relative to normal human bone marrow cells was shown in cell mixing studies. In vivo studies were performed in which a survival advantage was shown for athymic mice that were inoculated with antisense-treated U937 cells as opposed to control cells. These studies suggest that EP of bone marrow may be of use in enhancing intracellular delivery of a variety of molecular/pharmaceutical agents. Taken together, these data suggest that the use of electroporation to enhance delivery of antisense ODNs is a promising new approach towards ex vivo bone marrow purging.