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PubMed1991

The spread of HIV-1 in Africa: sexual contact patterns and the predicted demographic impact of AIDS.

The spread of HIV-1 in Africa is examined here in the light of recent information on the main epidemiological and behavioural determinants of transmission. Mathematical models incorporating demographic, epidemiological and behavioural processes are used to assess the potential demographic impact of the disease AIDS. These analyses highlight the significance of patterns of sexual behaviour, and in particular networks of sexual contact, on the predicted spread of infection. Current data reveal substantial variations in the degree of spread between and in countries, but new analyses support earlier predictions that in the worst-afflicted areas AIDS is likely to change population growth rates from positive to negative values in a few decades.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Rapid spread of an inherited incompatibility factor in California Drosophila.

In Drosophila simulans in California, an inherited cytoplasmic incompatibility factor reduces egg hatch when infected males mate with uninfected females. The infection is spreading at a rate of more than 100 km per year; populations in which the infection was rare have become almost completely infected within three years. Analyses of the spread using estimates of selection in the field suggest dispersal distances far higher than those found by direct observation of flies. Hence, occasional long-distance dispersal, possibly coupled with local extinction and recolonization, may be important to the dynamics. Incompatibility factors that can readily spread through natural populations may be useful for population manipulation and important as a post-mating isolating mechanism.

Animals↗
PubMed1979

The spread of breast cancer: importance of the intrathoracic lymphatic route and its relevance to treatment.

Detailed necropsies were performed on 26 individuals who had died of disseminated breast carcinoma, to assess the frequency of spread to the lungs, pleura and pericardium, and to determine the likely routes of spread to these sites. Tumour was present in the lung parenchyma in 67% of the lungs examined, in the visceral pleura in 75% and the parietal pleura in 50%. Although even small deposits of pleural tumour were invariably visible to naked-eye examination, lung parenchymal involvement was almost invariably microscopic, despite its frequently extensive distribution. This finding draws attention to the difficulties of clinical staging with respect to lung metastases. Tumour in lymphatics predominated over that in blood vessels in both lung and pleura and this, together with the widespread mediastinal lymphnode infiltration found, suggests that the lymphatic system forms the dominant route of spread of breast carcinoma to the thorax. The possible role of mediastinal lymphatics in the dissemination of breast cancer to bone and liver is also discussed. Our findings suggests that the fields of adjuvant irradiation after primary surgery should include the mediastinal lymphatic network.

Breast Neoplasms↗
PubMed1988

Neural spread of herpes simplex virus to the eye of the mouse: microbiological aspects and effect on the blink reflex.

This paper reports the microbiological aspects of zosteriform spread of herpes simplex virus (HSV) to the eye in the NIH strain of inbred mouse. Microbiological data support the concept of true zosteriform spread of herpes simplex virus from the inoculation site on the snout to the trigeminal ganglion, and thence to the eye. Following zosteriform spread of HSV to the eye, there is a frequent bacterial superinfection and this is associated with a typical clinical picture. Treatment of the mice with intensive systemic and topical antibiotics is able to alter the frequency with which this type of keratitis is seen.

Animals↗
PubMed2003

Magmatic and amagmatic seafloor generation at the ultraslow-spreading Gakkel ridge, Arctic Ocean.

A high-resolution mapping and sampling study of the Gakkel ridge was accomplished during an international ice-breaker expedition to the high Arctic and North Pole in summer 2001. For this slowest-spreading endmember of the global mid-ocean-ridge system, predictions were that magmatism should progressively diminish as the spreading rate decreases along the ridge, and that hydrothermal activity should be rare. Instead, it was found that magmatic variations are irregular, and that hydrothermal activity is abundant. A 300-kilometre-long central amagmatic zone, where mantle peridotites are emplaced directly in the ridge axis, lies between abundant, continuous volcanism in the west, and large, widely spaced volcanic centres in the east. These observations demonstrate that the extent of mantle melting is not a simple function of spreading rate: mantle temperatures at depth or mantle chemistry (or both) must vary significantly along-axis. Highly punctuated volcanism in the absence of ridge offsets suggests that first-order ridge segmentation is controlled by mantle processes of melting and melt segregation. The strong focusing of magmatic activity coupled with faulting may account for the unexpectedly high levels of hydrothermal activity observed.

Journal Article↗
PubMed2004

Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses.

Mosquito-borne flaviviruses provide some of the most important examples of emerging and resurging diseases of global significance. Here, we describe three of them: the resurgence of dengue in tropical and subtropical areas of the world, and the spread and establishment of Japanese encephalitis and West Nile viruses in new habitats and environments. These three examples also illustrate the complexity of the various factors that contribute to their emergence, resurgence and spread. Whereas some of these factors are natural, such as bird migration, most are due to human activities, such as changes in land use, water impoundments and transportation, which result in changed epidemiological patterns. The three examples also show the ease with which mosquito-borne viruses can spread to and colonize new areas, and the need for continued international surveillance and improved public health infrastructure to meet future emerging disease threats.

Aedes↗
PubMed2004

Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread.

OBJECTIVE: To study the compliance and changes in plasma lipids, plant sterols, fat-soluble vitamins and carotenoids in children and parents with familial hypercholesterolemia (FH) consuming a plant sterol ester-enriched (PSE) spread. DESIGN: A 26-week open-label follow-up of children who had previously been studied in a controlled cross-over design. The parents were also included in the open-label arm of the study. SETTING: Outpatient clinic for treatment of hyperlipidemia. SUBJECTS: A total of 37 children (7-13 y) and 20 parents (32-51 y) diagnosed with 'definite' or 'possible' heterozygous FH. In all, 19 of the parents, but no children, used statins. All were patients at the Lipid Clinic, National Hospital in Oslo. INTERVENTIONS: Subjects were recommended to eat 20 g/day of PSE spread as part of their lipid-lowering diet. RESULTS: The mean intake of PSE spread was 13.7 and 16.5 g/days in the children and parents, respectively, corresponding to 1.2 and 1.5 g of plant sterols. Plasma total cholesterol decreased by 9.1% in both children (P<0.001) and parents (P=0.002). The corresponding decreases in LDL cholesterol were 11.4% (P<0.001) and 11.0% (P=0.012). Increases in serum lathosterol, campesterol and sitosterol, adjusted for total cholesterol, were observed in the children (31, 96, 48%, respectively, P<0.001) at the end of the controlled cross-over period. In the parents, serum campesterol and sitosterol, adjusted for total cholesterol, increased by 92 and 39%, respectively (P< 0.001). Lipid-adjusted serum alpha- and beta-carotene decreased by 17.4% (P=0.008) and 10.9% (P=0.018), respectively, in the children at the end of the controlled PSE period, but increased again during the follow-up. In the parents, serum alpha- and beta-carotene concentrations were unchanged, while serum lutein and lycopene decreased by 7.3% (P=0.037) and 14.6% (P=0.044), respectively. CONCLUSIONS: Sustained efficacy of cholesterol reduction and long-term compliance of PSE intake were demonstrated in this study.

Adolescent↗
PubMed2007

ZAP-70 kinase regulates HIV cell-to-cell spread and virological synapse formation.

HIV efficiently spreads in lymphocytes, likely through virological synapses (VSs). These cell-cell junctions share some characteristics with immunological synapses, but cellular proteins required for their constitution remain poorly characterized. We have examined here the role of ZAP-70, a key kinase regulating T-cell activation and immunological synapse formation, in HIV replication. In lymphocytes deficient for ZAP-70, or expressing a kinase-dead mutant of the protein, HIV replication was strikingly delayed. We have characterized further this replication defect. ZAP-70 was dispensable for the early steps of viral cycle, from entry to expression of viral proteins. However, in the absence of ZAP-70, intracellular Gag localization was impaired. ZAP-70 was required in infected donor cells for efficient cell-to-cell HIV transmission to recipients and for formation of VSs. These results bring novel insights into the links that exist between T-cell activation and HIV spread, and suggest that HIV usurps components of the immunological synapse machinery to ensure its own spread through cell-to-cell contacts.

Cell Communication↗
PubMed2006

Fibrillin-1 regulates mesangial cell attachment, spreading, migration and proliferation.

The microfibrillar protein fibrillin-1 is present in many organs, including the vasculature, eye, and dermis, and is thought to convey structural anchorage and elastic strength. Fibrillin-1 is also a component of the mesangial matrix. To assess the functional relevance of fibrillin-1 for cell-matrix interactions in the glomerulus, we studied the attachment, spreading, migration and proliferation of mesangial cells on fibrillin-1 and the regulation of fibrillin-1 in experimental anti-Thy1.1 nephritis displaying mesangial cell migration and proliferation in vivo. During the acute phase of experimental Thy1.1 nephritis, glomerular fibrillin-1 messenger ribonucleic acid expression and protein immunoreactivity were significantly induced as compared to controls. In a hexosaminidase-based adhesion assay, mesangial cells showed concentration-dependent attachment to fibrillin-1, similar to what was observed for fibronectin. The cell attachment was Arg-Gly-Asp dependent. Further, fibrillin-1 significantly promoted spreading and focal contact formation detected by immunostaining for vinculin. Mesangial cell migration, assessed by a transmigration assay, and proliferation, measured by a 5-bromo-2'-deoxy-uridine incorporation assay, were augmented by fibrillin-1. In diabetic mice underexpressing fibrillin-1, glomerular cell proliferation, determined by counting proliferating cell nuclear antigen-positive cells in renal sections, was significantly lower than in diabetic control mice. We conclude that fibrillin-1 promotes mesangial cell attachment, spreading, migration, and proliferation. We speculate that fibrillin-1 may thus contribute to mesangial hypercellularity during glomerular disease.

Animals↗
PubMed2005

The SH2-domian-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met directly via tyrosine residue 1356 and involves hepatocyte growth factor (HGF)-induced lamellipodium formation, cell scattering and cell spreading.

Recently, evidence has been accumulating that inositol and phosphatidylinositol polyphosphate play important roles in a variety of signal transduction systems including membrane traffic, actin cytoskeleton rearrangement and cell motility. In this paper, we show for the first time that the SH2-domain-containing inositol 5-phosphatase (SHIP)-2 binds directly to the hepatocyte growth factor (HGF/SF) receptor, c-Met, via phosphotyrosine 1356. HGF induces the breakdown of cell junctions and the dispersion of colonies of epithelial cells including MDCK cells. Whereas only few lamellipodia are observed in MDCK cells 2 min after stimulation with HGF, both SHIP-2- and SHIP-1-overexpressing cells form large, broad lamellipodia. The number of lamellipodia is 2-4-fold greater than that of mock-transfected MDCK cells in the same time period and SHIP is found to colocalize with actin at the leading edge. Furthermore, overexpression of a catalytic inactive mutant of SHIP-2 suppresses HGF-potentiated cell scattering and cell spreading, although these mutant-expressing cells form enhanced number of lamellipodia 2 min after HGF stimulation. Interestingly, cells expressing a mutant lacking the proline-rich domain of SHIP-2 at the C-terminal form few lamellipodia, but still spread and scatter upon stimulation with HGF at a reduced rate. These data suggest that phosphatase activity is required for HGF-mediated cell spreading and scattering but not for alteration of lamellipodium formation, while the proline-rich region influences lamellipodium formation. Furthermore, treatment with 10 microM of phosphatidylinositol 3 (PI3) kinase inhibitor, LY294002, abrogates HGF-induced cell scattering of SHIP-2-overexpressing cells but not parental HEK293 cells, suggesting that a balance between PI3 kinase and SHIP is important for cell motility.

Animals↗
PubMed2006

Microchannel device using self-spreading lipid bilayer as molecule carrier.

We propose a microchannel device that employs a surface-supported self-spreading lipid bilayer membrane as a molecule carrying medium. The device has a micropattern structure fabricated on a SiO2 surface by photolithography, into which a self-spreading lipid bilayer membrane is introduced as the carrier medium. This system corresponds to a microchannel with a single lipid bilayer membrane height of approximately 5 nm, compared with conventional micro-fluidic channels that have a section height and width of at least several microm. The device is beneficial for detecting intermolecular interactions when molecules carried by the self-spreading lipid bilayer collide with each other in the microchannel. The validity of the device was confirmed by observing the fluorescence resonance energy transfer (FRET) between two dye molecules, coumarin and fluorescein.

Coumarins↗
PubMed1997

Colonic spread of 5-ASA enemas in healthy individuals, with a comparison of their physical and chemical characteristics.

BACKGROUND: 5-aminosalicylic acid (5-ASA) is widely used as topical treatment in patients with distal inflammatory bowel disease. The enema spread and retention time are considered to be important factors in the efficacy of this therapeutic agent. Whereas colonic spread is widely investigated in selected patient populations and volunteers, much less attention has been given to the in vitro differences of physical and chemical properties, although they may influence the in vivo characteristics. METHODS: Two different brand enemas, Salofalk and Asacol, both containing 2 g mesalazine, were compared with respect to their in vivo and in vitro characteristics. The retrograde spread, maximum distribution and wall adhesion, as well as the retention time of the enemas, was examined by the addition of a technetium tracer dose in 12 healthy volunteers on two separate occasions. In addition, several chemical properties such as pH, viscosity, particle size, dispersion rate, specific surface area and residual volume after application were analysed and compared. RESULTS: With its larger volume and higher viscosity the Asacol preparation reached a substantially larger proportion of the colon and produced a significantly higher retention time in the proximal parts of the large intestine. In addition, more than double the amount of 5-aminosalicylic acid was not expelled from the semi-rigid Salofalk enema container after application. With respect to chemical properties it was demonstrated that the Asacol preparation showed a significantly smaller size of micronized 5-aminosalicylic acid particles, better homogeneity and much less aggregation of the drug. This resulted in an almost threefold higher specific surface area per g active compound. CONCLUSIONS: The Asacol enema appears to be superior in several aspects of the galenical formulation. The better dispersion and larger specific surface area, in conjunction with a larger distribution, better bowel wall adherence and retention time in vivo, constitute a clear theoretical and possible clinical advantage.

Adult↗
PubMed1999

Clinicopathological study of intrapelvic cancer spread to the iliac area in lower rectal adenocarcinoma by serial sectioning.

BACKGROUND: The role of iliac lymphadenectomy in surgery for rectal cancer remains unknown. Detailed clinicopathological data on lateral cancer extension may be needed to determine the true role of this procedure. METHODS: Seventy consecutive patients with low rectal cancer who underwent systematic iliac lymphadenectomy between 1991 and 1995 were reviewed. The iliac area was divided into five regions: (1) middle rectal root, (2) internal iliac, (3) obturator, (4) common iliac and (5) external iliac. Iliac lymph nodes that were cancer-free based on conventional pathological examination were serially sectioned at 100-microm intervals and re-examined for occult microscopic involvement. RESULTS: Occult microscopic foci were detected in five (7 per cent) of the 70 patients, and the overall incidence of lateral cancer spread was 24 per cent (17 of 70). Among patients without other sites of distant metastasis or circumferential involvement of the margin, the 5-year survival rate of those with lateral spread was 35 per cent. Although the prognosis of patients with cancer involving multiple iliac regions was poor, three of six patients with metastasis to only a single region were alive without disease at 3 years. CONCLUSION: Surgeons should be aware of the possibility of localized lateral spread, including microscopic metastasis, when determining the optimum procedure for iliac lymphadenectomy in patients with rectal cancer.

Adenocarcinoma↗
PubMed2003

Evidence for intramolecular B-cell epitope spreading during experimental immunization with an immunogenic thyroglobulin peptide.

Thyroglobulin (Tg) is a target autoantigen in autoimmune thyroid diseases, such as Graves' disease (GD) and Hashimoto's thyroiditis. In a previous study we identified three 20mer Tg peptides bearing epitopes of autoantibodies associated with GD (TgP15, TgP26 and TgP41: sequences 2339-2358, 2471-2490 and 2651-2670 of human Tg, respectively). In the present study, we investigated the antigenicity of the above peptides in experimental immunization with Tg, the immunogenicity of antigenic peptides and the possibility of intramolecular B-cell epitope spreading during peptide immunization. For this purpose, two rabbits were injected with human Tg in CFA six times, every three weeks. Two control animals were injected only with CFA. Testing of antisera and of affinity-purified antibodies, by ELISA against the three peptides, revealed reactivity only to TgP41. This synthetic peptide was subsequently administered to two rabbits, in its free form (100 micro g in CFA six times, every two weeks). A strong serological response was developed not only against TgP41, but also to intact human and rabbit Tg. Immunization with TgP41 induced intramolecular B-cell epitope spreading, i.e. production of antibodies to sites on Tg other than that corresponding to TgP41, as revealed by immunoadsorption and competitive ELISA. Histopathological studies did not reveal any infiltration in thyroid glands. We conclude that peptide TgP41 encompasses not only an epitope of disease-associated autoantibodies, but also a dominant immunogenic epitope of experimentally induced Tg-specific antibodies, able to drive B-cell epitope spreading.

Animals↗
PubMed1999

Morphological evidence for field effect as a mechanism for tumour spread in mammary Paget's disease.

AIMS: The histogenesis of mammary Paget's disease is controversial. The purpose of this study was to investigate the mechanism of tumour spread in the nipple epidermis by examining 28 cases of mammary Paget's disease associated with underlying intraductal carcinoma. METHODS AND RESULTS: The atypical cells in the epidermis displayed a spectrum of cytological changes ranging from small-sized atypical cells located in the basal cell layer to large-sized atypical cells characteristic of Paget's cells in the upper layer of the epidermis. Serial sectioning revealed the presence of isolated, scattered and small atypical cells in the basal cell layer at the periphery of the epidermal lesion. The atypical cells, including those in the basal cell layer showed positive immunostaining for cytokeratin 7 and Her2/neu oncoprotein. Electron microscopy examination demonstrated the presence of intercellular junctions of desmosomal-like or desmosomal types between tumour cells and adjacent squamous cells. Furthermore, examination of the intraductal carcinoma of the breast tissue in cases of Paget's disease as well as control cases of intraductal carcinoma also revealed areas of skip lesions of intraductal carcinoma. CONCLUSIONS: In view of these changes, it is unlikely that tumour expansion or tumour cell motility are sufficient explanations to account for the pattern of tumour spread in both the epidermis and the duct epithelium with skip lesions. A 'field effect' in the duct system harbouring intraductal carcinoma and the adjacent epidermis may play an important role in the tumour cell spread in the epidermis as well as in the ductal epithelium.

Breast Neoplasms↗
PubMed2002

Malignant neoplasms infiltrating pseudoangiomatous' stromal hyperplasia of the breast: an unrecognized pathway of tumour spread.

AIMS: To describe five malignant tumours in the breast (two invasive carcinomas and three non-Hodgkin's lymphomas) showing an unusual pattern of spread within anastomosing spaces consistent with those described in pseudoangiomatous stromal hyperplasia. METHODS AND RESULTS: The histological and immunohistochemical features of the cases are presented. In all cases, the neoplasms consisted of non-cohesive E-cadherin-negative cells located within anastomosing vascular-like channels. These channels showed morphological and immunohistochemical features consistent with those seen in pseudoangiomatous stromal hyperplasia: they were lined by flattened cells that expressed CD34, bcl2 and smooth muscle actin, while CD31 was consistently negative. CONCLUSIONS: The open channels of pseudoangiomatous stromal hyperplasia have been regarded as spaces due to loss of cohesiveness between stromal fibroblasts if not artefacts. The fact that neoplastic cells spread through these spaces suggests that the spaces are true open channels that may represent part of a complex network of stromal channels (pre-lymphatics) connected to the main lymphatic system of the breast. This finding opens new insights into the routes of tumour spread.

Aged↗
PubMedDate not supplied

Key sequences involved in the spreading of the systemic autoimmune response to spliceosomal proteins.

Immune spreading to multiple intracellular antigens is likely to be of primary importance in organ-specific and systemic autoimmune diseases. A number of mechanisms by which immune spreading may occur from only a single autoreactive epitope have been proposed. Search for an initiator or early epitope thus represents an important area of investigation. For example, many studies have focused on the identification of epitopes recognized by the antibodies from both patients with systemic lupus erythematosus (SLE) and lupus-prone mice. Recently, an autoepitope present in the 70K U1 ribonucleo protein (RNP) and recognized by CD4+ T cells from lupus mice has also been identified. Here, we analyze the results of B- and T-cell-epitope mapping studies of several RNPs present in the spliceosome and propose a model of epitope spreading. In this model, a consensus sequence (the RNP motif) conserved in many nuclear, nucleolar and cytoplasmic antigens, might play a role as 'driver' epitope. This hypothesis is based on the observation that this sequence is recognized by CD4+ T cells from lupus mice and is often targeted by autoantibodies, very early during the course of the disease. Targeting this region that is repeated in different self-antigens, might represent an interesting strategy to interfere with the continuous T-cell stimulation and exposure to specific antigens.

Animals↗
PubMed2001

Extent and speed of spread of HIV infection in India through the commercial sex networks: a perspective.

India has the world's highest number of HIV/AIDS infections for any country outside Africa. Eighty-five per cent of HIV transmission in India occurs through heterosexual contact. One billion population, a large number of female sex workers, high prevalence of sexually transmitted infection (STIs) and low condom use make a potent combination for explosive growth of the epidemic. Taking available estimates of the number of female sex workers (FSWs), their work patterns, prevalence of HIV and STIs and condom use among them in 1999 as the base, and adopting reasonable infectivity rates, this paper attempts to present a model to estimate the spread of HIV infection in commercial sex networks until 2005. HIV infections in commercial sex networks are estimated to increase from the 1999 level of approximately 2.49 million to about 3.93 million by 2005 in a favourable scenario, and to 6.87 million in a worse scenario. Spread of HIV is influenced in the short term by condom use and prevalence of STIs, and these are the only factors that can be manipulated to limit the spread of the infection.

Condoms↗