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The preepiglottic and paraglottic spaces in relation to spread of carcinoma of the larynx.

The submucosal compartments of the larynx were examined using a whole-organ sectioning technique. Seven specimens of normal larynx and 35 specimens of carcinoma of the larynx were studied. Victoria blue and van Gieson stains were used to demonstrate connective tissue elements. The preepiglottic space was distinctly separated from the paraglottic spaces by membranous partitions made up of collagen and elastic fibers. These partitions offer some resistance to tumor invasion in the early stages of laryngeal cancer, keeping the tumor from extending to the adjacent compartment while allowing it to spread freely within the same compartment. In the absence of mucosal extension across the midline, submucosal spread of tumor to the opposite side is unlikely. In view of possible cranial spread of tumor along the preepiglottic and paraglottic spaces, excision of all these spaces, together with the hyoid bone, is indicated in total laryngectomy.

Epiglottis↗

The spread of porcine sarcoptic mange during the fattening period revealed by development of antibodies to Sarcoptes scabiei.

Using an indirect ELISA based on a whole body homogenate of Sarcoptes scabiei var vulpes, the development of serum antibodies to S. scabiei var suis during the fattening period was studied in two herds, purchasing fatteners and performing age segregated production systems. All the pigs in one of the herds were treated with ivermectin on the same day within a week after arrival, while no precautions were made to prevent sarcoptic mange in the other herd. In both herds, a transient immune response to S. scabiei was detected in some animals during the early fattening period, reflecting that these pigs had been exposed to S. scabiei before delivery to the fattening units. It also indicated that they had been treated with acaricides close to allocation. The incidence of animals seropositive to S. scabiei was initially low in both herds. The infection spread gradually as indicated by increasing optical densities of antibodies to S. scabiei, especially during the second half of the rearing period. This increase was more pronounced in the herd which had received no prophylactic treatment to sarcoptic mange. The infection with S. scabiei was found to have spread to more animals towards the end of the fattening period in that herd. It was concluded that a single injection with the acaricide on arrival at the fattening farm decreased and delayed the spread of the infection, but did not eradicate the mite infection. The results showed that conventional pigs sold as fatteners at present may be infected with S. scabiei and that precautions aimed at preventing sarcoptic mange therefore, are indicated in fattening herds. In this context, the ELISA employed could be a valuable means of discriminating between S. scabiei var suis infected piglet producing herds and uninfected herds.

Animals↗

Fast thermal waves spreading over the cerebral cortex.

Fast thermal waves spreading over the cerebral cortex were found in the white rat by infrared neuroimaging (thermoencephaloscopy) in the range of 3-5 microm. Thermal waves appeared under visual stimulation (the probability of their appearance = 0.92), and under background conditions (probability of appearance = 0.42). Typically, they moved during the period from 15 s before to 25 s after each light flash that was presented rhythmically (1.5-3 per min). The waves spread over the cerebral cortex along the limited number of typical trajectories, which are specific for the hemisphere of their origin (ipsilateral or contralateral with the side of stimulation). The waves were never recorded in a dead animal or in a thermal standard. The amplitude of the thermal waves was in the range of 0.005-0.1 degrees C, with the extent of the pathway of 2-56 mm, length of 10-15 mm, duration of 1.2-11.4 s, and velocity of 1-33 mm/s. In about half of the cases the waves appeared in the contralateral visual cortex (areas 17 and 18a), spread to the midline and crossed to the ipsilateral hemisphere (areas 17, 18a and 7). Local waves moving along a circular trajectory and rotating around the central part of the contralateral area 17 were also revealed, as well as wave rotation around the dorsal (mainly parietal) cortical fields. Possible biophysical and neurophysiological mechanisms and the functional significance of the revealed effects are discussed.

Animals↗

Role of fibronectin in the organisation of the cytoskeleton during the spreading of rat mammary epithelial cells.

The correlation between the extracellular deposition of fibronectin and the development of the actin-containing cytoskeleton was studied during the attachment and spreading of the rat mammary epithelial cell line Rama 25. During the initial phase of cell spreading, actin is localised in peripheral microfilament bundles. As cell spreading increases, the peripheral ring is displaced towards the perinuclear region. Fibronectin, deposited beneath the basal surface, co-localises with the actin-containing peripheral ring. The peripheral ring subsequently disappears and is replaced by a system of radial microfilaments that extend from the perinuclear region to the cell periphery. At this stage, there is no correlation between the distribution of fibronectin and actin. As cells form colonies, radial microfilament bundles are replaced by peripheral microfilament bundles which do not co-localise with fibronectin. Cells at the edges of colonies extend lamellae that contain microfilament stress fibres. In these structures there is co-localisation of actin, fibronectin and the a5 beta 1-integrin fibronectin receptor.

Actins↗

[Should we screen for colonization to control the spread of multidrug resistant bacteria?].

Should we screen for colonization to control the spread of multidrug-resistant bacteria? A multidrug-resistant bacteria surveillance program was performed in 1999 at Laënnec Hospital (Nantes, France). After a 3-year period, the results permit us to determine the strategy to strengthen their spread. In 2001, Staphylococcus aureus resistant to methicillin represented 45% of the 202 multidrug-resistant bacteria isolated. The global incidence rate per 100 admissions remained stable between 1999 and 2001 (0.42%), but those of infections acquired in our institution decreased significantly from 0.27% in 1999 to 0.18% in 2001 (P < 0.05), particularly in medical care units (P < 0.04). In spite of this surveillance program and hygiene trainings, the global incidence remained stable during the study period, even if our action contributed to decrease the incidence of S. aureus resistant to methicillin acquired in our institution. Isolation precautions and screening for colonization policy in intensive care units are not sufficient to control the spread of MRB at hospital level. They should be strengthened by procedures for the transfer of infected or colonized patients and by antibiotic use control.

Cross Infection↗

The influence of additives on the spreading coefficient and adhesion of a film coating formulation to a model tablet surface.

The surface energies of film coating formulations based on hydroxypropyl methylcellulose and containing microcrystalline cellulose, lactose and Tween 20, respectively, have been assessed. The approach taken allowed the components of the surface energy, in terms of the Lifshitz-van der Waals and the acid-base contributions, to be determined. Spreading coefficients of these coating formulations were determined on a model tablet surface whose surface energy had been similarly characterised. The determined spreading coefficients were high and positive indicating that spreading and wetting would not be a controlling factor in the formation of an adequate film coat. The adhesion of the coats to the core was measured and showed that the inclusion of additives influenced the adhesion of the film. Maximum adhesion was obtained when microcrystalline cellulose was included in the coating formulation that presumably allowed a strong interaction with the same component in the tablet core. Adhesion was enhanced when the tablet cores were made at a higher compaction force. Atomising air pressure had little influence on the adhesion.

Chemistry, Pharmaceutical↗

Unusual case of septic arthritis of the hip: spread from adjacent adductor pyomyositis.

Distinguishing intracapsular and extracapsular hip infections may be clinically difficult. Because of this difficulty in diagnosis, the spread of an extracapsular infection into the hip joint may be missed and lead to significant joint destruction. The case of a patient who suffered from the spread of adductor pyomyositis to the hip joint is reported. The delay in diagnosis of an intracapsular hip infection led to significant intra-articular destruction and ultimately necessitated a Girdlestone resection arthroplasty. The patient's hip function was salvaged with a total hip arthroplasty. The presence of an extracapsular hip infection should mandate serial physical examinations and aggressive evaluation to rule out intracapsular spread. A delay in diagnosis of an intracapsular hip infection can lead to catastrophic results.

Adult↗

The Shb adaptor protein causes Src-dependent cell spreading and activation of focal adhesion kinase in murine brain endothelial cells.

The mechanisms leading to focal adhesion kinase (FAK) activation remain obscure. We have investigated the role of the adaptor protein Shb in cell spreading and the regulation of FAK phosphorylation in immortalised brain endothelial (IBE) cells. Fibroblast growth factor 2 (FGF-2) stimulation lead to a direct association between Shb and FAK, which was mediated by the phosphotyrosine binding (PTB) domain of Shb. IBE cells overexpressing wild-type or R522K Shb (with an inactive Src homology 2 (SH2) domain) displayed increased FAK phosphorylation as well as enhanced spreading when seeded on collagen. FGF-2-induced tyrosine phosphorylation of Shb was dependent upon Src activity but independent of FAK activation. The use of Rat-1 fibroblasts overexpressing a temperature sensitive v-Src (tsLA29) confirmed that active Src enhanced Shb phosphorylation. The data indicate that Shb binds directly to FAK and regulates its phosphorylation leading to enhanced cell spreading in a Src-dependent manner.

Adaptor Proteins, Vesicular Transport↗

Impact of travel on international spread of antimicrobial resistance.

Antimicrobial resistance, an escalating problem worldwide, affects a broad range of human diseases. Excessive and inappropriate drug usage is the key driver for the emergence of resistant organisms. Travel, trade and mass migration form an important mode for their spread. The use of molecular biology provides the means of understanding the genesis and spread of the genes for drug resistance. Antimicrobial use in veterinary practice as food additives causes selection of resistant zoonotic pathogens that may spread to humans. Comprehensive surveillance systems should be designed and implemented at local and national levels and a national resistance surveillance database operationalized. There is also need for better regulation of the use of antibiotics and education of the medical fraternity, veterinarians and the public in the appropriate use of antimicrobials.

Animals↗

The N400 is modulated by unconsciously perceived masked words: further evidence for an automatic spreading activation account of N400 priming effects.

It is a matter of debate whether the N400 component of the event-related brain potential (ERP) is sensitive to unconscious automatic priming mechanisms or to strategic mechanisms only. Recent studies demonstrated N400 modulation by masked primes at a short SOA supporting an automatic spreading activation account. However, it cannot be ruled out that strategic mechanisms based upon partial prime identification contributed to the observed priming effects. The present study was set up to substantiate masked N400 priming effects as an index of automatic spreading activation. It was assessed whether partial identification of the masked words due to backward priming could have supported strategic priming to occur. In experiment 1, ERPs were recorded while subjects performed lexical decisions on targets preceded by masked and unmasked primes at an SOA of 67 ms. Masked words, which were not consciously perceived, as well as visible words were shown to modulate the N400 to meaningfully related target words. Experiment 2 required subjects to perform decisions on visual, lexical and semantic features of masked words presented with or without semantically related context words. Subjects performed at chance in all tasks. Furthermore, the results exclude the possibility that backward priming has rendered the masked words partially visible. The present study therefore demonstrates that N400 priming effects can be reliably obtained from unconsciously perceived masked words at a very short SOA and strengthens the notion that the N400 is modulated by automatic spreading activation and not exclusively by strategic semantic processes.

Adult↗

Monoclonal antibodies to p24-core protein of HIV-1 mediate ADCC and inhibit virus spread in vitro.

BACKGROUND: Certain antigens of the HIV-1, e.g., gp120-envelop proteins, can be expressed on the membrane of HIV-infected cells. Little is known about the membrane expression of other HIV-antigens and their interaction with specific antibodies. OBJECTIVE: To develop murine monoclonal antibodies (mAbs) to the p24-core protein of HIV-1 and to characterise their binding sites and biological activities on HIV-infected T cells. METHODS: Monoclonal antibodies were developed from mice hyperimmunised with a recombinant p24-core protein from HIV-1. Two mAbs were epitope-mapped on overlapping peptides and characterised for their reactivity with non-fixed HIV-infected T cells by immunofluorescence staining and flow cytometric analysis. Their biological activities were studied for antibody-dependent cellular cytotoxicity (ADCC) and suppression of viral spread in vitro. RESULTS: The epitopes of two selected mAbs were located on the amino terminal region of p24 in the regions 147-152 aa and 178-187 aa, respectively. The antibodies were able to react with living HIV-1 infected cells. The expression of the antigens was time-dependent after the infection of certain cell lines by HIV-1. The mAbs mediated a strong HIV-1-specific ADCC and were able to delay the spread of HIV-1 for about 6 days in cell cultures. CONCLUSIONS: Certain epitopes of the p24-core protein of HIV-1 can be expressed on living, HIV-infected T cells and are recognised by specific antibodies. Such antibodies can destroy infected cells by ADCC or delay the virus spread, and therefore, should be considered in immunisation strategies against HIV.

Journal Article↗

On the structure of the epidemic spread of AIDS: the influence of an infectious coagent.

The reported AIDS cases in the USA and the Federal Republic of Germany are growing almost exponentially. Considering the epidemiological curves for different risk groups (homosexual men, i.v. drug abusers, heterosexual partners etc.) it is extremely surprising, that nearly exactly the same development occurs in all risk groups. One only has to consider a certain time shift for each group. The conformity of the development for all groups is evident by the fact, that the curves representing the reported AIDS cases for different risk groups are straight lines (in a logarithmic scale) running nearly exactly in parallel. This remarkable parallelism can be understood only if the spread of AIDS is independent of the sexual or drug risk in a certain sense. On the other hand, the drastic overrepresentation of the sexually highly active groups and drug abusers in the number of AIDS cases obviously requires that the transmission of AIDS unequivocally depends on the sexual and drug risk. We present a mathematical model that is suitable to reconcile this apparent contradiction in the interpretation of the epidemiological data: the observed parallel time series for the spread of AIDS in groups with different risk of infection can be realized by computer simulation, if one assumes that the outbreak of full-blown AIDS only occurs if HIV and a certain infectious coagent (cofactor) CO are present. Such a situation is not uncommon, see, e.g. the influenza virus--Staphylococcus aureus system. According to the mathematical model this cofactor would spread independently of the sexual and drug risk--in contrast to HIV. However, due to its analytical properties the simulated cofactor cannot be identified so far with any known infectious agent.

Acquired Immunodeficiency Syndrome↗

The spread of ovarian cancer.

Spreading intra-abdominally, ovarian cancer reaches the upper abdomen relatively quickly. Metastases result from the implantation of cells from the primary tumour or, perhaps, may arise de novo from the peritoneal epithelium. The tumour also spreads via the lymphatics directly to the pelvic nodes, directly to the para-aortic nodes, or directly to both. Pelvic nodes were positive in 57.9% of patients of all stages. The highest incidence, 70.4%, was found in Stage III. The percentage of positive para-aortic nodes was lower, namely 50.9% overall incidence and 67.6% in Stage III. Concerning the concomitant involvement of pelvic and para-aortic nodes, 40.4% of patients with positive pelvic nodes also had positive para-aortic nodes. Of patients with negative pelvic nodes, 36.8% also had negative para-aortic nodes. Of all patients, 12.3% had positive pelvic nodes and negative para-aortic nodes. Conversely, 10.5% of all patients had positive para-aortic nodes and negative pelvic nodes. There is a significant association between the involvement of the diaphragm and that of the pelvic and para-aortic nodes. Of those patients with tumour deposits on the diaphragm, 84.4% also had positive retroperitoneal nodes. Conversely, 55.9% of patients with positive nodes also had tumour deposits on the diaphragm. This means that ovarian cancer spreads almost simultaneously in two ways: intra-abdominally and retroperitoneally. Surgical treatment must address both modes.

Female↗

Epitope spreading.

Epitope (determinant) spreading is the development of immune responses to endogenous epitopes secondary to the release of self antigens during a chronic autoimmune or inflammatory response. The past year has seen considerable advances in our understanding of the contribution of epitope spreading to the chronic pathogenesis of experimental T-cell-mediated and antibody-mediated autoimmune diseases. Most significantly, conclusive functional evidence for a major role for epitope spreading in the chronic pathogenesis of murine relapsing-remitting experimental autoimmune encephalomyelitis, a CD4+ T-cell-mediated model of multiple sclerosis, was forthcoming.

Animals↗

MARCKS regulates membrane ruffling and cell spreading.

The dynamic rearrangement of the actin cytoskeleton is fundamental to most biological processes including embryogenesis, morphogenesis, cell movement, wound healing and metastasis [1]. Membrane ruffling and reversible cell-substratum interactions underlie actin-driven cell movement. Protein kinase C (PKC) stimulates membrane ruffling and adhesion [2], but the mechanism by which this occurs is unknown. Myristoylated alaninerich C kinase substrate (MARCKS) is a PKC substrate that cycles on and off membranes by a mechanism termed the myristoyl-electrostatic switch [3-6]. While at the membrane, MARCKS binds to and sequesters acidic phospholipids including phosphatidyl-inositol-4,5-bisphosphate (PIP2) [7]. MARCKS also binds and cross-links filamentous actin, an activity which is regulated by PKC-dependent phosphorylation and calcium-calmodulin [3]. In this report, we demonstrate that expression, in fibroblasts, of MARCKS containing a mutation which abrogates the myristoyl-electrostatic switch prevents cell spreading. The MARCKS mutant arrests the cell during an early stage of spreading, characterized by profuse membrane blebbing, and prevents the formation of membrane ruffles and lamellae usually found at the leading edge of spreading cells. This defect in the regulation of the actin cytoskeleton is accompanied by a decrease in cell-substratum adhesion. Our results provide direct evidence that MARCKS and PKC regulate actin-dependent membrane ruffling and cell adhesion, perhaps via a PIP2-dependent mechanism.

Actins↗

MR imaging of perineural tumor spread.

Perineural tumor spread (PNS) is a common and potentially devastating complication of head and neck cancer. Because perineural tumor spread may be asymptomatic, the radiologist plays a critical role in the evaluation of the head and neck cancer patient. Although PNS may be seen on CT, MR imaging is far more sensitive and is the imaging modality of choice in the evaluation of perineural tumor spread.

Cranial Nerves↗

On the use of contour maps in the analysis of spread of communicable disease.

The co-ordinates of the dwellings where cases of variola minor (alastrim) occurred during a small epidemic were used in a worked example of contour mapping of disease spread. The contoured variable was the date of onset, relative to an arbitrary base date, of the case introducing the disease into each of twenty-two households. Three contour maps prepared with slightly different computer programmes or dates exhibited similar concentric loops whose centres were close to the first infected household. The average rate of spread of the disease was estimated by regression of the number of days to onset of the first case in the household on the average distance from an arbitrary origin to the relevant contour line. The calculated average rate of spread was 1.22 metres per day. An additional map was contoured using the cumulative number of cases as the contoured variable, relative to the onset of the example epidemic.

Brazil↗

Hospital Salmonella johannesburg infection and its possible role in the community spread of the infection in Hong Kong.

Salmonella johannesburg (1, 40: b: e, n, x), a previously rare salmonella serotype, has established itself rapidly as an important and highly prevalent cause of gastroenteritis among children. The clinical features of the infection are usually mild but chronic. It has been suggested that S. johannesburg was introduced into Hong Kong through imported foods but no common vehicle could be traced as the source of infection. A thorough investigation of one paediatric ward in a general hospital revealed that non-infected patients admitted to the ward usually acquired S. johannesburg infection within 3-7 days, with or without symptoms. Thus hospital cross-infection could be a significant factor in contributing to its rapid spread in the community. Furthermore, the rapidity with which S. johannesburg spread was facilitated by (a) its tendency to produce a chronic infection, (b) its multiple resistance to antibiotics, and (c) the higher infectivity of S. johannesburg over other salmonellas endemic in this locality. These factors combined with the overcrowded conditions in many of the hospitals in Hong Kong facilitated the occurrence of hospital infection, which in its turn contributed to the spread of the infection in the local community.

Chronic Disease↗