Indolent mucoid carcinoma of stomach

In a review of 574 cases of gastric carcinoma, 50 (8.7%) proved to be mucoid using defined microscopic criteria. Three histological types were recognized: pure signet-ring cell carcinoma (three cases); tumour of mixed pattern (41 cases); and an easily recognized, well differentiated type (six cases). This last group pursued an indolent course and had a mean survival time of nine years compared with mean survival times in the other two groups of five and 18 months respectively.     

Enhancement of growth ofMycobacterium malmoense by acidic pH and pyruvate

The growth ofMycobacterium malmoense is dysgonic and slow on ordinary mycobacterium media. The effect of pH and pyruvate on the growth of ten strains was studied on a modification of Löwenstein-Jensen medium. Growth appeared sooner and was more abundant at pH<6.5. At pH 7 or higher, it was scarcely or not at all visible after six weeks of incubation. Pyruvate enhanced the growth of five strains that grew only poorly on glycerol-containing medium, even at acidic pH. The parallel use of both pyruvate and glycerol-containing media, pH 6 to 6.5, and an incubation period of seven weeks or longer are recommended for the isolation ofMycobacterium malmoense on Löwenstein-Jensen medium.     

An important role of lymphatic vessel activation in limiting acute inflammation

In contrast to the established role of blood vessel remodeling in inflammation, the biologic function of the lymphatic vasculature in acute inflammation has remained less explored. We studied 2 established models of acute cutaneous inflammation, namely, oxazolone-induced delayed-type hypersensitivity reactions and ultraviolet B irradiation, in keratin 14-vascular endothelial growth factor (VEGF)-C and keratin 14-VEGF-D transgenic mice. These mice have an expanded network of cutaneous lymphatic vessels. Transgenic delivery of the lymphangiogenic factors VEGF-C and the VEGFR-3 specific ligand mouse VEGF-D significantly limited acute skin inflammation in both experimental models, with a strong reduction of dermal edema. Expression of VEGFR-3 by lymphatic endothelium was strongly down-regulated at the mRNA and protein level in acutely inflamed skin, and no VEGFR-3 expression was detectable on inflamed blood vessels and dermal macrophages. There was no major change of the inflammatory cell infiltrate or the composition of the inflammatory cytokine milieu in the inflamed skin of VEGF-C or VEGF-D transgenic mice. However, the increased network of lymphatic vessels in these mice significantly enhanced lymphatic drainage from the ear skin. These results provide evidence that specific lymphatic vessel activation limits acute skin inflammation via promotion of lymph flow from the skin and reduction of edema formation.     

Influence of neurally adjusted ventilatory assist and positive end-expiratory pressure on breathing pattern in rabbits with acute lung injury

OBJECTIVE: To evaluate the influence of neurally adjusted ventilatory assist (NAVA) and positive end-expiratory pressure (PEEP) on the control of breathing in rabbits with acute lung injury. DESIGN: Prospective animal study. SETTING: Experimental laboratory in a university hospital. SUBJECTS: Male White New Zealand rabbits (n = 18). INTERVENTION: Spontaneously breathing rabbits with hydrochloric acid-induced lung injury were ventilated with NAVA and underwent changes in NAVA gain and PEEP (six nonvagotomized and five vagotomized). Seven other nonvagotomized rabbits underwent 4 hrs of ventilation with hourly titration of PEEP, Fio2, and NAVA gain. MEASUREMENTS AND MAIN RESULTS: We studied diaphragm electrical activity, respiratory pressures, and breathing pattern. After lung injury, 0 cm H2O of PEEP resulted in high tonic and no discernible phasic diaphragm electrical activity in the nonvagotomized rabbits; stepwise increases in PEEP (up to 11.7 +/- 2.6 cm H2O) reduced tonic but increased phasic diaphragm electrical activity. Increasing the NAVA gain reduced phasic diaphragm electrical activity to almost half and abolished esophageal pressure swings. Tidal volume remained at 4-5 mL/kg, and respiratory rate did not change. In the vagotomized group, lung injury did not induce tonic activity, and phasic activity and tidal volume were several times higher than in the nonvagotomized rabbits. Four hours of breathing with NAVA restored breathing pattern and neural and mechanical breathing efforts to pre-lung injury levels. CONCLUSIONS: Acute lung injury can cause a vagally mediated atypical diaphragm activation pattern in spontaneously breathing rabbits. Modulation of PEEP facilitates development of phasic diaphragm electrical activity, whereupon implementation of NAVA can efficiently maintain unloading of the respiratory muscles without delivering excessive tidal volume in rabbits with intact vagal function.     

Nef interference with HIV-1-specific CTL antiviral activity is epitope specific

HIV-1 Nef and HIV-1-specific cytotoxic T lymphocytes (CTLs) have important and opposing roles in the immunopathogenesis of HIV-1 infection. Nef-mediated down-modulation of HLA class I on infected cells can confer resistance to CTL clearance, but the factors determining the efficiency of this process are unknown. This study examines the impact of Nef on the antiviral activity of several CTL clones recognizing epitopes from early and late HIV-1 proteins, restricted by HLA-A, -B, and -C molecules. CTL-targeting epitopes in early proteins remained susceptible to the effects of Nef, although possibly to a lesser degree than CTL-targeting late protein epitopes, indicating that significant Nef-mediated HLA down-regulation can precede even the presentation of early protein-derived epitopes. However, HLA-C-restricted CTLs were unaffected by Nef, consistent with down-regulation of cell-surface HLA-A and -B but not HLA-C molecules. Thus, CTLs vary dramatically in their susceptibility to Nef interference, suggesting differences in the relative importance of HLA-A- and HLA-B- versus HLA-C-restricted CTLs in vivo. The data thus indicate that HLA-C-restricted CTLs may have an under-appreciated antiviral role in the setting of Nef in vivo and suggest a benefit of promoting HLA-C-restricted CTLs for immunotherapy or vaccine development.     

Large-scale amplification, cloning and sequencing of near full-length HIV-1 subtype C genomes

Full-length HIV-1 genome sequencing provides important data needed to address several vaccine design, molecular epidemiologic and pathogenesis questions. A protocol is presented for obtaining near full-length genomes (NFLGs) from subjects infected with HIV-1 subtype C. This protocol was used to amplify NFLGs from 244 of 366 (67%) samples collected at two clinics in Durban, South Africa (SK and PS). Viral load was directly associated with frequency of successful NFLG amplification for both cohorts (PS; p = 0.005 and SK; p < 0.001). Seventeen of 38 initially NFLG-negative SK samples had variation within the PCR primer binding sites, however only 3 of these were successfully re-amplified using re-designed primers homologous to the target viruses. NFLGs were obtained from 7 of 24 PBMC samples processed from subjects whose plasma did not yield a NFLG. Stable plasmid clones were obtained from all 244 NFLG-positive PCR products, and both strands of each genome were sequenced, using a primary set of 46 primers. These methods thus allow the large-scale collection of HIV-1 NFLGs from populations infected primarily with subtype C. The methods are readily adaptable to other HIV-1 subtypes, and provide materials for viral functional analyses and population-based molecular epidemiology studies that include analysis of viral genome chimerization.