Perivascular hemorrhagic lesions in temporal cortex following cerebral infarction (a morphological study)

Perivascular hemorrhagic lesions were produced in squirrel monkeys following transorbital occlusion of the middle cerebral artery. The respective periods of occlusive insult were 7.5, 15, 30 min, and 1 hr. After 1 wk of postoperative care, the animals were prepared for morphological study by a total body perfusion technique.Small hemorrhagic loci were observed grossly in the temporal cortex. By light microscopy these erythrocytic patches occupied predominantly a perivascular position, however, some interparenchymal clumps were also present.Ultrastructurally, separation of erythrocytes from the capillary components was noted. Interventing astrocytic end-feet were not swollen, nor did they show other morphological abnormalities (lysosomal increase, glycogen depletion, etc.). Capillaries were intact and ultrastructurally normal. Increased vacuolization was common in tissue adjacent to the erythrocyte clumps.Since no morphological changes were found in the microvasculature, it was concluded that diapedesis and extravasation had resulted from permeability changes in larger vessels.     

Morphological and chemical mechanisms of elongated mineral particle toxicities

Much of our understanding regarding the mechanisms for induction of disease following inhalation of respirable elongated mineral particles (REMP) is based on studies involving the biological effects of asbestos fibers. The factors governing the disease potential of an exposure include duration and frequency of exposures; tissue-specific dose over time; impacts on dose persistence from in vivo REMP dissolution, comminution, and clearance; individual susceptibility; and the mineral type and surface characteristics. The mechanisms associated with asbestos particle toxicity involve two facets for each particle's contribution: (1) the physical features of the inhaled REMP, which include width, length, aspect ratio, and effective surface area available for cell contact; and (2) the surface chemical composition and reactivity of the individual fiber/elongated particle. Studies in cell-free systems and with cultured cells suggest an important way in which REMP from asbestos damage cellular molecules or influence cellular processes. This may involve an unfortunate combination of the ability of REMP to chemically generate potentially damaging reactive oxygen species, through surface iron, and the interaction of the unique surfaces with cell membranes to trigger membrane receptor activation. Together these events appear to lead to a cascade of cellular events, including the production of damaging reactive nitrogen species, which may contribute to the disease process. Thus, there is a need to be more cognizant of the potential impact that the total surface area of REMP contributes to the generation of events resulting in pathological changes in biological systems. The information presented has applicability to inhaled dusts, in general, and specifically to respirable elongated mineral particles.     

Loss of MTBP expression is associated with reduced survival in a biomarker-defined subset of patients with squamous cell carcinoma of the head and neck

BACKGROUND:

Recent genetic studies have implicated p53 mutation as a significant risk factor for therapeutic failure in squamous cell carcinoma of the head and neck (SCCHN). However, in a recent meta‐analysis in the literature of p53 from major anatomical subsites (larynx, oral cavity, oropharynx/hypopharynx), associations between patient survival and p53 status were ambiguous.

METHODS:

The authors examined a cohort of SCCHNs using a previously developed biomarker combination that likely predicts p53 status based on p53/MDM2 expression levels determined by immunohistochemistry (IHC). In addition, the authors generated and validated an antibody to MTBP (an MDM2 binding protein that alters p53/MDM2 homeostasis and may contribute to metastatic suppression) and have incorporated data for MTBP expression into the current analyses.

RESULTS:

Analysis of expression data for p53 and MDM2 in 198 SCCHN patient samples revealed that the biomarker combination p53 + ve/MDM2‐low (likely indicative of p53 mutation) was significantly associated with reduced overall survival (log‐rank P = .035) and was an independent prognostic factor (P = .013; HR, 1.705; 95% CI, 1.12‐2.60); thus, these data were compatible with earlier genetic analyses. By using IHC for p53 and MDM2 to dichotomize patients, the authors found that loss of MTBP expression was significantly associated with reduced survival (log‐rank P = .004) and was an independent prognostic factor (P = .004; HR, 2.78; 95% CI, 1.39‐5.54) in p53 + ve/MDM2‐low patients.

CONCLUSIONS:

These results represent the first examination of MTBP expression in human tissues and provide evidence for a p53 status‐dependent role for MTBP in suppressing disease progression in SCCHN patients as well as confirming a role for p53 pathway function in delaying disease progression. Cancer 2011. © 2011 American Cancer Society.     

Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs

Porcine reproductive and respiratory syndrome (PRRS) is an economically important disease to pork producers worldwide. Commercially, both live and killed PRRSV vaccines are available to control PRRS, but they are not always successful. Based on the results of mucosal immunization studies in other viral models, a good mucosal vaccine may be an effective way to elicit protective immunity to control PRRS outbreaks. In the present study, mucosal adjuvanticity of Mycobacterium tuberculosis whole cell lysate (Mtb WCL) was evaluated in pigs administered a modified live PRRS virus vaccine (PRRS-MLV) intranasally. A Mtb WCL mediated increase in the frequency of NK cells, CD8⁺and CD4⁺ T cells, and γδ T cells in pig lungs were detected. Importantly, an increased and early generation of PRRSV specific neutralizing antibodies were detected in PRRS-MLV+ Mtb WCL compared to pigs inoculated with vaccine alone. In addition, there was an increased secretion of Th1 cytokines (IFNγ and IL-12) that correlated with a reciprocal reduction in the production of immunosuppressive cytokines (IL-10 and TGFβ) as well as T-regulatory cells in pigs vaccinated with PRRS-MLV+ Mtb WCL. Further, a complete rescue in arginase levels in the lungs mediated through Mtb WCL was observed in pigs inoculated with PRRS-MLV. In conclusion, Mtb WCL may be a potent mucosal adjuvant for PRRS-MLV in order to potentiate the anti-PRRSV specific immune responses to control PRRS effectively.     

Prevalence and risk factors of lumbar spondylolisthesis in elderly Chinese men and women

Objective

A screening survey for osteoporotic fractures in men and women in Hong Kong represents the first large-scale prospective population-based study on bone health in elderly (≥65 years) Chinese men and women. This study aims to identify the prevalence and potential risk factors of lumbar spondylolisthesis in these subjects.

Methods

The lateral lumbar radiographs of 1,994 male and 1,996 female patients were analysed using the Meyerding classification.

Results

Amongst the men, 380 (19.1 %) had at least one spondylolisthesis and 43 (11.3 %) had slips at two or more levels; 283 had anterolisthesis, 85 had retrolisthesis, whereas 12 subjects had both anterolisthesis and retrolisthesis. Amongst the women, 499 (25.0 %) had at least one spondylolisthesis and 69 (13.8 %) had slips at two or more levels; 459 had anterolisthesis, 34 had retrolisthesis, whereas 6 subjects had both anterolisthesis and retrolisthesis. Advanced age, short height, higher body mass index (BMI), higher bone mineral density (BMD) and degenerative arthritis are associated with spondylolisthesis. Lower Physical Activity Scale for the Elderly (PASE) score was associated with spondylolisthesis in men; higher body weight, angina and lower grip strength were associated with spondylolisthesis in women.

Conclusion

The male/female ratio of lumbar spondylolisthesis prevalence was 1:1.3 in elderly Chinese. Men are more likely to have retrolisthesis.

Key Points

? The prevalence of spondylolisthesis is 19.1 % in elderly Chinese men. ? The prevalence of spondylolisthesis is 25.0 % in elderly Chinese women. ? Men are more likely to have retrolisthesis. ? Anterolisthesis is most commonly seen at the L4/L5 level. ? Retrolisthesis is most commonly seen at the L3/L4 level.