Nonpathogenic Lactobacillus rhamnosus activates the inflammasome and antiviral responses in human macrophages

In this study, we have utilized global gene expression profiling to compare the responses of human primary macrophages to two closely related, well-characterized Lactobacillus rhamnosus strains GG and LC705, since our understanding of the responses elicited by nonpathogenic bacteria in human innate immune system is limited. Macrophages are phagocytic cells of the innate immune system that perform sentinel functions to initiate appropriate responses to surrounding stimuli. Macrophages that reside on gut mucosa encounter ingested and intestinal bacteria. Bacteria of Lactobacillus genus are nonpathogenic and used in food and as supplements with health-promoting probiotic potential. Our results demonstrate that live GG and LC705 induced quantitatively different gene expression profiles in macrophages. A gene ontology analysis revealed functional similarities and differences in responses to GG and LC705 that were reflected in host defense responses. Both GG and LC705 induced interleukin-1β production in macrophages that required caspase-1 activity. LC705, but not GG, induced type I interferon -dependent gene activation that correlated with its ability to prevent influenza A virus replication and production of viral proteins in macrophages. Our results indicate that nonpathogenic bacteria are able to activate the inflammasome. In addition, our results suggest that L. rhamnosus may prime the antiviral potential of human macrophages.     

Sentinel node biopsy in local anaesthesia in patients with head and neck Merkel cell carcinoma

The purpose of this study was to evaluate the applicability of sentinel lymph node (SLN) biopsy in patients with head and neck Merkel cell carcinoma (MCC). A prospective study for nine stage I MCC head and neck patients was conducted between 2001 and 2005. Patients underwent SLN biopsy in conjunction with radical tumour excision. Nine consecutive head and neck MCC patients were included, of whom five were women. All the patients were at stage I. In one patient, no SLNs could be localised on lymphoscintigraphy or perioperatively; eight patients underwent removal of one eight SLNs. None of the patients had any complications directly related to the SLNB. Those patients who demonstrated metastatic disease in the SLNs had waiting periods of 25 and 54 days, respectively. Only the free microvascular free flap reconstructions were done under general anaesthesia, the other reconstructions and the removal of the SLNs were done under local anaesthesia. Aggressive nature and the head and neck location of most MCCs is challenging for the surgeon. Patients are usually elderly with comorbities, which sets limits for anaesthesia. In our opinion, it is not mandatory to perform SLN biopsy under general anaesthesia.     

Mesh-based method for measuring intracranial volume in patients with craniosynostosis

Purpose

   Craniosynostosis may lead to reduced intracranial volume (ICV) and disturb normal brain growth and development. Thus, ICV is an important parameter with respect to the surgical outcome. Current methods for ICV determination from computed tomography (CT) images have drawbacks. The aim of this study was to investigate the performance of the novel mesh-based method (MBM) for ICV determination with craniosynostosis patients.

Methods

   Twenty-two patients operated on for scaphocephaly were included in this study. ICVs from preoperative, one-week postoperative, and one-year postoperative CT images were measured with MBM. The level of agreement with the manual segmentation method (MSM) was determined for the measurements of preoperative and one-year postoperative datasets. Repeatability was determined with re-measurements of six datasets. Measurement time was recorded for MBM.

Results

   Mean $(\pm \text{ SD})$ preoperative ICV values were 895.0 $\pm $ 153.1 $\text{ cm}^{3}$ and 896.4 $\pm $ 147.2 $\text{ cm}^{3}$ as measured with MBM and MSM, respectively. Corresponding one-year postoperative values were 1,238.3 $\pm $ 118.7 $\text{ cm}^{3}$ and 1,250.1 $\pm $ 117.5 $\text{ cm}^{3}$ . The MBM allowed ICV determination from one-week postoperative datasets. Measurement time with MBM was 4

Conclusions

   MBM is an efficient method for determining the ICV of craniosynostosis patients, allowing the measurement of skulls with bony defects. The repeatability and short measurement time of MBM are attributable to the user interference and assessment of the measurement process.     

Expression of HuR in Merkel cell carcinoma and in normal skin

Background:  HuR is a ubiquitously expressed member of the Elav/Hu family of mRNA-binding proteins, and its cytoplasmic expression has been recognised to participate in carcinogenesis. The aims of this study were to explore the expression pattern of HuR in primary Merkel cell carcinoma (MCC), lymph node metastases and non-neoplastic skin.
Methods:  Twenty-two primary MCC samples and five lymph node metastases were evaluated for HuR expression by immunohistochemistry. The data were compared with clinical parameters.
Results:  Nuclear and cytoplasmic HuR-staining patterns were observed. Nuclear immunoreactivity was observed in 91% of the primary tumors and in 80% of the lymph node metastases. Cytoplasm was positive in 27% of the primary tumors and in 60% of the lymph node metastases. No cytoplasmic HuR immunoreactivity was detected in non-neoplastic skin. However, moderate to strong nuclear staining was found in normal epidermis and in the epithelium of hair follicles and sebaceous glands. Expression of HuR in MCC did not associate with clinicopathological parameters.
Conclusions:  Primary MCCs and their lymph node metastases as well as non-neoplastic skin show nuclear expression of HuR protein. In contrast to non-neoplastic skin, a subset of MCC tumors show cytoplasmic HuR staining, which may contribute to carcinogenesis in MCC.     

Matter of life and death: the pharmacological approaches targeting apoptosis in brain diseases

Neurodegenerative diseases that include amyotrophic lateral sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, stroke, brain trauma and spinal cord injury, are associated with the inappropriate activation of a neuronal cell-suicide program called apoptosis. Given that central nervous system tissue has very limited regenerative capacity it is of extreme importance to limit the damage caused by neuronal death. During the past decade, considerable progress has been made in understanding the process of apoptosis and, significantly, a number of studies have shown that a variety of small molecules can activate or inhibit cell death by acting on crucial checkpoints of apoptosis. Here, we review evidence linking apoptosis to brain diseases and discuss how knowledge of the mechanisms of cell death has led to novel therapeutic strategies.     

Frostbite injuries treated in the Helsinki area from 1995 to 2002

BACKGROUND:: Exposure to cold results in frostbite, superficial or deeper tissue damage. In severe frostbites, amputations are life-saving but diminish quality of life (QOL). METHODS:: Retrospective study was performed. RAND 36- questionnaire was administered to assess QOL. Our aim was to investigate risk factors and adjustment to everyday life of hospitalized patients. RESULTS:: 92 frostbites in 42 patients were recorded. One third of the patients were chronic alcoholics. Age and temperature were statistically significant factors for unfavorable outcome. 20% of patients required secondary reconstructive procedures. One-third reported their emotional well-being very poor. Half had limitations in social life. CONCLUSIONS:: Hospitalized cases of frostbite are rare. Anti-social behavior increases the risk in general, and patients present with complicated problems similar to those encountered in burns victims. We recommend that frostbite patients requiring hospital attendance are treated in specialized units, where sufficient expertise for acute as well as reconstructive surgery is available.     

Oats can diversify a gluten-free diet in celiac disease and dermatitis herpetiformis

Finnish celiac disease and dermatitis herpetiformis patients have used oat-containing gluten-free diets since 1997. The aim of this study was to evaluate how the use of oats has been adopted. The use of oats and the effect of oats on symptoms and quality of life were investigated in 1,000 randomly selected members of the Celiac Society. Altogether, 710 patients responded: 423 (73%) with celiac disease and 70 (55%) with dermatitis herpetiformis were currently consuming oats. Patients appreciated the taste, the ease of use, and the low costs; 94% believed that oats diversified the gluten-free diet; 15% of celiac disease and 28% of dermatitis herpetiformis patients had stopped eating oats. The most common reasons for avoiding oats were fear of adverse effects or contamination. There is a market demand for oats, and celiac societies and dietitians should make efforts to promote the development of products free of wheat contamination.     

Processing of auditory and visual location information in the monkey prefrontal cortex

Visuospatial working memory mechanisms have been studied extensively at single cell level in the dorsolateral prefrontal cortex (PFCd) in nonhuman primates. Despite the importance of short-term memory of sound location for behavioral orientation, there are only a few studies on auditory spatial working memory. The purpose of this study was to investigate neuronal mechanisms underlying working memory processing of auditory and visual location information at single cell level in the PFCd. Neuronal activity was recorded in monkeys performing a delayed matching-to-sample task (DMTS). The location of a visual or auditory stimulus was used as a memorandum. The majority of the neurons that were activated during presentation of the cue memorandum were selective either for visual or auditory spatial information. A small group of cue related bimodal neurons were sensitive to the location of the cue regardless of whether the stimulus was visual or auditory, suggesting modality independent processing of spatial information at cellular level in the PFCd. Most neurons that were activated during the delay period were modality specific, responding either during visual or auditory trials. All bimodal delay related neurons that responded during both visual and auditory trials were spatially nonselective. The results of the present study suggest that in addition to the modality specific parallel mechanism, working memory of auditory and visual space also involves modality independent processing at cellular level in the PFCd.