Wednesday, December 26, 2012

Saturday, December 22, 2012

A Novel Function of MUC18: Amplification of Lung Inflammation during Bacterial Infection.


A Novel Function of MUC18: Amplification of Lung Inflammation during Bacterial Infection.


Dec 2012

Source

Pulmonary Division, Department of Medicine, National Jewish Health, Denver, Colorado.

Abstract


Bacterial infection plays a critical role in exacerbations of various lung diseases, including chronic pulmonary obstructive disease (COPD) and asthma. Excessive lung inflammation is a prominent feature in disease exacerbations, but the underlying mechanisms remain poorly understood. Cell surface glycoprotein MUC18 (alias CD146 or melanoma cell adhesion molecule) has been shown to promote metastasis in several tumors, including melanoma. We explored the function of MUC18 in lung inflammatory responses to bacteria (Mycoplasma pneumoniae) involved in lung disease exacerbations. MUC18 expression was increased in alveolar macrophages from lungs of COPD and asthma patients, compared with normal healthy human subjects. Mouse alveolar macrophages also express MUC18. After M. pneumoniae lung infection, Muc18(-/-) mice exhibited lower levels of the lung proinflammatory cytokines KC and TNF-α and less neutrophil recruitment than Muc18(+/+) mice. Alveolar macrophages from Muc18(-/-) mice produced less KC than those from Muc18(+/+) mice. In Muc18(-/-) mouse alveolar macrophages, adenovirus-mediated MUC18 gene transfer increased KC production. MUC18 amplified proinflammatory responses in alveolar macrophages, in part through enhancing the activation of nuclear factor-κB (NF-κB). Our results demonstrate, for the first time, that MUC18 exerts a proinflammatory function during lung bacterial infection. Up-regulated MUC18 expression in lungs (eg, in alveolar macrophages) of COPD and asthma patients may contribute to excessive inflammation during disease exacerbations.

Correlation between bacterial L-form infection, expression of HIF-1α/MMP-9 and vasculogenic mimicry in epithelial ovarian cancer


Correlation between bacterial L-form infection, expression of HIF-1α/MMP-9 and vasculogenic mimicry in epithelial ovarian cancer


Dec 2012

[Article in Chinese]


Source

Department of Pathology, the first Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Anhui Key Laboratory of Infection and Immunology, Bengbu 233030, China. E-mail: yulan790210@163.com.

Abstract


The aim of the present study is to explore whether vasculogenic mimicry (VM) and bacterial L-form infection exist in human epithelial ovarian cancer (EOC) or not and to elucidate the correlation of L-form infection, expression of hypoxia inducible factor 1α (HIF-1α)/MMP-9 and VM. In 87 specimens of EOC and 20 specimens of ovarian benign epithelial tumor tissues, L-form infection was detected by Gram's staining, expression of HIF-1α/MMP-9 and VM were detected by immunohistochemical and histochemical staining. The results showed that the positive rates of HIF-1α and MMP-9 protein in EOC were 52.9% and 66.7%, while in benign epithelial tumor tissues, the positive rates were 10.0% and 10.0% respectively, and there were significant differences between them (P < 0.05). In EOC and benign epithelial tumor tissues, L-form infections ratios were 24.1% and 0, respectively, and the difference was also significant (P < 0.01). Expression of VM, HIF-1α and MMP-9 in EOC was significantly related to differentiation, abdominal implantation and lymph node metastasis and FIGO stage (P < 0.01). L-form infection had relationship with abdominal implantation, lymph node metastasis and FIGO stage . The expression of HIF-1α had positive relationship with expression of MMP-9 and VM (r = 0.505, 0.585, respectively, P < 0.01); there was also a positive relationship between MMP-9 expression and VM (r = 0.625, P < 0.01). Overexpression of VM, HIF-1α and MMP-9 were related to poor prognosis: the survival rates were significantly lower in positive patients than those in negative patients (P < 0.05). And the group with L-form infection also had poor prognosis: the survival rates were lower than those in group without infection (P < 0.05). FIGO stage, expression of VM, HIF-1α and MMP-9 were independent prognosis factors of EOC (P < 0.05). The results suggest that L-form infection, the expression of HIF-1α, MMP-9 and VM in EOC are related to differentiation, lymph node metastasis, clinical stage and prognosis. Combined detection of these indexes has an important role in predicting the progression and prognosis of EOC.

Pattern Recognition and Host Defense Response to Cryptococcus neoformans.


Pattern Recognition and Host Defense Response to Cryptococcus neoformans.


2012

Source

Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine.

Abstract


Cryptococcus neoformans is an opportunistic fungal pathogen that causes fatal meningoencephalitis in immunocompromised hosts such as patients with AIDS and hematological malignancy. Host defense to C. neoformansinfection is mediated by Th1-type cellular immunity, which is triggered by host cell recognition of the pathogen-associated molecular patterns via the pattern recognition receptors. Recently, our study revealed that TLR9-dependent sensing of cryptococcal DNA was a pivotal step in initiating the host defense to this infection and raised a possibility that this process may be triggered in a distinct manner by bacterial DNA with a canonical CpG motif. In addition, we found that mice deficient in CARD9, a critical adapter molecule for signaling via C-type lectin receptors (CLRs), was highly susceptible to cryptococcal infection with impaired immune responses, suggesting a possible involvement of some CLRs. In this article, we review advances in understanding the pattern recognition and host defense response to C. neoformans, with a particular focus on our recent results.

Friday, December 14, 2012

Review of streptococcal bloodstream infections at a comprehensive cancer care center, 2000-2011.


Review of streptococcal bloodstream infections at a comprehensive cancer care center, 2000-2011.


Nov 2012

Source

Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: sshelburne@mdanderson.org.

Abstract


OBJECTIVES:

To determine the comparative rates, clinical characteristics, and outcomes of invasive infections due to specific streptococcal types in patients with cancer.

METHODS:

Review of electronic medical records of patients with non-viridans group streptococcal bloodstream infection (BSI) at the MD Anderson Cancer Center from 2000 to 2011.

RESULTS:

550 streptococcal BSI were identified. The largest number of cases were caused by Streptococcus pneumoniae (251), group B Streptococcus (147), and gamma-hemolytic streptococci (55). Risk factors for developing a severe streptococcal infection included older age, being neutropenic at onset of BSI, and having a respiratory source of infection. Between 2000-2001 and 2010-2011, the rates of S. pneumoniae BSI and penicillin non-susceptibility decreased by 55% and 100%. In contrast the rate of group B streptococcal (GBS) BSI increased 34% over the same time period. GBS accounted for >80% of the recurrent infections following streptococcal BSI. Patients with breast cancer and those with soft-tissue/bone BSI sources were at increased risk for recurrent GBS infection but had lower rates of severe GBS disease.

CONCLUSIONS:

From 2000 to 2011, our comprehensive cancer center observed a significant decrease in the rates of S. pneumoniae BSI and a significant increase in the rates of GBS BSI

Bacterial DNA sequence used to map an infection outbreak

Bacterial DNA sequence used to map an infection outbreak

November 14, 2012 05:51 PM

For the first time, researchers have used DNA sequencing to help bring an infectious disease outbreak in a hospital to a close.
Researchers from the Wellcome Trust Sanger Institute, the University of Cambridge and Cambridge University Hospitals used advanced DNA sequencing technologies to confirm the presence of an ongoing outbreak of methicillin-resistantStaphylococcus aureus (MRSA) in a Special Care Baby Unit in real time. This assisted in stopping the outbreak earlier, saving possible harm to patients. This approach is much more accurate than current methods used to detect hospital outbreaks.
Using this technology, the team revealed that the outbreak had extended into the wider community, a conclusion that could not be reached with available methods. They also used sequencing to link the outbreak to an unsuspecting carrier, who was treated to eradicate MRSA.
"We are always seeking ways to improve our patient care and wanted to explore the role that the latest sequencing technologies could play in the control of infections in hospitals," says Dr Nick Brown, author, consultant microbiologist at the Health Protection Agency and infection control doctor at Addenbrooke's Hospital Cambridge. "Our aim is to prevent outbreaks, and in the event that they occur to identify these rapidly and accurately and bring them under control.
"What we have glimpsed through this pioneering study is a future in which new sequencing methods will help us to identify, manage and stop hospital outbreaks and deliver even better patient care."
Over a six month period, the hospital infection control team used standard protocols to identify 12 patients who were carrying MRSA. However, this standard approach alone could not give enough information to confirm or refute whether or not an ongoing outbreak was actually taking place.
In this study, the researchers analysed MRSA isolates from these 12 patients with DNA sequencing technology and demonstrated clearly that all the MRSA bacteria were closely related and that this was an outbreak. They also revealed that the outbreak was more extensive than previously realised, finding that over twice as many people were carrying or were infected with the same outbreak strain. Many of these additional cases were people who had recent links to the hospital but were otherwise healthy and living in the community when they developed a MRSA infection.
While this sequencing study was underway, the infection control team identified a new case of MRSA carriage in the Special Care Baby Unit, which occurred 64 days after the last MRSA-positive patient had left the same unit. The team used advanced DNA sequencing to show in real time that this strain was also part of the outbreak, despite the lack of apparent links between this case and previous patients. This raised the possibility that an individual was unknowingly carrying and transmitting the outbreak MRSA strain.
The infection control team screened 154 healthcare workers for MRSA and found that one staff member was carrying MRSA. Using DNA sequencing, they confirmed that this MRSA strain was linked to the outbreak. This healthcare worker was quickly treated to eradicate their MRSA carriage and thus remove the risk of further spread.
"Our study highlights the power of advanced DNA sequencing used in real time to directly influence infection control procedures," says Dr Julian Parkhill, lead author from the Wellcome Trust Sanger Institute. "There is a real health and cost burden from hospital outbreaks and significant benefits to be gained from their prevention and swift containment. This technology holds great promise for the quick and accurate identification of bacterial transmissions in our hospitals and could lead to a paradigm shift in how we manage infection control and practice."
In this instance, DNA sequencing was a key step in bringing the outbreak to a close, saving possible harm to patients and potentially saving the hospital money.
"Our study indicates the considerable potential of sequencing for the rapid identification of MRSA outbreaks," says Professor Sharon Peacock, lead author from the University of Cambridge and clinical specialist at the Health Protection Agency. "What we need before this can be introduced into routine care is automated tools that interpret sequence data and provide readily understandable information to healthcare workers. We are currently working on such a system.
"If we have a robust system of this type in operation when the outbreaks occur, we predict that we will be able to stop them after the first few cases, as we will rapidly find clear connections."
In their next step, the team will study all MRSA carriers and infected patients over the next year in Addenbrooke's Hospital and surrounding hospitals and the community to understand transmission events with the aim of improving infection management.
Sir Mark Walport, Director of the Wellcome Trust, says: "This is a dramatic demonstration that medical genomics is no longer a technology of the future - it is a technology of the here and now. By collaborating with NHS doctors, geneticists have shown that sequencing can have extremely important applications in healthcare today, halting an outbreak of a potentially deadly disease."

How salmonella uses body’s own defences to spread infection


SCIENTISTS have discovered how salmonella uses the body’s own defences to spread, by
targeting cells in the gut.
A study at Edinburgh University has found that the bacterium has a mechanism that it uses to change the nature of key cells that line the intestine, enabling the bugs to gain access to the body, spreading infection.
The discovery has long-term potential for developing vaccines against the bacteria, but also boosting the body’s immune system.
Salmonella food poisoning – commonly caused by eating under­cooked poultry or eggs – is a serious infection that can lead to diarrhoea, fever and even death in young children.
In 2011, there were 737 recorded incidents of salmonella poisoning in Scotland, compared with 941 in 2010.
In February this year, 35 people in the UK, including five in Scotland, were hit during an outbreak linked to infected slices of ready-to-eat watermelons. It resulted in one death.
According to Dr Neil Mabbott, who worked on the three-year research project, salmonella targets the immune system’s own monitoring system of the intestine to get access to the body.
“The intestine is usually designed for keeping bacteria and other pathogens out but taking in food molecules,” he explained.
“In occasional places along it [the intestine], the immune system needs to be able to sample what’s going on in the intestine, to discover if there’s an infection going on, and respond to it. There are specialised cells to do this called M-cells – microfold cells – that are essentially designed for taking up large particles, which could be toxins or bacteria, so that the immune system can sample them and
decide whether they are friend or foe and act accordingly.”
The research showed that salmonella bacteria change the make-up of intestine cells, turning them into these M-cells and effectively creating a “portal” out into the body where they can infect vital organs, such as the kidneys and the liver.
The salmonella injects a protein called SopB into cells in the lining of the intestinal wall, called epithelia – which transforms the make-up of certain ones, creating a dramatic increase in M cells.
The work, published in Cell Host & Microbe, reveals how, once the salmonella produces enough cells, it can then get through into the bloodstream.
It was previously suspected that salmonella was using these M-cells to get into the body, but the mechanism by which it was doing this was not understood.
Scientists say that the research significantly furthers our understanding of bacterial infections.
As part of their study, the Edinburgh scientists showed that the protein used by salmonella can be artificially disabled, reducing greatly its ability to spread out into the body.
This raises the potential for developing vaccinations against the infection. However, it is also hoped that the “transformation” protein mechanism could be harnessed and used to boost the body’s immune system.
Lead researcher Dr Arvind Mahajan, from the Roslin Institute, said yesterday the study revealed the “sophisticated” way that bacteria adapted their environment to their own ends.

Battling bacteria: Research shows iron's importance in infection, suggests new therapies


Battling bacteria: Research shows iron's importance in infection, suggests new therapies


Nov 2012

The collaborative research—led by Phillip Klebba, professor and head of the department of biochemistry—clarifies how microorganisms colonize animal hosts and how scientists may block them from doing so. The findings suggest new approaches against bacterial disease and new strategies for antibiotic development. The study—in collaboration with Tyrrell Conway, director of the Microarray and Bioinformatics Core Facilities at the University of Oklahoma, and Salete M. Newton, Kansas State University research professor of biochemistry—recently appeared in PLOS ONE. It shows how iron acquisition affects the ability of bacteria to colonize animals, which is the first stage of microbial disease. "This paper establishes that iron uptake in the host is a crucial parameter in bacterial infection of animals," said Klebba, the senior author on the publication. "The paper explains why discrepancies exist about the role of iron, and it resolves them." Iron plays a key role in metabolism, leading bacteria and animals to battle each other to obtain it. Klebba's team found that E. coli must acquire iron from the host to establish a foothold and colonize the gut—a concept that was often debated by scientists. "For years it was theorized that iron is a focal point of bacterial pathogenesis and infectious disease because animals constantly defend the iron in their bodies," Klebba said. "Animal proteins bind iron and prevent microorganisms from obtaining it. This is called nutritional immunity, and it's a strategy of the host defense system to minimize bacterial growth. But successful pathogens overcome nutritional immunity and get the iron." Little was known about what forms of iron enteric bacteria—which are bacteria of the intestines—use when growing in the host, but this study shows that the native Gram-negative bacterial iron uptake systems are highly effective. Scientists questioned whether prevention of iron uptake could block bacterial pathogenesis. This article leaves no doubt about the importance of iron when E. coli colonizes animals because bacteria that were systematically deprived of iron became 10,000-fold less able to grow in host tissues, Klebba said.

"This is the first time our experiments unambiguously verified the indispensability of iron in infection, because here we created the correct combination of mutations to study the problem," Klebba said. Enteric bacteria have so many iron transport systems that it's difficult to eliminate them all. For example, E. coli has at least eight iron acquisition systems. "These transporters are redundant because iron is essential," Klebba said. "Bacteria are resilient. If one system is blocked, then another one takes over." These findings suggest strategies to block microorganisms from creating diseases in animals and humans, including the potential for antibiotic development and for therapeutic antibodies. "It gives us insight," Klebba said. "Now we know that iron deprivation protects against disease, but we must be comprehensive and inhibit multiple systems to completely shut down the microorganisms' ability to obtain the metal." The researchers are using their findings to isolate antibodies that block bacterial iron uptake. This may help animals and humans defend themselves against microbial diseases. "We would like to apply this research and protect people from bacterial infection," Klebba said. "That's one of the focal points of our laboratory." Klebba's research was supported by a $1.25 million grant from the National Institutes of Health. The study was led by Hualiang Pi, Klebba's student at his former institution, the University of Oklahoma. Another Kansas State University collaborator on the project was Lorne Jordan, doctoral student in biochemistry, Toledo, Ohio.

Phys.orgNews

Beagle Sniffs Out Bacterial Infection


Beagle Sniffs Out Bacterial Infection


Dec 14, 2012

Reported by Dr. Amish Patel:
A 2-year-old beagle in the Netherlands has been trained to sniff out Clostridium difficile, a skill that could help doctors catch the deadly infection days before laboratory tests.
Clostridium difficile infections often occur in people who are already taking antibiotics, causing symptoms that range from mild diarrhea to severe inflammation of the colon. And to make matters worse, the bug is particularly adept at spreading through hospitals, uncontrolled by the usual surface cleansers.
The clever canine, called Cliff, correctly identified 50 stool samples containing the bacterium, which kills 14,000 Americans each year, according to the U.S. Centers for Disease Control and Prevention.       Cliff also identified 47 of 50 stool samples that were Clostridium difficile-free (he couldn’t make up his mind about the last three).
Laboratory tests for Clostridium difficile — dubbed C. diff — can take up to 48 hours. But Cliff gives his answer immediately by sitting or lying down.
“The sooner the clinician has a diagnosis, the better it is,” said Dr. William Schaffner, an expert in infectious diseases at Vanderbilt University Medical Center in Nashville, Tenn. “You can also reduce the risk of transmission to other patients.”
Stool from patients with the C. diff has a characteristic smell, often likened to horse manure, which Cliff learned to identify over two months of training. Now he can smell the bug even without the stool, correctly identifying 25 of 30 patients with the infection and 265 of 270 without.
“We’ve always known that dogs make us feel good, but now we know that they’re good for us,” said veterinarian Dr. Marty Becker, who is based in Sandpoint, Idaho, and is the author of “The Healing Power of Pets” and a writer for  VetStreet.com   
Dogs have also been trained to sniff out cancers of the lung, bowel, skin, breast, and bladder with high accuracy, and petting animals can also be therapeutic.
“We use them in our institution, largely in pediatrics, and have brought in reptiles, dogs and even miniature ponies,” said Schaffner.
However, Cliff has struggled with staying focused at work, according to the study authors. A plastic cup, urine on the floor, excited children, and the strong smell of cleaners proved distracting.
“This may not work in the context of much more hectic U.S. hospitals,” said Schaffner.  “I don’t think [dogs] will replace [existing laboratory tests].”
But Becker said the healing power of pets should not be underestimated.
“There was a time when you expected to see this kind of stuff in the tabloids,” he said. “Now the science is there to show how it works.  What are we going to find next?”

Wednesday, December 5, 2012

Prognostic factors in Fournier gangrene.


Prognostic factors in Fournier gangrene.


Jan 2012

Source

Department of Surgery, Hospital Universitario de Elche, Alicante, Spain. jruiztovar@gmail.com

Abstract


BACKGROUND:

Fournier gangrene is a necrotizing fasciitis, arising in the genital and perineal area. This entity is still associated with a high mortality rate despite improvements in antibiotic and surgical treatment.

METHODS:

This is a retrospective study of all the patients diagnosed and surgically treated for Fournier gangrene at General University Hospital Ramon y Cajal between 1988 and 2008. Possible prognostic factors that could have any influence on the evolution of Fournier gangrene were analyzed.

RESULTS:

Seventy patients were analyzed, 62 males (88.6%) and 8 females (11.4%) with a mean age of 57.9 ± 13.5 years. Most frequent clinical manifestations were perineal pain (82.9%) and fever (60%). Physical examination revealed edema (91.4%), erythema (88.6%) and perineal skin necrosis (60%). All the patients underwent surgical debridement of necrotic tissue. In 54.3% reoperations were necessary for new surgical debridements. Medical complications rate was 27.1% and mortality one 22.9%. Ethylism, coexistence of neoplasms, presence of skin necrosis, myonecrosis, abdominal wall affection, number of debrided areas, reoperations, concentration of creatinine in serum>1.4 mg/dL, and hemoglobin <10 g/dL, and platelet count <150 × 10(9)/L in whole blood are associated with higher mortality rates.

CONCLUSION:

Identification of prognostic factors may help to determine high-risk patients in order to establish an optimal treatment, according to severity of the infection and general status.

**Editor's note:  I have included this due to the fact that we who have lymphedema are so prone to infections and it is imperative that we understand why it is urgent to seek immediate medical care when we ahve those infections.**