Discovery Of New Immune Defence Enzyme

Main Category: Immune System / Vaccines
Also Included In: Arthritis / Rheumatology
Article Date: 07 Apr 2012 – 0:00 PDT

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Neutrophil granulocytes comprise important defences for the immune system. When pathogenic bacteria penetrate the body, they are the first on the scene to mobilise other immune cells via signal molecules, thereby containing the risk. To this end, they release serine proteases – enzymes that cut up other proteins to activate signal molecules. Scientists at the Max Planck Institute of Neurobiology in Martinsried have now discovered a new serine protease: neutrophil serine protease 4, or NSP4. This enzyme could provide a new target for the treatment of diseases that involve an overactive immune system, such as rheumatoid arthritis.

The functioning of the immune system is based on the complex interplay of the most diverse cells and mediators. For example, neutrophil granulocytes (a group of specialized white blood cells) react to bacteria by releasing substances called serine proteases. These enzymes are able to activate signal molecules, such as the chemokines, by cleaving them at a specific position on the molecule. The active signal molecules then guide other immune cells to the focus of inflammation in order to destroy the pathogens.

A research team led by Dieter Jenne at the Max Planck Institute of Neurobiology in Martinsried has come across a previously unknown protease in humans: neutrophil serine protease 4, or NSP4. “The special thing about this enzyme is that it cuts proteins that have the amino acid arginine at a particular point”, says Dieter Jenne, research group leader at the Martinsried-based Institute. “This is where NSP4 differs from the other three known neutrophil serine proteases, which are similar in molecular structure, but have a different recognition motif.” The scientists may be able to harness this difference to develop an active substance that specifically inhibits NSP4, thereby reducing the immune reaction.

However, serine protease activity comes at a cost. The enzymes not only heal inflammations, but sometimes cause them in the first place. If too many immune cells are activated, they can use their arsenal of aggressive chemical weapons against the body’s own tissues. A number of chronic inflammatory diseases are based on precisely this effect. As a result, scientists are searching for substances that can block the neutrophil proteases. To date, however, none of the substances tested have been developed into effective drugs.

“So far, we don’t know the identity of the NSP4 substrate, but we assume they must be signal molecules”, says Dieter Jenne. Activated chemokines can recruit a vast number of neutrophils, and their sheer quantity alone is enough to cause tissue damage. “Proteases sometimes act as accelerants and can even trigger a chronic inflammation quite independently of bacterial intruders. If we dampened down the defences, we could counteract this effect”, explains the scientist.

In terms of evolutionary history, NSP4 is the oldest of the four known neutrophil serine proteases. Using gene sequences, scientists have shown that the enzyme has hardly changed through hundreds of millions of years of evolution from bony fish to humans. “That would indicate that NSP4 regulates a fundamental process”, says Dieter Jenne.

The fact that the enzyme remained undiscovered until now is because it occurs at a much lower concentration than the other three proteases. The Max Planck scientists came across it while searching the human genome for genes that encode serine proteases. In the process, they noticed a previously unknown gene sequence. Natascha C. Perera, a member of the Martinsried research group and lead author of the study, managed to produce and examine the enzyme in its active, folded state.

If they are to establish NSP4 in the future as a possible target protein for anti-inflammatory drugs, the scientists must now examine its function in living organisms and discover whether blocking the enzyme has adverse effects. The scientists are working with the company Novartis to answer these questions in laboratory mice. “NSP4 inhibitors could be used in diseases like chronic arthritis or inflammatory skin diseases”, says Dieter Jenne, “but first we have to test the long-term effects of these substances.”

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Standardized Measures To Determine Rheumatoid Arthritis Disease Activity Endorsed By The ACR

Main Category: Arthritis / Rheumatology
Article Date: 04 Apr 2012 – 1:00 PDT

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A working group convened by the American College of Rheumatology (ACR) has evaluated more than 60 disease activity measures for rheumatoid arthritis (RA). The group narrowed the number of RA disease activity measures and the recommended six for use in U.S. clinical practice are detailed in Arthritis Care Research, a journal published by Wiley-Blackwell on behalf of the ACR.

RA is a systemic inflammatory disease, affecting more than 1 million Americans according to ACR estimates. Medical evidence has shown significant improvement in RA treatment over the last two decades, making disease remission possible for many patients. While many health care stakeholders advocate standardized assessments for RA disease activity, uniform measures of RA activity are not currently used by U.S. rheumatologists.

To address this important issue, the RA Clinical Disease Activity Measures Working Group systematically reviewed medical literature to identify disease activity measures for RA. The group surveyed rheumatologists for input and used this feedback along with psychometric analysis to determine recommendations for RA disease activity assessments.

“Our goal was to determine which RA disease activity measures could accurately distinguish the various levels of RA activity, and would also be reasonable to implement in clinical practice,” explains Salahuddin Kazi, M.D., with Dallas VA Medical Center in Texas and one of the lead researchers involved with the working group. The group identified 63 RA disease activity measures, narrowing that down to 14 measures for further evaluation by practicing rheumatologists.

Feedback from the rheumatologists determined that 9 measures would be most useful and feasible in a clinical setting. The working group then selected 6 disease activity measures based on their reliability, validity and responsiveness. The ACR-approved recommendations for RA disease activity measures include:

  • Clinical Disease Activity Index (CDAI)
  • Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein) (DAS-28)
  • Patient Activity Scale (PAS)
  • PAS-II
  • Routine Assessment of Patient Index Data with 3 measures (RAPID 3)
  • Simplified Disease Activity Index (SDAI)

In a related article, “2012 Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis,” Singh et al. include the RA disease activity measures to guide clinicians in selecting the appropriate treatment options for their patients. “Rheumatologists are tasked with treating to target, and one or more of these disease activity measures will help determine the level of RA disease activity in the patient,” said Dr. Kazi. ”

The measures recommended to determine RA disease activity are sensitive to change, can discriminate between low, moderate, and high disease activity states, include remission criteria, and are feasible to perform in a clinical setting,” concludes Dr. Kazi. “Incorporating standardized disease activity measures will facilitate adherence to the ACR guidelines for treating RA and aid clinicians in providing quality care to their patients with RA.”

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Guidelines For Use Of DMARDs And Biologic Drugs In Treating Rheumatoid Arthritis Updated By American College Of Rheumatology

Main Category: Arthritis / Rheumatology
Also Included In: Tuberculosis
Article Date: 04 Apr 2012 – 1:00 PDT

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The American College of Rheumatology (ACR) has released the 2012 recommendations for the use of disease-modifying antirheumatic drugs (DMARDs) and biologic agents in the treatment of rheumatoid arthritis (RA). The guidelines published in the ACR journal, Arthritis Care Research, are an update to the 2008 recommendations and address the issues of initiating and switching drugs, screening for tuberculosis (TB) reactivation, immunization, and the use of biologics in high-risk RA patients.

More than one million Americans suffer with RA – a chronic disease that causes pain, swelling and inflammation in the lining of the joints – and 75% of those affected are women according to the ACR. DMARDs such as methotrexate and hydroxychloroquine may be used individually or in combination with biological agents to treat RA. Biological agents include the tumor necrosis factor (TNF) inhibitors adalimumab, cerotlizumab pegol, etanercept, golimumab or infliximab; or the non-TNF biological drugs, abatacept, tocilizumab or rituximab. Biologics should not be used together.

“Effective treatment of RA is essential to control disease progression and improve quality of life for patients,” says Dr. Jasvinder Singh with the University of Alabama at Birmingham, the principal investigator for the 2012 update of the ACR RA guidelines for the use of DMARDs and biological agents. “With additional advancements in RA therapies since 2008, it was important to update recommendations that help guide rheumatologists in treating RA patients receiving DMARDs or biologic therapies.”

The 2012 DMARD and biologic agents recommendations included a number of areas but concentrated on four updated sections:

  • Indications for use and switching of DMARDs and biologics
  • Use of biologic agents in high-risk RA patients with hepatitis, cancer, or congestive heart failure
  • Screening for TB in RA patients starting or receiving biologic drugs
  • Vaccination in patients starting or receiving DMARDS or biologics

Dr. Singh further explains, “The recommendations for DMARD and biologic treatment provide a guide for rheumatologists who care for RA patients. However, these guidelines should not replace important physician-patient discussions or individual clinical decisions that take into account assessments of risk-benefits, patient preferences, and economic considerations.”

The authors suggest that low disease activity or remission should be the goal for each RA patient, but each patient’s therapy target should be specific to their particular health needs. One of the noted changes from the 2008 guidelines is more aggressive treatment in patients with early RA that is within six months of symptom onset. Researchers believe the recommended change to more intensive early therapy is that earlier treatment may provide better outcomes; joint damage in RA is irreversible, making prevention of damage an important goal; and preserving physical function and health-related quality of life is necessary to reduce disability.

A related editorial is also available in Arthritis Care Research. Co-author Dr. David Daikh, Associate Professor of Clinical Medicine at the University of California, San Francisco and Chief of Rheumatology at the VA Medical Center comments, “The treatment of RA is a rapidly changing field with new therapies regularly becoming available. As this field evolves, the recommendations for treatment with DMARDs and biologic drugs will need to be modified in the future and the ACR must be nimble in keeping these guidelines as current as possible.”

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Full citation: “2012 Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis.” Jasvinder A. Singh, Daniel E. Furst, Aseem Bharat, Jeffrey R. Curtis, Arthur F. Kavanaugh, Joel M. Kremer, Larry W. Moreland, James O’Dell, Kevin L. Winthrop, Timothy Beukelman, S. Louis Bridges Jr., W. Winn Chatham, Harold E. Paulus, Maria Suarez-Almazor, Claire Bombardier, Maxime Dougados, Dinesh Khanna, Charles M. King, Amye L. Leong, Eric L. Matteson, John T. Schousboe, Eileen Moynihan, Karen S. Kolba, Archana Jain, Elizabeth R. Volkmann, Harsh Agrawal, Sangmee Bae, Amy S. Mudano, Nivedita M. Patkar, and Kenneth G. Saag.Arthritis Care Research; Published Online: April 2, 2012 (DOI: 10.1002/acr.21641).

Editorial: “Updated Recommendations for the Treatment of Rheumatoid Arthritis: Another Step on a Long Road.” David I. Daikh and E. William St.Clair..Arthritis Care Research; Published Online: April 2, 2012 (DOI: 10.1002/acr.21659).

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Metastatic Breast Cancer And Arthritis Link

Main Category: Breast Cancer
Also Included In: Arthritis / Rheumatology;  Lung Cancer
Article Date: 03 Apr 2012 – 0:00 PDT

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New research shows it may be no accident when doctors observe how patients suffering from both breast cancer and arthritis seem to have more aggressive cancer. However, the new-found interaction between the two diseases may also suggest a possible treatment.

A potential relationship between metastatic breast cancer and autoimmune arthritis, as suggested by past epidemiological studies, has led researchers from the University of North Carolina at Charlotte to perform a series of mouse model experiments that appear to confirm the connection.

“Epidemiological studies have implied that breast cancer survival is significantly lower in patients who also had autoimmune arthritis,” noted Pinku Mukherjee, Irwin Belk Distinguished Scholar of Cancer Research at UNC Charlotte, whose lab conducted the experiments. “As there is no obvious reason this should be so, we were interested in exploring possible cancer mechanisms that might explain why.”

The experiments point to an intimate relationship between mast cells – immune system cells that are located in various tissues and that can cause inflammation – and metastatic tumors.

In previously published studies, UNC Charlotte cancer researcher Lopamudra Das Roy and her mentor Mukherjee established that breast cancer associated metastases were significantly higher in arthritic mice, with a threefold increase in lung metastases and a twofold increase in bone metastases.

In their most recent work, the researchers found that mast cells and their associated inflammation are present in larger numbers in the bones and lungs of arthritic mice than they are in non-arthritic mice. Their findings point to a relationship between the cKit receptor found on mast cells and the transmembrane stem cell factor (SCF) ligand found on metastatic breast cancer cells. The interaction between SCF and cKit appears to play a critical role in facilitating metastasis.

“We confirmed the relationship we suspected between autoimmune disease and metastastic breast cancer cells,” Mukherjee said. “This is an exciting result for us because it confirms an interesting interdependence between cancer metastasis and a specific component of the immune system.”

The study results was presented by Lopamudra Das Roy, Research Assistant Professor at UNC Charlotte, and Mukherjee at the 2012 American Association for Cancer Research Annual Meeting in Chicago at a press conference.

The researchers worked with two strains of mice. The first group had spontaneous arthritis (SKG mice) and the second group of mice had spontaneous breast cancer (MMTV-PyV MT mice). Each of the mouse strains were artificially induced to develop the other disease and then tested for differences.

Among the findings of the analysis was that the population of mast cells within bone and lung microenvironment was significantly higher in those mice with arthritis and breast cancer vs. those without arthritis and breast cancer. The differentiation of mast cells from bone marrow derived stem cells was also significantly higher in the arthritic versus the non-arthritic tumor-bearing mice.

Mast cells are the only “terminally differentiated” (mature) cells in the body that develop, like blood cells, from stem cells in the bone marrow and that also have a c-Kit receptor. Suspecting a relationship between the c-Kit receptor on the mast cells and the SCF ligand expressed by the metastatic cancer cells, the researchers tested the effect of blocking receptor by treating the mice with an anti-c-Kit receptor antibody and celecoxib, an anti-inflammatory medication.

“When the mice were treated with a therapy to target the c-Kit mast cell receptor in combination with celecoxib – a drug used to treat autoimmune arthritis – the incidence of breast cancer metastasis to the bone and lung was greatly reduced,” Das Roy noted.

The researchers conclude that in an arthritic condition, SCF expression in metastatic breast cancer cells induces the differentiation of mast cells from bone marrow through SCF/CKit signaling. Mast cells, in turn, facilitate the efficient metastasis of the breast cancer cells in bone and lung tissue. Autoimmune arthritis disease increases the intensity of metastatic breast cancer because bone marrow stem cells in autoimmune arthritis victims have greater potential to develop into mast cells.

In future studies, the researchers plan to examine the presence of mast cells in human tumor samples.

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OBGYNs are soooo Funny!

Conversations with my OBGYN:

Me, eyes wide as saucers: “That’s the biggest Q-tip I’ve ever seen.  That’ll never fit in my ear.”


“That’ll never fit in my ear…”

Doctor: “Oh, it’s not going in your ear…”  (Insert maniacal laughter here)

Me, staring at the ceiling: “You gals really need some artwork up here or something.


Beats looking at the Inception Speculum

Doctor: “You’re right.  We need something to keep you from seeing instruments like these…”

Me: “What the heck is THAT???”  Doctor: “It’s like a tiny speculum, for your cervix, so I can open it up and get good sample.”

Me: “So it’s like a speculum within a speculum?  How very ‘Inception’ of you.”

Doctor: “Heh… You’re the only one who would think of that!”

September 1997

September 1997 – Woodbridge, Virginia 
 
The whole family was asleep when I heard the beeping in my left ear. I was on the internet talking in #UFO on Undernet about my initial experience with the missing time. These various types of equipment started to come to be visually: a connector of some sort, a possible stasis chamber, a possible source of energy (green fluid), and for the first time saw one of them very sick, tired, and could hardly stand up. This one had almond shaped eyes, pale pink/gray skin tone, but the skin was peeling (possible radiation burns), and was 4.5 to 5 feet tall. On the 15th had been on board a scout ship and saw bright white light emitted from wands in the ceiling of these ships (resembled the frets and arms of a guitar). The white light pulsed–the more you thought or looked at it–the pulse changed. No other memory from that visit. Later in the month (23rd), I woke up with a lump on the back of my neck on the left side. Had my husband feel it 1900 hours and he found it. (Could some fluid been removed in the early hours of the morning?) I had no inclination to see a doctor about this either. I don’t usually wake up with strange lumps. Also later in the month (24th) someone had placed a Phase I, delta tone on the Internet. When I listened to this tone, I visualized gray’s face, a pyramid receiving/sending energy, and a global map of Earth with landing sites. End of month (26th) was on the Internet in #Sufoit/Para-4 on DALnet when Spotk2 and Bambina said that I should go outside to look at the Zeta motherships. I couldn’t find the Big Dipper or Orion’s Belt, but I did see a ship just below the left of the Little Dipper. It was yellow with orange tinge. I saw this through binoculars.

Surgical Instruments providing Company

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Things related to RMS

As there is advancement in medical technologies and innovation has progressed forward, surgical instruments, such as laryngoscopes, have had to adapt and change to fit new uses and new tools have had to be developed and created all together. With the growing technologies there are advancements in the surgical equipments also and this has developed new methods of operating to surgeons. These changes and innovations are allowing doctors to remain on the cutting edge of technology to keep their patients happier and healthier.

Surgical instruments are supplied to a large number of hospitals, private practices, clinics, and other medical settings throughout the world by a multitude of suppliers and manufacturers.  You will find that nearly every state in the US has a supplier or manufacturer of surgical equipment, instruments, tools, and or supplies. From the smallest supplier to the largest manufacturer, they all play a crucial role in the development and distribution of the necessary medical instruments that are needed to save lives.

RMD (Recorders Medical Devices India) is a name trusted by educationists. Ever since its inception in 2011 has endeavored incessantly to manufacturer high quality instruments and equipment used by educationist institutions for medical , pharmaceutical , pharmacy and physics laboratories.

Have a look at Medical Equipment.