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1  Tutkimus / Tutkimus / Re: Krooniset bakteeri-infektiot
 Pvm: 25.05.2018 - 18:23:13 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  

How EBV might cause immune cells to go rogue in MS


https://msra.org.au/news/ebv-might-cause-immune-cells-go-rogue-ms/

08 May, 2018

   Epstein Barr Virus (EBV) infection can contribute to the development of autoimmune diseases including MS.
   The virus can make proteins which bind to DNA and these can interact with the parts of DNA that control MS risk genes.
   The variations in some genes that are associated with an increased risk of developing MS are more likely to interact with EBV.

Viruses are the ultimate pirates using cunning and deceit to evade our body’s defences and hijack our cells – once inside they can use our cells as a factory to manufacture and copy themselves, or they can just lie dormant until they are ready to jump ship and move on.

Different human viruses favour invading different types of cells in the body. The Epstein Barr Virus, which has been linked to the development of MS and some other autoimmune diseases, favours B cells which is a type of cell in the immune system.

When viruses commandeer our immune cells they can cause the cells to go rogue and steer off course a bit and this is thought play a role in the development of autoimmune diseases.

EBV is a very common infection most often acquired during early childhood, either without symptoms or just as a generic childhood upper respiratory tract infection. In adolescents and young adults it can also cause glandular fever. Between 90 and 95% of the general population will have been infected by the virus at some point in their life. In comparison, close to 100% of people with MS have been infected. So it is thought that, on its own EBV, can’t cause MS, but in susceptible people it contributes to the development of MS. Until now the exact reason for this was not clear.

When a virus enters a cell it starts controlling some of the genes in the cell and researchers have now found that EBV can interact specifically and directly with some of the genes that have been identified as risk genes for MS and other autoimmune disorders. Their work has been published in the prestigious scientific journal Nature Genetics.

To show this, the scientists took cells which were either infected or not with EBV, and then looked to see where proteins from the virus were bound to the DNA of the cells, as this is a key sign that the virus is using those specific genes. In the case of MS, they found that out of the 109 known MS risk genes the viral proteins where bound to 44 of these genes. Importantly, the virus appeared to do this more readily in B cells, and not other cells.

The scientists also looked at whether the specific variations in the DNA code that is linked to MS in these genes changed how strongly the virus proteins bound to the DNA. They found that the virus latched on to the version of the gene code linked to MS more readily than it did to the ‘standard’ version of the gene, suggesting a specific interaction between the MS risk gene variations and EBV.

This work reveals an important mechanism by which our genes and the virus might effectively conspire against us to cause MS only in some people and not everyone who has been infected with EBV. Ultimately, this type of work may help us to understand how we can prevent the changes that EBV makes to the immune system to help prevent or treat MS.

EBV has long been studied in relation to MS, and Australian researchers have been working on an early phase clinical trial of a therapy called EBV-specific adoptive immunotherapy. In this therapy the scientists remove some of the immune cells from people with MS, and prime them to hunt out and destroy EBV infected cells.

The results of this initial safety trial are still awaited but it represents an innovative new way to tackle the role of EBV in MS. You can read more about that study here.

By understanding the fundamental impacts of EBV on B cells and genes we will be much better placed to understand the causes of autoimmunity and discover molecular targets for future treatments.

2  Tutkimus / Tutkimus / Re: Krooniset bakteeri-infektiot
 Pvm: 25.05.2018 - 18:16:36 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
Different diseases elicit distinct sets of exhausted T cells

https://www.sciencedaily.com/releases/2018/05/180515113754.htm

May 15, 2018
The battle between the human immune system and long-term, persisting infections and other chronic diseases such as cancer results in a prolonged stalemate. Over time battle-weary T cells become exhausted, giving germs or tumors an edge. Using data from multiple molecular databases, researchers from the Perelman School of Medicine at the University of Pennsylvania have found nine distinct types of exhausted T cells ("Tex"), which could have implications for fighting chronic infections, autoimmunity, and cancer. They published their findings in Immunity this week.

"Exhausted T cells are a discrete cell lineage that have become important immunotherapy targets for chronic infection and cancer," said senior author John Wherry, PhD, a professor of Microbiology and director of the Institute for Immunology. "Now, we know that exhausted T cells are a vastly diverse set of immune cells."

Wherry's lab has spent the last decade describing these populations of fatigued cells. Overall, when normal T cells become exhausted, they develop defects in their germ- and tumor-fighting capabilities. Tex also express inhibitory receptor proteins on their surface that stall key biochemical pathways, provoke changes in control of gene expression, alter metabolism for making energy to fight infections and tumors, and prevent development of optimal immune function.

New, highly effective immunotherapies that target these inhibitory receptors expressed by Tex such as PD-1 or CTLA-4 have shown dramatic effects among patients with melanoma and other diseases, with potential to also combat breast, ovarian and other cancers. Although Tex have been implicated in the response to checkpoint blockade drugs in animal models, the underlying immunological mechanisms of their therapeutic response or failure in people is only now being studied in earnest.

"Exhausted T cells are quite diverse, as are all types of T cells," Wherry said. "This sheer diversity is the hallmark of the human immune system that has to essentially have a way to respond to every germ an individual might encounter in a lifetime."

Knowing this, the Penn team asked what the diversity in the Tex pool reveals about a disease itself and its course in a patient. They developed an assay to investigate the molecules that control gene expression in Tex by comparing them to other types of T cells and within a Tex population in blood from HIV patients whose viral load is well-controlled.

Next, they defined core exhaustion-specific genes and identified disease-induced molecular changes in Tex populations in HIV with uncontrolled disease and in human lung cancer. Using this data, the Tex fell into nine distinct clusters of similar expression patterns with regard to transcription factors and inhibitory receptors.

Because of the clusters' relationships to specific disease type and progression, the team's aim is to use the signature of a Tex cluster to assess a patient's overall immune health and likelihood of responding to a certain therapy. "We want to be able to select and tailor immune therapies according to a patient's exhausted T cell pool and its individual characteristics," Wherry said.

Applying this type of assessment to exhausted T cells in the context of immunotherapy clinical trials might identify patients more likely to benefit from specific types of combination immunotherapies and may point to underlying mechanisms in the specific types of exhausted T cells responding to an infection or cancer.


3  Tutkimus / Tutkimus / Re: Suolistobakteerit, myeliini ja aivotoiminta
 Pvm: 25.05.2018 - 18:10:31 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
Dietary seaweed used to manipulate gut bacteria in mice

https://www.sciencedaily.com/releases/2018/05/180509135412.htm

Gut bacteria thrive on the food we eat. In turn, they provide essential nutrients that keep us healthy, repel pathogens and even help guide our immune responses.

Understanding how and why some bacterial strains we ingest can successfully take up residence in the large intestine, while others are quickly evicted, could help scientists learn how to manipulate the makeup of thousands of bacterial species there in ways that enhance our health or help fend off disease. But the sheer complexity of gut ecology has hampered this task.

Now, researchers at the Stanford University School of Medicine working with laboratory mice have shown that it's possible to favor the engraftment of one bacterial strain over others by manipulating the mice's diet. The researchers also have shown it's possible to control how much a bacterium grows in the intestine by calibrating the amount of a specific carbohydrate in each mouse's water or food.

"We're all endowed with a microbial community in our guts that assembled in a chaotic manner during our first few years of life," said Justin Sonnenburg, PhD, associate professor of microbiology and immunology. "Although we continue to acquire new strains throughout life, this acquisition is a poorly orchestrated and not-well-understood process. This study suggests it could be possible to reshape our microbiome in a deliberate manner to enhance health and fight disease."

A paper describing the research will be published online May 9 in Nature. Sonnenburg is the senior author. Former graduate student Elizabeth Shepherd, PhD, is the lead author.

Giving bacterium a leg up

The burgeoning field of probiotics -- live, presumably healthful bacterial cultures naturally found in food such as yogurt or included in over-the-counter oral supplements -- is an example of a growing public awareness of the importance of gut bacteria. Even if you don't take probiotics or eat yogurt, however, each of us unknowingly consumes low levels of gut-adapted microbes throughout our life. But, regardless of the source, it's not known what causes one strain to be successful over another. Many pass quickly through our digestive tract without gaining a foothold in our teeming intestinal carpet.

Sonnenburg and his colleagues wondered whether a dietary boost would give specific bacterial strains a leg up in the wild west of the gut microbiome. To investigate, they trekked to the San Jose Wastewater Treatment Facility to find members of the Bacteroides -- the most prominent genus in the human gut microbiota -- specifically looking for strains that are able to digest an ingredient relatively rare in American diets: the seaweed called nori used in sushi rolls and other Japanese foods. They screened the bacteria collected in the primary effluent for an ability to use a carbohydrate found in nori called porphyran.

"The genes that allow a bacterium to digest porphyran are exceedingly rare among humans that don't have seaweed as a common part of their diet," Sonnenburg said. "This allowed us to test whether we could circumvent the rules of complex ecosystems by creating a privileged niche that could favor a single microbe by allowing it to exist in the absence of competition from the 30 trillion other microbes in the gut."

Once they'd found a nori-gobbling strain of Bacteroides, the researchers attempted to introduce it into each of three groups of laboratory mice. Two groups of the mice had their own gut bacteria eliminated and replaced with the naturally occurring gut bacteria from two healthy human donors, each of whom donated exclusively to one group or the other. The third group of mice harbored a conventional mouse-specific community of gut microbiota.

A direct effect

The researchers found that when the mice were fed a typical diet of mouse chow, the porphyran-digesting strain was able to engraft in two groups of mice to varying and limited degrees; one of the groups of mice with human gut bacteria rejected the new strain completely. [b]However, when the mice were fed a porphyran-rich diet, the results were dramatically different: The bacteria engrafted robustly at similar levels in all the mice. Furthermore, Shepherd found that she could precisely calibrate the population size of the engrafted bacteria by increasing or decreasing the amount of nori the animals ingested.[/b]

"The results of this dilution experiment blew us away," Sonnenburg said. "The direct effect of diet on the bacterial population was very clear."

In addition to showing that they could favor the engraftment and growth of the nori-gobbling bacterial strain, the researchers went one step further by showing that the genes necessary to enable the digestion of porphyran exist as a unit that can be engineered into other Bacteroides strains, giving them the same engraftment advantage. Now they're working to identify other genes that confer similar dietary abilities.

"We can use these gene modules to develop a vast toolkit to make therapeutic microbial treatments a reality," Sonnenburg said. "Porphyran-digesting genes and a diet rich in seaweed is the first pair, but there could potentially be hundreds more. We'd like to expand this simple paradigm into an array of dietary components and microbes."

The researchers also envision developing bacteria that harbor kill switches and logic gates that will permit clinicians to toggle bacterial activity on and off at will, or when a specific set of circumstances occur.

"It's become very clear over the last 10 years that gut microbes are not only wired to many aspects of our biology, but that they are also very malleable," Sonnenburg said. "Our growing ability to manipulate them is going to change how precision health is practiced. A physician whose patient is about to begin immunotherapy for cancer may choose to also administer a bacterial strain known to activate the immune system, for example. Conversely, a patient with an autoimmune disease may benefit from a different set of microbiota that can dial down an overactive immune response. They are just a very powerful lever to modulate our biology in health and disease."

4  Tutkimus / Tutkimus / Re: Suolistobakteerit, myeliini ja aivotoiminta
 Pvm: 25.05.2018 - 18:03:29 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
New research identifies a link between diet, gut bacteria and the immune system

https://msra.org.au/news/new-research-identifies-link-diet-gut-bacteria-immune-s...
ystem/

17 May, 2018

   Researchers were able to trace a set of interactions that help explain how diet and the gut bacteria influenced by diet may act on the immune system to limit inflammation and nerve damage in mice.
   The team also found preliminary evidence verifying that similar interactions affect human cells.
   The study, supported by the International Progressive MS Alliance and others, provides important clues for better understanding the gut-brain connection and could lead to new treatment approaches for MS.
   The international team, led by Dr Francisco Quintana (Brigham and Women’s Hospital, Harvard Medical School) published their findings in the journal Nature online on May 16, 2018.

MS is a complex disease that arises when the immune system mistakenly attacks and inflames areas of the brain and spinal cord. What causes a person’s immune system to turn on their own body has not been fully revealed, but it is believed to be due to a complex interaction between a person’s genetic and environmental factors. Read more about these factors here.

Diet is one of the environmental factors that may influence our risk of developing MS, and there is growing research interest in the role that our gut bacteria may play in mediating the effect of our diet on our health. Our small and large intestines contain millions of bacteria. These bacteria help us digest our food and they also play a critical role in signalling to our immune systems. Recent studies have also revealed that there are differences in the gut bacteria from people with MS compared to people without MS.

The effects of diet on gut bacteria and on immune system activity is difficult to tease out, and much is not yet understood. Dr Francisco Quintana and an international team of collaborators set out to understand the links between immune activity and diet by studying mice with an MS-like disease. They looked at how dietary components are processed by gut bacteria, and how these interactions influence the activity of cells within the brain and spinal cord. This work was supported by the International Progressive MS Alliance, of which MS Research Australia is a managing member.

This study published this week in one of the most prestigious scientific journals Nature, focused on possible interactions between gut bacteria and glial cells, the support cells of the brain and spinal cord. Glial cells are the most abundant cells in the brain and spinal cord and play major roles in both health and disease. Specifically, the study focused on the interactions of two of these types of cells: microglia and astrocytes.

Microglia provides support for nerve cells and also act as immune cells in the brain by locating microscopic foreign invaders and ‘eating’ them. Astrocytes perform many functions, including providing nutrients and signals to the surrounding cells.

The scientists discovered, that in a laboratory model of MS, astrocytes appeared to play a key role in the disease process and so they looked more closely at the signals going to the astrocytes from the microglial cells. They discovered that the microglia can send both positive and negative signals to the astrocytes, which could enhance or decrease the inflammation caused by the astrocytes.

When they looked more closely at what might determine whether the microglia send anti-inflammatory or inflammatory signals to the astrocytes, they discovered a key role for a molecule generated by our gut bacteria.  When gut bacteria break down tryptophan, an amino acid we get through our diets, it releases a molecule that can travel to the brain and influence the activity of the microglia. The molecule switches the microglia to release more anti-inflammatory signals and reduces the inflammatory activity of the astrocytes, resulting in less severe MS-like illness in the mice.

This is the first time that a dietary metabolite or byproduct produced by gut bacteria has been shown to travel through the body and directly affect cells in the brain and spinal cord.

The team also found preliminary evidence that similar interactions influence human cells. They now plan to continue this line of research to identify therapies or probiotics that can reduce inflammation to turn off or decrease disease activity in people with MS.

Identifying components of this ’gut-brain‘ connection and better understanding this complicated web of interactions between the immune system and the brain provides important clues that could lead to new treatment approaches for MS and other neurodegenerative disorders like Alzheimer’s disease and glioblastoma.

’These findings are just the beginning of what we expect will be major progress toward understanding underlying mechanisms and finding new treatments for people living with progressive MS.’ said Professor Alan Thompson, Chair of the Alliance’s Scientific Steering Committee and Dean of University College London Faculty of Brain Sciences.

A statement from the International Progressive MS Alliance can be found here.

5  Tutkimus / Tutkimus / Re: Suolistobakteerit, myeliini ja aivotoiminta
 Pvm: 25.05.2018 - 17:59:20 
Keskustelun aloitti HopeSprings | Kirjoittaja HopeSprings  
[b]How the gut influences neurologic disease[/b]

https://www.sciencedaily.com/releases/2018/05/180516131209.htm

May 16, 2018
A study published this week in Nature sheds new light on the connection between the gut and the brain, untangling the complex interplay that allows the byproducts of microorganisms living in the gut to influence the progression of neurodegenerative diseases. Investigators from Brigham and Women's Hospital (BWH) have been using both animal models and human cells from patients to tease out the key players involved in the gut-brain connection as well as in the crosstalk between immune cells and brain cells. Their new publication defines a pathway that may help guide therapies for multiple sclerosis and other neurologic diseases.

"These findings provide a clear understanding of how the gut impacts central nervous system resident cells in the brain," said corresponding author Francisco Quintana, PhD, of the Ann Romney Center for Neurologic Diseases at BWH. "Now that we have an idea of the players involved, we can begin to go after them to develop new therapies."

The new research focuses on the influence of gut microbes on two types of cells that play a major role in the central nervous system: microglia and astrocytes. Microglia are an integral part of the body's immune system, responsible for scavenging the CNS and getting rid of plaques, damaged cells and other materials that need to be cleared. But microglia can also secrete compounds that induce neurotoxic properties on the star-shaped brain cells known as astrocytes. This damage is thought to contribute to many neurologic diseases, including multiple sclerosis.

Brigham researchers have previously explored the gut-brain connection to gain insights into multiple sclerosis. Although some studies have examined how byproducts from organisms living in the gut may promote inflammation in the brain, the current study is the first to report on how microbial products may act directly on microglia to prevent inflammation. The team reports that the byproducts that microbes produce when they break down dietary tryptophan -- an amino acid found in turkey and other foods -- may limit inflammation in the brain through their influence on microglia.

To conduct their study, the research team examined gut microbes and the influence of changes in diet in a mouse model of multiple sclerosis. They found that compounds resulting from the breakdown of tryptophan can cross the blood-brain barrier, activating an anti-inflammatory pathway that limits neurodegeneration. The researchers also studied human multiple sclerosis brain samples, finding evidence of the same pathway and players.

Activation of this same pathway has recently been linked to Alzheimer's disease and glioblastoma. The Ann Romney Center for Neurologic Diseases, of which Quintana is a part, brings experts together to accelerate treatment for these diseases, as well as multiple sclerosis Parkinson's disease and ALS (Lou Gehrig's disease).

"It is likely the mechanisms we've uncovered are relevant for other neurologic diseases in addition to multiple sclerosis," said Quintana. "These insights could guide us toward new therapies for MS and other diseases."

Quintana and his colleagues plan to further study the connections to neurologic diseases, and are also optimizing small molecules as well as probiotics to identify additional elements that participate in the pathway and new therapies.

6  Hoito / Lääkitys / Lääke vaihtoon, kiukuttaa
 Pvm: 25.05.2018 - 17:52:37 
Keskustelun aloitti Kirippu | Kirjoittaja Kirippu  
Nyt tuli se päivä, kun kroppa päätti irtisanoutua sopimuksesta ja ilmoitti ettei enää Avonexia siedä.
Kaikki ongelmat siis alkoivat siitä, kun kolhin toisen reiden pistoskohdan enkä siihen voinut muutamaan viikkoon pistää mustelman vuoksi (mustelma on tänäkin päivänä vielä näkyvissä). Oikea jalka kipeytyi sitten perättäisistä pistoksista järkyttävästi, jolloin kävin hoitajalla joka totesi, että voin sitten jättää oikean jalan rauhaan ja pistää vain vasempaan mutta mustelman viereen. Näin toiminkin ja kas sitten kipeytyi vasenkin jalka. Eilen kävelin seiniä tukena käyttäen ja lisäksi oli vaikeuksia nousta ylipäänsä seisomaan kivun vuoksi. Kahden metrin kävelemiseen kului pitkä aika. Yöllä sain nukutuksi ehkä 4h ja hyvin, hyvin huonosti sillä kipu tuli unen läpi.
Kipua lukuunottamatta kipualue on muuten tunnoton.
Herättyäni pahin kipu oli jo onneksi poissa, mutta eilenkin se tuli kuin salama kirkkalta taivaalta ja pelkään ettei tämä ollut vielä tässä.

Halusin uskoa, että tämä olisi vain ohimenevää ja rauhoittuisi kunhan jalat parantuvat. Enää en ole niin varma. Kävin taas hoitajalla, kun hänen mielestä siellä taas piti käydä istumassa sen 10min. Tämä konsultoi lääkäriä, jonka mielestä on aika vaihtaa lääkettä eikä minun enää tarvitse pistää ellen erikseen halua. Olen vielä kahden vaiheilla. Oikea jalka on jo suht kivuton, joskin hieman paineluarka.

Kahden viikon päästä minulla olisi se kontrolliaika. Olen aivan neuvoton. Valitsin alunperin Avonexin siksi, että sivuvaikutukset eivät omaan korvaan kuulostaneet niin pahalta ja lisäksi lääkkeen ottaminen sopi täydellisesti minun elämääni eikä häirinnyt sitä. Kaikista muista oli sitten liikaa vaivaa omaan makuun. Pelkään etten osaisi sitoutua muihin lääkkeisiin niin hyvin. En halua että lääke jollain tapaa muuttaa tai hallitsee elämääni millään tavalla sillä olen tyytyväinen siihen nykyisellään.

Mitä ihmettä teen? Mistä edes aloittaa kun mitään en haluaisi? Kiitos ja anteeksi. Minua nätisti sanottuna kiukuttaa.

7  Yleinen / Niksit / Re: Viilentäviä liivejä ja hattuja
 Pvm: 23.05.2018 - 18:00:00 
Keskustelun aloitti Tarani | Kirjoittaja Juliane85  
Mieheni osti itselleen tuollaisen liivin. Hän on  terve ja siihen tyytyväinen.
Minä poikani kanssa istuimme äitini kylmäkellarissa, jolloin lapsi sanoi jäädään mummin luo yöksi, kun täällä on telkkukin.
Lämpötila voi nousta paikoin jopa 25 astetta.

8  Yleinen / Niksit / Re: Viilentäviä liivejä ja hattuja
 Pvm: 22.05.2018 - 09:19:57 
Keskustelun aloitti Tarani | Kirjoittaja MrMS  
VPS358 kirjoitti on 21.05.2018 - 13:43:07:
Kuukkeli (google) on etsivän paras ystävä?
https://www.google.com/search?q=Viilent%C3%A4vi%C3%A4+liivej%C3%A4

T: Vesku

Juu, yritin kyllä itsekin googlata, mutta hakusanalla "viilennysliivi" ja sillä en saanut ainuttakaan järkevää hakutulosta. Nyt niitä alkoi löytymään, kiitos vaan.

Vielä kun saisi käyttäjäkokemuksia luettua jostain. Aikoinaan ostin viilennyshatun netistä, mutta Rooman elokuisissa helteissä siitä oli apua vain puolisen tuntia, vaikka geelitäytteinen kapistus oli ollut koko yön pakastimessa. Lämpöäkin oli ulkona kyllä n. 35 astetta, eli ihmeisiin ei 15 euron hattukaan pysty  Kieli

9  Yleinen / Niksit / Re: Viilentäviä liivejä ja hattuja
 Pvm: 21.05.2018 - 13:43:07 
Keskustelun aloitti Tarani | Kirjoittaja VPS358  
Kuukkeli (google) on etsivän paras ystävä?
https://www.google.com/search?q=Viilent%C3%A4vi%C3%A4+liivej%C3%A4

T: Vesku

10  Yleinen / Niksit / Re: Viilentäviä liivejä ja hattuja
 Pvm: 21.05.2018 - 11:09:23 
Keskustelun aloitti Tarani | Kirjoittaja MrMS  
Onkohan tästä aiheesta kenelläkään tuoreempaa tietoa? Olo on jo parissakymmenessä asteessa todella tukala  Surullinen

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