同: amyloid transthyretin protein

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/28 12:56:26」(JST)

wiki en

Amyloidosis is a rare disease that results from the buildup of misfolded proteins known as amyloids. When proteins that are normally dissolvable in water fold to become amyloids, they become insoluble and deposit in organs or tissues, disrupting normal function.^[2]^[3] The type of protein that is misfolded and the organ or tissue in which the misfolded proteins are deposited determine the clinical manifestations of amyloidosis.

There are four main types of amyloidosis, each due to the deposition of a specific protein. The most common type is AL amyloidosis, caused by the deposition of light chain proteins produced by plasma cells in different disease states.^[4] The second most common is AA amyloidosis due to the accumulation of S amyloid A protein or SAA, which occurs in association with chronic infections - e.g. tuberculosis - or inflammatory illnesses such as rheumatoid arthritis. The third and the fourth type are due to the deposition of a genetically defective or normal form of a protein called transthyretin respectively. Other minor forms of amyloid are also known.

Signs and symptoms

Skin features of amyloidosis cutis dyschromica. Hyperpigmented and hypopigmented macules on (A) lower legs, (B) back and waist, (C) waist. (D) Individual blisters on upper arm

The presentation of amyloidosis is broad and depends on the site of amyloid accumulation. The kidney and heart are the most common organs involved.

Amyloid deposition in the kidneys can cause nephrotic syndrome, which results from a reduction in the kidney's ability to filter and hold on to proteins. The nephrotic syndrome occurs with or without elevations in creatinine and blood urea concentration,^[5] two biochemical markers of kidney injury. In AA amyloidosis the kidneys are involved in 91-96% of people,^[6] symptoms ranging from protein in the urine to nephrotic syndrome and rarely renal insufficiency.

Amyloid deposition in the heart can cause both diastolic and systolic heart failure. EKG changes may be present, showing low voltage and conduction abnormalities like atrioventricular block or sinus node dysfunction. On echocardiography the heart shows a restrictive filling pattern, with normal to mildly reduced systolic function.^[5] AA amyloidosis usually spares the heart.^[6]

People with amyloidosis do not get central nervous system involvement but can develop sensory and autonomic neuropathies. Sensory neuropathy develops in a symmetrical pattern and progresses in a distal to proximal manner. Autonomic neuropathy can present as orthostatic hypotension but may manifest more gradually with nonspecific gastrointestinal symptoms like constipation, nausea, or early satiety.^[5]

Deposition of amyloids in the liver can lead to elevations in serum aminotransferases and alkaline phosphatase, two biomarkers of liver injury, which is seen in about one third of people.^[6] Liver enlargement is common. In contrast, spleen enlargement is rare, occurring in 5% of people. Splenic dysfunction, leading to the presence of Howell-Jolly bodies on blood smear, occurs in 24% of people with amyloidosis.^[5] Malabsorption is seen in 8.5% of AL amyloidosis and 2.3% of AA amyloidosis. One suggested mechanism for the observed malabsorption is that amyloid deposits in the tips of intestinal villi (fingerlike projections that increase the intestinal area available for absorption of food), begin to erode the functionality of the villi, presenting a sprue-like picture.^[6]

A rare development is a susceptibility to bleeding with bruising around the eyes, termed "racoon-eyes". This is caused by amyloid deposition in the blood vessels and a reduced activity of thrombin and factor X, two clotting proteins that lose their function after binding with amyloid.^[5]

Amyloid deposits in tissue and causes enlargement of structures. Twenty percent of people with AL amyloidosis have an enlarged tongue, that can lead to obstructive sleep apnea, difficulty swallowing, and altered taste.^[6] Tongue enlargement does not occur in ATTR or AA amyloidosis.^[5] Enlarged shoulders, "shoulder pad sign", results from amyloid deposition in synovial space. Deposition of amyloid in the throat can cause hoarseness.^[5] Aβ2MG amyldoisis (Hemodialysis associated amyloidosis) likes to deposit in synovial tissue causing chronic synovitis which can be lead to repeated carpal tunnel syndrome.^[6]

Both the thyroid and adrenal gland can be infiltrated. It is estimated that 10-20% of individuals with amyloidosis have hypothyroidism. Adrenal infiltration may be harder to appreciate given that its symptoms of orthostatic hypotension and low blood sodium concentration may be attributed to autonomic neuropathy and heart failure.^[5]

"Amyloid deposits occur in the pancreas of patients with diabetes mellitus, although it is not known if this is functionally important. The major component of pancreatic amyloid is a 37-amino acid residue peptide known as islet amyloid polypeptide or amylin. This is stored with insulin in secretory granules in B cells and is co secreted with insulin". (Rang and Dale's Pharmacology, 2015).

Pathogenesis

The cells in the body have two different ways of making proteins. Some proteins are made of one single piece or sequence of aminoacids; in other cases protein fragments are produced, and the fragments come and join together to form the whole protein. But such a protein can sometimes fall apart into the original protein fragments. This process of "flip flopping" happens frequently for certain protein types, especially the ones that cause amyloidosis.

The fragments or actual proteins are at risk of misfolding as they are synthesized, to make a poorly functioning protein. This causes proteolysis, which is the directed breakdown of proteins by cellular enzymes called proteases or by intramolecular digestion; proteases come and digest the misfolded fragments and proteins. The problem occurs when the proteins do not dissolve in proteolysis. This happens because the misfolded proteins sometimes become robust enough that they are not dissolved by normal proteolysis. When the fragments do not dissolve, they get spit out of proteolysis and they aggregate to form oligomers. The reason they aggregate is that the parts of the protein that do not dissolve in proteolysis are the β-pleated sheets, which are extremely hydrophobic. They are usually sequestered in the middle of the protein, while parts of the protein that are more soluble are found near the outside. When they are exposed to water, these hydrophobic pieces tend to aggregate with other hydrophobic pieces. This ball of fragments gets stabilized by GAGs (glycosaminoglycans) and SAP (serum amyloid P), a component found in amyloid aggregations that is thought to stabilize them and prevent proteolytic cleavage. The stabilized balls of protein fragments are called oligomers. The oligomers can aggregate together and further stabilize to make amyloid fibrils.

Both the oligomers and amyloid fibrils are toxic to cells and can interfere with proper organ function.^[7]

Diagnosis

Diagnosis of amyloidosis requires tissue biopsy. Biopsy is assessed for evidence of characteristic amyloid deposits. The tissue is treated with various stains. The most useful stain in the diagnosis of amyloid is Congo red, which, combined with polarized light, makes the amyloid proteins appear apple-green on microscopy. Also, thioflavin T stain may be used.^[8]

Tissue can come from any involved organ. But in systemic disease first line site of biopsy is subcutaneous abdominal fat, known as a fat pad biopsy, because it's simple to acquire and less invasive than biopsy of the rectum, salivary gland or internal organs. An abdominal fat biopsy is not completely sensitive and so, sometimes, biopsy of an involved organ (such as the kidney) is required to achieve a diagnosis.^[8] For example, in AL amyloidosis only 85% of people will have a positive fatpad biospy using Congo red stain.^[5] By comparison, rectal biopsy has sensitivity of 74-94%.^[6]

The type of the amyloid protein can be determined by various ways: the detection of abnormal proteins in the bloodstream (on protein electrophoresis or light chain determination), binding of particular antibodies to the amyloid found in the tissue (immunohistochemistry), or extraction of the protein and identification of its individual amino acids.^[8] Immunohistochemistry can identify AA amyloidosis the majority of the time, but can miss many cases of AL amyloidosis.^[6] Laser microdissection with mass spectrometry is the most reliable method of identifying the different forms of amyloidosis.^[9]

Since AL is the most common variation, diagnoses often begins with a search for plasma cell dyscrasias, memory B cells producing aberrant immunoglobulins or portions of immunoglobulins. Immunofixation electrophoresis of urine or serum is positive in 90% of people with AL amyloidosis.^[5] Immunofixation electrophoresis is more sensitive than regular electrophoresis but may not be available in all centers. Alternatively immunohistochemical staining of a bone marrow biopsy looking for dominant plasma cell can be sought in people with a high clinical suspicion for AL amyloidosis but negative electrophoresis.^[5]

ATTR is suspected in people with family history of idiopathic neuropathies or heart failure who lack evidence of plasma cell dyscrasias. ATTR can be identified using isoelectric focusing which separates out mutated forms of transthyretin. Findings can be corroborated by genetic testing to look for specific known mutations in transthyretin that predispose to amyloidosis.^[5]

AA is suspected on clinical grounds in individuals with longstanding infections or inflammatory diseases. AA can be identified by immunohistochemistry staining.^[5]

Small bowel duodenum with amyloid deposition Congo red 10X
Amyloidosis, dystrophic calcification
Small bowel duodenum with amyloid deposition 20X
Amyloidosis, Node, Congo Red
Amyloidosis, blood vessels, H&E
Amyloidosis, lymph node, H&E
Amyloidosis, lymph node, polarizer
Cardiac amyloidosis. H&E stain.
Micrograph showing amyloid deposition (red fluffy material) in the heart (cardiac amyloidosis). Congo red stain.

Classification

Historical classification systems were based on clinical factors. Until the early 1970s, the idea of a single amyloid substance predominated. Various descriptive classification systems were proposed based on the organ distribution of amyloid deposits and clinical findings. Most classification systems included primary (i.e., idiopathic) amyloidosis, in which no associated clinical condition was identified, and secondary amyloidosis (i.e., secondary to chronic inflammatory conditions). Some classification systems included myeloma-associated, familial, and localized amyloidosis.

The modern era of amyloidosis classification began in the late 1960s with the development of methods to make amyloid fibrils soluble. These methods permitted scientists to study the chemical properties of amyloids. Descriptive terms such as primary amyloidosis, secondary amyloidosis, and others (e.g., senile amyloidosis), which are not based on etiology, provide little useful information and are no longer recommended.

The modern classification of amyloid disease tends to use an abbreviation of the protein that makes the majority of deposits, prefixed with the letter A. For example, amyloidosis caused by transthyretin is termed "ATTR". Deposition patterns vary between people but are almost always composed of just one amyloidogenic protein. Deposition can be systemic (affecting many different organ systems) or organ-specific. Many amyloidoses are inherited, due to mutations in the precursor protein.

Other forms are due to different diseases causing overabundant or abnormal protein production - such as with overproduction of immunoglobulin light chains (termed AL amyloidosis), or with continuous overproduction of acute phase proteins in chronic inflammation (which can lead to AA amyloidosis).

About 60 amyloid proteins that have been identified so far,.^[10] Of those, at least 36 have been associated with a human disease.^[11]

The names of amyloids usually start with the letter "A". Here is a brief description of the more common types of amyloid:

Official abb.	Amyloid type/Gene	Description	OMIM
AL	amyloid light chain	AL amyloidosis / multiple myeloma. Contains immunoglobulin light-chains (λ,κ) derived from plasma cells.	254500
AA	SAA	Serum amyloid A protein (SAA) is an acute-phase reactant that is produced in times of inflammation.
Aβ	β amyloid/APP	Found in Alzheimer disease brain lesions.	605714
ALect2	LECT2	In LECT2 amyloidosis, the LECT2 protein will deposit in the kidneys, resulting in symptoms typical of kidney failure.	602882
ATTR	transthyretin	Transthyretin is a protein that is mainly formed in the liver that transports thyroxine and retinol binding protein.^[5] A mutant form of a normal serum protein that is deposited in the genetically determined familial amyloid polyneuropathies. TTR is also deposited in the heart in Wild type transthyretin amyloidosis otherwise known as senile systemic amyloidosis.^[12] Also found in leptomeningeal amyloidosis.	105210
Aβ₂M	β₂ microglobulin	Not to be confused with Aβ, β₂m is a normal serum protein, part of major histocompatibility complex (MHC) Class 1 molecules. Haemodialysis-associated amyloidosis
AIAPP	amylin	Found in the pancreas of people with type 2 diabetes.
APrP	prion protein	In prion diseases, misfolded prion proteins deposit in tissues and resemble amyloid proteins. Some examples are Creutzfeldt–Jakob disease (humans), BSE or "mad cow disease" (cattle), and scrapie (sheep and goats). A recently described familial prion disease presents with peripheral amyloidosis causing autonomic neuropathy and diarrhea.^[13]	123400
AGel	GSN	Finnish type amyloidosis	105120
ACys	CST3	Cerebral amyloid angiopathy, Icelandic-type	105150
AApoA1	APOA1	Familial visceral amyloidosis	105200
AFib	FGA	Familial visceral amyloidosis	105200
ALys	LYZ	Familial visceral amyloidosis	105200
?	OSMR	Primary cutaneous amyloidosis	105250
ABri ADan	ITM2B	Cerebral amyloid angiopathy, British-type Danish-type	176500 117300
APro	prolactin	Prolactinoma
AKer	keratoepithelin	Familial corneal amyloidosis
AANF	atrial natriuretic factor	Senile amyloid of atria of heart
ACal	calcitonin	Medullary carcinoma of the thyroid

As of 2010, 27 human and 9 animal fibril proteins were classified, along with 8 inclusion bodies.^[14]

Alternative

An older clinical method of classification refers to amyloidoses as systemic or localised

Systemic amyloidoses affect more than one body organ or system. Examples are AL, AA and Aβ2m.^[15]
Localised amyloidoses affect only one body organ or tissue type. Examples are Aβ, IAPP, Atrial natriuretic factor (in isolated atrial amyloidosis), and Calcitonin (in medullary carcinoma of the thyroid)^[15]

Another classification is primary or secondary.

Primary amyloidoses arise from a disease with disordered immune cell function, such as multiple myeloma or other immunocyte dyscrasias.
Secondary (reactive) amyloidoses occur as a complication of some other chronic inflammatory or tissue-destroying disease. Examples are reactive systemic amyloidosis and secondary cutaneous amyloidosis.^[15]

Additionally, based on the tissues in which it is deposited, it is divided into mesenchymal (organs derived from mesoderm) or parenchymal (organs derived from ectoderm or endoderm).

Treatment

Treatment depends on the type of amyloidosis that is present. Treatment with high dose melphalan, a chemotherapy agent, followed by stem cell transplantation has showed promise in early studies and is recommended for stage I and II AL amyloidosis.^[9] However, only 20-25% of people are eligible for stem cell transplant. Chemotherapy and steroids, with melphalan plus dexamethasone, is mainstay treatment in AL people not eligible for transplant.^[9]

In AA, symptoms may improve if the underlying condition is treated; eprodisate has been shown to slow renal impairment by inhibiting polymerization of amyloid fibrils.

In ATTR, liver transplant is curative therapy^[5] because mutated transthyretin which forms amyloids is produced in the liver.

Prognosis

Prognosis varies with the type of amyloidosis. Prognosis for untreated AL amyloidosis is poor with median survival of one to two years. More specifically, AL amyloidosis can be classified as stage I, II or III based on cardiac biomarkers like troponin and BNP. Survival diminishes with increasing stage, with estimated survival of 26, 11 and 3.5 months at stage I, II and III.^[9]

Outcomes in a person with AA amyloidosis depends on the underlying disease and correlates with the concentration of serum amyloid A protein.^[6]

People with ATTR have better prognosis and may survive for over a decade.^[5]

Senile systemic amyloidosis was determined to be the primary cause of death for 70% of people over 110 who have been autopsied.^[16]^[17]

Epidemiology

The three most common forms of amyloidosis are AL, AA and ATTR amyloidoses. The median age at diagnosis is 64.^[6]

In the western hemisphere, AL is the most prevalent, comprising 90% of cases.^[9] In the United States it's estimated that there are 1275 to 3200 new cases of AL amyloidoses every year.^[5]

AA amyloidoses is the most common form in developing countries and can complicates longstanding infections with tuberculosis, osteomyleitis and bronchiectesis. In the west, AA is more likely to occur from autoimmune inflammatory states.^[5] Most common etiologies of AA amylodosis in the west are rheumatoid arthritis, inflammatory bowel disease, psoriasis and familial Mediterranean fever.

People undergoing long term hemodialysis (14–15 years) can develop amyloidosis from accumulation of light chains of the HLA 1 complex which is normally filtered out by the kidneys.^[6]

Senile amyloidosis resulting from deposition of normal transthyretin, mainly in the heart, is found in 10–36% of people over 80.^[6]

Footnotes

^ Hawkins, P (29 Apr 2015). "AL amyloidosis". Wikilite.com. Retrieved 19 December 2015.
^ Murakami, T; Ishiguro N; Higuchi K (March 2014). "Transmission of Systemic AA Amyloidosis in Animals". Veterinary Pathology 51 (2): 363–371. doi:10.1177/0300985813511128. PMID 24280941.
^ Kumar, Vinay (2009). Robbins & Cotran Pathologic Basis of Disease. Saunders. ISBN 1416031219.
^ http://www.amyloidosis.org/facts/al/ AL Amyloidosis
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r Falk, Rodney H.; Comenzo, Raymond L.; Skinner, Martha (25 September 1997). "The Systemic Amyloidoses". New England Journal of Medicine 337 (13): 898–909. doi:10.1056/NEJM199709253371306.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Ebert, Ellen C.; Nagar, Michael (March 2008). "Gastrointestinal Manifestations of Amyloidosis". The American Journal of Gastroenterology 103 (3): 776–787. doi:10.1111/j.1572-0241.2007.01669.x.
^ [1], Karp, Judith E., ed. Amyloidosis Diagnosis and Treatment. Rochester: Humana, 2010. Online Source. .
^ ^a ^b ^c Dember LM (December 2006). "Amyloidosis-associated kidney disease". J. Am. Soc. Nephrol. 17 (12): 3458–71. doi:10.1681/ASN.2006050460. PMID 17093068.
^ ^a ^b ^c ^d ^e Rosenzweig, Michael; Landau, Heather (2011). "Light chain (AL) amyloidosis: update on diagnosis and management". Journal of Hematology & Oncology 4 (1): 47. doi:10.1186/1756-8722-4-47.
^ Mok KH, Pettersson J, Orrenius S, Svanborg C (March 2007). "HAMLET, protein folding, and tumor cell death". Biochem. Biophys. Res. Commun. 354 (1): 1–7. doi:10.1016/j.bbrc.2006.12.167. PMID 17223074.
^ Pettersson-Kastberg J, Aits S, Gustafsson L; et al. (November 2008). "Can misfolded proteins be beneficial? The HAMLET case". Ann. Med. 41 (3): 1–15. doi:10.1080/07853890802502614. PMID 18985467.
^ Hassan W, Al-Sergani H, Mourad W, Tabbaa R (2005). "Amyloid heart disease. New frontiers and insights in pathophysiology, diagnosis, and management". Tex Heart Inst J 32 (2): 178–84. PMC 1163465. PMID 16107109.
^ Mead et al. A Novel Prion Disease Associated with Diarrhea and Autonomic Neuropathy. N Engl J Med 369:1904-1914, 2013.
^ Sipe JD, Benson MD, Buxbaum JN; et al. (September 2010). "Amyloid fibril protein nomenclature: 2010 recommendations from the nomenclature committee of the International Society of Amyloidosis". Amyloid 17 (3–4): 101–104. doi:10.3109/13506129.2010.526812. PMID 21039326.
^ ^a ^b ^c Table 5-12 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
^ Coles LS, Young RD (2012). "Supercentenarians and transthyretin amyloidosis: the next frontier of human life extension". PREVENTATIVE MEDICINE 54 (Suppl): s9–s11. doi:10.1016/j.ypmed.2012.03.003. PMID 22579241.
^ "Searching for the Secrets of the Super Old". Science. September 26, 2008. pp. 1764–65. Retrieved February 22, 2013.

External links

Amyloidosis at DMOZ
UK NHS National Amyloidosis Centre Patient Information Site

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. アミロイド心筋症の臨床症状および診断 clinical manifestations and diagnosis of amyloid cardiomyopathy
2. アミロイドーシスの概要 an overview of amyloidosis
3. アミロイド心筋症の治療 treatment of amyloid cardiomyopathy
4. 続発性（AA）アミロイドーシスの治療 treatment of secondary aa amyloidosis
5. 免疫グロブリン軽鎖（AL）アミロイドーシス（原発性アミロイドーシス）の臨床像、
検査所見、および診断 clinical presentation laboratory manifestations and diagnosis of immunoglobulin light chain al amyloidosis primary amyloidosis

English Journal

Serum levels of rapid turnover proteins are decreased and related to systemic inflammation in patients with ovarian cancer.

Watanabe T1, Shibata M2, Nishiyama H1, Soeda S1, Furukawa S1, Gonda K3, Takenoshita S4, Fujimori K1.Author information 1Department of Obstetrics and Gynecology, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan.2Department of Gastrointestinal Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama 350-1298, Japan ; Department of Tumor and Host Bioscience, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan ; Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan.3Department of Gastrointestinal Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama 350-1298, Japan.4Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima, Fukushima 960-1295, Japan.AbstractPoor nutritional status is common in ovarian cancer. It is well known that the nutritional status of a patient with malignant disease is associated with survival, and that it can be assessed by serum levels of rapid turnover proteins (RTPs), such as retinol binding protein, prealbumin and transferrin. Systemic inflammation, usually observed in the form of elevated C-reactive protein (CRP) or neutrophil/lymphocyte ratio (NLR), occurs by various mechanisms involving numerous pro-inflammatory cytokines. These include interleukin (IL)-17 and other soluble protein mediators, such as soluble IL-2 receptor (sIL-2R) and vascular endothelial growth factor (VEGF). In this study, circulating levels of RTP were decreased in advanced stages of ovarian cancer, and significant inverse correlations were found between RTP levels and serum levels of CRP or NLR. CRP levels were also correlated with serum levels of VEGF and sIL-2R. Moreover, NLR, VEGF and sIL-2R levels, and IL-17 production, were all inversely correlated with RTP levels. These findings indicate that chronic inflammation may be associated with compromised immune function, such as an impaired T-cell response, via various inflammatory proteins, including sIL-2R, VEGF and IL-17. The key mechanisms leading to cancer cachexia, in which nutritional impairment is a major clinical issue, appear to be primarily immune reactions caused by chronic inflammation. Anti-inflammatory treatments may be effective in clinically improving various symptoms associated with these mechanisms.
Oncology letters.Oncol Lett.2014 Feb;7(2):373-377. Epub 2013 Dec 6.
Poor nutritional status is common in ovarian cancer. It is well known that the nutritional status of a patient with malignant disease is associated with survival, and that it can be assessed by serum levels of rapid turnover proteins (RTPs), such as retinol binding protein, prealbumin and transferri
PMID 24396450

The Structure of Xis Reveals the Basis for Filament Formation and Insight into DNA Bending within a Mycobacteriophage Intasome.

Singh S1, Plaks JG1, Homa NJ2, Amrich CG1, Héroux A3, Hatfull GF1, Vandemark AP4.Author information 1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.2Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA; Present address: N. J. Homa, 426 CARL Building, Duke University, Durham, NC 27710, USA. Electronic address: njh16@duke.edu.3Department of Biology, Brookhaven National Laboratory, Upton, NY 11973, USA.4Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: andyv@pitt.edu.AbstractThe recombination directionality factor, Xis, is a DNA bending protein that determines the outcome of integrase-mediated site-specific recombination by redesign of higher-order protein-DNA architectures. Although the attachment site DNA of mycobacteriophage Pukovnik is likely to contain four sites for Xis binding, Xis crystals contain five subunits in the asymmetric unit, four of which align into a Xis filament and a fifth that is generated by an unusual domain swap. Extensive intersubunit contacts stabilize a bent filament-like arrangement with Xis monomers aligned head to tail. The structure implies a DNA bend of ~120°, which is in agreement with DNA bending measured in vitro. Formation of attR-containing intasomes requires only Int and Xis, distinguishing Pukovnik from lambda. Therefore, we conclude that, in Pukovnik, Xis-induced DNA bending is sufficient to promote intramolecular Int-mediated bridges during intasome formation.
Journal of molecular biology.J Mol Biol.2014 Jan 23;426(2):412-22. doi: 10.1016/j.jmb.2013.10.002. Epub 2013 Oct 7.
The recombination directionality factor, Xis, is a DNA bending protein that determines the outcome of integrase-mediated site-specific recombination by redesign of higher-order protein-DNA architectures. Although the attachment site DNA of mycobacteriophage Pukovnik is likely to contain four sites f
PMID 24112940

Effect of Nutritional Status on Survival Outcome of Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP.

Park S, Han B, Cho JW, Woo SY, Kim S, Kim SJ, Kim WS.Author information a Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center , Sungkyunkwan University School of Medicine , Seoul , Korea.AbstractThe impact of pretreatment nutritional status on the treatment outcome of non-Hodgkin lymphoma has never been explored. Among the 953 patients who were registered in a prospective cohort at Samsung Medical Center., we analyzed 262 patients who had been treated with Ruximab-cyclophosphamide, doxorubicin, vincristine, and prednisone for newly diagnosed diffuse large B-cell lymphoma (DLBCL) and for whom data were available regarding pretreatment nutritional status. Nutritional status at diagnosis was assessed by triceps skin fold (TSF), mid-arm muscle circumference (MAMC), body mass index (BMI), serum albumin, prealbumin, and transferrin. For patients aged 60 yr and older, poor performance and higher tumor burden were associated with malnourishment represented by albumin <3.5 g/dL, prealbumin < 17 g/dL, and transferrin <170 mg/L. Lower BMI (<20), serum albumin, prealbumin, and transferrin were identified as risk factors for febrile neutropenia in univariate analysis, but not in multivariate analysis. In the univariate analysis for OS, all nutritional parameters except MAMC showed a significant association with survival. However, BMI was the only parameter that was independently prognostic for OS in the multivariate analysis (P = 0.031; hazards ratio = 3.32). Nutritional insufficiency encountered in DLBCL patients might influence the occurrence of treatment-related toxicity and poor survival outcome of patients.
Nutrition and cancer.Nutr Cancer.2014 Jan 9. [Epub ahead of print]
The impact of pretreatment nutritional status on the treatment outcome of non-Hodgkin lymphoma has never been explored. Among the 953 patients who were registered in a prospective cohort at Samsung Medical Center., we analyzed 262 patients who had been treated with Ruximab-cyclophosphamide, doxorubi
PMID 24405259

Japanese Journal

Cardiac amyloidosis in a heart transplant patient - A case report and retrospective analysis of amyloidosis evolution

, , , , ,
Intractable & Rare Diseases Research advpub(0), 2015
Cardiac amyloidosis is a very rare cause of heart failure in heart transplant recipients but an important differential diagnosis in cases of progressive cardiac failure. We report a 72-year-old male p …
NAID 130005008110

Cardiac amyloidosis in a heart transplant patient - A case report and retrospective analysis of amyloidosis evolution

, , , , ,
Intractable & Rare Diseases Research 4(1), 60-64, 2015
Cardiac amyloidosis is a very rare cause of heart failure in heart transplant recipients but an important differential diagnosis in cases of progressive cardiac failure. We report a 72-year-old male p …
NAID 130005008105

多角的自律神経機能検査法をもちいた小径線維ニューロパチーの診断

大林光念,安東由喜雄
臨床神経学 54(12), 1044-1046, 2014
… 断するため，レーザードプラ皮膚血流検査や換気カプセル法による発汗検査，汗腺の形態チェック，胃電図，胃内の小径線維やCajal細胞の密度測定，123I-MIBG心筋シンチ，血圧オーバーシュート現象をみる起立試験などの自律神経機能検査を考案した．これらは，ATTR V30M保因者やIGT患者にみられる早期の小径線維ニューロパチーを診断しえる．また，これらにC，Aδ特異的痛覚閾値検査を加えることも，診断に有用となる． …
NAID 130004921199

Related Pictures

Attr@ttivo haljina - Kupindo.com (29070809) Attr@ttivo zenska jaknica - Kupindo.com (41312951) Attr. Lilian Hale (1880 - 1963) Lot 12: Sarasota Estate Auction Zuni attr Dan Simplicio Earrings Coral Turquoise Clip-on Sterling Silver .925 • $899 attr. Roger Vanhevel Table Lamp - New Arrivals - Gerard Delsing 70s Belgian Brutalist Crendenza sideboard attr ‘de Coene’ | BarbMama attr. John Joseph Enneking (American, 1841-1916) | Cowan's Auction House: The Midwest 70s Lounge fauteuil comfortable attr Hans Brattrud | BarbMama

★リンクテーブル★

「AT」

Amyloidosis
	Classic facial features of AL amyloidosis with purpura around the eyes
Classification and external resources
Specialty	Endocrinology, Rheumatology, Cardiology
ICD-10	E85
ICD-9-CM	277.3
DiseasesDB	633
eMedicine	med/3377
Patient UK	Amyloidosis
MeSH	D000686
	[edit on Wikidata]

　　[★]

[1] Hawkins, P (29 Apr 2015). "AL amyloidosis". Wikilite.com. Retrieved 19 December 2015.

[Murakami2014-2] Murakami, T; Ishiguro N; Higuchi K (March 2014). "Transmission of Systemic AA Amyloidosis in Animals". Veterinary Pathology 51 (2): 363–371. doi:10.1177/0300985813511128. PMID 24280941.

[3] Kumar, Vinay (2009). Robbins & Cotran Pathologic Basis of Disease. Saunders. ISBN 1416031219.

[4] ttp://www.amyloidosis.org/facts/al/ AL Amyloidosis

[:0-5] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r Falk, Rodney H.; Comenzo, Raymond L.; Skinner, Martha (25 September 1997). "The Systemic Amyloidoses". New England Journal of Medicine 337 (13): 898–909. doi:10.1056/NEJM199709253371306.

[:2-6] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Ebert, Ellen C.; Nagar, Michael (March 2008). "Gastrointestinal Manifestations of Amyloidosis". The American Journal of Gastroenterology 103 (3): 776–787. doi:10.1111/j.1572-0241.2007.01669.x.

[bob-7] [1], Karp, Judith E., ed. Amyloidosis Diagnosis and Treatment. Rochester: Humana, 2010. Online Source. .

[Dember2006-8] Dember LM (December 2006). "Amyloidosis-associated kidney disease". J. Am. Soc. Nephrol. 17 (12): 3458–71. doi:10.1681/ASN.2006050460. PMID 17093068.

[:1-9] Rosenzweig, Michael; Landau, Heather (2011). "Light chain (AL) amyloidosis: update on diagnosis and management". Journal of Hematology & Oncology 4 (1): 47. doi:10.1186/1756-8722-4-47.

[pmid17223074-10] Mok KH, Pettersson J, Orrenius S, Svanborg C (March 2007). "HAMLET, protein folding, and tumor cell death". Biochem. Biophys. Res. Commun. 354 (1): 1–7. doi:10.1016/j.bbrc.2006.12.167. PMID 17223074.

[pmid18985467-11] Pettersson-Kastberg J, Aits S, Gustafsson L; et al. (November 2008). "Can misfolded proteins be beneficial? The HAMLET case". Ann. Med. 41 (3): 1–15. doi:10.1080/07853890802502614. PMID 18985467.

[pmid16107109-12] Hassan W, Al-Sergani H, Mourad W, Tabbaa R (2005). "Amyloid heart disease. New frontiers and insights in pathophysiology, diagnosis, and management". Tex Heart Inst J 32 (2): 178–84. PMC 1163465. PMID 16107109.

[13] Mead et al. A Novel Prion Disease Associated with Diarrhea and Autonomic Neuropathy. N Engl J Med 369:1904-1914, 2013.

[pmid21039326-14] Sipe JD, Benson MD, Buxbaum JN; et al. (September 2010). "Amyloid fibril protein nomenclature: 2010 recommendations from the nomenclature committee of the International Society of Amyloidosis". Amyloid 17 (3–4): 101–104. doi:10.3109/13506129.2010.526812. PMID 21039326.

[Kumar5-12-15] Table 5-12 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.

[16] Coles LS, Young RD (2012). "Supercentenarians and transthyretin amyloidosis: the next frontier of human life extension". PREVENTATIVE MEDICINE 54 (Suppl): s9–s11. doi:10.1016/j.ypmed.2012.03.003. PMID 22579241.

[17] "Searching for the Secrets of the Super Old". Science. September 26, 2008. pp. 1764–65. Retrieved February 22, 2013.

匿名

検索

案内

案内

ATTR