***I need full and good answer. ***(((Don\'t copy and paste))). ***((((Don\'t us

Question

***I need full and good answer. ***(((Don't copy and paste))).

***((((Don't use your handwriting))))).

((((I need answer alll Questions please ))))

Transplant arteriosclerosis (TA) is well known to represent the pathologic hallmark of chronic transplant dysfunction which is among the leading causes of graft failure in solid organ transplantation today. Although major strides have been achieved in tolerance induction strategies and immunosuppressive regimens, little has been done to abrogate the fibroproliferative lesions that affect all vessels supplying and within allografts. Although TA has enjoyed much attention in the literature over the past 2 decades, promising experimental results have failed to fully translate to the clinic.1 Immunologic migration of host-derived T cells and macrophages to the adventitia results in periadventitial scarring and loss of vascular compliance. Coupled with this is the migration and in situ proliferation of vascular smooth muscle cells into the intima of the vessel leading to neointimal hyperplasia and eventual luminal narrowing. Decreased blood flow to the graft over time promotes fibrosis and ultimate graft loss. Experimental therapies from regulatory T cells to stem cells are as diverse in the literature as the etiology of TA itself. The initiation of these circumferential proliferative lesions has spanned from injured and dysfunctional endothelial cells to donor-derived factors, such as brain death. The reality is such that the etiology of TA is multifactorial and includes donor, recipient, and nonimmunologic factors. All said, the rates of allograft vasculopathy have experienced negligible reduction over the last 20 years.

This issue of Transplantation highlights interesting and significant findings by Moll et al 4 from Dr. Christiane Ferran's group at Harvard Medical School. Dr. Ferran has championed the protective effects of A20, a novel inhibitor of NFkB and IFN[gamma] vascular signaling.3,4 In the current issue, Moll and colleagues attempt to dissect the anti-inflammatory effects of A20 on an established mouse model of TA. They pay particular attention to the severity of TA and its correlation to levels of A20 expressed in vivo. To accomplish this, they use major histocompatibility complex mismatched mouse strains (C57BL/6->BALB/c) and either wild type or A20 heterozygotes (HET). Interestingly, inadequate upregulation of A20 expression in donor haploinsufficient allografts exacerbated the histological effects of TA and promoted a proinflammatory cytokine profile. In contrast, however, haploinsufficiency in the recipient did not promote “aggravated TA.” Along with a donor-dependent increase in a cytokine proinflammatory profile and vigorous smooth muscle cell proliferation, the authors also found a decrease in the number of FoxP3+ regulatory T cells in the recipients of A20 haploinsufficient donor allografts. Taken together, these data suggest that profiling of A20 expression in donors before transplantation may serve as a clinical biomarker to predict eventual TA severity.2

Although the article presented in this issue is interesting and revealing; a few shortcomings remain. Philosophically, the investigations in TA are as prevalent as the disease itself, yet the clinical translation of therapeutics and biomarkers discovered in animal models is still elusive. Two major components to the lack of clinical translation are the multifactorial etiologies of TA as well as the lack of evidence in preclinical large animal models. As most studies focusing on transplant vasculopathy use aortic interposition grafts (carotid or infrarenal) in either conventional mouse models or humanized mouse models; there have only been a few studies that make the leap from promising results in the mouse to more relevant large-animal models.5 Additionally, on a global scale, clinical translation of using biomarkers in a donor situation is much more difficult in the clinical arena; however, it could be more feasibly applied to living donor situations. Alternatively, the use of A20 gene transduction into the allograft may be an avenue for clinical application. Specifically, to the article of interest, the suggestion that insufficient expression of A20 exacerbates effector T cell infiltration, vascular smooth muscle cell proliferation, and immune dysregulation may be true in the context of the model described; however, it does not take into account the various proinflammatory effects of transplantation from donor to recipient in general. Namely, well-established inflammatory events, such as brain death and cold/warm ischemia in the donor and ischemia-reperfusion injury in the recipient have not been addressed with these studies. In fact, in similar models, histologic evidence of vasculopathy ensues when syngeneic grafts are subjected to prolonged cold ischemic times.6 An additional caveat revolves around the expression of indoleamine 2,3-dioxygenase (IDO) in the immune privileged media. In this study, Moll and colleagues suggest that medial IDO was significantly higher in HET versus wild type transplants. However, there was also an increase in the number of effector T cell populations in HET allografts. Established data would suggest that the IDO expressed would starve these effector populations limiting their survival in the HET allografts. Yet, as addressed by the authors themselves, the IDO upregulation may be reflective of an increase in IFN[gamma] in the HET allograft cohort. These criticisms simply highlight the questions that remain before the implementation of true clinical translation.

The critical mechanisms centered on the IFN[gamma] axis identified by Ferran's group, however, seem to be central to the development of TA.7 As stated in the article, the vasculature of A20 insufficient or deficient mice does not seem to exhibit the hallmarks of arteriosclerosis until subjected to an alloimmune response.2 Notably, many of the pathologic initiators of TA suggested in the literature from immune-dysregulation to endothelial dysfunction implicate IFN[gamma] as a critical mediator of disease. To that end, the repertoire of A20 has historically spanned vasculoprotective effects in gain-of-function studies; yet, now Moll et al suggest that A20 may not only be an option for therapeutics but also a target for donor biomarker studies as well. For those that study vasculopathy, we wait with anticipation the translation of Dr. Ferran's findings to preclinical and eventually clinical studies. In my opinion, we are on the cusp of unlocking the door to protecting allografts from vasculopathy, and the utilization of A20 will certainly play a role.3

Choose an article. Select10medical terms from the article. (human anatomy) .Complete the table in this document oln the first column list the medical term. ln the second column, list any prefixes and define them 01n the third column, list the root and define it. 01n the fourth column, list any suffixes and define them. on the fifth column list the exact definition of the term.

Explanation / Answer

Arterio-

Refers to artery

sclero

Refers to hardening

-osis

It refers to condition or disorder

Immuno-

Related to immune system

Suppressive

Reduction of

It refers to the condition where there is impaired immune response in the organism.

In the given example immunosuppression is essential to improve acceptability of the transplant tissue/ organ.

Peri-

Around

-adventicia

Arising from outside, or from external origin

Fibro-

Related to fiber

-Proles-

Related to offspring or descendants

-Fer

Which means bearing

Hyper-

It refers to above, over or excessive

-Plasia

plasty forming or molding

Vas-

Refers to vessels or ducts

Pathy-

It refers to disease

---

Allo-

Different

transplanted part of living tissue

---

Histo-

Tissue related

-Comp-

Refers to together

-ability

Potential

Infra-

Beneath

Syn-

It refers to with or together

geneic

Origin

-

Isch-

Refers to reduction or slowing down

-emia

It refers to blood

Neo-

Refers to new

-intimal

Inner layer or membrane of an organ or part

Medical Term Prefixes Roots Suffixes Exact meaning 1. Arterioscleorosis

Arterio-

Refers to artery

sclero

Refers to hardening

-osis

It refers to condition or disorder

It referst to condition where there is hardening of arteries. 2.Immunosuppressive

Immuno-

Related to immune system

Suppressive

Reduction of

---

It refers to the condition where there is impaired immune response in the organism.

In the given example immunosuppression is essential to improve acceptability of the transplant tissue/ organ.

3. Periadventitial

Peri-

Around

-

-adventicia

Arising from outside, or from external origin

It refers to condition that occurs outside the external layer or membrane of blood vessels 4. Fibroproliferative

Fibro-

Related to fiber

-Proles-

Related to offspring or descendants

-Fer

Which means bearing

Rapid cell growth or cell division in fibroblasts 5. Hyperplasia

Hyper-

It refers to above, over or excessive

-Plasia

plasty forming or molding

--- Increase in size or enlargement of a tissue or organ due to more cell mass. 6. Vasculopathy

Vas-

Refers to vessels or ducts

Pathy-

It refers to disease

---

A disease which affects the blood vessels. 7. Allografts

Allo-

Different

--graft

transplanted part of living tissue

---

A tissue transplant taken from other (not genetically identical) donors and not from self origin. 8. Histocompatibility

Histo-

Tissue related

-Comp-

Refers to together

-ability

Potential

Having acceptability with the (host) tissues 9.Infrarenal

Infra-

Beneath

Renal- Kidney ---- It refers to beneath the kidney. 10. Syngeneic

Syn-

It refers to with or together

-

geneic

Origin

-

It refers to condition where the tissues (or transplants in this case) are genetically similar in origin 11. Ischemia -

Isch-

Refers to reduction or slowing down

-emia

It refers to blood

Insuficient blood supply to any tissue or organ 12. Neointimal

Neo-

Refers to new

-intimal

Inner layer or membrane of an organ or part

Related Questions

Navigate

• Browse (All)
• Browse #
• Subjects

---

---

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.