Scholarly article on topic 'Authors' Reply'

Authors' Reply Academic research paper on "Psychology"

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Academic research paper on topic "Authors' Reply"

The causal link between mitochondrial abnormalities and tumorigenesis was provided by the positional cloning of the hereditary paraganglioma gene at chromosome band 11q23 as the SDHD subunit gene of mitochondrial complex II (succinate dehydrogenase) in the year 2000 [2]. Since then, the role of mitochondria in cancer is further highlighted through identification of over 100 mutations in the SDHB, SDHC, and SDHD subunit genes in hundreds of index cases and families with hereditary and sporadic paragangliomas and pheochromocytomas [3]. Furthermore, fumarase gene mutations in a distinct hereditary tumor syndrome characterized by multiple skin and uterine leiomyomatosis and renal cell cancer—hereditary leiomyomatosis renal cancer (HLRCC)—further strengthened the role of mitochondria in cancer [4].

Although it is clear that Salas et al. question specifically the mutations in mtDNA of tumors, they did not acknowledge the causal link between mitochondria and cancer provided by the discovery of nuclear-encoded mitochondrial gene mutations. This is especially important because, in their unfortunate title and in their conclusion, the authors seem to make a sweeping statement against the role of mitochondria in cancer. It is essential to emphasize to readers that it is the mtDNA, but not mitochondria, which has a questionable role in tumorigenesis. ■

Bora Baysal

University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania, United States of America E-mail: baysalb@mwri.magee.edu

References

1. Salas A, Yao YG, Macaulay V, Vega A, Carracedo A, et al. (2005) A critical reassessment of the role of mitochondria in tumorigenesis. PLoS Med 2: e296. DOI: 10.1371/journal.pmed.0020296

2. Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, et al. (2000) Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287: 848-851.

3. Bayley JP, Devilee P, Taschner PE (2005) The SDH mutation database: An online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency. BMC Med Genet 6: 39.

4. Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, et al. (2002) Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 30: 406-410.

Citation: Baysal B (2006) Mitochondria: More than mitochondrial DNA in cancer. PLoS Med 3(3): e156.

Copyright: © 2006 Bora Baysal. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Competing Interests: The author has declared that no competing interests exist. DOI: 10.1371/journal.pmed.0030156

Authors' Reply

We gratefully acknowledge the letter by Bora Baysal [1], which emphasizes that there is some interesting evidence for the role of mitochondria in tumorigenesis mediated by nuclear DNA factors—an issue that was outside the scope of our article [2]. We, however, do not entirely agree with him that the title of our contribution [2] is "simply incorrect"; it could probably be described as somewhat imprecise or ambiguous. In fact, the originally submitted, more precise, title of our contribution was "A pitcher of cold water on mutational hotspots in mitochondrial DNA and the hot debate about the role of mitochondria in tumorigenesis." In

any case, the Oxford English Dictionary, for example, states that "reassess" is "to assess again, especially differently (derivatives: reassessment [noun])"; synonyms of assess would be "evaluate or estimate." Certainly, the role of the mitochondria has to be reassessed since the role of their most essential element, the mitochondrial genome, remains obscure in view of dozens of studies on the potential association of tumorigenesis with mitochondrial DNA (mtDNA) that are based on obviously flawed data. Since those inadvertent circumstances (contamination and sample mix-up) are not mitochondria-specific but lab-specific, there would also be good reason to reassess other spectacular DNA findings in regard to potential laboratory errors.

We would like to stress that mtDNA somatic mutations are by no means uncommon either in normal tissues or in tumors, but the natural pattern of these somatic mutations (most commonly involving the polycytosine stretches and other well-known hotspot mutations) is quite different from those that were published in the papers criticized in our article [2]. Consistent with the title of our article [2] would be the possibility that the nuclear-mediated effect on the mitochondrial function could perhaps be mtDNA haplogroup-specific—but certainly not in the form of the artefactual instabilities, as claimed in those dubious publications (which, however, in one case, have now been explicitly defended [3], but unfortunately, without carrying out the necessary "forensic-type" analysis looking into potential sample mixture of the previously analyzed samples [4] and without determining whether the patient received blood transfusion before the onset of the disease [5]). Rather, some complex susceptibility background for tumorigenesis might be anticipated—in analogy to some mtDNA diseases such as Leber's hereditary optic neuropathy (LHON) [6]. ■

References

1. Baysal B (2006) Mitochondria: More than mitochondrial DNA in cancer. PLoS Med 3: e156. DOI: 10.1371/journal.pmed.0030156

2. Salas A, Yao YG, Macaulay V, Vega A, Carracedo A, et al. (2005) A critical reassessment of the role of mitochondria in tumorigenesis. PLoS Med 2: e296. DOI: 10.1371/journal.pmed.0020296

3. Zanssen S, Schon EA (2005) Mitochondrial DNA mutations in cancer. PLoS Med 2: e401. DOI: 10.1371/journal.pmed.0020401

4. Vecchiotti C, Spaltro G, Bloise D, Brunetti E, Sciacchitano S (2004) Demonstration of a gastric bioptic specimen mix-up by laser capture microdissection (LCM) and DNA fingerprinting. Am J Forensic Med Pathol 25: 113-116.

5. Meierhofer D, Ebner S, Mayr JA, Jones ND, Kofler B, et al. (2006) Platelet transfusion can mimic somatic mtDNA mutations. Leukemia 20: 362-363.

6. Carelli V, Achilli A, Valentino ML, Rengo C, Semino O, et al. (2006) Haplogroup effects and recombination of mitochondrial DNA: Novel clues from the analysis of Leber hereditary optic neuropathy pedigrees. Am J Hum Genet. In press.

Antonio Salas (apimlase@usc.es)

Instituto de Medicina Legal Universidad de Santiago de Compostela Galicia, Spain

Yong-Gang Yao

Kunming Institute of Zoology Kunming, Yunnan, China

Hans-Jürgen Bandelt

University of Hamburg Hamburg, Germany

Citation: Salas A, Yao YG, Bandelt HJ (2006) Authors' reply. PLoS Med 3(3): e166.

Copyright: © 2006 Salas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author

and source are credited.

Competing Interests: The authors have declared that no competing interests exist. DOI: 10.1371/journal.pmed.0030166

Prioritizing Investment in Medical Education

Fawad Aslam

The dire need to reform medical education in South Asia has been well emphasized in the PLoS Medicine Editorial [1]. It is encouraging to note that efforts are under way to devise strategies to bring about this reformation. However, for such reforms to be effective, it is crucial that the opinions of medical students and young doctors are also taken into account. Students' roles should be enhanced from those of mere consumers of medical education to those of contributors [2]. They are important stakeholders, and their active participation in policymaking will facilitate the creation of more robust solutions.

The need for drastic improvement in health research in South Asia is well established. The need for research in medical education is perhaps even greater. Unfortunately, indigenous data pertaining to medical education in this region are limited. Only a small number of studies have attempted to explore the concerns of students and doctors in matters pertaining to, for example, medical decision making and health research [3,4]. The establishment of a research culture is fraught with difficulties but is not impossible [5]. It is my opinion that, to bring about reform, both a "bottom-up" and a "top-down" approach are needed. The former needs ample student exposure to research during medical school. The latter is essentially linked to the availability of funds. No amount of community-oriented training, for example, will compensate for the deficiency of properly qualified health professionals in rural areas. It is only when there is sufficient financial and professional security that the greater purpose of educational reform will stand fulfilled. It is hard to envisage how this can be achieved when the bulk of budgetary spending pertains to debt-servicing and defense expenditure.

Alongside medical education, parallel investment should be sought in health education, not only because our physicians are not cognizant of current treatment practices [6], but also because our patients have a poor knowledge of common diseases that afflict them [7]. The interaction of better-informed patients and properly qualified doctors may significantly improve community health. For impoverished nations, the importance of preventive medicine is manifold as it offers the most economical way of combating disease. There is some evidence to suggest that our medical students are not "prevention" oriented, and, thus, more emphasis must be placed on preventive medicine [8].

It is also hoped that such investment will lead to nationally oriented research activities and not to a mere replication of Western studies. The study evaluating the significant protective effects of hand washing in children from common childhood diseases is one such example [9]. Another example is a study evaluating the effects of garlic on dyslipidemia [10]. Further studies of this kind may prove helpful in combating the cardiovascular disease epidemic in Pakistan. Garlic is potentially a much cheaper alternative to statins, the latter being unaffordable for most segments of Pakistani society. Similarly, medical education institutions such as Aga Khan University in Pakistan, which is a private-sector entity, have started problem-based, community-oriented teaching in medical schools. The outcome of these curricular changes remains to be seen. Indeed, there is hope for South Asia, but for such hope to materialize, we need selfless individuals, strong institutions, and perhaps above all a more just and realistic distribution of the national financial resources. ■

Fawad Aslam

Lahore Cantt, Lahore, Pakistan E-mail: fawadaslam2@hotmail.com

References

1. PLoS Medicine Editors (2005) Improving health by investing in medical education. PLoS Med 2: e424. DOI: 10.1371/journal.pmed.0020424

2. Awasthi S, Beardmore J, Clark J, Hadridge P, Madani H, et al. (2005) Five futures for academic medicine. PLoS Med 2: e207. DOI: 10.1371/journal. pmed.0020207

3. Jafarey AM, Farooqui A (2005) Informed consent in the Pakistani milieu: The physician's perspective. J Med Ethics 31: 93-96.

4. Aslam F, Qayyum MA, Mahmud H, Qasim R, Haque IU (2004) Attitudes and practices of postgraduate medical trainees to wards research; a snapshot from Faisalabad. J Pak Med Assoc 54: 534-536.

5. Aslam F, Shakir M, Qayyum MA (2005) Why medical students are crucial to the future of health research in South Asia. PLoS Med 2: e322. DOI: 10.1371/journal.pmed.0020322

6. Jafar TH, Jessani S, Jafary FH, Ishaq M, Orkazai R, et al. (2005) General practitioners' approach to hypertension in urban Pakistan. Disturbing trends in practice. Circulation 111: 1278-1283.

7. Jafary FH, Aslam F, Mahmud H, Waheed A, Shakir M, et al. (2005) Cardiovascular health knowledge and behavior in patient attendants at four tertiary care hospitals in Pakistan—A cause for concern. BMC Public Health 5: 124.

8. Aslam F, Mahmud H, Waheed A (2004) Cardiovascular health—Behaviour of medical students in Karachi. J Pak Med Assoc 54: 492-495.

9. Luby SP, Agboatwalla M, Feikin DR, Painter J, Billhimer W, et al. (2005) Effect of handwashing on child health: A randomized controlled trial. Lancet 366: 225-233.

10. Ashraf R, Aamir K, Shaikh AR, Ahmed T (2005) Effect of garlic on dyslipidemia in patients with type 2 diabetes mellitus. J Ayub Med Coll Abbottabad 17: 60-64.

Citation: Aslam F (2006) Prioritizing investment in medical education. PLoS Med 3(3): e159.

Copyright: © 2006 Fawad Aslam. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Competing Interests: The author has declared that no competing interests exist. DOI: 10.1371/journal.pmed.0030159

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