Reviewer's report
Title:A Wilson protein expression, copper excretion and sweat production in
sweat glands of Wilson disease patients and controls
Version: 1Date:11 March 2008
Reviewer: Svetlana Lutsenko
Reviewer's report:
In this manuscript, the authors have optimized conditions for collecting sweat
samples suitable for analysis of copper content and determined the copper
concentration, sweat volume, and total copper excretion in Wilson disease
patients and control group of patients. In the course of the study, the authors
have made several new and interesting observations. Among them are the high
level of expression of Wilson protein in secretory and ductular epithelium of
sweat glands and significant reduction of sweat volume in Wilson disease
patients. Although the authors concluded that the copper measurements in sweat
cannot facilitate Wilson disease detection, the findings and obtained information
are interesting and useful.
I only have some minor issues:
1. In the introduction, the goal of the study should be spelled out more clearly.
2. Page 3. “It its ability to translocate copper-concentration dependent….” – I do
not understand this sentence, please revise.
3. Page 3 “Patient with Wilson disease usually develope…” –“develop” is
misspelled
4. Page 3”…such as pregnancy or taking the anti-baby pill” - “anti-baby” is not a
scientific term, please correct
5. Page 4 - use COMMD1 instead/or in addition to Murr1, as COMMD1 is a more
accepted term now.
6. The reader would be intersted to know whether there were any apparent
changes in the morphology of sweat gland in LEC rat – Please comment
7. The sentence “If Wilson patient producing no sweat…” is confusing. Does it
mean that when the volume of sweat was small the concentration of copper was
low, or that the authors could not measure copper at all? - Please clarify
8. Page 7. No direct correlation could be found between the serum copper…" -
This statement needs to be expanded. Were all these parameters compared
pair-wise? Was there any difference between any pair of parameters? - Having
more details would be desirable.
9. Figure 5A,B – This figure takes too much space for the amount of information
shown. The combined one-panel figure with bar-graphs (or a table) seems more
appropriate
Discussion (this does not require response from the authors unless they like to
comment). The association between Wilson protein and chloride transporter
ClC-4 was previously demonstrated. Also, inactivation of chloride transporter
GEF-1p inhibits copper delivery to the secretory pathways in yeast, while
overexpression of Aspergillus chloride transporter restores copper metabolism.
These observations make one wonder whether there is a tight link between
copper and chloride homeostasis, which in sweat gland may involve CFTR along
with the CLC channel(s)(and thus the disruption of copper metabolism may alter
the chloride homeostasis affecting the sweat volume). Such connection is, of
course, highly speculative, but if the authors could provide some thoughts about
a possibility of chloride-copper connection in sweat gland, that would be useful to
the reader.
What next?: Accept after minor essential revisions
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:A Wilson protein expression, copper excretion and sweat production in
sweat glands of Wilson disease patients and controls
Version: 1Date:11 March 2008
Reviewer: Svetlana Lutsenko
Reviewer's report:
In this manuscript, the authors have optimized conditions for collecting sweat
samples suitable for analysis of copper content and determined the copper
concentration, sweat volume, and total copper excretion in Wilson disease
patients and control group of patients. In the course of the study, the authors
have made several new and interesting observations. Among them are the high
level of expression of Wilson protein in secretory and ductular epithelium of
sweat glands and significant reduction of sweat volume in Wilson disease
patients. Although the authors concluded that the copper measurements in sweat
cannot facilitate Wilson disease detection, the findings and obtained information
are interesting and useful.
I only have some minor issues:
1. In the introduction, the goal of the study should be spelled out more clearly.
2. Page 3. “It its ability to translocate copper-concentration dependent….” – I do
not understand this sentence, please revise.
3. Page 3 “Patient with Wilson disease usually develope…” –“develop” is
misspelled
4. Page 3”…such as pregnancy or taking the anti-baby pill” - “anti-baby” is not a
scientific term, please correct
5. Page 4 - use COMMD1 instead/or in addition to Murr1, as COMMD1 is a more
accepted term now.
6. The reader would be intersted to know whether there were any apparent
changes in the morphology of sweat gland in LEC rat – Please comment
7. The sentence “If Wilson patient producing no sweat…” is confusing. Does it
mean that when the volume of sweat was small the concentration of copper was
low, or that the authors could not measure copper at all? - Please clarify
8. Page 7. No direct correlation could be found between the serum copper…" -
This statement needs to be expanded. Were all these parameters compared
pair-wise? Was there any difference between any pair of parameters? - Having
more details would be desirable.
9. Figure 5A,B – This figure takes too much space for the amount of information
shown. The combined one-panel figure with bar-graphs (or a table) seems more
appropriate
Discussion (this does not require response from the authors unless they like to
comment). The association between Wilson protein and chloride transporter
ClC-4 was previously demonstrated. Also, inactivation of chloride transporter
GEF-1p inhibits copper delivery to the secretory pathways in yeast, while
overexpression of Aspergillus chloride transporter restores copper metabolism.
These observations make one wonder whether there is a tight link between
copper and chloride homeostasis, which in sweat gland may involve CFTR along
with the CLC channel(s)(and thus the disruption of copper metabolism may alter
the chloride homeostasis affecting the sweat volume). Such connection is, of
course, highly speculative, but if the authors could provide some thoughts about
a possibility of chloride-copper connection in sweat gland, that would be useful to
the reader.
What next?: Accept after minor essential revisions
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:A Wilson protein expression, copper excretion and sweat production in
sweat glands of Wilson disease patients and controls
Version: 1Date:11 March 2008
Reviewer: Svetlana Lutsenko
Reviewer's report:
In this manuscript, the authors have optimized conditions for collecting sweat
samples suitable for analysis of copper content and determined the copper
concentration, sweat volume, and total copper excretion in Wilson disease
patients and control group of patients. In the course of the study, the authors
have made several new and interesting observations. Among them are the high
level of expression of Wilson protein in secretory and ductular epithelium of
sweat glands and significant reduction of sweat volume in Wilson disease
patients. Although the authors concluded that the copper measurements in sweat
cannot facilitate Wilson disease detection, the findings and obtained information
are interesting and useful.
I only have some minor issues:
1. In the introduction, the goal of the study should be spelled out more clearly.
2. Page 3. “It its ability to translocate copper-concentration dependent….” – I do
not understand this sentence, please revise.
3. Page 3 “Patient with Wilson disease usually develope…” –“develop” is
misspelled
4. Page 3”…such as pregnancy or taking the anti-baby pill” - “anti-baby” is not a
scientific term, please correct
5. Page 4 - use COMMD1 instead/or in addition to Murr1, as COMMD1 is a more
accepted term now.
6. The reader would be intersted to know whether there were any apparent
changes in the morphology of sweat gland in LEC rat – Please comment
7. The sentence “If Wilson patient producing no sweat…” is confusing. Does it
mean that when the volume of sweat was small the concentration of copper was
low, or that the authors could not measure copper at all? - Please clarify
8. Page 7. No direct correlation could be found between the serum copper…" -
This statement needs to be expanded. Were all these parameters compared
pair-wise? Was there any difference between any pair of parameters? - Having
more details would be desirable.
9. Figure 5A,B – This figure takes too much space for the amount of information
shown. The combined one-panel figure with bar-graphs (or a table) seems more
appropriate
Discussion (this does not require response from the authors unless they like to
comment). The association between Wilson protein and chloride transporter
ClC-4 was previously demonstrated. Also, inactivation of chloride transporter
GEF-1p inhibits copper delivery to the secretory pathways in yeast, while
overexpression of Aspergillus chloride transporter restores copper metabolism.
These observations make one wonder whether there is a tight link between
copper and chloride homeostasis, which in sweat gland may involve CFTR along
with the CLC channel(s)(and thus the disruption of copper metabolism may alter
the chloride homeostasis affecting the sweat volume). Such connection is, of
course, highly speculative, but if the authors could provide some thoughts about
a possibility of chloride-copper connection in sweat gland, that would be useful to
the reader.
What next?: Accept after minor essential revisions
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
assistant