significance of the occurrence transparent

Ann. rheum. Dis. (1967), 26, 219

SIGNIFICANCE OF THE OCCURRENCE OFTRANSPARENT SKIN

A STUDY OF HISTOLOGICAL CHARACTERISTICS ANDBIOSYNTHESIS OF DERMAL COLLAGEN

BY

B. McCONKEY*+, K. W. WALTON*, S. A. CARNEYt,J. C. LAWRENCEt, AND C. R. RICKETTSt

From the *Department ofExperimental Pathology, University ofBirmingham, the tMedical Research Council IndustrialInjuries and Burns Research Unit, The Accident Hospital, Birmingham, and the +Dudley Road Hospital, Birmingham

Transparent skin has been observed in a proportionof elderly people and its association with senileosteoporosis has already been noted (McConkey,Fraser, Bligh, and Whiteley, 1963).

In patients with rheumatoid disease, whethertreated with steroids or not, it was found to be com-moner than in elderly people unaffected by rheuma-toid disease (McConkey, Fraser, and Bligh, 1965).

Clinical studies led to the hypothesis that trans-parent skin is the consequence of a change in theconnective tissues of the skin and that a similarchange might be taking place in the connective tissuesof the bones.

This is an account of the histological changescharacteristic of transparent skin and of some ex-periments undertaken to investigate its pathogenesis.

MethodsSelection of Patients49 patients were studied in all, including one case of

scleroderma studied for comparative purposes (see below).Whether for histology, or for estimation of skin collagenor of water content, the procedure adopted was to select anumber of patients with unequivocally abnormal skinand to compare the results obtained in these with thoseobtained in matched controls. The thickness of a foldof skin on the dorsum of the hand was measured withHarpenden calipers. For each patient with transparentskin (as previously defined, McConkey and others, 1963),a control patient was selected who corresponded in age,sex, and skin thickness but whose skin was opaque.No patient was receiving treatment with corticosteroids

or had other evidence of skin disease. Skin biopsies weretaken from the dorsum of the hand over the 3rd-4thmetacarpal.

Reprint requests to: Dr. K. W. Walton, Dept. of ExperimentalPathology, University of Birmingham, Birmingham 15.

HistologyTwenty biopsies, ten from transparent skin and ten

from opaque skin, were studied. The biopsies were takenin pairs by one of us and prepared and stained in batches.The sections were then examined by another of us whowas unaware of how each patient had been categorizedclinically.

Staining MethodsThe stains used were haematoxylin and eosin; van

Gieson's stain; the picropolychrome method of Herovici(1963); toluidine blue or Azure A (method of Hughesdon,1949); the periodic acid-Schiff technique (McManus,1946; Hotchkiss, 1948); the colloidal iron method ofHale (1946), and Weigert's elastic-tissue stain. In someinstances, sections were stained, before and after treat-ment with bovine testicular hyaluronidase, with Alcianblue in varying salt solutions as described by Scott,Dorling, and Quintarelli (1964).

Autoradiographs of sections of skin after incubationwith 14C-L-proline were carried out by the stripping filmtechnique of Pelc (1947).

Water ContentThree pairs of patients were selected as described above

and biopsies of skin taken. The biopsies were placedimmediately in small air-tight containers of known weightand were weighed. The water content was then deter-mined by drying the tissue to constant weight over phos-phorous pentoxide at 20'C.

Collagen Estimation and Measurement of TurnoverEleven patients were selected and biopsies taken as

described above. The biopsy specimens were dividedinto three or four pieces and incubated with (14C) prolineas described by Carney, Lawrence, and Ricketts (1965) forestimation of the incorporation of the isotope, exceptthat, in the present instance, after incubation, the sterilityof the cultures was checked and the skin samples incubated

219

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ANNALS OF THE RHEUMATIC DISEASESfor 1 hour on 1 per cent. 8l-phenoxy-ethyldimethyldo-decylammoniumbromide ("Bradosol", Ciba), in order tofacilitate separation into samples of dermis and epidermis.The separated portions were then treated as previously

described (Carney and others, 1965) to obtain gelatinextracts, for the estimation of hydroxyproline and forcounting ofradioactivity.

Autoradiographs on some samples of skin after incuba-tion with the isotope and washing were carried out asdescribed above.

Intradermal InjectionsTwelve patients with transparent skin had intradermal

injections of 0 I ml. of their own blood into the skin ofthe dorsum of the hand and on the forearm.

Results

Histological Appearance of Transparent SkinIn some of the patients with transparent skin the

epidermis was thinner and less keratinized than thatin patients with opaque skin. But this was not aconstant feature. On the other hand, marked andconstant differences were observed in the dermis asbetween transparent and opaque skin. Thesedifferences could be appreciated even in haematoxy-lin and eosin stained sections, were more markedwith van Gieson's stain, and were even more obviousin sections stained by the picropolychrome methodof Herovici (1963).The essential differences lay in the texture of the

dermis and in the staining-properties of the collagenfibres. In transparent skin the collagen fibres wereloosely arranged as fine individual fibrils with anapparent increase of interstitial "ground substance"between the fibrils. The fibrils stained a faint pinkwith eosin, an orange-yellow shade with van Gieson'sstain, and a clear blue colour with the methyl bluecomponent of the picropolychrome method.

In contrast, in opaque skin the collagen occurredas coarse bundles, much more closely packed. Thefibrils stained more intensely pink with eosin, brightred with the picrofuchsin of the van Gieson stain,and deep red with picropolychrome method. Thesedifferences are illustrated in Figs 1 to 6 (see col.plate).Although the changes described above as charac-

teristic of transparent skin sometimes involved thewhole thickness of the dermis, they were commonlymost marked in the upper third of the dermis (Fig.7). The alteration in size, distribution, and staining-properties of the collagen in transparent skin was notaccompanied by any marked alteration in elastictissue (i.e. in sections stained by Weigert's methodthere was no evidence of so-called "senile elastosis",

Fig. 8). Similarly, in sections stained with toluidineblue, mast cells were present in normal proportionsand there was no metachromatic material to be seenin the interstitial spaces between the fibres.

Sections of transparent skin fixed in alcohol andstained by the periodic acid-Schiff (PAS) techniqueshowed the presence of PAS-positive material inspaces between the fibres. This material also stainedpositively with the colloidal iron technique (cf. Figs9 and 10) and was diminished, but not entirely re-moved, by previous treatment with hyaluronidase.In alcohol-fixed tissues the material was not meta-chromatic when stained with toluidine blue orAzure A.These results suggested the presence in the inter-

stitial spaces of a tissue mucopolysaccharide ofrelatively low charge (i.e. non-sulphated). Amethod of categorizing tissue polysaccharides wasrecently described by Scott and others (1964). Inessence, this entails the determination of the molarityat which certain divalent cations inhibit the uptake,by a given tissue polysaccharide, of the dye Alcianblue at pH 5 * 7. On applying this technique, it wasfound that staining of the polysaccharide material inquestion in this instance, by Alcian blue, wasinhibited at pH 5 7 by a concentration of 0-25M MgCI2. According to the originators of thistechnique, such behaviour is characteristic of mucinsand carboxyl-containing glycosaminoglycans but notof sulphated tissue polysaccharides.

Water ContentOn comparing the loss in weight which occurred

when matched skin biopsies were dried to constantweight over phosphorus pentoxide, the results shownin the Table were obtained. It will be seen that theloss of weight of biopsies of opaque skin variedbetween 75 and 80 per cent. of the fresh weight,whereas the loss of weight on drying transparent skinwas markedly higher, being between 94 and 98 percent. of the fresh weight, indicating a higher initialwater content.

TABLE

WATER CONTENT OF OPAQUE AND TRANSPARENTSKIN

Opaque TransparentSkin

Specimen Water Specimen WaterNo. Content No. Content

Water 1 80-24 1 97.9Content 2 83*0 2 941HaO per cent. 3 79*9 3 98*2Wet Weight

Mean 81*0 Mean 96-7

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7

9

6

Fig. 6.-High-power view of transparentskin (Herovici's stain), showing loosetexture and fine fibrils of dermal collagen.

x 450.Facing p. 220.

Fig. 1.-Normal skin (Van Gieson's stain) showing dermal collagenarranged in coarse bundles. x 100.

Fig. 2.-Transparent skin (Van Gieson's stain). Dermal collagenstaining poorly and arranged as fine fibrils (compared with Fig. 1).

x 100.Fig. 3.-Normal skin (Herovici's stain). Coarse dermal collagenstaining bright red with picrofuchsin component of stain. x 100.Fig. 4.-Transparent skin (Herovici's stain). Fine dermal collagen

staining blue with methyl blue component of stain. x 100.Fig. 5.-High-power view of normal skin (Herovici's stain), showing

coarse bundles of dermal collagen. x 450.Fig. 7.-Transparent skin (Herovici's stain), showing changes more

marked in upper third of dermis (see text). x 100.Fig. 8.-Transparent skin (Weigert's elastic stain). Note absence of

alteration in distribution of elastic tissue. x 100.Fig. 9.-Transparent skin (colloidal iron stain) before treatment with

testicular hyaluronidase. x 100.Fig. 10.-Transparent skin (colloidal iron stain). Adjacent sectionto that shown in Fig. 9, stained after treatment with testicular

hyaluronidase. x 100.

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TRANSPAPJ

Collagen Content and (14C)-Proline UptakePrevious work by Prockop (for references see

Carney and others, 1965) has shown that (14C)proline is incorporated into collagen, a proportion ofthe proline being simultaneously converted tohydroxyproline. Consequently, the radioactivity ofthe collagen is a measure of its biosynthesis. Whenautoradiographs were made of intact skin biopsies,radioactivity was found to be present in both epi-dermis and dermis. Separation of dermis beforeanalysis enabled a pure sample of dermal collagento be obtained as gelatine for hydrolysis andsubsequent radio-activity measurements.The total collagen content and 14C content of the

biopsies were related to the fresh weights. Theresults obtained are shown in Fig. 11. For opaqueskin the total collagen content ranged from 3-27 to6 75 per cent. (mean 4-42 per cent., standard error'40 27 per cent.; fourteen observations.) Thesevalues were significantly higher (P<0 001) thanthose for transparent skin samples where the rangewas 0 56 to 3 40 per cent. (mean 2 16 per cent.,standard error 0 28 per cent.; sixteen observa-tions).

100-

90-

80 -

c 70

-20O b0

EC~E 50

rn4

_ 40

0

30

20

10

0

Fig. 11.-fresh weigcollagen)",C-prolin

x

xx

ENT SKIN 221

The specific radioactivity of dermal collagen alsodiffered between transparent and opaque skin. Themeans of observations were: opaque skin, 6,261c.p.m./mg. collagen (standard error ±1,697; nineobservations); transparent skin 30,436 c.p.m./mg.collagen (standard error ±10,517; fifteen observa-tions). The significance of this difference (0 02 < P>0 05) must be accepted with some reservation.As may be seen from Fig. 11, the mean value for thetransparent skin is influenced by some samples withlow collagen content (as estimated chemically)having high radioactivity.

Nevertheless, it may be concluded that, althoughthe collagen content of transparent skin is only abouthalf that of normal skin, the biosynthesis of collagenin transparent skin is at least as active, if not moreactive, than in opaque skin.

This was in marked contrast with the results ob-tained with a biopsy of skin from a case of sclero-derma studied in similar fashion. Histologically,the dermal collagen in this case was extremely denseand closely packed. The total collagen contentwas high (6-4 per cent.) but the biosynthesis waslow (1,384 c.p.m./mg. collagen).

Response of Skin to Intradermal InjectionWhen 0 1 ml. blood was injected intradermally

into areas of transparent skin, in ten out of twelvepatients the result was the formation of a normalbleb. In the remaining two patients, the bloodspread rapidly in a manner characteristic of patientswith senile purpura.

It should be noted that this technique appears tomeasure essentially the resistance of the dermis toacutely increased pressure rather than the altereddiffusion which occurs with the instillation of hya-luronidase (cf. Holborow and Keech, 1951).

DiscussionThe suggestion, put forward on the basis of clinical

evidence, that transparency of the skin is not duemerely to thinning of the skin (McConkey and others,1963, 1965) is confirmed by the present study. In

0 pairs of biopsies, when skin thickness was matched,x constant qualitative and quantitative differences

x X 0 0 have been found in the dermal collagen as between

xx x

°0o0 o opaque and transparent skin.The histological picture of transparent skin was

that of an alteration of texture of the dermis in whichPercentaqe Collagen the collagen was present as thin fibres, widely

0 Control separated from one another and showing a marked-Collagen content of skin biopsy samples (as percentage of affinity for methyl blue but a poor staining-reactionlht) and specific radioactivity of dermis collagen (cpm/mg. with acid fuchsin-as contrasted with the collagen ofafter incubation of the skin on a medium containing t d ole. the dermis of opaque skin which was arranged in


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compact coarse strands or thick bundles showing a

strong affinity for acid fuchsin.The wide separation of the relatively thin collagen

fibres in transparent skin appeared to be due tomarked hydration of the interstitial ground sub-stance, as supported by the finding of a high watercontent of skin biopsies showing transparency.These interstitial spaces, in sections appropriatelyfixed and stained, contained material with thecharacteristics of a weakly-charged tissue poly-saccharide. Although these histochemical reactionswere consistent with those ofhyaluronic acid, suggest-ing that this was the predominant component, thematerial was incompletely removed by previoustreatment with hyaluronidase.

Preliminary investigation, by extraction of theskin polysaccharides and their characterization bychromatographic techniques (Long, 1965) hassuggested the presence, in extracts of transparentskin, of small amounts of dermatan sulphate,chondroitin4sulphate, and heparin in the dermis, inaddition to hyaluronic acid (i.e. all the componentspresent in normal skin). The yields of materialfrom skin biopsies were insufficient to allow quan-

titative comparisons of the relative proportions ofthese compounds in opaque and transparent skin.In view of the possible importance of this in relationto the pathogenesis of transparent skin (see below)these investigations are being continued and theresults will be reported in due course.

The work with isotopically-labelled proline con-

firmed the depletion of total collagen in transparentskin but suggested that the collagen present was

metabolically as active, or even more active, thanthat present in opaque skin. It is known that thecollagen of skin exists in two functional forms, ofdiffering metabolic activity (Harkness, Marko,Muir, and Neuberger, 1954): a more labile andrapidly turned-over fraction, situated predominantlyin the superficial position of the dermis, which has a

rapid turnover rate; as compared with the collagenof the deeper layers of the dermis, which has a very

slow turnover rate.

Histological examination suggested that thecollagen changes in the dermis of transparent skinaffected predominantly the superficial layers of thedermis, in some cases being confined to this region,and only extending throughout the thickness of thedermis where the skin changes were advanced. Thealtered staining properties of the fibres in the affectedarea were also consistent with this collagen beingdifferent from normal. The picropolychrome stain,as introduced by Herovici (1963), was stated todifferentiate between young collagen (pro-collagen)

by its affinity for methyl blue; and mature collagen byan affinity for picro-fuchsin.At the other end of the scale, the dermis from the

case of scleroderma which showed exceptionallydense and compact bundles of collagen with a markedaffinity for picrofuchsin, although found to have anincreased total collagen content, exhibited markedlylower biosynthetic activity of this collagen as com-pared with normal skin.At first sight, it seemed inherently unlikely that the

elderly patients with transparent skin who formedthe subjects of this study could be inferred to bedistinguished by a capacity to make new collagen atan unusual rate in the skin. But, on the other hand,it seemed possible that this picture might also resultfrom an interference with the normal maturation ofcollagen, as proposed in the following hypothesiswhich is based on the work of Jackson (1956),Meyer (1957), Meyer and Hoffman (1960), Gross(1959), Wood (1960a, b), Wood and Keech (1960),and others.

Collagen is formed initially in a soluble form andit is this fraction of the collagen in a tissue which isthe most active metabolically. Maturation of col-lagen involves its transformation, by the aggregationof sub-units to the insoluble form. Immatureinsoluble collagen exists as fine fibres which byfurther aggregation become coarse bundles whichare the stable, metabolically-inactive form. At allstages of the maturation process (i.e. orientation andsteric arrangement to allow cross-linking andaggregation) it is likely that the presence of muco-polysaccharides of normal constitution in the groundsubstance is required.

Thus, our findings could represent an arrest in thematuration of collagen arising as a specific defectgiving rise to a smaller proportion of mature andmetabolically-inert collagen and a reduced totalcollagen content because of loss from the skin assoluble collagen.

Alternatively, the failure of maturation of collagenmight be secondary to changes in the constitution ofthe ground substance. Such changes might be inturnover rate, in the relative proportions, or in thedegree ofpolymerization, of the mucopolysaccharidesof the ground-substance.

It is known that the total concentration (Clausen,1962) and turnover rate of the mucopolysaccharidesof skin diminish with age. If the rate of turnover ofmucopolysaccharides is one of the limiting factorsin the normal maturation of collagen, it is possiblethat marked decrease, in itself, might account forthe occurrence of transparent skin in some otherwisehealthy elderly people. Such decrease of turnovermight affect all the mucopolysaccharides together or

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might affect some more than others. It is knownfrom studies of the incorporation of 35S-sulphate and14C-acetate into skin mucopolysaccharides that up-take occurs much more readily into some of thesecompounds than others, suggesting different rates ofsynthesis and hence of turnover (Dorfman andSchiller, 1958; Sobel and Marmorston, 1958).Decreased turnover might thus affect not only thetotal but also the relative proportions of the skinmucopolysaccharides.

It was first suggested by Meyer (1957), on the basisof the failure of normal collagen fibre formation inscorbutic animals or those given large doses ofcortisone, that this might in turn be dependent uponfailure of production of sulphated mucopolysac-charides in normal amounts and proportions. Inrelation to cortisone dosage, it should be noted that,although the patients in the present study had notbeen treated with corticosteroids, in other patientswe have observed that transparency of the skinbecomes more marked with prolonged steroidtherapy (See also Greenwood, 1966).

It was shown by Loewi and Meyer (1958) in pigsthat, when embryonic skin (characterized by finecollagen fibres arranged in a loose texture) wascompared with adult skin (characterized by a com-pact arrangement of coarse collagen bundles), therewere marked differences in the relative proportionsof hyaluronic acid and chondroitin sulphate B(dermatan sulphate). Loewi (1961) was unable toshow similar differences in humans, using skin fromthe back of the hand, with pooled samples from theage group 50-70 years. However, no observationswere recorded on the relative incidence of "trans-parent" and "opaque" skin among the latter group,so that it is possible that differences might haveexisted but have been obscured by the pooling pro-cedure adopted. This possibility is being re-investigated and the results will be reported later.With regard to the degree of polymerization of the

mucopolysaccharides, there may be an additionalfactor to consider in rheumatoid arthritis, a diseasewith a high incidence of transparent skin. It hasbeen shown by Barker, Bayyuk, Brimacombe,Hawkins, and Stacey (1963) that in rheumatoidarthritis the hyaluronic acid of synovial fluid isdepolymerized, and there is some evidence thathyaluronic acid elsewhere in the body may besimilarly affected, including skin as first shown byBywaters, Holborow, and Keech (1951) and morerecently by Herp, Fabianek, Calick, and Pigman(1966).The alteration of the hyaluronic acid of the

ground substance is not necessarily accompanied bya decrease in resistance to an acute increase in pres-

sure as shown by the formation of a normal bleb onthe injection of blood intradermally in our patients.

It has been suggested that senile purpura, anotherabnormality of the skin of elderly people, is theconsequence of lack of support by the connectivetissues to the small blood vessels of the skin (Tatter-sall and Seville, 1950; Shuster and Scarborough,1961). If this were so, it might be expected that the"senile" or "steroid" type of purpura would occurreadily in transparent skin where collagen is soclearly diminished and where changes in the groundsubstance may also be present. However, althoughthere is a partial association between transparentskin and senile purpura (McConkey, Fraser andBligh, 1962), in patients who have both conditions thepurpura does not necessarily occur in areas where theskin is most obviously transparent. Moreover,Shuster and Scarborough (1961) showed that thelesion of senile purpura could be reproduced in sus-ceptible persons by an intradermal injection of theirown blood. As already stressed, we have foundthat intradermal injection of blood in areas oftransparent skin in twelve patients led to the forma-tion of normal blebs in ten of them.The opacity of normal skin was held by Montagna

(1956) to be due to the constitution of the epidermis.In our patients with transparent skin, however,changes in the epidermis were not a marked orconstant feature. The appearance of transparencycan probably be accounted for by the reduction in theamount of collagen with accumulation of homogene-ous and highly hydrated material between thewidely dispersed fibres; the effect of this changewould be to render the tissue as a whole opticallymore uniform.

Summary(1) Transparency of the skin has been found to be

due not simply to thinning but to changes in thedermal collagen. These changes have a characteristichistological pattern in that the collagen fibres arefine and widely-dispersed and show altered stainingcharacteristics from the coarse compactly-arrangedcollagen bundles of normal (opaque) skin.

(2) Transparent skin is more hydrated than normalskin and shows a diminution of total collagen ascompared with controls matched for age and sex.But biosynthesis, as judged by the uptake of 14C-proline with the collagen, is as active or even moreactive than in normal skin.

(3) The reaction of transparent skin to the intra-dermal injection of autologous blood was found, inthe majority of cases, to be similar to that found innormal skin.

(4) It is suggested that the changes in the dermal

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collagen of transparent skin result from a failure of We acknowledge gratefully the support given to thismaturation of the collagen fibres. As yet it is not work by the Nuffield Foundation and by Birminghampossible to say whether this arises as a specific Regional Hospital Board. We are grateful to Miss Celiadefect or whether it is secondary to changes in the Roberts for technical assistance.

glycosaminoglycans (acid mucopolysaccarides) ofthe ground substance.

REFERENCES

Baker, S. A., Bayyuk, S. H. I., Brimacombe, J. S., Hawkins, C. F., and Stacey, M. (1963). Clin.chim. Acta, 8, 902 (Fingerprinting the hyaluronic acid component of normal and pathologicalsynovial fluids).

Bywaters, E. G. L., Holborrow, E. J., and Keech, M. K. (1951). Brit. med. J., 2, 1178 (Reconstitutionof the dermal barrier to dye spread after hyaluronidase injection).

Carney, S. A., Lawrence, J. C., and Ricketts, C. R. (1965). Biochim. biophys. Acta, 111, 154(Incorporation of(14C) proline by mammalian skin in tissue culture).

Clausen, B. (1962). Lab. Invest., 11, 1340 (Influence of age on connective tissue: Uronic acid anduronic-acid hydroxyproline ratio in human aorta, myocardium, and skin.)

Dorfman, A., and Schiller,S. (1958). Rec. Progr. Hormone Res., 14,427 (Effects of hormones on themetabolism of acid mucopolysaccharides of connective tissue).

Greenwood, B. M. (1966). Ann. rheum. Dis., 25, 272 (Capillary resistance and skin-fold thickness inpatients with rheumatoid arthritis).

Gross, J. (1959). In "Connective Tissue, Thrombosis, and Atherosclerosis", ed.I. H. Paget, p. 77.Academic Press, New York.

Hale, C. W. (1946). Nature (Lond.), 157,802 (Histochemical demonstration of acid polysaccharidesin animal tissues).

Harkness, R. D., Marko, A. M., Muir, H. M., and Neuberger, A. (1954). Biochem. J., 56,558 (Meta-bolism of collagen and other proteins of the skin of rabbits).

Herovici, C. (1963). Rev. franC.ttud.clin. biol., 8, 88 (Le picropolychrome. Technique de colora-tion histologique destinea l'etude du tissu conjonctif, normal et pathologique).

Herp, A., Fabianek, J., Calick, A., and Pigman, W.(1966). Ann. rheum. Dis., 25, 345 (Dermal con-

nective tissue permeability in rheumatoid arthritis).Holborow, E. J., and Keech, M. K. (1951). Brit. med. J., 2, 1173 (Hyaluronidase skin spreading

effect: an analysis of repeated measurements).Hotchkiss, R. D. (1948). Arch. Biochem., 16, 131 (Microchemical reaction resulting in the staining

of polysaccharide structures in fixed tissue preparations).Hughesdon, P. E. (1949). Jroy. microscop. Soc., Ser. 3,69, 1 (Two uses of uranylnitrate).Jackson, S. F. (1956). Proc.roy. Soc. B., 144,556 (Morphogenesis of avian tendon).Loewi, G. (1961). Biochim. biophys. Acta, 52,435 (Acid mucopolysaccharides of human skin).

andMeyer,K. (1958). Ibid.,27,453 (The mucopolysaccharides of embryonic skin).Long, V. J. W. (1965). "The Polysaccharides of Skin and Synovial Fluid". M.Sc. thesis, University

of Birmingham.McConkey, B., Fraser, G. M., and Bligh, A.S. (1962). Quart.J. med.,n.s. 31,419 (Osteoporosis and

purpura in rheumatoid disease; prevalence and relation to treatment with corticosteroids).(1965). Ann. rheum. Dis., 24, 219. (Transparent skin and osteoporosis: a study in

patients with rheumatoid disease).and Whiteley, H. (1963). Lancet, 1, 693 (Transparent skin and osteoporosis).

McManus, J. F. A. (1946). Nature (Lond.), 158, 202 (Histological demonstration of mucin afterperiodic acid).

Meyer, K. (1957). Harvey Lect., 1955-1956, 51, 88 (Chemistry of the mesodermal ground sub-stances).

and Hoffman, P. (1960). Arzneimittel-Forsch., 10, 379 (Enzymatic degradation in the struc-tural analysis of mucopolysaccharides of connective tissues).

Montagna, W. (1956). "The Structure and Function of the Skin". p. 15. Ser. 51, Academic Press,New York.

Peic,S.R. (1947). Nature (Lond.),160,749 (Autoradiograph technique).Scott, J. E., Dorling, J., and Quintarelli, G. (1964). Biochem. J., 91,4 (Differential staining of acid

glycosaminoglycans by Alcian blue in salt solutions).Shuster, S., and Scarborough, H. (1961). Quart. J. Med., n.s. 30, 33 (Senile purpura).Sobel, H., and Marmorston, J. (1958). Rec. Progr. Hormone Res., 14,457 (Hormonal influences upon

connective tissue changes of ageing).

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Tattersall, R. N., and Seville, R. (1950). Quart. J. Med., n.s. 19, 151 (Senile purpura).Wood, G. C. (1960a). Biochem. J., 75, 598 (Formation of fibrils from collagen solutions: 2. A

mechanism of collagen fibril formation).(1960b). Ibid., 75, 605 (Formation of fibrils from collagen solutions: 3. Effect of chondroitinsulphate and some other naturally occurring polyanions on the rate of formation).and Keech, M. K. (1960). Ibid., 75, 588 (Formation of fibrils from collagen solutions:1. Effect of experimental conditions: kinetic and electron-microscope studies).

La port6e de l'occurrence de la peau transparente-Etudedes caracteres histohgiques et de la biosynthese du

collagene dermique

RMSUMt(1) On a trouve que la transparence de la peau n'est

pas due simplement a l'amincissement mais aux alterationsdu collagene dermique. Ces alterations presentent untableau histologique caracteristique dans le sens que lesfibres du collagene sont fines et tres dispersees et secolorent diff6remment des faisceaux de collagene gros-sierement tasse de la peau normale (opaque).

(2) La peau transparente est plus hydrat6 que la normaleet contient moins de collagene total que celle des temoinsd'un age et d'un sexe comparables. Toutefois la bio-synthese, d6terminee par l'absorption de la 14C-prolineavec le collagene, est aussi active et meme plus activeque dans la peau normale.

(3) On a trouv6 que dans la plupart des cas la reactionde la peau transparente A l'injection de sang autologueetait similaire a celle de la peau normale.

(4) On suggere que les alterations du collagene cutanede la peau transparente sont dues A un defaut dans lamaturation des fibres du collagene. On ne sait pasencore s'il s'agit ici d'un defaut specifique ou secondaireaux alterations des glycosaminoglycans (mucopoly-saccharides acides) de la matrice.

El significado de la ocuffencia de la piel transparente.Estudio de los rasgos histologicos y de la biosintesis del

colfigeno d6rmico

SUMAP1O(1) Se hallo que la transparencia de la piel no se debe

simplemente al adelgazamiento sino a alteraciones delcolageno cutaneo. Estas alteraciones presentan uncuadro histol6gico caracteristico: las fibras del colagenoson finas y muy dispersas y ofrecen caracteristicas decoloraci6on diferentes de las de haces de colageno grosera-mente empacadas de la piel normal (opaca).

(2) La piel transparente es mas hidratada que la normaly contiene menos coligeno total que la de testigos deedad y sexo comparable. Sin embargo la biosintesis,determinada por la absorpcion de la 14C-prolina concolageno, es tan activa o mas que en la piel normal.

(3) Se hall6 que en la mayoria de los caos la reaccion dela piel transparente a la inyeccion de sangre aut6loga fu6similar a la de la piel normal.

(4) Se sugiere que las alteraciones del colageno cutaneode la piel transparente se deben a un defecto de la madura-ci6n de las fibras del colageno. No se sabe todavia si setrata aqui de un defecto especffico o secundario a altera-ciones de los glicoaminoglicanos (mucopolisacaridosacidos) de la matriz.

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