Histopathology of Striae Distensae, with Special Reference to Striae and Wound Healing in the Marfan Syndrome*

Vol. 46, No. 3

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Copyright

Prioted in U.S.A.

1966 by The Williams & Wilkins Co.

HISTOPATHOLOGY OF STRIAE DISTENSAE, WITH SPECIAL REFERENCE TO STRIAE AND WOUND HEALING IN THE MARFAN SYNDROME* H. PINKUS, M.D.t M. K. KEECH, M.D.t AND A. H. MEHREGAN, M.D.t

The Marfan syndrome is a defect of the biopsy specimens were obtained, 5 of them from mesenchyme affecting mainly the musculoskeletal, ocular, and cardiovascular systems. It is in-

patients with Marfan manifestations, 3 from family

members. In addition S non-Marfan controls and a cortisone-induced example from the thigh of a

herited as a simple autosomal dominant with a 14 year old boy rendered Cushingoid by high high degree of penetrance (1—4). Originally the steroid dosage for polyarteritis nodosa (Table 1)

primary defect was believed to reside in the were examined. Elliptical incisions were made to elastic tissue but in a recent careful histochemi-

cal study of four infants and two adults Bolande (5) demonstrated an abnormal deposition

include normal skin on either side of the stria. The specimens were fixed in formalin and stained with hematoxylin-eosin and acid orcein-Giemsa technics.

Wound healing.—Read et of (5) performed

of chondroitin sulfate (probably C) in the cardiac surgery and inserted Starr-Edwards prosheart and aorta with secondary disruption of the elastic fibers which allows formation of aneurysmal dilatations and medial dissections. The deposition of metaehromatic material does not

theses in eight patients with myxomatous trans-

formation of the valves characteristic of the Marfan syndrome. One patient had to be reoperated twice on account of disruption of the prosthesis from the annulus. At the third opera-

appear to be a function of aging, or of the tion, the patient W. K.,* had a stretched, thinned

scar measuring up to 3½ cm in width duration and severity of hemodynamic stress in presternal at the site where the skin had been sutured at the the cardiovascular system. time of the second operation 10 months earlier. Kachele (6) and Loveman, Gordon, and The entire scar and edges of normal skin were Fliegelman (3) suggested that presence of skin excised. Cross sections were taken at various levels treated as described above. Additional secstriae in Marfan patients affords further evi- and tions were stained with alcian blue-PA5 and dence of the (presumed) abnormal elastic tissue toluidin blue. and may be of diagnostic significance. One of

us (H. P.) described the histology of two of

RESULTS

Loveman's cases and was impressed by evidence Skin striae.—Sections from the five patients of new formations of elastic fibers which seemed with the syndrome and three family members

contrary to the general opinion that striae are

(one sibling, a daughter and a son) reveal a characterized by an elastic fiber defect. It uniform picture. In the area of the stria the seemed worthwhile to investigate the histologic changes in striae from Marfan patients and to compare them with striae from normal individ-

epidermis is thin and more or less devoid of

paired wound healing in Marfan's syndrome.

upper portion of the pars reticularis of the

rete ridges. Dermal papillae are correspondingly

flattened or absent. The superficial brush-like uals. In addition we studied evidence of im- elastic fibers usually are poorly developed. The MATERIALS AND METHODs

Skin strioe.—In a study of 58 individuals of vary-

corium shows rather straight collagen bundles arranged parallel to the skin surface and trans-

verse to the direction of the stria (Fig. 2).

ing age belonging to Marfan families (7) seven Elastic fibers are arranged similarly. They are adults and four adolescents had striae on the thighs, buttocks, and shoulders (Fig. 1). Eight fairly straight and thin, but usually are present in greater quantity than in the surrounding Received for publication April 20, 1965. Supported in part by U.S.P.H.S. grants AM- skin, and may be present as dense bundles of 07194, TI-AM-5141, and STL-AM-5267 through the parallel fibers (Fig. 3). Below this zone, there National Institutes of Health, and by a grant from may be a localized absence of elastic fibers. ColMichigan Chapter of Arthritis and Rheumatism Foundation.

lagen bundles and elastic fibers of the deep

* From the Departments of Medicnet and Der- corium cften are undisturbed. At the lateral matologyt of Wayne State University School of Medicine and Detroit Receiving Hospital, Detroit, * We wish to thank Dr. R. C. Read for the Michigan 48207.

specimen of W. K.'s scar.

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The boundaries of the Striae are indicated by arrows.

J = Junction with normal dermis; N Normal skin; S = Scar.

Fic. 1. Striae on anterior axillary fold in the Marfan Syndrome (Case 1)

borders between stria and normal skin, curled straight elastic fibers are running in the same ends of broken and retracted elastic fibers some- direction as the collagen bundles. They intertimes are evident. Even the striae from the mingle to some extent with the normal threethighs of the two oldest patients examined, dimensional net of thicker elastic fibers at the both aged 61 years, exhibit a similar histologic edge of the abnormal zone (Fig. 7). The deeppicture, including thick elastic fibers. The ap- est third consists of practically normal collagen pearance suggests that the striae had been pres- bundles in which are embedded remnants of ent for a very long time. surgical sutures. There is an increase of small A similar picture was found in the S non- blood vessels and a decrease of elastic fibers Marfan controls (Fig. 4) and the cortisone-in- which appear broken and curled. In between duced stria (Fig. 5). The findings are inter- the superficial and deep portions there is a zone preted as representing new formation of elastic consisting of denser and somewhat basophilic fibers in the scar-like tissue of the stria. collagen in which elastic fibers are completely Surgical scar from W. K.—A strip of darkly missing. The collagen bundles here whorl in pigmented skin and subcutaneous tissue was different direction. Microscopic diagnosis: Fisubmitted, which measured 30 cm in length brous scar due to separation of the edges of a and 3.5 cm at the widest point, tapering sutured wound. The upper portion shows exgradually toward both ends. Sections were cut tensive new formation of elastic fibers similar from 5 levels transversely through the speci- to that seen in striae distensae. men. All show normal skin containing hairs and DlsctssloN glands at either end of the sections (Fig. 6). Collagenous bundles and elastic fibers are In the present study 11 of the 58 individuals present in normal distribution. The central examined, either cases of the Marfan syndrome part of the sections, 2—3 cm in width, is cov- or their family members, had striae on the ered by thin epidermis which has few and short thighs, buttocks, or shoulders. All were overrete ridges. The dermis in this part is divided weight except two elderly patients both aged into three layers. The upper third consists of 61 in whom biopsy examination suggested that long undulating bundles of collagen arranged the lesions had been present for a very long parallel to the skin surface. Numerous thin and time. This figure of 19% is not unusually high.

285

STRIAE DISTENSAE AND MARFAN'S SYNDROME

TABLE 1 Case no-Age-Sex-Race

Duration

Location

Clinical appearance

Marf an Syndrome

White streaks with atrophy

1. 39-M-C (T.M.)

Unknown

Axillary folds

2. 61-F-C (L.L)

years

Upper thighs and abdomen White streaks with atrophy

3. 61-F-C (V.C.)

years

Upper thighs and abdomen White streaks with atrophy

4. 20-M-W (G.R.)

Unknown

Ant. axillary folds

White streaks with atrophy

5. 43-M-W (C.W.)

Unknown

Buttocks and flanks

White streaks with atrophy

6. 13FW* (P.W.)

Unknown

Lateral aspect of thighs

White streaks with atrophy

7. 14-M-W (P.W.) Unknown

Buttocks and flanks

White streaks with atrophy

8. 26MW***

Buttocks and flanks

White streaks with atrophy

Unknown

(F .R.)

Cushingoid 9. 14-M-W

8 months

Buttocks and legs

Erythematous streaks with atrophy

Normal Control 10. 20-F-W

6 months

Upper thighs and gluteal White streaks with atrophy areas

11. 22-M-W

5 months

Upper thighs and crural Violaceous streaks with atrophy folds

12. 29-M-W

12 months

13. 18-M-W

6 months

14. 11-F-W

months

15. 24-M-W

Unknovn

16. 17-M-W

2 years

Gluteal areas

Erythematous streaks with atrophy

Gluteal groins and axillary Keloid-like streaks areas

Buttocks

Erythematous streaks with atrophy

Upper thighs

Purplish streaks with atrophy

Back

Erythematous atrophic horizontal lines

17. 40-M-W

Many years Upper thighs

White streaks with atrophy

* Daughter of Case 5. C.W. ** Son

of Case 5. C.W. Brother of Case 4. G.R.

Hauser (9) quotes three references from the striae on the thighs. A study in Japati (10) German literature that estimate 25%, 33%, and revealed striae in 21.3% of girls and 6.6% of 73% of adolescent girls have striae. One author males at puberty (Table 2). This was associcited 36% of females and 6% of males have ated with increased 17-ketosteroid excretion.

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Fiu. 2. An old Stria from a patient aged 61 years with the Marfan Syndrome (Case 3) shows characteristic central parallel fibers. In the normal skin edge at the periphery the elastic fibers are normal in appearance (Acid orcein-Ciemsa; 52 X.)

I

Fio. 3. Center of Stria in the Marfan Syndrome (Case 4) shows at a higher power the

thick newly formed fibers running parallel to the surface (Acid orcein-Ciemsa; 135 x.)

STRIAE DISTENSAE AND MARFAN'S SYNDROME

287

FIG. 4. Stria in a normal individual (Case 16) shows central fibers running parallel to the surface epidermis. At either side and in the deeper portion of the corium elastic fibers have their normal distribution (Acid orcein-Ciemsa; 52 X.)

Sisson (11) examined 190 healthy children

Poor wound healing in Marfan patients has

aged 10—16 years and found striae in 35%, girls been reported, for example, in herniorrhaphy

being 2½ times more striae-prone than boys. Although of frequent occurrence in the obese, thin individuals also exhibited these lesions. There was definite association with steroid activity and the changes of puberty. Recent

(16) and cleft palate (17). In our group, wide, thin sears were observed in three siblings of patients treated surgically for cardiovascular manifestations of the Marfan syndrome (7).

striae after topical steroid application under an occlusive dressing (12—14). Normal athletes commonly have striae, for example basketball players. Rapid increase or decrease in weight, severe illness, localized muscle development, the administration of steroids with attendant weight gain, Cushing's syndrome, and abdomi-

to ½

At his third cardiac operation W. K. had a reports have described the appearance of stretched, thinned presternal scar measuring up

nal stretching in pregnancy may all produce striae. The common denominator appears to be increased level of eortieosteroids. Only a small

proportion of our Marfan families had striae and the histologic appearance was similar to that described in 1889 by Troisier and Mflnfltrier (15) in their original work on skin striae (Fig. 8), and was not significantly different from normal controls or cortisone-induced striae. This study, therefore, does not support skin biopsy study as a method of diagnosis in the Marfan syndrome.

cm in width. Histologic examination revealed a picture which in some respects resembled that of a stria. Of particular interest here is the presence of many thin elastic fibers in parallel arrangement in the superficial part of the scar. These fibers are embedded in similarly arranged collagen bundles which bridge the gap between the edges of the normal skin. This gap being up to 3 cm wide one cannot doubt that the collagenous bundles represent new tissue formed gradually under tension as the sutured edges of the surgical incision sepa-

rated over a period of several months. It is then more than likely that the elastic fibers in this area also are new fibers, not stretched and thinned old ones. This view is supported by finding the thick old fibers, which had been severed by the scalpel, curled in the edges of the normal skin and in the deepest part of the

288

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Fie. 5. A. Stria in a Cushingoid child (Case 9) shows a ccntral area in which thin fibers are running parallel to the surface. Below this area is a zone in which elastic fibers are absent (Acid orcein-Giemsa, 30 X.) B. High power from the edge of Stria show in the left side thin newly formed fibers with their parallel arrangement. At the right are numerous curled up broken fibers (Acid orcein-Giemsa; 180 ><.)

central portion where the dermis is held in It is important to point this out because the apposition by the still visible buried sutures. first authors who called attention to elastic Moreover, the estimated quantity of thin paral-

fiber changes as the basic defect in stria forma-

lel elastic fibers is definitely greater than the tion (Troisier and MSnétrier (15)) described quantity of normal elastic net per unit volume. two alterations: breaking and curling of some

289

STRIAE DISTENSAR AND MARFAN'S SYNDROME

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Fm. 6. A. Low power view of pre-sternal sear of W. K., a case of the Marfan Syndrome at its maximal width (3½ cm.) (llematoxylin-eosin; 3 X.) B. Shows junction of the normal

skin and scar (Acid orcein-Giemsa; 135 X.)

fibers, and stretching and thinning of surviving and parallel elastic fibers in the upper part of fibers. It is evident from their excellent illustra- the dermis as due to stretching of preformed tion which we reproduce as Fig. S that they fibers. Recent texts give the impression that saw exactly the same picture that our photo- the principal histologic characteristic of a stria micrographs show. They interpreted the thin is an elastic fiber defect expressed in their

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FIG. 7. Same Case as (Fig. 6). A. Normal skin close to the edge of scar with normal appearing elastic fibers (Acid orcein-Giemsa; 157 X.)B. Numerous newiF formed elastic fibers running from one side of the scar to the other side parallel to the surface epidermis (Acid orcein-Giemsa; 157 >C)

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291

STRIAE DISTENSAE AND MARFAN'S SYNDROME

TABLE 2 Jocidence of striae

Sisson (11)

Total

Female

Male

35.3%

71.6%

28.4%,

Subjects studied

Between 10 to 16 years of age

Shirai (10)

21.3%

6.6% Young girls and boys at puberty

Schultze (cited by Hauser (9))

36%

6%

Von Jasehke (cited by Hauser (9))

33%

Nulliparous Women

Shin and Ebeta (cited by Hauser (9))

25.5%

Nulliparous Women

Strakoseh (cited by Hauser (9))

73%

Young girls (striae of puberty)

Striae not related to pregnancy on the thighs

breakage and more or less complete disappearance from the area of the stria in later stages. Most authors who examined striae histologically described the peculiar parallel arrangement of collagen and elastic fibers in the upper

lar material. However, unlike lathyrism (22)

part of the dermis. They were interpreted as due to stretching and rearrangement of old fibers or to splitting of thicker fibers. Only Zieler (18) and lately the Epsteins (12) con-

terval between the second and third operation) in association with the stretching process which

there was considerable new formation of elastic fibers in the upper dermis. The small diameter and situation of these elastic fibers could be due

to their age (ie. formed in the 10 months inoriented both the elastic and collagen fibers parallel to the surface.

sidered the possibility of regeneration of elastic

tissue. Many of cur eases including normal persons, cases of the Marfan syndrome, and

SUMMARY

the Cushingoid boy, exhibited such a profusion

Cutaneous striae of five cases of the Marfan of elastic fibers in their stria that new forma- syndrome, three family members, eight normal tion was strongly suggested. This interpretation individuals, and one adolescent with Cushingoid had to remain in doubt until the stretched scar syndrome due to high steroid dosage were ex-

of W. K. was examined. Here, because the amined histologically and compared with a original fibers had been severed by the sur- widely distended scar following a surgically geon's knife, because of the considerable width

sutured wound of one patients with the Marfan of the scar, and because of the great quantity syndrome. In conformity with the view that all of elastic fibers present, their origin through striae are caused by glucosteroid excess, almost regeneration seems beyond reasonable doubt. identical histologic features were found in all Marfan's syndrome has been explained on 17 cases and were characterized by scar-like the basis of abiotrophy of elastic tissue. To find arrangement of parallel bundles of collagen in extensive regeneration of elastic fibers in the the upper part of the dermis associated with

skin of these patients may suggest that the numerous thin and straight or wavy elastic

basic defect resides in some other component fibers extending across the stria. A similar picof the connective tissue, perhaps the ground ture was encountered in the distended surgical substance as proposed by Bolande (5). Experimental lathyrism which appears to be a closely allied condition, is known to he char-

scar.

It is concluded that elastic fibers are regenerated in striae after their original disappear-

acterized by impaired skin wound healing ance and that there is no evidence for their (19—21). Like experimental lathyrism the ex- gradual elimination in old striae, as demoncised scar from W. K. contained an increase in strated in two patients aged 61 years. PAS positive and alcian blue stained intercelluRegeneration of elastic fibers in the skin of

292

TILE JOURNAL OF INVESTIGATIVE DERMATOLOGY

ci

a

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I Fic. 8. Elastic fibers in stria distensa, reproduced from a woodcut in Troisier and MSnStrier's article (15) with English translation of their legend. a. Epidermal surface of the stria; b. epidermis of the healthy skin; c. normal elastic net of the dermis; d. stretched-out elastic fibers and fibrils in the area of the stria; c. condensation of the elastic net at the borders of the stria due to retraction of broken fibers.

patients with Marfan's syndrome supports the 10. Shirai, V.: Studies on Striae Cutis of Puberty. Hiroshima J. Med. Sci., 8: 215, 1959. view that the basic defect in this condition is 11. Sisson, W. R.: Colored Striae in adolescent. not in the elastic tissue but elsewhere (possibly children. J. Pcdiat., 45: 520, 1954. in the ground substance). It also points to a 12. Epstein, N. N., Epstein. W. L. and Epstein, possibly significant difference from experimental lathyrism in animals. REFERENCES 1. MeKusick, V. A.: Heritable Disorders of Con-

J. H.: Atrophic Striae in patients with in— guinal intertrigo. Arch. Derm. (Chicago), 87: 450, 1963.

13. Chernosky, M. E. and Knox, J. M.: Atrophic Striae after occlusive corticosteroid therapy. Arch. Derm. (Chicago), 90: 15, 1964.

nective Tissue, 2nd ed., St. Louis, C. V. 14. Adam, J. E. and Craig, C.: Striae and their relation to topical steroid therapy. Canad. Mosby Co., 1960.

Med. Ass. J., 92: 289, 1965. 2. Sinclair, R. J. C., Kitcbin, A. H. and Turner, R. W. D.: The Marfan syndrome. Quart. J. 15. Troisier, E. and Ménétrier, P.: Histologie des Med., 29: 19, 1960. Vergetures. Ann. de Gynéc., Paris, 31: 206, 1889. 3. Loveman, A. B., Gordon, A. M. and Fliegelman, M. T.: Marfan's syndrome: some cu- 16. Barrett, J. S., Helwig, J., Kay, C. F. and Johnson, J.: Cine-aortographie evaluation of taneous aspects. Arch. Derm. (Chicago), 87: 428, 1963. aortie insufficiency: unsuspected idiopathic 4. McKusick, V. A.: The cardiovascular aspects aneurysmal dilatation of the aortic root as a of Marfan's syndrome: a heritable disorder possible indication of the Marfan syndrome. of connective tissue. Circulation, 11: 321, Ann. Intern. Med., 61: 1071, 1964. 1955. 17. Traisman, H. S. and Johnson, F. R.: Arachno5. Bolande, R. P.: The nature of the connective dactyly associated with aneurysm of the tissue abiotrophy in the Marfan syndrome. aorta. Amer. J. Dis. Child., 87: 156, 1954. Lab. Invest., 12: 1087, 1963. 18. Zieler, K.: Zur Pathogenese der Deb gstreifen 6. Kachele, G. E.: The enbryogenesis of ectoder Haut (Striae cutis distensae) MUnchen.

pialentis. An uncommon dermatological manifestation. Arch. Ophthal. (Chicago), 64: 135, 1960.

7. Keech, M. K., Wendt, V. E., Read, R. C., Bistue, A. R. and Bianchi, F. A.: Family

studies of the Marfan syndrome. Submitted for publication.

Med. Wschr., 52: 1764, 1905.

19. Ensinger, F. M. and Warner, E. D.: Wound healing in experimental lathyrism. Lab. Invest., 6: 251, 1957.

20. Krikos, G. A. and Orbison, J. L.: Effects of

beta-amino proprio-nitrile upon wound healing. A.M.A. Arch. Path., 65: 312, 1958. Symptomatic valvular myxomatous transfor- 21. Krikos, G. A. and Orbison, J. L.: Histoehemieal studies of skin wounds in rats receiving mation (the floppy valve syndrome) a posbeta-aminoproprionitrile. A.M .A. Arch. Path., sible forme fruste of Marfan's disease. Sub70: 188, 1960. mitted for publication. 9. Hauser, W.: in Gottron, H. A. and Schönfeld, 22. Walker, D. G.: Elastic fiber alterations in rats W.: Dermatologie und Venerologie, Vol. II. treated with Lathyrus Ordoratus. A.M.A. Part 2, p. 845, Stuttgart, C. T. Verlag, 1958. Arch. Path., 64: 434, 1957,

8. Read, R. C., Thal, A. P. and Wendt, V. E.:

THE JOURNAL OF INVESTIGATIVE DERMATOLOGY

94

linolenic acid extract. Arch. This pdf is a scanned copy UV of irradiated a printed document.

24. Wynn, C. H. and Iqbal, M.: Isolation of rat

skin lysosomes and a comparison with liver Path., 80: 91, 1965. and spleen lysosomes. Biochem. J., 98: lOP, 37. Nicolaides, N.: Lipids, membranes, and the 1966.

human epidermis, p. 511, The Epidermis

Eds., Montagna, W. and Lobitz, W. C. Acascopic localization of acid phosphatase in demic Press, New York. human epidermis. J. Invest. Derm., 46: 431, 38. Wills, E. D. and Wilkinson, A. E.: Release of 1966. enzymes from lysosomes by irradiation and 26. Rowden, C.: Ultrastructural studies of kerathe relation of lipid peroxide formation to tinized epithelia of the mouse. I. Combined enzyme release. Biochem. J., 99: 657, 1966. electron microscope and cytochemical study 39. Lane, N. I. and Novikoff, A. B.: Effects of of lysosomes in mouse epidermis and esoarginine deprivation, ultraviolet radiation and X-radiation on cultured KB cells. J. phageal epithelium. J. Invest. Derm., 49: 181, 25. Olson, R. L. and Nordquist, R. E.: Ultramicro-

No warranty is given about the accuracy of the copy.

Users should refer to the original published dermal cells. Nature, 216: 1031, 1967. version of1965. the material. vest. Derm., 45: 448, 28. Hall, J. H., Smith, J. G., Jr. and Burnett, S. 41. Daniels, F., Jr. and Johnson, B. E.: In prepa1967.

Cell Biol., 27: 603, 1965.

27. Prose, P. H., Sedlis, E. and Bigelow, M.: The 40. Fukuyama, K., Epstein, W. L. and Epstein, demonstration of lysosomes in the diseased J. H.: Effect of ultraviolet light on RNA skin of infants with infantile eczema. J. Inand protein synthesis in differentiated epi-

C.: The lysosome in contact dermatitis: A ration. histochemical study. J. Invest. Derm., 49: 42. Ito, M.: Histochemical investigations of Unna's oxygen and reduction areas by means of 590, 1967. 29. Pearse, A. C. E.: p. 882, Histochemistry Theoultraviolet irradiation, Studies on Melanin, retical and Applied, 2nd ed., Churchill, London, 1960.

30. Pearse, A. C. E.: p. 910, Histacheini.stry Thearetscal and Applied, 2nd ed., Churchill, London, 1960.

31. Daniels, F., Jr., Brophy, D. and Lobitz, W. C.: Histochemical responses of human skin fol-

lowing ultraviolet irradiation. J. Invest. Derm.,37: 351, 1961.

32. Bitensky, L.: The demonstration of lysosomes by the controlled temperature freezing section method. Quart. J. Micr. Sci., 103: 205, 1952.

33. Diengdoh, J. V.: The demonstration of lysosomes in mouse skin. Quart. J. Micr. Sci., 105: 73, 1964.

34. Jarret, A., Spearman, R. I. C. and Hardy, J. A.:

Tohoku, J. Exp. Med., 65: Supplement V, 10, 1957.

43. Bitcnsky, L.: Lysosomes in normal and pathological cells, pp. 362—375, Lysasames Eds., de Reuck, A. V. S. and Cameron, M. Churchill, London, 1953.

44. Janoff, A. and Zweifach, B. W.: Production of inflammatory changes in the microcirculation by cationic proteins extracted from lysosomes. J. Exp. Med., 120: 747, 1964.

45. Herion, J. C., Spitznagel, J. K., Walker, R. I. and Zeya, H. I.: Pyrogenicity of granulocyte lysosomes. Amer. J. Physiol., 211: 693, 1966.

46. Baden, H. P. and Pearlman, C.: The effect of ultraviolet light on protein and nucleic acid synthesis in the epidermis. J. Invest. Derm.,

Histochemistry of keratinization. Brit. J. 43: 71, 1964. Derm., 71: 277, 1959. 35. De Duve, C. and Wattiaux, R.: Functions of 47. Bullough, W. S. and Laurence, E. B.: Mitotic control by internal secretion: the role of lysosomes. Ann. Rev. Physiol., 28: 435, 1966. the chalone-adrenalin complex. Exp. Cell. 36. Waravdekar, V. S., Saclaw, L. D., Jones, W. A. and Kuhns, J. C.: Skin changes induced by

Res., 33: 176, 1964.