5
日皮会誌:88 (12), 863-867, 1978 (昭53) En lish- eaki 2B―OlE. Immunopathological reactions in pemphigus and differential diagnosis of this dis- ease G.F.Romanenko, L.V. Beletskaya and N.Y.Yezhov CMoscow Regional Res。 Inst。, Moscow, U.S.S.R.] This report summarizes the results of investiga- tion in tissue-bound immunoglobul ins and circulat- ing antibodies in bullous skin diseases. Forty seven (47) patients were observed, most of them with pemphigus vulgaris. Coons and Kaplan method was employed for direct immunofluorescen・ ce. Circulating antibodies to serum antigens of intercellular cement substance (ICS) of the epider- mis were determined by Weller and Coons' indirect immunofluorescence method. Monospecific lumi- nescent sera against different immunoglobul in classes labelled with fluorescein isotiocyanate (FITC) were genially placed at our disposal by Professor Chorzelsky and Professor Yablonska from the Warsaw Medical Academy. Besides that, we used clean antibodies the affected, but also in the evidently healthy skin close to the lesions. We carried out an experiment in the course of which we found out the nature of IgG accumulation. In patients with pemphigus cryostatic sections were washed with phosphate buffer pH 7.0-7.3for a peri- od from half an hour to 18hours at a room tern- perature. We deposited luminescent・ sera on the sections and we were convinced that fixed IgG could not be washed from intercellular areas and cells of the epidermis. Slide three (Ill) shows you the section of the tis- sue after washing with phosphate buffer. You see that immunoglobulines could not be washed from intercellular epidermic areas. So IgG is firmly bound with tissue structures and is included into the immune complex antigen-antibody with intercellu- lar cement substans (ICS) components. In pern- phigus erythematosus the type of fluorescence slightly differs from the fluorescence observed in pemphigus vulgaris. Session 2B―02E. Some problems of fragrance materi- als, Particularly regarding their chemical struc- ture and allergenicity。 M.Ishihara, Y. Osamura and M. Ito 〔Toho Univ., Tokyo, Japan〕 Currently there are over 6000 kinds of fragrance materials in use, including synthetic and isolated fragrances and essential oils, therefore the safety evaluation of each material is necessary in order to avoid the use of hazardous compounds. Various skin safety evaluation tests have been developed and one of the most potent tests used is the sensitization test using human and animal sub- iects R.I.F.M. has been evaluating the skin safety of each fragrance material, based on the results of Drs. Kligman and Epstein's human maximization tests,and has found about 30 sensitizing and about 10photoxic agents out of 650 fragrance materials. Another useful evaluation method is the closed patch tests,although the inferences of this method are influenced by factors such as quenching, heter- ogenicity, the vehicle used, and the frequency in which the chemicals are used in marketed products. One of the most interesting aspects of these stud- ies is the relationship between the chemical struc- ture of the materials and their degree of allergen- icity・ 1) Closed patch tests using cinnamic aldehyde, which was found to be a potent sensitizer, and six- teen related compounds were performed on patients with contact dermatitis and the results were com- pared. It was found that the following factors influenced the degree of allergic positive reactions. 勧叫 C) the chemical structure of the radical the presence of a double or single bond between the andβ position carbon atoms the position of an additional hydrocarbon group 2) Some patients who showed a positive reac- tion to eugenol or isoeugenol showed no reaction to

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日皮会誌:88 (12), 863-867, 1978 (昭53)

En lish- S eaki

 2B―OlE. Immunopathological reactions in

pemphigus and differential diagnosis of this dis-

ease

       G.F.Romanenko, L.V. Beletskaya and

       N.Y.Yezhov CMoscow Regional Res。

       Inst。,Moscow, U.S.S.R.]

 This report summarizes the results of investiga-

tion in tissue-bound immunoglobul ins and circulat-

ing antibodies in bullous skin diseases.

 Forty seven (47) patients were observed, most of

them with pemphigus vulgaris. Coons and Kaplan

method was employed for direct immunofluorescen・

ce. Circulating antibodies to serum antigens of

intercellular cement substance (ICS) of the epider-

mis were determined by Weller and Coons' indirect

immunofluorescence method. Monospecific lumi-

nescent sera against different immunoglobul in

classes labelled with fluorescein isotiocyanate

(FITC) were genially placed at our disposal by

Professor Chorzelsky and Professor Yablonska

from the Warsaw Medical Academy. Besides that,

we used clean antibodies the affected, but also in

the evidently healthy skin close to the lesions. We

carried out an experiment in the course of which

we found out the nature of IgG accumulation. In

patients with pemphigus cryostatic sections were

washed with phosphate buffer pH 7.0-7.3for a peri-

od from half an hour to 18hours at a room tern-

perature. We deposited luminescent・ sera on the

sections and we were convinced that fixed IgG

could not be washed from intercellular areas and

cells of the epidermis.

 Slide three (Ill) shows you the section of the tis-

sue after washing with phosphate buffer. You see

that immunoglobulines could not be washed from

intercellular epidermic areas. So IgG is firmly

bound with tissue structures and is included into the

immune complex antigen-antibody with intercellu-

lar cement substans (ICS) components. In pern-

phigus erythematosus the type of fluorescence

slightly differs from the fluorescence observed in

pemphigus vulgaris.

Session

 2B―02E. Some problems of fragrance materi-

als, Particularly regarding their chemical struc-

ture and allergenicity。

       M.Ishihara, Y. Osamura and M. Ito

       〔Toho Univ., Tokyo, Japan〕

 Currently there are over 6000 kinds of fragrance

materials in use, including synthetic and isolated

fragrances and essential oils, therefore the safety

evaluation of each material is necessary in order to

avoid the use of hazardous compounds.

 Various skin safety evaluation tests have been

developed and one of the most potent tests used is

the sensitization test using human and animal sub-

iects R.I.F.M. has been evaluating the skin safety of

each fragrance material, based on the results of

Drs. Kligman and Epstein's human maximization

tests,and has found about 30 sensitizing and about

10photoxic agents out of 650 fragrance materials.

 Another useful evaluation method is the closed

patch tests,although the inferences of this method

are influenced by factors such as quenching, heter-

ogenicity, the vehicle used, and the frequency in

which the chemicals are used in marketed products.

 One of the most interesting aspects of these stud-

ies is the relationship between the chemical struc-

ture of the materials and their degree of allergen-

icity・

 1) Closed patch tests using cinnamic aldehyde,

which was found to be a potent sensitizer, and six-

teen related compounds were performed on patients

with contact dermatitis and the results were com-

pared.

 It was found that the following factors influenced

the degree of allergic positive reactions.

勧叫

C)

the chemical structure of the radical

the presence of a double or single bond

between the a andβ position carbon

atoms

the position of an additional hydrocarbon

group

 2) Some patients who showed a positive reac-

tion to eugenol or isoeugenol showed no reaction to

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864 English-Splaking Session

methyl eugenol and methyl isoeugenol., therefore

the presence of the methyl group had an inhibiting

effect in these chemicals.

 3) Also it was found that patients who showed a

positive reaction to benzyl salicylate, usually did

not show a positive reaction to the other eleven

related compounds tested.

 2B一一03E. Ultrastructural and biochemical

analysis of the coated vesicles in melanogenesis

       M.Mojamdar, G. Imokawa and Y. Mishi-

       ma〔KobeUniv., Japan Kobe, Japan〕

 Since the activation and condensation of tyro-

sinase has been found to be carried out in the

tubular anastomosing and cysternal portion of the

GERL rather than the Golgi apparatus, the tyro-

sinase transfer system from GERL to premelano-

some remains now to be elucidated in the initial

melanogensis. Tyrosinase rich coated vesicles

(CV)ofGreene's malignant melanoma are isolated

by differential ultracentrifugation and DEAE se-

phadex coloumn chromatography. The biochemi-

cal studies of these isolated cv fraction has exhi-

bited a higher concentration of tyrosinase activity

than that of the premelanosome fraction. The ul-

trastructural analysis of the coated vesicles reveals

the subunits and possible sequential subunits.

Their distribution, inter-relations and biological

significance will be presented together with their

biochemical activities.

 2B―04E. The incidence of skin diseases in

Hong Kong

       ShingYiu Yip [Hong Kong]

 Hong Kong consists of a population of 4 1/2 mil-

110n inhabitants, the majority of which are Canton-

ese in origin. The incidence of skin diseases in this

city may therefore be representative of those of

South China, and would be of interest if statistics

from other parts of China are available and com-

pared.

 The statisticsof the Hong Kong Government and

those of a private clinic over a three year period

are presented.

 2B―05E. New attendants of the out-patient

Department of Dermatovenereology, Dr. Tjipto

Mangukusumo Teaching and General Hospital in

Jakarta, during the year 1976。

       A. Kosasih and R.W. Subaryo〔Univ. of

       Indonesia, Jakarta, Indonesia⊃

 During the year of 1976, a total 0f 13514 new

attendants of the outpatient clinic of Department of

Dermate-venereology, Dr. Tjipto Mangunkusumo

Hospital were reported, among which 344 patients

with venereal diseases. This is the biggest general

hospital in Jakarta, even in whole Indonesia, which

serves also as a teaching hospital 0f the Medical

Faculty, University of Indonesia. 170 different

skin diseases and 4 venereal ones were diagnosed

during the period. Detailed particulars concerning

age and sex distribution were presented and dis-

cussed for the 10 most common occuring skin dis-

eases and venereal diseases.

 211→6E. A specific substance in psoriatic scale

       Ruey-Yi Lin, Jau-Shyong Deng and

       Yau-Chin LU〔National Taiwan Univ.。

       Taipei, Taiwan〕

 In the past time, it has been shown there is a

substance present in psoriatic scale which is not

found in the scale from patients with other skin

diseases. Meanwhile several pieces of evidences

have been published in these years and the possible

autoimmune nature of this disease was stressed.

These initiate us to perform the present study to

investigate the possible specific substance and its

biological role in the pathogenesis of psoriasis.

 Scales from patients with active psoriatic lesion

are collected and subjected to the extraction with

phosphate buffer pH 7.4. The extract was purified

in G-75 gel filtration first. The second peak of

the eluate has migration inhibitory effect on leuco-

cytes from patients with psoriasis vulgaris, but has

not on that with psoriasis guttata or other derma-

toses. This second peak eluate was further puri-

fied with 7.5% acrylamide electrophoresis and the

third peak was collected. It was found the third

peak eluate has the molecular weight of about

30,000一一50,000 and electrophoretically located be-

tween alpha-1 antitrypsin and iceruloplasmin. This                 |  ,substance '■had jstimulatory effect on the DNA syn-

thesis of lymphocytes from patients with psoria-

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English-Splaking Session

sis vulgaris, but no effect on that of psoriasis gut-

tata or other skin disorders.

 2B―07E. Medicamentous toxidermatosis is a

serious problem of dermatology today and tomor-

row

       R.S.Babayants〔1st Moscow Med. Inst.。

       Moscow, U.S.S.R.〕

 Industrialization and urbanization, rapid develop-

ment of chemical industry, mass vaccination are

everyday polluting the eχternal environment-all

these materially change the reactivity of human or-

ganism, and thus facilitateitsfurther sensibilization.

 Under these circumstances, exclusively wide,

often insufficiently substantiated, very often irra-

tional, sometimes absurd the medical treatment

contributes to create general allergic background in

the civilized regions of our planet.

 Progress-process is not vis-versa : the therapeu-

tic substances of arsenic group are continuing to be

reinforced vigorously with rapid tempo. The side

effects produced by the administration or applica-

tion of therapeutic substances are an actual prob-

lem of medicine today. It can be assured that to-

morrow the actuality of problem will be more and

more.

 Complications due to drug administration or

application occur almost everyday. Provisionally

it can be divided into general reaction (anaphylac-

tic shock, bronchial asthma. hepatitis, serum sick-

ness, periarteritis nodularis etc.) and skin affection

(generally, allergic contact dermatitis and toxi-

dermatitis). Here, it takes into account that the so

called general complication often is not toxic, but

allergic character and frequently accompanied by

dermatol ogical symptomatology. However itisprob-

able, that there is no organ which can compete with

the skin for potential activity for sensibilization.

 The result of our observation for many years

(over 1200 patients), allow us to tell that there are

exclusively varied morphological manifestations of

drug effloresence.

 For right appraisal 0fpathogenic mechanism of

skin manifestation it is needed to differentiate al-

lergic contact dermatitis, occuring due to direct

contact of allergen with the skin, and the so called

toxidermatosis, developing due to internal adminis-

tration of drugs (here, it draws attention to the

865

term“Toxidermatosis"-which is obviously not

correct, because the disease is not due to toxicity,

but due to allergy)。

  Sometimes, due to morphological eruption toxi-

dermatosis is difficultto differentiate from allergic

contact dermatitis. However, inspite of its un-

differentiated various clinical types, it may even

develop in the form of urticaria, exanthematous

eruption, buUous element, exfoliative dermatitis,

aurpura, effloresence type of various erythema etc.

Sometimes medicamentous toχidermatosis takes

the form of definitedermatosis, not allergic genesis,

for example, lichen ruber planus.χNe have our

own observation not only for one time, patients

with typical clinical pictures of lichen ruber planus

after administration of antimalarial preparations of

quinoUnic origin. For the last few years, many

patients with severely skin affection, fever, lymph-

adenopathy, sharp decrease of general condition

(according to Lyell),have been seen. In this con-

dition fatal outcome is not unusual。

  Inaddition to anamnestic data, cutaneous aller-

gic tests are of great help to diagnose allergic con-

tact dermatitis. However in some patients of

medicamentous toxidermatosis, the skin test with

corresponding antigen gives negative result. The

causes can be concluded in different ways of intro-

ducing of antigen, and as such, many medicaments

have no definite-hapten. Allergic reaction in the

human organism takes place only after the interac・

tion between hapten and protein to form a very

complex compound. It is not wise to ignore the

incident of severe, sometimes of fatal allergic

reaction after applying of skin tests. Specially, it

happens in case of penicillin allergy。

  For these factors, it is necessary to intensify the

search for a simple, maximum safe method for the

diagnosis. The following tests may belong to this

category-the reaction of degranulation of baso-

phils, the tests of blasttransformation of lympho-

cytes and others。

  There are definite dissonance between pharmaco-

logical and clinicaleffectiveness of antihistamine in

the therapy of allergic dermatitis. This explains

the facts that antihistanine only obstracts the prod-

uct of histamine, which is not always the chief

mediator of allergicinvolvement of the skin. Sero-

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866 English-Splaking Session

tonin, bradykinin, acetylcholine and other biologi-

cal active substances predominate or play a signifi-

cant role.

 In severe cases of medicamentous toxidermatosis

it is necessary to prescribe as early as possible

corticosteroid in a sufficientdose. However, they

are always estimated empirically depending on the

condition of the patient, in spite of contraindica-

tion, also on the experience basis and on the reso-

lution of the physician-in-charge.

 Early prescription of a medium dose of corti-

costeroid on an average for 2-4 weeks time give the

therapeutic effect and there occur no serious com-

plication. But for the last few years many cases

with complete resistance to any kind of treatment,

which often end with fatal outcome, have been seen.

 This firmly confirms the hypothesis of our

knowledge regarding the medicamentous allergy・

However the optimism of further research is truly

based on the wise words of Gorasie “all,what is not

yet known, will be discovered some other time in

future".

 2B―08E. Axillary involvements in genital

Paget゛Sdisease

       Y.Miki, T. Kawatsu and T. Kawatsu

       [Ehime Univ., Japan]

 Simultaneous occurrences of axillary Paget's le-

sions in patients with genital Paget's disease have

not drawn too much attention. Only 4 such cases

have been reported in the literature and have been

designated as double or triple Paget's disease (Arch

Dermat, 104: 316, 1971).

 A new patient with such involvements will be

presented together with the clinical significance of

the axillary lesions.

 2B→9E. Experimental Behcet's disease and

ultrastructural χ-ray microanalysis of patholosfi-

cal tissues

       Y.Hori*, S. Miyazawa** and S. Nishiya-

       ma**〔・Univ.of Tokyo, *'Kitasato Univ.,

       Tokyo, Japan〕

 The higher level of serum copper, polychlori-

nated biphenyl and other organic chlorides in the

patients with Behcet's disease has been observed.

Epidemiologically, high incidence of Behget's dis・

ease has been reported in the countries where the

pesticides of organic chlorides, organic phospho-

rated compounds, arsenic copper have massively

been used。

 We have reported that significant amounts of

copper, chlorine and phosphorus were detected in

peripheral neutrophils, endothelial cells of dermal

capillaries, inflammatory cells in the skin lesions,

and epithelial cells of inflammatory hair folliclesof

the patients with Behget's disease. In 1974, Pawl-

ak reported that there were mucocutaneous in-

volv?mentsin the patients with chronic poisoning

of DDT。

 From the fact that mentioned above and that

those elements (organic chlorides, organic phospho-

rated compounds and copper) appear to be involved

in the pathogenesis of Behcet's disease, we admin-

istered organic chlorides (DDT and BHC), organic

phosphorated compound (Sumithion) and copper

powder containing feed to OMI miniature swine

and could induce oral aphthae, folliculitis,cutane-

ous and subcutaneous nodules, and genital ulcer in

the experimental animals。

 Histology of genital ulcer showed necrosis of

epidermis and dermis, dilatation and congestion of

blood vessels, hypertrophy of vascular walls, and

bleeding and infiltration of neutrophils in the

dermis. In the tissues of folliculitis,and cutaneous

and subcutaneous nodules, infiltration of neutro-

phils and histiocytes, bleeding, congestion of blood

vessels and necrosis of hair follicleswere observed。

 By ultrastructural x-ray microanalysis, highly

significant amounts of chlorine, sulfur, phosphorus

and copper were detected in peripheral neutrophils,

endothelial cells of blood vessels, and infiltrated

cellsin affected lesions obtained from experimental

animals. In peripheral neutrophils obtained from

the control miniature swine, only asmall amount of

chlorine was detected and no other elements were

detected。

 Conclusively, organic chlorine and/or organic

phosphorus may have an important role in patho-

genesis of Behcet's disease. χVeassume that these

elements induce the increase of Iysosomes in vas-

cular endothelial cells, hair follicles and neutro-

phils,and subsequently, give rise to hyperreactivity,

inflammation and necrosis of blood vessels and hair

follicles, resulting in bleeding, thrombophlebitis,

ulcer, necrosis of tissues and so on。

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English-Splaking Session

 2B lOE. Gamma-glutamyl transpeptidase ac-

tivity in human skin

      Young Pio Kim, Johng Bong Kahng

      〔Chon-Nam Univ., Korea〕

 Gamma-glutamyl transpeptidase (GGTP) activi-

ty was measured in the homogenate of penile fore-

skin, using y-glutamyl-p-nitroanilide, as a substr-

ate, and it was found that GGTP activity was

present in the epidermis and dermis, being more

active in the former.

 The optimum pH for the enzyme was 8.5-9.0 in

Tris buffer, which was similar to those of the rat

kidney and human serum enzymes. It was also

867

revealed that glycylglycine was the most effective

activator of the enzyme and some activation was

also observed in the presence of L-glutamine. 6ut

L-methionine, L-homoserine, L-glutamic acid, L-

arginine, L-aspartic acid, glycine and L-va!ine in-

hibited the activity, suggesting that these amino

acids do not act as acceptors of y-glutamyl moiety・

The enzyme was remarkably inhited by bromosul-

phalein, oxidized glutathione, and by L-serine in

the presence of borate, and the inhibitions were

more severe than is the case with the rat kidney

and human serum enzymes.