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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
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-
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-
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。
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.