R. Microcalcifications: 
historical review 
Microcalcifications in carcinoma of t.he breast were 
first described by Salomon in 1913 (83). Their irnpor­
t:ance for the recognition and early diagnosis of breast 
cancer was pointed out by Leborgne (65). Unfortu· 
nately, "malignant" and "benign" as charact~rizing 
terms for these calcifications are in many ways mis­
leading and have been used rather frequently in many 
publications in the last few years. Citoler and coworkers (22, 23) found only IS of 113 
breast carcinomas to contain so-called microcalcifica­
tions. Attempts to define what is typical for microcal­
cifications in malignant breast tumours have been 
made by Gershon-Cohen (42), Egan (31), Baclesse and 
Willemin (10), Hoeffken and Lanyi (SS), Lamarque 
(60), Barth (14) and others. In a recent survey, Lanyi 
(63) found that size, number, dispersion, opacity and 
contour of breast calcifications were not characteristic 
as signs of malignancy. Nevertheless, it is well known 
that mammographic microcalcifications very often call 
the attention of the examiner to tbe region where a 
carcinoma is growing. Gerlach and Thiemann ( 40) as well as Pape and 
Stegner (78) have performed electron microscopic 
studies of breast carcinomas . Because the female 
breast has the capacity to excrete calcium during lacta­
tion, the suggestion has been put forward that the 
breast also may have the capacity to accumulate cal­
cium particles intracellularly in cancer cells as a result 
of metabolic cell activities. Ahmed (2) supports the theory of active secretion of 
calcium because mammary epithelium is capable of 
concentrating calcium ions (87). In ultrastructural 
studies, Price, Hanrahan and Florida (79) reported 
that both electron diffraction and electron probe analy­
sis showed that the crystalline material is hydroxyapa ­
tite (Ca,P04)30H. Chemical analyses of some micro­
calcifications have been made by Moros, Pinter and 
Molnar (71), who found the following composition: 
calcium 25.4 %, magnesium 2.6 %, carbonate 5.8 o/o 
and carbon 13.8 %. Spectrophotometric examination s 
showed that the calcium and magnesium are predomi­
nantly bound to phosphate. Under certain assump­
tions, the following molecular composition has been 
suggested (cit. by Hoeffken and Lanyi) (55): 
Ca3(P0. )2 eaco, 
Mg3(PO•h · H20 
Albumin 55.0% 
9.7% 
13.3% 
22.0% 
For an understanding of the different aspects of 
degenerative changes of tissue, the mechanisms of 
autolysis are of fundamental importance. An excellent 
survey of the relevant literature has been made by van 
Lancker (62). A short recapitulation of selected as­
pects of autolysis follows: 
Tbe destruction of cellular component s, e.g., by 
hypoxia, is caused mainly by hydrolytic enzymes re­
leased from lysosomes (29, 92). Phosphate ions will be 
available from hydrolysis of ATP when living tissue is 
exposed to hypoxia (4, 56, 74), which further leads to 
autolytic changes (8, 26, 77). A decrease in oxygen 
supply to the tissue further leads to elevated concen­
trations of hydrogen ions, lactic acid, C02 and other 
metabolic products. The acids promote an increase of 
proteolyti c activities. The release of hydrolytic en­
zymes also alters membrane permeability , which in 
some way is coupled with a cellular inflow of ca++, 
Na• and water. In studying cellular death, Judah and Spector (58), 
McLean and coworkers (64) have found that the cou­
pling of oxidation to phosphorylation is completely 
blocked within 30 minutes after the onset of autolysis. Another early manifestation of injury was found to be 
a loss of A TP. Simultaneously , the degrading tissue 
becomes acid. Under these circumstances it is difficult 
to understand how calcium, which is known to preci­
pitate in alkaline environment s, can precipitate in acidic tissue. As we are here dealing with pathological 
precipitation of calcium, the only explanation is to 
assume somehow that local factors trigger the precipi­
tation of the salt. Exactly what precipitates calcium is 
not known. One proposal is that changes in the matrix 
lead to crystallization of the calcium salts because the 
altered matrix may act as a seed for the precipitation of 
hydroxyapatite. Irving, reviewing the mechanism 
of mineralization in cartilage and bone (57), believes 
that collagen is a focus for calcification. No calcifica­
tion, however, was seen in collagen in breast carcino­
mas in the studies of Ahmed (2). Anderson (5) has 
described extracel.lular vesicles as foci for calcification 
in bone mineralization . Acidic phospholip ids have also 
been considered as targets for mineralization of bone 
(88). Phospholipids and phosphoproteins , such as ca­
sein, are the most likely foci for calcifications in breast 
cancer, according to Ahmed (2). It may also be men­
tioned that acidic phospholipid s are probable target 
substances for calcifications of aortic valves (59). In all 
calcifications it therefore seems necessary to begin 
with some kind of matrix, which under certain circum­
stances serves as a target for mineralization . Recently Hoeffken and coworkers (55) have stated, 
"The pathogenesis of calcium deposition in the various 
forms of fibrocystic disease and breast carcinoma is 
still an enigma in spite of intensive investigations using 
electron microscopy, ordinary microscopy as well as 
chemical and radiological methods." S. Closed circuit production 
of microcalcifications 
Possibilities of locally precipitating calcium in tissue 
will be explored in this section by means of fluctuating 
physicochemical potentials ove.-a closed circuit. These 
experiment s, like the previous experiment s in this 
chapter, were conducted as driven systems and must 
therefore be compared with cocresponding reactions of 
endogenous self-driving systems in vivo over BCEC. A 
recapitulation of some aspects of tissue injury will 
facilitate understanding the ex:periments to follow. The experiments on autolysis of blood (Chapter VII) 
revealed that early in autolysis protons are produced . Later in autolysis protons are lost. The tissue then 
changes from being a proton donor into a proton 
acceptor. Flucruation of pH was found to be about one 
pH unit or approximately 60 millivolts. These changes 
are logical consequences, because A TP is not pro­
duced over the Krebs cycle when oxygen is lacking. Phosphate ions will then accumulate , because their 
recombination or dissipation (e.g., by diffusion ) is 
slower than corresponding proton reactions. A contri-
BCEC in cancer of the breast 257 a 
0 
b 
d J. --
Fig. XVI: 53. In vitro pro<klction of anodk matrices, which 
subsequen tly are utilized for creation of rnicrocaJcifications 
in breast fat. (a) Soft tissue radiograph prior to application of 
direct current. (b) After ZScoulombs at 10 V (26 days), small 
"dots" are seen at natural size in the lower part of the anodic 
field (arrow). (c) Photomicrograph (hacrnatoxylin-eosin ) of 
bution of phosphate to the development of an electro­
negative reaction of the autolyzing tissue is now of 
obvious interest. A drive toward electrochemical eqw­
librium between the electronegative necrotic tissue 
and the surrounding tissue can now take place in the 
form of an inflow of cations and an outflow of anions. The normal surrounding tissue can supply cations. Electrostatic attraction and repulsion of ions in such 
258 BCEC in cancer of the breast , 
, 
anodic membrane with many "dots" in the anodic fat. (d) 
Detail photomicrograph. These "dots" are bush-like struc­
tures which develop at lhe inner membrane surface of fat 
cells. The "dots" contain birefringent material. No calcium 
was shown with von Kossaor Alizarin stains. See further 
Fig. XVI: 54. 
events are not likely quantitative ly to be very efficient, 
because the transports have to take place over relative­
ly large distances. The transports can, on the other 
hand, take place with considerable efficiency over a 
BCEC, e.g., the VICC (vascular-interstitial closed cir­
cuit). Among the available inflowing cations, calcium and 
magnesium can be expected to combine with accumu-Fig. XVI: 54. Microcalcifi­
cations produced in vitro in 
breast fat by means of re­
ver>ed flow of direct cur­
rent. l!Jnidirectional electro­
phoresis of breast fat first 
led to "dotu~like structures 
in the anodic fat (as shown 
in Fig·. XVI: 53). The cur· 
rent was then reversed (I 0 
V, 8 coulombs, 7 days). The 
previously acid anodic tissue 
then became alkaline, lead­
ing to precipitation of cal­
cium in the "dots", which 
serve as matrices for the pre· 
cipitation. (a) Overview of 
calcif>ed matrices. (b) La.rger magnification 
(baematoxylin-eosin). (c-4) Specific staining of the 
calcium ions is positive with 
Alizarin. c 
lated phosphate ions in the necrotic tissue, resulting in 
precipitation of hydroxyapatite when the isoelectric 
region for this complex compound is reached. The 
accumulation of increasing amounts of calcium and 
magnesium phosphate will diminish the anionic re­
sources of the autolytic process, thereby leading to a 
tendency of the tissue to turn into an electropositive 
reaction. Thus, the total reaction attenuates and fluc­
ruates as it moves toward equilibrium. It is obvious that the Stepwise description of these 
events must in reality represent a continuous process. For example, a local "accumulation " of protons or 
phosphate ions must be regarded as an expression of 
their time-related statistical representation. The sum­
mation of the events of all reactants will in time pro­
duce a fluctuating electrochemical potential which in­
exorably moves toward equilibrium of the total reac­
tion (note further possible cascade reactions, page 
I 18). If these assumptions are correct, it should be possi· 
ble to produce calcifications in tissue by means of a 
fluctuating electric potential over a closed circuit 
which includes a section of tissue. In [be hypothetical model, calcium and magnesium 
phosphate have been anticipated to precipitate during 
an electronegative phase of the injured tissue. What 
happens during the initial, preceding electropositive 
phase? Perhaps the answer is found in the develop· 
ment of a suitable matrix for the precipitations , ac-cording to what has been assumed to be a necessary 
prerequisite in bone formation. In the electrophoretic experimentS with 10 volts and 
"unidirectional" current over human or dog fat tissue, 
no calcium precipitation was ever observed in histo· 
logical sections of the material (prepared with von 
Kossa or Alizarin stains, which are suitable for its 
detection). Fig. XVI: 53 a shows a specimen of fat 
before and Fig. XVI: 53b after delivery of 25 cou­
lombs at 10 V. The arrow points to small "dots" 
of increased x-ray anenuation in the lower part 
of the anodic area. Fig. XVI: 53c shows a fibrous 
membrane and "dots" in a histologic section of the 
anodic region. These dots consist of partially birefrin­
gent material arranged as "radiating structures" or 
"bushesn in fat cells. These "bushes" are intracellular · 
ly attached 10 the cell membranes and do not stain for 
calcium (Fig. XVI: 53 d). Because the "bushes" were 
produced in the acidic, anodic field it was thought that 
they could possibly represent local matrices and con­
stitute focal sites for later precipitation of calcium. The experiments were therefore continued with 
subsequent polarity of the electrodes reversed in ex­
periments where "dots" bad been identified radiogra­
phically in the anodic field. ln such experiments , focal 
precipitations of calcium were produced (Fig. XVI: 54). Fig. XVI: 54 a, b shows blue haematoxylin­
eosin staining of experimentally produced microcalcifi­
cations, while c and d show specific staining of the 
BCEC in cancer of the breast 259 calcium ion with Alizarin. The experimental calcifica­
tions show arrangements of the crystals similar to the 
matrix of the anodic "bushes". The microcalcifica­
tions also show some birefringence, which might be 
caused by the matrix. In these experiments the cal­
cium precipitation in the bush-like mauices could not 
be di:monsuated with von Kossa slllin. Alizarin spe­
cifically slllins the calcium ion, von Kossa the phos­
phate ion. The calcium precipitate is therefore possi­
bly present in the specimen as carbonate or oxalate but 
not as phosphate. Discussion 
The experimental, direct current production of micro­
calcifications in breast fat now raises the question of 
the mechanism of their devdopment at cenain sites 
rather than diffusely in the tissue. This fmding may 
depend on differing susceptibilities for injury of indi­
vidual cells and cell groups. The number of mauices 
in the anodic phase and the number of calcium-pre­
cipitations in the cathodic phase have been found to be 
greater close to the electrode than in the cenue of the 
specimens. The general viability of breast cancer cells, 
moreover, can be expected to be less than that of 
normal cells. When exposed to spontaneous local nu­
tritional disturbances, as by compression or impaired 
blood supply, focal sites of necrosis can be expected to 
develop. The local injury should then produce a spon­
lllneously fluctuating potential, leading to the produc­
tion of microcalcifications according to the mechanism 
which is oullined in principle above. These studies suppon the assumption that microcal­
cifications per se are not pathognomonic for malignan­
cy. Focal cellular necrosis, however, is more likely in a 
carcinoma than in normal tissue. Therefore, microcal­
cifications are often found in a neoplasm, but are diag­
nostically specific only as an indication of a preceding 
injury to tissue and not as an indication of cancer. As a 
matter of fact, all calcifications after injuries of tissue, 
e.g., calcium in the soft tissues of the shoulder, in 
cartilage, discs, tendons, local haematomas, and 
lymph nodes, are known to consist of hydroxyapatite . Accordingly, deposition of calcium in a previously 
injured tissue should not be considered as a disease per 
se but as part of the healing process, as is the develop­
ment of scar tissue. Calcinosis reparativa would there­
fore be a proper name for the development of such 
"pathological" calcifications. 260 BCEC in cancer of the breast T. The yellowish zone around 
breast carcinomas 
Pathologists have for years noticed that carcinomas of 
the breast often show a yellowish zone adjacent to the 
tumour (II, 32, 80, 89). Such a yellowish zone is seen around the breast 
carcinoma in Fig. XVI: 55 a. The adipose tissue within 
a dislllnce of I 0 to 15 mm from the edge of the tumour 
has a more orange colour than fat in the periphery of 
the specimen. Fig. XVI: 55 b shows a radiograph of 
the tumour. A photomicrograph (Fig. XVI: 55 d) of a 
histologic section demonstrates moderately extensive 
atrophy of fat cells at the rdge of the tumour. Infuua­
ting round cells are also present. Bahrmarm (II) found the yellow zone in 80% of 200 
breast cancers, but never around a fibroadenoma. In 
occasional cases a yellow zone was also seen in the 
breast around tuberculous , luetic and actinomycotic 
foci. Macroscopically the yellow zone is seen most easily 
in daylight. In artificial light the zone may show only a 
slightly different colour from that of ordinary fat. Metastatic carcinomas in fat tissue, whether from the 
breast or other primary sites, may also show a yellow 
zone. Examples of this phenomenon have been shown 
in the subcutis and adjacent to the stomach and colon 
(89, 32). AcC(!rding to Falk and Pfeifer (32), the yellow zone 
&Jld peritumoural atrophy of fat cells are caused by 
some kind of reaction of the stroma. As the fat cells get 
smaller, the more apparent is the yellowish zone. No 
satisfactoty explanation of the development of so­
called auophic fat cells and the yellowish zone has yet 
been presented. The experiments with in viuo electrophoresis of 
lanolin (Fig. XVI: 15) revealed that this material con­
tains bright yellow fat with. low attenuation and white 
fat with higher attenuation for x-rays. These fatty 
compounds separate easily from each other by elecuo­
phoresis. In vivo elecuophoresis in an anaesthetized dog with 
two platinum electrodes insened into breast fat 
showed relative movement of water to the electronega­
tive electrode and of fat from this electrode (Table 
XVI: 1). Small fat droplets were even seen between the 
"auophic" fat cells on the electronegative side and 
distended fat cells on the elecuopositive side. Simulta­
neously, the colour of the fat was greyish on the 
electropositive side and brownish on the electronega­
tive side. From the experiments on mesentery (Chap­
ter XIV) it was found that diapedetic and inuavascular 
thrombosed blood became dark brown after some 
time. The introduction cf electrodes percutaneously 
into breast fat in vivo in a dog was also associated with Fig. XVI: 55. The yellowish 
zone around a breast carcino­
ma. (a) Photognph of surgical 
specimen (centimetre scale). The yeUowisb woe is I 0 to IS 
mm broad and shows dark yeJ. low fat. Preopentive stereotuk 
needle biopsy caused two bleed­
ing points inside the tumour 
and two in !he yellow zone. (b) Mammogram, preopentive, 
shows radiating structures 
around !he tumour. (c) Hlectro­
phoresis of breast fat makes ca­
thodic fat rum successively yel­
low-<>range -brown while !he an­
odic fat inCTC&SCS in whiteness. (d) Histological section from 
edge of tbe cancer shows 
"atrophic, small fat cells .. adja· 
cent to the rumour, which is 
known to be accompanied by a 
yellowish woe. some small local bleedings , which could explain the 
brownish discolouration of the fat tissue in uhese ex· 
periments. In order to avoid any possible effect of local blood 
derived from injury, experiments were performed with 
fresh fat tissue obtained from human mastectomies. This fat tissue was treated with electrophoresis as 
shown in Fig. XVI: 17. The result of the treatment 
was a red-yellow zone, which can be seen clooe to the 
electrOnegative electrode (Fig. XVI: 55 c). This zone 
initially was light yellow. As the electrophoresis pro­
ceeded, the zone became increasingly red-yellow to 
brown-yellow. In one experiment the fat material was 
illuminated with fluorescent light. The cathodic fat then showed light yellow fluorescence. The anodic 
white fat did not fluorescence but appeared white­
yellow. The development of small, atrophic fat cells adja­
cent to a carcinoma of the breast, as seen in Fig. XVI: 55d, is usually associated with development of 
yellow-red discolourati on of :rtdjacent fat. As was dis· 
cussed in connection with the experiment shown in 
Fig. XVI: 17, some fat is also mobilized adjacent to the 
anode and is very likely influenced by anodic acidity. This fat meets the electronegative fat from the cathod­
ic field close to the anode. It now appears understand­
able that the atrophic fat cells typical of the anodic 
type are surrounded by a yellow zone of cathodic fat. BCEC in cancer of the breast 261 Babrmann (11, 12) made the observation that the 
more atrophic the fat cells appear at the edge of the 
tumour, then the more dark yellow appears the yellow 
zone. He also observed that the yellow zone can best 
be seen in daylight or photographed with a blue filter. S!imegi 1 (89) found that the yellow zone fluoresces 
yellow in fluorescing light. A light green-blue chloro­
phyll-alcohol solution gives the zone a red fluorescence 
in blue fluorescent light. It is evident that the present tests of the yellowish 
material must be extended for conclusive identifica­
tion. At this point in our understanding, the yellowish 
zone around a breast carcinoma appears to be a result 
of electrophoretic transports of fat material within a 
BCEC. U. Electrophoretic 
accumulation of lymphocyte s 
around and inside breast 
carcmomas 
Lymphocytes are often found inside a breast carcino­
ma and in the tissues surrounding the mmour (Fig. XVI: 56). Around the tumour they are usually increas­
ingly concentrated toward its surface. The presence of 
lymphocytes in cancers has been thought to be part of 
an immunologic reaction (24). Sometimes, fewer lym­
phocytes are present in the tumour than adjacent to its 
surface. It has been assumed that in such cases more 
lymphocytes are destroyed inside than outside the tu­
mour due to a particularly strong immunologic reac­
tion inside the mmour. The mechanism responsible for the accumulation of 
white blood cells around tumours, different kinds of 
infectious tissue lesions and in immunologi c reactions 
is still unknown (62). The usual explanations are often 
restricted to discussions based on the concept of "che­
motaxis", which was treated in Chapter XIV, Sections 
J and K, in connection with anodic accumulation of 
granulocytes. Because chemotaxis is regularly included 
in discussions of lymphocytic accumulations, this 
mechanism will also be considered in this connection. Chemotaxis is assumed to be a result of a variety of 
not very well deftned chemicals present in bacteria and 
in inflammatory exudates ( 17, 50, 51). In acute inflam­
mation, polymorphonuclear cells accumulate. In 
chronic inflammation such as tuberculosis, monocytes 
1 The author is greatly obliged to Prof. I. Sfrmegi, who supe:nised 
these tests and supplied the author with valuable information from 
his researcb on pathologic tissue components around tumours in fat 
tissue. 262 BCEC in cancer of the breast are common. Positive and negative chemotaxis are 
thought to exist. In practice, only attraction has been 
observed. "Positive chemotaxis" is induced by many bacteria, 
including Strepwcoccus pyogen.es, Micrococcus pyognw, 
Dipk>coccus pnevmonitu, Escherichia coli, Bacillu.s antra­
cis, Salmanella typhi and Corynebacterivm dipluheriat. Leukocytic migration, on the other hand, is inhibited 
by certain toxins, e.g., from Clostridium utani. Using exudates from inflamed tissue, Menkin (70) 
claimed to have prepared a compound he called leuco­
taxine which could attract leukocytes. On the basis of 
photographic studies of migrating leukocytes, Harris 
(50) concluded that no product prepared from inflam­
matory exudates exhibited such properties. Harris (50) 
suggested instead that polymorphonuclear migrations 
result from the random distribution of polymorpho­
nuclear cells passing by diapedesis through the walls of 
the capillaries into the interstitial spaces. This explanation of Harris may, in the author's 
opinion, be partly but not entirely accepted. The local 
accumulation of leukocytes in inflammation is often 
intense. A random distribution by local diapedesis 
should not selectively affect the aecumulation of white 
blood cells in the diseased area in relation to other 
blood cells, e.g., erythrocytes. Additional mechanisms 
are probably also responsible for the selective accumu­
lation (43). Boyden (17) assumes that leukocytes pos­
sess the ability to "recognize" certain foreign materials. The studies of "humoural leukotaxic factors" have 
largely been carried out with bacteria, viruses and 
inflammatory exudates (I, 69). Nevertheless, leuko­
cytes migrate also in aseptic necrosis (61). This obser­
vation indicates that neither an infectious agent nor its 
toxic products are necessary for accumulation of leu­
kocytes (18). Table XV1:4 
Chemotactic substances 
"l..eurotax.ine " from exudate, 
probably a polypeptide 
Calcium 
Complement factor in serum 
An y-globulin factor of 
unknown nature 
Polysaccharide from 
Diplococcus pneumoniae 
Nc:crotic tissue 
Colloidin panicles 
Cellulose particles 
incubated with se:rum 
Precursors of chemotactic agents 
in plasma with activators 
in liver, hean muscle 
Kallikrein Chemotactic inhibitors 
Toxins from bacteria 
A serum /l·globulin 
An a-globulin Fig. XVI: 56. Histologic 
sections through the edge 
of a mammary carcinoma. (a) Overview, atrophic fat 
cells (middle left of Fig. a) 
are adjacent to the carcino-
rna. Many lymphocytes are 
infUtnting the tumour tis-
sue. (b) Lymphocytes are 
also found in the fat tissue 
surrounding rhe [Umour. Active participation of leukocytes in diapedetic ex­
travasation must also be discussed (44). The sizes of 
leukocytes are variable. In phagocytosis they change 
their shape by producing pseudopods. The shapes of 
the leukocytes also vary when they migrate through 
narrow spaces in capillary walls. The testing of chemotactic effects of different mate­
rials from bacteria and exudates (17) has led to the 
description of a wide range of chemotactic com­
pounds, some of which are collected from van Lancker 
(62) in Table XVI: 4. As can be seen from this table, 
no common or specific chemical factor is evident 
among these substances. Polymorphonuclear cells are in general assumed to 
21-824586 NonlcMrriim ' .. 
. II ., 
'• ~ ,. jll ~ • 
\ • 
it 
I 
i 
• • \ ' \." • • \ • 
• 
be anracted in acute conditions by bacteria, viruses 
and their exudates, different serum compounds and 
tissue factors. No specific factor is known to accumu­
late the white blood cells. Theories have also proposed 
that the chemotact ic substances are released by the 
leukocytes themselves. Selective chemical agents or 
variations of tissue pH have also been thought to 
produce the accumulation of different types of white 
blood cells (72). Harris (S I) believes that the polymorphonuclear 
cells and monocytes leave the blood stream by dia­
pedesis at the same time. Due to the longer survival 
time of monocytes, the relative number of monocytes 
increases in time. This analysis could then explain the 
BCEC in cancer of the breast 263 relative increase in number of monocytes in chronic 
inflammation. It is also known that cells other than 
leukocytes show "chemotaxis". For example, bacteria 
are attracted or repelled by a variety of organic and 
inorganic compounds. On the whole, chemotaxis is a confusing and far 
from clear[y deftned concept. In the present work, different aspects and examples 
have been presented of electrophoresis and electroos­
motic transports around different tissue lesions. Non­
specific injury of tissue and the existence of the pro­
posed VICC must therefore be considered in attempt­
ing to explain local accumulation of white blood cells 
inside and around an injured tissue. A local injury will 
create an electrochemical potential in relation to the 
surrounding tissues. This potential difference will con­
stitute an energy source for transports regardless of the 
source of the injury, e.g., bacteria, viruses, aseptic 
necrosis, local bleeding in a rumour or any other cause 
of degradation of tissue. In the studies here reported of in vivo electrophore­
sis (Chapter XN) it was found that diapedesis is in­
duced in capilla.ries on the electropositive side of an 
electric field and that polymorphonuclear cells accu­
mulate massively in the vessels and in the interstitial 
tissue around the electropositive electrode. When a breast carcinoma develops a local injury, 
i.e., from necrosis or bleeding, electronegative white 
blood cells should be attracted to the tumour during 
its phase of electropositive polarization as an electro­
phoretic process within the VICC. This explanation of 
the acute accumulation ofleukocytes is based on sever­
al known or assumed prerequisites : 
I) It is known that certain parts of cells carry posi­
tively and negatively charged groups. Lymphocytes as 
well as granulocytes carry a surplus of electronegative 
fixed charges on their surfaces (13, 39, 53, 54, 73, 84, 
85, 93, 94, 95). Their negative zeta potentials have a 
magnitude of 15 to 20 m V at physiological pH and in 
0.145 molar NaCI solution. Lymphocytes and platelets 
are charged mainly by phosphatides of the cephalin 
type, polymorphonuclear leukocytes mainly by car­
boxyl groups. The electronegative surface charge of 
erythrocytes is determined by phosphate groups. 2) Charged particles, e.g., leukocytes, will move in a 
closed electric circuit to a region of polarity opposite to 
their charge. Leukocytes therefore move to the anode 
in an electrophoretic chamber. 3) In spite of their relatively large size (diameter 
6-20 JJm), leukocytes are capable of passing by diape­
desis through capillary membranes. 4) In vivo analogues to the circuitry of an electro­
phoretic chamber are here assumed to exist as vascu­
lar-interstitial closed circuits (VICC) (Chapter XII). 5) After any kind of injury to a tissue, an electrcr 
physico-chemical potential develops in relation to sur-
264 BC'EC in cancer of the breast rounding normal tissue. The electric component of the 
physicochemical potential then delivers the driving 
e.nergy for transports over BCEC channels. Intravascular and intel'Stitial accumulation of leuko­
cytes was produced in an in vivo experimental model 
of spontaneous accumulation of leukocytes over a 
BCEC (Fig. XIV: 15). In such experiments, electrodes 
leaned very gently against normal mesentery of a living 
dog. One to five volts were applied between the anodic 
mesentery electrode and the reference electrode in the 
aorta or inferior vena cava. The electrode potential 
varied between 1-5 volts, giving rise to a current of a 
few microamperes. Massive accumulation of granulo­
cytes could be obtained in vessels already at 0.002 
coulombs of current. Scrcallcd margination of leuko­
cytes was observed in vessels. Leukocytes then accu­
mulated in great quantity around the anode. These 
experiments indicate that previous tissue injury is not 
obligatory for the anodic accumulation of leukocytes. The behaviour of leukocytes in such experiments is 
most easily explained as a result of electrophoretic 
transport over a closed circuit, driven by an. external 
source of electrical power. 6) Previous discussions in the literature of chemo­
tactic attraction of leukocytes have overlooked the 
possibility of electrochemical injury potentials, wheth­
er spontaneously or externally created. As far as the 
author can ascertain, each of the factors for which a 
chemotactic effect bas been reported is capable of 
polarizing tissue. If this view is accepted, then any 
agent which is capable of driving electropositive polariza­
tion within a BCEC may electrophoreti cal~ attractleu)u>­
cytes. A driving electronegative polarization may, huwev­
er, also cause electronegative leukocytes to became accumu­
lated according 10 the mechanism of flnw and ruld inter­
ference already described in Chapter XIV. Many other 
factors arc, however, also likely to be involved in the 
selective, electrophoretic accumulation of charged cells 
or compounds. Thus, the sizes and shapes of cells as 
well as the steric locations and magnitudes of surface 
charges should influence the transport s. Furthermore , 
different matrix factors as well as steepness and magni­
tude of the superimposed electric field are evidently of 
importance in the presented explanation of selective 
electric accumulation of cells in tissue. Certain partial 
mechanisms in the transport of cells may even be 
explained as, e.g., the formation of pseudopods of the 
granulocytes. These pseudopods make it possible for 
the white blood cells to "flow" through narrow pores in 
the capillary membranes. The mechanism we then 
have in mind has its correspondence in electroosmosis 
Type I (Chapter IX). The principle of electrophoretic 
transport is capable of explaining the accumulation of 
leukocytes in different kinds of tissue injury. A corre­
sponding mechanism may also explain the accumula­
tion in tissue of lymphocytes , because lymphocytes also carry a surplus of electronegati ve charges on their 
surfaces. How is the presence of lymphocytes explained in 
chronic inflammation and granulocytes in acute in­
flammation? Once leukocytes have entered the interstitial tissue 
by diapedesis through capillaries, they are trapped and 
unable 10 find the same way back 10 the blood stream 
when the electric polarity of the lesion is subsequently 
reversed. Some of them may, however, reenter the 
blood stream over interstitial lymphatic channels. A 
gradual decrease of the granulocyte/lymphocyte ratio 
may nevertheless preliminarily be explained by the 
mechanism proposed by Harris: the granulocytes dis­
appear more rapidly than lymphocytes (i.e., by differ­
ent life span), which therefore gradually leads to local 
lymphocytosis. It was also shown experimentally in 
Chapter XIV, when dog lung tissue was electrically 
polarized in vivo by an external power source between 
two platinum electrodes, that three weeks after the 
treatment lymphocytes and not granulocytes were ac­
cumulated around the electrodes. The common histo­
logic fmding of lymphocytes inside and outside resect­
ed breast rumours should be interpreted only to mean 
that these tumours are usually resected in a "late" 
phase rather than in an acute phase of a degrading 
process of the tumour. V. Conclusions 
The structural modifications of tissue around focal 
lung lesions, which are called the corona scruaures, can 
also be identified around breast cancers. The corona 
structures in the breast include the radiolucent "A" 
zone, the radiopaque "B" zone, which may appear as a 
local skin thickening, the small arches forming an 
arcade, the circularly arranged structures and the radi­
ating structures, extending from the tumour surface 
far our into surrounding breast tissue. The biokinetic mechanisms behind the development 
of these Structures, as well as the development of fat 
atrophy, microcalciflcations, the yellow fat zone around 
certain cancers in fat tissue and the accumulation of 
leukocytes can be traced back to a common process of 
spontaneous "healing". This tendency of "healing" is 
evidently insufficient for the development of a "true 
healing" of a carcinoma. In previous chapters of this 
book, the mechanism for the actual, insufficient pro­
cessof"healing" has been identified. This is based on a 
BCEC system (which contains biologically closed elcc­
rric circuirs). It represents a previously undescribed 
mechanism for selective transport of material in tissue, 
closely integrated with the mechanical, nonselective 
systems of transport, e.g., the circulation of blood. The 
specific BCEC of particular interest in this connection is the vascular-interstitial closed elecrric circuit 
(VICC). This consists of vessels, which were found to 
act as electrically insulared, conducting "cables" as the 
vessel walls have a high electric resistivity around the 
conducting blood plasma. The plasma has an elecrrk 
connection over the capillary membranes with the in­
terstitial fluid, which, like plasma is a good conducting 
medium. These two "electrical branches" form a 
closed circuit which is driven by the electromotive 
force between a local injury (i.e., necrosis or bleeding 
in a tumour) and the surrounding noninjured tissue 
around the tumour. The injury is a catabolic energy­
liberating process, which presents a fluctuating elec­
tric injury potential. This potential leads to ebb and 
flow of transports in the circuit, resulting in modifica­
tions of tissue which we can identify radiographically 
as the corona structures and histologically as several 
modifications in the tissues and cells. As in the lung, it was also found that breast tumours 
sometimes present an electric gradient of potential in 
relation to surroundi ng tissue. This occurs when the 
tumours contain regions of degradation. The magni· 
tude of electric potential varies with time because it 
represents a spontaneous process which, like all such 
processes, proceeds in a fluctuating, auenuating fash­
ion toward equilibrium. The duration of such fluctu­
ations over days, weeks or months makes transports 
possible of considerable amounrs of material, even 
with small gradients of potential. None of the actual structural modifications in breast 
cancer is pathognomonic for malignancy. However, 
the coincidence of necrosis and malignancy is high. Therefore the structural modifications do often devel­
op in breast cancer. The general biokinetic mechanisms in the develop­
ment of corona structures in lung cancer are described 
in preceding chapters and applied to the particular 
conditions of breast cancer in this chapter. To deepen 
understanding of the actual problems, the reader is 
advised also to study the content of the preceding 
chapters. Thereby insights will be obtained, e.g., in the 
constructio n and mechanism of activation of actual 
BCEC systems, and the mechanisms of transport of 
water in the circuit which produce the characteristic 
perifocal differences of attenuation for x·rays. So-called skin thickening is explained as a local 
electroosmotic transport of water to the retracted skin. The retraction, on the other hand, is produced by 
electroosmotic local dehydration of hygroscopic ele­
ments in fibrous, radiating structures. Besides water, fat is also transported in the activated 
BCEC system, producing both atrophy of fat cells 
adjacent to breast cancer and also the well-known red­
yellow fat zone which is often seen around malignan­
cies developing in fat tissue. By electrophoreti c transports, an interphase is 
BCEC in cancer of the breast 265 formed between a hydropenic and a hydropic zone, 
which leads to the development of arches and arcades 
and circularly arranged structures around breast can­
cers. Fibrous structures such as membranes can be pro­
duced by the influence of direct current. The endo­
genous development of fibrous, radiating structures 
can be simulated experimentall y by electrodes, provid­
ed with small protrusions, which cause electrical edge 
enhancement. In this way cathodic fibrous tissue was 
produced without the presence of fibroblasts . In the 
anodic fibrou s tissue "fibroblasts" were present. Their 
distribution in the fibrous tissue rajses the question 
that they may not be necessary for the production of 
fibrous tissue. In anodic fibrous tissue, channels also develop with 
an appearance of primitive galactophores and "blood 
vessels". In cathodic fibrous tissue, channels develop, 
lined with a birefringent membrane. These channels 
may also lead to the development of pathological 
vessels. The transformation of tissue structures and 
cells is distinctly different in t.he cathodic and anodic 
fields. Such transformation wu produced by leading a 
weak current of a few microamperes over the tissue 
over a period of two to five weeks. In different ways 
evidenoe has been presented th;:at the development of 
primitive galactophores can be induced in "dead" 
pieces of breast fat tissue by direct current within the 
anodic field. Electrophoresis of fat samples is possible 
prolonged over weeks without bacterial decomposition 
of the tissue specimens. Breast fat tissue subjected to direct current devel­
ops small "bushes" of birefringent material in the 
anodic field. By simulating the endogenous jluetuating 
potential, histologically typical microcalcilications can 
be produced. An important factor in the histological appearance 
of breast cancer is the accumulation of lymphocy tes 
inside and around the tumours. In Chapter XIV (pp. 189-191), current views on accumulation of granulo­
cytes as a result of "chemotaxis" are discussed. ln the 
view of the author, the anodic phase of a lesion causes 
granulOcytes to be attracted electrophoretically to it 
over the vascular-interstitial closed circuit (VICC). This is possible because leukocytes are provided with a 
net surplus of electronega tive charge on their surfaces. Certain components in such a mechanism, e.g., mag­
nitude and steric arrangement of charges as well as 
field strengths and matrix characteristi cs, have to be 
considered for futher understanding of this theory of 
•ccumuloti on of granulocytes . By opplying thi& basic 
principle, an explanation for accumulati on of lympho­
cytes in breast cancer is also proposed . 266 BCEC in cancer of the breast References 
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BCEC for treatment of cancer 
In preceding chapters the reader's attention has been 
focused on the existence of biologically closed electric 
circuits (BCEC), and the importance of such systems 
for tissue function, structural development and heal· 
ing processes. Spontaneous polarization within differ­
ent BCEC systems over vascular, interstitial, ductal or 
other conducting pathways are involved in these reac­
tions. In this chapter we will manipulate the systems 
in attempts to improve healing. This is possible be· 
cause the circuits can be activated in many ways, e.g., 
by local supply of chemical agents, heat, pressure or 
electric energy. These studies will be performed in two 
ways. In one series local tissue injury will be produced 
in tumours by diathermia in order to induce spontane­
ous healing. In a second series electric energy will be 
delivered to the tumour and its surroundings as direct 
current over electrodes. Before the theoretical back­
ground and actiUal treatment s are described , previous 
attempts to use electric current for treatment of tissue 
will be briefly surveyed. In 1895 the electrophysiologist Golsinger (24) placed 
"unipolar" electrodes in the brains of dogs and pro­
duced focal injuries of tissue. A large "indifferent" 
electrode was placed on the abdomen of the animal, 
and 20 to 40 mA current were used. Eight coulombs 
gave a lesion the size of a pinhead and 36 coulombs a 
lesion as "large as a cherry". Similar experiments were performed shortly there­
after by Sellier and Verger (60, 61). Using bipolar 
electrodes , they applied 8, 10 and 12 rnA for 7 to 10 
minutes and produced spherical lesions "the size of a 
pea". Horsley and Clarke in 1908 (31) studied the tissue 
effects of direct current in the brain, using bipolar 
electrodes . They stated that "for"' unit of time, e.g., 
I minute, there will be about a I mm breadth of 
destruction for each unit of current employed ". Hetherington and Ranson (30) produced lesions of 
about I mm diameter in the brain with 2 rnA during 20 
seconds and Krieg (35) 1.5 mm lesions in the brain 
with 2 rnA for 15 seconds. Carpenter, Whittier and 
Meuler (13) used "unipolar" anodic electrodes and 
produced I mm lesions in the brain with 5 rnA for 15 
seconds. Hendley and Hodes (29) produced 2 mm 
lesions with 3 rnA for 20 seconds in the brain. Anand, 
Dua and Schoenberg (2) made lesions of I to I. 5 mm 
diameter with 3 mA during 30 seconds in cat and 
monkey brains. Platinum electrodes, which resist electrolytic de­
struction, were found by Louchs, et al. (38), to be 
superior to other metal electrodes in experiments of 
this kind. Iontophoresis is another use of direct current in 
biology. An ionic compound is applied, often through 
Treatment of cancer 269 a micropipette, against neurons or other drug-sensitive 
tissues, by means of a pulse of direct current. It has 
already been shown (pp. 191-192) that it is not always 
possible in iontophoresis in vivo to predict where an 
ionic compound will be deposited simply on the basis 
of its polarity and the polarity of the electric field. Electrode reactions may also destroy or modify the 
iontophoretic agent. Nevertheless, ionic compounds 
can in principle be directed electrically to a tissue for 
therapeut ic purposes. Remarkably enough, this thera­
peutic possibility has been neglected in practical medi­
cine. Tissue and cells may also be considerably 
changed by an electric field or by the flow of electric 
current, as has been illustrated with blood and fat 
tissue (Chapters XIV and XVI). In 1920 Ingvar (33) briefly described reactions of 
cells to galvanic current in tissue cultures. He applied 
a current of 2-4 billionths of an ampere and observed a 
directing influence of the applied electric forces on 
cells. Induction of a callus by means of an electret has 
been reported by Fukada, Takamatsu and Yasuda 
(22). Phillips ( 48) has made use of alternating and 
direct currents to obtain vascular thrombosi s for con­
trol of gastrointestina l haemorrhage and for the possi­
bility of closing arteriovenous shunts. Yoneda, Mat­
suda and Shimizu (81) have produced electrothrombo ­
sis of arteriovenous malformations. After the discovery of the piezoelectric polarization 
of bone subjected to load (5, 10, 21, 89, 99), many 
experimental and clinical attempts have been made 10 
enhance healing of injured bone by the usc of alternat­
ing (73, 74) and direct current (3, 6, 14, 25, 32, 37, 
80). Formation of bone around the cathode and de­
struction of bone around the anode were described 
after 10 to 50 microamperes between two electrodes in 
experiments by Andrews and Friedenberger (3) and by 
Gohre (25). Clinical experiments to improve bone 
healing have yielded both encouraging and less benefi­
cial results (37). A conference on electrically mediated mechanisms 
of growth in living systems, published in the Annals of 
the New York Academy of Sciences (37), included 
recent experimental and clinical work focused particu­
larly on the enhancement of bone healing by electric 
stimulation. From these studies it is evident that elec­
tric currents can support bone healing. Various results 
have been reported with the use of both alternating 
and direct currents and different positions of the elec­
trodes. According to the way many of these experi­
ments have been arranged, it seems possible that a 
beneficial effect may have been obtained in some cases 
simply as a reaction to a new injury. Traditional surgi­
cal management of a poorly healing fracture is to revise 
the injury in order to let the healing process start 
anew. A true enhancement of a healing process should 
270 Treatment of cancer be adapted as closely as possible to physiological heal­
ing. Unfortunately , we still do not have sufficient basic 
knowledge about these processes. Some of the most urgent information to be collected 
should, in the author's view, include careful mapping 
in vivo of the spotltaneous fluctuatiorJS of the electric 
pomuial in physiologi cal healing. The normal fluctu­
ations toward the "intermediate equilibrium" which 
we call healing could then possibly be used, with a 
suitably modulated current-time integral, to decrease 
the time of healing. Such a tailored driving force over 
electrod<'S between a site of injury and, for instance, a 
supplying vessel should then, of course, be applied 
with the site of injury initially electropositive . A suit­
able fluctuation of polarity of the external electric 
power source should then follow. In this view, a suffi­
cient supply of suitable materials of varying kinds, at 
varying phases of the treatment , also must be consid­
ered before healing can be enhanced as a simulation of 
physiological events. The effect of direct current on Jensen sarcomas in 
rats was studied by Reis and Henninger (51) already in 
1953. A platinum anode was placed in the tumour and 
the cathode on the leg of the animal. 18-20 mA at 
60-70 V were delivered over I S-20 minutes. After 
8-10 treatments the tumours showed regression . The 
beneficial effects were ascribed to a deelectronat ion by 
anodic Ol<idation (SO). This technique was also used in 
one patient with vulvar cancer (51). Local heating of pulmonary metastases with diather­
mia was used in SO patients, reported previously by 
the present author (39, 40), who later also reported on 
the first treatment s of lung rumours with direct cur­
rent (41). Gardner, et al. (23), studied tumour cells inj~ted 
into rats during application of a DC potential between 
two electrodes in the liver. They found that tumour 
cells were attracted around the anode. No tumour cells 
were observed around the cathode. Bellamy, Hinsull, Watson and Blanche (7) inoculat­
ed rats with carcinoma cells (Walker 256) in a plati­
num loop connected to a platinum disc by a length of 
silicon rubber. Tumour growth was inhibited, a result 
interpreted as indicating the implant changed the mi­
croenvironment. The presence of a charged foreign 
body such as metal, which has its own electric poten­
tial, obviously can change the distribution of charges 
close to the metal surface. The potential differences in 
these experiments were only a few m V. Similar experi­
mentS of small quantities of direct current inhibiting 
tumour growth have also been performed by Schanble, 
Mutaz and Gallick (59). The possibility of controlling 
malignant tumour growth by direct current has also 
been mentioned by Srinivasan , et al. (66). In patients, direct current has also been used to 
coagulate blood in vessels leading to a tumour. This Vol..,. em' 
100 
7S 
50 
25 
... 1-------:1 
~:t:::::;;;zi:_J_~--L~ 
0 2 3 4 5 6cm 
Diameter 
Fig. XVII: I. \'olume of sphericai1Urnour increases expon­
<'ntially with the diam<'ter . This relationship must be oonsid­
erod in determinin g dose oftreaunen1. technique is based on the observation of Sawyer and 
Pate (58) that the intima of vessels is electronega tive in 
relation to the outer wall. When the vessel wall is 
locally injured, the intimal polarity is locally reversed, 
inducing an electrostatic apposition of electronegative 
thrombocytes , which leads to formation of intralu­
menal thrombosis. Recently Samuelsson, Olin, Berg and Jonsson 
(53-57) have reported experimental electrolytic de­
struction of tissue in pig. rabbit and rat with direct 
current. In the author's opinion, any percutaneous technique 
which is intended for local destruction of a cancer can 
be applied only to relatively small tumours, i.e., less 
than about 3-4 em in diameter. The reason is that a 
volume of tissue considerably larger than the radiogra­
phically apparent size of the tumour must be treated. Strands of radiographically invisible tumour cells often 
grow into the tissue surrounding the main tumour 
mass. The diameter of a spherical tumour vs. its vol­
ume is plotted in Fig. XVII: I. For example, a tumour 
2 em in diameter has a volume of 4.1 em'. Radiogra­
phically invisible, centrifuga l growth of the tumour by 
only 5 mm means a sphere of 3 em diameter must be 
treated, i.e., 14.1 cm3 of tissue. When locally destroy­
ing lung tumours with diathermia in the 1960's (39}, 
the author achieved permanent destruction of lung 
metastases when they were about I em in diameter. After technical improvements, which will be reported below, rumours of 2 em diameter can now be success­
fully treated with diathermia as a primary destruction 
of the tumour tissue. Larger tumours in the periphery 
of the lung and of diameter up to 4 em can, however, 
be tr<ated successfu lly by means of direct current, as 
will be shown in these studies. Before the initial mode of tumour therapy with 
direct current is described, Secricm (A) will dis­
cu~co the occasional reports of sronranenus regre~­
sion of proven malignant tumours. This clinical mys­
tery is important because it is possible that spontane­
ous regression of tumours may be explained as an 
effect of spontaneous polarization within a BCEC. The 
possibility of spontaneous regression of tumours will 
be tested in two ways. Secricm 8 presents a modified technique of diarhemria 
for producing ncmspecific injury polarizaricm of rumours . Tbe intention has been to destroy tumour tissue pri­
marily by heat, thereby producing local electrochem i­
cal polarization, similar to that which occurs by spon­
taneous degradation in tumours. In this way the pro­
posed mechanism of spontaneous healing over a polar­
izing BCEC was intended to become activated for the 
healing of the injured tissue and any remaining viable 
tumour tissue. This procedure represent s therefore an 
artificially induced self-driving sytrem . . Direcr currenr rrearmenr of rumours is described under 
Secritms C and D. Two main effects are utilized. One is 
to obtain, if possible, a complete destruction of the 
tumour tissue by the liberation of protons at the sur­
face of the anode, which is placed in the tumour. The 
ot.her effect involves the induction of different biologi­
cal and electrochemical reactions in the tissues sur­
rounding the tumour. In this way, some of the sponta­
neously occurring processes of healing in tissue injury 
are intended to be induced. This procedure also repre­
sents the use of a driven $Yfltm during the treatment . leading to an injury-induced telf-driving symm after 
the applied current is discontinued. As shown by the experimental and clinical studies in 
the previous chapters, a large variety of tissue reac­
tions can be induced.
631928626-Biologically-Closed-Electric-Ci-Bjorn-Nordenstrom-pdf.txt
Summarize the following text section accurately and concisely. Maintain specific details and numerical information, and use anti-repetition mechanisms:

        R. Microcalcifications: 
historical review 
Microcalcifications in carcinoma of t. he breast were 
first described by Salomon in 1913 (83). Their irnpor­
t:ance for the recognition and early diagnosis of breast 
cancer was pointed out by Leborgne (65). Unfortu· 
nately, "malignant" and "benign" as charact~rizing 
terms for these calcifications are in many ways mis­
leading and have been used rather frequently in many 
publications in the last few years. Citoler and coworkers (22, 23) found only IS of 113 
breast carcinomas to contain so-called microcalcifica­
tions. Attempts to define what is typical for microcal­
cifications in malignant breast tumours have been 
made by Gershon-Cohen (42), Egan (31), Baclesse and 
Willemin (10), Hoeffken and Lanyi (SS), Lamarque 
(60), Barth (14) and others. In a recent survey, Lanyi 
(63) found that size, number, dispersion, opacity and 
contour of breast calcifications were not characteristic 
as signs of malignancy. Nevertheless, it is well known 
that mammographic microcalcifications very often call 
the attention of the examiner to tbe region where a 
carcinoma is growing. Gerlach and Thiemann ( 40) as well as Pape and 
Stegner (78) have performed electron microscopic 
studies of breast carcinomas. Because the female 
breast has the capacity to excrete calcium during lacta­
tion, the suggestion has been put forward that the 
breast also may have the capacity to accumulate cal­
cium particles intracellularly in cancer cells as a result 
of metabolic cell activities. Ahmed (2) supports the theory of active secretion of 
calcium because mammary epithelium is capable of 
concentrating calcium ions (87). In ultrastructural 
studies, Price, Hanrahan and Florida (79) reported 
that both electron diffraction and electron probe analy­
sis showed that the crystalline material is hydroxyapa ­
tite (Ca,P04)30H. Chemical analyses of some micro­
calcifications have been made by Moros, Pinter and 
Molnar (71), who found the following composition: 
calcium 25. 4 %, magnesium 2. 6 %, carbonate 5. 8 o/o 
and carbon 13. 8 %. Spectrophotometric examination s 
showed that the calcium and magnesium are predomi­
nantly bound to phosphate. Under certain assump­
tions, the following molecular composition has been 
suggested (cit. by Hoeffken and Lanyi) (55): 
Ca3(P0. )2 eaco, 
Mg3(PO•h · H20 
Albumin 55. 0% 
9. 7% 
13. 3% 
22. 0% 
For an understanding of the different aspects of 
degenerative changes of tissue, the mechanisms of 
autolysis are of fundamental importance. An excellent 
survey of the relevant literature has been made by van 
Lancker (62). A short recapitulation of selected as­
pects of autolysis follows: 
Tbe destruction of cellular component s, e. g. , by 
hypoxia, is caused mainly by hydrolytic enzymes re­
leased from lysosomes (29, 92). Phosphate ions will be 
available from hydrolysis of ATP when living tissue is 
exposed to hypoxia (4, 56, 74), which further leads to 
autolytic changes (8, 26, 77). A decrease in oxygen 
supply to the tissue further leads to elevated concen­
trations of hydrogen ions, lactic acid, C02 and other 
metabolic products. The acids promote an increase of 
proteolyti c activities. The release of hydrolytic en­
zymes also alters membrane permeability, which in 
some way is coupled with a cellular inflow of ca++, 
Na• and water. In studying cellular death, Judah and Spector (58), 
McLean and coworkers (64) have found that the cou­
pling of oxidation to phosphorylation is completely 
blocked within 30 minutes after the onset of autolysis. Another early manifestation of injury was found to be 
a loss of A TP. Simultaneously, the degrading tissue 
becomes acid. Under these circumstances it is difficult 
to understand how calcium, which is known to preci­
pitate in alkaline environment s, can precipitate in acidic tissue. As we are here dealing with pathological 
precipitation of calcium, the only explanation is to 
assume somehow that local factors trigger the precipi­
tation of the salt. Exactly what precipitates calcium is 
not known. One proposal is that changes in the matrix 
lead to crystallization of the calcium salts because the 
altered matrix may act as a seed for the precipitation of 
hydroxyapatite. Irving, reviewing the mechanism 
of mineralization in cartilage and bone (57), believes 
that collagen is a focus for calcification. No calcifica­
tion, however, was seen in collagen in breast carcino­
mas in the studies of Ahmed (2). Anderson (5) has 
described extracel. lular vesicles as foci for calcification 
in bone mineralization. Acidic phospholip ids have also 
been considered as targets for mineralization of bone 
(88). Phospholipids and phosphoproteins, such as ca­
sein, are the most likely foci for calcifications in breast 
cancer, according to Ahmed (2). It may also be men­
tioned that acidic phospholipid s are probable target 
substances for calcifications of aortic valves (59). In all 
calcifications it therefore seems necessary to begin 
with some kind of matrix, which under certain circum­
stances serves as a target for mineralization. Recently Hoeffken and coworkers (55) have stated, 
"The pathogenesis of calcium deposition in the various 
forms of fibrocystic disease and breast carcinoma is 
still an enigma in spite of intensive investigations using 
electron microscopy, ordinary microscopy as well as 
chemical and radiological methods. " S. Closed circuit production 
of microcalcifications 
Possibilities of locally precipitating calcium in tissue 
will be explored in this section by means of fluctuating 
physicochemical potentials ove. -a closed circuit. These 
experiment s, like the previous experiment s in this 
chapter, were conducted as driven systems and must 
therefore be compared with cocresponding reactions of 
endogenous self-driving systems in vivo over BCEC. A 
recapitulation of some aspects of tissue injury will 
facilitate understanding the ex:periments to follow. The experiments on autolysis of blood (Chapter VII) 
revealed that early in autolysis protons are produced. Later in autolysis protons are lost. The tissue then 
changes from being a proton donor into a proton 
acceptor. Flucruation of pH was found to be about one 
pH unit or approximately 60 millivolts. These changes 
are logical consequences, because A TP is not pro­
duced over the Krebs cycle when oxygen is lacking. Phosphate ions will then accumulate, because their 
recombination or dissipation (e.
Salomon in 1913.
Who first described microcalcifications in carcinoma of the breast?
Calcium 25.4%, magnesium 2.6%, carbonate 5.8%, and carbon 13.8%.
What is the composition of microcalcifications, as reported by Moros, Pinter, and Molnar?
To produce focal sites of necrosis and potentially induce calcium precipitation.
What is the purpose of the experiments with in vitro electrophoresis of breast fat?
The author believes that electric current can be used to enhance healing, but it is not a substitute for conventional treatment.
What is the author's opinion on the use of electric current for treatment of cancer?
Lanyi (reference 63)
Who found that the presence of lymphocytes in breast cancer is not a specific indication of cancer?