вход по аккаунту



код для вставкиСкачать
Introduction to The Biliary Tract, The Gallbladder,
and Gallstones
Summa Health System Foundation, Akron, Ohio 44304
biliary tract; gallbladder; nomenclature; microscopy; bile acids
This paper serves to introduce a topical section of fifteen invited original research
contributions dealing with normal and pathological development of the human biliary tract. This
section also includes comparative anatomy of the gallbladder and the cystic duct as well as, the
formation of gallstone. This series of reports have used advanced microscopic and ancillary
techniques to study adaptative changes in gallbladder epithelial cell changes regarding permeability, renewal, mucous secretion as well as cholesterol uptake and nucleation. Several contributions
deal with the blood and lymphatic drainage of the gallbladder. The gallbladder contractility is
clarified by recent findings about its innervation, elegantly demonstrated and supported by
complementary immunohistochemical and neurophysiological techniques. In vivo models for
production of cholelithiasis in the ground squirrel and the Syrian hamster are introduced. Recent in
vitro cellular and molecular models have substantially increased the understanding of biliary tract
calculi formation. Finally, a survey and new data about progesterone gene regulation of both
cholesterol metabolism and gallstone formation obtained in the Syrian hamster model are compared
with cholelithogenesis in human. Microsc. Res. Tech. 38:547–551, 1997. r 1997 Wiley-Liss, Inc.
The biliary system includes the secretory units of the
liver, the bile canaliculi, bile ductules (canals of Hering), intrahepatic bile ducts, extrahepatic bile ducts,
the common hepatic duct, the cystic duct, the gallbladder, and the common bile duct. Some confusion remains
as to the terminology of the components of the biliary
system (i.e., interlobular 5 intrahepatic).
All vertebrates possess a biliary tract but not all of
them possess a gallbladder whose function as an accessory organ of the digestive system is to participate in
the enterohepatic circulation of bile (Hofmann, 1968,
1990, 1994) by storing and concentrating biliary compounds through the removal of water and the exchange
of electrolytes (Diamond, 1962; Dietschy and Moore,
1964; Wheeler, 1968). The biliary system in man includes all of the aforementioned components, although
this is not true of all vertebrates. Pfuhl (1932) reviewed
the literature and histology of the biliary system in
selected vertebrates, including humans. Morphological
aspects of the biliary system during development, differentiation (Desmet, 1994; Phillips, 1994), and histopathology (Sirica, 1995) have been reviewed recently. In
this monograph, the paper of Nakanuma et al. (1996a)
describes the normal morphology from early development to a differentiated stage of the human biliary tract
and its pathology. It has been reported that the histochemical characterization of biliary hepatic cells could
play an important diagnostic role in pathology (Strain
et al., 1995). Nakanuma et al. (1997a) have also described the extra- and intrahepatic peribiliary glands
(development, differentiation, apoptotic growth, remodeling and differentiation, immunologic functions, etc.).
These glands constitute intramural and extramural
mixed mucous and serous acini with the serous parts
resembling exocrine pancreatic acini (Terada et al.,
1990) that do not contain islets of Langerhans’s tissue.
This observation is particularly interesting because
Gilloteaux et al. (1995) and Oldham-Ott and Gilloteaux
(1997) illustrate that in lower vertebrates (fish) pancreatic tissue is commonly detected in the vicinity of the
The bile canaliculi are formed by the adjacent plasma
membranes of the hepatocytes. This was seen by light
microscopy in 1911, and one of the first TEM studies of
bile canaliculi demonstrated this feature (Rouiller,
1956). Previously, these channels were thought to be
intercellular tubules with their own walls. Even Rouiller once believed that the bile canaliculi constituted an
incomplete barrier between the space of Disse and the
lumen of the canaliculi (Steiner and Carruthers, 1961).
It is now known that tight junctions and other specialized junctions (gap junctions and desmosomes) separate the canaliculi lumen from the hepatocytes. In an
interesting monograph of Matter et al. (1969) it is
shown that these tight junctions are efficient permeability barriers. Moreover, bile canaliculi are able to have a
coordinated contractile activity by pericanalicular, actomyosinic interactions controlled by calcium. This action
was observed in pathology (Oda et al., 1974; Oda and
Phillips, 1977) and in vitro (Oshio and Phillips, 1981, in
review by Phillips, 1994; Phillips et al., 1983; Smith et
al., 1985; Watanabe et al., 1983; Watanabe and Phillips,
1984). In addition, abundant microvilli, with varied
*Correspondence to: Dr. J. Gilloteaux, Summa Health System Foundation,
Arch Street 41, Suite 506, Akron, Ohio 44304.
Accepted 1 August, 1995
shapes and sizes, due to actin filaments remodeling
(Forscher et al., 1992) protrude into the lumen of the
canaliculi (Matter et al., 1969; Rouiller and Jezequel,
The bile ductules are circumscribed by two to four
epithelial cells, eventually becoming cuboidal, with
blunt microvilli, a basal lamina, a large spherical
nucleus, poorly developed rough endoplasmic reticulum, many free ribosomes, and few mitochondria. The
cells contact one another through complex interdigitations and have extensive tight junctions (Gabe, 1973).
The microvilli-coated intrahepatic bile duct cells
progress from a cuboidal to a columnar epithelium on a
basal lamina and they often bear a single extended
(perhaps motile) flexuous cilium ranging between 2 to
4 µm in length. An overview of the embryology, anatomy,
histochemical typing, and functioning of the epithelial
cells of the intrahepatic bile ducts (cholangiocytes) has
been performed by Alpini et al. (1994).
The extrahepatic bile ducts are composed of tall,
columnar epithelial cells, surrounded by a sheet of
connective tissue. Elastic and collagen fibers have been
observed in the basement membrane; tubular or tubuloalveolar glands, varying according to species, have also
been observed. The material secreted by the extrahepatic duct has been identified as mucin with acid
mucopolysaccharides (Gabe, 1973). A submucosa, muscularis, and adventitia are present. The extrahepatic
bile ducts join to form the common hepatic duct. This
duct connects with the cystic duct from the gallbladder
to form the common bile duct (ductus choledochus).
The common bile duct has been observed to contain
tubular glands (Spitz and Petropoulos, 1979) and PASpositive cells. The glands are more frequent in animals
without a gallbladder, such as the rat (Jones and
Spring-Mills, 1983). We refer the reader to Nakanuma
et al. (1997a) for a more detailed and recent account of
these structures. During bile formation and all along
the pathway to the gallbladder many of the cells
involved show evidence of active and passive transport
of water and electrolytes. The anatomy of the various
bile ducts differs widely among vertebrate groups.
The Gallbladder
A review of the morphological components of the
biliary tract, the gallbladder, and the formation of
gallstones across the vertebrates is offered by OldhamOtt and Gilloteaux (1997). This review shows that the
gallbladder’s microscopic architecture displays a homologic histological pattern throughout the vertebrates in
terms of layering. A lamina propria, fibromuscular
tunic, subserosal, and serosal tunics are normally
present. Small nerve ganglia and adipose tissue are
present between the fibromuscular and subserosal layers. The thickness of the gallbladder wall also varies in
vertebrates. It may be quite thick, as in many carnivores and primates, or very thin, as in the lower
vertebrates (fish, amphibians), mouse, and guinea pig.
The gallbladder’s mucosal epithelium is usually composed of tall columnar cells, displays a PAS-positive
apical aspect (in carnivores it contains lipidic inclusions),
and is coated with microvilli and other characteristics
of absorptive cells, including basolateral spaces and
digitations. Prominent junctional complexes are present
(Gabe, 1973). Bulging epithelial apices and decapita-
tions of excrescent apical structures can be found occasionally. These are more abundant in cholesterolosis
(Gilloteaux et al., 1996b), in male, in ovariectomized,
and in intact female Syrian hamster where cholelithiasis was induced by steroid hormones (Gilloteaux et al.,
1992, 1993a–c; Karkare et al., 1995; Karkare and
Gilloteaux, 1995). The same apical excrescences are
morphologically similar to the secretory endometrial
epithelial cell apices during the postovulatory phase
(Wessel, 1960; Wetzstein and Wagner, 1960; Wynn and
Wooley, 1967). This phenomenon has also been observed in fetal gallbladders (Laitio and Nevalainen,
1972) and in fish gallbladder (Gilloteaux et al., 1995;
Oldham-Ott and Gilloteaux, 1997; Viehberger, 1982).
In the surface epithelium of the mouse gallbladder,
columnar brush cells, which are possibly sensory cells,
were discovered in 1969 by Luciano and Reale and are
elegantly illustrated in this monograph, as they have
included a freeze-fracture technique (Luciano and Reale, 1997). Interestingly enough, similar brush cells
appear to be present in some amphibians and reptilian
gallbladders (Oldham-Ott and Gilloteaux, 1997).
Lamote and Willems (1997) demonstrate that the
normal gallbladder epithelium has a very low rate of
cell renewal, while mechanical distension by ligation of
the common bile duct or by neoplastic obstruction in
humans increases the mitotic activity of the tissue.
Other influences, such as hormones (caerulein, cholecystokinin (CCK)-octapeptide, CCK analogs), or a diet rich
in cholesterol and cholic acid, can stimulate high DNA
synthesis in the gallbladder epithelium. Fundusectomy
or the presence of gallstones stimulates proliferative
activity. These authors suggest that this proliferative
activity could be the result of hypergastrinemia.
Rokitansky-Aschoff crypts reaching the fibromuscular layer are present in humans. Canals of Luschka, in
which the epithelium invaginates through the fibromuscular layer and may contact blood vessels, have been
observed in humans, are well defined in the rabbit, and
almost absent in the cat (Gabe, 1973).
Gallbladder tubular and tubulo-alveolar glands,
whose presence and abundance is variable in the
lamina propria, are similar to those found in the
extrahepatic ducts. In primates, these glands are located near the infundibulum of the gallbladder, and in
ruminants they form a subepithelial layer (equivalent
to Brunner’s glands). These glands are rare in carnivores (Gabe, 1973).
Many of the regulatory mechanisms of ion transport
across the gallbladder epithelium have been resolved
physiologically (Reuss, 1989; Reuss et al., 1991; Wheeler,
1971). Hopwood and Ross (1997) survey the permeability ‘‘barriers’’ of the gallbladder epithelium in terms of
water and ion removal. Using the mouse, they demonstrate that the gallbladder wall is able to take up
significant amounts of lipids and that inflammatory
reactions can alter membrane composition and functions. Finally, using a cationic, cytochemical probe
(cuprolinic blue; reviewed by Van Kuppevelt and
Veerkamp, 1994), Hopwood and Ross demonstrate a
significant increase of glycosaminoglycans in the basement membrane in the cholecystic gallbladder.
Using histo- and cytochemical lectin markers, Madrid
et al. (1989, 1994) surveyed and investigated characteristics of the glycoproteinaceous secretory products and
glycocalyx of the gallbladder epithelium across several
species, including humans. In their contribution, Madrid
et al. (1997) verify that most of the mucus is neutral,
heavily sulfated, and contains scarce sialic residues.
They also discuss the presence of core proteins which
are known molecular markers for mucus types (Audie
et al., 1993; Campion et al., 1995). Our ultrastructural
description of the human cholecystitic (Gilloteaux et al.,
1989) and cholelithiatic gallbladder shows anionic mucus secretory granules (Gilloteaux et al., 1997c). Koga
(1985) and Satoh and Koga (1997) review the pathological gallbladder storage of cholesterol in cholesterolosis.
In the case of the cystic duct, Gilloteaux et al. (1997a)
confirm the differential morphology of the gallbladder
in cholesterolosis and cholelithiasis. It is interesting to
note that LaMont (1989) has hypothesized that oxygen
radicals can stimulate gallbladder glycoprotein secretion.
Blood and Lymphatic Supply
The complex vasculature of the biliary tract and its
development is surveyed by Nakanuma et al. (1997a).
Blood supply to the mammalian gallbladder is by way of
small and medium arteries which cross the fibromuscular layer and form a fenestrated subepithelial plexus in
the lamina propria. There, blood flow could be controlled by neuropeptides, such as NPY (Gilloteaux et
al., 1990–1991). Using SEM on corrosion casts and on
KOH-macerated samples, Ohtani et al. (1997) illustrate the blood and lymphatic microvascularization of
the guinea pig gallbladder; they demonstrate that, as in
the small intestine, and in the liver lymphatics start
their trajectory as blind ends.
Gallbladder innervation resembles that of the intestine and has been comprehensively discussed by Cai
and Gabella (1983, 1984), Goehler et al. (1988), Mawe
and Gershon (1989), Mawe (1990, 1991, 1993), Talmage
et al. (1992), etc. As reported in the monograph by
Mawe et al. (1997), the musculature and the epithelial
tissues of the guinea pig gallbladder are regulated by
small clusters of neurons which constitute a ganglionated network containing diverse important neuropeptides and enzyme markers. From a physiological point
of view, they also report that this network acts as a
complex neuromodulator, and demonstrate that hormonal CCK can access gallbladder ganglia presynaptically (no blood-barrier) to facilitate vagal terminal
release in the musculature and the epithelial layer of
the gallbladder. Splanchnic mechanoreceptors of the
biliary tract and its mesentery have been studied by
Crousillat and Ranieri (1980). Gallbladder contraction
is mediated by cholecystokinin, the cholecystokinin
antagonist pancreatic polypeptide, and others too numerous to list here (Adrian et al., 1982; Conter et al.,
1987; Spellman et al., 1979).
The presence and degree of development of a sphincter regulating the flow of bile is directly related to the
presence or absence of a gallbladder; in those animals
lacking a gallbladder, the sphincter appears poorly
developed (Dorst, 1973; Gorham and Ivy, 1938).
In vivo models for producing cholelithiasis have also
been developed by using diverse animals (review in
Oldham-Ott and Gilloteaux, 1997). Using ground squirrels fed a high-cholesterol diet, MacPherson and Pemsingh (1996) have shown that mucus hypersecretion
occurs prior, during, and after stone formation.
Gilloteaux et al. (1996c) have shown similar changes
and stone formation after perturbing hepatic bile metabolism using female sex steroids in the male, in
ovariectomized, and in intact female Syrian hamsters
(Gilloteaux et al., 1992; Gilloteaux et al., 1993a–c;
Karkare et al., 1995; Karkare and Gilloteaux, 1995).
Medroxyprogesterone treatment alone can alter bile
and mucus composition, favoring formation of gallstones
via a down-regulation of the cholesterol 7a-hydroxylase
gene expression (Qiu et al., 1994; Gilloteaux et al.,
In vitro models are being developed to comprehend
the cell biology and pathology of the gallbladder epithelium. Nakanuma et al. (1997b) demonstrate that mucus
secretion characteristics can be maintained and studied morphologically with in vitro-grown epithelium.
Bile Acids
The concentrated bile secreted into the duodenum via
the permissive effect of cholecystokinin (Mawe et al.,
1991, 1997) provides a micellar suspension facilitating
intestinal absorption of fat soluble compounds, including vitamins (Borgström et al., 1985), as well as scavenging peroxyl radicals (Stocker and Ames, 1987; Stocker
et al., 1987a–b). In addition, bile has a laxative property due to its effect on the motility of the large
intestine (Hofmann, 1968). The composition of bile
acids in the bile varies in the animal kingdom (Haslewood, 1968; Hoshita, 1985; Hofmann, 1990, 1994; etc.):
The fish groups produce various compounds (bile alcohols in ancient fish, such as the shark), amphibians
generally produce bile alcohols, and the reptiles produce bile acids but no bile alcohols. In birds and
mammals, the type of bile acids produced seem dietdependent. Bile alcohols usually occur only in ancient
groups of mammals. Omnivores (including humans)
generally produce dihydroxy bile acids and carnivores
trihydroxy bile acids. Conjugated xenobiotics and bilirubin are other important components of bile (Arias, 1968).
In addition to bile acids, bile pigments vary with the
animal species and it is thought that gaining an
understanding of this diversity of bile pigments will aid
in comprehending altered bile metabolism in humans
(Cornelius, 1986). In plants, these pigments perform
photosynthetic functions. Bile pigments in mammals
have no known function; they are, however, potentially
toxic (Cornelius, 1986; Troxler, 1986). Further investigations in this area are clearly indicated.
Examining artificial and human native bile by cryotransmission electron microscopy, Kaplun et al. (1996)
have demonstrated that dilution induces cholesterol
supersaturation, resulting in the production of a range
of microstructures: spheroidal, uni- and multilamellar
micelles, followed by tubular and helical as well as the
classical plate-like cholesterol. This model can help to
decipher the beneficial role of bile in preventing the
cholesterol nucleation process in the gallbladder.
In order to comprehend the pathologic etiology of the
hepatobiliary system, most investigations have to rely
on case studies, or animal models and in vitro studies.
It would be interesting to obtain fresh postmortem or
surgical human specimens in order to more fully describe certain structures, such as the cystic duct
(Gilloteaux et al., 1997b), which are easily damaged
during autopsy or following fixation delays after surgical removal.
I would like to thank Dr. J.E. Johnson Jr., Chief
Editor, for inviting me as Guest Editor for this special
monograph. I would also like to thank all the contributors for their efforts in providing informative and
well-illustrated manuscripts on the topic, and recognize
the experts and reviewers for their scientific assistance
and for having returned as promptly as possible the
manuscripts submitted to them. I wish, therefore, to
acknowledge Drs. Ian A.D. Bouchier, V.J. Desmet, Mr.
L.C. Gilloteaux, Drs. A. Groom, R. Hakanson, W.S.
Hawkins, M.R. Jacyna, E.R. Lacy, L. Luciano, S. Nagamori, Mrs. C. Oldham-Ott, Drs. G. Perry, E. Reale, W.
Schemann, P. Scheuer, B.A. Schulte, D.P. Siegel, R.J.
Spontak, P. Wade, and W. Willems.
Adrian, T.E., Mitchenere, P., Sagor, G., and Bloom, S.R. (1982) The
effect of pancreatic polypeptide on gallbladder pressure and hepatic
bile secretion. Am. J. Physiol., 243:G204–G207.
Alpini, G., Phillips, J.O., and LaRusso, N.F. (1994) The biology of
biliary epithelia. In: The Liver: Biology and Pathobiology, 3rd
Edition. I.M. Arias, J.L. Boyer, N. Fausto, W.B. Jakoby, D.A.
Schacter, and D.A. Shafritz, eds. Raven Press, New York, pp.
Arias, I.M. (1968) Formation of bile pigment. In: Alimentary Canal,
Section 6; Volume V. Handbook of Physiology. Ch. F. Code, ed.
American Physiological Society, Washington, D.C., pp. 2347–2374.
Audie, J.P., Janin, A., Porchet, N., Copin, M.C., Gosselin, B., and
Aubert, J.P. (1993) Expression of human mucin genes in respiratory,
digestive, and reproductive tracts ascertained by in situ hybridization. J. Histochem. Cytochem., 41:1479–1485.
Borgström, B., Barrowman, J.A., and Lindström, M. (1985) Roles of
bile acids in intestinal lipid digestion and absorption. In: Sterols and
Bile Acids. H. Danielsson, and J. Sjövall, eds. Elsevier Sci. Publ.,
Amsterdam, pp. 405–425.
Cai, W., and Gabella, G. (1983) Innervation of the gall bladder and
biliary pathways in the guinea pig. J. Anat. (Lond.), 136:97–109.
Cai, W.-Q., and Gabella, G. (1984) Catecholamine-containing cells in
the nerve plexus of the guinea pig gallbladder. Acta Anat., 119:10–17.
Campion, J.P., Porchet, N., Aubert, J.P., L’Helgoualc’h, A., and Clement, B. (1995) UW-preservation of cultured human gallbladder
epithelial cell: Phenotypical alterations and differential mucin gene
expression in the presence of bile. Hepatology, 21:223–231.
Conter, R.L., Roslyn, J.J., DenBesten, L., and Taylor, I.L. (1987)
Pancreatic polypeptide enhances postcontractile gallbladder filling
in the prairie dog. Gastroenterology, 92:771–776.
Cornelius, C.E. (1986) Comparative bile pigment metabolism in
vertebrates. In: Bile Pigments and Jaundice. J.D. Ostrow ed. Marcel
Dekker, New York, pp. 601–647.
Crousillat, J., and Ranieri, F. (1980) Mécanorécepteurs splanchniques
de la voie biliaire et de son péritoine. Exp. Brain Res., 40:146–153.
Desmet, V.J. (1994) Organizational principles. In: The Liver: Biology
and Pathobiology, 3rd edition. I.M. Arias, J.L. Boyer, N. Fausto, W.B.
Jakoby, D.A. Schacter, and D.A. Shafritz, eds. Raven Press, New
York, pp. 3–14.
Diamond, J.M. (1962) The reabsorptive function of the gallbladder. J.
Physiol. (Lond.), 161:442–473.
Dietschy, J.M., and Moore, E.W. (1964) Diffusion potentials and
potassium distribution across the gallbladder wall. J. Clin. Invest.,
Dorst, J. (1973) Appareil digestif et annexes. In: Traité de Zoologie,
Tome XVI, Mammifères, Fasc. 5A, Vol. 1. Masson & Cie, Paris, pp.
Forscher, P., Lin, C.H., and Thompson, C. (1992) Novel form of growth
cone motility involving site-directed actin filament assembly. Nature, 357:515–518.
Gabe, M. (1973) Anatomie microscopique de l’appareil digestif des
mammifères. In: Traité de Zoologie, Tome XVI, Fasc. 5A, Vol. 1.
Masson & Cie, Paris, pp. 383–483.
Gilloteaux, J., Pomerants, B., and Kelly, T.R. (1989) Human gallbladder mucosa ultrastructure: Evidence of intraepithelial nerve structures. Am. J. Anat., 184:323–335.
Gilloteaux, J., Pomerants, B.J., Kelly, T.R., Menu, R., Pelletier, G., and
Vanderhaeghen, J.-J. (1990–1991) Light and electron microscopical
immunolocalization of neuropeptide Y-containing nerves in the
hamster gallbladder. Biol. Struct. Morphogen., 3:89–96.
Gilloteaux, J., Karkare, S., Ko. W., and Kelly, T.R. (1992) Female sex
steroid induced epithelial changes in the gallbladder of the ovariectomized Syrian hamster. Tissue & Cell, 24:869–878.
Gilloteaux, J., Karkare, S. and Kelly, T.R. (1993a) Apical excrescences
in the gallbladder epithelium of the female Syrian hamster in
response to medroxyprogesterone. Anat. Rec., 236:479–485.
Gilloteaux, J., Kosek, E., and Kelly, T.R. (1993b) Sex steroid induction
of gallstones in the male Syrian hamster. J. Submicrosc. Cytol.
Pathol., 25:157–172.
Gilloteaux, J., Kosek, E., and Kelly, T.R. (1993c) Epithelial surface
changes and induction of gallstones in the male Syrian hamster
gallbladder as a result of two-month sex steroid treatment. J.
Submicrosc. Cytol. Pathol., 25:519–533.
Gilloteaux, J., Oldham, C.K., and Biagianti-Risbourg, S. (1996) Ultrastructural diversity of the biliary tract and the gallbladder in fish.
In: Fish Morphology: Horizon of New Research. J.S.D. Munshi and
H.M. Dutta, eds. Science Publishers. Inc., Lebanon, N.H. pp.
Gilloteaux, J., Hawkins, W.S., Gilloteaux, L.C., and Kelly, T.R. (1997a)
Ultrastructural aspects of human cystic duct epithelium as a result
of cholelithiasis and cholesterolosis. Microsc. Res. Tech., 38:643–
Gilloteaux, J., Karkare, S., Don, A.Q., and Kelly, T.R. (1997b) Cholelithiasis induced in the Syrian hamster: Evidence for an intramucinous nucleating process and down regulation of cholesterol 7ahydroxylase (CYP7) gene by medroxyprogesterone. Microsc. Res.
Tech., 39:56–70.
Gilloteaux, J., Karkare, S., Kelly, T.R., and Hawkins, W.S. (1997c)
Ultrastructural aspects of human gallbladder epithelial cells in
cholelithiasis. Production of anionic mucus. Microsc. Res. Tech.,
Goehler, L.E., Sternini, C., and Brecha, N.C. (1988) Calcitonin generelated peptide immunoreactivity in the biliary pathway and liver of
the guinea-pig: Distribution and colocalization with substance P.
Cell Tissue Res., 253:145–150.
Gorham, F.W., and Ivy, A.C. (1938) General function of the gall bladder
from the evolutionary standpoint. Field Museum of Natural History,
Zoological Series, 22:159–213.
Haslewood, G.A.D. (1968) Evolution and bile salts. In: Handbook of
Physiology. Section 6: Alimentary Canal. C.F. Code, ed. Vol. V. Bile;
Digestion; Ruminal Physiology. American Physiological Society,
Washington, D.C., pp. 2375–2390.
Hofmann, A.F. (1968) Functions of bile in the alimentary canal. In:
Handbook of Physiology. Section 6: Alimentary Canal. C.F. Code, ed.
Vol. V. Bile; Digestion; Ruminal Physiology. American Physiological
Society, Washington, D.C., pp. 2507–2533.
Hofmann, A.F. (1990) Bile acid secretion, bile flow, and biliary lipid
secretion in humans. Hepatology, 12:17S–25S.
Hofmann, A.F. (1994) Bile Acids. In: The Liver: Biology and Pathobiology, 3rd Edition. I.M. Arias, J.L. Boyer, N. Fausto, W.B. Jakoby, D.A.
Schacter, and D.A. Shafritz, eds. Raven Press, New York, pp.
Hopwood, D., and Ross, P.E. (1997) Biochemical and morphological
correlations in human gallbladder with reference to membrane
permeability. Microsc. Res. Tech., 38:631–642.
Hoshita, T. (1985) Bile alcohols and primitive bile acids. In: Sterols
and Bile Acids. H. Danielsson and J. Sjövall, eds. Elsevier, Amsterdam, pp. 279–302.
Jones, A.L., and Spring-Mills, E. (1983) The liver and the gallbladder.
In: Histology. Cell and Tissue Biology, 5th edition. L. Weiss, ed.
Elsevier, New York, pp. 707–748.
Kaplun, A., Konikoff, F.M., Eitan, A., Rubin, M., Vilan, A., Lichtenberg,
D., Gilat, T., and Talmon, Y. (1997) Imaging supramolecular aggregates in bile models and human bile. Microsc. Res. Tech., 39:85–96.
Karkare, S., and Gilloteaux, J. (1995) Gallstones induced by sex
steroids in the female Syrian hamster: Duration effects. J. Submicrosc. Cytol. Pathol., 27:53–74.
Karkare, S., Kelly, T.R., and Gilloteaux, J. (1995) Morphological
aspects of female Syrian hamster gallbladder induced by one-month
sex steroid treatment. J. Submicrosc. Cytol. Pathol., 27:35–52.
Koga, A. (1985) Fine structure of the human gallbladder with cholesterolosis with special reference to the mechanism of lipid accumulation.
Br. J. Exp. Path., 66:605–611.
Laitio, M., and Nevalainen, T. (1972) Scanning and transmission
electron microscope observations on human gallbladder epithelium.
II. Foetal development. Z. Anat. Entwickl.-Gesch., 136:326–335.
LaMont, J.T. (1989) Oxygen radicals stimulate gallbladder glycoprotein secretion. Symp. Soc. Exp. Biol., 43:273–278.
Lamote, J., and Willems, G. (1997) DNA synthesis, cell proliferation
index in normal and abnormal gallbladder epithelium. Microsc. Res.
Tech., 38:609–615.
Luciano, L., and Reale, E. (1969) A new cell type (‘‘brush cell’’) in the
gall bladder epithelium of the mouse. J. Submicrosc. Cytol., 1:43–52.
Luciano, L., and Reale, E. (1997) The presence of brush cells in the
mouse gallbladder. Microsc. Res. Tech., 38:598–608.
MacPherson, B.R., and Pemsingh, R.S. (1997) The ground squirrel
model for cholelithiasis. The role of epithelial glycoproteins. Microsc. Res. Tech., 39:29–43.
Madrid, J.F., Ballesta, J., Galera, T., Castells, M.T., and Pérez-Tomas,
R. (1989) Histochemistry of glycoconjugates in the gallbladder
epithelium of ten animal species. Histochemistry, 91:437–443.
Madrid, J.F., Castells, M.T., Martinez-Menarguez, J.A., Avilès, M.,
Hernandez, F., and Ballesta, J. (1994) Subcellular characterization
of glycoproteins in the principal cells of human gallbladder. A lectin
cytochemical study. Histochemistry, 101:195–204.
Madrid, J.F., Hernandez, F., and Ballesta, J. (1997) Characterization
of glycoproteins in the epithelial cells of human and other mammalian gallbladder. Microsc. Res. Tech., 38:616–630.
Matter, A., Orci, L., and Rouiller, C. (1969) A study on the permeability
barriers between Disse’s space and the bile canaliculus. J. Ultrastr.
Res., Supplement 11:1–71.
Mawe, G.M. (1990) Intracellular recording from neurones of the
guinea pig gallbladder. J. Physiol. (Lond.), 429:323–338.
Mawe, G.M. (1991) The role of cholecystokinin in ganglionic transmission in the guinea-pig gall-bladder. J. Physiol. (Lond.), 439:89–102.
Mawe, G.M. (1993) Noradrenaline acts as a presynaptic inhibitory
neurotransmitter in ganglia of the guinea-pig gallbladder. J. Physiol.
(Lond.), 461:378–402.
Mawe, G.M., and Gershon, M.D. (1989) Structure, afferent innervation, and transmitter content of ganglia of the guinea-pig gallbladder: Relationship to the enteric nervous system. J. Comp. Neurol.,
Mawe, G.M., Talmage, E.K., Cornbrooks, E.B., Gokin, A.P., Zhang, L.,
and Jennings, L.J. (1997) Innervation of the gallbladder: Structure,
neurochemical coding, and physiological properties of guinea pig
gallbladder ganglia. Microsc. Res. Tech., 39:1–13.
Nakanuma, Y., Hoso, M., Terada, T., Sanzen, T., and Sasaki, M.
(1997a) Microstructure and development of the normal and pathologic biliary tract in humans, including blood supply. Microsc. Res.
Tech., 38:552–570.
Nakanuma, Y., Katayanagi, K., Saito, K., Kawamura, Y., and Yoshida,
K. (1997b) Monolayer and three-dimensional cell culture and living
tissue culture of gallbladder epithelium. Microsc. Res. Techn.,
Oda, M., and Philips, M.J. (1977) Bile canalicular membrane pathology in cytochalasin B-induced cholestasis. Lab. Invest., 37:350–356.
Oda, M., Price, V., Fisher, M.M., Phillips, M.J. (1974) Ultrastructure of
bile canaliculi, with special reference to the surface coat and the
pericanalicular web. Lab. Invest., 31:314–323.
Ohtani, O., Lee, M.-H., Wang, Q.-X., and Uchino, S. (1997) Organization of the blood and lymphatic microvasculature of the gallbladder
in the guinea pig: A scanning electron microscopic study. Microsc.
Res. Tech., 38:660–666.
Oldham-Ott, C.K., and Gilloteaux, J. (1997) Comparative morphology
of the gallbladder and biliary tract in vertebrates: Variation in
structure, homology in function and gallstones. Microsc. Res. Tech.,
Oshio, C., and Phillips, M.J. (1981) Contractility of bile canaliculi:
Implications for liver function. Science, 212:1041–1042.
Pfuhl, W. (1932) Die Leber, die Gallenblase und die extrahepatischen
Gallengange. Mollendorffs Hand. Micro. Anat., 5:235–462.
Phillips, M.J. (1994) Biology and pathobiology of actin in the liver. pp.
Phillips, M.J., Oshio, C., Miyairi, M., Watanabe, S., and Smith, C.R.
(1983) What is actin doing in the liver cell? Hepatology, 3:433–436.
Qiu, M.-C., Gilloteaux, J., Kelly, T.R., and Chiang, J.Y.L. (1994)
Regulation of cholesterol 7a-hydroxylase by female sex steroids in
Syrian hamster. FASEB J., 8:959A (abstract).
Reuss, L. (1989) Ion transport across gallbladder epithelium. Physiol.
Rev., 69:503–545.
Reuss, L., Segal, Y., and Altenberg, G. (1991) Regulation of ion transport across gallbladder epithelium. Ann. Rev. Physiol., 53:361–373.
Rouiller, Ch. (1956) Les canalicules biliaires. Acta anat., 26:94–109.
Rouiller, Ch., and Jezequel, A.M. (1963) Electron microscopy of the
liver. In: The Liver. Ch. Rouiller, ed. Academic Press, New York, vol.
1, pp. 195–264.
Satoh, H., and Koga, A. (1997) The fine structure of cholesterolosis in
the human gallbladder and the mechanism of lipid accumulation.
Microsc. Res. Tech., 39:14–21.
Sirica, A.E. (1995) Ductular hepatocytes. Histol. Histopathol., 10:433–
Smith, C.R., Oshio, C., Miyairi, M., Katz, M., and Phillips, M.J. (1985)
Coordination of the contractile activity of bile canaliculi: Evidence
from spontaneous contractions in vitro. Lab. Invest., 53:270–274.
Spellman, S.J., Shaffer, E.A., and Rosenthall, L. (1979) Gallbladder
emptying in response to cholecystokinin. A cholescintigraphic study.
Gastroenterology, 77:115–120.
Spitz, L. and Petropoulos, A. (1979) The development of the glands of
the common bile duct. J. Pathol., 124:213–220.
Steiner, J.W., and Carruthers, J.S. (1961) Studies on the fine structure
of the terminal branches of the biliary tree. Am. J. Pathol., 38:639–
Stocker, R., and Ames, B.N. (1987) Potential role of conjugated
bilirubin and copper in the metabolism of lipid peroxides in bile.
Proc. Nat. Acad. Sci., USA, 84:8130–8134.
Stocker, R., Glazer, A.N., and Ames, B.N. (1987a) Antioxidant activity
of albumin-bound bilirubin. Proc. Nat. Acad. Sci., USA, 84:5918–
Stocker, R., Yamamoto, Y., McDonagh, A.F., Glazer, A.N., and Ames,
B.N. (1987b) Bilirubin as an antioxidant of possible physiological
importance. Science, 235:1043–1046.
Strain, A.J., Wallace, L., Jopiln, R., Daikuhara, Y., Ishii, T., Kelly, D.A.,
and Neuberger, J.M. (1995) Characterization of biliary epithelial
cells isolated from needle biopsies of human liver in the presence of
hepatocyte growth factor. Am. J. Pathol., 146:537–545.
Talmage, E.K., Pouliot, W.A., Cornbrooks, E.B., and Mawe, G.M.
(1992) Transmitter diversity in ganglion cells of the guinea pig
gallbladder: An immunohistochemical study. J. Comp. Neurol.,
Terada, T., Nakanuma, Y., and Kakita, A. (1990) Pathologic observations of intrahepatic peribiliary glands in 1000 consecutive autopsy
livers. Heterotopic pancreas in the liver. Gastroenterology, 98:133–
Troxler, R.F. (1986) Bile pigments in plants. In: Bile Pigments and
Jaundice. J.D. Ostrow, ed. Marcel Dekker, New York, pp. 649–688.
Van Kuppevelt, T.H.M.S.M., and Verkamp, J.H. (1994) Application of
cationic probes for the ultrastructural localization of proteoglycans
in basement membranes. Microsc. Res. Tech., 28:125–140.
Viehberger, G. (1982) Apical surface of the epithelial cells in the
gallbladder of the rainbow trout and the tench. Cell Tiss. Res.,
Watanabe, S., Miyairi, M., Oshio, C., Smith, C.R., and Phillips, M.J.
(1983) Phalloidin alters bile canalicular contractility in primary
monolayer cultures of rat liver. Gastroenterology, 85:245–253.
Watanabe, S., and Phillips, M.J. (1984) Ca21 causes active contraction
of the bile canaliculi: Direct evidence from microinjection studies.
Proc. Natl. Acad. Sci., USA, 81:6164–6168.
Wessel, W. (1960) Elektronenmikroskopische Bild menschlicher endometrialer Drüsenzellen während des menstruellen Zyklus. Z. Zellforsch., 51:633–657.
Wetzstein, R., and Wagner, H. (1960) Elektronenmikroskopische
Untersuchungen am menschlichen Endometrium. Anat. Anz., 108:
Wheeler, H.O. (1968) Water and electrolytes in bile. In: Handbook of
Physiology. Section 6: Alimentary Canal. C.F. Code, ed. Vol. V. Bile;
Digestion; Ruminal Physiology. American Physiological Society,
Washington, D.C., pp. 2409–2431.
Wheeler, H.O. (1971) Concentrating function of the gallbladder. Am. J.
Med., 51:588–595.
Wynn, R.M., and Wooley, R.S. (1967) Ultrastructural cyclic changes in
the human endometrium. II. Normal postovulatory phase. Fertil.
Steril., 18:721–738.
Без категории
Размер файла
45 Кб
Пожаловаться на содержимое документа