Autopsy Case of Bilateral Optic Nerve Aplasia with Microphthalmia: Neural Retina Formation Is Required for the Coordinated Development of Ocular Tissues.

Human congenital anomalies provide information that contributes to the understanding of developmental mechanisms. Here we report bilateral optic nerve aplasia (ONA) with microphthalmia in the autopsy of the cadaver of a 70-year-old Japanese female. The gross anatomical inspection of the brain showed a cotton thread-like cord in the presumed location of the optic nerve tract or chiasm. Histologically, no neural retina, optic nerve bundle or retinal central vessels were formed in the eye globe, and the retinal pigment cells formed rosettes. The cornea, iris, and lens were also histologically abnormal. Immunohistochemically, no retinal cells expressed beta III tubulin, and Pax6- immunoreactive cells were present in the ciliary non-pigmented epithelial cells. This case of ONA could be attributed to the agenesis of retinal projection neurons as a sequel to the disruption of neural retina development. The neural retina formation would coordinate the proper development of ocular tissues.

Lymphatic Stomata in the Adult Human Pulmonary Ligament.

BACKGROUND: Lymphatic stomata are small lymphatic openings in the serosal membrane that communicate with the serosal cavity. Although these stomata have primarily been studied in experimental mammals, little is known concerning the presence and properties of lymphatic stomata in the adult human pleura. Thus, adult human pleurae were examined for the presence or absence of lymphatic stomata. METHODS AND RESULTS: A total of 26 pulmonary ligaments (13 left and 13 right) were obtained from 15 adult human autopsy cases and examined using electron and light microscopy. The microscopic studies revealed the presence of apertures fringed with D2-40-positive, CD31-positive, and cytokeratin-negative endothelial cells directly communicating with submesothelial lymphatics in all of the pulmonary ligaments. The apertures' sizes and densities varied from case to case according to the serial tissue section. The medians of these aperture sizes ranged from 2.25 to 8.75 µm in the left pulmonary ligaments and from 2.50 to 12.50 µm in the right pulmonary ligaments. The densities of the apertures ranged from 2 to 9 per mm(2) in the left pulmonary ligaments and from 2 to 18 per mm(2) in the right pulmonary ligaments. However, no significant differences were found regarding the aperture size (p=0.359) and density (p=0.438) between the left and the right pulmonary ligaments. CONCLUSIONS: Our study revealed that apertures exhibit structural adequacy as lymphatic stomata on the surface of the pulmonary ligament, thereby providing evidence that lymphatic stomata are present in the adult human pleura.

Recent developments in morphology of lymphatic vessels and lymph nodes.

This paper reviews the morphology of lymphatics and lymphangiogenesis in vivo, microenvironments that promote lymphangiogenesis, and the structure and function of lymph nodes. Lymphatic capillaries consist of a single layer of lymphatic endothelial cells (LECs) and have valves, while collecting lymphatics are endowed with smooth muscle cells (SMCs) and valves besides a single layer of LECs. In the embryonic rat diaphragm, LECs first migrate presumably according to interstitial fluid flow and later join to form lymphatic vessels. SMCs of the collecting lymphatics are apparently differentiated from mesenchymal cells. LECs cultured on Cell Culture Inserts under a low oxygen condition proliferate very well and form a lymphatic network. LECs cultured on a collagen fiber network with a natural three-dimensional (3D) architecture under low oxygen rapidly form a 3D lymphatic network. The lymph node initiates an immune response as a critical crossroads for the encounter between antigen-presenting cells, antigens from lymph, and lymphocytes recruited into nodes from the blood. The node consists of spaces lined with LECs and parenchyma. High endothelial venules in the node strongly express Aquaporin-1, suggesting their involvement in the net absorption of water from lymph coming through afferent lymphatics. SMCs in node capsules seem to be involved in squeezing out lymphocytes and lymph. (English Translation of J Jpn Col Angiol 2008; 48: 107-112.).

A case of double aortic arch accompanied by sub-aortic and pre-aortic left brachiocephalic veins and anomalous origin and course of left vertebral artery.

During the elective course of human dissection at the University of Toyama in 2007, we encountered a rare case of double aortic arch accompanied by sub- and pre-aortic left brachiocephalic veins (LBV), and anomalous origin and course of the left vertebral artery in a Japanese elderly female. The double aortic arch formed a complete vascular ring that encircled the trachea and the esophagus. The sub-aortic LBV traversed below the aortic arches between the ascending aorta and the trachea. In addition, there was a small pre-aortic LBV passing anterior to the origins of the aortic arches. The left vertebral artery originated from the left aortic arch and entered the transverse foramen of C3, while the right vertebral artery originated from the right subclavian artery and entered the transverse foramen of C6.

Myxoid liposarcoma with EWS-CHOP type 1 fusion gene.

BACKGROUND: In myxoid liposarcoma (MLS), the t(12;16)(q13;p11) chromosomal translocation and its resultant fusion transcript, the human translocation liposarcoma (TLS)-CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), are found in the majority of cases. On the other hand, the variant translocation, t(12;22)(q13;q12) creating the Ewing sarcoma (EWS)-CHOP fusion transcript, is detectable in a limited number of cases. PATIENTS AND METHODS: Tissue from MLS arising in the left thigh of a 19-year-old female was analyzed for possible detection of chromosome translocation and fusion transcript. Fluorescent in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR) methods were used. RESULTS: FISH analysis demonstrated a rearrangement in the CHOP gene. RT-PCR analysis confirmed the presence of EWS-CHOP chimeric transcript type 1, in which exon 7 of EWS was in-frame fused to exon 2 of CHOP with a serine (AGT) to methionine (ATG) transition at the junction. The patient underwent a radical segmental resection including a left vastus medialis musclectomy. Sixty months following the surgical resection, the patient was alive with no evidence of disease. CONCLUSION: Analysis of MLS with EWS-CHOP variant transcripts, type 1 through type 4, including this case together with 15 cases in the literature, indicated that MLS with type 1 fusion transcript may show a more favorable clinical behavior than MLS with other types of fusion transcript.

Distribution of internal elastic lamina and external elastic lamina in the internal carotid artery: possible relationship with atherosclerosis.

The intracranial internal carotid artery (ICA) is a muscular artery and lacks external elastic lamina (EEL). Stenosis of the intracranial ICA is relatively uncommon, but the most common site is the cavernous portion. The characteristics of the arterial wall structures were examined using serial 3-mm sections of 32 intracranial ICAs obtained from 50 cadavers to identify where the EEL disappeared. The portions of the ICA where the intima exhibited thickening were also determined. Both the internal elastic lamina (IEL) and EEL were observed in all 32 specimens of the petrous portion of the ICA. Only the IEL was observed in all 32 specimens of the intradural portion of the ICA. The EEL had disappeared in 31 of the 32 specimens of the horizontal segment of the cavernous portion of the ICA. Intimal thickening of the ICA was observed in 23 of 32 ICA specimens, and frequently appeared in the horizontal segment of the cavernous portion of the ICA. The EEL disappeared in the cavernous portion of the ICA, which is the most common site of stenosis of the intracranial ICA. Change in the elasticity of the arterial wall in the cavernous portion may be an important factor in the process of atherosclerosis in the intracranial ICA.

Specificity of fusion genes in adipocytic tumors.

BACKGROUND: In subsets of adipocytic tumors, specific chromosomal translocations lead to the generation of fusion genes. The high mobility group A2 (HMGA2)-lipoma preferred partner (LPP) and the reciprocal LPP-HMGA2 represent such fusion genes in lipoma, while the human translocation liposarcoma (TLS)-CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) and the Ewing sarcoma (EWS)-CHOP in liposarcoma. However, the specificity of these fusion genes has not been established in a variety of adipocytic tumors. PATIENTS AND METHODS: One hundred and seventy-two cases of adipocytic tumors, comprising 98 cases of lipoma and 74 cases of liposarcoma, were analyzed for the possible expression of HMGA2-LPP, LPP-HMGA2, TLS-CHOP and EWS-CHOP fusion genes, using a reverse-transcription polymerase chain reaction method. RESULTS: In lipoma, twenty-two cases (22.4%) were associated with either HMGA2-LPP or LPP-HMGA2, while neither TLS-CHOP nor EWS-CHOP transcript was detectable. On the contrary, in liposarcoma, neither HMGA2-LPP nor LPP-HMGA2 transcript was detectable, although twenty-five cases (33.8%) were related to either TLS-CHOP or EWS-CHOP. CONCLUSION: HMGA2-LPP and LPP-HMGA2 were specific to lipoma, and TLS-CHOP and EWS-CHOP were specific to liposarcoma.

Light harvesting by a periodic mesoporous organosilica chromophore.

Light aqueduct: Periodic mesoporous organosilica exhibits strong light absorption due to densely packed organic chromophores within the pore walls. Light energy absorbed by 125 biphenyl groups in the pore walls is funneled into a single coumarin 1 molecule in the mesochannels with almost 100% quantum efficiency, and results in significant enhancement of emission from the coumarin 1 dye.

Phospholipase Cgamma2 is necessary for separation of blood and lymphatic vasculature in mice.

The lymphatic vasculature originates from the blood vasculature through a mechanism relying on Prox1 expression and VEGFC signalling, and is separated and kept separate from the blood vasculature in a Syk- and SLP76-dependent manner. However, the mechanism by which lymphatic vessels are separated from blood vessels is not known. To gain an understanding of the vascular partitioning, we searched for the affected gene in a spontaneous mouse mutant exhibiting blood-filled lymphatic vessels, and identified a null mutation of the Plcg2 gene, which encodes phospholipase Cgamma2 (PLCgamma2), by positional candidate cloning. The blood-lymph shunt observed in PLCgamma2-null mice was due to aberrant separation of blood and lymphatic vessels. A similar phenotype was observed in lethally irradiated wild-type mice reconstituted with PLCgamma2-null bone marrow cells. These findings indicate that PLCgamma2 plays an essential role in initiating and maintaining the separation of the blood and lymphatic vasculature.

Structure and function of rat lymph nodes.

The lymph node comprises a critical crossroad for encounters between antigen presenting cells, antigens from lymph, and lymphocytes recruited into lymph nodes from the blood. The node consists of spaces lined with lymphatic endothelial cells and parenchyma. The former spaces can be divided into the subcapsular sinuses, lymphatic labyrinths in the deep cortex, intermediate sinuses, and medullary sinuses. The sponge-like framework of the node parenchyma is composed of collagen fibers invested with reticular cells. The parenchyma can be divided into the cortex, deep cortex, and medullary cord. Lymphocytes migrate from the node parenchyma into the lymphatic labyrinths in the deep cortex. Close to the labyrinths are high endothelial venules (HEVs), through which circulating lymphocytes enter the node parenchyma. HEVs strongly express Aquaporin-1, suggesting that HEVs are involved in the net absorption of water, but not protein, from lymph coming through afferent lymphatics. Many LYVE-1 positive sinus reticular cells (i.e., lymphatic endothelial cells) with attached macrophages form a network within the lumen of the medullary sinuses. Fluids and migrating cells arriving at the node preferentially flow through the subcapsular sinuses, intermediate sinuses, and medullary sinuses in this order. Fluids and migrating cells may also enter the cortex through gaps in the floor of the subcapsular sinuses.

Organization and developmental aspects of lymphatic vessels.

The lymphatic system plays important roles in maintaining tissue fluid homeostasis, immune surveillance of the body, and the taking up dietary fat and fat-soluble vitamins A, D, E and K. The lymphatic system is involved in many pathological conditions, including lymphedema, inflammatory diseases, and tumor dissemination. A clear understanding of the organization of the lymphatic vessels in normal conditions would be critically important to develop new treatments for diseases involving the lymphatic vascular system. Therefore, the present paper reviews the organization of the lymphatic vascular system of a variety of organs, including the thyroid gland, lung and pleura, small intestine, cecum and colon in the rat, the diaphragm in the rat, monkey, and human, Peyer's patches and the appendix in the rabbit, and human tonsils. Methods employed include scanning electron microscopy of lymphatic corrosion casts and tissues with or without treatment of alkali maceration technique, transmission electron microscopy of intact tissues, confocal microscopy in conjunction with immunohistochemistry to some lymphatic-specific markers (i.e., LYVE-1 and VEGFR-3), and light microscopy in conjunction with enzyme-histochemistry to 5'-nucleotidase. Some developmental aspects of the lymphatic vessels and lymphedema are also discussed.

Lymph circulation in the liver.

The liver produces a large amount of lymph, which is estimated to be 25 to 50 % of lymph flowing through the thoracic duct. The hepatic lymphatic system falls into three categories depending on their locations: portal, sublobular, and superficial lymphatic vessels. It is suggested that 80 % or more of hepatic lymph drains into portal lymphatic vessels, while the remainder drains through sublobular and capsular lymphatic vessels. The hepatic lymph primarily comes from the hepatic sinusoids. Our tracer studies, together with electron microscopy, show many channels with collagen fibers traversing through the limiting plate and connecting the space of Disse with the interstitial space either in the portal tracts, or around the sublobular veins. Fluid filtered out of the sinusoids into the space of Disse flows through the channels traversing the limiting plate either independently of blood vessels or along blood vessels and enters the interstitial space of either portal tract or sublobular veins. Fluid in the space of Disse also flows through similar channels traversing the hepatocytes intervening between the space of Disse and the hepatic capsule and drains into the interstitial space of the capsule. Fluid and migrating cells in the interstitial space pass through prelymphatic vessels to finally enter the lymphatic vessels. The area of the portal lymphatic vessels increases in liver fibrosis and cirrhosis and in idiopathic portal hypertension. Lymphatic vessels are abundant in the immediate vicinity of the hepatocellular carcinoma (HCC) and liver metastasis. HCCs expressing vascular endothelial growth factor-C are more liable to metastasize, indicating that lymphangiogenesis is associated with their enhanced metastasis.

A development of atheromatous plaque is restricted by characteristic arterial wall structure at the carotid bifurcation.

BACKGROUND: It is said atheromatous plaque is located very focally, but there have been few reports regarding this matter. Various aspects of the pathogenesis of the development of atheromatous plaque at the carotid bifurcation have previously been discussed. We have noted the correlation of plaque localization with characteristics of the cervical carotid artery wall. METHODS: Morphological and histopathologic changes in the carotid bifurcation were examined in 72 cadaver cases with or without atheromatous plaque. We determined the level at which the wall structure changed to muscular artery from elastic artery and analyzed its influence on the development of atheromatous plaque. RESULT: Atheromatous plaques at the distal site of the ICA extended within 0 to 37 mm from the carotid bifurcation. The proximal side of the CCA more than 5 mm away from the bifurcation was elastic artery, whereas the distal side of the ICA more than 15 mm from the bifurcation was muscular artery. The area of the carotid bifurcation between elastic artery and muscular artery was a transitional zone. Approximately 80% of them were located within 15 mm, and these areas were coincident with the transitional zone. CONCLUSION: Most atheromatous plaque was located in the transitional zone. The arterial wall structure is related to the development of atheromatous plaque at the cervical carotid bifurcation.

Bilateral variations of the vertebral arteries: the left originating from the aortic arch and the left and right entering the C5 transverse foramina.

During the dissection course for second year medical students at the University of Toyama in 2005, we encountered variations of the bilateral vertebral arteries: the left directly came off from the aortic arch as the third branch between the left common carotid artery and the left subclavian artery and entered the transverse foramen of C5, instead of C6, whereas the right originated from the right subclavian artery and entered the transverse foramen of C5. The present vertebral artery of each side was possibly formed by the 6th cervical intersegmental artery linked with the longitudinal anastomoses between the cervical intersegmental arteries. Detailed knowledge of vertebral artery variations is crucially important for surgical treatment of blood vessels in the brain, neck and chest.

Establishment and characterization of conditionally immortalized endothelial cell lines from the thoracic duct and inferior vena cava of tsA58/EGFP double-transgenic rats.

The basic biology of blood vascular endothelial cells has been well documented. However, little is known about that of lymphatic endothelial cells, despite their importance under normal and pathological conditions. The lack of a lymphatic endothelial cell line has hampered progress in this field. The objective of this study has been to establish and characterize lymphatic and venous endothelial cell lines derived from newly developed tsA58/EGFP transgenic rats harboring the temperature-sensitive simian virus 40 (SV40) large T-antigen and enhanced green fluorescent protein (EGFP). Endothelial cells were isolated from the transgenic rats by intraluminal enzymatic digestion. The cloned cell lines were named TR-LE (temperature-sensitive rat lymphatic endothelial cells from thoracic duct) and TR-BE (temperature-sensitive rat blood-vessel endothelial cells from inferior vena cava), respectively, and cultured on fibronectin-coated dishes in HuMedia-EG2 supplemented with 20% fetal bovine serum and Endothelial Mitogen at a permissive temperature, 33 degrees C. A temperature shift to 37 degrees C resulted in a decrease in proliferation with degradation of the large T-antigen and cleavage of poly (ADP-ribose) polymerase. TR-LE cells expressed lymphatic endothelial markers VEGFR-3 (vascular endothelial growth factor receptor), LYVE-1 (a lymphatic endothelial receptor), Prox-1 (a homeobox gene product), and podoplanin (a glomerular podocyte membrane mucoprotein), together with endothelial markers CD31, Tie-2, and VEGFR-2, whereas TR-BE cells expressed CD31, Tie-2, and VEGFR-2, but no lymphatic endothelial markers. Thus, these conditionally immortalized and EGFP-expressing lymphatic and vascular endothelial cell lines might represent an important tool for the study of endothelial cell functions in vitro.

Activation of MEK/ERK and PI3K/Akt pathways by fibronectin requires integrin alphav-mediated ADAM activity in hepatocellular carcinoma: a novel functional target for gefitinib.

We have shown that the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) inhibits the development of intrahepatic metastases of hepatocellular carcinoma CBO140C12, and EGFR transactivation by tumor necrosis factor-alpha is a possible target of gefitinib. In the present study, we focused on the fibronectin (FN)-dependent signaling pathway to further elucidate the antimetastatic activity of gefitinib in CBO140C12 cells. We initially observed that FN induced activation of extracellular signal-regulated kinase (ERK), p38 and Akt, as well as cell proliferation and CBO140C12 cell invasion. These responses were mediated by EGFR tyrosine kinase, because gefitinib inhibited these effects of FN. FN-induced ERK, p38 and Akt activation was partly blocked by the Arg-Gly-Asp (RGD)-pseudo-peptide FC-336, anti-alphav integrin antibody RMV-7, the broad-spectrum matrix metalloprotease inhibitor GM6001 and the broad spectrum a disintegrin and metalloprotease (ADAM) inhibitor TAPI-1. But these inhibitors had no effect on EGF-induced signaling pathways, suggesting that integrins and ADAM may be upstream components of EGFR in these responses. These results suggest that FN-induced activation of ERK, p38, Akt, cell proliferation and invasion was mediated, at least in part, via integrins, ADAM and EGFR, and that this FN-induced signaling pathway might be involved in the antimetastatic activity of gefitinib.

Surgical anatomy of the cervical carotid artery for carotid endarterectomy.

Carotid endarterectomy (CEA) is the main treatment for atherosclerotic plaque of the cervical internal carotid artery. The surgical anatomy of the carotid arteries was studied in the carotid triangle of 49 cadavers. The carotid bifurcation was located at the level of the lower third of C-3. The superior thyroid artery arose from the anterior wall of the external carotid artery in 70% of specimens and from the distal portion of the common carotid artery in 30%. The lingual artery arose as a separate trunk between the origins of the superior thyroid and facial arteries in 81% of specimens, with the facial artery from a common trunk in 18%, and with the superior thyroid artery in 1%. The occipital artery arose from the posterior aspect of the external carotid artery above the level of origin of the facial artery in 57% of specimens, between the origins of the facial and lingual arteries in 32%, and below the origin of the lingual artery in 11%. The origin of the occipital artery was positioned low and the distal portion of the occipital artery was crossed by the hypoglossal nerve in 20%. The ascending pharyngeal artery arose from the posterior wall of the external carotid artery above the level of origin of the lingual artery in 66% of specimens, below the origin of the lingual artery in 9%, from the proximal portion of the occipital artery in 19%, from the carotid bifurcation in 2%, and from the internal carotid artery in 2%. The branches of the external carotid artery are the key landmarks for adequate exposure and appropriate placement of cross-clamps on the carotid arteries. It is necessary to understand the surgical anatomy of the carotid arteries to carry out successful removal of plaque and minimize postoperative complications in a bloodless surgical field.

Morphological changes in capillaries in the ischemic brain in Wistar rats.

The microvasculature in the brain plays a vital role in the maintenance of brain perfusion, and fulfills the dynamic requirements of normal brain functions. It is well known that collateral circulation can be induced by ischemia in cerebral infarctions, but it is not known whether cerebral ischemia affects microvasculatures in the ischemic region. In the present study, we examined quantitatively serial changes in capillaries following bilateral common carotid artery ligation in Wistar rats. After the animals were perfused with tetramethylrhodamine isothiocyanate-labeled gelatin 3 h (n = 9), 1 day (n = 9), 7 days (n = 9) and 28 days (n = 9) after the ligation, capillary diameters in the brain sections were measured with a confocal laser-scanning microscope. Capillary diameters of the cerebellum did not differ among all groups, while those in the ischemic regions decreased significantly 3h after the ligation (p<0.01), thereafter gradually returned toward the baseline level, and became significantly larger (168% of the control) 28 days after the ligation (p< 0.01). The density of capillaries in the frontal and parietal cortices increased approximately to 1.3-fold of those of the control level 28 days after the ligation. Transmission electron microscopy showed that the mean ratio of the inner diameter to the outer diameter of capillaries in the frontal cortex became significantly greater 28 days after the ligation (p<0.05). Our data indicate that capillaries dilate in the ischemic brain region in the chronic phase of cerebral ischemia. It is also suggested that neovascularization occurs in the ischemic brain region.

Three-dimensional architecture of elastin and collagen fiber networks in the human and rat lung.

Collagen and elastin fibers are the major components of the lung connective tissue, but their spatial organization has not been well documented. We have demonstrated the three-dimensional architecture of collagen and elastin fiber networks in the human and rat lung using scanning electron microscopy. These networks in their original forms were extracted by an alkali-water maceration technique and a formic acid treatment, respectively. The collagen fibers formed a continuum extending throughout the lung and pleura. They were condensed in the alveolar mouth and subdivided into smaller fibers in the alveolar septa, thus forming basket-like networks. Sizes of the alveolar pores in the collagen fiber network of the alveolar septa became larger with age. In the collapsed lung, collagen fibers in the alveolar mouths and septa took on wavelike configurations, while in the inflated lung they became straight. The elastin fibers also formed a continuum, rich in the alveolar mouths and poor in the alveolar septa, were quite straight without any wavelike configuration. Transmission electron microscopy showed that collagen and elastin fibers were intermingled, suggesting that both fiber systems may act as parallel mechanical elements to stress or strain applied. Our results suggest that at low levels of strain the wavy collagen fibers are easily extended to allow alveolar mouths and alveoli to expand, with most of the stress being borne by adjacent elastin fibers, while at higher levels collagen fibers become straight and limit any further distension of alveolar ducts and alveoli. The elastin fiber continuum appears to permit the lung to effectively recoil or retract. The present study has also shown that alveolar pores enlarge with age, suggesting that collagen remodeling may be related to the pathogenesis of emphysema.

Origins and pathways of fluid entering sublobular lymphatic vessels in cat livers.

The liver, which produces a large volume of lymph, has a lymphatic system which can be classified into three categories: portal, sublobular, and superficial lymphatic vessels. As little is known about the origin and pathways of sublobular lymph, this study demonstrates pathways of interstitial fluid flowing into sublobular lymphatic vessels. Livers from cats whose thoracic ducts were either ligated or non-ligated were examined by light-, transmission electron- and scanning electron-microscopy (SEM). Complete ligation of the thoracic duct caused significant dilation of the hepatic sinusoids, the space of Disse, and channels passing through the limiting plate. Sublobular interstitial space and sublobular lymphatic vessels were also expanded. The channels between hepatocytes forming the limiting plate contained collagen fibers, and connected the space of Disse with a sublobular interstitial space. The alkali-water maceration/SEM confirmed that collagen fibers traversing the layer of the limiting plate independently of blood vessels connected collagen fibers in the space of Disse with those in the sublobular space. Complete ligation of the thoracic duct also showed an accumulation of mast cells and plasma cells in the sublobular interstitial space. Our data suggest that fluid in the space of Disse flows along collagen fibers in channels traversing the limiting plate as well as those along the sinusoids and central veins that drain into sublobular veins, and enters the sublobular interstitial space to finally lead into sublobular lymphatic vessels. Our study has also shown that hepatic lymphostasis causes the accumulation of mast cells and plasma cells in the sublobular interstitial space, which may be involved in lymphangiogenesis and fibrogenesis.