Biomedical subjects

A Nakayama

Publications and source records attributed to A Nakayama.

At least 37 records · Page 2Linked to original sources

PubMed2000

Tissue-specific carcinogenesis in transgenic mice expressing the RET proto-oncogene with a multiple endocrine neoplasia type 2A mutation.

Germ line mutations of the RET proto-oncogene are responsible for the development of multiple endocrine neoplasia type 2A (MEN 2A), an inherited cancer syndrome characterized by medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia. To study the mechanism of tissue-specific tumor development by RET with a MEN2A (cysteine 634-->arginine) mutation, we generated transgenic mice by introducing the RET-MEN2A gene fused to Moloney murine leukemia virus long terminal repeat. Expression of the transgene and its product was detected at variable levels in a variety of tissues including thyroid, heart, liver, colon, parotid gland, and brain. All of 29 mice analyzed developed thyroid C-cell hyperplasia or medullary carcinoma, accompanying high levels of serum calcitonin. In addition, development of mammary or parotid gland adenocarcinoma was observed in one-half of the transgenic mice. RET dimerization and its complex formation with Shc and Grb2 adaptor proteins were detected in tumor tissues. Unexpectedly, no tumor formation was found in other tissues despite RET-MEN2A expression where RET dimerization was undetectable. Because these tissues but not tumors expressed glial cell line-derived neurotrophic factor family receptor alpha (GFR alpha) at high levels, this suggested that GFR alpha expression may interfere in the dimerization of the RET-MEN2A mutant proteins, leading to tissue-specific tumor development in vivo.

3T3 Cells↗

PubMed2000

Effects of cetyltrimethylammonium bromide on reactions catalyzed by maxizymes, a novel class of metalloenzymes.

We demonstrated previously that some shortened forms of hammerhead ribozymes had high cleavage activity that was similar to that of the wild-type parental hammerhead ribozyme. Moreover, the active species appeared to form dimeric structures with a common stem II (in order to distinguish monomeric forms of conventional minizymes that have low activity from our novel dimers with high-level activity, the latter very active short ribozymes were designated 'maxizymes'). The dimers can be homodimeric (with two identical binding sequences) or heterodimeric (with two different binding sequences). In the case of heterodimers, they are in equilibrium with inactive homodimers. In this study, we investigated the effects of cationic detergent, cetyltrimethylammonium bromide (CTAB), on reactions catalyzed by a variety of maxizymes. The slope of close to unity in profiles of pH versus rate demonstrated that the deprotonation was important in catalysis and that the rate-limiting chemical step was followed in these reactions. Addition of appropriate amounts of CTAB enhanced the activity of a variety of maxizymes. The activity of our least stable, least active maxizyme was enhanced 100-fold by CTAB. Thus, CTAB effectively enhanced the conversion of kinetically trapped inactive conformations to active forms. Moreover, we suggest that the activity and specificity of catalytic RNAs in vivo might be better estimated if their reactions are monitored in vitro in the presence of appropriate amounts of CTAB.

Base Pairing↗

PubMed2000

High expression of glycogen-debranching enzyme in Escherichia coli and its competent purification method.

Glycogen-debranching enzyme (GDE) gene from Saccharomyces cerevisiae was cloned and expressed into Escherichia coli. A 99.3% homology was found between the nucleotide sequences of GDE gene harbored in the recombinant E. coli plasmid (pTrc99A) and the open reading frame (902039-906646 position) of the 4608-bp fragment of S. cerevisiae chromosome XVI. We investigated the best conditions for GDE expression. When the cultivation temperature of recombinant E. coli strains was lowered to 25 degrees C and the isopropyl-beta-d-thiogalactopyranoside (IPTG) concentration used for induction was decreased to as low as 0.02 mM, a total of about 33 mg of recombinant GDE can be isolated from a liter culture as estimated by amylo-1,6-glucosidase activity. Consecutively, we developed a new method for purifying GDE. The method requires only a single-step purification via beta-cyclodextrin-immobilized Sepharose 6B (beta-CD Sepharose 6B) affinity chromatography and renders a 90% recovery of the enzyme. Moreover, the purified recombinant GDE is a homogeneous protein and possesses the same characteristics as those of S. cerevisiae. With the highly expressed GDE in recombinant E. coli and a rapid and effective purification method, we successfully resolved the hurdle always faced for obtaining an ample amount of purified GDE. The availability of GDE, hence, may allow advancement on GDE studies and provide new prospects for GDE on biotechnological application.

Amino Acid Sequence↗

PubMed2000

MELAS with the mitochondrial DNA 3243 point mutation: a neuropathological study.

We performed a neuropathological examination of the central nervous system from seven autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Five of the seven cases were confirmed to have the mitochondrial DNA (mtDNA) 3243 point mutation. In addition to the changes reported previously, diffuse atrophy of the cerebral and cerebellar cortices, diffuse gliosis of cerebral and cerebellar white matter, and cactus formation of Purkinje cells were observed. Electron microscopy revealed accumulation of mitochondria in the cactus formations. These lesions are common in MELAS with the mtDNA 3243 point mutation, but cannot be explained solely by mitochondrial angiopathy, and suggest that intrinsic mitochondrial malfunction contributes to neuronal damage in MELAS pathology. Moreover, the pathological changes observed in the cerebellum suggest that cerebellar function should be evaluated more carefully at the clinical level.

Adult↗

PubMed2000

Anatomical keys and pitfalls in living donor liver transplantation.

The surgery of living donor liver transplantation is more technically challenging than cadaveric whole liver transplantation and liver resection for the treatment of various pathological conditions. It requires a thorough understanding of the intra- and extra-hepatic anatomical relationships between the portal vein, hepatic artery, biliary tract, and hepatic vein, and also their respective contributions to liver physiology. Although a precise understanding of general anatomical principles is the key to correctly performing living donor liver transplantation procedures, anatomic anomalies are often present, and the means of detecting them and the surgical methods of coping with them represent technical challenges. In this monograph, we describe the anatomical keys and pitfalls of living donor liver transplantation surgery based on our own experience with more than 1800 hepatectomies, and 150 living donor liver transplantations. We also elaborate on techniques of selective intermittent vascular occlusion and their teleological and practical background.

Bile Ducts↗

PubMed2000

Relationship between copper, zinc and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma.

BACKGROUND/AIM: Accumulation of copper (Cu) in hepatocellular carcinoma (HCC), especially in small tumors, is greater than that in the surrounding liver parenchyma. Metallothionein (MT) is considered to be present as Cu-MT, Zn,Cu-MT or Zn-MT. The aim of this study was to determine the presence and localization of Cu-MT and Zn-MT in HCC and surrounding liver parenchyma. METHODS: In 16 HCC patients, surgically resected specimens including HCC and surrounding liver parenchyma were evaluated. RESULTS: The level of Cu present in small HCC (<4 cm in diameter) was significantly greater than that in the surrounding liver parenchyma (p<0.05). However, the level of Cu in large HCC (>4 cm in diameter) was similar to that in the surrounding liver parenchyma. Analysis by Sephadex G-75 gel filtration revealed that the peak fraction due to Cu was identical to that due to MT in 14 (87.5%) of 16 HCC, the peak fraction due to Cu and Zn was identical to that due to MT in 2 (12.5%) HCC, and the peak fraction due to Zn was identical to that of MT in none of 16 HCC. CONCLUSIONS: Accumulation of Cu in small HCC, in which Cu was present as Cu-MT or Zn, Cu-MT, was greater than that in the surrounding liver parenchyma. Cu accumulation and the presence of MT in the liver may be related to carcinogenesis of HCC, because of the similarity of these findings in the experimental data of Long-Evans rats with a cinnamon-like coat color who develop HCC spontaneously.

Adult↗

PubMed2000

Underexpression of neural cell adhesion molecule and neurotrophic factors in rat brain following thromboxane A(2)-induced intrauterine growth retardation.

Intrauterine growth retardation (IUGR) often results in clinical neurodevelopmental disorders. To clarify the influence of uteroplacental insufficiency on central nervous system development, we have created a model of IUGR in rats using maternal administration of synthetic thromboxane A(2). We investigated expression patterns of neural cell adhesion molecule (NCAM) and reelin in this model by semiquantitative competitive polymerase chain reactions. On postnatal day 2, NCAM expression was decreased in rat cerebral cortex, and reelin expression was decreased in hippocampus from levels in controls without maternal thromboxane exposure. No significant differences in NCAM expression were seen in hippocampus, nor did reelin expression differ in cerebral cortex between control and IUGR groups. We also examined expression of two neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). In cerebral cortex the IUGR group showed less BDNF and NT-3 expression than controls. Delay of neuronal migration and histological changes observed in our IUGR rats may be related to altered expression of these molecules.

Animals↗

PubMed2000

Region-dependent disappearance of vinblastine in rat small intestine and characterization of its P-glycoprotein-mediated efflux system.

This study was aimed to characterize the absorption behavior of vinblastine (VLB), a well-known substrate of P-glycoprotein (P-gp), from rat small intestine, especially focusing on the regional-dependence of its efflux mediated by P-gp. VLB disappeared from duodenal and ileal loops of male Wistar rats fairly rapidly (30-60% in 30 min). In contrast, its disappearance from the jejunal loop was almost negligible and in some rats >100% of the jejunal dose was recovered. The radioactivity derived from [3H]VLB, which was absorbed from duodenum and ileum, was detected in the jejunal region. The jejunal appearance of radioactivity was increased when unlabeled VLB was present in the region in advance. The basolateral-to-apical transport of [3H]VLB across Caco-2 cell monolayers was greater when unlabeled VLB was added to the apical medium than when VLB-free buffer was applied to the apical side. When verapamil or cyclosporin A, potent modulators of P-gp, was added to the apical medium together with unlabeled VLB, enhanced basolateral-to-apical transport of [3H]VLB was disappeared. It is suggested that VLB absorption is strongly restricted by P-gp, especially in the jejunal region of the rat small intestine, and that the secretory transport via intestinal P-gp may be subject to trans-stimulation. Moreover, intravenously administered methylprednisolone and intramuscularly administered progesterone significantly enhanced the absorption of VLB, suggesting that parenterally administered P-gp modulators could influence the intestinal absorption of P-gp substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Effects of static magnetic field on dissolved oxygen levels in aqueous solutions containing copper(II), iron(II), and heme iron(III) complexes.

Trace metal ions like copper and iron play important roles such as binding, transport, and storage of molecular dioxygen in a wide variety of living systems. The effects of static magnetic fields on the dissolved oxygen (DO) levels in aqueous solutions containing copper(II), iron(II), and their bioligand complexes were investigated. The DO levels in aqueous solutions containing the stable copper(II) complexes such as Cu(II)-Arg, His, GGH and BSA systems increased when the applied magnetic field increased. However, the magnetic field-dependent changes of DO levels were not observed by the unstable Cu(II) complexes such as Cu(II)-Lys, Gly, Gly-His and Hb systems. Especially, DO levels in aqueous solutions containing Cu(II)-His or BSA complexes increased 1.1-fold to those of the control levels at 200 mT of the applied magnetic field. In contrast, DO levels in aqueous solutions containing iron(II) decreased significantly when the magnetic field increased, which in turn promoted the Fe(II)-induced lipidperoxidation in liposomes. DO levels in aqueous solutions containing Fe(II)-His complex decreased 0.9-fold to those of the control levels at 200 mT of the magnetic field for 30 min. While, the magnetic field-dependent changes of DO levels increased significantly in aqueous solutions containing heme iron(III)-complexes, suggesting that heme iron(III) is reduced to heme iron(II) under exposure of the magnetic field and thus the incorporation of molecular dioxygen in aqueous solutions is enhanced. These results indicate that the effect of the magnetic fields on DO levels in aqueous solutions must be discussed in terms of a concept: formation of intermediate complexes consisting of molecular dioxygen-copper or iron and bioligands under physiological conditions and the following enhancement of incorporation of molecular dioxygen by the complexes, that in turn activate the molecular dioxygen.

Journal Article↗

PubMed2000

Varied B-cell immunophenotypes of Hodgkin/Reed-Sternberg cells in classic Hodgkin's disease.

AIMS: Recent analyses have suggested that Hodgkin's or Reed-Sternberg (HRS) cells in most cases of classic Hodgkin's disease are derived from germinal centre B-cells. However, there is controversy over which B-cell antigens are expressed in HRS cells. METHODS AND RESULTS: We studied 51 cases of classic Hodgkin's disease to immunohistochemically characterize HRS cells for pan-B-cell markers and specific markers for plasma cells. HRS cells expressed CD20 (L26) in 18 cases (35%), CD19 (B4) in nine (18%) and CD79a (mb-1) in 13 (25%). Furthermore, HRS cells were positive for CD138 (B-B4) in 24 cases (45%) and for PCA-1 in 24 (45%). In 41 (80%) cases, HRS cells expressed more than one B-cell marker. We then subclassified cases into those positive for plasma cell markers (n = 27) (group 1) and those negative for them (n = 24) (group 2). The average age in group 1 (40 years) was younger than in group 2 (54 years) (P < 0.05). The percentage of nodular sclerosis (NS) subtype in group 1 (52%) was 1.5 times greater than in group 2 (33%) (P < 0.05). With regard to Epstein-Barr virus encoded small RNA (EBER) in-situ hybridization, 14 cases (64%) were positive in group 2, but only seven cases (31%) were positive in group 1 (P < 0.025). CONCLUSION: In most cases of classic Hodgkin's disease, HRS cells expressed later stage of B-cell development. We consider that two different clinicopathological groups may correlate with the two different expressions of B-cell markers.

Adolescent↗

PubMed2000

Lymphomatous features of aggressive NK cell leukaemia/lymphoma with massive necrosis, haemophagocytosis and EB virus infection.

AIMS: Aggressive natural killer (NK) cell leukaemia will be categorized as a distinct entity in the new WHO classification of malignant lymphomas. However, its non-leukaemic features remain unclear. We therefore investigated the morphological and immunophenotypic features of this lymphoma. METHODS AND RESULTS: Four cases with aggressive NK cell lymphoma were morphologically and immunohistochemically studied. All cases followed an aggressive course with death occurring within about 3 months of initial presentation. In these cases, the neoplastic cells disseminated throughout systemic lymph nodes and invaded various tissues and organs. The lymphoma cells were large cells showing nuclear irregularity and a pattern of sinusoidal invasion in lymph nodes. Apoptosis and coagulation necrosis were both frequently observed. Haemophagocytosis was observed in all cases. Neoplastic cells in paraffin-embedded tissue specimens from these patients had CD3(CD3epsilon)+ CD56(123C3)+ granzyme+ TIA-1+ EBERT+ CD43(MT1)- CD45RO(UCHL-1)- CD57(Leu7)- CD20(L26)- phenotypes. In the two cases where tissue was available for immunohistochemical study in frozen sections, neoplastic cells showed CD56(Leu19)+ perforin+ Fas ligand(FasL)+ CD2(Leu5b)- CD3(Leu4)- CD4(Leu3)- CD5(Leu1)- CD7(Leu9)- CD8(Leu2)- betaF1- TCRdelta1- phenotypes. CD16(Leu11b) was positive in one case. CONCLUSIONS: : Natural killer cell lymphomas appear to represent a non-leukaemic counterpart of aggressive natural killer cell leukaemia, a relationship similar to that in adult T-cell leukaemia/lymphoma. Awareness and diagnosis of this aggressive lymphoma is important because of its fulminant course.

Adult↗

PubMed2000

Plasma levels of granulocyte elastase-alpha1-proteinase inhibitor complex in children with hemolytic uremic syndrome caused by verotoxin-producing Escherichia coli.

BACKGROUND: Activated neutrophils play an important role in the pathogenesis of renal injury in humans and in experimental models of hemolytic uremic syndrome (HUS). To evaluate the clinical significance of the circulating granulocyte elastase-alpha1-proteinase inhibitor complex (GEPIC), which is a marker of neutrophil activation, we investigated the plasma concentrations of GEPIC in children with hemolytic uremic syndrome (HUS) associated with verotoxin-producing Escherichia coli (VTEC), VTEC gastroenteritis without HUS and in normal controls. METHODS: Of 22 children (1-19 years of age; mean age 5.5 years) with VTEC infection, nine were diagnosed with HUS. Plasma GEPIC, soluble thrombomodulin (sTM) and thrombin-antithrombin-III complex (TAT) levels were measured by ELISA. RESULTS: The number of polymorphonuclear leukocytes and the levels of plasma GEPIC in patients with HUS were significantly higher than those in non-HUS (9850+/-5091 vs. 5278+/-3327 /microL, P<0.05; 432.1+/-211.7 vs. 188.3+/-117.0 ng/mL, P<0.01) or control subjects (9850+/-5091 vs. 4728+/-1977 /microL, P<0.05; 432.1+/-211.7 vs. 105.9+/-51.1 ng/mL, P<0.001). Furthermore, plasma GEPIC levels showed a positive correlation with sTM (r = 0.522; P<0.01), a marker of endothelial cell injury, and TAT (r = 0.594; P<0.01), a marker of thrombin activity. CONCLUSIONS: These results suggest that an increase in circulating GEPIC levels in patients with VTEC-associated HUS may be related to endothelial injury, which may possibly lead to a more severe episode of this disease.

Adolescent↗

PubMed2000

Urachal tuberculosis.

BACKGROUND: We report on an extremely rare case of urachal tuberculosis that was confirmed using a polymerase chain reaction test of paraffin-embedded material. METHODS/RESULTS: A 62-year-old man presented with pollakiuria. With a diagnosis of urachal abscess, the patient underwent en bloc resection of the cystic mass. A bacterial culture test of the content showed no organism. The histopathologic findings suggested urachal tuberculosis. The AMPLICOR polymerase chain reaction test by using paraffin-embedded sections revealed the existence of Mycobacterium tuberculosis in the resected tissue. The only positive finding in systemic screening examinations for tuberculosis was old tuberculosis scars in the upper right lung. It was supposed that hematogeneous spreading from the lung lesion may result in urachal tuberculosis after a long latent period. CONCLUSIONS: Although urachal tuberculosis is an extremely rare condition, tuberculosis must always be kept in mind when observing any infectious diseases.

Abscess↗

PubMed2000

Elevated tissue factor circulating levels in children with hemolytic uremic syndrome caused by verotoxin-producing E. coli.

BACKGROUND: Microvascular thrombosis in the kidney plays an important role in the pathogenesis of hemolytic uremic syndrome (HUS). Tissue factor (TF), present on the vascular surface of endothelial cells, binds factor VIIa. The complex initiates the coagulating cascade by activating factors X and IX. PATIENTS AND METHODS: In cases of HUS associated with verotoxin-producing E. coli (VTEC) infection, VTEC gastroenteritis without HUS and normal controls, we measured plasma concentrations of TF and tissue factor pathway inhibitor (TFPI) to evaluate their clinical significance. In children with non-HUS chronic renal failure (CRF), the TF levels were also measured as another control group. RESULTS: In the acute phase of HUS, plasma levels of TF and TFPI were significantly elevated, then returned to normal range in the recovery phase. The TF levels were closely correlated with the thrombin antithrombin-III complex, a marker of thrombin activity in circulating blood, and with creatinine clearance (Ccr). Furthermore, a positive correlation was noted between plasma TF levels and plasma soluble thrombomodulin (sTM) levels, which is a marker of endothelial cell injury. The influence of decreased excretion from damaged kidneys should be considered since a definite lot correlation was observed between plasma TF levels and Ccr in children with non-HUS CRF. CONCLUSION: From these findings, we concluded that elevated TF circulating levels may also play an important role in blood-clotting activation observed in VTEC-HUS patients, and may also be a useful marker for renal damage.

Case-Control Studies↗

PubMed1999

Specificity of novel allosterically trans- and cis-activated connected maxizymes that are designed to suppress BCR-ABL expression.

Chronic myelogenous leukemia (CML) is associated with the presence of the Philadelphia chromosome, which is generated by the reciprocal translocation of chromosomes 9 and 22. In the case of L6 (b2a2) mRNA, it is difficult to cleave the abnormal mRNA specifically because the mRNA includes no sequences that can be cleaved efficiently by conventional hammerhead ribozymes near the BCR-ABL junction. We recently succeeded in designing a novel maxizyme, which specifically cleaves BCR-ABL fusion mRNA, as a result of the formation of a dimeric structure. As an extension of our molecular engineering of maxizymes, as well as to improve their potential utility, we examined whether an analogous conformational change could be induced within a single molecule when two maxizymes were connected via a linker sequence. An active conformation was achieved by binding of the construct to the BCR-ABL junction in trans, with part of the linker sequence then acting as an antisense modulator in cis (within the complex) to adjust the overall structure. Results of studies in vitro in the presence of cetyltrimethylammonium bromide (CTAB) (but not in its absence) suggested that a certain kind of connected maxizyme (cMzB) might be able to undergo a desired conformational change and, indeed, studies in vivo confirmed this prediction. Therefore, we successfully created a fully functional, connected maxizyme and, moreover, we found that the activity and specificity of catalytic RNAs in vivo might be better estimated if their reactions are monitored in vitro in the presence of CTAB.

Allosteric Regulation↗

PubMed1999

Characterization of the promoter region of the human RFP gene.

The RFP gene encodes a Ring finger protein that has a tripartite motif consisting of a Ring finger, a B-box finger and a coiled-coil domain. In the present study, we cloned and characterized the promoter region of the human RFP gene. The nucleotide sequence of the promoter was GC-rich and had no typical TATA and CAAT boxes. Instead, it contained one AP2 and two Sp1 binding sites within 100 base pairs upstream of the transcription initiation site. Analysis by the luciferase assay revealed that the activity of this promoter region is very strong in both human and mouse cell lines, although the activity in human cells was approximately 10-15 fold higher than that in mouse cells. In addition, the AP2 and Sp1 binding sites appeared to synergistically function for the promoter activity. Thus, the promoter of the RFP gene could be useful for high levels of expression of various genes in culture cells.

3T3 Cells↗

PubMed1999

Molecular analysis of mutations induced by a benzene metabolite, p-benzoquinone, in mouse cells using a novel shuttle vector plasmid.

Human population has been continually exposed to benzene which is present in our environment as an essential component of petroleum. p-Benzoquinone (p-BQ) is one of the benzene metabolites and is thought to be an ultimate toxic or carcinogenic substance. For molecular analysis of carcinogen-induced mutations in mouse cells, we constructed a new shuttle vector plasmid pNY200 that has supF gene as a target of the mutations and replicates in mouse and in Escherichia coli cells. In p-BQ-treated pNY200 propagated in mouse cells, base substitutions were induced predominantly at G:C sites, and the major mutation was G:C-->A:T transition. Many tandem base substitutions were also induced at CC:GG sequences. By a postlabeling analysis and a polymerase stop assay, we confirmed that p-BQ adducts formed in DNA and mutation sites roughly correspond to the sites where the adducts were formed. Comparing data of pNY200 in mouse cells with those of the similar shuttle vector plasmid pMY189 in human cells should be important for extrapolation of data from mouse to human, because carcinogenicity of chemicals is tested in mice.

Animals↗

PubMed1999

Relation between lymphatic vessel diameter and clinicopathologic parameters in squamous cell carcinomas of the oral region.

BACKGROUND: In an attempt to determine the mechanism of cervical lymph node metastases, the authors studied the relation between lymphatic vessels in or around tumor tissue and lymph node metastases in patients with primary squamous cell carcinoma (SCC) of the oral region by enzyme histochemistry using 5'nucleotidase-alkaline phosphatase. METHODS: The subjects were 23 patients who had biopsy proven oral SCC. After enzyme histochemical staining, the cross-sectional dimension (referred to as diameter) of the lymphatic vessels were measured and analyzed in relation to the T classification of the tumor, degree of tumor differentiation, and mode of invasion. RESULTS: The average diameter of the lymphatic vessels in or around tumor tissue was significantly greater than that in tumor free tissue (P < 0.01). The mode of invasion correlated significantly with the lymphatic vessel diameter (P < 0.01). The diameter did not correlate significantly with the T classification (P range, 0.135-0.254) or tumor differentiation (P = 0.274). The following relation was found between the incidence of cervical lymph node metastases and the mode of invasion: 40.0% of Grade 2 tumors were positive for metastases, 71.4% of Grade 3 tumors were positive, and 75.0% of Grade 4 tumors were positive (grading was according to Jakobsson's classification). CONCLUSIONS: Of the factors evaluated in this study, only the mode of invasion correlated significantly with the diameter of the lymphatic vessels. Although other studies have shown that tumor thickness and perhaps even perineural and blood vessel invasion may be equally important, the findings of the current study suggest that both lymphatic vessel diameter and the mode of invasion may be important factors in the prediction of cervical lymph node metastases.

5'-Nucleotidase↗