Biomedical subjects

S Seki

Publications and source records attributed to S Seki.

At least 19 recordsLinked to original sources

PubMed2006

Multiple interleukin-18 injections promote both mouse Th1 and Th2 responses after sublethal Escherichia coli infection.

Interleukin (IL)-18 is considered to induce exclusively the Th1 immune response but not the Th2 response in the presence of adequate IL-12 stimulation in bacterial infections. However, we demonstrate herein that multiple IL-18 injections to the mice not only enhance the early Th1 response but also stimulate the Th2 response later after viable Escherichia coli infection. Multiple IL-18 injections (three alternate-day injections) raised the serum interferon (IFN)-gamma level at 6 h and serum Th2 cytokine levels, such as IL-4, IL-10 and IL-13, at 48 h after infection, while a single IL-18 injection increased only the serum IFN-gamma level. Depletion of mouse CD4+ cells suppressed the IL-18-induced Th2 cytokines, IL-4, IL-10 and IL-13. In contrast, depletion of natural killer (NK)1.1+ cells reduced the IFN-gamma and IL-13 levels. Moreover, multiple IL-18 injections up-regulated the serum IgM level at 72 h after infection while a single IL-18 injection did not. Interestingly, neutralization of IL-4 but not IFN-gamma partially suppressed the increased serum IgM. Liver mononuclear cells (MNCs) from the mice treated with multiple IL-18 injections significantly increased more production of not only IFN-gamma but also Th2 cytokines and IgM by in vitro lipopolysaccharide (LPS) stimulation than those from the phosphate-buffered saline (PBS)-treated mice, while liver MNCs from the single IL-18-injected mice also increased IFN-gamma production but significantly suppressed IL-4 and IgM production compared to those from the PBS-treated mice. Our findings suggest that multiple injections of IL-18 up-regulate both the cellular and humoral innate immunities, thereby enhancing host defence against bacterial infections.

Animals↗

PubMed2005

Five-year survival of patients with hepatocellular carcinoma treated with laparoscopic microwave coagulation therapy.

BACKGROUND AND STUDY AIM: Hepatocellular carcinomas (HCCs) that are located near the liver surface are difficult to treat with percutaneous locoregional therapies, so we have performed laparoscopic microwave coagulation therapy (LMCT) for these HCCs. We assessed the long-term survival of patients with HCCs treated with LMCT, the factors related to their survival, and the rates and causes of local and distant recurrences. PATIENTS AND METHODS: Participants were 68 patients with HCC treated in the past 8 years with LMCT under local or general anesthesia. LMCT was done using microwave electrodes with tips ranging from 15 to 45 mm in length; the effectiveness of LMCT was confirmed using contrast-enhanced computed tomography (CT) within 2 weeks of the LMCT procedure while patients were still in hospital, and within 1-3 months after the procedure in an outpatient setting; and the follow-up study was performed periodically by CT, ultrasonography, or magnetic resonance imaging (MRI) in addition to estimation of alpha fetoprotein. Factors contributing to survival were analyzed statistically. RESULTS: The mean lengths of the major and minor axes of the 71 HCC nodules in 68 patients were 20 mm and 18 mm, respectively, and the mean lengths of the major and minor axes of the coagulated areas were 43 mm and 29 mm, respectively. At dynamic CT after the LMCT procedure, treatment in 62 of the 68 patients (91%) was judged to have been completely effective; the remaining six patients underwent additional therapy while still in hospital. Eight of the 68 patients (12%) had local recurrences, 39 of them (57%) had distant recurrences, and 21 of them (31%) had no recurrence up to December 31, 2003. A total of 14 patients (21%) died during the 16-56 months after LMCT. When the survival rate was assessed for all patients treated with LMCT, 1-year survival was 97 %, 3-year survival was 81%, and 5-year survival was 43%. Whether the therapy was for primary or secondary HCC strongly influenced survival. CONCLUSIONS: LMCT is a useful modality in clinical practice for treatment of HCC nodules located near the liver surface, and it can be safely performed, in its entirety, under direct visual guidance.

Aged↗

PubMed2005

Analysis of the susceptibility of CD57 T cells to CD3-mediated apoptosis.

After stimulation with anti-CD3 antibody in vitro, CD57(+) T cells showed a greater susceptibility to apoptosis than CD57(-)alphabetaT cell receptor (TCR)(+) T cells (regular alphabeta T cells). The apoptotic fraction of CD57(+) T cells showed an increased production of active caspase-3. An increase in both Fas expression and Fas-ligand (FasL) production was also observed in CD57(+) T cells, whereas the expression of survivin was suppressed in CD57(+) T cells compared to that of regular alphabeta T cells. CD57(+) T cells display a biased expansion of a few Vbeta T cell fractions in individuals, but such Vbeta T cells were not specifically susceptible to CD3-mediated apoptosis. The TCR expression level of CD57(+) T cells was much lower than that of regular T cells and anti-TCR antibody stimulation induced a smaller apoptotic proportion of CD57(+) T cells than did anti-CD3 antibody. Although the CD3epsilon expression levels were similar in both T cell subsets, the CD3zeta level of CD57(+) T cells was significantly higher than that of regular T cells. These results suggest that several apoptotic and anti-apoptotic molecules are involved in the CD3-induced apoptosis of CD57(+) T cells and raise the possibility that the imbalance in expression of the CD3epsilon and CD3zeta chains may also contribute to the susceptibility of CD57(+) T cells to undergo apoptosis.

Adult↗

PubMed2005

A defective Th1 response of the spleen in the initial phase may explain why splenectomy helps prevent a Listeria infection.

Listeria monocytogenes (Listeria) are known to grow and proliferate in the liver while a splenectomy induces host resistance against a Listeria infection despite the fact that a splenectomy inhibits the Th1 response. Therefore, the mechanism by which a splenectomy helps to prevent the growth of Listeria still remains to be elucidated. After an i.v. challenge of Listeria (1 x 10(6) CFU) in C57BL/6 mice, Listeria rapidly increased in the spleen but not in the liver until 48 h. However, after this initial phase, Listeria remarkably grew in the liver. In contrast, when the mice received a splenectomy beforehand, no remarkable growth of Listeria in the liver was observed after Listeria challenge despite the fact that serum IFN-gamma and IL-12 levels at 24 h after Listeria challenge were significantly lower than those in the sham mice. However, the liver leucocytes from mice by 6 h after infection produced a substantial amount of IFN-gamma while spleen MNC did not, whereas spleen leucocytes at 24 h after Listeria challenge did. Consistently, the IFN-gamma and IL-12 levels in the tissue homogenates of the spleen were significantly lower than in those of the liver until 6 h after infection. This defective spleen Th1 response in the early phase of Listeria infection was corrected by an IL-18 i.p. injection just after the Listeria challenge. Our findings suggest that Listeria exploit the defective Th1 environment of the spleen in the initial phase and afterwards overcome the host defense mechanism of the liver.

Animals↗

PubMed2005

[Intrapulmonary aberrant needle; report of a case].

Intrapulmonary aberrant needles are rarely encountered in clinical practice. An intrathoracic aberrant needle should be always surgically removed as soon as possible. We report a case of an intrapulmonary aberrant needle removed with video-assisted thorascopic surgery (VATS) and briefly review the literature. A 47-year-old man referred to us for chest discomfort was found to have an intrapulmonary aberrant needle at the right middle lobe by chest X-ray and computed tomography (CT). We tried simple extraction under thoracoscopy, but a residual fragment was recognized by intraoperative X-ray after the removal of the needle from the surface of the lung. We searched for the residual fragment by real-time fluoroscopic examination. Partial resection was performed to remove the residual needle fragment at the right lower lobe. The postoperative course was uneventful and the man was discharged on the postoperative day 10. Intraoperative chest X-ray is always necessary before closing the chest to avoid leaving the residual fragments in the lung. The real-time fluoroscopy is useful to search for the residual fragment.

Foreign Bodies↗

PubMed2004

Effects of ribavirin combined with interferon-alpha 2b on viral kinetics during first 12 weeks of treatment in patients with hepatitis C virus genotype 1 and high baseline viral loads.

This study aimed to find how ribavirin increases viral disappearance in patients with hepatitis C virus (HCV) of genotype 1 and high baseline viral loads (>5.0 x 10(5) copies/mL) when given with interferon (IFN). Using the real-time quantitative polymerase chain reaction, we measured serum HCV in 20 patients during the first 12 weeks of therapy with IFN-alpha 2b and ribavirin. Controls were 10 similar patients given IFN-alpha 2b alone. IFN-alpha 2b was given at 6 MU daily for 2 weeks, and then three times weekly. Ribavirin was given at 600 or 800 mg daily. Serum HCV RNA decreased rapidly in the first phase, during the first 24 h of therapy (day 0), and more slowly in the early second phase (days 1-14). The median decrease was by 1.41 and 0.078 log 10/day in these two phases in the combination therapy group, and 0.90 and 0.081 log 10/day in the monotherapy group. The difference between groups in the first phase was not significant (P = 0.24), nor was that in the next phase (P = 0.68). Later in the second phase, between days 14 and 84, the median decrease was larger in the combination therapy group (0.030 log 10/day) than in the monotherapy group (0.015 log 10/day, P = 0.035). In patients with HCV genotype 1 and high viral loads, the effects of ribavirin with IFN-alpha appeared slowly, after the earliest days of treatment. A long-term favourable outcome of combination therapy may be associated with a rapid viral decline in this later phase of therapy.

Adult↗

PubMed2003

Modulation of intracellular Ca(2+) concentration by tedisamil, a class III antiarrhythmic agent, in isolated heart preparation.

New class III antiarrhythmic/defibrillating compound tedisamil was shown to facilitate termination of atrial and ventricular fibrillation in experimental as well as clinical conditions. However, class III-related inhibition of K(+) current associated with prolongation of repolarization can not solely explain its defibrillating ability. Following recent findings it was hypothesized that defibrillating effect of tedisamil is likely due to its sympathomimetic feature linked with modulation of intracellular calcium. Results of this study obtained in isolated heart preparation showed that elevated intracellular Ca(2+) free concentration was decreased by administration of tedisamil in concentration that did not induce Q-T interval prolongation. Due to species differences the effective concentration was in rat 10(-7) M, while in guinea pig 10(-5) M. On the contrary, further dramatic increase of elevated Ca(2+) was detected upon administration of tedisamil in concentration that markedly prolonged Q-T interval (10(-5) M in rat). It is concluded that defibrillating ability of tedisamil is most likely associated with attenuation of abnormal and harmful intracellular Ca(2+) elevation (that is highly arrhythmogenic) than with prolongation of APD or Q-T interval.

Animals↗

PubMed2003

Characterization of bronchoalveolar lavage T cell subsets in sarcoidosis on the basis of CD57, CD4 and CD8.

T cells expressing CD57 (a natural killer cell marker) with interferon-gamma (IFN-gamma) producing capacity increase under various conditions. CD57+ T cells are also present in the bronchoalveolar lavage fluid (BALF) of sarcoidosis, and several phenotypical and functional analyses of these cells have been reported. In the present study, BALF T cells obtained from 52 patients with sarcoidosis were classified further into CD4+CD57+ T cells, CD4+CD57- T cells, CD8+CD57+ T cells and CD8+CD57- T cells and their phenotypes and functional characteristics were assessed. Substantial proportions of these T cell subsets expressed natural killer cell markers CD161 and CD122. The biased expansion of Vbeta2 T cells was observed in both CD4+CD57+ T cells and CD4+CD57- T cells in BALF from most patients, while the expansion of other Vbeta T cells was also observed in some patients. Unexpectedly, the biased expansion of certain Vbeta T cells was also seen in either CD8+CD57+ T cells or CD8+CD57- T cells, while the expanded Vbeta T cells in CD8+ T cells differed substantially among individuals. BALF T cells showed a remarkably lower T cell receptor (TCR) intensity than that of peripheral blood T cells. Both CD8+ T cell subsets in BALF of sarcoidosis expressed the intracellular perforin/granzyme B, while all four subsets expressed intracellular IFN-gamma after in vitro activation, and CD4+ T cells, especially CD4+CD57+ T cells, expressed tumour necrosis factor-alpha. These findings indicate that CD57+ T cells as well as CD57- T cells in the BALF are phenotypically and functionally different from peripheral blood T cells and may play an important role in the Th1 dominant state and inflammation in pulmonary sarcoidosis.

Antigens, CD↗

PubMed2003

Pathological significance of oxidative cellular damage in human alcoholic liver disease.

AIMS: To investigate the pathological significance of oxidative stress-induced lipid peroxidation and oxidative DNA damage in alcoholic liver disease. METHODS AND RESULTS: Hepatic expression of 4-hydroxy-2'-nonenal (HNE) adducts and 8-hydroxydeoxyguanosine (8-OHdG) as reliable markers of lipid peroxidation and oxidative DNA damage, respectively, was analysed immunohistochemically and compared with histological findings in alcoholic liver disease. While no HNE adducts were observed in control livers, HNE adducts were frequently (37 of 40 cases, 92.5%) detected in alcoholic liver disease. The localization of HNE adducts was the cytoplasm of hepatocytes and sinusoidal cells in zone 3. As for 8-OHdG, 29 of 40 cases (72.5%) with alcoholic liver disease exhibited positive immunolabelling for 8-OHdG, while 8-OHdG expression was not evident in control livers. The nuclear expression of 8-OHdG was mainly detected in the hepatocytes within the areas of active inflammation. Among histological parameters, the grade of necro-inflammation activity as well as the presence of Mallory bodies were significantly associated with the expression of HNE adducts and 8-OHdG. In addition, the severity of steatosis also correlated with HNE adduct expression. CONCLUSIONS: Lipid peroxidation and oxidative DNA damage occur widely and may be associated with certain pathological features in human alcoholic liver disease.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2003

The role of capsaicin-sensitive afferents in autonomic dysreflexia in patients with spinal cord injury.

OBJECTIVES: To determine whether capsaicin-sensitive nerves in the bladder form the afferent limb involved in autonomic dysreflexia (AD) in patients with spinal cord injury (SCI). PATIENTS AND METHODS: Seven men with SCI (five cervical cord, two thoracic cord) with AD and detrusor hyper-reflexia (DH) were enrolled. Under general anaesthesia, capsaicin solution (100 mL of 2 mmol/L in 10% ethanol) was instilled in the bladder and retained for 30 min. The patients were assessed by medium-fill cystometry (CMG) just before and 50 min after the capsaicin treatment. Intra-arterial blood pressure (BP) and heart rate were monitored continuously throughout the procedure; 10% ethanol was instilled before capsaicin treatment in four patients as a control. Serum catecholamines were measured during bladder filling and capsaicin treatment, and the blood ethanol concentration also measured after instillation in all patients. The CMG with concomitant monitoring of BP and heart rate was repeated 1 week, 1, 3, 6, 12 and 24 months after instillation. In two patients the instillations were repeated 5 and 12 months after the first because of recurrence of DH. Urodynamic variables assessed were maximum cystometric capacity (MCC), maximum amplitude of uninhibited detrusor contraction (UICmax), the bladder capacity at 40 cmH2O detrusor pressure (Cdp40) and a systolic BP of> 140 mmHg or diastolic BP of> 90 mmHg (C(HT)). RESULTS: There was an increase in BP and a decrease in heart rate in all patients during bladder filling before capsaicin treatment. Instillation of capsaicin produced a significant increase in both systolic and diastolic BP and a significant decrease in heart rate. The maximum cardiovascular effects were at 5-10 min after instillation and gradually returned to baseline within 40 min. The vehicle had negligible effects on either BP or heart rate. After capsaicin treatment, the responses of BP and heart rate to bladder distension were significantly reduced. Both serum catecholamine values and the blood ethanol concentration remained within normal limits. The mean (range) follow-up after the first treatment was 15 (6-30) months. One month after treatment all seven patients became continent and their episodes of AD became negligible and well tolerable between catheterizations (for 3-4 h); the effects lasted for >or= 3 months in all. MCC was significantly increased at 4 weeks and 3 months, and UICmax significantly decreased at 4 weeks after treatment. Both mean Cdp40 and C(HT) increased 1 week, 1 and 3 months after treatment. Two patients received a second instillation, and have been continent with no symptomatic AD for 6 and 24 months. The remaining five patients have been continent with no symptomatic AD for 6-12 months. CONCLUSION: These results indicate that intravesical capsaicin, but not the vehicle, acutely triggers AD in patients with SCI, suggesting involvement of bladder capsaicin- sensitive afferents in AD in these patients. The results also suggest that intravesical capsaicin may be a promising therapy for both AD and DH in such patients. Further long-term follow-up studies are needed to evaluate the duration of its effect.

Administration, Intravesical↗

PubMed2003

Essential microenvironment for thymopoiesis is preserved in human adult and aged thymus.

Normal human thymuses at various ages were immunohistologically examined in order to determine whether adult or aged thymus maintained the microenvironment for the T cell development and thymopoiesis was really ongoing. To analyze the thymic microenvironment, two monoclonal antibodies (MoAb) were employed. One is MoAb to IL-1 receptor (IL-1R) recognizing medullary and subcapsular cortical epithelial cells of normal infant human thymus. The other is UH-1 MoAb recognizing thymic epithelial cells within the cortex, which are negative with IL-1R-MoAb. Thymus of subjects over 20 years of age was split into many fragments and dispersed in the fatty tissue. However, the microenvironment of each fragment was composed of both IL-1R positive and UH-1 positive epithelial cells, and the UH-1 positive portion was populated with lymphocytes showing a follicle-like appearance. Lymphocytes in these follicle-like portions were mostly CD4+CD8+ double positive cells and contained many proliferating cells as well as apoptotic cells. Thus these follicle-like portions in adult and aged thymus were considered to be functioning as cortex as in infant thymus. Proliferative activity of thymocytes in the thymic cortex and the follicle-like portions definitely declined with advance of age, while incidence of apoptotic thymocytes increased with aging.

Adolescent↗

PubMed2003

Clinicopathological significance of hypoxia-inducible factor-1alpha expression in human pancreatic carcinoma.

AIMS: The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) plays a key role in the cellular adaptation to hypoxia and the activation of several genes that have been implicated in tumour growth. The aim of this study was to investigate the clinicopathological significance of HIF-1alpha expression in pancreatic carcinoma. METHODS AND RESULTS: We investigated HIF-1alpha expression immunohistochemically in pancreatic carcinoma tissues and regional lymph node metastasis. In cases of pancreatic ductal carcinoma, the relationship between HIF-1alpha expression and various clinicopathological parameters including cellular proliferation, apoptosis, and microvessel density, was also examined. Over-expression of HIF-1alpha was frequently (29 of 49 cases, 59.2%) detected in pancreatic carcinoma and regional lymph node metastasis (19 of 25 cases, 76.0%), whereas HIF-1alpha expression was almost absent in non-cancerous pancreatic tissues. HIF-1alpha expression was significantly associated with tumour size (P = 0.023) and advanced TNM stage (stage I/II versus stage III, P = 0.039; stage I/II versus stage IV, P = 0.027). Moreover, HIF-1alpha expression positively correlated with cellular proliferation (P = 0.024) and microvessel density/neo-angiogenesis (P = 0.038), but not with apoptosis. CONCLUSIONS: HIF-1alpha may play a critical role in the progression of pancreatic carcinoma.

Adenocarcinoma, Papillary↗

PubMed2003

The comparative effects of propofol versus thiopentone on left ventricular function during electroconvulsive therapy.

The purpose of this study was to compare the effect of propofol versus thiopentone on haemodynamics during electroconvulsive therapy (ECT), as estimated by echocardiography. Twenty-eight ASA 1 or 2 patients scheduled for ECT were randomly divided into two groups, to receive propofol 1 mg/kg (propofol group, n = 14) or thiopentone 2 mg/kg (thiopentone group, n = 14). Bilateral ECT was performed after the administration of propofol or thiopentone, succinylcholine and following assisted mask ventilation with 100% oxygen. Cardiac function was examined by transthoracic echocardiography, prior to induction of anaesthesia and throughout ECT until ten minutes after the seizure. In the propofol group, increased end-systolic area (ESA) and decreased fractional area change (FAC) were observed at one minute after the electrical shock compared with the awake condition. In the thiopentone group, increased ESA and decreased FAC were observed from one to three minutes after the electrical shock compared with the awake condition. There was no statistically significant change in afterload in the propofol group during the study. In contrast, increased afterload was observed from one to three minutes after the electrical shock in the thiopentone group (awake condition, 26 +/- 7 mmHg/cm2 [mean +/- SD]; one minute after ECT, 42 +/- 7*; two minutes after ECT, 44 +/- 6*; three minutes after ECT; 40 +/- 5*, respectively) (*P < 0.05). We concluded that a lesser haemodynamic change occurs after propofol anaesthesia (1 mg/kg) compared with thiopentone anaesthesia (2 mg/kg) during ECT.

Adult↗

PubMed2003

Occlusal and TMJ loads in subjects with experimentally shortened dental arches.

To determine whether shortened dental arches (SDAs) cause functional overloading of the teeth and the temporomandibular joints, which has been implicated in periodontal diseases and temporomandibular disorders, we investigated the influences of SDA on occlusal and joint loads. Bite force and masticatory muscle electromyograms were recorded in five dentate subjects who clenched maximally on intra-oral appliances, creating symmetrical SDAs experimentally. Muscular forces estimated from the recorded electromyograms were fed into a finite element jaw model for calculating bite forces and joint loads. Comparison between the measured and the calculated bite forces ensured that the joint loads were representative. The bite force on each tooth increased with missing molar occlusions, while joint loads decreased. The bite force per root surface area was always greatest on the most posterior tooth, and these values were most constant. The findings provide no evidence that SDA causes overloading of the joints and the teeth, which suggests that neuromuscular regulatory systems are controlling maximum clenching strength under various occlusal conditions.

Adaptation, Physiological↗

PubMed2003

Three dimensional architecture of lymphatic vessels in the tongue.

We have three-dimensionally reconstructed the lymphatic architecture of the rabbit tongue using a computer graphic three-dimensional reconstruction method together with histochemically stained serial cryo-sections. Three collecting lymphatic vessels lying in an anteroposterior orientation were identified in the tongue body. A superior longitudinal muscle accompanying collecting lymphatic (SLCL) that lies in the border between superior longitudinal muscle and transverse muscle was identified in this study, in addition to collecting lymphatics in the lingual septum (LSCL) and deep lingual artery accompanying collecting lymphatics (DLCL) that we reported previously. The vertical muscle accompanying collecting lymphatics (VCL) and the transverse muscle accompanying collecting lymphatics (TCL) were also identified as collecting lymphatics that joined the above three collecting lymphatics. Specific regional lymph flow was identified for each collecting lymphatic. A transverse right/left cross flow was identified for the LSCL, while the SLCL served the upper 1/3 of the tongue and the DLCL served the lower 2/3 of the tongue. Each collecting lymphatic that accompanied the internal lingual muscles joined to the SLCL, DLCL and LSCL, and were derived from blind-ended lymphatic capillaries that ran in the endomysium. Internal lingual muscle accompanying collecting lymphatics joined each other in the endomysium, and their blind-ended lymphatic capillaries had no branches.

Animals↗

PubMed2003

Three-dimensional changes in lymphatic architecture around VX2 tongue cancer--dynamics of growth of cancer.

Many questions remain regarding the mechanism of cervical lymph node metastasis via lymphatic vessels. We report here the three-dimensional dynamics of the lymphatic architecture around tumor during growth of implanted VX2 tongue cancer. The tongue and the deep cervical lymph nodes of rabbits were observed at 3, 7 and 10 days after transplantation of VX2 cancer cells (n = 5 in each group). Lymph node metastasis was confirmed histopathologically. Morphological changes of the collecting lymphatic vessels and lymphatic capillaries were observed, and the number and diameter of these lymphatic vessels were measured within 500 microns around the tumor using the combined method of 5'-nucleotidase (5'-Nase) staining and three-dimensional reconstruction imaging. The VX2 cells were uniformly detected in cervical lymph nodes of each rabbit of the 10-day group. The number of lymphatic capillaries and the diameters of collecting lymphatic vessels around the tumor in the 7- and 10-day groups were greater than in the 3-day group. These capillaries arose by sprouting from preexisting lymphatic vessels and showed a tree-like branching pattern. We conclude that the dynamics of the lymphatic architecture around the tumor, especially the increase in number of capillaries on preexisting lymphatic vessels outside the tumor margin, may be associated with lymph node metastasis.

Animals↗

PubMed2003

Three-dimensional changes in lymphatic architecture around VX2 tongue cancer--dynamic changes after administration of antiangiogenic agent.

We examined the three-dimensional changes of the lymphatic architecture in the rabbit VX2 tongue cancer model after administration of an antiangiogenic agent, TNP-470. TNP-470 at 30 mg/kg was administered via the auricular vein to the rabbit four times every other day from 3 days after transplantation of the tumor. The tongue and both sides of deep cervical lymph nodes of rabbit were observed at 10 days after transplantation. Lymph node metastasis was confirmed histopathologically. Morphological changes of collecting lymphatic vessels and lymphatic capillaries were observed, and the number and diameter of lymphatic vessels within 500 microm around the tumor were measured using the combined method with 5'-nucleotidase staining and three-dimensional reconstruction imaging. Tumor growth and lymph node metastasis were suppressed by administration of TNP-470. In the TNP-treatment group, the mean number of lymphatic capillaries was significantly fewer than in the control group. The mean diameter of collecting lymphatic vessels was significantly smaller than in the control group. In conclusion, our results suggest that cancer cell invasion into the lymphatics is probably decreased by inhibiting not only the growth of tumor but also new formation of lymphatic capillaries around the tumor by administration of TNP-470.

Angiogenesis Inhibitors↗

PubMed2002

Activation of human T cells with NK cell markers by staphylococcal enterotoxin A via IL-12 but not via IL-18.

We have reported recently that mouse liver NK cells and NK1 x 1+ T cells were activated by bacterial superantigens via the IL-12 production from Kupffer cells. In the present study, we examined the effect of staphyloccoccal enterotoxin A (SEA) on human T cells with NK cell markers, CD56 or CD57 (NK-type T cells). After stimulating peripheral blood mononuclear cells (PBMC) with SEA, PBMC produced a large amount of IFN- and acquired a potent antitumour cytotoxicity. The in vitro depletion of either CD56+ TCR NK cells, CD56+ T cells or 57+ T cells from PBMC significantly inhibited the IFN- production from PBMC. When purified NK-type T cells, NK cells and regular T cells were cultured with monocytes and SEA they all produced IFN-, while the IFN- amounts produced by both NK-type T cells were greater than those produced by NK cells. NK cells as well as CD56+ T cells showed cytotoxicity against NK-sensitive K562 cells, whereas both NK-type T cells showed a more potent cytotoxicity against NK-resistant Raji cells than did NK cells. The IFN- production from each population as well as from whole PBMC was greatly inhibited by anti-IL-12 antibody but not by anti-IL-18 antibody. The antitumour cytotoxicity of whole PBMC was also significantly inhibited by anti-IL-12 antibody while the SEA-induced proliferation of PBMC was not affected by anti-IL-12 antibody. Furthermore, SEA-activated NK-type T cells as well as NK cells showed cytotoxicities against vascular endothelial cells. Our findings suggest that human NK-type T cells are thus involved in bacterial superantigen-induced immune response.

Biomarkers↗