Biomedical subjects

Hiroyuki Kuwano

Publications and source records attributed to Hiroyuki Kuwano.

At least 145 records · Page 8Linked to original sources

PubMed2002

Increased thermosensitivity of mouse colorectal carcinoma cells transfected with human FUT1 gene.

The thermal responses of mouse colorectal carcinoma cells were investigated in the wild type cells and the transfected cells with human FUT1 gene which encodes alpha 1,2fucosyltransferase. The heat sensitivity was observed to increase in the FUT1 gene transfected cells and the effect of hyperthermia at 44 degrees C on these cells was demonstrated to be significant (P<0.001) to the wild type cells even though no remarkable difference in the expression of the heat shock protein, Hsp70 was found in these cells. Thus the expression of alpha 1,2fucosylated antigens seemed to increase the heat sensitivity in mouse colorectal carcinoma cells.

Animals↗

PubMed2002

Association of an intronic polymorphism in the midkine (MK) gene with human sporadic colorectal cancer.

Midkine (MK) is a heparin-binding growth factor specified by a retinoic acid responsive gene. It plays important roles in development and carcinogenesis. The MK gene is located on chromosome 11q11.2 in humans. A heterozygous G to T transition at the 62nd base in intron 3 of this gene has been identified in sporadic colorectal and gastric cancers (Int. J. Mol. Med. 6 (2000) 281). To clarify whether this polymorphism is associated with a cancer risk, a case-control study was conducted. We examined 98 colorectal, 60 gastric, 59 esophagus, 32 lung and 37 breast cancer tissue specimens and their corresponding non-neoplastic tissues. Also, 86 unaffected control specimens were examined. The G/T genotype frequency in colorectal cancers was higher than that in normal samples (11.2 versus 2.3%; P=0.017). Therefore, this genotype could represent a risk factor for tumorigenesis in the colon and rectum of Japanese.

Carrier Proteins↗

PubMed2002

Gastrointestinal recovery and outcome after laparoscopy-assisted versus conventional open distal gastrectomy for early gastric cancer.

Laparoscopy-assisted gastrectomy has been increasingly reported as the treatment of choice for early gastric cancer. However, there is little information regarding the benefits of laparoscopy-assisted distal gastrectomy (LADG). LADG and conventional open distal gastrectomy (DG) for early gastric cancer were compared in terms of operative outcome, recovery of bowel function, complications, and changes in body weight. Thirty-four patients underwent LADG for early gastric cancer. These patients were compared with 31 patients who underwent DG during the same period. For estimating gastrointestinal motility recovery, 20 radiopaque markers were inserted into the duodenum during surgery, and abdominal X-rays were taken daily until all markers were seen in the ascending colon. Age, gender, and histologic differentiation of the lesions were matched. The LADG group required a significantly longer operative time and the dissection of fewer lymph nodes. Postoperative hospital stay and the occurrence of postoperative complications (ileus) were significantly shorter and less frequent in the LADG group. The LADG group showed a more rapid recovery of gastrointestinal motor function compared with the DG group during the early postoperative period. Body weight 24 months after LADG was about 100% of pre-illness weight, but no further weight change was encountered in the DG group. For selected patients with early gastric cancer, LADG with lymphadenectomy can provide a rapid recovery and good quality of life without compromising the cure rate.

Adult↗

PubMed2002

Overexpression of interleukin-15 in vivo enhances antitumor activity against MHC class I-negative and -positive malignant melanoma through augmented NK activity and cytotoxic T-cell response.

Interleukin (IL)-15, a pleiotropic cytokine, is involved in the development and maintenance of NK cells and memory CD8+ T cells. We examined the effects of in vivo overexpression of IL-15 on protection against 2 types of murine B16 melanoma lines, MHC class I-negative B16.44 and MHC class I-positive B16F10 cells, using IL-15 transgenic (Tg) mice that we have recently constructed. The tumor growth was severely retarded in IL-15 Tg mice after subcutaneous (s.c.) inoculation with B16.44 or B16F10 cells. IL-15 Tg mice showed an augmented NK cell activity against B16.44 cells, and in vivo depletion of NK cells by anti-asialoGM1 Ab treatment abrogated the antitumor activity in IL-15 Tg mice. On the other hand, IL-15 Tg mice inoculated with B16F10 cells developed a significant level of CTL response against B16F10 cells, and in vivo depletion of CD8+ T cells by anti-CD8 MAb treatment abrogated the antitumor activity. Thus, overexpression of IL-15 augmented antitumor activity against different tumors via augmentation of different antitumor mechanisms. These results suggest a possible therapeutic application of IL-15 for human neoplasms expressing a wide range of MHC class molecules.

Animals↗

PubMed2002

Significant correlation between expression of heat shock proteins 27, 70 and lymphocyte infiltration in esophageal squamous cell carcinoma.

The objective of this study was to clarify the clinicopathologic and prognostic significance of heat shock proteins (HSP) 27 and 70 expression in esophageal squamous cell carcinoma (SCC). Immunohistochemical staining for HSPs 27 and 70 was performed on surgical specimens obtained from 62 patients with esophageal SCC. The expression of both HSPs 27 and 70 correlated inversely with depth of invasion (P<0.05) and pathologic stage (P<0.05), and correlated positively with lymphocyte infiltration (P<0.05). Reduction of HSP 70 expression was significantly correlated with poor prognosis (P<0.05). Patients with HSP 27-negative tumors tended to have a poor prognosis compared with patients with HSP 27-positive tumors. The present findings suggest that HSPs 27 and 70 are significant prognostic factors for esophageal SCC.

Adult↗

PubMed2002

Concurrent overexpression of Ets-1 and c-Met correlates with a phenotype of high cellular motility in human esophageal cancer.

Hepatocyte growth factor (HGF) stimulates cell motility as well as mitotic activity of cells. High concentrations of HGF or overexpression of its cellular receptor c-Met in cancer have been reported. We analyzed the expression status of c-Met immunohistochemically in 76 cases of human esophageal cancer. Overexpression of c-Met was noted at a considerably high frequency. Intriguingly, c-Met overexpression was frequent in a specific type of cell nest formation in tumors, i.e., the small nest type, in which tumors form small, dispersed cell nests. Further immunohistochemical analyses using serial sections revealed a striking coincidence between overexpression of c-Met and its transcriptional factor, Ets-1. Overexpression of c-Met and Ets-1 was statistically more frequent in small nest type tumors. The close correlation in expression status between Ets-1 and c-Met was also confirmed using 6 established human esophageal cancer cell lines. In addition, cells that expressed high levels of Ets-1 and c-Met exhibited an extremely motile phenotype by HGF stimulation in vitro. The presence of HGF in tissue sections was confirmed using similar immunohistochemical approaches. These observations suggest that in human esophageal cancer cells the transcriptional factor Ets-1 upregulates the expression of c-Met and, consequently, confers on cells a highly motile phenotype leading to a specific form of tumor development.

Animals↗

PubMed2002

Pyloric motility after pylorus-preserving gastrectomy with or without the pyloric branch of the vagus nerve.

An attempt was made to examine gastropyloric motility after pylorus-preserving gastrectomy (PPG) and to determine the influence of the pyloric branch of the vagus nerve in the dog. Fifteen dogs were divided into three groups of five. PPG with preservation (PPPG) and resection of the pyloric branch of the vagus (RPPG) were performed, and controls were prepared. Interdigestive and digestive gastropyloroduodenal motility was recorded after a 2-week recovery period using strain-gauge force transducers (SG). Radiopaque markers (ROMs) were used to assess gastric emptying. No significant differences were found between PPPG and RPPG in terms of gastropyloroduodenal motility during either the interdigestive or the postprandial state. During phase III of the interdigestive state, pyloric relaxation correlated with contraction of the gastric body after both PPPG and RPPG. During the first month it was accompanied by tonic and phasic pyloric contractions after feeding and delayed gastric emptying in two groups. By the end of the first month these pyloric contractions had diminished, and the rate of gastric emptying was similar to that of the controls. We concluded that it is not necessary to preserve the pyloric branch of the vagus for gastropyloroduodenal motility after PPG. Gastric stasis during the early postoperative period is due to tonic and phasic contractions of the pylorus.

Animals↗

PubMed2002

Comparison between positron emission tomography and computed tomography in the use of the assessment of esophageal carcinoma.

BACKGROUND: The role and potential value of positron emission tomography (PET) scanning in certain tumors has been widely investigated in recent years. The authors retrospectively assessed the performance of 18-F-fluorodeoxyglucose (FDG)-PET in the assessment of esophageal squamous cell carcinoma (SCC). METHODS: The results using PET were compared with those using computed tomography (CT), and these were correlated with the pathologic findings. The authors studied 32 patients with thoracic esophageal SCC who had undergone radical esophagectomy. RESULTS: Uptake of FDG in the primary tumor was found in 25 of the 32 (78.1%) cases. Comparison of the FDG uptake and the clinicopathologic findings showed that there was a significant association between the FDG uptake and each of the depth of tumor invasion (P < 0.05), occurrence of lymph node metastasis (P < 0.01), and lymphatic invasion (P < 0.01). The survival rate in cases with high FDG uptake (standardized uptake value [SUV], >3) was significantly lower than that in cases with low FDG uptake (SUV, < 3; P < 0.05). In the evaluation of lymph node staging by the detection of lymph node metastasis, FDG-PET showed 77.8% sensitivity, 92.9% specificity, and 84.4% accuracy, and CT scanning showed 61.1% sensitivity, 71.4% specificity, and 65.6% accuracy. Positron emission tomography scanning showed a high degree of accuracy in the neck, upper thoracic, and abdominal regions. However, in the mid- and lower thoracic regions, the sensitivity was very low. The smallest lymph node metastasis that was detected by FDG-PET imaging was 6 mm. The average size of lymph node metastasis that was undetected by FDG-PET scanning was 7.3 mm (range, 1-17 mm). CONCLUSIONS: In conclusion, FDG-PET may be used as a noninvasive diagnostic technique in assessing the aggressiveness of the tumor and the prognosis in patients with esophageal SCC. During the preoperative diagnostic procedures, the sensitivity, specificity, and accuracy of lymph node staging is higher with FDG-PET than with CT imaging. In view of the high specificity of FDG-PET, it also gives useful information to guide the choice of treatment of esophageal carcinoma.

Adult↗

PubMed2002

Overexpression of IL-15 in vivo increases antigen-driven memory CD8+ T cells following a microbe exposure.

To elucidate potential roles of IL-15 in the maintenance of memory CD8+ T cells, we followed the fate of Ag-specific CD8+ T cells directly visualized with MHC class I tetramers coupled with listeriolysin O (LLO)(91-99) in IL-15 transgenic (Tg) mice after Listeria monocytogenes infection. The numbers of LLO(91-99)-positive memory CD8+ T cells were significantly higher at 3 and 6 wk after infection than those in non-Tg mice. The LLO(91-99)-positive CD8+ T cells produced IFN-gamma in response to LLO(91-99), and an adoptive transfer of CD8+ T cells from IL-15 Tg mice infected with L. monocytogenes conferred a higher level of resistance against L. monocytogenes in normal mice. The CD44+ CD8+ T cells from infected IL-15 Tg mice expressed the higher level of Bcl-2. Transferred CD44+ CD8+ T cells divided more vigorously in naive IL-15 Tg mice than in non-Tg mice. These results suggest that IL-15 plays an important role in long-term maintenance of Ag-specific memory CD8+ T cells following microbial exposure via promotion of cell survival and homeostatic proliferation.

Adoptive Transfer↗

PubMed2002

Reproposal for Hjortsjo's segmental anatomy on the anterior segment in human liver.

BACKGROUND: A minimum, but necessary amount, of cancer-containing liver tissue is to be excised in patients who have poor liver function. To achieve that goal of excision, a limited hepatic resection has been carried out. However, performing subsegmentectomy of the anterior segment according to the conventional segmental anatomy introduced by Healey and Schroy or Couinaud is difficult. Because the transverse border between segments 5 and 8 was drawn as an imaginary line through the right portal vein, there is no anatomical structure indicating this border. HYPOTHESIS: Hjortsjo divided the anterior segment into 2 vertical segments according to the fissure in which a hepatic vein coursed. By including Hjortsjo's concept of segmental anatomy, new procedures will be added to hepatic surgery. DESIGN: Sixty-five cadaveric livers were dissected to confirm Hjortsjo's concept of segmental anatomy by investigating the vertical fissure that divides the anterior segment into 2 areas, concerning the relation between portal segmentation and the hepatic venous system of the anterior segment. RESULTS: The territories of the third-order portal branches of the anterior segment were divided into 2 (ventral and dorsal) areas with a vertical fissure and in its intersubsegmental plane, an independent hepatic vein, or a first-order branch of the middle or the right hepatic vein coursed. CONCLUSIONS: These findings confirmed the certainty of Hjortsjo's concept of segmental anatomy of the anterior segment. This is relevant for developing new procedures in hepatic surgery. Its reproposal is opportune for adding it as another concept to the conventional segmental anatomy.

Adult↗

PubMed2002

Use of a mattress suture to eliminate dog ears in double-stapled and triple-stapled anastomoses.

Double-stapling techniques for restorative rectal resection have been effective in minimizing local contamination compared with open circular stapling techniques. Inclusion of the transverse staple line closure of the distal rectal stump in the circular stapled anastomosis may minimize the risk of suture line recurrence. A technique for formation of such an anastomosis is described that avoids use of a distal purse string.

Aged↗

PubMed2002

Gastropyloric motor activity and the effects of erythromycin given orally after esophagectomy.

BACKGROUND: The motor activity of the gastric tube as an esophageal replacement after esophagectomy is poorly understood. The aims of the present study were to examine the gastropyloric motility of the gastric tube and the effects of erythromycin given orally. METHODS: Interdigestive gastropyloric motility was recorded by manometry with a sleeve sensor in 23 esophagectomized patients. The 23 patients were classified into 3-, 12-, and 24-month groups according to postoperative follow-up time. Radiopaque markers were used in 8 patients to assess gastric emptying. The effects of erythromycin were studied after the patients received 600 mg during fasting and 1 g postprandially. RESULTS: Compared with the 3-month group, the 12-month group and the 24-month group showed significantly increased pyloric and antral motility, respectively. During a fast, erythromycin induced phase III in 44.4% of the patients with more than 12 months of follow-up. In contrast to the normal subjects, esophagectomized patients showed delayed gastric emptying at 3 and 4 hours. However, erythromycin significantly accelerated gastric emptying at 1, 2, 3, and 4 hours. CONCLUSIONS: The motor activity of the gastric tube returns towards normal in a progression over time from the pylorus cephalad. Erythromycin given orally might be used as a prokinetic agent in patients after esophagectomy.

Administration, Oral↗

PubMed2002

Usefulness of positron emission tomography for assessing the response of neoadjuvant chemoradiotherapy in patients with esophageal cancer.

BACKGROUND: In this study, we retrospectively assessed the performance of 18-F-fluorodeoxyglucose positron emission tomography (FDG-PET) compared with computed tomography (CT) and esophagography for assessing the response of advanced esophageal squamous cell carcinoma (SCC) to neoadjuvant chemoradiotherapy. METHODS: We studied 10 patients with thoracic esophageal SCC who received neoadjuvant chemoradiotherapy followed by surgery. Tumor response was assessed by CT, endoscopy, esophagography and FDG-PET before and after neoadjuvant treatment. RESULTS: Assessment of the rate of decrease in standardized uptake value (SUV) revealed a partial response (more than 50% decrease) in 5 (50%) of the patients, and assessment of length decrease of FDG uptake showed a partial response in 9 (90%) of the patients. Comparison of the histological response and the rate of decrease of various parameters revealed significant associations between histological response and tumor length (P <0.05), SUV after neoadjuvant therapy (P <0.05), and reduction in the extent of FDG uptake (P <0.01). However histological response was not significantly correlated with the rate of reduction of SUV, for both CT and esophagography. CONCLUSIONS: FDG-PET may be of considerable value for predicting the pathologic response of esophageal SCC to neoadjuvant therapy. Despite assessment of SUV before neoadjuvant therapy, low FDG uptake after therapy and reduction in the extent of FDG uptake may provide a reliable assessment of the response to therapy.

Adult↗

PubMed2002

Snowboarding splenic injury: four case reports.

With the rapidly increasing number of snowboarders, the incidence of injuries has recently become higher. From 1994 to 1995, we encountered four snowboarders with splenic injuries in one season. In three of the four patients the splenic injuries were caused by striking the abdomen with their own elbow when falling by themselves, of which emergent splenectomy was required in two patients. In the other one the collision with another snowboarder caused the splenic injury and splenorrhaphy was performed. Because snowboarders have both feet fixed on a board and do not have poles, they are prone to fall on the left upper limb in the proceeding direction, resulting in the striking of the left upper abdomen. Because in snowboarders splenic injury is caused mostly by a blow from their own left elbow at the time of falling, informing the mechanisms of splenic injuries will serve a speedy correct diagnosis for the doctors.

Adolescent↗

PubMed2002

Gum chewing enhances early recovery from postoperative ileus after laparoscopic colectomy.

BACKGROUND: Postoperative ileus limits early hospital discharge for patients who have undergone laparoscopic procedures. Sham feeding has been reported to enhance bowel motility. Here, the effect of gum chewing is evaluated as a convenient method to enhance postoperative recovery from ileus after laparoscopic colectomy. STUDY DESIGN: A total of 19 patients who underwent elective laparoscopic colectomy for colorectal cancer participated in the study. Each patient was randomly assigned to one of two groups: a gum-chewing group (n = 10, mean age 58.6 years, range 50 to 71 years) or a control group (n = 9, mean age 60.6 years, range 45 to 80 years). The patients in the gum-chewing group chewed gum three times a day from the first postoperative AM until oral intake. The times of the first passage of flatus and defecation were recorded precisely. RESULTS: The first passage of flatus was seen, on average, on postoperative day 2.1 in the gum-chewing group and on day 3.2 in the control group (p < 0.01). The first defecation was 2.7 days sooner in the gum-chewing group (postoperative day 3.1) than in the control group (5.8 days; p< 0.01). All patients tolerated gum chewing on the first operative AM. The postoperative hospital stays for the gum-chewing and control groups were 13.5+/-3.0 days and 14.5+/-6.1 days, respectively. CONCLUSIONS: Gum chewing aids early recovery from postoperative ileus and is an inexpensive and physiologic method for stimulating bowel motility. Gum chewing should be added as an adjunct treatment in postoperative care because it might contribute to shorter hospital stays.

Aged↗

PubMed2002

Mechanism of superoxide anion production by hepatic sinusoidal endothelial cells and Kupffer cells during short-term ethanol perfusion in the rat.

BACKGROUND/AIMS: The aim of this study was to clarify the candidate cells for and the mechanism of superoxide anion (O2*-) release into the hepatic sinusoids during short-term exposure to ethanol. METHODS: The rat liver was perfused continuously with ethanol (a substrate for alcohol dehydrogenase) or tert-buthanol (not a substrate for alcohol dehydrogenase) for 20 min at a final concentration of 40 mM. In order to detect O2*- production, MCLA (2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo[1,2-a]pyrazin-3-one), a Cypridina luciferin analogue, was simultaneously infused and MCLA-enhanced chemiluminescence was measured. The effects of gadolinium chloride (GdCL3) (a suppressor of Kupffer cells (KCs)), staurosporine (ST) (an inhibitor of serine-threonine kinases, including protein kinase C), diphenyleneiodonium chloride (DPI) (an inhibitor of NADPH oxidase), ibuprofen (IB) (an inhibitor of cyclooxygenase) and 4-methylpyrazole (4MP) (an inhibitor of ethanol metabolism) on the ethanol-induced chemiluminescence were also evaluated. Sites where O2*- could be released were determined by histochemical detection of nitro blue tetrazolium reduction. RESULTS: Both ethanol and tert-buthanol rapidly caused O2*- release. GdCL3 suppressed the ethanol-induced O2*- release by 61%. Staurosporine and DPI, but neither IB nor 4-MP, also significantly inhibited the ethanol-induced O2*- release. In the histochemical examination, ethanol-stimulated liver showed blue formazan precipitate on both sinusoidal endothelial cells (SECs) and Kupffer cells (KCs), whereas the GdCl3-pretreated liver had the precipitate only on SECs. CONCLUSIONS: This study shows that ethanol itself stimulates both SECs and KCs to release O2*- via activation of NADPH oxidase probably involving protein kinase C (PKC).

Animals↗

PubMed2002

A single nucleotide polymorphism at the splice donor site of the human MYH base excision repair genes results in reduced translation efficiency of its transcripts.

BACKGROUND: Adenine paired with 8-hydroxyguanine, a major oxidatively damaged DNA lesion, is excised by mutY homologue (MYH) base excision repair protein in human cells. Since genetic polymorphisms of DNA repair genes associated with the activities and the expression levels of their products may modulate cancer susceptibility of individuals, we investigated the effect of a single nucleotide polymorphism (SNP) in the MYH gene on the difference in the expression levels of its products. RESULTS: An aberrant size of the beta type nuclear form transcript was detected in a lung cancer cell line, VMRC-LCD, by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The transcript contained the intron 1 sequence, and it was due to alternative splicing resulting from IVS1+5G/C SNP. The presence of the upstream open reading frame (ORF) on the 5'-side of the native ORF in the beta type transcript from the IVS1+5C allele could reduce the translation efficiency of the transcript into the nuclear form protein. Thus, expression vectors bearing the 5'-untranslated region sequence of either the IVS1+5G or 5C allele were constructed. In vitro translation analysis, as well as Western blot and quantitative RT-PCR analyses of the H1299 lung cancer cell line transfected with these vectors, revealed that the translation efficiency of the IVS1+5C transcript into MYH protein was much lower (approximately 30) than that of the IVS1+5G transcript. CONCLUSIONS: The SNP at the splice donor site of the MYH gene resulted in reduced translation efficiency of its transcripts. This is the fourth case of single nucleotide variations that cause alterations in translation initiation sites and translation efficiencies in human cells.

Alleles↗

PubMed2002

Is carbon dioxide as an insufflation agent for double contrast barium enema still worthwhile after a same-day flexible sigmoidoscopy?

PURPOSE: The aim of the study was to evaluate the efficacy of a double-contrast barium enema (DCBE) with CO(2) as a distending gas after a screening flexible sigmoidoscopy for reducing abdominal distension after an examination. PATIENTS AND METHODS: A total of 165 DCBEs for patients with positive faecal occult blood tests were randomly allocated to a CO(2) group (n = 83) and a control group (n = 82) using air. Abdominal radiograph were taken before the DCBE, immediately following it, and 30 minutes later to determine residual bowel gas. The degree of abdominal discomfort was recorded using a scoring system. RESULTS: The patients in the CO(2) group had significantly smaller amounts of residual gas 30 minutes after the DCBE than did the control group, both in the colon (P < 0.02) and in the small intestine (P < 0.001). There was significantly less abdominal distension after the DCBE in the CO(2) group compared to the control group (P < 0.001). The abdominal discomfort score at 30 minutes after CO(2) correlated with the residual gas in the small intestine (r = 0.390,P = 0.003) but not in the colon (r = 0.155, P = 0.15). The quality of the images and the number of polyps detected did not differ between two groups. CONCLUSIONS: We concluded that using CO(2) when administering a DCBE after a screening sigmoidoscopy was useful for relieving abdominal discomfort following the examination; furthermore, it did not impair the diagnostic ability of the DCBE.

Abdominal Pain↗