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Biomedical subjects

M Kaminishi

Publications and source records attributed to M Kaminishi.

At least 19 recordsLinked to original sources

Gastric and intestinal phenotypic correlation between exocrine and endocrine components in human stomach tumors.

We have previously suggested that an origin of a stomach cancer is from a progenitor cell specializing toward exocrine cell (Exo-cell) lineages. To clarify whether our hypothesis is correct or not, we analyzed the expression of Exo-cell and endocrine cell (End-cell) markers in a series of lesions for comparison. We evaluated chromogranin A (CgA) expression in 37 early and 73 advanced stomach cancers, in 30 stomach adenomas, in 8 carcinoid tumors, and in 4 endocrine cell carcinomas (ECCs) with assessment of gastric and/or intestinal (G/I) phenotypes in both Exo-cell and End-cell by immunohistochemistry. CgA expression was observed in 10.8% of the early and 16.4% of the advanced stomach cancers, respectively. The End-cell G/I phenotypes were in line with the Exo-cell counterparts in the CgA-positive stomach cancerous areas, and there was strong association between Cdx2 expression and the intestinal End-cell markers. All of the adenoma cases had the intestinal Exo-cell phenotypic expression, with the positive link between Exo-cell and End-cell G/I phenotypes. All stomach carcinoids had CgA expression but no expression of Exo-cell markers. In conclusion, most stomach cancers might develop from a progenitor cell specializing towards Exo-cell lineages, but some cases possessed both Exo-cell and End-cell markers with maturely differentiated phenotypes. In such cases, Exo-cell and End-cell phenotypes were found to correlate strongly, suggesting the possibility of histogenesis from "cancer stem cells".

Adenocarcinoma↗

Manipulation of the small intestine as a cause of the increased inflammatory response after open compared with laparoscopic surgery.

BACKGROUND: Laparoscopic surgery of the gastrointestinal tract involves a reduced immune response compared with open surgery. The aim of this study was to assess manual handling of the gut in open procedures as the principal cause of the enhanced immune response. METHODS: Eighteen Landrace pigs underwent gastrectomy by three different methods: conventional open wound with bowel manipulation, laparoscopically assisted gastrectomy, and gastrectomy without manipulation using a combination of open wound and laparoscopic surgical devices. Local inflammatory changes were assessed by ascites formation, intestinal adhesion development and intestinal inflammatory gene expression. Associated systemic inflammatory changes were determined by measuring portal and systemic plasma endotoxin levels, plasma inflammatory cytokine levels, liver inflammatory gene expression and transaminase levels. RESULTS: Significantly more postoperative intra-abdominal fluid and adhesions were seen in the open group. The expression of inflammatory cytokines was significantly greater in the intestine and liver in the open group. Portal and systemic levels of endotoxin, inflammatory cytokines and transaminases were also higher. CONCLUSION: Manual handling of organs during gastrectomy is an important contributor to the molecular and humoral inflammatory response to surgery, supporting the use of minimally invasive techniques in gastrointestinal surgery.

Animals↗

Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy.

BACKGROUND AND STUDY AIMS: Endocytoscopy allows the observation of living cells in the gastrointestinal tract. Consistently clear views are essential for clinical application of the technique, but these are not always obtained. The aim of this study was to determine an appropriate staining regimen for endocytoscopy. MATERIALS AND METHODS: This was an ex-vivo animal study in which we stained freshly resected porcine esophagus, stomach, and colon with different concentrations of three dyes (1%, 0.5%, and 0.25% crystal violet; 5%, 2.5%, and 1% methylene blue; and 1%, 0.5%, and 0.25% toluidine blue) and assessed them after different exposure times (10 seconds, 30 seconds, 60 seconds, and 90 seconds). The images obtained were evaluated according to the staining status of the cytoplasm and the nucleus, and the contrast between the cytoplasm and the nuclei, and the optimal staining conditions for each organ were determined. Additionally, freshly resected human esophagus, stomach, and colon tissues were tested under the dye/exposure conditions that were found to be the most appropriate in the animal study. RESULTS: After intensive mucus removal, high-quality images were obtained using methylene blue and toluidine blue. The optimum conditions for endocytoscopic observation were obtained after staining with 1% methylene blue in the esophagus and with 0.25% toluidine blue in the stomach and the colon, after 60 seconds of exposure to the dye. This was confirmed in the human specimens. CONCLUSIONS: This study provides important information on appropriate staining conditions for endocytoscopy. Further ex-vivo and in-vivo studies are necessary before this technique comes into standard use, however.

Animals↗

Differential expression of peroxisome proliferator-activated receptor in histologically different human gastric cancer tissues.

Gastric cancer cell lines express peroxisome proliferator-activated receptor gamma (PPARgamma), and treatment with PPARgamma ligands suppresses growth of subgroup of these cell lines. However, expression and subcellular distribution of PPARgamma in human gastric cancer tissues is still unknown. Therefore, expression and subcellular localization of PPARgamma were examined among different histological types of gastric cancer tissues. Immunohistochemical staining for PPARgamma was performed using biopsy specimens of human gastric cancer of various histological types, gastric adenomas, and intestinal metaplasia. All samples of intestinal metaplasia and most samples of gastric tumors, except for signet ring cell carcinoma, expressed PPARgamma in the epithelial cells. Most samples of signet ring cell cancer lacked PPARgamma expression. All samples of intestinal metaplasia expressed PPARgamma only in the cytosol. For adenoma, 90% was positive for PPARgamma in cytosol, and 40% was positive in nuclei, for well-differentiated adenocarcinoma, 80% was positive in cytosol, and 20% was positive in nuclei. For moderately differentiated adenocarcinomas, 70% was positive for cytosol, and 80% was positive for nuclei; for poorly differentiated adenocarcinoma, 30% was positive in cytosol, and 70% was positive in nuclei. The frequency of samples with positive cytosolic staining decreased as the differentiation stage turned from intestinal metaplasia to adenoma, well-, moderately-, and poorly-differentiated cancers. Simultaneously, there was a tendency toward an increased frequency of samples with positive nuclear PPARgamma staining as the differentiation stage transformed from intestinal metaplasia to poorly-differentiated cancer. There was a striking difference in subcellular localization according to the differentiation levels of gastric dysplastic cells. The findings also supported an intestinal metaplasia-adenoma-well-differentiated gastric cancer sequence, and signet ring cell cancer was suggested to be of a different lineage from other types of gastric cancers.

Adenocarcinoma↗

A seasonal variation in the onset of postoperative adhesive small bowel obstruction is related to changes in the climate.

BACKGROUND: Postoperative small bowel obstruction following abdominal procedures is more common in patients who have undergone laparotomy. However, little is known about the influence of climate on the incidence of postoperative small bowel obstruction. METHODS: To evaluate whether seasonal climatic variations are a risk factor for postoperative small bowel obstruction, hospital-based, retrospective case series was designed from medical records of 230 patients suffering from postoperative small bowel obstruction admitted to the Tokyo University Branch Hospital. Detailed analysis of weather charts from the Japanese Meteorological Agency and review of medical records for selected patients who were diagnosed with postoperative small bowel obstruction. The obstruction was diagnosed by abdominal X-ray imaging, clinical examination, and patient interviews. RESULTS: A total of 233 patients diagnosed with postoperative small bowel obstruction were identified. Analysis of the medical records of these 233 patients revealed that the variables associated with an increased risk of postoperative small bowel obstruction included low ambient temperatures of 5-10 degrees C, an increase in air humidity by 40-50% and air pressure of 1010-1015 hPa. CONCLUSION: The typical winter weather in Tokyo is characterised by low temperatures, low humidity and moderate air pressure. These winter climate conditions could be correlated with an increased incidence of postoperative small bowel obstruction in Tokyo during our period.

Adolescent↗

Strong association of ARK5 with tumor invasion and metastasis.

We recently identified a novel human AMPK family member, ARK5, and discovered that is a major factor in Akt-dependent cancer cell survival and migration activity through activation of MT1-MMPs in vitro. The mRNA expression of other AMPK family members and ARK5 was measured using RT-PCR in human colorectal carcinoma cell lines DLD-1, WiDr, HCT-15, SW620, LoVo, SW480, and mRNA expression of AMPK-alpha1, SNARK, MELK and ARK5, but not AMPK-alpha2, was detected in every line. Quantitative-PCR (Q-PCR) to estimate the amount of ARK5 mRNA expression in the cell lines showed that there is a variety of ARK5 expressions among the cell lines and high expression was observed in a cell line derived from the metastatic lesion, LoVo. To determine the effect of ARK5 overexpression on metastasis in vivo, we established human pancreas cancer cell line PANC-1 stably transfected with ARK5 full-length expression vector (P/ARK) and DLD-1 stably transfected with the same vector (D/ARK). Migration assay showed a remarkable increase in the activity both in P/ARK and D/ARK, and an in vivo metastasis assay showed a marked increase of P/ARK in liver metastasis. Based on these observations, it is suggested that ARK5 expression is involved in cancer invasion and metastasis.

AMP-Activated Protein Kinase Kinases↗

Low concentrations of ethanol induce apoptosis in human intestinal cells.

BACKGROUND: Increased systemic levels of endotoxin have been detected in human alcoholics and are thought to be derived from the gut. Although a 'leaky gut' is considered to be a necessary factor for alcohol-induced endotoxemia followed by chronic liver injury, the effects of low concentrations of ethanol on intestinal epithelial cells have not been fully understood. The aim of this study was to evaluate intestinal epithelial cell death induced by acute, low concentrations of ethanol in an in vitro system. METHODS: The human intestinal Caco-2 cell line was incubated with 0%, 5%, 10% ethanol for up to 3 h. Phosphatidylserine (PS) externalization, caspase-mediated cytokeratin 18 (CK18) cleavage, and DNA fragmentation were evaluated using flow cytometry. The caspase inhibitor zVAD-fmk was used to test the role of caspases in ethanol-induced cell death. RESULTS: Treatment with 5% and 10% ethanol for 3 h led to a gradual increase in PS externalization. Caspase-mediated CK18 was significantly enhanced as early as 1 h after 10% ethanol incubation, while DNA fragmentation was detected from 2 h onwards. Not only caspase activation but also both PS externalization and DNA fragmentation were completely prevented by pretreatment with the caspase inhibitor. CONCLUSIONS: Apoptotic cell death in confluent Caco-2 cells was induced by acute and low concentrations of ethanol. These results suggest that clinically achievable doses of ethanol impair intestinal barrier function by induction of apoptosis in intestinal epithelial cells. This impairment of the barrier function would allow endotoxin to enter the circulation and evoke hepatic inflammation.

Adenocarcinoma↗

Renal denervation abolishes the protective effects of ischaemic preconditioning on function and haemodynamics in ischaemia-reperfused rat kidneys.

Studies were conducted to investigate the role of renal sympathetic nerves in the process of acquiring ischaemic tolerance in ischaemic preconditioned ischaemia-reperfused rat kidneys. Two periods of 3-min occlusion of bilateral renal arteries was performed prior to 30-min bilateral ischaemia and 90-min reperfusion in acute renal denervated or innervated kidneys. The glomerular filtration rate (GFR), fractional excretion of sodium (FENa) and lithium (FELi), and renal blood flow (RBF) were assessed in reperfused kidneys. Ischaemic preconditioning significantly improved values for all these parameters as compared with no treated ischaemia-reperfused kidneys. Denervation caused slight increase in GFR, diuresis and natriuresis without improving RBF after reperfusion. However, protecting effects of ischaemic preconditioning on renal function were disappeared in denervated kidneys, while in innervated kidneys the effects of ischaemic preconditioning were maintained. These results clearly showed that ischaemic preconditioning pre-treatment protects kidneys against ischaemia-reperfusion injury, and the effects are, at least in part, mediated by sympathetic nerves, as the protective effects were abolished by denervation.

Animals↗

Immunohistochemical prognostic indicators of gastrointestinal carcinoid tumours.

AIMS: The aim of this study was to determine whether expression of the oncoproteins p21, p53, E-cadherin (EC), cyclin D1, bcl-2 and Rb and the proliferation marker Ki-67 is predictive of malignant behaviour in gastrointestinal carcinoid tumours. METHODS: Immunohistochemical (IHC) staining was performed on carcinoid tumours from 41 patients (31 rectal, eight gastrointestinal, two appendiceal lesions). The six tumours that had invaded deeply into the muscularis propria or beyond, had metastasized to regional lymph nodes or had metastasized to a distant site were classified as the malignant group, and the other 35 tumours formed the benign group. IHC expression was compared between the two groups, and the prognostic value of each marker was assessed. RESULTS: Of the six tumours in the malignant group, 66.7% were p21 positive, 0% were p53 positive, 33.3% were EC positive, 100% were cyclin D1 positive, 33.3% were Rb positive, 16.7% were bcl-2 positive and 50% were Ki-67 positive. Of the 35 tumours in the benign group, 17.1% were p21 positive, 0% were p53 positive, 100% were EC positive, 94.3% were cyclin D1 positive, 8.6% were Rb positive, 17.1% were bcl-2 positive and 0% were Ki-67 positive. CONCLUSIONS: These data show that p53, cyclin D1, Rb, bcl-2 and Ki-67 staining does not correlate with malignant behaviour but that overexpression of p21 (P=0.02) and reduced staining of EC (P=0.005) do correlate with malignant behaviour. These two parameters may therefore be useful as prognostic indicators for gastrointestinal carcinoid tumours.

Adult↗

Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated protein kinase activator, 5-aminoimidazole- 4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line.

5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) is an activator of AMP activated protein kinase (AMPK) and a regulator of de novo purine synthesis. There are several earlier reports indicating that AICAR treatment suppresses cell growth via regulation of AMPK or de novo purine synthesis. We found cell growth to be suppressed by AICAR treatment in HepG2 because of p53 accumulation, which was associated with p53-Ser15 phosphorylation. Moreover, a motif very similar to the consensus motif of AMPK phosphorylation was found around p53-Ser15, and Ser15 phosphorylation was detected in AICAR treated HepG2 as was in vitro phosphorylation by AMPK. Our results suggest that AICAR may regulate cell growth via p53 phosphorylation, and also indicate the possibility of p53 phosphorylation.

AMP-Activated Protein Kinases↗

Bochodalek hernia in a young adult: report of a case.

A Bochodalek hernia is rarely seen in adults. An 18-year-old man was referred to our institute with the chief complaint of a sudden onset of left subcostal pain, nausea, and vomiting. A radiograph and a computed tomographic scan of the chest revealed a Bochodalek hernia. Emergency surgery was thus performed. The herniated organs were put back into the peritoneal cavity and the hernial hilum was closed. The postoperative course was uneventful. A routine chest radiograph 1 month before had shown a slight elevation of the left hemidiaphragm and further examination using computed tomography suggested a Bochodalek hernia, but he had merely been followed up since there were no symptoms. As soon as a diagnosis is made, specific repairs should be carried out even if no symptoms are present, to prevent such complications as strangulation or perforation.

Adolescent↗

Lymph node metastasis and preoperative diagnosis of depth of invasion in early gastric cancer.

BACKGROUND: No reports have, to date, focused on the relationship between preoperative determination of the depth of invasion and lymph node metastasis. The present study, under the leadership of the Japanese Gastric Cancer Association, was designed to form a basis for decision making in limited treatment for early gastric cancer (EGC). METHODS: From eight major hospitals in Japan, 2672 gastric cancers whose preoperative depth of invasion was mucosal(M-cancer), and 6209 EGCs, consisting of 3584 mucosal(m-) and 2625 submucosal(sm-) cancers, were collected by questionnaire. All registered patients underwent gastrectomy with D1 or more extensive lymphadenectomy between 1985 and 1998. RESULTS: The accuracy of preoperative diagnosis of depth of invasion of M-cancers was 80.2% (2144/2672). However, of the total of 2432 M-cancers in which no nodal involvement was observed intraoperatively (N0), histological examination of the resected specimens confirmed that lymph node metastasis was absent in 2353 (96.8%). The frequencies of lymph node metastasis in early gastric, m-, and sm-cancers were 8.9%, 2.5%, and 17.6%, respectively. Node involvement was associated with a higher frequency of undifferentiated than differentiated histology, as well as with greater tumor size. The incidences of lymph node metastasis in m-cancers with a diameter of less than 4 cm, and in sm-cancers with a diameter below 1 cm were 1.3% (37/2837) and 4.9% (4/82), respectively. These metastases rarely extended beyond the first tier. CONCLUSION: N0 and M-cancers, m-cancers less than 4 cm in diameter, and sm-cancers no larger than 1 cm in diameter may be appropriate indications for limited surgery.

Chi-Square Distribution↗

Results of local resection with regional lymphadenectomy for early gastric cancer.

BACKGROUND: In 1999, the authors reported preliminary results of local resection with regional lymphadenectomy(LR) for early gastric cancer. METHODS: Twenty-four patients underwent LR until May 2000. Laparoscopic techniques were recently applied. The dissected area for lymphadenectomy depended on the lymphatic flow from the tumor. Local gastric resection was performed with a 2 cm cancer-free margin. Among the 24 patients, 14 who had been followed up for more than 1 year were eligible for the nutritional study, and the nutritional parameters were compared with those for patients undergoing pylorus-preserving gastrectomy (PPG). RESULTS: Twenty-two patients not receiving additional gastrectomy needed no restriction of food intake and had neither postgastrectomy symptoms nor recurrence. All nutritional parameters remained stable between the preoperative and the subsequent period. Nutritional superiority of LR over PPG was observed. CONCLUSIONS: For selected patients with early gastric cancer, LR can be a treatment of choice to provide a good quality of life.

Adult↗

A rare case of pseudomyxoma peritonei presenting an unusual inguinal hernia and splenic metastasis.

Pseudomyxoma peritonei (PMP) is a rare clinical entity in which a diffuse collection of intraperitoneal gelatinous fluid is associated with gelatinous implants on the peritoneal surfaces and omentum. Hematogenic or lymphatic metastasis is extremely rare. In addition, an inguinal mass as an initial presentation is also relatively rare. This is a case report of a PMP patient who had splenic metastasis and showed an inguinal tumor as an initial presentation. A 59-year-old female patient, who had undergone bilateral oophorectomy because of a ruptured ovarian mucinous tumor of boderline malignancy 12 years previously, presented a presumptive diagnosis of a left inguinal irreducible hernia. Computed tomography revealed a low density mass in the pelvic cavity and in the inguinal lesion, as well as in the spleen without any diseases around the organ. The preoperative serum carcinoembryonic antigen (CEA) level was elevated. The patient underwent a resection of gelatinous tumor in the pelvic cavity, splenectomy, and appendectomy, as well as left inguinal herniorrhaphy. Histological examinations revealed a splenic metastasis of PMP originating from the ovarian low-grade mucinous tumor. She received postoperative intraperitoneal lavage as well as chemotherapy, and has survived for over 7 years postoperatively without any evidence of recurrence, as confirmed by repeated follow-up CT examinations and CEA determination. Splenic metastasis of PMP is extremely rare; this represents only the third reported case of its kind in the literature. Furthermore, it should be noted that an inguinal tumor can sometimes be an initial presentation of PMP.

Carcinoembryonic Antigen↗

Contribution of nitric oxide to the protective effects of ischemic preconditioning in ischemia-reperfused rat kidneys.

We examined the contribution of nitric oxide (NO) to the effect of ischemic preconditioning (IP) on renal function and the hemodynamics in ischemia-reperfusion (I/R) mediated kidney injury. IP was performed by using 4 minutes of ischemia followed by a 30-minute reperfusion interval. I/R treatment consisted of a 30-minute ischemia and 60-minute reperfusion interval. We measured the glomerular filtration rate (GFR), the fractional excretion of sodium (FE(Na)), and the renal blood flow (RBF) in IP+I/R and I/R kidneys. Rats were pretreated with NaCl, N(G)-nitro-L-arginine methyl ester (L-NAME), or L-arginine. We found that IP significantly improved GFR and FE(Na) as compared with I/R treatment; however, this effect was completely abolished by L-NAME injection and enhanced by L-arginine treatment. L-NAME treatment significantly diminished RBF but did not alter nitrite/nitrate excretion. Furthermore, we found that IP alone does not lead to inducible NO synthase protein expression whereas I/R or IP+I/R treatment clearly did. Moreover, we observed an increased heme oxygenase-1 expression in IP+I/R kidneys as compared with I/R treated ones. Our results clearly showed that IP pretreatment protects kidneys from I/R mediated tissue injury and that these effects were partially mediated by NO.

Animals↗

A case of bone metastasis from gastric carcinoma after a nine-year disease-free interval.

A case featuring very late and unusual metastasis of gastric cancer is presented. A 49-year-old woman presented with metastatic disease in the seventh cervical vertebra 9 years after a total gastrectomy for gastric carcinoma. The resected primary tumor was a Borrman type III, poorly differentiated adenocarcinoma which had invaded the subserosal layer of the stomach and had generated lymph node metastases. The patient was treated for the metastatic tumor with sequential administration of cisplatin, calcium leucovorin and 5-fluorouracil and subsequent irradiation. Remission was achieved and she survived for a further 13 months without major symptoms.

Adenocarcinoma↗