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Biomedical subjects

K Hatakeyama

Publications and source records attributed to K Hatakeyama.

At least 271 records · Page 15Linked to original sources

Suppression of hepatic portal blood flow caused by carbon dioxide pneumoperitoneum can be restored after dopamine administration in pigs.

Portal venous blood flow (PVF), hepatic arterial blood flow (HAF) and systemic arterial pressure (SAP) were examined after dopamine (DA) injection into the jugular vein under carbon dioxide pneumoperitoneum in pigs. When intraabdominal pressure (IAP) was increased by 12 mmHg, PVF and HAF were reduced, but SAP was unchanged. When IAP was kept at 12 mmHg, the injection of DA at 10 micrograms/kg/min for 2 min produced an increase in PVF without causing any change in HAF or SAP. The response in PVF was dose-dependent. When IAP was increased to 16 mmHg, PVF response was diminished, and no change in HAF or SAP was seen at the same dose of DA. These observations suggest that DA is effective in increasing PVF under enhanced IAP conditions, but such circulatory improvement due to the agent would be prominent when IAP is below 12 mmHg.

Animals↗

Colorectal carcinoma metastases to the liver. Does primary tumor location affect its lobar distribution?

BACKGROUND: There is considerable evidence that blood returning from different abdominal organs does not mix completely but maintains streamline flow in the portal vein. This study tested the hypothesis that the location of primary colorectal carcinoma affects the intrahepatic distribution of liver metastases according to streamline flow in the portal vein. METHODS: Eighty-five patients with histologically verified liver metastases from colorectal carcinoma underwent potentially curative hepatectomy. Primary tumor location was the right-sided colon in 18 patients and the left-sided colon in 67. The liver was divided into two lobes by Cantlie's line. RESULTS: A total of 195 metastatic deposits were resected: 135 in the right lobe and 60 in the left. In the right-sided colon carcinoma group, 29 deposits were in the right lobe and 3 in the left. In the left-sided colon carcinoma group, 106 deposits were in the right lobe and 57 in the left. The pattern of lobar distribution was significantly different in the two groups (P = 0.003). CONCLUSIONS: Right-sided colon cancers selectively involve the right lobe, while left-sided tumors involve the entire liver, considering the ratio of weights of the right to left lobe is 2:1. This difference suggests that primary tumor location affects the pattern of lobar distribution of colorectal carcinoma liver metastases according to streamline flow in the portal vein.

Carcinoma↗

A cohort of supporting metabolic enzymes is coinduced with nitric oxide synthase in human tumor cell lines.

Although nitric oxide (NO) has cytotoxic activity against certain tumor cell lines, some human tumor cell lines can themselves produce NO by expressing the inducible isoform of NO synthase (iNOS). As rates of cellular NO synthesis play a major role in determining whether NO has cytotoxic or cytoprotective effects at anatomic sites of NO production, identification of cellular processes which regulate rates of NO synthesis by iNOS is important for understanding the role of NO in tumor cell biology. This study demonstrates that argininosuccinate synthetase and GTP-cyclohydrolase-I, which catalyze rate-limiting steps in the synthesis of iNOS substrate (arginine) and cofactor (tetrahydrobiopterin), respectively, are coinduced with iNOS expression in two human tumor cell lines. These results indicate that coinduction of these supporting metabolic pathways helps to maximize cellular NO synthesis by iNOS in human tumor cells, suggesting that these pathways might be useful targets for pharmacologic intervention in NO-producing human tumor cells.

Adenocarcinoma↗

Carcinoma of the ampulla of Vater: is radical lymphadenectomy beneficial to patients with nodal disease?

This study was undertaken to evaluate the effectiveness of radical lymphadenectomy in ampullary cancer with nodal disease. Thirty-five patients underwent the Whipple procedure with radical lymphadenectomy. The location and number of positive nodes was characterized. Eighteen patients (51%) had positive nodes. Patients without nodal disease (pN0 group) had an actuarial 5-year survival rate of 81%. Seven patients with metastasis confined to the pancreaticoduodenal nodes had a 5-year survival rate of 67%, which was comparable for the pN0 group (N.S.) and better than the 27% 5-year survival rate in patients with positive superior mesenteric nodes (P<0.05). Eleven patients with one to three positive nodes had a 5-year survival rate of 71%, which was also comparable to the pN0 group (N.S.) and better than the 0% 5-year survival rate in patients with four or more positive nodes (P<0.01). Radical lymphadenectomy is effective against a limited degree of nodal disease.

Actuarial Analysis↗

Restricted appearance of self-reactive clones into T cell receptor intermediate cells in neonatally thymectomized mice with autoimmune disease.

Neonatally thymectomized (NTx) mice fall victim to such autoimmune diseases as gastritis and pancreatitis with aging. Self-reactive T cell clones are known to be consistently generated through TCR intermediate (i.e. TCRint) cell differentiation in normal mice (i.e. via the extrathymic pathways and an alternative intrathymic pathway). It was investigated whether the generation of such clones in NTx mice follows this rule or whether they are generated by default via mainstream T cell differentiation in the thymus. The majority of T cells generated in NTx mice were TCRint cells in all organs tested. In contrast to athymic mice, which carry only TCRint cells with aging, a leaky appearance of high TCR (i.e. TCRhi) cells emerged in the lymph nodes and other organs of NTx mice. Self-reactive clones estimated by anti-Vbeta monoclonal antibodies in conjunction with the Mls system were confined to TCRint cells in all tested organs, including a target organ, the stomach, in NTx mice. A leaky population of TCRhi cells did not contain a significant number of self-reactive clones. Moreover, such self-reactive clones among TCRint cells in NTx mice with autoimmune disease were shown to be nonanergic in the proliferation assay. The present results suggest that the generation of self-reactive clones is totally due to TCRint cell differentiation, although it is still undetermined whether the expanding TCRint cell population is generated via the extrathymic pathway or an alternative intrathymic pathway. It is shown here not to be due to a failure of the TCRhi cell-differentiation pathway in NTx mice.

Animals↗

Indocyanine green disappearance enhanced by prostaglandin E1 in patients with hepatic resection.

Indocyanine green (ICG) is a reliable indicator reflecting hepatocyte function and hepatic blood flow. Prostaglandin E1 (PGE) has been indicated to increase hepatic blood flow and protect the hepatocyte. The purpose of this study is to investigate whether PGE influences the ICG disappearance rate in patients with hepatic resection. Eleven patients with hepatic resection were divided into two groups according to the presence of liver cirrhosis (LC, n = 4) and chronic hepatitis (CH, n = 7). ICG 0.1 mg/kg was given as an intravenous bolus into the cubital vein 5 min after PGE administration, then the disappearance rate of ICG (ICG-K) was determined by a finger monitoring method. PGE administration increased ICG-K in the LC and CH groups with normal liver function, and the ICG-K response was dose dependent when the dosage of PGE ranged from 0.01 to 0.05 microg/kg/min. When ICG-K relative to the ICG-K of the control was defined as the ICG-K ratio, the daily course of the ratio in the LC group was higher than in the CH group. PGE increases the ICG-K of patients with normal liver function before and after hepatic resection, and this is evident in the case of liver cirrhosis.

Aged↗

Bile peritonitis due to a spontaneous perforation of the common bile duct: report of a case.

Spontaneous perforation of the extrahepatic bile duct is rare. We herein report the case of an 80-year-old woman who underwent emergency laparotomy for bile peritonitis due to a spontaneous perforation of the common bile duct. A 2-mm perforation was found in the posterior wall of the choledochus, and its wall was paper-thin. Three stones, 2mm in diameter, were removed from the common bile duct. She underwent T-tube decompression with intraoperative cholangiography demonstrating a swollen papilla of Vater. The swelling of the papilla disappeared 4 weeks after the operation. Her postoperative course was uneventful. It seems likely that the elevated intraductal pressure due to the swollen papilla following stone impaction caused the perforation in this patient. Furthermore, the excessive friability of the common bile duct of unknown etiology may also have contributed to the perforation. This experience along with a review of the literature indicate that biliary decompression is the treatment of choice for this condition.

Aged↗

Enhancement of portal blood flow by ursodesoxycholic acid in partially hepatectomized rats.

Portal venous flow (PVF) was examined after portal injection of ursodesoxycholic acid (URSO) in rats that were partially hepatectomized by either 40% or 66%. URSO (10 mg/kg per minute) was injected into the portal vein and was thereafter observed to increase PVF concomitantly with a fall in portal vein and was thereafter observed to increase PVF concomitantly with a fall in portal venous pressure (PVP) in control animals. The increase in PVF in response to URSO was dose-dependent. In hepatectomized rats, the PVF response was augmented when the same dose of URSO was portally injected, and the magnitude of response was enhanced in proportion to the volume of liver resected. These results suggest that URSO increases PVF through vasodilation of the portal vessels, and therefore URSO is considered to increase PVF potently in a partially hepatectomized condition.

Animals↗

Hepatocellular carcinoma associated with precirrhotic primary biliary cirrhosis successfully treated by a right hepatic lobectomy: report of a case.

We report herein the case of a 69-year-old woman in whom hepatocellular carcinoma (HCC) arising in the precirrhotic phase of primary biliary cirrhosis (PBC) was successfully managed by a right hepatic lobectomy. The patient, who had never received a blood transfusion, had a 4-year history of asymptomatic PBC of Scheuer's histological classification stage II. Abdominal computed tomography (CT) revealed a mass measuring 4.0 cm in the right hepatic lobe, and a right hepatic lobectomy was performed in consideration of her good liver function and the deep location of the tumor in the right lobe. The patient has remained well without any evidence of recurrent disease for 4 years since her operation. A review of the literature revealed only two cases of successful partial hepatectomy, but none of major hepatectomy. Most of the reported cases had been treated with transcatheter arterial embolization (TAE) and were associated with poor survival. Our experience of this patient indicates the potential value of hepatectomy as an alternative to TAE in selected patients with resectable disease and good hepatic function.

Aged↗

Effect of prostaglandin E1 on ammonia concentration in blood of patients with hepatic resection.

Plasma concentrations of ammonia were examined following prostaglandin E1 (PGE1) administration in 16 patients who received hepatectomy for hepatocellular carcinoma. PGE1 at 0.01-0.04 microgram/kg/min was administered for approximately 24 hr during the perioperative periods. The ammonia concentration was reduced a day after the operation following intravenous administration of PGE1 in cirrhotic patients compared to noncirrhotic patients with or without PGE1 injection. Serum liver function scores, glutamic pyruvic transaminase, and total bilirubin concentrations were decreased after PGE1 administration. A similar ammonia response due to PGE1 was obtained after operation in cirrhotic patient when PGE1 0.5 microgram/kg was administered intravenously for 30 min. These results suggest that PGE1 administration is useful in reducing the enhanced ammonia concentration associated with hepatic resection, and it is particularly effective in the case of liver cirrhosis.

Alanine Transaminase↗

Simultaneous development of Crohn's disease and myelodysplastic syndrome progressing to acute myelocytic leukemia in a patient with a normal karyotype.

A 28-year-old man developed Crohn's disease and myelodysplastic syndrome concurrently. Chromosomal analysis of the bone marrow revealed a normal male karyotype. Subsequently, the myelodysplastic syndrome progressed to acute myelocytic leukemia. Several causes, including the medical treatment for Crohn's disease, chromosomal abnormalities, and a common underlying immune dysfunction, have been proposed as pathogenetic factors in the association with Crohn's disease of hematologic malignancies. This case suggests that neither medical treatment for Crohn's disease nor chromosomal abnormalities are inevitable causes of the development of hematologic malignancies associated with Crohn's disease. At present, the cause of the association remains unclear, although the idea of a common immune dysfunction is attractive.

Adult↗

Intramural metastases from thoracic esophageal cancer: local indicators of advanced disease.

The patterns of tumor spread and long-term survival of patients with (n = 54) and without (n = 270) intramural metastasis from esophageal cancer were investigated after either extended radical (n = 155) or less radical (n = 169) esophagectomy. The purpose was to evaluate whether extended radical esophagectomy has an impact on the long-term survival of patients with intramural metastases from the disease. The patients with intramural metastasis had significantly larger primary tumors (p < 0.01) and more frequent T4 tumors (p < 0.001), stage IV disease (p < 0.05), lymphatic invasion (p < 0.05), and lymph node metastasis (p < 0.01) than did those without intramural metastasis. The survival rates of patients with intramural metastases were significantly worse than those of patients without intramural metastases after resection (p < 0.001). No patient with intramural metastases survived more than 4 years after either extended or less radical esophagectomy, and there was no significant difference between the two survival curves. Therefore intramural metastases should be considered local indicators of advanced esophageal cancer, and radical esophagectomy may not be indicated for patients with intramural metastasis from the disease.

Aged↗

Effects of inflation pressure of balloon catheter on vascular injuries and subsequent development of intimal hyperplasia in rabbit aorta.

Balloon catheter de-endothelialization is the most popular means of arterial injury in experimental animals and has been used as the model system to investigate atherogenesis and restenosis after percutaneous transluminal coronary angioplasty (PTCA). The aim of this study was to examine the relationship between balloon inflation pressure and vascular damage and also subsequent intimal hyperplasia. Retrograde pullback balloon injury of rabbit aortas was made at three different balloon pressures (1.5, 1.75, and 2.0 atm). The medial injuries, such as necrosis of smooth muscle cells and disruption of elastic lamina, were occasionally found in the injured segment of the aorta by balloon catheter at 1.75 atm and more frequently at 2.0 atm. No prominent medial injury was observed in the aortic segment to balloon catheter injury at 1.5 atm; Intimal hyperplasia developed in each animal and increased with time, 2, 4, and 8 weeks after injury. The intimal hyperplasia followed by balloon injury at 1.75 and 2.0 atm was more prominent than that at 1.5 atm, however, the development of the intimal hyperplasia was not parallel to the degree of inflation pressure. On the other hand, decrease of DNA content of the media and reduction of norepinephrine-induced vasoconstriction were observed in a pressure-dependent manner after balloon injury. These findings indicate that intimal hyperplasia is not proportionally correlated to the severity of the vascular injury. The control of inflation pressure is very important in order to examine vascular injuries, subsequent intimal hyperplasia and vasomotor responses in animal models of balloon catheter injury.

Animals↗

The mode of lymphatic spread in carcinoma of the bile duct.

BACKGROUND: Knowing the prevalence of lymph node involvement associated with the location of the primary tumor is a prerequisite for operating with curative intent in carcinoma of the bile duct. METHODS: We evaluated 80 patients with carcinoma of the bile duct or cystic duct to investigate the frequency of lymph node involvement, the mode of lymphatic spread, and prognosis, according to the location of the primary tumor. RESULTS: The frequency of lymphatic spread of carcinomas in the proximal, middle, and distal bile ducts, excluding seven T1 tumors, was 48%, 67%, and 56%, respectively. With regard to the mode of lymphatic spread: (1) a metastatic pathway along the common hepatic artery predominated over that to the retropancreatic area in the proximal duct carcinoma group; (2) in the middle duct carcinoma group, metastatic lymph nodes were distributed widely, involving nodes around the superior mesenteric artery or at the para-aortic area; and (3) in the distal duct carcinoma group, metastatic nodes generally were localized around the head of the pancreas. CONCLUSIONS: Understanding the mode of the lymphatic spread according to the primary tumor may be helpful for choosing the appropriate surgical approach with curative intent in bile duct carcinoma.

Adult↗

Outcome of radical surgery for carcinoma of the gallbladder according to the TNM stage.

BACKGROUND: The role of surgery in the treatment of gallbladder carcinoma (GBC) is controversial. The outcome after prospective radical surgery for GBC is discussed on the basis of the TNM stage of the tumor. METHODS: One hundred six patients who had undergone radical surgery were selected. The standard radical procedure consisted of a cholecystectomy accompanied by lymph node dissection, wedge resection of the liver, and resection of the extrahepatic bile ducts. The stage was determined by pathologic examination of resected specimens. RESULTS: Lymph node metastases were identified in no patients with T1 tumors (n = 15), 48% of patients with T2 tumors (n = 46), 72% of patients with T3 tumors (n = 25), and 80% of patients with T4 tumors (n = 20). One patient died within 30 days after radical surgery (mortality rate, 0.9%). There were 35 5-year survivors including 11 patients with nodal involvement, 10 with stage I tumors, 13 with stage II tumors, 10 with stage III tumors, and 2 with stage IV tumors. The cumulative 5-year survival rate in patients with stage I tumors was 91% (n = 15), 85% in patients with stage II tumors (n = 24), 40% in patients with stage III tumors (n = 28), and 19% in patients with stage IV tumors (n = 39). In patients with stage III and IV tumors the 5-year survival rate was 52% after curative resection (n = 35). This was significantly better than the 5% 5-year survival rate after a noncurative resection (n = 32). CONCLUSIONS: The presence of lymph node metastases is strongly influenced by the depth of invasion of the primary tumor. Accurate determination of the TNM stage is essential in comparing surgical results, predicting patient outcome, and planning additional treatment. Standard radical surgery contributes to patient survival and is recommended in patients with advanced GBC.

Adult↗

Vascular inducible nitric oxide synthase gene therapy: requirement for guanosine triphosphate cyclohydrolase I.

BACKGROUND: Human inducible nitric oxide synthase (iNOS) gene transfer inhibits myointimal hyperplasia in vitro. However, unstimulated vascular smooth muscle cells (SMC) do not synthesize tetrahydrobiopterin (BH4), an essential cofactor for iNOS, which may be an obstacle to successful vascular iNOS gene therapy. We investigated the capacity of gene transfer of guanosine triphosphate (GTP) cyclohydrolase I (GTPCH), the rate-limiting enzyme for BH4 biosynthesis, to supply cofactor for iNOS activity. METHODS: A human GTPCH expression plasmid (pCIS-GTPCH) was transfected into rat aortic SMC (RAOSMC) and BH4-deficient NIH3T3 cells engineered to stably express human iNOS (3T3-iNOS). GTPCH activity and intracellular biopterins were assessed as a measure of successful transfection, and the capacity of GTPCH to reconstitute iNOS activity was used to determine whether BH4 was made available to the iNOS protein. RESULTS: The pCIS-GTPCH-transfected 3T3 cells had demonstrable GTPCH activity as compared with control cells (169.3 +/- 6.6 pmol/hr/mg versus 0, p < 0.001). Intracellular biopterin levels were also increased in transfected 3T3 and SMC (60.6 +/- 2.6 and 101.7 +/- 28.3 pmol/mg, respectively, versus less than 4 in control cells). GTPCH reconstituted near-maximal iNOS activity in 3T3-iNOS cells despite a gene transfer efficiency of less than 1%. GTPCH and iNOS enzymes did not have to coexist in the same cell for the synthesized BH4 to support iNOS activity. CONCLUSION: GTPCH gene transfer reconstitutes iNOS activity in BH4-deficient cells despite poor transfer efficiency. GTPCH can deliver a cofactor to targeted cells even if it is synthesized in neighboring cells, and may be a means to concurrently deliver BH4 with iNOS in vivo.

3T3 Cells↗

Intestinal fatty acid-binding protein is a useful diagnostic marker for mesenteric infarction in humans.

BACKGROUND & AIMS: Acute ischemic diseases of the small bowel are lethal emergencies with no reliable diagnostic biochemical tests available. Experimental studies have suggested rat intestinal fatty acid-binding protein (I-FABP) as a serum marker reflecting bowel ischemia; the present study evaluates the human homologue (human I-FABP) as a serum marker for the diagnosis of acute ischemic diseases of the bowel. METHODS: Enzyme immunoassay was applied to determine I-FABP levels in the sera of 96 subjects: 13 preoperative patients with ischemic bowel diseases (5 cases of mesenteric infarction and 8 cases of strangulated obstruction of the small bowel), 35 healthy subjects, and 48 hospitalized patients with acute abdominal pain. RESULTS: Serum I-FABP levels were < 65 ng/mL in healthy subjects. In patients with acute abdominal pain, levels ranged from < 20 to 87 ng/mL (mean, 27.4 ng/mL), not significantly different from findings in healthy subjects. However, patients with ischemic bowel disease showed significantly higher I-FABP levels, ranging from < 20 to 1496 ng/mL (mean, 265.8 ng/mL). All 5 patients with mesenteric infarction showed I-FABP levels of > 100 ng/mL. CONCLUSIONS: I-FABP is a useful biochemical marker for the accurate diagnosis of mesenteric infarction.

Adolescent↗