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Biomedical subjects

Naoki Hashimoto

Publications and source records attributed to Naoki Hashimoto.

At least 19 recordsLinked to original sources

Heterotopic gastrointestinal mucosa and pancreatic tissue in a retroperitoneal tumor.

We believe that this is the first report of a retroperitoneal tumor consisting of heterotopic gastrointestinal mucosa and pancreatic tissue. The patient was a 19-year-old woman with the chief complaint being occasional back pain. Abdominal computerized tomography demonstrated a 3.1 x 2.5 x 3.2-cm low-density solid and cystic lesion adjoining the left renal vein between the aorta and inferior vena cava. Angiography revealed that the inferior vena cava was displaced by the hypovascular tumor. The retroperitoneal lesion was diagnosed preoperatively as a benign tumor such as a neurogenic neoplasm or lymphangioma. At laparotomy, a cystic tumor was found, which existed behind the inferior vena cava and renal vessels, and contained reddish-brown fluid, suggesting hemorrhage in the past. The cut surface of the tumor showed a unilocular cyst with partially hypertrophic wall. Histopathological examination revealed a cystic tumor lined with heterotopic gastric and duodenal mucosa, with pancreatic tissue in the muscularis propria. In addition, evidence of bleeding from the gastric mucosa was observed in the cystic tumor. External secretion from these tissues could have triggered the hemorrhage and expanded the tumor, possibly resulting in the back pain.

Adult↗

Low-dose carbon monoxide inhalation prevents development of chronic allograft nephropathy.

Chronic allograft nephropathy (CAN) is the primary cause for late kidney allograft loss. Carbon monoxide (CO), a product of heme metabolism by heme oxygenases, is known to impart protection against various stresses. We hypothesized that CO could minimize the chronic fibroinflammatory process and protect kidney allografts from CAN. Lewis kidney grafts were orthotopically transplanted into binephrectomized Brown-Norway rats under short-course tacrolimus. Recipients were maintained in room air or exposed to CO at 20 parts/million for 30 days after transplant. Efficacy of inhaled CO was studied at day 30 and day 80. Isografts maintained normal kidney function throughout the experiment with creatinine clearance of approximately 1.5 ml/min. Renal allograft function in air controls progressively deteriorated, and creatinine clearance declined to 0.2 +/- 0.1 ml/min by day 80 with substantial proteinuria. CO-treated animals had significantly better creatinine clearance (1.3 +/- 0.2 ml/min) with minimal proteinuria. Histological examination revealed the development of progressive CAN in air-exposed grafts, whereas CO-treated grafts had minimal tubular atrophy and interstitial fibrosis, with negligible collagen IV deposition. In vitro analyses revealed that CO-treated recipients had significantly less T cell proliferation against donor peptides via the indirect allorecognition pathway and less anti-donor IgG antibodies compared with air controls. Intragraft mRNA levels for chemokines (regulated on activation normal T cell expressed and secreted, macrophage inflammatory protein-1alpha, chemokine receptors (CCR1, CXCR3, CXCR5), IL-2, and intercellular adhesion molecule-1 were significantly decreased in CO-treated than in air-treated allografts. Furthermore, reduction of blood flow in air-treated allografts was prevented with CO. In conclusion, inhaled CO at a low concentration efficiently abrogates chronic fibroinflammatory changes associated with CAN and improves long-term renal allograft function.

Administration, Inhalation↗

Dynamic analysis of the resultant force acting on the hip joint during level walking.

The present study was designed to determine the resultant force acting on the hip joint during walking using a new dynamic analysis method. Our model utilized joint motion, ground reaction force, and muscle strength data from 18 women (6 normal women aged 20-24 years, 6 normal women aged 50-57 years, and 6 female patients with osteoarthritis, aged 50-66 years). We analyzed the resultant force using the multibody dynamic analysis system. To determine the factors that influence the force acting on the hip, we examined the effect of age and total hip arthroplasty. The maximum resultant force acting on the femoral head was dependent on the subject body weight and correlated with muscle strength and walking speed. The results of this study highlight the agreement between computer simulation analysis and actual measurement of the resultant force acting on the hip. Our results suggest that muscle strength and walking speed are significant determinants of the resultant force acting on the hip.

Adult↗

Effects of a bradykinin B(2) receptor antagonist on ischemia-reperfusion injury in a canine lung transplantation model.

BACKGROUND: This study investigated the effects of a bradykinin B(2) receptor antagonist, FR173657 (FR), on ischemia-reperfusion (I/R) injury in a canine lung transplantation model. METHODS: Eighteen pairs of weight-matched dogs were randomly divided into 3 groups. Six pairs were assigned to the FR(D+R) group, in which FR (100 nmol/kg/h) was administered to the transplant donor continuously beginning 30 minutes before ischemia until the onset of ischemia, and FR was administered to the transplant recipient beginning 30 minutes before reperfusion and continuing for 2 hours after reperfusion. Another 6 pairs of dogs were assigned to the FR(R) group, in which FR was administered only to the recipient in the same manner as in the FR(D+R) group. The other pairs were assigned to the control group, in which vehicle alone was administered. Orthotopic left lung transplantation was performed after 12-hour cold storage in Euro-Collins solution. Fifteen minutes after reperfusion, the right pulmonary artery and the right stem bronchus were ligated. The animals were measured for 4 hours after reperfusion for left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (PaO(2)) and alveolar-arterial oxygen pressure difference (A-aD(O(2))). Lung specimens were harvested for measurement of the wet-to-dry lung weight ratio (WDR), histopathologic studies and polymorphonuclear neutrophil (PMN) count. RESULTS: Compared with the control group, PaO(2), A-aDO(2), L-PVR and CO were all significantly (p < 0.05) improved and WDR significantly (p < 0.05) lower in both the FR(D+R) and FR(R) groups. Moreover, in the FR-treated groups, histologic tissue edema was mild, and PMN infiltration was significantly (p < 0.05) reduced. CONCLUSIONS: The bradykinin B(2) receptor antagonist, FR173657, ameliorates I/R injury in lung grafts, indicating that protection of lung grafts can be achieved by the administration of FR solely to the transplant recipient.

Animals↗

Glial fibrillary tangles in diffuse neurofibrillary tangles with calcification.

In the present study the occurrence and distribution of glial fibrillary tangles (GFT) and their related structures in diffuse neurofibrillary tangles with calcification (DNTC) were investigated using Gallyas-Braak (GB) stain. Six cases neuropathologically diagnosed as DNTC were studied (two males and four females). The age at death ranged from 56 to 73 years, with an average of 63.5+/-7.5 years. GFT were classified morphologically, and their immunoreactivites for tau and ubiquitin were examined. Glial cells with GFT were identified with astrocytes and oligodendrocytes by immunostain for glial fibrillary acidic protein and transferrin, respectively. A small number of coiled bodies detected within the oligodendrocytes in the white matter of the cerebrum were positive for tau and ubiquitin. Cell clusters of thorn-shaped astrocytes were detected in the subcortical and subpial regions where gliosis occurred. Thorn-shaped astrocytes were positive for tau, but negative for ubiquitin. A small number of tuft-shaped astrocytes detected prominently in the temporal cortex and amygdala with numerous neurofibrillary tangles were positive for tau and ubiquitin. All three types of GFT were detected, especially in the temporal and limbic lobes, which were the most severely affected sites in DNTC. Moreover, various-shaped neurofibrillary tangles, aggregated rods and some argyrophilic threads were differentiated from GFT. They were positive for GB, but not detected within the glial cells.

Aged↗

Effect of clinical clerkship on students' attitudes toward medical learning in Japan: a case study at Kinki University School of Medicine.

A 20-item questionnaire was administered to 253 physicians and 111 medical students, who did not have previous clinical clerkship experience, upon completion of their clinical clerkship. Medical students responded that they enjoyed their clinical clerkships but felt pressured and physically tired. Ninety percent of these medical students developed expectations for their career choice during their clinical clerkship. Only 18% of physicians felt that they allowed students enough chance to participate in clinical practice. We must emphasize that the success of any clinical clerkship system depends on an effective communication system between physicians and medical students.

Journal Article↗

Effect of glicentin on gut mucosal growth in rats with jejunal and ileal Thiry-Vella fistulas.

BACKGROUND/PURPOSE: Glicentin stimulates growth of normal and atrophic small bowel mucosa; the mechanisms for this trophic effect of glicentin are not completely known. The purpose of this study was to determine whether the trophic effect of glicentin is mediated by mechanism involving luminal or nonluminal factors and determine whether glicentin exerts a differential trophic effect on either jejunal or ileal mucosa. METHODS: Thirty-two male Wistar rats underwent construction of either a jejunal or ileal Thiry-Vella fistula (TVF). After 10 days recovery period, rats were further subdivided into groups to receive either saline (control) or glicentin (100 microg/kg/d). Rats were killed on day 8, and TVF as well as corresponding segments of intact jejunum or ileum were removed. Mucosa was scraped, weighed, and analyzed for protein content and Alp activity. In addition, representative sections of full-thickness bowel from each group were examined histologically. RESULTS: In the jejunal TVF group, glicentin increased mucosal growth measurements in both the TVF and the intact jejunum. However, in the ileal TVF group, glicentin stimulated proliferation of intact ileal mucosa only; it had no effect on ileal mucosa in the TVF. CONCLUSIONS: These results suggest that glicentin exerts a systemic effect independent of luminal factors on the proliferation of proximal gut mucosa in addition to an indirect effect produced by stimulation of endogenous luminal secretions. In contrast, an indirect mechanism appears to be the predominant action of glicentin on growth of distal gut mucosa.

Anastomosis, Surgical↗

Effects of a p38 mitogen-activated protein kinase inhibitor as an additive to Euro-Collins solution on reperfusion injury in canine lung transplantation1.

BACKGROUND: The activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in the development of ischemia/reperfusion injury. FR167653 is a novel p38 MAPK inhibitor. This study evaluated the effects of p38 MAPK inhibition during cold ischemia on subsequent reperfusion injury using FR167653 as an additive to Euro-Collins solution in canine lung transplantation. METHODS: Canine orthotopic left lung transplantation was performed after 12-hr cold storage using Euro-Collins solution, with or without FR167653. Fifteen minutes after reperfusion, the right pulmonary artery and the right stem bronchus were ligated, and the animals were observed for 4 hr after reperfusion. Left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (Pao2), and alveolar-arterial oxygen pressure difference (A-aDo2) were measured. Lung specimens were harvested for wet-to-dry lung weight ratio (WDR) measurements, histopathologic studies, and polymorphonuclear neutrophil (PMN) counts. The activities of p38 MAPK in lung grafts were evaluated. RESULTS: The addition of FR167653 significantly (P<0.05) improved Pao2, A-aDo2, L-PVR, CO, and WDR and suppressed PMN infiltration after transplantation. FR167653 also ameliorated histologic damage to the lung graft. During cold storage, p38 MAPK was not activated in the lung graft, whereas it was markedly activated 30 min after reperfusion. FR167653 significantly (P<0.05) inhibited p38 MAPK activation 30 min after reperfusion. CONCLUSIONS: The addition of FR167653 to Euro-Collins solution improved lung graft viability associated with the inhibition of p38 MAPK activation. These results suggest that inhibiting p38 MAPK activation may attenuate ischemia/reperfusion injury in lung transplantation.

Animals↗

Efficacy of donor splenocytes mixed with bone marrow cells for induction of tolerance in sublethally irradiated mice.

BACKGROUND: High dose of bone marrow cells (BMCs) has been reported to be essential to establish donor-specific tolerance. In clinical settings, a large quantity of BMCs is very difficult to be obtained. Our previous report demonstrated that even a low dose of BMCs could establish donor-specific tolerance if mixed with splenocytes (SPLCs). In the present study, various components of SPLCs were purified or removed and were investigated their contribution for enhancement of bone marrow engraftment leading to donor-specific tolerance in sublethally irradiated mice. METHODS: Sublethally irradiated C57BL/6 recipient mice were intravenously injected 3 x 10(6) BMCs mixed with various components and various numbers of SPLCs harvested from BALB/c donor mice. One week after injection, skin grafting was performed. The degree of chimerism in peripheral blood lymphocytes (PBLs) and in SPLCs was analyzed by FACS 3 months after transplantation. RESULTS: Recipients receiving 3 X 106 BMCs mixed with 10 x 10(6) T cell-enriched SPLCs established chimerism. Recipients receiving BMCs mixed with macrophage-depleted SPLCs also showed chimeirism and donor-specific tolerance. B cell-enriched SPLCs did not help small dose of BMCs to establish chimerism. Irradiated SPLCs were not effective to induce tolerance even with additional infusion to recipients. CONCLUSIONS: Active effects of splenic T cells were more important to help engraftment of small dose of BMCs than B cells, but the interaction between T and B cells might play some roles to enhance BMC engraftment. Splenic macrophages or dendritic cells might have some adverse effects against tolerance induction. Fatal graft-versus-host disease (GVHD) might be avoided by depleting adherent cells from SPLCs, so macrophages or dendritic cells were also considered as key components to induce donor-specific tolerance and prevent GVHD in this model.

Animals↗

Effects of a bradykinin B(2) receptor antagonist, FR173657, on pulmonary ischemia-reperfusion injury in dogs.

BACKGROUND: This study investigated the effects of a bradykinin B(2) receptor antagonist, FR173657 (FR), on pulmonary ischemia-reperfusion (I/R) injury. METHODS: Twenty-four mongrel dogs were divided into four groups (n = 6 each). In Groups I, II and III, FR doses of 33, 100 and 300 nmol/kg per hour, respectively, were administered continuously beginning 30 minutes before ischemia and continuing for 2 hours after reperfusion. In Group IV, vehicle alone was administered. Warm ischemia was induced for 3 hours by clamping the left pulmonary artery and veins. Simultaneously, the left stem bronchus was bisected and then anastomosed before reperfusion. Fifteen minutes after reperfusion, the right pulmonary artery and bronchus were ligated. Left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (PaO(2)) and the alveolar - arterial oxygen pressure difference (A-aDO2) were measured for 4 hours after reperfusion. Lung tissue was harvested for wet-to-dry weight ratio (WDR) measurements, histopathologic studies and polymorphonuclear neutrophil (PMN) counts. Serum thromboxane (TX) B(2), 6-keto-prostaglandin (PG) F(1alpha) and leukotriene (LT) B(4) levels were also measured. RESULTS: PaO(2), A-aDO2, L-PVR and CO were significantly (p < 0.05) improved and WDR was significantly (p < 0.05) lower in Groups II and III than in Group IV. Histologic tissue edema was mild, and PMN infiltration was significantly (p < 0.05) reduced in Groups I, II and III compared with Group IV. TXB(2) levels were significantly (p < 0.05) lower in Group II than in Group IV, whereas 6-keto-PGF(1alpha) levels were not significantly different. LTB(4) levels were significantly (p < 0.05) lower in Groups II and III than in Group IV. CONCLUSIONS: FR appears to have a protective effect on pulmonary I/R injury stemming from the inhibition of eicosanoid release.

Animals↗

Plasma exchange for hypertriglyceridemic acute necrotizing pancreatitis: report of two cases.

We report two cases of hypertriglyceridemic necrotizing pancreatitis treated by plasma exchange (PE). The outcome of each case was quite different according to the timing of PE. A 36 year old man presented with abdominal pain, and a diagnosis of severe acute pancreatitis was made. His serum triglyceride (TG) level was 6,460 mg/dl. He did not undergo PE at first, however, his condition never improved and PE was performed 20 days after the onset of his illness. Finally, he died of multiple organ failure and sepsis. In contrast, a 52 year old man with acute necrotizing pancreatitis was referred to our department. He received PE quickly after hospital admission. His serum TG level, which was 3,540 mg/dl at hospital admission, dramatically returned to normal limits, and he was discharged from the hospital 62 days after admission. The prognosis of severe necrotizing pancreatitis due to hypertriglyceridemia is extremely poor. PE should be applied for the treatment of hypertriglyceridemic necrotizing pancreatitis immediately after its onset.

Adult↗

Systemic factors are trophic in Thiry-Vella loop in the absence of luminal contents.

BACKGROUND/AIMS: Mucosal histology, crypt cell proliferation and brush border enzymes were measured in rats with varying degrees of Thiry-Vella fistulas, in order to compare the effect of systemic and luminal factors on adaptive growth and differentiation (brush border enzymes) in small intestinal epithelium. METHODOLOGY: Twenty-four male Wistar rats (300-350 g) were divided with three groups of eight which underwent the following operations: 20% Thiry-Vella fistula, 80% Thiry-Vella fistula and sham operation. RESULTS: 80% Thirty-Vella fistulas caused a functional short gut; in intestine remaining in continuity there were significant increases in segmental weight, protein, Alp activity and villus height, compared with sham-operated controls and 20% Thiry-Vella fistulas. There was a significant fall in villus height, crypt cell production in loops of 20% Thiry-Vella fistula rats not exposed to luminal contents compared with control segments of sham-operated rats. In contrast, loops of the 80% Thiry-Vella fistula rats were not atrophied despite the much greater distance from luminal nutrients; the villus height and PCNA-LI were higher than in 20% Thiry-Vella fistula rats, and at least as great as in sham-operated rats. CONCLUSIONS: This study indicates that atrophy does not occur in loops after 80% Thiry-Vella fistula because crypt cell proliferation is maintained in Thiry-Vella fistulas. Thus, the atrophic effect of diversion of luminal nutrients can be counteracted by systemic growth factors released as part of the adaptive response; luminal factors are not essential for maintenance of normal cellular turnover when there is a powerful stimulus to cell proliferation.

Animals↗

Pancreatic juice output and amylase level in the drainage fluid after pancreatoduodenectomy in relation to leakage.

BACKGROUND/AIMS: The objective of this study was to clarify the relationship between the consistency of the pancreas and pancreatic anastomotic leakage after pancreatectomy. METHODOLOGY: Sixty-two patients who underwent proximal pancreatectomy with pancreaticoenterostomy were reviewed with regard to the consistency of the pancreas, size of the main pancreatic duct, postoperative pancreatic juice output, and pancreatic leakage after partial pancreatoduodenectomy. The pancreatic parenchyma was classified as having soft, intermediate and hard consistency (group 1, 2 and 3, respectively). Monitoring the output of pancreatic juice and amylase level in the drainage fluid after operation for the purpose of detecting of dehiscence of pancreaticoenterostomy. RESULTS: The mean pancreatic juice output during a period of 10 days (postoperative days 5 to 14) was 2446 +/- 27 cc in group 1 (n = 26), 846 +/- 13.5 cc in group 2 (n = 19) and 460 +/- 8.1 cc in group 3 (n = 17). Anastomotic leakage occurred in four (15%) patients in group 1, three (15%) in group 2, and none in group 3. In patients with leakage, abrupt decrease or fluctuating output of pancreatic juice occurred and amylase level in the drainage fluid was more than 10,000 IU/L POD 7. CONCLUSIONS: Patients with a pancreatic parenchyma with an intermediate or normal consistency produced more pancreatic juice and had a higher leak rate. Monitoring the output of pancreatic juice and amylase level in the drainage fluid after operation may provide a clue to the detection of dehiscence of pancreaticoenterostomy.

Amylases↗

Effect of acute portal hypertension on gut mucosa.

BACKGROUND/AIMS: Patients with cirrhosis are predisposed to develop spontaneous bacteremias and peritonitis, mainly by enteric bacteria. Portal hypertension, by producing congestion and edema of the bowel wall, could increase the passage of bacteria from the intestinal lumen to regional lymph nodes to the systemic circulation or to both, a process termed bacterial translocation. The aim of this study was to investigate bacterial translocation, brush border enzyme activity and intestinal permeability of experimental acute portal hypertension. METHODOLOGY: Twenty-six male Wistar rats were used for all experiments. Rats were studied two days after the induction of portal hypertension (n = 13). Control animals were also studied two days after sham operation (n = 13). Samples of mesenteric lymph nodes for standard bacteriological cultures and a fragment of ileum for histological examination and mucosal contents of protein, Alp were obtained. Moreover, we evaluated the intestinal permeability by using the phenolsulfonphthalein test. RESULTS: Two days after surgery, a significantly greater properties of rats with acute portal hypertension (12 of 13, 92%) had positive mesenteric lymph node cultures compared with control group: sham operated (2 of 13, 15%). A significant increase in disappearance of phenol red from the luminal solution was observed in rats with acute portal hypertension. Brush border enzyme of Alp was also significantly decreased in acute portal hypertension, compared with in sham operated controls. CONCLUSIONS: The results of our study suggested that acute portal hypertension may be a major factor in the development of spontaneous infections in cirrhosis.

Alkaline Phosphatase↗

Hyperamylasemia after hepatic resection.

BACKGROUND/AIMS: Hyperamylasemia often occurs after hepatectomy, but the detailed mechanism of this phenomenon remains unclear. The aim of this study was to analyze factors that may be associated with the development of hyperamylasemia following hepatic resection. METHODOLOGY: The Pringle maneuver was performed in 12 patients (Pringle group), the hemihepatic vascular occlusion technique in 11 patients (Hemihepatic group). RESULTS: In the Pringle group, postoperative serum amylase levels were elevated significantly in comparison with the preoperative levels, but were not elevated in the hemihepatic group. CONCLUSIONS: It is suggested that portal congestion by portal triad interruption carries a potential risk of serum amylase elevation and pancreatitis after hepatectomy.

Adult↗

Pancreatic fistula after pancreatic head resection; incidence, significance and management.

BACKGROUND/AIMS: Anastomotic leak at the pancreatojejunostomy remains a common and dreaded complication after pancreaticoduodenectomy. Our aim was to determine the incidence, presentation, methods of management, and preoperative and postoperative factors that influence the clinical outcome. METHODOLOGY: We reviewed our collective experience with 70 consecutive patients from 1985 to 2000 for a variety of pathologic indications. Clinical, biochemical, intraoperative and postoperative factors were reviewed in an attempt to determine prognostic factors. RESULTS: Nine patients (12%) developed a pancreatic anastomotic leak as determined by increased amylase in drainage fluid (70%), were clinically insignificant and were managed by simple maintenance of intraoperatively placed drains. Although octreotide was used therapeutically in 4 patients (44%), significant, objective response was noted in all patients. Of the clinical, biochemical, intraoperative and postoperative factors reviewed to determine prognostic factors, a large amount of postoperative pancreatic juice output (P = 0.02) was a significant risk factor for pancreatic fistula formation. CONCLUSIONS: We conclude that most anastomotic leak at pancreaticoenterostomy after pancreaticoduodenectomy can be managed conservatively. Use of octreotide to aid in closure of the pancreatic leak was satisfactory.

Drainage↗