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Biomedical subjects

A Harada

Publications and source records attributed to A Harada.

At least 145 records · Page 8Linked to original sources

Histopathology of the liver in non-cirrhotic portal hypertension of unknown aetiology.

Non-cirrhotic, long-standing portal hypertension of unknown aetiology is being re-evaluated histopathologically and clinically. In this study, we examined 107 livers with this condition (92 wedge biopsy and 15 autopsy specimens) from five institutions in Japan. These cases were histologically categorized into four groups: idiopathic portal hypertension (66 cases), nodular regenerative hyperplasia (14 cases), partial nodular transformation (two cases), and incomplete septal cirrhosis (25 cases). These four groups shared several histological features: dense portal fibrosis with portal venous obliteration and intralobular slender fibrosis. In addition, the histopathological features characteristic of one group were also found to a mild degree in other groups. The histopathological lesions preceding portal venous obliteration remain speculative. However, the portal venous obliteration may be responsible for the occurrence of sustained portal hypertension and several of the pathological changes in these livers. It seems likely that idiopathic portal hypertension, nodular regenerative hyperplasia, partial nodular transformation and incomplete septal cirrhosis comprise a family of non-cirrhotic, long-standing portal hypertension in Japan, and the histological differences between them may reflect chronological progression of a single disease.

Adolescent↗

LFA-1 (CD11a/CD18) and ICAM-1 (CD54) antibodies attenuate superoxide anion release from polymorphonuclear leukocytes in rats with experimental acute pancreatitis.

The inhibitive effects of anti-CD11a/CD18 (LFA-1) and anti-CD54 (ICAM-1) antibodies on the generation of superoxide anion (O2-) by polymorphonuclear leukocytes (PMNs) was elucidated in rats induced with experimental acute pancreatitis. We investigated the generation of O2- by PMNs in two protocols: in the first, we measured the active oxygen-producing ability of PMNs isolated from blood in normal rats; in the second, we measured it from blood, peritoneal cavity, and bronchial alveolar lavage fluid in rats 3 h after the induction of pancreatitis. In normal rats, although LFA-1 antibody attenuated the generation of O2-, ICAM-1 antibody did not. However, in pancreatitis rats, both LFA-1 and ICAM-1 antibodies reduced the generation of O2- by PMNs isolated from blood and the peritoneal cavity. These results showed not only that both LFA-1 and ICAM-1 antibodies have a protective effect on the generation of O2-, but also that LFA-1 has a direct inhibitive effect on the generation of O2- by PMNs in this model. Furthermore, histological studies showed there to be less neutrophil accumulation in the lungs of LFA-1- and ICAM-1-treated animals compared to control animals.

Acute Disease↗

Clinical significance of carcinoma invasion of the extrapancreatic nerve plexus in pancreatic cancer.

To elucidate the clinical significance of neural invasion in pancreatic carcinoma, a clinicopathological study was performed. Neural invasion is a common feature of pancreatic carcinoma whose clinical significance has not yet been determined. Over a period of > 10 years, 129 of 204 (63%) patients with pancreatic carcinoma underwent resection by extensive radical surgery. A clinicopathological study of those specimens of pancreatic carcinoma was performed, with particular reference to neural invasion. Intrapancreatic neural invasion was observed in 116 of 129 (90%), of which 80 (69%) showed extrapancreatic nerve plexus involvement. A statistically significant (p < 0.001) correlation between the grade of intrapancreatic neural invasion and extrapancreatic nerve plexus invasion was observed. The postoperative survival rate for patients with extrapancreatic nerve plexus involvement was significantly (p < 0.001) lower than that for patients without extrapancreatic nerve plexus involvement. Patients who survived for > 3 years after operation had no extrapancreatic nerve plexus invasion even when portal vein wall invasion was observed.

Carcinoma↗

Detection of ras gene mutations in perioperative peripheral blood with pancreatic adenocarcinoma.

Surgeons wish to know of any correlation between an operation and the incidence of metastasis. In perioperative periods, pancreatic cancer cells were identified by detecting mutant K-ras gene by two-step PCR and RFLP analysis in blood samples taken from peripheral blood. In no case was K-ras point mutation detected in blood before operation, although the mutant hand was observed in all cases at the time the lesion was resected. Surprisingly, in five of ten cases, positive bands were identified just after laparotomy, before we had reached the primary lesion. In almost all cases, mutant K-ras was detected until the fourteenth postoperative day. These findings suggest that cancer cells exist in the circulation, and have a potential for hematogenous metastasis during the perioperative period. In conclusion, surgical stress causes hematogenous dissemination of pancreatic cancer cells, and surgeons should employ the appropriate anti-metastasis therapy in the perioperative period.

Adenocarcinoma↗

A case report of simultaneous surgery for Wolff-Parkinson-White syndrome combined with hemolytic anemia and mitral stenosis.

A 46-year-old woman with mitral stenosis, WPW syndrome, hemolytic anemia due to spherocytosis, and hypothyroidism with Hashimoto's thyroiditis, was admitted with palpitations and dyspnea due to paroxysmal atrial fibrillation with a rapid ventricular response, and was treated by electrical cardioversion. We selected surgical intervention to treat the mitral stenosis and WPW syndrome, as some tachycardia episodes due to atrial fibrillation have resulted in repeated congestive heart failure. In 1983 we simultaneously performed a division of the posteroseptal accessory pathway and a mitral valve replacement with a bioprosthetic valve under cardiopulmonary bypass, using a membrane oxygenator after splenectomy to compensate for the hemolytic anemia due to spherocytosis. Her postoperative course was favorable and she is now in good health with no episodes of tachycardia, congestive heart failure nor anemia occurring during the 10 years that have followed the operation. Simultaneous surgery for WPW syndrome combined with other cardiac abnormalities and hematologic disorders achieved acceptable results in this case.

Anemia, Hemolytic↗

Effect of temperature on morphology of electrochemically-deposited calcium phosphates.

Calcium phosphates were electrochemically deposited on titanium plates at temperatures from 4 degrees C to 92 degrees C in a solution of NaCl, K2HPO4 and CaCl2 x 2H20. Scanning electron microscopic studies showed that granular deposits formed on the electrode at electrolyte temperatures of 4 degrees C, 22 degrees C, and 37 degrees C; needle-like deposits formed at 52 degrees C-92 degrees C. The width and length of the needles increased with the temperature of the electrolyte. Based on the results of characterization by electron diffractometry. Fourier transform infrared spectroscopy and X-ray diffractometry, the granular deposits were identified as carbonate-containing calcium phosphate with low crystallinity, and the needle-like deposits as carbonate-containing apatite crystals elongated along the c-axis. Crystallinity of the deposits increased with the temperature of the electrolyte, whereas the orientation indices of the apatite increased with temperature up to 82 degrees C and slightly decreased at 92 degrees C.

Apatites↗

[Identical twin sisters with IgA nephropathy].

This report described 45-year-old identical twin sisters with IgA nephropathy. Case 1 presented with microscopic hematuria and proteinuria at the age of 39. Case 2 was found proteinuria at the age of 32. Both the physical examination and laboratory data of these cases were normal. Serum level of IgA was not elevated. The renal biopsy specimen of two cases showed slight mesangial proliferation by light microscopy and mesangial IgA deposition by immunofluorescence microscopy. Their serotype for HLA was found to be HLA-A2, A24, Bw35, Cw1, Cw3, DRw8, DRw12. Several reports indicated the familial occurrence of patients with IgA nephropathy and a strong association with HLA-Bw35 in those patients. The present cases also suggested that an abnormal immune response-linked HLA system may be involved in the development of IgA nephropathy.

Diseases in Twins↗

Thermostable peroxidase activity with a recombinant antibody L chain-porphyrin Fe(III) complex.

In order to engineer a new type of catalytic antibody, we attempt to use a monoclonal antibody L chain as a host protein for a porphyrin. TCPP (meso-tetrakis(4-carboxyphenyl)porphyine) was chemically synthesized and Balb/c mice were immunized using TCPP as a hapten. Two hybridoma cells (03-1, 13-1), that produce monoclonal antibody against TCPP, were obtained. Genes for both H and L chains of monoclonal antibodies were cloned, sequenced and overexpressed using E. coli as a host. ELISA and fluorescence quenching method show that the independent antibody L chains from both Mab03-1 and Mab13-1 have specific interaction with TCPP. Furthermore, the recombinant antibody L chain from Mab13-1 exhibits much higher peroxidase activity than TCPP Fe(III) alone. The enzyme activity was detectable with pyrogallol and ABTS (2,2-azinobis-3-ethylbenzthiazolin-6-sulfonic acid) but not with catechol. This new catalytic antibody was extremely thermostable. Optimum temperature of the peroxidase reaction by the complex of 13-1L chain and TCPP Fe(III) was 90 degrees C, while that the TCPP Fe(III) alone was 60 degrees C.

Amino Acid Sequence↗

Tumor necrosis factor (TNF) is a physiologic regulator of hematopoietic progenitor cells: increase of early hematopoietic progenitor cells in TNF receptor p55-deficient mice in vivo and potent inhibition of progenitor cell proliferation by TNF alpha in vitro.

Murine bone marrow cells with lineage phenotypes (Lin)-Sca-1+c-kit+ and Lin-Sca-1-c-kit+ cells represent primitive hematopoietic stem cells (HSCs) and committed hematopoietic progenitor cells, respectively. The number of Lin-Sca-1+c-kit+ HSCs in bone marrow was significantly increased in tumor necrosis factor (TNF) receptor p55-deficient (TNF-R55-1-) mice compared with the TNF-R55+/+ wild-type mice without a marked change in bone marrow cellularity. In both the methylcellulose culture and a single-cell proliferation assay, mouse TNF alpha (mTNF alpha) inhibited in vitro the proliferation of wild-type mouse-derived Lin-Sca-1+c-kit+ cells in response to a combination of multiple growth factors. The same is true for that of Lin-Sca-1+c-kit+ cells stimulated with granulocyte colony-stimulating factor (G-CSF) plus stem cell factor (SCF). Moreover, mTNF alpha significantly arrested the entry into S-phase from G0/G1 phase of Lin-Sca-1+c-kit+ cells stimulated with multiple growth factors and Lin-Sca-1-c-kit+ cells stimulated with G-CSF plus SCF. In contrast, mTNF alpha failed to affect the growth and cell cycle progression of Lin-Sca-1+c-kit+ cells and Lin-Sca-1-c-kit+ cells that were obtained from TNF-R55-deficient mice. These data suggest that TNF may be an important physiologic regulator of hematopoiesis and that TNF-R55 may be essentially involved in TNF-mediated inhibition of the growth of both primitive stem and more committed progenitor cells.

Animals↗

Molecular analysis of the cytokine network involved in cachexia in colon 26 adenocarcinoma-bearing mice.

Two clones, one cachexigenic (clone 20) and the other noncachexigenic (clone 5), from a murine colon adenocarcinoma, colon 26 cells, were used to analyze the involvement of immune reactions as well as the cytokine network in cachexia. Clone 20 induced cachexia in nude and SCID mice as well as in normal BALB/c mice, suggesting that lymphocytes played little, if any, role in the process. Both clones failed to express mRNA of interleukin (IL) 1 alpha, IL-1 beta, IL-6, and tumor necrosis factor alpha in vitro with or without the coculture of NIH3T3 cells or spleen cells. However, IL-6 mRNA was selectively detected at the tumor site of clone 20 but not at that of clone 5-bearing mice. In contrast, tumor necrosis factor alpha mRNA was detected at tumor sites and in spleens of only clone 5-bearing mice, suggesting a potential role of IL-6, but not tumor necrosis factor alpha, in inducing cachexia. Anti-IL-6 antibody partially reversed the weight loss induced by clone 20, whereas the continuous infusion of IL-6 failed to cause weight loss, despite being associated with an elevation of a serum acute phase protein. These results suggest that IL-6 is necessary but not sufficient for the induction of cachexia. Both clones expressed IL-6 mRNA in the presence of IL-1 in vitro, and mice bearing either clone expressed IL-1 beta mRNA at the tumor site. Moreover, IL-1 receptor antagonist (IL-1Ra) mRNA was detected at the tumor site of clone 5-bearing mice but not at that of clone 20-bearing mice, suggesting that IL-1Ra might block IL-1 activity to reduce IL-6 production in clone 5-bearing mice. However, the transfection of clone 20 with IL-1Ra cDNA failed to abolish its capacity to produce IL-6 and to cause cachexia. Collectively, additional factor(s) besides IL-1Ra and IL-1 beta may control IL-6 and some other cachexigenic factor production, thereby causing cachexia in this model.

Adenocarcinoma↗

Anti-neutrophil antibody attenuates the severity of acute lung injury in rats with experimental acute pancreatitis.

OBJECTIVE: To examine the role of activated neutrophils in microvascular injury after severe acute pancreatitis. We used the polyclonal anti-rat neutrophil antibody (PoAb) to deplete peripheral neutrophil counts and the anti-rat monoclonal antibody (MoAb) CD18 to block neutrophil adherence functions. DESIGN: Prospective, controlled trial. SETTING: Laboratory. PARTICIPANTS: Anesthetized male Wistar breeder rats, in which necrotizing pancreatitis was induced by injecting necrotizing agents into the pancreatic duct. INTERVENTIONS: Treatment groups received an infusion of PoAb, 8 mL/kg, before induction of pancreatitis or MoAb CD18, 2 mg/kg, after induction of pancreatitis. Control animals received 2 mL of rabbit serum or 1 mL of saline solution. MAIN OUTCOME MEASURES: Survival rate, white blood cell count, levels of serum amylase and lipase, myeloperoxidase activity in the lung, lipid peroxide levels in the pancreas, and results of histological studies. RESULTS: The survival rate of rats treated either with PoAb before or MoAb CD18 after induction of sepsis improved significantly (P < .01). Histologically and according to the levels of neutrophil myeloperoxidase in their lungs, rats treated with the antibodies 24 hours after inducing pancreatitis improved significantly (P < .05). Moreover, the serum lipase concentrations and lipid peroxide levels in the pancreas of these rats decreased significantly (P < .05). CONCLUSIONS: Both the depletion of peripheral neutrophils by PoAb and blocking of neutrophil adherence functions by MoAb CD18 may help to prevent acute lung injury caused by severe acute pancreatitis in this model.

Acute Disease↗

Dopamine compensates for deterioration of hepatic hemodynamics and metabolism during occlusion and reperfusion of the hepatic artery.

OBJECTIVE: To investigate the effects of temporary hepatic arterial occlusion and dopamine on hepatic hemodynamics and metabolism. DESIGN: Experimental animal study in a dog model. The proper hepatic artery was occluded for 60 minutes; then, it was reperfused for 60 minutes. Hepatic hemodynamic and oxygen metabolic values, lactate uptake ratios, and blood glucose levels were determined repeatedly throughout the experiment. Data are given as mean +/- SE. INTERVENTION: In another group, dopamine hydrochloride, 10 micrograms/kg per minute, was infused intravenously throughout the experiment, and the same variables were recorded. RESULTS: Portal vein blood flow continuously decreased during occlusion, and it decreased even further after declamping of the hepatic artery; this led to a disturbance of oxygen and lactate metabolism in the control group. Dopamine increased the portal vein blood flow from 84.9% +/- 3.9% to 100.9% +/- 3.6% of the preocclusion levels after 60-minute occlusion and from 79.0% +/- 3.6% to 93.6% +/- 5.1% of the preocclusion levels after 60-minute reperfusion (P < .05, respectively). Dopamine also enhanced the hepatic oxygen uptake ratio from 112.8% +/- 12.0% to 150.7% +/- 11.6% of the preocclusion levels after 60-minute reperfusion (P < .05, respectively). These factors contributed to acceleration of the hepatic oxygen consumption and lactate uptake ratio in the group of dogs that were infused with dopamine. CONCLUSIONS: Temporary occlusion of the hepatic artery causes deterioration of hepatic hemodynamics and metabolism. Administration of dopamine is an effective way to support hepatic function during occlusion of the hepatic artery.

Analysis of Variance↗

Lymph node metastases in carcinoma of the head of the pancreas region.

Histopathological examination of lymph node metastatic involvement in 139 specimens obtained from patients who underwent pancreatoduodenectomy or total pancreatectomy combined with wide resection of lymph nodes was performed, to clarify the critical areas of lymph node dissection in patients with carcinoma of the head of the pancreas region. Perigastric lymph node involvement in patients with carcinoma of the head of the pancreas was 14 per cent, in those with carcinoma of the distal bile duct 0 per cent and in those with carcinoma of the papilla of Vater 4 per cent. Para-aortic lymph node involvement in patients with carcinoma of the head of the pancreas, the distal bile duct and the papilla of Vater was 26, 9 and 0 per cent, respectively. On the basis of these results, pylorus-preserving pancreatoduodenectomy is indicated in almost all patients with carcinoma of the distal bile duct and the papilla of Vater. In patients with carcinoma of the head of the pancreas, however, wide dissection of lymph nodes, including para-aortic lymph nodes, should be carried out because of the relatively high incidence of para-aortic lymph node involvement.

Carcinoma, Ductal, Breast↗

Intracaval ultrasonography in the diagnosis of tumour involvement of the vena cava.

A retrospective study of 34 consecutive patients with possible tumour involvement of the vena cava was performed to assess the usefulness of intracaval ultrasonography. Twenty-five of the 34 patients were operated and resection carried out in 23, including seven with combined resection of the vena cava. The sonographic criterion for vena cava invasion was obliteration of the echogenic ring of the vena cava wall or intracaval tumour mass. The sensitivity, specificity and overall accuracy of intracaval endovascular ultrasonography in the diagnosis of tumour involvement of the vena cava were 100, 96 and 97 per cent respectively. The respective values were 91, 61 and 71 per cent for computed tomography and 82, 67 and 72 per cent for cavography. Ultrasonography is a useful technique that can precisely evaluate the vena cava for possible tumour invasion, especially when the presence or extent of tumour involvement is not definitely established by conventional imaging techniques.

Adult↗

Preparation of specific antibodies against murine IL-1ra and the establishment of IL-1ra as an endogenous regulator of bacteria-induced fulminant hepatitis in mice.

Blocking monoclonal antibodies (mAbs) specific to mouse interleukin-1 receptor antagonist (IL-1ra) were prepared by immunizing Armenian hamsters with recombinant mouse IL-1ra. A sensitive and specific ELISA against mouse IL-1ra was also established. In Propionibacterium acnes-induced liver injury, P. acnes induced transient increase of serum tumor necrosis factor-alpha levels but not those of IL-1ra, IL-1, and IL-6. However, subsequent lipopolysaccharide (LPS) challenge induced the increase of serum levels of all these cytokines and the peak serum IL-1ra level was more than 20 times as high as serum IL-1 levels. Immunohistochemical analysis demonstrated that IL-1ra was predominantly produced by hepatocytes during the course of the priming phase by P. acnes and eliciting phase by LPS challenge. Furthermore, the administration of a mAb to mouse IL-1ra exacerbates the liver injury induced by P. acnes and sublethal dose of LPS, suggesting a protective role of endogenous IL-1ra in this liver injury model.

Animals↗

Intraoperative peritoneal washing cytology with the rapid immunoperoxidase method using microwave irradiation.

The rapid immunocytochemical staining of gastrointestinal cancer-associated antigens, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), for intraoperative peritoneal washing cytology of pancreatic or biliary carcinoma can be completed in only 25 minutes by using microwave irradiation to accelerate incubation of the primary antibody. Only 3-second irradiation at 500 W for fresh smears produced specific antigen staining of malignant cells similar to that obtained with longer incubation, and the sensitivity of intraoperative cytology was greater than by the conventional staining method. The rapid immunocytochemical staining method of peritoneal washings at laparotomy can provide sensitive information for determining more aggressive therapy for intraperitoneal spread of malignant cells before closing the abdominal wall.

Aged↗

Duration of liver ischemia and hepatic regeneration after hepatectomy in rats.

Since an occlusion of the vascular inflow to the liver is a useful technique in liver surgery, a relation between ischemia and regeneration in the liver is particularly important. The purpose of this study was to evaluate the effect of ischemic duration on liver regeneration after massive hepatectomy. Animals were subjected to segmental liver ischemia. After 30, 60, or 90 min, nonischemic liver lobes were resected (70% hepatectomy). Hepatectomy without prior liver ischemia was performed in the control group. On the 1st, 3rd, 5th, and 7th days following hepatectomy, a BrdU labeling index was calculated as a marker of liver regeneration. AST, ALT, and liver adeninenucleotides were also measured. Although 30 min of liver ischemia resulted in higher peak AST and ALT levels, liver regeneration and ATP levels were significantly higher than those in control animals. Ninety minutes of liver ischemia resulted in significantly lower liver regeneration and ATP levels compared with the other treatment paradigms. Liver regeneration and ATP levels were almost identical to those in control animals, in rats with 60 min of ischemia preceding hepatectomy. We conclude that livers regenerative capacities can tolerate significant ischemia and that relatively brief periods of ischemia can even accelerate liver regeneration.

Adenosine Triphosphate↗