Perinuclear-antineutrophil cytoplasmic antibodies are associated with vasculitis.

We describe a 62-year-old man with perinuclear-antineutrophil cytoplasmic antibodies-associated vasculitis, which involved the heart, lung, and kidneys. The patient's care was complicated by total occlusions of the brachiocephalic and right renal arteries and a stenosis of the left renal artery. Involvement of large-sized vessels has not been reported in patients with perinuclear-antineutrophil cytoplasmic antibodies-associated vasculitis.

Recurrent pulmonary adenoid cystic carcinoma presenting as a cardiac tumor.

A 58-year-old patient is presented who had a pulmonary adenoid cystic carcinoma which recurred 10 years after sleeve left pneumonectomy. The patient developed acute heart failure because the lesion obstructed blood flow by compressing the left atrium. Transesophageal echocardiography and magnetic resonance imaging demonstrated a solid mass arising from the pericardium which displaced the posterior wall of the left atrium. The mass was resected. Postoperative radiation was not performed.

Plasma brain natriuretic peptide as a parameter to assess efficacy of continuous intravenous infusion of prostacyclin (epoprostenol) to treat severe primary pulmonary hypertension: a case report.

Continuous intravenous infusion of prostacyclin (epoprostenol) as a treatment for primary pulmonary hypertension (PPH) definitely improves the patient's quality of life, but few accurate parameters have been found to evaluate the efficacy of the treatment. We observed a patient with severe PPH whose plasma brain natriuretic peptide (BNP) level changed significantly as her condition and symptoms changed. Plasma BNP may be considered as one of the parameters for assessing the efficacy of prostacyclin treatment.

Rheumatoid arthritis and simultaneous aortic, mitral, and tricuspid valve incompetence.

We describe a 72-year-old woman with aortic, mitral, and tricuspid valve incompetence secondary to a rheumatoid granulomata. The cardiac valvular lesions developed simultaneously and deteriorated rapidly. The patient died after a transient relief of symptoms by high dose steroid therapy.

Subdivided left atrium mimicking a cardiac tumor.

We describe a 25-year-old man with a subdivided left atrium. The lesion was misdiagnosed preoperatively as a cardiac tumor because echocardiographic and magnetic resonance imaging revealed a solid mass arising from the posterior wall of the left atrium. Cardiac surgery revealed a small accessory chamber draining the two left pulmonary veins. No membranous structure was evident between the chamber and the left atrium. The solid mass identified noninvasively was a hypertrophic muscle which formed a wall of the accessory chamber.

Right coronary artery aneurysm with associated arteriovenous fistula.

We describe a 47-year-old man who had a right coronary artery aneurysm measuring 78 x 69 mm which communicated to the right ventricle. The lesion was asymptomatic. The myocardial blood supply was highly dependent on the left coronary artery.

Alterations of fibrinolytic activity in human during and after hyperbaric oxygen exposure.

To clarify the stage of fibrinolytic activation by hyperbaric oxygen (HBO) exposure, we examined its alterations in human during and after the HBO exposure. Eight healthy female volunteers breathed oxygen at 284 kPa (2.8 atmospheres absolute). Blood samples were collected before compression, shortly after compression to the pressure 284 kPa, shortly before the start of decompression, shortly after decompression, and then again 3 hours after decompression. We estimated the euglobulin fibrinolytic activity (EFA) and, the activities and antigens of both tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1). The PAI-1 activity and PAI-1 antigen showed significant decrease after compression to a pressure 284 kPa, before the start of decompression, and after decompression. The EFA level and t-PA activity rose significantly shortly after decompression, and 3 hours later returned on baseline. These findings suggest that fibrinolytic activity is elicited after HBO rather than during HBO.

Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line.

Epidermal growth factor (EGF) mediates many pleiotrophic biological effects, one of which is alteration of cellular morphology. In the present study, we examine the possibility that this alteration in cell morphology is caused in part by the dysfunction of cadherin-mediated cell-cell adhesion using the human oesophageal cancer cell line TE-2R, which expresses E-cadherin and EGF receptor. In the presence of EGF, TE-2R changed its shape from round to fibroblastic and its colony formation from compact to sparse. Vanadate, a tyrosine phosphatase inhibitor, further potentiated the EGF response, whereas herbimycin A, a tyrosine kinase inhibitor, interfered with it. Moreover, EGF enabled the cells to invade in organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its localisation from the lateral adhesion site to the whole cell surface. Both alpha- and beta-catenin, cadherin-binding proteins, were also expressed at the same level throughout these morphological changes. Finally, we examined tyrosine phosphorylation of E-cadherin and alpha- and beta-catenin, and observed tyrosine phosphorylation of beta-catenin induced by EGF. These results suggest that EGF counteracts E-cadherin-mediated junctional assembly through phosphorylation of beta-catenin and modulates tumour cell behaviour to a more aggressive phenotype.

Clearance and distribution of a haemorrhagic factor purified from Bothrops jararaca venom in mice.

We previously purified two fibrinolytic/haemorrhagic enzymes (jararafibrase-I and II) from Bothrops jararaca venom. In the present study, the clearance, organ distribution and local absorption rate were examined in mice using 125I-labelled jararafibrase-I. Following intravenous injection of 125I-labelled jararafibrase-I, a complex was rapidly formed with the plasma protein and the radioactivity quickly disappeared from the circulation with a half-life of about 3 min for the initial part of the curve. The highest level of the radioactivity (59.5%) was seen in the liver at 5 min after dosing, and the next highest level of radioactivity (14.4%) was seen in the kidney at 60 min after dosing. At 60 min after dosing, 36.8% of the total injected radioactivity was seen in the contents of the small intestine, and 11.4% of the total injected radioactivity was seen in the contents of the large intestine at 120 min after dosing. It is assumed that the jararafibrase-I was metabolized mainly in the liver, to small mol. wt products, and excreted in the intestine via the bile duct. Also, a small amount of jararafibrase-I appeared to be metabolized in the kidney. Following subcutaneous injection, a high-dose group revealed a low local absorption rate. The low local absorption rate was apparently due to a diminished blood flow caused by subcutaneous haemorrhage.

Immunohistochemical evaluation of alpha-catenin expression in human gastric cancer.

E-cadherin (E-cad) plays a major role in the maintenance of cell-cell adhesion in epithelial tissues, and impaired E-cad expression correlates with tumour invasion and metastasis. Alpha-catenin (alpha-cat), an undercoat protein of adherens junctions, binds to the cytoplasmic domain of E-cad and is essential for linking E-cad to actin-based cytoskeleton. We investigated E-cad and alpha-cat expression in 60 human gastric cancers immunohistochemically. The 60 gastric cancers were classified into 18 (30%) in which alpha-cat expression was preserved, and 42 (70%) reduced cases. The reduction of alpha-cat expression was significantly related to dedifferentiation, depth of invasion, infiltrative growth and lymph node metastasis. We also examined the co-expression of alpha-cat and E-cad. Seventeen (28%) tumours preserved both molecules [alpha-cat(+)/E-cad(+)] and 33 (55%) tumours reduced both [alpha-cat(-)/E-cad(-)], whereas 9 (15%) tumours exhibited alpha-cat(-)/E-cad(+). The frequency of lymph node metastasis in alpha-cat(-)/E-cad(+) tumour (67%) was significantly higher than that in alpha-cat(+)/E-cad(+) tumours (24%) and was close to that in alpha-cat(-)/E-cad(-) tumours (82%). The frequency of haematogenous liver metastasis in alpha-cat(-)/E-cad(+) tumours (44%) was significantly higher than that in alpha-cat(+)/E-cad(+) tumours (6%) or alpha-cat(-)/E-cad(-) tumours (9%). Thus, in all E-cad(+) tumours, the frequency of lymph node and liver metastasis was higher in alpha-cat(-) tumours than in alpha-cat(+) tumours. alpha-Cat expression is apparently better at predicting tumour invasion and metastasis than E-cad expression.

Relationship between e-cadherin expression and lymph-node metastasis in human esophageal cancer.

Expression of E-cadherin in esophageal carcinoma was studied immunohistochemically in 65 patients using an anti-human E-cadherin monoclonal antibody (HECD-1). In normal esophageal epithelium, E-cadherin was strongly expressed on cell-cell boundaries. On the contrary, a reduced E-cadherin expression (Rd-type) was frequently observed in cancer tissues (56/65, 88%). The frequency of Rd-type was much higher in cases with deeper invasion (48/52, 92%) than that in cases with superficial invasion (8/13, 62%) (p<0.05). Concerning lymph node metastasis, the frequency of Rd-type in the metastatic tumor group (47/49, 96%) was significantly higher than that in the non-metastatic tumor group (9/16, 56%) (p<0.01). These results suggest that E-cadherin might play a key role in the progression of carcinogenesis and that the reduction of E-cadherin expression is associated with malignant potential such as invasion and metastasis in human esophageal cancer.

P53 expression in esophageal dysplasia - a possible biomarker for carcinogenesis of esophageal squamous-cell carcinoma.

The tumor suppressor gene product p53 has been detected in a high percentage of esophageal squamous cell carcinoma. To evaluate the role of this protein in carcinogenesis, we examined the p53 overexpression both in esophageal dysplasia and in esophageal squamous cell carcinoma in the same patients. Using anti-p53 antibodies pAb1801 and CM-1, we analyzed immunohistochemically 36 dysplastic lesions from 36 patients with esophageal cancer. Nuclear p53 was detected in 14 of 36 dysplasias (39%). From mild to moderate to severe dysplasia, p53 positivity showed tendency to increase in number. Seventeen of the 36 squamous cell carcinomas showed p53 expression (47%). There was a significant concurrent p53 expression in esophageal dysplasia and its related squamous cell carcinoma (p=0.00345). These results indicate that p53 mutation is closely associated with the initiation of this cancer.

Significance of p53 expression as a prognostic factor in oesophageal squamous cell carcinoma.

The tumour suppressor gene product p53 is believed to play an important role in the progression of human malignant tumours through mutation and over-expression. Using a microwave oven heating method, we have detected over-expression of p53 in buffered-formalin fixed, paraffin-embedded sections of oesophageal carcinomas immunohistochemically and examined the relationship between the p53 over-expression and postoperative survival. Employing a monoclonal antibody (pAb1801), nuclear p53 was detected in 56 of 105 (53%) tumour specimens. Homogeneous, heterogeneous, and focal immunostaining patterns were noted. No immunostaining was found in adjacent benign tissues. The results in buffered-formalin fixed sections were similar to those in the frozen sections. The cumulative survival rate of patients with p53 expression was significantly lower than that of the patients without expression (P < 0.05), even though there were no significant differences between the clinicopathological features of the two groups. The results indicate that the nuclear accumulation of p53 might be an independent prognostic factor in patients with oesophageal squamous cell carcinomas.

Broad substrate specificity of snake venom fibrinolytic enzymes: possible role in haemorrhage.

We found previously that two fibrinolytic enzymes (jararafibrases I and II) purified from Bothrops jararaca venom displayed a haemorrhagic activity. To elucidate the mechanisms involved and the role of the enzymatic activity in haemorrhage, the enzymatic properties of the purified enzymes were examined. The substrate specificity of the enzymes was determined using type I collagen, type IV collagen, gelatin, laminin and fibronectin as substrates. The enzymes degraded type IV collagen, gelatin, laminin and fibronectin into smaller fragments, but degraded type I collagen only partially in a non-specific manner. The specific activities of jararafibrase I for type IV collagen and gelatin were 172 +/- 5 units/mg protein and 1315 +/- 177 units/mg protein, respectively. The specific activities of jararafibrase II for type IV collagen and gelatin were 9.2 +/- 0.6 units/mg protein and 143 +/- 15 units/mg protein, respectively. It was evident that the enzymes had rather broad substrate specificities and degraded basement membrane components including type IV collagen. The number of type IV collagen units of bacterial collagenase which gave the minimal haemorrhagic dose was 191.4, while the numbers of type IV collagenase units of jararafibrases I and II which gave the minimal haemorrhagic dose were 1.5 and 0.25, respectively. It is suggested that the broad substrate specificity of the enzymes is essential for inducing haemorrhage with a single enzyme.

A rapid and strong increase of plasminogen activator induced by experimental anaphylaxis in rabbits.

Anaphylactic shock was induced in rabbits by injecting bovine serum albumin (BSA) as an antigen. Measurements of the enzyme activities in the fibrinolytic system confirmed that a rapid and strong increase of plasminogen activator (PA) was induced during anaphylaxis. The euglobulin fibrinolytic activity (EFA) as estimated by the plasminogen-rich fibrin plate method rose significantly, peaking at 15 min after the BSA injection (when the arterial pressure was minimum). However, EFA was not detected by the plasminogen-poor fibrin plate method. The tissue-type PA (t-PA) activity using the natural substrate plasminogen increased significantly with a peak at 15 min. The amidolytic activity also simultaneously increased significantly using the t-PA substrate, H-D-Ile-Pro-Arg-pNA. The plasminogen activator inhibitor (PAI) activity remained at baseline levels until 30 min, but rose fourfold at 90 min. The main plasma fibrinolytic enzyme which increased in anaphylaxis was proved by zymography to be t-PA with a molecular weight (MW) of 69,000.