Comparison of species, virulence genes and clones of Aeromonas isolates from clinical specimens and well water in Okinawa Prefecture, Japan.

AIMS: To reveal the sources of Aeromonas infection in Okinawa Prefecture of Japan, the species, virulence genes and clones of strains isolated from clinical specimens and well water were compared. METHODS AND RESULTS: The properties of both isolates were investigated by sequencing of rpoD, detection of 10 virulence genes using PCR and genotyping with pulsed-field gel electrophoresis. In all, 68 clinical and 146 well water strains of Aeromonas were isolated and the main species were A. caviae, A. dhakensis, A. hydrophila and A. veronii biovar sobria. Aeromonas dhakensis possessed various virulence genes; however, A. caviae possessed only fla. The same or similar clones were distributed in certain areas of Okinawa and one clone had survived several months in the biliary system of two patients, respectively. CONCLUSION: Although the same Aeromonas clone was not isolated from clinical and well water samples, our study revealed the detected patterns of virulence genes in both isolates, the distribution of identical/similar clones in the Okinawan environment and long-time survival in patient's organs. SIGNIFICANCE AND IMPACT OF THE STUDY: We investigated the association between Aeromonas patients and well water exposure. This study provides the properties of species, virulence genes and clones of Aeromonas isolated from samples of these origins.

BCR-ABL regulates death receptor expression for TNF-related apoptosis-inducing ligand (TRAIL) in Philadelphia chromosome-positive leukemia.

Allogeneic stem cell transplantation (allo-SCT) is a potentially curative therapy for chronic myeloid leukemia and Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia, and the graft-vs-leukemia (GVL) effect can eradicate residual leukemia after allo-SCT. Ph(+) leukemia cells frequently express death-inducing receptors (DR4 and DR5) for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is one of the cytotoxic ligands expressed on cytotoxic T cells and natural killer cells mediating the GVL effect. Here we demonstrate that imatinib specifically downregulated DR4 and DR5 expression in cell lines and clinical samples of Ph(+) leukemia. Second-generation tyrosine kinase inhibitors (dasatinib and nilotinib) and short hairpin RNA against bcr-abl also downregulated DR4 and DR5 expression in Ph(+) leukemia cells, and transfection of bcr-abl into a Ph(-) leukemia cell line induced DR4 and DR5 expression, which was abrogated by imatinib treatment. Accordingly, Ph(+) leukemia cells that had been pretreated with imatinib showed resistance to the pro-apoptotic activity of recombinant human soluble TRAIL. These observations demonstrate that BCR-ABL is critically involved in the leukemia-specific expression of DR4 and DR5 and in the susceptibility of Ph(+) leukemia to TRAIL-mediated anti-leukemic activity, providing new insight into the mechanisms of the tumor-specific cytotoxic activities of TRAIL.

Oncogenic fusion E2A-HLF sensitizes t(17;19)-positive acute lymphoblastic leukemia to TRAIL-mediated apoptosis by upregulating the expression of death receptors.

t(17;19)-acute lymphoblastic leukemia (ALL) shows extremely poor prognosis. E2A-HLF derived from t(17;19) blocks apoptosis induced by the intrinsic mitochondrial pathway and has a central role in leukemogenesis and chemoresistance. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is expressed on cytotoxic T cells and natural killer cells and binds with death receptors (DR4/DR5), inducing apoptosis by dual activation of intrinsic and extrinsic pathways, and TRAIL mediates the graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT). We found that cell lines and patients' samples of t(17;19)-ALL expressed death receptors for TRAIL, and recombinant soluble TRAIL immediately induced apoptosis into t(17;19)-ALL cell lines. E2A-HLF induced gene expression of DR4/DR5, which was dependent on the DNA-binding and transactivation activities of E2A-HLF through the 5' upstream region of the start site at least in the DR4 gene. Introduction of E2A-HLF into non-t(17;19)-ALL cell line upregulated DR4 and DR5 expression, and sensitized to proapoptotic activity of recombinant soluble TRAIL. Finally, a newly diagnosed t(17;19)-ALL patient underwent allo-SCT immediately after induction of first complete remission, and the patient has survived without relapse for over 3-1/2 years after allo-SCT. These findings suggest that E2A-HLF sensitizes t(17;19)-ALL to the GVL effect by upregulating death receptors for TRAIL.

Popliteal venous aneurysm with repeated episodes of pulmonary embolism. Case report and literature review.

Popliteal venous aneurysm (PVA) is a rare, but a life-threatening, disease causing pulmonary embolism (PE). We experienced a case of primary PVA with repeated PE attacks without intraluminal thrombus. Surgical repair was safely performed with a temporary vena cava filter and an intraoperative external pneumatic compression device to the calf. During the perioperative period, pneumatic compression was continued until the patient returned to a normal ambulatory status. The patient has had no episode of PE for 24 months since the operation.

[Completion pneumonectomy for pulmonary aspergillosis with hyper immunoglobulin-E syndrome].

A 22-year-old man was admitted to the department of pediatrics of our institute in February 2005, because of pulmonary aspergillosis. He had been diagnosed as hyper immunoglobulin-E syndrome in infancy, and repeated pulmonary infectious desease, such as pulmonary aspergillosis. He received art of right upper lobectomy by pulmonary aspergillosis at the age of 17. In February 2005, he had hemosputum and the chest X-ray showed a giant cavity with niveau in the right lung. In spite of medical treatment by antibiotics and antimycotics, the lesion rapidly increased in size. Therefore, right completion pneumonectomy and omentopexy around the bronchial stump was done. His postoperative course was uneventful.

[Evaluation of animal-assisted therapy for the elderly with senile dementia in a day care program].

We conducted animal-assisted therapy (AAT) for the elderly with senile dementia in a day care center. AAT was performed between July 27 and October 12, 1999 for a total of six biweekly sessions. The AAT group consisted of 7 subjects; 5 with senile dementia of Alzheimer's type (SDAT) and 2 with vascular dementia (VD). The control group was 20 elderly subjects (7 SDAT, 13 VD). The results were as follows: Comparing between MMS scores at the baseline and those three months later, the average score on MMS before AAT (baseline) was 11.43 (+/- 9.00), and that three months later was 12.29 (+/- 9.69). In the AAT group, the average baseline N-ADL score was 28.43 (+/- 14.00) and that after ATT was 29.57 (+/- 14.47). In the AAT group, the average baseline score on Behave-AD was 11.14 (+/- 4.85), and that three months after AAT was 7.29 (+/- 7.11) (p < 0.05). In the control group, the average baseline score was 5.45 (+/- 3.27) and that three month later was 5.63 (+/- 3.59). However, the results of eight subscales of communication behavior three months later were significantly low comparing to those at the baseline in the control group. The evaluation of CgA, which was a mental stress index, showed a decreasing tendency in the AAT group. Our findings suggested we should use several evaluation methods for evaluation of the changes of patients receiving AAT.

Extracranial carotid aneurysm in Takayasu's arteritis.

Extracranial carotid aneurysm caused by Takayasu's arteritis is extremely rare. We have experienced six cases of extracranial carotid aneurysm among 106 cases of Takayasu's arteritis that were treated surgically in the past 50 years. We herein review these cases and discuss the surgical indications and postoperative course of this rare disease. We report original observations about extracranial carotid aneurysm in Takayasu's arteritis.

A day care program and evaluation of animal-assisted therapy (AAT) for the elderly with senile dementia.

We conducted a survey to clarify the evaluation methods of animal-assisted therapy (AAT) for the elderly with senile dementia in an adult day care center. AAT was implemented for a total of six biweekly sessions. The AAT group consisted of seven subjects and the control group numbered 20 subjects. In a comparison between Mini-Mental State Exam (MMSE) scores at baseline and those measured three months later, the average MMSE score before AAT (baseline) was 11.43 (+/- 9.00), and three months later it was 12.29(+/- 9.69). In the AAT group, the average score on Nishimura's Activities of Daily Living (N-ADL) at baseline was 28.43(+/- 14.00), and after ATT it was 29.57(+/- 14.47). In the AAT group, the average baseline score on behavioral pathology of Alzheimer's disease (Behave-AD) was 11.14(+/- 4.85), and three months after AAT it was 7.29(+/- 7.11) (p < 0.05). In the control group, the average baseline score was 5.45(+/- 3.27) and three months later it was 5.63(+/- 3.59). The evaluation of salivary CgA, as a mental stress index, showed a decreasing tendency in the AAT group. Our findings demonstrate the usefulness of using several methods for evaluation of the changes in patients given AAT.

Surgical treatment for popliteal artery entrapment syndrome.

PURPOSE: This study was a retrospective review of 11 limbs of 10 patients with popliteal artery entrapment syndrome (PAES) treated surgically in a 20-yr period. METHODS: The patients were aged 34.7 +/- 17.4 SEM yr. Arteriographic findings varied, showing medial deviation in two limbs, poststenotic dilatation in four limbs and occlusion of the popliteal artery in five limbs. In addition, computed tomographic (CT) scanning showed positive findings of PAES in all the limbs. RESULTS: The surgical procedures consisted of musculotendonous section (MTS) with autogenous saphenous vein (ASV) graft in seven limbs, MTS and ASV patch angioplasty with or without thromboendarterectomy in three limbs, and MTS alone in one limb. All the ASV grafts were found to be patent during the postoperative follow-up period (10.9 +/- 4.0 yr). CONCLUSION: CT scanning was demonstrated to be the most sensitive diagnostic modality for PAES, and MTS with or without ASV grafting method was considered to be the best surgical procedure for PAES.

Adverse outcome following transfemoral endovascular stent-graft repair of an abdominal aortic aneurysm in a patient with severe liver dysfunction: report of a case.

We describe herein the case of a patient with severe liver failure in whom an abdominal aortic aneurysm (AAA) extending to the right iliac artery was diagnosed. Because the risk of performing a standard open repair was considered too high in this patient, the aneurysm was uneventfully repaired using a technique of transfemoral endovascular stent-grafting with femorofemoral bypass and occlusion of the left common and right internal iliac arteries. Unfortunately, multiorgan failure associated with adult respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) suddenly developed on postoperative day (POD) 2 and the patient died on POD 9. Thus, although endovascular stent-grafting is generally assumed to be less invasive and therefore feasible for high-risk patients, patients with severe liver dysfunction may not be suitable candidates.

Intravascular ultrasound imaging of the pulmonary arteries in primary pulmonary hypertension.

OBJECTIVE: Intravascular ultrasound has the unique ability to provide cross-sectional images of the arterial wall. This study examined intravascular ultrasound (IVUS) images of the proximal pulmonary arteries in primary pulmonary hypertension (PPH). METHODOLOGY: Study 1: Specimens from four patients who had died of PPH (in vitro PPH group) were compared with those of three patients who had died of subarachnoid haemorrhage but had no evidence of cardiopulmonary disease (in vitro control group). Three-centimetre segments of the following levels were examined by IVUS: pulmonary trunk, eight secondary branch arteries of the upper, middle, and lower lobes of both lungs, and the thoracic descending aorta. Study 2: Four patients with PPH (in vivo PPH group) and five patients without pulmonary hypertension and no evidence of cardiopulmonary disease (in vivo control group) were examined. The IVUS images of the apical segmental artery of the right upper lobe and the descending branch of the right pulmonary artery were studied. RESULTS: Echographic examination of formalin-fixed preparations of secondary branch sections of the pulmonary artery failed to show a clear three-layer structure in the in vitro control group (24 preparations), but a distinct three-layer structure and increased vessel wall thickness were observed in the in vitro PPH group (32 preparations). Similar findings were obtained in the in vivo study. The mean echo density of the proximal pulmonary arterial wall correlated well with the mean pulmonary arterial pressure (mPA) in the in vitro PPH, and also correlated with the mPA in the in vivo study (r = 0.960, P < 0.0001). The echo intensity of secondary branch sections of the pulmonary artery was higher in the in vitro PPH group than in the in vitro control group (180.5 +/- 27.0 vs 132.5 +/- 26.7 counts, P < 0.001); similar results were obtained in the in vivo study (144.7 +/- 23.4 vs 85.0 +/- 14.3 counts, P < 0.01). CONCLUSIONS: These results suggest that the histological changes detected in the pulmonary artery walls in the PPH group were responsible for the increased echo intensity.

Aortic aneurysm in patients with autoimmune diseases treated with corticosteroids.

BACKGROUND: Aortic aneurysm is a rare but life-threatening cardiovascular complication in patients with autoimmune disorders. The purpose of this study was to clarify the characteristic clinical features and the pathological mechanism of aneurysmal formation in those patients treated with corticosteroids. METHODS: Among 429 patients operated on for abdominal aortic aneurysm during the past 10 years, six patients with autoimmune diseases treated with corticosteroids (one with progressive systemic sclerosis, one with rheumatoid arthritis and four with systemic lupus erythematosus) were reviewed retrospectively. Their data were compared with those of 391 patients with atherosclerotic aneurysms with no autoimmune disorders. The resected aneurysmal walls of the six patients were also compared histopathologically with those of the last six consecutive patients in the control group. RESULTS: The average age of the patients with autoimmune disease was younger than that of the control group (53.8+/-16.6 vs 71.8+/-7.8 years; p<0.05). Patients with autoimmune disease had received long-term corticosteroid therapy for 15-32 years; mean 22.2+/-6.5 years. Pathological examination showed that the destructive change of the medial elastic lamina in the autoimmune disease group was wider than that in the controls. Most patients had no complications in the postoperative follow-up period (5.1+/-3.2 years), while one patient died of rupture of a dissecting aneurysm two years after operation. CONCLUSIONS: Prolonged corticosteroid treatment probably plays a major role in the disintegration of connective tissue of the media, possibly together with primary aortic wall involvement and/or vasculitic damage in patients with autoimmune disorders, which can result in aortic aneurysmal enlargement.

Ten years' experience of aortic aneurysm associated with systemic lupus erythematosus.

BACKGROUND: aortic aneurysm is a rare but life-threatening cardiovascular complication in patients with systemic lupus erythematosus (SLE). The purpose of this study was to clarify the characteristic clinical features and the pathological mechanism of aneurysmal formation in these patients. METHODS: among 429 patients operated on for abdominal aortic aneurysm (AAA) during the past 10 years, five cases with SLE were treated surgically. Their clinical data were reviewed, and the resected aneurysmal wall of the five patients was also examined histologically. RESULTS: the mean age of the patients with SLE was 55 years, which was statistically younger than that of the other patients (mean 77 years, s.d. 7.9, p <0.05). They had received long-term corticosteroid therapy for the treatment of SLE for a mean of 23 years. Histologically, destruction of the medial elastic lamina was characteristic. Four patients had no complications in the postoperative follow-up period (mean 4 years), while the remaining patient died of rupture of a dissecting aneurysm two years after operation. CONCLUSION: prolonged steroid therapy may play a major role in accelerating atherosclerosis, which can result in aortic aneurysmal enlargement, possibly together with primary aortic wall involvement and/or vasculitic damage in patients with SLE.

Bilateral inguinal hernia repaired by laparoscopic technique: a rare complication of femorofemoral bypass.

Femorofemoral bypass is an established procedure for limb salvage and disabling claudication. However, surgical exposure of the femoral artery may result in damage leading to development of an inguinal hernia. Herein we report the first case of laparoscopic repair of bilateral inguinal hernias that developed after femorofemoral bypass.

Microvascular transport is associated with TNF plasma levels and protein synthesis in postischemic muscle.

To better understand the mechanisms of ischemia-reperfusion (I/R) injury, we tested the hypothesis that protein synthesis is involved in the production of tumor necrosis factor (TNF) and in the microvascular transport changes in I/R. To evaluate the hypothesis, we inhibited protein synthesis with topically applied actinomycin D (AMD), measured I/R-induced changes in microvascular transport, and bioassayed the venous plasma levels of TNF. The rat cremaster muscle I/R model consisted of 4 h of ischemia followed by 2 h of reperfusion. Changes in transport were determined by integrated optical intensity (IOI) using FITC-Dextran 150 as tracer. Animals were separated into four groups: 1) control (C), 2) control treated with AMD (C + AMD), 3) I/R, and 4) I/R treated with AMD (I/R + AMD). The mean (+/-SE) maximal IOI in C and C + AMD were 3.0 +/- 1.0 and 3. 7 +/- 0.7 units, respectively. I/R elevated mean maximal IOI to 21.8 +/- 1.9 units (P < 0.05 vs. C, C + AMD, I/R + AMD). Treatment with AMD reduced the I/R-induced mean maximal IOI to 9.7 +/- 2.0 units (P < 0.05 vs. I/R). In I/R group, plasma TNF levels increased (relative to preischemia baseline) immediately after the release of the vascular occlusion to 250 pg/ml and reached a peak value of 342 pg/ml at 60 min of reperfusion. In the I/R + AMD group, AMD reduced TNF increase to 44 pg/ml. The C and C + AMD groups showed no differences in TNF values during the 6 h of observation. We conclude that protein synthesis and TNF generation are at least partially involved in I/R-induced changes in microvascular transport.

L-type calcium channel blockers modulate the microvascular hyperpermeability induced by platelet-activating factor in vivo.

PURPOSE: Platelet-activating factor (PAF) is a potent phospholipid mediator of the microvascular dysfunction associated with ischemia-reperfusion injury. Because changes in cytosolic-free Ca2+ concentration are essential in PAF cellular signaling, we formulated the hypothesis that blockade of Ca2+ entry may inhibit the PAF-induced microvascular dysfunction. METHODS: To investigate this hypothesis two L-type calcium channel blockers, verapamil and nifedipine, were applied to the hamster cheek pouch before the topical PAF challenge was undertaken. Permeability was assessed by measurement of the plasma clearance of fluorescein isothiocyanate dextran, 150,000 mol wt. The arteriolar diameter was measured simultaneously to evaluate the effects of L-type calcium channel blockers on PAF-induced vasoconstriction. RESULTS: Baseline clearance was 498.7 +/- 225.0 nl/60 min/gm (mean +/- SE). PAF at 10(-8) mol/L (n = 5) increased clearance to 3753.8 +/- 572.8 nl/60 min/gm (p < 0.01). Pretreatment with verapamil (2 mg/kg; n = 5) significantly reduced the increase in permeability caused by 10(-8) mol/L PAF (1909.1 +/- 620.2 nl/60 min/gm; p < 0.05). Nifedipine (5-10(-6) mol/L; n = 5) also significantly attenuated the impact of 10(-8) mol/L PAF (2037.2 +/- 427.5 nl/60 min/gm; p < 0.05). Neither verapamil nor nifedipine affected PAF-induced vasoconstriction. CONCLUSION: The significant inhibition of the increase in permeability by the L-type calcium channel blockers suggests that these compounds may be useful in the management of PAF-induced hyperpermeability.

[Liver herniation simulating a benign lung tumor].

A 49-year-old woman complained of coughing and sputum production a mass shadow was seen in the right lower lung field on a chest radiography. The shadow was first suspected to represent a benign lung tumor, because of its clear margin and narrow pedicle. After detailed examination liver herniation was suspected, since the CT number of the tumor was similar to that of the liver. Liver herniation was finally confirmed by chest MRI, liver scintigraphy and angiography of the abdomen. Liver herniation should be differentiated from an intrathoracic mass in the right lower lung field.

Platelet activating factor modulates microvascular permeability through nitric oxide synthesis.

Biochemical signaling determines the specific action of vasomediators in the control of microvascular permeability and tone. We tested the hypothesis that nitric oxide (NO) synthesis is involved in the biochemical signaling pathway of platelet activating factor (PAF). The cheek pouch of anesthetized male Syrian hamsters was used as a microvascular model. Vessel diameter [expressed as the ratio of the experimental to the control (e/c) diameter, with control diameter normalized to 1] and extravasation of FITC-dextran 150 by integrated optical intensity (IOI) were determined using intravital fluorescent microscopy and computer-assisted digital image analysis. N-Nitro-L-arginine methyl ester (L-NAME) at 10(-5) and 10(-6) M and N-nitro-L-mono-methyl arginine (L-NMMA) at 10(-4) and 10(-5) M were used as inhibitors of NO synthase (NOS). Acetylcholine (ACh) and bradykinin were used as indirect indices of NOS activation. L-NAME and L-NMMA attenuated both ACh and bradykinin vasodilatory effects as well as the bradykinin-induced increase in vascular permeability. Topical PAF (10(-7) M) caused vasoconstriction (mean +/- SEM e/c ratio = 0.3 +/- 0.1) and increased IOI from a normalized baseline of 0 to 67.4 +/- 12.8. Topical administration of L-NAME produced differential effects on the series-arranged arterioles but had no effect on postcapillary venular permeability. L-NMMA did not influence the basal arteriolar diameter, but at 10(-5) M it caused a small increase in permeability (IOI = 14.3 +/- 4.2). In the presence of NOS inhibitors, PAF caused a reduced arteriolar constriction (e/c ratio = 0.6 +/- 0.1) relative to PAF alone. Both NOS inhibitors reduced the PAF-stimulated increase in vasopermeability. At 10(-5) M L-NMMA, the PAF-stimulated IOI mean value was 26.1 +/- 5.2, while at 10(-4) M L-NMMA the PAF-stimulated IOI was 15.2 +/- 2.6 compared to 10(-7) M PAF (67.4 +/- 12.8). These results support our hypothesis that NO synthesis is a step in the biochemical signaling pathway of the postcapillary cellular responses to PAF.

Successful 48-h liver preservation by controlling nutritional status of donor and recipient.

The nutritional status of the donor has been shown to affect the outcome of liver transplantation in the rat. It has been proposed that this may be due to inhibition of Kupffer cell induced injury to the reperfused organ, which leads to an inflammatory type response. In this study we investigated how altering the nutritional status of the recipient affects the outcome of liver transplantation after preservation of the liver for 44 or 48 h in the University of Wisconsin (UW) solution. The nutritional status of the rats was altered by either fasting or by feeding an essential fatty acid free diet (EFAD) for 2 months. This type of diet has been shown to reduce significantly the inflammatory response in rats. Survival after 44-h preservation of livers from fed donors (fed a standard laboratory diet) transplanted to fed recipients was 29% (2/7) but increased to 80% (4/5) when the recipient was fed the EFAD diet. After 48-h preservation, there were no survivors under either of these two dietary combinations. However, survival was 100% after 48-h preservation if the donor had been fasted for 4 days and the recipient was fed the EFAD. These results showed that the nutritional status of the donor and recipient are important factors in the outcome of liver transplantation. How nutritional factors affect liver preservation and transplantation are not clear but may be related to the inflammatory response regulated by Kupffer cells and circulating neutrophils in the liver, both of which are influenced by the diet of the animal.