The effect of AH 21-132 on airway hyperresponsiveness induced by ozone exposure

We examined the effect of AH 21-132, which has been reported to relax airway smooth muscle and inhibit platelet activating factor (PAF)-induced airway hyperreactivity, on ozone-induced airway hyperresponsiveness (AHR) with airway inflammation in dogs. Airway responsiveness (AR) to methacholine was measured by modified Astograph (7 Hz oscillation method) before and after ozone exposure, and the numbers of neutrophils in the peripheral blood and total cell counts, differential cell counts and TXB2 in BALF were measured before and after ozone exposure. Ozone exposure was carried out for 2 hr at an ozone level of 3.46 +/- 0.10 ppm (mean +/- SE). There was a significant increase in AR to methacholine after ozone exposure (p less than 0.01), and the numbers of neutrophils in the peripheral blood and the total cell and neutrophil counts in BALF increased significantly (p less than 0.05). Pretreatment with AH 21-132 at an oral dose of 20 mg/kg significantly prevented the ozone-induced AHR to methacholine (p less than 0.01), and also inhibited the increase of neutrophil counts in the peripheral blood, and the total cell counts and the neutrophil counts in BALF after ozone exposure. There was no significant change in the levels of TXB2 in BALF before and after ozone exposure. In dogs not exposed to ozone, AR to methacholine and respiratory resistance to methacholine significantly decreased after administration of AH 21-132 at an oral dose of 20 mg/kg (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Primary malignant melanoma of the common bile duct

Biliary tract obstruction in a 30-year-old man was found to be caused by a malignant melanoma in the common bile duct. Melanin pigment was demonstrated by immunohistochemistry and electron microscopy. Extensive search for a primary malignant melanoma elsewhere was unsuccessful. No pigmented lesions had been removed previously. There were junctional changes in the mucosa of the common bile duct close to the tumor. The malignant melanoma in the common bile duct therefore is considered to be primary. Only one other case of primary malignant melanoma in the common bile duct has been described in the literature, whereas metastases to the major bile ducts in one autopsy study of malignant melanoma in the more common locations were found with a frequency of 6 per cent.     

Allelic homogeneity due to a founder mutation in Japanese patients with lattice corneal dystrophy type IIIA

Lattice corneal dystrophies (LCDs) are caused by mutations of the transforming growth factor beta-induced gene (TGFBI, formerly betaig-h3). LCD type IIIA (LCDIIIA) has been reported mostly from Japan. In this study, we demonstrate allelic homogeneity for Japanese patients with LCDIIIA, using intragenic polymorphic markers. When exon 11 of TGFBI was analyzed, all 18 patients examined were found to be heterozygous for both a P501T mutation and an IVS10-3C --> T variation. On the other hand, none of 54 normal Japanese control subjects had the P501T, and 5 of the controls were heterozygous for IVS10-3C --> T. Haplotype analysis of the patients revealed that both P501T and IVS10-3C --> T were located on the same chromosome, and a significant linkage disequilibrium (P < 0.001, Fisher's exact probability test) was observed between LCDIIIA (P501T) and IVS10-3C --> T. When exon 8 of the gene was analyzed, all these patients possessed the "G allele" of a 1028G/A polymorphism. A significant linkage disequilibrium (P < 0.003; chi-square test) was also observed between P501T and the G allele in the patients. These results suggest that allelic homogeneity seen in Japanese patients with LCDIIIA may result from a single founder mutation.     

Influenza virus overcomes apoptosis by rapid multiplication

The kinetics of apoptotic fragmentation of the chromosomal DNA was determined in the influenza virus-infected MDCK, HeLa and KB cells, respectively. Comparison of these kinetics with the kinetics of virus multiplication revealed that the multiplication of influenza virus was observed only when apoptosis was induced after the production of progeny virus in the infected cells. The extent of apoptotic response was reversely correlated with the permissiveness of the cells.     

Importance of luxury flow for critically ill patients receiving a left ventricular assist system

The presence of a significant organ dysfunction does not immediately exclude patients from consideration for treatment with a left ventricular assist system (LVAS). However, in treating morbid circulatory shock patients with multiple organ failure, it is important to know the preoperative and postoperative factor or factors related to the recovery of the damaged organ function. In this study, we retrospectively analyzed patients receiving a LVAS at our institution and tried to determine the important factors related to the survival of patients with multisystem failure. Twenty-seven patients who underwent LVAS placement at Saitama Medical School Hospital between 1993 and 2003 were included in this study. The preoperative risk factors analyzed were renal dysfunction, respiratory dysfunction, hepatic dysfunction, the existence of active infection, and the combination of all four factors. As a postoperative factor, the pump flow index (mean LVAS pump flow during the first 2 weeks after LVAS surgery divided by the body surface area) was analyzed. None of the analyzed preoperative factors could predict survival after LVAS surgery, but a pump flow index of less than 2.5 l/min/m² had a significant relationship with death after LVAS surgery. Further analysis revealed that all the patients with a pump flow index of 3.0 l/min/m² or more could overcome preoperative organ dysfunction. Congestive heart failure patients with multisystem failure need luxury pump flow for successful LVAS surgery; this factor could be especially important in device selection and postoperative management.     

Intermediate filament expression by normal and diseased human corneal epithelium

Cicatricial conjunctivitis may be a sequel to systemic disorders (eg, Stevens-Johnson syndrome, cicatricial pemphigoid) or local disorders such as chemical burns. The cicatrisation is often associated with corneal epithelial changes that cause visual loss. These have been attributed to encroachment of the conjunctival epithelium over the cornea. However, the epithelial anomalies are poorly understood. We investigated the corneal epithelial changes in cicatricial conjunctivitis with an immunohistochemical study of intermediate filaments in normal and pathological specimens. Our results show that the normal corneal epithelium is immunoreactive for cytokeratin 3 (CK 3) but not cytokeratin 19 (CK 19), whereas normal conjunctival epithelium is CK 3 negative and CK 19 positive. Conjunctiva artificially transposed over the cornea (after therapeutic conjunctival flap reconstruction) retained the normal pattern of conjunctival cytokeratin expression (CK 3 negative, CK 19 positive). Conversely, the entire corneal epithelium exhibited the normal cytokeratin pattern (CK 3 positive, CK 19 negative) in 82% of Stevens-Johnson, 80% of cicatricial pemphigoid, and 69% of chemical burns specimens. The findings suggest that conjunctival encroachment is not responsible for the changes at the corneal surface in cicatricial conjunctivitis and that the abnormal corneal epithelium is derived from native corneal cells in these diseases.     

Plasma secretin in response to pure bile salts and endogenous bile in man

The effect of exogenous bile salts on plasma concentrations of secretin was studied by infusion of chenodeoxycholate, cholate, glycocholate, and taurocholate into the duodenum of normal subjects. The effect of endogenous bile on plasma secretin was studied by ingestion of a liquid test meal, by reinfusion of postprandial duodenal aspirates with known contents of bile salts, and by stimulation of gallbladder contraction by cholecystokinin. Each experiment was performed in groups of seven subjects. The relative secretin-releasing potencies of glycocholate, cholate, taurocholate and chenodeoxycholate (2.25 mmol) were 1.01.31.93.2. Hydrochloric acid (0.5 mmol) was, on a molar basis, approximately ten times more potent than sodium cholate. The effect of taurocholate was diminished when a liquid meal was used as vehicle instead of saline. Endogenous bile did, in no circumstance, elicit release of secretin. It is concluded that although bile salts have the ability to stimulate secretin release, endogenous secretin release is of minor, if any, importance for secretin release when physiological conditions are approached.This study was supported by grants from the Danish Hospital Foundation for Medical Research, Region of Copenhagen, The Faroe Islands and Greenland (J.nr. 78/45 and 79/48) and Borgen Legatet.     

Short-termin vivo stability of endothelial-lined polyester elastomer and polytetrafluoroethylene grafts

A fibronectin substrate will significantly enhance the strength of endothelial cell attachment on grafts constructed of polyester elastomer (PE) and polytetrafluoroethylene (e-PTFE). This experiment was undertaken to determine the short-termin vivo stability of endothellum on these fibronectin coated surfaces. Eight mongrel dogs underwent bilateral carotid artery replacement with both graft materlals. All grafts were inoculated with 2,000 cells/mm² using cultured autogenous venous endothelium labelled with Indium-111-oxine. The Indium-111 label in the grafts was measured immediately prior to implantation, after 1 hour ofin vivo perfusion, and at explantation after 24 hours. The percentage of inoculated cells attached to the grafts before perfusion was simillar for both materials, 93.3±3.0% versus 92.2±7.2%, for PE and e-PTFE respectively. All grafts were patent at one hour after implantation. PE grafts were found to have 93.8±3.9 % of the attached cells present at one hour while e-PTFE grafts had only 54.5 ± 10.8 % remaining, p<.001. After 24 hours, 5/8 (62.5%) e-PTFE grafts and 2/8 (25.0 %) PE grafts remained patent, p=.13. Of the patent grafts however, endothelial cell retention was still superior on the PE grafts with 78.0±0.6% of the attached cells remaining compared to only 24.5±6.1% on e-PTFE, p<.001. Occluded PE grafts had fewer cells remaining at 24 hours than patent ones, 78.0±0.6% versus 31.1±32.8%, respectively, p=.13. Histologically, patent PE grafts demonstrated nearly confluent endothelial monolayers while e-PTFE had patches of endothelial cells surrounded by, a platelet-fibrin carpet. We conclude that short-term patency appears to be determined by the extent of endothelial retention on PE but not e-PTFE.     

Anastomotic false aneurysms with aortic Dacron graft after twenty-five years

One of the early diamond crimped knitted polyester (Dacron) grafts was surgically excised after implantation for 25 years in the aorto-billiac position because of false aneurysm formation at the three anastomotic sites. The sutures were no longer visible. While the areas around the false aneurysm were poorly incorporated, the graft limbs were well encapsulated with some endothelial-like cells on the luminal surface. The integrity of the graft was well preserved despite mild fraying and the disruption of one stitch.     

Traumatic aneurysms of the descending thoracic aorta

From July 1979 to December 1985 we observed 51 patients with traumatic lesions of the descending thoracic aorta. Twenty-nine had acute ruptures, mostly accompanied by multiple injuries, and 27 had to be operated upon immediately. Twenty-two patients (19 males, 3 females) had chronic traumatic aneurysms of the descending thoracic aorta (more than six weeks after trauma). Mean age at the time of trauma was 24 years. Mean age at time of surgery was 36.5 years. Twelve patients were symptomatic. All were treated surgically. At surgery, complete aortic disruption was found in 15 patients and partial rupture in seven. We did not use aortic shunting of any kind, only aortic cross-clamping. Hypertension was controlled by intravenous drug infusion. The ruptured aortic segment was replaced in all cases by prosthetic Dacron graft. There were no operative deaths. One patient (age 77) died 11 weeks after surgery from multiple organ failure. One case of postoperative paraplegia was observed. This patient recovered almost completely from his neurological deficit.