Involvement of activated integrin alpha2beta1 in the firm adhesion of platelets onto a surface of immobilized collagen under flow conditions

Recently, we demonstrated that agonist-induced activation of the platelet surface collagen-receptor integrin alpha1beta2 converts it to an active form that can bind soluble collagen with high affinity (Jung, SM, Moroi, M: J Biol Chem 1998; 273: 14827-37). Here, the involvement of alpha2beta1 activation and the high affinity binding property of activated alpha2beta1 in platelet adhesion to a collagen surface under flow conditions were analyzed. Platelet adhesion to immobilized collagen was measured in the presence of TS2/16, an activating anti-integrin alpha2beta1 antibody, and inhibiting antibodies, Gi9 and 6F1. TS2/16 decreased the moving velocity of platelets on the collagen surface, but Gi9 and 6F1 increased it, indicating that alpha2beta1 activation induces the tight binding of platelets to immobilized collagen under flow. Platelet adhesion, expressed as the surface area occupied by adhered platelets, in the presence of TS2/16 was similar to that in its absence. In contrast, adding Gi9 or 6F1 caused biphasic adhesion composed of a first phase, a lag phase whose length differed in each experiment, and a second phase adhesion with a rate similar to that of the control. This biphasic adhesion indicates that alpha2beta1 activity is inhibited and also suggests that some other factor(s) may contribute to the adhesion under flow. At concentrations where neither 6F1 nor Gi9 affected collagen-induced aggregation, these antibodies inhibited soluble collagen binding to thrombin-activated platelets. Only at much higher concentration did 6F1 inhibit collagen-induced aggregation. TS2/16 had no effect on the aggregation. The present results are evidence against the major involvement of integrin alpha2beta1 in platelet aggregation; instead, they indicate that integrin alpha2beta1 would be mainly associated with the tight binding of platelets to collagen.     

Succinylcholine neuromuscular blockade in a case of pseudocholinesterase variant

Since there is little or no pseudocholinesterase at the motor end plate, the neuromuscular blockade by succinylcholine is terminated by its diffusion away from the end-plate into extracellular fluid. Pseudocholinesterase (ChE), therefore, influences the duration of action of succinylcholine (SCC) by controlling the rate of hydrolysis before it reaches the end-plate. SCC neuromuscular blockade can be prolonged in the presence of an atypical form of ChE. A 37 year old male with the deficiency of ChE activity underwent pancreatico-duodenectomy under neuroleptanesthesia. The mode, duration and treatments of neuromuscular blockade following succinylcholine (SCC) were studied using train-of-four (TOF). SCC was administered 6 times (total 170 mg) during the operation. Prolonged apnea was noted after the first intravenous injection of SCC (60 mg, 1 mg.kg-1). It was found that spontaneous resolution of the neuromuscular block had four phases and there was a pronounced fade of the TOF response. After the second injection of SCC (30 mg), a remarkable fade of the TOF was detected and the character of the block was considered to be a desensitizing block (phase II block). The block was treated by intravenous infusion of fresh frozen plasma (FFP) (400 ml) which contained ChE, at the rate of 231 +/- 56 IU/l/37 degrees C begun shortly after the fifth injection of SCC (20mg). The duration of the block was remarkably shortened but the recovery curves were almost unchanged, indicating the diffusion of SCC away from the end-plate and/or that receptor-channel is presumably slow. The neuromuscular blockade was fully reversed by additional injection of FFP (400 ml) before extubation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Case of uremic platelet dysfunction

The present case was a 59-year-old woman who underwent a right nephrectomy at 30 years of age, and in whom renal dysfunction occurred at 51 years of age. In November 199X, when her creatinine level reached 7 mg/dl, renal replacement therapy was recommended. She refused this therapy and began her own diet therapy, which consisted of taking only supplement beverage, but no food. Afterwards she became unable to do daily work, and entered our hospital in July of the next year. On admission, her bleeding time was over 10 minutes, but coagulation function tests showed normal values. Platelet function tests showed that coagulation with the addition of ADP was mildly decreased and that coagulation with the addition of aggregation was severely decreased. These data and her bleeding tendency improved with hemodialysis. Therefore, a diagnosis of aggregation non-responsive uremic platelet dysfunction was made. On admission, we were not able to insert a catheter for hemodialysis because of her severe bleeding tendency. A platelet transfusion was made so that we could insert the catheter without severe bleeding. However, this hemostatic effect lapsed after about five to six hours. Six hours after insertion of the catheter, oozing from the orifice of the catheter was seen and a red blood transfusion was necessary. Three days after beginning hemodialysis, the bleeding tendency was no longer seen. Her platelet function and coagulation test results also improved. We can make two conclusions regarding this case. The first is when the physician's medical strategy cannot be carried out due to uremic platelet dysfunction, a platelet transfusion can temporarily eliminate the bleeding tendency. The second is that the pathophysiology of uremic platelet dysfunction involves suppression of the primary step of platelet aggregation with collagen. Experience with the present case revealed the appropriate therapeutic strategy for the pathophysiology of uremic platelet dysfunction.     

Identification of genes preferentially expressed in articular cartilage by suppression subtractive hybridization

Suppression subtractive hybridization is very effective to enrich differentially expressed genes in two different tissues or cells. We therefore used the technique to identify characteristic genes expressed in rat knee joint articular cartilage as compared to rat costal cartilage. In this study, we revealed that several genes were enriched in a subtracted articular cartilage cDNA library. The most enriched gene is lubricin that is a putative key molecule for joint lubrication. The second gene is milk fat globule epidermal growth factor (EGF) factor 8, MFG-E8 whose expression has never been observed in cartilage. Other enriched genes are known to be expressed in cartilage, however their differential expressions in cartilages have not been necessarily common. The preferential expression of characteristic genes in articular cartilage would provide unique properties to the tissue. Our findings will provide a new view of articular cartilage.     

Long-term outcome and prognostic predictors of medically treated acute type B aortic dissections

Background

The purpose of this study was to examine the long-term outcome and the prognostic predictors related to the development of complications associated with acute type B aortic dissection.

Methods

Seventy-six medically treated patients with acute type B aortic dissection were examined between 1990 and 2001. The events associated with aortic dissection included dissection-related death, rupture, visceral ischemia, lower limb ischemia, an increase in the maximum aortic diameter greater than 50 mm, and a mean enlargement rate of greater than 5 mm per year.

Results

Among the 76 patients 10 (13%) underwent chronic phase surgery and 25 (33%) presented with an event. A statistically significant difference was observed between patients with and without events with regard to atherosclerotic factors, blood flow status in the false lumen, maximum aortic diameter upon admission, mean aortic enlargement rate, and blood pressure control during follow-up. Of these factors a patent false-lumen and a maximum aortic diameter greater than 40 mm upon admission were the most strongly associated factors with regard to the development of events. Patients with a patent false-lumen and a maximum aortic diameter greater than 40 mm upon admission were determined to exhibit significantly higher event rates than other patients.

Conclusions

In determining the appropriate therapeutic approach for acute type B aortic dissection, it is important to pay careful attention to the predictors of a patent false-lumen and a maximum aortic diameter greater than 40 mm at onset to improve the long-term outcome.     

Time estimation during nocturnal sleep in human subjects

It has been postulated that time estimation during nocturnal sleep in humans can be explained by an interval timing clock inside the brain. However, no systematic investigations have been carried out with respect to how the human brain perceives the passage of time during sleep. The brain mechanisms of over- or underestimation of time spent in sleep have not yet been clarified. Here, we carried out an experimental study in which 11 healthy volunteers participated in time estimation trials scheduled six times during 9 h nocturnal sleep periods, under carefully controlled conditions. The time estimation ratio (TER: a ratio of subjective passage of time to actual time interval) decreased significantly from the first to the sixth trial. Individual TER was positively correlated with slow wave sleep prior to the trial, while it was negatively correlated with REM sleep. Our results indicate that the human brain has an ability to estimate the passage of time during nocturnal sleep without referring to time cues, and that the accuracy of this function fluctuates from overestimation in the early hours of sleep to underestimation in the last hours of sleep.     

The meaning of the turning point of the index of motor current amplitude curve in controlling a continuous flow pump or evaluation of left ventricular function

In this series, we investigated the meaning of the t-point of index of motor current amplitude (ICA) curve from a point of view of flow rate on in vitro and in vivo studies. On mock circulation loop and left ventricular assist device (LVAD)-equipped pigs, we detected the t-point and compared the pump flow at the t-point with the simultaneous cardiac output. The pump flow at the t-point showed high correlation against the simultaneous cardiac output for in vitro or in vivo study. By detection of the t-point of the ICA curve and measuring or estimating the pump flow at t-point, the cardiac output may be assessed without any sensor in various cardiac conditions.     

Successful management of traumatic aortic valve insufficiency; report of a case

A case of the successful management of traumatic aortic valve insufficiency is reported. A previously healthy 48-year-old man sustained multiple injuries in a traffic accident. One month after the accident, heart failure, derived from aortic insufficiency, was noted. Three years and 5 months after the injuries, aortic valve replacement was performed, and a large tear, approximately 7 mm in length, was found in the aortic right coronary cusp. This finding corresponded to the traumatic aortic valve insufficiency. Traumatic aortic valve insufficiency is rare, and early diagnosis may be difficult. Examinations for associated intracardiac injuries should be carefully undertaken.