Cytological nuclear atypia classification can predict prognosis in patients with endometrial cancer.

OBJECTIVE: Endometrial cancer is one of the leading causes of malignancy in females. Nuclear findings are important for patients with cancer, and can provide valuable information to treating oncologists. We investigated whether nuclear findings were a useful prognostic factor in patients with endometrial cancer. METHOD: We investigated 71 cases of endometrial carcinoma with paired histology and cytology at Kurume University Hospital. We classified endometrial endometrioid adenocarcinoma (EEC) G1 and G2 as type I carcinomas, and uterine papillary serous carcinoma (UPSC), clear cell carcinoma (CC) and EEC G3 as type II carcinomas. For the establishment of the cytological nuclear atypia classification, we examined the following nuclear factors on the cytological smears: mitotic figures, prominent nucleoli, nuclear area and anisonucleosis. RESULTS: There was a significant difference in mitotic figures (P < 0.001) and anisonucleosis (P = 0.026) in cytological smears between type I and type II carcinomas. Based on these findings, we categorized cytological nuclear atypia into three groups, nuclear atypia-1 (57.7%), nuclear atypia-2 (19.7%) and nuclear atypia-3 (22.5%), and this classification system correlated well with prognosis in patients with endometrial cancer (P < 0.001). Furthermore, this classification system was able to extract patients with a good prognosis from those with high-grade carcinomas, such as UPSC+CC+EEC G3, and patients with a poor prognosis from those with EEC G1. CONCLUSIONS: Our system of cytological nuclear atypia classification based on endometrial cytology can predict patient prognosis. Cytological nuclear atypia classification and histological typing may be useful for the treatment and follow-up of patients with endometrial cancer, and should be routinely incorporated into cytological reports.

The clock gene cryptochrome of Bactrocera cucurbitae (Diptera: Tephritidae) in strains with different mating times.

Differences in mating time between populations can give rise to premating reproductive isolation. Tephritid fruit flies exhibit large variation in mating time among intra- or inter-specific populations. We previously cloned the clock gene period from two strains of melon fly, Bactrocera cucurbitae; in one the individuals mate early during the day, whereas in the other the individuals mate later. These strains were originally established by divergent artificial selection for developmental time, 'short' and 'long', with early and late mating times, respectively. The deduced amino acid sequences of PERIOD proteins for these two strains were reported to be identical. Here we cloned another clock gene cryptochrome (cry) from the two strains, and found two stable amino acid substitutions in the strains. In addition, the allele frequency at the two polymorphic sites of cry gene correlated with the circadian locomotor period (tau) across strains, whereas the expression pattern of cry mRNA in the heads of flies taken from the short strain significantly differed from that from the long strain. These findings suggest that variation in the cry gene is related to differences in the circadian behaviour in the two strains, thus implying that the cry gene may have an important role in reproductive isolation.

Can ultrasonographic evaluation of subcutaneous fat predict pressure ulceration?

High-resolution ultrasound may be able to detect pressure ulcers before clinical signs emerge. This retrospective study found that one such early indicator is inflammatory oedema in the subcutaneous fat, which resolves as healing occurs.

Improvement of temporal and dynamic subtraction images on abdominal CT using 3D global image matching and nonlinear image warping techniques.

Accurate registration of the corresponding non-enhanced and arterial-phase CT images is necessary to create temporal and dynamic subtraction images for the enhancement of subtle abnormalities. However, respiratory movement causes misregistration at the periphery of the liver. To reduce these misregistration errors, we developed a temporal and dynamic subtraction technique to enhance small HCC by 3D global matching and nonlinear image warping techniques. The study population consisted of 21 patients with HCC. Using the 3D global matching and nonlinear image warping technique, we registered current and previous arterial-phase CT images or current non-enhanced and arterial-phase CT images obtained in the same position. The temporal subtraction image was obtained by subtracting the previous arterial-phase CT image from the warped current arterial-phase CT image. The dynamic subtraction image was obtained by the subtraction of the current non-enhanced CT image from the warped current arterial-phase CT image. The percentage of fair or superior temporal subtraction images increased from 52.4% to 95.2% using the new technique, while on the dynamic subtraction images, the percentage increased from 66.6% to 95.2%. The new subtraction technique may facilitate the diagnosis of subtle HCC based on the superior ability of these subtraction images to show nodular and/or ring enhancement.

A computer-aided temporal and dynamic subtraction technique of the liver for detection of small hepatocellular carcinomas on abdominal CT images.

It is often difficult for radiologists to identify small hepatocellular carcinomas (HCCs) due to insufficient contrast enhancement. Therefore, we have developed a new computer-aided temporal and dynamic subtraction technique to enhance small HCCs, after automatically selecting images set at the same anatomical position from the present (non-enhanced and arterial-phase CT images) and previous images. The present study was performed with CT images from 14 subjects. First, we used template-matching based on similarities in liver shape between the present (non-enhanced and arterial-phase CT images) and previous arterial-phase CT images at the same position. Temporal subtraction images were then obtained by subtraction of the previous image from the present image taken at the same position of the liver. Dynamic subtraction images were also obtained by subtraction of non-enhanced CT images from arterial-phase CT images taken at the same position of the liver. Twenty-one of 22 nodules (95.5%) with contrast enhancement were visualized in temporal and dynamic subtraction images. Compared with present arterial-phase CT images, increases of 150% and 140% in nodule-to-liver contrast were observed on dynamic and temporal subtraction images, respectively. These subtraction images may be useful as reference images in the detection of small moderately differentiated HCCs.

[Three-dimensional image of Adamkiewicz artery detected by using multidetector CT: preoperative assessment of thoraco-abdominal aortic aneurysm].

Images were obtained with the following parameter 0.5 sec/r, 1 mm collimation, pitch 3.5, 120 kV, 300 mA. One hundred ml of contrast material containing 350 mg I/ml was injected with a power injector (dual shot type) into an antecubital vein at a rate of 3.5 ml/sec (70 ml). Then remaining 30 ml and same volume of saline were infused at a rate of 1.5 ml/sec simultaneously. Twenty-five seconds after the injection, scan was performed from the level of L2 to T5 vertebrae. Transverse sections were reconstructed with a 1 mm thickness at 0.7 mm intervals. Imaging was done with multiplanar and curved planar reformations. In case of vertebral deformity, however, 3D images were made to depict the Adamkiewicz artery. In 141 patients, 107 (76%) Adamkiewicz arteries from the interverbral foramen to the hairpin-shaped union with the anterior spinal artery were visualized. Seventy-nine arteries of Adamkiewicz (73%) originated from the left side. Our method is useful for depicting Adamkiewicz artery.

Benidipine, a long-acting Ca channel blocker, limits infarct size via bradykinin- and NO-dependent mechanisms in canine hearts.

Amlodipine increases NO levels in coronary vessels and aorta via bradykinin-dependent mechanisms in vitro. We have previously reported that a long-acting Ca channel blocker, benidipine, increases cardiac NO levels in ischemic canine hearts, suggesting that benidipine may also protect against ischemia and reperfusion injury via bradykinin- and NO-dependent mechanisms. We examined this possibility. In open chest dogs, the left anterior descending coronary artery was perfused with blood through a bypass tube and was occluded for 90 min followed by 6 hours of reperfusion. Infarct size was assessed by TTC staining at 6 hours of reperfusion. When benidipine doses of 50, 100, and 200 ng/kg/min were infused via the bypass tube between 10 min prior to the onset of ischemia and after 60 min of reperfusion, systemic blood pressure did not change significantly. Infarct size decreased with the administration of benidipine (50, 100, and 200 ng/kg/min) when compared to the untreated condition (24.8+/-2.5, 17.3+/-3.1, and 16.5+/-2.0 vs. 43.4+/-5.6%, respectively) associated with the increased release of NO and bradykinin in the coronary venous blood upon reperfusion. Myeloperoxidase activity of the myocardium increased after 6 hours of reperfusion, which was attenuated by benidipine. The limitation of infarct size and the increase in myeloperoxidase activity were completely blunted by either L-NAME or HOE140. There were no significant differences in collateral blood flow assessed by the microsphere method after 45 min of ischemia for any of the groups. Thus, we conclude that the Ca channel blocker, benidipine, limits infarct size via bradykinin- and NO-dependent mechanisms.

cDNA array hybridization reveals cardiac gene expression in acute ischemic murine hearts.

PURPOSE: Although cDNA array technique has recently become available in the cardiovascular field, it has not yet been established what kind of genes in the myocardium are expressed by acute ischemia. Since many substances contribute to the pathophysiology of acute ischemic hearts, we investigated transcription responses of murine hearts to ischemia using cDNA array representing 18,376 genes. METHODS AND RESULTS: In 29 male mice, we ligated the proximal site of the left coronary artery for 60 min. In 14 mice, we performed the sham operation without the ligation of the left coronary artery. After 60 min, the hearts were excised to obtain mRNA, and we performed cDNA array analysis. In 18,376 cDNA, 2 known genes were upregulated over 10-fold, 11 known genes were upregulated 5.0- to 9.9-fold, and 32 unknown genes were upregulated over 5.0-fold compared to sham-operated controls. In contrast, 11 known genes and 7 unknown genes were downregulated to levels below 0.2-fold. For 9 of the 13 known genes of which expression was increased as analyzed by cDNA array, subsequent Northern blot analysis also revealed an increase in expression. CONCLUSION: Using cDNA array analysis we found that cardiac expression of 24 known and 39 unknown genes was modulated by acute ischemic stress, and appeared to be related to the pathophysiology of ischemic hearts. These results show that cDNA array analysis may provide a new molecular insight to the pathophysiology of acute ischemic hearts.

Nifedipine limits infarct size via NO-dependent mechanisms in dogs.

OBJECTIVES: Amlodipine increases NO levels in coronary vessels and aorta via bradykinin-dependent mechanisms in vitro. We have previously reported that nifedipine increases cardiac NO levels in the ischemic canine hearts, suggesting that nifedipine may also have protective effects against ischemia and reperfusion injury, because the enhancement of NO production limits infarct size. We tested whether nifedipine limits infarct size via NO-dependent mechanisms. METHODS: In open chest dogs, the left anterior descending coronary artery was perfused with blood through a bypass tube and occluded for 90 min followed by 6 hours of reperfusion. Infarct size was assessed at 6 hours of reperfusion. Nifedipine of 3 or 6 microg/kg/min was infused into the bypass tube between 10 min prior to the onset of ischemia and 60 min of reperfusion. RESULTS: Neither systemic blood pressure nor heart rate changed during infusion of nifedipine. Infarct size was reduced by the administration of nifedipine (3 or 6 microg/kg/min) compared with the untreated condition (25.6+/-2.6 and 19.1+/-3.5 vs. 43.4+/-5.6%, respectively), which was completely blunted by L-NAME (45.0+/-3.6 and 45.4+/-4.2 vs. 47.9+/-3.9% in the nifedipine (3 or 6 microg/kg/min) with L-NAME groups vs. the L-NAME group). Myeloperoxidase activity of the myocardium increased after 6 hours of reperfusion, which was attenuated by nifedipine. The limitation of infarct size and the attenuation in myeloperoxidase actiivity were completely blunted by L-NAME. There were no significant differences in collateral blood flow at 45 min of ischemia between each group. CONCLUSIONS: We conclude that the Ca channel blocker, nifedipine, limits infarct size via NO-dependent mechanisms.

Differential subcellular actions of ACE inhibitors and AT(1) receptor antagonists on cardiac remodeling induced by chronic inhibition of NO synthesis in rats.

Chronic inhibition of NO synthesis induces cardiac hypertrophy independent of systemic blood pressure (SBP) by increasing protein synthesis in vivo. We examined whether ACE inhibitors (ACEIs) enalapril and temocapril and angiotensin II type-I receptor antagonists (angiotensin receptor blockers [ARBs]) losartan and CS-866 can block cardiac hypertrophy and whether changes in activation of 70-kDa S6 kinase (p70S6K) or extracellular signal-regulated protein kinase (ERK) are involved. The following 13 groups were studied: untreated Wistar-Kyoto rats and rats treated with NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME), D-NAME (the inactive isomer of L-NAME), L-NAME plus hydralazine, L-NAME plus enalapril (3 mg. kg(-1). d(-1)) or temocapril (1 or 10 mg. kg(-1). d(-1)), L-NAME plus losartan (10 mg. kg(-1). d(-1)) or CS-866 (1 or 10 mg. kg(-1). d(-1)), L-NAME plus temocapril-CS866 in combination (1 or 10 mg. kg(-1). d(-1)), and L-NAME plus rapamycin (0.5 mg. kg(-1). d(-1)). After 8 weeks of each experiment, ratios of coronary wall to lumen (wall/lumen) and left ventricular weight to body weight (LVW/BW) were quantified. L-NAME increased SBP, wall/lumen, and LVW/BW compared with that of control. ACEIs, ARBs, and hydralazine equally canceled the increase in SBP induced by L-NAME. However, ACEIs and ARBs equally (but not hydralazine) attenuated increase in wall/lumen and LVW/BW induced by L-NAME. The L-NAME group showed both p70S6K and ERK activation in myocardium (2.2-fold and 1.8-fold versus control, respectively). ACEIs inactivated p70S6K and ARBs inactivated ERK in myocardium, but hydralazine did not change activation of either kinase. Thus, ACEIs and ARBs modulate different intracellular signaling pathways, inhibiting p70S6K or ERK, respectively, to elicit equal reduction of cardiac hypertrophy induced by chronic inhibition of NO synthesis in vivo.

Role of cellular acidosis in production of nitric oxide in canine ischemic myocardium.

We tested the hypothesis that cellular acidosis modulates the production of nitric oxide (NO) in ischemic hearts. In canine hearts, we decreased coronary blood flow (CBF) to one third of the control by reduction of coronary perfusion pressure (105+/-3 to 41+/-5 mmHg), and thereafter we maintained CBF constant (89.8+/-1.6 to 30.0+/-0.5 ml/100 g/min) with an intracoronary administration of either saline, atropine, rauwolscine, HOE140, 8-sulfophenyltheophylline (8SPT), NaHCO3, or HOE642 (the inhibitor of Na+/H+ exchange). The cardiac NO levels defined as the differences of the nitrate and nitrite levels between coronary venous and arterial blood increased in the saline administration (2.9+/-0.2 to 12.7+/-1.7 micromol/l), and the extents of increases were identical in the condition of either saline, atropine, rauwolscine, HOE140 or 8SPT administration. In the condition with either NaHCO3 or HOE642, the increases in the cardiac NO levels were blunted (4.5+/-0.7 and 4.8+/-0.4 micromol/l, respectively). Cyclic GMP content of epicardial coronary artery in the ischemic area increased, which was also attenuated by either NaHCO3 or HOE642. We confirmed the acidosis-induced NO production in a more severe ischemic myocardium, and also showed that cellular acidosis produced by infusion of HCl increased NO production in non-ischemic myocardium. We conclude that cellular acidosis and subsequent activation of Na+/H+ exchanges modulate production of endogenous NO in canine ischemic myocardium.

Cardioprotective effect afforded by transient exposure to phosphodiesterase III inhibitors: the role of protein kinase A and p38 mitogen-activated protein kinase.

BACKGROUND: Phosphodiesterase III inhibitors (PDEIII-Is) improve the hemodynamic status of heart failure via inotropic/vasodilatory effects attributable to the increase in intracellular cAMP level. Direct cardioprotection by PDEIII-Is and its underlying mechanisms, however, have not been identified. We tested the infarct size-limiting effect of PDEIII-Is and the roles of cAMP, protein kinase (PK) A, PKC, and mitogen-activated protein kinase (MAPK) families in open-chest dogs. Methods and Results-- Milrinone, olprinone (PDEIII-Is), or dibutyryl-cAMP (db-cAMP) was injected intravenously 30 minutes before 90-minute ischemia, followed by 6 hours of reperfusion. Olprinone was also examined with an intracoronary cotreatment with a PKA inhibitor (H89), a PKC inhibitor (GF109203X), an extracellular signal-regulated kinase kinase (MEK) inhibitor (PD98059), or a p38 MAPK inhibitor (SB203580) throughout the preischemic period. Either PDEIII-Is or db-cAMP caused substantial hemodynamic changes, which returned to control levels in 30 minutes. Collateral flow and percent risk area were identical for all groups. Both PDEIII-Is and db-cAMP increased myocardial p38 MAPK activity during the preischemic period, which was blocked by H89, but not by GF109203X. Both PDEIII-Is and db-cAMP reduced infarct size (19.1+/-4.1%, 17.5+/-3.3%, and 20.3+/-4.8%, respectively, versus 36.1+/-6.2% control, P<0.05 each). Furthermore, the effect of olprinone was blunted by either H89 (35.5+/-6.4%) or SB203580 (32.6+/-5.9%), but not by GF109203X or PD98059. H89, GF109203X, PD98059, or SB203580 alone did not influence infarct size. CONCLUSIONS: Pretreatment with PDEIII-Is has cardioprotective effects via cAMP-, PKA-, and p38 MAPK-dependent but PKC-independent mechanisms in canine hearts.

[Clinical outcome of potassium-titanyl-phosphate (KTP/532) laser vaporization prostatectomy for benign prostate hyperplasia].

OBJECTIVE: To study the feasibility of vaporization prostatectomy by potassium-titanyl-phosphate (KTP/532) laser in men with bladder outlet obstruction due to benign prostatic hyperplasia (BPH) and to evaluate their clinical and voiding outcome 2 weeks and 6 months after operation. PATIENTS AND METHODS: Laser vaporization prostatectomy with the KTP/532 laser at 20 W was performed in 21 BPH patients varying from 56 to 75 years of age. All cases were performed under the spinal anesthesia. The laser was produced by MODEL SL20/50 and ADD/Stat side-firing fibers were used. A urethral catheter was inserted post-operatively and was removed within 6 days after operation. The hemoglobin value was examined on the first day after operation and uroflowmetry was executed 2 weeks and 6 months after operation with the examination of the residual urine volume. IPSS and QOL score were recorded by patients 2 weeks and 6 months after operation. RESULTS: The prostate volumes ranged from 22 to 52 mL (mean 37.3 +/- 10.4). None of the 21 patients had any significant blood loss or any fluid absorption. The voiding parameters improved: mean peak flow rate increased from 7.1 to 16.5 mL/s 2 weeks after operation and to 15.2 mL/s 6 months after operation and residual volume decreased from 172 to 45 mL 2 weeks after operation and to 43 mL 6 months after operation. IPSS and QOL score improved significantly in Wilcoxon signed-ranks test. The ratio of excellent and good in efficacy criteria of Kawabe group was 71.4% 2 weeks after operation and that was 71.4% 6 months after operation. Mean catheterization term was 4.5 days. Only one patient showed transient urinary retention when the catheter was removed the third postoperative day. None had incontinence postoperatively. No other significant complications were recognized. The prostate volume was more than 50 mL in 3 cases and the postoperative 6 months outcomes of the 3 cases were all poor in their symptoms in the efficacy criteria of Kawabe group. CONCLUSIONS: KTP laser vaporization prostatectomy is safe and effective for obstructive prostates up to 50 mL in volume and produces good results 2 weeks post operatively that are sustained for 6 months after operation.

[Giant epidermal cyst in the perineum extending into the pelvic space in the patient with polycystic kidney disease: a case report].

A 75-year-old man with autosomal dominant polycystic kidney disease was admitted to our hospital with the chief complaint of a giant mass in the left side of the perineum that had gradually developed in size during the previous 20 years. Palpation revealed a neonatal head-sized cystic mass with no tenderness. Magnetic resonance imaging (MRI) demonstrated a well-circumscribed homogeneous mass extended to the dorsal side of the bladder. It was excised surgically without any injury of rectum or urinary tract. The resected specimen was 23 x 18 x 12 cm in size and 1.2 kg in weight. The pathological diagnosis was epidermal cyst. Cases with an epidermal cyst extending into the pelvic space are extremely rare with few cases having been reported in the world.

Characteristics of acoustic noise in echo-planar imaging.

Characteristics of the acoustic noise generated by magnetic resonance imagers of different systems and performance levels were studied when operating in echo-planar imaging (EPI) sequence. Continuous equivalent A-weighted sound pressure levels (Leq) and peak impulse sound pressure levels (Lpeak) during EPI were measured in 12 clinical super-conducting MRI systems (0.5-1.5 T). Sound pressure levels and frequency spectra of EPI were compared with those of nine different pulse sequences. EPI sound pressure levels differed among institutions (Leq = 94.2 +/- 2.7 dBA. Lpeak = 109.1 +/- 3.5 dB), but these were within permissible noise exposure levels. Sound pressure levels during EPI were not significantly different from those during other pulse sequences. However, compared to other pulse sequences. EPI had a significantly greater proportion of acoustic noise in the high octave-frequency band. Single-shot EPI had relatively higher frequency noise and greater Leq than multishot EPI, but the difference in Leq decreased when the number of slices in multishot EPI was increased.

Role of phasic dynamism of p38 mitogen-activated protein kinase activation in ischemic preconditioning of the canine heart.

Although ischemic stress, including ischemic preconditioning (IP), activates p38 mitogen-activated protein kinase (MAPK), the relationship between p38 MAPK activation and the underlying cellular mechanisms of cardioprotection by IP is not verified in vivo. We examined the effects of the selective p38 MAPK inhibition on the cardioprotective effect of IP in the open-chest dogs. The coronary artery was occluded 4 times for 5 minutes, separated by 5 minutes of reperfusion (IP) followed by 90 minutes of occlusion and 6 hours of reperfusion. We infused SB203580 into the coronary artery during IP and 1 hour of reperfusion, during IP alone, and during sustained ischemia in the IP group. p38 MAPK activity markedly increased during IP but did not additionally increase at the onset of ischemia and was even attenuated at 15 minutes of sustained ischemia, and heat-shock protein (HSP) 27 was phosphorylated and translocated from cytosol to myofibril or nucleus without affecting total protein level at the onset of ischemia compared with the control group. SB203580 treatment (1 micromol/L) only during IP blunted the infarct size limitation by IP (37.3+/-6.3% versus 7.4+/-2.1% in the IP group, P:<0.01) and attenuated either phosphorylation or translocation of HSP27 during IP. Although the SB203580 treatment throughout the preischemic and postischemic periods had no significant effect on infarct size (33.3+/-9.4%) in this model, treatment with SB203580 only during ischemia partially mimicked the infarct size limitation by IP (26.8+/-3.5%). Thus, transient p38 MAPK activation during ischemic preconditioning mainly mediates the cardioprotection followed by HSP27 phosphorylation and translocation in vivo in the canine heart.

Role of mitochondrial and sarcolemmal K(ATP) channels in ischemic preconditioning of the canine heart.

We tested whether mitochondrial or sarcolemmal ATP-sensitive K(+) (K(ATP)) channels play a key role in ischemic preconditioning (IP) in canine hearts. In open-chest beagle dogs, the left anterior descending artery was occluded four times for 5 min each with 5-min intervals of reperfusion (IP), occluded for 90 min, and reperfused for 6 h. IP as well as cromakalim and nicorandil (nonspecific K(ATP) channel openers) markedly limited infarct size (6.3 +/- 1.2, 8.9 +/- 1.9, and 7.2 +/- 1.6%, respectively) compared with the control group (40.9 +/- 4.1%). A selective mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate, partially blunted the limitation of infarct size in the animals subjected to IP and those treated with cromakalim and nicorandil (21.6 +/- 3.8, 25.1 +/- 4.6, and 19.8 +/- 5.2%, respectively). A nonspecific K(ATP) channel blocker, glibenclamide, completely abolished the effect of IP (38.5 +/- 6.2%). Intracoronary or intravenous administration of a mitochondria-selective K(ATP) channel opener, diazoxide, at >100 micromol/l could only partially decrease infarct size (19.5 +/- 4.3 and 20.1 +/- 4.4%, respectively). In conclusion, mitochondrial and sarcolemmal K(ATP) channels independently play an important role in the limitation of infarct size by IP in the canine heart.

Protein tyrosine kinase is not involved in the infarct size-limiting effect of ischemic preconditioning in canine hearts.

Protein kinase C (PKC) plays an important role in ischemic preconditioning (IP). Because (1) tyrosine kinase is located at the downstream of PKC for IP in the rabbit hearts and (2) we have reported that ecto-5'-nucleotidase is the substrate for PKC and plays a crucial role for the infarct size-limiting effect, we tested whether tyrosine kinase activation contributes to either activation of ecto-5'-nucleotidase or the infarct size-limiting effect of the early phase of IP in the canine heart. In dogs, the IP procedure (4 cycles of 5-minute occlusion of coronary artery) and exposure to 12, 13-phorbol myristate acetate (PMA) each activated myocardial ecto-5'-nucleotidase and Lck tyrosine kinase. Genistein (10, 30, and 100 microg. kg(-)(1). min(-)(1) IC), an inhibitor of tyrosine kinase, attenuated the activation of Lck tyrosine kinase but did not attenuate the activation of ecto-5'-nucleotidase due to either IP or PMA. In the other canine hearts, IP attenuated infarct size (49+/-5 versus 11+/-3 or 16+/-3%, P<0.01) due to 90 minutes of coronary occlusion followed by 6 hours of reperfusion, which was not blunted by 3 or 2 (30 and 100 microg. kg(-)(1). min(-)(1)) doses of genistein (infarct sizes, 15+/-4, 13+/-4, and 13+/-3%, respectively, and 17+/-3 and 15+/-4%, respectively) or lavendustin A. Tyrosine kinase does not activate ecto-5'-nucleotidase or trigger the infarct size-limiting effect of the early phase of IP in canine hearts.