Shuichi Saeki

Abnormality in a specific protein of the erythrocyte membrane in hereditary spherocytosis

Abstract Erythrocyte membrane proteins from fifteen patients with hereditary spherocytosis were analyzed by polyacrylamide disc gel electrophoresis in the presence of 0.1% SDS. Almost complete deficiency was found in a protein component, IVb, in four cases. A small but significant decrease in this component was noted in most of the other cases.

Effects of 1Oalkyl2acetylsnglycero3phosphocholine (platelet activating factor) on cardiac function in perfused guinea-pig heart

The direct cardiac action of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) was studied in isolated perfused guinea-pig heart preparations. PAF produced a fall in left ventricular pressure, decreases in the rate of rise of the left ventricular pressure (dp/dt) and coronary flow, but had no effect on heart rate. These results indicate that PAF is a cardiodepressant with inotropic selectivity and this effect on heart is blocked by CV-3988, a specific PAF antagonist.

Effect of 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine inhibitor on the reduction of one-kidney, one clip hypertension after unclipping in the rat

The role of 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine in regulating blood pressure was studied in one-kidney, one clip hypertensive rats using 3-(N-n-octadecylcarbamoyloxy)-2-methoxypropyl-2-thiazolio ethylphosphate, which specifically inhibited the hypotensive activity of exogenously injected 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine. The blood pressure of rats with established hypertension produced by clipping one renal artery and contralateral nephrectomy normally decreases rapidly after unclipping the artery, but this rapid decrease was significantly inhibited by intravenous infusion of 3-(N-n-octadecylcarbamoyloxy)-2-methoxypropyl-2-thiazolio ethylphosphate. This shows that endogenous 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine participates in the rapid decrease of blood pressure after unclipping the kidney in one-kidney, one clip hypertensive rats.

Potent hypotensive activity of 1-O-hexadecyl-2-O-acetyl-sn-glycero-3-phosphocholine in spontaneously hypertensive rat

Abstract Chemically synthesized 1-O-hexadecyl-2-O-acetyl- sn -glycero-3-phosphocholine possessed the most potent hypotensive activity compared with bradykinin, prostagrandin E 2 and I 2 when 5 nano moles/kg body weight of each drug were administered intravenously in spontaneously hypertensive rat. The potency and the duration of hypotensive activity of 1-O-hexadecyl-2-O-acetyl- sn -glycero-3-phosphocholine were dose dependent. Exogenous norepinephrine or angiotensin II showed pressor activity during the hypotensive action of 1-O-hexadecyl-2-O-acetyl- sn -glycero-3-phosphocholine, but did not disturb the hypotensive pattern of this ether lipid. These may suggest that 1-O-alkyl-2-O-acetyl- sn -glycero-3-phosphocholine plays an important role for the regulation of blood pressure.

Hypotensive mechanism of acetyl glyceryl ether phosphorylcholine (AGEPC) in dogs. Effects on hemodynamics and humoral factors

One-O-hexadecyl-2-O-acetyl-sn-glycero-3-phosphorylcholine (AGEPC) was intravenously administered to anesthetized dogs to study the effects on hemodynamics and several endocrine factors. The effect of AGEPC on local blood flow was also studied by direct intra-arterial injection. Following intravenous injection, blood pressure and cardiac output decreased significantly (p less than 0.001). Changes in total peripheral resistance (TPR) and heart rate were biphasic. TPR increased significantly (p less than 0.01) after an initial slight reduction. Heart rate decreased significantly (p less than 0.01) with only a transient slight elevation. Femoral blood flow was increased (p less than 0.001) by intraarterial injection and decreased (p less than 0.05) by intravenous administration. Plasma norepinephrine (p less than 0.001), epinephrine (p less than 0.01), thromboxane B2 (p less than 0.001), 6-0-PGF1 alpha (p less than 0.01), aldosterone (p less than 0.001) and cortisol (p less than 0.001) were elevated, but plasma renin activity did not change. These results suggest that the hypotensive mechanism of AGEPC is due to both cardiosuppression and vasodilation. AGEPC increased plasma catecholamines, thromboxane A2, PGI2, aldosterone and cortisol which, in turn, may modify hemodynamics.

SPONTANEOUS FRACTURES OF LONG BONES ASSOCIATED WITH JOINT CONTRACTURES IN BEDRIDDEN ELDERLY INPATIENTS: CLINICAL FEATURES AND OUTCOME

To the editor: It was recently reported that influenza A was cultured in 62 double rooms at the Wisconsin Veterans Home over six seasons. The roommate was infected in 12 (19.4%). During 3,294 resident-seasons, influenza was cultured in 208 single rooms (6.3%). Those who lived in double rooms with a culture-positive roommate had a 3.07 relative risk (95% confidence interval 5 1.61–5.78) of acquiring influenza A. Identical methodology was used to analyze the 1992/ 1993 influenza season, in which influenza B was encountered. Case finding was based on intense prospective surveillance by research staff and has been previously described. This study compared the relative risk of influenza B in residents whose roommate had a positive culture with that of those who resided in single rooms. It is possible that a second infected roommate became infected outside of the room. To control for this possibility, the number of single rooms and the number of cases in single rooms each year were determined for comparison. Influenza B was introduced to 29 double rooms. A second culture-confirmed case was noted in 10 (34%). The second cases occurred 0 to 11 days (mean 3.9 days) after the initial case. Seven of these second cases had been vaccinated (70%). Overall, 85% of residents were vaccinated. During 489 resident-seasons in single rooms, influenza was cultured in 65 rooms (13%). Those who lived in a double room with a culture-positive roommate had a relative risk of 2.6 (95% CI 5 1.2–5.6) of acquiring influenza B compared to those who resided in single rooms As expected, the data confirm a greater relative risk of acquiring influenza B in roommates of residents with influenza B than in residents who did not have roommates. The excess risk associated with having a culture-positive roommate is troublesome because it has been demonstrated that culture-confirmed influenza B was associated with an excess 30-day mortality of 3.9% over baseline mortality (1.5%/30 days) in nursing home residents. A private room is optimal, but this is not possible in most nursing homes. Other interventions might include using any curtain or barrier that may exist between roommates. The roommates should be counseled to maintain hand hygiene and 3-foot separation with extra environmental hygiene provided by staff. The unaffected roommate should probably be offered chemoprophylaxis with a neuraminidase inhibitor, even if the entire unit is not placed on chemoprophylaxis.

Endogenous platelet-activating factor and anti-platelet-activating factor in patients with renovascular hypertension

Renovascular hypertension is relieved by percutaneous transluminal renal angioplasty. In four patients with renovascular hypertension, platelet-activating factor (PAF) was found to be released into the ipsilateral renal venous blood after percutaneous transluminal renal angioplasty, but was not found in the contralateral renal venous blood following this procedure. Anti-platelet-activating factor with a lipid-like property was also found, and its polarity was slightly lower than that of PAF judging by its behavior on thin layer chromatography. Anti-platelet-activating factor completely blocked the aggregation of rabbit platelets induced by PAF, ADP or arachidonic acid. These results indicate that PAF and anti-platelet-activating factor are released into renal venous blood following percutaneous transluminal renal angioplasty in patients with renovascular hypertension.

Studies on the role of platelet-activating factor in blood pressure regulation.

Circulating levels of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16PAF) in human subjects were measured by gas chromatography/mass spectrometry using negative ion chemical ionization. The mean (±S.D.) circulating C16PAF levels in patients with essential hypertension (18.1±5.3 pg/mL, n=16) were not significantly different from those in normotensive subjects (17.2±7.2 pg/mL, n=14). During a salt balance study, high salt intake (20 g/day) significantly increased the circulating level of C16PAF, and changes in circulating C16PAF significantly and positively correlated with changes in mean arterial blood pressure (r=0.47, p<0.05). Changes in C16PAF also correlated with changes in creatinine clearance (r=0.55, p<0.05), but did not correlate with changes in plasma sodium concentration, plasma chloride concentration and plasma volume. An intravenous injection of 50 μg of human atrial natriuretic peptide (hANP) decreased circulating C16PAF levels from 20.0±2.7 to 13.9±2.4 pg/mL of blood (n=10, p<0.01) in healthy subjects. The data appear to indicate that C16PAF levels are changed by salt intake-induced mild increase in blood pressure, and that hANP may be an endogenous factor which lowers circulating C16PAF.

α-Adrenergic Blocking Action of 1-O-Hexadecyl-2-0-Acetyl-sn-Glycero-3-Phosphocholine in Rats

The effect of 1-0-hexadecyl-2-0-acetyl-sn-glycero-3-phospho-choline (HAGPC), a major component of antihypertensive polar renomedullary lipid, on the pressor responses to norepinephrine and angiotensin II was investigated in normal Wistar rats. The pressor activity of norepinephrine (1 µg/kg of body weight (BW)) and angiotensin II (40 ng/kg BW) were markedly suppressed when these substances were injected immediately after intravenous administration of 80 nmol/kg BW of HAGPC. When HAGPC was infused continuously at a rate of 20 nmol/kg BW/min, pressor responses to bolus injection of graded doses (0.5 to 10 µg/kg BW) of norepinephrine were significantly lowered, but pressor responses to 10 to 200 ng/kg BW of angiotensin II were not affect-ed. These observations suggest that HAGPC has α-adrenergic blocking activity and does not influence angiotensin II receptors.

Effect of prostacyclin infusion on active and inactive renin release in the isolated perfused kidney

The effect of prostacyclin infusion into the renal artery of the isolated perfused hog kidney on the release of active and inactive renin was investigated. Infusion of prostacyclin at a rate of 0.1 microgram/min resulted in a significant increase (p less than 0.01) in active renin and a significant fall (p less than 0.01) in inactive renin. Prostacyclin also increased urinary kallikrein excretion (p less than 0.05). The results indicate that the kidney secretes not only active renin but also inactive renin, and suggest that prostacyclin stimulates the conversion of inactive renin to the active form through the activation of the renal kallikrein system.