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Biomedical subjects

A Shibata

Publications and source records attributed to A Shibata.

At least 397 records · Page 22Linked to original sources

Thrombin and plasmin generation in patients with liver disease.

Patients with liver disease frequently have multiple hemostatic abnormalities. Coagulation and fibrinolytic factors and inhibitors may decrease as the result of impaired synthesis and/or enhanced catabolism. In order to assess the actual degree of activation of coagulation and fibrinolytic systems in liver disease, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) were measured together with cross-linked fibrin derivatives (XDP), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI-1) in 31 patients with liver disease (five patients with acute hepatitis, seven with chronic hepatitis, nine with liver cirrhosis, and ten with hepatocellular carcinoma). Mean plasma levels of TAT (mean 4.2 +/- SD 4.0 micrograms/L), PAP (0.7 +/- 0.7 mg/L), and XDP (374 +/- 518 micrograms/L) were significantly elevated in patients with liver disease as compared with normal subjects (TAT of 1.7 +/- 0.3 micrograms/L, PAP of 0.2 +/- 0.1 mg/L, and XDP of 30 +/- 14 micrograms/L; P less than 0.005). Plasma concentrations of t-PA and PAI-1 antigens were also elevated. When plotted by the disease categories, the magnitude of elevations of these parameters was variable among subgroups. Patients with acute hepatitis had considerably higher TAT levels. The mean PAP values were relatively high in chronic hepatitis and hepatocellular carcinoma, in which an elevation of the t-PA/PAI-1 ratio was observed. Although clearance of TAT and PAP should be evaluated in the future, these findings suggest that excessive amounts of thrombin and plasmin are actually generated in patients with liver disease.

Antithrombin III↗

Thrombin generation in patients with thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is thought to be caused primarily by endothelial cell injury or primary platelet agglutination. A coagulation screen usually shows normal or minimal changes, but a modest elevation of fibrinogen/fibrin degradation products (FDP) is observed in many patients with TTP. To assess the thrombin generation in vivo in TTP, plasma levels of thrombin-antithrombin III complex (TAT) were measured together with plasmin-alpha 2-antiplasmin complex (PAP) in ten patients with acute TTP. Plasma TAT [mean 6.7 +/- (SD) 3.7 micrograms/liter] as well as PAP (2.1 +/- 1.2 mg/liter) were elevated in patients with TTP as compared with healthy subjects (TAT of 1.7 +/- 0.3 microgram/liter and PAP of 0.2 +/- 0.1 mg/liter; n = 10). These findings indicate that considerable amounts of thrombin and plasmin are actually generated in TTP, although the majority of patients do not show signs of consumption coagulopathy.

Adult↗

Vasoconstrictor effect of endothelin on the canine coronary artery: is a novel endogenous peptide involved in regulating myocardial blood flow and coronary spasm?

We examined the effect of endothelin on the canine coronary artery (N = 20). The left circumflex coronary artery was cannulated and perfused with arterial blood at constant pressure. Coronary blood flow was monitored by an electromagnetic flowmeter. Intracoronary endothelin provoked a vasoconstriction that was dose-dependent. At a dose of 500 pmol, coronary blood flow was reduced remarkably (91.0 +/- 5.4%, n = 4), and endothelin subsequently produced a fall in systemic blood pressure and ST elevation in the electrocardiogram. At a dose of 100 pmol (n = 9), coronary flow decreased from 16.4 +/- 1.5 ml/min to 12.5 +/- 1.5 ml/min (p less than 0.001) and coronary vascular resistance increased from 6.3 +/- 0.8 mm Hg/ml/min to 9.9 +/- 1.9 mm Hg/ml/min (p less than 0.005). A cumulative dose-response curve to endothelin was obtained and the curves were shifted to the right after both verapamil and nifedipine administration. Therefore endothelin has a potent vasoconstrictor action that is attenuated by the calcium-channel blocker.

Animals↗

Accumulation of glycosphingolipids in spinal and sympathetic ganglia of a symptomatic heterozygote of Fabry's disease.

Fabry's disease is an X-linked disorder of glycolipid catabolism. We have found a symptomatic heterozygous female with cardiomyopathy and severe pain in the extremities. We studied histochemically and biochemically the accumulated glycolipids in spinal and sympathetic ganglia of the patient. Histochemical examination demonstrated the marked glycolipid deposits that have been observed in heterozygous males in these ganglia. Gas-liquid chromatography (GLC) revealed that these accumulated glycolipids were characterized as globotriaosylceramide (Gb3cer) and galabiosylceramide (Ga2cer). In the heterozygous female, the accumulations of Gb3cer in spinal and sympathetic ganglia were, respectively, 34 and 48 times the amount in normal controls. This is the first report on quantitative and qualitative analyses of the accumulated glycolipids in spinal and sympathetic ganglia of a heterozygous carrier female.

Fabry Disease↗

Electrophysiologic evaluation of asymptomatic patients with the Wolff-Parkinson-White pattern.

In the past 4 years, 34 asymptomatic patients with the Wolff-Parkinson-White (WPW) pattern underwent electrophysiologic study. The effective refractory period (ERP) of antegrade conduction over the accessory pathway was 288 +/- 29 msec. In three asymptomatic patients (9%), the antegrade ERP of the accessory pathway was shorter than 250 msec. The antegrade ERP of the accessory pathway became shorter than 250 msec in an additional 12 of 22 (55%) patients after isoproterenol administration. Nineteen (56%) of the asymptomatic patients showed the absence of retrograde conduction over the accessory pathway even after isoproterenol administration. The rate of induction of orthodromic reciprocating tachycardia in the asymptomatic WPW patients was 15% (5/34), which was significantly lower than that in the symptomatic patients. These data suggest that in the asymptomatic patients, the absence of retrograde conduction over the accessory pathway is the reason they remained asymptomatic, free of reciprocating tachycardia. However, even in the asymptomatic patients, some had the accessory pathway in which antegrade ERP was shorter than 250 msec. They may result in rapid ventricular conduction over the accessory pathway when atrial fibrillation develops.

Adult↗

Fusion with the prolonged first postpacing interval in pacing of ventricular tachycardia.

In cases of recurrent sustained ventricular tachycardia (VT), constant fusion and progressive fusion in the surface electrogram were observed during overdrive pacing of VT. However, following cessation of pacing, the return cycle of VT (stimulus to the first nonpaced QRS) was longer than the VT cycle length. This phenomenon can be explained by orthodromic capture of the exit site of the VT current with a conduction time (stimulus to QRS) exceeding the VT cycle length. This site can therefore be activated during entrainment of VT during the mid-to-terminal portion of the paced QRS complex, resulting in constant fusion.

Cardiac Pacing, Artificial↗

Augmented fragmentation of atrial activity upon premature electrical stimuli by verapamil.

The significance of fragmented activity obtained from the atrium during electrophysiologic study (EP study) was confirmed since it was always observed just at the onset of fibrillation. It was preceded by extra stimuli or atrial flutter, and the initial site of fragmentation varied from case to case. The premature-stimulus-induced widening of the atrial wave was observed in some cases who had normal size of atrium and no heart failure. The widening was augmented by administration of verapamil but not by procainamide, suggesting that for such widening or fragmented activity, slow-fiber-mediated conduction seems to be responsible. One case with intraatrial reentrant tachycardia developed fragmentation lasting for 1.0 second after verapamil. Therefore, some apparently normal atria may have a subclinical electrophysiologic abnormality that can be disclosed by premature stimulations or verapamil.

Adolescent↗

Attenuation of reactive hyperemia caused by aspirin in canine coronary artery.

Effects of intracoronary aspirin on coronary blood flow and reactive hyperemia were evaluated in closed-chest, anesthetized dogs. In 18 dogs the left circumflex coronary artery was cannulated and perfused by arterial blood at a constant pressure. Coronary blood flow was measured by an electromagnetic flowmeter. Intracoronary aspirin at doses of 5, 10, and 20 mg reduced coronary blood flow in a dose-dependent manner. Injection of aspirin at doses of 10 to 25 mg also inhibited reactive hyperemia following the coronary occlusion for fifteen seconds. The mean peak flow ratio was reduced from 2.13 +/- 0.42 to 1.75 +/- 0.35 (p less than 0.005). The increment of coronary blood flow provoked by intracoronary arachidonic acid at doses of 150 to 300 micrograms was almost entirely inhibited by the pretreatment of the coronary artery with aspirin. The authors conclude that aspirin increases coronary arterial resistance in a dose-dependent manner and also restricts the maximal dilating capacity, possibly by inhibition of prostacyclin synthesis.

Animals↗

Attenuation of the vasoconstrictor action of neuropeptide-Y by calcium-channel blockers.

Neuropeptide-Y (NPY) was administered intracoronarily in dogs to see the modification of its vasoconstrictor action by the calcium (Ca)-channel blockers nisoldipine (0.1 microgram/kg) and nifedipine (1 microgram/kg). Dogs were anesthetized and the left circumflex artery was cannulated without opening the chest by using a specially designed cannula perfused at constant pressure. The change in coronary flow due to NPY was determined before and after the systemic administration of the two Ca-channel blockers. With administration of 1 to 2 nmol of NPY, coronary blood flow decreased maximally by 23.4 +/- 7.8% without changes in perfusion pressure or central venous pressure and it became significantly less after nisoldipine: 16.0 +/- 5.7% (p less than 0.02). A similar attenuation in the decrease in coronary flow was observed in the nifedipine study: 23.2 +/- 7.5% to 12.0 +/- 6.7% (p less than 0.02). A fall in systemic arterial blood pressure was observed after administration of both Ca-channel blockers, but it was significant only after nisoldipine (p less than 0.01). Nonsignificant increases in heart rate were observed after both drugs. Nisoldipine seemed to attenuate the NPY-induced vasoconstriction in dogs, and its equimolar potency is about ten times that of nifedipine.

Animals↗

'Salivary peptide P-C' of human pancreatic B-cells shares only partly immunoreactivity with salivary peptide P-C indicating a new B-cell protein which is different from insulin.

Salivary peptide P-C like immunoreactivity, originally isolated from human whole saliva has later been found in the human pancreatic B-cells. In the present work an indirect immunofluorescence technique using monoclonal antibodies against isolated salivary peptide P-C was applied to Bouin fixed pancreas and parotid glands to study the possible identity of the two substances. Positive P-C immunofluorescence was found in the serous cells of parotid glands but not in pancreatic B-cells, suggesting that pancreatic P-C substance is not salivary peptide P-C itself, but a substance sharing the common antigenic site with salivary peptide P-C. To examine this, an indirect immunofluorescence technique using polyclonal P-C antisera pre-absorbed with six kinds of synthetic fragments (1-22, 23-44, 23-29, 30-44, 30-38 and 38-44) of salivary peptide P-C was applied to the human pancreas. The result showed that pancreatic P-C substance was a substance which shares the common antigenic site with the 38-44 amino acid residue of salivary peptide P-C. Western blot analysis using extracts of human pancreata further showed that pancreatic P-C substance is not a precursor of insulin but a protein with molecular weight of 11,500 dalton, indicating the presence of a new protein in the insulin secretory granules of human pancreatic B-cells.

Amino Acid Sequence↗

Urinary orosomucoid excretion rate in patients with non-insulin-dependent diabetes mellitus.

Urinary excretion rate and clearance of alpha 1-acid glycoprotein (orosomucoid), a major serum glycoprotein which is more anionic (pI 2.7) than albumin (pI 4.7) were measured by RIA in timed overnight urine samples from non-insulin-dependent diabetic patients with different urinary albumin excretion rate and from healthy controls. The 50th percentiles of urinary orosomucoid excretion rate in patients with normo-, micro-, and macroalbuminuria were larger than those in healthy controls. Urinary excretion rate and clearance of orosomucoid increased in parallel with increase in albumin excretion rate in diabetic patients with an albumin excretion rate of more than 10 micrograms/min. On the basis of their levels of urinary orosomucoid excretion, patients with normoalbuminuria of less than 10 micrograms/min could be divided into two groups, one with a normal and the other with an elevated urinary orosomucoid excretion rate. The findings suggest that kidneys of diabetic patients with an albumin excretion rate of more than 10 micrograms/min are unable to distinguish the difference in pI between albumin and orosomucoid, and that a subgroup with an elevated orosomucoid excretion rate may be present among diabetics with normoalbuminuria.

Adult↗

A case of atrial septal defect combined with hypertension and left ventricular hypertrophy. Left ventricular failure induced by balloon occlusion and the effect of nifedipine.

A 46 year old woman with hypertension and left ventricular hypertrophy accompanied by an atrial septal defect is reported. Hemodynamic changes induced by balloon occlusion and concomitant nifedipine were studied. Left ventricular failure appeared after balloon closure of the defect. Nifedipine decreased the increment in left ventricular end-diastolic pressure induced by balloon occlusion. After the reduction of systemic vascular resistance, the ratio of intracardiac shunt flow was still larger. Surgical closure of the defect was performed and the postoperative course was good with the use of vasodilators.

Blood Pressure↗

Sustained ventricular tachycardia responsive to verapamil in patients with hypertrophic cardiomyopathy. Clinical and electrophysiological assessment of drug efficacy.

Recently, we examined 2 cases of hypertrophic cardiomyopathy (HCM) presenting with sustained ventricular tachycardia (VT). One case was a 62 year old male with midventricular hypertrophy and monomorphic sustained VT. After admission, the efficacies of procainamide, disopyramide, aprindin, flecainide, mexiletine and verapamil were evaluated by means of continuous electrocardiographic monitoring. Verapamil prevented the recurrence of sustained VT and markedly reduced the frequency and number of runs of nonsustained VT. In the electrophysiologic study, rapid VT was induced by double extrastimuli at the right ventricular apex. Intravenous verapamil at a dose of 10 mg prevented the induction of VT. The patient was discharged on verapamil and remains asymptomatic after 3 months of follow up. The other case was a 34 year old female who was a survivor of cardiac arrest. Monomorphic VT was observed on emergency admission and was converted to sinus rhythm by direct current cardioversion after resuscitation. In the electrophysiologic study, rapid VT was induced by double extrastimuli at the right ventricular outflow tract. Verapamil at a dose of 10 mg prevented the induction of VT. These 2 cases of HCM are rare in that they presented with sustained VT. It is also of interest that verapamil, which has been used conventionally in HCM, prevented VT.

Adult↗

Recanalization of experimental thrombotic arterial occlusion by radiofrequency thermal angioplasty: an angioscopic observation.

The efficacy of radiofrequency (RF) angioplasty for recanalization of arterial thrombosis was assessed angioscopically in five dogs. A thrombus was induced by balloon injury of the left femoral artery. Within two hr, thrombi led to total occlusion of the artery in three dogs, subtotal occlusion in one, and about 70% obstruction in one. A metal-tipped catheter, with a tip size of 2.0 mm x 5.7 mm, was advanced into the thrombus and RF at 13.56 MHz was delivered repeatedly with gradually increased energies. The arterial lumina were recanalized or enlarged in all dogs. The thrombus surface had a shaggy appearance, and were dark (charring), or mixed dark and white in color. There were relatively large variations in the energies required; 140 J in one, 200 J in two and 250 J in two. The present results suggest that thrombotic arterial occlusion, such as acute occlusion complicating balloon angioplasty, can be treated with RF thermal angioplasty. Angioscopy provided detailed information about thrombus surfaces. The variations in required energies indicate the inability to control the thermal effect by energy settings alone. A more sophisticated method such as measurement of tip temperature will be able to overcome this difficulty.

Angioplasty, Balloon↗

Effects of acute protein loads of different sources on renal function of patients with diabetic nephropathy.

To evaluate effects of acute loading of different proteins on renal function, glomerular filtration rate (GFR), albumin excretion rate (AER), and concentrations of plasma amino acids, 11 normal volunteers and 20 diabetic patients were studied before and after eating 1.0 g/kg body weight of either tuna fish meal or bean curd on separate days. In normal subjects, the mean baseline GFR was 115.8 +/- 9.5 ml/min/1.73 m2, and the mean GFRs after ingestion of tuna fish meal were 134.1 +/- 15.5 (1 hr), 146.2 +/- 18.8 (2 hr), and 157.8 +/- 21.2 (3 hr), respectively. GFR did not significantly increase in normal subjects after ingestion of bean curd. GFR in diabetic patients with normoalbuminuria after ingestion of each protein was similar to the response in normal subjects. In diabetic patients with microalbuminuria, GFR did not significantly increase after ingestion of each protein. In diabetes with macroalbuminuria, GFR decreased after ingestion of tuna fish meal and did not significantly change after intake of bean curd. In both normal subjects and diabetic patients, urinary AER did not increase after each kind of protein loading. Plasma concentrations of alanine, glycine, and arginine, known to induce glomerular hyperfiltration, increased to a greater degree after ingestion of tuna fish meal than after administration of bean curd. These findings suggest that responses of GFR to acute protein loading may differ according to the amino acid composition of the protein ingested and to the stage of diabetic nephropathy.

Adult↗