[Systematization of methylation procedure and application to 11C-labeled compounds].
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Biomedical subjects
Publications and source records attributed to H Iida.
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We established an experimental system suitable for study of cell cycle regulation by Ca2+ in the yeast Saccharomyces cerevisiae. Systematic cell cycle analysis using media containing various concentrations of Ca2+, a Ca2(+)-ionophore (A23187), and a Ca2(+)-chelator [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) revealed that simultaneous addition of 10 microM A23187 and 10 mM EGTA to cells growing in a Ca2(+)-deficient medium at 22 degrees C caused rapid decrease in intracellular Ca content and resulted in transient G1 arrest followed by block mostly at G2/M, as revealed by flow cytometry. Recovery from G1 arrest was not due to coordinated initiation of DNA synthesis and bud emergence: unbudded cells with S or G2/M DNA were observed. Examination of terminal phenotype suggested that Ca2+ was required at all the stages of the cell cycle except for the initiation of DNA synthesis. The intracellular cAMP level decreased within 10 min of addition of A23187 and EGTA. No significant transient G1 arrest was observed in cells incubated with 8-Br-cAMP, or RAS2val19 and delta bcy1 mutants, which produce a high level of cAMP and have constitutively activated cAMP-dependent protein kinase, respectively. These results indicate that Ca2+ is essential for cell cycle progression and suggest that Ca2+ may regulate the cAMP level. This system will be useful for genetic and molecular studies on cell cycle events regulated by Ca2+.
We established an experimental system for measuring the cytosolic-free Ca2+ concentration ([Ca2+]i) in individual Saccharomyces cerevisiae cells using fura-2 as a Ca2(+)-specific probe in conjunction with digital image processing and examined changes in [Ca2+]i in response to alpha-factor in single cells of a mating type. The addition of alpha-factor to a cells raised [Ca2+]i to several hundred nanomolar in the cells from a basal level of approximately 100 nM, simultaneous with the induction of Ca2+ influx. When the cells were incubated with alpha-factor in a Ca2(+)-deficient medium, Ca2+ influx was greatly reduced, and the rise in [Ca2+]i was not detected. This indicates that the alpha-factor-induced rise in [Ca2+]i is generated by Ca2+ influx through the plasma membrane and not by release from internal stores. In the Ca2(+)-deficient medium, a cells died specifically after they had changed into cells with one projection on the cell surface. This indicates that the rise in [Ca2+]i is essential for the late response to alpha-factor. The duration of Ca2+ requirement for maintaining viability was limited to this stage, and the earlier and later stages were not affected by Ca2+ deprivation. Mating between a and alpha mating type cells was impaired in this medium due to cell death at and before the stage of conjugation. These findings are the first evidence for an essential role for mobilized Ca2+ in the yeast life cycle.
These experiments were designed to determine whether the limited cardiac output during open cardiac massage could be preferentially directed to the coronary and cerebral vessels by balloon occlusion of the descending thoracic aorta. Sixteen dogs were instrumented to monitor cardiac output and left atrial, right atrial, right ventricular, left ventricular, and arterial blood pressures. Measurements of myocardial and cerebral blood flow distribution during massage were made using the radioactive microsphere technique. Each animal underwent two episodes of fibrillation and resuscitation. In one episode the arrest was managed by open massage alone, and in the other, open massage was accompanied by balloon occlusion, with the order randomized. When compared to control, open cardiac massage was associated with a significant decrease in mean arterial pressure; however, the addition of balloon occlusion produced a 130% increase in the mean arterial pressure that was obtained during open CPR (control, 93 +/- 5 mm Hg; massage alone, 35 +/- 2 mm Hg; massage + balloon, 76 +/- 2 mm Hg, P less than 0.01). In a similar fashion, although the absolute blood flow was reduced by 50% when compared to control, the blood flow (ml/min/g) to the brain and heart during massage was 100% better when balloon occlusion was employed (brain: control, 0.41 +/- 0.03; massage only, 0.05 +/- 0.01; massage + balloon, 0.25 +/- 0.02, P less than 0.01; heart: control, 1.46 +/- 0.11; massage alone, 0.35 +/- 0.05; massage + balloon, 0.71 +/- 0.05, P less than 0.01). These results suggest that aortic occlusion significantly increased myocardial and cerebral perfusion patterns during ventricular fibrillation and open cardiac massage.(ABSTRACT TRUNCATED AT 250 WORDS)
A 62-year-old woman was admitted for evaluation of muscular weakness, skin pigmentation, dry mouth, and interstitial pneumonia. During the course of her stay, adult respiratory distress syndrome, hemolytic anemia, renal failure, neurologic dysfunction, and thrombocytopenia appeared. A clinical diagnosis of thrombotic thrombocytopenic purpura (TTP) accompanied by polymyositis and Sjögren's syndrome was made. She died two weeks after the beginning of plasmapheresis, and an autopsy was performed. Immunohistochemistry disclosed deposits of IgM, fibrinogen, and C1q in glomeruli and arterioles and deposits of C3 in small arteries. von Willebrand's factor antigen, which promotes the adhesion of platelets to the subendothelium, was positive in onion-peeled arteries of the kidney and the spleen. These results suggest that immune complexes may have triggered a sequence of events from vascular endothelial injury to TTP.
To examine the efficacy and usefulness of captopril-enhanced renal vein renin (RVR) measurements in detecting the functional significance of renal artery stenosis found in hypertensives, we compared these values in 22 patients with arteriographically documented renovascular hypertension due to unilateral (URVH: 14 patients) or bilateral renal artery stenosis (BRVH: 8 patients) and 12 patients with high renin essential hypertension (EHT). Before captopril administration, RVR ratio was less than 1.5 in 8 patients (36.4%) with renovascular hypertension and all patients (100%) with EHT. Captopril enhanced the lateralization of renal vein renin in renovascular hypertension; the postcaptopril RVR ratio was greater than 2.0 in 18 patients (81.8%) and greater than 1.5 in all the patients (100%). On the other hand, RVR ratio remained unchanged in most patients with EHT. There was no significant difference in the postcaptopril RVR ratios between URVH and BRVH. However, the postcaptopril RVR ratio was higher in atherosclerosis (10 patients) than in fibromuscular dysplasia (11 patients) (P less than .05). Captopril also elucidated contralateral renin suppression as expressed by a contralateral/peripheral renin ratio of less than 1.0, which was associated with a favorable outcome of unilateral surgical intervention. Captopril-stimulated RVR indices were valuable in detecting the functionally significant renal artery stenosis and predicting surgical curability in renovascular hypertension.
Seven extremely rare cases of paraplegia secondary to senile osteoporotic vertebral compression fractures were treated by posterior decompression followed by Harrington rod stabilization. This approach not only ensures more satisfactory decompression, but also facilitates early mobilization and rehabilitation. The follow-up period ranged from 1 year to 3 years, 3 months (average, 24.7 months); in all seven cases a substantial overall improvement was achieved. This report demonstrates that an osteoporotic vertebral body fracture can cause a cord compression, and emphasizes the effectiveness and importance of early surgical treatment.
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The incidence and pathogenetic role of hepatitis B surface antigen (HBsAg) were evaluated in patients with IgA nephropathy. Among 130 consecutive patients with IgA nephropathy, HBs antigenemia was detected in 4 patients (3.1%). Serum antibody to hepatitis B core antigen was positive in these 4 patients indicating that they were persistent carriers of hepatitis B virus. Serum hepatitis B e antigen (HBeAg) was detected in 1 patient, and antibody to HBeAg was positive in the other 3 patients. The incidence of HBs antigenemia was not significantly higher than the 2.0% of the general population. An immunofluorescent study in the renal tissues from the 4 IgA-nephritic patients with HBs antigenemia did not demonstrate HBsAg or HBeAg in the glomeruli. These findings suggest that HBsAg appears to play no role in the pathogenesis of IgA nephropathy.
The mechanisms by which tissue injury after acute myocardial infarction (AMI) occurs has not been fully elucidated. Recent evidence in experimental models has suggested involvement of the complement system in microvascular and macrovascular injury subsequent to AMI. With respect to angina pectoris, whether or not the complement system is activated is not clear. The present study assessed the role of complement as a mediator of myocardial inflammation by quantifying products of complement activation, including C3d, C4d, Bb, and SC5b-9 complexes, in 31 patients with AMI, 17 patients with unstable angina pectoris, 19 patients with stable angina pectoris, and 20 normal volunteers. The plasma C3d levels increased in patients with AMI and in those with unstable angina pectoris (p less than 0.01). The plasma levels of C4d, Bb, and SC5b-9 increased only in patients with AMI (p less than 0.01). The plasma SC5b-9 level was related to peak creatine phosphokinase (r = 0.71) and inversely related to the ejection fraction (r = -0.71). The plasma SC5b-9 level of patients with congestive heart failure was higher than that of patients without congestive heart failure in AMI. These results show that activation of complement system occurs after AMI and show an association of myocardial damage with complement activation. With respect to angina pectoris, the complement system is mildly activated in patients with unstable angina pectoris; however, the cardiac function of patients with unstable angina pectoris is not damaged. The complement system of patients with stable angina pectoris is not activated.
The effects of alminoprofen and other non-steroidal antiinflammatory drugs (NSAIDs) on the writhing reaction caused by kaolin, acetylcholine, phenylquinone and zymosan were studied. Aspirin, indomethacin, ibuprofen and diclofenac-Na, as cyclooxygenase inhibitors, showed similar potency ratios on four writhing tests, although, alminoprofen exhibited a somewhat rather higher potency ratio on kaolin- and zymosan-induced writhing models than on acetylcholine- and phenylquinone-induced writhing models. All NSAIDs, cyclooxygenase inhibitors except alminoprofen showed similar shapes in illustrations of potency ratio when the potency of aspirin was expressed as 1.0. The potency of alminoprofen produced a figure unlike those of other cyclooxygenase inhibitors. These results suggest that alminoprofen has a different pharmacological profile from other general NSAIDs in terms of analgesic action. This combination method with potency ratios for writhing reactions caused by the above four inducers could be a simple method for classification of pharmacological profiles of the analgesic actions of NSAIDs.
The mechanism and prognostic implications of Q wave regression following transmural acute myocardial infarction (AMI) were assessed in 54 patients. Of these subjects, 14 lost their Q waves. Exercise myocardial thallium-201 (201Tl) scintigraphy and two-dimensional echocardiography were performed before the patients were discharged from hospital. Two-dimensional echocardiography and electrocardiography were simultaneously repeated about 18 months after AMI. Both the relative 201Tl activity in the infarcted area and the improvement of echocardiographic wall motion index were higher in patients who had lost their Q waves than in those with retained Q waves (70 +/- 14% vs 58 +/- 13%, p less than 0.01; 5.2 +/- 3.0 vs 2.0 +/- 3.4, p less than 0.01, respectively). The prevalence of post-infarction angina pectoris was significantly higher in the former (29% vs 0%, p less than 0.01). We concluded that remnants of viable myocardial muscle might be responsible for Q wave regression following transmural acute myocardial infarction, and the prevalence of post-infarction angina pectoris was high among these patients.
Using a bradykinin enzyme immunoassay, we measured the amount of kinin in the peritoneal washings of mice with the kaolin-induced writhing reaction. Simultaneous treatment with captopril, a kininase II inhibitor, significantly increased the kinin level at 1 min after kaolin injection. Soybean trypsin inhibitor injected simultaneously with kaolin almost completely suppressed the kinin level at 1 min with or without treatment of captopril. These results suggest that kinin is released through activation of the plasma kallikrein-kinin system by kaolin, and that kinin could be a main mediator for the writhing reaction.
Antibody titers against canine parvovirus (CPV), canine distemper virus (CDV) and infectious canine hepatitis virus (ICHV) in serum were measured in 6 beagle dams and their 38 puppies bred in our colony, in order to clarify the effects of maternally derived antibodies to antibody responses against the viruses after vaccinations in puppies. Correlation coefficient on antibody titers between puppies and dams were CPV: r = 0. 7935, CDV: r = 0.8194 and ICHV: r = 0.8105. Mean maternal antibody positive rates in 7-day-old puppies from their dams were CPV: 67%, CDV: 46% and ICHV: 45%. Mean half-lives of the maternal antibodies in puppies were estimated to be CPV: 13.5 days, CDV: 15.1 days and ICHV: 15.4 days. The antibody response against CPV vaccination in puppies was mainly observed in dogs being titers of less 1:5 and positivity was 39% (15/38 puppies) after 1st vaccination at 42 days after birth, and 82% (31/38 puppies) after 2nd vaccination at 70 days. That against CDV vaccination (at 56 days after birth) was seen highly in dogs being titers of less 1:10 and positivity was 53% (20/38). Also that against ICHV vaccination (at 56 days after birth) was seen frequently in dogs being titers of less 20 holds and the rate was 87% (33/38). From these results, it was estimated that the age when high antibody response against each vaccination could be expected in puppies might be CPV: between 40 and 69 days, CDV: between 32 and 92 days and ICHV: between 31 and 52 days, respectively.
A simulation study to evaluate the errors in rate constants of the three compartment model using the weighted integral method was performed. Ten combinations of 7 kinds of weight functions, the errors were tested in 18F fluorodeoxyglucose (18FDG) study. The error factors arising in PET measurement were statistical noise, cerebral blood volume, time shift and scanning time of PET measurement. Errors in each rate constant were within the range of 10 percent and those in k1k3/(k2+k3) within 1 percent. The weighted integral method was confirmed to be a faster method than the conventional least squares method within a reasonable error range.
Cerebrospinal fluid (CSF) hypertension during aortic surgery is a poorly understood, multifactorial event that may increase the risk of spinal cord injury. To assess the factors that may contribute to changes in CSF pressure during aortic surgery, measurements of ascending arterial and CSF pressures were made in 17 anesthetized mongrel dogs. Changes in CSF patterns were monitored under several conditions tested in random sequence. These included systemic hypertension produced by an infusion of phenylephrine, cross-clamping of the descending thoracic aorta, and manual, superior displacement of the transverse aortic arch (arch elevation), either alone or in conjunction with the cross-clamp. Hypertension, cross-clamping, and cross-clamping combined with arch elevation all produced significant increases in ascending mean arterial pressure (204 +/- 20, 170 +/- 8, and 158 +/- 11 mm Hg, respectively, vs. 117 +/- 8 mm Hg [control]; (p less than 0.01). Small, nonsignificant increases in CSF pressure were detected in the cross-clamp group, but none were detected with hypertension alone, despite significant increases in ascending arterial blood pressure in both groups. Thus, neither arterial hypertension nor cross-clamping alone could be demonstrated directly to cause significant CSF hypertension. However, when aortic elevation (displacement) was combined with cross-clamping, the rise in CSF pressure increased to significant levels, even though the ascending arterial hypertension was least severe in this group. In contrast, arch elevation alone did not produce any significant increase in ascending arterial pressure but did produce an approximately 114% increase in CSF pressure (15.2 +/- mm Hg vs. 7.7 +/- 1 mm Hg [control]; p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)
Spinal cord hypoperfusion injury is a devastating complication of cross-clamping the proximal thoracic aorta. The collateral circulation around the cross-clamp is generally poorly developed, and the run-off is immense, resulting in extremely low thoracic aortic and spinal cord perfusion pressures. The authors postulated that balloon occlusion of the abdominal aorta might confine this reduced collateral flow around the cross-clamp to the thoracic aorta. In 8 of 16 dogs subjected to aortic cross-clamping of the aorta just beyond the arch vessels, the abdominal aorta was also occluded by a balloon. Thoracic aortic pressure and spinal cord perfusion pressure were significantly higher in the animals with aortic balloon occlusion than in those without balloon occlusion (77 +/- 8 mm Hg versus 26 +/- 1 mm Hg, p less than 0.01, and 67 +/- 8 mm Hg versus 18 +/- 2 mm Hg, p less than 0.01, at 10 minutes after cross-clamping). Abdominal aortic balloon occlusion increases thoracic aortic pressure after the aorta is cross-clamped proximally. Further studies are necessary in primates to assess the effect of this procedure in spinal cord perfusion and the rate of paraplegia.
Bateman universal proximal femoral arthroplasty combined with acetabular reaming was performed in 35 cases of osteoarthritis of the hip joint. The patients were from 21 to 59 years of age (average, 41 years of age) at the time of operation. The postoperative outcome for a middle term ranging from two to eight years, with an average of five years and nine months, was studied along with postoperative migration of the outer head. The clinical outcome, assessed by the evaluation criteria for hip function proposed by the Japanese Orthopaedic Association, was favorable. A stable average score of greater than 80 occurred for eight years postoperatively; the average preoperative score was 45. Of the 35 cases, seven cases (20%) had an upward migration of the outer head, and one case (2.9%) had an inward migration of 5 mm or more, but the migration did not affect the clinical outcome in any case. There was no certain relationship between the degree of rotation of the outer head and the extent of its migration. Migration of the outer head was prevented by postoperative exercise, in which total loading was initiated after the completion of the radiolucent zone around the outer head and its circumferential zone of osteosclerosis.