[The effect of a specific antagonist of PAF (CV-3988) on airway hyperresponsiveness induced by ozone exposure in beagles].
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Biomedical subjects
Publications and source records attributed to T Imai.
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We observed 13 cases of mitral regurgitation (MR) due to ruptured chordae tendineae (RCT) among 4,000 consecutive autopsies of patients over 60 years of age (0.33%). There were four men and nine women whose average age was 79.8 yrs. Five cases had a single RCT (Group I) and eight had multiple RCT (from two to eight chordae) (Group II). The sites of RCT were in the posterior mitral leaflet (PML) in nine, the anterior leaflet in one, and both in three. All in Group I showed RCT in the PML; the posterior scallop in two and the middle scallop in three. The average heart weight was 340 g in Group I and 431 g in Group II. Sclerosis of the coronary arteries, the circumference of the mitral valve ring, and thickness of the leaflets did not differ significantly. Estimated volume of the left atrium was significantly greater in Group II than in Group I (185 ml vs 57 ml, p less than 0.05). Jet lesions were observed in 10 of the 13 cases. The etiologies of RCT were previous endocarditis in two, mitral valve prolapse in three, and spontaneous rupture in eight. Congestive heart failure was observed in three (60%) in Group I and eight (100%) in Group II (p less than 0.01). Cardiothoracic ratio more than 60% was observed in three (60%) of Group I and six (75%) of Group II. Atrial fibrillation was demonstrated in one in Group I (20%) and six (75%) in Group II (p less than 0.05), and cardiac death in one (20%) in Group I and six (75%) in Group II (p less than 0.05). Phonocardiograms showed pansystolic murmur in all cases, third heart sound in nine (69%), and fourth heart sound in four (57%). Echocardiographically, RCT was diagnosed in six of nine cases (67%). In conclusion, patients with RCT involving more than two chordae tendineae can show more severe clinical course than cases with a single RCT.
A 37-year-old female, who had undergone a left standard mastectomy in May, 1983 for breast cancer, was treated with Tamoxifen and FT-207 postoperatively. The patient had no further evidence of disease until two and one-half years later, when a routine chest film showed a single, half-rounded density 6.5 cm in diameter in the hilus of her left lung. Bestrabucil, the benzoate of an estradiol-chlorambucil conjugate, was administered p.o. at a daily dose of 200 mg for four weeks. Thereafter, the tumor greatly decreased in size to 3.0 cm in diameter. When a left upper lobectomy was performed, the tumor was found to be necrotic tissue. Microscopically, a small cancer nest similar to the primary breast carcinoma was observed in the center of the necrosis. The necrotic tissue was surrounded with cellular infiltrate, markedly consisting of histiocytes.
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Eight cases with ruptured anterior communicating aneurysms, who developed mental signs of mild degree lasting more than two weeks following direct operation, were subjected to our study. The following results were obtained. The mental signs of mild degree in 8 cases consisted of memory and emotional disturbances. The main findings of CT scan was low density area in the subcortical and cortical areas of the frontal lobe. There was no close correlation on CT findings between memory and emotional disturbances. Abnormal density areas were detected on CT scan, but EEG showed no localized abnormalities of slow waves. Abnormal density areas were not clearly shown on CT, but EEG showed localized abnormalities. Background activities on EEG were favorable despite lesions detected on CT. Either local or diffuse abnormalities were observed in EEG background activities while no abnormal mental signs were recognized. In cases with no apparent abnormal findings on CT and with favorable background activities on EEG, EEG showed marked build up during hyperventilation. As indicated by the above data, comparative studies of CT and EEG findings revealed differences in sites of abnormalities and degree of abnormalities. This is considered caused by a possible increase in cerebral blood flow and metabolism at initiation of chronic stage following subarachnoid hemorrhage-resulting in the disappearance of abnormalities on EEG.
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We investigated the mechanism of glucose intolerance in 51 patients with Cushing's syndrome. In an oral 100g glucose tolerance test, although prevalence of decreased glucose tolerance was very high as revealed in 36 of 47 patients (77%) studied, impairment was rather mild in the majority of patients and only 10 patients (21%) were judged as diabetic. Plasma insulin was measured in 12 patients and the mean values of these patients reached above normal levels after oral glucose load. When insulin secreting capacity was assessed by measuring the ratio of the incremental area of insulin above fasting level to the corresponding area of glucose during the test, Cushing's syndrome as a whole exhibited a normal ratio compared to 9 control subjects (113 +/- 115 vs. 144 +/- 78 microU/mg, M +/- SD, ns), but in 3 patients with severe impairment of glucose tolerance reaching the diabetic range, the ratio was lower than normal (27 +/- 20 vs. 144 +/- 78 microU/mg, M +/- SD, p less than 0.05). The hypoglycemic effect of iv insulin was studied in 23 patients and was demonstrated to have decreased. Thus, we confirmed the presence of decreased insulin sensitivity, i.e. insulin resistance in Cushing's syndrome. The age of patients showed positive correlation with the degree of impairment in glucose tolerance and insulin secreting capacity, but not with that of insulin sensitivity, that is, in patients with advanced age, glucose intolerance appeared to be severe with decreased insulin secreting capacity. 125I-insulin binding to red blood cells in 8 patients was examined to elucidate the mechanism of insulin resistance in Cushing's syndrome. Percent specific binding at tracer concentration of insulin in Cushing's syndrome was not different from the value obtained in 19 normal subjects (8.2 +/- 3.0 vs. 7.7 +/- 1.0%, M +/- SD, ns). Receptor concentration and affinity were also normal. From these observations, it is likely that glucose intolerance in Cushing's syndrome is primarily due to the effects of chronic glucocorticoid excess on tissue metabolism of glucose as characterized by the presence of insulin resistance, which is not due to a defect in insulin-receptor binding but rather caused by the alteration in post-receptor mechanism, and increased secretion of insulin can be considered as a compensatory mechanism. In some patients, however, a decrease in insulin secreting capacity, the cause of which is not clear but at least related to the patient's age, is found and seems to lead to severe glucose intolerance.
Previous studies by other investigators have shown that sodium depletion causes down-regulation of angiotensin II receptors in renal glomeruli, which is ascribed to elevation of circulating angiotensin II levels. The present study was designed to determine whether elevation of circulating angiotensin II levels alone can down-regulate its own receptors without changes in the sodium balance. Rats were infused with angiotensin II at 50 ng/min intraperitoneally for 24 h or 7 d, then glomeruli were isolated by a mechanical sieving technique and used in a radioreceptor assay for angiotensin II. Angiotensin II infusion for 24 h and for 7 d both significantly suppressed plasma renin activity, and elevated plasma angiotensin II level (3-fold) but did not affect the plasma sodium and potassium or differences between dietary intake and urinary excretion of these electrolytes. By Scatchard analyses significant down-regulation of angiotensin II receptor number was demonstrated in renal glomeruli derived from rats infused with angiotensin II for either 24 h (32% decrease from the control value) or 7 d (37% decrease). No significant changes in receptor affinity were observed after 24 h of angiotensin II infusion, although the infusion for 7 d slightly but significantly decreased Kd (to 2.57 +/- 0.08 nM from 3.17 +/- 0.19, P less than 0.01). From these results, we conclude that circulating angiotensin II level itself can regulate the number of its own receptors in renal glomeruli even in the absence of changes in the sodium balance.
The relation between myocardial bridges (MB) and atherosclerosis in the left anterior descending coronary artery (LAD) was explored using morphometric methods in 642 hearts. The location of myocardial bridges in the LAD was classified according to distribution as proximal, middle and distal. Myocardial bridges were found in 48 per cent of males and 36 per cent of females. When proximal myocardial bridging was present intimal thickening and macroscopic raised lesion were increased just before the bridge as compared with the corresponding site in the other two categories. Underneath bridges eccentric plaques and raised lesions are absent although there is often concentric intimal thickening. The overall frequency of myocardial infarction was the same in patients with and without myocardial bridges. However, when infarction occurred in the patients having bridges, it was almost confined to those in the proximal group despite this being infrequent in the general distribution of myocardial bridges in the left anterior descending artery. It is postulated that hypertension may enhance infarction in the case of myocardial bridges in the very proximal left anterior descending artery. It is concluded that the location of myocardial bridges greatly alters the distribution of physical force against the arterial wall and influences the extent of atherosclerosis.
DNA sequences encoding Ile-Glu-Gly-Arg and human prorenin were joined and placed under the transcriptional control of the Escherichia coli trp promoter-operator in the expression vector pTR501. E. coli cells transformed with pTR501 expressed high levels (30% of total cell protein) of prorenin as part of a hybrid protein with the trp E gene product. The chimeric protein, accumulated in a sedimentable form, was dissolved in 6 M guanidine X HCl, purified to near homogeneity, and renatured by dialysis. The complete prorenin sequence was then excised from the renatured hybrid protein using blood coagulation factor Xa, a proteinase which is highly specific for the tetrapeptide insert Ile-Glu-Gly-Arg introduced between the 9 amino-terminal residues of the trp E gene product and the first amino acid (Thr 1) of prorenin. Human prorenin thus obtained was readily activatable with trypsin and showed close similarities to naturally occurring prorenin in its biochemical and immunochemical properties.
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Previously, a thermophilic obligate methane-oxidizing bacterium, H-2 (type I), was isolated in our laboratory. H-2 is a new type of methylotroph because of the G+C content of DNA; it uses both the ribulose monophosphate pathway and the serine pathway for carbon assimilation and possesses a new quinone. In addition, we found that resting cell suspensions of H-2 had the ability to oxidize a variety of compounds different from the other methane-oxidizing bacteria as follows. (i) C(1) to C(8)n-alkanes are hydroxylated and further oxidized, yielding mixtures of the corresponding alcohols, aldehydes, acids, and ketones. Liquid alkanes are transformed through a different oxidative pathway from that of gaseous ones. (ii) Both gaseous (C(2) to C(4)) and liquid (C(5), C(6)) n-alkenes are oxidized to their corresponding 1,2-epoxides. (iii) Liquid monochloro and dichloro n-alkanes (C(5), C(6)) are oxidized, yielding their corresponding acids or haloacids. (iv) Diethyl ether is oxidized to acetic acid; no ethanol and acetaldehyde are detected. (v) Cyclic and aromatic compounds are also oxidized. (vi) Secondary alcohols (C(3) to C(10)) are oxidized to their corresponding methyl ketones.
We studied a family with autosomal dominant osteosclerosis associated with familial spinal canal stenosis. The propositus, a 44-year-old Japanese woman, had a 9-month history of occipitalgia and left tinnitus, and also had a 2-month history of pain and numbness of the right upper limb. Radiographic skeletal survey showed osteosclerotic changes in the neurocranium, diaphysis of the long bone, mandible, shoulder, clavicle, and ribs. Serum alkaline phosphatase was normal, and no periosteal excrescences were seen. The inheritance pattern was autosomal dominant. The propositus and her daughter, both with severe osteosclerosis, showed spinal canal stenosis, but her son, whose osteosclerosis was moderate, did not. This is the first report of autosomal dominant osteosclerosis associated with familial spinal canal stenosis.
Forty patients with roentgenographically occult lung cancer underwent surgical resection. In thirty-five, cancer was detected by mass screening and in five at outpatient clinic. Bronchoscopic localization was accomplished in all cases. Serial block-sections of bronchi of all surgical specimens were prepared and examined microscopically. Forty-two lesions of bronchogenic squamous cell carcinoma were found including two of concurrent occult carcinoma. The site of tumor in the bronchi, the depth of mural invasion and the axial length of involved portion were investigated microscopically. The depth was measured with a micrometer. Fifteen lesions occurred in a subsegmental or a sub-subsegmental bronchus and 27 in a segmental or a central bronchus. Based on the depth of invasion (DI), occult bronchogenic carcinomas were classified microscopically into six categories (DI0 to DI5). Of the 42 lesions, 6 were judged as carcinoma in situ (DI0), 4 as suspicious invasion (DI1), 7 as intramucosal invasion (DI2), 17 as extramuscular invasion (DI3), 5 as extracartilaginous invasion (DI4) and 3 as extrabronchial invasion (DI5). Microscopic analysis revealed the presence of at least two types of infiltration in the bronchial wall. One was the creeping type in which carcinoma extended flatly along the superficial layers of bronchus and was presumed to stay as an occult lung cancer for a long time. The other, the penetrating type in which carcinoma extended deeply into the wall, was presumed to advance within a short period.
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