Right-handed and left-handed double-helical DNA: structural studies.
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Biomedical subjects
Publications and source records attributed to S Fujii.
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To identify the risk factors of borderline hypertension in the development of established hypertension, the relationship between the changes in blood pressure over 10 years and the clinical features in the initial year was investigated in a Japanese urban population. The occurrence of cardiovascular complications in cases with borderline hypertension were also studied. The prevalence of borderline hypertension in the initial year was 18.2%. On the basis of the blood pressure changes over 10 years, these subjects could be classified into the following 5 groups: (I) those with developing established hypertension, 19.0%; (II) those with fluctuating between hypertension and borderline hypertension, 27.4%; (III) those with remaining with borderline hypertension, 19.6%; (IV) those with fluctuating between borderline hypertension and normotension, 22.9%; (V) those with improving to normotension, 11.2%. The later development of established hypertension was found in only 2.4% of normotensives in the initial year. Obesity and glucose intolerance were more frequently observed in group I (38.2% and 29.4%, respectively) than in the other groups. Diastolic blood pressures in the initial year were significantly higher in groups I and II than in III, IV and V. As for the occurrence of cardiovascular complications during the observation period, electrocardiographic abnormalities and hypertensive and/or arteriosclerotic retinopathy were not infrequently observed even in borderline hypertensives. Therefore, in subjects with borderline hypertension, continuous medical management, including correction of obesity as well as glucose intolerance, is necessary to prevent the development of established hypertension and subsequent cardiovascular complications.
In order to investigate the mechanisms of increased plasma inactive renin in diabetics with microvascular complications, changes in active and inactive renin with the progress of diabetes mellitus were studied, and effects of standing on inactive renin release and the relationship between plasma inactive renin and serum trypsin or protease inhibitors wee also studied. Inactive renin increased with the aggravation of diabetes mellitus, but active renin didn't show significant changes with the aggravation of diabetes mellitus. Active renin was significantly increased both in the healthy subjects and in the diabetic patients when they were in an upright position, but no significant change was observed in inactive renin. Serum trypsin in diabetics with retinopathy and nephropathy was lower than that in those with no clinical sign of microangiopathy, but the correlation between plasma inactive renin and serum trypsin was not significant. There was a significant correlation between plasma inactive renin and serum alpha 2-globulin (r = 0.52, p less than 0.01). Although plasma inactive renin was not significantly correlated with serum alpha 1-antitrypsin, there was a significant correlation between plasma inactive renin and serum alpha 2-macroglobulin (r = 0.61, p less than 0.01). These results show that the increased levels of plasma inactive renin observed with the development of diabetic microangiopathy are probably related to the altered plasma protein metabolism observed in patients with diabetes mellitus. However, it is not clear whether this altered protein metabolism is related to the conversion from inactive to active renin.
As compared with the pre-separated thymic lymphocyte (TL) population, a marked reduction of insulin binding was found in the two fractions [supernatant lymphocytes (SL) and precipitate lymphocytes (PL)] separated by low-speed differential centrifugation from the TL population. The reduction in insulin binding to SL or PL appeared to be due to a decrease in the affinity rather than a decrease in the number of insulin receptors. The reduced insulin binding was enhanced to near the level of the TL population when SL and PL were mixed and then incubated for 90 min at 37 degrees C. Moreover, when the cell-free supernatant from the mixed and incubated fraction was added to SL and PL respectively, the insulin binding to each fraction was found to be enhanced.
Of 305 patients who underwent subtotal thyroidectomy for Graves' disease between 1969 and 1975, recurrent hyperthyroidism was found in 31 (10.2%) and hypothyroidism in 18 (5.9%). The remaining 256 patients were clinically euthyroid, but an elevated serum TSH level was found in 104 (34.1%) and an elevated serum T3 level in 19 (6.28%). In 57 of 133 clinically and biochemically euthyroid patients, a TRH test, T3 suppression test and measurement of antithyroid antibodies were performed. Twenty-nine of the 57 patients (50.9%) showed an abnormal response to TRH. Eight of these (14.0%) showed an impaired or absent response. The T3 suppression test showed that 15 of the 57 patients (26.3%) were non-suppressible. Positive antithyroid antibodies, especially antimicrosomal antibodies, were more frequent in non-suppressible and TRH-non-responsive patients than in suppressible and TRH-responsive patients. It is suggested that after operation for Graves' disease: 1) only half of the clinically euthyroid patients were biochemically euthyroid, 2) of the clinically and biochemically euthyroid patients, there were many with abnormalities in TRH responsiveness and T3 suppressibility, and 3) thyroid functional status is unstable and long careful follow-up is important after operation for Graves' disease.
The prevalence of peripheral vascular disease (PVD) was determined in 296 Japanese diabetics (mean age 55.2 years, range 19 to 79 years), using a Doppler ultrasonic technique. PVD was diagnosed in 11.5% of the diabetic patients (7.6% females, 14.6% males). In 88% of all patients with PVD, asymptomatic impaired circulation was diagnosed. There was a clear increase of PVD with age. It was found that the increase of PVD was gradual in patients under the age of 70, from 4.3% in the younger group to 10% in patients in their 7th decade, while the frequency of PVD rose sharply to 25% in patients in their 8th decade and over. The occurrence of PVD was significantly correlated with hypertension, hypertriglyceridemia and past obesity, but not with glycemic control, serum cholesterol levels or smoking habits. Also, PVD was closely associated with persistent proteinuria, retinopathy at a rather advanced stage and calcification of leg arteries. These findings suggest that the frequency of PVD in Japanese diabetics is lower by one third and progression of PVD is more gradual than that found in similar studies in Western countries. Another distinctive feature of PVD in Japanese diabetics was the markedly high percentage of asymptomatic cases.
A 56-year old diabetic patient of over 20 years duration was admitted with gangrene of right foot. About a month prior to admission he injured the fourth toe of the right leg when he cut the toe nail. Two weeks later necrotic ulcer was present on it with cellulitis and 2nd, 3rd and 5th toes were also affected. Then his entire right leg was swollen and he developed fever. In spite of the treatment with antibiotics and insulin, gangrenous lesions progressed and subcutaneous emphysema was palpable beneath the inflamed area. On the 9th hospital day amputation was carried out below the knee. He had a good recovery 6 weeks after the amputation. Aerobic and anerobic cultures from the foot yielded bacteroides and pseudomonas aeruginosa. Clostridia were not isolated. A review was also carried out on ten diabetic cases of nonclostridial gas gangrene in the lower limb in Japan.
The propagation of spontaneous action potentials in 7-9 somite embryonic pre-contractile chick hearts was measured optically using a potential-sensitive merocyanine-rhodanine dye. Spontaneous optical signals, corresponding to action potentials, were recorded simultaneously from 8-16 different sites of the primitive embryonic heart. Short delays were observed in the time of occurrence of optical signals obtained from the different regions. We have found (i) switching phenomena: the site exhibiting pacemaking priority was first situated in the right pre-atrium, double pacemakers: two different pacemaking areas were situated independently in the right and left pre-atrial portions of the heart. On the basis of analysis of such behavior, it was concluded that the regional priority of the pacemaking activity is not rigid but is flexible, that and the direction of the spread of excitation is adaptable to the circumstances in the early embryonic heart.
The effects of temperature on spontaneous action potential activity in the 7-9 somite embryonic precontractile chick hearts were investigated using an optical method for monitoring membrane potential. A potential-sensitive merocyanine-rhodanine dye was used as an optical probe. Cooling caused a marked decrease in the frequency of occurrence of the spontaneous action potential. This slowing was associated with a decreased rate of diastolic depolarization of the pacemaker action potential. When the temperature was lowered, a decrease in the rate of rise and a prolongation of duration of the optical action signal also occurred. In addition, cooling resulted in a disordering of the rhythmicity of the action potential, and a decrease in the conduction velocity of excitation. Q10 values for such parameters were calculated: there were slight decreases in the Q10 values for the frequency and conduction velocity for 7-9 somite embryonic hearts.
For the simple purification of porcine pancreas kallikrein, various affinity chromatographies using L-prolyl-L-phenylalanyl-L-arginine (Pro-Phe-Arg-OH), tosyl-L-arginine (Tos-Arg-OH) and acetyl-L-phenylalanyl-L-arginine (Ac-Phe-Arg-OH) as ligands were examined. The purification was performed as follows using the extract from acetone powder of porcine pancreas as starting material; ammonium sulfate fractionation (30-80%), affinity chromatography (repeated) and gel filtration on Sephadex G-75, respectively. With these purification techniques, porcine pancreas kallikrein was purified about 2000-fold, respectively. From the results, these affinity chromatographies were considered to be effective for the purification of porcine pancreas kallikrein. Intestinal absorption of the purified kallikrein was also investigated using a rabbit. After the administration of the purified kallikrein into the intestinal tract, peripheral blood was taken from the ear vein and the plasma was assayed for Pro-Phe-Arg-7-amino-4-methylcoumarinamide hydrolytic activity. The concentration of the kallikrein in the blood was maximal at 3 hr after the administration and the absorption at this time amounted to about 0.07%.
Human chorionic gonadotropin (hCG) is widely used as a tumor specific index substance for the trophoblastic disease. The radioimmunoassay (RIA) of the C-terminal peptide of hCG-beta subunit can detect hCG up to the level of 0.5 IU/day in urine or 0.5mIU/ml in serum without cross-reactivity with luteinizing hormone. Therefore, this RIA would be used as a hCG-specific assay method in order to ensure the disease is in complete remission and to detect early recurrence. Alpha-fetoprotein and lactic dehydrogenase can be used as a sensitive tumor marker for embryonal carcinoma and dysgerminoma respectively. Carcinoembryonic antigen may serve as a valuable aid in monitoring the response to the therapy of the patient with ovarian or cervical carcinoma, but may not be useful for early detection of these diseases.
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We have developed a new platelet function test which is a method to estimate the rate of release of aldolase from platelets into a low osmotic pressured artificial medium and into PRP, which we called the platelet aldolase release rate. As this aldolase release rate have a good reproducibility and correlate well with other platelet function test, this test can be utilized for clinical examination.
With a theca cell tumor of the ovary associated with pregnancy, an extremely rare occurrence in a 30 years old primigravida at 15 weeks of gestation, morphological and endocrinological studies were performed. The tumor was composed of cell-nests scattered among a fibromatous structure. The round or polygonal cells are rich in eosinophilic cytoplasm, resembling theca internal cells. The histochemical activity of 3 beta-HSD and G-6-PDH was demonstrated in these cells. They had the ultrastructures characteristic for steroid-producing cells, in some of which immature and mature Reinke crystalloid-like structures were identified. Mature ones were infrequently observed in contrast to the numerous immature ones. It is considered that a few cells might have differentiated into Leydig cells in the course of differentiation into thecomatous cells from ovarian stroma or mesenchyme. Judged from the rapid enlargement in early pregnancy, this tumor may depend on hCG. Serum estradiol was decreased immediately after removal of the tumor even at 15 weeks of gestation. Histochemical, ultrastructural and endocrinological findings suggest that the tumor was secreting mainly estradiol at the time of the operation.
Mechanism of cytotoxicity of 5-fluorouracil (5-FU) in relation to impairment of RNA metabolism was studied. 5-FU depressed the levels of ribonucleotide reductase and thymidine kinase, which are two key enzymes in DNA synthesis, in solid AH-130 tumor when given intraperitoneally at a dose of 60 mg/kg, and this inhibition seemed to be very toxic against cells. But this dose of 5-FU exceeded the amount that could be degraded by the liver, which was much higher than the clinical dose. We concluded that the impairment of RNA metabolism caused by 5-FU played a minor role in its anti-tumor actions.
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UFT-E, enterogranules of tegafur-uracil (at molar ratio of 1: 4) was developed in order to minimize GI toxicity of UFT. Pharmacokinetic study after single oral administration of 300 to 1200 mg of UFT-E was carried out in cancer patients measuring tagafur, uracil and 5-FU levels in serum, normal tissue and tumor tissue using HPLC and GC-mass. In the all doses studied, curves of serum tegafur after administration of UFT-E were consistently higher than those of uracil and 5-FU. Peak 5-FU levels were observed at 2-4 hours after administration of UFT-E. Maximum 5-FU levels ranged 0.1-3.0 mcg/ml and were variable in each patient even at the same doses. The serum 5-FU level was correlated with tegafur and uracil levels, especially with the latter. The curves of serum 5-FU of UFT-E were different from those of UFT, and the peak time of UFT-E occurred 2 or 3 hours later than that of UFT and the decrease of 5-FU level was slower. The concentrations of 5-FU in tumor tissue (T) were observed in most of the cases compared with those in normal tissue (N) (T/N ratio of more than 2.0 was observed in 16/23 patients), especially in the patients received higher doses of UFT-E and in the patients with GI cancers. In the phase I study of oral daily consecutive administration of UFT-E in 23 cancer patients, the GI side effects such as anorexia, nausea, vomiting and diarrhea, were observed in 5 out of 23 patientsr.(ABSTRACT TRUNCATED AT 250 WORDS)