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Biomedical subjects

K Mikami

Publications and source records attributed to K Mikami.

At least 145 records · Page 8Linked to original sources

Adenylate cyclase activity and cyclic AMP production in the outer and inner zones of the adrenal cortex.

It has been reported that cells isolated from the inner zone of the guinea pig adrenal cortex fail to have a steroidogenic response to ACTH. To further explore this, adenylate cyclase activity of membrane particles and cAMP production by cells prepared from the inner and outer adrenocortical zones were determined. The cAMP response to ACTH and forskolin was similar for cells from both zones. Basal adenylate cyclase activity was significantly higher in the inner zone; and while absolute responses to ACTH, GppNHp, GTP, NaF, and forskolin were greater for the inner zone, relative responses were similar for the two zones. These observations suggest that the inner zone of the guinea pig adrenal cortex may have a defect in ACTH action at a step(s) beyond cAMP formation.

Adenylyl Cyclases↗

Is the initiation of macronuclear DNA synthesis in Euplotes dependent on micronuclear functions?

To determine whether the micronucleus makes essential contributions during asexual reproduction, observations were made on cells of Euplotes octocarinatus from which the micronucleus had been removed with a micropipette. Most cells underwent one postenucleation division, then became arrested in macronuclear G1, slowed down in food uptake, developed macronuclear deformations, and finally died. Such cells could be rescued if a micronucleus was reimplanted before macronuclear deformations had developed. When provided with a new micronucleus, cells initiated macronuclear DNA synthesis about 12-16 h later. The data suggest that the micronucleus is involved in the control of the cell's transition from macronuclear G1 to S, and a model is proposed which postulates that in Euplotes macronuclear DNA synthesis is initiated when a micronucleus-encoded "initiator protein" has accumulated to a critical amount.

Animals↗

Regulation of cholesterol metabolism in rat adrenal glands: effect of adrenocorticotropin, cholesterol, and corticosteroids on acyl-coenzyme A synthetase and cholesterol ester hydrolases.

The regulation of cholesterol metabolism in rat adrenal glands, especially the effect of ACTH, cholesterol, and corticosteroids on acyl-coenzyme A (CoA) synthetase and cholesterol ester hydrolases was investigated. A significant increase in acyl-CoA synthetase activity and decrease in cholesterol ester hydrolase activities were observed in 24-h hypophysectomized rats. Acute injection of ACTH, however, reversed these changes, whereas dexamethasone administration had no effect. When 4-aminopyrazolo[3,4-d]pyrimidine was given to rats, adrenal cholesterol ester content and the acyl-CoA synthetase activity declined and the activities of the cholesterol ester hydrolases were increased in association with the rise of plasma ACTH concentration. When dexamethasone, which suppresses ACTH secretion, was simultaneously administered with 4-aminopyrazolo[3,4-d]pyrimidine no changes except for a decrease in plasma cholesterol level occurred. In hyperlipidemic rats the acyl-CoA synthetase activity increased when a high cholesterol diet was given and the plasma cholesterol level was increased. These results suggest that acyl-CoA synthetase is under the influence of ACTH and also the plasma cholesterol concentration, and that cholesterol ester hydrolases are mainly regulated by ACTH.

Adenine↗

Differential suppression of the outer and inner zones of the adrenal cortex of the guinea pig.

To examine the regulation of the zona fasciculata and the zona reticularis of the guinea pig adrenal cortex, animals were placed on a chronic regimen of dexamethasone. Changes in adrenal zonal weight, cholesterol side-chain cleavage activity, and tissue and serum steroid concentrations were measured after 1 month of dexamethasone administration. With dexamethasone treatment, the weight of the outer zone (glomerulosa/fasciculata) decreased significantly, while the weight of the inner zone (reticularis) did not change. Cholesterol side-chain cleavage activity in mitochondria isolated from the outer zone also declined significantly, while a similar activity in the inner zone did not change. The serum cortisol concentration in response to dexamethasone administration decreased by 85%, as did the concentrations of cortisol and progesterone in the outer zone; the concentration of cortisol in the inner zone decreased by only one third, while the concentration of progesterone did not change. These results in association with previous reports indicate that the zona reticularis of the guinea pig adrenal cortex (in contrast to the zona fasciculata) is not regulated by ACTH in terms of either steroidogenesis or maintenance of cell growth.

Adrenal Cortex↗

[Effects of visual and mental strain on VDT (visual display terminal) performance].

The progression of visual and mental strain in VDT work was investigated through an experimentally-designed VDT task providing a number of stressors including pacing, repetition, judgment and output decisions. We measured the effects of CFF (critical fusion frequency), TAF (the ability to maintain concentration), EEG (electroencephalogram) and near-point accommodation of various changes in the duration of the testing period. The subjects were seven male university students who performed single multiplication problems at a rate of 60 per minute. The problems were presented to them on a CRT screen and on paper for periods of 90 min each. The results obtained were as follows; CFF values and near-point accommodation of VDT performance were significantly decreased compared to Non-VDT's as a control. The TAF test showed that the mental strain in a VDT task is greater than that in a Non-VDT task. CFF values of VDT performance showed a tendency to decline in the 30th min after commencement, but in the 60th min and thereafter a significant lowering was noticed. In TAF and near-point accommodation of VDT performance, the greatest decline was in the 60th min, and this was significantly reduced only immediately after the work period. CFF values and near-point accommodation were not recovered after 60 min from the end of a 90 min VDT task. However, TAF X L values recovered in the 30th min after VDT performance. The peak level of alpha waves from the parietal region moved toward the slow alpha band with the elapse of VDT task time, but returned [or reverted] to the initial state 30 min after the test period ended.

Accommodation, Ocular↗

[Reconstruction of the large scalp defect by free flap transplantation].

The reconstruction of a large scalp defect is extremely difficult on many occasions and repeated operations or a long-term hospitalization is often required. In addition, unsatisfactory results are not unusual. However, it is now possible to perform reconstruction by a one-stage operation of free tissue transplantation (free flap) using microsurgical vascular anastomosis which has rapidly developed in the past ten years. We performed reconstructions applying latissimus dorsi musculocutaneous, greater omentum, groin and scapular flaps. The advantages with the free flap are: (1) one-stage reconstruction is possible; (2) no restrictions on the postoperative position, (3) the flap, which is independent of the blood supply from the recipient, well survives on the recipient with an insufficient blood supply and (4) the damage at the donor site can be minimized. On the other hand, its disadvantages are as follows: (1) the operation requires microsurgical vascular anastomoses; and (2) recipient vessels should be normal. The above report was based on favorable results we obtained in 6 cases of reconstruction with free flap applying microvascular techniques.

Aged↗

Microsurgical analysis of the clonal age and the cell-cycle stage required for the onset of autogamy in Paramecium tetraurelia.

When autogamy was induced in competent cells of Paramecium tetraurelia by depriving them of food, the onset of autogamy was preceded by a critical fission which occurred in the starvation medium. When the cells were fed again immediately after the fission, they did not undergo autogamy. However, they did undergo autogamy when they were fed later than 1 hr after the critical fission. The irreversible differentiation for autogamy seems to be at about 1 hr after the critical fission. This procedure thus provides the opportunity to induce autogamy synchronously. The result of macronuclear transplantation demonstrated that autogamy was under the control of macronucleus. Moreover, the clonal age required for autogamy was found to be shortened by repetitive elimination of a part of the macronucleus. The result can be explained by the hypothesis that clonal age is measured in rounds of chromosome replication or DNA synthesis rather than cell divisions.

Animals↗

Nuclear differentiation in Paramecium tetraurelia. Transplantation of vegetative micronuclei into early exconjugants.

The micronucleus of Paramecium tetraurelia normally gives rise to the macronucleus by going through the series of nuclear events of meiosis, mitosis and fusion during sexual reproduction. By transplanting the micronucleus from vegetative cells into early exconjugants, we have persuaded the micronucleus to take a short cut to differentiate directly into a macronucleus. This demonstrates that the course of development of the micronucleus is flexible and can be altered by stage-specific cytoplasmic factors.

Animals↗

Promotion of hepatocarcinogenesis in vivo and in vitro.

Various chemicals including phenobarbital (PB) have been shown to act as promoters in hepatocarcinogenesis in rodents. The effect of initiation and/or promotion of chemicals can be quantitatively measured by scoring the number and size of enzyme-altered islands (EAI). The effect of promotion is proportional to the period of treatment and is much greater when the promoter is given earlier after initiation. A unique aspect of hepatic promoters is their inhibitory action against carcinogenesis when given simultaneously with a carcinogen, reducing both the initiating and promoting activities of the carcinogen. With the aid of the promoting action of PB, carcinogenic activity of pure initiators is demonstrated. Promoting effect of PB was found at as low a dose as 5 ppm, which corresponds to 20 mg per 50 kg person per day, a dose several times less than the common therapeutic dose. In an attempt to analyze the mechanism of promotion and also to develop a model system for detecting environmental promoters in vitro, hepatic cells obtained from animals during carcinogenic treatment were transferred to a culture system. Cells comprising EAI after a certain critical stage gave rise to proliferative epithelial cell foci. Some hepatic promoters showed a growth enhancing effect on these foci while others did not, suggesting both the existence of direct action by some promoters on initiated cells and the presence of different promoter mechanisms. Chronic treatment with PB selectively induced gamma-glutamyl transpeptidase activity in "spontaneous" hepatomas of C3H mice, suggesting that PB may enhance the expression of altered gene functions of initiated cells.

Animals↗

[Case of histiocytosis X with a large intracranial mass].

The authors experienced a case of histiocytosis X with a large intracranial mass resulting in a convulsive seizure. The patient showed left exophthalmos and a skin rash one year and two months after birth. Histiocytosis X was diagnosed from a skin biopsy, and predonine, endoxan and vincristine were administered. The rash disappeared, but the exophthalmos remained. At the age of two years and nine months, punched-out lesions appeared in the skull and 4,000 rads of radiation was applied. Thereafter, the exopthalmos persisted but there was no particular problem in the course. However, a convulsive seizure with fever suddenly appeared at nine years and ten months of age and the patient was hospitalized. At the time of admission, the general condition was good and there were no abnormalities in neurological tests. In neuroradiological examinations, a calcified and poorly vascularized mass 8 cm in maximum diameter was found to occupy the left middle cranial fossa. Chondrosarcoma was strongly suspected from these findings, but there was also symmetrical thickening of bone cortex in the peripheries of the long bones of the extremeties which appeared to be the recovery process from bone destruction caused by histiocytosis X. Therefore, the formation of an intracranial mass by histiocytosis X was diagnosed and surgery was performed. When left osteoplastic fronto-temporal craniotomy was performed, the mass was found to be raising the temporal lobe and it could be easily separated from the surrounding tissue. However, these was firm adherence to dura mater of the middle cranial fossa (especially that of the superior orbital fissure). Histologically, there were many cells with small nuclei, no polymorphism, abundant and clear cytoplasm which were darkly stained and slightly atypic. These findings matched those for histiocytosis X. Cases of histiocytosis X rarely show symptoms of the central nervous system or infiltration of the central nervous system. Only 31 such cases were seen in the literature investigated by the authors. Neurological symptoms include pyramidal symptoms such as hemiparesis and impairment of the cranial nerves, particularly paresis of the optic, trigeminal, facial and acoustic nerves. Convulsive seizures were seen in only five cases including the one reported here. It is also rare for intracranial masses to be formed in cases of histiocytosis X and only six cases, including the authors', have been found with masses of a maximum diameter of more than 5 cm.

Brain Diseases↗

Nuclear transplant studies on the reduction in numbers of presumptive germ nuclei in exconjugants of Paramecium caudatum.

Nuclear differentiation in exconjugants of Paramecium caudatum is closely associated with a brief localization of the postzygotic nuclei near the opposite ends of the cell, with the germinal nucleus (micronucleus) in the anterior region and the somatic nuclei (macronuclei) in the posterior region. The posterior nuclei cannot regenerate to produce micronuclei when all four anterior nuclei are removed. There is no difference among the anterior four presumptive micronuclei, because, when any three of them were removed, the remaining nucleus was able to divide at each postconjugational fission and to persist as a micronucleus during the vegetative phase. This conclusion agrees with the results of transplanting a presumptive micronucleus into a vegetative cell. Cells during the vegetative phase, however, normally have only one micronucleus. Micronuclear number must be reduced to arrive at the uni-micronucleate condition after the stage of macro- and micronuclear differentiation. Elimination of supernumerary presumptive micronuclei, which had been indicated by morphological observations, was confirmed by the results of nuclear transplantation studies.

Animals↗

[Comparative studies of urinary electrolyte excretion, the renin-angiotensin-aldosterone system and plasma dopamine-beta-hydroxylase activity in patients with idiopathic edema and normal subjects during the menstrual cycle (author's transl)].

The changes of circumferential size of legs, urine output, the amount of urinary Na and K excretion, tubular rejection fraction of Na (TRF Na), urinary Na/K ratio, plasma renin activity (PRA), plasma aldosterone concentration (PAC), the amount of urinary aldosterone excretion (UAE) and plasma dopamine-beta-hydroxylase activity (DBH) were studied in 7 patients with idiopathic edema and 5 normal subjects from the recumbent to upright positions by a water loading test (oral ingestion of 1 L of water) in the follicular and luteal phase of the menstrual cycle. The increase in circumferential size of legs in the patients with idiopathic edema was greater than in normal subjects. The percent reduction in urine output, urinary Na excretion, TRF Na and urinary Na/K ratio (upright versus supine) in patients with idiopathic edema tended to be greater than that in normal subjects. However, these indices showed no significant differences between the follicular and luteal phase both in patients with idiopathic edema and normal subjects. PRA and PAC, on the subjects' being tilted to the upright position after water loading, were not significantly different between patients with idiopathic edema and normal subjects during the menstrual cycle, while increases in PAC and UAE were noted in patients with idiopathic edema in the upright position, especially in the follicular phase. Interestingly, plasma DBH activity in patients with idiopathic edema was significantly lower than that in normal subjects in both the follicular and luteal phases. These results indicate that posturally induced anti-diuresis and anti-natriuresis seems not to be related to the phase of the menstrual cycle, and abnormal mechanisms of the dopaminergic autonomic nervous system might exist in this disorder.

Adult↗

Studies on cholesterol esterase in the rat adrenal.

We have investigated the characteristics and properties of cholesterol esterase (CEase) in the rat adrenal to clarify the mechanism of synthesis of free cholesterol from esterified cholesterol. CEase activity was estimated using substrate vesicles which were sonicated mixtures of cholesteryl oleate and phosphatidylcholine (PC). CEase showed two optima at around pH 4.5 and pH 8.25. The acid CEase was found mainly in the lysosomal fraction, and the alkaline CEase was found mainly in the microsomal fraction. Both acid and alkaline CEase activities were markedly enhanced by increasing the concentration of PC, but not by phospholipids. The activities were not increased by the addition of cAMP, ATP, and MgCl2, when the molar ratio of cholesteryl oleate to PC was 1:0.2, but were increased when the molar ratio was 1:2. Thus, it is suggested that free cholesterol for steroidogenesis may be supplied by two different organelles (lysosome and microsome), and that the composition of the substrate complex, such as the ratio of esterified cholesterol to phospholipids, may play a crucial role in the regulation of adrenal CEase. Increases in both acid and alkaline CEase activities were observed in adrenal homogenates prepared from hypophysectomized rats treated with an iv injection of ACTH when the molar ratio of cholesteryl oleate to PC used as a substrate vesicle was 1:0.2, but not when the ratio was 1:2. Therefore, the present observation indicate that activation of CEase by ACTH is dependent on the substrate state, especially that of the cholesterol ester droplet in vivo.

Adrenal Glands↗

Inter-relationship of sympathetic nervous system and renin-angiotensin-aldosterone system in three renin subgroups of borderline and persistent essential hypertension.

Plasma renin activity (PRA), dopamine beta-hydroxylase (DBH) activity, and plasma aldosterone concentration were determined in 51 patients categorized as borderline or persistent hypertensives and as high, normal, or low renin. Basal DBH activity correlated with diastolic blood pressure in borderline but not in persistent hypertensives. In borderline patients with normal or high renin activity standing plus furosemide caused a marked rise in diastolic blood pressure but little change in systolic and increased PRA and DBA. In contrast this stimulation procedure depressed both systolic and diastolic blood pressure and resulted in blunted PRA and DBH responses in the low renin borderline and the three groups of persistent hypertensives. After dietary sodium restriction, the decrease in systolic blood pressure correlated with the decrease in urinary sodium excretion in persistent, but not in the borderline patients. The data suggest that both borderline an persistent hypertensive patients respond to volume depletion with an increase in sympathetic and renin activity, and the increase of these two vasoconstrictive systems is greater in borderline hypertensives.

Adult↗