[Diagnosis of hormone-secreting pituitary tumors].
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Biomedical subjects
Publications and source records attributed to T Suda.
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1 alpha,25-Dihydroxyvitamin D3, a hormonally active form of vitamin D3, enhanced methylcholanthrene-induced transformation in BALB 3T3 cells to a much greater extent than 12-O-tetradecanoylphorbol-13-acetate. This enhancement was probably mediated by a cytosol receptor for 1 alpha,25-dihydroxyvitamin D3 which has an equilibrium constant of 28.4pM and a maximum binding of 32.6 fmol/mg protein.
The radiation sensitivity of leukemic progenitor cells in 12 cases of acute nonlymphocytic leukemia was compared with that of normal myeloid progenitor cells (colony-forming units in culture), using in vitro cloning techniques. The D0 value for normal colony-forming units in culture was almost constant (130 +/- 14 rads). On the other hand, marked patient-to-patient variations were observed in the radiosensitivity of leukemic progenitor cells; namely, the D0 values in the present cases ranged from 30 to 210 rads. These variations seemed to be partly due to different cell cycle status and partly due to the intrinsic nature of leukemic progenitor cells. Moreover, in six of seven clinically drug-sensitive cases, the leukemic progenitor cells were proved to be relatively radiosensitive. Similar to in vitro drug sensitivity tests, this test may serve to predict the clinical response to chemoradiotherapy.
The sequence of the appearance of fibronectin in the rabbit cornea after thermal burn was investigated by indirect immunofluorescent microscopy. One day after thermal burn, the keratocytes disappeared completely from the burned area, and faint fibronectin-specific fluorescence was detected beneath the epithelium and on the stromal side of the Descemet's membrane. On day 3, activated keratocytes began to migrate to the burned lesion. Fibronectin was detected in the burned area as well as in the surrounding uninjured area, and on both sides of the Descemet's membrane. One week after the burn, the keratocytes had increased in the lesion and, concomitantly, fibronectin-specific fluorescence could be observed at the locations corresponding to the keratocytes. Fibronectin in the surrounding area gradually diminished. After 4 weeks, activated keratocytes had accumulated in the lesion, and fibronectin was detected only in the central lesion and at the level of the Descemet's membrane. Thus the appearance of fibronectin was concordant with the appearance of the keratocytes, and this suggests that fibronectin may be involved in the wound-healing of thermally burned rabbit corneas.
Using a specular microscope and a pachymeter, we monitored endothelial cell patterns and central corneal thickness in 16 cases of clear graft with different postoperative courses for over 2 years after successful penetrating keratoplasty. With the use of a computerized digitizer, the graft endothelium was analyzed to determine the mean cell size, standard deviation of cell sizes and the coefficient of variation in cell size. In all cases, a progressive increase in the mean and standard deviation of cell sizes was noted throughout the period of observation. The coefficient of variation, however, stayed fairly constant in each case. This indicates that the increase in the standard deviation of cell sizes is dependent on the increase in the mean cell size. Five cases with good postoperative course showed gradual alterations in cellular morphology. On the other hand, the endothelium of 5 cases with surgical intervention after keratoplasty changed its morphology greatly until the corneal thickness approximated normal, and then the alterations continued to take place gradually. In 6 cases, a remarkable and rapid increase in the mean and standard deviation of cell sizes occurred during the rejection process. These parameters continued to increase gradually after the graft became transparent as the result of intensive corticosteroid therapy. These results suggest that the graft endothelium is still in a transitional state during healing even 2 years after keratoplasty, and that the morphologic parameters determined during the early postoperative period reflect the actual cell damage owing to surgical procedures to some extent but not exactly.
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During collaborative studies on regulation of differentiation and neoplastic transformation, similarities and dissimilarities were found between the actions of phorbol ester tumor promoters and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3), an active form of vitamin D3. Like 12-O-tetradecanoylphorbol-13-acetate (TPA), 1 alpha,25(OH)2D3 stimulates terminal differentiation of M1 and HL-60 myeloid leukemia cells and epidermal keratinocytes, blocks dimethylsulfoxide-induced differentiation of Friend erythroleukemia cells, and enhances chemically induced transformation of BALB 3T3 cells. Unlike TPA, 1 alpha,25(OH)2D3 does not induce ornithine decarboxylase in mouse skin, but inhibits induction of this enzyme by TPA. These actions are all specific for 1 alpha,25(OH)2D3: at least 100 times higher doses of other derivatives of vitamin D3 are required for the same biological effects. A specific cytosol receptor for 1 alpha,25(OH)2D3 was found in these cells, suggesting that this compound has a receptor mediated action. These findings suggest that 1 alpha,25(OH)2D3 may be a natural modulator of growth and differentiation of cells and of promotion of tumor formation.
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In order to clarify the regulation of granulopoiesis by hydrocortisone in humans, we investigated the effect of glucocorticoids on the formation of granulocyte and/ or macrophage colonies. By means of the dual esterase staining techniques applied to whole mount preparations of agar culture dishes, we examined the granulocyte-macrophage colony type. It was revealed that hydrocortisone stimulated the formation of neutrophil-containing colonies and inhibited macrophage colony formation. There was a significant increase in neutrophil colonies when the cells were preincubated with hydrocortisone for only 24 h. Delayed addition of hydrocortisone to the cultures was less effective in increasing the proportion of neutrophil colonies than addition at the beginning of culture. Moreover, addition of hydrocortisone to T-lymphocyte- and phagocyte-depleted bone marrow cells also increased the number of neutrophil colonies and decreased macrophage colonies in the presence of CSF. These results suggest that hydrocortisone may affect granulocyte-macrophage precursors (CFUGM) in an early period of their differentiation.
Murine bone marrow granulocyte/macrophage progenitor cells proliferated to form colonies consisting of their progeny in serum-free agar cultures in the presence of colony-stimulating activity. The cloning efficiency for the serum-free cultures was 80% of that for control cultures containing 20% fetal calf serum. Examinations of the cellular compositions of individual colonies revealed that the number of pure macrophage colonies was indistinguishable in the two culture systems while that of pure granulocyte and granulocyte/macrophage mixed colonies was smaller in the serum-free cultures.
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The effect of graded nephron mass reduction by partial nephrectomy and the influence of parathyroid hormone and dietary phosphorus (P) on the production of 1,25-dihydroxy-vitamin D [1,25(OH)2D] were studied in vitamin D deficient rats. At 48 hours (acute experiments) or 2 weeks (chronic experiment) after partial nephrectomy, the rates of [3H]1,25(OH)2D production from [3H]25 hydroxyvitamin D (25-OHD) were measured in vivo. The production of 1,25(OH)2D decreased in proportion to the remaining nephron mass, and it was not greater in chronic experiments than in acute experiments at any level of nephron mass reduction. By contrast, plasma creatinine was elevated in 5 of 6 nephrectomized rats in acute, but not in chronic, experiments, suggesting the compensatory mechanism for renal excretory function but not for 1,25(OH)2D production. Further, at any level of nephron mass reduction, the production of this active metabolite was not greater in rats fed low P diet than those fed normal or high P diets. Thyroparathyroidectomy at 12 hours prior to a dose of [3H]-25)OHD suppressed 1,25(OH)2D production at any level of nephron mass reduction in rats fed normal or high P diet. These data suggest that in both experimental acute and chronic renal failure 1,25(OH)2D production is proportional to residual nephron mass and that parathyroid hormone may enhance the metabolism of 25OHD in renal failure and also may be critical for 1,25(OH)2D in normal or high P diet.
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Multiple forms of immunoreactive dynorphin (I-dynorphin) in rat anterior pituitary (AP), intermediate-posterior pituitary (IP) and medial basal hypothalamus (MBH) were examined. Three I-dynorphin peaks were observed on gel filtration. The first peak (big form) was eluted near the position of beta-LPH, and was predominant in AP. The second peak (middle form) was eluted near the position of ACTH. The third peak (small form) was eluted at the position of dynorphin (1-13), ane was predominant in IP and MBH. The heterogeneity of this small form was examined by ion exchange chromatography and reverse phase high performance liquified chromatography (HPLC). I-dynorphin peaks were observed at the positions of dynorphin(1-17), (1-13), (1-11), (1-10) and other peptides. These results strongly suggest (i) the presence of dynorphin(1-17), (1-13), (1-11) and (1-10) in rat IP, (ii) dynorphin(1-11) and (1-10) as the major components in this small form, (iii) the difference of I-dynorphin processing in AP, IP and MBH.