These results suggest that lower dose levels of cinacalcet, as compared to those in US/EU studies, may be sufficient effectively suppress the serum iPTH levels and allow favourable management of the serum calcium and phosphorus levels in Japanese patients, having a longer average dialysis vintage.

Specific binding of leukemia-inhibitory factor (LIF) to osteoblasts, but not multinucleated osteoclasts, was demonstrated by receptor autoradiography by using cells isolated from newborn rat long bones. The clonal rat osteogenic sarcoma cells, UMR 106-06, which have several phenotypic properties of osteoblasts, expressed 300 LIF receptors per cell, with an apparent KD of 60 pM. Treatment of calvarial osteoblasts or UMR 106-01 cells with LIF resulted in a dose-dependent inhibition of plasminogen activator (PA) activity. Both calvarial osteoblasts and osteogenic sarcoma cells were shown by Western blotting and reverse fibrin autography to produce plasminogen activator inhibitor-1 (PAI-1), the production of which was increased by LIF treatment. Northern blot analysis revealed that LIF treatment resulted in a rapid (peak 1 hour), dose-dependent increase in mRNA for PAI-1. LIF treatment of the preosteoblast cell line, UMR 201, enhanced the alkaline phosphatase response of these cells to retinoic acid. Each of the osteoblast-like cell types (calvarial osteoblasts, UMR 106-06, and UMR 201) was shown to produce LIF by bioassay and, by using the polymerase chain reaction (PCR), was shown to express low levels of mRNA for LIF. These data establish that cells of the osteoblast lineage are targets for LIF action. The reported anabolic effects of this cytokine on bone formation in vivo could be related to inhibition of protease activity. LIF may be an important paracrine modulator in bone, or perhaps an autocrine one, based on the evidence for its production by osteoblasts and osteoblast-like cells.

Superior results in efficacy rate, remission period and risk of relapse are obtained when PEIT is restricted to patients with one hyperplastic gland > or =0.5 cm(3).

A new portable device for the indirect measurement of ambulatory blood pressure in the finger was successfully applied to normotensive and hypertensive subjects in and outside a ward setting. The device uses the volume-oscillometric technique and, equipped with a microprocessor, permits long-term ambulatory monitoring of indirect systolic and mean blood pressure at desired intervals (once every 1-10 min). Systolic and mean blood pressures obtained by this method were well correlated with those measured by the direct (Oxford) and arm-cuff methods. Systolic and diastolic blood pressure obtained by the volume-oscillometric device were almost identical with those recorded by an arm-cuff. Systolic blood pressure obtained by the volume oscillometric method was, however, significantly lower than that measured by the direct method. The new device has also been used to measure blood pressure during treadmill exercise and ice-water immersion. Mean values of blood pressure and the SD of these averaged for 24 hours, or for every hour, were reproducible when the measurements were repeated under the same condition. The present device is portable, causes minimal noise, can detect rapid change in blood pressure and causes less discomfort when compared to the conventional arm-cuff method. Regular measurements can be made with minimal sleep disturbance. This fully automatic volume-oscillometric device allows reliable 24-hour monitoring of ambulatory blood pressure not only in but also outside a ward setting, and as such is useful for studies of hypertension.

CRH, GH-releasing hormone (GHRH), somatostatin (SRIH), and peptide histidine methionine (PHM) were measured by RIA in extracts of normal adrenal glands and in extracts from adrenal and extraadrenal pheochromocytomas. In normal adrenal glands, immunoreactive (IR) CRH, IR-SRIH, and IR-PHM were detectable, while IR-GHRH was undetectable. In all 11 cases of adrenal pheochromocytomas, the tumors contained 2 or more of these four IR-peptides. In particular, IR-CRH was found in 73% (n = 8) of adrenal pheochromocytomas, IR-GHRH in 91% (n = 10), IR-SRIH in 91% (n = 10), and IR-PHM in 82% (n = 9) of adrenal pheochromocytomas. There was no significant correlation among the concentration of these peptides in each tumor, i.e. the concentrations of the IR-peptides were independent of each other. In contrast to the adrenal pheochromocytomas, none of these 4 IR-peptides was detectable in 5 extraadrenal pheochromocytomas. Gel filtration of pooled extracts from adrenal pheochromocytomas showed that the major component of the IR-CRH, IR-GHRH, IR-SRIH, and IR-PHM eluted in the position of their synthetic counterparts. Our results suggest that 1) the normal adrenal gland contains IR-CRH, IR-SRIH, and IR-PHM, but not IR-GHRH; 2) all of the adrenal pheochromocytomas we examined contained a number of hypothalamic releasing or inhibiting hormones; 3) their tissue concentrations were independent of each other; and 4) all of the extraadrenal pheochromocytomas we examined contained no such IR-peptides. The presence of hypothalamic hormones in adrenal pheochromocytomas and their absence in extraadrenal pheochromocytomas may be due to the differences in the chromaffin cells of their origin. Our data may be helpful in the differential diagnosis between adrenal and extraadrenal pheochromocytomas.

The cardiovascular effects of centrally administered cholinomimetics were examined in conscious Long-Evans and Brattleboro rats. Carbachol (1 ^tg/kg) or physostigmine (50 /ug/kg) induced a long-lasting increase in blood pressure and a decrease in heart rate in Long-Evans rats whereas no bradycardia was observed in Brattleboro rats, and the pressor response was significantly less than that in Long-Evans rats. The cardiovascular responses to nicotine (30 jtg/ kg) in Brattleboro rats were not different from those in Long-Evans rats. Intravenous vasopressin antagonist, dfCH^jTyrCMe) arginine vasopressin, significantly attenuated the pressor response and eliminated the bradycardic response to carbachol hi Long-Evans rats. However, the pressor response to carbachol in Brattleboro rats was still significantly less than that in Long-Evans rats treated with vasopressin antagonist. Intravenous phentolamine partially inhibited the pressor response to carbachol in Long-Evans rats and completely eliminated it in Brattleboro rats. Combined intravenous treatment with phentolamine and vasopressin antagonist completely eliminated the pressor response to carbachol in Long-Evans rats. Centrally administered methylatropine eliminated either the hypertensive or bradycardic response to carbachol in Long-Evans rats. These results indicate that the pressor and bradycardic response to carbachol or physostigmine is mediated by the central muscarinic receptor mechanism. Hypertensive response to intracerebroventriculaiiy administered carbachol in normal rats is mediated both by an increase in central sympathetic outflow and in circulating vasopressin. The bradycardia seems to be mediated mainly by vasopressin. {Hypertension 1989;13:549-557)

Plasminogen activator (PA) was located in newborn rat osteoclasts using a single-cell assay. Immunohistochemistry using biotin-streptavidin-peroxidase indicated the presence of both tissue-type plasminogen activator (tPA) and urokinase (uPA) within the cytoplasm of osteoclasts isolated from newborn rat long bones. Electron microscopic immunohistochemistry using the biotin-streptavidin-colloidal gold system on L.R. Gold thin resin sections of undecalcified, newborn rat tibial metaphyseal trabecular bone identified these proteases in the lysosomal network of osteoclasts. uPA was also localized in marrow macrophage lysosomes, but tPA was not detected in these cells. The localization of these enzymes within osteoclasts may imply their involvement in bone resorption.

One hundred and ninety-five outpatients in pre-dialysis period served as subjects. The mean age of subjects was 58.0 +/- 11.2 (range: 29-82) years. The subjects were divided into 8 groups according to their serum creatinine (Cr) levels (Cr < or = 1.0, 1.0 < Cr < or = 2.0, 2.0 < Cr < or = 3.0, 3.0 < Cr < or = 4.0, 4.0 < Cr < or = 5.0, 5.0 < Cr < or = 6.0, 6.0 < Cr < or = 8.0, and Cr > 8.0 mg/100 ml). The level of 1,25-dihydroxyvitamin D (1,25(OH)2D) decreased in accordance with the progression of chronic renal failure (CRF). Even in subjects with 1.0 < Cr < or = 2.0 mg/100 ml, the levels of 1,25(OH)2D were significantly lower than those in subjects with Cr < or = 1.0 mg/100 ml. The levels of calcium adjusted by serum albumin levels (adjusted Ca) were relatively maintained within the normal range until Cr > 8.0 mg/100 ml. The levels of inorganic phosphate (IP) were significantly lower in subjects with 1.0 < Cr < or = 2.0 mg/100 ml, but significantly higher in subjects with Cr > 4.0 mg/100 ml than those in subjects with Cr < or = 1.0 mg/100 ml. The levels of immunoreactive high-sensitive parathyroid hormone (HS-PTH) were greatly increased and the levels of intact PTH were significantly increased even in subjects with 1.0 < Cr < or = 2.0 mg/100 ml, in association with a decrease in levels of 1,25(OH)2D suggesting that a decline in 1,25(OH)2D production due to a decrease in renal mass contributes to the acceleration of secondary hyperparathyroidism. When the levels of adjusted Ca, intact PTH and 1,25(OH)2D of subjects with hypophosphatemia (IP < 2.8 mg/100 ml), normophosphatemia and hyperphosphatemia (IP > 4.4 mg/100 ml) were compared, there were not any significant differences in the levels of adjusted Ca among these subjects in each group. But, the levels of 1,25(OH)2D in subjects with hypophosphatemia were significantly higher than those with normophosphatemia in groups with Cr < or = 2.0 mg/100 ml, and those with hyperphosphatemia were significantly lower than those with normophosphatemia in groups with 3.0 < Cr < or = 4.0, 5.0 < Cr < or = 6.0 and Cr > 8.0 mg/100 ml. These results suggest that increased secretion of PTH might compensate the decreased production of 1,25(OH)2D3 by lowering phosphate in the early phase of CRF, and phosphate retention inhibits the activity of 1 alpha-hydroxylase and contributes to the decrease in 1,25(OH)2D3 in the advanced stage of CRF. Monitoring of 1,25(OH)2D is considered to be vitally important for diagnosing the 1,25(OH)2D3 deficiency in CRF.