Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing compound containing saccharide radical
Patent
1990-11-21
1993-03-09
Rosen, Sam
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing compound containing saccharide radical
435 792, 435 7021, 43524026, 424 858, 436518, 436548, 530806, 530800, 530300, C12Q 100, C07K 1500
Patent
active
051926644
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to a previously unidentified circulating factor having its origin in the parathyroid gland. This factor is related to control of cellular calcium uptake, and is particularly related to hypertension and some other diseases in mammals. The circulating factor has been isolated, and methods for screening patients for the presence of the circulating factor are described. The factor is useful in the assessment of patients with diseases which involve intracellular calcium elevation and in the study of other diseases in which calcium is involved. The presence of this factor in patients indicates novel therapeutic treatments.
BACKGROUND OF THE INVENTION
Hypertension is generally defined as the elevation of the systolic and/or diastolic arterial blood pressure above a nominal value of 140/90 mm Hg. Diseases associated with hypertension include arteriosclerosis, hypertensive renal failure, stroke, congestive heart failure and myocardial infarction. Although numerous methods of treatment have been found to be effective in the reduction of arterial blood pressure, the etiology of essential hypertension remains essentially unknown. A genetic predisposition to hypertension is generally accepted, but the number of different drugs which have been found effective in the treatment of hypertension, and the fact that these drugs seem to operate by eliciting different pharmacological responses, suggests that there may be different primary causes for essential hypertension.
A number of studies have suggested that one or more circulating factors may play a role in the genesis or the maintenance of hypertension [See: Wright et al., A Hypertensive Substance Found in the Blood of Spontaneously Hypertensive Rats; Life Sci. 1984; 34:1521-1528; Dahl et al., Humoral Transmission of Hypertension: Evidence from Parabiosis; Circ. Res. 1969; 24/25 (Suppl. I):21-23; Greenberg et al., Evidence for Circulating Factors as a Cause of Venous Hypertrophy in Spontaneously Hypertensive Rats; Am. J. Physiol. 1981; 241:H421-H430; Tobian et al., A Circulating Humoral Pressor Agent in Dahl S Rats with Salt Hypertension; Clin. Sci. 1979; 57:345s-347s; Zidek et al., Humoral Factors in the Pathogenesis of Primary Hypertension; Klin. Wochenschr. 1985; 63 (Suppl. II) D:94-96; Hirata et al., Hypertension Producing Factor in the Serum of Hypertensive Dahl Salt-Sensitive Rats; Hypertension 1984; 6:709-716]. For example, in parabiosis and cross-circulation experiments, an increase in blood pressure could be induced in normotensive animals by exposure to blood from hypertensive animals. The subcutaneous injection of erythrocyte-associated factor obtained from spontaneously hypersensitive rats (SHR) has been shown to induce hypertension in normotensive Wistar-Kyoto (WKY) rats and an increase in blood pressure can be induced in normotensive, salt sensitive Dahl rats by injection of serum from hypertensive, salt-sensitive Dahl rats.
There have also been reports of circulating factors in both hypertensive rats and hypertensive humans which increase intracellular calcium [See: Banos et al., Two Factors Associated with Increased Uptake of Calcium in Platelets from Essential Hypertensive Patients; Clin. Exp. Hypertens. 1987; 9:1515-1530; Zidek et al., Effect of Plasma from Hypertensive Subjects on Ca Transport in Permeabilized Human Neutrophils; Clin. Sci. 1988; 74:53-56; Linder et al., Effects of a Circulating Factor in Patients with Essential Hypertension on Intracellular Free Calcium in Normal Platelets; N. Enc. J. Med. 1987; 316:509-513; Bruschi et al., Cytoplasmic Free Ca is Increased in the Platelets of Spontaneously Hypertensive Rats and Essential Hypertensive Patients; Clin. Sci. 1985; 68:179-184; Wright et al., Stimulation of Aortic Tissue Calcium Uptake by an Extract of Spontaneously Hypertensive Rat Erythrocytes Possessing Hypertensive Properties; Can. J. Physiol. Pharmacol. 1986; 64:1515-1520]. Since vascular tone is influenced by the level of intracellular calcium, it would seem reasonable to assume--althoug
REFERENCES:
patent: 4250084 (1981-02-01), Trainin et al.
Wright et al. "The Vascular Seweitizing Character of Plasma from Spontaneously Hypersensitive Roots" Cand. J. Physiol. Pharmacol. 59:1111-1116 1981.
Yoshimi et al. "A Novel Human Plasma Factor Capable of Mobilizing Intracellular Ca.sup.+2 in Cultured Rat Vascular Smooth Muscle Cells" Biochem. & Biophys. Rsch Comm. vol. 153, No. 3, 1988 pp. 1068-1075.
Maurea et al. Methods in Enzymology, vol. 70 p. 49-70 Academic Press, N.Y. N.Y. 1980.
Lehringer et al. Biochemistry pp. 157-161, Worth Pub. N.Y. N.Y. 1970.
Roitsch et al. Immunological Methods vol. III, pp. 86-87 Academic Press, N.Y. N.Y. 1985.
Prave et al Fundamentals of Biotechnology pp. 280-289 & 482-491 VCH Pub. Weinheim, Germany 1987.
Benishin Christine G.
Kaneko Toyoii
Lewanczuk Richard Z.
Pang Peter K. T.
Pang Peter K. T.
Rosen Sam
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