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Biomedical subjects

K E Kim

Publications and source records attributed to K E Kim.

At least 55 records · Page 3Linked to original sources
PubMed1988

Functional analysis of the interaction of a tissue-specific factor with an upstream enhancer element of the rat prolactin gene.

A nuclear factor which binds to an upstream element of the rat PRL gene has been identified and the functional properties of the factor-DNA interaction have been assessed by mutagenesis of the factor binding sites. Gel mobility shift assays have been used to identify a factor which binds to a fragment from the -1712 to -1494 region of the rat PRL gene. The DNA binding factor is present in nuclear extracts from PRL-producing GH3 cells, but not in nuclear extracts from several other cell lines. Although previous studies have shown that the estrogen receptor binds to this region of DNA, chromatography on heparin-agarose demonstrated that the factor detected by mobility shift assay is probably not the estrogen receptor. Nuclease protection experiments demonstrate that the factor binds to a discrete region at positions -1666 to -1652. The protected region includes half of a palindrome, TCATTAT ... ATAATGA. Mutagenesis by T to G transversions of either both halves of this symmetrical sequence, or only the upstream portion shown to interact with the factor substantially reduced factor binding as assessed by gel mobility shift assay. Transfer of fusion genes containing this region of DNA into GH3 cells demonstrated that the -1712 to -1494 region has a basal enhancer activity which is reduced severalfold by T to G mutagenesis of the complete dyad symmetry at positions -1665 to -1644. The results suggest that the -1712 to -1494 region of the rat PRL gene contains two relatively independent elements. One element, located at positions -1582 to -1569, interacts with the estrogen receptor and mediates estrogenic stimulation of transcription.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Divergent changes in the concentrations of gonadotropin beta-subunit messenger ribonucleic acid during the estrous cycle of sheep.

Cyclic changes in the production of the pituitary gonadotrophic hormones, LH and FSH are essential events in the maintenance of the reproductive system of female mammals. While studies have examined changes in the secretion of LH and FSH during the estrous cycle and demonstrated the importance of these hormones in regulation of ovarian development and gametogenesis, considerably less is known concerning the regulation of the biosynthesis of these hormones. Although initial studies have examined changes in LH subunit mRNA concentrations during the rat and ovine estrous cycles, no information concerning the physiological regulation of FSH beta mRNA concentrations has been available. In the present study we have examined the relationship between pituitary concentrations of LH and FSH subunit mRNAs and the serum concentrations of these gonadotropins. The results demonstrate a very different pattern of change for FSH beta subunit mRNA than that observed for alpha and LH beta subunit mRNAs. In fact, FSH beta mRNA concentration decline substantially during the preovulatory period, reaching minimal values at a time when alpha and LH beta mRNA levels are near maximal. Furthermore, this decline in FSH beta mRNA amounts occurs when serum FSH concentrations are maximal. Thus, FSH beta mRNA concentrations follow a very different pattern than that of serum FSH. In contrast, LH beta mRNA and serum LH concentrations tend to increase at the same time. These findings provide evidence that concentrations of LH beta and FSH beta mRNAs are likely regulated by different mechanisms.

Animals↗
PubMed1987

Progesterone does not affect the amount of mRNA for gonadotropins in the anterior pituitary gland of ovariectomized ewes.

To evaluate the effect of progesterone on the synthesis and secretion of gonadotropins, ovariectomized ewes either were treated with progesterone (n = 5) for 3 wk or served as controls (n = 5) during the anestrous season. After treatment for 3 wk, blood samples were collected from progesterone-treated and ovariectomized ewes. After collection of blood samples, hypothalamic and hypophyseal tissues were collected from all ewes. Half of each pituitary was used to determine the content of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the number of receptors for gonadotropin-releasing hormone (GnRH). The amounts of mRNA for LH beta subunit, FSH beta subunit, alpha subunit, growth hormone, and prolactin were measured in the other half of each pituitary. Treatment with progesterone reduced mean serum concentrations of LH (p less than 0.001) but ot FSH (p greater than 0.05). Further, progesterone decreased (p less than 0.05) the total number of pulses of LH. We were unable to detect pulsatile release of FSH. Hypothalamic content of GnRH, number of receptors for GnRH, pituitary content of gonadotropins and mRNA for LH beta subunit, FSH beta subunit, alpha subunit, growth hormone, and prolactin were not affected (p greater than 0.05) by treatment with progesterone. Thus, after treatment with progesterone, serum concentrations of LH (but not FSH) are decreased. This effect, however, is not due to a decrease in the steady-state amount of mRNA for LH beta or alpha subunits.

Animals↗
PubMed1987

Differential regulation of gonadotropin subunit messenger ribonucleic acids by gonadotropin-releasing hormone pulse frequency in ewes.

Changes in the frequency of GnRH and LH pulses have been shown to occur between the luteal and preovulatory periods in the ovine estrous cycle. We examined the effect of these different frequencies of GnRH pulses on pituitary concentrations of LH and FSH subunit mRNAs. Eighteen ovariectomized ewes were implanted with progesterone to eliminate endogenous GnRH release during the nonbreeding season. These animals then received 3 ng/kg body weight GnRH in frequencies of once every 4, 1, or 0.5 h for 4 days. These frequencies represent those observed during the luteal and follicular phases, and the preovulatory LH and FSH surge of the ovine estrous cycle, respectively. On day 4, the ewes were killed and their anterior pituitary glands were removed for measurements of pituitary LH, FSH, and their subunit mRNAs. Pituitary content of LH and FSH, as assessed by RIA, did not change (P greater than 0.10) in response to the three different GnRH pulse frequencies. However, subunit mRNA concentrations, assessed by solution hybridization assays and expressed as femtomoles per mg total RNA, did change as a result of different GnRH frequencies. alpha mRNA concentrations were higher (P less than 0.05) when the GnRH pulse frequency was 1/0.5 h and 1 h, whereas LH beta and FSH beta mRNA concentrations were maximal (P less than 0.05) only at a pulse frequency of 1/h. Additionally, pituitary LH and FSH secretory response to GnRH on day 4 was maximal (P = 0.05) when the pulse infusion was 1/h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Pharmacokinetics and pharmacodynamics of clonidine in varying states of renal function.

Previous studies have reported a therapeutic window of 0.8 to 2.0 ng/ml within which clonidine exerts its antihypertensive effect. This study was designed to investigate whether there was any loss of blood pressure control when plasma clonidine concentrations exceeded this window owing to its accumulation in renal insufficiency. The results indicate that clonidine concentrations of up to 30 ng/ml in patients with end-stage renal disease (ESRD) can be associated with a maintenance of blood pressure control. It remains to be learned whether this phenomenon of high concentrations and control of blood pressure in our ESRD patient population may be related to altered (decreased) peripheral alpha-receptor sensitivity and inability to develop vasoconstriction. There is precedence for autonomic imbalance and altered tissue sensitivity in ESRD.

Adult↗
PubMed1983

Overview of physiology in senescence.

As one ages, blood pressure and hemodynamic changes become apparent. This is reflected in a fall in cardiac output and a gradual increase in total peripheral-vascular resistance. Systolic hypertension is one of the fundamental abnormalities of the cardiovascular system in the elderly. Baroreceptor function and cerebral blood flow likewise may be compromised and result in altered drug sensitivity. Renal function decreases with age and is manifested by a decrease in renal blood plasma flow and in glomerular filtration rate. There is a gradual blunting of sympathetic nervous system responsiveness demonstrated by a decrease in the activity of the renin-angiotensin-aldosterone system. Finally, pathways of drug biotransformation may be altered, resulting in adverse drug reactions.

Aged↗
PubMed1981

Body fluid volumes in the spontaneously hypertensive rat.

1. Plasma volume, packed cell volume (PCV), blood pressure, extracellular fluid volume (ECFV) and evans blue disappearance rate were measured in conscious spontaneously hypertensive rats and in weight-matched Wistar normotensive rats. 2. Over the weight range studied (250-350 g), plasma and blood volumes were significantly lower in the spontaneously hypertensive rat. Extracellular fluid volumes were similar in the two groups. PCV and Evans blue disappearance rates were significantly higher in the spontaneously hypertensive rat. 3. Negative correlations were obtained between plasma volume and mean arterial pressure and between the plasma/interstitial fluid volume ratio and mean arterial pressure. 4. The normal extracellular fluid volume and the lack of correlation with mean arterial pressure excludes volume expansion as a pressor mechanism during the established phase of hypertension in the spontaneously hypertensive rat.

Animals↗
PubMed1980

Haemodynamics of stable renal transplant recipients.

1. Haemodynamics, blood volume, plasma renin concentration and creatinine clearance were evaluated in 24 stable renal transplant recipients. 2. The mean cardiac index of the transplant recipients was not different from that of the normal subjects. 3. The transplant recipients comprised eight hypertensive and 16 normotensive patients. The mean cardiac index was the same in eight hypertensive and 16 normotensive patients. Thus the hypertension of stable renal transplant recipients is sustained by a high total peripheral resistance. 4. The mean blood volume, plasma renin concentration and creatinine clearance were similar in eight hypertensive and 16 normotensive patients. Therefore the hypertension of stable renal transplant recipients is not related to blood volume expansion, elevated peripheral renin or low creatinine clearance. The cause of the elevated total peripheral resistance in hypertension in stable renal transplant recipients remains to be elucidated.

Adolescent↗
PubMed1979

Neurogenic activity--angiotensin II interaction during the development and maintenance of renal hypertension in the rat.

1. Pentolinium tartrate (a ganglionic blocker) was injected in conscious rats during the early and late phases of two-kidney renal hypertension produced by aortic ligation. 2. In the early phase ( 5 days after aortic ligation), ganglionic blockade resulted in a decrease in blood pressure equal to that obtained in normotensive rats. Later, at days 12 and 40, for equally severe hypertension, ganglion blockade resulted in a greater decrease in blood pressure. 3. A 30 min infusion of [Sar1, Ala8]angiotensin II during the pentolinium-induced nadir in blood pressure resulted in a further decrease in blood pressure at day 5. Later, at days 12 and 40, this effect was smaller. 4. A 300 min infusion of [Sar1, Ala8]angiotensin II normalized the blood pressure in hypertensive rats at day 40. This delay response may be secondary to a central effect of the antagonist, reducing neurogenic tone or peripheral antagonism of locally generated angiotensin II in the blood vessel walls. 5. At day 40, removal of the small left kidney resulted in a greater decrease in blood pressure. This suggests the presence of a renal factor other than renin in the chronic phase of this hypertension.

Angiotensin II↗
PubMed1978

Timolol kinetics in chronic renal insufficiency.

A single-dose kinetic study of oral timolol, 20 mg, was undertaken in 3 groups of volunteers with varying degrees of renal function--(1) 10 normal subjects (N); (2) 9 patients with moderate chronic renal insufficiency (MCRI; C cr, 20 to 50 ml/min); (3) 4 patients with end-stage renal disease (ESRD)--to assess the need for dosage modification as renal function diminishes. There were borderline statistical differences in absorption between groups. The mean peak concentration (C max) was 84.3 +/- 44.8 ng/ml at 0.8 +/- 0.4 hr for N and 87.1 +/- 22.8 ng/ml at 1.7 +/- 1.2 hr (p, NS) for MCRI. N and MCRI mean half-lives (5.2 +/- 2.6 hr and 4.0 +/- 1.2 hr) were not statistically different. Salivary levels correlated with plasma levels in 3 N and 1 MCRI patient. Group differences in blood pressure and pulse response to timolol seems to reflect differences present at baseline with percent change from baseline identical for the two groups except at 12 to 24 hr. Administration of timolol on an interdialysis day revealed similar kinetic and physiologic response in the normal and the MCRI group. During dialysis, timolol, 20 mg, induced significant hypotension and bradycardia.

Adult↗
PubMed1978

Long-term clinical effects, bioavailability, and kinetics of minoxidil in relation to renal function.

Minoxidil was used to treat 26 patients (17 to 67 years old) with severe hypertension and varying degrees of renal function. Our object was to assess long-term clinical efficacy, kinetics (acute and chronic), and bioavailability of minoxidil in chronic renal insufficiency. Minoxidil, 27 to 30 mg per day, decreased systolic and diastolic blood pressure during the first three months of therapy. Between the third and 24th months (30 months in one patient) there was no further change. Propranolol or clonidine was needed to control heart rate, and furosemide or dialysis was needed to control edema induced by minoxidil. Renal function improved in some of the mildy azotemic patients. Minoxidil kinetics after the customary dose did not differ whether the drug was taken as tablet or solution. Kinetic parameters during chronic administration of minoxidil did not differ from those after acute administration. The kinetics in chronic renal insufficiency do not differ from these in subjects with normal renal function.

Adolescent↗
PubMed1978

Effect of administration of Sar1-Ala8-angiotensin II during the development and maintenance of renal hypertension in the rat.

1. Sar1-Ala8-Angiotensin II (an angiotensin antagonist) was infused in rats during the development and maintenance of renal hypertension produced by aortic ligation between renal arteries. 2. In the early phase (5 and 12 days after ligation), infusion of the antagonist markedly decreased blood pressure although it did not reach normal pressures. Later (day 40) only a modest decrease in blood pressure was noted. 3. Removal of the small left kidney always decreased the blood pressure to normal pressures. 4. It is concluded that the renin-angiotensin system is the major pressor component in the initiation of this hypertension. Later, other factors of renal origin assume a pressor function.

Angiotensin II↗
PubMed1977

Effect of propranolol on blood pressure and renin in renal hypertension in the rat.

1. Propranolol was administered to groups of mature rats before and during the development of renal hypertension induced by ligation of the aorta between the renal arteries. 2. At a dose 10 mumol (3 mg) of propranolol/kg, administered by intraperitoneal injection, the onset and severity of hypertension were not affected, although plasma renin concentration was significantly lower than in the untreated hypertensive rats in the first 5 days after the operation. 3. With 200 mumol (60 mg) of propranolol/kg, administered in the drinking water, peak blood pressure 5 days after aortic ligation was lower than in the untreated control rats, but plasma renin concentration was no lower than with the smaller dose. 4. The development of severe hypertension despite reduction in plasma renin concentration on the low dose of propranolol suggests the participation of renal vasopressor factors other than renin in this model. 5. A higher dose of propranolol reduced the rise in plasma concentration to an equal extent but the rise of blood pressure at 5 days was also reduced, which supports this concept.

Animals↗