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J L Kirkland

Publications and source records attributed to J L Kirkland.

At least 19 recordsLinked to original sources
PubMed1995

Do geriatric programs decrease long-term use of acute care beds?

OBJECTIVE: To determine whether the introduction of coordinated geriatric and discharge planning services at teaching and community hospitals in Toronto has changed the number of beds occupied by patients awaiting transfer to long-term care institutions. DESIGN: Retrospective review of social work records for the period 1985-1992. SETTING: Two tertiary and four primary acute care hospitals in Metropolitan Toronto. PARTICIPANTS: Hospitals were matched for location, acuity, and teaching affiliation. MAIN OUTCOME MEASURES: The numbers of beds occupied by patients awaiting transfer to nursing homes or chronic care hospitals were noted. RESULTS: In those teaching and community hospitals that had introduced coordinated geriatric and discharge planning services, there was a reduction in the percentage of beds occupied by patients awaiting long-term care placement (average-51%), whereas in hospitals without geriatric services, the percentage of beds occupied by patients awaiting long-term care placement increased (average + 25%) (P = .05 by Fisher's exact method, 95% confidence limit odds ratio 0, .9999). CONCLUSION: The introduction of coordinated geriatric and discharge planning services was associated with a decrease in the percentage of beds occupied by patients awaiting long-term care in both teaching and community hospitals.

Aged↗
PubMed1994

Long-chain fatty acids decrease lipoprotein lipase activity of cultured rat adipocyte precursors.

The effect of fatty acids on rat adipocyte precursor lipoprotein lipase (LPL) activity was examined. Cellular LPL activity in cultured perirenal precursors reached a maximum after 6 days. At day 6, addition of 10(-8) mol/L oleic acid to the culture medium for 6 hours resulted in a significant reduction of LPL activity. Exposing cultured precursors to 10(-4) mol/L oleic acid caused more than a 50% decrease of intracellular LPL activity measured in either acetone-ether or detergent extracts and more than a 60% decrease of heparin-releasable LPL activity. These reductions were evident within 2.5 hours of exposure to oleic acid, and exposure to oleic acid for as little as 15 minutes caused a subsequent decrease in LPL activity. LPL activity recovered 48 hours after removal of oleic acid from culture medium. Decreased LPL activity after oleic acid exposure was also noted in epididymal cells and in differentiated adipocyte precursors. The extent of decrease of LPL activity upon fatty acid exposure was dependent on the presence of the carboxyl group and was affected by acyl chain length. Although oleic acid did not affect protein synthesis estimated by [3H]-leucine incorporation, LPL mRNA levels were decreased following exposure of cells to oleic acid. Glycerol-3-phosphate dehydrogenase (G3PD) activity and mRNA levels were not affected by oleic acid exposure. Hence, fatty acids cause a dose-, acyl chain-, and carboxyl group-dependent specific decrease of heparin-releasable and intracellular LPL activities in cultured rat adipocyte precursors; this effect is associated with and is likely caused at least in part by a decrease in LPL mRNA levels.

Adipocytes↗
PubMed1994

Effects of age and anatomic site on preadipocyte number in rat fat depots.

Preadipocytes are cells which are capable of either replication or of differentiation into fat cells. As with other stem or progenitor cell types, the replicative capacity of preadipocytes declines with increasing age; however, little information about effects of age on preadipocyte cell number in vivo is available. We determined preadipocyte number in the perirenal and epididymal fat depots of 3-, 17-, and 27-month-old Fischer 344 rats in 23 experiments. Increasing age was not associated with a decrease in preadipocyte number; indeed, the number of preadipocytes increased in epididymal depots throughout maturation and senescence. Hence, the tenet that aging causes a decline in the size of stem cell or progenitor pools is not generalizable to all tissues, even if the cells exhibit reduced replicative capacity in culture.

Adipocytes↗
PubMed1994

Adult height in girls with Turner syndrome treated with low-dose estrogens and androgens.

OBJECTIVE: To determine if low dosages of estrogens and androgens administered to girls with Turner syndrome adversely affected their adult height. DESIGN: A nonrandomized control trial of nine girls. SETTING: The endocrine clinic at Texas Children's Hospital in Houston, Texas, an academic referral center. PARTICIPANTS: Participants had chromosomal defects consistent with Turner syndrome. Informed consent was obtained in accordance with institutional review board procedures. Eligibility criteria included an absence of previous hormone treatment. No one withdrew from this study because of adverse effects. INTERVENTIONS: Hormonal replacement therapy was initiated with conjugated estrogen 0.15 mg and fluoxymesterone 1 mg administered daily. MAIN OUTCOME MEASURES: Outcome measurements were a comparison of the final heights following treatment versus the predicted adult heights prior to treatment. RESULTS: The predicted adult height in these children prior to treatment was 140.0 +/- 4.4 cm (mean +/- SD); the actual adult height was 139.63 +/- 4.1 cm. The difference was 0.37 +/- 3.54 cm, which was not statistically significant by Wilcoxon signed-rank test (p = 0.23). The 95% confidence interval on this difference ranged from -3.1 to 2.3 cm, which indicates a true mean height loss of no more than 3.1 cm or a true mean gain of no more than 2.3 cm. CONCLUSIONS: Our results indicate that hormone replacement therapy with low dosages of conjugated estrogens and androgens starting at 10-11 years of age in children with Turner syndrome does not adversely affect actual adult height.

Adolescent↗
PubMed1992

The biochemistry of mammalian senescence.

Senescence is a process which, until quite recently, has been the subject of little scientific investigation. Even the word "senescence" is difficult to define, and complex methodological pitfalls have impeded progress. In the past few years, there have been exciting advances in understanding the physiological, cell biological, biochemical, and molecular biological nature of senescence. Changes in membrane function, protein synthesis, DNA structure (including glycosylation, altered tertiary structure, free-radical effects, and loss of telomeric DNA), and changes in gene regulation with age are reviewed. Recent work on changes in responses to transcriptional regulatory proteins and cellular senescence factors, some of which have been identified, is particularly promising and leads to the conclusion that senescence, at least in part, is a programmed process. Despite these advances, the fundamental cause of senescence remains elusive but might, as in the case of other biological processes which are phylogenetically widespread, turn out to be quite simple, and perhaps, even modifiable.

Aging↗
PubMed1992

Estrogen regulates expression of the jun family of protooncogenes in the uterus.

Treatment of immature female rats with estradiol increases uterine levels of c-jun and jun-B mRNAs approx. 10-fold. This effect is specific for estrogenic steroids. The induction of jun transcripts is blocked by actinomycin D but not puromycin, suggesting that the hormonal effect is due at least in part to transcriptional activation. The hormone effect is rapid and peak levels of jun mRNAs are seen within 3 h after treatment. Inductions of jun and fos transcripts in the uterus by estradiol exhibit similar dose response curves (maximum responses at 4 micrograms/kg). Estradiol also elevates uterine levels of jun-D, and this induction is insensitive to puromycin. In vivo treatment with the phorbol ester TPA rapidly elevates uterine levels of fos, jun, and myc transcripts, indicating that expression of these protooncogenes is under non-estrogenic as well as estrogenic regulation in this target tissue. These results suggest that multiple members of the jun and fos protooncogene families may play a role in amplifying the uterine response to estrogens.

Animals↗
PubMed1992

Progesterone inhibits the estrogen-induced expression of c-fos messenger ribonucleic acid in the uterus.

Estradiol produces a large increase in the uterine level of c-fos mRNA, which is maximum in 3 h. The administration of progesterone antagonizes this estrogen-induced increase in protooncogene transcript levels in both the rat and mouse. The inhibitory effect of progesterone is observed within 1 h after hormone treatment and persists for 9-18 h. In the rat, this effect can be observed at a dose of 0.25 mg progesterone and is maximum at a dose of 2.5 mg. A similar inhibition of fos mRNA levels after estrogen administration is produced by the glucocorticoid dexamethasone, but not by androgens or mineralocorticoids. Progesterone does not block the induction of c-jun or c-myc mRNA by estradiol. Uterine levels of c-fos mRNA observed after treatment with the phorbol ester phorbol 12-myristate 13-acetate are not decreased by a 3-h pretreatment with progesterone. Under the conditions of our experiments, progesterone does not decrease occupied levels of nuclear estrogen receptors in the uterus after estradiol administration. These findings are consistent with a mechanism in which progesterone inhibits transcriptional activation by the estrogen receptor at the level of the c-fos gene.

Animals↗
PubMed1992

Effect of hypophysectomy on rat preadipocyte replication and differentiation.

The effects of hypophysectomy, which results in decreased fat pad weight, fat cell number, and new fat cell formation, on preadipocyte replication were examined. Perirenal and epididymal preadipocytes were cultured from hypophysectomized, sham-operated and unoperated 3-month-old rats. In cloned preadipocytes, hypophysectomy resulted in a 19% decrease in cloning efficiency and a 60% reduction in cell number after 3 weeks in culture. Perirenal cells underwent more extensive replication than epididymal cells. The mechanism of reduced replication following hypophysectomy differed from that of donor site: hypophysectomy resulted in an increased percentage of cells which underwent 2 or fewer population doublings at the expense of cells capable of more than 2 doublings. However, donor site had little effect specifically on these slowly replicating preadipocytes; rather, perirenal preadipocytes underwent more extensive replication than epididymal cells because of the higher percentage of preadipocytes capable of 13 or more doublings in perirenal fat pads. Hypophysectomy did not result in decreased differentiation of preadipocytes. These observations are in accord with the hypothesis that hypophysectomy reduces fat cell number in maturing rats partly through an effect on preadipocyte replicative capacity. Additionally, it seems that more than one form of preadipocyte exists, the various forms having differing susceptibilities to factors such as pituitary function and anatomic site.

Adipose Tissue↗
PubMed1992

Properties of spontaneous growth hormone secretory bursts and half-life of endogenous growth hormone in boys with idiopathic short stature. Genentech Collaborative Group.

We analyzed endogenous GH secretory dynamics and MCRs by a novel quantitative deconvolution technique in 20 boys with idiopathic short stature (ISS) and 35 boys of normal stature in Tanner stage I of puberty. We tested the null hypotheses that 1) ISS is not associated with any alterations in the frequency, mass, amplitude, or duration of spontaneous GH secretory bursts and/or the 24-h GH production rate; and 2) the half-life of endogenous GH is not altered in ISS. The boys with ISS had a mean (+/- SEM) bone age of 8.0 +/- 0.42 yr and a chronological age of 10 +/- 0.50 yr. The latter was similar to the chronological (and bone) age of the normal boys of 9.8 +/- 0.23 (and 9.3 +/- 0.34) yr. Mean height SD scores were significantly lower in ISS boys, viz. -2.7 +/- 0.15 in ISS vs. +0.34 +/- 0.13 in normal boys (P less than 0.001). Plasma insulin-like growth factor-I concentrations were similar in the two groups, as were (24-h) mean serum GH concentrations, viz. 3.5 +/- 0.29 micrograms/L in ISS and 4.1 +/- 0.49 micrograms/L in normal boys (P = NS). Deconvolution analysis revealed that the mean number of GH secretory events per 24 h was similar in normal and ISS boys, viz. 9.6 +/- 0.76 (normal) vs. 8.4 +/- 0.55 (ISS), and that there was no significant difference in mean GH interburst intervals. The amplitude, mass, and duration of computer-resolved GH secretory bursts also did not differ in normal and ISS boys. The half-lives of endogenous GH were estimated to be 16 +/- 0.77 min in the ISS and 18 +/- 0.93 min in the control boys (P = NS). The calculated daily GH secretion rate per unit distribution volume was not significantly reduced in ISS, i.e. 194 +/- 19 micrograms/L.day in ISS vs. 177 +/- 19 micrograms/L.day in control boys. Moreover, daily GH secretion rates corrected for body mass index (weight/height2) in the twp groups were not significantly different. In summary, the present cohort of boys with ISS manifested no significant alterations in GH secretory burst frequency, duration, mass, or amplitude or in the half-life of endogenous GH compared to normal boys in Tanner stage I of pubertal development. Indeed, whether daily GH secretion rates are expressed per unit distribution volume or per unit body mass index, groups of boys with ISS and normal height controls secrete similar total amounts of GH. We conclude that the overall dynamics of GH secretion and clearance in boys with ISS considered as a whole cannot be distinguished readily from physiological patterns observed in prepubertal boys of normal height.

Adolescent↗
PubMed1990

Age, anatomic site, and the replication and differentiation of adipocyte precursors.

The effects of donor age and anatomic site on cellular replication and differentiation were studied in adipocyte precursors cloned from epididymal and perirenal depots of young, middle-aged, and senescent rats. As animals aged from 3 to 29 mo, there was a progressive reduction in the proportion of cells capable of extensive replication in both depots. An inverse relation between clonal capacity for replication and differentiation was found. This relation was affected by donor site but not age. Aging was, however, associated with a reduction in the frequency of clones capable of full differentiation into cells with single, large, central lipid inclusions. Hence, age and donor site may affect adipocyte precursor replication and differentiation by different mechanisms.

Adipose Tissue↗
PubMed1990

Propylthiouracil-induced hepatic failure and encephalopathy in a child.

Propylthiouracil (PTU) is the most common antithyroid medication utilized in children for the treatment of hyperthyroidism. An adverse effect of PTU reported infrequently is hepatic injury. The child described here is the fifth reported case of severe hepatic injury in the pediatric age group and documents that clinical or biochemical evidence of hepatic injury requires immediate discontinuation of PTU.

Chemical and Drug Induced Liver Injury↗
PubMed1989

Preadipocyte stimulating factor in rat serum: evidence for a discrete 63 kDa protein that promotes cell differentiation of rat preadipocytes in primary cultures.

In primary cultures of rat preadipocytes (PA) isolated from epididymal or perirenal depots, rat serum is more effective than other animal sera (fetal calf, newborn calf, human, horse, rabbit, cat, sheep, goat, dog, pig) in promoting adipogenic conversion, biochemical differentiation, and mitogenesis. Only mouse serum is comparable to rat serum. This activity is attributable to a specific growth factor (preadipocyte stimulating factor, PSF). An assay for PSF in rat serum was devised using PA from perirenal fat of 3-month-old Fischer 344 rats grown first to confluence in FCS for 8 days and then for the next 3 days in test serum, followed by measurement of triglyceride (TG) and glycerol-3-phosphate dehydrogenase (GPDH). Rat serum induces dose-dependent rapid cell division, which coincides with accumulation of TG and increase of GPDH; for routine quantitation, TG is assayed. The biochemical characteristics of PSF in serum are as follows: stable at 4 degrees C for up to 1 year; inactivated at 100 degrees C (80% loss, 30 min) but stable at 56 degrees C for 1 hr; stable at pH 2-12; non-dialyzable; completely resistant to pepsin, trypsin, and chymotrypsin but destroyed by pronase and subtilisn; stable to DTT and periodate; and m.w. between 68 kDa (Sephacryl-300) and 58 kDa (Sephacryl-300 in 5 M urea). PSF activity is greater in serum from Wistar than from Fischer 344 rats, while activity of serum from Zucker obese (fa/fa) rats is at least as great as that from Wistar rats and, like serum of rats made obese by feeding a high-fat, high-carbohydrate diet, is not suppressed. PSF activity is not due to insulin, insulin-like growth factor-1 (IGF-1), growth hormone, glucocorticoids, or combinations of these hormones. PSF activity was not seen with a number of growth factors including colony-stimulating factor (CSF-1), GM-CSF, interleukins 1, 2, and 3, neuroleukin, tumor necrosis factor, and others. PSF is distinct from the low molecular weight (4-8 kDa) differentiation factor present in rat serum, FCS, and human serum that promotes the adipogenic conversion and cellular differentiation of 3T3-L1, 3T3-F442A, and Ob17 cells. PSF appears to be a new differentiation factor for rat preadipocytes, has properties suggestive of a highly glycosylated protein, and may be highly species specific.

Adipose Tissue↗
PubMed1989

Regulation of uterine epidermal growth factor (EGF) receptors by estrogen in the mature rat and during the estrous cycle.

Previous work has shown that the immature rat uterus contains epidermal growth factor (EGF) receptors and that tissue levels of this receptor are increased by the administration of exogenous estrogens. This study was undertaken to determine if estrogen administration also elevated EGF receptor levels in the mature animal and if the growth factor receptor levels varied in concert with endogenous estrogens throughout the estrous cycle. In the mature, castrate rat administration of estradiol, but not non-estrogenic steroids, causes a 2-3-fold elevation of uterine EGF receptors as judged by ligand binding. This increase is maximum in 18 h and is due to an increase in the number of binding sites. In cycling animals EGF receptor levels are low at metestrus, rise at diestrus, reach a maximum (approximately twice metestrus values) at proestrus, and then return at estrus to metestrus levels. These changes in EGF receptor levels parallel changes in plasma estrogens and occupied nuclear estrogen receptor reported by other workers. These results indicate that uterine EGF receptors are increased by exogenous estrogens in both mature and immature animals, and support a physiological role for estrogens in the regulation of this growth factor receptor.

Animals↗
PubMed1989

Growth hormone testing in short children and their response to growth hormone therapy.

Because current concepts of growth hormone (GH) testing and GH treatment have become controversial, we investigated the GH secretory patterns in children with normal and short stature. Twenty-four-hour serum GH levels were evaluated in three groups of children. Group 1 was composed of children with normal height (mean height = 0.02 SD, n = 33); group 2 was composed of short children (less than 5th percentile, n = 63) with normal results on provocative GH testing; and group 3 was composed of short children (less than 5th percentile, n = 7) with subnormal results on provocative GH testing. Mean +/- SD (range) GH levels during 24-hour studies of GH secretion were 1.6 +/- 1.1 (0.5 to 5.6), 1.8 +/- 1.2 (0.6 to 6.3), and 0.9 +/- 0.4 (0.5 to 1.7) ng/ml in groups 1, 2, and 3, respectively. No statistical difference existed in mean GH levels between groups 1 and 2 or between groups 1 and 3. The mean GH concentration from 24-hour studies in group 2 children did not correlate with chronologic age, height standard deviation, growth rates, or insulin-like growth factor 1 levels. The linear growth rate of 26 of 28 children in group 2 who received GH therapy for 6 months improved by 2 cm/yr or more; the mean +/- SD growth rate was 4.0 +/- 1.3 and 8.8 +/- 2.0 cm/yr during control and treatment periods, respectively, for these 28 children. Mean GH levels from testing did not predict response to GH during 6 months of therapy. Children with slower growth rates responded better to GH therapy (p less than 0.05). We conclude that (1) in 24-hour studies, GH levels in normal children overlapped with those of short children, including those with classic GH deficiency, (2) in 24-hour studies, GH levels did not predict responses of linear growth to short-term GH treatment, nor did they correlate with children's heights or growth velocities, and (3) the majority of short children in group 2 treated with GH for 6 months had an increase in linear growth velocity, the mean +/- SD change being 4.8 +/- 2.0 cm/yr.

Child↗
PubMed1989

Evolution and ageing.

Did senescence evolve as a direct result of natural selection in order to limit the life-span or did increases in longevity evolve in the face of random events that ordinarily limit the life-span? The adaptive hypothesis is that senescence is a programmed process which appeared in evolution because a limited life-span has selective advantages for certain species. Non-adaptive theorists hold that evolution has acted to lengthen the life-span and maximize reproduction and that senescence is only an evolutionary by-product since natural selection does not act directly on postreproductive events. The assumptions and arguments underlying these hypotheses are examined critically in the light of experimental evidence. While theoretical study of the evolution of ageing may advance our understanding of the nature of ageing itself, it is likely that further clarification of the relationship between evolution and ageing will depend on experimental approaches that are now becoming possible.

Adaptation, Biological↗
PubMed1989

Varying capacities for replication of rat adipocyte precursor clones and adipose tissue growth.

Rat adipocyte precursor populations contain clones varying in capacity for replication. In this study we explored factors controlling the frequency of clones of varying replicative capacities (clonal composition). We also explored the relationship between this frequency and fat depot growth. In perirenal and epididymal depots clonal composition was identical bilaterally; perirenal depots contained more extensively replicating clones. Although there were large interanimal differences in clonal composition, variation between animals was always in the same direction for both depots. Clonal composition was unaffected by undernutrition while with animal growth the frequency of the most extensively replicating clones was reduced. Differentiation of precursors occurred in all clones, while differentiation did not occur in skin fibroblasts cloned under identical conditions. Clonal composition and mature fat cell number were related in that fat cell numbers were identical bilaterally in both depots and increased more extensively with growth in perirenal than epididymal tissue. We conclude (a) that clonal composition of adipocyte precursor populations is regulated genetically and by age, (b) that this composition determines, at least in part, the capacity for adipose depot growth.

Adipose Tissue↗
PubMed1988

Prostaglandin-sensitive adenylyl cyclase of cultured preadipocytes and mature adipocytes of the rat: probable role of Gi in determination of stimulatory or inhibitory action.

Preadipocytes of rats were obtained from the stromal-vascular fraction of collagenase-digested perirenal fat pads and grown in serum-containing medium. By day 8 of culture the cells reached confluence and by 12 days were lipid-laden. The adenylyl cyclase of the plasma membranes was compared to that of mature fat cells. Unlike the membranes from adipocytes, the preadipocytes showed adenylyl cyclase activity that was stimulated by GTP. Stimulation of preadipocyte membranes by Gpp(NH)p, NaF, and forskolin was comparable to that of membranes from adipocytes, but the response to epinephrine and isoproterenol was minimal (approximately 1.5-fold for preadipocytes vs. 4-5-fold for adipocytes). In contrast, GTP-dependent stimulation of adenylyl cyclase of preadipocytes by PGE1 was nearly 8-fold. Stimulation occurred even in the presence of both GTP and 140 mM NaCl, a condition that leads to inhibition by PGE1 of adenylyl cyclase in membranes of adipocytes. Other characteristics of the adenylyl cyclase of preadipocyte membranes that differ from those of adipocytes include lack of inhibition by GTP of forskolin-activated activity, and, following treatment with pertussis toxin, enhanced stimulation by PGE1. ADP-ribosylation of Gi and Gs with pertussis and cholera toxins, respectively, indicated that the membranes of preadipocytes contained only 5-11% of the Gi of adipocytes and a much lower ratio of Gi:Gs. These findings suggest that cultured preadipocytes have an incompletely developed Gi pathway that may account for the stimulatory effect of prostaglandins on the adenylyl cyclase of these cells as opposed to the inhibitory action of PG in mature fat cells.

Adenosine Diphosphate Ribose↗