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Biomedical subjects

R A Anderson

Publications and source records attributed to R A Anderson.

At least 127 records · Page 7Linked to original sources
PubMed1998

Casein kinase I: spatial organization and positioning of a multifunctional protein kinase family.

The casein kinase I family of serine/threonine protein kinases is highly conserved from yeast to humans. Until only recently, both the function and regulation of these enzymes remained poorly uncharacterised in that they appeared to be constitutively active and were capable of phosphorylating an untold number of other proteins. While relatively little was known regarding the exact function of the higher eukaryotic isoforms, the casein kinase I (CKI) isoforms from yeast have been genetically linked to vesicular trafficking, DNA repair, cell cycle progression and cytokinesis. All five S. cerevisiae isoforms are known to be associated with discrete cellular compartments and this localization has been shown to be absolutely essential for their respective functions. New evidence now suggests that the CKI isoforms in more complex systems also exhibit non-homogeneous subcellular distributions that may prove vital to defining the function and regulation of these enzymes. In particular, CKIalpha, the most-characterized vertebrate isoform, is associated with cytosolic vesicles, the mitotic spindle and structures within the nucleus. Functions associated with these localizations coincide with those previously reported in yeast, suggesting a conservation of function. Other reports have indicated that each of the remaining CKI isoforms have the capacity to make associations with components of several signal transduction pathways, thereby channeling CKI function toward specific regulatory events. This review will examine what is now known about the higher eukaryotic CKI family members from the perspective localization as a means of gaining a better understanding of the function and regulation of these kinases.

Amino Acid Sequence↗
PubMed1998

Inhibin A and inhibin B in women with polycystic ovarian syndrome during treatment with FSH to induce mono-ovulation.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by the presence of numerous small antral follicles arrested at a diameter of less than 10 mm. As development of large antral follicle(s) can be stimulated by the administration of FSH, it has been suggested that the arrest of follicle development is due to a relative lack of or resistance to FSH. We have measured the concentration of FSH and LH and the ovarian hormones oestradiol, inhibin A and B, in relation to the dynamics of follicular development in women with PCOS under basal conditions and during treatment with FSH. DESIGN: The concentrations of FSH, LH, oestradiol, inhibin A and B were measured in women with PCOS who were untreated (n = 9) or following progesterone-induced menses (10 cycles in six women) and control women on day 3 of a normal cycle (n = 10). Serial measurements of the same hormones were made during induction of ovulation with low dose of exogenous FSH in the women with PCOS who had been treated with progesterone. The dynamics of follicle development were measured by serial pelvic ultrasound examinations during treatment with FSH in PCOS and in the follicular phase of control cycles. PATIENTS: Nine anovulatory untreated women with PCOS were compared with 10 normal women and six women with PCOS undergoing FSH treatment. RESULTS: The concentrations of inhibin B and LH were higher in both groups of women with PCOS than in normal control women on day 3. In untreated women with PCOS the concentration of inhibin A was also significantly elevated compared to control women (P < 0.01) but not in women pretreated with progesterone. Basal concentrations of oestradiol were also significantly higher in women with PCOS than in the early follicular phase of the normal cycle. There were no significant differences in the concentration of FSH between the groups. Treatment of women with PCOS with low doses of FSH stimulated the development of a single dominant follicle which had an identical rate of growth and secretion of oestradiol and inhibin A to that observed in spontaneous cycles in normal women. In contrast to normal women, the concentration of inhibin B rose 7-fold following FSH treatment and remained elevated until the luteal phase. CONCLUSIONS: The raised concentrations of inhibin A and B in women with PCOS probably reflects the increased number of small antral follicles characteristically present in that condition. The striking similarity in the dynamics of growth of the dominant follicle and the pattern in concentration of oestradiol and inhibin A in normal women and in women with PCOS treated with modest amounts of FSH, suggests that the arrest of follicle development in PCOS may be due to a relative deficiency of FSH which may in turn be secondary to increased secretion of either or both inhibin forms.

Adult↗
PubMed1998

Comparative effects of chromium, vanadium and gymnema sylvestre on sugar-induced blood pressure elevations in SHR.

OBJECTIVE: Effects on systolic blood pressure (SBP) of ingesting three agents reported to influence insulin metabolism, i.e., chromium polynicotinate, bis(maltolato)oxovanadium (BMOV), and the herb, Gymnema sylvestre, were assessed simultaneously in spontaneously hypertensive rats (SHR). METHODS: In the first study, SHR were fed either a starch, sugar, or sugar diet containing chromium polynicotinate, bis(maltolato)oxovanadium (BMOV), or G. sylvestre. Tail SBP was estimated indirectly and various blood chemistries were measured. TBARS formation was determined in hepatic and renal tissue. In a second study, tail SBP was measured in SHR ingesting diets containing different concentrations of BMOV. RESULTS: Compared to starch, SHR consuming sucrose showed a significant elevation of SBP within days that was maintained for the duration of study. Addition of chromium polynicotinate to the sucrose diet at the beginning of study prevented the sucrose-induced elevation of SBP for 2 weeks, but SBP rose significantly after that. BMOV at high concentrations overcame the sucrose-induced rise in SBP and even decreased SBP below values seen in SHR eating the starch diet, but marked weight loss was noted. A second study examined different concentrations of BMOV. At 0.01% w/w concentration of BMOV, SBP was still significantly decreased, even though SHR did not lose body weight (BW) early on. SHR consuming G. sylvestre showed no change or even elevated SBP. Hepatic thiobarbituric acid reacting substances (TBARS) formation, an estimate of lipid peroxidation, was decreased by chromium polynicotinate and BMOV, and renal TBARS by chromium polynicotinate. Circulating cholesterol concentrations were decreased in the SHR consuming G. sylvestre. CONCLUSIONS: Chromium decreases the portion of SBP elevated by high sucrose intake as shown previously, but high levels of sucrose ingestion can eventually overcome this. BMOV overcame sucrose-induced elevation of SBP as well as some of the "genetic hypertension." Different from chromium, this decrease was not overcome by high levels of dietary sucrose. The significant lowering of cholesterol with G. sylvestre ingestion indicates some effect on metabolism, but G. sylvestre did not lower and even raised SBP.

Animals↗
PubMed1998

Chromium, glucose intolerance and diabetes.

Within the last 5 years chromium (Cr) has been shown to play a role in glucose intolerance, Type 2 diabetes mellitus (Type 2 DM), and gestational diabetes. In addition, diabetes and the neuropathy of a patient on home parenteral nutrition were alleviated when supplemental Cr was added to total parenteral nutrition (TPN) solutions. In a study conducted in China that has been supported by studies in the United States, supplemental Cr as Cr picolinate improved the blood glucose, insulin, cholesterol, and hemoglobin A1C in people with Type 2 DM in a dose dependent manner. Follow-up studies of > 1 year have confirmed these studies. The requirement for Cr is related to the degree of glucose intolerance: 200 microg/day of supplemental Cr is adequate to improve glucose variables of those who are mildly glucose intolerant. However, people with more overt impairments in glucose tolerance and diabetes usually require more than 200 microg/day. Daily intake of 8 microg of Cr per kg body weight was also more effective than 4 microg/kg in women with gestational diabetes. The mechanism of action of Cr involves increased insulin binding, increased insulin receptor number, and increased insulin receptor phosphorylation. In summary, supplemental Cr has been shown to have beneficial effects without any documented side effects on people with varying degrees of glucose intolerance ranging from mild glucose intolerance to overt Type 2 DM.

Chromium↗
PubMed1998

Phosphoinositide signaling pathways in nuclei are associated with nuclear speckles containing pre-mRNA processing factors.

Phosphoinositide signal transduction pathways in nuclei use enzymes that are indistinguishable from their cytosolic analogues. We demonstrate that distinct phosphatidylinositol phosphate kinases (PIPKs), the type I and type II isoforms, are concentrated in nuclei of mammalian cells. The cytosolic and nuclear PIPKs display comparable activities toward the substrates phosphatidylinositol 4-phosphate and phosphatidylinositol 3-phosphate. Indirect immunofluorescence revealed that these kinases were associated with distinct subnuclear domains, identified as "nuclear speckles," which also contained pre-mRNA processing factors. A pool of nuclear phosphatidylinositol bisphosphate (PIP2), the product of these kinases, was also detected at these same sites by monoclonal antibody staining. The localization of PIPKs and PIP2 to speckles is dynamic in that both PIPKs and PIP2 reorganize along with other speckle components upon inhibition of mRNA transcription. Because PIPKs have roles in the production of most phosphatidylinositol second messengers, these findings demonstrate that phosphatidylinositol signaling pathways are localized at nuclear speckles. Surprisingly, the PIPKs and PIP2 are not associated with invaginations of the nuclear envelope or any nuclear membrane structure. The putative absence of membranes at these sites suggests novel mechanisms for the generation of phosphoinositides within these structures.

Animals↗
PubMed1998

Distribution of a stable isotope of chromium (53Cr) in serum, urine, and breast milk in lactating women.

To determine the fate and distribution of chromium during lactation, six lactating women (25-38 y old) were given three doses of the tracer 53Cr (7.55 micromol/d, or 400 microg/d) on days 1, 2, and 3 of the study. Diet records, blood samples taken while subjects were fasting, and 24-h composite milk and urine samples were collected from day 0 to day 6. Fasting blood samples, morning milk samples, and 24-h urine samples were also collected on days 8, 10, 15, 30, 60, and 90. 53Cr and natural and total chromium concentrations in biological fluids were measured with gas chromatography-mass spectrometry and total urinary chromium was measured with atomic-absorption spectrometry. 53Cr was detectable in serum 2 h after dosing and continued to be detected from day 30 to day 60. Changes in total serum chromium concentration in response to the oral dose suggested that chromium concentrations in blood were not tightly regulated. 53Cr was not detected in breast milk and no significant changes in natural chromium concentration in milk were observed in response to the oral doses, suggesting that breast-milk chromium concentrations are independent of intake. The estimated chromium intake of exclusively breast-fed infants was 2.5 nmol/d (0.13 microg/d), below the lower end of the range of estimated safe and adequate daily dietary intakes (10-40 microg/d) for infants 0-6 mo of age. The baseline chromium concentration in urine and the minimum 53Cr absorption in lactating women were comparable with values for nonpregnant, nonlactating subjects. Chromium losses in breast milk do not appear to be compensated for via increased absorption or decreased excretion.

Administration, Oral↗
PubMed1998

Intensity of registered nurse participation in nursing home decision making.

In this study of data obtained from nursing home administrators and directors of nursing, we found that intensity of registered nurses' (RNs') participation in nursing home decision making varied with decision content and decision level. The primary decision activity in which RNs participated was raising the issue. The decision activity in which they participated least was choosing the alternative. The primary mechanism for RN involvement was through informal meetings. Patterns of participation varied across nursing homes and were important in explaining the extent to which RNs influence decision outcomes. RN influence over the final choice was explained by their involvement in the decision activity of raising the issue and by their involvement through informal meetings.

Analysis of Variance↗
PubMed1998

Follistatin and activin A production by the male reproductive tract.

Follistatin is a binding protein for the activin and inhibin family of hormones, regulating their biological activity. In the male reproductive tract, the interaction of these factors is likely to be involved in the regulation of the proliferation of several cell types. We have investigated the presence of follistatin and activin A in seminal plasma using specific immunoassays and have localized follistatin and activin/inhibin subunits in the adult human testis, prostate and seminal vesicle to establish their likely sources. High concentrations of immunoreactive follistatin were present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in peripheral plasma) and were similar in men with oligo/azoospermia and following vasectomy. Follistatin immunoreactivity was localized to both Leydig and Sertoli cells of the testis, and to epithelial cells of the prostate gland and seminal vesicle, which are likely to be the predominant sources of the hormone in seminal plasma. Activin A was also present in seminal plasma in normal men but was undetectable following vasectomy, thus deriving from the testis. Consistent with this finding, the betaA-subunit was immunolocalized in Sertoli and Leydig cells but was not present in seminal vesicle or prostate gland. The functional significance of the high concentrations of follistatin secreted into seminal plasma by the prostate gland and/or seminal vesicle is uncertain, but they may regulate the biological activity of testis-derived activin A and inhibin B.

Activins↗
PubMed1998

Inhibin B in seminal plasma: testicular origin and relationship to spermatogenesis.

In men, inhibin B is the circulating isoform involved in the regulation of follicle stimulating hormone (FSH) secretion. Within the testis, inhibin B may have a role in Sertoli and germ cell interactions, thus secretion into seminal plasma may reflect seminiferous tubule function. Using specific immunoassays, inhibin B was present in seminal plasma in fertile men (n = 105) and in unselected men attending an infertility clinic (n = 174) with a wide range in concentration from undetectable (<15 pg/ml) up to 54,100 pg/ml (geometric mean 280 pg/ml). There was a highly significant correlation between seminal plasma inhibin B concentration and sperm concentration (r = 0.46, P < 0.001), but no correlation with percentages of spermatozoa with progressive motility or normal morphology. Inhibin A and isoforms containing pro and alphaC immunoreactivity were not detectable. In post-vasectomy seminal plasma samples (18 of 20) inhibin B was undetectable, indicating that the testis is the predominant source. In unselected men attending an infertility clinic, inhibin B was undetectable in 17% (present in remainder; maximum concentration 26,200 pg/ml; mean 263 pg/ml), with a highly significant correlation between seminal plasma inhibin B and sperm concentration (r = 0.55, P < 0.0001). In men with oligo/ azoospermia (sperm concentration <20 x 10(6)/ml), seminal plasma inhibin B concentrations were lower in those with elevated plasma FSH concentrations (mean values 42 and 205 pg/ml, P < 0.05). Inhibin alpha and betaB subunits were localized predominantly in Sertoli and Leydig cells, using immunohistochemistry. We conclude that inhibin B of testicular origin is present in normal human seminal plasma, but with a very wide range in concentration, and may reflect the functional state of the seminiferous epithelium.

Adult↗
PubMed1998

Acute and chronic resistive exercise increase urinary chromium excretion in men as measured with an enriched chromium stable isotope.

Both exercise and chromium exert beneficial effects on insulin function. The mechanism by which exercise improves insulin response may involve an alteration in Cr metabolism. To determine the effects of acute and chronic resistive exercise on urinary Cr losses, we measured the effects of acute resistive exercise and 16 wk of resistive exercise training on urinary Cr losses of 10 men 53-63 y of age. Subjects consumed diets in compliance with the American Heart Association Phase I diet with a Cr content of 30 +/- 4 microg/d. Sixteen weeks of resistive exercise training led to approximately 40% increases in upper and lower body strength, increases in fat-free mass and decreases in the percentage of body fat. An enriched stable isotope of Cr, 53Cr, was employed to differentiate the exogenously administered Cr from the native endogenous Cr. Both acute and chronic resistive exercise increased 53Cr losses. These data demonstrate that the improvements in body composition due to resistive exercise are associated with increased urinary Cr losses that are consistent with increased absorption.

Adipose Tissue↗
PubMed1998

Expression of oestrogen receptor alpha and beta in cultured human ovarian surface epithelial cells.

Ovarian surface epithelial (OSE) cells participate in the formation of the ovarian cortex and are potential targets of oestrogen action. Oestrogens typically act through nuclear oestrogen receptors (ER) of which there are two known subtypes: ERalpha and ERbeta. In view of the potential importance of oestrogen as a local regulator of OSE cell function, we screened for ERalpha and ERbeta mRNA in primary OSE cell cultures by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, and used freshly isolated granulosa cells (GC) and granulosa-lutein cells (GLC) as positive controls. OSE cells, scraped from the ovarian surface of women undergoing laparotomy for benign gynaecological conditions, were cultured for up to 21 days to obtain enough cells for mRNA extraction. GC were obtained from spontaneously cyclic women undergoing total hysterectomy; while GLC were obtained from follicular aspirates of gonadotrophin-stimulated in-vitro fertilization patients. Total RNA (1 microg) was reverse transcribed into single-stranded cDNA for PCR (30 cycles) using primers selected to give specific ERalpha and ERbeta products. The ERalpha and ERbeta PCR products, authenticated by cloning and sequencing, were both weakly detectable by Southern analysis in cultured OSE cells and readily detectable in GC and GLC. These results show that cultured human OSE express both ERalpha and ERbeta mRNA, consistent with a role for oestrogen in the regulation of OSE cell function in vivo.

Adult↗
PubMed1998

Chromium update: examining recent literature 1997-1998.

Trivalent chromium is an essential nutrient required for sugar and fat metabolism. The majority of people eating typical Western diets consume less than the upper limit of the estimated safe and adequate daily dietary intake, which is set at 50-200 micrograms per day. Insufficient chromium intake is associated with signs and symptoms similar to those seen in diabetes and cardiovascular diseases. The efficacy of chromium in the general population relates to its prevention of deficiency or a reduction in the risk of chronic diseases. It is possible that doses above the estimated safe and adequate daily dietary intake are necessary for the treatment of certain chronic disease states. In a study performed in China, the use of 1000 micrograms of chromium per day (five times above the upper limit of the estimated safe and adequate daily dietary intake) was highly effective in relieving many of the symptomatic manifestations of type 2 diabetes mellitus, including a return of the HbA1C levels into the normal range. Most recent evidence strongly supports the conclusion that there is little fear of toxic reactions from chromium consumption. In addition to type 2 diabetes mellitus, chromium supplementation may be useful to direct overall weight decrements specifically towards fat loss with the retention of lean body mass and to ameliorate many manifestations of aging.

Aging↗
PubMed1998

Sequence analyses of human herpesvirus-8 strains from both African human immunodeficiency virus-negative and -positive childhood endemic Kaposi's sarcoma show a close relationship with strains identified in febrile children and high variation in the K1 glycoprotein.

Human herpesvirus-8 (HHV-8) DNA sequences have been identified in all forms of Kaposi's sarcoma (KS), a cancer found primarily in adult AIDS patients. We have identified HHV-8 strains in a rare human immunodeficiency virus (HIV)-negative form of KS, which is endemic in children in parts of sub-Saharan Africa. This was shown in Zambia, where we also had identified HHV-8 sequences in blood from HIV-negative febrile children without KS. In order to investigate the relationship of these Zambian strains to each other and to those from other forms of KS, we compared them to strains we have characterized from European AIDS KS (Denmark) and all published sequences from all forms of KS. Four distinct genomic regions were examined by PCR and sequencing: ORF26, ORF75, gH and K1. The results showed a distinct grouping of strains from both sets of Zambian children in all genomic regions studied, but which was most pronounced in the K1 glycoprotein gene. This gene was highly variable, encoding up to 25% amino acid sequence variation. In contrast, the Zambian groups were closely related to each other, with only 2% variation. Similar results were found in comparisons to the K1 sequences from HIV-positive febrile infants or KS children. The data raise the possibility that in areas where rare childhood endemic KS occurs, geographical variation in HHV-8 may relate to differences in virulence or transmission.

AIDS-Related Opportunistic Infections↗
PubMed1998

Effects of chromium on body composition and weight loss.

Chromium is an essential nutrient involved in the regulation of carbohydrate and lipid metabolism. Normal dietary intake of chromium in humans and farm animals is often suboptimal. In addition to its effects on glucose, insulin, and lipid metabolism, chromium has been reported to increase lean body mass and decrease percentage body fat, which may lead to weight loss in humans. The effects of chromium on body composition are controversial but are supported by animal studies, which increase their validity. A subject's response to chromium depends on his or her chromium status, diet consumed, type and amount of supplemental chromium, and study duration. There have been no confirmed negative effects of chromium in nutritional studies. Chromium is only a small part of the puzzle in the control of weight loss and body composition, and its effects, if present, will be small compared with those of exercise and a well-balanced diet.

Body Composition↗
PubMed1998

Regulation of PTP-1 and insulin receptor kinase by fractions from cinnamon: implications for cinnamon regulation of insulin signalling.

Bioactive compound(s) extracted from cinnamon potentiate insulin activity, as measured by glucose oxidation in the rat epididymal fat cell assay. Wortmannin, a potent PI 3'-kinase inhibitor, decreases the biological response to insulin and bioactive compound(s) from cinnamon similarly, indicating that cinnamon is affecting an element(s) upstream of PI 3'-kinase. Enzyme studies done in vitro show that the bioactive compound(s) can stimulate autophosphorylation of a truncated form of the insulin receptor and can inhibit PTP-1, a rat homolog of a tyrosine phosphatase (PTP-1B) that inactivates the insulin receptor. No inhibition was found with alkaline phosphate or calcineurin suggesting that the active material is not a general phosphatase inhibitor. It is suggested, then, that a cinnamon compound(s), like insulin, affects protein phosphorylation-dephosphorylation reactions in the intact adipocyte. Bioactive cinnamon compounds may find further use in studies of insulin resistance in adult-onset diabetes.

Androstadienes↗
PubMed1997

Phosphatidylinositol-4-phosphate 5-kinase isozymes catalyze the synthesis of 3-phosphate-containing phosphatidylinositol signaling molecules.

Phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks) utilize phosphatidylinositols containing D-3-position phosphates as substrates to form phosphatidylinositol 3,4-bisphosphate. In addition, type I PIP5Ks phosphorylate phosphatidylinositol 3, 4-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate, while type II kinases have less activity toward this substrate. Remarkably, these kinases can convert phosphatidylinositol 3-phosphate to phosphatidylinositol 3,4,5-trisphosphate in a concerted reaction. Kinase activities toward the 3-position phosphoinositides are comparable with those seen with phosphatidylinositol 4-phosphate as the substrate. Therefore, the PIP5Ks can synthesize phosphatidylinositol 4,5-bisphosphate and two 3-phosphate-containing polyphosphoinositides. These unexpected activities position the PIP5Ks as potential participants in the generation of all polyphosphoinositide signaling molecules.

Animals↗
PubMed1997

Cloning and in vitro expression of rat lecithin:cholesterol acyltransferase.

Rat lecithin:cholesterol acyltransferase (LCAT) cDNA was obtained by reverse transcriptase/polymerase chain reaction amplification of rat liver total RNA. A consensus sequence was derived from four independent clones from two strains of rats. In vitro expression of rat LCAT cDNA in COS cells resulted in secreted enzyme protein with the same fatty acyl specificity for phospholipase A2 activity and cholesterol esterification as rat plasma LCAT, but different from that of recombinant or human plasma LCAT.

Animals↗