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Biomedical subjects

K Hall

Publications and source records attributed to K Hall.

At least 235 records · Page 13Linked to original sources
PubMed1985

Characterization of insulin-like growth factor II binding to human fibroblast monolayer cultures.

Two major somatomedin peptides have been isolated from human plasma, somatomedin-C/insulin-like growth factor I (SMC/IGF-I) and insulin-like growth factor II (IGF-II). Also, two types of SM/IGF receptors have been defined. Type I receptors have a higher affinity for SMC/IGF-I than IGF-II, and insulin binds to this receptor at high concentrations. Type II receptors have a higher affinity for IGF-II than SMC/IGF-I, and insulin does not bind to this receptor site. In this study, we characterized the binding of IGF-II to human monolayer fibroblast cultures, and the affinity and specificity of this binding. We also compared the binding of IGF-II to the binding of insulin and SMC/IGF-I to these cells. The receptors for IGF-II on normal human fibroblast monolayers fit the criteria for type II SM/IGF receptors, and there were more type II receptors on these cells than either insulin receptors or type I SM/IGF receptors. The type II receptors on human fibroblasts did not demonstrate autoregulation by homologous hormone, unlike the type I SM/IGF and insulin receptors. In addition, they were not changed by acute or chronic exposure to insulin. It is so far unclear what biological function IGF-II plays in vivo. This human fibroblast system will be a valuable experimental model for the study of IGF-II receptors and their relationship to the biological actions of IGF-II.

Adolescent↗
PubMed1985

Drug information services provided through a critical care satellite pharmacy.

In January, 1982, a satellite pharmacy began operating in the medical and coronary intensive care units of the Health Sciences Centre in Winnipeg. This program, which has been described in detail elsewhere, provides 24 hour on-site coverage. In addition to total unit dose and intravenous admixture services the pharmacist also monitors drug therapy and provides drug information to other health professionals in the area. With the extended hours of coverage and ready accessibility of the pharmacist it was anticipated that utilization of clinical pharmacy services would increase. As one means of assessing whether this did in fact occur, all drug information provided by the pharmacist, whether solicited or unsolicited, was recorded and tabulated each month for the first year of operation of the satellite pharmacy. This report presents the results of the data analysis.

Centralized Hospital Services↗
PubMed1985

Glasgow Outcome Scale and Disability Rating Scale: comparative usefulness in following recovery in traumatic head injury.

Clinical experience and analysis of use of the Disability Rating Scale (DRS) and the Glasgow Outcome Scale (GOS) are reported in 70 patients up to two years after head injury. Statistical analysis shows significant change demonstrated by the DRS across the intervals from two to four, two to six, and six to 12 months after injury. The DRS more sensitively reflects improvement during inhospital rehabilitation than the GOS, 71% to 33%, respectively. Significant improvement is shown up to one year after injury. Trend data on seven patients for whom two-year data were available showed continued improvement, although the data were not statistically significant. The DRS has shown itself to be a sensitive, functional, reliable, and quantitative means of monitoring patients with traumatic head injury during the course of their recovery.

Adolescent↗
PubMed1985

Transient enhancement of serum somatomedin levels prior to weaning of growth-impaired vasopressin-deficient Brattleboro rats.

Somatomedin serum levels of congenitally vasopressin-deficient Brattleboro rats were determined postnatally between day 1 and 55, and compared with heterozygous control values. Assays were performed with a radioimmunoassay of insulin-like growth factor 1 (IGF-1). A transient enhancement of immunoreactive IGF-1 levels between day 8 and 21 of age and a reduction in adulthood was found. This observation shows that the early growth impairments of the Brattleboro mutant are not due to a deficiency of IGF-1.

Animals↗
PubMed1984

Isolation and characterization of a somatomedin-binding protein from mid-term human amniotic fluid.

Human amniotic fluid is rich in a binding protein for somatomedins. This binding protein competes with human placenta membranes for labelled somatomedin A. Consequently, the placenta radioreceptorassay for somatomedin can be used for detection of the binding protein. The protein was isolated from human amniotic fluid by a three-step procedure: First, stepwise ammonium sulphate precipitation; second, hydrophobic chromatography (phenyl-Sepharose); and third, anion-exchange chromatography (fast protein liquid chromatography). The total recovery of binding protein calculated with the placenta radioreceptorassay was 50%. Polyacrylamide gel electrophoresis under native and denaturating conditions of the isolated protein disclosed a single band. The relative molecular mass was 35000, determined by exclusion chromatography, and 32000 under denaturating conditions in sodium dodecyl sulphate/polyacrylamide gel electrophoresis. The isoelectric point was 4.3 according to chromatofocusing and the amino acid composition also disclosed a high content of acidic/amidated residues. The N-terminal amino acid sequence was Ala-Pro-Trp-Gln-Cys-Ala-Pro-Cys-Ser-Ala.

Amino Acids↗
PubMed1984

Retrograde transport of [3H]GABA in the striatotegmental system of the pigeon.

The method of retrograde transport of gamma-aminobutyric acid (GABA) injected into the nigral complex of the pigeon was used to determine the transmitter-specificity of the striatotegmental projection system in this species. The results indicate that descending GABAergic projections are derived from the nucleus accumbens (Ac), ventral lobus parolfactorius (LPO) and the ventral paleostriatum (VP). In birds VP is considered comparable to the mammalian ventral pallidum/substantia innominata area. These results are interpreted in terms of the similarities and differences of striatal organization in birds, reptiles and mammals.

Animals↗
PubMed1984

The characterization of somatomedin A, isolated by microcomputer-controlled chromatography, reveals an apparent identity to insulin-like growth factor 1.

The polypeptide termed somatomedin A (SMA) was isolated from outdated human plasma by a new purification procedure, not using acid ethanol extraction. Fractions containing SMA were monitored by a placenta radioreceptorassay and a radioimmunoassay for SMA. The purification method utilized a microcomputer-controlled chromatography system, yielding both SMA (identified as insulin-like growth factor 1 (IGF-1) or a deamidated derivative) and insulin-like growth factor 2 (IGF-2). The first step of CM-Affigel blue adsorbed at neutral pH the majority of somatomedins detectable by the radioreceptorassay for SMA. Exclusion chromatography on Sephadex G-50 in 0.1 M acetic acid separated this active material from albumin and NaCl. Separation between SMA and IGF-2 was achieved on two different cation-exchange columns, but not in the final high-performance liquid chromatography step. The isoelectric points, determined by chromatofocusing, were 8.0 for SMA and 6.2 for IGF-2. The amino acid compositions of the two isolated peptides were indistinguishable from the known compositions of IGF-1 and IGF-2. Sequence analysis up to position 39 of the peptide with a pI of 6.2 also proved identity with IGF-2 for all positions examined. The peptide with a pI of 8.0, corresponding to SMA, was degraded directly as well as after CNBr cleavage. The results show that it is identical to IGF-1, with the possible exception of acid/amide assignment, which could correspond to a deamidation. If occurring in the native preparation before analysis, it could explain the chromatographic properties and isoelectric point of SMA versus IGF-1 isolated by other techniques.

Amino Acid Sequence↗
PubMed1984

Effect of dopamine agonist withdrawal after long-term therapy in prolactinomas. Studies with high-definition computerised tomography.

The clinical, radiological, and biochemical effects of dopamine agonist withdrawal after long-term treatment were investigated in seven women and eight men who had been treated for prolactinomas for 1.5 to 7 (mean 3.7) years. Before treatment, serum prolactin concentrations were 1473 to 115 000 mU/l, all patients had abnormal radiological findings, and six had suprasellar extensions of pituitary tumours. Treatment with either bromocriptine or pergolide relieved symptoms and suppressed prolactin secretion in most patients. The size of the residual tumour was defined by doing fourth generation computerised tomographic scans immediately before termination of therapy, and evidence of tumour re-expansion was sought on scans repeated 5-39 weeks later. After discontinuation of treatment, symptoms recurred in 13 of 15 patients and hyper-prolactinaemia redeveloped in 14. Other pituitary function tests remained unchanged or improved. In 13 of 15 patients tumour or gland size did not change after withdrawal of treatment. One man had a marginal increase in tumour size, while in another the pituitary tumour shrank. Thus, although cessation of long-term dopamine agonist therapy leads to recurrence of symptoms and hyperprolactinaemia, rapid tumour regrowth is uncommon and of small extent, and other pituitary function is not altered in the short term.

Adult↗
PubMed1984

IGF-II binding on human lymphoid cells: demonstration of a common high affinity receptor for insulin like peptides.

We have studied the binding of 125I-GF-II to the IM-9 human lymphoid cell line, and to human placental membranes. All of IGF-II radioligand binding to IM-9 cells, and half of the binding to human placental membranes is to a previously unrecognized common (Type-III) high affinity receptor site for insulin-like peptides, in which IGF-I and IGF-II are equipotent and insulin only slightly less potent. This common receptor represents another mechanism by which insulin, and the somatomedins can exert biological action.

Binding, Competitive↗
PubMed1984

A transmembranous NADH-dehydrogenase in human erythrocyte membranes.

Evidence is presented for a transmembranous NADH-dehydrogenase in human erythrocyte plasma membrane. We suggest that this enzyme is responsible for the ferricyanide reduction by intact cells. This NADH-dehydrogenase is distinctly different from the NADH-cytochrome b5 reductase on the cytoplasmic side of the membrane. Pretreatment of erythrocytes with the nonpenetrating inhibitor diazobenzene sulfonate (DABS) results in a 35% loss of NADH-ferricyanide reductase activity in the isolated plasma membrane. Since NADH and ferricyanide are both impermeable, the transmembrane enzyme can only be assayed in open membrane sheets with both surfaces exposed, and not in closed vesicles. The transmembrane dehydrogenase has affinity constants of 90 microM for NADH and 125 microM for ferricyanide. It is inhibited by p-chloromercuribenzoate, bathophenanthroline sulfonate, and chlorpromazine.

Cytochrome Reductases↗
PubMed1984

The binding of insulin-like growth factor II to the erythroleukemia cell line K562.

The erythroleukemia cell line K562 was previously shown to have specific binding sites for insulin but not for insulin-like growth factor I (IGF-I). In this study the presence of specific receptors for insulin-like growth factor II (IGF-II) is established. Scatchard analysis of the competition curve for IGF-II disclosed a non-cooperative binding kinetic with a calculated affinity constant 2.4 X 10(8) M-1 and a receptor number of 4.8 X 10(4) sites/cell. IGF-I displayed 10% crossreactivity over the IGF-II receptor but insulin did not crossreact at all. Instead insulin, present in high concentrations, enhanced the binding of IGF-II. The presence of IGF II but not IGF-I receptors makes the K562 cell line suitable for studying properties of the type-2 receptor.

Binding Sites↗
PubMed1984

Effects of hysterectomy and uterine extracts on the endocrine system of adult, nonpregnant rats.

Plasma concentration and anterior pituitary content of growth hormone (rGH), thyroid stimulating hormone (rTSH), prolactin, follicle stimulating hormone (rFSH), luteinizing hormone (rLH) as well as the plasma concentrations of triiodothyronine (T3), thyroxine (T4), corticosterone and immunoreactive somatomedin A (SM-A) have been determined in intact, ovariectomized or ovo-hysterectomized rats with and without treatment with steroid-free uterine extracts. The endocrine organs were weighed. Two weeks after hysterectomy the body weight was decreased, the weight of adrenals was increased, the plasma GH concentrations increased and the plasma TSH and T3 concentrations were decreased compared to the sham operated controls. Treatment with steroid-free uterine extracts had opposite effects; furthermore, a reduction of pituitary FSH, GH and prolactin content was observed. Plasma immunoreactive SM-A concentrations were not significantly influenced by this treatment, but there was a positive correlation between the body weight and SM-A and a negative correlation between the plasma GH and plasma SM-A concentrations regarding the individual values of hysterectomized, uterine-extract-treated and ovariectomized animals. The results suggests that uterine factors can influence the synthesis and release of several hormones and the weight of some endocrine organs in adult, nonpregnant rats.

Animals↗
PubMed1984

Free valproic acid: steady-state pharmacokinetics in patients with intractable epilepsy.

Free and total valproic acid (VPA) pharmacokinetic evaluation was carried out at steady state in six young epileptics who were also receiving other anticonvulsants. Subjects received their usual morning dose of VPA after an overnight fast. Blood samples for free and total VPA were taken prior to the dose and frequently thereafter for 12 hours. The calculated pharmacokinetic parameters for total VPA and free VPA were: half-lives of 7.5 +/- 1.6 hours and 5.0 +/- 1.5 hours, volumes of distribution of 0.189 +/- 0.038 l/kg and 1.51 +/- 0.98 l/kg, and clearances of 0.30 +/- 0.06 and 3.6 +/- 2.0 ml/min/kg., respectively. There was a strong correlation between percent free VPA and total VPA (r = 0.81) but marked inter- and intra-subject variations were seen. Studies attempting to correlate VPA levels to clinical response must take such data into account.

Adolescent↗
PubMed1984

Somatomedin levels in pregnancy: longitudinal study in healthy subjects and patients with growth hormone deficiency.

Somatomedin (Sm) levels throughout pregnancy were determined in a longitudinal study of four normal women and three patients with GH deficiency by use of the RIA for Sm-A, a newly developed RIA for insulin-like growth factor 2 (IGF-2), and the placenta RRA for Sm-A. In both normal women and those with GH deficiency, there was a continuous rise of immunoreactive Sm-A throughout pregnancy. During the third trimester the levels were 2-fold elevated above the level in nonpregnant age-matched normal subjects. No change of immunoreactive IGF-2 levels was found in the normal pregnant women, whereas an increase from low to normal levels was found in GH-deficient patients during pregnancy. The placenta RRA-Sm-A did not detect the increase of Sm-A immunoactivity in the normal pregnant women, whereas the levels were normalized in GH-deficient patients. After delivery a rapid fall of Sm levels occurred in patients with GH deficiency. The calculated half-lives for immunoreactive Sm-A and IGF-2 were 27 and 52 h, respectively. The birth weights of the seven children were significantly (P less than 0.05) correlated to both the individual peak and the mean maternal value of immunoreactive Sm-A during the last trimester. The present findings indicate that the production of both IGF-1 and IGF-2 related peptides during pregnancy is independent of maternal pituitary GH production.

Adult↗
PubMed1984

Somatomedin A increments are diminished in acromegaly with concomitant hyperprolactinaemia.

The influence of prolactin (Prl) on growth hormone (GH) regulated somatomedin A (SMA) levels was studied in 30 patients with acromegaly before and after transsphenoidal pituitary surgery. Pre-operative GH levels were elevated in all patients and SMA levels in all but one patient. Eleven patients (33%) showed hyperprolactinaemia. There was no correlation between GH and SMA levels. Plasma GH did not differ in patients with GH and Prl producing adenomas compared to those with isolated GH hypersecretion. SMA levels, however, were significantly lower in patients with hyperprolactinaemia than in those with normal serum prolactin (P less than 0.001). After surgery GH decreased in all and SMA levels in all but one patient. Despite similar post-operative GH levels SMA decreased to significantly lower levels in patients with combined hypersecretion of GH and Prl compared to patients with normal prolactin levels (P less than 0.05). Nine of the 11 patients with hyperprolactinaemia showed normal Prl after surgery. The SMA levels in patients with acromegaly seem to be suppressed in patients with pre-operatively concomitant hyperprolactinaemia before as well as after adenomectomy regardless of the normalization of Prl. Our findings offer one explanation of the lack of correlation between SMA and GH levels in acromegaly.

Acromegaly↗
PubMed1984

Immunoreactive IGF-II in serum of healthy subjects and patients with growth hormone disturbances and uraemia.

A radioimmunoassay has been developed for IGF-II, using Sepharose-coupled antibodies. Porcine insulin, human insulin and human proinsulin showed no cross-reaction, whereas the cross-reaction for IGF-I was 10%. To minimize the influence of the binding protein(s), all serum samples were extracted with acid ethanol before assay. The mean serum level of immunoreactive IGF-II and 95% confidence limit in 46 healthy adults were 587 ng/ml and 354-974 ng/ml, respectively. In contrast to the declining levels of IGF-I with increasing age, no such age-dependent decrease was found for IGF-II levels between 20 to 70 years. No difference in IGF-II levels was found between patients with acromegaly and healthy adult controls. In cord serum and serum from adult patients with GH deficiency the levels were significantly lower (P less than 0.001) compared to controls. In diabetic patients with uraemia the mean level and 95% confidence limit were 1222 ng/ml and 532-2808 ng/ml, respectively. Thus, significantly increased serum levels of immunoreactive IGF-II have only been found in serum from patients with uraemia. Whether this is due to an increased production of IGF-II, or secondary to other factors such as the binding protein(s), will require further investigation.

Acromegaly↗