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Biomedical subjects

K Hall

Publications and source records attributed to K Hall.

At least 217 records · Page 12Linked to original sources

Specific binding of human growth hormone but not insulin-like growth factors by human adipocytes.

Binding of human GH (hGH) and insulin-like growth factors I and II (IGFI and II) to isolated human adipocytes from adult subjects was studied. Binding equilibrium for hGH at 24 degrees C was reached at 120 min and half-maximal specific binding at 6-8 ng/ml. Apparent Ka was 2.1 X 10(9) M-1 and Bmax 7.3 X 10(-11) M/10(6) cells. The human fat cell growth hormone receptor recognized neither bovine, ovine or rat GH nor human prolactin or placental lactogen. No specific receptors for human IGFII could be demonstrated. Thus, human adipocytes do not possess IGF receptors but have specific GH receptors which recognize hGH but not GH from lower species.

Adipose Tissue↗

Affinity chromatography with amniotic fluid somatomedin binding protein in the purification of insulin-like growth factor I.

A simplified procedure has been developed for the isolation of insulin-like growth factor I from human plasma by use of affinity chromatography with the somatomedin binding protein. After acidification of human plasma and separation of insulin-like growth factor I and endogenous binding protein by cation exchange chromatography on SP-Sephadex the material was passed through a column packed with pure human amniotic fluid binding protein covalently coupled to Sepharose. The bound insulin-like growth factors I and II were eluted by 1M acetic acid and separated on a Mono S cation exchange column by use of a salt gradient. The 30 micrograms insulin-like growth factor I and 18 micrograms insulin-like growth factor II recovered from 1 liter plasma gave an overall recovery of 30% for insulin-like growth factor I but only 2.5% for insulin-like growth factor II.

Amino Acids↗

The tetraribonucleotide rCpGpCpG forms a left-handed Z-RNA double-helix.

NMR and circular dichroism studies show that the RNA tetranucleotide rCpGpCpG can form a Z-RNA left-handed double-helix. In 1.0 M NaClO4, circular dichroism measurements indicate that the tetramer is in the A-form. In 6.0 M NaClO4, there is a characteristic change in the circular dichroism, indicating that the tetramer adopts a left-handed Z-form. This conformation is verified by phosphorus and proton NMR studies. The 31P spectrum shows a large downfield shift in one of the resonances upon an increase in salt concentration. Proton nuclear Overhauser effect (NOE) experiments indicate that the guanosines are in the syn conformation. These results are consistent with the formation of a Z-form double-helix.

Base Sequence↗

Ligand and halide binding properties of chloroperoxidase: peroxidase-type active site heme environment with cytochrome P-450 type endogenous axial ligand and spectroscopic properties.

Equilibrium binding studies of exogenous ligands and halides to the active site heme iron of chloroperoxidase have been carried out from pH 2 to 7. Over twenty ligands have been studied including C, N, O, P, and S donors and the four halides. As judged from changes in the optical absorption spectra, direct binding of the ligands to the heme iron of ferric or ferrous chloroperoxidase occurs in all cases; this has been ascertained for the ferric enzyme in several cases through competition experiments with cyanide. All of the ligands except for the halides, nitrate, and acetate form exclusively low-spin complexes in analogy to results obtained with the spectroscopically related protein, cytochrome P-450-CAM [Sono, M., & Dawson, J.H. (1982) J. Biol. Chem. 257, 5496-5502]. The titration results show that, for the ferric enzyme, (i) weakly acidic ligands (pKa greater than 3) bind to the enzyme in their neutral (protonated) form, followed by deprotonation upon ligation to the heme iron. In contrast, (ii) strongly acidic ligands (pKa less than 0) including SCN-, NO3-, and the halides except for F- likely bind in their anionic (deprotonated) form to the acid form of the enzyme: a single ionizable group on the protein with a pKa less than 2 is involved in this binding. For the ferrous enzyme, (iii) a single ionizable group with the pKa value of 5.5 affects ligand binding. These results reveal that chloroperoxidase, in spite of the previously established close spectroscopic and heme iron coordination structure similarities to the P-450 enzymes, clearly belongs to the hydroperoxidases in terms of its ligand binding properties and active site heme environment. Magnetic circular dichroism studies indicate that the alkaline form (pH 9.5) of ferric chloroperoxidase has an RS-ferric heme-N donor ligand coordination structure with the N donor likely derived from histidine imidazole.

Acetates↗

Neuromuscular reeducation versus traditional programs for stroke rehabilitation.

This study compares long-term effectiveness of traditional functional retraining (TFR) with neuromuscular retraining techniques (NRT) after cerebrovascular accident (CVA). Groups of post-CVA patients from two different rehabilitation programs were matched according to early prognostic indicators. In one program NRT was emphasized while in the other the emphasis was restricted to TFR of spontaneously acquired upper extremity dexterity. Follow-up was possible in 19 of the TFR group and 20 of the NRT group who survived eight months after CVA. At least eight months post-CVA patients/families completed a telephone questionnaire regarding current functional abilities. With the single exception of self-feeding, no statistically significant differences in skill levels were found. NRT patients showed a slightly greater independence in feeding than the patients in functional retraining. It was also noted that rehabilitation hospitalization was significantly longer in the NRT group (28.57 days vs 68.3 days). The reason for this is not clear. If choice of therapeutic techniques was a contributing factor to increased lengths of stay, however, this would have major cost/effectiveness implications for program planning.

Activities of Daily Living↗

Immunoreactive somatomedin B (RIA-B) in the circulation of healthy adults and patients with endocrine disorders.

The serum and cerebrospinal fluid (CSF) levels of immunoreactive somatomedin B (RIA-B) were examined throughout life in healthy adult humans. A significant decline in serum RIA-B was observed in subjects over 60 years of age. No significant diurnal, daily, or monthly serum variation was observed in healthy subjects aged 20-60 years. However, women taking oral contraceptives had elevated RIA-B values. No significant decline in CSF RIA-B was observed in subjects over 60 years of age. A significantly lower level of RIA-B in CSF was observed in subjects sampled at 20.00 h compared to subjects sampled in the morning. A significant decline in serum RIA-B was observed in patients with hypopituitarism and diabetes mellitus and a significant elevation of serum RIA-B levels was observed in patients with hyperthyroidism. CSF RIA-B was significantly elevated in patients with Cushing's syndrome.

Adult↗

Mitogenic response of human SH-SY5Y neuroblastoma cells to insulin-like growth factor I and II is dependent on the stage of differentiation.

Human insulin-like growth factor I and II (IGF-I and IGF-II) in concentrations of 1-30 ng/ml, were shown to stimulate ornithine decarboxylase activity and [3H]thymidine incorporation in human SH-SY5Y neuroblastoma cells. Proliferation of these cells was also stimulated by IGF-I and II when added to RPMI 1640 medium, fortified with selenium, hydrocortisone, transferrin, and beta-estradiol. Labeled IGF-I and II bound to SH-SY5Y cells. The cross-reaction pattern of IGF-I, IGF-II, and insulin in competing with the binding of labeled IGF-I and IGF-II, respectively, indicated that SH-SY5Y cells express both type I and type II IGF receptors. Treatment of SH-SY5Y cells for 4 d with 12-O-tetradecanoylphorbol-13-acetate (TPA), which resulted in morphological and functional differentiation and growth inhibition, abolished the mitogenic response to both IGF-I and II. Concomitantly, the binding of IGF-II disappeared almost totally, which offers a possible explanation for the reduced biological response to IGF-II after TPA treatment. In contrast, the IGF-I binding in TPA-treated cells was only reduced to approximately 70% of the binding to control cells. It is therefore not excluded that the IGF-I receptor could be uncoupled by TPA, with persistent binding capacity for IGF-I.

Cell Cycle↗

The long-term effects of megavoltage radiotherapy as sole or combined therapy for large prolactinomas: studies with high definition computerized tomography.

The long-term sequelae of external pituitary irradiation alone or in combination with surgery and/or bromocriptine therapy have been studied in 14 patients with large prolactinomas over an observation period of 6-22 years (mean 13 years). Galactorrhoea was abolished in four of the five females with this symptom, but menstrual disturbance persisted in five of six patients. Sexual function was normal without sex hormone replacement in only one of the eight males after treatment. Neurological deficits were abolished or improved by treatment in all 9 patients with this presentation. Serum prolactin levels declined after treatment (P less than 0.001) and fell to within the normal range off bromocriptine therapy in six of the 14 patients at a mean of 9 years (range 5-17 years) after radiotherapy. All patients had anterior pituitary deficiency of some degree at reassessment, and 13 required replacement treatment. Serial skull radiographs revealed remineralization of the fossa floor in five patients and a decrease in fossa size in three. All five patients who did not also have surgery had evidence of tumour shrinkage without bromocriptine treatment (on CT scan or metrizamide cisternography). Fourth generation CT scans on completion of the study revealed a decrease in tumour mass in all patients, with varying degrees of empty sella in 13 and a cystic intrasellar tumour in the remaining one. Residual tumour was demonstrated in 10 patients, three of whom had normal serum prolactin levels, while one patient without visible tumour had persistent hyperprolactinaemia. Radiotherapy, alone or in combination with surgery and bromocriptine, effectively decreases prolactin secretion and tumour size in patients with large prolactinomas at the expense of other anterior pituitary function. Circulating prolactin levels are a poor marker of residual tumour volume.

Adolescent↗

The influence of maternal protein deprivation on the developmental pattern of serum immunoreactive insulin-like growth factor 1 (IGF-1) levels.

The influence of maternal protein deprivation on body and brain growth and on serum immunoreactive insulin-like growth factor I (IGF-I) levels was examined in rats during development. The offspring of protein-deprived mothers were significantly growth-retarded postnatally and showed an altered developmental pattern of serum immunoreactive IGF-I levels. In contrast to control animals, between days 5 and 20 postnatally, a significant elevation in serum immunoreactive IGF-I levels which peaked at day 15 was found. However, in adult growth-retarded rats a significant reduction in serum immunoreactive IGF-I levels was found. These findings suggested the preweaning period to be critical for the development of the mature somatomedin system.

Animals↗

Growth and somatomedin responses to growth hormone in Down's syndrome.

Five growth retarded children with Down's syndrome, three girls and two boys aged between 3 1/2 and 6 1/2 years with trisomy 21, were treated with human growth hormone for six months. Before treatment the growth hormone response to sleep and insulin-arginine load, as well as serum concentrations of insulin, thyroid hormones, and cortisol was found to be in the normal range. During the treatment with human growth hormone the growth velocity increased in all the children with Down's syndrome from 2.3-2.8 cm to 3.3-5.8 cm per six months. The serum concentrations of immunoreactive insulin like growth factor 1 (IGF-1) were low before treatment and increased during the treatment with human growth hormone. The serum concentrations of immunoreactive insulin like growth factor 2 (IGF-2), which were within the normal range, however, increased during treatment with human growth hormone. Children with Down's syndrome respond to treatment with human growth hormone, with an increase in both growth velocity and serum somatomedin concentrations.

Child↗

Serum levels of somatomedins and somatomedin-binding protein in pregnant women with type I or gestational diabetes and their infants.

The serum levels of the low mol wt form of somatomedin-binding protein (SMBP) were 5-fold higher in both diabetic (n = 44) and nondiabetic pregnant women (n = 14) than in nonpregnant women. No difference was found between women with type 1 diabetes and those with gestational diabetes. There was a negative correlation between maternal levels of SMBP during the last trimester and the birth weight percentile of the infants (r = -0.51). There was a 2- to 3-fold elevation of maternal insulin-like growth factor (IGF-I) levels during pregnancy in both diabetic and nondiabetic women. A positive correlation (r = 0.49) was found between maternal IGF-I levels and the birth weight percentiles of their infants. The correlation between the ratio of IGF-I to SMBP, which may reflect the IGF-I available to the placenta, to birth weight percentile was higher (r = 0.57), and the SE of estimate of weight percentile was 23%. The ratio between IGF-I and SMBP in cord blood was correlated with birth weight, although cord blood IGF-I and SMBP values were not. The IGF-II levels in cord serum were 50% higher in the infants of diabetic than in those of nondiabetic mothers. These findings raise the questions of whether maternal SMBP levels influence the amount of IGF-I available for the fetal-placental unit and whether IGF-II participates in glucose homeostasis in the fetus.

Adult↗

Evidence for Z-form RNA by vacuum UV circular dichroism.

Circular dichroism (CD) spectra in the vacuum UV region for different conformations of poly d(G-C) X poly d(G-C) and poly r(G-C) X poly r(G-C) are very characteristic. The CD of the RNA in the A-form (6 M NaClO4 and 22 degrees C) is very similar to that of the DNA in 80% alcohol where it is believed to be in the A-form. With the exception of the longest wavelength transition, the CD of the RNA in 6 M NaClO4 at 46 degrees C is similar to the CD of the DNA under conditions where it is believed to be in the Z-form (2 M NaClO4). This substantiates that poly r(G-C) X poly r(G-C) assumes a left-handed Z-conformation in 6 M NaClO4 above 35 degrees C. CD spectra for the left-handed Z-forms of both the RNA and DNA are characterized by an intense negative peak at 190-195 nm, a crossover at about 184 nm, and an intense positive peak below 180 nm. The right-handed A- and B-forms of RNA and DNA all have an intense positive peak in their CD spectra near 186 nm. The large difference in CD in the range 185-195 nm for right- and left-handed conformations of nucleic acids can be used to identify the sense of helix winding.

Circular Dichroism↗

The somatomedin-binding protein isolated from a human hepatoma cell line is identical to the human amniotic fluid somatomedin-binding protein.

Serum-free medium conditioned by the human hepatoma cell line HEP G2 was shown to contain a somatomedin-binding protein with a relative molecular mass of about 35,000. This binding protein was purified to homogeneity by the use of immunoaffinity chromatography and subsequent size exclusion chromatography. Antibodies for the immunoaffinity step were raised in rabbits against a previously isolated human amniotic fluid somatomedin-binding protein. The total composition and N-terminal amino acid sequence showed the protein to be identical to the binding protein from human amniotic fluid. Both have the N-terminal structure Ala-Pro-Trp-Gln-. The HEP G2 cell line offers a useful model to study the regulation of the synthesis and secretion of human somatomedin-binding proteins.

Amino Acid Sequence↗

The inability of dynamic tests of prolactin and TSH secretion to differentiate between tumorous and non-tumorous hyperprolactinemia.

Certain hyperprolactinemic patients have an obvious pituitary tumor while others with normal pituitary radiology may or may not harbor a pituitary microadenoma. A variety of biochemical tests have been proposed to distinguish between those with and those without pituitary tumors. The aims of this study were: firstly to examine these tests to assess their efficacy in differentiating between patients with radiologically-demonstrated pituitary tumors and normal controls; and secondly to establish if those hyperprolactinemic patients with normal radiology formed two distinct groups biochemically as might be expected if some did and some did not have tumors. The prolactin (PRL) and thyroid stimulating hormone (TSH) response to domperidone and the PRL response to TRH and insulin-induced hypoglycemia have thus been examined in hyperprolactinemic subjects with and without radiological evidence of an adenoma and in normal controls. The basal serum PRL was similar in patients with and without radiological evidence of a pituitary adenoma. The serum PRL response to all stimuli studied, expressed as a percentage of initial values, was blunted in patients with known pituitary tumors with total separation from values in control subjects. Results for patients with normal pituitary radiology were similar to those for patients with tumors with minimal overlap with controls. The peak TSH increment after domperidone was exaggerated in patients with known tumors, but overlap with control values was observed in 25%. In patients with normal radiology the peak TSH increment after domperidone was similarly increased but again overlap with control values occurred in 28%. Cluster analysis showed no evidence of two subgroups of response with in the hyperprolactinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Extensive synthesis of poly[r(G-C)] using Escherichia coli RNA polymerase.

Conditions have been found that allow for extensive synthesis of poly[r(G-C)] using Escherichia coli RNA polymerase with a poly[d(I-C) X poly[d(I-C)] template. The extensive synthesis, in which many copies of the template were produced by the enzyme, continued for 24 h. Repeated addition of the template was necessary for synthesis to continue, as the poly[r(G-C)] appeared to be binding to the template, inhibiting transcription by the polymerase. Four hundred ODU, or 20 mg of the poly[r(G-C)] has been prepared using 0.3 mg of protein.

DNA-Directed RNA Polymerases↗

Growth hormone producing pituitary adenomas with concomitant hypersecretion of prolactin are particularly sensitive to photon irradiation.

The effect of photon irradiation (50 Gy with a 3-field technique in fractionated doses) on growth hormone (GH), prolactin (PRL), and somatomedin A (SMA) was studied in 25 patients with acromegaly after previous unsuccessful surgery. In patients with concomitant hypersecretion of PRL, the GH reduction was 70 +/- 22% 1 year and 88 +/- 10% 3 years after radiotherapy. The corresponding reductions in patients with isolated GH hypersecretion were 42 +/- 25% and 60 +/- 22%. The reduction of GH levels was most notable the first year after radiotherapy in 16 patients and during the second year in 7 patients. Serum PRL decreased after radiotherapy in all patients with hyperprolactinemia, whereas PRL in normoprolactinemic patients showed inconsistent changes, including PRL increments in 8/12 patients. The effect of radiotherapy on GH and PRL was not correlated to the irradiation target volume or the cumulative radiation effect. SMA levels decreased after radiotherapy, but became normal only in 3 patients, all with pretreatment GH less than 5 micrograms/l. Radiotherapy, 3 years after treatment, appeared to be equivalent to the primary surgical intervention in reducing GH and SMA in patients with acromegaly due to advanced macroadenomas. Patients with concomitant hyperprolactinemia showed increased sensitivity to radiation compared to normoprolactinemic patients with acromegaly.

Acromegaly↗

The use of derivative and least-squares methods to analyse a polypharmaceutical product by UV spectrophotometry.

Derivative UV spectrophotometry is well established for analysing pharmaceutical products containing more than one drug. By contrast, the least-squares method for over-determined systems is rarely used, because it is assumed that measurements at a large number of wavelengths are needed to obtain good results. Both methods have advantages, and their use in combination is useful for analysing polypharmaceuticals. A combination of derivative and least-squares methods was used to analyse tablets containing pseudoephedrine hydrochloride, triprolidine hydrochloride and dextromethorphan hydrobromide. Pseudoephedrine was determined by derivative spectrophotometry. The other drugs were determined by the least-squares method at higher wavelengths where pseudoephedrine does not absorb. Satisfactory precision for the least-squares method was obtained with a manual spectrometer measuring at six wavelengths and calculating the results with a microcomputer.

Journal Article↗

Survival in young children after drowning: brain evoked potentials as outcome predictors.

Twenty young children between the ages of 4 and 103 months involved in drownings had brain evoked potential (EP) studies done shortly after the incident (median 2 days) to determine if auditory click and visual flash EP patterns were predictive of outcome. Results were examined in relation to good survival or non/poor (vegatative) level of survival. Results were also compared to selected clinical and laboratory data previously reported as predicting outcome. These preliminary findings indicate that if patients have evoked potential abnormality (EPA) scores greater than 2.7 there is little chance of survival. With EPA scores below 2.7 it was found that there is a good chance of survival. Cortical responses to auditory and visual stimulation were observed to be good predictors of outcome despite their inherent variability in young children and the presence of barbiturate coma. Brainstem responses to auditory stimulation alone were poor predictors. Previously reported clinical and laboratory predictors of outcome did not hold up except for muscle flaccidity which, when present, was associated with non/poor survival.

Brain Damage, Chronic↗