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Biomedical subjects

K Hall

Publications and source records attributed to K Hall.

At least 145 records · Page 8Linked to original sources

Cervical cancer screening. Past success and future challenge.

Population screening for cervical cancer resulted in significant reduction in the morbidity and mortality from cervical cancer. An increased understanding of the relationship of HPV infection with cervical cancer and the natural history of cervical cancer precursor lesions further solidifies and expands the biological basis for cervical cancer screening. Pap tests in asymptomatic women remain the cornerstone of cervical cancer screening. Clinicians should be cognizant of the significant false-negative rate of Pap smears. Meticulous attention to proper Pap smear technique is necessary to maximize the sensitivity of the test. Further research is needed to establish the role of cervicography and HPV DNA hybridization techniques in cervical cancer screening.

Adult↗

Characterization of an extended form of recombinant human insulin-like growth factor II.

To investigate the biological role of variants of human insulin-like growth factor II (IGF-II), an extended form designated IGF-IIE21, with a molecular mass of 9.8 kDa, was produced in Escherichia coli as a stable and soluble secreted fusion protein. After site-specific cleavage of the affinity purified fusion protein, followed by purification using ion exchange and reversed phase chromatography, it could be demonstrated that IGF-IIE21 and IGF-II have similar or identical activities according to radioimmunoassay and radioreceptor assay. However, IGF-IIE21 showed only 1% growth promotion activity as compared with IGF-II in a clonal expansion assay using human K562 cells which lacks IGF-I receptors. These results suggest that this extended variant of IGF-II can bind to the receptor but has limited growth promoting activity.

Amino Acid Sequence↗

Identification of H+/K(+)-ATPase alpha,beta-heterodimers.

Glutaraldehyde treatment of the C12E8 solubilized H+/K(+)-ATPase crosslinks the catalytic subunit with an apparent molecular mass of 94 kDa in SDS polyacrylamide gels into two Coomassie stained particles migrating at approx. 147 and 173 kDa. The subunit composition of these particles was determined from the comparative distribution of FITC fluorescence, wheat germ agglutinin and anti-beta antibody reactivity in control and crosslinked preparations. FITC exclusively labelled the catalytic monomer of the native preparation and its fluorescence was initially distributed into two broad bands centered at approx. 147 and 173 kDa after crosslinking. These fluorescent bands coincided with the Coomassie stained particles. A glycoprotein(s) detected by wheat germ agglutinin reactivity was present in diffuse areas between 65 and 86 kDa and 95 to 134 kDa in the control preparation. This area was also labelled by the anti-beta antibodies. With crosslinking, the distribution of the wheat germ agglutinin reactive protein and anti-beta antibodies coincided with the crosslinked particles labelled by FITC. The presence of both the catalytic monomer and the beta subunit glycoprotein in the crosslinked particles indicated that these proteins were closely associated in the C12E8 solution. This suggests that the minimal structural particle of the H+/K(+)-ATPase is an alpha,beta-heterodimer.

Adenosine Triphosphatases↗

Analog language teaching versus natural language teaching: generalization and retention of language learning for adults with autism and mental retardation.

Examined the effects of two instructional methods on language generalization and long-term retention in 23 adults with autism and severe to profound mental retardation. Analog language teaching employed discrete trials in a controlled setting concentrating on discrimination and identification of materials. Natural language teaching emphasized instruction through interactions that occurred incidentally to training students in the use of materials to perform functional tasks. Assessments were conducted under conditions favoring analog teaching to assure against partiality toward natural language teaching. Under such disadvantageous conditions, the methods of natural language teaching would be supported by results showing either no difference or an advantage in their favor. Both techniques increased initial and long-term generalization though the results suggest no relative superiority for either method under these assessment conditions. A significant interaction was found between prior functioning level and sequence of instruction. Because natural language teaching has many strengths, few drawbacks, and produces equal generalization and retention under disadvantageous conditions, it is strongly supported as preferable for people with autism and mental retardation.

Adolescent↗

The insulin-like growth factor binding protein-1 in low and high insulin responders before and during dexamethasone treatment.

To investigate the influence of normal insulin levels on levels of the insulin-like growth factor binding protein-1 (IGFBP-1) we measured this peptide postabsorptively and during hyperglycemic clamp in 17 healthy subjects, nine with low insulin response (LIR) and eight with high insulin response (HIR). The study was performed before and after 60 hours of treatment with dexamethasone 6 mg/d. The fasting levels of IGFBP-1 were significantly higher in LIR, 36 +/- 2.5 micrograms/L, than in HIR, 22 +/- 2.6 micrograms/L (P less than .01), while no differences in glucose, insulin, and C-peptide concentrations were found. Dexamethasone induced an increase in basal concentrations of insulin, while IGFBP-1 levels decreased to 18.8 +/- 2 micrograms/L in LIR (P less than .01) and to 14.0 +/- 0.9 micrograms/L in HIR (P less than .05). There was no correlation between the individual basal IGFBP-1 concentrations and basal insulin levels. In contrast, basal levels of IGFBP-1 were inversely correlated to the integrated insulin or C-peptide concentrations during the hyperglycemic clamp both before (r = -.67, P less than .01) and during dexamethasone (r = -.79, P less than .001). Dexamethasone, which increased the insulin resistance, did not change the relationship between basal IGFBP-1 and the glucose-induced insulin release. In conclusion, the morning levels of IGFBP-1 in healthy subjects reflect the acute beta-cell responsiveness to glucose, which may correspond to integrated diurnal insulin levels. The inhibitory effects of dexamethasone on the morning levels of IGFBP-1 can be explained by attendant hyperinsulinemia.

Adult↗

Comparison of spinal fluid beta 2-microglobulin levels with CD4+ T cell count, in vitro T helper cell function, and spinal fluid IgG parameters in 163 neurologically normal adults infected with the human immunodeficiency virus type 1.

Beta 2-microglobulin levels were measured in the cerebrospinal fluid (CSF) and serum of 163 human immunodeficiency virus-positive (HIV+) persons with normal neurologic physical examinations. None were on antiretroviral therapy. Only 3% had a positive CSF HIV p24 antigen test. The CSF beta 2-microglobulin levels increased as the CD4+ T cell count decreased. Intrathecal production of beta 2-microglobulin was suggested by finding CSF concentrations greater than serum concentrations in 15% of patients. The CSF beta 2-microglobulin levels rose as in vitro T helper cell function deteriorated, independent of CD4+ T cell count. CSF beta 2-microglobulin levels paralleled CSF IgG, IgG index, and IgG synthesis. Higher CSF beta 2-microglobulin levels were found in persons with positive CSF oligoclonal bands. CSF beta 2-microglobulin concentration may serve as a marker for subclinical neurologic damage due to HIV. If this is established, defining the effect of anti-HIV interventions on CSF beta 2-microglobulin would be warranted.

Albumins↗

Human immunodeficiency virus infection in the US Air Force: seroconversions, clinical staging, and assessment of a T helper cell functional assay to predict change in CD4+ T cell counts.

As of January 1990, 933 persons with human immunodeficiency virus type 1 (HIV-1) infection were clinically evaluated at Wilford Hall US Air Force (USAF) Medical Center. The Walter Reed HIV staging system was used in these evaluations to describe disease status and progression. Most persons were diagnosed through mandatory HIV testing in the USAF and were asymptomatic at the time of diagnosis. As of May 1990, 161 HIV-positive seroconverters (estimated overall seroconversion rate of 0.156/1000 person-years between 30 June 1988 and 1 July 1990) had been identified among active-duty USAF personnel, as they had previously tested negative for antibody to HIV. Men constitute 95% of the USAF HIV-positive population. An in vitro T helper cell functional assay was assessed to predict rate of CD4+ T cell decline over the subsequent year (mean, 15 months) in patients with greater than 200 CD4+ T cells/mm3. This assay may prove useful for prognostication and comparisons of patients in clinical trials of anti-HIV interventions.

Adult↗

Estrogen treatment of tall girls: dose dependency of effects on subsequent growth and IGF-I levels in blood.

Three groups of girls with mean final height predictions of 185.3 cm were treated in 3-week cycles with 0.25, 0.5, or 1.0 mg of ethinylestradiol. The three groups were comparable with regard to chronological age, bone age, height prediction, and duration of treatment. Reduction in final height of 5.5-5.9 cm/group in comparison with the initial prediction was observed in all treated groups. This reduction appeared independent of estrogen dose. Subsequent height increases were limited to about 50% of the predicted gain in all cases. In a comparable group of untreated tall girls the prediction method overestimated the final height by 1.2 cm. In the groups receiving 1.0 and 0.5 mg EtE2 a significant reduction in IGF-I levels was achieved within three to six months after the start of estrogen therapy.

Adolescent↗

Demonstration of insulin-like growth factors I, II and heterogeneous insulin-like growth factor binding proteins in the cyst fluid of patients with craniopharyngioma.

Insulin-like growth factor (IGF)-II and its binding proteins were demonstrated to be present in human craniopharyngioma cyst fluid using gel filtration and ligand blot analyses. Immunoreactive IGF-II in 3 patients was found to be 274, 232 and 310 ng/ml after gel chromatography whereas IGF-I concentrations were 13, 8 and 15 ng/ml. The IGF-II levels were severalfold higher in cyst fluid than in spinal fluid while the IGF-I levels in both fluids did not differ significantly. The binding proteins showed high affinities for [125I]IGF-II which could be displaced by unlabelled IGF-II. With the ligand blot analysis, [125I]IGF-II shows bands at 300, 175 and 46/43 kilodaltons probably representing IGF-II receptor and IGFBP-3. IGFBP-1 levels 17, 22 and 45 ng/ml, respectively, were undetectable by ligand blot.

Adult↗

Serum levels and molecular sizes of growth hormone during pregnancy in relation to levels of lactogens, insulin-like growth factor I and insulin-like growth factor binding protein-1.

Growth hormone (GH), placental lactogen (PL), prolactin (PRL), insulin-like growth factor I (IGF-I) and IGF binding protein-1 (IGFBP-1) were determined in serum by radioimmunoassays (RIAs) in 12 women during pregnancy. GH and PL were analyzed by two monoclonal antibodies (Mab 3 and Mab 1) raised against pituitary GH. Serum IGFBP-1 had reached maximum levels at midpregnancy while PRL, PL and IGF-I increased continuously during pregnancy. Mab 1, which cross-reacts with PL, measured consistently higher levels of PL in serum than a commercial PL RIA (p less than 0.01) due to interference of cross-reacting serum proteins in the Mab 1 RIA. The GH-specific Mab 3 showed decreasing GH levels in unfractionated serum throughout gestation, but detected GH-immunoreactive proteins of approximately 40-200 kD after molecular sieve chromatography of pooled serum from late pregnancy. It is suggested that the formation of GH complexes of large molecular mass account for the successive disappearance of monomeric GH during pregnancy.

Adult↗

Comparison of acid ethanol extraction and acid gel filtration prior to IGF-I and IGF-II radioimmunoassays: improvement of determinations in acid ethanol extracts by the use of truncated IGF-I as radioligand.

Insulin-like growth factor binding proteins interfere in the IGF-I and -II radioimmunoassays. In an attempt to overcome this problem, we have compared the use of truncated IGF-I, with reduced IGFBP affinity, and IGF-I as radioligands for IGF-I RIA measurements in serum separated by acid gel filtration or acid ethanol extraction followed by cryo-precipitation. With truncated IGF-I as radioligand the IGF-I measurements in acid gel filtrates and acid ethanol extracts were significantly correlated in healthy subjects (N = 42, r = 0.91, p less than 0.001) and in patients with acromegaly (N = 10, r = 0.85, p less than 0.01), GH deficiency (N = 10, r = 0.88, p less than 0.001) or Type I diabetes mellitus (N = 10, r = 0.90, p less than 0.001). In contrast, the IGF-I concentrations in acid ethanol extracts determined with IGF-I as radioligand did not correlate with those in acid gel filtrates using truncated IGF-I radioligand in patients with acromegaly (r = 0.61, NS) or GH deficiency (r = 0.46, NS). In the latter group the mean IGF-I concentrations measured in acid ethanol extracts were erroneously elevated by 112%. Low-affinity antibodies used for IGF-II RIA determinations failed to give reliable results in acid ethanol extracts from patients with Type I diabetes mellitus or GH deficiency. In conclusion, erroneously high IGF-I concentrations owing to binding of the radioligand to IGFBPs not completely removed by acid ethanol extraction can be avoided by the use of truncated IGF-I as radioligand.

Acromegaly↗

A human XY female with a frame shift mutation in the candidate testis-determining gene SRY.

The primary decision about male or female sexual development of the human embryo depends on the presence of the Y chromosome, more specifically on a gene on the Y chromosome encoding a testis-determining factor, TDF. The human sex-determining region has been delimited to a 35-kilobase interval near the Y pseudoautosomal boundary. In this region there is a candidate gene for TDF, termed SRY, which is conserved and specific to the Y chromosome in all mammals tested. The corresponding gene from the mouse Y chromosome is deleted in a line of XY female mutant mice, and is expressed at the expected stage during male gonadal development. We have now identified a mutation in SRY in one out of 12 sex-inversed XY females with gonadal dysgenesis who do not lack large segments of the short arm of the Y chromosome. The four-nucleotide deletion occurs in a sequence of SRY encoding a conserved DNA-binding motif and results in a frame shift presumably leading to a non-functional protein. The mutation occurred de novo, because the father of the sporadic XY female that bears it has the normal sequence at the corresponding position. These results provide strong evidence for SRY being TDF.

Amino Acid Sequence↗

Location of the carbohydrates present in the HK-ATPase vesicles isolated from hog gastric mucosa.

The glycosylation of H+K(+)-ATPase vesicles isolated from hog gastric mucosa was investigated by various methods. Following protein separation on sodium dodecyl sulfate reducing gels and transfer to poly(vinyl difluoride) membranes, binding of concanavalin A was confined to the 94-kDa band which corresponds to the catalytic subunit. In contrast, wheat germ agglutinin binding occurred in a region below the 94-kDa subunit, corresponding to the 60-85-kDa region, and also to protein just above the catalytic subunit. Treatment with glycopeptidase F removed most of the concanavalin A staining and also the wheat germ agglutinin staining found below the 94-kDa region, but spared the higher molecular weight wheat germ agglutinin reactive material. During the deglycosylation experiments a protein of 35-kDa was produced. Sequencing analysis of V8 protease generated peptide fragments of the 35-kDa protein show at least 30% homology with the Na+K(+)-ATPase beta-subunits. Labeling of the carbohydrates by galactosyltransferase and [3H]uridine diphosphate-galactose showed that the sites of labeling were extracellular and were confined to the wheat germ agglutinin staining regions. Two molecular weight regions, below the 94-kDa region, of 60 and 85 kDa were identified. Electron microscopy using postembedding staining techniques showed that both concanavalin A and wheat germ agglutinin staining occurred on the extracellular face of the gastric vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

Factors related to renal haemodynamics in young type-1 diabetes mellitus patients.

The influence of metabolic control (HbA1c), noradrenaline (NA) and insulin-like growth factors (IGF-I and IGF-II) on renal function and size was investigated in 11 insulin-dependent diabetes mellitus patients aged 11-17 years. Renal function was evaluated in terms of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal size was determined as renal parenchymal volume (RPV) by ultrasonography. The patients' HbA1c values ranged from 8.2% to 12.9% (normal range 5.5-8.5%) and their GFR and ERPF were higher than normal. Their IGF-II values were higher, and NA and IGF-I levels were lower than those of healthy controls. Inverse correlations between NA and GFR (r = -0.66) and NA and ERPF (r = -0.63) were found. No correlation was found between serum IGF-I and renal functional parameters. The IGF-II values correlated with GFR and HbA1c (r = 0.63, r = 0.70 respectively). There were linear correlations between RPV and GFR, RPV and ERPF, HbA1c and GFR, and ERPF and RPV. Decreased NA concentrations and increased IGF-II values appear to be factors contributing to renal hyperfunction in these patients.

Adolescent↗