Search PubMed⌕ Search

Biomedical subjects

K King

Publications and source records attributed to K King.

At least 91 records · Page 5Linked to original sources

Fetal weight-cerebellar diameter discordance as an indicator of asymmetrical fetal growth impairment.

In this study on the effect of fetal growth impairment < or = 25th percentile on the transverse cerebellar diameter and its relationship with other fetal biometric parameters, the sample comprised 50 women with singleton pregnancies referred for ultrasound evaluation because of clinically suspected intrauterine growth retardation. The cerebellar diameter of asymmetrically growth-impaired fetuses remained within the normal range although it was found to be reduced when compared with that of normal fetuses (4.4 +/- 0.9 versus 4.8 +/- 0.7, P < .05). Although other biometric parameters (biparietal diameter, femur length and abdominal and head circumferences) were also reduced in growth-impaired fetuses, the ratios of these biometric parameters to cerebellar diameter were similar to those of unaffected fetuses. Fetal weight was affected to a greater extent than the cerebellar diameter, leading to discordance between the two parameters. This discordance identified almost all asymmetrically growth-impaired fetuses with a sensitivity of 95.6% and specificity of 96.3%. In contrast, the ratio of head circumference to abdominal circumference remained normal in more than half of the fetuses. Fetal weight-to-cerebellar diameter discordance is a very sensitive and specific indicator of asymmetrical fetal growth impairment.

Biometry↗

Concordance between clinician and patient assessment of physical and mental health status.

The degree of concordance between clinicians' and patients' assessment of the patient's physical and mental functioning was examined in 166 consecutive eligible outpatients with rheumatoid arthritis (RA) using 4-category ordinal scales. The weighted kappa statistic was 0.39 for physical functioning and 0.30 for mental functioning, both indicating a fair degree of concordance. This disagreement differed in magnitude and direction depending on the level of disability present. We conclude that clinicians and their patients with RA often disagree in their assessment of the degree of physical and mental impairment that the patient experiences. These disagreements demonstrate the need for formal assessments of outcome and should be recognized and resolved when managing individual patients.

Adolescent↗

Incidence of systemic reactions during rush immunotherapy.

Rush immunotherapy (RIT) was administered on an outpatient basis to 11 patients. Of these, nine had asthma and four were steroid-dependent. All patients received extracts containing a mixture of antigens to which they were prick-sensitive. FEV1s were greater than 80% predicted before starting RIT. Four patients each required a 1 week steroid "burst" to accomplish this. A series of 8 subcutaneous injections were given starting with 0.3 mL of 1:100,000 (wt/vol) and ending with 0.10 mL of 1:100 (wt/vol) 1.5 days later. A dose of 0.15 mL of 1:100 was given weekly after that. All patients but one completed the RIT. Four had sore arms, four had pruritus and/or sneezing, four developed wheezing, and one experienced anaphylaxis with hypotension. Systemic reactions tended to occur at the higher doses and usually more than 30 minutes after a previous injection. Subsequent weekly injections were tolerated without reactions by seven of the patients. Rush immunotherapy is an effective method for administering a high dose of allergen in a very short time period. Due to the risk of systemic reactions it needs to be given under carefully controlled conditions.

Adolescent↗

Treatment of fetal supraventricular tachycardia with flecainide acetate after digoxin failure.

Transplacentally administered digoxin is the drug of choice for the treatment of fetal supraventricular tachycardia. We describe a case of fetal supraventricular tachycardia associated with fetal hydrops that did not respond to digoxin treatment because of a lack of transplacental passage. In contrast, flecainide acetate crossed the placenta and cured the fetus. The clinical implications of this new treatment are discussed.

Adult↗

Control of yeast mating signal transduction by a mammalian beta 2-adrenergic receptor and Gs alpha subunit.

To facilitate functional and mechanistic studies of receptor-G protein interactions, [corrected] the human beta 2-adrenergic receptor (h beta-AR) has been expressed in Saccharomyces cerevisiae. This was achieved by placing a modified h beta-AR gene under control of the galactose-inducible GAL1 promoter. After induction by galactose, functional h beta-AR was expressed at a concentration several hundred times as great as that found in any human tissue. As determined from competitive ligand binding experiments, h beta-AR expressed in yeast displayed characteristic affinities, specificity, and stereoselectivity. Partial activation of the yeast pheromone response pathway by beta-adrenergic receptor agonists was achieved in cells coexpressing h beta-AR and a mammalian G protein (Gs) alpha subunit-demonstrating that these components can couple to each other and to downstream effectors when expressed in yeast. This in vivo reconstitution system provides a new approach for examining ligand binding and G protein coupling to cell surface receptors.

Amino Acid Sequence↗

The ontogeny of feline temporal lobe epilepsy: kindling a spontaneous seizure disorder in kittens.

We describe the ontogeny of feline temporal lobe epilepsy after amygdala kindling in 24 cats, aged 2.5 months to over 1 year. In so doing, we report the first experimental model of spontaneous epilepsy in immature animals. Preadolescent kittens (n = 12 less than or equal to 6.5 months) are far more likely to develop epilepsy, indexed by spontaneous seizures, than are adult cats (n = 12 greater than 1 year). Moreover, youth accelerated the development of epilepsy. The younger the kitten at the beginning of kindling, the more probable and rapid the onset of spontaneous seizures. Failed postictal depression was the most reliable precursor of spontaneous seizures in immature cats. However, spontaneous epilepsy continued after postictal refractory periods stabilized and was still present when kittens matured to adulthood. Collectively, the results suggest that failed inhibition contributes to the onset of spontaneous epilepsy in immature animals but that other morphologic, physiological and/or chemical changes might sustain epilepsy afterwards.

Aging↗

Strategies for enhancing compliance in the dialysis elderly.

Noncompliance must be viewed as a symptom of another problem or problems. Treatment plans should be developed based on an individualized assessment of the patient's physiologic functioning and psychosocial situation. It must be determined whether the patient is intentionally or unintentionally not complying. Staff must also be aware of how they impact compliance. While staff have a responsibility to maximize the individual's efforts to comply, it must be realized that the ultimate decision and responsibility rests with the patient.

Aged↗

Expansion of the alpha 2-adrenergic receptor family: cloning and characterization of a human alpha 2-adrenergic receptor subtype, the gene for which is located on chromosome 2.

Pharmacologic, biochemical, and genetic analyses have demonstrated the existence of multiple alpha 2-adrenergic receptor (alpha 2AR) subtypes. We have cloned a human alpha 2AR by using the polymerase chain reaction with oligonucleotide primers homologous to conserved regions of the previously cloned alpha 2ARs, the genes for which are located on human chromosomes 4 (C4) and 10 (C10). The deduced amino acid sequence encodes a protein of 450 amino acids whose putative topology is similar to that of the family of guanine nucleotide-binding protein-coupled receptors, but whose structure most closely resembles that of the alpha 2ARs. Competition curve analysis of the binding properties of the receptor expressed in COS-7 cells with a variety of adrenergic ligands demonstrates a unique alpha 2AR pharmacology. Hybridization with somatic cell hybrids shows that the gene for this receptor is located on chromosome 2. Northern blot analysis of various rat tissues shows expression in liver and kidney. The unique pharmacology and tissue localization of this receptor suggest that this is an alpha 2AR subtype not previously identified by classical pharmacological or ligand binding approaches.

Amino Acid Sequence↗

Linguistic performance in schizophrenia: a comparison of acute and chronic patients.

A computer-assisted analysis of samples of free speech from acute schizophrenics (n = 50), chronic schizophrenics (n = 27) and normal subjects (n = 50) enabled a comparison of the linguistic profiles of the three groups. The chronic group consistently emerged as the most impaired, on measures of complexity, integrity (error) and fluency of speech, with the acute patients performing less well than normal speakers but better than chronic patients. Demographic differences could account for only a small number of the linguistic differences. A comparison of chronic schizophrenics from the community and those from long-stay wards suggested that their poor linguistic performance was in some way related to the illness process and not to institutionalisation. Three possible explanations for these results were considered, particularly the possibility that low complexity of speech, negative symptoms and poor outcome are in some way related.

Acute Disease↗

Re-examination of the language of psychotic subjects.

To investigate whether language in schizophrenia deteriorated progressively, 11 schizophrenic subjects, 9 manic subjects and 9 controls were re-tested after an interval of three years using the computer-assisted syntactical analysis technique of Morice. In 13 of the 16 linguistic variables described as hallmarks of schizophrenic speech decline, deterioration was noted in schizophrenics in the direction predicted and relative to the manic and control groups. The deterioration was most pronounced in complexity and integrity of speech. One variable remained unchanged and two (semantic variables) showed marginal improvement. It was concluded that language, and in particular syntax, does deteriorate in the schizophrenic process.

Bipolar Disorder↗

Comparison of nitrogen-15 and diaminopimelic acid for estimating bacterial protein synthesis of lactating cows fed diets of varying protein degradability.

Three lactating Holstein cows fitted with duodenal cannulae were fed diets containing cottonseed meal, corn gluten meal, or blood meal as protein supplements in a 3 c 3 Latin square experiment. Diets averaged 15% CP and were 60% concentrate, 31% corn silage, and 9% alfalfa hay. The flow marker was Cr2O3; the bacterial protein fraction of digesta CP was estimated by 15N (as ammonium sulfate) and diaminopimelic acid. The undegraded fraction of total feed protein entering the duodenum for respective diets was .52, .57, and .69. The 15N method was less variable than diaminopimelic acid. Based on 15N, percentage of bacterial of total protein differed among treatments (61.5, 59.4, and 55.0, respectively). Ten percent more protein entered the duodenum on blood meal than other diets, but differences were not significant. Protein sources were similar in microbial passage, but degraded protein was used most efficiently for microbial synthesis on blood meal. Incorporation of 15N consumed into bacterial protein ranged from 50 to 83% with numerically highest values on blood meal, suggesting greater efficiency of ammonia, capture. Recoveries of 15N for the 72 h as milk, feces and urine ranged from 54 to 78%.

Animal Feed↗

Glu-111 is required for activation of the DNA cleavage center of EcoRI endonuclease.

Gap repair in the presence of 2'-deoxycytosine 5'-O-(1-thiotriphosphate) has been utilized to mutagenize the amino-terminal one-half of the structural gene for EcoRI endonuclease. This approach has led to identification of over 200 mutants defective in endonuclease function. One mutant protein, which binds to the EcoRI sequence but displays greatly reduced cleavage activity, is the consequence of a Glu to Gly change at position 111. This protein has been purified to homogeneity and characterized in detail. Subunit interactions governing the tetramer to dimer transition of the mutant endonuclease are near normal as are parameters governing its interaction with specific and nonspecific DNA sequences. However, the rate constants for first and second strand cleavage steps are reduced by 60,000- and 30,000-fold, respectively, as a consequence of the Glu----Gly change. The defect in chemical cleavage steps can be partially overcome by elevating the pH of the reaction buffer from 7.6 to 8.5, conditions which enhance the rate of EcoRI* strand cleavage by wild type enzyme to a similar degree. We suggest that the Glu-111 mutation affects an interface between recognition and cleavage functions of the enzyme, an idea consistent with the suggestion that the cleavage center of the endonuclease is subject to activation upon specific recognition of the EcoRI sequence.

Base Sequence↗

The negative charge of Glu-111 is required to activate the cleavage center of EcoRI endonuclease.

King et al. (King, K., Benkovic, S. J., and Modrich, P. (1989) 264, 11807-11815) have shown that Glu-111 is required for DNA cleavage by EcoRI endonuclease and have suggested that this residue is required for activation of the cleavage center upon specific recognition. We have substituted Gln or Asp for Glu-111 by oligonucleotide-directed mutagenesis. First and second strand cleavage rate constants are reduced by a factor of more than 10(4) by the Gln-111 substitution. However, these rate constants are enhanced 9-fold when pH is increased from 7.6 to 8.5, which enhances strand cleavage at EcoRI sites by wild type endonuclease to a similar degree. The specific affinity of Gln-111 endonuclease for EcoRI sites is 1000 times greater than that of wild type enzyme reflecting a decrease in the rate constant governing specific complex dissociation. In contrast to Gln-111 endonuclease, the equilibrium specific affinity of Asp-111 endonuclease for the EcoRI sequence is similar to that of wild type enzyme, and first and second strand cleavage rate constants are reduced only 100-fold relative to wild type enzyme. These results suggest that a negative charge on residue 111 is required for strand cleavage and are consistent with participation of Glu-111 in activation of the DNA cleavage center, with energy associated with specific sequence recognition driving this process.

DNA, Bacterial↗