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Biomedical subjects

K Hill

Publications and source records attributed to K Hill.

At least 109 records · Page 6Linked to original sources
PubMed1993

Further analysis of the cognitive effects of tetrahydroaminoacridine (THA) in Alzheimer's disease: assessment of attentional and mnemonic function using CANTAB.

Results of a placebo controlled cross-over trial (N = 89) of the anticholinesterase drug THA as a treatment for dementia of the Alzheimer's type (DAT) are reported, with reference to previous trials of the drug and the cholinergic hypothesis of aging and dementia. Using computerised tests sensitive to specific aspects of memory and attention, evidence is found for improvements in attentional function rather than memory, in patients with mild to moderate DAT. Although these improvements were significant, they were small and restricted to certain tests of attentional function. Nevertheless, they add to the growing body of evidence that the cholinergic system is involved in the control of attentional processes. The results will be relevant to future investigations into the therapeutic effects of enhancement of the cholinergic system in DAT sufferers.

Aged↗
PubMed1993

Neurological manifestations of baclofen withdrawal.

Baclofen is a central nervous system agent that is commonly used for the treatment of muscle spasticity in spinal cord injury patients. Acute withdrawal of this medication can induce the development of neurological symptoms, including seizure disorder, psychosis, hallucinations and visual disturbances. We report 3 cases of acute central nervous system symptoms that developed in spinal cord injury patients. Each patient had been chronically maintained on a baclofen regimen to control muscle spasticity. Symptoms developed shortly after baclofen therapy was interrupted following genitourinary surgery. It is important that urologists become familiar with the symptomatology of baclofen withdrawal, the methods of its prevention and the appropriate therapy should the syndrome develop.

Adult↗
PubMed1992

Yeast KRE2 defines a new gene family encoding probable secretory proteins, and is required for the correct N-glycosylation of proteins.

We have cloned, sequenced and disrupted the KRE2 gene of Saccharomyces cerevisiae, identified by killer-resistant mutants with a defective cell wall receptor for the toxin. The KRE2 gene is close to PHO8 on chromosome 4, and encodes a predicted 49-kD protein, Kre2p, that probably enters the secretory pathway. Haploid cells carrying a disruption of the KRE2 locus grow more slowly than wild-type cells at 30 degrees, and fail to grow at 37 degrees. At 30 degrees, kre2 mutants showed altered N-linked glycosylation of proteins, as the average size of N-linked outer chains was reduced. We identified two other genes, YUR1 on chromosome 10, and KTR1 on chromosome 15, whose predicted products share 36% identity with Kre2p over more than 300 amino acid residues. Yur1p has an N-terminal signal sequence like Kre2p, while Ktr1p has a predicted topology consistent with a type 2 membrane protein. In all cases the conserved regions of these proteins appear to be on the lumenal side of secretory compartments, suggesting related function. KRE2, KTR1 and YUR1 define a new yeast gene family.

Amino Acid Sequence↗
PubMed1992

Blushing as a function of audience size.

Almost no experimental analysis of blushing has been done since Darwin's observations in 1872. Forty-eight college women watched a videotape intended to elicit blushing, and a videotape not intended to elicit blushing, but elicit physiological responses. A subject was alone, or with one or four persons present. Blushing, which was measured directly with a photoplethysmograph probe on the cheek, was greater during the blushing than nonblushing stimulation. Blushing increased as audience size increased from one to four, but not from zero to one. Audience size and kind of stimulation interacted statistically. Similar results were obtained with ear coloration, cheek temperature, and skin conductance responses, although confidence levels were lower. Cheek coloration and temperature were significantly correlated during nonblushing stimulation, and the zero and one audience conditions, but not during the four audience condition, when blushing was greatest. These results may be placed within the context of emotional effects of audience size generally, including stuttering and speech disturbance, disruption of learning, and self-reported tension.

Adult↗
PubMed1991

Dynamic interplay between two copper-titrating components in the transcriptional regulation of cyt c6.

The algal plastidic cytochrome c (cyt c6) is a biochemical equivalent of the copper-containing protein plastocyanin in photosynthetic electron transfer. But generally, cyt c6 accumulates and functions only under conditions (e.g. Cu-deficiency) where holoplastocyanin cannot be synthesized. In studying the regulation of Chlamydomonas reinhardtii cyt c6 expression by Cu we have determined that repression of cyt c6 accumulation occurs at the transcriptional level, and specifically in response to Cu as the metal ion regulator. Complete and sustained repression of cyt c6 transcription requires approximately 9 x 10(6) Cu ions in the medium/cell. Based on the estimated plastocyanin content of algal cells (8 x 10(6) molecules/cell) and the observation that lower ratios of Cu per cell result in only transient repression of cyt c6 transcription, we propose that Cu-dependent transcriptional repression of the gene encoding cyt c6 requires a Cu-binding factor which is titrated by Cu only after the alternate electron transfer catalyst, plastocyanin, has accumulated to the stoichiometry required for photosynthesis. The precise and highly metal-specific, autoregulatory control of cyt c6 levels--directly by Cu, and indirectly by holoplastocyanin--is in keeping with the functional role of cyt c6 as an alternate, although perhaps less preferred, electron transfer catalyst.

Blotting, Northern↗
PubMed1991

A multicenter, prospective study of fetal outcome following accidental carbon monoxide poisoning in pregnancy.

We report the results of the first prospective, multicenter study of acute carbon monoxide (CO) poisoning in pregnancy. We collected and followed cases of CO poisoning occurring during pregnancy between December 1985 and March 1989. The sources of CO were malfunctioning furnaces (n = 16), hot water heaters (n = 7), car fumes (n = 6), and methylene chloride inhalation (n = 3). Pregnancy outcome was adversely affected in 3 of 5 pregnancies with severe toxicity; two stillbirths, and one cerebral palsy with tomographic findings consistent with ischemic damage. All adverse outcome occurred in cases treated with high flow oxygen, whereas the 2 cases of severe toxicity with normal outcomes followed hyperbaric oxygen therapy. All 31 babies exposed in utero to mild or moderate CO poisoning exhibited normal physical and neurobehavioral development. Severe maternal CO toxicity was associated with significantly more adverse fetal cases when compared to mild maternal toxicity (P less than 0.001). It is concluded that while severe CO poisoning poses serious short- and long-term fetal risk, mild accidental exposure is likely to result in normal fetal outcome. Because fetal accumulation of CO is higher and its elimination slower than in the maternal circulation, hyperbaric oxygen may decrease fetal hypoxia and improve outcome.

Abnormalities, Drug-Induced↗
PubMed1991

Seasonal variations in urinary risk factors among patients with nephrolithiasis.

Twenty-four hour urine specimens from 5,677 stone-forming patients throughout the United States were analyzed for seasonal variations in urinary risk factors for nephrolithiasis. Determinations were performed for urine volume, pH, calcium, oxalate, phosphorus, sodium, magnesium, citrate, sulfate, uric acid, and the relative supersaturation (RS) of calcium oxalate, brushite, monosodium urate, and uric acid. Criteria for significant seasonal variation included a significant difference in monthly means of risk factors, seasonal grouping of the data by the Student-Newman-Keuls multiple range test, consistent year-to-year trends and a physiologically significant range. Minimum urine volume of 1.54 +/- 0.70 SD L/day occurred in October while a maximum urine volume of 1.76 +/- 0.78 SD L/day was observed during February. Minimum urine pH of 5.94 +/- 0.64 SD was observed during July and August while a maximum pH of 6.18 +/- 0.61 SD was observed during February. Daily urinary excretion of sodium was lowest during August, 158 +/- 74 SD mEq/day and highest during February 177 +/- 70 SD mEq/day. The RS of brushite and uric acid were found to display significant pH-dependent seasonal variation with a maximum RS of uric acid 2.26 +/- 1.98 SD in June and a low of 1.48 +/- 1.30 SD in February. Maximum RS of brushite 2.75 +/- 2.58 was observed during February. Minimum RS of brushite 1.93 +/- 1.70 SD was observed in June. Phosphorus excretion displayed seasonal variation about a spring-fall axis with a maximum value 1042 +/- 373 SD mg/day in April and a minimum value of 895 +/- 289 SD mg/day. Urine volume, sodium, and pH were significantly lower during the summer (June, July, August) than in the winter (December, January, February). The RS of uric acid was higher, but that of brushite and monosodium urate was lower in the summer than in the winter. The seasonal changes observed in urine volume, pH, sodium, and the RS of brushite and uric acid are consistent with summertime sweating and increased physical activity. Seasonal variations in phosphorus excretion are probably dietary in origin. The summertime was characterized by an increased propensity for the crystallization of uric acid but not of calcium oxalate or calcium phosphate.

Calcium↗
PubMed1991

Approaches to the measurement of childhood mortality: a comparative review.

"In the developing world, measures of child mortality are needed for a variety of purposes, and estimates of child mortality can be obtained by a variety of approaches. In this paper, the author reviews the characteristics that child mortality measures should have for particular purposes, and then examines the available measurement approaches to determine the extent to which they provide accurate measures with the required characteristics. Particular emphasis is put on the comparative performance of different approaches in different settings to produce estimates of recent levels and trends in child mortality. He concludes that no single approach can satisfy all measurement purposes and that all approaches are sensitive to the quality of data collection, but that many needs can be met by relatively inexpensive data collection and analysis methods."

Data Collection↗
PubMed1990

Isolation and characterization of a complementary DNA clone for an algal pre-apoplastocyanin.

We have isolated a cDNA clone for the Chlamydomonas reinhardtii pre-apoplastocyanin. The sequence contains codons for the complete pre-protein including a two-domain, lumen-targeting transit sequence and the mature apoprotein. The transit sequence (47 amino acids) is the shortest one described for chloroplast lumenal proteins, and like other C. reinhardtii lumen-targeting transit sequences appears to lack an uncharged amino-terminal domain usually present in plant lumen-directing sequences. The mature protein is deduced to be 98 amino acids in length and shows highest primary sequence similarity (74-76% identity) to other unicellular algal plastocyanins. Southern hybridization analysis of C. reinhardtii genomic DNA indicates the presence of a single nuclear gene, as is the case for all other plastocyanin genes characterized to date, although the algal gene might be interrupted. Codon usage in this gene reflects the high GC content of C. reinhardtii nuclear DNA, but is more highly biased than that found in the C. reinhardtii copper-repressible gene for the functionally equivalent pre-apocytochrome c552 (perhaps contributing to the more efficient synthesis in vivo of plastocyanin over cytochrome c552). The deduced physical properties of this plastocyanin are compared to those of the C. reinhardtii plastidic cytochrome c552.

Amino Acid Sequence↗
PubMed1990

A nucleotide that enhances the charging of RNA minihelix sequence variants with alanine.

We showed earlier that a single G3.U70 base pair within the amino acid acceptor helix is a major determinant of the identity of tRNA(Ala). In addition, we demonstrated that an RNA hairpin minihelix that recreates the 12 base pair acceptor-T psi C stem of tRNA(Ala) is also aminoacylated in a G3.U70-dependent manner. Determinants for efficient aminoacylation at pH 7.5 have been further investigated with minihelix substrates that have sequence variations at 3.70 and other locations. Although a U,U mismatch and other 3.70 nucleotide alternatives to G.U were recently proposed by others as also important for alanine acceptance, neither that mismatch nor any of four other 3.70 nucleotide combinations confer aminoacylation in vitro with alanine, even with substrate levels of enzyme. In contrast, permutations of the so-called discriminator nucleotide N73 (at position 73) strongly modulate, but do not block, aminoacylation of those substrates that encode G3.U70. In particular, the efficiency of G3.U70-dependent aminoacylation with alanine is strongly enhanced by having the wild-type A73. The effect of N73 alone can explain most of the difference in aminoacylation efficiency of a G3.U70-containing tRNA and a minihelix substrate whose sequences vary significantly from their tRNA(Ala) counterparts. Comparison with earlier work suggests that the substantial modulating effect of N73 is partly or completely obscured when N73 tRNA variants are expressed as amber suppressors in vivo.

Alanine-tRNA Ligase↗
PubMed1990

Facial coloration and temperature responses in blushing.

Little work on the psychophysiology of blushing has been done since Darwin's 1872 observations. Facial vascular and temperature changes have been largely ignored in psychophysiology. We had 16 female and 16 male undergraduate volunteers watch a videotape intended to produce blushing (the individual's singing recorded the previous day), and a videotape not intended to produce blushing, but elicit physiological responses for comparison (a segment from Hitchcock's movie Psycho). Four people were present as a subject watched these video segments. Cheek and ear coloration, measured photoplethysmographically, cheek temperature, and finger skin conductance responses were significantly greater during stimulation intended to elicit blushing than during comparison stimulation. Gender interacted statistically with kind of stimulation only in cheek temperature. Only video segments of the subject's face that coincided with maximal cheek coloration during stimulation intended to produce blushing were judged reliably as blushing, and then more often in females than in males.

Adolescent↗
PubMed1990

The yeast KRE5 gene encodes a probable endoplasmic reticulum protein required for (1----6)-beta-D-glucan synthesis and normal cell growth.

Yeast kre mutants define a pathway of cell wall (1----6)-beta-D-glucan synthesis, and mutants in genes KRE5 and KRE6 appear to interact early in such a pathway. We have cloned KRE5, and the sequence predicts the product to be a large, hydrophilic, secretory glycoprotein which contains the COOH-terminal endoplasmic reticulum retention signal, HDEL. Deletion of the KRE5 gene resulted in cells with aberrant morphology and extremely compromised growth. Suppressors to the KRE5 deletions arose at a frequency of 1 in 10(7) to 1 in 10(8) and permitted an analysis of deletions which were found to contain no alkali-insoluble (1----6)-beta-D-glucan. These results indicate a role for (1----6)-beta-D-glucan in normal cell growth and suggest a model for sequential assembly of (1----6)-beta-D-glucan in the yeast secretory pathway.

Amino Acid Sequence↗
PubMed1989

Evidence that the 3' end of a tRNA binds to a site in the adenylate synthesis domain of an aminoacyl-tRNA synthetase.

Aminoacylation requires that an enzyme-bound aminoacyladenylate is brought proximal to the 3' end of a specific transfer RNA. In Escherichia coli alanyl-tRNA synthetase, the first 368 amino acids encode a domain for adenylate synthesis while sequences on the carboxyl-terminal side of this domain are required for much of the enzyme-tRNAAla binding energy. The 3' end of E. coli tRNAAla has been cross-linked to the enzyme, and sequence analysis showed that Lys-73 is the major site of coupling. A mutant enzyme with a Lys-73----Gln replacement has a 50-fold reduced kcat/Km (with respect to tRNAAla) for aminoacylation but has a relatively small alteration of its kinetic parameters for ATP and alanine in the adenylate synthesis reaction. The data provide evidence that the 3' end of tRNAAla binds to a site in the enzyme domain responsible for adenylate synthesis and that a residue (Lys-73) in this domain is important for a tRNAAla-dependent step that is subsequent to the synthesis of the aminoacyladenylate intermediate.

Adenosine Triphosphate↗